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

Abstract

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.

Preventive Analgesia with Intravenous Paracetamol for Post-cesarean section Pain Control

“…Acetaminophen inhibits cyclooxygenase activity (COX-3) in central nervous system (CNS). In addition, paracetamol is a weak COX-1 and COX-2 inhibitor (anti-inflammatory effect) (8,13,19). In this study, measurements of blood pressure and heart rate in patients throughout the study period suggest that paracetamol does not have cardiovascular effects.…”

A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery

“…Likewise, Dodwell et al [24] reviewed NSAID for postoperative pain treatment in seven high-quality retrospective studies in spine surgery and did not find an increased risk of pseudoarthrosis from shortterm NSAID use during a 12-month follow-up period. On the other hand, NSAIDs have demonstrated significant analgesic properties with reduced need of opioids followed by reduced levels of PONV [25]. Thus, we included treatment with ibuprofen until discharge as part of the standard treatment protocol.…”

Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty

“…Multimodal analgesia in THA usually includes analgesics such as opioids, gabapentin, NSAIDs, acetaminophen, glucocorticoids, and local infiltration (Kardash et al 2008, Kerr and Kohan 2008, Toms et al 2008, Fredheim et al 2011, Maund et al 2011, Zhang et al 2011). …”