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Cochrane Database of Systematic Reviews

Paracetamol (acetaminofeno) o fármacos antiinflamatorios no esteroideos, solos o combinados, para el alivio del dolor de la otitis media aguda en niños

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Information

DOI:
https://doi.org/10.1002/14651858.CD011534.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 15 December 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Acute Respiratory Infections Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Alies Sjoukes

    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

  • Roderick P Venekamp

    Julius Center for Health Sciences and Primary Care & Department of Otorhinolaryngology, University Medical Center Utrecht, Utrecht, Netherlands

  • Alma C van de Pol

    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

  • Alastair D Hay

    Centre for Academic Primary Care, NIHR School for Primary Care Research, School of Social and Community Medicine, Unversity of Bristol, Bristol, UK

  • Paul Little

    Primary Care and Population Sciences, Faculty of Medicine, Aldermoor Health Centre, University of Southampton, Southampton, UK

  • Anne GM Schilder

    evidENT, Ear Institute, Faculty of Brain Sciences, University College London, London, UK

  • Roger AMJ Damoiseaux

    Correspondence to: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

    [email protected]

    [email protected]

Contributions of authors

Protocol drafted by: AS, RPV, ACvdP, AGMS, RAMJD
Screening search results: AS, RPV
Extracting data: AS, RPV
Assessing risk of bias: AS, RPV
Entering data into RevMan: AS, RPV
Carrying out analysis: AS, RPV
Interpreting the analysis: all authors
Writing the review: all authors
General advice on the review: all authors

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • The Netherlands Organisation for Health Research and Development (ZonMw), Netherlands.

    The authors of this review received a grant from the The Netherlands Organisation for Health Research and Development (ZonMw) to conduct a pragmatic, cluster‐randomised clinical trial on pain management for children with AOM in primary care. This trial is currently ongoing.

  • NIHR Research Professorship Award, UK.

    Professor Anne Schilder has received an NIHR Research Professorship Award in 2012

Declarations of interest

Roger AMJ Damoiseaux (RAMJ) is an Editor of the Cochrane Acute Respiratory Infections Group. Roger is an investigator of the PIM‐POM study, an ongoing cluster randomised clinical trial to optimise pain management in children with acute otitis media which is funded by a research grant from The Netherlands Organisation for Health Research and Development/SBOH no. 80‐83910‐98‐13006 (PIM‐POM study 2014).

Alastair D Hay (ADH) is funded by NIHR Research Professorship (NIHR‐RP‐02‐12‐012) and principal investigator of the ongoing UK primary care based RCT comparing the clinical‐ and cost‐effectiveness of anaesthetic (benzocaine‐phenazone) eardrops versus placebo drops and no drops in children aged 12 months to 10 years with AOM (CEDAR)

Paul Little (PL) is an Editor of the Cochrane Acute Respiratory Infections Group and investigator of the ongoing UK primary care based RCT comparing the clinical‐ and cost‐effectiveness of anaesthetic (benzocaine‐phenazone) eardrops versus placebo drops and no drops in children aged 12 months to 10 years with AOM (CEDAR).

Anne GM Schilder (AGMS) is Joint Co‐ordinating Editor of Cochrane ENT. Her team, evidENT, at the Ear Institute, University College London, is supported by an NIHR Research Professorship award. Anne is an investigator of the PIM‐POM study, an ongoing cluster randomised clinical trial to optimise pain management in children with acute otitis media which is funded by a research grant from The Netherlands Organisation for Health Research and Development/SBOH no. 80‐83910‐98‐13006 (PIM‐POM study 2014).

Alies Sjoukes (AS) is an investigator of the PIM‐POM study, an ongoing cluster randomised clinical trial to optimise pain management in children with acute otitis media which is funded by a research grant from The Netherlands Organisation for Health Research and Development/SBOH no. 80‐83910‐98‐13006 (PIM‐POM study 2014).

Roderick P Venekamp (RPV) is an Editor of the Cochrane Acute Respiratory Infections and ENT Groups. Roderick is an investigator of the PIM‐POM study, an ongoing cluster randomised clinical trial to optimise pain management in children with acute otitis media which is funded by a research grant from The Netherlands Organisation for Health Research and Development/SBOH no. 80‐83910‐98‐13006 (PIM‐POM study 2014).

Alma C van de Pol (ACvdP) is an investigator of the PIM‐POM study, an ongoing cluster randomised clinical trial to optimise pain management in children with acute otitis media which is funded by a research grant from The Netherlands Organisation for Health Research and Development/SBOH no. 80‐83910‐98‐13006 (PIM‐POM study 2014).

Acknowledgements

We gratefully acknowledge the assistance received from the staff at the Cochrane Acute Respiratory Infections editorial base and thank Sarah Thorning for designing the initial search strategy and Justin Clark for his support with the updated search strategy and searches. We also thank the following people for commenting on the draft review: Sallie Bernard, Tam Watson, Sebastian Straube, Sheena Derry, Conor Teljeur, and Tom Fahey.

Version history

Published

Title

Stage

Authors

Version

2023 Aug 18

Paracetamol (acetaminophen) or non‐steroidal anti‐inflammatory drugs, alone or combined, for pain relief in acute otitis media in children

Review

Joline L.H. Sévaux, Roger AMJ Damoiseaux, Alma C de Pol, Vittoria Lutje, Alastair D Hay, Paul Little, Anne GM Schilder, Roderick P Venekamp

https://doi.org/10.1002/14651858.CD011534.pub3

2016 Dec 15

Paracetamol (acetaminophen) or non‐steroidal anti‐inflammatory drugs, alone or combined, for pain relief in acute otitis media in children

Review

Alies Sjoukes, Roderick P Venekamp, Alma C van de Pol, Alastair D Hay, Paul Little, Anne GM Schilder, Roger AMJ Damoiseaux

https://doi.org/10.1002/14651858.CD011534.pub2

2015 Feb 13

Paracetamol (acetaminophen) or non‐steroidal anti‐inflammatory drugs, alone or combined for pain relief in acute otitis media in children

Protocol

Alies Sjoukes, Roderick P Venekamp, Alma C van de Pol, Anne GM Schilder, Roger AMJ Damoiseaux

https://doi.org/10.1002/14651858.CD011534

Differences between protocol and review

We excluded studies that focused on hospitalised children because we aimed to summarise evidence on analgesics for children with AOM applicable to every day clinical practice. Hospitalisation secondary to AOM is now rare in high‐income countries and any evidence on this study population is not easily transferable to every day clinical practice. This was not specifically mentioned in our published protocol (Sjoukes 2015).

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figures and Tables -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Forest plot of comparison: 1 Paracetamol versus placebo, outcome: 1.1 Pain at 48 hours
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Paracetamol versus placebo, outcome: 1.1 Pain at 48 hours

Forest plot of comparison: 2 NSAIDs versus placebo, outcome: 2.1 Pain at 48 hours
Figures and Tables -
Figure 5

Forest plot of comparison: 2 NSAIDs versus placebo, outcome: 2.1 Pain at 48 hours

Forest plot of comparison: 3 NSAIDs versus paracetamol, outcome: 3.2 Pain at 48 to 72 hours
Figures and Tables -
Figure 6

Forest plot of comparison: 3 NSAIDs versus paracetamol, outcome: 3.2 Pain at 48 to 72 hours

Comparison 1 Paracetamol versus placebo, Outcome 1 Pain at 48 hours.
Figures and Tables -
Analysis 1.1

Comparison 1 Paracetamol versus placebo, Outcome 1 Pain at 48 hours.

Comparison 1 Paracetamol versus placebo, Outcome 2 Adverse events.
Figures and Tables -
Analysis 1.2

Comparison 1 Paracetamol versus placebo, Outcome 2 Adverse events.

Comparison 1 Paracetamol versus placebo, Outcome 3 Fever at 48 hours.
Figures and Tables -
Analysis 1.3

Comparison 1 Paracetamol versus placebo, Outcome 3 Fever at 48 hours.

Comparison 2 NSAIDs versus placebo, Outcome 1 Pain at 48 hours.
Figures and Tables -
Analysis 2.1

Comparison 2 NSAIDs versus placebo, Outcome 1 Pain at 48 hours.

Comparison 2 NSAIDs versus placebo, Outcome 2 Adverse events.
Figures and Tables -
Analysis 2.2

Comparison 2 NSAIDs versus placebo, Outcome 2 Adverse events.

Comparison 2 NSAIDs versus placebo, Outcome 3 Fever at 48 hours.
Figures and Tables -
Analysis 2.3

Comparison 2 NSAIDs versus placebo, Outcome 3 Fever at 48 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 1 Pain at 24 hours.
Figures and Tables -
Analysis 3.1

Comparison 3 NSAIDs versus paracetamol, Outcome 1 Pain at 24 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 2 Pain at 48 to 72 hours.
Figures and Tables -
Analysis 3.2

Comparison 3 NSAIDs versus paracetamol, Outcome 2 Pain at 48 to 72 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 3 Pain at 4 to 7 days.
Figures and Tables -
Analysis 3.3

Comparison 3 NSAIDs versus paracetamol, Outcome 3 Pain at 4 to 7 days.

Comparison 3 NSAIDs versus paracetamol, Outcome 4 Adverse events.
Figures and Tables -
Analysis 3.4

Comparison 3 NSAIDs versus paracetamol, Outcome 4 Adverse events.

Comparison 3 NSAIDs versus paracetamol, Outcome 5 Mild pain at 24 hours.
Figures and Tables -
Analysis 3.5

Comparison 3 NSAIDs versus paracetamol, Outcome 5 Mild pain at 24 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.
Figures and Tables -
Analysis 3.6

Comparison 3 NSAIDs versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.
Figures and Tables -
Analysis 3.7

Comparison 3 NSAIDs versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.

Comparison 3 NSAIDs versus paracetamol, Outcome 8 Mean pain score at 24 hours.
Figures and Tables -
Analysis 3.8

Comparison 3 NSAIDs versus paracetamol, Outcome 8 Mean pain score at 24 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 9 Mean pain score at 48 to 72 hours.
Figures and Tables -
Analysis 3.9

Comparison 3 NSAIDs versus paracetamol, Outcome 9 Mean pain score at 48 to 72 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 10 Mean pain score at 4 to 7 days.
Figures and Tables -
Analysis 3.10

Comparison 3 NSAIDs versus paracetamol, Outcome 10 Mean pain score at 4 to 7 days.

Comparison 3 NSAIDs versus paracetamol, Outcome 11 Fever at 24 hours.
Figures and Tables -
Analysis 3.11

Comparison 3 NSAIDs versus paracetamol, Outcome 11 Fever at 24 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 12 Fever at 48 to 72 hours.
Figures and Tables -
Analysis 3.12

Comparison 3 NSAIDs versus paracetamol, Outcome 12 Fever at 48 to 72 hours.

Comparison 3 NSAIDs versus paracetamol, Outcome 13 Fever at 4 to 7 days.
Figures and Tables -
Analysis 3.13

Comparison 3 NSAIDs versus paracetamol, Outcome 13 Fever at 4 to 7 days.

Comparison 3 NSAIDs versus paracetamol, Outcome 14 Re‐consultations.
Figures and Tables -
Analysis 3.14

Comparison 3 NSAIDs versus paracetamol, Outcome 14 Re‐consultations.

Comparison 3 NSAIDs versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.
Figures and Tables -
Analysis 3.15

Comparison 3 NSAIDs versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 1 Pain at 24 hours.
Figures and Tables -
Analysis 4.1

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 1 Pain at 24 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 2 Pain at 48 to 72 hours.
Figures and Tables -
Analysis 4.2

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 2 Pain at 48 to 72 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 3 Pain at 4 to 7 days.
Figures and Tables -
Analysis 4.3

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 3 Pain at 4 to 7 days.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 4 Adverse events.
Figures and Tables -
Analysis 4.4

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 4 Adverse events.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 5 Mild pain at 24 hours.
Figures and Tables -
Analysis 4.5

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 5 Mild pain at 24 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.
Figures and Tables -
Analysis 4.6

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.
Figures and Tables -
Analysis 4.7

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 8 Mean pain at 24 hours.
Figures and Tables -
Analysis 4.8

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 8 Mean pain at 24 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 9 Mean pain at 48 to 72 hours.
Figures and Tables -
Analysis 4.9

