Chiefs’ Inquiry Corner – March 17th, 2019

Propofol is a short-acting, intravenous sedative-hypnotic that is metabolized by the liver and excreted in the urine as conjugates of 2,6-diisopropyl-1,4 quinol. The pharmacokinetics of propofol favor its use for the induction/maintenance of anesthesia and for sedation in the critical care setting, however prolonged use can increase the risk for adverse effects. Propofol-related infusion syndrome (PRIS) is a rare life threatening condition characterized by acute refractory bradycardia and one or more of the following: metabolic acidosis, rhabdomyolysis, hyperlipidemia and enlarged or fatty liver. Diagnosis requires a high index of suspicion and close monitoring of basic labs plus urine samples in any patient who has been maintained on prolonged and/or high dose infusions. Propofol induced urine discoloration is also a rare side effect of propofol infusion and is attributed to the presence of the above phenolic metabolites in alkalinized urine. However, despite its concerning appearance, these metabolites are benign and do not reflect or alter urine function (nor have they been correlated to the development of PRIS).

References: Clinical significance of rare and benign side effects: propofol and green urine  

Guillain-Barré syndrome (GBS) is an immune-mediated progressive polyneuropathy characterized by autoimmune targeting of peripheral myelin or the motor axon itself. This results in classic symptoms of ascending symmetrical weakness and areflexia, and can critically compromise respiratory and autonomic function. While there are several potential antecedent triggers for this immune response, vaccination – specifically influenza vaccination – has been the subject of much controversy. Most data linking influenza vaccination to GBS comes from the 1976 H1N1 pandemic vaccine – a vaccine surveillance program at the time cited a 9-fold increase in risk of GBS after this monovalent vaccination. However, several rigorous studies of subsequent influenza vaccines have failed to show remotely close to as strong an association as reported in 1976. A meta-analysis of surveillance program data from the 2009 H1N1 pandemic vaccine demonstrated a small increased risk commensurate to 1.6 people affected per 1 million people vaccinated; subsequent studies comparing post vaccination period to control periods have shown that GBS is in fact more common following healthcare encounters for influenza itself than for influenza vaccination. Given the modest risk of GBS that vaccination poses, and the tremendous importance of influenza primary prevention each season, the risk of GBS is best placed secondary to the task of primary influenza prevention.

References: Influenza and GBS  

Pneumocystis jirovecii (previously carinii) has long been known to cause pulmonary disease in patients with AIDS; however this pathogen can also cause disease in patients with other causes of immunocompromise, especially in those with solid organ or liquid transplants, chronic steroid use, chemotherapeutics, and other immunosuppressive medications. As the use of immunosuppressive agents has increased in recent years, so has the rate of non-HIV associated Pneumocystis pneumonia (PCP). The use of steroids in HIV-infected patients with PCP has been well established, but the role of steroids in HIV-uninfected patients is much less clear. Patients with PCP who are not infected with HIV have a mortality of 20-50%, higher than in patients with HIV. A recent retrospective study of 323 patients with PCP concluded that the addition of early corticosteroids to anti-Pneumocystis therapy in patients without HIV was not associated with improved respiratory outcomes. Other, older studies have also shown no benefit, or even some evidence of harm in this population.

References: Steroids and PCP in HIV Uninfected Patients