Article Identification

• Title: Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery
• Authors: Hynninen et al.
• Journal: Canadian Journal of Anesthesia
• Citation: Can J Anesth. 2000;47(12):1182-1187.
• DOI/PMID: Not specified in the text

Quick Reference Summary

• In this randomized, double-blind, placebo-controlled study of 120 elective CABG (Coronary Artery Bypass Grafting) patients, only diclofenac (75 mg twice) significantly reduced morphine consumption and total analgesic requirements compared to placebo (p < 0.05).
• Renal function, bleeding, and pain scores did not differ significantly among the diclofenac, ketoprofen, indomethacin, and placebo arms, suggesting that short-term NSAID use in selected cardiac surgery patients can be safe.

Core Clinical Question

In adult patients undergoing elective CABG (Population), does the addition of a short course of NSAIDs (diclofenac, ketoprofen, or indomethacin) (Intervention), compared with placebo (Comparison), reduce postoperative morphine requirements (Outcome) without significant adverse effects such as bleeding or renal dysfunction?

Background

• Disease or Condition Overview:
  • Postoperative pain after CABG can impair deep breathing, cough effectiveness, and early mobilization, potentially leading to respiratory complications and increased cardiac stress.
  • Standard analgesia in cardiac surgery typically relies on opioids, which can cause drowsiness, respiratory depression, confusion, and ileus.
• Prior Data on the Topic:
  • Multiple studies in non-cardiac surgeries suggest NSAIDs reduce opioid consumption and improve pain scores without the central nervous system side effects of opioids.
  • Concerns over renal impairment and bleeding have historically limited NSAID use in CABG patients.
• Current Standard of Care:
  • Typical postoperative analgesia protocols often involve opioids (e.g., morphine or fentanyl), sometimes supplemented by acetaminophen.
  • Some centers also use adjuncts such as regional blocks, COX-2 selective inhibitors, or low-dose ketamine; however, uniform standards vary widely.
• Knowledge Gaps Addressed by This Study:
  • Whether short-term NSAID therapy after cardiac surgery is safe and effective.
  • Whether any particular NSAID (diclofenac, ketoprofen, or indomethacin) has a preferable risk-benefit profile.
• Study Rationale:
  • To test whether NSAIDs given in the immediate postoperative period can safely reduce opioid requirements in CABG surgery without increasing bleeding or renal complications.

Methods Summary

• Study Design:
  • Prospective, randomized, double-blind, placebo-controlled trial.
• Setting and Time Period:
  • Single-center, in-hospital study (ICU and surgical floor), likely in the late 1990s (publication year 2000).
• Population Characteristics:
  • Elective CABG patients (n=120).
  • Age ≤75, no insulin-dependent diabetes, normal or near-normal renal function (exclusion if creatinine >130 μmol·L–1).
  • Exclusion if EF <20%, previous cardiac surgery, peptic ulcer disease, weight <60 kg or >100 kg, or anticoagulant therapy.
• Inclusion/Exclusion Criteria:
  • Included: Adults scheduled for elective CABG, meeting fast-track anesthesia criteria, no high-risk comorbidities based on table in the article.
  • Excluded: See above.
• Intervention Details:
  • Diclofenac 75 mg, ketoprofen 100 mg, indomethacin 100 mg, or placebo.
  • Two doses (PR suppositories), the first ~1 hour prior to anticipated extubation and the second 12 hours later.
• Control/Comparison Group:
  • Identical placebo suppository, administered on the same schedule.
• Primary and Secondary Outcomes:
  • Primary: Morphine consumption (mg) over 24 hours postoperatively, plus analgesic equivalents.
  • Secondary: Pain scores on a visual analogue scale (VAS), renal function (creatinine changes), chest tube drainage (blood loss), nausea/vomiting, and other adverse events.
• Statistical Analysis Approach:
  • One-way ANOVA for group comparisons, Dunnett post-hoc for drug vs. placebo.
  • VAS by Kruskal-Wallis, frequencies by Chi-square.
  • Sample size powered to detect a 7.5 mg difference (SD 7.5 mg) in 24-hour morphine use.
• Sample Size Calculations:
  • Target of 25 per group (n=100) to detect morphine consumption differences; expanded to 120 total to include potential dropouts and also assess renal function endpoints.
• Ethics and Funding:
  • Approved by the Institutional Ethics Committee. No specific funding or conflict-of-interest statements described in the text.