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 9 Mean pain at 48 to 72 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 10 Mean pain at 4 to 7 days.
Figures and Tables -
Analysis 4.10

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 10 Mean pain at 4 to 7 days.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 11 Fever at 24 hours.
Figures and Tables -
Analysis 4.11

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 11 Fever at 24 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 12 Fever at 48 to 72 hours.
Figures and Tables -
Analysis 4.12

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 12 Fever at 48 to 72 hours.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 13 Fever at 4 to 7 days.
Figures and Tables -
Analysis 4.13

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 13 Fever at 4 to 7 days.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 14 Re‐consultations.
Figures and Tables -
Analysis 4.14

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 14 Re‐consultations.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.
Figures and Tables -
Analysis 4.15

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 16 Serious complications.
Figures and Tables -
Analysis 4.16

Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 16 Serious complications.

Summary of findings for the main comparison. Paracetamol versus placebo for acute otitis media in children

Paracetamol versus placebo for acute otitis media in children

Patients: children with acute otitis media
Setting: outpatients in four centres
Intervention: paracetamol
Control: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with paracetamol

Pain at various time points

24 hours

no data available

n/a

n/a

n/a

48 to 72 hours (48 hours)

Study population

RR 0.38
(0.17 to 0.85)

148
(1 RCT)

⊕⊕⊝⊝
low¹

NNTB based on the study population risk was 1/(253 to 96)*1000 = 7

253 per 1000

96 per 1000
(43 to 215)

4 to 7 days

no data available

Adverse events

Study population

RR 1.03
(0.21 to 4.93)

148
(1 RCT)

⊕⊝⊝⊝
very low²

40 per 1000

41 per 1000
(8 to 197)

Mean time to resolution of pain

no data available

n/a

n/a

n/a

Mean pain score at various time points

no data available

n/a

n/a

n/a

Fever at various time points

24 hours

no data available

n/a

n/a

n/a

48 to 72 hours (48 hours)

Study population

RR 1.03
(0.07 to 16.12)

148
(1 RCT)

⊕⊝⊝⊝
very low³

13 per 1000

14 per 1000
(1 to 215)

4 to 7 days

no data available

n/a

n/a

n/a

Re‐consultations

no data available

n/a

n/a

n/a

Delayed antibiotic prescriptions

no data available

n/a

n/a

n/a

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; NNTB: number needed to treat to benefit; RR: Risk ratio; RCT: randomised controlled trial;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹ We downgraded the evidence from high to low quality due to study limitations and questions about the applicability of evidence.

² We downgraded the evidence from high to very low quality due to study limitations and imprecise effect estimate (small sample size and infrequent occurrence of the outcome).

³ We downgraded the evidence from high to very low quality due to study limitations, imprecise effect estimate (infrequent occurrence of the outcome) and questions about the applicability of evidence.

Figures and Tables -
Summary of findings for the main comparison. Paracetamol versus placebo for acute otitis media in children
Summary of findings 2. NSAIDs versus placebo for acute otitis media in children

NSAIDs versus placebo for acute otitis media in children

Patients: children with acute otitis media
Setting: outpatients in four centres
Intervention: ibuprofen
Control: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with ibuprofen

Pain at various time points

24 hours

no data available

n/a

n/a

n/a

48 to 72 hours (48 hours)

Study population

RR 0.28
(0.11 to 0.70)

146
(1 RCT)

⊕⊕⊝⊝
low¹

NNTB based on the study population risk was 1/(253 to 71)*1000 = 6

253 per 1000

71 per 1000
(28 to 177)

4 to 7 days

no data available

n/a

n/a

n/a

Adverse events

Study population

RR 1.76
(0.44 to 7.10)

146
(1 RCT)

⊕⊝⊝⊝
very low²

40 per 1000

70 per 1000
(18 to 284)

Mean time to resolution of pain

no data available

n/a

n/a

n/a

Mean pain score at various time points

no data available

n/a

n/a

n/a

Fever at various time points

24 hours

no data available

n/a

n/a

n/a

48 to 72 hours (48 hours)

Study population

RR 1.06
(0.07 to 16.57)

146
(1 RCT)

⊕⊝⊝⊝
very low³

13 per 1000

14 per 1000
(1 to 221)

4 to 7 days

no data available

n/a

n/a

n/a

Re‐consultations

no data available

n/a

n/a

n/a

Delayed antibiotic prescriptions

no data available

n/a

n/a

n/a

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; NNTB: number needed to treat to benefit; RR: Risk ratio; RCT: randomised controlled trial;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹ We downgraded the evidence from high to low quality due to study limitations and questions about the applicability of evidence.

² We downgraded the evidence from high to very low quality due to study limitations and imprecise effect estimate (small sample size and infrequent occurrence of the outcome).

³ We downgraded the evidence from high to very low quality due to study limitations, imprecise effect estimate (infrequent occurrence of the outcome) and questions about the applicability of evidence.

Figures and Tables -
Summary of findings 2. NSAIDs versus placebo for acute otitis media in children
Summary of findings 3. NSAIDs versus paracetamol for acute otitis media in children

NSAIDs versus paracetamol for acute otitis media in children

Patients: children with acute otitis media
Setting: community, primary care, secondary care
Intervention: ibuprofen
Control: paracetamol

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with paracetamol

Risk with ibuprofen

Pain at various time points

24 hours

Study population

RR 0.83
(0.59 to 1.18)

39
(2 RCTs)

⊕⊝⊝⊝
very low¹

778 per 1000

646 per 1000
(459 to 918)

48 to 72 hours

Study population

RR 0.91
(0.54 to 1.54)

183
(3 RCTs)

⊕⊕⊝⊝
low²

178 per 1000

162 per 1000
(96 to 274)

4 to 7 days

Study population

RR 0.74
(0.17 to 3.23)

38
(2 RCTs)

⊕⊝⊝⊝
very low¹

188 per 1000

139 per 1000
(32 to 606)

Adverse events

Study population

RR 1.71
(0.43 to 6.90)

197
(2 RCTs)

⊕⊝⊝⊝
very low³

30 per 1000

51 per 1000
(13 to 207)

Mean time to resolution of pain

no data available

n/a

n/a

n/a

Mean pain score at various time points**

24 hours

The mean pain score with ibuprofen ranged from 2.5 to 3.9

The mean pain score with paracetamol was on average 0.10 lower (0.67 lower to 0.47 higher)

n/a

39

(2 RCTs)

⊕⊝⊝⊝
very low¹

48 to 72 hours

The mean pain score with ibuprofen ranged from 1.6 to 2.4

The mean pain score with paracetamol was on average 0.19 lower (0.65 lower to 0.27 higher)

n/a

39

(2 RCTs)

⊕⊝⊝⊝
very low¹

4 to 7 days

The mean pain score with ibuprofen ranged from 1 to 2.2

The mean pain score with paracetamol was on average 0.30 higher (1.78 lower to 2.38 higher)

n/a

31

(2 RCTs)

⊕⊝⊝⊝
very low¹

Fever at various time points

24 hours

Study population

RR 0.69
(0.24 to 2.00)

39
(2 RCTs)

⊕⊝⊝⊝
very low¹

294 per 1000

203 per 1000
(71 to 588)

48 to 72 hours

Study population

RR 1.18
(0.31 to 4.44)

182
(3 RCTs)

⊕⊕⊝⊝
low²

33 per 1000

39 per 1000
(10 to 148)

4 to 7 days

Study population

RR 2.75
(0.12 to 60.70)

39
(2 RCTs)

⊕⊝⊝⊝
very low¹

0 per 1000

0 per 1000
(0 to 0)

Re‐consultations

Study population

RR 1.13
(0.92 to 1.40)

53
(1 RCT)

⊕⊝⊝⊝
very low¹

815 per 1000

921 per 1000
(750 to 1.000)

Delayed antibiotic prescriptions

Study population

RR 1.32
(0.74 to 2.35)

53
(1 RCT)

⊕⊝⊝⊝
very low¹

407 per 1000

538 per 1000
(301 to 957)

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

** Hay 2009 assessed fever‐associated discomfort using a validated comfort scale (no comfort; not quite normal; some pain/distress; crying/very distressed), whereas Little 2013 assessed ear pain using a validated symptom score (ranging from 0 to 6 with 0 = no problem and 6 = as bad as it could be).

