Rare: estimated incidence of 0.2 % of patients on an antipsychotic treatment. 

Drugs involved:

-         most often: conventional neuroleptics: haloperidol, chlorpromazine and fluphenazine

-         possibly: atypical neuroleptics: risperisone, olanzapine, clozapine

-         rarely: metoclopramide, domperidone, baclofen, triptans, antidepressant SSRI

Mechanism: blockade of dopamine D2 receptors at the level of the basal ganglia and the hypothalamus and dysfunction of the mechanisms controlling muscle contraction (ryanodine receptors or adjacent ?).

Clinical signs:

-         disorders of consciousness: delusions, catatonia, mutism, coma

- 'lead pipe' muscle stiffness (cogwheel rigidity), high CPK level

-  hyperthermia (> 39 °C)

-  dysautonomic disorders: tachycardia, tachypnea, labile BP, profuse sweating, sialorrhea, DIC.

Complications: rhabdomyolysis, 10-20 % mortality.

Diagnostic criteria (DMS IV): severe muscle rigidity and hyperthermia associated with at least two of the following signs: profuse sweating, tachycardia, hypertension or  labile blood pressure, disorders of consciousness, dysphagia, mutism, tremor, leukocytosis, elevated CPK level.

Treatment: bromocryptine and/or dantrolene (at least 2-3 mg/kg/day for several days), rehydration, prevention of renal failure, controlled ventialtion.

Anesthetic implications: 

check blood electrolytes, kidney function. Although the association with malignant hyperthermia is controversial, it is recommended to take the same precautions: avoiding succinylcholine and halogenated agents (including pre-anesthetic flushing of the ventilator), TIVA propofol. Avoid neuroleptics: droperidol, domperidone, metoclopramide, alizapride.

References : 

• Bhalla T, Maxey D, Sawardekar A, Tobias JD. 
  Anesthetic management of a pediatric patient with neuroleptic malignant syndrome. 
  J Anesth 2012; 26: 250-3.

Updated: January 2019