Hung-Yu Wang1, Tien-Yu Chen2, Dian-Jeng Li3, Pao-Yen Lin4, Kuan-Pin Su5, Min-Hsien Chiang6, Andre F Carvalho7, Brendon Stubbs8, Yu-Kang Tu9, Yi-Cheng Wu10, Michael Roerecke11, Lee Smith12, Ping-Tao Tseng13, Kuo-Chuan Hung14. 1. Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan. 2. Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan. 3. Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan. 4. Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 5. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. 6. Department of Anesthesiology, Shin Huey Shin Hospital, Kaohsiung, Taiwan. 7. IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia. 8. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; Positive Ageing Research Institute (PARI), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK. 9. Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. 10. Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan. 11. Independent Scientist, Institute for Mental Health Policy Research, PAHO/WHO Collaborating Centre for Addiction and Mental Health, Centre for Addiction and Mental Health (CAMH), Dalla Lana School of Public Health (DLSPH), University of Toronto, Canada. 12. Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK. 13. Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address: ducktseng@gmail.com. 14. Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. Electronic address: ed102605@gmail.com.
Abstract
STUDY OBJECTIVE: This updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA). DESIGN: Network meta-analysis (PROSPERO registration: CRD42020179483). SETTING: Postoperative recovery area. PATIENTS: Pediatric patients undergoing GA with sevoflurane. INTERVENTIONS: Pharmacological interventions applied during GA with sevoflurane. MEASUREMENTS: This network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia. MAIN RESULTS: Seventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium. CONCLUSIONS: This network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings.
STUDY OBJECTIVE: This updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA). DESIGN: Network meta-analysis (PROSPERO registration: CRD42020179483). SETTING: Postoperative recovery area. PATIENTS: Pediatric patients undergoing GA with sevoflurane. INTERVENTIONS: Pharmacological interventions applied during GA with sevoflurane. MEASUREMENTS: This network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia. MAIN RESULTS: Seventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium. CONCLUSIONS: This network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings.