Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.
OBJECTIVE
To investigate age-related differences in morphine requirements and metabolism in full-term neonates.


METHODS
Randomized double-blind study in the pediatric surgical intensive care unit.


METHODS
Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery.


METHODS
After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores.


RESULTS
Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant.


CONCLUSIONS
Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.
Bouwmeester
Nancy J
NJ
Department of Anesthesia, Erasmus Medical Center/Sophia Children's Hospital Rotterdam, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. j.bouwmeester.1@erasmusmc.nl
Hop
Wim C J
WC
van Dijk
Monique
M
Anand
K J S
KJ
van den Anker
John N
JN
Tibboel
Dick
D
D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001724:Birth Weight; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000097:blood; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000139:chemically induced; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine