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Many studies have evaluated conscious sedation regimens commonly used in pediatric patients. Recent advances in capnography equipment now enable physicians to assess respiratory parameters, specifically end-tidal CO2 (et-CO2), more accurately in spontaneously breathing sedated children than was possible in the earlier studies. This study was designed to: 1) compare the safety and efficacy of intravenous fentanyl, intravenous fentanyl combined with midazolam, and intramuscular meperidine-promethazine-chlorpromazine (MPC) compound when used for painful emergency department (ED) procedures; and 2) to determine whether the addition of et- CO2 monitoring enabled earlier identification of respiratory depression in this population.Forty-two children requiring analgesia and sedation for painful ED procedures were randomly assigned to receive either fentanyl, fentanyl-midazolam, or MPC compound. Vital signs, oxygen saturation, and et-CO2 were monitored continuously. Pain, anxiety, and sedation scores were recorded every five minutes.Respiratory depression (O2 saturation ≤ 90% for over one minute or any et-CO2 ≥ 50) occurred in 20% of fentanyl, 23% of fentanyl-midazolam, and 11% of MPC patients (P=NS). Of those patients manifesting respiratory depression, 6/8 were detected by increased et-CO2 only. MPC patients required significantly longer periods of time to meet discharge criteria than fentanyl and fentanyl-midazolam patients (P<0.05). No differences were noted in peak pain, anxiety, or sedation scores.Fentanyl, fentanyl-midazolam, and MPC produced a high incidence of subclinical respiratory depression. End-tidal CO2 monitoring provided an earlier indication of respiratory depression than pulse oximetry and respiratory rate alone. MPC administration resulted in a significantly delayed discharge from the ED.