1. 2025;28;E359-E369Preemptive Acetaminophen for Postoperative Analgesia in Children Undergoing Surgery: A Systematic Review and Meta-Analysis
   Systematic Review
   Xin-yi Hua, MMed, Ru-yi Zhang, PhD, Hua Xie, MMed, Zhong-xian Zhu, MMed, and Wei-bing Tang, PhD.

BACKGROUND: Preemptive analgesia is an antinociceptive intervention aimed at inhibiting hyperexcitability in both the peripheral and central nervous systems, diminishing the intensity of postoperative pain. Pre-analgesic acetaminophen has been employed extensively in diverse surgical procedures among adult individuals; however, its efficacy in pediatric patients remains controversial.

OBJECTIVES: This review aimed to evaluate the impact of preemptive acetaminophen on postoperative pain, rescue analgesia, and nausea and vomiting in children. 

STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs).

SETTING: The electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and Sino-Med were searched. The protocol was previously registered in the PROSPERO database under the registration number CRD 42023469972.

METHODS: We adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Thirteen RCTs examining the effects of preemptive APAP in pediatrics were incorporated. The risk of bias for each included study was independently assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. A systematic review and meta-analysis were performed using Review Manager Software version 5.4.

RESULTS: A total of 13 studies, observing 718 patients, were included. Our research found that children who received preoperative acetaminophen had a reduction in pain scores within one-2 hours (standardized mean difference [SMD], -2.83; 95% confidence interval [CI], -3.69 to -1.96; P < 0.001), and 6-8 hours (SMD,-2.23; 95% CI, -2.84 to -1.61; P < 0.001) postoperatively on the VAS scale and a lower incidence of rescue analgesia (odds ratio [OR], 0.50; 95% CI, 0.3-0.82; P = 0.006).

LIMITATIONS: The main limitation of this meta-analysis is the potential bias in the few studies included.

CONCLUSION: Preemptive acetaminophen in pediatric patients could effectively alleviate postoperative pain and decrease the need for additional rescue analgesic interventions.

KEY WORDS: Acetaminophen, paracetamol, preemptive analgesia, pain management, pediatric surgery, pain score, rescue analgesia, postoperative nausea, vomiting