Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children

Abstract

Background and objectives: Perioperative pain in children can be effectively managed with systemic opioids, but addition of paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce opioid requirements and potentially improve analgesia and/or reduce adverse effects.

Methods: A systematic literature search was conducted to identify trials evaluating postoperative opioid requirements in children and comparing NSAID and/or paracetamol with placebo. Studies were stratified according to design: continuous availability of intravenous opioid (PCA/NCA) vs intermittent 'as needed' bolus; and single vs multiple dose paracetamol/NSAIDs. Primary outcome data were extracted, and the percentage decrease in mean opioid consumption was calculated for statistically significant reductions compared with placebo. Secondary outcomes included differences in pain intensity, adverse effects (sedation, respiratory depression, postoperative nausea and vomiting, pruritus, urinary retention, bleeding), and patient/parent satisfaction.

Results: Thirty-one randomized controlled studies, with 48 active treatment arms compared with placebo, were included. Significant opioid sparing was reported in 38 of 48 active treatment arms, across 21 of the 31 studies. Benefit was most consistently reported when multiple doses of study drug were administered, and 24 h PCA or NCA opioid requirements were assessed. The proportion of positive studies was less with paracetamol, but was influenced by dose and route of administration. Despite availability of opioid for titration, a reduction in pain intensity by NSAIDs and/or paracetamol was reported in 16 of 29 studies. Evidence for clinically significant reductions in opioid-related adverse effects was less robust.

Conclusion: This systematic review supports addition of NSAIDs and/or paracetamol to systemic opioid for perioperative pain management in children.

Figure 1

Flow chart of literature search with summary of excluded and included studies and grouping according to study design.

Figure 2

Percentage reduction in opioid requirements in pair-wise comparisons of mean opioid dose requirements in active treatment arms (paracetamol; NSAID; combination = NSAID + paracetamol) vs control/placebo. Studies reporting no statistically significant difference from control are designated as 0% reduction. Solid line = mean of NSAID arms; dotted line = mean of paracetamol arms. Treatment groups comprise Group A = PCA/NCA + study drug ≥24 h; Group B = PCA/NCA + study drug ≤6 h; Group C: intermittent opioid + study drug ≥24 h; Group D = intermittent opioid + study drug ≤6 h.