title: The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, The University of Melbourne, Victoria.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chiam
authors.affiliation: Department of Surgery and Centre for Anesthesia, Perioperative and Pain Medicine, The University of Melbourne, Victoria.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weinberg
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Victoria.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Department of Surgery, The University of Melbourne, Victoria.|Department of Anesthesia, Austin Hospital, The University of Melbourne, Victoria.
authors.forename: Larry
authors.initials: L
authors.lastname: McNicol
authors.affiliation: The University of Melbourne, Victoria.|Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005079:Excipients / Q000009:adverse effects / Q000737:chemistry; D005260:Female; D064368:Healthy Volunteers; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D007262:Infusions, Intravenous; D008297:Male; D008353:Mannitol / Q000009:adverse effects / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D005079:Excipients; D000082:Acetaminophen; D008353:Mannitol
keywords: acetaminophen; adverse event; blood pressure; haemodynamic; intravenous; paracetamol