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Keywords:

  • Adolescent;
  • Anti-Inflammatory Agents, Non-Steroidal [*adverse effects];
  • Pain, Postoperative [*drug therapy];
  • Postoperative Hemorrhage [*chemically induced];
  • Postoperative Nausea and Vomiting [prevention & control];
  • Randomized Controlled Trials as Topic;
  • Tonsillectomy [*adverse effects];
  • Child;
  • Child, Preschool;
  • Humans;
  • Infant

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. However, as they inhibit platelet aggregation and prolong bleeding time, they could cause increased perioperative bleeding. The overall risk remains unclear. This review was originally published in 2004 and was updated in 2010.

Objectives

The primary objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy. Our secondary outcome was to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 6); MEDLINE (inception until May 2010); EMBASE (inception until May 2010); Current Problems (produced by the UK Medicines Control Agency), MedWatch (produced by the US Food and Drug Administration) and the Australian Adverse Drug Reactions Bulletins (to May 2010). The original search was performed in August 2004. We also contacted manufacturers and researchers in the field.

Selection criteria

We included randomized controlled trials assessing NSAIDs in children, up to and including 16 years of age, undergoing elective tonsillectomy or adenotonsillectomy.

Data collection and analysis

Two authors independently assessed trial quality and extracted the data. We contacted study authors for additional information, where necessary.

Main results

We included 15 trials that involved 1046 children in this updated review. This included one trial that was added as a result of updating our search and another trial that we had incorrectly excluded from our previous review. All included trials compared NSAIDs with other analgesics or placebo and looked at bleeding requiring surgical intervention. NSAIDs did not significantly alter the number of perioperative bleeding events requiring surgical intervention: Peto odds ratio (OR) 1.32 (95% confidence interval (CI) 0.47 to 3.70). Eight trials involving 532 children looked at bleeding not requiring surgical intervention. NSAIDs did not significantly alter the number of perioperative bleeding events not requiring surgical intervention: Peto OR 1.00 (95% CI 0.39 to 2.53). Twelve trials involving 928 children looked at postoperative nausea and vomiting. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used: OR 0.49 (95% CI 0.29 to 0.83).

Authors' conclusions

NSAIDs did not cause any increase in bleeding that required a return to theatre. There was significantly less nausea and vomiting when NSAIDs were used compared to alternative analgesics.

Plain Language Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) do not significantly increase bleeding in children having their tonsils out, and there is less nausea and vomiting when NSAIDs are used.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. Bleeding is a recognised complication of this procedure but NSAIDs can interfere with blood clotting so there has been concern that these drugs will increase the risk of bleeding. If bleeding is severe this may result in the child being re-admitted to hospital, having a blood transfusion or returning to theatre. It was therefore important to establish whether these drugs are safe to use in children having their tonsils out. The review focused on clinically significant bleeding that results in the child requiring additional treatment rather than measured blood loss.

We also wanted to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia.

The review found that NSAIDs did not significantly increase bleeding. There were insufficient data to compare the risk of bleeding with each individual type of NSAID. However, we were able to compare ketorolac, which has been perceived as having a greater risk of bleeding, with the other NSAIDs and found no increased risk of bleeding. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used.

The main limitation of our review is that bleeding following tonsillectomy is an uncommon event (occurring in 3% to 5% of children). We found all the data that are currently available (15 trials studying approximately 1000 children) but a very large number of participants are required to provide an adequate number of events to give a significant result. It is possible that the numbers of participants are too small to establish whether NSAIDs increase bleeding. However, currently there is no evidence to support withholding NSAIDs for paediatric tonsillectomy.


Background

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children (Tawalbeh 2001). They are proven analgesics (Dahl 1991) and reviews (Kokki 2003; Romsing 1997) have shown that they are effective in the management of mild to moderate postoperative pain in children. NSAIDs may also reduce postoperative nausea and vomiting (Sutherland 1998), the time to adequate oral intake and time to discharge (Tawalbeh 2001). They provide an opioid-sparing effect and, therefore, reduce opioid-induced side effects (Forrest 1997); by using NSAIDs for postoperative analgesia it may be possible to avoid excessive sedation, respiratory depression, emesis and urinary retention. However, NSAIDs reversibly inhibit thromboxane A2 production (Romsing 1997) and, therefore, inhibit platelet aggregation and prolong bleeding time. This has led to concerns about increased perioperative bleeding following tonsillectomy and in particular concerns about increased rates of secondary haemorrhage, which sometimes require operative intervention.

Two meta-analyses (Marret 2003; Moiniche 2003) reviewed the use of NSAIDs and the risk of bleeding after tonsillectomy in both adult and paediatric patients. Marret et al concluded that NSAIDs increase the risk of re-operation for haemostasis after tonsillectomy but Moinchie et al concluded that NSAIDs should be used cautiously until further data were available.

Our original review (Cardwell 2005) concluded that there is currently no evidence that using NSAIDs caused any statistically significant increase in bleeding requiring further clinical intervention. However, bleeding requiring further surgical intervention following tonsillectomy is an uncommon event (Collison 2000). Therefore, a large number of participants are required to provide an adequate number of events to give a significant result. It remains unknown whether the various NSAIDs may have different tendencies to cause bleeding following tonsillectomy in children.

Objectives

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

The objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy.

As discussed in the background, there is good evidence (Kokki 2003; Romsing 1997) to show that NSAIDs are effective analgesics in children. It was not the remit of our review to question this but rather to assess the risk of bleeding when using NSAIDs for pain relief following paediatric tonsillectomy.

Our secondary outcome was to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia.

Methods

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Criteria for considering studies for this review

Types of studies

We included randomized controlled trials (RCTs).

Types of participants

We included children, aged to and including 16 years of age, who underwent elective tonsillectomy or adenotonsillectomy. We included all indications for tonsillectomy and all surgical techniques.

We excluded patients with a bleeding tendency and those with contraindications to the use of NSAIDs (asthma, renal disease).

Types of interventions

All drugs reviewed were NSAIDs. Doses prescribed were on a mg/kg basis, as recommended by the British National Formulary (BNF 2010). We included all routes of administration. Drugs were given pre, intra or postoperatively. We excluded any trials that included aspirin, as aspirin is no longer recommended for use in children. We did not include the cyclo-oxygenase-2 (COX-2) inhibitors because these are known to have no effect on platelets (Meade 1993). Also, none of the COX-2 inhibitors are approved for use in children.

Types of outcome measures
  • 1.
    Bleeding requiring further surgical intervention
  • 2.
    Need for blood transfusion
  • 3.
    Nausea or vomiting, or both
  • 4.
    Prolonged hospital stay
  • 5.
    Postoperative pain scores in the first 24 hours
  • 6.
    Other side effects of NSAIDs

Search methods for identification of studies

We searched MEDLINE (from inception to May 2010) and EMBASE (from inception until May 2010) on all fields using the search strategies found in Appendix 1 and Appendix 2.

We also performed an advanced search of the Cochrane Central Register of Controlled Trials (CENTRAL) using the search strategy found in Appendix 3 and looked at all trials under the term 'tonsil*' (The Cochrane Library, Issue 6 2010). The Cochrane Anaesthesia Review Group Trials Search Co-ordinator performed handsearching as required. Our original search was performed in August 2004.

We also searched Current Problems (produced by the UK Medicines Control Agency), MedWatch (produced by the US Food and Drug Administration) and the Australian Adverse Drug Reactions Bulletins (to May 2010).

We contacted all the pharmaceutical companies that manufactured NSAIDs and sought conference proceedings and sources of ongoing and unpublished studies. We also checked references of all identified RCTs to identify potentially relevant citations.

We did not impose language restrictions.

Data collection and analysis

Selection of studies

We included all papers studying children up to and including 16 years of age who underwent elective tonsillectomy or adenotonsillectomy and received NSAIDs. The NSAIDs were given preoperatively, intraoperatively or postoperatively; and by any route. Our principal outcome measures included bleeding requiring surgical intervention; need for blood transfusion; and nausea or vomiting, or both.

Data extraction and management

Two authors (Dr M Cardwell and Dr G Siviter) independently screened titles and abstracts identified from the electronic searches and handsearches. We applied the inclusion criteria and graded their methodological quality. We assessed trial quality according to the method set out in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008), taking into account allocation concealment, patient blinding, and completeness of data.

We resolved disagreements by discussion between the authors. We contacted the study authors for clarification, when necessary.

Two authors (Dr M Cardwell and Dr G Siviter) independently extracted data and, again, any disagreement was resolved by consensus. If agreement was not found, we sought independent expert advice (Dr A Smith).

Assessment of risk of bias in included studies

Each included study was appraised according to the criteria described below.

Under the following criteria the response 'Yes' indicates a low risk of bias, 'No' represents a high risk of bias and 'Unclear' means that insufficient information was available to make a judgment.

1. Adequacy of the sequence generation (randomization)

Yes: adequate sequence generation was reported using computer-generated random numbers or codes or sealed envelopes.

No: used a system involving trial numbers randomized in blocks. 

Unclear: did not describe one of the adequate methods but mentioned randomization.

2. Adequacy of allocation concealment

Yes: a randomization method was described that would not allow an investigator or participant to know or influence allocation to an intervention group before an eligible participant entered the study, such as drug prepared by a pharmacist not otherwise involved in the study.

No: an inadequate method of allocation was used, such as alternate medical record numbers or unsealed envelopes; or there was information in the study report indicating that investigators or participants were aware of group allocation.

Unclear: the trial report mentioned randomization but there was no information on the method used, or a method was reported that was not clearly adequate.

3. Blinding of participants

This item was graded as 'Yes' for blinding participants, 'Unclear' if the relevant information was not stated in the trial report and 'No' for unblinded participants.

