Dexmedetomidine, intestinal injury and survival after intestinal ischemia-reperfusion
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.