Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery.
BACKGROUND
Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr.


METHODS
After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing.


RESULTS
One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively.


CONCLUSIONS
Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.
Sinatra
Raymond S
RS
Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. raymond.sinatra@yale.edu
Jahr
Jonathan S
JS
Reynolds
Lowell W
LW
Viscusi
Eugene R
ER
Groudine
Scott B
SB
Payen-Champenois
Catherine
C
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000368:Aged; D016058:Analgesia, Patient-Controlled; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D019637:Orthopedic Procedures; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018401:Sample Size
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D011355:Prodrugs; D000082:Acetaminophen; D009020:Morphine