Extrahepatic metabolism of sevoflurane in children undergoing orthotopic liver transplantation.

BACKGROUND: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation. METHODS: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode. RESULTS: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 microM (sevoflurane group) versus 1.4 +/- 0.5 microM (isoflurane group) P < 0.05). CONCLUSIONS: These results demonstrate the existence of an extrahepatic metabolism of sevoflurane at least in children with end-stage liver disease.

Hepatopulmonary syndrome and liver transplantation: a review of the peroperative management of seven paediatric cases.

Until recently, hypoxaemia was considered as a relative contraindication for liver transplantation. The hepatopulmonary syndrome associated with a right to left shunt of blood through the lungs is reversible in adults and children after correction of the cirrhosis by liver transplantation. However, concerns have been raised regarding the risks of anaesthesia in such hypoxaemic patients. Since the peroperative management of children undergoing liver transplantation and suffering from hepatopulmonary syndrome and severe hypoxemia has never been described, we report here our experience in seven children. Despite the fact that severe arterial desaturation was recorded throughout the procedure, no major complications were recorded peroperatively. The postoperative intubation time was 58 +/- 21 h, five children being extubated while still hypoxaemic. All seven patients reversed their hepatopulmonary syndrome after a mean postoperative period of 24 +/- 10 weeks. This shows that liver transplantation can be successfully achieved in severely hypoxaemic children and that postoperative correction of the right to left shunt is then obtained.

Combination of inhaled nitric oxide with i.v. nitroglycerin or with a prostacyclin analogue in the treatment of experimental pulmonary hypertension.

We have studied the effect of combining inhaled nitric oxide (NO) with an i.v. vasodilator agent, nitroglycerin, or ciloprost, a prostacyclin analogue, during acute pulmonary hypertension in pigs, induced by continuous infusion of a thromboxane analogue (U46619), adjusted to maintain mean pulmonary artery pressure (MPAP) at 40 mm Hg. The effects of the different treatments on MPAP and pulmonary resistances were determined. In the first part of the study, we determined the dose-response to increased NO concentrations from 5 to 40 ppm. This showed a maximum pulmonary effect with NO 5 ppm, but with no systemic effects. The effect of NO 10 ppm was then compared with two i.v. drugs. Nitroglycerin was less effective than NO on pulmonary vessels but induced significant arterial hypotension. Pulmonary vasodilatation induced by ciloprost was greater than that by NO but with the same side effects as nitroglycerin on systemic variables. We also found that the combination of NO and nitroglycerin had the same pulmonary effects as NO 10 ppm but that adding ciloprost to NO decreased pulmonary pressures significantly more than either drug used alone. We conclude that inhaled NO may be usefully combined with i.v. ciloprost but not with i.v. nitroglycerin.

Extrahepatic glucuronidation of propofol in man: possible contribution of gut wall and kidney.

OBJECTIVE: Results from clinical pharmacokinetic studies of propofol indicate that this i.v. anaesthetic agent may undergo significant extrahepatic glucuronidation. We have investigated whether glucuronidation of propofol takes place in the kidney and/or the gut wall. First, propofol concentrations were measured in arterial (radial artery) and portal venous blood of 12 cirrhotic patients with trans internal jugular porto-systemic shunting (TIPSS). RESULTS: In 7 of the 12 patients arterial propofol concentrations were higher than portal venous concentrations. In the remaining patients, propofol concentrations were higher in the portal vein than the radial artery. Since an additional study in 5 patients anaesthetized with propofol while undergoing cholecystectomy showed propofol and an acid-labile conjugate of it in bile, it is difficult to interpret the results in patients with TIPSS due to the possibility of enterohepatic cycling. Next, in vitro studies with human liver (n = 5), kidney (n = 5) and small intestinal (n = 5) microsomes showed that all three tissues were capable of forming propofol glucuronide. Vmax for propofol glucuronidation was approximately 3 to 3.5 times higher in kidney (5.56 nmol.min-1.mg-1 protein) than liver (1.80 nmol.min-1.mg-1 protein) and small intestine (1.61 nmol.min-1.mg-1 protein). CONCLUSION: Based on these in vitro results, it is concluded that extrahepatic glucuronidation in the small intestine and especially in the kidney may contribute to the overall glucuronidation of propofol in man.

Anaesthetic considerations in progressive familial intrahepatic cholestasis (Byler's disease).

Progressive familial intrahepatic cholestasis (PFIC) or Byler's disease is one of the most common forms of intrahepatic cholestasis of metabolic and genetic origin. Affected children progress to terminal cirrhosis before adulthood and at present the only curative treatment of PFIC is orthotopic liver transplantation (OLT). We present a retrospective review of 40 general anaesthetics administered in our hospital to 22 patients with PFIC undergoing various procedures. The clinical features of PFIC and the anaesthetic implications of chronic cholestasis in children (malnutrition, cirrhosis, portal hypertension, chronic hypoxaemia) are reviewed.

