50% xenon (about 0.31-0.58 MAC), when applied for 5 min, reversibly, albeit modestly, inhibited AMPA peak amplitudes and receptor-mediated excitatory postsynaptic currents (Image source: Thinkstock)

Xenon is a noble gas. Its anesthetic properties have been recognized for almost 60 years. When compared to desflurane’s blood gas partition coefficient of 0.424, xenon’s blood/gas partition coefficient of 0.115 makes it the least soluble anesthetic agent. It may have many attractive properties as an anesthetic, but it is also quite expensive. It cannot be synthesized and is instead extracted from the atmosphere. About 12 years ago, Anesthesiology featured a nice review article on the drug. In this month’s edition of the journal, Dr. Tatsuro Kohno (Associate Professor, Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan) and colleagues analyzed the effect of xenon on spinal ventral horn neurons and published their findings in “Effect of Xenon on Excitatory and Inhibitory Transmission in Rat Spinal Ventral Horn Neurons.” Indeed, minimum alveolar concentration for volatile anesthetics is dependent on lack of movement in response to a noxious stimulus and as such is caused by anesthetic effects on the spinal cord rather than the brain.

For the experiment, the authors removed the lumbosacral segment of the spinal cord of animals, which was then cut into 500-μm transverse slices. Individual neurons were identified and whole cell patch clamp recordings, where a very high-resistance seal is made between a micropipette and a membrane, were made from the large lamina IX neurons. Concentration-response curves were obtained for the agonists α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA), N-methyl-D-aspartate (NMDA), γ-aminobutyric acid (GABA), and glycine on the spinal lamina IX neurons with and without exposure to xenon.

AMPA elicited an inward current. NMDA, GABA, or glycine elicited an outward current. With tetrodotoxin, an inhibitor of presynaptic phenomena, no effect was observed, so the effects seen were postsynaptic. When applied for 5 min, 50% xenon (about 0.31-0.58 MAC) reversibly, albeit modestly, inhibited AMPA peak amplitudes and receptor-mediated excitatory postsynaptic currents (EPSCs). Xenon had no effect on NMDA-induced currents, NMDA receptor-mediated EPSCs, GABA-induced currents, or glycine.

These findings, though modest, might mean that spinal ventral horn neurons are not the site of action for immobilization by xenon. Additional study is needed.

Franz Kehl, M.D., Ph.D., D.E.A.A., (Karlsruhe, Germany) delivered a ”State of the Art” lecture about volatile anesthetic-induced organ protection. The experimental data were summarized regarding pre- and postconditioning against myocardial ischemia, as well as the anti-ischemic effects of volatile anesthetics. It is of note that volatile anesthetics exert their beneficial properties above and beyond the beneficial hemodynamic alterations that favorably rebalance the oxygen supply and demand ratio of ischemic myocardium. Signal transduction cascades were discussed and depicted and the opposing roles of hyperglycemia and diabetes mellitus demonstrated. In addition to volatile anesthetic-induced cardioprotection, there is demonstrable evidence of neuro- and nephroprotection as well as lung and liver protection. These benefits account for the use of the generic when describing the overall phenomenon (i.e., volatile anesthetic-induced “organ” protection). The usefulness of volatile anesthetic-induced balanced anesthesia was also discussed in the context of anesthesia for patients at risk in the clinical setting.

Alexander Russnikov, M.D., Ph.D., (Moscow, Russia) gave a presentation on the merits of xenon as a gaseous anesthetic. There are virtually no drawbacks of using xenon except for price, which is high even in Russia, and where common sense would suggest otherwise due to it being produced as a byproduct of liquefying air to obtain liquid oxygen for use as a propellant in the rocket industry. Preliminary data were shown on the clinical effects of xenon´s potential of inducing neuroprotection. Xenon obviously mediates its effects along the same pathways as volatile anesthetics. In this elaborate lecture some wise remarks were made and even Confucius was cited: “The hardest thing of all is to find a black cat in a dark room, especially if there is no cat.”

Elisabeth Justiniano, M.D., (Bolivia) gave a presentation on dipyrone, also known as metamizole, the most widely used analgesic in Bolivia for in-hospital and over-the-counter pain relief. About 80% of Bolivia’s population has a chance of receiving metamizole at least once in the span of their lifetime. Because of legislation restricting or banning its availability in some countries due to its 1:1,000,000 potential for inducing agranulocytosis (though this number has also been reported to be much higher in other research), a sometimes but seldom fatal complication, Dr. Justiniano discussed other drugs with the same potential of inducing agranulocytosis, among them ticlopidine and trimethoprim, drugs widely used in many countries. As of now, metamizole is still available, and in light of the minute chance of acquiring metamizole-induced agranulocytosis, its use is advocated.

Gabriel Gurmann, M.D., (Negev, Israel) discussed propofol infusion syndrome (PRIS). PRIS is a syndrome that was first described in children receiving propofol infusion for sedation in excess of 4mg/kg/hr and is characterized by lactic acidosis, elevated liver enzymes, and rhabdomyolysis. As a differential diagnosis, sepsis (of any cause) and compartment syndome have to be considered. Caution must be exercised in any case where there is an increased need for higher doses of propofol, particularly in combination with catecholamines and corticosteroids. A sedation dose above 4 mg/kg/hr and duration of use longer than 48 hrs is discouraged.

Franz Kehl, M.D., Ph.D., D.E.A.A., (Karlsruhe, Germany) shared insights gleaned from using the AnaConDa^® system to deliver volatile anesthetics in the ICU and gave a broad overview of experience on short- and long-term sedation with volatile anesthetics. At present, it is only possible to deliver either sevoflurane or isoflurane for sedation purposes with the AnaConDa system. All clinical data are reassuring and demonstrate the superior potential of volatile anesthetics as almost ideal agents for sedation in the ICU. Neither tolerance nor dependence development has been observed, the metabolism is negligible compared to intravenous drugs, and titration of sedation level is easy. Drawbacks include the potential of inducing malignant hyperthermia in predisposed patients, increasing intracranial pressure in patients with acute head injury, and a potential of inducing hepatic failure due to the formation of trifluoroacetic acid. This last problem can be avoided by using sevoflurane, as it is not metabolized to trifluoroacetic acid.

Overall, participating in the World Congress is very interesting as one is exposed to the views, opinions, and challenges of different countries in addition to having the opportunity to meet anesthesiologists from around the world. Argentina was a fantastic host featuring an interesting history, friendly people, and possessing a wealth of natural beauty. Argentine tango is a must-see. Buenos Aires is an inviting capitol with many fantastic restaurants, people walking in the streets all night long, the enduring legacy of Evita, and the incredible cemetery of La Recoleta (where Eva Perón was incidentally buried). Natural wonders abound, but time did not allow for a full exploration of the country; it did, however, instill the desire to return and visit the magnificent Iguazú Falls, named one of the New Seven Wonders of Nature by the New Seven Wonders of the World Foundation.

The beneficial effects of propofol beyond hypnosis may be related, at least in part, to its free radical scavenging ability.

Propofol has been shown to have a variety of protective effects. For example, propofol has a neuroprotective effect on cerebral ischemia. There has been little study, though, of the drug’s free radical scavenging activity. Like the tocopherols (e.g., alpha-tocopherol, butylated hydroxytoluene), propofol is a substituted phenol with antioxidant and free radical scavenging activity. This activity is accomplished through electron and hydrogen transfer. In the article “In Vitro Kinetic Evaluation of the Free Radical Scavenging Ability of Propofol,” published online first on 23 April 2011, Dr. Chenggang Zhang (Professor, Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing, China) and coauthors used the synthetic stable free radical 2,2’-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^—), which is dark green in solution, to probe the kinetics of free radical scavenging of propofol as it is converted to colorless ABTS compounds by antioxidants. Propofol covalently reduced ABTS^— to ABTS and several propofol-ABTS compounds in vitro. Its rate of ABTS^— consumption was rapid and stable. It was estimated that 10 propofol molecules could scavenge approximately 36 – 37 ABTS^— molecules when dissolved in methanol. The three clinical propofol formulations tested had similar free radical scavenging activity. These in vitro effects of propofol were observed at concentrations below clinically effective concentrations. In addition to its hypnotic effect, propofol has been reported to have a beneficial effect in ischemia reperfusion injury. These results suggest that the beneficial effects of propofol beyond hypnosis may be related, at least in part, to its free radical scavenging ability.

“Surgery is a profession defined by its authority to cure by means of bodily invasion. The brutality and risks of opening a living person’s body have long been apparent, the benefits only slowly and haltingly worked out.”

How is it possible that this mammoth volume of procedures can be performed to benefit patients in countless ways without being invasive and dangerous? Dr. Gawande answers this question with two words: anesthesia and antisepsis.

Anesthesia: October 16, 1846, was the landmark day when William Morton, a dentist, performed the first public demonstration using ether anesthesia to facilitate surgery at Massachusetts General Hospital. Of course, I can’t pass up the opportunity to remind everyone that there is some controversy surrounding the date of the first clinical use of ether anesthesia, as others credit Crawford Long, of Jefferson, Georgia, and the University of Pennsylvania, with administering diethyl ether by inhalation to James Venable in order to remove a tumor on the latter’s neck on March 30, 1842.

Gawande captures the monumental significance of the clinical use of anesthesia as he describes this seminal event: “The crucial spark of transformation — the moment that changed not just the future of surgery but of medicine as a whole — was the publication on November 18, 1846, of Henry Jacob Bigelow’s groundbreaking report, “Insensibility during Surgical Operations Produced by Inhalation.” With anesthesia blunting pain, surgeons could advance their specialty in many ways interestingly and insightfully outlined by Gawande in the full text of his article.

I strongly encourage anesthesiologists to read “Two Hundred Years of Surgery” for its interesting perspective on the growth and development of surgery. It is clear that Gawande recognizes that it is the anesthesiologist who has made it all possible!

As part of the NEJM’s 200th anniversary celebration, the NEJM has produced some documentaries that summarize medical progress over the course of its history. One video summarizes a portion of what’s contained in the article.

Click here to view the video on YouTube.

Norepinephrine seems to be the best first-line drug in patients with cardiac dysfunction related to septic shock. (Image source: Thinkstock)

If a patient is in septic shock, how should their cardiac dysfunction be treated? Indeed, cardiac dysfunction secondary to septic shock is a significant contributor to mortality secondary to septic shock. In patients with circulatory shock, early use of vasopressors with fluid resuscitation is recommended. Should drugs with both vasopressor and inotrope properties be used, or is a drug with only vasopressor properties appropriate? Specifically, should norepinephrine, epinephrine, or phenylephrine be utilized? In the study “Comparison of Equipressor Doses of Norepinephrine, Epinephrine, and Phenylephrine on Septic Myocardial Dysfunction,” published in this month’s edition of Anesthesiology, Dr. Bruno Levy (Professor, Groupe Choc Contrat Avenir Inserm, U961, Faculte de Medecine, Nancy Universite; Service Réanimation Médicale, CHU Nancy-Brabois) and colleagues used a rat model of septic shock to characterize global hemodynamics and cardiac contractility when comparing the three drugs.

Septic shock was induced by puncturing the cecum, extruding its contents, and then returning it to the abdomen. The animals were resuscitated with saline. Myocardial performance was evaluated using either a conductance catheter placed in the left ventricle or micro positron emission tomography scanning. The animals received norepinephrine, epinephrine, or phenylephrine, all titrated to keep mean arterial pressure within 20% of baseline values.

Mortality was 21% before vasopressor infusion. Impaired LV function, characterized by decreased vascular responsiveness hypotension, and lactic acidosis were seen after peritonitis induction. LV dilation was seen after fluid resuscitation. Each drug increased mean arterial pressure and heart rate. With phenylephrine, ventricular afterload was increased, though contractile force was not. Epinephrine and norepinephrine each improved vascular hyporesponsiveness, myocardial dysfunction, and ventriculoarterial coupling. Supraventricular and/or ventricular arrhythmias were higher in animals treated with epinephrine, and heart rate, lactate level, and myocardial oxygen consumption were higher than with norepinephrine. Norepinephrine, then, seems to be the best first-line drug used in patients with cardiac dysfunction related to septic shock.

Inflammatory changes after acute kidney injury can affect the lungs, heart, liver, intestines, and brain.

In this month’s issue of Anesthesiology, Drs. Steven C. Yap and H. Thomas Lee, in their article “Acute Kidney Injury and Extrarenal Organ Dysfunction, New Concepts and Experimental Evidence,” summarized the relationship between acute kidney injury and organ dysfunction. The incidence of acute kidney injury in ICU patients is as high as 20% and mortality after acute kidney injury and organ dysfunction is 50%.

Clinical pearls

How is acute kidney injury (AKI) defined?
In 2004, the Acute Dialysis Quality Initiative Group based acute kidney injury on changes in serum creatinine, glomerular filtration rate, or urine output. Given that mortality can increase with changes in creatinine as small as 0.3 mg/dl, the term “acute kidney injury” is preferable to “acute kidney failure.”

Are there animal models of AKI?

In one model, renal ischemia reperfusion is performed by transiently occluding the renal artery. Such a model can replicate patients who undergo suprarenal aortic aneurysm repair, partial nephrectomy, renal transplantation, contrast-induced nephropathy, shock, and cardiac arrest. The injured renal tubules then release cytokines and chemokines.

Unilateral or bilateral nephrectomy can demonstrate decreased or absent renal function without reperfusion syndrome effects superimposed.

There are nephrotoxic injury and sepsis models, though they do not reliably produce AKI in mice. Furthermore, not all studies in animals match what is seen in humans. For example, it is difficult to induce contrast-induced nephropathy with contrast alone or gentamicin-induced nephrotoxic studies with gentamicin alone. Previous exposure to renal insults is also required.

What is the relationship between AKI and pulmonary dysfunction?

Certainly, AKI can make weaning off of mechanical ventilation difficult, though this relationship is more than a function of increased volume status. For one, injury to renal tubule cells or extrarenal cells can result in the inflammatory cascade which causes increased concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). TNF-α and IL-6 can result in increased permeability, leukocyte trafficking, and edema and result in injury to distal organs such as the lung. Impaired vascular permeability results in fluid accumulation within the lung that then leads to pulmonary edema and compromised lung mechanics. Fluid in the alveoli also inactivates surfactant. Ischemic AKI also down-regulates the sodium potassium pump and aquaporin activity (membrane water channels), which upsets the lung’s intrinsic compensatory mechanism for lung interstitial edema.

Does AKI affect gastrointestinal function?

The intestines have immunologic and barrier functions so intraluminal proinflammatory antigens cannot get into the bloodstream through portal circulation. Kidney injury through either ischemia reperfusion or bilateral nephrectomy can result in uncontrolled expression of interleukin-17A (IL-17A) in the small intestines. IL-17A is a pro-inflammatory cytokine that can cause disruption of intestinal barrier integrity, leading to intraluminal antigens that drain into the portal celebration. TNF-α and IL-6 are then expressed by the liver, which potentiates liver injury. The liver, when stressed, triggers production of reactive oxygen species that can trigger and maintain the inflammatory response. In animals, anti-inflammatory agents such as isoflurane have been shown to reduce this injury.

What is the relationship between AKI and cardiac function?

In cardiorenal syndrome, both the heart and kidneys fail and either organ can be primarily responsible. Cardiorenal syndrome type 3 is defined as heart failure secondary to AKI. Cardiac dysfunction after AKI can be due to fluid overload, which also contributes to pulmonary edema, acidemia, which causes pulmonary vasoconstriction, untreated uremia, which results in pericarditis and decreased myocardial contractility, and hyperkalemia, which can result in arrhythmias. Inflammatory cytokines expressed after significant renal injury are associated with heart failure. TNF-α and IL-6, with neurohormones that lead to salt and water retention, can lead to progressive left ventricular dysfunction, pulmonary edema, left ventricular remodeling, myocyte hypertrophy, and apoptosis.Interestingly, at least in animals, mild renal ischemia followed by reperfusion can protect the heart from ischemia.

What is the relationship between AKI and cerebral dysfunction?

There is a relationship between uremia and encephalopathy, though whether the encephalopathy is due to uremia or UKI is not clear. With AKI, the blood-brain barrier is disrupted. This results in cerebral edema. In addition, metabolites and toxins that are normally not permeable can affect the brain.

These ideas are presented in much more detail in the full article.

Length of survival was increased and intestinal injury was reduced when dexmedetomidine, at a dose equivalent to 0.8 μg • kg-1 • h-1 in humans, was administered before intestinal injury.

If blood flow is interrupted, tissue becomes ischemic. If blood flow is then restored, reperfusion injury can result. If this process occurs in the intestine, it is known as intestinal ischemia-reperfusion (I/R) injury. Such injury can result from hemorrhagic shock, severe burns, and some surgical procedures including cardiopulmonary bypass, small bowel transplantation, and abdominal aortic surgery. When this occurs in patients cared for in an intensive care unit, mortality is high.

Dexmedetomidine is used for sedation in intensive care units. Interestingly, in animals, studies have shown that for ischemic-reperfusion injury in the heart, kidney, brain, or testis, dexmedetomidine has a protective effect. In their study titled “Dexmedetomidine Administration before, but Not after, Ischemia Attenuates Intestinal Injury Induced by Intestinal Ischemia-Reperfusion in Rats,” published this month in Anesthesiology, Dr. Ke-Xuan Liu (Professor, Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China) and colleagues sought to determine whether different doses of dexmedetomidine, given before or after ischemia, would have a similar effect on I/R injury in the intestine.

In the authors’ rat model, the superior mesenteric artery was clamped for 1 h, and then reperfusion was allowed for 2 h. Dexmedetomidine was infused for 1 h at 3 different doses either before or after ischemia. Each study group included 12 animals.

With the highest dose of dexmedetomidine, 10 μg•kg^-1•h^-1, the animals had severe hemodynamic instability. When the rats were infused with the lowest dose of dexmedetomidine, 2.5 μg•kg^-1•h^-1, no signs of intestinal protection were seen. Due perhaps to its slow onset, no effect was seen at any dose when the drug was administered at the beginning of reperfusion.

Length of survival as well as different measures of intestinal injury showed that when the middle dose, 5 μg•kg^-1•h^-1 dexmedetomidine, equal to about 0.8 μg•kg^-1•h^-1 in humans, was administered to the rats before injury, degree of injury was reduced; serum TNF-α concentration was reduced, suggesting that the inflammatory response was reduced; and intestinal mucosal epithelial cell apoptosis was reduced. Yohimbine hydrochloride, an α₂ adrenoceptor antagonist, abolished the protective effect of the middle dose of dexmedetomidine when given before ischemia; this indicates that α₂-adrenoreceptor activation plays an important role in the intestinal protection afforded by dexmedetomidine.

Whether improved outcome will be seen when dexmedetomidine is administered as early as possible during a patient’s illness in the clinical setting remains to be seen.

Question: Based on visits, name 1 of the top 3 cities where people come from who visit Page2Anesthesiology.

From January 1, 2012, to May 9, 2012, the top three cities, with the top city first, are:

Manila
New Delhi
New York

Many guessed cities within the United States. The United States is the country that overall has the most visits, though in terms of cities, New York comes in as #3.

The winner is Frank Banzali, who won an Amazon.com gift certificate. Congratulations, Frank!

Environmental impact should also be considered when deciding which anesthetic is appropriate to use. (Image source: Thinkstock)

Anesthesia journals usually publish articles examining the effect of drugs on patients or animals. In the article “Life Cycle Greenhouse Gas Emissions of Anesthetic Drugs,” Dr. Jodi Sherman (Yale School of Medicine, Department of Anesthesiology) and colleagues instead analyzed resource extraction, drug manufacturing, transport to healthcare facilities, drug delivery to the patient, and disposal or emission to the environment of different anesthetic drugs we use. Energy, material inputs, and emissions, e.g., for fuel combustion to produce electricity, were calculated for each stage. Energy requirements for drug synthesis were based on assumed synthesis routes since manufacturers do not make that particular information available. Transportation of drugs to the corresponding author’s institution via diesel trucks was the basis for the transport portion of the model. In calculating disposal costs, a 50% wastage rate was assumed.

Desflurane had the greatest amount of greenhouse gas emissions. Isoflurane and sevoflurane were similar in terms of their greenhouse gas emission profiles. If an air/oxygen mixture is used, isoflurane produces more emissions than sevoflurane since isoflurane has a high radiative forcing effect. Propofol has the least amount of greenhouse gas impact of all the anesthetics. The greatest impact of propofol is a result of the energy needed to operate the pump. Propofol’s impact is four orders of magnitude lower than that of desflurane or nitrous oxide.

Uncertainty in the analysis is mostly due to the fact that the synthesis of the drugs is not precisely known. The analysis, however, highlights the fact that environmental impact should also be considered when deciding which anesthetic is appropriate to use.

Electrical impedance tomography at bedside in the ICU. Note the flexible band around the patient’s chest. (Source: Draeger medical, used with permission)

This “In the Lab” post is based on the article “Spontaneous Breathing during General Anesthesia Prevents the Ventral Redistribution of Ventilation as Detected by Electrical Impedance Tomography: A Randomized Trial,” authored by Dr. Oliver C. Radke (Assistant Clinical Professor, San Francisco General Hospital, Department of Anesthesia & Perioperative Care, University of California San Francisco, San Francisco, California, and Senior Attending Anesthesiologist, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Fetscherstr, Dresden, Germany) and colleagues, which appeared online first on 23 April 2012.

Most interesting research questions arise from discussions with residents about what we do every day. When we talked about patients with laryngeal mask airways (LMAs), we wondered how the different ways to ventilate (spontaneous breathing, pressure control or pressure support) might change the way air is distributed in the lungs.

One possible way to find the answer to this question would be to perform an animal study in the lab. However, animal studies are always artificial to some extent, and we wanted to know what actually happens during the anesthesia we perform daily in the OR. Despite deciding against doing an animal study, the trip we took our pulmonary research group to in the animal lab was invaluable, because they had a device that we could borrow for our own research in the operating room.

Defining the primary outcome parameter
The device we found uses a method called “electrical impedance tomography,” otherwise known as EIT. It is a noninvasive method to visualize the distribution of impedances in a cross-section of the thorax. Air causes high impedance while blood and tissue cause low impedance. During ventilation, the air content of the lungs has the highest impact on changes in the impedances; thus, the EIT device allows us to assess the changes in air distribution in real time and without radiation.

In short, our study plan was to compare the influence of spontaneous breathing, pressure-controlled ventilation and pressure support ventilation on the dorsoventral distribution of air in the lungs during general anesthesia in patients with LMAs. While writing the study protocol, we drafted a standardized anesthesia regimen that would work with all three modes of ventilation.

Data acquisition
After finding this method to assess our primary outcome and drafting a study protocol, we had to find a way to turn our operating room into a research lab. To reduce confounding factors, we had to make sure that we could control for as many variables as possible. Additionally, we had to find a way to collect and analyze all the relevant data.

Ventilator
One of the anesthesia machines we routinely use in clinical practice is the ZEUS^® (Dräger Medical, Lübeck, Germany). A unique feature of the ZEUS is its ventilator design: The ZEUS is capable of running as a completely closed system. In a closed system, instead of dialing a fresh gas flow and opening up the vapor to mix in the volatile anesthetic, we set the desired inspired oxygen concentration (FiO₂) and the desired end-tidal volatile fraction. The machine measures these concentrations and by means of a feedback algorithm it adjusts the gas concentrations as necessary. As a result, we achieve completely stable gas concentrations throughout the case, an ideal situation for our clinical study where we want to control as many independent variables as possible.

Another advantage of the ZEUS is that it is completely computerized and all of the relevant parameters such as airway pressure, CO₂ levels, flow rates and even waveforms can be extracted from the machine via a standardized interface port (MEDIBUS).

Monitor
The patient monitors we use in our operating rooms (Philips MP70, Philips Deutschland GmbH, Hamburg, Germany) do not offer a direct means to download the data. However, all the monitors are connected to a central server, and this server allows all the data to be displayed in a web browser. The data in the web browser’s window can easily be copied into a spreadsheet or database program. All the measured vital signs (heart rate, blood pressure, oxygen saturation) and even the BIS values are available to us.

EIT data
The EIT device (EIT Evaluation Kit 2, Dräger Medical) is capable of recording real-time (20 Hz) two-dimensional images for extended periods of time. The raw data (several gigabytes) can be extracted by using a USB storage device for offline processing.

The EIT device uses a flexible electrode belt positioned around the patient’s chest. Because we didn’t want to get in the surgeon’s way, we chose knee, foot and ankle surgery cases for our study. The EIT device doesn’t take much time to set up, so integrating the EIT device into the clinical workflow was easy.

EIT data analysis
The EIT device provides some algorithms to analyze the EIT data, but it does not allow custom algorithms. However, the data format of the raw data stream is documented, so we decided to write our own software to analyze the data.

Screenshot of the analyzer program for raw EIT data. (Source: author)

The screenshot shows the raw data in the top left corner and two different functional images below. The functional images basically map the impedance change across a transverse cross- section of the patient’s chest. Simply put, the lighter the colors, the more air has moved into that part of the lung.

The top graph shows the raw total impedance. The second graph shows several continuously calculated values. On the bottom are histograms of the dorsoventral distribution of the tidal variation.

All of the calculated values end up in a large table (partially seen in the lower right corner). Our primary outcome parameter was the center of ventilation (COV). This table can be exported from the EIT device and then imported into a database program.

Baseline EIT recording of Patient #29 during awake spontaneous breathing in supine position. Lighter colors indicate higher impedance, i.e. more air. The majority of air is seen in the mid-dorsal aspects of the lung.

