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A Quick Post-Surgical Wake-Up Call

Researchers find that giving rats the common stimulant Ritalin can revive them during general anesthesia.
September 21, 2011

After they’ve undergone general anesthesia, patients typically experience hours of sleepiness, disorientation, and confusion. But perhaps patients could be quickly stimulated into alertness. That’s the surprising suggestion of a new study in the October issue of Anesthesiology, which finds that, in rats, the common stimulant methylphenidate (Ritalin) can help speed recovery from general anesthesia.

Suddenly awake: The rats shown here are in a sealed chamber suffused with the anesthesia drug isoflurane, which normally keeps them immobile and unconscious. But a minute after an injection of methylphenidate (Ritalin), the animals are actively moving even as they continue to inhale isoflurane.

The study showed that an injection of methylphenidate revives anesthetized animals faster than a saline injection, which was used as a control. In one experiment, rats were anesthetized in a chamber filled with the anesthetic gas isoflurane, and then, five minutes before the isoflurane treatment was discontinued, injected with methylphenidate. The researchers measured the time it took for the rats, which were lying on their backs, to right themselves. The animals receiving the stimulant roused themselves much faster than the control group.

The rats received the stimulant while still maintained on a dose of anesthetic sufficient to keep them unconscious so that the researchers could see whether the drug was actively inducing arousal rather than simply counteracting the effect of the anesthetic. At the highest tested dose, the rats began moving and twisting within 30 seconds, and exhibited alert behavior even while the anesthetic persisted.

Emery Brown, an anesthesiologist at Massachusetts General Hospital (MGH) and MIT, who led the study with Ken Solt, an anesthesiologist at MGH and Harvard Medical School, notes that while anesthesiologists use medication to put patients in a stable state similar to a coma, “we don’t give you anything that brings you out of that state.” He points out that recovery after many surgeries is fastest when patients get up, walk around, and breathe on their own as soon as possible. “If you can facilitate that [with a drug], you’d probably facilitate recovery,” he says. The drug could also be used as an emergency treatment in the case of an anesthesia overdose, Brown says, and he speculates it might help people recover from comas.

“For the last 150-plus years, anesthesia has been reversed passively,” says Max Kelz, an anesthesiologist at the University of Pennsylvania School of Medicine who was not involved in the study. “Having a way to actively antagonize the action of general anesthesia has merit.” For instance, Kelz points out, after neurosurgery it can be difficult to distinguish post-anesthesia disorientation from a potential warning sign of a complication. The treatment could be especially useful for the subset of patients who wake up abnormally slowly from anesthesia. What’s not clear, he says, is whether methylphenidate is a unique drug or whether any stimulant would have the same effect.

The researchers chose Ritalin because of its ability to inhibit neurons from sopping up the neurotransmitters dopamine and norepinephrine, allowing these neurotransmitters to remain longer in the synapses between neurons. Because the drug is already widely used to treat attention-deficit hyperactivity disorder, the team hopes that it can be brought to human studies relatively easily.

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