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1.
Perioperative Opioid-sparing Strategies: Utility of Conventional NSAIDs in Adults.
Martinez, L, Ekman, E, Nakhla, N
Clinical therapeutics. 2019;(12):2612-2628
Abstract
PURPOSE Opioids have long been used to treat acute postsurgical and postprocedural pain; however, opioid-related adverse events (AEs) contribute to poor patient outcomes. In addition, perisurgical exposure to opioids can potentially increase the risk for opioid-use disorder. NSAIDs reduce pain and inflammation by a mechanism different from that of opioid analgesics and may be useful in reducing the need for opioid drugs as part of a multimodal analgesia strategy. We conducted this review to assess the effectiveness and tolerability of adjunctive conventional NSAIDs given systemically in the perioperative setting in terms of opioid-sparing effects observed postoperatively. METHODS Clinical trials published since 2000 that have assessed the opioid-sparing effects of conventional, nonselective NSAIDs were identified by a literature search using the PubMed search engine. Search terms were identified for the treatment of interest, the timing of the intervention, and the drugs of interest (NSAIDs). Data from studies that assessed opioid consumption outcomes with systemic NSAID administration were included in the review; data from studies in which NSAIDs were administered topically or via periarticular injection, local infiltration, or regional block were excluded. FINDINGS Upon full-text review of the search results, 32 studies were chosen for inclusion in this literature review. These studies included those that assessed diclofenac, ketorolac, ibuprofen, ketoprofen, dexketoprofen, flurbiprofen, lornoxicam, tenoxicam, meloxicam, and piroxicam. In studies in which NSAIDs were associated with opioid-sparing effects within the setting of patient-controlled analgesia, opioid use was reduced by 17%-∼50% with diclofenac, 9%-66% with ketorolac, 22%-46% with ibuprofen, 34%-66% with ketoprofen, 36%-50% with dexketoprofen, 38%-41% with tenoxicam, 36%-54% with lornoxicam, and ∼50% with flurbiprofen. No opioid-sparing effect was noted with meloxicam (1 study). The majority of studies that reported on pain-score changes revealed either pain reductions with NSAIDs versus placebo or similar pain scores between groups, indicating that NSAIDs did not compromise pain control. Although many studies found no difference in the prevalence of AEs in NSAID-treated patients compared with controls, several studies noted lower rates of nausea, vomiting, sedation, and pruritus with NSAIDs versus placebo. Conversely, NSAID-related AEs were few overall but included gastrointestinal bleeding, injection site reactions, transient oliguric renal failure, and dizziness. No surgery-related bleeding complications were observed. IMPLICATIONS NSAIDs have the potential to play an important role in reducing postoperative opioid requirements. Reducing the amount of opioids used could be expected to reduce opioid-related side effects and contribute to reversing the opioid epidemic.
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Adjuvants in clinical regional anesthesia practice: A comprehensive review.
Prabhakar, A, Lambert, T, Kaye, RJ, Gaignard, SM, Ragusa, J, Wheat, S, Moll, V, Cornett, EM, Urman, RD, Kaye, AD
Best practice & research. Clinical anaesthesiology. 2019;(4):415-423
Abstract
Adjuvants are medications that work synergistically with local anesthetics to help enhance the duration and quality of analgesia in regional techniques. Regional anesthesia has become more prevalent as evidence continues to show efficacy, enhancement of patient care, increased patient satisfaction, and improved patient safety. Practitioners in the perioperative setting need to not only be familiar with regional techniques but also the medications used for them. Some examples of adjuvant medications for regional techniques include dexamethasone, alpha 2 agonists such as clonidine and dexmedetomidine, midazolam, buprenorphine, NMDA antagonists, including ketamine and magnesium, neostigmine, sodium bicarbonate, epinephrine, and non-steroidal anti-inflammatory drugs. The aim of the present investigation, therefore, is to provide a comprehensive review of the most commonly used non-opioid adjuvants in clinical practice today. Regional adjuvants can improve patient safety, increase patient satisfaction, and enhance clinical efficacy. Future studies and best practice techniques can facilitate standardization of regional anesthesia adjuvant dosing when providing nerve blocks in clinical practice.
