A young woman with h/o polysubstance abuse and seizures was admitted to hospital with status epilepticus. She was treated with a propofol infusion at 5mg/kg/hr which was maintained due to perceived continuing seizure activity. On hospital day 5, she developed an acute metabolic deterioration – rhabdomyolysis : CPK 100,000, AG metabolic acidosis (HCO3 18) and non-oliguric AKI. Her EKG also became abnormal (RBBB). The diagnosis was propofol infusion syndrome.
What is propofol Infusion Syndrome (PRIS)?
Like many syndromes, PRIS is a conglomeration of clinical and biochemical manifestations. Based on 83 case reports from 1992-2007, PRIS is characterized by:
1) Metabolic acidosis, (pH less than 7.30 or HCO3 less than 19)
2) Rhabdomyolysis (CPK more than 10K)
3) Renal failure
4) Cardiac dysfunction (Brugada-like EKG pattern, asystole, PEA, sustained VTs, heart failure, or bradycardia)
5) Hypertriglyceridemia (TG more than 400)
7) Hypotension (or use of vasopressor agent)
8) Hepatic transaminitis
9) Hypoxia (PO2 less than 60mmHg).
The first 5 manifestations are the most common. While there is no requirement for the number of clinical manifestations a patient must exhibit to meet diagnosis for PRIS, a prospective study showed that most patients exhibit at least 3 defining manifestations within 3 days of propofol use. In the same study, the incidence of PRIS was found to be a low 1% --similar to other estimates. However, PRIS is associated with high mortality, up to 30% in some studies. Moreover, because many of these manifestations are common, the presence of any of them could be attributed to another etiology, thus delaying diagnosis of PRIS. For instance, in the case vignette, the initial rise of CK was attributed to seizure rather than PRIS.
Pathophysiology of PRIS
Inhibition of electron flow along the mitochondrial electron transport chain/ impairs oxygen utilization. Propofol or its metabolites inhibits fatty-acid oxidation leading to buildup of toxic fatty acid intermediates. As described in this nice review.
Risks of PRIS?
Critical illness (especially, CNS illness); Use of propofol dosage more than 4 mg/kg/hr —the usual adult maintenance dose is 0.3 to 3mg/kg/hr; duration of Propofol use greater than 24hr; exogenous cathecholamines and corticosteroids; poor intake of carbohydrate, see this reference.
Management of PRISEarly recognition/diagnosis; Cessation of propofol infusion; Cardiopulmonary support; Hemodialysis (strongly advocated by expert opinion and outcome of case series). However, there are no known RCT of use of renal replacement therapy in the treatment of PRIS. Nonetheless, in case series, survivors of PRIS are more likely to have received HD/CVVH. Therefore, prolonged use of HD/CVVH is worth considering by renal consult service. Because propofol is lipophilic and has volume of distribution of 20-40L, it is poorly cleared by HD/CVVH, prolonged RRT is likely needed for PRIS management.
The patient in the case was treated with CVVH overnight, and then transitioned to intermittent HD. At the time of her discharge, she was off HD with her Cr back to baseline.
See this previous post by Nate on PRIS.
Posted by Opeyemi Olabisi