Disposition and respiratory effects of intrathecal morphine in children

Background: The extent and duration of respiratory depression after opioid administration are poorly defined in infants and children. Methods: The disposition and respiratory effects of intrathecal morphine were studied in ten patients (ages 4 months-15 yr) after repair of craniofacial defects. Morphine, 0.02 mg/kg, was administered intrathecally before the end of surgery. Postoperatively, we determined the minute ventilation (V(E)) in response to increasing partial pressure of end-tidal carbon dioxide (PET(CO₂)) during carbon dioxide rebreathing. The slope (V(E)/PET(CO₂)) and intercept (V(E) at PET(CO₂) 60 mmHg, V(E) 60) of the carbon dioxide response curve were calculated at 6, 12, and 18 h after morphine administration. Cerebrospinal fluid (CSF) and blood were analyzed for morphine concentration by radioimmunoassay. Results: Mean V(E)/PET(CO₂) decreased from a preoperative value of 35.1 ± 3.7 to 16.3 ± 2.8 ml · kg^-1 · min^-1 · mmHg^-1 at 6 h after morphine, and remained depressed to 23.4 ± 2.9 and 23.5 ± 3.3 ml · kg^-1 · min^-1 · mmHg^-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) V(E)/PET(CO₂) at 6 h were 21, 4, and 27 ml · kg^-1 · min^-1 · mmHg^{- 1}. Mean V(E) 60 decreased from 874 ± 125 to 276 ± 32 ml · kg^-1 · min^{- 1} at 6 h, but then recovered at 12 and 18 h to 491 ± 68 and 567 ± 82 ml · kg^-1 · min^-1, respectively. The infants' V(E) 60 at 6 h were 350, 142, and 245 ml · kg^-1 · min^-1. Mean CSF morphine concentration was 2,860 ± 540 ng/ml at 6 h, and decreased to 640 ± 220 and 220 ± 150 ng/ml at 12 and 18 h, respectively. Conclusions: Intrathecal morphine, 0.02 mg/kg, depressed the ventilatory response to carbon dioxide for up to 18 h concomitant with increased CSF morphine concentrations. Infants (4-12 months of age) did not exhibit greater ventilatory depression than did children (2-15 yr of age).