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Disposition and respiratory effects of intrathecal morphine in children
D G Nichols1, M Yaster, A M Lynn
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Insights
Intrathecal morphine depressed respiratory drive in children for up to 18 hours. Infants showed similar ventilatory depression to older children after receiving morphine.
Area of Science:
- Pediatric Anesthesiology
- Pharmacokinetics
- Respiratory Physiology
Background:
- The effects of opioid administration on respiratory function in pediatric patients are not well understood.
- Limited data exists on the duration and extent of respiratory depression following opioid use in infants and children.
Purpose of the Study:
- To investigate the respiratory effects and disposition of intrathecal morphine in pediatric patients.
- To determine the duration of ventilatory depression after intrathecal morphine administration.
Main Methods:
- Ten pediatric patients (4 months-15 years) received intrathecal morphine (0.02 mg/kg) post-craniofacial surgery.
- Carbon dioxide rebreathing was used to assess ventilatory response (VE/PETCO2 slope and VE 60 intercept) at 6, 12, and 18 hours post-administration.
- Cerebrospinal fluid (CSF) and blood morphine concentrations were measured via radioimmunoassay.
Main Results:
- Minute ventilation response to carbon dioxide was significantly depressed for up to 18 hours post-morphine administration.
- Infants (4-12 months) did not experience greater ventilatory depression compared to older children (2-15 years).
- CSF morphine concentrations remained elevated for 18 hours, correlating with depressed ventilatory response.
Conclusions:
- Intrathecal morphine at 0.02 mg/kg causes prolonged depression of the ventilatory response to carbon dioxide in pediatric patients.
- The study found no significant difference in ventilatory depression between infants and older children.
- Findings highlight the need for careful monitoring of respiratory function after intrathecal morphine in pediatric populations.
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 (VE) in response to increasing partial pressure of end-tidal carbon dioxide (PETCO2) during carbon dioxide rebreathing. The slope (VE/PETCO2) and intercept (VE at PETCO2 60 mmHg, VE 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 VE/PETCO2 decreased from a preoperative value of 35.1 +/- 3.7 to 16.3 +/- 2.8 ml.kg-1 x min-1 x mmHg-1 at 6 h after morphine, and remained depressed to 23.4 +/- 2.9 and 23.5 +/- 3.3 ml.kg-1 x min-1 x mmHg-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) VE/PETCO2 at 6 h were 21, 4, and 27 ml.kg-1 x min-1 x mmHg-1. Mean VE 60 decreased from 874 +/- 125 to 276 +/- 32 ml x kg-1 x min-1 at 6 h, but then recovered at 12 and 18 h to 491 +/- 68 and 567 +/- 82 ml.kg-1 x min-1, respectively. The infants' VE 60 at 6 h were 350, 142, and 245 ml.kg-1 x 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).