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Meta-Analysis
. 2016 Dec 15;12(12):CD011534.
doi: 10.1002/14651858.CD011534.pub2.

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

Alies Sjoukes  1 , Roderick P Venekamp  2 , Alma C van de Pol  1 , Alastair D Hay  3 , Paul Little  4 , Anne Gm Schilder  5 , Roger Amj Damoiseaux  1
Affiliations
Meta-Analysis

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

Alies Sjoukes et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children.

Objectives: Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016).

Selection criteria: We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors.

Data collection and analysis: Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate the overall quality of evidence for each outcome of interest.

Main results: We included three RCTs (327 children) which were assessed at low to moderate risk of bias.One RCT included 219 children with AOM, and used a three-arm, parallel group, double-blind design to compare paracetamol versus ibuprofen versus placebo. All children also received antibiotics and those with fever > 39 °C could have received paracetamol (30 mg to 60 mg) additionally to the studied treatments.Another RCT involved 156 febrile children (26 of whom had AOM). The study design was a three-arm, parallel group, double-blind design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol.The third RCT included 889 children with respiratory tract infections (82 of whom had AOM). This study applied a 3 x 2 x 2 factorial, open-label design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. Study participants were randomised to one of the three treatment groups as well as two dosing groups (regular versus as required) and two steam inhalation groups (steam versus no steam).Authors of two RCTs provided crude subgroup data on children with AOM. We used data from the remaining trial to inform comparison of paracetamol versus placebo (148 children) and ibuprofen versus placebo (146 children) assessments. Data from all included RCTs informed comparison of ibuprofen versus paracetamol (183 children); data from the two RCTs informed comparison of ibuprofen plus paracetamol versus paracetamol alone (71 children).We found evidence, albeit of low quality, that both paracetamol and ibuprofen as monotherapies were more effective than placebo in relieving pain at 48 hours (paracetamol versus placebo: proportion of children with pain 10% versus 25%, RR 0.38, 95% CI 0.17 to 0.85; number needed to treat to benefit (NNTB) 7; ibuprofen versus placebo: proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6). Very low quality evidence suggested that adverse events did not significantly differ between children treated with either paracetamol, ibuprofen or placebo.We found insufficient evidence of a difference between ibuprofen and paracetamol in relieving ear pain at 24 hours (2 RCTs, 39 children; RR 0.83, 95% CI 0.59 to 1.18; very low quality evidence), 48 to 72 hours (3 RCTs, 183 children; RR 0.91, 95% CI 0.54 to 1.54; low quality evidence) and four to seven days (2 RCTs, 38 children; RR 0.74, 95% CI 0.17 to 3.23; very low quality evidence).Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two RCTs that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates and we were consequently unable to draw any firm conclusions (very low quality evidence).

Authors' conclusions: Despite explicit guideline recommendations on its use, current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in relieving pain in children with AOM is limited. Low quality evidence indicates that both paracetamol and ibuprofen as monotherapies are more effective than placebo in relieving short-term ear pain in children with AOM. There is insufficient evidence of a difference between ibuprofen and paracetamol in relieving short-term ear pain in children with AOM, whereas data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone were insufficient to draw any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

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Conflict of interest statement

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).

Figures

1
1
Study flow diagram
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
4
4
Forest plot of comparison: 1 Paracetamol versus placebo, outcome: 1.1 Pain at 48 hours
5
5
Forest plot of comparison: 2 NSAIDs versus placebo, outcome: 2.1 Pain at 48 hours
6
6
Forest plot of comparison: 3 NSAIDs versus paracetamol, outcome: 3.2 Pain at 48 to 72 hours
1.1
1.1. Analysis
Comparison 1 Paracetamol versus placebo, Outcome 1 Pain at 48 hours.
1.2
1.2. Analysis
Comparison 1 Paracetamol versus placebo, Outcome 2 Adverse events.
1.3
1.3. Analysis
Comparison 1 Paracetamol versus placebo, Outcome 3 Fever at 48 hours.
2.1
2.1. Analysis
Comparison 2 NSAIDs versus placebo, Outcome 1 Pain at 48 hours.
2.2
2.2. Analysis
Comparison 2 NSAIDs versus placebo, Outcome 2 Adverse events.
2.3
2.3. Analysis
Comparison 2 NSAIDs versus placebo, Outcome 3 Fever at 48 hours.
3.1
3.1. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 1 Pain at 24 hours.
3.2
3.2. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 2 Pain at 48 to 72 hours.
3.3
3.3. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 3 Pain at 4 to 7 days.
3.4
3.4. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 4 Adverse events.
3.5
3.5. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 5 Mild pain at 24 hours.
3.6
3.6. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.
3.7
3.7. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.
3.8
3.8. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 8 Mean pain score at 24 hours.
3.9
3.9. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 9 Mean pain score at 48 to 72 hours.
3.10
3.10. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 10 Mean pain score at 4 to 7 days.
3.11
3.11. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 11 Fever at 24 hours.
3.12
3.12. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 12 Fever at 48 to 72 hours.
3.13
3.13. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 13 Fever at 4 to 7 days.
3.14
3.14. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 14 Re‐consultations.
3.15
3.15. Analysis
Comparison 3 NSAIDs versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.
4.1
4.1. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 1 Pain at 24 hours.
4.2
4.2. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 2 Pain at 48 to 72 hours.
4.3
4.3. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 3 Pain at 4 to 7 days.
4.4
4.4. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 4 Adverse events.
4.5
4.5. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 5 Mild pain at 24 hours.
4.6
4.6. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 6 Mild pain at 48 to 72 hours.
4.7
4.7. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 7 Mild pain at 4 to 7 days.
4.8
4.8. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 8 Mean pain at 24 hours.
4.9
4.9. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 9 Mean pain at 48 to 72 hours.
4.10
4.10. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 10 Mean pain at 4 to 7 days.
4.11
4.11. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 11 Fever at 24 hours.
4.12
4.12. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 12 Fever at 48 to 72 hours.
4.13
4.13. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 13 Fever at 4 to 7 days.
4.14
4.14. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 14 Re‐consultations.
4.15
4.15. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 15 Delayed antibiotic prescriptions.
4.16
4.16. Analysis
Comparison 4 NSAIDs + paracetamol versus paracetamol, Outcome 16 Serious complications.
See this image and copyright information in PMC

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Sjoukes 2015
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