Pharmacokinetics of ropivacaine in patients with chronic end-stage liver disease.
BACKGROUND
Ropivacaine is mainly eliminated by hepatic metabolism. The authors studied the effect of chronic end-stage liver disease on the pharmacokinetics of ropivacaine.


METHODS
Thirteen patients with chronic end-stage liver disease and eight healthy volunteers received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'-pipecoloxylidide were measured in venous plasma and urine.


RESULTS
Peak ropivacaine plasma concentrations were similar. Patients with chronic end-stage liver disease had, on average, 60% lower total (P=0.001) and 56% lower unbound plasma clearance (P=0.002), 59% higher steady state volume of distribution (P=0.03), and 4.2-fold longer half-life (P<0.001) of ropivacaine. Of the variation in total ropivacaine clearance, 69% was accounted for by variation in albumin, 57% in prealbumin, 25% in international normalized ratio of plasma thromboplastin time, and 24% in galactose half-life. The patients excreted a larger fraction of the original dose as unchanged ropivacaine (2.1% vs. 0.3%; P<0.001) and a smaller fraction as 3-hydroxyropivacaine (11% vs. 27%; P=0.001). The fraction excreted as 2',6'-pipecoloxylidide (4.7% vs. 5.0%) was similar.


CONCLUSIONS
Ropivacaine clearance is decreased in chronic end-stage liver disease. A normal dose can be considered for a single block in patients with liver impairment, because the peak plasma concentrations were essentially similar. When using a postoperative ropivacaine infusion in a patient with end-stage liver disease, the lowest effective dose should be used for the shortest possible time and the patient should be monitored closely, because systemic toxicity cannot be ruled out. Because of wide interindividual differences in pharmacokinetics in patients with liver disease, no definitive dosing instructions can be given.
Jokinen
Mika J
MJ
Department of Anesthesia and Intensive Care Medicine, Clinic of Transplantation and Liver Surgery, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mika.jokinen@hus.fi
Neuvonen
Pertti J
PJ
Lindgren
Leena
L
Höckerstedt
Krister
K
Sjövall
Jan
J
Breuer
Olof
O
Askemark
Yvonne
Y
Ahonen
Jouni
J
Olkkola
Klaus T
KT
D000328:Adult; D000577:Amides / Q000009:adverse effects / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D015209:Cholangitis, Sclerosing / Q000378:metabolism; D002908:Chronic Disease; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology; D005260:Female; D019693:Hepatitis, Autoimmune; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D019388:Cytochrome P-450 CYP1A2