This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
Objective The purpose of our study was to perform a systematic review and meta-analysis of randomized, blinded, placebo-controlled studies that, following third-molar extraction, utilized either a combination of acetaminophen (600 mg) with codeine (60 mg) or ibuprofen (400 mg) for pain management. Design We searched PubMed, and the trial registry ClinicalTrials.gov databases with the keywords "molar or molars," "tooth or teeth," "extraction," and "pain." Selected studies were: (1) randomized, blinded, placebo controlled, (2) utilized either a single-dose combination acetaminophen (600 mg) with codeine (60 mg) (A/C) or ibuprofen, and (3) recorded standardized pain relief (PR) at 6 hours, or summed total pain relief over 6 hours (TOTPAR6). Of the 2,949 articles that were identified, 79 were retrieved for full-text analysis, and 20 of these studies met our inclusion criteria. Results For A/C, the weighted, standardized mean difference (SMD) for TOTPAR6 was 0.796 (95% confidence interval [CI], 0.597–0.995), P < .001, and for PR at 6 hours, the SMD was 0.0186 (0.007 to 0.378; P = .059), whereas for ibuprofen the SMD for TOTPAR6 was 3.009 (1.283 to 4.735; P = .001), and for PR at 6 hours, the SMD was 0.854 (95% CI, 0.712–0.996; P < .001). A SMD of 0.8 or larger is indicative of a large effect. Conclusions Our data indicate that single dose of ibuprofen (400 mg) is an effective pain reducer for post third molar extraction pain.
The purpose of this systematic review was to determine the analgesic efficacy and adverse effects of ibuprofen in comparison with other traditional non-opioid analgesics after third molar surgery. A total of 17 full texts were identified in PubMed and assessed using the Cochrane Collabo-ration’s risk of bias tool by two independent researchers. The sum of pain intensity differences, total pain relief, the overall evaluation, the number of patients requiring rescue analgesics, and adverse effects were collected. Data were analyzed using the Review Manager Software 5.3. for Windows. A total of 15 articles met the criteria. The qualitative and quantitative analysis showed that ibuprofen is more effective to relieve post-operative dental pain than acetaminophen, meclofenamate, aceclofenac, bromfenac, and aspirin. Moreover, ibuprofen and traditional non-steroidal anti-inflammatory drugs have a similar safety profile. In conclusion, ibuprofen 400 mg appears to have good analgesic efficacy and a safety profile similar to other traditional non-steroidal anti-inflammatory drugs after third molar surgery.
BACKGROUND: This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal 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. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions.
OBJECTIVES: To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level.
SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries.
SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain.
DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE, and created 'Summary of findings' tables.
MAIN RESULTS: This updated review included 24 studies; six additional studies added 1001 participants involved in comparisons of ketoprofen or dexketoprofen and placebo, with a 12% increase in participants taking ketoprofen and a 65% increase for dexketoprofen. Most participants (70%) were women. Dental studies typically involved young participants (mean age 20 to 30 years); other types of surgery involved older participants (mean age 37 to 68 years). Overall, we judged the studies at high risk of bias only for small size, which can lead to an overestimation of benefit.Ketoprofen doses ranged between 6.5 mg and 150 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual ketoprofen oral dose of 50 mg was 57%, compared to 23% with placebo, giving an NNT of 2.9 (95% CI 2.4 to 3.7) (RR 2.5, 95% CI 2.0 to 3.1; 594 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 1.8) than other surgery (NNT 4.2). The proportion of participants using rescue medication within six hours was lower with ketoprofen (32%) than with placebo (75%), giving a number needed to treat to prevent use of rescue medication (NNTp) of 2.3 (95% CI 1.8 to 3.1); 263 participants; 4 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with ketoprofen (18%) and placebo (11%) (RR 1.6, 95% CI 0.98 to 2.8; 342 participants; 5 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence).Dexketoprofen doses ranged between 5 mg and 100 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual dexketoprofen oral dose of 20 mg or 25 mg was 52%, compared to 27% with placebo, giving an NNT of 4.1 (95% CI 3.3 to 5.2) (RR 2.0, 95% CI 1.6 to 2.2; 1177 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 2.7) than other surgery (NNT 5.7). The proportion of participants using rescue medication within six hours was lower with ketoprofen (47%) than placebo (69%), giving an NNTp of 4.7 (95% CI 3.3 to 8.0); 445 participants; 5 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with dexketoprofen (14%) and placebo (10%) (RR 1.4, 95% CI 0.89 to 2.2; 536 participants, 6 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence).
AUTHORS' CONCLUSIONS: 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 2.9 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 for 50 mg dose). Dexketoprofen is also effective with an NNT of 4.1 in the dose range 10 mg to 25 mg. Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual. Both drugs were well tolerated in single doses.
