|
Neuroleptic malignant syndrome (NMS) is an idiosyncratic condition associated with administration of antipsychotic and other central dopaminergic blockers, and characterized by hyperthermia, muscular rigidity, autonomic dysfunction and altered consciousness. NMS occurs in approximately 1-2/10,000 of patients treated with antipsychotics (all age groups; male:female ratio 2:1 in some studies; higher rates reported in the past). In about 16% of patients, NMS occurs within 24 hours after the initiation of the antipsychotic treatment, 66% within the first week, and less commonly within 30 days. NMS manifests by hyperthermia, muscular rigidity and tremor, mental status alteration and autonomic dysfunction. The signs may include profuse diaphoresis, tachycardia, tachypnea, labile blood pressure, acidosis, incontinence, elevated serum creatinine phosphokinase and transaminases, and rhabdomyolysis with risk of subsequent renal failure. Once symptoms develop, they last on average 7-10 days, with peak intensity within the first 72 hours. NMS is thought to result from dopamine receptor blockade. All antipsychotic agents, typical or atypical, may trigger the syndrome, although potent neuroleptics (haloperidol, fluphenazine) are more frequently associated with NMS. Risk factors are: physical exhaustion, agitation, dehydration, use of restraints, use of high doses and acute parenteral forms of antipsychotics, and rapid antipsychotics dosage increase. As NMS is a diagnosis of exclusion, the differential diagnosis is of prime importance. It includes malignant hyperthermia of anesthesia, serotonin syndrome (see these terms), heat stroke, idiopathic malignant catatonia, infections (sepsis, meningitis, encephalitis), serotonin syndrome, delirium tremens, status epilepticus, salicylate poisoning, endocrinopathies, stroke, and brain trauma. Immediate cessation of the antipsychotic medication and supportive measures (volume resustitation, physical cooling) are essential in management. Specific treatments are unproven. Benefits in cases treated with benzodiazepines, dopaminergic agents (bromocriptine, amantadine), dantrolene (in cases with extreme hyperthermia) and electroconvulsive therapy have been reported. Careful monitoring for cardiorespiratory failure, renal failure, aspiration pneumonia and coagulopathies is required. Ventilatory assistance and dialysis may be required. Without therapy and after discontinuation of the psychotropic agent, NMS may resolve in 1-2 weeks in most cases. However, the syndrome is still potentially lethal. Death may result from sudden cardiopulmonary arrest, aspiration pneumonia, pulmonary emboli, myoglobinuric renal failure, or disseminated intravascular coagulation. Mortality rate, once reported at 20-30%, is now estimated at 5-10%. Most patients recover completely but amnestic syndromes, extrapyramidal and cerebellar disorders, peripheral neuropathy, myopathy and contractures have been reported in rare cases. |