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3.
Ketorolac for postoperative pain in children.
McNicol, ED, Rowe, E, Cooper, TE
The Cochrane database of systematic reviews. 2018;(7):CD012294
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Abstract
BACKGROUND Children who undergo surgical procedures in ambulatory and inpatient settings are at risk of experiencing acute pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce moderate to severe pain without many of the side effects associated with opioids. However, NSAIDs may cause bleeding, renal and gastrointestinal toxicity, and potentially delay wound and bone healing. Intravenous administration of ketorolac for postoperative pain in children has not been approved in many countries, but is routinely administered in clinical practise. OBJECTIVES To assess the efficacy and safety of ketorolac for postoperative pain in children. SEARCH METHODS We searched the following databases, without language restrictions, to November 2017: CENTRAL (The Cochrane Library 2017, Issue 10); MEDLINE, Embase, and LILACS. We also checked clinical trials registers and reference lists of reviews, and retrieved articles for additional studies. SELECTION CRITERIA We included randomised controlled trials that compared the analgesic efficacy of ketorolac (in any dose, administered via any route) with placebo or another active treatment, in treating postoperative pain in participants zero to 18 years of age following any type of surgery. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We analyzed trials in two groups; ketorolac versus placebo, and ketorolac versus opioid. However, we performed limited pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE, and created a 'Summary of findings' table. MAIN RESULTS We included 13 studies, involving 920 randomised participants. There was considerable heterogeneity among study designs, including the comparator arms (placebo, opioid, another NSAID, or a different regimen of ketorolac), dosing regimens (routes and timing of administration, single versus multiple dose), outcome assessment methods, and types of surgery. Mean study population ages ranged from 356 days to 13.9 years. The majority of studies chose a dose of either 0.5 mg/kg (as a single or multiple dose regimen) or 1 mg/kg (single dose with 0.5 mg/kg for any subsequent doses). One study administered interventions intraoperatively; the remainder administered interventions postoperatively, often after the participant reported moderate to severe pain.There were insufficient data to perform meta-analysis for either of our primary outcomes: participants with at least 50% pain relief; or mean postoperative pain intensity. Four studies individually reported statistically significant reductions in pain intensity when comparing ketorolac with placebo, but the studies were small and had various risks of bias, primarily due to incomplete outcome data and small sample sizes.We found limited data available for the secondary outcomes of participants requiring rescue medication and opioid consumption. For the former, we saw no clear difference between ketorolac and placebo; 74 of 135 (55%) participants receiving ketorolac required rescue analgesia in the post-anaesthesia care unit (PACU) versus 81 of 127 (64%) receiving placebo (relative risk (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.00, P = 0.05; 4 studies, 262 participants). For opioid consumption in the PACU, we saw no clear difference between ketorolac and placebo (P = 0.61). For the time period zero to four hours after administration of the interventions, participants receiving ketorolac received 1.58 mg less intravenous morphine equivalents than those receiving placebo (95% CI -2.58 mg to -0.57 mg, P = 0.002; 2 studies, 129 participants). However, we are uncertain whether ketorolac has an important effect on opioid consumption, as the data were sparse and the results were inconsistent. Only one study reported data for opioid consumption when comparing ketorolac with an opioid. There were no clear differences between the ketorolac and opioid group at any time point. There were no data assessing this outcome for the comparison of ketorolac with another NSAID.There were insufficient data to allow us to analyze overall adverse event or serious adverse event rates. Although the majority of serious adverse events reported in those receiving ketorolac involved bleeding, the number of events was too low to conclude that bleeding risk was increased in those receiving ketorolac perioperatively. There was not a statistically significant increase in event rates for any specific adverse event, either in pooled analysis or in single studies, when comparing ketorolac and placebo. When comparing ketorolac with opioids or other NSAIDs, there were too few data to make any conclusions regarding event rates. Lastly, withdrawals due to adverse events were vary rare in all groups, reflecting the acute nature of such studies.We assessed the quality of evidence for all outcomes for each comparison (placebo or active) as very low, due to issues with risk of bias in individual studies, imprecision, heterogeneity between studies, and low overall numbers of participants and events. AUTHORS' CONCLUSIONS Due to the lack of data for our primary outcomes, and the very low-quality evidence for secondary outcomes, the efficacy and safety of ketorolac in treating postoperative pain in children were both uncertain. The evidence was insufficient to support or reject its use.
