Emergence after isoflurane anesthesia is faster when methylphenidate (Ritalin) is added
Scatterplot shows faster emergence time after methylphenidate (Image source: Anesthesiology; fig 2C from cited article)
Most probably know of methylphenidate as Ritalin®. If an anesthesiologist were asked about the relationship between methylphenidate and anesthesia, the response may relate more to possible interactions between anesthesia and methylphenidate rather than specifically how the drug may affect emergence from anesthesia. When asked about a drug that might reverse the effects of anesthesia, some might think of physostigmine, though clinical studies of anesthesia reversal with physostigmine have shown mixed results.
In their study “Methylphenidate Actively Induces Emergence from General Anesthesia,” the authors determined whether emergence time from isoflurane anesthesia decreased after methylphenidate administration and whether this was due to central effects or the drug`s effects on increasing minute ventilation. Since methylphenidate increases brain levels of dopamine, the authors also included droperidol, a dopamine receptor antagonist, in their study.
In the first study, rats were anesthetized with isoflurane 1.5% in a chamber. After 40 min they received either methylphenidate or placebo and then, after 5 min, they were taken out of the chamber. Methylphenidate decreased emergence time.
In the next study, three different doses of methylphenidate were administered during continuous administration of isoflurane and righting reflex was measured. Before methylphenidate administration, the average isoflurane dose needed to maintain righting reflex loss was 0.9%. Return of righting reflex during isoflurane anesthesia and methylphenidate showed a dose-dependent response. Droperidol 0.5 mg/kg reversed return of righting reflex when given before the highest dose of methylphenidate (5 mg/kg).
In a third study, extradural electroencephalogram electrodes were implanted and then, at least seven days later, recordings were made during isoflurane anesthesia before and after methylphenidate injection. EEG power was shifted from delta (less than 4 Hz) to theta (4 – 8 Hz) within 30 s of methylphenidate administration. Droperidol inhibited EEG changes.
In a fourth study, plethysmography determinations were made before and after methylphenidate. Minute ventilation increased after methylphenidate administration. Droperidol inhibited minute ventilation changes.
Further study in humans is needed to show whether wake-up times and respiratory depression are affected by the drug. Admittedly, older studies (>30 years) showed mixed results.