4. Blinding of outcome assessors

This item was graded as 'Yes' for blinded outcome assessment, 'Unclear' if the relevant information was not stated in the trial report and 'No' for un-blinded outcome assessment.

5. Incomplete outcome data addressed

Yes: numbers of withdrawals per group, with reasons, provided; or clear from report that there were no withdrawals.

No: some withdrawal evident but numbers per group and reasons not provided.

Unclear: unclear from trial report whether there were any withdrawals.

6. Incomplete outcome data addressed (use of intention-to-treat (ITT) analysis)

We defined ITT analysis as having been conducted when all trial participants were analysed in the group to which they were randomized, regardless of which (or how much) of the treatment they actually received and regardless of other protocol irregularities, such as ineligibility.

Yes: trial report stated that ITT was undertaken and this was confirmed on study assessment, or not stated but evident from study assessment that ITT was undertaken.

No: ITT not confirmed on study assessment (patients who were randomized were not included in the analysis because they did not receive the study intervention, they withdrew from the study or they were not included because of protocol violation), regardless of whether analysis described as ITT.

Unclear: described as ITT analysis but unable to confirm on study assessment, or not reported and unable to confirm by study assessment.

7. Free of other sources of bias

Yes (low risk of bias): the trial appears to be free of other components that could put it at risk of bias.

No (high risk of bias): there are other factors in the trial that could put it at risk of bias, e.g., no sample size calculation made, early stopping, or an extreme baseline imbalance.

Unclear (uncertain risk of bias): the trial may or may not have been free of other components that could put it at risk of bias.

Dealing with missing data

We contacted the authors for clarification where data were missing or unclear. Some participants that were enrolled were excluded for a variety of reasons. In these cases we attempted to include them in our figures in order to follow the ITT principle.

Assessment of heterogeneity

Clinical heterogeneity was assessed through careful evaluation of populations, interventions and outcomes within each study.

The Chi2 test and I2 statistic were used to estimate the extent of heterogeneity.

Data synthesis

The results of each study were plotted as treatment effect estimates, shown in the forest plots. Where data permitted, we combined similar outcome measurements. For studies similar enough to support meta-analysis, we performed this using Review Manager (RevMan 5.0.24). We used Peto odds ratios for rare events as recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008) and odds ratio (OR) for analyses not dealing with rare events. Due to the large degree of heterogeneity we chose a random-effects model.

We had to adjust our outcome measures from those in the protocol as some were not specifically mentioned in the included trials. We had wanted to look at the need for blood transfusion, but as this was not specifically reported we altered our outcome measure to 'bleeding not requiring surgical intervention'. This included intravenous fluid therapy, prolonged observation and nonsurgical haemostasis. Our third outcome measure was nausea or vomiting, or both. In the majority of papers, postoperative nausea and vomiting were measured as number of emetic episodes, although vomiting is unlikely to occur without nausea. Only one paper (St Charles 1997) attempted to separate nausea and vomiting, with nausea being measured by either nurse questioning or observation, or discussion with the primary care giver. In this case, there were two patients who experienced nausea without vomiting and we included this figure in our analysis. In the interests of clarity, we changed our third outcome measure to nausea or vomiting, or both. The outcome measure of increased hospital stay was not specifically reported, although it is implied by the need for further intervention. Our pain data were not fully comprehensive as we only included those papers that had bleeding as an outcome. Also, pain was measured in a variety of different ways, making direct comparisons impossible. There is already good evidence (Kokki 2003; Romsing 1997) to show that NSAIDs provide good postoperative analgesia. After discussion with the Cochrane Anaesthesia Review Group we decided to exclude pain from our results and focus this meta-analysis on the risk of bleeding associated with the use of NSAIDs in paediatric tonsillectomy. Other side effects of NSAIDs were not mentioned in any of the included trials. Therefore, our revised outcome measures were:

  • 1.
    bleeding requiring surgical intervention;
  • 2.
    bleeding not requiring surgical intervention;
  • 3.
    nausea or vomiting, or both.
Subgroup analysis and investigation of heterogeneity

In the papers we identified with respect to the different NSAIDs, we were unable to perform subgroup analysis on all the individual NSAIDs as there were insufficient trials to do this. We were particularly interested in ketorolac as it is perceived to have a greater risk of bleeding and is not recommended for intra-operative use. Therefore, a subgroup analysis was performed on this drug alone as there were sufficient papers to do so. All doses of drugs that fall within recommended limits were included.

We were unable to perform subgroup analysis for the timing of administration as only two papers looked at this.

We were unable to look at surgical technique or underlying indication for tonsillectomy and the effects on bleeding outcomes as there were insufficient papers assessing these.

Sensitivity analysis

A sensitivity analysis was performed by removing all the trials that had some risk of bias and comparing the result with low risk of bias studies to when those studies that had some element of bias were included.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

The original search resulted in 13 studies being included in our review. As a result of our updated search (Appendix 1; Appendix 2; Appendix 3) we did a full paper review of 11 further studies and an additional paper is awaiting assessment. There were several different reasons for exclusion (see ‘Characteristics of excluded studies’ formore information). Some papers did not study bleeding;many studies were retrospective; some looked only at adults, or amixture of adult and children where the data from the children could not be extracted separately despite contacting the authors (Courtney 2001;Dommerby 1984; Petrusen 1991; Schmidt 2001); and some were excluded due to other quality issues. Several of the studies that we included had pain rather than bleeding as their primary outcome (Antila 2006; Sutherland 1998). However, bleeding was measured and the studies were therefore included. The flow chart shows the results of the literature search (the number of hits) from 2004 to May 2010 and the culling process to reduce the total to 11 study reports which had a full paper review (Figure 1).

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Figure 1. Search flow diagram

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Risk of bias in included studies

We included 15 trials, which met our inclusion criteria. All but two of these (St Charles 1997; Tawalbeh 2001) were described as randomized controlled double-blind trials. These two were randomized but blinding was unclear (Tawalbeh 2001) or there was no evidence from the paper that it had been performed (St Charles 1997). In several papers it was not clear how randomization was performed (Keidan 2004; Oztekin 2002; Rusy 1995; St Charles 1997; Tawalbeh 2001) or randomization occurred in blocks (Thiagarajan 1993). We included these studies in our review but recognized that this may introduce bias. We then considered other possible causes of bias. A possible cause of bias is that there may have been different surgeons and different surgical techniques used, as this was not stated in most of the papers. One paper stopped the study prematurely because of excessive bleeding (Romsing 1998), which was found to be caused by one particular surgeon. This surgeon was then excluded from the trial and the trial continued. To eliminate performance bias, we have taken data only from after the trial was resumed. One of the papers (Harley 1998) did not mention the anaesthetic technique used. A ‘Risk of bias’ graph and a ‘Risk of bias’ summary are shown in Figure 2 and Figure 3. There were eight trials with a low risk of bias as all domains were rated ‘Yes’ (Antila 2006; Gunter 1995; Kokki 2002; Pickering 2002; Romsing 1998; Splinter 1996; Sutherland 1998; Sutters 1995). All trials were free of selective reporting except one (Harley 1998).

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Figure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3. Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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A sensitivity analysis was performed by removing all the trials that had some risk of bias and the results remained the same, Peto odds ratio 1.10 (95%CI 0.29 to 4.14). The funnel plots (Figure 4) also confirm the absence of bias.

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Figure 4. Funnel plot of comparison: 1 Nonsteroidal versus other analgesic, outcome: 1.1 Bleeding requiring surgical intervention.

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There was potential for exclusion bias in some of the papers (Keidan 2004; Kokki 2002; Pickering 2002; Romsing 1998; Sutters 1995) as some participants that were enrolled were excluded for a variety of reasons. In these studies we attempted to include all these participants in our figures in order to follow the intention-to-treat (ITT) principle. In some studies (Keidan 2004; Kokki 2002; Pickering 2002; Romsing 1998; Sutters 1995) this involved writing to the authors to obtain extra information about the patients that had been excluded. In only one paper (Thiagarajan 1993) we were not able to account for all the exclusions, as we were unable to get in touch with the author.

We do not believe that there was the possibility of detection bias as our main outcomes were not at all subjective: they either occurred or they did not (for example return to theatre).

In our protocol we stated that if there were enough data we would create subgroups for individual drugs. After our search, we found that we had inadequate numbers of papers to do this for all the NSAIDs. However, we were able to do this for ketorolac.

Effects of interventions

A total of 15 studies involving 1046 children compared NSAIDs with another analgesic or placebo and assessed bleeding requiring surgical intervention (see Analysis 1.1). NSAIDs did not significantly alter perioperative bleeding that required surgical intervention (Peto OR 1.32, 95% CI 0.47 to 3.70).

Eight trials involving 532 children assessed bleeding not requiring surgical intervention (see Analysis 1.2). NSAIDs did not significantly alter bleeding that did not require surgical intervention, Peto OR 1.00 (95% CI 0.39 to 2.53).

Twelve trials involving 928 children assessed postoperative nausea or vomiting, or both (see Analysis 1.3). NSAID use was associated with significantly less nausea and vomiting, OR 0.49 (95% CI 0.29 to 0.83) using a random-effects model.

Six trials involving 388 children compared ketorolac against other analgesics and assessed bleeding requiring surgical intervention (see Analysis 2.1). Ketorolac did not significantly alter bleeding that required surgical intervention, Peto OR 3.12 (95% CI 0.53 to 18.38).

Eight trials involving 597 children compared NSAIDs other than ketorolac against other analgesics and assessed bleeding requiring surgical intervention (see Analysis 3.1). NSAIDs excluding ketorolac did not significantly alter bleeding that required surgical intervention, Peto OR 0.67 (95% CI 0.20 to 2.24).

Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Summary of main results

The conclusions of our updated review remain the same as in our original review (Cardwell 2005). There is no evidence that using NSAIDs caused any statistically significant increase in bleeding requiring further clinical intervention. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime, compared to when NSAIDs were not used. We therefore conclude that there is no evidence to support withholding NSAIDs for paediatric tonsillectomy. They also confer the added benefit of a reduction in nausea and vomiting.

We updated our search from 2004 to 2010. We did a full paper review of 11 new studies from our updated search, of which we excluded 10 (Bhattacharya 2005; Bhattacharya 2009; Hardy 2010; Heaney 2007; Hiller 2004; Jeyakumar 2008; Kedek 2005; Louizos 2006; McKean 2008; Nikanne 2005) and included one (Antila 2006). We have one study awaiting classification (Sun 2009). We also included a study (Pickering 2002) which had been incorrectly excluded from our previous review (Cardwell 2005). This study had been excluded because it studied COX-2 inhibitors, but it also had an ibuprofen group and a placebo group so data were used from these two groups.

The focus of our review was clinically relevant outcomes that affect patients, therefore our first outcome was bleeding requiring a return to theatre. We did not include millilitres of blood as this was less relevant in paediatric cases. We accept, however, that there may still be a difference in the amount of bleeding that is subclinical.

Our second outcome was bleeding not requiring surgical intervention. This included methods of nonsurgical haemostasis, intravenous fluid therapy and increased hospital stay. For bleeding not requiring further surgical intervention, we found no evidence of a difference between the two groups.

Our third outcome measure was nausea or vomiting, or both. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used. This may be a reflection of improved postoperative analgesia or because of an opioid-sparing effect and therefore a reduction in opioid-induced side effects.

Overall completeness and applicability of evidence

There were insufficient data available to perform subgroup analysis on all the individual NSAIDs except for ketorolac. There were six papers (Gunter 1995; Keidan 2004; Romsing 1998; Rusy 1995; Splinter 1996; Sutters 1995) which looked at ketorolac. The subgroup analysis did not show a statistically significant increase in bleeding that required surgical intervention with ketorolac. When subgroup analysis was performed for all NSAIDs excluding ketorolac, and analysis of bleeding requiring surgical intervention performed, there was again no statistically significant increase in bleeding that required surgical intervention.

There were insufficient data available to perform subgroup analysis on the timing of administration. There were two papers (Kokki 2002; Romsing 1998) that compared giving a NSAID at induction and postoperatively with control. In order to include these papers in the analysis we needed the results to be presented as two treatment groups. We therefore took the data for the NSAID given at induction against control and analysed those data, and then we took the data for NSAID given postoperatively against control and analysed these data separately. We found that using either set of data the overall conclusions remained the same. We decided to use the data from the NSAID given at induction against control as this was the case in the majority of papers. There were insufficient data to assess whether the indication for tonsillectomy or the surgical technique had any effect on bleeding.

Quality of the evidence

Bleeding requiring further surgical intervention following tonsillectomy is an uncommon event. Assessing the pooled numerical values for the number of events, we have approximately 500 patients in each group and only a very small number of bleeding events. The results of the pooled data, shown on the forest plot, showed no statistically significant increase in bleeding. A problem with this review is that a very large number of participants are required to provide an adequate number of events to give a significant result. All the papers studied had insufficient numbers to be able to demonstrate any significant difference.

Potential biases in the review process

Three papers studied ibuprofen (Harley 1998; Pickering 2002; St Charles 1997) and used doses of 5 mg/kg. However, ibuprofen is now prescribed to children in a dose of 10 mg/kg so the doses studied are half that now given, which may have an effect on the potential to cause bleeding.

The symmetrical funnel plot (Figure 4) would suggest that there is an absence of bias. However, only eight of the 15 studies are included as a Peto odds ratio could not be generated for the other seven studies as there were no bleeding events in either the study or control groups.

Agreements and disagreements with other studies or reviews

Two meta-analyses (Marret 2003; Moiniche 2003) reviewed the use of NSAIDs and the risk of bleeding after tonsillectomy in both adult and paediatric patients. Marret et al concluded that NSAIDs increase the risk of re-operation for haemostasis after tonsillectomy. Moinchie et al concluded that NSAIDs should be used cautiously until further data were available.

The first review (Marret 2003) studied paediatric and adult data but only included trials published in English. The paper has not been updated since then. Our review includes a further two papers which have been published since that review. The outcome measures in that review were the need for surgical electrocautery to stop the bleeding and postoperative bleeding requiring a change in postoperative management. The primary outcome which required a return to theatre was different from ours, and the need for surgical electrocautery probably overestimated the bleeding as this can be part of the primary surgical procedure. The papers included in the review were not exactly the same as ours as they included two that only studied adult participants and the review did not include eight papers which we included. It is unclear from the review why these were not included but three papers (Kokki 2002; Oztekin 2002; Pickering 2002) do not appear to have been reviewed at all as they are not mentioned or referenced. We considered all three of these studies to be of sufficient quality to include in our review.

In the second review (Moiniche 2003) the papers reviewed were similar to ours except adult studies were included and no papers published after December 2001 were included. The significance of their results was dependent on the method used. They found re-operation because of bleeding more often with NSAIDs. The Peto OR was statistically significant (Peto OR 2.33, 95% CI 1.12 to 4.83) and was borderline significant using the method described by Shadish and Haddock (Sadish 1994) (OR 1.92, 95% CI 1.00 to 3.71); the NNT was 60 (95% CI 34 to 277). However, they did not find interoperative blood loss, postoperative blood loss or hospital admission to be more common with NSAIDs and therefore concluded that NSAIDs could be used cautiously until further data became available.

Authors' conclusions

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Implications for practice

The objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy. For the data available to date, there is no evidence that using NSAIDs caused any statistically significant increase in bleeding that required further clinical intervention. Bleeding requiring further surgical intervention following tonsillectomy is an uncommon event. Our results showed a large confidence interval (95% CI 0.47 to 3.70), which indicates that the total number of participants studied is inadequate and further studies need to be performed. This limitation of our original review remains as only two papers were added to the updated review. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime compared to when NSAIDs were not used. We therefore conclude that there is no evidence to support withholding NSAIDs for paediatric tonsillectomy. NSAIDs also confer the added benefit of a reduction in nausea and vomiting.

Implications for research

There are currently insufficient data to review the effects of individual NSAIDs. Currently none of the selective cyclo-oxygenase-2 inhibitors are approved for use in children and there remains limited information to support their use in treating pain following paediatric tonsillectomy. Both these issues could be researched further.

Two of the papers that we looked at tried to address the issue of the timing of when NSAIDs should be given and whether this has an effect on bleeding. There were not enough data to perform a subgroup analysis. We feel that this is an issue that needs further investigation.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

We would like to thank Dr Mina Nishimori who translated the two papers by Azuma et al. (Azuma 1982) and Tamura et al (Tamura 1972) from Japanese to English.

We would like to thank Mrs D Dunton, a librarian at North Manchester General Hospital, who provided support for our searches.

We would like to thank Drs Iveta Simera and Igor Burceff for help with the translation of the paper by Gonchar et al (Gonchar 1974)

We would like to thank Dr Nicola Petrucci for help with the translation of the study by Calvet et al (Calvet 1969).

We would like to thank William Pollard for the translation of study by Lacomme et al (Lacomme 1978).

We would also like to thank Dr Jane Ballantyne, Prof Nathan Pace, Dr A E Pickering, Dr Allan Cyna and Amy Godfrey Arkle, Kathie Godfrey, Janet Wale and Iveta Simera for their help and editorial advice during the preparation of the original review (Cardwell 2005). CARG's consumer panel helped to write the plain language summary section.

Characteristics of studies

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Characteristics of included studies [ordered by study ID]

Antila 2006
Methods Randomized, parallel group trial
Participants
  • 45 children undergoing inpatient tonsillectomy with or without adenoidectomy

  • ASA I

  • Age: 9-15 years (mean 12.5±2.3, 11.9±2.4)

  • Sex distribution: M/F (6/9, 7/8)

  • Country: Finland

Interventions 1. Saline 10ml at induction followed by 100mls over 6 hours 2. Ketoprofen 2mg/kg at induction followed by 2mg/kg postoperation over 6 hours 3. Tramadol 1mg/kg at induction followed by 1mg/kg postoperation over 6 hours
Outcomes 1. Pain assessed by VAS scores 2. Number of fentanyl PCA requests in the first 24 hours 3. Measured blood loss in theatre 4. Bleeding requiring a return to theatre 5. Nausea and vomiting
Notes The study had three groups (placebo, ketoprofen & tramadol). Data taken from the two treatment groups (ketoprofen & tramadol).
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Nurse not involved with the treatment of the patient prepared the treatment syringes
Blinding? All outcomes Yes Investigaters blinded to study drug
Incomplete outcome data addressed? All outcomes Yes No incomplete data
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Gunter 1995
Methods Randomized, parallel group trial
Participants
  • 97 children 1-12 years undergoing tonsillectomy

  • ASA I-II

  • Sex distribution not stated

  • Country: USA

Interventions 1. Ketorolac 1 mg/kg intravenously at end of surgery 2. Morphine 0.1 mg/kg intravenously at end of surgery
Outcomes 1. Bleeding requiring surgical intervention at less than 24 hours 2. Bleeding requiring surgery at more than 24 hours 3. Bleeding requiring non-surgical intervention at less than 24 hours 4. Bleeding requiring non-surgical intervention at more than 24 hours 5. Increased hospital stay 6. Emetic episodes
Notes No analgesia given in theatre. Paracetamol 20 mg/kg given in recovery to all patients. Morphine 0.05 mg/kg twice in recovery as rescue analgesia. One withdrawal from the morphine group due to an arterial bleed. This was included so an ITT analysis could be performed.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Study drug prepared by pharmacist or anaesthetist not involved with the care of the patient
Blinding? All outcomes Yes Investigaters blinded to study drug
Incomplete outcome data addressed? All outcomes Yes Study terminated at 97 patients after interim analysis revealed excessive bleeding in the study group. One exclusion included in the data in order to follow the ITT principle
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Tables 1 and 2 in paper
Harley 1998
Methods Randomized, parallel group trial
Participants
  • 27 children undergoing tonsillectomy or adenotonsillectomy