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Single-dose intravenous diclofenac for acute postoperative pain in adults.
McNicol, ED, Ferguson, MC, Schumann, R
The Cochrane database of systematic reviews. 2018;(8):CD012498
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BACKGROUND Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES To assess the analgesic efficacy and adverse effects of single-dose intravenous diclofenac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS We searched the following databases without language restrictions: the Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online), MEDLINE, and Embase on 22 May 2018. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA We included randomized trials that compared a single postoperative dose of intravenous diclofenac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data.Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, AEs, and for any cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related AEs. We performed a post hoc analysis of opioid-related AEs, to enable indirect comparisons with other analyses of postoperative analgesics.For subgroup analysis, we planned to analyze different doses and formulations of parenteral diclofenac separately.We assessed the overall quality of the evidence for each outcome using GRADE and created two 'Summary of findings' tables. MAIN RESULTS We included eight studies, involving 1756 participants undergoing various surgeries (dental, mixed minor, abdominal, and orthopedic), with 20 to 175 participants receiving intravenous diclofenac in each study. Mean study population ages ranged from 24.5 years to 54.5 years. Intravenous diclofenac doses varied among and within studies, ranging from 3.75 mg to 75 mg. Five studies assessed newer formulations of parenteral diclofenac that could be administered as an undiluted intravenous bolus. Most studies had an unclear risk of bias for several domains and a high risk of bias due to small sample size. The overall quality of evidence for each outcome was generally low for reasons including unclear risk of bias in studies, imprecision, and low event numbers.Primary outcomeThree studies (277 participants) produced a number needed to treat for an additional beneficial outcome (NNTB) for at least 50% of maximum pain relief versus placebo of 2.4 (95% confidence interval (CI) 1.9 to 3.1) over four hours (low-quality evidence). Four studies (436 participants) produced an NNTB of 3.8 versus placebo (95% CI 2.9 to 5.9) over six hours (low-quality evidence). No studies provided data for the comparison of intravenous diclofenac with another NSAID over four hours. At six hours there was no difference between intravenous diclofenac and another NSAID (low-quality evidence).Secondary outcomesFor secondary efficacy outcomes, intravenous diclofenac was generally superior to placebo and similar to other NSAIDs.For time to rescue medication, comparison of intravenous diclofenac versus placebo demonstrated a median of 226 minutes for diclofenac versus 80 minutes for placebo (5 studies, 542 participants, low-quality evidence). There were insufficient data for pooled analysis for comparisons of diclofenac with another NSAID (very low-quality evidence).For the number of participants using rescue medication, two studies (235 participants) compared diclofenac with placebo. The number needed to treat to prevent one additional harmful event (NNTp) (here, the need for rescue medication) compared with placebo was 3.0 (2.2 to 4.5, low-quality evidence). The comparison of diclofenac with another NSAID included only one study (98 participants). The NNTp was 4.5 (2.5 to 33) for ketorolac versus diclofenac (very low-quality evidence).The numbers of participants withdrawing were generally low and inconsistently reported (very low-quality evidence). Participant withdrawals were: 6% (8/140) diclofenac versus 5% (7/128) placebo, and 9% (8/87) diclofenac versus 7% (6/82) another NSAID for lack of efficacy; 2% (4/211) diclofenac versus 0% (0/198) placebo, and 3% (4/138) diclofenac versus 2% (2/129) another NSAID due to AEs; and 11% (21/191) diclofenac versus 17% (30/179) placebo, and 18% (21/118) diclofenac versus 15% (17/111) another NSAID for any cause.Overall adverse event rates were similar between intravenous diclofenac and placebo (71% in