Only a small reduction in morphine use with adding NSAIDs, paracetamol or COX-2 inhibitors to patient controlled morphine in the 24 h after major surgery
- Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Correspondence to Hance Clarke
Toronto General Hospital, Eaton N. 3EB – 317, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada;
Objectives and overview
The objective of this study was to determine which class of non-opioid analgesics – paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors – was the most effective at reducing intravenous. Morphine consumption and opioid related adverse events following major surgery.
The authors conducted a systematic review which combined a review by Elia and colleagues1 with the results of 20 new studies. All studies were randomised controlled trials (RCTs) that reported postoperative 24 h cumulative morphine consumption. The other outcomes of interest were morphine-related adverse events and postoperative bleeding. With the aid of a biostatistician, the authors report a series of mixed treatment comparisons.
Results and major conclusions
The major finding of this article was that compared to placebo (45.26 mg) NSAIDs or COX-2 inhibitors reduced by 10.9 mg, and paracetamol reduced by 6.3 mg, 24 h postoperative morphine use. Multiple analyses and tables were presented which postulated that non-opioid adjuncts were marginally beneficial in reducing adverse events and bleeding outcomes. The authors conclude that taking the evidence as a whole (ie, the small reductions in morphine consumption and the wide CIs for the adverse events), there is not a strong case for suggesting routine addition of any of the three adjuncts to patient-controlled analgesia (PCA) morphine for 24 h after surgery. The authors also recommend that future trials testing new analgesics in conjunction with morphine should focus on morphine-related adverse events, ensuring that the power calculation is based on morphine-related adverse outcomes rather than morphine consumption.
I commend the authors for tackling this topic. Unfortunately they are limited by the data presented. Their analysis is certainly sufficient and their conclusions fit with the data presented but I would suggest that additional data are needed to truly support their conclusion; namely (1) morphine consumption beyond the 24 h point, (2) more comprehensive data on adverse events and (3) pain scores reported concomitantly with measures of morphine consumption.
The authors' conclusions should not be made based solely on the 24 h postoperative time point. For many years, the primary modality used for postoperative pain has been opioid-based analgesia. However, the side effects of opioid-based analgesics often impair patient progress and recovery after surgery.2 The increased morbidity associated with opioid-only strategies, and the fact that opioid medications tend to be ineffective at relieving movement evoked pain, have created a movement in perioperative pain practice to adopt multimodal analgesic strategies.
There are several shortcomings from a clinical perspective. First, the significant variation in opioid consumption among the studies cited 8.6 mg (SD 5.2) to a maximum of 141.5 mg (SD 74.9) brings into question the severity of pain that these patients experienced within the first 24 h after surgery. With the advances in the understanding of the pathophysiology of pain, multimodal analgesia has become the standard of practice to treat moderate to severe postsurgical pain following major surgery.3 In studies that demonstrated minimal morphine consumption, one could argue (as the authors have done) that the use of multimodal analgesia may not add to a clinically significant decrease in immediate postoperative morphine use (ie, <24 h). If postoperative PCA use was higher (reflecting a more painful postoperative acute pain experience), it is likely that the demonstrated NSAID, COX-2 and paracetamol decreases in morphine consumption would have been higher. Furthermore, it is clear that although single-agent therapy may attenuate central nociceptive processing, studies have demonstrated that multimodal analgesic therapy is more effective, and is often associated with fewer side effects compared with high-dose, single-agent opioid therapy over the entire perioperative period.4 5 Research is ongoing with respect to the preventive effects of multimodal analgesia6 and its possible contribution to the reduction of chronic postsurgical pain.7 Furthermore, many adverse events occur beyond the 24 h postoperative period and I would suggest that researchers power future studies based on functional outcomes such as movement related end points, in addition to opioid related adverse events.
Notwithstanding the authors' assumptions that pain was well controlled by the use of intravenous PCA, the absence of a measure of pain at the 24 h mark, measured concomitantly with the morphine consumption is a methodological flaw that confounds the interpretation of the difference in morphine consumption. It is possible that pain scores were significantly different between the groups raising the question of what the magnitude of difference in morphine consumption would have been had the groups not differed in pain intensity. While admittedly this is conjecture, it is essential to report pain scores in any study or review article that deals with analgesic consumption since the two covary so closely.6
Once again, the authors should be commended for the systematic review. With respect to current nursing practices, this study suggests that multimodal analgesia is not necessary and may not be clinically significant within the early postoperative setting. Unfortunately, this would mean a change in current perioperative pain practices which in many institutions is based on evidence that supports the superiority of multimodal analgesia versus opioid based only postoperative pain strategies. Future RCTs are needed to examine the use of multimodal analgesic strategies on pain, functional outcomes and opioid-related adverse events after major surgery before the field reverts to opioid only strategies.