Snapshot A 21-year-old man presents into the emergency department after being involved in a fight. The patient was noted by bystanders to be talking to himself and became combative because he felt his life was in danger. He has a medical history of illicit substance use disorder and was most recently admitted after ingesting phencyclidine. The patient tried to hit hospital staff and was eventually restrained and given intramuscular haloperidol. He had to be restrained multiple times and was given intramuscular haloperidol. After being admitted to the medical floor, the patient became progressively confused over the course of 3 days. The patient's temperature is 103°F (39.4°C), blood pressure is 165/90 mmHg, pulse is 115/min, and respirations are 24/min. On physical examination the patient is profusely diaphoretic with diffuse lead-pipe rigidity. Introduction Overview life-threatening neurologic and psychiatric emergency associated with neuroleptic (antipsychotic) medication use classic clinical syndrome tetrad altered mental status fever rigidity autonomic instability Epidemiology demographics typically seen in young adults can occur at any age risk factors antipsychotic use first- and second-generation antiemetic use e.g., metoclopramide and prochloreperazine antiparkinson medication withdrawal also called neuroleptic malignant-like syndrome or parkinsonism hyperpyrexia syndrome Pathophysiology unknown but dopamine receptor blockade in the central nervous system is believed to be involved Associated conditions psychiatric disorders that require high or frequent doses of antipsychotic medications Prognosis natural history of disease most cases resolve within 2 weeks survival with treatment improved Presentation History tetrad usually occurs over the course of 1-3 days after neuroleptic use Physical exam altered mental status agitated delirium confusion catatonia mutism fever ≥ 38°C rigidity typically diffuse can be described as a "lead-pipe rigidity" patients may also have a tremor (45-92% of cases) autonomic instability tachycardia patients may develop dysrhythmias hypertension or labile blood pressure tachypnea diaphoresis hyporeflexia Studies Labs ↑ creatine kinase usually > 1000 U/L basic metabolic panel hypo- or hypernatremia hyperkalemia hypomagnesemia hypocalcemia metabolic acidosis acute renal failure may occure if myoglobinuria ↓ iron concentration sensitive but not specific Tested Differential Serotonin syndrome key distinguishing factors acute onset myoclonus hyperreflexia mydriasis (large pupils) Malignant hyperthermia key distinguishing factors offending agents are halogenated inhalational anesthetics succinylcholine Prevention Conservative use of antipsychotics Gradual titration of antopsychotics Treatment Lifestyle supportive care indication first-line in preventing further complications intravenous fluids to prevent dehydration and acute kidney injury from myglobinuria electrolyte repletion to prevent cardiac arrythmias and seizures Pharmacologic discontinue the offending agent indication first-line to prevent further progression of neuroleptic malignant syndrome benzodiazepines indication usually initially used along with dantrolene in moderate or severe cases medication lorazepam diazepam dantrolene indication usually given with benzodiazepines in moderate or severe cases effective in relaxing skeletal muscles bromocriptine indication administered after benzodiazepines, and dantrolene is administered in order to restore dopaminergic tone alternative agent amantadine Complications Seizure Cardiac dysrhythmia Myocardial infarction Respiratory failure Hepatic failure Acute renal failure Deep venous thrombosis Disseminated intravascular coagulation