both groups, 2 studies, 296 participants) and between intravenous diclofenac and another NSAID (55% and 58%, respectively, 2 studies, 265 participants) (low-quality evidence for both comparisons). Serious and specific AEs were rare, preventing meta-analysis.There were sufficient data for a dose-effect analysis for our primary outcome for only one alternative dose, 18.75 mg. Analysis of the highest dose employed in each study demonstrated a relative benefit compared with placebo of 1.9 (1.4 to 2.4), whereas for the group receiving 18.75 mg, the relative benefit versus placebo was 1.6 (1.2 to 2.1, 2 studies). Compared to another NSAID, the high-dose analysis demonstrated a relative benefit of 0.9 (0.8 to 1.1), for the group receiving 18.75 mg, the relative benefit was 0.78 (0.65 to 0.93). For direct comparison of high dose versus 18.75 mg, the proportion of participants with at least 50% pain relief was 66% (90/137) for the high-dose arm versus 57% (77/135) in the low-dose arm. There were insufficient data for subgroup meta-analysis of different diclofenac formulations. AUTHORS' CONCLUSIONS The amount and quality of evidence for the use of intravenous diclofenac as a treatment for postoperative pain is low. The available evidence indicates that postoperative intravenous diclofenac administration offers good pain relief for the majority of patients, but further research may impact this estimate. Adverse events appear to occur at a similar rate to other NSAIDs. Insufficient information is available to assess whether intravenous diclofenac has a different rate of bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was insufficient information to evaluate the efficacy and safety of newer versus traditional formulations of intravenous diclofenac. There was a lack of studies in major and cardiovascular surgeries and in elderly populations, which may be at increased risk for adverse events.
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New Advances in Acute Postoperative Pain Management.
Mitra, S, Carlyle, D, Kodumudi, G, Kodumudi, V, Vadivelu, N
Current pain and headache reports. 2018;(5):35
Abstract
PURPOSE OF REVIEW Postoperative pain remains one of the most common challenges following inpatient and outpatient surgeries. With our advances in modern medicine, pain following surgical procedures still remains a challenge, though significant accomplishments have been made over the past few decades. This article highlights some of the promising new advances and approaches in postoperative pain management. RECENT FINDINGS Over the last decade, Enhanced Recovery after Surgery (ERAS) pathways and protocols are becoming the benchmark standards for enhancing postoperative recovery. Multimodal analgesia (MMA) is an essential component of such care. Further, in the wake of serious and persistent concern on the opioid epidemic in the USA, there has been a recent renewal of interest in non-opioid alternatives or adjuncts in controlling postoperative pain, often in the context of MMA. Intravenous (IV) acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), magnesium, ketamine, dexmedetomidine, liposomal bupivacaine, and newer neuraxial and peripheral regional techniques as well as patient-controlled modalities are gaining importance. Gabapentinoids have become popular but recent meta-analytic reviews have cast doubt on their routine use in perioperative settings. Among opioids, sublingual sufentanil, IV oxycodone, and iontophoretic transdermal fentanyl hold promise. Acupuncture and transcutaneous electrical nerve stimulation may be useful as adjuncts in MMA packages. Genetic testing, derivatives of herbal preparations, and an extended role of acute pain services may emerge as potential areas of importance in the future. There are, however, critical gaps in good quality evidence in many of the practice guideline recommendations. In the era of opioid epidemic, several lines of evidence have emerged to support non-opioid-based drugs and approaches along with a few newer opioid formulations for postoperative pain management, although more research is needed to find the right balance of efficacy and safety.
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Analgesic Effects of Locally Administered Ketorolac-based Analgesics After Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.
