Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review.

Non-opioid analgesics, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase 2 (COX-2) inhibitors are often given along with morphine as part of multimodal analgesia after major surgery. We have undertaken a systematic review and a mixed treatment comparison (MTC) analysis in order to determine explicitly which class of non-opioid analgesic, paracetamol, NSAIDs, or COX-2 inhibitors is the most effective in reducing morphine consumption and morphine-related adverse effects. Sixty relevant studies were identified. The MTC found that when paracetamol, NSAIDs, or COX-2 inhibitors were added to patient-controlled analgesia (PCA) morphine, there was a statistically significant reduction in morphine consumption: paracetamol [mean difference (MD) -6.34 mg; 95% credibility interval (CrI) -9.02, -3.65], NSAIDs (MD -10.18; 95% CrI -11.65, -8.72), and COX-2 inhibitors (MD -10.92; 95% CrI -12.77, -9.08). There was a significant reduction in nausea and postoperative nausea and vomiting with NSAIDs compared with placebo (odds ratio 0.70; 95% CrI 0.53, 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared with paracetamol or COX-2 inhibitors. There was no statistically significant difference in sedation between any intervention and comparator. On the basis of six trials (n=695), 2.4% of participants receiving an NSAID experienced surgical-related bleeding compared with 0.4% with placebo. The MTC found that there is a decrease in 24 h morphine consumption when paracetamol, NSAID, or COX-2 inhibitors are given in addition to PCA morphine after surgery, with no clear difference between them. Similarly, the benefits in terms of reduction in morphine-related adverse effects do not strongly favour one of the three non-opioid analgesics.

[1]  C. McArdle,et al.  DOUBLE-BLIND COMPARISON OF THE MORPHINE SPARING EFFECT OF CONTINUOUS AND INTERMITTENT I.M. ADMINISTRATION OF KETOROLAC , 1991 .

[2]  N. Woolacott,et al.  Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review. , 2010, Health technology assessment.

[3]  S. Schug,et al.  Safety Aspects of Postoperative Pain Management , 2006 .

[4]  N. Welton,et al.  Addressing between‐study heterogeneity and inconsistency in mixed treatment comparisons: Application to stroke prevention treatments in individuals with non‐rheumatic atrial fibrillation , 2009, Statistics in medicine.

[5]  J. Geddes,et al.  Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis , 2009, The Lancet.

[6]  Simon Wandel,et al.  Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis , 2007, The Lancet.

[7]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[8]  M. Tramèr,et al.  Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective Cyclooxygenase-2 Inhibitors and Patient-controlled Analgesia Morphine Offer Advantages over Morphine Alone?: Meta-analyses of Randomized Trials , 2005, Anesthesiology.

[9]  B. Cotton,et al.  Does the opioid-sparing effect of rectal diclofenac following total abdominal hysterectomy benefit the patient? , 2002, British journal of anaesthesia.

[10]  Nicola J Cooper,et al.  Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation. , 2006, Archives of internal medicine.

[11]  M. Stuart-Taylor,et al.  Comparative study of analgesic efficacy and morphine-sparing effect of intramuscular dexketoprofen trometamol with ketoprofen or placebo after major orthopaedic surgery. , 2003, British journal of clinical pharmacology.

[12]  Georgia Salanti,et al.  Evaluation of networks of randomized trials , 2008, Statistical methods in medical research.

[13]  G. Kenny,et al.  The morphine sparing effects of diclofenac sodium following abdominal surgery , 1987, Anaesthesia.

[14]  H. Owen,et al.  Sustained-Release Ibuprofen as an Adjunct to Morphine Patient-Controlled Analgesia , 1996, Anesthesia and analgesia.

[15]  F. Bonnet,et al.  Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. , 2005, British journal of anaesthesia.

[16]  H. Kehlet,et al.  The Value of “Multimodal” or “Balanced Analgesia” in Postoperative Pain Treatment , 1993, Anesthesia and analgesia.

[17]  E. Cassinelli,et al.  Ketorolac Use for Postoperative Pain Management Following Lumbar Decompression Surgery: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial , 2008, Spine.

[18]  C. McArdle,et al.  The morphine sparing effect of ketorolac tromethamine , 1987, Anaesthesia.

[19]  Deborah M Caldwell,et al.  Simultaneous comparison of multiple treatments: combining direct and indirect evidence , 2005, BMJ : British Medical Journal.

[20]  P. Beaulieu.  Non-opioid strategies for acute pain management , 2007, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[21]  P. Zufferey,et al.  Effects of Nonsteroidal Antiinflammatory Drugs on Patient-controlled Analgesia Morphine Side Effects: Meta-analysis of Randomized Controlled Trials , 2005, Anesthesiology.

[22]  Douglas G Altman,et al.  Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses , 2003, BMJ : British Medical Journal.

[23]  S. Brull,et al.  The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery. , 1997, Journal of clinical anesthesia.