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 (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).
Nichols
D G
DG
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Yaster
M
M
Lynn
A M
AM
Helfaer
M A
MA
Deshpande
J K
JK
Manson
P N
PN
Carson
B S
BS
Bezman
M
M
Maxwell
L G
LG
Tobias
J D
JD
D000280:Administration, Inhalation; D000293:Adolescent; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects*; D012120:Respiration Disorders / Q000139:chemically induced*
D002245:Carbon Dioxide; D009020:Morphine