Search

Background This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. Objectives To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children. Search methods We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles. Selection criteria Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children. Data collection and analysis Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. Main results We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants. Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours. For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event. Authors' conclusions Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.

Background Lidocaine administration produces pain due to its acidic pH. Objectives The objective of this review was to determine if adjusting the pH of lidocaine had any effect on pain resulting from non-intravascular injections in adults and children. We tested the hypothesis that adjusting the pH of lidocaine solution to a level closer to the physiologic pH reduces this pain. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to June 2010); Ovid MEDLINE (1966 to June 2010); EMBASE (1988 to June 2010); LILACS (1982 to June 2010); CINAHL (1982 to June 2010); ISI Web of Science (1999 to June 2010); and abstracts of the meetings of the American Society of Anesthesiologists (ASA). We checked the full articles of selected titles. We did not apply any language restrictions. Selection criteria We included double-blinded, randomized controlled trials that compared pH-adjusted lidocaine with unadjusted lidocaine. We evaluated pain at the injection site, satisfaction and adverse events. We excluded studies in healthy volunteers. Data collection and analysis We separately analysed parallel-group and crossover trials; trials that evaluated lidocaine with or without epinephrine; and trials with pH-adjusted lidocaine solutions < 7.35 and ≥ 7.35. To explain heterogeneity, we separately analysed studies with a low and higher risk of bias due to the level of allocation concealment; studies that employed a low and a higher volume of injection; and studies that used lidocaine for different types of procedures. Main results We included 23 studies of which 10 had a parallel design and 13 were crossover studies. Eight of the 23 studies had moderate to high risk of bias due to the level of allocation concealment. Pain associated with the infiltration of buffered lidocaine was less than the pain associated with infiltration of unbuffered lidocaine in both parallel and crossover trials. In the crossover studies, the difference was -1.98 units (95% confidence interval (CI) -2.62 to -1.34) and in the parallel-group studies it was -0.98 units (95% CI -1.49 to -0.47) on a 0 to 10 scale. The magnitude of the pain decrease associated with buffered lidocaine was larger when the solution contained epinephrine. The risk of bias, volume of injection, and type of procedure failed to explain the heterogeneity of the results. Patients preferred buffered lidocaine (odds ratio 3.01, 95% CI 2.19 to 4.15). No adverse events or toxicity were reported. Authors' conclusions Increasing the pH of lidocaine decreased pain on injection and augmented patient comfort and satisfaction.

Scoliosis surgery is often associated with substantial blood loss and potential detrimental effects in children. Antifibrinolytic agents are often used to reduce perioperative blood loss. Clinical trials have evaluated their effect in children undergoing surgical correction of scoliosis but no systematic review has been published. We performed a systematic review on the efficacy and safety of antifibrinolytic drugs in children undergoing scoliosis surgery.To assess the efficacy and safety of aprotinin, tranexamic acid and aminocaproic acid in reducing blood loss and transfusion requirements in children undergoing scoliosis surgery.We searched CENTRAL (The Cochrane Library 2007, Issue 3), OVID MEDLINE (1950 to September 3rd 2007), LILACS (1992 to June 20th 2007) and EMBASE (1980 to July 23rd 2007). We also searched conference proceedings from 2003 to 2007 and the clinicaltrials.gov registry. No language restriction was applied.We included blinded or unblinded randomized controlled trials that evaluated the effect of antifibrinolytics on perioperative blood loss in children that were 18 years of age or younger and undergoing scoliosis surgery.Two authors independently performed the data extraction. Primary outcomes were mortality and number of patients transfused. Secondary outcomes were number of patients transfused with allogeneic blood, amount of total blood transfused, total blood loss and adverse events. To assess heterogeneity we used the I(2) test and for the quantitative analysis we used a fixed-effect model.Six studies fulfilled the inclusion criteria. The total number of participants was 254, of whom 127 were allocated to placebo and 127 to antifibrinolytic drugs. Aprotinin, tranexamic acid and aminocaproic acid were evaluated in two studies each. All studies had placebo as the control group intervention. There were no deaths or any serious adverse events in any study, in either the active or the control group. The risk of being transfused was similar in patients receiving antifibrinolytic drugs or placebo. Antifibrinolytics drugs decreased the amount of blood transfused by 327 ml (95% CI -469.04 to -185.78) and the amount of blood loss by 427 ml (95% CI -602.51 to -250.56). There was no indication of publication bias, however, we cannot rule it out due to the small number of studies included.The effect of antifibrinolytic drugs on mortality could not be assessed. Antifibrinolytic drugs reduced blood loss and the amount of blood transfused in children undergoing scoliosis surgery; however, their effect on the number of children requiring blood transfusion remains unclear. Aprotinin, tranexamic acid and aminocaproic acid seem to be similarly effective.