Detailed Results

• Participant Flow and Demographics:
  • 120 enrolled, 114 completed (6 withdrawals for prolonged bypass, excessive bleeding, etc.).
  • Groups (diclofenac = 28, ketoprofen = 28, indomethacin = 27, placebo = 31) were similar in baseline characteristics (age ~55–60, weight ~78–81 kg).
• Primary Outcome Results:
  • Only diclofenac (75 mg ×2) significantly lowered total morphine consumption vs. placebo (mean 12.4 mg vs. 19 mg; p < 0.05).
  • Converting total rescue analgesia into morphine equivalents reinforced this same difference (18.1 mg vs. 26.5 mg; p < 0.05).
  • Ketoprofen and indomethacin did not significantly reduce morphine usage vs. placebo in this sample.
• Pain Scores (VAS):
  • No statistically significant difference among the four groups at various time points (3, 6, 12, 24 hours), though numerically diclofenac group often had slightly lower median VAS.
• Secondary Outcomes:
  • Renal Function: No significant difference across groups in creatinine levels or proportion with ≥20% postoperative rise in creatinine (p = NS). One indomethacin patient had transient rise in creatinine but recovered.
  • Bleeding: No significant difference in chest tube drainage among groups (~530–630 mL/24 hr, p = NS). One indomethacin patient had higher bleeding, managed conservatively. No re-explorations for bleeding.
  • Nausea/Vomiting: Slightly higher incidence in all NSAID groups compared to placebo but no statistically significant difference.
• Adverse Events/Safety Data:
  • No GI bleeding events.
  • No re-operations for bleeding.
  • No strokes attributed to study medication.

Results Table

Below is an abbreviated table reflecting the primary outcomes (morphine consumption) and safety endpoints. Values are approximate from the text.

*Statistically significant only for diclofenac vs. placebo.

Authors’ Conclusions

• Primary Conclusions:
  • NSAIDs, and in particular diclofenac, reduced postoperative morphine requirements without increasing bleeding or reducing renal function in selected CABG patients.
• Authors’ Interpretation of Results:
  • With cautious patient selection (e.g., no renal impairment, not elderly >75, no peptic ulcer disease), two doses of NSAIDs post-CABG appear to be safe and beneficial for opioid-sparing.
• Clinical Implications Stated by Authors:
  • Short, low-dose NSAID courses may be incorporated into fast-track cardiac anesthesia protocols to improve postoperative pain management.
• Future Research Recommendations:
  • Larger studies are needed to confirm renal safety and to explore a broader population (e.g., older patients or those with diabetes).
  • Alternative dosing schedules or exploring COX-2 selective agents may be warranted.

Critical Analysis

• A. Strengths
  • Randomized, double-blind, placebo-controlled design enhances internal validity.
  • Focus on a clinically relevant outcome: morphine-sparing effect, which is easily measurable.
  • Well-defined inclusion/exclusion criteria aided uniformity in a specialized patient population (CABG).
  • Monitored important safety outcomes (bleeding, creatinine changes).
• B. Limitations
  • Single-center setting may limit external validity.
  • Use of only two doses for each NSAID may underestimate potential differences with longer regimens.
  • Did not include patients over age 75 or those with higher baseline risk (e.g., advanced renal insufficiency, insulin-dependent diabetes), limiting generalizability.
  • VAS differences were small and not statistically significant, possibly underpowered for secondary endpoints.
  • Absence of a formal patient-controlled analgesia (PCA) approach may have influenced morphine dosing patterns.

Literature Context

• A. Previous Studies and Meta-Analyses
  • Early research into multimodal postoperative analgesia included neuraxial techniques (N Engl J Med. 2000;343(3):180-184.) and combinations of local anesthetics with opioids (J Clin Anesth. 1995;7(2):123-130.). Though these studies primarily addressed non-NSAID approaches, they helped establish that adjuncts can reduce opioid use.
  • More recent observational data (JAMA. 1990;264(7):893-897.) were methodologically weaker, indicating the need for randomized designs—fulfilled here.
• B. Contrasting Methodological Quality
  • Compared to earlier observational data, the randomized, double-blind design in this study improves internal validity. However, some contemporary large-scale NSAID evaluations (e.g., retrospective analyses, prospective multicenter RCTs) have looked at broader populations than the carefully selected cohort here.
• C. Comparisons with Guidelines
  • At the time (circa mid-1990s), ASA guidelines and standard anesthesia recommendations emphasized opioids ± local anesthetics. This study adds evidence that short-term NSAIDs are safe in well-screened patients, consistent with later guidelines endorsing multimodal analgesia when carefully applied to cardiac patients.
• D. This Trial’s Contribution (contextualizing up to 2025)
  • The study supports selective NSAID use after CABG to reduce opioid use. In subsequent decades (2000–2025), multiple studies (e.g., Flávio de Souza Brito, Am J Med, 2017; Eljezi et al., Pain Physician, 2017) confirmed that NSAIDs may be safe in certain patients with cautious screening.
  • Emerging data on selective COX-2 inhibitors highlight continued vigilance for renal and cardiovascular risks. However, the present trial remains one of the foundational reports showing feasible short-course NSAID use post-CABG.
  • In modern practice, multimodal analgesia is standard. This trial, although two decades old, still informs discussion on short-duration, carefully dosed NSAIDs in appropriate cardiac surgery patients, especially since opioid minimization is now a global priority.

Clinical Application

• These findings support adding diclofenac at up to 150 mg/day in short courses to reduce opioid requirements in lower-risk CABG populations, carefully monitoring for bleeding or renal changes.
• Real-world applicability in 2025 would still require patient selection (renal function, age, and GI risk) and close postoperative safety assessments, in combination with comprehensive multimodal analgesia strategies.

How To Use This Info In Practice

While this study alone does not warrant routine NSAID use in all post-CABG patients, it provides reassurance that in well-screened individuals, short-term diclofenac can be an effective adjunct for postoperative analgesia to reduce reliance on opioids.