Droperidol-induced neuroleptic malignant syndrome
Authors: Edgar J 
Published: May 2014

A 21-year-old female was admitted to the general medical wards via casualty with a suspected overdose of unknown amounts of procyclidine, diazepam and alcohol. She had been a known intravenous drug addict for 3 years.

On examination she was drowsy, agitated and smelling of alcohol. She had venepuncture sites in her antecubital fossae. Her cardiorespiratory observations were normal and her abdomen was soft and non-tender. Glasgow Coma Score was 9 (E4, M4, V1). Her pupils were dilated but equal and reacting to light. Her tone was normal, as was her temperature. Investigations revealed a normal urea and electrolyte screen and a normal full blood picture. Drug screen was positive for benzodiazepines but negative for paracetamol, salicylates, opiates and amphetamines. Electrocardiography showed a sinus rhythm.

She was initially treated with flumazenil 500 μg intravenously and naloxone 1.6 mg intravenously with some improvement in her conscious state. She was given droperidol 10 mg intramuscularly (IM) for agitation and was admitted to a medical ward.

Two days after admission she was increasingly unmanageable, requiring two staff members to control her at all times. She was having auditory and visual hallucinations and was restless. Further droperidol 10 mg IM was given. At this stage, cardiorespiratory observations were still normal, as was temperature. Pupils were dilated, equal and slow to react. Tone was normal. She was reviewed by the psychiatrists who diagnosed drug-induced psychosis, secondary to procyclidine. She was given further droperidol 30 mg IM and transferred to the psychiatric ward for observation. She developed an acute dystonic reaction which was treated with a total of 20 mg of procyclidine IM.

By day 3 she was sweaty, rigid and psychotic. Her temperature was 37.4°C, with a pulse rate of 120 and arterial pressure of 140/90 mm Hg. She was noted to have extensive bruising over her arms and legs. Creatinine phosphokinase was elevated at 1597 mmol/litre (normal < 170 mmol/litre).

During that evening she became tachycardic (pulse 140 beats per minute), hypotensive (blood pressure 50/30 mmHg), tachypnoeic (respiratory rate 50 breaths per minute) and hyperpyrexial, and was found to have a rectal temperature of 42°C. Her pupils were dilated, equal and reacting but she had generalized increased tone and was vasoconstricted. An arrest call was put out and after initial resuscitation she was rapidly transferred to the surgical intensive therapy unit, with a presumed diagnosis of neuroleptic malignant syndrome.

She was intubated and ventilated with 100% oxygen, and received a total of 120 mg dantrolene intravenously. Active cooling measures were initiated. Over several hours her temperature dropped from 42°C to 36.1°C. She was noted to be oliguric (urine output ≈10 ml/hr) with blood-stained urine, positive for myoglobin. She was oozing from venepuncture sites and had a coagulation screen consistent with acute fulminant disseminated intravascular coagulation (prothrombin time 34 secs (normal 12–14 secs), fibrinogen level 1.8 g/litre (normal 2.5–4 g/litre), platelets 100x109/litre (normal 150–400×109/litre), D-Dimer >8 mg/litre (normal <0.5 mg/litre), haemoglobin 99 g/litre (normal 110–115 g/litre)). She had a marked metabolic acidosis (H+ 49 mmol/litre (normal 36–43 mmol/litre) (base excess -10)). Her potassium was normal. Her urea and creatinine were 10.6 mmol/litre and 259 μmol/litre respectively (normal 2.5–7.5 mmol/litre and 40–130 μmol/litre). An infective screen was normal. She continued to deteriorate rapidly, despite inotropic support, volume replacement, frusemide infusion and transfusion of fresh frozen plasma, platelets and concentrated red cells.

Early next morning (day 4) she was diagnosed as having multisystem organ failure and developed fixed dilated pupils, the latter presumed due to cerebral haemorrhage. Active treatment was withdrawn and she died shortly afterwards. A post-mortem showed pulmonary oedema but no apparent cerebral haemorrhage.