Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial

• Published in: Anaesthesia Vol. 71; no. 10; pp. 1153 - 1162
• Main Authors: Kelly, S. J., Moran, J. L., Williams, P. J., Burns, K., Rowland, A., Miners, J. O., Peake, S. L.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-10-2016
• Subjects: Acetaminophen - administration & dosage; Acetaminophen - adverse effects; Acetaminophen - pharmacology; Aged; Analgesics; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - pharmacology; Anesthesia; Clinical trials; Critical care; Critical Care - methods; Critical Illness; critically ill; Drug Administration Routes; Drug therapy; Female; Hemodynamics - drug effects; Humans; hypotension; Hypotension - chemically induced; Infusions, Parenteral - methods; Male; Middle Aged; paracetamol; parenteral; pharmacokinetics; Prospective Studies; hypotension; parenteral; pharmacokinetics; paracetamol; critically ill
• ISSN: 0003-2409; 1365-2044
• DOI: 10.1111/anae.13562

Summary
Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single‐centre, prospective, open‐label, randomised, parallel‐arm, active‐control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l−1 [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97–8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.