Same patient #29, but this time during pressure controlled ventilation. The air content is now predominantly in the mid-ventral part of the lung.

Putting it all together
We created a database in Microsoft Access with several tables. One table holds the patient demographics, a second table contains all the measured parameters, and a third table holds all the results that were produced by our analyzer software. The database application allows us to filter, group and aggregate the data and prepare neatly aligned tables for statistical analysis.

The tables from Access were imported into the statistical software program SPSS. SPSS allows us to analyze the data and compare the groups in numerous ways. The results of these tests allowed us to differentiate with reasonable confidence between findings that were related to the difference in ventilation and findings that were caused by random chance.

Conclusion
Conducting a clinical study in a busy orthopedic operating room is quite demanding. It took us more than half a year to successfully recruit 30 patients, but owing to a great research team, a meticulous study plan, and invaluable help from our nurses, all patients who were enrolled successfully completed the study. Since we used the standard anesthesia equipment for data acquisition (except for the EIT device), turning the operating room into a research lab was accomplished in a matter of minutes. Thus we avoided delays, didn’t need much additional space, and kept our orthopedic surgeons happy.

Contact address:
Oliver C. Radke, MD, PhD, DEAA
Assistant Clinical Professor, San Francisco General Hospital, Department of Anesthesia & Perioperative Care University of California San Francisco, 1001 Potrero Ave, San Francisco, CA 94110
Senior Attending Anesthesiologist, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Fetscherstr. 74, 01307 Dresden, Germany

Sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in a considerable number of morbidly obese patients. (Image source: Thinkstock)

Can sugammadex reliably reverse a rocuronium-induced neuromuscular blockade even in morbidly obese patients? If so, how should we calculate the optimal dose to arrive at a safe reversal in these patients who are at risk for postoperative upper airway collapse?

Drug dosing is generally based on the volume of distribution for the loading dose. Muscle relaxants are hydrophilic and their volume of distribution is minimally affected by obesity: their dosage is based on ideal body weight (IBW). In contrast, the loading dose of lipophilic anesthetics is based on total body weight (TBW).

Sugammadex is a modified γ-cyclodextrin, with a lipophilic core and a hydrophilic periphery, so it is important to ask whether the sugammadex dose in obese patients should be calculated based on IBW or TBW.

It is already known that when given at dosages of 2-16 mg/kg, sugammadex can rapidly reverse all depths of neuromuscular blockade as well as allow for the complete recovery of pharyngeal muscles in the nonobese patient population. In the article “Sugammadex Ideal Body Weight Dose Adjusted by Level of Neuromuscular Blockade in Laparoscopic Bariatric Surgery,” published online first on 30 April 2012, Dr. Antoni Sabaté (Professor, Department of Anesthesiology, Reanimation and Pain Clinic, Hospital Universitari de Bellvitge, Universitat de Barcelona Health Campus, Barcelona, Spain) and coauthors administered sugammadex 4 mg/kg IBW to morbidly obese patients undergoing bariatric surgery in order to reverse deep (<2 posttetanic twitches) rocuronium-induced (median:100 mg) neuromuscular blockade in an important observational and pharmacological study. In patients with persistent partial paralysis (train-of-four ratio <0.9), they administered another dose of sugammadex 2 mg/kg IBW. The authors found that 39.5% of the patients presenting with deep neuromuscular blockade showed inadequate reversal with IBW-based sugammadex 4 mg/kg, but all recovered promptly following the additional sugammadex dose.

The authors concluded that a sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in a considerable number of morbidly obese patients.

Though not explicitly studied by Sabaté and colleagues, it is reasonable to draw the clinical conclusion that in obese patients, sugammadex, the drug with a lipophilic core and a hydrophilic periphery, should be dosed by keeping its lipophilicity in mind, based on patients’ TBW.

Is a sevoflurane-based anesthetic safer than a propofol-based anesthetic for patients whose surgery is performed in BCP? (Image source: Thinkstock)

Shoulder surgery is commonly performed in the beach chair position (BCP) because it’s easier to perform it in that manner. In that position, though, patients may be prone to greater risk than if they were supine. Indeed, blood flow to the brain decreases when the head is higher than the heart since gravity affects blood flow. Jugular venous bulb oxygen saturation (SjvO₂) and externally placed cerebral oxygen probes indirectly represent cerebral blood flow and cerebral oxygenation. Dr. Kyung Y. Yoo (Professor, Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Chonnam, Gwangju, South Korea) and colleagues, in their article titled “Cerebral Oxygen Saturation Measured by Near-infrared Spectroscopy and Jugular Venous Bulb Oxygen Saturation during Arthroscopic Shoulder Surgery in Beach Chair Position under Sevoflurane-Nitrous Oxide or Propofol-Remifentanil Anesthesia,” compared jugular venous bulb and regional cerebral tissue oxygen saturation in patients who received either sevoflurane or propofol for shoulder surgery in the beach chair position.

Regional cerebral tissue oxygen saturation (SctO₂) was measured using cerebral oximeter probes that were placed on the right and left forehead. Central venous saturation was measured by placing a central venous oximetry catheter retrograde in the jugular bulb opposite the side of surgery. Forty-two patients were enrolled in the study; two were withdrawn because the central venous oximetry catheter could not be inserted. Mean arterial pressure decreased after both sevoflurane and propofol postinduction and after patients were moved to BCP, though it was higher for patients who received sevoflurane. Central venous oxygen saturation decreased after beach chair positioning, though the decrease was less in patients who received sevoflurane. No difference in SctO₂ was seen. The incidence of hypotension, defined as a mean arterial pressure less than 50 mm Hg, was lower in the sevoflurane group. Ephedrine use was greater in the sevoflurane group; however, total amount of ephedrine did not differ between groups. Incidence of SjvO₂ less than 50% was greater in the propofol group. SctO₂ and the incidence of cerebral desaturation (more than 20% decrease from baseline) did not significantly differ between groups. Jugular venous bulb and regional cerebral tissue oxygen saturation correlated weakly.

Is a sevoflurane-based anesthetic safer than a propofol-based anesthetic for patients whose surgery is performed in BCP? Perhaps. Intraoperative measurement changes are not always associated with adverse outcome after the anesthetic. Though a low SjvO₂ might represent low cerebral perfusion, metabolic demands during anesthesia are less than they are when one is awake. Indeed, in the current study, though some patients did have low SjvO₂, postoperatively no patient was observed to have major neurologic deficits. All patients in this study were free of cerebral pathology: it is unclear whether the same results would be found in patients with cerebral pathology. Given this study’s findings, a sevoflurane- vs. a propofol-based anesthetic might provide a greater margin of safety; however, more study is needed.

Organ failure rates increased as tidal volume increased. (Image source: Thinkstock)

Most would agree that for patients with acute lung injury, tidal volumes should be low since higher tidal volumes can lead to lung trauma. Ventilation with high tidal volumes has also been shown to be a risk for lung injury. Can tidal volume influence outcome for patients who undergo cardiac surgery? Such patients usually have normal lungs before surgery. Respiratory mechanics are probably little affected during the short period that cardiac surgery patients are ventilated, yet systemic inflammation may be secondary to cardiopulmonary bypass and multiple transfusions, and inappropriately high ventilation may make it worse. Low ventilation, however, may result in atelectasis. In the study “High Tidal Volumes in Mechanically Ventilated Patients Increase Organ Dysfunction after Cardiac Surgery,” Dr. Francois Lellouche (Adjunct Professor, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec) and colleagues hypothesized that higher tidal volumes, delivered after surgery, would increase organ failure.

The authors studied patients who underwent cardiac surgery procedures that used sternotomy and cardiopulmonary bypass. Upon arrival in the ICU, patients were ventilated using low (< 10 ml/kg predicted body weight), traditional (10-12 ml/kg predicted body weight) or high (> 12 ml/kg) tidal volume. This was an observation study: patients were not randomized to receive different tidal volumes.

Some 3,434 patients were analyzed. Organ failure rates increased as tidal volume increased and in patients who had prolonged intubation, hemodynamic instability and renal failure. Based on multivariate analysis, high tidal volume was an independent risk factor for organ failure and multiple organ failure, mechanical ventilation more than 24 h and hemodynamic instability. Traditional tidal volume was an independent risk factor for hemodynamic instability. BMI > 30 kg/m² and female gender were risk factors for use of high tidal volumes.

Patients were not randomized, PEEP was not separately analyzed, and the volume groupings were arbitrary. Nonetheless, the study provides evidence to support use of lower tidal volumes. In the accompanying editorial, “Tidal Volumes during General Anesthesia: Size Does Matter!,” Drs. Paolo Pelosi (Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy) and Marcelo Gama de Abreu (Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany) note:

“Certainly, clinical trials addressing the use of protective ventilation with low tidal volumes in the general surgical population are required. However, we do believe that until such trials have been conducted, and provided there are no contraindications, tidal volumes less than 10 ml/kg set according to predicted rather than actual body weight should be the standard. For now, there is enough evidence and a strong rationale to support those recommendations. For the future, the questions to be addressed are how low tidal volumes have to be and how much positive end-expiratory pressure is needed during general anesthesia.”

Low Activity residents reported significantly more depression, anxiety and stress than Friend-Focused or Family-Focused residents. (Image source: Thinkstock)

Residents have free time? In the article “What Do Residents Do When Not Working or Sleeping? A Multispecialty Survey of 36 Residency Programs,” published in the April 2012 issue of Academic Medicine, Dr. DeWitt C. Baldwin (scholar-in-residence, Education Division, Accreditation Council for Graduate Medical Education, Chicago, Illinois) and coauthors report that depending on the specialty, residents now have about 40 to 50 hours a week that consists of time that is free from clinical duties or sleep. Although the ACGME instituted a strict 80-hour-per-week limit on duty hours in 2003 primarily in an effort to decrease resident fatigue and improve patient safety, the effect on house staff well-being and lifestyle has also been of interest. The authors of this study surveyed 759 first- and second-year residents in 36 residency programs in the US and asked them what they were doing with the available significantly increased nonsleep free time.

The authors reported that the majority of residents (both PGY-1s and PGY-2s) spend time on the Internet every day. Several times a week they watch TV, exercise, spend time with family and friends, or do household chores. Less time was reported for reading professional journals or books for fun, going to movies, or moonlighting. Included with this detailed survey were three validated scales of sleepiness, depression and anxiety. The residents were then clustered into three groups depending on the type of activities they reported engaging in and time spent doing so, specifically the “Friend-Focused” cluster, the “Family-Focused” cluster, or the “Low Activity” cluster.

An interesting result of the survey was that the Low Activity residents also reported significantly more depression, anxiety and stress than residents in the other two groups. They also reported more workload-related patient errors, longer hours and fewer friends in their program. Although the study was not set up to examine this cluster in more detail, it does alert us to the fact that a subset of residents have difficulties with work-life balance and this may be impacting their happiness as well as their training and patient care. We should increase our awareness of these residents. When we are carrying out the 6-month reviews of resident progress, it might advisable to pay more attention to what our residents are doing with their free hours.

Members of the Currie lab (2010-2011); From left to right: Kevin Currie, Sarah McDavid, Lei Zhu, Rebecca Brindley and Mark Jewell.

The May issue of Anesthesiology includes a research paper from Kevin Currie’s lab in the Department of Anesthesiology, Vanderbilt University School of Medicine, titled “Gabapentin inhibits catecholamine release from adrenal chromaffin cells.” In this “visit to the lab,” we learn more about the research interests of the Currie lab and the approaches used in the current paper.

Research in the Currie lab focuses on regulation of voltage-gated calcium channels and calcium-dependent exocytosis, the fundamental cellular/molecular mechanism underlying synaptic transmission and neuroendocrine hormone release. Primarily we investigate adrenal chromaffin cells that release a complex cocktail of catecholamines and other neuroendocrine hormones to mediate diverse physiological effects, including the sympathoadrenal stress response. Chromaffin cells also provide a versatile model that enables detailed mechanistic insight into stimulus-secretion coupling. Our overall goal is to understand the regulation of calcium channels and transmitter release under physiological conditions, and identify potential therapeutic targets for treatment of nervous and endocrine system disorders in which these finely tuned processes are disrupted.

David Todd (left panel) is shown preparing samples taken from dishes of chromaffin cells treated with gabapentin or vehicle for ~18-24 hours. The cells were then exposed to various stimuli for 5minutes and samples were collected and prepared for HPLC analyses of catecholamine levels. Ray Johnson (top right), manager of the Vanderbilt Neurochemistry Core, helped analyze the samples. Bottom right panel shows some of the core lab HPLC equipment.

David Todd, first author of the study, entered the Currie lab as a B.H. Robbins Scholar. This program, named in honor of the first chair of the Vanderbilt Department of Anesthesiology, provides protected time for a mentored research experience during anesthesiology residency. Dr. Todd’s clinical interest is in pain medicine, and together with Dr. Currie he conceived of this study in order to investigate the cellular mechanisms of gabapentin.

Sarah McDavid is shown preparing patch pipettes for whole cell patch clamp electrophysiology. The pipette puller enables carefully controlled heating and pulling of borosilicate glass capillary tubes into patch pipettes with precise size and shape. These are then used to record ion channel currents from individual chromaffin cells.

Although primarily used to treat chronic neuropathic pain, gabapentin has a variety of other uses, including evidence that acute preoperative dosing can reduce postoperative pain scores/opioid use and blunt hemodynamic responses to direct laryngoscopy and tracheal intubation. We postulated that hemodynamic stabilization and perhaps other stress-related effects of gabapentin might involve reduced catecholamine release from adrenal chromaffin cells.

To address this question we used high performance liquid chromatography (HPLC) to quantify catecholamine release from populations of chromaffin cells plated in tissue culture dishes. The data gathered showed for the first time that gabapentin inhibits catecholamine release from chromaffin cells.

Calcium entry through voltage-gated calcium channels is the trigger for both neurotransmitter release and catecholamine release from chromaffin cells. Gabapentin is known to bind with high affinity to the α2δ subunit of some calcium channels, and reduced calcium entry would be expected to reduce catecholamine secretion. However, this had never been tested in chromaffin cells and the effects of gabapentin on calcium channel currents (I_Ca) are variable in other cell types. To determine if altered Ca²⁺ entry could explain the reduced catecholamine release in our experiments, we used two approaches: fluorescent imaging of single cells loaded with the calcium-sensitive dye Fura-2, and patch clamp electrophysiology to record whole-cell voltage-gated calcium channel currents.

For patch clamp recording, a pipette puller is used to make so-called “patch pipettes” from capillary glass tubes. These patch pipettes, which have a precise size and shape, are then filled with an intracellular-like salt solution and attached to the headstage of a patch clamp amplifier.

Cells plated on glass coverslips are placed in a recording chamber and a perfusion system permits exchange of the extracellular bath solution. The cells are visualized with an inverted microscope and a micromanipulator is used to position the pipette (tip ~1 µm) so that it touches a single cell (cell diameter ~10-15 µm). The patch clamp “rig” sits on a vibration isolation table and is enclosed in a Faraday cage to shield set-up from ambient electrical noise. We found that gabapentin did not inhibit I_Ca or calcium entry in chromaffin cells under our recording conditions.

Rebecca Brindley is shown recording voltage-gated calcium channel currents from a chromaffin cell using the whole cell patch clamp technique. Some components of the “rig” are labeled.

To gain more precise mechanistic insight into the inhibition of catecholamine release by gabapentin, we utilized carbon fiber amperometry. The decrease in catecholamine release could be due to fewer vesicles fusing with the plasma membrane and/or less catecholamine release from each vesicle. Amperometry is very sensitive and can detect catecholamine release from individual secretory vesicles to address this question. The equipment in these experiments is similar to patch clamp electrophysiology, but a carbon fiber electrode is used rather than a patch pipette. We found that the number of vesicles that fuse with the plasma membrane was reduced by gabapentin, but the amount and kinetics of catecholamine release from each vesicle were unaltered.

Mark Jewell is shown recording catecholamine release from an individual chromaffin cell with carbon fiber amperometry. As displayed in the cartoon, a carbon fiber electrode (5 µm diameter) is positioned adjacent to a chromaffin cell and a potential of +700 mV applied, which rapidly oxidizes any catecholamines released from the cell. When vesicles fuse with the plasma membrane and release their catecholamine content, it is oxidized at the carbon fiber, resulting in an electrical current with a characteristic “spike” waveform. These spikes can be analyzed to quantify number of fusion events and the amount and kinetics of catecholamine release from each vesicle.

Overall, our data show that Ca²⁺ entry is not reduced by gabapentin; however, it is less effective at triggering vesicle fusion and catecholamine release. This identifies altered adrenal catecholamine release as a potential contributor to some of the beneficial perioperative effects of gabapentin. Our work also demonstrates the utility of chromaffin cells as a physiologically relevant model to dissect the cellular mechanisms of gabapentin.

Emergence from AZD-3043-induced hypnosis was rapid.

Propanidid is a short-acting hypnotic because of its metabolically labile ester moiety. It was withdrawn from the market because it was formulated in Cremophor EL^®, which caused histamine release and adverse hemodynamic changes. AZD-3043 is a chemical analog of propanidid that was designed to be a rapidly metabolized hypnotic, like propranidid, but is formulated in a lipid emulsion, like propofol. In “AZD-3043: A Novel, Metabolically Labile Sedative-Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis,” published online first on 23 April 2012, Dr. Talmage D. Egan (Professor of Anesthesiology, Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah) and colleagues characterized the pharmacokinetic and pharmacodynamic aspects of AZD-3043.

AZD-3043 was metabolized rapidly by hepatic microsomes from a number of species and in the whole blood of some. It potentiated GABAA receptor-mediated chloride currents through positive allosteric modulation of receptor activity, suggesting that it should potentiate GABAA-mediated inhibition of CNS neurotransmission. It produced rapid onset, bolus dose-dependent EEG activity suppression in rats, the recovery from which was rapid and relatively independent of the dose administered. A consistent depth of hypnosis was easily maintained by an infusion of AZD-3043 with minimal dose adjustment. The synergy of AZD-3043 and remifentanil was greater than that of propofol and remifentanil, but its synergy with fentanyl was similar to that of propofol. Emergence from AZD-3043-induced hypnosis was rapid and less affected by dose and infusion duration than emergence from propofol-induced hypnosis. First-in-human studies of AZD-3043 have been conducted.

Emergence after propofol anesthesia was faster when methylphenidate was added. (Image source: Thinkstock)

In October 2011, based on a study published in Anesthesiology, Page2Anesthesiology described how methylphenidate, or Ritalin^®, might decrease emergence time from isoflurane anesthesia. In the article “Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate,” that appeared in this month’s Anesthesiology, Dr. Ken Solt (Assistant Professor, Department of Anaesthesia, Harvard Medical School; Assistant Anesthetist, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; and Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology) and colleagues examine the relationship between methylphenidate and recovery after propofol anesthesia.

Rats received either a bolus dose or continuous infusion with propofol. Some rats had implanted extradural electrodes that were used for electroencephalogram (EEG) experiments. Rats received 8 mg/kg propofol intravenously as a bolus dose. For propofol infusion, the final target concentration of propofol was 0.5 µg/ml above the highest propofol dose where purposeful movements occurred.

Rats who received a propofol bolus took 735 s to emerge, i.e, to regain the righting reflex, vs. 448 s for the animals that received the propofol bolus and 5 mg/kg intravenous methylphenidate. During propofol infusion, after administration of methylphenidate, all rats promptly showed signs of reversal; within 4 min, they had restoration of righting reflex. Using EEG measurements and with higher doses of propofol, methylphenidate administration resulted in an EEG consistent with arousal, though righting reflex was not immediately restored.

As noted in the previous Page2Anesthesiology post, further study is needed in humans. Certainly, patients who take methylphenidate require higher doses of propofol. In the accompanying editorial, “From the Edge of Oblivion: The Dance between Intrinsic Neuronal Currents and Neuronal Connectivity,” Drs. Max Kelz and Jamie Sleigh note that this and other studies “give us some valuable insight into the delicate dance between general anesthetic drugs and the natural wake and sleep systems of the brain.”

Giving risperidone after cardiac surgery only to patients with evidence of delirium avoids using the drug on patients who do not need it: extra cost and possible side effects can be avoided. (Image source: Thinkstock)

Moving forward, it is quite likely that we will see more patients with postoperative delirium. This is because the population is aging, older patients undergo more surgery (particularly cardiac surgery) than their younger counterparts, and delirium is common after cardiac surgery. Last month, Page2Anesthesiology summarized a study that showed the relationship between obstructive sleep apnea and postoperative delirium in patients undergoing elective single knee replacement surgery. Risperidone is used to prevent and treat delirium in patients with schizophrenic disorders. In the study “Early Treatment with Risperidone for Subsyndromal Delirium after On-pump Cardiac Surgery in the Elderly: A Randomized Trial,” published in the May issue of Anesthesiology, Dr.  Sameh M. Hakim (Associate Professor, Department of Anesthesiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt) and colleagues studied the relationship between risperidone and postoperative delirium in patients ≥ 65 years after on-pump cardiac surgery.

Patients who experienced subsyndromal delirium (SSD), i.e., those who experienced some, but not all features of delirium, were randomized to receive either 0.5 mg risperidone or placebo every 12 h by mouth. Subsyndromal delirium was diagnosed using the Intensive Care Delirium Screening Checklist (ICDSC), a tool based on assessment using eight items shown to have high sensitivity (99%) and acceptable specificity (64%) for delirium detection. SSD was defined as a score of 1-3 using the ICDSC. The Diagnostic and Statistical Manual of Mental Disorders (DSM) was used to confirm the delirium diagnosis.

Over almost 3 years, 177 patients were enrolled who met eligibility criteria and agreed to participate, and 101 experienced SSD and were randomized to receive either drug or placebo. Delirium was reduced by almost 60%: eight (16%) patients in the risperidone group and 19 (38%) patients in the placebo group had a score of 4 or greater and were considered to be possibly delirious. Delirium was confirmed using DSM criteria in 7 (13%) patients in the risperidone group and 17 (34%) patients in the placebo group, a statistically significant difference. The number needed to treat was 4.9. Intensive care unit stay, length of hospital stay, and extrapyramidal side effects that are known to be associated with risperidone were not different between groups. No patient developed an abnormal QTc interval. Haloperidol rescue was to be used if symptoms were not controlled by risperidone, though the need for the drug was no different between groups.

Based on the strategy utilized in this study, giving the drug only to patients with some evidence of delirium avoids using the drug on patients who do not need it since extra cost and possible side effects can be avoided. As Drs. Leif Saager and Daniel I. Sessler (Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio) noted in the accompanying editorial entitled “Targeted Prophylaxis of Postoperative Delirium,” the authors

“…confirm that risperidone is effective for preventing postoperative delirium. Importantly, they extend previous reports by showing that targeted prophylaxis substantially reduces the number of patients requiring drug administration.”

The American Society of Anesthesiologists offers CME credit based on this post and its accompanying article.

Helicopter transportation, based on regression analysis, was associated with a greater change in odds of survival compared to ground transportation. (Image source: Thinkstock)

For me, at least, the hospital’s helicopter looks impressive. We’re able to view it from one of the hallways leading to the OR. Patients like looking at it as they are wheeled into the operating room. Though perhaps an additional benefit is that it feeds into the hospital’s marketing, an important reason the helicopter is there is to transport traumatically injured patients. Does this make a difference? Indeed, transport by helicopter is expensive and its availability is limited. Is ground transportation just as good? In the study “Association Between Helicopter vs Ground Emergency Medical Services and Survival for Adults With Major Trauma,” published in the 18 April 2012 issue of JAMA, Dr. Samuel M. Galvagno Jr, DO, PhD, (Division of Trauma Anesthesiology, Shock Trauma Center, Program in Trauma, Department of Anesthesiology, University of Maryland School of Medicine, University of Maryland Medical Center, Baltimore, MD) and colleagues retrospectively compared patients older than 15 years of age who were transported by helicopter or ground emergency services to a level I or II trauma center.

The authors compiled data from the 2007-2009 versions of the American College of Surgeons National Trauma Data Bank. Patients transported by other means were not included. They used the Injury Severity Score (ISS) to quantify the severity of trauma and included only those patients whose score was greater than 15. The primary outcome of interest was survival to discharge from hospital. The authors analyzed 61,909 patients who were transported by helicopter and 161,566 who were transported by ground. Unadjusted mortality was significantly higher for patients transported by helicopter, though more patients who were transported by helicopter had ISS scores higher than 24. However, based on regression analysis, helicopter transportation was associated with a greater change with regard to odds of survival. Data suggested that patients in the helicopter group had higher injury severity compared to patients transported by ground since more patients transported by helicopter were discharged to rehabilitation and to intermediate facilities. More patients in the ground transportation group were discharged from a level I center to a nursing home.

Who was caring for patients while they were in the helicopter and the intervention they provided is not known. This was a retrospective study and missing data was high for some variables. It is unlikely, though, that a randomized clinical trial comparing the two types of transport will be undertaken. If providers have the option, this study would favor helicopter use.

Early Treatment with Risperidone for Subsyndromal Delirium after On-pump Cardiac Surgery in the Elderly: A Randomized Trial and Targeted Prophylaxis of Postoperative Delirium

Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate and From the Edge of Oblivion: The Dance between Intrinsic Neuronal Currents and Neuronal Connectivity

Objective Assessment of the Immediate Postoperative Analgesia Using Pupillary Reflex Measurement: A Prospective and Observational Study and Pupillometry to Guide Postoperative Analgesia

Optic Nerve Sheath Diameter Used as Ultrasonographic Assessment of the Incidence of Raised Intracranial Pressure in Preeclampsia: A Pilot Study and
Imaging Intracranial Pressure: An Introduction to Ultrasonography of the Optic Nerve Sheath

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There is an increased risk of difficult mask ventilation and unplanned hospital admission in the patients whom experience uLMA™ failure. (Image source: Thinkstock)

In the study “Predictors and Clinical Outcomes from Failed Laryngeal Mask Airway Unique™: A Study of 15,795 Patients,” published online first on 16 April 2012, Dr. Satya Krishna Ramachandran (Assistant Professor, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan) and colleagues studied risk factors predicting laryngeal mask airway (LMA Unique™, uLMA™; LMA North America, Inc., San Diego, CA) failure. The primary outcome of the study was uLMA™ failure, which was defined as an airway event requiring uLMA™ removal and tracheal intubation. The secondary outcomes were the incidences of difficult mask ventilation and unplanned hospital admission.

Data were obtained by reviewing the prospective perioperative electronic clinical information available within authors’ anesthesiology department. Of the 15,795 cases in the study, 1.1% of patients experienced uLMA™ failure. Within the aforementioned group, 60% suffered from hypoxia, hypercarbia, or airway obstruction, and 42% presented with inadequate ventilation related to leaks. There were four independent predictors for failed uLMA™: surgical table rotation, male gender, poor dentition, and elevated body mass index. Unplanned hospital admission occurred in 13.7% of ambulatory patients with uLMA™ failure. Difficult mask ventilation occurred in 5.6% of patients with uLMA™ failure, a 3-fold increase.

This study confirmed that the use of uLMA™ is an effective supraglottic device with a low failure rate of 1.1%. However, there is an increased risk of difficult mask ventilation and unplanned hospital admission in the patients whom experience uLMA™ failure.

In the accompanying editorial, “Complications with Supraglottic Airways: Something to Worry About or Much Ado About Nothing?,” published online first on 12 April 2012, Dr. Takashi Asai (Department of Anesthesiology, Kansai Medical University, Takii Hospital, Osaka, Japan) notes,

“…recent studies of a large number of patients (including the study of Ramachandran et al.) indicate that there is also no doubt that even now the incidence of complications associated with the use of a supraglottic airway is not low enough.”

Furthermore, his conclusion as stated in the editorial is,

“We need to make further efforts not only to elucidate causative factors of complications and difficulties with the use of a supraglottic airway, but also to perform accurate preoperative assessment of patients’ conditions and provide adequate depth of anesthesia, to establish a safe use of a supraglottic airway.”

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Finger cuff – the only sensor on the patient.

In many surgical procedures, continuous pressure measurement with an arterial line may not be required. However, noninvasive blood pressure measured intermittently often lacks sufficient resolution to detect rapid hemodynamic changes. In such cases, continuous noninvasive blood pressure measurement may be beneficial.  In the article, “Noninvasive Continuous Arterial Blood Pressure Monitoring with Nexfin” that appeared online first on 12 March 2012, Dr. Berend E. Westerhof, Clinical Program Manager, BMEYE B.V., Amsterdam, The Netherlands, and Senior Research Fellow, Laboratory for Clinical Cardiovascular Physiology, AMC Heart Failure Research Center, Amsterdam, The Netherlands and colleagues described their study with the Nexfin^® monitor, a novel monitoring tool that noninvasively measures arterial blood pressure with finger cuff technology.

Continuous noninvasive measurement of arterial blood pressure is based on the volume-clamp method proposed by Czech physiologist Jan Peňáz. This method uses an inflatable cuff around a finger with a plethysmograph inside and a fast control loop that applies pressure to the cuff mirroring arterial blood pressure.

Several early devices using finger cuff technology were developed for space programs. Developments continued and the technology evolved into an easy-to-use monitor designed for routine clinical use. Several improvements were made, e.g., the “heart reference system” that corrects for hydrostatic differences when the finger is not at heart level. Furthermore, a physiological model reconstructs the brachial blood pressure wave shape and pressure levels from the finger pressure. The Nexfin monitor, a noninvasive blood pressure measurement device, incorporates all of these features. The objective of this study was to assess the accuracy and precision of noninvasive arterial blood pressure measured by the Nexfin monitor. The study was conceived as a concerted action by the Departments of Internal Medicine, Anesthesiology and Cardiothoracic Surgery of the Academic Medical Center of the University of Amsterdam.

Astronaut at the MIR space station, connected to a device built with finger cuff technology in 1993 (photo courtesy of CNES)

Dr. Hollmann, anesthesiologist, sees the real-time, beat-to-beat cardiac output derived by Nexfin from the arterial blood pressure waveforms as a very useful tool for guiding perioperative fluid optimization. Dr. de Mol, cardiothoracic surgeon, sees multiple uses for the Nexfin given its easy operation and transportability. In the future, he even envisages the possibility of home monitoring in heart failure patients. Dr. van Lieshout, internist in acute medicine, has been working with finger cuff technology for many years. Besides using it in his Acute Medical Care Unit, he applies it in research on brain perfusion.

Co-authors from left to right - Dr. van Lieshout, Dr. de Mol, Dr. Hollmann.

Biomedical Engineer Jerson Martina, first author of the study to be featured in ANESTHESIOLOGY (online first on 12 March 2012).

The authors conclude that arterial blood pressure can be reliably measured noninvasively and continuously with the Nexfin. Jerson Martina says, “I think that we showed that continuous blood pressure monitoring without an arterial line is a real option. We’ll be considering the use of Nexfin for numerous applications in the near future.”

Anesthetics were generally more soluble in rat, rabbit, and dog blood than they were in human blood while they were less soluble in cattle blood than in human blood. (Image source: Thinkstock)

Accurate potent volatile anesthetic blood-gas partition coefficients are necessary for predicting the potency of anesthetics, modeling their pharmacokinetics, and calculating their blood and tissue concentrations from their measured end-tidal concentrations at steady-state. Blood-gas partition coefficients are affected by a variety of factors and may vary between species. In the article “Solubility of Haloether Anesthetics in Human and Animal Blood,” published online on April 16, 2012, Dr. Robert J. Brosnan (Associate Professor, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis) and colleagues described how they measured partition coefficients of desflurane, sevoflurane, isoflurane, and methoxyflurane in the blood of rats, rabbits, cats, dogs, goats, sheep, pigs, cattle, horses, and humans. All samples were adjusted to similar hematocrits before testing because hematocrit affects anesthetic solubility. The anesthetics were generally more soluble in rat, rabbit, and dog blood than they were in human blood; however, they were less soluble in cattle blood than they were in human blood. The solubilities of all agents tested in goat blood were similar to their solubilities in human blood. The solubilities in blood of all anesthetics studied were positively correlated with plasma triglyceride concentrations, which differed among species, though this only accounted for 25% of the interspecies variability. Since red blood cells are significant carriers of inhalational anesthetics in blood, interspecies differences in hemoglobin and erythrocyte membrane anesthetic binding may also contribute to the species-related differences, as could interspecies differences in binding to plasma proteins.

“Mother is god, father is god and teacher is god.”
-The Vedas

“Mẹ là trời, cha là trời và thầy là trời”
-Kinh Vệ Đà

I recently returned from an opportunity to teach at the Hospital for Traumatology and Orthopaedics in Ho Chi Minh City, Viet Nam. This was made possible through a Society for Education in Anesthesia (SEA)-Health Volunteers Overseas (HVO) Traveling Fellowship. The stated goal of HVO is that it is a network of healthcare professionals, organizations, corporations and donors united in a common commitment to improving global health through education. This paper was born out of some wisdom gained teaching anesthesia abroad. It focuses mainly on strategies for facilitating the communication and absorption of knowledge through a dense language barrier. Peripherally, there are some observations about the obstacles to health systems building and global anesthesia promotion encountered along the way.

Situational analysis

The first step of teaching is lesson planning. One explicitly needs to ask himself/herself, “What am I teaching? Who am I teaching? What do I want them to carry away?” These questions become more difficult to answer when the audience is in a distant land that one may or may not know anything about.

Context

Packing for an international trip is difficult enough. Warm clothing? Outlet adapters? Mosquito repellent? It is the challenge of being prepared for the unknown. Lesson planning for an unfamiliar culture, hospital, and audience is only that much more challenging. In truth, the developing world is a large place. It is unified by important economic and political distinctions, but the countries that constitute it differ as much from each other as they do the developed world. Political stability, social structure, and regional economics set the stage for locale-specific healthcare delivery systems in different stages of evolution. The conditions of sub-Saharan Africa are vastly different from those of Southeast Asia, as are the needs of trainees. Indeed, within a single country, the needs of urban hospitals vary greatly from the local or provincial centers. Any information gathered at the outset not only makes for safer travel but also more successful teaching. Country information can be found on the U.S. Department of State website and regional health statistics can be found at the WHO Global Health Observatory.

One should try to familiarize oneself with the types of procedures, volume, and patient population (public vs. private) seen at the specific site. In urban areas, hospitals may be divided by specialties such as orthopedics, obstetrics, or cardiology. The state of the art at the institution will help guide what topics should be taught and at what level. In terms of technical details, the physical setting and resources of the classroom (i.e., video projectors, laptops, internet access, or white board) may determine what teaching modalities are available and appropriate. Knowing when lectures fit into the daily schedule can help give a sense of one’s competing obligations. Finally, trip reports from previous volunteers provide the most valuable experience and site-specific information. With that being said, however, one can never fully prepare oneself through literature or the experience of others. Flexibility and resourcefulness are virtues when teaching, when traveling abroad, and for life in general.

Gần đây tôi có dịp giảng dạy tại Bệnh Viện Chấn Thương Chỉnh Hình ở Thành Phố Hồ Chí Minh, Việt Nam. Tôi có được cơ may nầy nhờ chương trình Du Lịch Học Bổng của Hội Giảng Huấn Thuật Gây Mê (SEA) và Cơ Quan Y Tế Tình Nguyện Hải Ngoại (HVO). Mục tiêu của Cơ Quan Y Tế Tình Nguyện Hải Ngoại là liên kết các chuyên viên, các tổ chức, các xí nghiệp và các thành viên hỗ trợ y tế thành một hệ thống nhất trí trong quyết tâm cải thiện y tế thế giới bằng thuật giảng huấn. Bài viết nầy thoát thai từ kinh nghiệm giảng day thuật gây mê ở nước ngoài. Trọng tâm của nó là đề nghị những cách thế làm gia tăng hiệu năng của sự truyền đạt và tiếp thu kiến thức xuyên qua bức tường dày của ngôn ngữ. Ngoài ra, chúng tôi cũng xin nêu lên vài nhận xét về những trở ngại trong sự hình thành hệ thống y tế quốc tế và sự bành trướng thuật gây mê.

Phân tích Thực trạng

Bước đầu của sự giảng dạy là soạn bài. Người dạy cần tự hỏi thật cặn kẽ: Tôi dạy cái gì? Dạy cho ai? Tôi muốn họ lĩnh hội điều gì? Những câu hỏi trên đây càng khó trả lời hơn khi người ta đứng trước đám thính giả ở một vùng đất xa xôi mà có lẽ mình không biết gì về họ.

Hành Trang

Nguyên việc chuẩn bị hành trang cho một chuyến đi ra nước ngoài cũng đã khó. Liệu có nên mang theo quần áo ấm không? Ổ cắm bộ chuyển đổi điện thế? Thuốc chống muỗi? Đó là cái khó để tiên liệu cho cái bất trắc, cái không dự đoán được. Soạn bài dạy cho một văn hóa, một bệnh viện, một nhóm thính giả xa lạ càng khó hơn bội phần. Quả thật, cái Thế Giới Đang Phát Triển là một vùng rộng lớn bao la. Nó được thống nhất bởi nhiều yếu tính đặc thù về kinh tế và chính trị, nhưng các quốc gia kết thành cái thế giới đó khác xa nhau không kém gì các quốc gia trong Thế Giới Phát Triển. Một hệ thống cung cấp y tế mang sắc thái địa phương phải được xây dựng trên cơ sở của sự ổn định chính trị, cơ cấu xã hội và điều kiện kinh tế trong vùng ngõ hầu có thể uyển chuyển bước đi sát cánh với từng giai đoạn khác nhau trong lịch trình tiến hóa của địa phương đó. Những điều kiện của Nam Phi khác Đông Nam Á rất nhiều do đó những nhu cầu của các cán sự y tế của họ cũng phải khác nhau. Thật vậy, trong cùng một quốc gia, yêu cầu của các bệnh viện thành phố khác hẳn với yêu cầu của những trung tâm y tế tỉnh lỵ hay thôn ấp. Thông tin thu thập lúc đầu không những giúp cho hành trình an toàn hơn mà còn làm cho việc giảng huấn thành công hơn. Website của Bộ Ngoại Giao Hoa kỳ cho thông tin quốc gia và Đài Quan Sát Y Tế Toàn Cầu của WHO cho thống kê y tế.

Bạn cũng cần tìm hiểu các thủ tục, khối lượng và tổng số bệnh nhân (công và tư) được khám bệnh ở một địa điểm nhất định. Tại những đô thị lớn, các bệnh viện có thể được phân ra theo chuyên khoa như chỉnh hình, sản khoa, hay tim mạch. Các viên chức cao cấp sẽ hướng dẫn bạn về đề tài và trình độ giảng huấn. Các chi tiết kỹ thuật, phòng học, dụng cụ (như video, máy chiếu, máy vi tính xách tay, truy cập internet, hay bảng trắng) có thể giúp bạn biết phải chọn phương pháp giảng huấn nào trong điều kiện thực tế. Biết được các bài thuyết trình của bạn nằm vào thời điểm nào trong thời khóa biểu hàng ngày giúp bạn ý thức được mình phải tranh thủ với những đối lực nào. Sau cùng, phúc trình của các tình nguyện viên đến trước cho kinh nghiệm và thông tin xác thực nhất. Tuy nhiên, không ai có thể dự liệu cho mình mà hoàn toàn tùy thuộc vào phúc trình và kinh nghiệm của người khác. Linh hoạt và tháo vát là hai đức tính mà người giảng dạy hay du ngoạn nước ngoài phải có.

When ECG abnormalities were included in a model to predict risk of cardiac events, intermediate-risk participants had reclassification of their risk level. (Image source: Thinkstock)

Should a resting ECG be routinely ordered before an older patient (> 70 yrs) undergoes anesthesia for surgery? Based on current evidence, the answer to that question is no. Certainly, the incidence of cardiovascular disease and abnormal ECG increases with age. ECG also is safe, widely available, and equipment cost is not high. In the study “Association of Major and Minor ECG Abnormalities With Coronary Heart Disease Events,” from the 11 April 2011 issue of JAMA, Dr. Reto Auer (Department of Epidemiology and Biostatistics, University of California) and colleagues sought to determine whether baseline major and minor ECG abnormalities and development of new abnormalities and persistent abnormalities in black and white adults of both genders between 70-79 years of age were associated with increased coronary heart disease events.

Almost 2200 patients were included. Participants were excluded if at baseline they had overt cardiovascular disease. ECGs were recorded in the resting supine position at baseline and at a year 4 visit and were analyzed at a central site. Data was collected over 8 years, between 1997-1998 and 2006-2007. Mean age at baseline was 73.5 years; 55% of study patients were female and 41% were black. At baseline, major (13%) and minor (23%) ECG abnormalities were associated with an increased risk of heart disease. Three hundred fifty-one patients at follow-up of about 8 years had cardiac events; both major and minor ECG abnormalities were also associated with increased risk of cardiac disease after adjustment for traditional risk factors.

When ECG abnormalities were included in a model to predict risk of cardiac events, 14% of intermediate-risk participants and 7% of the overall sample had reclassification of their risk. Specifically, 8% of intermediate-risk participants were reclassified as high-risk and 15% of those individuals experienced events. Conversely, 6% were reclassified as low-risk and 5% of those experienced events. Using another method of calculation, the greatest effect of adding ECG abnormalities to the model was in reclassifying intermediate-risk patients without events into the lowest risk category. During follow-up (median 6.4 years), risk increased from those with no ECG abnormality and abnormality at baseline only compared with those with persistent abnormality at 4 years.

In the accompanying editorial, “Should the Resting Electrocardiogram Be Ordered as a Routine Risk Assessment Test in Healthy Asymptomatic Adults?,” Dr. Philip Greenland (Departments of Preventive Medicine and Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois) notes,

“Although the results reported by Auer et al add new information pertinent to older adults and now include black as well as white individuals, the study results are consistent with the prior extensive literature on risks associated with abnormalities on the resting ECG in asymptomatic persons.”

He also states that,

“For the time being, in the absence of clear evidence of benefit and no clear implications for costs, the best advice is not to perform ECGs in asymptomatic patients, regardless of age. However, a careful and detailed cost-effectiveness analysis would be a useful next step in the translation of the cumulative risk information into an evidence-based practice recommendation.”

Image source: Thinkstock

Dr. Kathryn E. McGoldrick reads “April Pain: Aftermath of a Colleague’s Suicide”, her Mind to Mind poem that is published in this month’s issue of Anesthesiology.  Last week, she discussed the basis for the poem.

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5-yr overall survival was higher in the epidural group compared to the traditional pain management group. (Image source: Thinkstock)

When patients undergo colectomy for colorectal cancer, should better pain control be the only reason epidural analgesia is offered for post-procedure pain?  Certainly, regional technique use has been associated with lower cancer recurrence rates for breast  and prostate cancer.   Is the same true of colorectal cancer?  In the article “A Comparison of Epidural Analgesia and Traditional Pain Management Effects on Survival and Cancer Recurrence after Colectomy: A Population-based Study,” published in this month’s issue of Anesthesiology, Dr. Kenneth C. Cummings III (Assistant Professor of Anesthesiology, Departments of General Anesthesiology and Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio) used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to compare patients who either received or did not receive epidural anesthesia and/or analgesia for open resection of nonmetastatic colorectal cancer.  They sought to determine whether there was a difference in survival and cancer rates.  This database contains patient-specific information about cancer cases from more than 12 cancer registries and links this information with Medicare information.  For this study, patients who were diagnosed between 1996 and 2005 were included.

When applying different inclusion and exclusion criteria, over 40,000 patients were identified.  Approximately 23% received epidural analgesia and/or anesthesia.  Patients who received an epidural were slightly younger and had lower comorbidity scores.  There was no significant association between epidural use and perioperative complications.  5-yr overall survival was higher in the epidural group compared to the traditional pain management group (61% vs. 56%) and median survival was also higher (7.2 yr vs. 6.1 hr).  Though overall 4-yr cancer recurrence was higher in the epidural group (14.3% vs. 13.8%), this difference was not significant when the comparison was adjusted for demographic and clinical covariates.

Whether the findings are due to unmeasured elements or other cause and effect associations is unclear.  The beauty of the study was that the database was large and the cancer and Medicare databases are linked.   Prospective studies will better help to determine whether there is a true cause and effect relationship between epidural use and both survival and cancer recurrence rates.

Mast cell accumulation and degranulation into the skin of an injured limb can induce nociceptive sensitization. (Image source: Thinkstock)

Inflammation is a component in the first months of complex regional pain syndrome (CRPS).  Pain, limb warmth, skin reddening, edema, motor function loss, trophic changes, and osteopenia are seen.  Type 1 CRPS does not involve primary nerve injury and is frequently seen after fracture of the distal tibia and radius.  Mast cells, when activated during injury, release histamine and inflammatory mediators. In the manuscript “Substance P Signaling Controls Mast Cell Activation, Degranulation, and Nociceptive Sensitization in a Rat Fracture Model of Complex Regional Pain Syndrome,” published in this month’s edition of Anesthesiology, Drs. Wen-Wu Li (Senior Research Scientist, Physical Medicine and Rehabilitation Service, Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, and Department of Anesthesiology, Stanford University School of Medicine, Stanford, California), Dr. J. David Clark (Professor of Anesthesiology, Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, and Department of Anesthesiology, Stanford University School of Medicine), and colleagues asked first whether neuropeptide substance P causes mast cell inward migration, activation and degranulation.  Then, since neuropeptide substance P, acting through neurokinin-1 (NK-1) receptors, initiates an interleukin-1b response in skin, does NK-1 mediate mast cell degranulation?

Using adult rats, a tibia fracture was performed during anesthesia.  Next, the hip, knee, and ankle were flexed and a spica cast was applied.  The animals received buprenorphine to control pain.  At four weeks, the cast was removed.  Fracture site union was seen in all animals.  To determine whether substance P signaling might regulate mast cell activity, rats were randomized to receive either an NK-1 antagonist or placebo.

In another group of animals, sciatic nerve electrical stimulation was performed to see if it would cause mast cell degranulation and nociceptive sensitization in hind limb skin and whether this was mediated by substance P.  Using anesthesia, rats received either nothing, sciatic nerve stimulation for 30 min, or stimulation with an NK-1 antagonist.

In those animals that underwent fracture, mast cells and degranulation were seen in the upper dermis next to basal membrane 4 weeks after fracture.  Degranulation was prominent near the dermal-epidermal boundary.  In those who were treated with the NK-1 antagonist, the increase in mast cells was not seen.  Mast cells were seen near peptidergic nerve fibers.  Sciatic nerve stimulation produced mast cell activation, degranulation and nociceptive sensitization.  The NK-1 antagonist blocked this response.  Acute administration of substance P injection four weeks after fracture caused mast cell degranulation.  Mast cell degranulation enhanced post-fracture allodynia but had no effects on weightbearing or warmth.  Chronic mast cell degranulation partially reversed hind paw allodynia.  Acute administration of a highly selective H1 histamine receptor blocker demonstrated that histamine was not required for the warmth, edema, and allodynia seen in the model.  In this model, then, neuron-mast cell signaling after fracture can cause mast cell accumulation and degranulation into the skin of the injured limb and induce nociceptive sensitization.

In the accompanying editorial, “Mast cells: source of inflammation in complex regional pain syndrome?,” Drs. Tanja Schlereth and Frank Birklein (Department of Neurology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany) note that in rats, chronic regional pain syndrome commonly occurs though in humans, the association is uncommon.  Also, in humans, the amount of mast cell degranulation related to substance P is much less than in rats.  Though for a different strain of Wistar rats than was used in this study, degranulation by substance P is seen after use of more physiologic nanomoler doses.  According to the authors:

 If there were a similar genetic variance in humans, this could explain why only a minority experiences CRPS after distal extremity fracture. It clearly would be valuable to be able to identify this minority. The findings of Li et al.(link:) may guide us by providing a detailed analysis of how MC are involved in trauma related inflammation. It is now up to CRPS researchers to develop diagnostic or therapeutic tools in humans to verify or refute Li et al.’s hypothesis. If verification could be achieved, another piece of the CRPS puzzle might be found.”

We didn't actually use a hammer (Image source: Thinkstock)

Unfortunately, malware hit the Page2Anesthesiology site, probably originating via one of the computers we use to generate material.  The computer’s been fixed, virus protection software is installed,  and Page2Anesthesiology has been restored with material beginning from one month ago (14 March).  We’ll be busy manually adding posts from after the backup and will have new Journal material starting on Monday, April 16.  Links on social media sites based on our posts may work, though we cannot guarantee that they will.  Thank you for your understanding and patience.  Please feel free to send us a note if you have any questions.

Image source: Thinkstock

Dr. Kathryn E. McGoldrick discusses “April Pain: Aftermath of a Colleague’s Suicide”, her Mind to Mind essay that is published in this month’s issue of Anesthesiology.

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Clinical pearls

Why is connected consciousness a better goal of anesthesia than amnesia?

If an anesthetic produces unconsciousness, amnesia and substantial suppression of the effects of noxious stimuli are secondary effects.  Though memory may be ablated with small anesthetic doses, a noxious stimulus will produce arousal.  There are many instances where an individual is conscious but has no recollection of an event (e.g., recall of breakfast a month ago).  Individuals during NREM sleep tend not to recall any mentation, though during REM sleep, consciousness and dreams are commonly reported.  Similar to REM sleep, dreams have been reported during anesthesia with either desflurane or propofol; in a study of dreaming reported after anesthesia, no patient who dreamt had recall of intraoperative events.

How do theories of consciousness and unconsciousness relate to anesthesia?

Theories of consciousness focus on corticothalamic network function.  Cortical integration then leads to consciousness.  With general anesthesia, there is a breakdown of connectivity within this network.  Lower levels of anesthesia or sedation may not suppress corticothalamic connectivity whereas with deeper levels, this connectivity is reduced and a patient is not conscious.

 What mechanisms are there to explain connectedness?

It is unlikely that connectedness can be explained by a single neurotransmission system, though specific neuromodulators might be responsible.  Histaminergic signaling and orexin may not account for maintained connected consciousness during anesthesia; however, unperturbed norepinephrinergic neurotransmission may be important.  This might explain why a-2 agonists, e.g., clonidine, supplementation of a GABAergic anesthetic, may reduce connected consciousness.

What mechanisms are there to explain unresponsiveness?

Corticothalamic connectivity is not important in the mechanism of unresponsiveness.  Different subcortical regions, particularly the putamen and amygdala, and reduced histamine release into these areas, may be important for producing unresponsiveness.  Anesthetic effects on the amygdala may be why patients who respond with the isolated forearm technique (a tourniquet is inflated before muscle relaxants are injected) rarely report pain and furthermore, why patients who report anesthesia awareness do not report pain.

What are the clinical implications?

An adequate depth of anesthesia is one wherein patients are disconnected from the environment but not necessarily unconscious.

