Acute Postoperative Pain In Adults Research Articles

Single dose oral gabapentin for established acute postoperative pain in adults.

Gabapentin is an antiepileptic drug, also used in the treatment of neuropathic pain, which is the subject of a Cochrane review, currently under revision. Its efficacy in treating established acute postoperative pain has not been demonstrated. To assess the efficacy and safety of single dose oral gabapentin compared with placebo in established acute postoperative pain using methods that permit comparison with other analgesics. We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database. Additional studies were sought from reference lists of retrieved articles and reviews. Clinical trials databases were searched for unpublished studies; clinical trial reports of several unpublished studies have been made public following litigation in the US. Single oral dose, randomised, double-blind, placebo-controlled trials of gabapentin for relief of established moderate to severe postoperative pain in adults. Studies were assessed for methodological quality and data extracted by two review authors independently. Numbers of participants with at least 50% of maximum possible total pain relief (TOTPAR) or summed pain intensity difference (SPID) with gabapentin or placebo were calculated and used to derive relative benefit (RB) or risk (RR), and number-needed-to-treat-to-benefit (NNT). Numbers of participants using rescue medication, and time to its use, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Four unpublished studies met inclusion criteria; in three, participants had pain following dental surgery, and one followed major orthopaedic surgery; 177 participants were treated with a single dose of gabapentin 250 mg, 21 with gabapentin 500 mg, and 172 with placebo. At least 50% pain relief over 6 hours was achieved by 15% with gabapentin 250 mg and 5% with placebo; giving a RB of 2.5 (95% CI 1.2 to 5.0) and an NNT of 11 (6.4 to 35). Significantly fewer participants needed rescue medication within 6 hours with gabapentin 250 mg than with placebo; NNT to prevent use 5.8. About one third of participants reported adverse events with both gabapentin 250 mg and placebo. No serious adverse events occurred with gabapentin. Gabapentin 250 mg is statistically superior to placebo in the treatment of established acute postoperative pain, but the NNT of 11 for at least 50% pain relief over 6 hours with gabapentin 250 mg is of limited clinical value and inferior to commonly used analgesics. Gabapentin 250 mg is not clinically useful as a stand-alone analgesic in established acute postoperative pain, though this is probably the first demonstration of analgesic effect of an antiepileptic in established acute pain.

Good Evidence Supports Ibuprofen as an Effective and Safe Analgesic for Postoperative Pain: A critical summary of Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev 2009;(3):CD001548.

Good Evidence Supports Ibuprofen as an Effective and Safe Analgesic for Postoperative Pain: A critical summary of Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev 2009;(3):CD001548.

Single dose oral diflunisal for acute postoperative pain in adults.

Diflunisal is a long-acting non-steroidal anti-inflammatory drug (NSAID) most commonly used to treat acute postoperative pain or chronic joint pain from osteoarthritis and rheumatoid arthritis. This review analyses the effectiveness and harm of different doses of diflunisal in the context of moderate to severe postoperative pain. To assess efficacy, duration of action, and associated adverse events of single dose oral diflunisal in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2010. Randomised, double blind, placebo-controlled trials of single dose orally administered diflunisal in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Nine studies in dental, orthopedic and gynaecological surgery met the inclusion criteria, testing doses of diflunisal from 125 mg to 1000 mg.For diflunisal 1000 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.1 (1.8 to 2.6) (6 studies, 391 participants); the NNT to prevent remedication within 6 hours was 1.9 (1.7 to 2.3), and within 12 hours was 2.2 (1.9 to 2.7) (6 studies, 409 participants). More participants experienced adverse events with diflunisal 100 mg than with placebo, but none were serious or led to withdrawal.For diflunisal 500 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.6 (2.1 to 3.3) (6 studies, 357 participants); the NNT to prevent remedication within 6 hours was 2.6 (2.1 to 3.4) (6 studies, 390 participants), and within 12 hours was 2.9 (2.3 to 4.0) (5 studies, 329 participants). Adverse events did not differ significantly from placebo. Diflunisal has an analgesic effect similar to other NSAIDs in single dose, but benefits from providing significant analgesia for about twelve hours. This property may be useful when regular dosing is needed, or when taking several doses of a shorter acting analgesic is impractical.

