[Evaluation of renal function during orthotopic liver transplantation]. / Valutazione della funzione renale in corso di trapianto ortotopico di fegato.

BACKGROUND: Orthotopic liver transplantation (OLI) is a recognised means of therapy for endstage liver failure (ESLF). Both the preoperative alterations of renal function, closely correlated with the ESLF, and the frequent and abrupt changes of circulating blood volumes occurring during the various phases of OLT are able to significantly alter renal function during the perioperative period. METHODS: In order to define the specific changes of renal function during the various phases of OLT, six postnecrotic cirrhotic patients undergoing their first OLT entered a prospective study protocol. All the patients had standard and anesthetic techniques including the venovenous bypass (VVBP) during the anhepatic phase. At standard intervals (baseline, during hepatic dissection, during the anhepatic phase, following reperfusion, at the end of surgery) together with complete hemodynamic and metabolic profiles, arterial blood and urine samples were obtained to determine electrolytes and creatinine concentrations, blood levels of atrial natriuretic factor, aldosterone and renin activity. Using standard formulas creatinine clearance (Ccreat) and Na absolute and fractional excretions (FeNa%) were calculated. RESULTS: Major changes in the hemodynamic profile occurred during the anhepatic phase in spite of the use of the VVBP (reduced cardiac index, reduced pulmonary wedge pressure, increased systemic vascular resistances). Concomitantly a significant decrease in Ccreat (-67%) and in urinary output, was present while aldosterone and renin activity increased. The changes in Ccreat persisted at the end of surgery in spite of the optimal hemodynamic profile. Aldosterone and renin activity returned to values close to baseline at the end of surgery. CONCLUSIONS: From these data it is possible to conclude that renal function markedly deteriorates during OLT and it has to be considered at increased risk in the immediate postoperative period. The use of VVBP does not seem to prevent the intraoperative renal impairment.

Lactate blood levels in the perioperative period of orthotopic liver transplantation.

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P < or = 0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/l in 47 of 49 patients from group A, while they plateaued above 4 mmol/l in all patients from group B. Group A patients had lower alanine aminotransferase levels (P < or = 0.001), higher prothrombin activity, (P < or = 0.01), and greater bile flow (P < or = 0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Changes in circulating levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation in humans.

Atrial natriuretic factor (ANF) is a 28 amino acid peptide secreted by the atrial cardiocytes. Clearance is via the lung (50%) and the liver (25%). The main stimulus to ANF secretion is atrial distension but vasoconstrictors, sympathetic stimulation, catecolamines and tachycardia are able to enhance its circulating blood levels. ANF blood concentrations were measured during orthotopic liver transplantation in six postnecrotic cirrhotic patients. Significant increases in ANF blood levels occurred at the end of the anhepatic phase (P < or = 0.02 vs baseline) associated with low cardiac filling pressures (P < or = 0.02 vs baseline) and increased systemic vascular resistances (P < or = 0.02 vs preanhepatic phase). Aldosterone blood levels showed a similar behaviour, increasing significantly (P > or = 0.001 vs baseline) at the end of the anhepatic phase. ANF fell after reperfusion of the graft and returned towards baseline values at the end of the procedure. Since most of the total body clearance of ANF is performed by the lungs, its sharp increase at the end of the anhepatic phase could be considered a counterregulatory response to vasoconstricting stimulation and to fluid-sparing mechanisms in the presence of relative hypovolaemia. Its decrease after reperfusion could be related to volume normalization and partly to the enhanced clearance performed by the newly grafted liver.

Somatomedin C (IGF I) plasma levels after orthotopic liver transplantation (OLT) in end-stage cirrhotic patients.

Insulin-like growth factors [IGF I and II or somatomedins (SMS)] are polypeptides chemically and biologically correlated with insulin. The main source of synthetic activity and secretion is the liver, although many other tissues have been demonstrated to synthesize SMS. In the circulation, they are not present in a free form, but are mostly bound to a specific carrier protein independently synthesized in the liver. Hepatic or extrahepatic storage organs have not been demonstrated; the half life of the SMS-binding protein complex is between 3 and 4. Synthesis of SMS is regulated by GH, insulin, thyroxine and nutrition (caloric and protein intake, and nitrogen balance). The role of corticosteroids is still a matter of debate: in patients treated with steroids SMS blood levels have been shown to be within normal limits, while biological activity has been demonstrated to be significantly reduced by SMS inhibitors, probably induced by corticosteroid therapy. The biological properties of SMS are related to their structural homology with insulin, and can be summarized as follows: A. Insulin-like activity (glucose oxidation, lipogenesis, glycogen synthesis, inhibition of lipolysis and glycogenolysis); B. Sulphation activity (incorporation of sulphate and leucine into glycosaminglycans of the cartilage); C. Stimulation of fibroblast multiplication; D. Amplification of other hormone activities (GH); E. Complementary anabolic activity with insulin. Low levels of SMS have been demonstrated in hypopituitarism (secondary) or in other diseases independent of GH reduced secretion (primary) such as malnutrition, malabsorption, acute or chronic liver failure and uraemia. Negative nitrogen balance, hypocaloric and/or low protein diets are usually correlated with low levels of SMS. Recently, Schalch et al. reported on the role of orthotopic liver transplantation (OLT) in normalizing SMS blood levels in a group of end-stage liver diseased patients. This preliminary paper deals with changes in IGF-I plasma levels (somatomedin C) in a group of patients affected by end-stage liver cirrhosis before and after OLT.

Determination of the ketone body ratio in fulminant hepatic failure.

The ratio of acetoacetate to beta-hydroxybutyrate, the ketone body ratio, was measured in arterial blood from 28 patients with fulminant hepatic failure as an index of the hepatic energy charge. The ketone body ratio was significantly reduced in the total group of patients with fulminant hepatic failure as compared with control subjects (0.27 +/- 0.03 SE as compared with 0.48 +/- 0.03; p less than 0.001). Patients who survived had significantly less reduction of the ketone body ratio on admission than those who died (0.39 +/- 0.06, n = 10 as compared with 0.20 +/- 0.02, n = 19; p less than 0.02). In seven patients who died, in whom ketone body ratio was measured less than 12 hours before death there was a significant decrease in ketone body ratio as compared with that on admission (0.24 +/- 0.05 to 0.15 +/- 0.04; p less than 0.05). In contrast, in seven patients who survived there was no significant change in ketone body ratio when measured within 12 hours of regaining consciousness as compared with the figures on admission. Measurement of arterial ketone body ratio may give an indication of prognosis, and may be of use in testing the efficacy of treatments which aim to enhance hepatic regeneration or to remove toxic substances that may reduce the hepatic energy charge.