Considering these ideas, are there better tools, i.e., monitors, to measure connectivity?

Measures using transcranial magnetic stimulation and high-density electroencephalogram show promise since they measure corticothalamic integration of information.  Measures of connected consciousness are also needed.  Mid-latency auditory-evoked potentials may represent one possibility of this measure.

Much more detail of these ideas is presented in the article.  An example of unresponsiveness that’s unrelated to unconsciousness was presented last week on Page2Anesthesiology in the book review of an individual (Robert C. Samuels) who, because of Guillian-Baré, was paralyzed save for his ability to move his eyes from side-to-side, yet was fully cognizant.

Airway anatomy of simulation manikins is not similar to the anatomy of real patients. (Image source: Thinkstock)

Simulation has become a mainstay of medical education. It provides learners with unlimited opportunities to practice patient care techniques sans associated risk to patients (i.e., physical harm or inappropriate treatment) or to the students (e.g., anxiety of performing a new technical skill). The assumed quid pro quo of simulation education is that learning will be realistic because manikins are, as oft touted, “just like real patients.”

Dr. Karl Schebesta (resident and research associate, Medical Simulation and Emergency Management Research Group, Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria) and colleagues present their data in  the article “Degrees of Reality: Airway Anatomy of High-Fidelity Human Patient Simulators and Airway Trainers,” published online on April 4, 2012, providing us with an answer to the question of whether airway-training manikins are “the real McCoy,” substituting for actual patients.

Using radiographic evidence, the authors have documented that the airway anatomy of the simulation manikins is not similar to the anatomy of real patients. Their primary outcome measurement was pharyngeal airspace, which was appreciably larger in all of the manikins when compared to patients.

The authors conclude their study with a warning that their data should give anesthesiologists pause in two specific areas. First, using airway-simulation manikins to teach patient airway management may not be a reliable and valid way to provide this education and second, utilizing them as a standard in research focused on evaluation of airway devices and techniques may result in invalid conclusions that cannot be applied to real patient care. Based upon the data gleaned from this study, anesthesiology educators and investigators can say with certainty that airway- training manikins are not “the real McCoy!”

Image source: Thinkstock

This review is based on Robert C. Samuels’s “Blue Water, White Water.

Forty years ago, medical students learned anatomy, physiology and pathology during the first 2 years of medical school, the years of book learning, never to see a patient. Modern day medical education is much more enlightened; from day one, physicians-to-be are taught that personalities, emotions, empathy and relationships are essential subjects to study and they learn this from interactions with real patients early on in their studies. Today’s medical school curriculum introduces future physicians to as many psychosocial aspects of illness and patient care as possible. In our school, The Perelman School of Medicine, for example, students are assigned to small groups in a course titled “Doctoring.”

Some of the vast array of topics students consider in “Doctoring” include death and dying, substance abuse, gender and geriatric bias, the doctor-patient relationship and the care of patients with disabilities. Several examples will demonstrate the psychosocial imperative of these topics.

There is no substitute for the exercise medical students experience as each plebe negotiates the real world, sitting in a wheelchair steered by a classmate, confronting what patients with disabilities deal with day-in and day-out. It’s also always fascinating to watch these novices observe “real” doctors talk with patients, their families and other members of the healthcare team. Quickly, the medical students realize that these interactions are often condescending, abusive, or so obscure that it’s a wonder anyone understands what is going on.

“Doctoring moments,” as we call them, are all of the events medical students experience, most often as observers, learning how to (or not to) be a doctor from the “role models.” Doctoring moments are snippets in time that patients remember for a lifetime.

Doctors schooled before the implementation of the modern curriculum may have rarely thought about these issues. Others may have considered them only when a problem occurred. Few have learned them well when they themselves became patients and were subjected to care provided by egocentric doctors and nurses. Is there a way to expose physicians to the topics and lessons of the modern day medical school curriculum? Is there a way to heighten awareness of professionalism, one of the six core competencies stressed by the Accreditation Council for Graduate Medical Education?

An answer to these questions can be found reading Robert C Samuels’ Blue Water, White Water. Stricken with Guillain-Barré syndrome more than 25 years ago, Samuels, a newspaper writer, penned his astute observations, few joys and many tribulations during his total dependence upon others. This recently published personal account of his ordeal over many months in a community hospital and a prestigious university hospital describes how his body was totally paralyzed save for his ability to move his eyes from side-to-side to communicate yes and no. He relates to each reader what he was cognizant of, yet others around him failed to recognize; while his body was limp, his mind was not paralyzed and was, in fact, as sharp as could be, comprehending everything that was taking place. With words that express Samuels’ very raw emotions, Blue Water, White Water offers insights for physicians who forget, forgot or never learned what it is that patients experience. Noted New York Times medical writer Abigail Zuger sums up Samuels’ situation pointedly: “With nothing to do but watch and remember, Mr. Samuels assembled the sketchbook of a professional observer, brisk, unsentimental, sardonic and altogether deadly.”¹

Take the wheelchair as an example. Limp and strapped into the chair, Samuels recounts his nurse wheeling him outside the hospital for sun and fresh air; he, however, felt terror that his nurse might lose control of his chariot on a steep ramp or high curb and he would be unable to save himself from a harmful crash. Repeatedly, Samuels tells of his torment when being disconnected from the ventilator to be suctioned or moved. His description of feeling the onset of oxygen desaturation sends chills up one’s spine. Samuels constantly paints pictures of those who cared for him, especially the nurses who displayed a variety of personality traits (e.g., bravado performing medical tasks they did not know how to do yet were unwilling to admit such deficiency or superiority, believing the patient’s improvement was solely the result of their nursing care and not from any others administering to their charge). Here is Samuels’ description of one of the many nurses entrusted with his life:

“I have some strange nurse who doesn’t even bother to tell me her name. She’s so mechanical. I call her The Robot…To get her attention, I swing my eyes back and forth like a spoiled kid banging his fist on a table. She reads the list on the poster to find out what I need. Sometimes I need suctioning, but usually what I want is turning…She does it so mechanically.”

Read Blue Water, White Water to place yourself in the patient’s role; the thought of it might be threatening, yet it’s most worthwhile. Abigail Zuger’s New York Times Book Review makes this abundantly clear:

 Just when it seems long past time for the age of memoir to be over — just when it seems impossible that any ailing person with literary inclinations could find anything new to say about illness, and the list of not-to-be-missed ‘patients are people too’ books should be closed and locked — yet another book comes along. And despite all the above, no one with even a passing interest in the experience of illness should miss Robert C. Samuels’s ‘Blue Water, White Water’…”¹

Topical brimonidine lowered mean intraoperative intraocular pressure; albumin or crystalloid differences were not significant. (Image source: Thinkstock)

Vision loss after spine surgery performed in the prone position is disastrous. Intraocular pressure is known to increase as the length of a procedure performed in the prone position increases. Though the relationship between intraocular pressure and vision loss is not clear, it would seem that intraocular pressure should be minimized. In the study “Effects of Crystalloid versus Colloid and the α-2 Agonist Brimonidine versus Placebo on Intraocular Pressure during Prone Spine Surgery: A Factorial Randomized Trial,” Dr. Ehab Farag (Professional Staff, Departments of General Anesthesiology and Outcomes Research, Cleveland Clinic, Cleveland, Ohio) and coauthors measured intraocular pressure in patients undergoing complex spine surgery in the prone position who received either goal-directed 5% albumin or lactated Ringer’s solution; and either topical brimonidine, an α-2 agonist used to treat glaucoma, or placebo.

Patients who were to undergo spine surgery in the prone position were randomized to one of four groups. One drop of brimonidine or placebo was administered 1 hour before surgery and then every 8 hours for 24 hours. At the authors’ institution, a patient’s head is placed in skill pins, the patient’s head is elevated 5 degrees and for surgery, patients are positioned on a Jackson frame. Lactated Ringer’s solution was used for maintenance fluid administration and esophageal Doppler was used to guide additional fluid administration with lactated Ringer’s solution or 5% albumin. A phenylephrine bolus or infusion was used to keep mean arterial blood pressure within 20% of preoperative baseline. Patients randomized to receive lactated Ringer’s solution could receive colloid boluses if blood pressure could not be kept at the target level despite adequate aortic flow and the use of vasoactive drugs. During the procedure, if IOP exceeded 50 mmHg, patients were hyperventilated, they received diuretics and mean arterial pressure was increased by 10%. Intraocular pressure measurements were made before surgery, once after anesthesia induction, every 30 minutes while prone, and then hourly after surgery for 4 hours.

Sixty patients were studied over a 21-month period. Overall, intraocular pressure increased 12 ± 6 mmHg when the patient moved from the supine to the prone position. The mean duration of anesthesia was 5.7 h. No interaction between type of fluid and eye drops was seen. On average, the intraocular pressure for patients who received brimonidine was 4 mmHg lower than that of patients who received placebo. There was not any intraocular pressure difference between types of fluid, though the hourly increase in intraocular pressure was less for patients who received albumin. Patients who received albumin also had less facial edema in the PACU, though the difference disappeared by postoperative day 1 or 2.

Whether the risk of visual injury is related to brimonidine eye drops or type of fluid administered is unclear. Larger studies are needed to determine if there are any differences.

The overall 5-year revision rate for metal-on-metal implants was 6.2%, higher than the revision rate for other types of hip replacement surgery. (Image source: Thinkstock)

Hip surgery is a common surgical procedure.  The safety of metal-on-metal hip implants has been questioned recently since their failure rate is higher than that of other hip replacement systems.  This question of safety is based in part on the article “Failure rates of stemmed metal-on-metal hip replacements: analysis of data from the National Joint Registry of England and Wales” published online on March 13, 2012, and in print on March 31 in The Lancet.

Dr. Alison J. Smith (Orthopaedic Surgery, Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, Avon Orthopaedic Centre [lower level], Southmead Hospital, Bristol, BS10 5NB, UK) and colleagues used the National Joint Registry of England and Wales to determine whether implant survival was affected by metal-on-metal bearing surfaces.  They used the database to analyze over 400,000 primary stemmed total hip replacement surgery procedures performed in over 400 units by over 2500 consultant surgeons between April 2003 and September 2011.  They used a multivariable flexible parametric survival model that estimated the risk of revision adjusting for the risk of death.

Metal-on-metal prostheses were used in over 30,000 or about 8 % of the total number of hip replacement procedures.  The overall 5-year revision rate was 6.2%, higher than the revision rate for other types of hip replacement surgery.  Patients who received larger head sizes were more likely to need replacement.  Each 1 mm increase in head size was associated with a 2% increased risk of revision. Younger women were more likely to need implant revision.  An age effect was minimal for men.  Revision rates were higher for women even with the same head size as for men.  Revision rates in women for stemmed metal-on-metal implants was up to four times higher than that seen with other types of surfaces.  Aseptic loosening and pain were the most common reasons for revision and these reasons were significantly higher in those receiving the metal-on-metal implant.  Revisions related to dislocation were slightly lower in men.  Infection and other complications were higher after the metal-on-metal implants, which was likely related to local adverse reactions to the metal.

In the accompanying editorial, “Metal-on-metal failures—in science, regulation, and policy,” Dr. Art Sedrakyan (Weill Cornell Medical College, New York, NY) summarized failures in regulation, science and politics that allowed metal-on-metal implants to be approved and accepted.  Outdated and low-threshold regulatory pathways; lack of a strong post-marketing infrastructure; and research funding that, until recently, was more interested in new discoveries versus comparisons of safety and effectiveness are all reasons why this problem was not realized until now.  In closing his editorial Dr. Sedrakyan concluded, “We are left with more than 500 000 patients with metal-on-metal prostheses in the USA and more than 40 000 in the UK who are at elevated risk of device failure, which will inevitably result in the burden of further surgical treatment as well as billions of dollars in costs to taxpayers.”

Dr. Luc Buée’s lab, “Alzheimer & Tauopathies,” is located in Lille, in the north of France

Editor’s note: This “In the Lab” feature is based on the article “Tau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment” published in this month’s issue of Anesthesiology. The study was also summarized yesterday in a Page2Anesthesiology blog entry.

Dr. Luc Buée’s lab is part of the Labex (laboratory of excellence, Investment for the Future) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).

The team is composed of 30-40 people. All authors are present on this picture with the exception of Pauline Patin and Gilles Lebuffe. (From left to right, top row: Valérie Buée-Scherrer, Ph.D., Jonathan Brouillette, Ph.D., Hélène Le Frêche, M.Sc., M.D.; middle row: Raphaëlle Caillierez, M.Sc., Nicolas Sergeant, Ph.D., Francisco Jose Fernandez-Gomez, Ph.D., David Blum, Ph.D.; bottom row: Luc Buée, Ph.D. and Nadège Zommer, B.Sc.)

Located on the campus of this Lille University Hospital, Luc Buee’s lab is interested in the biology of the microtubule-associated tau proteins, which are components of intracellular filaments leading to neurofibrillary degeneration in Alzheimer’s disease (AD) and related disorders. In these disorders, tau phosphorylation is a post-translational modification that is not reversible and may lead to neurodegeneration. Phosphorylated tau proteins are early biomarkers found in  the cerebrospinal fluid of patients presenting with prodromal AD.

In 2008, Hélène Le Frêche, chief resident in anesthesiology, came to the laboratory with the willingness and desire to study post-operative cognitive decline (POCD) in experimental models since her practice has lead her to questions about this phenomenon, especially in elderly people.

Dr. Hélène Le Frêche, chief resident in anesthesiology

She has read the early literature of Emmanuel Planel’s group showing that in animals, anesthesia is associated with an increase in tau phosphorylation that may be due to hypothermia.   Following our discussion, she developed a project to study the effect of repeated anesthesia in adult mice on memory, tau phosphorylation and signal transduction with two post-doctoral fellows, Jonathan Brouillette and Francisco J. Fernandez-Gomez.

Shown is the setup for sevoflurane administration

We evaluated the effect of sevoflurane exposure on tau phosphorylation both acutely and after chronic episodic exposure over a period of 5 months. In addition to tau phosphorylation and its reversibility, cognitive function was evaluated in a Morris water maze at 4 months post-exposure.

Mice were anesthetized by exposition to vapors of sevoflurane. For this inhalation procedure, mice were placed in a closed plastic box, receiving low-dose or high-dose sevoflurane in 100% oxygen. All anesthetized mice were breathing spontaneously and the body temperature was monitored with a rectal probe and maintained between 36.0 and 37.0°C using a heating pad. The data indicate that tau phosphorylation increases in the hippocampus 1 hour post-exposure and that this level is reduced to the basal level 24h after exposure.

Jonathan Brouillette

Jonathan Brouillette analysed tau phosphorylation and activation of kinases by immunoblotting. Immunoreactive signals were visualized by chemiluminescence, and then integrated by LAS 3000 software and quantified by Multigauge software.

Francisco J. Fernandez Gomez

After repeated monthly exposure (5 times over 5 months), tau phosphorylation was still increased even when it was measured a month after the last exposure. analyses quality of Coomassieblue-stained acrylamide gels. Such two-dimensional gel electrophoresis allows for determining the global level of tau phosphorylation (lower pH).

Learning in the MWM was unaffected. However, 72h after learning trials, animals exposed to sevoflurane manifested a memory deficit that is consistent with hippocampal dysfunction.

Learning was measured using the Morris water maze. No deficit in learning was observed after repeated sevoflurane anesthesia but deficit in memory was demonstrated.

We concluded that in normothermic mice, sevoflurane anesthesia resulted in an increase in tau phosphorylation, which was transient with a single anesthetic but long-lasting after repeated exposure and was associated with memory impairment. Our study suggests an association between anesthesia and POCD.

On the four main predictors factors of PONV (female gender, previous history of PONV, non-smoker and postoperative opioid), Dr. Tong J. Gan indicated that a previous history of PONV or motion sickness is the most important factor.

The first- and second-line pharmacologic antiemetics recommended for PONV prophylaxis in adult patients at moderate to severe risk for PONV include the 5-hydroxytryptamine (5-HT3) receptor antagonists, steroids, phenothiazines, butyrophenones, antihistamines, anticholinergic and neurokinin-1 (NK-1) receptor antagonists. While PONV prevention is recommended in a subset of patients, current evidence does not support giving prophylactic antiemetics to all patients who undergo surgical procedures. At the present, the Society for Ambulatory Anesthesia (SAMBA) is in the process of  developing an update of PONV consensus guidelines.

In the practical, real world, patients with obstructive sleep apnea have surgery on an ambulatory surgical basis.  Dr. Frances Chung reported on a systematic review of outcome of patients with obstructive sleep apnea undergoing ambulatory surgery. There was neither anesthetic-related unanticipated hospital admission nor mortality after ambulatory surgery. However, the quality and number of patients in the studies were limited.

Dr. Chung discussed the use of a higher STOP-Bang score (loud snoring, tiredness or daytime sleepiness, observed apnea, high blood pressure, BMI >35, age>50, neck circumference > 40 cm, male gender), specifically 6-8  to identify patients with moderate to severe OSA.  Essentially, OSA patients with optimized medical conditions and treated with CPAP can have ambulatory surgery safely provided that postoperative opioid requirements can be limited. The final decision on whether OSA patients can undergo ambulatory surgical procedure is dependent on the clinical expertise and experience of the anesthesiologists and surgeons. SAMBA is also in the process of developing guidelines on OSA patient selection in ambulatory surgery.

Dr. Holly Muir discussed the various methods of evaluation of airway and the different devices available for difficult intubation. She mentioned an acronym to use in the evaluation of airway, namely the word “LEMON.” In this acronym, “L” stands for  “Look”;  “E” stands for  “evaluate” (e.g., hyoid-mental distance); “M” stands for  “Mallampati”; “O” stands for  “Obstruction”; and “N” stands for “Neck mobility”.  The use of videoscopes has greatly facilitated intubation and makes difficult intubation easier. She suggested that each anesthesiologist be familiar with all of the new equipment.

After repeated anesthesia, memory impairment was seen and persistent tau hyperphosphorylation was also present. (Image source: Thinkstock)

The occurrence of postoperative cognitive dysfunction (POCD) is a concern, particularly if, after surgery, it results in impairment of activities of daily living. Do anesthetics influence POCD development? Earlier animal studies that have shown a relationship have been faulted in part because the animals were allowed to get cold. Tau proteins contribute to axonal integrity and, in abnormal forms, are associated with Alzheimer’s disease and other neurodegenerative disorders. In the study “Tau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment” published in this month’s edition of Anesthesiology, Dr. Luc Buée, CNRS Senior Research Director, Institut National de la Santé et de la Recherche Médicale, UMR837, Alzheimer & Tauopathies, Institut de Médecine Prédictive et de Recherche Thérapeutique, and University of Lille, Faculté de Médecine, Jean-Pierre Aubert Research Centre, and Centre Hospitalier Régional Universitaire (CHRU-Lille), Lille, France, and colleagues , measured the effect in adult mice of acute or repeated exposure to sevoflurane on hippocampal tau phosphorylation and spatial memory using normothermic conditions.

Mouse temperature was maintained between 36 and 37° C. Adult (5-month-old) mice received low- (1.5%) or high-dose (2.5%) sevoflurane for 1 h; or , every month from the age of 6 months until the age of 10 months, mice received either low- or high-dose sevoflurane. Mice who received monthly exposure to sevoflurane were tested at 9 months with a spatial learning and memory test. Antibody and two-dimensional electrophoresis were used to measure tau and tau phosphorylation.

An increase in tau phosphorylation after 1 hour of sevoflurane anesthesia was dose related, though no more was detected 24 h after anesthesia, even after the higher dose. After repeated anesthesia, memory impairment was seen and persistent tau hyperphosphorylation was also present. Repeated anesthesia was associated with an activation of AkT and Erk kinases and GSK3 inactivation, which may be why persistent tau hyperphosphorylation occurred.

In humans, whether anesthesia alone may be responsible for POCD and neurodegeneration is not known. It is also unknown whether one anesthetic is better than another. In the accompanying editorial, “Postoperative Cognitive Decline: Where Art Tau?,” Drs. Roderic G. Eckenhoff, Department of Anesthesiology & Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, and Emmanuel Planel, Centre Hospitalier de l’Université Laval Neurosciences, Québec, Canada, noted that

…we breathed a collective sigh of relief when it was carefully demonstrated that anesthesia-associated hypothermia was the culprit, rather than the drug itself, and that the effects were quickly reversible. The article in this month’s ANESTHESIOLOGY by Le Freche et al. suggests we may have relaxed too soon”.

As they further stated,

Unlike the researchers of the human studies, Le Freche et al. are able to link the anesthetic alone with both phosphorylated tau and memory effects. But as with the human studies, they are unable to make the link between phosphorylated tau and the memory effects. At this point, it is simply an intriguing association, but it allows the hypothesis that tau and perhaps microtubule dysfunction may underlie altered cognition after surgery.

It will be interesting to see if drugs that affect the pathology and symptom onset of Alzheimer’s and other neurodegenerative disorders might also benefit patients with POCD.

Considering their analysis, using a threshold of 50 ml blood loss, type and screen is not needed. (Image source: Thinkstock)

Many tests are performed preoperatively, though there’s little evidence-based data to guide practice. A type and screen is performed to identify important, commonly found and possibly unexpected red cell antibodies. What is the basis for performing this test? Dr. Franklin Dexter, Professor and Director, Division of Management Consulting,
Department of Anesthesia, University of Iowa, Iowa City, Iowa, and colleagues describe how they used anesthesia information management system data to help provide a basis for performing a type and screen in their paper “Systematic Criteria for Type and Screen Based on Procedure’s Probability of ErythrocyteTransfusion”  published in this month’s issue of Anesthesiology.

The authors used anesthesia information system data from all anesthetics performed at a single hospital from November 2005 through January 2011. Patients were excluded if their procedure was emergent, they underwent procedures where blood is routinely prepared for all patients (cardiac surgery and liver transplant procedures), and if their age was less than 18 yrs.

Table 2 from the article describes the method to determine for which procedure a type and screen is not indicated. They used a criterion for transfusion based on the incidence of transfusion rather than the number of units transfused for a procedure. To classify probability of transfusion, calculations are not possible for procedures where there were less than 19 cases; even for procedures where there were less than 163 procedures, reliability estimates were difficult but not difficult now given the material presented in figure 2 from the article. Broader category classification resulted in larger groups. Since the actual procedure is never known before the case is performed (i.e., when the type and screen decision is made preoperatively), the authors did all their work using scheduled procedures. Considering their analysis, using a threshold of 50 ml blood loss, type and screen is not needed.

As Drs. David L. Reich, Department of Anesthesiology, Mount Sinai School of Medicine, New York, New York, and Melissa S. Pessin, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, note in the accompanying editorial, “Rational Preoperative Blood Type and Screen Testing Criteria,”:

One aspect of the Maximal Surgical Blood Ordering Schedule (MSBOS) that has received less emphasis is the decision as to which procedures that will have not have blood cross-matched should require a preoperative blood type and screen. As Dexter et al. demonstrate, a huge proportion of this testing is wasted effort. Anesthesiologists and blood bank professionals have an obligation to use our expertise to create rational local guidelines for preoperative blood type and screen.

Although the cumulative data are considerable, some critical studies are contradictory and inconsistent, so further studies, particularly regarding the translation of these data to clinical situations, are essential.  Hearing the evidence presented, it is a wonder that the mammalian system survives anesthesia largely functionally intact! Under carefully controlled conditions in terms of developmental stage, drug selection, concentration and duration of exposure, and genetic background of the model, neurotoxicity has been demonstrated in numerous studies over the past decade. The available data raise significant concerns to the clinical anesthetist, issues raised by the speakers in their presentations (R. Eckenhoff, V. Jevtovic-Todorovic, H. Wei, R. Whittington) and that dominated the subsequent discussion. Based on the efforts by the speakers to translate their findings to humans, as well as the current treatment of the subject matter in the media, it is not surprising that the discussion centered on this issue. The evidence shows that both the developing (fetal/neonatal) and aging brain are most sensitive to the potentially toxic effects of anesthesia. Factors that enhance neurotoxicity include hypothermia, neuroinflammation (enhanced by surgery), and polypharmacy. In the developing brain, combinations of drugs appear to be particularly damaging, though much of the experimental evidence is limited to single agents in the absence of surgical stimulation, which evidence shows can make the damage worse. However, while raising caution, clinical evidence is lacking to support much of the data presented, and given the logistical obstacles, such clinical data are unlikely to be forthcoming, at least in the near term. Interestingly, in spite of the lack of such clinical evidence, most of the speakers have altered their clinical practice, sending an important message to the public. Although the human implications are unclear, the cumulative animal data indicate that markers of neurotoxicity, as well as evidence for functional consequences of such neurological damage, occur acutely and in some cases persist following anesthesia. In the absence of solid clinical data, the development of sensitive noninvasive biomarkers and imaging techniques to detect neurotoxicity in humans is clearly a research priority that should be helpful in addressing the question of the relevance of the experimental evidence to clinical anesthesia, a question that continues to predominate discussion in this area.

The elimination clearance of parecoxib, which results in the formation of valdecoxib, increased by approximately 5% per year of age. (Image source: Thinkstock)

The prodrug parecoxib is nearly completely converted to the cyclooxygenase-2 (COX-2)specific inhibitor valdecoxib by carboxylesterases. When parecoxib is administered intravenously to adults to manage their postoperative pain, it has been reported to be opioid sparing and to improve patient satisfaction. Though carboxylase activity has been reported to increase throughout childhood, children as old as age 10 have less carboxylesterase activities than adults; therefore, children might be expected to require different parecoxib doses than do adults. However, neither parecoxib nor valdecoxib have been studied in children.

