|NSAID-analgesia, pain control and morbidity in cardiothoracic surgery
|Bainbridge D, Cheng D C, Martin J E, Novick R
This review assessed the effects of non-steroidal anti-inflammatory drugs (NSAIDs) combined with narcotic or regional analgesia in patients undergoing cardiothoracic surgery. It concluded that NSAID use reduced pain and narcotic consumption, but that there were no significant differences in side-effects and hospital length of stay. The conclusions of this well-conducted review appear reliable.
To assess whether non-steroidal anti-inflammatory drugs (NSAIDs), adjunctive to either opioid or regional analgesia, can reduce post-operative pain, narcotic requirements, morbidity and resource utilisation in patients undergoing cardiothoracic surgery.
MEDLINE, the Cochrane CENTRAL Register, EMBASE, DARE, NEED, INAHTA and Current Contents were searched from inception to September 2005 for studies in any language; the search terms were reported. Electronic searches of related articles and handsearches of bibliographies, meeting abstracts and related journals were also performed.
Study designs of evaluations included in the review
Randomised controlled trials (RCTs), both blinded and unblinded, were eligible for inclusion.
Specific interventions included in the review
Studies of an NSAID analgesic regimen compared with a non-NSAID narcotic or regional analgesic regimen, given pre-, intra- or postoperatively, were eligible. Studies of cyclooxygenase-2 selective NSAIDs and regional anaesthesia studies in which the regional block was not offered to both treatment groups were excluded. The included treatments and dosing schedules varied widely between studies: 11 drugs were under investigation, either singly or in combination, with the most commonly assessed being ketorolac, diclofenac and indomethacin. The control treatments were placebo alone or with morphine, papaveretum, midazolam, famotidine or local anaesthetic; morphine alone; or sham suppository. The duration of NSAID treatment ranged from a single dose to up to 72 hours post-operatively.
Participants included in the review
Eligible participants were adults undergoing cardiac or thoracic surgery. In the included studies, participants were generally restricted to those aged younger than 70 years, who had no history of gastrointestinal haemorrhage and had normal renal function. The average patient age was 52.7 years in the control group and 54.2 years in the treatment group, and 23% of patients were female.
Outcomes assessed in the review
The eligibility criteria specified that studies had to report at least one pertinent clinical or economic outcome; no further details were given. The primary outcome assessed was the visual analogue scale score for pain 24 hours after surgery. The secondary outcomes included cumulative morphine-equivalents needed during the first 24 hours after surgery, the need for supplementary narcotic rescue analgesia during hospitalisation, all-cause mortality, all-cause bleeding, acute myocardial infarction, atrial fibrillation, post-operative nausea and vomiting, gastrointestinal bleeding and disturbances, blood transfusions, renal failure, serum creatinine, pneumonia, reintubation, excess sedation and adverse events. Resource use outcomes were duration of ventilation, intensive care unit length of stay (LOS) and hospital LOS.
How were decisions on the relevance of primary studies made?
Two reviewers independently assessed studies for inclusion.
Assessment of study quality
Study validity was assessed using the Jadad scale, which assesses randomisation, blinding and loss to follow-up. The maximum possible score was five. Two reviewers independently assessed validity, with any disagreements resolved by consensus.
Two reviewers independently extracted the data. The means and standard deviations of continuous outcomes were extracted, while the odds ratio (OR) and 95% confidence intervals (CIs) were calculated for binary outcomes.
Methods of synthesis
How were the studies combined?
Pooled ORs and weighted mean differences (WMDs) were obtained using either a fixed-effect or random-effects model, depending on the presence of statistical heterogeneity. Where possible, analyses were conducted on an intention-to-treat basis. Publication bias was assessed using funnel plots.
How were differences between studies investigated?
The Q-statistic was used to assess heterogeneity (p<0.10 suggested significant statistical heterogeneity). Predefined subgroup analyses assessed: elderly patients (aged over 70); cardiac versus thoracic surgery; patients with pulmonary disease, heart failure or renal failure at baseline; and trials including regional anaesthetic techniques. Sensitivity analyses were conducted to assess the effect of trial quality, publication status and studies without intention-to-treat analyses (assuming a worse-case scenario for missing data).
Results of the review
Twenty RCTs (n=1,065) were included.
The median Jadad score was 3 (range: 0 to 5). There was no evidence of publication bias for any outcome.
Pain scores after 24 hours were significantly reduced in the NSAID group compared with the control group (WMD -0.91, 95% CI: -1.48, -0.34; based on 7 studies). The consumption of morphine-equivalents in the first 24 hours after surgery was also significantly reduced for the NSAID group (WMD -7.67 mg, 95% CI: -8.97, -6.38; based on 13 studies). There was significant heterogeneity for both of these outcomes (I-squared 66% and 70%, respectively). There were no were statistically significant differences between the groups for any of the other outcomes. Subgroup analyses showed a significant difference between thoracic and cardiac surgery for morphine-equivalents consumption. Thoracic patients had a greater reduction in consumption: a mean of 9.55 mg (range: 7.78 to 11.32) compared with 5.31 mg (range: 3.42 to 7.2) for cardiac patients. Sensitivity analyses showed that excluding unpublished trials, lack of intention-to-treat analyses, and study quality did not affect the results.
The costs were not reported in any of the studies. Other measures of resource use were insufficiently reported to allow for pooled analyses.
Patients undergoing cardiothoracic surgery who were given NSAIDs in addition to narcotics experienced reduced pain and narcotic consumption. Risks such as bleeding, renal failure, and wound and bone healing were not shown to be higher with NSAID use, but further research is required to investigate risks and potential reductions in resource use.
This review had clear inclusion criteria, although relevant outcomes were not specified. The search was adequate with efforts made to locate unpublished studies and no restrictions by language. Study validity was assessed and the results reported for each study, although the Jadad scale used was limited as it only assessed three aspects of potential validity. Methods were used to reduce bias and error by having two reviewers independently perform the study selection, validity assessment and data extraction processes. Publication bias was assessed: the authors stated that there was no evidence of any but did not present any plots. Studies were pooled using random-effects models in the presence of statistical heterogeneity and subgroup analyses, which were planned before data were obtained, were used to assess clinical and methodological sources of heterogeneity. Overall, this was a well-conducted review and its conclusions are likely to be reliable.
Implications of the review for practice and research
Practice: The authors stated that short-term peri-operative use of NSAIDs in addition to narcotic analgesia should be encouraged in patients undergoing cardiothoracic surgery.
Research: The authors stated that further research is needed to rule out the existence of potentially important differences in risks associated with NSAID use, particularly in high-risk patients. Further trials are needed to explore whether NSAIDs reduce resource use (length of stay, ventilation time, transfusion requirements and costs). NSAIDs added to multi-modal therapy with epidural analgesia also requires further study.
Department of Anesthesia and Perioperative Medicine.
Bainbridge D, Cheng D C, Martin J E, Novick R. NSAID-analgesia, pain control and morbidity in cardiothoracic surgery. Canadian Journal of Anesthesia 2006; 53(1): 46-59
Subject indexing assigned by NLM
Age Factors; Analgesia /methods; Analgesics, Opioid /therapeutic use; Anti-Inflammatory Agents, Non-Steroidal /adverse effects /therapeutic use; Cardiovascular Surgical Procedures /methods /mortality; Drug Therapy, Combination; Female; Humans; Middle Aged; Odds Ratio; Pain Measurement /methods; Pain, Postoperative /prevention & Postoperative Complications /epidemiology; Randomized Controlled Trials as Topic /statistics & Thoracic Surgical Procedures /methods /mortality; control; numerical data
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.