CI: Confidence interval; NNTB: number needed to treat to benefit; RR: Risk ratio; RCT: randomised controlled trial;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹ We downgraded the evidence high to very low quality due to study limitations and imprecise effect estimate (very small sample size).

² We downgraded the evidence from high to low quality due to study limitations and questions about the applicability of evidence.

³ We downgraded the evidence from high to very low quality due to study limitations and imprecise effect estimate (small sample size and infrequent occurrence of the outcome).

Figures and Tables -
Summary of findings 3. NSAIDs versus paracetamol for acute otitis media in children
Comparison 1. Paracetamol versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain at 48 hours Show forest plot

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

0.38 [0.17, 0.85]

2 Adverse events Show forest plot

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.21, 4.93]

3 Fever at 48 hours Show forest plot

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.07, 16.12]

Figures and Tables -
Comparison 1. Paracetamol versus placebo
Comparison 2. NSAIDs versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain at 48 hours Show forest plot

1

146

Risk Ratio (M‐H, Fixed, 95% CI)

0.28 [0.11, 0.70]

2 Adverse events Show forest plot

1

146

Risk Ratio (M‐H, Fixed, 95% CI)

1.76 [0.44, 7.10]

3 Fever at 48 hours Show forest plot

1

146

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.07, 16.57]

Figures and Tables -
Comparison 2. NSAIDs versus placebo
Comparison 3. NSAIDs versus paracetamol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain at 24 hours Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.59, 1.18]

2 Pain at 48 to 72 hours Show forest plot

3

183

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.54, 1.54]

3 Pain at 4 to 7 days Show forest plot

2

38

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.17, 3.23]

4 Adverse events Show forest plot

2

197

Risk Ratio (M‐H, Random, 95% CI)

1.71 [0.43, 6.90]

5 Mild pain at 24 hours Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.31, 3.73]

6 Mild pain at 48 to 72 hours Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.62, 2.91]

7 Mild pain at 4 to 7 days Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.37, 2.23]

8 Mean pain score at 24 hours Show forest plot

2

39

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.47, 0.67]

9 Mean pain score at 48 to 72 hours Show forest plot

2

39

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.27, 0.65]

10 Mean pain score at 4 to 7 days Show forest plot

2

31

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐2.38, 1.78]

11 Fever at 24 hours Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.24, 2.00]

12 Fever at 48 to 72 hours Show forest plot

3

182

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.31, 4.44]

13 Fever at 4 to 7 days Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

2.75 [0.12, 60.70]

14 Re‐consultations Show forest plot

1

53

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.92, 1.40]

15 Delayed antibiotic prescriptions Show forest plot

1

53

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.74, 2.35]

Figures and Tables -
Comparison 3. NSAIDs versus paracetamol
Comparison 4. NSAIDs + paracetamol versus paracetamol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain at 24 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.78, 1.47]

2 Pain at 48 to 72 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.42, 1.20]

3 Pain at 4 to 7 days Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [0.58, 4.72]

4 Adverse events Show forest plot

1

56

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Mild pain at 24 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.02, 1.74]

6 Mild pain at 48 to 72 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.24, 1.62]

7 Mild pain at 4 to 7 days Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.17, 1.43]

8 Mean pain at 24 hours Show forest plot

2

40

Mean Difference (IV, Random, 95% CI)

0.32 [‐0.59, 1.23]

9 Mean pain at 48 to 72 hours Show forest plot

2

40

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐0.77, 1.97]

10 Mean pain at 4 to 7 days Show forest plot

2

33

Mean Difference (IV, Fixed, 95% CI)

0.7 [‐1.01, 2.41]

11 Fever at 24 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

1.48 [0.73, 2.99]

12 Fever at 48 to 72 hours Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [0.60, 7.60]

13 Fever at 4 to 7 days Show forest plot

2

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

14 Re‐consultations Show forest plot

1

56

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.58, 1.11]

15 Delayed antibiotic prescriptions Show forest plot

1

56

Risk Ratio (M‐H, Fixed, 95% CI)

1.27 [0.71, 2.26]

16 Serious complications Show forest plot

2

71

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 4. NSAIDs + paracetamol versus paracetamol