In the study “Development of a Population Pharmacokinetic Model for Parecoxib and Its Active Metabolite Valdecoxib after Parenteral Parecoxib Administration in Children,” published online first in Anesthesiology on 23 March 2012, Dr. Bruce Hullett, Consultant Anaesthetist, Department of Anaesthesiology, Princess Margaret Hospital for Children, Subiaco, Australia, and colleagues described their study of the population pharmacokinetics of parecoxib and its active metabolite valdecoxib in 38 children aged 1.1 to 12.7 years to whom parecoxib was administered intravenously at the time of induction of anesthesia. The elimination clearance of parecoxib, which results in the formation of valdecoxib, increased by approximately 5% per year of age. The pharmacokinetics of valdecoxib also changed with age. The age-related pharmacokinetics of these drugs were used to develop dosing guidelines for postoperative pain control in children aged 2 to 12 years and weighing 10 to 70 kg. The recommended doses are predicted to produce analgesic plasma valdecoxib concentrations for a median duration of at least 12 hours.

Spending for gastrointestinal endoscopy when weighted to the national level tripled between 2003-2009. (Image source: Thinkstock)

Should a low-risk patient, i.e., one with an ASA physical status level of 1 or 2, receive general anesthesia for gastrointestinal endoscopy? If the use of anesthesia services increases cost for such patients, should it be allowed? Both questions are difficult to answer, yet the numbers of patients undergoing such procedures and the percent who receive anesthesia are also increasing. In the article “Utilization of anesthesia services during outpatient endoscopies and colonoscopies and associated spending in 2003-2009” published in the 21 March 2012 issue of JAMA, Dr. Soeren Mattke, RAND Corporation, Boston, Massachusetts, and colleagues describe their use of insurance claims data for patients with Medicare or commercial insurance who underwent upper gastrointestinal endoscopies and colonoscopies between 2003 and 2009. About 14% of commercial insurance patients had ASA status coded; for the remainder of patients with commercial insurance and those with Medicare, ASA status was based on a multivariate logistic model.

Between 2003 and 2009, 2.2 million gastroenterology procedures were performed on patients with Medicare insurance and 7.0 million on patients with commercial insurance. In patients with commercial insurance, the number of gastroenterology procedures increased by over 50% between the years of study; however, for patients with Medicare, the number of gastroenterology procedures stayed fairly constant. For both groups, the proportion of patients who received anesthesia services increased similarly with commercial insurance increasing from 13.6% to 35.5% and Medicare from 13.5% to 30.2%. Patients in the West region of the United States had the lowest use of anesthesia services; the highest use was in the Northeast. The proportion of anesthesia services delivered to patients with ASA status 1 or 2 decreased in patients with Medicare from 79% to 64% between the years of study while in patients with commercial insurance the proportion was constant. Though annual payments for anesthesia services per 1 million enrollees for patients with Medicare doubled, the cost per procedure remained constant. For patients with commercial insurance, annual payments per 1 million enrollees increased more than 4-fold and the cost per procedure increased by 14% between the years of study. Spending when weighted to the national level tripled between the years of study, with an increase to $1.3 billion, specifically $1.1 billion in 2009 for Medicare patients and $945 million for patients with commercial insurance.

Dr. Lee A. Fleisher, Department of Anesthesiology and Critical Care, Perelman School of Medicine, and Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, in the accompanying editorial, “Assessing the value of ‘discretionary’ clinical care: the case of anesthesia services for endoscopy,” noted:

Should patients be denied the opportunity to undergo endoscopy or colonoscopy with the added benefit of anesthesiologists or anesthetists who can provide deeper sedation and incremental monitoring even if anesthesia is a discretionary service? Careful implementation of new policies regarding ‘potentially’ discretionary services need to incorporate the patient and clinician perspective while continuing to implement change that bends the cost curve. This may require all parties, including patients, clinicians, and facilities, to have a greater stake in the financial consequences of their action.

Immediately postoperatively, the pupillary dilatation reflex was shown to correlate with pain intensity. (mage source: Thinkstock)

The gold standard for assessing pain is verbal or written report.  “Do you hurt?”  “How much do you hurt?”  These are questions we regularly ask nearly every patient upon recovery from general anesthesia after surgery.  In some patients it’s not possible to get a response and in others we’re less than certain how reliable it is.  In their manuscript “Objective Assessment of the Immediate Postoperative Analgesia Using Pupillary Reflex Measurement: A Prospective and Observational Study” published online first on 22 March 2012, Dr. Marc Beaussier, Professor of Anesthesiology and Intensive Care, Department of Anesthesia and Intensive Care, Assistance Publique, Hôpitaux de Paris, Saint-Antoine University Hospital, Paris, France, University Pierre & Marie Curie, Paris, France, and colleagues  studied how a simple reflex, described over 150 years ago, might help in such cases.

In this study, French investigators examined the pupillary dilatation reflex (PDR) in 100 patients awakening from general anesthesia after abdominal surgery or thyroidectomy.  First they asked patients to rate their pain on a 0-4 verbal scale from no pain to extreme pain, and then they examined the PDR in response to a calibrated amount of pressure applied adjacent to the surgical wound.  Due to effective multimodal analgesia during surgery, only 39 patients rated their pain as more than mild on the verbal scale.  A PDR value of 23% or greater identified those patients with more than mild pain with a  sensitivity and specificity of 91% and 93% respectively.

So, can we use PDR instead of talking to patients or alternatively to find out whether they really have pain or are drug seeking instead?  Although these findings are positive, we’re far from being able to definitively say yes yet.  The PDR measures a response to an additional noxious stimulus, so it isn’t exactly measuring baseline pain per se.  It requires quite a bit of patient cooperation, some additional equipment, and hasn’t been tested in the populations where it might be most useful.  However, this paper certainly leads the way for more research towards helping us sort out pain and analgesia in the complicated setting of the postanesthesia care unit.

In the accompanying editorial, “Pupillometry to Guide Postoperative Analgesia,”  Dr. Merlin D. Larson, Department of Anesthesia, University of California, San Francisco, San Francisco, California, and Dr. Daniel I. Sessler, Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, note that:

The PDR has substantial potential value to the extent that can be used as a measure of analgesia, especially in uncommunicative patients. Certainly, pupillary dilation as a measure of analgesia has distinct advantages over other autonomic responses to pain, such as blood pressure and heart rate, neither of which is sensitive or specific.

Carolina Breast Cancer Study map

Increasing evidence suggests that opioids promote tumor growth.  Clinical data regarding the influence of exogenous opioids on cancer outcomes are limited because of the imperative to treat cancer pain.  In this setting, we felt that an observational study examining the association between a functional genetic polymorphism in the µ-opioid receptor gene and cancer survival might be useful because if opioid pathways are involved in tumor growth, then genetic variants that influence the function of the µ-opioid receptor should be associated with breast cancer survival.

First we sought to find a prospective cancer cohort study.  Fortunately, the University of North Carolina is the home of many large-scale prospective observational studies, including The Carolina Breast Cancer Study.  This is a population-based study designed to identify causes of breast cancer among Caucasian and African-American women who are residents of a 24-county area of central and eastern North Carolina.

Dr. Millikan

We approached Dr. Millikan, the principal investigator of the Carolina Breast Cancer Study, regarding this collaboration and he kindly agreed.  Genotyping was performed on patient blood samples using the TaqMan® platform (Applied Biosystems Inc., Foster City, CA) at the A118G SNP (rs1799971, located within the first exon) and five other informative SNPs within other parts of the µ-opioid receptor gene OPRM1.  Work was performed in the UNC Mammalian Genotyping Core by Jason Kuo and Amanda Beaty.

Amanda Beaty, UNC Mammalian Genotyping Core

TRYUMPH Research Program

Genetic results were delivered to the TRYUMPH Research Program in the UNC Department of Anesthesiology.

Dr. Bortsov

Associations between opioid polymorphisms and breast cancer survival were performed by Dr Andrey Bortsov.  Dr. Bortsov used HapMap software to identify linkage disequilibrium plots, and SAS software to perform Cox proportional hazards regression analysis and Kaplan-Meier plots by genetic polymorphisms and cancer survival.

Obstructive sleep apnea (OSA) was a significant predictor of postoperative delirium (POD) using multivariate analysis. (Image source: Thinkstock)

Can we predict whether an older patient, aged 65 years or older, will develop postoperative delirium? Specifically, are there medical conditions that can help predict this condition? In the study “Obstructive Sleep Apnea and Incidence of Postoperative Delirium after Elective Knee Replacement in the Nondemented Elderly,” Dr. Madan M. Kwatra, Associate Professor, Department of Anesthesiology, Duke University Medical Center and colleagues studied 106 healthy patients ≥ 65 years of age undergoing elective single knee replacement surgery. They excluded patients with dementia and other central nervous system disorders. Patients received either general or regional anesthesia for the procedure at the discretion of the anesthesiologist caring for the patient. The diagnosis of delirium was made by the study psychiatrist. The diagnosis of sleep apnea was confirmed in 15 patients, 12 of whom had polysomnography reports.

Despite patient exclusion, 25% developed postoperative delirium, a value similar to other studies that did not have such stringent entry criteria. Delirium incidence, of mild severity, was highest on the second day after surgery, though the majority of patients had recovered by day 3. Obstructive sleep apnea (OSA) was the only significant predictor of postoperative delirium (POD) using multivariate analysis. Patients with delirium also had lower hemoglobin values but hemoglobin value was not retained in the multivariate analysis. Slightly more than 50% of patients with obstructive sleep apnea developed postoperative delirium.

The mechanism for the relationship between sleep apnea and postoperative delirium was not specifically studied. The authors proposed reduced oxygen metabolism, postoperative hypoxemia and an increase in proinflammatory cytokines all as possible factors that deserve future study.

In the accompanying editorial, “Obstructive Sleep Apnea Predicts Adverse Perioperative Outcome. Evidence for an Association between Obstructive Sleep Apnea and Delirium,” Drs. Brian T. Bateman (Department of Anesthesiology, Critical Care, and
Pain Medicine, Massachusetts General Hospital, Harvard Medical School) and Matthias Eikermann (Department of Anesthesiology, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and Klinik fuer Anaesthesiologie und Intensivmedizin, Universitaetsklinikum Essen, Dusiburg-Essen University, Essen, Germany) noted that the mechanisms for the association between OSA and POD was not directly assessed, though airway collapse leading to episodes of hypoxia may be the reason. If there is a relationship between OSA and POD, might strategies to decrease OSA also decrease the incidence of POD? As they note, “If it turns out that OSA does cause POD and that there are effective strategies to prevent it from doing so, than the paper by Flink et al. will be a landmark in the quest to address this most challenging perioperative complication.” More research is needed.

The American Society of Anesthesiologists offers CME credit based on this post and it’s accompanying article.

It's not clear if the effect that was observed is solely due to endogenous opioids or whether opioids prescribed by doctors have any influence (Image source: Thinkstock)

In vitro and animal studies indicate a relationship between µ-opioid receptor activation and tumor growth and progression. Would the same be seen in humans?  In the study “µ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer” published in the April issue of Anesthesiology, Dr. Andrey V. Bortsov, Assistant Professor, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, and colleagues studied women with breast cancer who were diagnosed between 1993 and 2001. The gene associated with µ-opioid receptor function has several genetic variants. The most common variant, A118G SNP, results from a single nucleotide polymorphism. Individuals with this variant have a reduced response at the receptor for opioid binding and, when in pain, a higher opioid requirement. The authors hypothesized that individuals with this genetic variant would have increased breast cancer survival.

Dr. Bortsov and coauthors studied 2,039 African-American or European-American patients through 2006 who were part of the Carolina Breast Cancer Study. They obtained sociodemographic and clinical data and performed genotyping. The median follow-up period was 9 years. Patients with the A118G phenotype had lower cancer-specific mortality. If a patient had only one copy of the G allele, her mortality was lower than patients with the A/A genotype. This effect was limited to those with invasive cancer and effect size increased with cancer stage at diagnosis. Women with at least one copy of the G allele presented at an earlier stage of cancer or were more likely to have carcinoma in situ.

This was a retrospective study and specific opioid intake of study participants was not known. Furthermore, it is unclear whether endogenous or exogenous opioids are responsible for the effect. It’s also not clear if this specific polymorphism or another is responsible. In April’s issue there are additionally two other articles and a clinical concepts and commentary review on the relationship between the µ-opioid receptor and cancer; Dr. James Eisenach, editor-in-chief, provided an overview of these articles last week.

Page2Anesthesiology had an email exchange with Dr. Bortsov subsequent to the study’s publication:

Why were only breast cancer patients considered?

We chose breast cancer patients because of the local availability of a large population-based study of breast cancer patients which included blood collection for DNA evaluation (the Carolina Breast Cancer Study).

Why were only African-American or European-American patients studied?

The Carolina Breast Cancer Study cohort included only African-American and European-American patients.

What is the takeaway message?

Our hope is that other researchers can perform studies similar to ours, with their own patient data, to see if they get similar results. If they do, then this would increase the likelihood that this is a true finding. If this finding is true, then it might open up new opportunities for treating cancer using relatively non-toxic treatments. Of note, we did not have information on the types of pain medication that women in the study were taking. Therefore, we don’t know if the effect we observed is solely due to endogenous opioids or whether opioids prescribed by doctors have any influence.

A major increase in mortality was seen with a burn size > 60% of total body surface area. (Image source: Thinkstock)

Clearly the likelihood of survival after a burn decreases as the size of the burn increases. Most studies that provide the basis for this relationship have been performed with adults. In the article “Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study” published in the March 17, 2012 issue of The Lancet, Dr. Marc G Jeschke, Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Department of Surgery, Division of Plastic Surgery University of Toronto, Sunnybrook Research Institute and colleaguesstudied this problem in children.

This was a single-center study. Between 1998 and 2008, 952 children with burns of at least 30% of total body surface area (TBSA) were studied. Patients with inhalation injury and older children had larger burn size. Mortality rates were higher in patients with inhalation injury. Patients with larger burns stayed longer in the ICU, underwent more operations, and had a higher incidence of multi-organ failure. There was a large increase in mortality starting at a burn size of 60% of TBSA. Using multiple logistic regression analysis, mortality rates increased ten times for those patients with burns covering greater than 60% of TBSA. In patients with inhalation injury, mortality rates were three times higher than those without inhalation injury.

In a study in rats, a 30-minute infusion of methoxycarbonyl etomidate resulted in longer periods of EEG burst suppression (Image source: Thinkstock)

Methoxycarbonyl etomidate is an etomidate analog that was designed to be rapidly metabolized by esterases to methoxycarbonyl etomidate carboxylic acid, which has less than 1% of methoxycarbonyl etomidate’s hypnotic potency.    Single bolus administration of this drug to rats produces hypnosis of extremely short duration.  Although the EEG burst suppression ratio returns to baseline soon after bolus administration of methoxycarbonyl etomidate, with prolonged administration of the drug the EEG burst suppression ratio remains elevated and its hypnotic effects persist long after termination of the infusion.

In the study “Electroencephalographic Recovery, Hypnotic Emergence, and the Effects of Metabolite after Continuous Infusions of a Rapidly Metabolized Etomidate Analog in Rats” published online ahead of print on 13 March 2012, Dr. Douglas E. Raines, Associate Professor of Anesthesia, Harvard Medical School, and Associate Anesthetist, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and colleagues found that in rats, recovery of the EEG burst suppression ratio after administration of methoxycarbonyl etomidate had both fast and slow components.  After administration as a bolus or an infusion lasting up to five minutes the fast component dominated, reflecting rapid redistribution of the lipophilic methoxycarbonyl etomidate from the brain.  However, when methoxycarbonyl etomidate was infused for 30 minutes, the slow component dominated, reflecting concentrations of methoxycarbonyl etomidate carboxylic acid produced by metabolism of methoxycarbonyl etomidate in the brain that were high enough to contribute to or produce EEG burst suppression that persisted because of the slow removal of the hydrophilic methoxycarbonyl etomidate carboxylic acid from the brain.

Study is next needed in humans to determine whether the accumulated metabolite, after longer infusions, has any effect on recovery.

 μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer

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A Comparison of Epidural Analgesia and Traditional Pain Management Effects on Survival and Cancer Recurrence after Colectomy: A Population-based Study

The μ-Opioid Receptor in Cancer Progression: Is There a Direct Effect? 

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Blood pressure decrease was associated with the occurrence of postoperative stroke

When we care for our patients intraoperatively, blood pressure is a concern.  Though we might be very meticulous in maintaining blood pressure at a certain level, does this have any effect on patient outcome?  In this month’s issue of Anesthesiology, Dr. Jilles B. Bijker, Anesthesiologist, Division of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, The Netherlands, and colleagues studied 48,241 patients over a 7-year period in order to determine the relationship between hypotension and ischemic stroke within ten days of surgery and published their findings in the article “Intraoperative Hypotension and Perioperative Ischemic Stroke after General Surgery: A Nested Case-control Study.”

This was a single institution study.  Patients who underwent a cardiac or neurosurgical procedure were excluded.  Hypotension was classified as a systolic blood pressure less than 100, 90, 80, and 70 mmHg, a mean blood pressure less than 70, 60, 50, and 40 mmHg, and a decrease in systolic or mean blood pressure of 10%, 20%, 30%, and 40% from baseline, and then this variable was measured as the time in minutes that the blood pressure remained at or below the hypotension level.  Baseline blood pressure was the mean blood pressure measured at the preoperative clinic and blood pressures measured in the operating room before the induction of anesthesia.  Ischemic stroke was based on a new focal neurologic deficit without hemorrhage seen for more than 24 hrs on CT scan and occurring within 10 days after surgery.  They also chose six control patients for every patient with postoperative stroke matched by age and type of surgery and who also had surgery close to the time of the patient who had a stroke.

53 patients had suggestive criteria for stroke based on CT criteria, though 42 or 0.09% definitely had a stroke based on CT or clinical signs.  252 control patients were selected.  The study authors found that if mean blood pressure decreased more than 30% from baseline, this was associated with the occurrence of a postoperative stroke.

This was a single institution study.  Though there might be an association between stroke and hypotension, this was a retrospective study and hence there could be other reasons these patients had a stroke.

The American Society of Anesthesiologists offers CME credit based on this article.

First-attempt intubation success was significantly higher in the C-MAC group compared to the standard laryngoscope group. (Image source: Thinkstock)

If confronted with a patient with a predicted difficult airway and you have determined that you would insert an endotracheal tube, how would you approach intubation?  Would you first try to use a laryngoscope blade and have a video larynoscope available as backup or would you first use the video laryngoscope?  Dr. Michael F. Aziz, Assistant Professor, Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, and colleagues compared success rates using the two devices in 296 patients thought potentially difficult to intubate in the study “Comparative Effectiveness of the C-MAC Video Laryngoscope versus Direct Laryngoscopy in the Setting of the Predicted Difficult Airway” published in this month’s issue of Anesthesiology.  To be enrolled, patients had to have at least one of the following: reduced cervical motion; Mallampati classification score ≥ III; < 3 cm mouth opening; or medical record-based history of difficult direct laryngoscopy.  Intubation was performed with the patient in the “sniffing position”; if obese, in a ramped position; or if with cervical precautions, using in-line stabilization.  Paralysis during intubation was determined using the DigiStim III.  Experienced providers, including attending anesthesiologists, CRNAs, or resident physicians with at least 6 months of experience, performed intubation.  Intubation was performed utilizing the C-MAC® video laryngoscope or a standard laryngoscope, size #3 or # 4 for either device.

First-attempt intubation success was significantly higher in the C-MAC group (93%) compared to the 84% rate in the standard laryngoscope group.  The ability to view the larynx was higher in the C-MAC group.  The need to use a gum-elastic bougie and/or external laryngeal manipulation was lower in the C-MAC group.  However, the time required to intubate the trachea was 10 s lower in the standard laryngoscope group.  Trauma related to intubation was no different between the two groups.

Different types of video laryngoscopes are available and it’s not clear if one is better than another.  As noted by Dr. Takashi Asai, Department of Anesthesiology, Kansai Medical University, Takii Hospital, Osaka, Japan, in the accompanying editorial “Videolaryngoscopes -Do They Truly Have Roles in Difficult Airways?,”

…there is still insufficient evidence to judge whether tracheal intubation using a videolaryngoscope is less likely to traumatize the airway or to prolong apnea time, both of which may lead to serious airway complications. It is also not clear when each videolaryngoscope may fail, and how such a difficulty can be predicted preoperatively. In the era of evidence-based medicine, the efficacy and the safety of each videolarynogoscope should be compared with a conventional direct laryngoscope, with the other videolaryngoscopes, and with the other types of intubation devices (e.g., a fiberoptic bronchoscope) to establish true role of videolaryngoscopes in patients with difficult airways.”

In this particular vignette, humidification of oxygen is described.  At the time, oxygen therapy was not as sophisticated as it is today.

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This study reinforces the consideration that early surgery should be considered for patients with drug-resistant temporal lobe epilepsy (Image source: Thinkstock)

We don’t often see patients in the operating room undergoing surgical treatment for epilepsy.  Should surgery be considered as a treatment of last resort for medically intractable temporal lobe epilepsy or earlier in the course of the disease? In their JAMA (7 March 2012 issue) study entitled “Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial,” Dr. Jerome Engel Jr., Department of Neurology, David Geffen School of Medicine at UCLA, and colleagues randomized patients to either receive surgery soon after failure of 2 antiepileptic drugs or to continue to receive pharmacotherapy.  This was a multicenter trial performed at 16 epilepsy surgery centers in the United States.  Patients were followed for 24 months.  Patients who underwent surgery had anteromesial temporal resection.  Both groups of patients received the same pharmacotherapy adjusted to eliminate seizures with minimal adverse effects.

The original intent was to enroll 200 patients; however only 38 patients were randomized due to enrollment issues.  Of those, 15 were randomized to undergo surgery and 14 underwent surgery.  In the group randomized to receive medical treatment, 16 received medical treatment and 7 received surgery.  Despite the small number of patients studied, outcome after surgery was better than receiving only pharmacotherapy.  Considering those with complete data in year 2, 0 of 19 patients in the medical group versus 11 of 13 in the surgical group were seizure free.  Those who were seizure free also did not experience auras.  Quality of life was additionally significantly improved for those patients who underwent surgery.

In their practice parameter on temporal lobe and localized neocortical resections for epilepsy (link: http://www.ncbi.nlm.nih.gov/pubmed/12601090),the American Academy of Neurologyrecommends that epilepsy surgery, undertaken at an epilepsy surgery center, should be considered for patients compromised by seizures.  This study reinforces the consideration that early surgery ought to be considered

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1. Next to the United States, in which country does Page2Anesthesiology have the most readers? India. Person to first answer and receive a prize: Ritika Gandhi
2. Which Anesthesiology editor was the first to provide audio highlights of the current month`s issue? Dr. Tim Brennan, Assistant Editor-In-Chief for Anesthesiology.
3. Which book review has had the most page views? The Immortal Life of Henrietta Lacks.
4. Which website referred the most visitors to Page2Anesthesiology? Facebook. Person to first answer and receive a prize: Michael Aziz.

Congratulations to our winners.

The American Society of Anesthesiologists has developed practice guidelines for central venous access. (Image source: Thinkstock)

Several organizations have developed guidelines for central venous access. The American Society of Anesthesiologists has authored “Practice Guidelines for Central Venous Access: A Report by the American Society of Anesthesiologists Task Force on Central Venous Access” which was published in this month`s edition of Anesthesiology. These guidelines differ from those published by other organizations in that upper body insertion site is emphasized, real-time ultrasound to help guide placement is considered, and verification of catheter location is described.

Guidelines in summary

What resources should be made available?

The environment should allow for use of aseptic techniques. Standardized equipment sets should be made available. A checklist ought to be used for placement and maintenance of central venous catheters. An assistant should be available to help place these catheters.

Should antibiotic prophylaxis be routinely administered?

Routine antibiotic prophylaxis is not recommended. Immunocompromised patients or high-risk neonates may receive antibiotics based upon the individual judgment of a physician.

What is the recommended approach towards asepsis, including the use of antiseptic solutions?

Hands should be washed before catheters are placed and the individual inserting the catheter should wear a sterile gown, gloves, cap, and mask (both mouth and nose should be covered). A full-body patient drape should be used. A chlorohexidine-containing solution should be used to cleanse the skin, though for neonates, clinical judgment and institutional protocol can determine practice. If a chlorohexidine-containing solution is contraindicated, povidone-iodine or alcohol can be used.

Should catheters that contain antimicrobial agents be used?

The use of catheters coated with antibiotics or a combination of chlorhexidine and silver sulfadiazine should be based on infectious risk, cost, and how long it is thought that the catheter will be used. The use of such catheters does not obviate the use of additional infection precautions.

Where should catheters be inserted?

Insertion location should be based on clinical need. The intended site should not be or potentially become contaminated. For adults, upper body insertion is preferred because of possible lower levels of contamination.

How should catheters be affixed to the skin?

There is insufficient literature evidence to recommend the use of sutures, staples or tape. Use of the aforementioned tools should be based on local or institutional recommendations.

What type of insertion site dressing should be used?

Transparent bio-occlusive dressings should be used and, unless contraindicated, dressings may also contain chlorhexidine. For neonates, chlorhexidine sponge dressings may be used instead of transparent bio-occlusive dressings that contain chlorhexidine, though use of either type of dressing should be based upon institutional protocol and clinical judgment.

How should catheters be maintained?