  • ASA I-II

  • Age 6-16 years, distribution in each group not stated

  • Sex distribution: M/F 17/10 (distribution of the two groups not stated)

  • Country: USA

Interventions 1. Ibuprofen 5 mg/kg 6 hourly as required postoperatively 2. Paracetamol 10 mg/kg and codeine 0.4 mg/kg mixture as required postoperatively
Outcomes 1. Bleeding requiring surgical intervention 2. Postoperative pain scores
Notes Dose of paracetamol was low.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Randomization code
Allocation concealment? Yes Randomization and study medications maintained by pharmacy staff
Blinding? All outcomes Yes Study medications maintained by pharmacy staff
Incomplete outcome data addressed? All outcomes No No details on why 3 participants did not complete the study
Free of selective reporting? No As a result of factors such as follow-up compliance not all patients were available for each statistical comparison
Free of other bias? Unclear No details of demographic data given
Keidan 2004
Methods Randomized, parallel group trial
Participants
  • 60 children undergoing adenotonsillectomy

  • ASA I -II

  • Age: 1.7-10 years (mean 4.3±2.6, 5.6±2.6)

  • Sex distribution: M/F (19/9, 18/4)

  • Country: Israel

Interventions 1. Ketorolac 1 mg/kg at induction 2. Fentanyl 2 µg/kg at induction
Outcomes 1. Emetic episodes 2. Pain assessed by the PACU nurse using The Objective Pain Scale 3. Agitation 4. Bleeding
Notes Incomplete data on sex distribution data of the groups in the paper
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Unclear Not clear how randomization was performed
Allocation concealment? Unclear No details given
Blinding? All outcomes Yes Nurses blinded to study group recorded study variables
Incomplete outcome data addressed? All outcomes Yes Incomplete data included in order to follow the ITT principle
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Kokki 2002
Methods Randomized, parallel group trial
Participants
  • 110 children for elective tonsillectomy

  • ASA I

  • Age 3-16 years (mean 10, 11)

  • Sex distribution: M/F (23/24, 7/13)

  • Country: Finland

Interventions 1. Ketoprofen 0.5 mg/kg at induction followed by placebo postoperatively and ketoprofen infusion 3 mg/kg over 24 hours postop 2. Saline at induction followed by ketoprofen 0.5 mg/kg postoperatively and ketoprofen infusion 3mg/kg over 24hrs postop 3. Placebo. Saline bolus 10mls at induction and postoperatively then saline infusion over 24hrs postop
Outcomes 1. Bleeding requiring surgical intervention 2. Postoperative pain 3. Postoperative nausea and vomiting
Notes Study had two ketoprofen groups. Put in data for each treatment group against control to see how this affects results. No difference in results for either group so decided to use data from induction group against control as this was the case in the majority of papers.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Drug given by anaesthetist not involved with the assessment of the patients
Blinding? All outcomes Yes Prescription sealed in an envelope
Incomplete outcome data addressed? All outcomes Yes Excluded data included in order to follow ITT principle. Placebo group much smaller than study group
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Oztekin 2002
Methods Randomized, parallel group trial
Participants
  • 40 children for elective tonsillectomy and/or

adenoidectomy or myringotomy
  • ASA I-II

  • Age: 5-14 years (mean 8.4±0.53, 8.9±0.45)

  • Sex distribution: M/F (6/14, 8/12)

  • Country: Turkey

Interventions 1. Diclofenac suppository prior to surgical incision 2. Nothing given
Outcomes 1. Pain assessed by VAS scores 2. Total morphine consumption at 1 hour and at discharge 3. Incidence of nausea and vomiting 4. Bleeding episodes requiring nasopharyngeal packing or re-operation
Notes No placebo suppository given.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Unclear Not clear how randomization was performed
Allocation concealment? Unclear No details given
Blinding? All outcomes Yes Assessor blinded to study group
Incomplete outcome data addressed? All outcomes Yes All data complete
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Pickering 2002
Methods Randomized, parallel group trial
Participants
  • 103 children for elective tonsillectomy or

adenotonsillectomy
  • ASA I-II

  • Age 3-15 years (mean 7.0, 7.0)

  • Sex distribution: M/F (21/19, 7/11)

  • Country: UK

Interventions 1. Rofecixib 0.625 mg/kg preoperatively 2. Ibuprofen 5 mg/kg preoperatively 3. Placebo preoperatively
Outcomes 1. Need for early postoperative analgesia 2. Interoperative blood loss 3. Time to first postoperative analgesia 4. Pain scores 5. Analgesic consumption in the first 24hrs 6. Vomiting and antiemetic use 7. Incidence of primary and secondary haemorrhage
Notes Study had three groups. Data from the ibuprofen and placebo groups used in the review.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Pharmacy prepared trial drug
Blinding? All outcomes Yes Investigators and patients both blinded
Incomplete outcome data addressed? All outcomes Yes Contacted authors for information on exclusions or deviations from protocol in order to follow the ITT principle
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Romsing 1998
Methods Randomized, parallel group trial
Participants
  • 60 children undergoing tonsillectomy or adenotonsillectomy

  • ASA I-II

  • Age: 5-15 years (mean 9.4±3.2, 8.8±3.2)

  • Sex distribution: M/F (5/15, 6/14)

  • Country: Denmark

Interventions 1. Ketorolac 1 mg/kg intravenously preoperatively and saline postoperation 2. Saline preoperatively and ketorolac 1 mg/kg intravenously postoperation 3. Saline pre and postoperation
Outcomes 1. Intra-operative blood loss 2. Pain 3. Vomiting
Notes Pain was primary outcome. Study stopped after first 15 children because of worries about a surgeon causing excess bleeding. Data taken from when study resumed (45 patients). Study had two ketorolac groups. Put in data for each treatment group against control to see how this affects results. No difference in results for either group so decided to use data from pre op group against control as this was the case in the majority of papers.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Drug given by anaesthetist not involved with assessing the patients
Blinding? All outcomes Yes All personnel involved in patient management and data collection blinded
Incomplete outcome data addressed? All outcomes Yes Excluded data included in order to follow ITT principle
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Rusy 1995
Methods Randomized, parallel group trial
Participants
  • 50 children undergoing tonsillectomy and or adenoidectomy

  • ASA I-II

  • Age 2-15 years (means for each group not given but said to be the same for both groups)

  • Sex distribution not given

  • Country: USA

Interventions 1. Ketorolac 1 mg/kg at induction 2. Paracetamol 35 mg/kg at induction
Outcomes 1. Bleeding requiring surgical intervention 2. Measured blood loss 3. Extra haemostatic measures required during surgery and measured blood loss 4. Amount of rescue analgesia required
Notes
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Unclear Not clear how randomization was performed
Allocation concealment? Unclear Not enough detail in paper
Blinding? All outcomes Yes Data collected by staff unaware of the treatment group
Incomplete outcome data addressed? All outcomes Yes All data complete
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Unclear Demographic data described as being comparable in both groups but data not available in paper
Splinter 1996
Methods Randomized, parallel group trail
Participants
  • 64 undergoing elective tonsillectomy or adenotonsillectomy

  • ASA I-II

  • Age 2-12 years (7.1±3.1, 6.8±2.7)

  • Sex distribution not stated

  • Country: Canada

Interventions 1. Ketorolac 1 mg/kg intravenously at induction 2. codeine 1.5 mg/kg intramuscularly at induction
Outcomes 1. Bleeding requiring surgical intervention 2. Increased hospital stay 3. Measured blood loss 4. Postoperative nausea and vomiting
Notes Study designed to look at nausea and vomiting. Study discontinued because of increased bleeding.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Computer generated
Allocation concealment? Yes Bandaid placed on the thigh on all patients
Blinding? All outcomes Yes Single blinding. Study scientist blinded but anaesthetist not blinded
Incomplete outcome data addressed? All outcomes Yes Study terminated early at 64 patients because of excessive bleeding during interim analysis
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in both groups
St Charles 1997
Methods Randomized, parallel group trial
Participants
  • 110 children undergoing tonsillectomy with or without other procedures

  • ASA status not stated

  • Age 16-168 months (mean 77, 67)

  • Sex distribution: M/F (3.2, 3.2)

  • Country: USA

Interventions 1. Ibuprofen 5 mg/kg orally postoperation 2. Paracetamol up to 15 mg/kg and codeine 1 mg/kg orally postoperation
Outcomes 1. Bleeding requiring surgical intervention 2. Bleeding requiring nonsurgical treatment 3. Mild postoperative bleeding 4. Pain (mild or moderate or severe) 5. Nausea and emesis
Notes Surgical technique included electro-dissection or cold dissection and snare techniques. No precise data available as to which patients had which technique.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Unclear Not clear how randomization was performed
Allocation concealment? Unclear No details given in paper
Blinding? All outcomes No No evidence from paper that blinding occurred
Incomplete outcome data addressed? All outcomes Yes No incomplete data
Free of selective reporting? Yes All expected outcome measures reported
Free of other bias? No Two different surgical techniques used in the study although the two techniques were equally distributed in the two groups
Sutherland 1998
Methods Randomized, parallel group trial
Participants
  • 50 children undergoing elective tonsillectomy and/or adenoidectomy, myringotomy or submucous diathermy of inferior turbinates (SMIT)

