Introduction
Dr. Sanjay Gupta takes a closer look at propofol – the drug at the center of the Michael Jackson death trial. – CNN
Rare, potentially fatal complication of propofol infusion in general anaesthesia:
History:
Propofol use was approved by the food and drug administration (FDA) in November 1989. The first reported death associated with propofol infusion was of a 3-year-old girl in Denmark in 1990. This patient developed high anion gap metabolic acidosis (HAGMA), hypotension, and polyorgan failure. In 1992 Parke TJ reported the deaths of five children who had similar presentations to the Danish case while being on propofol infusion. The term “propofol infusion syndrome” (PRIS) first appeared in pediatric literature and was proposed by Bray RJ who had reviewed 18 pediatric cases. The clinical spectrum of PRIS consists of bradycardia, cardiovascular collapse, HAGMA, rhabdomyolysis, hepatomegaly, and lipemia.
Later, in 1996, the first adult case of lactic acidosis associated with propofol administration was reported. The patient was a 30-year-old female who was admitted for bronchial asthma exacerbation and who had developed unexplained lactic acidosis. Propofol infusion was stopped, and the lactic acidosis resolved with a favorable outcome. Unfortunately, in 1998 a first adolescent mortality associated with propofol use was reported in a 17-year-old male with refractory status epilepticus.
Propofol
Propofol is a sedative-hypnotic medication commonly used as an induction agent for preoperative sedation, prior to endotracheal intubation and other procedures as well as for sedation in the intensive care unit
Advantages of propofol:
- Rapid onset of action (within seconds after administration)
- Short duration of action (up to 15 minutes)
- Sedative, anxiolytic, and anticonvulsant properties
- Beneficial anti-inflammatory and antioxidative effects
- Neuroprotective properties including reduction of intracranial pressure
Common side effects:
- Braducardia
- Hypotension
- Bacterial infection
- Hypertriglyceridemia (predisposes to pancreatitis)
Mechanism of action:
- Stimules γ-aminobutyric acid receptors
- Blocks N-methyl-D-aspartate receptors
- Diminishes calcium influx via slow calcium ion channels
Aetiology
Risk factors:
- Inappropriate propofol doses and durations of administration (≥ 4 mg/kg/hr for ≥ 48 hr
- Carbohydrate depletion
- Severe illness
- Concomitant administration of catecholamines and glucocorticosteroids
The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels.
Clinical features
Cardiovascular manifestations:
- Widening of QRS complex
- Brugada syndrome-like ECG patterns (particularly type 1): Elevated ST-segment and coved T-wave
- Ventricular tachyarrhythmias
- Cardiogenic shock, and asystole
Skeletal muscle manifestations:
Skeletal muscle injury may be complicated by hyperkalemia and acute kidney injury.
- Myopathy
- Overt rhabdomyolysis
Metabolic manifestations:
- High anion gap metabolic acidosis (HAGMA): Due to elevation in lactic acid)
- Hyperkalemia: Due to concurrent myopathy
- Metabolic acidosis can further worsen hyperkalemia due to increased transcellular shift
Hepatic manifestations:
- Elevated liver enzymes
- Hepatomegaly
- Steatosis
- Hypertriglyceridemia (expected in propofol use)
Differential diagnosis:
PRIS lacks specific signs and symptoms (other than propofol administration) and its presentation overlap greatly with other conditions leading to critical illness (various forms of shock, renal disease due to other causes, etc.). Therefore, clinicians should keep a broad differential in mind while managing a patient with possible PRIS.
Management
Management of overt PRIS requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in refractory cases.
Prevention:
Given the high mortality of propofol infusion syndrome, the best management is prevention.