The catheter site should be checked daily. When the catheter is no longer clinically needed, or when infection of the insertion site is suspected, it should be removed. In the case of suspected infection, use of a new insertion site is preferable.

When solutions are injected into or blood is withdrawn from central venous catheters, what aseptic techniques ought to be used?

Ports should be wiped with an appropriate antiseptic and stopcocks or access ports should be covered when they are not being used.

Should ultrasound be used to place central venous catheters?

Static ultrasound imaging in elective situations should be utilized in order to identify the anatomy and localize the internal jugular vein, though not all agree that real-time ultrasound imaging is useful. Use of static or real-time ultrasound imaging for subclavian or femoral vein cannulation is equivocal.

How should proper catheter placement be verified?

For catheters placed in the operating room, pressure waveform analysis, blood gas analysis, ultrasound, or fluoroscopy should be used to assure proper location of the catheter. Then, immediately postoperatively, a chest radiograph should be performed in order to assure proper catheter tip location.

What should be done if an artery is cannulated with a dilator or a large-bore catheter?

In an adult, if artery cannulation was not intended, leave the dilator or catheter in place and immediately consult a general or vascular surgeon or an interventional radiologist. For neonates, infants, or children, catheter removal should be based on the judgment and experience of the practitioner. Regardless, a discussion between the anesthesiologist and surgeon as to the advisability of continuing with the procedure or delaying the procedure while the patient is observed should take place.

These guidelines are provided in much greater detail and the reader is encouraged to read them in their entirety.

Sevoflurane formulated in a dibranched fluropolymer was stable for up to 1 year. (Image source: Thinkstock)

Inhalation anesthetics are commonly used to administer anesthesia. Instead of patients breathing inhalation anesthetics, can they be injected intravenously? An intravenous pump could be substituted for a vaporizer and vaporizers might then become obsolete. Lipid emulsions with Intralipid^® or other fats have been tried, though such formulations are limited in part by solubility. Dr. Robert A. Pearce, Ralph M. Waters Distinguished Chair of Anesthesiology, Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin, and colleagues, in their article “Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics” published in this month`s issue of Anesthesiology, describe the development of 20% (volume/volume) emulsion of sevoflurane with perfluorooctyl bromide, a stabilizing agent, and combinations of linear fluorinated diblock copolymer and a novel dibranched fluorinated diblock copolymer used as a surfactant. This dibranched fluoropolymer was stable for up to 1 year, the maximum time for testing. When injected into rats, loss of righting reflex occurred after 18 s; recovery of the righting reflex was also rapid. It is unclear whether or not the same described techniques could be used for other inhalation agents, particularly with desflurane, which boils at room temperature.

As noted in the accompanying editorial “Getting Oil and Water to Mix” written by Dr. Evan D. Kharasch, Division of Clinical and Translational Research, Department of Anesthesiology and the Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri, several questions arise from the aforementioned work:

“…what are the fate, effect, and safety of the excipients and coformulation agents in the sevoflurane emulsion? How will the pharmacokinetics and pharmacodynamics of the new IV sevoflurane compare with that of inhaled sevoflurane or other volatile anesthetics? Although emulsions can obviously change the route of volatile anesthetic administration, will they influence the route and kinetics of elimination: pulmonary clearance and exhalation? Can the new sevoflurane emulsion be used for maintenance of anesthesia? How will exhaled IV volatile anesthetics be scavenged? If an anesthetic circuit is needed for scavenging, does this obviate one potential advantage of emulsions of not needing an anesthesia machine? Or can available nonanesthesia machine-based scavenging masks, which can also provide oxygen, be used? What are the relative advantages and disadvantages of IV emulsion versus inhalation-based administration of volatile anesthetics? Might IV anesthetic emulsions lead to new clinical indications in addition to that for which volatile anesthetics were originally approved?”

Though this is a fascinating study, more work on the subject is needed.

Environmental enhancement reversed some adverse neurocognitive effects of sevoflurane. (Image source: Thinkstock)

Recently there have been several studies suggesting that if a neonate is exposed to an anesthetic, development could be adversely affected. This is perhaps true, though neonatal rodents are usually the subjects studied. Furthermore, if a neonate needs surgery, no one would suggest that anesthesia should not be used. Is there anything that could be done to ameliorate the effect of the anesthetic? In the study “Delayed Environmental Enrichment Reverses Sevoflurane-induced Memory Impairment in Rats,” Dr. Greg Stratmann (Associate Professor, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California) and co-authors randomized rats to environmental enrichment or normal housing to test the hypothesis that cognitive decline is treatable.

Seven-day-old rats were exposed to 1 MAC sevoflurane for four hours. At four weeks, they were randomized to environmental enrichment or normal housing. The environmental rats were exposed to a running wheel, a ramp, a rope, and other toys. Then, at eight weeks the rats underwent neurocognitive testing. Testing consisted of fear conditioning and a variety of memory tests. They found that sevoflurane alone caused long-term neurocognitive effects and that environmental enrichment improved performance, specifically with regard to short-term memory and other aspects of neurocognition.

In the accompanying editorial entitled “Neurotoxicity and the Need for Anesthesia in the Newborn: Does the Emperor Have No Clothes?“ Dr. Andrew J. Davidson first noted that in 2011, of almost half of the papers that dealt with pediatric anesthesia, the point of study related to the neurotoxicity of anesthesia on the developing brain. He furthermore noted that

“A common criticism when translating animal to human data is that there are a multitude of influences on outcome in humans and that an anesthesia exposure may only be one minor insult compared with many other more significant events in childhood. Shih et al.’s findings [ed. note: Dr. Stratmann is the corresponding author] might provide some hint that the toxic effects of anesthesia are indeed relatively mild compared with other environmental influences. This leaves the clinician somewhat less concerned that the anesthesia has a significant effect.”

More study is needed. And here’s a little hint: more studies on this topic will be appearing in Anesthesiology.

In this particular vignette, an overview of anesthesia equipment manufacture is described. At the time, pre-packaged endotracheal tubes were not even available.

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Rate of recovery in patients with severe traumatic brain injury was faster with use of amantadine (Image source: Thinkstock)

Is there new reason for hope in treating patients with severe traumatic brain injury, the most common cause of death and disability in individuals aged 15-30? Amantadine has been tried in two randomized trials of patients with the aforementioned brain injury, though small sample sizes and unbalanced groups make it difficult to form definitive conclusions. In their New England Journal of Medicine original article entitled “Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury,” Dr. Joseph T. Giacino, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, and co-authors conducted a multi-center, 3-country, prospective double-blind study that included patients 16-65 years of age who sustained a nonpenetrating traumatic injury 4 to 6 weeks before enrollment. In addition, patients had to be in a vegetative or minimally conscious state. The primary outcome was improvement in the disability rating scale (DSR), a score that includes measures of “eye opening, verbalization, and motor response (derived from the Glasgow Coma Scale); cognitive understanding of feeding, dressing, and grooming; degree of assistance and supervision required; and employability.” Higher scores indicate higher disability. Study eligibility included a DRS scale greater than 11.

One hundred eighty-four patients received either placebo or treatment with amantadine starting at 100 mg twice daily; the dose was increased to 150 mg twice daily after 14 days and at the fourth week to 200 mg with increases based on lack of DRS score improvement by 2. After 4 weeks, the study drug was tapered over 2-3 days and patient evaluation continued through week 6.

Though both groups improved, the amantadine group recovered faster than the control group. Faster recovery was particularly apparent if patients were enrolled earlier after injury and if they were in a minimally conscious state rather than a vegetative state at the time of enrollment. Improvement slowed after treatment stopped. More patients who received amantadine had a favorable outcome on the DRS and fewer were in a vegetative state. At 6-week followup, DRS score improvement was similar, suggesting that response is dependent on receiving the study drug.

Long-term outcome is not clear. Is it better with the drug or does amantadine get a patient to the same point more quickly? More research is needed.

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Revised practice guidelines for preanesthesia evaluation have been published. (Image source: Thinkstock) Â

In this month`s issue of Anesthesiology, “Practice Advisory for Preanesthesia Evaluation: An Updated Report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation” was published. This is a revision of the original Practice Advisory that was published in 2002. Although the actual recommendations did not change, the evidence for them did.

Guidelines in summary

How is preanesthesia evaluation defined?

Preanesthesia evaluation is defined as “the process of clinical assessment that precedes the delivery of anesthesia care for surgery and for nonsurgical procedures.” The anesthesiologist is responsible for this care. Multiple sources are considered to be part of preanesthesia evaluation and can include patient interview, review of the patient`s medical records, examination of the patient, and consideration of medical tests and evaluations. Other healthcare professionals can be consulted. Preoperative tests can serve to identify diseases or disorders, verify diseases or disorders, and/or be utilized to develop plans and alternatives that might affect perioperative anesthesia care. Such assessments can help educate patients, organize resources and assist in the formulation of plans for care of the patient intraoperatively and postoperatively, including pain management.

Criteria for anesthesia testing, intervention and consultation

When testing, intervention and consultation are performed (or consultation alone), one expectation is that the benefit(s) will exceed any potential harm. For example, if the time that an operation is performed might be altered, the delay or cost associated with the delay should not exceed the expected benefit.

The impact of preanesthesia history and physical examination

There is insufficient evidence to show that medical record review or the performance of a physical examination has any clinical impact. Yet, studies have shown a relationship between patient characteristics, e.g., high BMI and extremes of age and/or specific preexisting conditions, e.g., diabetes, lung disease, hypertension, history of myocardial infarction, and smoking history relative to postoperative morbidity and mortality. The evidence to show that such knowledge might have an impact on outcome has not been demonstrated, however.

When should preanesthesia evaluation occur?

Many feel that for patients undergoing surgical procedures that are highly invasive or for those patients with high disease severity, medical record review, patient interview and physical examination should be initially performed the day before surgery. Opinions are mixed as to whether or not medical records for patients undergoing surgical procedures that have medium invasiveness should be reviewed the day prior to surgery; however, if patients have low severity of disease, they can be interviewed and examined either on the day of or the day before surgery. Patients who undergo procedures with low surgical invasiveness and who have low severity of disease can have their medical records assessed, be interviewed, and examined either on the day of or the day prior to surgery.

What ought to be included in the physical examination?

At minimum, the airway should be examined, the lungs should be auscultated, and the heart should be examined.

Of what should the medical review consist?

Medical review may include, but not be limited to, a description of current diagnoses, treatments that include medications and alternative therapies, and determinations of the patient`s condition.

Laboratory tests

Routine preoperative testing should not be performed. Selective testing can be used to guide or optimize perioperative management. Age alone should not be used to determine whether ECG testing ought to be performed, though ECG may be indicated for patients with cardiovascular risks. Chest radiographs should not routinely be performed in patients with age extremes, smoking history, stable COPD, stable cardiac disease, or if the patient has recently had an upper respiratory tract infection that has resolved. Routine hemoglobin or hematocrit measurement is not indicated; however, it may be considered based on the surgical procedure, history of liver disease, age extreme, history of anemia, bleeding or other blood disorders. Coagulation tests may be performed based on the invasiveness of the procedure, whether the patient has bleeding disorders, renal dysfunction, or liver dysfunction, or if the patient is taking anticoagulant medications or other alternative therapies. There is not enough data to show that coagulation tests are justified before a patient undergoes regional anesthesia. Serum chemistries can be considered if the patient is undergoing certain therapies, has an endocrine disorder, liver or kidney dysfunction, or is taking certain medications or alternative therapies. Urinalysis is indicated only for certain procedures or if a patient has urinary tract symptoms. Pregnancy testing may be offered if the result would alter management.

Generally, if a patient`s history has not changed significantly, laboratory tests obtained 6 months before a procedure are acceptable. If a patient`s medical history has changed or if a test might affect whether a specific anesthesia technique is selected, then more recent tests might be optimal.

The reader is encouraged to read “Practice Advisory for Preanesthesia Evaluation: An Updated Report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation” in its entirety wherein the basis for these revised guidelines is provided in much greater detail.

Intubation times were no different when comparing the GlideScope Cobalt® Video to a Miller 1 blade. (Image source: Thinkstock)

Fortunately, the effectiveness of devices we use in medicine is now tested. Unfortunately, these devices are tested in the adult population and their possible use in children is frequently an afterthought. Use of the GlideScope^® in adults has become increasingly popular: when last checked, there were almost 200 published manuscripts where the GlideScope^® was the reason for study. Fewer than 10% of these studies were performed in infants and none have compared the use of a standard laryngoscope blade to the GlideScope^® in actual patients. In the study “A Prospective Randomized Equivalence Trial of the GlideScope Cobalt^® Video Laryngoscope to Traditional Direct Laryngoscopy in Neonates and Infants,” Dr. John E. Fiadjoe (Assistant Professor of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, and The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania) compared intubation times in 60 patients less than 12 m of age undergoing elective surgery requiring tracheal intubation. Use of the GlideScope Cobalt^®with a size 2 blade or intubation with a Miller 1 blade was compared. The Miller 1 blade was chosen in part because it is the most commonly used blade for such patients. Attending anesthesiologists performed all intubations and had experience using both blades.

Intubation times were no different for the two blades. Though the best view was obtained with the GlideScope^® blade since the image is brighter, it took longer to insert the endotracheal tube.

Attending anesthesiology physicians, not anesthesiology residents/fellows, pediatric residents/fellows, or attending neonatologists, were part of the study. In addition, only children with normal anatomy were studied. As with adult studies where patients with abnormal anatomy are studied, this too is needed in infants or children. Nonetheless, this study is a welcome start.

1. Special article: Practice guidelines for perioperative acute pain
2. Pediatric anesthesia: management of laryngospasm
3. What are moderate sedation, deep sedation and general anesthesia?
4. Try and hold your breath while reading this blog!
5. Thoracoabdominal aortic aneurysm repair: clinical concerns

Experience can lead to expertise, but we ought not mistake our clinical years for lifelong competence (Image source: Thinkstock)

The article “Association between Anesthesiologist Age and Litigation” by Dr. Michael J. Tessler, Associate Professor, Department of Anesthesia, Jewish General Hospital, McGill University, and colleagues will be of interest to us all. Based on litigation reports from three Canadian provinces, the authors of this article found that anesthesiologists older than 51 years of age, and especially those older than age 65, had a higher proportion of legal complaints than their younger colleagues. In his editorial “More Than Just Taking the Keys Away…,” Dr. Mark A. Warner commented on the aforementioned article, noting that it opens up an important dialogue about physician aging and their performance with regard to providing patient care.

Furthermore, this also gives us an opportunity to examine the relationship between experience and expertise. One would expect a direct relationship between years of experience in clinical practice and superior performance, but studies have not demonstrated this, especially in simulation research. When performing simulation scenarios, experienced anesthesiologists did not outperform senior residents as was expected. Clinical experience might well lead to expertise if deliberate practice occurs, however. Dr. K. Anders Ericsson, a psychologist from Florida State University, has been influential in popularizing the theory that talent is useful but that deliberate practice is the key to expertise. Deliberate practice must be used to both train and maintain medical competency, and simulation training represents a conscious effort to do accomplish this. In 2010, the ABA introduced simulation as a method to demonstrate maintenance of certification (MOCA). Close to 30 ASA-endorsed simulation centers presently exist for the delivery of high-quality simulation training. It seems inevitable that full-scale simulation will be an integral part of all anesthesiologists` training (deliberate practice) and might be used in high-stakes evaluations such as certification and recertification. Experience can lead to expertise, but we ought not mistake our clinical years for lifelong competence.

Comments?

A certain je ne sais quoi is missing (Image source: Thinkstock)

You may note that the look of Page2Anesthesiology on the iPad has changed since January. The add-on we were using to make that exquisite iPad look (OnSwipe) was upgraded in January and all went downhill after that. We thought it was working properly on Monday and Tuesday, but it was apparent by Wednesday that there were problems. It doesn`t look bad now, but a certain je ne sais quoi is missing. When we get it working properly, we will let you know. Thank you for your patience.

This is the largest study to date that has examined the relationship of age and gender to classic or non-classic symptoms at the time of admission for MI and to the likelihood of in-hospital mortality. Â (Image source: Thinkstock)

Chest pain and discomfort are the classic presenting symptoms for myocardial infarction. Women tend not to have these classic presenting symptoms, however. Those who do not present in this fashion tend to present later, are not treated as aggressively, and, in the short-term, have a higher likelihood of death. Is lack of chest pain associated with higher mortality, particularly in younger women?

In the study “Association of Age and Sex With Myocardial Infarction Symptom Presentation and In-Hospital Mortality” published in the February 22/29 issue of JAMA, Dr. John G. Canto, Watson Clinic and Lakeland Regional Medical Center, Lakeland, Florida, and co-authors used the National Registry of Myocardial Infarction to study 1,143,513 MI patients. About 40% of those patients were women. Women were significantly older than men (74 yrs compared to 66 yrs). Women (42%) were more likely to present without chest pain/discomfort than men (31%). This difference was more pronounced for younger patients, particularly for women younger than 45 years of age, though the difference decreased as age increased. Myocardial infarction without chest pain was also more likely for patients with diabetes and to delay hospital arrival, and these differences were seen irrespective of age or gender. In-hospital mortality was higher for women (15%) than for men (10%). For those younger patients who presented without chest pain, in-hospital mortality was higher for women than for men, though with increasing age, this difference decreased or even reversed.

This was a retrospective study and MI diagnosis was dependent on a review of medical records. Patients who died before hospital admission were not included. Nonetheless, this is the largest study to date that has examined the relationship of age and gender to classic or non-classic symptoms at the time of admission for MI and to the likelihood of in-hospital mortality.

Authors from left to right: Dr. Ravi Aron, Professor Maqbool Dada, Dr. Kayode Williams, Professor John Ulatowski, Dr. Douglas Hough, and Dr. Chester Chambers at the Blaustein Pain Treatment Center, Johns Hopkins.

The April issue of Anesthesiology will include the article “Using Process Analysis to Assess the Impact of Medical Education on the Delivery of Pain Services: A Natural Experiment” authored by Dr. Kayode A. Williams, Assistant Professor, Department of Anesthesiology and Critical Care Medicine, Division of Pain Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland and co-authors.

Conventional wisdom is that the delivery of health care in an academic medical center (AMC) must be less efficient than in systems functioning in private practice. Various works utilizing accounting data or billing records confirm that costs at AMCs are indeed higher than private practice costs because of the added complexity of combining a teaching mission with patient care.

Our main claim is that situations exist in which AMCs have advantages in terms of operational performance (as opposed to medical performance) when compared with private practice. Such a hypothesis is almost impossible to test directly because the two settings typically differ in terms of resource levels, scheduling rules, case complexity, process designs, and philosophies of care. In looking at process improvement efforts in an AMC at the Johns Hopkins Blaustein Pain Treatment Center, we stumbled upon a natural experiment. A free-standing private practice pain clinic within the Hopkins system but without a teaching mission was merged into the AMC. The clinical director of the private practice was appointed to manage the clinic in the AMC. Coincidentally, it just so happened that this director had been systematically gathering data on patient flows and process times for years prior to the merger.

This positioned us to ask a more basic question, specifically, “If these settings had identical schedules, how would process performance compare?” This question is impossible to answer by observation alone because the two settings will optimally not implement the same scheduling rules. We can circumvent this problem by using discrete event simulations of the two clinical settings. This allows us to ask how the private practice would perform if it utilized the schedule in place at the AMC and vice versa. Thus, a natural experiment is combined with simulation to compare the performance of two systems in a way that controls for all major differences except for differences in process design stemming from medical education.

Figure 1: Discrete event simulation is used to follow

Figure 2: Simulating a four-hour clinical session thousands of times allows us to collect data on waiting times, utilization levels, completion times, etc.

By implementing this approach, we are able to demonstrate that in many ways, an AMC is more efficient than a comparable PP. This is achieved primarily through the parallel processing that takes place when residents or fellows interact with patients while the attending is busy in another examination room. The result is that even though the patient experiences more processing, his/her total time spent in the clinic can be reduced in an AMC.

The clinic area with the four consulting rooms. From left to right: Heather Freeman, research associate responsible for collecting the activity times for the flow study; Dr. Janine Whitson-West, anesthesiology resident; Dr. Chitra Ramasubbu, pain fellow; Ms. Dorothea Mont, clinical associate responsible for initial patient intake; Dr. Ami Naik, anesthesiology resident.

The conference room where the some of the

We work as a team. (Image source: Thinkstock)

Editor`s note: This is the second of two blog entries on the same article. See yesterday`s post on the importance of a discussion with administrators about staffing issues and first starts.

It is time for a reality check: We don`t practice medicine by ourselves. Even if you argue that you are in solo anesthesiology practice and give one-on-one care (the MD-only model), you have to admit that you rely on a team in order to demonstrate excellence. The team is made up of surgeons, nurses, technicians, aides, and other anesthesiologists…as well as the patient! (Especially in pediatric anesthesia, parental insight and input are very valuable.)

Here`s a second reality check: Teams don`t succeed if the members don`t know their limits and don`t know how to ask for help. Put another way, individual egos can and do get in the way of successful teamwork. In life or in medicine, how many errors occur either because the person did not ask for help or recognize his/her own limits?

In the article “Influence of Supervision Ratios by Anesthesiologists on First-case Starts and Critical Portions of Anesthetics” published in this month`s issue of Anesthesiology, Drs. Richard H. Epstein (Professor, Department of Anesthesiology, Jefferson Medical College, Philadelphia, PA) and Franklin Dexter (Professor, Division of Management Consulting, Department of Anesthesia, University of Iowa, Iowa City, IA) used an anesthesia information management system (AIMS) and study-specific definitions of critical portions of anesthesia care and examined when these portions overlapped between rooms covered by the same anesthesiologist.

In my opinion, the biggest problem with the study design is that the authors ignored the factor of teamwork in their analysis.

As an anesthesiologist who works in an anesthesia care team model (with residents and CRNAs), I live with the reality of schedule flexibility and rely on my colleagues to help me when the inevitable situation occurs wherein two of my patients need my attention at the same time. As a group of anesthesiologists, we work together to help each other out, provide timely and appropriate care, and are available to attend to patients as needed.

Further, if I must devote myself to one patient exclusively, as a group of anesthesiologists, we are flexible in terms of helping each other out, including covering all of the rooms, as a team.

Finally, I have to be engaged in all of my patients` care in order to have the “situational awareness” to recognize if a critical portion will be happening soon and to plan care in both rooms so as to avoid potential overlaps. I plan ahead! In other words, if I am needed in one room to manage emergence with the resident and turnover is going on in the other room, then I might choose to delay the induction of the second patient until either another anesthesiologist is available or I am personally available to attend to the care of that patient.

Simply looking at the times of critical events and which anesthesiologist is assigned to that specific room gives neither a complete picture of how an anesthesia care team operates nor does it recognize the teamwork that anesthesiologists practice every day.

Teach administrators about staffing issues and first starts (Image source: Thinkstock)

Editor’s note: This is one of two blog posts on the same article. Tomorrow’s post will highlight a different aspect of the article.

As a parent, one of our duties is to have the proverbial and infamous “talk” with our children. In our family, we used a book by Laurie Krasny Brown and Marc Brown titled What’s the Big Secret? The best advice we received on the topic of how to approach the “sex talk”was this: Talk to your children before they learn about it from another source. In this way you can be sure that your children are at least receiving the correct information with the added benefit of letting them know that they can come to you with questions and concerns. If you don’t use this approach, you run the very real risk that your children will feel that they can’t talk to you and that they will get their information about the subject from their peers and the internet. I think we all know how accurate both of those sources can be!

Similarly, as anesthesiologists, you should adopt the responsibility of educating administrators about the realities of staffing. In the article “Influence of Supervision Ratios by Anesthesiologists on First-case Starts and Critical Portions of Anesthetics“ published in the March 2012 issue of Anesthesiology, Drs. Richard H. Epstein (Professor, Department of Anesthesiology, Jefferson Medical College, Philadelphia, Pennsylvania) and Franklin Dexter (Professor, Division of Management Consulting, Department of Anesthesia, University of Iowa, Iowa City, Iowa) used an Anesthesia Information Management System (AIMS) to look at first-case starts and the impact of anesthesia care team ratios. It comes as no surprise that the authors found that anesthesiologists cannot duplicate themselves and therefore can’t be in two places simultaneously. In other words, if I have two rooms to cover and start, I obviously can’t start both rooms at the exact same moment.

It’s pretty elementary, right?

However, how many of you work in an anesthesia care team model and have all of the ORs with the same start time…at least on paper? The reality is that you either have extra help (e.g., a post-call anesthesiologist or a non-clinical anesthesiologist) or you stagger the starts. Those are your only two options if you intend to be there for induction.

The typical argument against staggering starts is that should there be a delay, your earlier start will be ready at the same time as the theoretically later start and then you are forced to deal with the problem you set out to correct in the first place, namely having two rooms ready at the same time. In fact, the argument for having the same start time in all rooms is that in reality, patients and surgeons are not all ready at the same time and therefore you can stagger the starts anyway.

The other reality is that sometimes the surgeon just has to wait for you to become available. In other words, when both rooms are ready at the same time, logic dictates that one room will have to wait.

My point here is that you must take the initiative and teach administrators about staffing and first starts; otherwise, they will learn about it from someone who might not fully understand the issue, or, worse yet, has a different agenda than you do. Overall, the surrounding issues are not so dissimilar to the ones behind giving your children the “sex talk.”

Thank you to everyone including readers, contributors, and those working “behind the scenes”; you all have helped to make Page2`s launch year a resounding success!

