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Single dose oral ibuprofen plus codeine for acute postoperative pain in adults

  1. Sheena Derry,
  2. Samuel M Karlin,
  3. R Andrew Moore*

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 28 FEB 2013

DOI: 10.1002/14651858.CD010107.pub2


How to Cite

Derry S, Karlin SM, Moore RA. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010107. DOI: 10.1002/14651858.CD010107.pub2.

Author Information

  1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

*R Andrew Moore, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. andrew.moore@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 28 MAR 2013

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This is not the most recent version of the article. View current version (05 FEB 2015)

 
Characteristics of included studies [ordered by study ID]
Cooper 1982

MethodsRandomised, double-blind, 6 parallel groups. Single oral dose

Medication administered when baseline pain reached a moderate to severe intensity

Pain assessed at 0, 1, 2, 3, 4 hours


ParticipantsSurgical removal of 1 to 4 impacted third molars

N = 249

M = 83, F = 166

Mean age 23 years


InterventionsIbuprofen + codeine 400/60 mg, n = 41

Ibuprofen 400 mg, n = 38

Aspirin/codeine 650 mg/60 mg, n = 45

Aspirin 650 mg, n = 38

Codeine 60 mg, n = 41

Placebo, n = 46


OutcomesPI: standard 4-point scale

PR: standard 5-point scale

PGE: standard 5-point scale

Use of rescue medication

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5

Rescue medication allowed after 1 hour


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Low riskPharmaceutical company held randomisation code and packaged bottles, which were identified by sequential code number only

Blinding of participants and personnel (performance bias)
All outcomes
Low riskTablets "appeared identical for every patient"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskTablets "appeared identical for every patient"

SizeHigh risk< 50 participants per treatment group

Daniels 2011

MethodsRandomised, double-blind, 5 parallel groups. Single oral dose

Medication administered when baseline pain reached a moderate to severe intensity, and ≥ 50/100 mm

Pain assessed at baseline then 0.25, 0.5, 0.75, 1, 1.5, 2 hours and hourly to 12 hours


ParticipantsSurgical removal of ≥ 3 impacted third molars (2 mandibular)

N = 678

M = 271, F = 407

Mean age 20 years


InterventionsIbuprofen 400 mg + codeine 25.6 mg, n = 169
Paracetamol 1,000 mg + codeine 30 mg, n = 113
Ibuprofen 200 mg + paracetamol 500 mg, n = 173
Ibuprofen 400 mg + paracetamol 1000 mg, n = 168
Placebo, n = 55


OutcomesPI: standard 4-point scale

PR: standard 5-point scale

PGE: standard 5-point scale

Use of rescue medication

Adverse events

Withdrawals


NotesOxford Quality Score: R2, DB2, W1. Total = 5/5

Rescue medication (tramadol if < 4 hours, paracetamol/hydrocodone if 4 hours+) allowed after 1.5 hours


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"computer-generated system"

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Each treatment consisted of 2 white tablets of a similar size and was administered as a single dose taken with approximately 300 mL of water"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Each treatment consisted of 2 white tablets of a similar size and was administered as a single dose taken with approximately 300 mL of water"

SizeUnclear risk50 to 199 participants per treatment arm

Frame 1986

MethodsRCT, DB, single oral dose, parallel groups

Medication administered when baseline pain reached a moderate to severe intensity
Assessed at 0, 1, 2, 3, 4, 5 hours


ParticipantsSurgical removal of impacted third molar
N = 135

M/F "balanced" but numbers not provided
Mean age 24 years


InterventionsIbuprofen 200 mg + codeine 15 mg, n = 32

Ibuprofen 400 mg + codeine 30 mg, n = 26

Ibuprofen 800 mg + codeine 60 mg, n = 26

Aspirin 600 mg, n = 25
Placebo n = 26


OutcomesPI: non-standard 9-point scale
PR: standard 5-point scale
Global assessment (no scale reported)

Use of rescue medication
Adverse events

Withdrawals


NotesOxford Quality Score: R = 1, DB = 2, W = 1. Total = 4/5

Rescue medication (paracetamol) allowed after 2 h


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Low riskSealed sachets

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"aspirin specially formulated to match the other drugs"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"aspirin specially formulated to match the other drugs"

SizeHigh risk< 50 participants per treatment arm

McQuay 1989

MethodsRCT, DB, 2-group cross-over, multiple dose (data reported for first dose)

Medication administered when baseline pain reached a moderate to severe intensity
Assessed at 0, 0.5, 1, 2, 3, 4, 5, 6 hours


ParticipantsSurgical removal of impacted mandibular third molar (one at each phase of cross-over)

N = 25
M = 6, F = 19
Mean age 24 years


InterventionsIbuprofen 400 mg + codeine 20 mg, n = 25 (24 analysed)
Ibuprofen 400 mg, n = 25 (23 analysed)


OutcomesPI: standard 4-point scale and 100 mm VAS

PR: standard 5-point scale and 100 mm VAS

PGE: standard 5-point scale

Adverse events

Withdrawals


NotesOxford Quality Score: R = 1, DB = 2, W = 1. Total = 4/5

Second dose available for inadequate pain relief


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"The white tablets were identifiable only by the patient and treatment numbers"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"The white tablets were identifiable only by the patient and treatment numbers"

SizeHigh risk< 50 participants per treatment arm

Petersen 1993

MethodsRCT, DB, 2-group cross-over, 2-dose (data reported for first dose) (Due to carryover effects data analysed as parallel study using first phase only)

Medication administered when baseline pain reached a moderate to severe intensity
Assessed at 0, 0.5, 1, 2, 3, 4, 5, 6 hours


ParticipantsSurgical removal of impacted mandibular third molar (one at each phase of cross-over)

N = 60
M = 38, F = 22
Mean age 23 years


InterventionsIbuprofen 400 mg + codeine 60 mg, n = 29
Ibuprofen 400 mg, n = 31


OutcomesPI: 100 mm VAS

Adverse events for both doses

Withdrawals


NotesOxford Quality Score: R = 1, DB = 2, W = 1. Total = 4/5

Second dose available after 2 hours for inadequate pain relief


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"All tablets were of identical appearance"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"All tablets were of identical appearance"

SizeHigh risk< 50 participants per treatment arm

Sunshine 1987

MethodsRandomised, double-blind, 5 parallel groups. Single oral dose

Medication administered when baseline pain reached a moderate to severe intensity

Pain assessed at 0, 0.5, 1, 2, 3, 4 hours


ParticipantsEpisiotomy, Caesarian section or gynaecological operations

N = 195

All F

Mean age 26 years


InterventionsIbuprofen + codeine 200/30 mg, n = 40

Ibuprofen + codeine 400/60 mg, n = 40

Ibuprofen 40 mg, n = 38

Codeine 60 mg, n = 37

Placebo, n = 40


OutcomesPI: standard 4-point scale

PR: standard 5-point scale

Use of rescue medication

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5

Rescue medication allowed after 1 hour


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"All unit doses were identical in appearance and packaging"

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"All unit doses were identical in appearance and packaging"

SizeHigh risk< 50 participants per treatment arm

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Carlos 1989Short abstract

Cater 1985Participants remedicating not correctly analysed (diaries continued)

Giles 1985Did not state which scale was used

Giles 1986Inappropriate study design - data from patients remedicating were not handled correctly

Hellman 1992No suitable (placebo or same dose of ibuprofen alone) comparator

McQuay 1992No suitable (placebo or same dose of ibuprofen alone) comparator

Norman 1985Participants remedicating not correctly analysed (diaries continued)

Walton 1990Medication administered preoperatively

 
Comparison 1. Ibuprofen 400 mg + high dose codeine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with ≥ 50% pain relief4443Risk Ratio (M-H, Fixed, 95% CI)4.09 [2.82, 5.93]

 2 Participants with any adverse event4443Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.84, 1.66]

 
Comparison 2. Ibuprofen + codeine (all doses) versus same dose of ibuprofen alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with ≥ 50% pain relief3204Risk Ratio (M-H, Fixed, 95% CI)1.26 [1.01, 1.57]