Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

Abstract

Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo. Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were main...

Analgesia in the Emergency Department: A GRADE-based Evaluation of Research Evidence and Recommendations for Practice

“…Th ree articles compared fentanyl and morphine (PICO #1); fi ve articles assessed hydromorphone (PICO #2), two of which analyzed the 1 + 1 hydromorphone protocol (PICO #3); three articles compared oral hydromorphone and oxycodone (PICO #4); eight articles compared non-specifi c NSAIDs and co deine-acetaminophen (PICO #5); two articles compared specifi c NSAIDs and co deine-acetaminophen (PICO #6); and fi ve articles compared oxycodone and codeine (PICO #7). Th e same reviewer assessed the full text articles and determined that 14 of the 26 off ered quantitative results that could be analyzed using the GRADE-pro software [28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Th e remaining 12 articles were excluded because they did not compare both drugs assessed in a PICO question [42][43][44][45][46][47], compared analgesics not addressed in the seven P ICO qu estions (such as acetaminophen alone) [48,49], used unconventional medication dosing [50,51], used non-validated pain me asurement scales [52,53], and/or unusual study designs [50].…”

“…However, although the number of studies used to make our recommendations may seem low, our re commendations take into consideration the quality of evidence of the studies. Pragmatic derivations of the seven PICO questions, their recommendations, and the rationale for these recommendations are listed in Table 4 [28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Furthermore, we also developed a fl owchart as a suggested approach to analges ia in the ED (Fig.…”

“…We recommend oxycodone-acetaminophen as marginally superior to codeineacetaminophen (weak recommendation, low quality evidence) Rationale [39][40][41] • This recommendation is based on two Cochrane reviews that compared each of these drugs with placebo • There are few studies that directly compare these two drugs, especially in an adult emergency department setting • However, the Cochrane reviews and single studies consistently show that oxycodone with acetaminophen is slightly better at relieving pain than acetaminophen-codeine…”

Digital Drugs

“…aspirin for prevention of stroke) it may be well over 1000; that is over 1000 persons need to receive the drug, including paying for it and suffering possible side effects, for one to obtain a therapeutic benefit [27]. As a point of contrast everyday paracetamol (acetaminophen) which a dentist may give you after an extraction has an NNT of around 4.5 for post-operative pain [28].…”

Strategies Aimed at Preventing Chronic Post-surgical Pain: Comprehensive Perioperative Pain Management after Total Joint Replacement Surgery

“…80 The most common indications are for headache, migraine, fever, menstrual pain, toothache, dental pain, muscular and joint pain, and neuralgia. [81][82][83][84] The antiinflammatory effects of acetaminophen are much weaker than those of NSAIDs; 85 acetaminophen lacks antirheumatic effects, which presumably reflects the modest peripheral inhibiting effect on prostaglandin synthesis produced by this drug.…”