Single dose oral codeine, as a single agent, for acute postoperative pain in adults.
BACKGROUND
Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription.


OBJECTIVE
To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain.


METHODS
We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009.


METHODS
Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults.


METHODS
Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected.


RESULTS
Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants, mostly non-dental); the mean time to its use was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo; the difference was not significant and none were serious. Two adverse event withdrawals occurred with placebo.


CONCLUSIONS
Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.
Derry
Sheena
S
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Moore
R Andrew
RA
McQuay
Henry J
HJ
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D003061:Codeine / Q000008:administration & dosage*; D006801:Humans; D010149:Postoperative Pain / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000701:Analgesics, Opioid; D003061:Codeine
Clin Pharmacol Ther. 1988 May;43(5):529-35
3365916
Control Clin Trials. 1996 Feb;17(1):1-12
8721797
BMJ. 1997 Sep 13;315(7109):635-40
9310564
Pharmacotherapy. 1986 Sep-Oct;6(5):205-10
3540870
Clin Ther. 1987;9(6):578-84
3326676
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD004233
18843655
Cochrane Database Syst Rev. 2009 Jan 21;(1):CD001547
19160199
Pain. 1998 Dec;78(3):209-216
9870574
Pain. 1996 Aug;66(2-3):229-37
8880845
Pharmacotherapy. 1982 May-Jun;2(3):162-7
6763202
J Clin Pharmacol. 1998 Jun;38(6):554-60
9650546
Clin Pharmacol Ther. 1987 Dec;42(6):634-40
3690941
Clin Pharmacol Ther. 1987 Oct;42(4):374-80
3311548
J Clin Pharmacol. 1984 Nov-Dec;24(11-12):486-92
6392354
Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004309
19370600
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD004602
18843665
Pain. 2005 Aug;116(3):322-331
15979792
Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004234
19160232
Br Med J (Clin Res Ed). 1988 May 7;296(6632):1313-6
3133061
Lancet. 1999 Nov 27;354(9193):1896-900
10584742
BMJ. 1995 Feb 18;310(6977):452-4
7873954
Cochrane Database Syst Rev. 2009 Jul 08;(3):CD001548
19588326
Curr Ther Res Clin Exp. 1976 Jan;19(1):58-65
812666
J Clin Pharmacol. 1984 Jan;24(1):35-42
6368614
Pain. 2004 Jan;107(1-2):86-90
14715393
J R Soc Med. 1982 Sep;75(9):705-8
7120254
Postgrad Med J. 2005 Mar;81(953):155-60
15749790
Pharmacotherapy. 1986 Sep-Oct;6(5):211-8
3540871
Cochrane Database Syst Rev. 2009 Oct 07;(4):CD004604
19821329
Ann Intern Med. 1987 Aug;107(2):224-33
3300460
Clin Ther. 1987;9(6):585-93
3326677
J Clin Pharmacol. 1980 Apr;20(4):243-9
6991540
Eur J Clin Invest. 2003 Nov;33 Suppl 2:17-22
14641552
Clin Pharmacol Ther. 1988 Jun;43(6):663-7
3288432
J Med. 1985;16(4):439-52
3913726
Pharmacotherapy. 1983 Sep-Oct;3(5):299-303
6359083
J Clin Pharmacol. 1984 Feb-Mar;24(2-3):96-102
6371063
J Oral Maxillofac Surg. 1990 Aug;48(8):785-90
2197381
Curr Med Res Opin. 1983;8(7):481-6
6354602
Pain. 2001 Mar;91(1-2):189-94
11240091
Pain. 1997 Jan;69(1-2):127-30
9060022
Pain. 1996 Aug;66(2-3):239-46
8880846
Pain. 1997 Feb;69(3):287-294
9085303
Int J Clin Pharmacol Ther Toxicol. 1981 Apr;19(4):152-7
7021431
Am J Med. 1988 May 20;84(5A):16-22
3287907
Pain. 1997 Feb;69(3):311-315
9085306
Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004768
19370609
Oral Surg Oral Med Oral Pathol. 1993 May;75(5):539-46
8387662
Curr Med Res Opin. 1978;5(7):525-35
359245
Eur J Clin Pharmacol. 1986;31(3):355-8
3792434
Pain. 1997 Aug;72(1-2):95-7
9272792