While a large number of studies has examined the efficacy of opioid-sparing analgesics in adult surgical populations, fewer studies are available to guide postoperative pain treatment in pediatric patients. We systematically reviewed available publications on the use of systemic nonopioid agents for postoperative analgesia in pediatric surgical populations. A comprehensive literature search identified meta-analyses and randomized controlled trials (RCTs) assessing the effects of systemic, nonopioid agents on postoperative narcotic requirements or pain scores in pediatric surgical populations. If a meta-analysis was located, we summarized its results and any RCTs published after it. We located and reviewed 11 acetaminophen RCTs, 1 nonsteroidal anti-inflammatory drug (NSAID) meta-analysis, 2 NSAID RCTs, 1 dexamethasone meta-analysis, 3 dexamethasone RCTs, 2 ketamine meta-analyses, 5 ketamine RCTs, 2 gabapentin RCTs, 1 clonidine meta-analysis, 3 magnesium RCTs, 2 dexmedetomidine meta-analyses, and 1 dextromethorphan RCT. No meta-analyses or RCTs were found assessing the perioperative efficacy of intravenous lidocaine, amantadine, pregabalin, esmolol, or caffeine in pediatric surgical patients. The available evidence is limited, but suggests that perioperative acetaminophen, NSAIDs, dexamethasone, ketamine, clonidine, and dexmedetomidine may decrease postoperative pain and opioid consumption in some pediatric surgical populations. Not enough, or no, data exist from which to draw conclusions on the perioperative use of gabapentin, magnesium, dextromethorphan, lidocaine, amantadine, pregabalin, esmolol, and caffeine in pediatric surgical patients. Further pharmacokinetic and pharmacodynamics studies to establish both the clinical benefit and efficacy of nonopioid analgesia in pediatric populations are needed.
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: Dipyrone (metamizole) is a nonsteroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in other countries because of an association with life-threatening blood disorders. This review replaces a 2010 Cochrane review that has been withdrawn.
OBJECTIVES: To assess the analgesic efficacy and associated adverse events of single dose dipyrone for moderate to severe acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS to 11 August 2015; the Oxford Pain Relief Database; two clinical trial registries; and the reference lists of articles.
SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials of single dose dipyrone for relief of established moderate to severe postoperative pain in adults. We accepted oral, rectal, intramuscular, and intravenous routes of administration.
DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used summed total pain relief or pain intensity difference (TOTPAR or SPID) over four to six hours to calculate the number of participants achieving at least 50% pain relief. From derived results, we calculated the risk ratio and number needed to treat for an additional beneficial outcome (NNT), with 95% confidence intervals (CI), for one participant to experience at least 50% pain relief over four to six hours compared to placebo. We looked at use of rescue medication and time to use of rescue medication as additional measures of efficacy. We also looked for information on adverse events and withdrawals.
MAIN RESULTS: We included eight studies, involving 809 participants, comparing oral dipyrone 500 mg (143 participants), oral dipyrone 1000 mg (57 participants), and intramuscular dipyrone 2000 mg (35 participants) with placebo (236 participants). In addition to placebo, all studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen; 338 participants). Seven studies used the oral route of administration, and one study used the intramuscular route. The mean age ranged from 23 to 62 years. Six studies included both men and women, and two studies included only women. All the studies were small, but were otherwise of moderate to good quality.Over 70% of participants experienced our primary outcome of at least 50% pain relief over four to six hours with oral dipyrone 500 mg compared to 30% with placebo (five studies, 288 participants; NNT 2.4 (95% CI 1.8 to 3.1)) (moderate quality evidence). There were insufficient data to assess other doses or routes of administration of dipyrone.Fewer participants needed rescue medication within four to six hours with dipyrone 500 mg than with placebo (7% with dipyrone versus 34% with placebo; four studies, 248 participants) (low quality evidence). The data on numbers of participants experiencing any adverse event was inconsistently reported and no analysis was possible. No serious adverse events or adverse event withdrawals were reported (very low quality evidence). There were too few data to compare dipyrone directly with other active treatments.
AUTHORS' CONCLUSIONS: Based on very limited information, a single dose of dipyrone 500 mg provides good pain relief to about 70% of people treated, compared to about 30% with placebo. For every five people given dipyrone 500 mg, two people would experience this level of pain relief over four to six hours who would not have done with placebo, and fewer people would need rescue medication. We were unable to compare dipyrone directly with other active treatments, or to assess the effects of different doses or routes of administration, or the number of participants experiencing adverse events, because of insufficient data and inadequate reporting.
BACKGROUND: Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'.
OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015.
SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects.
MAIN RESULTS: This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast-acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence).
AUTHORS' CONCLUSIONS: Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.
This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
