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Title: The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.
Austin Authors: Chiam, Elizabeth;Weinberg, Laurence ;Bailey, Michael;McNicol, Larry;Bellomo, Rinaldo 
Affiliation: Department of Surgery, The University of Melbourne, Victoria, Australia
Department of Surgery and Centre for Anesthesia, Perioperative and Pain Medicine, The University of Melbourne, Victoria
Department of Epidemiology and Preventive Medicine, Monash University, Victoria
Department of Surgery, The University of Melbourne, Victoria
Department of Anaesthesia, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Apr-2016 2016-01-25
Publication information: British journal of clinical pharmacology 2016; 81(4): 605-12
Abstract: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
DOI: 10.1111/bcp.12841
ORCID: 0000-0001-7403-7680
Journal: British journal of clinical pharmacology
PubMed URL: 26606263
Type: Journal Article
Subjects: acetaminophen
adverse event
blood pressure
Appears in Collections:Journal articles

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