Technology, entertainment, design: TED.com (Image source: Thinkstock)

As anesthesiologists, we are fascinated with oxygen, carbon dioxide, and respiration (or at least we should be!).

One of the earliest lessons that I teach new residents is the relationship of end-tidal CO₂ and respiration. I ask the following question, “If your oxygen saturation is 100% and you hold your breath, what would your oxygen saturation be when you have to breathe?”

Further, when teaching intubation, one is struck by how long it takes for oxygen saturation to begin declining in a pre-oxygenated, healthy adult who has been given neuromuscular blockers under general anesthesia.

With that in mind, the fact that magician David Blaine was able to hold his breath (without any rebreather or carbon dioxode absorber) for 17 minutes is truly mind-boggling! Even more fascinating, however, is hearing him speak about how he performed this feat and his journey to reach that record. I suggest that you go to TED.com and watch for yourself.

TED.com is a fascinating website. I have realized that I belong to an older generation. YouTube clearly has entertaining videos, but such videos are buried among millions of others that are simply a waste of time at best and a miasma of detritus at worst. TED.com, on the other hand, gives experts in a field 12 to 18 minutes to present an idea or concept for your consideration. And, to sweeten the deal, all videos are free.

I first heard of TED conferences on the national news when Bill Gates and others took the stage to share their thoughts. However, it was only recently that I discovered the treasure trove that is the website. Now, when I find that I need a short break, I go surfing not on the Internet at large but on the TED.com website.

So, here is my challenge: Go and listen to Dave Blaine talk about holding his breath for 17 minutes. Then, search for a topic. For my children, I chose the keyword “magic” and found some great video (check out brain magic or mathemagic).

When you`re finished, please come back and tell me what you think (leave a comment)!

Rats were treated with morphine, imatinib, or both drugs intrathecally and then the authors examined the substantia gelatinosa for immunoprecipitation and immunoblotting. PDGFR-β phosphorylation was increased with morphine and the effect was blocked by imatinib. Next, for 7 days they administered morphine intrathecally and then administered imatinib on days 1, 3, or 5. Imatinib co-administration did not change the morphine`s analgesic potency. When administered on day 1, morphine tolerance was eliminated. Administration of imatinib on days 3 or 5 reversed tolerance within 2 days. Tolerance was, however, temporary. A similar effect was observed when imatinib treatment was started soon after continuous high-dose morphine. The authors also demonstrated that imatinib did not have a latent analgesic effect and that it did not inhibit clonidine analgesic tolerance.

When the authors developed a fusion construct of platelet-derived growth factor receptor-β (PDGFR-β) and an antibody to the Fc portion of PDGFR-β, PDGFR-β-Fc completely reversed tolerance. Analgesia was not affected. PDGF subunit B homodimer (PDGF-BB) administration alone caused morphine tolerance.

PDGFR-β signaling in rats thus has a role in the elimination of analgesia tolerance to morphine without altering its acute analgesic effects. If the same findings are seen in humans, those suffering from constant, intractable pain might be able to be effectively treated chronically with morphine without developing tolerance to it.

Association between Anesthesiologist Age and Litigation and the editorial, More than Just Taking the Keys Away

Practice Advisory for Preanesthesia Evaluation: An Updated Report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation

Practice Guidelines for Central Venous Access: A Report by the American Society of Anesthesiologists Task Force on Central Venous Access

Case Scenario: Postoperative Liver Failure after Liver Resection in a Cirrhotic Patient

Influence of Supervision Ratios by Anesthesiologists on First-case Starts and Critical Portions of Anesthetics

In an in vitro model, Lipofundin extracts local anesthetics better than Intralipid. (Image source: Thinkstock)

A little more than 15 years ago, a report in this journal showed that in rats, Intralipid® increased the dose required to produce asystole. Eight years later, this journal published one of two examples of successful resuscitation utilizing Intralipid® in patients. Is extraction better using long-chain (Intralipid®) or mixed medium- and long-chain (Lipofundin®) triglyceride emulsion? In the article entitled “A Mixed (Long- and Medium-chain) Triglyceride Lipid Emulsion Extracts Local Anesthetic from Human Serum In Vitro More Effectively than a Long-chain Emulsion” published in the February issue of Anesthesiology, Dr. Deborah French, Assistant Professor, Department of Laboratory Medicine, University of California-San Francisco, and coauthors attempted to answer that very question.

The authors used human drug-free serum and added bupivacaine, ropivacaine, or mepivacaine each at a concentration of 10 µg/ml, or bupivacaine 100 µg/ml at pH 7.4, and, in another experiment, bupivacaine 10 µg at pH 6.9. 20% Intralipid®, which has long-chain triglycerides, or 20% Lipofundin®, which contains a 50-50% mixture of medium- and long-chain triglycerides, was then added at 1, 2, or 4% of total volume. The mean decrease in serum drug concentration was then calculated.

The authors` in vitro model showed overall that Lipofundin® was significantly better than Intralipid® in extracting the drugs from serum. The relative degree of extraction was bupivacaine > ropivacaine > mepivacaine. This order is consistent with the relative partition constant of each drug. As higher concentrations of either Intralipid® or Lipofundin® were used, the percent decrease of bupivacaine increased and a greater effect was seen with Lipofundin® at each % of lipid. A larger percent decrease in serum bupivacaine was observed after 100 µg/ml bupivacaine compared to 10 µg/ml for both Intralipid® and Lipofundin®, and Lipofundi®n extracted more bupivacaine than Intralipid® at each concentration of either lipid. The effect of pH on sequestering bupivacaine was not significant.

Whether the same results would be seen in in vivo studies remains to be seen. Also, Lipofundin® is currently commercially unavailable in the United States. Indeed, though the study was performed in the United States, the Lipofundin emulsion that was used was a gift from the manufacturer B. Braun Melsungen AG (Melsungen, Germany).

For February of 2012, one “Anesthesiology Reflection” features “Analgine by H. K. Mulford of Philadelphia.” Such a delicate glass cylinder (for housing tablets) poses a challenge for any courier seeking to protect and hand-carry it through airport security and across borders. My favorite strategy to accomplish this is one that I stumbled onto over 20 years ago as a last-minute courier for chloroform drop bottles.

Back then, one my earliest “museum acquisition safaris” took me to the Pacific Northwest. My mission: to meet a potential Canadian donor who lived in the city of Victoria on Vancouver Island. With my older son, Colin Davy Bause, in tow, I flew to Seattle. After shuttling to Seattle Harbor, we reached Victoria Harbor by knifing through impressive waves aboard a hydrofoil ferry at its “normal foilborne speed” of 37 knots (42 miles per hour). Colin seemed a little “green around the gills,” but otherwise neither of us actually succumbed to seasickness during that rough leg of the trip.

We were warmly welcomed to Victoria by a Canadian pioneer of ambulatory anesthesia, Dr. Eric Webb. He clearly understood that my primary interest was in his American Meter nitrous oxide apparatus. However, I did mention that our mutual friend, Wood Library-Museum Trustee Rod Calverley, M.D., considered “the Webb Chloroform Collection [to be] one of the world`s finest.”

To my amazement, Dr. Webb offered to donate his entire bottle collection to the Wood Library-Museum! Now I was in a bind. I was on an island off Canada`s Pacific coast with a fabulous collection of breakable items that I had to hand-carry back to the Wood Library-Museum. My simple solution? I purchased a box of disposable baby diapers, or “nappies,” from a corner store. Often described by the diplomatic Rod Calverley as a raconteur with an “earthy sense of humor,” Dr. Webb seemed almost disappointed when I assured him that, before touching his bottles, the diapers had never been soiled.

Disposable diapers can be a museum courier`s best friend. Besides keeping small, fragile items dry and softly padded, these Pampers (this particular brand) featured reusable tape on two sides for securing…and releasing…and re-securing items in the diaper packaging. (This is particularly helpful at border crossings where authorities enjoy unwrapping hollow, bomb-shaped objects that they spy on X-ray screenings.)

Dr. Webb chuckled after I quipped that I had enjoyed “pampering his breakables.” Sadly, he passed away before my next visit to Victoria. I am confident, however, that he died a happy man— secure in the knowledge that the “Eric Webb Collection” had been safely “pampered” to survive both the hydrofoil and the air legs of the journey back to Chicagoland`s Wood Library-Museum of Anesthesiology.

George S Bause, MD, MPH, is Clinical Associate Professor of Anesthesiology and Perioperative Medicine and of Oral and Maxillofacial Surgery, Schools of Medicine and of Dental Medicine, Case Western Reserve University. Since 1987, Dr. Bause has served as the curator at the Wood Library-Museum of Anesthesiology, Park Ridge, Illinois.

The second Versailles International Neurointensive Care Symposium is on June 21 and 22, 2012.

The second Versailles International Neurointensive Care Symposium will take place on June 21 and 22, 2012, in Versailles, France, and will bring together world-renowned experts in basic and translational neuroscience to discuss research related to the theme of “Brain Injury, Brain Repair.” The main objective is to highlight important scientific developments on biological mechanisms, diagnostic approaches, and therapeutic or rehabilitation trials in acute brain injury. This conference is jointly organized by the Société Française d`Anesthésie-Réanimation (SFAR) and the Société de Réanimation de Langue Française (SRLF) with the support of the Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) and the Johns Hopkins University (Baltimore, USA), as well as several other prestigious institutions and societies. All relevant information regarding the conference is available at http://www.vincs.fr.

Page2Anesthesiology will be there.  We hope to see you there as well!

The incidence of permanent complications after thyroid surgery was not simply positively related to surgeons` length of practice. (Image source: Thinkstock)

Operating room anesthesiologists observe the quality of a surgeon`s performance. Which factors determine what we consider quality? Certainly the more times a surgeon has performed an operation, the more the surgeon`s expertise should theoretically improve. Few studies have examined how a surgeon`s performance is related to objective outcome measures, however. In the article “Influence of experience on performance of individual surgeons in thyroid surgery: prospective cross sectional multicentre study,” which was published online in January 2012 and appeared in the February 2012 print issue of BMJ, Dr. Antoine Duclos (Assistant Professor of Public Health, Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, Université de Lyon, Equipe d`Accueil Mixte and Center for Surgery and Public Health, Brigham and Women`s Hospital, Harvard Medical School, Boston, MA) and coauthors determined the relationship between surgeon experience and performance as measured by postoperative complications.

The study was prospective and took place between 1 April 2008 and 31 December 2009. Five academic medical centers were chosen where at least 500 thyroidectomies were performed yearly. Permanent recurrent laryngeal nerve palsy and hypoparathyroidism were the major outcomes studied, initially determined within 48 hours postoperatively and then assessed 6 months later to diagnose permanent complications.

During the study period, 3574 procedures were completed. Length of experience and number of thyroidectomies performed by surgeons were correlated with the surgeons` age. Univariate analysis showed that permanent hypoparathyroidism was more common for surgeons who spent either the shortest or longest time practicing after graduation. Multivariate analysis showed that the only factor associated with an increased chance of both recurrent laryngeal nerve palsy and hypoparathyroidism was more than 19 years of experience. Nerve palsy alone was more commonly associated with female gender, whereas hypothyroidism was more commonly associated with younger patients and inexperienced surgeons.

Whether the same is true for other operations is not known. This study also did not have a large number of surgeons whose experience was intermediate. Might the same also be found for certain procedures performed by anesthesiologists? Might other unknown factors substitute for surgeon age?

Figure 1: Members of the

The research of our team (Figure 1) focuses on structure-function relationships involved in the activation of a specific subclass of ion channels that are expressed in nociceptors, that belong to the transient receptor potential (TRP) superfamily, and exhibit restricted specificity for temperature stimuli. The ultimate goal of our research is to provide new insight into the basic biology of the peripheral nervous system and to better understand the molecular mechanisms of the processes through which various nociceptive or innocuous stimuli activate and modulate these unique channels.

The experiments for our study, “Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel” published online on February 6, 2012, in Anesthesiology, were done with whole-cell patch-clamp electrophysiology in combination with a fast multi-fluorescence time-lapse imaging system to monitor camphor-induced membrane current responses and simultaneously measure the fluorescence resonance energy transfer between two spectrally distinct fluorescent proteins as a sensitive readout of changes in the plasma membrane phospholipid PIP₂ (Figure 2). This study was only made possible by collaboration among our “TRP team,” including RNDr. Jan Krusek, Ph.D., who contributed expertise to the microfluorescence techniques, and with electro-engineer Ivan Dittert, Dipl. Ing., Ph.D. (Figure 3), who constructed a superfusion system allowing fast exchange and precise temperature control of solutions used for thermal and chemical stimulation of the TRP channels (Figures 2 and 4).

The research was performed by our “TRP team” at the Department of Cellular Neurophysiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague. You may visit our department by going to http://www2.biomed.cas.cz/d331/.

Figure 2: Lenka Marsakova, Ph.D. student, monitors the camphor-induced activity from TRPV1-transfected HEK293T cells using the combination of patch-clamp and microfluorimetry.

Figure 3: Ivan Dittert, Dipl. Ing., Ph.D., electrical engineer.

Figure 4: Tissue culture dish with HEK293T cells under the inverted microscope, the outlet of the drug application system (left), patch clamp pipette (right), and illumination system used for simultaneous current and microfluorimetric measurements.

The American Society of Anesthesiologists has published a revised practice advisory for perioperative visual loss associated with spine surgery. (Image source: Thinkstock)

In this month`s issue of Anesthesiology, “Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Visual Loss” was published, a revision of the original Practice Advisory that was published in 2006. Though the actual recommendations did not change, the evidence for them did.

Advisory in summary

Preoperative evaluation

There is no agreement as to whether or not preoperative evaluation is useful in identifying patients who are at risk for perioperative visual loss, in part because there aren`t specific and identifiable preoperative patient characteristics that increase the likelihood of visual loss. The risk of visual loss is increased in patients with vascular risk factors (e.g., hypertension, diabetes, peripheral vascular disease, coronary artery disease), preoperative anemia, prolonged procedures (duration > 6.5 h), large blood loss (averaging 45% of estimated blood volume), and prolonged procedures combined with substantial blood loss.

Intraoperative management

Blood pressure management should be continuous in high-risk patients. The decision to use deliberative hypotension during spine surgery ought to be individualized. If there is a large amount of blood loss, crystalloid and colloid use should be used, and in high-risk patients, central venous pressure monitoring should be considered. There is no evidence to show at what level blood transfusion is appropriate. The use of α-adrenergic agonists should be individualized. Patients should obviously be positioned so that there is no pressure on the eye. For the high-risk patient, the head should be level with or higher than the heart and the head should be neutral (e.g., the neck should not be significantly flexed, extended, or rotated). In addition, consideration should be given to staging of a spinal procedure.

Postoperative care

When a patient is awake and vision loss is suspected, an ophthalmologist should be urgently consulted. In this situation, optimal hemoglobin, hemodynamic and arterial oxygenation values should be obtained. Magnetic resonance imaging should be considered as a means to rule out possible other causes of visual loss. Other measures such as the use of antiplatelet agents, steroids, or intraocular pressure-lowering agents do not have a role.

The reader is encouraged to read “Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Visual Loss” in its entirety. The basis for these revised guidelines is provided in much greater detail.

The Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality was used to study peripartum subarachnoid hemorrhage. (Image source: Thinkstock)

One of the challenges resulting from improved safety and outcomes is that it becomes harder to study the poor outcomes and complications. Most institutions and practitioners still rely on the “N=1″ method for quality improvement following rare events. In other words, when a bad outcome occurs, the case is reviewed and improvements are based on those rare events.

Obviously, studying a larger population may result in identifying warning signs or risk factors for a rare event. At this time, we must rely on billing, coding, and administrative databases to do these studies as seen in “Peripartum Subarachnoid Hemorrhage: Nationwide Data and Institutional Experience,” an article written by Dr. Brian Bateman (Assistant Professor, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts) and colleagues and published in the February edition of Anesthesiology.

Last month, Page2Anesthesiology used the N=1 analogy to discuss preoperative medical consultation use based on a population-based administrative database in Ontario, Canada. In the current article, by using data from the Nationwide Inpatient Sample, an administrative and coding database that is part of the Healthcare Cost and Utilization Project and is maintained by the Agency for Healthcare Research and Quality, Dr. Bateman and coauthors were able to identify 639 cases of peripartum SAH, about 5.8 cases per 100,000 deliveries. The authors were able to identify risk factors associated with hemorrhage and also discovered less mortality in peripartum versus non-peripartum SAH, since peripartum SAH was not usually the result of a ruptured aneurysm.

As noted in Bateman et al.`s discussion and in the study`s accompanying editorial entitled “A Terrible Headache in Obstetric Anesthesia” by Drs. Pamela Flood, Department of Anesthesia, University of California, San Francisco, San Francisco, California, and Guohua Li, Department of Anesthesiology, Columbia University, New York, New York, this type of database has many limitations. However, for now it helps to identify potential foci of future research.

Hopefully, with the incorporation of more electronic systems and quality reporting systems, future generations will actually use clinically focused databases to examine these rare cases. Until then, we must use the billing, coding, and administrative databases while understanding the limitations thereof.

This is definitely better than simply using the N=1 model of quality improvement, though!

I am happy to both blog and brag about the World Federation of Societies of Anaesthesiologists^® (WFSA), of which I have been president for the past four years. We are an umbrella society composed of various individual societies and, as members of the ASA, you all belong. We have a website, www.anaesthesiologists.org, where you can read in detail about our activities. In short, we focus on bringing improved anesthesia education to colleagues in economically disadvantaged parts of the world. We do this in a variety of ways, including fellowship training, publications, workshops, seminars and so on. We collaborate widely with anesthesia and other organizations such as the ASA, the WHO and IASP, to mention just a few. We have a global view regarding anesthesia issues, a fact which is quite useful when working with national societies.

The World Congress of Anaesthesiologists^® is our quadrennial meeting. It will be held in Buenos Aires in March 2012. It is one of the few meetings where you can hear cutting-edge science on the one hand and how to give anesthetics with almost nothing and in the most challenging of circumstances on the other. It is humbling to learn how well many of our colleagues do when faced with immense challenges. The Congress presents a wonderful opportunity to meet colleagues from all over the world and perhaps to begin to get involved in anesthesia activities in a global context.

I’m sure many of you have heard of our Lifebox project, which was featured at the ASA meeting in October. If not, please go to www.lifebox.org to read all about it. There will be more information about Lifebox featured in Buenos Aires. “Saving Lives through Safer Surgery” is the current theme and our goal is to “Make It Zero,” “it” being the mortality rate from anesthesia. In some parts of the world that mortality rate can be as high as 1:150. By providing oximeters and the education that goes with them, including the use of the Surgical Safety Checklist, we hope to reduce the mortality rate significantly.

If all of these reasons are not enough to entice you to join us in Buenos Aires, just think about the great food and wine, the massive Andes, the wide Pampas and the spectacular Iguazú Falls. Argentina awaits you and so do your colleagues from all over the world!

I`ll see you there!

Dr. Angela Enright is president of the World Federation of Societies of Anaesthesiologists (WFSA)

Processed electroencephalogram may be used, albeit crudely, to guide anesthetic depth. (Image source Thinkstock)

One of the major debates in healthcare today that will continue into the future is what constitutes sedation, moderate and deep, versus general anesthesia. The purpose of defining these clinical states is to determine who can more safely provide the level of care. The risks of care increase as the sedation moves from moderate to deep to general anesthesia.

Currently, the objective measurements are to use scoring scales based on observation (e.g., University of Michigan Sedation Scale [UMSS]) or by definitions based on responsiveness to voice or pain which are not precise (e.g., definitions used by the Centers for Medicare & Medicaid Services [CMS] and the ASA).

The lack of a monitor leads different practitioners to view the same care as being at different points on the continuum. In other words, a gastrointestinal specialist may view the care as “deep sedation” while an anesthesiologist views the same care as general anesthesia.

In this month`s issue of Anesthesiology, there are two studies and one editorial examining spectral entropy monitors. If you are unfamiliar with this type of monitoring (as opposed to BIS or EEG monitoring), I strongly urge you to read Dr. Gregory Crosby and Dr. Deborah J. Culley`s editorial entitled “Processed Electroencephalogram and Depth of Anesthesia: Window to Nowhere or into the Brain?” The authors are both from Harvard Medical School, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital. They do an excellent job of explaining the issues of depth of anesthesia monitoring, how spectral entropy differs from BIS, the limitations of our current knowledge, and the implications of the study by Dr. Ngai Liu, Associate Professor of Anesthesia, Service d’Anesthésie, Hôpital Foch, Suresnes, France, and colleagues (“Feasibility of Closed-loop Titration of Propofol and Remifentanil Guided by the Spectral M-Entropy Monitor“).

The authors examined whether an algorithm could be used to titrate TIVA (propofol and remifentanil) to provide general anesthesia using a closed-loop M-Entropy controller. As the editorial points out, this was a small study done with only two specific anesthetic agents in adults. The authors found that the human did as well as the computer, but the other way to look at the results is that the computer did as well as the human!

What I found especially intriguing was the evidence that spectral entropy might be used to differentiate depth of consciousness along the sedation-anesthesia continuum.

The second study in this month`s edition of Anesthesiology addressing this issue was performed by Dr. Jaakko G.M. Klockars, Staff Anesthesiologist, Department of Anesthesiology and Intensive Care Medicine, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland, and colleagues. In “Spectral Entropy as a Measure of Hypnosis and Hypnotic Drug Effect of Total Intravenous Anesthesia in Children During Slow Induction and Maintenance,” Klockars et al. examined the use of spectral entropy with the same TIVA agents (propofol and remifentanil) in children. The authors performed a slow induction and sought to correlate spectral entropy scores with the movement from sedation to anesthesia. Ultimately they found a good age and agent-specific correlation. Although this was a small study, the results are promising.

It is important to note the large role age played with regard to where a patient was in the sedation-anesthesia continuum even between patients with the same plasma concentration! Clearly, experience and training are critical in developing safe plans of care for the many varied patients who need it.

However, perhaps we will soon have one more tool to help us optimize our care: a spectral entropy monitor.

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In a rat model, regional and whole body hypothermia was effective in reducing measures of neuropathic pain at an early stage following nerve injury.

Millions are afflicted by neuropathic pain and this pain can last for years after injury. There is some evidence to show that hypothermia might be effective in treating certain types of neuropathic pain. In the study “Effects of Regional and Whole-body Hypothermic Treatment before and after Median Nerve Injury on Neuropathic Pain and Glial Activation in Rat Cuneate Nucleus” published in the February 2012 issue of Anesthesiology, Dr. Yi-Ju Tsai, Associate Professor, School of Medicine, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan, and colleagues used an experimental model of chronic constriction injury on the median nerve that they developed in order to determine whether hypothermia might relieve neuropathic pain and attenuate different changes in the cuneate nucleus.

The animals were anesthetized and the median nerve was ligated. For one group, during general anesthesia a temperature therapy pad was placed around the same forelimb, and for 4 h the animals were exposed to temperatures that varied from 37ºC to 28ºC. For another group of animals, a temperature therapy pad was wrapped around the entire body, and during general anesthesia they were exposed to the same temperatures as the first group. Temperature exposure was timed to occur either before the injury or 5 h, 1 day, 3 days, or 5 days after injury. Seven days after median nerve injury, different measures were obtained. Behavioral testing included measuring mechanical allodynia and thermal hyperalgesia. Electrophysiologic measurements of the median nerve were made. Then, different qualitative and quantitative measures of glial activation and proinflammatory cytokines were obtained.

Regional hypothermia administered either before injury or 5 h after injury decreased measures of neuropathic pain and the glial activation response in the ipsilateral cuneate nucleus. The use of whole-body hypothermia expanded the time of effectiveness based on measures of neuropathic and glial activation up to 3 days after injury. On day 5, only deep (28º) hypothermia was effective. Proinflammatory cytokine levels were decreased up to 5 days after injury in the animals exposed to whole-body hypothermia.

Can we expect the same results in humans? In the accompanying editorial entitled “Another Intriguing Application of Hypothermia: And Some Words of Caution,” Dr. Michael M. Todd, Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, Iowa, notes,

“Unfortunately, despite literally thousands of laboratory experiments and an equal number of articles extolling the benefits of cooling and studying ways to cool people or measuring associated clinical changes (without ever bothering to ask whether it is beneficial), the track record for the human application of cooling is limited and frankly unimpressive. Perhaps the only unequivocal value of cooling is for controlled circulatory arrest during cardiac surgery, and that requires deep hypothermia.”

The authors` work is fascinating, though more study is needed to determine the possible applicability of these results for humans in a clinical setting.

The American Society of Anesthesiologists has published revised practice guidelines for perioperative acute pain management.

In this month`s issue of Anesthesiology, a revised version of “Practice Guidelines for Acute Pain Management in the Perioperative Setting: An Updated Report by the American Society of Anesthesiologists Task Force on Acute Pain Management,” developed by the ASA, was published. Though the actual recommendations did not change, the evidence for the recommendations did.

