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Myoclonus, fever may signal serotonin syndrome.

NEW YORK -- A patient who presents with acute changes in behavior, myoclonus, hyperreflexia, fever, and sweating may be exhibiting symptoms of the serotonin syndrome, which is one of the highest-risk adverse drug reactions emergency physicians are likely to see, Dr. Robert S. Hoffman said at a meeting sponsored by the American College of Emergency Physicians.

Serotonin syndrome can be caused by a selective serotonin reuptake inhibitor alone or in combination with any drug that prevents the reuptake of this neurotransmitter, such as the tricyclic antidepressants, meperidine, and dex-tromethorphan. It also can be caused by agents that increase presynaptic availability of serotonin, such as monoamine oxidase (MAO) inhibitors, or drugs that themselves cause the release of serotonin, such as cocaine.

The MAO inhibitors are a particular hazard in this regard. While they are less commonly used now as antidepressants, the new antimicrobial linezolid (Zyvox) is a weak MAO inhibitor that has been implicated in cases of serotonin syndrome. "You should never give anything to a patient on an MAO inhibitor without looking it up for potential interactions, and document that you've looked it up," Dr. Hoffman said.

Management involves stopping the offending agent and rapidly cooling the patient. "It's the hyperthermia that kills patients with serotonin syndrome," said Dr. Hoffman, who is director of the New York City Poison Center and attending physician, department of emergency medicine, Bellevue Hospital Center, New York.

"We pack them in ice like fish, which is very efficient and can bring down temperatures as high as 114[degrees]F in 10-15 minutes," he said.

Cooling using a small fan with mist is not likely to suffice. "The data on mist and fanning all come from the military, where the fan is a helicopter blade. They put patients on a hammock, get them wet, and spin the helicopter blades," he said.

"And placing ice packs on the pulse in the neck, armpits, and groin is probably the worst thing you could do. The idea behind this practice was to cool the carotid and areas where there is a lot of blood flow, but if the brain has any autoregulatory activity left and you efficiently cool the carotid, it tells the brain that the rest of the body is cool and every attempt to dissipate heat south of the neck will fail," he said.

Treatment also involves sedation with benzodiazepines, along with neuromuscular blockade if needed. Avoid succinylcholine in this circumstance, however, because a hyperthermic patient with clonus and hyperreflexia is probably already breaking down muscle.

The serotonin antagonist cyproheptadine can be administered as an antidote, but its use is limited, he said.

Two other types of hyperthermic syndromes clinically resemble serotonin syndrome but are quite different. Neuroleptic malignant syndrome can occur with exposure to any drug that affects the central dopaminergic system, such as haloperidol or lithium. Approximately 0.2% of patients receiving a neuroleptic agent may develop this reaction.

It results from blockade of the dopaminergic receptors in the corpus striatum, and is characterized by spasticity of the skeletal muscle and generation of excessive heat. Impaired hypothalamic thermoregulation then leads to autonomic dysfunction that impairs heat dissipation, according to Dr. Hoffman.

Patients present with fever, rigidity, and altered mental status, and possibly elevated creatine phosphokinase.

Treatment is similar to that for serotonin syndrome, with rapid cooling and sedation.

A second similar syndrome is malignant hyperthermia, which also is characterized by muscle rigidity and hyperthermia that can reach 113[degrees]F. This typically is triggered by exposure to an inhalation anesthetic, and also can result in hypotension, tachycardia, dysrhythmias, and disseminated intravascular coagulation.

The syndrome results from an autosomal dominant genetic defect in the ryanodine receptor. Treatment involves cooling and volume resuscitation, and must always include administration of the antidote dantrolene, he said.

BY NANCY WALSH

New York Bureau
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Title Annotation:Across Specialties
Author:Walsh, Nancy
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Aug 1, 2007
Words:632
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