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

 

Abstract

Background

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.

Objectives

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.

Search methods

We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.

Authors' conclusions

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.

 

Plain language summary

Single dose oral paracetamol (acetaminophen) plus codeine for postoperative pain relief in adults

Pain is commonly experienced after surgical procedures, and is not always well controlled. Combining analgesics from different classes has the potential to provide adequate pain relief with reduced dose-dependent adverse events. This review assessed data from twenty-six studies comparing paracetamol plus codeine with placebo, and fourteen studies comparing paracetamol plus codeine with the same dose of paracetamol alone. The combination provided effective pain relief for about 40% of participants experiencing moderate to severe pain after an operation with 600 to 650 mg paracetamol plus 60 mg codeine, the dose most commonly used in these studies, and about 50% of participants with 800 to 1000 mg paracetamol plus 60 mg codeine, the dose most commonly used in clinical practice. The addition of codeine provided effective pain relief to about 10% more participants than the same dose of paracetamol alone. These single dose studies did not associate paracetamol plus codeine with any serious side effects.

 

摘要

背景

單一劑量paracetamol(acetaminophen)有或沒有合併codeine作為手術後止痛

這是一個Cochrane 回顧在 1998年第4期出版的更新版本。結合從不同分級的藥品，不同的作用模式，有較好的機會來提供可能達到理想的療效和耐受性，使用每種藥物較低的劑量來達到同樣程度的疼痛緩解。以前，我們的結論是，paracetamol加上 codeine 提供了更多的疼痛緩解，但也增加副作用。至今新的研究已經出版。本次回顧試圖評估paracetamol 加上codeine 的有效性和安全性，並採用最新數據，來比較與其他類似止痛藥的結果評價。

目標

評估單一劑量口服paracetamol 與codeine合併使用對急性手術後疼痛的效果及是否因codeine 成分而提高療效，以及相關的副作用。

搜尋策略

我們搜查CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database 2008年10月做此更新。

選擇標準

隨機，雙盲設計，安慰劑組控制的試驗，將paracetamol與codeine合併使用，來與單獨使用安慰劑或相同劑量的paracetamol，來比較在成人急性手術後疼痛緩解的效果。

資料收集與分析

資料分別由二個回顧者擷取而且試驗是有品質保證的。總合的痛苦強度和疼痛緩解被擷取和轉換成二分訊息產生使患者獲得至少50% 的止痛的病患數。使用這計算對一位病患在4 – 6小時與安慰劑組別作比較，獲得至少50% 疼痛緩解的相對好處和需要治療數目。副作用使用計算相對風險和需要傷害的數目(NNH)。

主要結論

26項試驗，共2295受試者，納入paracetamol 加上codeine與安慰劑作比較。paracetamol 800到1000 毫克加上 codeine 60 毫克結果有明顯的劑量反應，在四到六小時內至少減輕50% 疼痛的NNT 是2.2 (95% 信賴區間3.8 – 5.4) ，而paracetamol 600到650 毫克加上 codeine 60 毫克NNT是3.9 (2.9 – 4.5) ，而paracetamol 300 毫克加上codeine 30 毫克NNT是 6.9 (4.8 – 12) 。需使用救援藥物在paracetamol加上codeine組別是在4小時這時間點，而在安慰劑組別是在2小時這時間點。在paracetamol 600毫克加上codeine 60 毫克4到6小時避免再次給藥NNT為 5.6(4.0至9.0)。輕度到中度副作用在paracetamol 加上codeine組比安慰劑組增加。14項研究，共926位受試者，納入在比較paracetamol 加 codeine與單獨相同劑量的paracetamol。加入codeine提高受試者在4至6小時，10至15％的人數達到至少50％的緩解疼痛的比例，增加受試者使用救援藥物時間約1小時，並減少受試者需使用救援藥物的比例約15 ％(NNT，避免再次給藥 6.9(4.2至19)。副作用主要是輕度至中度嚴重程度而發生率在不同族群之間並沒有不相同。

作者結論

此更新回顧證實了以前paracetamol加上codeine在臨床上提供約50％的患者在中度至重度手術後疼痛約50％疼痛的緩解 ，而安慰劑緩解疼痛小於20％。新的資訊顯示合併使用，與相同劑量的paracetamol相比，延長止痛持續時間約一小時。在更高劑量，更多的受試者有的充分緩解疼痛，但現有的資料量在1000毫克paracetamol加60codeine毫克方面是很少的，而且資訊訊息是有限的。

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

疼痛是外科手術之後常見的經驗，而且大部分不是控制的很好。結合不同種類止痛藥有可能提供足夠的疼痛緩解，同時降低劑量依賴性的不良反應。本次回顧評估26個研究是關於paracetamol加codeine與安慰劑比較，而14個研究是關於paracetamol加codeine與相同劑量的paracetamol比較。共同使用600到650毫克paracetamol加60毫克codeine這2種藥物在受試者手術後中度至重度疼痛，提供了約40％疼痛的緩解，是在這些研究中最常用的劑量，約50％的受試者使用800到1000毫克paracetamol加60毫克codeine，是在臨床使用上最常用的劑量。加上codeine提供了受試者比單獨使用相同劑量paracetamol，有更多有效的緩解疼痛約10％。這些單一劑量研究與paracetamol加codeine任何嚴重的副作用沒有關聯性。