piperidines and Liver-Failure

Topics: Adenine; Aged; Aged, 80 and over; Hepatitis B virus; Humans; Liver Failure; Lymphoma, Non-Hodgkin; Male; Middle Aged; Piperidines

Opioids and especially fentanyl are widely used during the intensive care unit management of intracranial pressure in fulminant hepatic failure patients as well as during and after liver transplantation. The newer synthetic opioid remifentanil is also increasingly being used in critical care patients. Due to a lack of data relating to the influence of acute hepatic failure on remifentanil and fentanyl pharmacokinetics, this study was designed in order to determine the impact of this condition on the blood levels of these opioids using a pig model.. Twenty pigs were randomly assigned to one of two groups: A group with surgically induced acute hepatic failure by hepatic devascularization (acute hepatic failure, n=10) and a control group (SHAM, n=10), subjected to a SHAM operation. Postoperatively, five animals in each group were administered remifentanil (1 microg kg-1 min-1) or fentanyl (0.2 microg kg-1 min-1) by continuous intravenous infusion. Blood samples for determination of drug concentrations were withdrawn at 0 h and 0.5, 1, 5, 7, 9 h after initiation of dosing.. Significantly higher blood concentrations were found in animals with acute hepatic failure compared to SHAM-operated animals receiving remifentanil at 5 h (P=0.003), 7 h (P=0.007) and 9 h (P=0.004) and fentanyl at 7 h (P<0.0005) and 9 h (P=0.05). The small number and the great variability in drug concentrations did not allow a detailed kinetic analysis to be performed. Approximate clearance values were found to be greater for the SHAM compared with the acute hepatic failure animals for both fentanyl and remifentanil.. Hepatic devascularization in our porcine acute hepatic failure model, appears to have significantly altered the disposition of fentanyl and unexpectedly remifentanil. These changes were thought to be brought about by severe disruption of blood flow and biotransformation in the liver, as well as by haemodynamic changes in the acute hepatic failure animals.

Topics: Acute Disease; Animals; Female; Fentanyl; Hemodynamics; Liver Failure; Models, Animal; Piperidines; Remifentanil; Swine

We describe the use of remifentanil in three infants with complex medical issues (hepatic failure, cyanotic heart disease and renal compromise). The short duration of opioid effect even after a long period of drug infusion (18 h) suggests this drug may be useful in some infants. Continued study is warranted.

Topics: Analgesics, Opioid; Down Syndrome; Ductus Arteriosus, Patent; Endocardial Cushion Defects; Heart Failure; Hemodynamics; Humans; Infant; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Kidney Diseases; Liver Failure; Male; Piperidines; Remifentanil; Rubinstein-Taybi Syndrome

We describe a 73-yr-old woman anaesthetized for a laminectomy. She suffered from hepatic failure with mild encephalopathy complicated by several exacerbations associated with sedative and opioid therapy. The challenge for anaesthesia management was to provide adequate analgesia and avoid causing hepatic encephalopathy during and after the surgery. We used remifentanil to provide intraoperative and postoperative analgesia, because it has a short duration of action and does not require hepatic metabolism. We closely monitored the respiratory and the neurological status throughout the administration and conclude that remifentanil can provide perioperative analgesia in patients at risk of developing hepatic encephalopathy.

Topics: Aged; Analgesia; Analgesics, Opioid; Arachnoid Cysts; Chronic Disease; Contraindications; Female; Humans; Laminectomy; Liver Failure; Pain, Postoperative; Piperidines; Remifentanil