Propofol Related Infusion Syndrome (PRIS)

In the Rapid Review series, I briefly review the key points of a clinical review paper (which often extends to multiple papers because I can’t help myself). The topic this time: Propofol Related Infusion Syndrome (PRIS).

Like many rapid review topics, this was chosen for my own education because I have next to no experience with the topic, so I can report what the literature says, but have little to add or critique based on my personal expertise.

The paper:

Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth. 2019 Apr;122(4):448-459. doi: 10.1016/j.bja.2018.12.025. PMID: 30857601

What is it?

There is no widely accepted definition. The clinical data is mostly from a collection of case reports. The authors of this review suggest: “propofol infusion syndrome occurs in critically ill patients receiving propofol infusions, typically either high dose (>5 mg kg1 h1) or of long duration (>48 h), and is characterized by one or more of otherwise unexplained metabolic acidosis, rhabdomyolysis, or ECG changes, with or without AKI, hyperkalaemia, lipidaemia, cardiac failure, fever, elevated liver enzymes, or raised lactate.”

Who gets it?

Propofol related infusion syndrome was originally described in children, but is now also well established in adults. It is thought to be related to the cumulative total dose of propofol. However, there are case reports in patients receiving normal doses. (These are somewhat difficult to interpret without a gold standard definition of the disease. All of these patients are critically ill at baseline, and so some organ failure is expected and likely to be unrelated to propofol.) The median propofol doses received are pretty high in reported cases (494 mg/kg total in children and 380 mg/kg in adults).

Aside from propofol dose, other risk factors for PRIS include critical illness, use of vasopressors and steroids, starvation or malnutrition, and subclinical mitochondrial disease. 

What are the symptoms?

The syndrome is characterized by multi-organ failure. In this review, there was no single clinical feature present in all reported cases. 

The primary features are a high anion gap metabolic acidosis, ECG changes (wide QRS, bradycardia, ventricular arrhythmias), and rhabdomyolysis. Secondary features include acute kidney injury, hyperkalemia, lipidemia, heart failure, fever, elevated liver enzymes, and elevated lactate.

(Given how common all of these symptoms are in the ICU, and how common propofol use is, you can see why it is hard to definitely tie the clinical syndrome to propofol.)

How is it diagnosed?

There are no diagnostic tests. Most importantly, although you should discontinue propofol as soon as PRIS is expected, propofol infusion syndrome is a diagnosis of exclusion. There are many other causes of metabolic acidosis, renal failure, heart failure, hypotension, etc. It would be a mistake to overlook a more common etiology. 

What causes it?

There are many theories, from accumulation of propofol metabolites to mitochondrial inhibition, but we really just don’t know.

What is the prognosis?

Outcomes are bad, with an overall mortality of about 50%.

How common is it?

It is rare. This review only found a total of 168 cases in the entirety of the medical literature, although worldwide numbers will definitely be higher, as this is no longer really a case-reportable entity. Considering how widely propofol is used worldwide, the risk for any individual patient is very small. 

What is the treatment?

There is no specific treatment or antidote, but stopping the propofol is obviously essential. Supportive care focuses on the patient’s specific symptoms. In the setting of significant kidney injury, there may be a role of hemofiltration, because although it will not eliminate the lipid soluble propofol, it will eliminate water soluble metabolites. ECMO is also a possible consideration.

Why do I, an emergency doctor, need to know this?

For the most part, propofol infusion syndrome is a problem for the ICU. Issues only seem to arise with very high doses or prolonged infusions. Propofol is still an excellent initial sedative for the emergency department. However, the outcomes in propofol infusion syndrome are bad, so don’t be surprised if an intensivist asks you to transition to a different agent (especially in pediatrics, where this was first described). Furthermore, we should be aiming for the lowest effective dose, specifically treating pain rather than just increasing sedation, and using sedation scales to monitor sedation.

Other FOAMed

Propofol-related Infusion Syndrome on LIFTL

Propofol Infusion Syndrome in Children on Pediatric EM Morsels

PROPOFOL-RELATED INFUSION SYNDROME on DTFB

Propofol infusion syndrome on Deranged Physiology

Other references

Krajčová A, Waldauf P, Anděl M, Duška F. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015 Nov 12;19:398. doi: 10.1186/s13054-015-1112-5. PMID: 26558513

Mirrakhimov AE, Voore P, Halytskyy O, Khan M, Ali AM. Propofol infusion syndrome in adults: a clinical update. Crit Care Res Pract. 2015;2015:260385. doi: 10.1155/2015/260385. Epub 2015 Apr 12. PMID: 25954513