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Preoperative celecoxib is beneficial, but effects modest
ESRA Academy. Joshi G. Mar 7, 2017; 170349
Girish Joshi
Girish Joshi
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Non-steroidal anti-inflammatory drugs (NSAIDs), which include both traditional NSAIDs and selective cyclooxygenase (COX)–2 specific inhibitors (COXIBs), have been demonstrated to play an important role in multimodal analgesia (1–3). Although controversial, it is suggested that administration of an analgesic prior to surgery may provide superior pain relief (i.e. preemptive analgesia). However, traditional NSAIDs are administered towards the end of surgery due to concerns about increased bleeding and acute kidney injury. In contrast, it is generally accepted that COX–2 specific inhibitors (e.g., celecoxib) do not influence perioperative bleeding, as they do not have any effects on platelet function and, therefore, they may be administered prior to surgery.
Khan et al performed a systematic review and meta-analysis of randomised controlled trails evaluating the analgesic effects of celecoxib when administered prior to surgery. The authors concluded that preoperative celecoxib provides a ‘slight’ reduction in 24-hour postoperative opioid consumption and pain scores. In addition, the improved pain relief was not influenced by the dose (200 mg versus 400 mg) or by continued administration in the postoperative period. Overall, this study does not provide us with any new information, even if the authors have used fashionable statistical analyses, such as trial sequential analysis and random effects model.
Not surprising, similar to majority of the systematic reviews (4), the studies included in this systematic review had significant heterogeneity, including the type of surgical procedure, type of anaesthetic (general anaesthesia, spinal anaesthesia, and local anaesthesia), timing of administration, dose of celecoxib (200 mg versus 400 mg), and the duration of administration in the postoperative period (i.e., single dose versus multiple doses postoperatively). Also the analgesic techniques used in the various studies varied significantly. Furthermore, placebo-controlled trails have a major limitation, that is, they do not reflect modern clinical practice in which patients receive combinations of analgesics, not just one analgesic (e.g. only opioids in the placebo group).
Given such an heterogeneity, and the varied effects of the variable factors on postoperative pain, the clinical applicability of this study is negligible. The finding that continued postoperative administration of celecoxib does not provide any further benefit does not make any sense, which again highlights the usefulness of such systematic reviews. Overall, although preemptive analgesia has been shown to have significant analgesic benefits in animal models, clinical studies have provided controversial conclusions. Therefore, the timing of analgesic administration should depend upon the pharmacokinetics of the drug and type of surgical procedure (1).

1. Joshi GP, Schug S, Kehlet H. Procedure specific pain management and outcome strategies. Best Pract Res Clin Anaesthesiol 2014; 28: 191-201.
2. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, executive committee, and administrative council. J Pain 2016; 17: 131–57.
3. Schug SA, Palmer GM, Scott DA, et al; APM: SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015), Acute Pain Management: Scientific Evidence (4th edition), ANZCA & FPM, Melbourne. Available at: http://www.anzca.edu.au/resources/college-publications (accessed 9 February 2017).
4. Kehlet H, Joshi GP. Systematic reviews and meta-analyses of randomized controlled trials on perioperative outcomes: an urgent need for critical reappraisal. Anesth Analg 2015; 121: 1104–7.

BACKGROUND:

Postoperative pain continues to be undertreated after noncardiac surgery. Preoperative analgesic administration may enhance postoperative analgesia.

OBJECTIVE:

To determine the effects of preoperative administration of celecoxib in noncardiac surgery on pain and postoperative outcomes.

DESIGN:

Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES:

MEDLINE, EMBASE, CENTRAL, CINHAL Web of Sciences and ProQuest databases were searched from inception to 2014. Reference lists of retrieved articles and grey literature were searched for additional trials.

ELIGIBILITY CRITERIA:

Articles were included if they enrolled patients of at least 18 years of age and randomised patients to receive celecoxib within 4 h of noncardiac surgery. Studies were excluded if they were animal studies, reviews/meta-analyses, did not report pain as an outcome or used epidural analgesia.

RESULTS:

Twenty trials met the eligibility criteria. Preoperative celecoxib in 14 studies (994 patients) amenable to meta-analysis demonstrated a significant decrease in 24-h parenteral morphine-equivalent consumption (mean difference -4.13 mg, 95% confidence interval -5.58 to -2.67, I = 94%). Eleven studies (755 patients) assessed postoperative pain scores at 24 h and found a significant decrease with celecoxib use [mean difference (on a 0-10 pain scale) -1.02, 95% confidence interval -1.54 to -0.50, I = 99%]. The risks of postoperative nausea and vomiting were also decreased by 44% (P = 0.01) and 38% (P = 0.03), respectively. Preoperative celecoxib did not improve patient satisfaction or length of recovery room stay, or increase intraoperative bleeding. Subgroup analyses indicated no difference between celecoxib 200 and 400 mg or between a single preoperative dose and continued postoperative dosing.

CONCLUSION:

Results of this study are limited by significant heterogeneity and inclusion of mainly small trials. However, there appears to be a slight to modest benefit of preoperative celecoxib on reducing postoperative morphine consumption, pain, nausea and vomiting.

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