Propofol pharmacokinetics in children with biliary atresia.

We studied the pharmacokinetics of an i.v. bolus dose of propofol 2.5-3.0 mg kg-1 in eight children (age 4-24 months) with biliary atresia and in six control (ASA I) children (age 11-43 months). Blood samples were obtained for 4 h after administration of propofol. Blood concentrations of propofol were measured by high pressure liquid chromatography. Systemic clearance of propofol (CI) and volume of distribution at steady state (Vss) showed a highly significant correlation with body weight. Propofol CI and Vss, normalized for body weight, were similar in children with biliary atresia (mean 37.5 (SD 8.3) ml min-1 kg-1 and 3.5 (1.6) litre kg-1, respectively) compared with control children (38.7 (6.8) ml min-1 kg-1 and 2.4 (0.8) litre-1 kg-1, respectively). We conclude that in children with biliary atresia the pharmacokinetics of propofol are similar to those of healthy children.

Hemostasis in children undergoing liver transplantation.

We reviewed the records of 200 children who underwent 238 orthotopic liver transplantations in order to determine which preoperative factors could predict intraoperative blood loss. A coagulation abnormality score (CAS) was calculated by allowing one point for each abnormality in six preoperative coagulation tests. The mean CAS values were significantly greater in children suffering from fulminant hepatic failure (Fulm) or post-necrotic cirrhosis (PNC) and those having retransplantation (ReTx) than in those with disease of other etiologies. No correlation was found between the CAS and the mean blood requirements in the different etiology groups. According to the amount of blood transfused, children could be divided in two groups. Group 1 were those with biliary atresia and ReTx, who received more than 200 ml/kg. Group 2 included those with PNC, Fulm, metabolic diseases, and Alagille syndrome and Byler disease, who received less than 140 ml/kg. The mean CAS was significantly lower and the PT significantly better in Group 1. We conclude that preoperative coagulation tests were weak predictors of intraoperative bleeding. The etiology of the underlying liver disease and previous abdominal surgery play an important role in the occurrence of severe bleeding. Intraoperatively, children presented the same hemostatic changes as adults.

Lessons from 1100 pediatric caudal blocks in a teaching hospital.

METHODS: The demographic and technical data of all the pediatric caudal blocks (CBs) performed from August 1986 to September 1989 in our teaching hospital were prospectively collected on a computerized protocol. Except for 22 high-risk ex-premature infants, all CBs were performed under halothane or isoflurane anesthesia, after premedication with atropine. Moreover, they were performed using local anesthetic solutions containing 1:200,000 epinephrine. A total of 1100 CBs were performed in children younger than 7 years; 203 patients weighed 5 kg or less; 260, 5.1-10 kg; 300, 10.1-15 kg; and 337, more than 15.1 kg. The CBs were also analyzed according to the anesthesiologist's experience with CB: 184 were performed by anesthesiologists who had performed fewer than 10 CBs (Group A); 210, 10-20 CBs (Group B), and 704, more than 20 CBs (Group C). RESULTS: We found difficult landmarks in 11.2% of our patients. Moreover, it was significantly more frequent (p = 0.0004) if the patients weighed less than 10 kg, because of poor anatomy or obesity. There were 76 bloody taps (BTs, 6.9%); although there was a statistically insignificant trend toward a lower incidence of BTs in the 5.1-10-kg group, experience seemed to influence the incidence of BTs, as it decreased from 11.4% in Group A to 8.9% and 5.4% in Groups B and C, respectively (p less than 0.05). There were eight systemic reactions (i.e., brisk onset of tachycardia during or shortly after the CB), which were all short-lived and responded quickly to hyperventilation with oxygen. Two occurred despite repositioning the needle after a previous BT, but six occurred with no previous evidence of blood and were thus called "concealed" BTs. Moreover, all occurred in children weighing 10 kg or less. There was only one dural tap. Only nine CBs (0.81%) failed to provide effective intraoperative anesthesia, and 93% of the patients left the recovery room without having required narcotic or non-narcotic analgesics. CONCLUSIONS: Our results confirm that CB is a reliable technique, easy to perform by beginners. It should be stressed, however, that small infants are at increased risk of concealed BTs.

Guillain-Barre syndrome after obstetrical epidural analgesia.

Guillain Barre Syndrome (GBS) occurred 24 hours post-partum following an obstetrical epidural anesthetic (OEA) procedure. Clinical diagnosis was confirmed by cerebrospinal fluid (CSF) findings and nerve conduction velocity studies. GBS is an immune mediated process. Because of short latency between the onset of symptoms and the performance of the epidural block, a cause and effect relationship between epidural block and GBS in this patient is unlikely.

Malignant hyperthermia: routine monitoring and early detection.

A case of malignant hyperthermia during an emergency operation is described. The anesthetic management for the same patient undergoing a subsequent operation is also described. The importance of adequate monitoring during anesthesia is discussed.