Barden Jodie, Derry Sheena, McQuay Henry J, Moore R Andrew
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Cochrane Database Syst Rev. 2009 Oct 7(4):CD007355. doi: 10.1002/14651858.CD007355.pub2.
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.
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 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.
酮洛芬是一种用于治疗急慢性疼痛病症的非选择性非甾体抗炎药（NSAID）。右酮洛芬是（S）-对映体，被认为具有镇痛作用。理论上，右酮洛芬预期能以一半的剂量提供与酮洛芬等效的镇痛效果，从而减少胃肠道不良事件。
评估单剂量口服酮洛芬和右酮洛芬对成人急性术后疼痛的疗效、作用持续时间及相关不良事件。
我们检索了Cochrane中心对照试验注册库、医学期刊数据库、荷兰医学文摘数据库以及牛津疼痛缓解数据库，检索截至2009年8月的研究。
对成人中重度急性术后疼痛进行单剂量口服酮洛芬和右酮洛芬的随机、双盲、安慰剂对照试验。
两位综述作者独立评估试验质量并提取数据。提取疼痛缓解或疼痛强度数据，并转换为在4至6小时内疼痛缓解至少50%的参与者数量这一二分结果，据此计算相对危险度和需治疗人数以获益（NNT）。收集特定时间段内使用解救药物的参与者数量以及使用解救药物的时间，作为疗效的额外衡量指标。收集不良事件和退出试验的信息。
14项研究比较了主要为25毫克和50毫克剂量的酮洛芬（968名参与者）与安慰剂（520名参与者）。7项研究比较了主要为10毫克至25毫克剂量的右酮洛芬（681名参与者）与安慰剂（289名参与者）。研究报告质量良好，参与者在牙科、骨科、产科、妇科及普通外科手术后出现疼痛。牙科手术和其他类型手术的研究之间存在相当大的临床异质性，尤其是拇囊炎切除术，这限制了分析。酮洛芬剂量在12.5毫克至100毫克之间时，4至6小时内疼痛缓解至少50%的NNT为2.4至3.3。仅对于牙科研究，较高剂量时有疗效增加的趋势，NNT从12.5毫克时的2.4降至100毫克时的1.6。10/12.5毫克和20/25毫克剂量的右酮洛芬在4至6小时内疼痛缓解至少50%的NNT分别为3.2和3.6，无明显剂量反应。与安慰剂相比，使用酮洛芬和右酮洛芬的参与者使用解救药物的人数明显更少。使用酮洛芬时再次用药的中位时间约为5小时，使用右酮洛芬时为4小时。未证明右酮洛芬半剂量与酮洛芬具有预期的等效疗效。两种药物不良事件均不常见，且与安慰剂无显著差异。
25毫克至100毫克剂量的酮洛芬对中重度急性术后疼痛是一种有效的镇痛药，50毫克剂量时疼痛缓解至少50%的NNT为3.3。这与常用的非甾体抗炎药如布洛芬（400毫克剂量时NNT为2.5）和双氯芬酸（50毫克剂量时NNT为2.7）相似。作用持续时间约为5小时。右酮洛芬在10毫克至25毫克剂量范围内也有效，NNT为3.2至3.6。两种药物单剂量时耐受性良好。