Guidelines in summary

1. Concerning perioperative pain management, institutions should provide education and training for healthcare providers, monitor pain management outcomes, document monitoring used for pain management, have anesthesiologists available at all hours, and have a dedicated pain management service. Training for healthcare providers is associated with better pain control, greater patient satisfaction, and less nausea and vomiting. Standardized and validated tools should be used to measure both the positive and negative aspects of pain management therapy.
2. Pain management should be planned preoperatively. Patient medications should be reviewed in part since a withdrawal syndrome can result if certain medications are stopped. Treatment to reduce pain and anxiety preoperatively should be considered. Postoperative multimodal pain management can start with the administration of drugs preoperatively. In addition, patients and their families can receive education preoperatively, including behavioral therapy on managing postoperative pain. Patient education can include an explanation of how to best use patient-controlled analgesia (PCA), including, if used, patient-controlled epidural analgesia.
3. Different techniques that can be used to manage postoperative pain include the use of neuraxial opioid analgesics, PCA, and peripheral regional analgesic techniques. Since there are risks and benefits associated with each of these techniques, the optimal technique should be considered on an individual basis for patients.
4. Pain management can be more effective if the combined use of different drugs that act at different sites or by different mechanisms, administered either by the same or different routes, should be considered.
5. Pain management of children, older patients, and critically ill or cognitively impaired patients deserves special attention. For these different groups, pain is frequently undertreated and these individuals may have difficulty communicating to caregivers that they are in pain. Children can have emotional components to their pain and these should be considered. Certain aspects of pain management are no different for children or adults, though caudal analgesia is more commonly used for children. Older and critically ill patients may need lower drug doses for pain management than younger patients.

The reader is encouraged to read “Practice Guidelines for Acute Pain Management in the Perioperative Setting: An Updated Report by the American Society of Anesthesiologists Task Force on Acute Pain Management” in its entirety. The basis for these different guidelines is provided in much greater detail.

Reflection in practice and on practice is essential for self-advancement and mastery of professional skills

During medical training, students need to monitor and assess their own performance if they are to master their professional development. This is a skill they must learn in medical school and residency because it has implications in terms of ongoing maintenance of competency. Reflective practice means self-assessment and self-directed learning. Reflection causes the student to examine an experience or action and subsequently integrate the newly acquired knowledge, skills or values into a new context. In his book The Reflective Practitioner: How Professionals Think In Action, Donald Schön outlines the need for professionals to “reflect in action.” He uses the term “technical rationality” to describe the solid professional knowledge base that each profession teaches, expecting the student to draw on it to solve well-constructed problems.

However, problems are not always discrete, solvable entities and factual knowledge might not cover all situations, especially complex ones. Professionals are required to be able to identify a situation that is unique, reflect upon it, problem solve, and create new solutions. This should be done continuously as part of professional development. Graduating physicians are well aware that their knowledge cannot remain static and that their ability to practice according to current standards will require constant update. There are many years of practice ahead where the student is completely responsible for the upkeep of competency. With our focus on short-term goals such as licensing examinations, we might not be steering our medical students and residents to the tools they need for lifelong learning.

A recent article in Academic Medicine reviews the attitudes of family medicine residents towards lifelong learning. It is a qualitative study of interviews on the topic. While all of the residents valued the concept of self-directed learning, they felt they lacked the skills to do it and did not think that they were taught how to engage in this type of learning in their previous training. They found self-directed learning to be especially difficult in the clinical setting, though patient care was a powerful stimulus to utilize it. Although they spent a good deal of time in the clinical setting, a lot of their work was perceived as a service obligation. Duty hours decreased the number of hours each individual resident worked but placed an increased burden on those actually at work in the hospital. They felt they had little time for the “reflection in action” that Schön felt necessary for professional development. In the clinical setting, guidance from faculty regarding how to develop skills in self-directed learning would be welcome.

There are many barriers to developing reflective practice. The work environment in many medical settings is not conducive to quiet moments of reflection. This is not a classroom with the opportunity to stop the action. Reflection also implies change. What often happens to novice students is that they find a system that works well enough most of the time. It takes encouragement to take the risk to try another approach, especially when the first tries don`t go as smoothly as their previous method. The residents who do best are those who reflect and change because they practice the concept of self-directed learning while still having the safety net of supervision. Having enough time to practice and perfect skills over time is also a benefit and might be more important than innate talent. Students in medical education at every level need directed attention to self-assessment and reflection. Medical educators should be skilled at encouraging and aiding the student as the student develops these skills while still under supervision. Reflection in practice and on practice is essential for self-advancement and mastery of professional skills.

A single dose of ketamine can relieve depression for at least 72 h. (Image source: Thinkstock)

The discussion on this Tuesday`s Talk of the Nation concerned the use of ketamine as an antidepressant. Page2Anesthesiology has had several posts on ketamine. In December we posted a summary of ketamine`s effect on ventilation and airway muscles; then, last August we summarized a study that showed how ketamine relieves depression-like behaviors induced by neuropathic pain in rats. In the February 2012 issue of Clinical Pharmacology and Therapeutics, JW Murrough, Mood and Anxiety Disorders Program, Department of Psychiatry, Department of Neuroscience and Fridman Brain Institute, Mount Sinai School of Medicine, has summarized how low-dose ketamine acts to treat depression in the article “Ketamine as a novel antidepressant: from synapse to behavior.”

In many studies, ketamine has been shown to relieve depression after a single low dose, e.g., 0.5 mg/kg over 40 min. This effect peaks within 72 h. Ketamine may also reduce acute suicidal ideation unlike conventional antidepressant agents that can worsen suicidal ideation over the short term. Ketamine is an NMDAR antagonist and more generally can modulate the glutamate system. Other drugs that target the same areas might also be shown to treat depression.

The studies that are described use ketamine doses around 0.5 mg/kg, much lower than what is used for general anesthesia. This dose used is similar to the dose used in a study that appeared in the September 2010 issue of Anesthesiology (before Page2Anesthesiology started), where 0.5 mg/kg intravenous ketamine on induction of anesthesia and then a continuous infusion at 10 μg kg^-1min^-1 reduced opiate consumption in the 48-h postoperative period and had an effect up to 6 weeks postoperatively in patients with chronic pain who were opiate dependent. Whether the same is true for doses we use for anesthesia is unclear and deserves more study.

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Measures to help prevent laryngospasm are illustrated (Image source: Anesthesiology).

Laryngospasm is the bane of pediatric anesthesiologists. In the case scenario series, Dr. G. A. Orliaguet, Professor of Anesthesiology and Critical Care Medicine, Vice Chair of the Department of Anesthesiology and Critical Care, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Faculté de Médecine, Paris, France, and coauthors describe such a case and then review epidemiology, morbidity, pathophysiology, and anesthetic management in their article “Case Scenario: Perianesthetic Management of Laryngospasm in Children.”

The authors have also provided a simulation video that shows management of such a case.

Clinical pearls

Who is more likely to develop laryngospasm?

Children (about two times more frequently than are adults), those with URI in the past 2 weeks, a history of wheezing at exercise or more than three times in the last year, nocturnal cough, eczema present or in the last year, and those with a family history of asthma, atopy, or smoking are more likely develop laryngospasm. The highest incidence is seen in preschool children. Patients undergoing procedures that involve the pharynx and larynx and urgent procedures are also more likely to develop laryngospasm. Inadequate depth of anesthesia, either at the start or end of a procedure, is also associated with this problem.

What is the nerve pathway that`s associated with laryngospasm?

Sensory pathways include the trigeminal nerve for the nasopharynx, the glossopharyngeal nerve for the oropharynx and hypopharynx, and the superior and recurrent laryngeal nerves and both branches of the vagus nerve for the larynx and trachea. The laryngeal closure reflex is affected by the superior laryngeal nerve. The laryngeal closure reflex involves the laryngeal intrinsic muscles (lateral cricoarytenoid, thyroarytenoid, and cricothyroid muscles) and causes vocal folds adduction. Both skeletal and smooth muscles are involved in the reflex.

How is laryngospasm diagnosed?

With complete laryngospasm there is neither air movement nor breath sounds; the reservoir bag does not move and the capnogram is flat. With partial laryngospasm there are varying degrees of airway obstruction and signs include suprasternal retraction, supraclavicular retractions, tracheal tug, paradoxical chest, and abdominal movements.

How should laryngospasm be treated?

Manipulation of the airway should first be tried. Such manipulations include chin lift, jaw thrust, continuous positive airway pressure, positive pressure ventilation with a facemask, and use of 100% oxygen. Some have also tried pressure in the “laryngospasm notch” and digital elevation of the tongue.

Propofol can also be tried, though of course intravenous access is needed. Doses from 0.25 to 0.8 mg/kg have been used in various studies. Propofol will probably not work, however, if the patient has complete laryngospasm. Succinylcholine is the most common and most effective muscle relaxant that has been used. It can be administered both through a vein (no less than 0.5 mg/kg) and in the muscle (1.5 to 4 mg/kg) and even intraosseous injection has been tried. Onset is most rapid when the drug is injected intravenously. In the article, the use of other medications is described.

Can the incidence of laryngospasm be reduced?

Whether simulation can help decrease the incidence of laryngospasm is unclear. See the simulation video provided by the authors.

The American Society of Anesthesiologists offers CME credit based on this post and it’s accompanying article.

Blood pressure management during general anesthesia for endovascular arterial revascularization of occluded large vessels is important. (Image source: Anesthesiology)

Some have questioned the safety of using general anesthesia for patients undergoing endovascular arterial revascularization of occluded large vessels who have suffered an acute stroke. Though sedation can work for most, patients who don`t hold still and/or who have airway or other issues need general anesthesia in order for the procedure to be successful. Is outcome the same regardless of whether patients receive sedation or general anesthesia?

In the article “Anesthetic Management and Outcome in Patients during Endovascular Therapy for Acute Stroke” published in the February 2012 issue of Anesthesiology, Dr. M.J. Davis, Assistant Professor, Department of Anesthesia, Foothills Medical Center, Calgary, Alberta, Canada, and coauthors retrospectively reviewed the experience of 96 such patients at their institution between January 2003 and September 2009. For each patient, the decision to use anesthesia was determined by the stroke neurologist and neuroradiologist, and choice of anesthesia, i.e., conscious sedation (administered by the neurologist), deep sedation (including intubation of the trachea), or general anesthesia, was made by those individuals in concert with the anesthesiologist. When clinical outcome at 3 months was analyzed, 60% of patients who received local anesthesia had good outcome compared to 15% of those who received general anesthesia. Mortality rates were also higher for those who received general anesthesia. The use of local anesthesia and lowest blood pressure equal to 140 were predictors of good outcome when adjusted for stroke severity. Blood pressure was lower in those individuals who received general anesthesia. However, it is worth noting that those who received general anesthesia had more severe strokes and the proportion of patients who had peri-procedural critical events was greater in those who received general anesthesia.

The study`s sample size was both small and retrospective and data came from a single institution. Yet, as noted in the accompanying editorial entitled “What Matters during Endovascular Therapy for Acute Stroke: Anesthesia Technique or Blood Pressure Management?” written by Dr. E.J. Heyer, Departments of Anesthesiology and Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, and co-authors,

“This study underlines the importance of blood pressure management during anesthetic management in patients experiencing acute stroke. It is the first study to find that systolic blood pressures less than 140 mmHg significantly contributed to poor outcome. In our opinion, this is the most important result of this study.”

As the authors later state,

“Although the study stated that the goals of blood pressure management are to maintain blood pressures within 10% [of] the patient’s baseline values, it is highly probable that this goal was not met during the induction of general anesthesia. These results underline the importance of avoiding hypotension in these patients.”

The meeting kicked off on Wednesday last week with two workshops. The “Anesthesia Essentials Course 101″ is a one-of-a-kind STA program that explains to industry representatives how anesthesiologists work in the real world. During this course, engineers, sales representatives, and senior management can meet with physicians to hear how their equipment is used in patient care, get opinions about new devices, or ask about improvements to existing products. The second workshop covered the essentials of anesthesia information management systems.

The meeting officially began on Thursday, and Richard Dutton, MD, gave the keynote address. He discussed the Anesthesia Quality Institute, explaining why it was created and how it works. This is a technology meeting, so of course there was a good discussion of how the database was created and how it works. Next up was an interesting session on closed-loop anesthesia. The first speaker discussed how to control depth of anesthesia using EEG and other parameters. The next two sessions discussed how automated systems can control a ventilator using parameters such as PaO₂ and PaCO₂ and how intelligent systems can control blood pressure. Although a human anesthesiologist still needs to supervise these systems, the possibility of allowing a computer to handle the minute-to-minute workload of managing vital signs and infusion rates is intriguing. Thursday`s session wrapped up with a FAER-sponsored session on translational research, bringing new products to market, and how to create a mutually productive relationship between industry and academia.

Stay tuned for a summary of Friday`s talks.

CABG surgery-related bleeding was no greater when cangrelor was used as bridging therapy before surgery. (Image source: Thinkstock)

A patient receives dual antiplatelet therapy to decrease the risk of atherothrombotic events. If such a patient should undergo a surgical procedure, the risk of bleeding is increased and platelet function needs to recover. Therapy discontinuation can increase ischemia risk, particularly for patients with drug-eluting stents, where discontinuation can lead to myocardial ischemia and death. Heparin and glycoprotein IIb/IIIa do not reduce stent thrombosis incidence and heparin and increase platelet reactivity. Cangrelor, a P2Y₁₂ inhibitor, limits platelet aggregate amplification and stabilization with quick onset and offset. As such, it can serve as a bridge for patients in whom antiplatelet therapy needs to be stopped. In the study “Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery” published in the January 18, 2012, issue of JAMA, Dr. Eric J. Topol (Scripps Translational Science Institute, La Jolla, California) and co-authors studied 210 patients from 34 global sites who were randomized to receive cangrelor or placebo as bridging therapy prior to coronary artery bypass graft surgery.

All patients received a thienopyridine before randomization and CABG surgery occurred between 48 hours and 7 days after randomization. Median time from thienopyridine discontinuation and study drug infusion was 29 hours. Median infusion time of cangrelor was 2.8 days. Median time from study drug discontinuation to surgical incision was 3 hours. There was no difference in CABG surgery-related bleeding between groups, though minor bleeding events, mostly ecchymosis at the venipuncture site, were greater in the cangrelor group. Ischemic and overall adverse events were low; there was no difference in adverse events between groups.

Whether this drug would be useful for other types of surgery is unclear at this time. This study was also not specifically powered to measure ischemia-related adverse events. The FDA has not yet approved this drug.

Anesthesiology`s February 2012 cover (Image source: Anesthesiology)

The February 2012 issue of Anesthesiology has posted. As Editor-in-Chief for the Journal, I am pleased to discuss some of the issue`s highlights for Page2Anesthesiology:

Concerning practice parameters from ASA: note the expanded format. The beginning of each article has an explanation of why the practice parameter is being produced and if a revision, how and why the revision differs from the previous version.

Practice Guidelines for Acute Pain Management in the Perioperative Setting: An Updated Report by the American Society of Anesthesiologists Task Force on Acute Pain Management

Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Blindness

Case Scenario: Perianesthetic Management of Laryngospasm in Children

SpHb value is limited for patients undergoing abdominal or pelvic surgery where anticipated blood loss is high and hemoglobin value is low.

For certain operations, particularly for abdominal or pelvic surgery, patients lose blood and then transfusion is administered. Both anemia and transfusion administration are associated with worse outcome. The Food and Drug Administration has approved a new device that can measure pulse hemoglobin, derived from pulse cooximetry, continuously. In their study entitled “Evaluation of Pulse Cooximetry in Patients Undergoing Abdominal or Pelvic Surgery,” Dr. Richard L. Applegate II, Professor, Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, and co-authors studied the effectiveness of this device in patients undergoing extensive resection of abdominal or pelvic cancers or open abdominal major vascular procedures. Stroke volume variation provided by a computerized arterial pulse waveform cardiac output device was used to guide intraoperative fluid administration. Transfusion was administered at the discretion of the attending anesthesiologist for the operation and provided during surgery to keep hemoglobin levels between 8 and 10 g/dl. A radial arterial catheter was inserted to monitor blood pressure and analyze arterial hemoglobin by use of a cooximeter.

Ninety-two patients were enrolled, although for one individual, the equipment malfunctioned. Average estimated blood loss percentage was 16%, and for 21 patients it was more than 20% of estimated blood volume. Three-hundred sixty time-matched SpHb and arterial hemoglobin measurements were analyzed and the average time interval between measurements was 48 min from start to first measurements and then 60 min for subsequent measurements. Mean difference between the two measures was 0.5 g/dl and larger differences were seen in patients with large blood loss or lower hemoglobin. SpHb was higher than arterial hemoglobin when hemoglobin was low: when hemoglobin was less than 9 g/dl, the difference in SpHb was 1.3 and the difference was larger when arterial hemoglobin was less than 8. Correlation between paired changes in arterial hemoglobin and SpHb was weak (R²=0.48).

The value of SpHb is limited for patients undergoing abdominal or pelvic surgery where anticipated blood loss is high and hemoglobin value is low. Perhaps future software revisions will show better performance.

Amniotic fluid embolism, though rare, can have catastrophic outcomes. (Image source: Anesthesiology)

Amniotic fluid embolism (AFE) is fortunately rare; however, it can have serious consequences for both mother and child. Dr. Laura S. Dean, Department of Anesthesiology, Section of Obstetric Anesthesia, Wake Forest School of Medicine, Forsyth Medical Center, and coauthors, in their article “Case Scenario: Amniotic Fluid Embolism,” published in the January 2012 issue of Anesthesiology, describe a 42-year-old patient who, after receiving a second epidural dose of 3% 2-chloroprocaine for intended vaginal delivery, had a grand mal seizure and then cardiovascular collapse. Advanced cardiac life support with chest compressions was provided, and a bedside cesarean section was performed. The patient was then brought to the operating room where resuscitation included treatment of uterine atony; administration of crystalloid, colloid, and blood products; and hysterectomy. After the procedure, the patient was moved to the ICU where her situation gradually improved. Ventilator support was discontinued after 48 hours and after 5 days the patient was discharged home without neurologic deficit.

Clinical pearls

What are the presenting signs and symptoms of AFE?

Amniotic fluid embolism can affect many organs. Presenting signs include sudden anxiety, dyspnea or agitation, and up to 50% of patients have seizures. Oxygen saturation and end-tidal carbon dioxide can suddenly decrease and then cardiovascular collapse follows. In the second phase, coagulopathy and hemorrhage can occur. DIC can develop, though this is not seen in all patients with AFE. In the third phase, tissue injury and organ failure occur, and clinical signs match those organs that are failing.

Amniotic fluid in the circulation can cause pulmonary hypertension with right heart strain or failure and then ischemic myocardial injury due to hypoxemia. Coagulopathy, if it occurs, is related to either a consumptive process or massive fibrinolysis. Encephalopathy is also felt to be secondary to hypoxemia. The majority of patients with AFE who survive have residual neurologic deficits.

What clinical factors are associated with AFE?

Multiple clinical factors and diagnoses are associated with AFE, but no clinical predictors have been identified.

What`s the pathogenesis of AFE?

There are two lines of thought with regard to this. In one, due to a tumultuous labor, abnormal placentation, surgical trauma, or any other breach between maternal blood and amniotic fluid, amniotic fluid is forced into the systemic circulation and leads to obstruction of the pulmonary circulation. Yet, no study has found amniotic debris either from radiologic study or autopsy. The second line of evidence is that because of amniotic fluid in the circulation, inflammatory mediators are made active that then cause a humoral or immunologic response. Amniotic fluid has vasoactive and procoagulant products that can trigger coagulation, and constriction of bronchioles and coronary vessels. Understanding the pathophysiology of AFE needs better development.

How is AFE diagnosed?

AFE diagnosis is one of exclusion. If there is not another medical explanation, AFE should be considered.

How should patients with suspected AFE be managed?

Patients should be managed with oxygenation, circulatory support and management of coagulopathy. If the fetus remains, then left uterine displacement is important, though the presence of the fetus can hamper cardiopulmonary resuscitation and immediate cesarean section should be considered. Transesophageal echocardiography can help in managing fluid replacement and vasopressor therapy. If there`s uterine hemorrhage, then hysterectomy may be necessary. The figure shown above is taken from the article and provides more detail for the management of AFE. For better resolution, consider accessing the original article.

Postoperative pain control needs to be better optimized. (Image source: Thinkstock)

A few months ago, the Texas Pain Society`s annual meeting was held from November 4–6, 2011, at the Lost Pines Hyatt in Bastrop, Texas. The whole day we listened to statements about how there has been an increase in the incidence of opioid-related adverse events and deaths secondary to prescribed opioids. I pondered and asked myself, “Why are we not addressing the root cause of this problem?” The first question we must ask is why there is such an explosion in the prescription of opioids. Haven`t we as physicians played a role in this emerging catastrophe? Should we not be the gatekeepers of these prescriptions?

Opioids are used during anesthesia. They are prescribed for postsurgical pain. Did we not expose these patients to opioids in the first place? Persistence of pain past three months or otherwise beyond the normal period of healing is defined as “chronic pain.” There are no finite criteria to define chronic pain. Once these patients are labeled as having chronic pain, they are referred to the pain clinic and continued on opioid therapy.

Pain research has provided evidence on how the use of “multimodal analgesia” can help prevent “acute pain” from becoming “chronic pain.” Despite the knowledge gleaned from this research, we are still solely using opioids to treat postsurgical pain. We must move into the 21st century. Anesthesiologists and surgeons need to develop multimodal analgesia plans, and together we need to educate nurses about postoperative pain control in surgical patients. In addition, discussion about postoperative analgesia must take place during the preoperative interview.

Multimodal analgesia should include the cocktail of medications that need to be administered preoperatively, before surgical trauma is inflicted, and should be continued postoperatively. These medications should treat the nociceptive, inflammatory and neuropathic pain. In addition, multimodal analgesia is similar to balanced anesthesia; the cocktail of medications consists of NSAIDs, neuropathic pain medications, local anesthetics and opioids. Opioids should occupy the last spot in the algorithm and ought to be used sparingly.

Regional anesthesia is at times frowned upon as it takes time to establish the neural blockade. In the interest of time, many surgeons will ask the anesthesiologists not to perform regional anesthesia. But my question is, if the patient is educated about multimodal analgesia, understands the benefits of regional anesthesia and demands it, will the surgeon deny that option to the patient? If the investment of a few extra minutes in administering regional anesthesia and multimodal analgesia can prevent the development of chronic pain, should we not strive for it? We have quality control measures in place for the administration of beta blockers, preoperative administration of antibiotics and the maintenance of normothermia. Why don`t we have such measures in place for adequate postoperative pain control? Oughtn`t we do outcome studies to demonstrate how adequate treatment of acute pain can prevent chronic pain? These could then let us establish quality control measures. It is interesting to note that that every patient in labor can have an epidural to ease the pain of labor. Why isn`t such a privilege granted to the postsurgical patient for postoperative pain control?

Anesthesiologists are experts in acute pain control. Therefore, as anesthesiologists, we should take the initiative to educate the patients, our colleagues and the nurses in order to improve postsurgical pain control for a better outcome for our patients. This can prevent overprescription, overuse, abuse and diversion of opioids. Consequently, it can minimize and possibly eliminate both unwanted consequences and untimely deaths from opioids. This can be the real success story demonstrating the art and science of anesthesiology!

Daneshvari Solanki, MBBS, is Director of Interventional Pain Management and Regional Anesthesia and Laura Bragg McDaniels Professor of Anesthesiology, The University of Texas Medical Branch Department of Anesthesiology.

Patients over 65 years of age may also be excellent candidates for kidney transplantation. (Image source: Thinkstock)

Should age 65 years be used as the upper limit, above which patients should not be allowed to receive a transplant kidney? Before that question is answered, the reader may wonder why 65 years specifically is used as a limit. In the United States, because of the Social Security Act, the age at which individuals became eligible for full benefits was set at 65 years. This version of the act was signed into law by FDR in 1935 under the umbrella of the New Deal, when the average American lifespan was almost 62 years and when over half of America`s senior citizens lived in poverty. Today the average American lifespan is almost 80 years, fewer seniors live in poverty, and the age at which full payments are available under Social Security are dependent on the retiree`s year of birth (e.g., in its current iteration, individuals born after 1960 cannot receive full benefits until age 67).

In the January issue of the Journal of the American Geriatrics Society, Dr. Dorry Segev, Departments of Epidemiology and Surgery, School of Medicine, the Johns Hopkins University, and coauthors, in their article “Candidacy for Kidney Transplantation of Older Adults,” used U.S. Renal Data System data from 1999–2006 to first develop a model to estimate outcomes after kidney transplantation for patients older than 65 years and then to use that model on Medicare data for patients with end-stage renal disease to see how many patients in that age group would have been good candidates for the procedure.

Multivariate logistic regression models were used to fit the demographic and comorbidity outcome data. Almost 7,000 individuals 65 years and older were used for the prediction model. Twenty-one patient characteristics were included in the model of 3-year transplant survival. When the model was then applied to 128,850 individuals 65 years and older who also did not have contraindications to kidney transplantation, e.g., dementia and HIV, almost 12,000 and more than 40,000 were classified as excellent and good candidates, respectively. Furthermore, more than 75% of excellent candidates and more than 90% of good candidates were never placed on a kidney transplant waiting list nor were they referred for living-donor kidney transplantation. The mean age of excellent candidates was 70 years and 73 years for good candidates. Using the model, if all excellent candidates who did not have access to kidney transplantation had been referred for same, an additional 996 patients would have received a kidney transplant.

As noted in the accompanying editorial, entitled “Age and Access to Kidney Transplantation,” by Dr. Ann M. O`Hare, Department of Medicine, University of Washington, Department of Medicine, Veterans Affairs Puget Sound Healthcare System, Group Health Research Institute,

“It seems likely that more complex prognostic models of the sort described here—that include age, but also capture information on a range of other measures also associated with survival—will be needed to distinguish between people of similar ages with differing life expectancy.”

Unfortunately, changes in the process of allocating kidneys will cause an even greater reduction of kidneys made available to older patients.

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