Abstract
Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.
Highlights
Two previous human studies reported that rocuronium infusion requirement was not significantly reduced in the anhepatic phase of liver transplantation[5,6]
The current study consisted of a human study which examined the requirement of rocuronium to maintain neuromuscular blockade in anhepatic phase of orthotopic liver transplantation (OLT), and rat studies to determine the possible contribution of the kidneys to rocuronium clearance under the condition of impaired bile secretion
The reduction of rocuronium infusion requirement during the anhepatic phase of OLT was examined in 16 children with congenital biliary atresia
Summary
Experiments were conducted on 7 or 28 days after ligating the bile duct. Potential contribution of the renal excretion vs. hepatic secretion on rocuronium clearance was examined by functionally removing the liver vs. kidneys (pharmacodynamics) and by concentration determination (pharmacokinetics). The underlying mechanisms focused on Oatp[1] and Oatp[2] in kidneys were explored by Oatp[2] knock-down and Oatp[1] overexpression via adeno-associated virus (AAV)
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