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

 

Abstract

Background

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.

Objectives

To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults.

Search methods

We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009.

Selection criteria

Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain.

Data collection and analysis

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.

Main results

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.

 

Plain language summary

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

A single dose of ketoprofen 25 mg to 100 mg provides a high level of pain relief to 60% to 70% of those with moderate or severe postoperative pain. It has similar efficacy to other commonly used analgesics at standard doses, including ibuprofen and naproxen, with a duration of action around 5 hours. Single dose dexketoprofen at 10 mg to 25 mg provides a high level of pain relief to 45% to 50% of patients for about 4 hours. Adverse events were generally mild to moderate in severity, and no more common with either drug than with placebo in these singe dose studies.

 

摘要

背景

單一劑量口服ketoprofen和dexketoprofen於成人急性手術後疼痛

Ketoprofen是一種非選擇性非類固醇消炎藥(NSAID)用於治療急性和慢性疼痛的狀況。Dexketoprofen是右旋(S)對映體，它被認為是提供鎮痛。理論上半劑量的dexketoprofen被預期將提供相當於ketoprofen的鎮痛，因而減少了胃腸道副作用。

目標

為了評估單一劑量口服ketoprofen 和 dexketoprofen在成人急性手術後疼痛治療效果，作用時間，和所有相關的副作用。

搜尋策略

我們檢索Cochrane CENTRAL，MEDLINE，EMBASE和Oxford Pain Relief Database 來進行研究至2009年8月。

選擇標準

口服單一劑量ketoprofen 和 dexketoprofen緩解成人急性中度至重度術後疼痛的隨機，雙盲，安慰劑對照的臨床試驗。。

資料收集與分析

兩位獨立審查者評估列入審查試驗的品質，並擷取數據。疼痛緩解或疼痛強度的數據擷取並轉換到受試者4至6個小時至少有50 ％的疼痛緩解的兩分歧結果，而計算相對風險(RR)和numberneededtotreattobenefit (NNT)。受試者需使用拯救鎮痛藥物在特定時間內的人數，使用救援鎮痛藥的時間點，被認為是需要額外措施的效果。副作用的訊息和退出研究的人數也被蒐集。

主要結論

14個研究比較Ketoprofen (968位受試者)，主要是在25毫克和50毫克與安慰劑相比較(520位受試者)。7項研究比較dexketoprofen(681人位受試者)，主要是在10毫克至25毫克與安慰劑相比較(289位受試者)。研究報告的品質是夠水準的，而研究是追蹤受試者的牙科，骨科，產科，婦科和一般外科手術後的疼痛。臨床研究牙科及其他類型的手術，有相當大的異質性，特別是拇指滑液囊腫切除術，限制了分析. Ketoprofen在劑量為12.5毫克和100毫克，產生至少50％的緩解疼痛超過4至6個小時的NNTs為2.4 到3.3。對牙科研究只存在一種趨勢，在更高劑量下有更好的療效，與NNT在12.5毫克從2.4下降為至100毫克1.6。Dexketoprofen 的劑量10/12.5毫克和20/25 毫克，產生至少50％的緩解疼痛超過4至6個小時NNTs的3.2和3.6，而沒有明顯的劑量反應。服用ketoprofen 和dexketoprofen來和安慰劑組相比，很明顯的受試者使用較少的救援藥物。ketoprofen再重新服藥的中位數時間為約5小時，而dexketoprofen 則為4小時。預期中的效果，在半劑量dexketoprofen相當於ketoprofen不是明顯的.兩種藥物的副作用都很少見，與安慰劑組相比並沒有顯著不同。

作者結論

Ketoprofen 的劑量在25毫克至100毫克在對中度至重度急性術後疼痛是一種有效的止痛藥。在50毫克劑量下，在至少50％的疼痛緩解，NNT病人數是3.3。這和普遍使用的NSAIDs是類似，如ibuprofen(NNT在劑量400毫克為2.5)和diclofenac(NT在劑量50毫克為2.7)。藥效持續時間約5小時。Dexketoprofen也是有效的，在劑量10毫克至25毫克，NNTs 3.2到3.6範圍。這兩種藥物單一劑量的耐受性都是良好的。

翻譯人

本摘要由三軍總醫院詹舜名翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

單一劑量口服ketoprofen和dexketoprofen於成人急性手術後疼痛：單一劑量ketoprofen 25毫克至100毫克提供中度或重度術後疼痛患者，一個高水準的60％至70％的疼痛減輕。它與其他常用止痛藥的標準劑量，包括ibuprofen和naproxen，也有類似的療效，其藥效持續時間約5小時。單一劑量dexketoprofen在10毫克至25毫克對患者提供一個高水準的45％至50％疼痛減輕，時間持續約4小時。副作用一般是輕度至中度的嚴重程度，而兩種藥物單一劑量副作用與安慰劑相比，也沒有更常見。