Can propofol (2,6-diisopropylphenol) cause hyperthermia (fever)?

From the Guidelines

Propofol typically does not cause hyperthermia (fever) and is actually known for its antipyretic (fever-reducing) properties. In fact, propofol is sometimes associated with hypothermia rather than fever during anesthesia, as it affects the body's temperature regulation mechanisms through its action on GABA receptors in the central nervous system 1. However, in rare cases, some patients may develop a condition called propofol-related infusion syndrome (PRIS), particularly with high doses or prolonged infusions, which can include fever among its symptoms, such as metabolic acidosis, rhabdomyolysis, kidney failure, and cardiovascular collapse 1.

Some key points to consider when administering propofol include:

• Propofol's pharmacological properties, including its rapid onset and short duration of action, which can be beneficial for patients requiring frequent awakenings for neurologic assessments 1
• The potential for propofol to cause dose-dependent respiratory depression and hypotension, which may be more pronounced when administered with other sedative and opioid medications 1
• The importance of monitoring patients receiving propofol for unexpected temperature changes and investigating any fever that develops during propofol administration, as fever is not a typical side effect of propofol but can occur in the context of PRIS or other conditions 1

If a patient develops a fever while receiving propofol, clinicians should consider other more common causes of fever, such as infection, transfusion reaction, or drug reaction to other medications, rather than attributing it to the propofol itself 1. The clinical pharmacology of sedatives, including propofol, is summarized in tables that outline their onset, elimination half-life, active metabolites, loading doses, maintenance dosing, and adverse effects 1.

Overall, while propofol is not typically associated with hyperthermia, it is crucial for healthcare providers to be aware of the potential for PRIS and other adverse effects, and to monitor patients closely during propofol administration to ensure their safety and well-being 1.

From the FDA Drug Label

Animal studies and limited experience in susceptible patients have not indicated any propensity of propofol injectable emulsion to induce malignant hyperthermia.

Propofol is not likely to cause hyperthermia (fever) according to the available information. However, it is essential to note that the provided text does not explicitly state that propofol cannot cause hyperthermia, but rather that it does not induce malignant hyperthermia, a specific and severe condition.

• The FDA drug label does mention that there have been reports of fever associated with microbial contamination of the product due to failure to use aseptic technique when handling propofol injectable emulsion 2, 2. However, this is not directly related to the pharmacological effects of propofol itself.

From the Research

Propofol and Hyperthermia

• Propofol, also known as 2,6-diisopropylphenol, has been reported to cause hyperthermia (fever) in some cases, as seen in a study published in the Journal of Anesthesia 3.
• This study presented a case of propofol-induced drug fever in a 57-year-old woman who underwent hepatic segmentectomy and was sedated with propofol and dexmedetomidine in the intensive care unit (ICU).
• The patient developed a fever of 38-39.5 °C two hours after admission to the ICU, which persisted until day 5 after surgery, despite the initiation of antibiotics on day 4 3.
• Discontinuation of propofol infusion on day 5 after surgery led to a rapid decrease in the patient's temperature, suggesting a possible link between propofol and the development of fever 3.

Incidence of Febrile Syndromes

• Another study published in Pharmacoepidemiology and Drug Safety found a temporal association between the use of propofol for sedation during gastrointestinal endoscopic procedures and the development of self-limited febrile syndromes 4.
• The study identified 74 cases of febrile illnesses in patients who received propofol for sedation during endoscopy, with a rate of 36 reactions per 1000 procedures, compared to a baseline rate of 0.6 per 1000 4.
• The majority of patients experienced self-limited fever, chills, or myalgia, and blood samples from five patients showed no growth of organisms, suggesting that the febrile syndromes were not due to infection 4.

Side Effects of Propofol

• Propofol has been reported to have a range of side effects, including dose-dependent hypotension, hypertriglyceridemia, and pancreatitis 5.
• High-dose propofol infusions have also been associated with the "propofol syndrome," a potentially fatal complication characterized by severe metabolic acidosis and circulatory collapse 5.
• However, propofol is generally considered to have a remarkable safety profile, and its use is well established in the sedation of adults in the intensive care unit 6, 7.