Chen, JY, Feng, IJ, Loh, EW, Wang, LK, Lin, CC, Tam, KW
The Clinical journal of pain. 2018;(6):577-584
Abstract
OBJECTIVE Reducing postoperative pain following breast surgery is crucial for rapid recovery and shortening hospital stay. Ketorolac, a nonsteroidal anti-inflammatory drug, has been used as a postoperative analgesic in many surgical procedures. We conducted a systemic review and meta-analysis on the efficacy of locally administered ketorolac-based analgesics in managing pain after breast surgery. METHODS We searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry for randomized control trials (RCTs) published up to September 2016. The primary outcome was pain level assessed using a visual analog scale (VAS) at 1 and 6 hours following breast surgery. RESULTS We reviewed 4 RCTs with 255 patients. For meta-analysis, VAS at 1 and 6 hours of 3 similar RCTs were compared. At 1 hour, VAS scores were significantly lower in patients administered a ketorolac solution [weighted mean difference (WMD)=-2.04; 95% confidence interval (CI): -3.08 to -1.00] or ketorolac-bupivacaine solution (WMD=-2.30; 95% CI, -4.07 to -0.54) than in controls. At 6 hours, the ketorolac-bupivacaine solution reduced VAS scores significantly (WMD=-1.40; 95% CI, -2.48 to -0.32) compared with controls. However, at 1 hour, the ketorolac solution was significantly more effective than the bupivacaine solution was (WMD=-1.70; 95% CI, -2.81 to -0.59). DISCUSSION The effects of ketorolac-based analgesics vary as per the surgery and disease type. Locally administered ketorolac-based analgesics decreased postoperative pain in breast surgery patients, and the effect of local ketorolac was better than local bupivacaine. Therefore, ketorolac-based analgesics demonstrate considerable local infiltration during pain management after breast surgery.
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Diclofenac Potassium in Acute Postoperative Pain and Dysmenorrhoea: Results from Comprehensive Clinical Trial Reports.
Moore, RA, Derry, S
Pain research & management. 2018;:9493413
Abstract
We compared the efficacy of diclofenac potassium in unpublished clinical study reports (CSRs) and published reports to examine publication bias, industry bias, and comprehensiveness. Novartis provided CSRs of randomised double-blind trials of diclofenac potassium involving postoperative patients following third molar extraction (3 trials, n=519), gynaecological surgery (3 trials, n=679), and dysmenorrhoea (2 trials, n=711) conducted in 1988-1990. Searches identified published reports of 6 trials. Information from 599/1909 patients was not published; trials with 846/1909 patients were published in a defunct journal. Greater methodological information in CSRs contributed to lesser risk of bias than published trials. Numbers needed to treat (NNT) from CSRs for all six postoperative trials for at least 50% of maximum pain relief over 6 h were 2.2 (95% confidence interval, 1.9-2.6) and 2.1 (1.8-2.4) for 50 and 100 mg diclofenac potassium, respectively. A Cochrane review of published trial data reported NNTs of 2.1 and 1.9, and one comprehensive analysis reported NNTs of 2.2 and 2.1, respectively. All analyses had similar results for patients remedicating within 8 h. No data from dysmenorrhoea CSRs appeared in a Cochrane review. CSRs provide useful information and increase confidence. Stable efficacy estimates with standard study designs reduce the need for updating reviews.
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Updates on Multimodal Analgesia for Orthopedic Surgery.
Pitchon, DN, Dayan, AC, Schwenk, ES, Baratta, JL, Viscusi, ER
Anesthesiology clinics. 2018;(3):361-373
Abstract
Pain control after orthopedic surgery is challenging. A multimodal approach provides superior analgesia with fewer side effects compared with opioids alone. This approach is particularly useful in light of the current opioid epidemic in the United States. Several new nonopioid agents have emerged into the market in recent years. New agents included in this review are intravenous acetaminophen, intranasal ketorolac, and newer nonsteroidal anti-inflammatory drugs, and the established medications ketamine and gabapentinoids. This article evaluates the evidence supporting these drugs in a multimodal context, including a brief discussion of cost.
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Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.
Esparza-Villalpando, V, Pozos-Guillén, A, Masuoka-Ito, D, Gaitán-Fonseca, C, Chavarría-Bolaños, D
Drug development research. 2018;(2):47-57
Abstract
Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect.
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10.
Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.
Gaskell, H, Derry, S, Wiffen, PJ, Moore, RA
The Cochrane database of systematic reviews. 2017;(5):CD007355
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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 dexketoprofen (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.