Single dose oral codeine, as a single agent, for acute postoperative pain in adults

Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants, mostly non-dental); the mean time to its use was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo; the difference was not significant and none were serious. Two adverse event withdrawals occurred with placebo. Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.

Good Evidence Supports Acetaminophen As an Effective and Safe Reliever of Acute Postoperative Pain

Good Evidence Supports Acetaminophen As an Effective and Safe Reliever of Acute Postoperative Pain

Increase in Quality, but Not Quantity, of Clinical Trials in Acute Pain: 1992 Versus 2007

The annual number of published clinical trials in acute postoperative pain in adults has changed little in 15 yr and, as a fraction of all clinical trials published in the six highest impact journals in anesthesiology, has actually decreased from 16% (95% confidence interval: 12-20) to 11% (95% confidence interval: 9-15). However, the methodological quality of reports has improved, with explicit statements on power analysis, allocation concealment, and specification of primary end points exceeding 90% of reports in 2007. There has been a shift in hypothesis interests away from neuraxial analgesia and toward multimodal analgesia.

Single dose oral fenbufen for acute postoperative pain in adults

Fenbufen is a non-selective non-steroidal anti-inflammatory drug (NSAID), used to treat acute and chronic painful conditions. There is no known systematic review of its use in acute postoperative pain. To assess efficacy, duration of action, and associated adverse events of single dose oral fenbufen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief database for studies to June 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered fenbufen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Searches identified only one study with (90 participants in total, 31 taking fenbufen). The study compared oral fenbufen 800 mg, fenbufen 400 mg, and placebo in participants with established postoperative pain. Fenbufen at both doses had apparent analgesic efficacy, but the numbers of participants was too small to allow sensible analysis. Gastrointestinal adverse events were noted in 4 of 15 participants taking fenbufen 800 mg. In the absence of evidence of efficacy for oral fenbufen in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes which are effective, there is no urgent research agenda for this particular drug.

Single dose oral rofecoxib for acute postoperative pain in adults.

Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke in a study of secondary prevention of adenoma recurrence. Further information is available at www.vioxx.com.Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor previously licensed for treating acute and chronic pain; it was associated with fewer gastrointestinal adverse events than conventional NSAIDs. An earlier Cochrane review (Barden 2005) showed that rofecoxib is at least as effective as conventional non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain. To assess the analgesic efficacy and adverse effects of rofecoxib in single oral doses for moderate and severe postoperative pain. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered rofecoxib in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Twenty new studies and seven from the earlier review met the inclusion criteria. Twenty-four studies were in dental surgery and three in other types of surgery. In total, 2636 participants were treated with rofecoxib 50 mg, 20 with rofecoxib 500 mg, and 1251 with placebo. The NNT for at least 50% pain relief over 4 to 6 hours with rofecoxib 50 mg was 2.2 (2.0 to 2.3) in all studies combined, 1.9 (1.8 to 2.0) in dental studies, and 6.8 (4.6 to 13) in other types of surgery. The median time to use of rescue medication was 14 hours for rofecoxib 50 mg and 2 hours for placebo. Significantly fewer participants used rescue medication following rofecoxib 50 mg than with placebo. Adverse events did not differ from placebo. Rofecoxib 50 mg (two to four times the standard daily dose for chronic pain) is an effective single dose oral analgesic for acute postoperative pain in adults, with a relatively long duration of action.

Single dose oral sulindac for acute postoperative pain in adults.

