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Background: Surgery of the posterior fossa often produces intense postoperative pain. However, this pain is infrequently treated because of concern that opioid administration may mask the postoperative neurologic examination and/or produce hypercarbia. In this prospective, randomized controlled trial, we sought to determine whether IV patient-controlled analgesia (PCA) would lead to reductions in postoperative pain after neurosurgical procedures of the posterior fossa compared with conventional IV nurse-administered as-needed (PRN) therapy., Methods: Eighty patients (age range, 18-82 years) undergoing elective posterior fossa surgery were randomized to receive postoperative IV fentanyl PRN 25 to 50 μg every 30 minutes or via PCA 0.5 μg/kg/dose, with a maximal dose limit of 50 μg, and 15-minute lockout (4 doses/hour). We measured pain (Numerical Rating Scale, 0-10), analgesic use, sedation (Ramsay Sedation Scale and Glasgow Coma Scale), respiration, hemodynamics, and adverse events hourly., Results: Sixty-five patients completed the study. Thirty-one patients received IV PCA and 34 received PRN analgesia. Patient demographics did not differ between groups. Patients in the PCA group reported less pain at rest (mean [95% confidence interval]: 3.7 [3.0, 4.4] vs 5.2 [4.5, 5.8], P = 0.003) and received more fentanyl (mean [95% confidence interval]: 54.8 [42.1, 67.6] vs 29.9 [24.2, 35.7] μg/h, P = 0.002) than those in the PRN group. There were no differences in side effects and no adverse events related to analgesic therapy., Conclusions: IV PCA use resulted in reduction in postoperative pain compared with PRN analgesic therapy after surgery of the posterior fossa. Larger studies will be required to determine the safety of IV PCA in this patient population.

Background: Opioid-induced side effects, such as pruritus, nausea, and vomiting are common and may be more debilitating than pain itself. A continuous low-dose naloxone infusion (0.25 μg/kg/h) ameliorates some of these side effects in many but not all patients without adversely affecting analgesia. We sought to determine the optimal dose of naloxone required to minimize opioid-induced side effects and to measure plasma morphine and naloxone levels in a dose escalation study., Methods: Fifty-nine pediatric patients (24 male/35 female; average age 14.2 ± 2.2 years) experiencing moderate to severe postoperative pain were started on IV patient-controlled analgesia morphine (basal infusion 20 μg/kg/h, demand dose 20 μg/kg, 5 doses/h) and a low-dose naloxone infusion (initial cohort: 0.05 μg/kg/h; subsequent cohorts: 0.10, 0.15, 0.25, 0.40, 0.65, 1, and 1.65 μg/kg/h). If 2 patients developed intolerable nausea, vomiting, or pruritus, the naloxone infusion was increased for subsequent patients. Dose/treatment success occurred when 10 patients had minimal side effects at a naloxone dose. Blood samples were obtained for measurement of plasma morphine and naloxone levels after initiation of the naloxone infusion, processed, stored, and measured by tandem mass spectrometry with electrospray positive ionization., Results: The minimum naloxone dose at which patients were successfully treated with a <10% side effect/failure rate was 1 μg/kg/h; cohort size varied between 4 and 11 patients. Naloxone was more effective in preventing pruritus than nausea and vomiting. Concomitant use of supplemental medicines to treat opioid-induced side effects was required at all naloxone infusion rates. Plasma naloxone levels were below the level of assay quantification (0.1 ng/mL) for infusion rates ≤0.15 μg/kg/h. At rates >0.25 μg/kg/h, plasma levels increased linearly with increasing infusion rate. In each dose cohort, patients who failed therapy had comparable or higher plasma naloxone levels than those levels measured in patients who did not fail treatment. Plasma morphine levels ranged between 3.52 and 172 ng/mL, and >90% of levels ranged between 10.2 and 61.6 ng/mL. Plasma morphine levels were comparable between patients who failed therapy and those patients who achieved symptom control., Conclusions: Naloxone infusion rates ≥1 μg/kg/h significantly reduced, but did not eliminate, the incidence of opioid-induced side effects in postoperative pediatric patients receiving IV patient-controlled analgesia morphine. Patients who failed therapy generally had plasma naloxone and morphine levels that were comparable to those who had good symptom relief suggesting that success or failure to ameliorate opioid-induced side effects was unrelated to plasma levels.