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Meta-Analysis
. 2018 Jul 7;7(7):CD012294.
doi: 10.1002/14651858.CD012294.pub2.

Ketorolac for postoperative pain in children

Ewan D McNicol  1 , Emily Rowe, Tess E Cooper
Affiliations
Meta-Analysis

Ketorolac for postoperative pain in children

Ewan D McNicol et al. Cochrane Database Syst Rev. .

Abstract

Background: Children who undergo surgical procedures in ambulatory and inpatient settings are at risk of experiencing acute pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce moderate to severe pain without many of the side effects associated with opioids. However, NSAIDs may cause bleeding, renal and gastrointestinal toxicity, and potentially delay wound and bone healing. Intravenous administration of ketorolac for postoperative pain in children has not been approved in many countries, but is routinely administered in clinical practise.

Objectives: To assess the efficacy and safety of ketorolac for postoperative pain in children.

Search methods: We searched the following databases, without language restrictions, to November 2017: CENTRAL (The Cochrane Library 2017, Issue 10); MEDLINE, Embase, and LILACS. We also checked clinical trials registers and reference lists of reviews, and retrieved articles for additional studies.

Selection criteria: We included randomised controlled trials that compared the analgesic efficacy of ketorolac (in any dose, administered via any route) with placebo or another active treatment, in treating postoperative pain in participants zero to 18 years of age following any type of surgery.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We analyzed trials in two groups; ketorolac versus placebo, and ketorolac versus opioid. However, we performed limited pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE, and created a 'Summary of findings' table.

Main results: We included 13 studies, involving 920 randomised participants. There was considerable heterogeneity among study designs, including the comparator arms (placebo, opioid, another NSAID, or a different regimen of ketorolac), dosing regimens (routes and timing of administration, single versus multiple dose), outcome assessment methods, and types of surgery. Mean study population ages ranged from 356 days to 13.9 years. The majority of studies chose a dose of either 0.5 mg/kg (as a single or multiple dose regimen) or 1 mg/kg (single dose with 0.5 mg/kg for any subsequent doses). One study administered interventions intraoperatively; the remainder administered interventions postoperatively, often after the participant reported moderate to severe pain.There were insufficient data to perform meta-analysis for either of our primary outcomes: participants with at least 50% pain relief; or mean postoperative pain intensity. Four studies individually reported statistically significant reductions in pain intensity when comparing ketorolac with placebo, but the studies were small and had various risks of bias, primarily due to incomplete outcome data and small sample sizes.We found limited data available for the secondary outcomes of participants requiring rescue medication and opioid consumption. For the former, we saw no clear difference between ketorolac and placebo; 74 of 135 (55%) participants receiving ketorolac required rescue analgesia in the post-anaesthesia care unit (PACU) versus 81 of 127 (64%) receiving placebo (relative risk (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.00, P = 0.05; 4 studies, 262 participants). For opioid consumption in the PACU, we saw no clear difference between ketorolac and placebo (P = 0.61). For the time period zero to four hours after administration of the interventions, participants receiving ketorolac received 1.58 mg less intravenous morphine equivalents than those receiving placebo (95% CI -2.58 mg to -0.57 mg, P = 0.002; 2 studies, 129 participants). However, we are uncertain whether ketorolac has an important effect on opioid consumption, as the data were sparse and the results were inconsistent. Only one study reported data for opioid consumption when comparing ketorolac with an opioid. There were no clear differences between the ketorolac and opioid group at any time point. There were no data assessing this outcome for the comparison of ketorolac with another NSAID.There were insufficient data to allow us to analyze overall adverse event or serious adverse event rates. Although the majority of serious adverse events reported in those receiving ketorolac involved bleeding, the number of events was too low to conclude that bleeding risk was increased in those receiving ketorolac perioperatively. There was not a statistically significant increase in event rates for any specific adverse event, either in pooled analysis or in single studies, when comparing ketorolac and placebo. When comparing ketorolac with opioids or other NSAIDs, there were too few data to make any conclusions regarding event rates. Lastly, withdrawals due to adverse events were vary rare in all groups, reflecting the acute nature of such studies.We assessed the quality of evidence for all outcomes for each comparison (placebo or active) as very low, due to issues with risk of bias in individual studies, imprecision, heterogeneity between studies, and low overall numbers of participants and events.

Authors' conclusions: Due to the lack of data for our primary outcomes, and the very low-quality evidence for secondary outcomes, the efficacy and safety of ketorolac in treating postoperative pain in children were both uncertain. The evidence was insufficient to support or reject its use.

PubMed Disclaimer

Conflict of interest statement

EM: none known. EM is a pharmacist with a Master's degree in Pain Research, Education and Policy, and manages patients with acute pain.

ER has received support from Pfizer for travel and accommodation (2015). ER is a pharmacist with a Master's degree in Pain Research, Education and Policy, and manages paediatric patients with acute pain.

TC: none known.

The protocol for this review was identified in a 2019 audit as not meeting the current definition of the Cochrane Commercial Sponsorship policy. At the time of its publication it was compliant with the interpretation of the existing policy. A new author team fully compliant with the 2014 policy completed the review. As with all reviews, new and updated, at update this review will be revised according to 2020 policy update.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Forest plot of comparison: 1 Ketorolac versus placebo, outcome: 1.1 Participants using rescue medication in the PACU
1.1
1.1. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 1: Participants using rescue medication in the PACU
1.2
1.2. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 2: Opioid consumption (mg IV morphine equivalents) in PACU
1.3
1.3. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 3: Opioid consumption (mg IV morphine equivalents): 0 to 4 h
1.4
1.4. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 4: Participants reporting nausea
1.5
1.5. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 5: Participants reporting vomiting
1.6
1.6. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 6: Participants reporting nausea and vomiting
1.7
1.7. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 7: Participants reporting pruritus
1.8
1.8. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 8: Participants experiencing respiratory depression
1.9
1.9. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 9: Participants reporting urinary retention
1.10
1.10. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 10: Participants experiencing bleeding
1.11
1.11. Analysis
Comparison 1: Ketorolac versus placebo, Outcome 11: Participants experiencing renal dysfunction
2.1
2.1. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 1: Participants using rescue medication in the PACU
2.2
2.2. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 2: Participants reporting any adverse event
2.3
2.3. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 3: Participants reporting pain on infusion
2.4
2.4. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 4: Participants reporting nausea
2.5
2.5. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 5: Participants reporting vomiting
2.6
2.6. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 6: Participants reporting pruritus
2.7
2.7. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 7: Participants experiencing respiratory depression
2.8
2.8. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 8: Participants reporting allergy, rash, or local reaction
2.9
2.9. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 9: Participants experiencing bleeding
2.10
2.10. Analysis
Comparison 2: Ketorolac versus opioid, Outcome 10: Participants experiencing renal dysfunction
See this image and copyright information in PMC

Update of

References

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