EFFECT OF INCREASED INTRAABDOMINAL PRESSURE ON HEPATIC EXTRACTION ANDCLEARANCE OF FENTANYL IN NEONATAL LAMBS

Fentanyl, an opioid metabolized by hepatic mixed function oxidases, is commonly administered as the primary anesthetic for neonates undergoi ng surgery. Pharmacokinetic studies have suggested that abdominal surg ery in neonates decreases fentanyl clearance, contending that this res ults from increases in intra-abdominal pressure (IAP) decreasing hepat ic blood flow. To examine the effects of IAP on hepatic blood flow and fentanyl clearance, we infused fentanyl to eight neonatal lambs, meas ured regional blood flows by using the radionuclide-labeled microspher e technique and determined hepatic fentanyl extraction and clearance a nd hepatic oxygen extraction and consumption at three levels of IAP: 0 , 12 and 18 mm Hg. Increased IAP did not affect portal or hepatic bloo d flow or ductus venosus shunt. Fentanyl extraction was 16.5 +/-3.0% ( mean+/-S.E) at 0 mm Hg of IAP. Increased IAP decreased hepatic extract ion of fentanyl, thereby decreasing fentanyl clearance. Increased IAP did not affect hepatic oxygen extraction or consumption. in two additi onal animals in which serial measurements of hepatic blood flow were o btained, increased IAP (15 mm Hg) transiently decreased hepatic blood flow with recovery to control values at 2 hr. The authors conclude tha t fentanyl is poorly extracted by neonatal livers, in contrast to its large extraction ratio in adults. The decrease in fentanyl clearance w ith increased IAP is consistent with pharmacokinetic studies demonstra ting decreased clearance in neonates undergoing abdominal surgery. How ever, the present study suggests that the mechanism of decreased clear ance is decreased hepatic function (decreased fentanyl extraction) rat her than decreased hepatic blood flow.