  • ASA I-II

  • Age 3-10 years (mean 6.2, 5.8)

  • Sex distribution: M/F (12/13, 13/11)

  • Country: UK

Interventions 1. Tenoxicam 0.75 mg/kg intramuscularly at induction 2. Morphine 0.2 mg/kg intramuscularly at induction
Outcomes 1. Blood loss requiring surgical intervention 2. Pain (measured rescue analgesia) 3. Vomiting
Notes Study originally designed to look at pain. One withdrawal from morphine group included in our analysis so an ITT analysis could be performed.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Randomization using sealed envelopes
Allocation concealment? Yes Child, parents nursing staff and investigators unaware of type of analgesia given
Blinding? All outcomes Yes Investigators unaware of study drug used
Incomplete outcome data addressed? All outcomes Yes Data for excluded child included in order to follow ITT principle.
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 in paper
Sutters 1995
Methods Randomized, parallel group trial
Participants
  • 87 children having tonsillectomy

  • ASA I-II

  • Age 7-16 years (mean 84.7 months±28.9, 85.0±26.7)

  • Sex distribution: M/F (26/19, 22/20)

  • Country: USA

Interventions 1. Ketorolac 1 mg/kg intramuscularly at completion of surgery 2. Saline intramuscularly at completion of surgery
Outcomes 1. Bleeding requiring surgical intervention 2. Bleeding requiring nonsurgical intervention 3. Mild bleeding that stops spontaneously 4. Measured blood loss
Notes Fentanyl iv given in repeated doses 0.5 µ/kg in recovery. Child from control group excluded by authors due to postoperative oedema but included so an ITT analysis could be performed.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Yes Sealed envelopes for group allocation
Allocation concealment? Yes Identification of study drug not revealed to nurses parents or investigator
Blinding? All outcomes Yes Study drug arrived in a sealed envelope
Incomplete outcome data addressed? All outcomes Yes One exclusion which was included in order to follow the ITT principle.
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Tables I, II and III in paper
Tawalbeh 2001
Methods Randomized, parallel group trial
Participants
  • 80 children undergoing tonsillectomy or adenotonsillectomy

  • ASA status not stated

  • Age 3-14 years, distribution in each group not stated

  • Sex distribution not stated

  • Country: Jordan

Interventions 1. Diclofenac 1-3 mg/kg per rectum x 2 doses, first dose end of surgery, second dose 8 hours postoperation 2. Paracetamol 10-15 mg/kg orally 6 hourly postoperatively
Outcomes 1. Bleeding requiring surgical intervention 2. Increased hospital stay 3. Postoperative nausea and vomiting
Notes Fentanyl 200-400 µg also given in theatre.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? Unclear Not clear how randomization was performed
Allocation concealment? Unclear No details given in paper
Blinding? All outcomes Unclear No mention in paper that blinding took place
Incomplete outcome data addressed? All outcomes Yes No withdrawals from study
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Unclear Details of the demographic data of the two groups not included in the paper
Thiagarajan 1993
Methods Randomized, parallel group trial
Participants
  • 198 children undergoing tonsillectomy

  • ASA I-II

  • Age 1-12 years (mean 5.6±2.2, 5.7±2.5)

  • Sex distribution not stated

  • Country: UK

Interventions 1. Diclofenac 1 mg/kg intramuscularly at induction 2. Papaveretum 0.2 mg/kg intramuscularly at induction
Outcomes 1. Bleeding requiring surgical intervention 2. Measured blood loss (subjective) 3. Postoperative pain scores 4. Postoperative nausea and vomiting
Notes Papaveretum now withdrawn. Intramuscular analgesia now considered inappropriate for children. 15 withdrawals mentioned in paper, 9 could be accounted for to perform an ITT analysis. Unable to get in touch with author to account for the rest.
Risk of bias
ItemAuthors' judgementDescription
Adequate sequence generation? No Trial numbers were randomized in blocks
Allocation concealment? Yes Trial drug prepared by pharmacy
Blinding? All outcomes Yes Investigators unaware of which group the patient was in
Incomplete outcome data addressed? All outcomes No Unable to account for some of the withdrawals as unable to get in touch with the author
Free of selective reporting? Yes All expected outcomes reported
Free of other bias? Yes Demographic data appeared to be comparable in Table 1 and 2 in paper

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion
Agrawal 1999 Retrospective study.
Aho 2003 Adult participants.
Azuma 1982 Not a randomized controlled study.
Bailey 1997 Adult participants.
Balli 1973 Both treatment and control groups took a nonsteroidal anti-inflammatory drug.
Bhattacharya 2005 Does not look at bleeding.
Bhattacharya 2009 No control group.
Bone 1988 Does not look at bleeding.
Calvet 1969 An uncontrolled study.
Courtney 2001 A mixture of adult and paediatric participants. We obtained the original data from the authors to separate the two types of participants but it was not possible to determine exactly who had experienced bleeding.
De Lima Pontes 1985 Bleeding not assessed.
Dommerby 1984 A mixture of adult and paediatric data. We wrote to the authors to try to separate the data but did not receive a reply.
Fassolt 1974 Adult participants.
Francois 1994 Bleeding not assessed.
Gallagher 1995 Retrospective study.
Gonchar 1974 Not a randomized controlled trial.
Hardy 2010 Bleeding not studied.
Heaney 2007 No control group.
Hiller 2004 Adult participants.
Jeyakumar 2008 Retrospective study.
Judkins 1996 Retrospective study.
Kedek 2005 No detail on bleeding in paper. We emailed the author but did not receive a reply.
Knudsen 1995 Adult participants.
Kotecha 1991 Adult participants.
Kristensen 1986 Adult participants. No control group.
Lacomme 1978 Bleeding not assessed.
Lee 1996 Postoperative survey.
Lindgren 1985 A second drug was included with trial drug, therefore no proper control.
Louizos 2006 Adult participants.
Mahadevan 1995 Audit.
Martinez-Gallardo 1997 Adult participants.
Mather 1995 Blood loss not studied.
McKean 2008 Adult participants.
Mendham 1996 No control group.
Nakayama 1982 Only one study group.
Nikanne 2005 Adult participants.
Nordbladh 1991 Adult participants.
Parker 1986 Adult participants.
Pasquale 1993 Insufficient detail in the paper. We wrote to the authors but did not receive a reply.
Petrusen 1991 Mainly adult participants with a few older children. We were unable to separate out the paediatric and adult data.
Purday 1995 Re-analysis of a retrospective study.
Robb 1995 Re-analysis of a retrospective study.
Robinson 1994 Retrospective study.
Romsing 2000 All participants received diclofenac during the surgery. Randomization to either paracetamol or diclofenac occurred on the first day postoperatively.
Rorarius 1993 Adult participants.
Salonen 2001 Adult participants.
Salonen 2002 All patients received ketoprofen. No control group.
Schmidt 2001 Unable to separate adult and paediatric data.
Smith 1999 Retrospective study.
Stage 1988 Studies aspirin, which is no longer used in children.
Swanepoel 1999 Does not compare a nonsteroidal anti-inflammatory drug with a control. Both groups took diclofenac: one orally and one rectally.
Tamura 1972 Bleeding not assessed.
Tarkkila 1999 Adult participants.
Valijan 1989 Adult participants.
Virtaniemi 1999 Adult patients.
Watters 1988 Bleeding not assessed.
Young 1987 Adult participants.

Characteristics of studies awaiting assessment [ordered by study ID]

Sun 2009
Methods Awaiting translation of paper
Participants Children undergoing adenotonsillectomy
Interventions 1. Diclofenac suppository 12.5mg after intubation 2. Diclofenac suppository 12.5mg immediately postoperation 3. Control group - no diclofenac
Outcomes 1. Extubation time and time spent in the post-anaesthetic unit 2. Modified Aldrete and pain score 3. Paediatric emergence delirium scale
Notes The study has three groups. Will put data from each treatment group against control to see how this affects results. If no difference in results for either group will use data from group given diclofenac post intubation as this is the case in the majority of the papers

Data and analyses

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES
Table Comparison 1.. Nonsteroidal versus other analgesic
Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 Bleeding requiring surgical intervention 15 1046 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.32 [0.47, 3.70]
2 Bleeding not requiring surgical intervention 8 532 Peto Odds Ratio (Peto, Fixed, 95% CI) 1.00 [0.39, 2.53]
3 Nausea and/or vomiting 12 928 Odds Ratio (M-H, Random, 95% CI) 0.49 [0.29, 0.83]
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Figure Analysis 1.1. Comparison 1 Nonsteroidal versus other analgesic, Outcome 1 Bleeding requiring surgical intervention.

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Figure Analysis 1.2. Comparison 1 Nonsteroidal versus other analgesic, Outcome 2 Bleeding not requiring surgical intervention.

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Figure Analysis 1.3. Comparison 1 Nonsteroidal versus other analgesic, Outcome 3 Nausea and/or vomiting.

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Table Comparison 2.. Ketorolac versus other analgesia
Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 Bleeding requiring surgical intervention 6 388 Peto Odds Ratio (Peto, Fixed, 95% CI) 3.12 [0.53, 18.38]
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Figure Analysis 2.1. Comparison 2 Ketorolac versus other analgesia, Outcome 1 Bleeding requiring surgical intervention.

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Table Comparison 3.. Nonsteroidals other than ketorolac versus other analgesia
Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 Bleeding requiring surgical intervention 9 658 Peto Odds Ratio (Peto, Fixed, 95% CI) 0.67 [0.20, 2.24]
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Figure Analysis 3.1. Comparison 3 Nonsteroidals other than ketorolac versus other analgesia, Outcome 1 Bleeding requiring surgical intervention.

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Appendices

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Appendix 1. Search strategy for MEDLINE (Ovid SP)

1. exp tonsillectomy/ or tonsil*.ti,ab.

2. exp Anti-inflammatory agents/ or exp Analgesics-non-narcotic/ or exp cyclooxygenase-inhibitors/ or (Ketorolac or Ibuprofen or Diclofenac or Naproxen or Piroxicam or ketoprofen or indomethacin).mp. or exp Postoperative-Hemorrhage/ or (postoperative adj3 h?emorrhage).mp.

3. 1 and 2

4. ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (animals not (humans and animals)).sh.

5. 3 and 4

Appendix 2. Search strategy for EMBASE (Ovid SP)

1 exp tonsillectomy/ or tonsil*.ti,ab.

2 exp antiinflammatory agent/ or exp analgesic-agent/ or exp postoperative-hemorrhage/ or (Ketorolac or Ibuprofen or Diclofenac or Naproxen or Piroxicam or ketoprofen or indomethacin).mp.

3 1 and 2

4 (randomized-controlled-trial/ or randomization/ or controlled-study/ or multicenter-study/ or phase-3-clinical-trial/ or phase-4-clinical-trial/ or double-blind-procedure/ or single-blind-procedure/ or (random* or cross?over* or factorial* or placebo* or volunteer* or ((singl* or doubl* or trebl* or tripl*) adj3 (blind* or mask*))).ti,ab.) not (animals not (humans and animals)).sh.

5 3 and 4

Appendix 3. Search strategy for CENTRAL (The Cochrane Library)

#1 MeSH descriptor Tonsillectomy explode all trees

#2 tonsil*

#3 (#1 OR #2)

#4 MeSH descriptor Anti-Inflammatory Agents explode all trees

#5 MeSH descriptor Analgesics, Non-Narcotic explode all trees

#6 Ketorolac or Ibuprofen or Diclofenac or Naproxen or Piroxicam or ketoprofen or indomethacin

#7 MeSH descriptor Cyclooxygenase Inhibitors explode all trees

#8 (#4 OR #5 OR #6 OR #7)

#9 MeSH descriptor Postoperative Hemorrhage explode all trees

#10 (#3 AND ( #8 OR #9 ))

What's new

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Last assessed as up-to-date: 23 August 2010.

DateEventDescription
24 August 2010 New search has been performed We updated our search from 2004 to 2010. We did a full paper review of 11 new studies from our updated search of which we excluded 10 (Bhattacharya 2005; Bhattacharya 2009; Hardy 2010; Heaney 2007; Hiller 2004; Jeyakumar 2008; Kedek 2005; Louizos 2006; McKean 2008; Nikanne 2005) and included one (Antila 2006). An additional paper is awaiting further assessment as it needs to be translated (Sun 2009). This new study does not change our conclusions.
24 August 2010 Amended We included a study (Pickering 2002) which had been incorrectly excluded from our previous review (Cardwell 2005). This study had been excluded because it studied COX-2 inhibitors; but it also had an ibuprofen group and a placebo group, so data were used from these two groups.
24 August 2010 New search has been performed We completed a risk of bias table, risk of bias graph and risk of bias summary.

History

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Protocol first published: Issue 2, 2002

Review first published: Issue 2, 2005

DateEventDescription
1 August 2008 New search has been performed Converted to new review format.

Contributions of authors

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

Updated review

Conceiving the review: Dr M Cardwell, Dr G Siviter

Designing the review: Dr M Cardwell, Dr G Siviter, Prof A Smith

Co-ordinating the review: Dr M Cardwell

Undertaking manual searches: Dr M Cardwell, Dr G Siviter

Screening search results: Dr M Cardwell, Dr G Siviter, Dr A Smith

Organizing retrieval of papers: Dr M Cardwell

Screening retrieved papers against inclusion criteria: Dr M Cardwell, Dr G Siviter, Prof A Smith

Appraising quality of papers: Dr M Cardwell, Dr G Siviter, Prof A Smith

Abstracting data from papers: Dr M Cardwell, Dr G Siviter

Writing to authors of papers for additional information: Dr M Cardwell, Dr G Siviter

Providing additional data about papers: Dr M Cardwell, Dr G Siviter

Obtaining and screening data on unpublished studies: no unpublished studies found

Data management for the review: Dr M Cardwell, Dr G Siviter

Entering data into Review Manager (RevMan 5.0.24): Dr M Cardwell, Dr G Siviter

RevMan statistical data: Dr M Cardwell, Dr G Siviter, Prof A Smith

Other statistical analysis not using RevMan: not applicable

Double entry of data: (data entered by person one: Dr M Cardwell; data entered by person two: Dr G Siviter)

Interpretation of data: Dr M Cardwell, Dr G Siviter, Prof A Smith

Statistical inferences: Dr M Cardwell, Dr G Siviter, Prof A Smith

Writing the review: Dr M Cardwell, Dr G Siviter

Providing guidance on the review: Prof A Smith

Securing funding for the review: not applicable

Performing previous work that was the foundation of the present study: not applicable

Guarantor for the review (one author): Dr M Cardwell

Person responsible for reading and checking review before submission: Dr M Cardwell

Original review (Cardwell 2005)

Dr G Siviter and Dr M Cardwell conceived the idea for the review and wrote the protocol. Professor A Smith helped to design the protocol.

Dr M Cardwell and Dr G Siviter wrote the review with advice and editing from Professor A Smith.

Differences between protocol and review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES

In our protocol, we stated that if there were enough data we would create subgroups for individual drugs. After our search, we found that we had inadequate numbers of papers to do this for all the NSAIDs. However, we were able to do this for ketorolac.