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral sulindac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. To assess the efficacy of single dose oral sulindac in acute postoperative pain, and any associated adverse events. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies up to June 2009. Randomised, double-blind, placebo-controlled clinical trials of oral sulindac for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. We planned to use area under the "pain relief versus time" curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. No studies were identified by the searches that examined oral sulindac in patients with established postoperative pain. In the absence of evidence of efficacy, at present, for oral sulindac in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.

Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 2.4 to 3.3. For dental studies only there was a trend to more efficacy at higher doses, with NNT decreasing from 2.4 at 12.5 mg to 1.6 at 100 mg. Dexketoprofen at doses of 10/12.5 mg and 20/25 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 3.2 and 3.6, with no obvious dose response. Significantly fewer participants used rescue medication with ketoprofen and dexketoprofen than placebo. The median time to remedication was about 5 hours with ketoprofen and 4 hours with dexketoprofen. The expected equivalent efficacy with a half dose of dexketoprofen compared to ketoprofen was not demonstrated.Adverse events were uncommon with both drugs, and not significantly different from placebo. Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 3.3 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 at 50 mg dose). Duration of action is about 5 hours. Dexketoprofen is also effective with NNTs of 3.2 to 3.6 in the dose range 10 mg to 25 mg. Both drugs were well tolerated in single doses.

Single dose oral nabumetone for acute postoperative pain in adults.

Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 1000 mg daily, and higher doses are not advised in older patients. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral nabumetone in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish whether drugs have analgesic properties. To assess the efficacy of single dose oral nabumetone in acute postoperative pain, and any associated adverse events. We searched The Cochrane Library (Issue 2, 2009), MEDLINE (May 2009); EMBASE via Ovid (May 2009); and the Oxford Pain Relief Database. Randomised, double-blind, placebo-controlled clinical trials of oral nabumetone for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with nabumetone and placebo experiencing at least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The 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 was also collected. No studies were identified by the searches that examined oral nabumetone in participants with established postoperative pain. In the absence of evidence of efficacy, at present, for oral nabumetone in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.

The Cochrane Database of Systematic Reviews ‐ Issue 3 2009

The Cochrane Database of Systematic Reviews ‐ Issue 3 2009

Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults.

Dexibuprofen (S(+)-ibuprofen) is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. It is an active isomer of ibuprofen. This review sought to evaluate the efficacy and safety of oral dexibuprofen in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. To assess efficacy, duration of action, and associated adverse events of single dose oral dexibuprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. Randomised, double blind, placebo-controlled clinical trials of oral dexibuprofen for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. In the single included study, both S(+)-ibuprofen (dexibuprofen, an active isomer of ibuprofen) 200 mg and 400 mg gave high levels of response, with 31/51 (61%) and 35/50 (70%) respectively having at least 50% pain relief over 4 to 6 hours, compared with 2/25 (8%) with placebo. The median time to additional analgesic use was 5.8 hours, 6.1 hours, and 1.8 hours respectively. The numbers of participants was too small to calculate NNTs with any meaning. The information from the single trial in acute postoperative pain suggests it to be a useful analgesic, but at doses not very different from racemic ibuprofen.

Single dose oral acemetacin for acute postoperative pain in adults

Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral acemetacin in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. To assess the efficacy of single dose oral acemetacin in acute postoperative pain, and any associated adverse events. We searched CENTRAL (Issue 2, 2009), MEDLINE via Ovid (1966 to May 2009); EMBASE via Ovid (1980 to May 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles. Randomised, double-blind, placebo-controlled clinical trials of oral acemetacin for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with acemetacin and placebo experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals. The 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 was also collected. No study fulfilled the inclusion criteria. In the absence of randomised evidence of efficacy for oral acemetacin in acute postoperative pain, we cannot, at present, make any conclusions regarding its effectiveness. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this kind and similar classes, there is no urgent research agenda for this drug.

Single dose oral diclofenac for acute postoperative pain in adults.

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on 'Single dose oral diclofenac for postoperative pain'. To assess single dose oral diclofenac for the treatment of acute postoperative pain. Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours for diclofenac 100 mg. Adverse events were reported at a similar rate to placebo, with no serious events. Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. Significantly more participants experienced at least 50% pain relief over 4 to 6 hours with diclofenac potassium than with diclofenac sodium. There was no significant difference between diclofenac and placebo in the incidence of adverse events.

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

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. 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. We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. 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. 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. 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 mainly mild to moderate in severity and incidence did not differ between groups. This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information.

Single dose oral naproxen and naproxen sodium for acute postoperative pain in adults.

Naproxen, a non-steroidal anti-inflammatory drug, is used to treat various painful conditions including postoperative pain, and is often administered as the sodium salt to improve its solubility. This review updates a 2004 Cochrane review showing that naproxen sodium 550 mg (equivalent to naproxen 500 mg) was effective for treating postoperative pain. New studies have since been published. To assess efficacy, duration of action, and associated adverse events of single dose oral naproxen or naproxen sodium in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to October 2008. Randomised, double blind, placebo-controlled trials of single dose orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over four to six hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. The original review included 10 studies with 996 participants. This updated review included 15 studies (1509 participants); 11 assessed naproxen sodium and four naproxen. In nine studies (784 participants) using 500/550 mg naproxen or naproxen sodium the NNT for at least 50% pain relief over four to six hours was 2.7 (95% CI 2.3 to 3.2). No dose response was demonstrated over the range 200/220 mg to 500/550 mg, but limited data was identified. Median time to use of rescue medication was 8.9 hours for naproxen 500/550 mg and 2.0 hours for placebo. Use of rescue medication was significantly less common with naproxen than placebo. Associated adverse events were generally of mild to moderate severity and rarely led to withdrawal. Doses equivalent to 500 mg and 400 mg naproxen administered orally provided effective analgesia to adults with moderate to severe acute postoperative pain. About half of participants treated with these doses experienced clinically useful levels of pain relief, compared to 15% with placebo, and half required additional medication within nine hours, compared to two hours with placebo. Associated adverse events did not differ from placebo.

Intravenous parecoxib for acute postoperative pain in adults.

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the efficacy and adverse effects of single dose parecoxib in studies of acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.

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

This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on 'Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain'. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. Area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 500 mg NNT 3.5 (2.7 to 4.8); 600 to 650 mg NNT 4.6 (3.9 to 5.5); 975 to 1000 mg NNT 3.6 (3.4 to 4.0). There was no dose response. Sensitivity analysis showed no significant effect of trial size or quality on this outcome.About half of participants needed additional analgesia over four to six hours, compared with about 70% with placebo. Five people would need to be treated with 1000 mg paracetamol, the most commonly used dose, to prevent one needing rescue medication over four to six hours, who would have needed it with placebo. Adverse event reporting was inconsistent and often incomplete. Reported adverse events were mainly mild and transient, and occurred at similar rates with 1000 mg paracetamol and placebo. No serious adverse events were reported. Withdrawals due to adverse events were uncommon and occurred in both paracetamol and placebo treatment arms. A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Peri‐operative ketamine for acute post‐operative pain: a quantitative and qualitative systematic review (Cochrane review)

Post-operative pain management is usually limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. The objective of this systematic review was to evaluate the effectiveness and tolerability of ketamine administered peri-operatively in the treatment of acute post-operative pain in adults. Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by hand searching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer AS, Lysaker, Norway) provided search results from their in-house database, PARDLARS. Randomized and controlled trials (RCTs) of adult patients undergoing surgery, being treated with peri-operative ketamine, placebo or an active control were considered for inclusion. Eighteen trials were excluded. Thirty-seven trials were included. Twenty-seven out of 37 trials found that peri-operative ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24-h patient-controlled analgesia (PCA) morphine consumption and post-operative nausea and vomiting (PONV). Adverse effects were mild or absent. In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.