Propofol-Related Infusion Syndrome in Intensive Care Patients

Stephanie Mallow Corbett, PharmD; Isaac D. Montoya, PhD; Frederick A. Moore, MD

Disclosures

Pharmacotherapy. 2008;28(2) 

In This Article

Propofol and Its Adverse Effects

Propofol is a sedative-hypnotic agent approved by the FDA in 1993 for use as a sedative for mechanically ventilated patients in the ICU.[58] It is a phenol derivative that demonstrates low aqueous solubility. Therefore, it is formulated in an oil-in-water emulsion containing 1% propofol, 10% soybean oil, 1.2% egg phosphatide, and 2.25% glycerol.[59] Four propofol products are on the U.S. market. Each product has the same key ingredients, but with different preservatives and pH ranges: ethylenediaminetetraacetic acid (pH 7-8.5), sodium metabisulfate (pH 4.5-6.4), benzyl alcohol (pH 7-8.5), and a combination of benzyl alcohol and sodium benzoate (pH 7-8.5).[60]

The rapid distribution of propofol and its ease of administration make it the ideal agent for postoperative patients, patients with head injuries, and those in whom quick weaning to extubation is anticipated. Compared with other sedative agents (e.g., midazolam or lorazepam), patients who received propofol experienced shorter time to awakening and extubation, and had more predictable levels of sedation.[61,62,63,64]

The most common adverse event associated with propofol use is hypotension, which occurs in approximately 26% of patients and is more common with bolus dosing.[58,65,66] Other documented adverse effects are bradycardia,[5,25,66] respiratory depression,[58,65] and metabolic acidosis.[5,6,7,8] The lipid vehicle in which propofol is formulated poses additional risks for adverse effects. It provides a potential source for infection[56,58,65,66] as well as venous irritation, which occurs in 8-45% of patients.[58,65,66] The lipid formulation contains 1.1 kcal/ml, which can cause hypertriglyceridemia (triglyceride concentration ≥ 500 mg/dl) in as many as 18% of intensive care patients who are given propofol for at least 24 hours.[56,58,59,65,67]

Tolerance to the sedative effects of propofol has been reported with infusions administered for longer than 7 days and has led to high infusion rates and an increased likelihood of hyperlipidemia.[66] Rarely, patients have developed pancreatitis with or without hyperlipidemia after receiving short-term or long-term infusions of propofol.[65,67] One manufacturer of propofol recently revised its package insert to indicate that once-daily sedation-awakening trials or abrupt discontinuation of propofol should be avoided because rapid awakening may cause anxiety, agitation, and resistance to mechanical ventilation.[68] Finally, perhaps the most profound adverse event is propofol-related infusion syndrome. The frequency of this syndrome is unclear, but its consequences can be devastating.

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