REFERENCES

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Characteristics of studies
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Differences between protocol and review
  18. REFERENCES
  • References to studies included in this review
  • Antila 2006 {published data only}
  • Antila H, Manner T, Kuurila K, Salantera S, Kujala R, Aantaa R. Ketoprofen and tramadol for analgesia during early recovery after tonsillectomy in children. Paediatric Anaesthesia 2006;16:548-53. [MEDLINE: 16677265]
  • Gunter 1995 {published data only}
  • * Gunter JB, Varughese AM, Harrington JF, Wittkugel EP, Patankar SS, Matar MM, et al.Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Anesthesia and Analgesia 1995;81(6):1136-41. [MEDLINE: 07486094]
  • Harley 1998 {published data only}
  • * Harley EH, Dattolo RA. Ibuprofen for tonsillectomy pain in children: Efficacy and complications. Otolaryngology - Head and Neck Surgery 1998;119(5):492-6. [MEDLINE: 09807075]
  • Keidan 2004 {published data only}
  • Keidan I, Zaslansky R, Eviatar E, Segal S, Sarfaty SM. Intraoperative ketorolac is an effective substitute for fentanyl in children undergoing outpatient adenotonsillectomy. Paediatric Anaesthesia 2004;14:318-23. [EMBASE: 2004187894]
  • Kokki 2002 {published data only}
  • * Kooki H, Salonen A. Comparison of pre-and postoperative administration of ketoprofen for analgesia after tonsillectomy in children. Paediatric Anaesthesia 2002;12:162-7. [MEDLINE: 11882229]
  • Oztekin 2002 {published data only}
  • Oztekin S, Hepaguslar H, Kar AA, Ozzeybek D, Artikaslan O, Elar Z. Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy. Paediatric Anaesthesia 2002;12(8):694-9. [MEDLINE: 12472706]
  • Pickering 2002 {published data only}
  • Pickering AE, Bridge HS, Nolan J, Stoddart PA. Double-blind placebo controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children. British Journal of Anaesthesia 2002;88(1):72-7. [MEDLINE: 11881888]
  • Romsing 1998 {published data only}
  • * Romsing J, Ostergaard S, Walther-Larsen, Valentin N. Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy. Acta Anaesthesiologica Scandinavica 1998;42:770-5. [MEDLINE: 09698951]
  • Rusy 1995 {published data only}
  • * Rusy LM, Houck CS, Sullivan LJ, Ohlms LA, Jones DT, McGill TJ, et al.A double blind evaluation of ketorolac tromethamine versus acetaminophen in paediatric tonsillectomy: analgesia and bleeding. Anesthesia and Analgesia 1995;80:226-9. [MEDLINE: 07818104]
  • Splinter 1996 {published data only}
  • * Splinter WM, Rhine EJ, Roberts DW, Reid CW, MacNeil HB. Preoperative ketorolac increases bleeding after tonsillectomy in children. Canadian Journal of Anaesthesia 1996;43(6):560-3. [MEDLINE: 08773860]
  • St Charles 1997 {published data only}
  • * St Charles CS, Matt BH, Hamilton MM, Katz BP. A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient. Otolaryngology - Head and Neck Surgery 1997;117:76-82. [MEDLINE: 09230328]
  • Sutherland 1998 {published data only}
  • * Sutherland CJ, Montgomery JE, Kestin IG. A comparison of intramuscular tenoxicam with intramuscular morphine for pain relief following tonsillectomy in children. Paediatric Anaesthesia 1998;8(4):321-4. [MEDLINE: 09672930]
  • Sutters 1995 {published data only}
  • * Sutters KA, Levine JD, Dibble S, Savedra M, Miaskowski C. Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain 1995;61(1):145-53. [MEDLINE: 07644238]
  • Tawalbeh 2001 {published data only}
  • * Tawalbeh MI, Nawasreh OO, Hushan AM. Comparative study of diclofenac sodium and paracetamol for treatment of pain after adenotonsillectomy in children. Saudi Medical Journal 2001;22(2):121-3. [MEDLINE: 11299404]
  • Thiagarajan 1993 {published data only}
  • * Thiagarajan J, Bates, Hitchcock M, Morgan-Hughes J. Blood loss following tonsillectomy in children. A blind comparison of diclofenac and papaveretum. Anaesthesia 1993;47:132-5. [MEDLINE: 08460760]
  • References to studies excluded from this review
  • Agrawal 1999 {published data only}
  • * Agrawal A, Gerson CR, Seligman I, Dsida RM. Postoperative haemorrhage after tonsillectomy: use of ketorolac tromethamine. Otolaryngology - Head and Neck Surgery 1999;120(3):335-9. [MEDLINE: 10064634]
  • Aho 2003 {published data only}
  • Aho M, Kokki H, Nikanne E. Nimesulide versus ibuprofen for postoperative tonsillectomy pain. Clinical Drug Investigation 2003;23(10):651-60. [EMBASE: 2003424478]
  • Azuma 1982 {published data only}
  • * Azuma F. The clinical efficacy and plasma concentration of a 25 mg suppository of diclofenac sodium in children with post-tonsillectomy pain and inflammation. Practica Otologica 1982;75(6):1445-53. [EMBASE: 1982200723]
  • Bailey 1997 {published data only}
  • * Bailey R, Sinha C, Burgess LP. Ketorolac tromethamine and haemorrhage in tonsillectomy: A prospective, randomized, double-blind study. The Laryngoscope 1997;107(2):166-9. [MEDLINE: 09023238]
  • Balli 1973 {published data only}
  • * Balli R. Results and observations of the action of the combination of indomethacin and d-propoxyphene in tonsillectomised patients [Risultati e considerazioni sull'azione della associazione indometacina e d-propossifene nel decorso dei tonsil- lectomizzati]. L'Oto Rino Laringologia Italiana 1973;39:171-84. [MEDLINE: 04549858]
  • Bhattacharya 2005 {published data only}
  • Bhattachcharya D, Mohan CM, Dasgupta S, Chakraborty R. A comparison of rectal diclofenac with intravenous pethidine for pain relief following tonsillectomy and adenoidectomy in children. Journal of Anaesthesiology Clinical Pharmacology 2005;21(2):143-6. [EMBASE: 2007207227]
  • Bhattacharya 2009 {published data only}
  • Bhattacharya D, Mazumdar S, Chowdhury S, Basu S, Saha S. Single dose IV dexamethasone with preemptive transdermal diclofenac patch reduces opioid requirement and postoperative morbidity following tonsillectomy. Journal of Anaesthesiology Clinical Pharmacology  2009;25(1):29-32.
  • Bone 1988 {published data only}
  • * Bone ME, Fell D. A comparison of rectal diclofenac with intramuscular papaveretum placebo for pain relief following tonsillectomy. Anaesthesia 1998;43:277-80. [MEDLINE: 03377147]
  • Calvet 1969 {published data only}
  • * Calvet J, Torossian F. Use of phenylbutazone combined with deglycerated liquorice juice in postoperative care following tonsillectomy and adenotonsillectomy [Sull'uso del fenilbutazone associato al liquirizia deglicirrizzinizzato nel trattamento dei tonsillectomizzati e degli adenoidectomizzati]. La Clinica Otorinolaringoiatrica 1969;21(5):319-25. [MEDLINE: 05405073]
  • Courtney 2001 {published data only}
  • * Courtney MJ, Cabraal D. Tramadol vs diclofenac for post tonsillectomy analgesia. Archives of Otolaryngology - Head and Neck Surgery 2001;127:385-8. [MEDLINE: 11296045]
  • De Lima Pontes 1985 {published data only}
  • * De Lima Pontes PA, Gregorio LC. Double-blind clinical trial: naproxen sodium suspension vs placebo in post-operative adeno-tonsillectomy in children [Ensaio clinico duplo-cego de naproxen sodico suspensao vs placebo no pos-operatorio de adenoamigdalectomias em criancas]. Revista Brasileira de Medicina 1985;42(3):57-61. [EMBASE: 1985185817]
  • Dommerby 1984 {published data only}
  • * Dommerby H, Rasmussen OR. Diclofenac (Voltaren). Pain-relieving effect after tonsillectomy. Acta Otolaryngology 1984;98:185-92. [MEDLINE: 06380210]
  • Fassolt 1974 {published data only}
  • Fassolt A. The control of pain after tonsillectomy with mefenamic acid [Mefenaminsaure zur kontrolle des wundschmerzes nach tonsillektomie]. Schweizerische Rundschau Fur Medizin Praxis 1974;63(34):1040-3. [MEDLINE: 04417046]
  • Francois 1994 {published data only}
  • Francois M, Consten L, Rezvani Y, De Gaudemar I, Aboucaya J-P, Florant A, Narcy P. The efficacy and tolerance of tiaprofenic acid versus paracetamol after tonsillectomy in children [Etude comparative de l'efficacite et de la tolerance de l'acide tiaprofenique et du paracetamol dans les suites d'amygdalectomie chez l'enfant]. Journal Francais d'oto-rhino-laryngologie 1994;43(6):437-40. [EMBASE: 1995001032]
  • Gallagher 1995 {published data only}
  • * Gallagher JE, Blauth J, Fornadley JA. Perioperative ketorolac tromethamine and postoperative hemorrhage in cases of tonsillectomy and adenoidectomy. The Laryngoscope 1995;105(6):606-9. [MEDLINE: 07769943]
  • Gonchar 1974 {published data only}
  • * Gonchar D I. Nitrous oxide analgesia in combination with seduxen, analgin and fentanyl in tonsillectomy [Anal'geziia zakis'iu azota v sochetanii s seduksenom, anal'ginom i fentanilom pri tonzillektomii]. Vestnik Otorinolaringologii 1974;0(4):70-1. [MEDLINE: 04428588]
  • Hardy 2010 {published data only}
  • Hardy M.Z.R, Zayuah M.S, Baharudin A, Wan Aasim W.A, Shamsul K.H, Hashimah I, et al.The Effects of topical viscous lignocaine 2% versus per-rectal diclofenac in early post-tonsillectomy pain in children. International Journal of Pediatric Otorhinolaryngology  2010;74(4):374-7. [PUBMED: 20129679]
  • Heaney 2007 {published data only}
  • Heaney M, Looney Y, Mckinstry C, O'Hare B. Sequential clot strength analyses following diclofenac in pediatric adenotonsillecomy. Paediatric Anaesthesia 2007;17(11):1078-82. [MEDLINE: 17897274]
  • Hiller 2004 {published data only}
  • Hiller A, Silvanto M, Savolainen S, Tarkkila P. Proparacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta Anaesthesiologica Scandinavica 2004;48(9):1185-9. [MEDLINE: 15352967]
  • Jeyakumar 2008 {published data only}
  • Jeyaumar A, Brickman TM, Williamson ME, Hirose K, Krakovitz P, Whittemore K, et al.Nonsteroidal anti-inflammatory drugs and postoperative bleeding following adenotonsillecomy in pediatric patients. Archives of Otolaryngology - Head and Neck Surgery 2008;134(1):24-7. [MEDLINE: 18209131]
  • Judkins 1996 {published data only}
  • * Judkins JH, Dray TG, Hubbell RN. Intraoperative ketorolac and post tonsillectomy bleeding. Archives of Otolaryngology - Head and Neck Surgery 1996 September;122(9):937-40. [MEDLINE: 08797556]
  • Kedek 2005 {published data only}
  • Kedek A, Derbent A, Uyar M, Bilgen C, Uyar M, Kirazli T, et al.Pre-emptive effects of ibuprofen syrup and lidocaine infiltration on post-operative analgesia in children undergoing tonsillectomy. The Journal of International Medical Research 2005;33:188-95. [MEDLINE: 15790130]
  • Knudsen 1995 {published data only}
