Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support.
The pharmacokinetics of morphine have not been previously studied in children following cardiac surgery for tetralogy of Fallot (TOF) or transposition of the great arteries (TGA). Morphine steady-state pharmacokinetics were studied in 21 children undergoing repair of TOF, TGA, or atrio-ventricular septal defects (AVSD). Children with TOF or TGA had increased right-sided pressures with no differences between the groups. Children with TOF had significantly faster clearance rates of morphine (1.39 +/- 0.37 L/kg/h) than children following the Fontan procedure (0.86 +/- 0.31 L/kg/h, P < 0.01). When stratifying children by their postsurgical needs for inotropic support, those needing epinephrine, dopamine, or dobutamine at more than 10 micrograms/kg/min had significantly slower clearance rates (0.73 +/- 0.3 L/kg/h) when compared to the rest of the patients (1.5 +/- 0.41 L/kg/h, P < 0.05). Because most children needing inotropic support underwent the Fontan procedure, it is conceivable that their cardiovascular status had a major impact on morphine metabolism. These results suggest a 50% reduction in morphine dosage in children requiring inotropic support following cardiac surgery.
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario.
O
O
Dagan
J
J
Klein
D
D
Bohn
G
G
Barker
G
G
Koren
D001794:Blood Pressure / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004280:Dobutamine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D006343:Heart Septal Defects / Q000378:metabolism / Q000601:surgery; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013771:Tetralogy of Fallot / Q000378:metabolism / Q000601:surgery; D014188:Transposition of Great Vessels / Q000378:metabolism / Q000601:surgery
D002316:Cardiotonic Agents; D004280:Dobutamine; D009020:Morphine; D004298:Dopamine; D004837:Epinephrine