  • * Knudsen KE, Brofeldt S, Mikkelsen S, Bille M, Brennum J, Dahl JB. Peritonsillar infiltration with low-dose tenoxicam after tonsillectomy. British Journal of Anaesthesia 1995;75:286-8. [MEDLINE: 07547044]
  • Kotecha 1991 {published data only}
  • * Kotecha B, O'Leary G, Bradburn J, Darowski M, Gwinnutt CL. Pain relief after tonsillectomy in adults: Intramuscular diclofenac and papaveretum compared. Clinical Otolaryngology and Allied Sciences 1991;16:345-9. [MEDLINE: 01934546]
  • Kristensen 1986 {published data only}
  • Kristensen S, Tveteras K, Outzen KE, Poulsen HB. Treatment of pain after tonsillectomy. Comparison between naproxen and acetylsalicylic acid [Smertebehandling efter tonsillektomi. En sammenlignende undersogelse af naproxen ( Naprosyn) og acetylsalicylsyre (Kalcatyl)]. Ugeskrift for Laeger 1986;148(44):2832-5. [MEDLINE: 03538591]
  • Lacomme 1978 {published data only}
  • * Lancomme Y, Pessey J-J. Effects of a niflumic acid derivative in tonsil surgery in children - controlled study [Effet d'un derive de l'acide influmique dans la chiruriqie amygdalienne chez l'enfant -essai controle]. Revue de Laryngologie - Otologie - Rhinologie 1978;99(1-2):159-63. [MEDLINE: 00353942]
  • Lee 1996 {published data only}
  • * Lee WC, Sharpe JF. Complications of paediatric tonsillectomy post-discharge. Journal of Laryngology and Otology 1996;110(2):136-40. [MEDLINE: 8729496]
  • Lindgren 1985 {published data only}
  • Lindgren L, Saarnivaara L. Comparison of paracetamol and aminophenazone plus diazepam suppositories for anxiety and pain relief after tonsillectomy in children. Acta Anaesthesiologica Scandinavica 1985;29:679-82. [MEDLINE: 04072592]
  • Louizos 2006 {published data only}
  • Louizos AA, Pandazi AB, Koraka CP, Davilis DI, Georgiou LG. Preoperative administration of rofecoxib versus ketoprofen for pain relief after tonsillectomy. Annals of Otology, Rhinology and Laryngology 2006;115(3):201-4. [MEDLINE: 16572610]
  • Mahadevan 1995 {published data only}
  • * Mahadevan M, Bartley J. Paediatric day case tonsillectomy: Early green lane experience. Australian Journal of Otolaryngology 1995;2(2):150-2. [EMBASE: 1995328062]
  • Martinez-Gallardo 1997 {published data only}
  • Martinez-Gallardo F. Post tonsillectomy analgesia with diclofenac sodium [Analgesia postamigdalectomia con diclofenac sodico]. Prensa Medica Mexicana 1977;42(5-6):264-6. [EMBASE: 1978246256]
  • Mather 1995 {published data only}
  • * Mather ST, Peutrell JM. Postoperative morphine requirements, nausea and vomiting following anaesthesia for tonsillectomy. Comparison of intravenous morphine and non opioid techniques. Paediatric Anaesthesia 1995;5:185-8. [MEDLINE: 7489439]
  • McKean 2008 {published data only}
  • Mckean SA, Lee MS, Hussain SS. Comparative study of posttonsillectomy hemorrhage with the use of diclofenac versus dihydrocodeine for postoperative analgeisa and review of the literature. Otolaryngology - Head and Neck Surgery 2008;37(4):577-81. [MEDLINE: 19128596]
  • Mendham 1996 {published data only}
  • * Mendham JE, Mather SJ. Comparison of diclofenac and tenoxicam for postoperative analgesia with and without fentanyl in children undergoing adenotonsillectomy or tonsillectomy. Paediatric Anaesthesia 1996;6:467-73. [MEDLINE: 08936545]
  • Nakayama 1982 {published data only}
  • * Nakayama K. Analgesic effect of voltaren suppository following tonsillectomy in children. Practica Otologica 1982;75:1455-60. [EMBASE: 1982200724]
  • Nikanne 2005 {published data only}
  • Nikanne E, Kokki H, Salo J, Linna T-J. Celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial. Otolaryngology - Head and Neck Surgery 2005;132:287-94. [MEDLINE: 15692543]
  • Nordbladh 1991 {published data only}
  • * Nordbladh I, Ohlander B, Bjorkman R. Analgesia in tonsillectomy: A double-blind study on pre and post-operative treatment with diclofenac. Clinical Otolaryngology and Allied Sciences 1991;16:554-8. [MEDLINE: 01782718]
  • Parker 1986 {published data only}
  • * Parker DA, Gibbin KP, Noyelle. Syrup formulations for post-tonsillectomy analgesia. The Journal of Laryngology and Otology 1986;100:1055-60. [MEDLINE: 03531373]
  • Pasquale 1993 {published data only}
  • * Pasquale G, Scaricabarozzi I, D'Agostino R, Taborelli G, Vallarino R. An assessment of the efficacy and tolerability of nimesulide versus paracetamol in children after adenotonsillectomy. Drugs 1993;46:234-7. [MEDLINE: 7506181]
  • Petrusen 1991 {published data only}
  • * Petrusen. The analgesic effect of diclofenac (voltaren) after tonsillectomy [Den smartstillande effekten av diclofenac (Voltaren) efter tonsillectomi]. OPMEAR 1991;36:65-7. [EMBASE: 1991316041]
  • Purday 1995 {published data only}
  • * Purday J, Telford R, Saunders M, Pringle M. Diclofenac and post-tonsillectomy haemorrhage. Anaesthesia 1995;50(9):827-8. [MEDLINE: 7573885]
  • Robb 1995 {published data only}
  • * Robb PJ, Rollin AM, Saunders DA. Diclofenac and post-tonsillectomy haemorrhage. Clinical Otolaryngology and Allied Sciences 1995;20(5):483-4. [MEDLINE: 8582086]
  • Robinson 1994 {published data only}
  • * Robinson PM, Ahmed I. Diclofenac and post-tonsillectomy haemorrhage. Clinical Otolaryngology and Allied Sciences 1994;19(4):344-5. [MEDLINE: 07994893]
  • Romsing 2000 {published data only}
  • * Romsing J, Ostergaard D, Drozdziewicz D, Schultz P, Ravin G. Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients. Acta Anaesthesiologica Scandinavica 2000;44(3):291-5. [EMBASE: 2000089118]
  • Rorarius 1993 {published data only}
  • * Rorarius MG, Baer GA, Siirtola M, Lahti T, Laippala P. Effect of intravenous diclofenac or indomethacin on the emergence from anaesthesia for tonsillectomy. Acta Anaesthesiologica Scandinavica 1993;37(6):616-21. [MEDLINE: 08213031]
  • Salonen 2001 {published data only}
  • * Salonen A, Kokki H, Tuovinen K. I.v. ketoprofen for analgesia after tonsillectomy: Comparison of pre- and post-operative administration. British Journal of Anaesthesia 2001;86(3):377-81. [MEDLINE: 11573528]
  • Salonen 2002 {published data only}
  • * Salonen A, Kokki H, Nuutinen J. The effect of ketoprofen on recovery after tonsillectomy in children: a 3-week follow-up study. International Journal of Pediatric Otorhinolaryngology 2002;62(2):143-50. [MEDLINE: 11788147]
  • Schmidt 2001 {published data only}
  • * Schmidt A, Bjorkman S, Akeson J. Preoperative rectal diclofenac versus paracetamol for tonsillectomy: effects on pain and blood loss. Acta Anaesthesiologica Scandinavica 2001;45:48-52. [MEDLINE: 11152033]
  • Smith 1999 {published data only}
  • * Smith I, Wilde A. Secondary tonsillectomy haemorrhage and non-steroidal anti-inflammatory drugs. The Journal of Laryngology and Otology 1999;113(1):28-30. [MEDLINE: 10341915]
  • Stage 1988 {published data only}
  • * Stage J, Jensen JH, Bonding P. Post-tonsillectomy haemorrhage and analgesics. A comparative study of acetylsalicylic acid and paracetamol. Clinical Otolaryngology and Allied Sciences 1988;13(3):201-4. [MEDLINE: 03402096]
  • Swanepoel 1999 {published data only}
  • * Swanepoel A, Semple P. Oral versus rectal diclofenac for postoperative tonsillectomy pain in children. Anaesthesia 1999;54(3):298-9. [MEDLINE: 10364873]
  • Tamura 1972 {published data only}
  • * Tamura M, Yamamura M, Yoshioka A, Makimoto K, Kotera A. On the effect of a non-steroid antipyretic GP 45 840 [In Japanese]. Jibiinkoka-Rinsho 1972;65(6):583-9.
  • Tarkkila 1999 {published data only}
  • * Takkila P, Saarnivaara L. Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults. British Journal of Anaesthesia 1999;82:56-60. [MEDLINE: 10325837]
  • Valijan 1989 {published data only}
  • Valijan A. Pain relief after tonsillectomy. Effect of benzydamine hydrochloride spray on postoperative pain relief after tonsillectomy. Anaesthesia 1989;44:990-1. [MEDLINE: 02619026]
  • Virtaniemi 1999 {published data only}
  • Virtaniemi J, Kokki H, Nikanne E, Aho M. Ketoprofen and fentanyl for pain after uvulopalatopharyngoplasty and tonsillectomy. Laryngoscope 1999;109(12):1950-4. [MEDLINE: 10591353]
  • Watters 1988 {published data only}
  • * Watters CH, Patterson CC, Matthews HMC, Campbell W. Diclofenac sodium for post-tonsillectomy pain in children. Anaesthesia 1988;43:641-3. [MEDLINE: 03421455]
  • Young 1987 {published data only}
  • * Young JR. A comparative study of benzydamine hydrochloride ("Difflam" pump spray) and placebo as analgesics following tonsillectomy. International Journal of Tissue Reactions 1987;IX(2):131-3. [MEDLINE: 03610511]
  • References to studies awaiting assessment
  • Sun 2009 {published data only}
  • Sun Y, Xu W-Y, Hu J, Wang Y-T, Bai J. Effects of diclofenac sodium suppositories on emergence agitation after sevoflurane maintenance in children undergoing adenotonsillectomy. Journal of Shanghai Jiaotong University (Medical Science) 2009;29(7):842-4.
  • Additional references
  • BNF 2010
  • British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. British Medical Association and Royal Pharmaceutical Society of Great Britain, March 2010. [: ISBN-10: 0853699291]
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  • Collison PJ, Mettler B. Factors associated with post-tonsillectomy haemorrhage. Ear Nose and Throat Journal 2000;79(8):640-9. [PUBMED: 10969475]
  • Dahl 1991
  • Dahl JB, Kehlet H. Non-steroidal anti-inflammatory drugs: rational for use in severe postoperative pain.. British Journal of Anaestheisa 1991;66:703-12. [MEDLINE: 02064886]
  • Forrest 1997
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  • Meade 1993
  • Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclo-oxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. Journal of Biological Chemistry 1993;268:6610-4. [EMBASE: 1993099364]
  • Moiniche 2003
  • Moiniche S, Romsing J, Dahl JB, Tramer MR. Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesthesia and Analgesia 2003;96:68-77. [MEDLINE: 12505926]
  • RevMan 5.0.24
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5.0.24. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2010.
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  • Sadish 1994
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  • References to other published versions of this review
  • Cardwell 2005
  • Cardwell ME, Siviter G, Smith AF. Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD003591.pub2.]