Acute liver failure: managing coagulopathy and the bleeding diathesis.

Acute liver failure (ALF) is defined as a severe, sudden liver dysfunction that induces encephalopathy and coagulopathy (prothrombin time [PT/INR] > 1.5) within 26 weeks of the onset of symptoms (usually jaundice) in patients without previous liver disease. Quantitative and qualitative platelet dysfunction, reduced synthesis of clotting factors, increased consumption of factors (mainly II, V, VII, X), reduced clearance of both activated factors, and/or factor inhibitor complexes are among the most important proposed pathogenetic factors. A possible role might be also played by the diminished degradation of anticoagulants. Plasminogen activator inhibitor 1 (PAI-1) is increased, shifting the balance toward hypofibrinolysis, despite the elevated levels of tissue plasminogen activator (tPA). Although changes in coagulation parameters provide crucial information for the management of the patient with ALF, the optimal management of the hemostatic defects is far from being defined. Because spontaneous bleeding occurs rarely during ALF, measures to improve the bleeding diathesis (fresh frozen plasma, cryoprecipitate, platelet transfusion) are recommended only in patients with clinically significant bleeding or before placement of invasive devices. Antifibrinolytic drugs are used in some cases, but often empirically. The role of rFVIIa, even if promising, is still under debate.

[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.

[Effectiveness and modality of continuous infusion administration of atracurium dibesylate]. / Attuabilità e modalità di somministrazione di atracurium dibesilato in infusione continua.

One-hundred and five patients with ASA I-II were scheduled for general surgery. Atracurium was the muscle-relaxant of choice. A bolus dose of atracurium (0.5 mg/kg-1) was administered immediately before thiopentone. After 15 minutes began the infusion of atracurium diluited in saline solution and administered through a simple infusion set. The neuromuscolar function was investigated evaluating the amplitude of response to TOF and DBS. This procedure proved to be safe, reliable and easily performed in every operating room.

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.

[Anesthesia and perioperative care in radical cystectomy]. / Anestesia ed assistenza perioperatoria nella cistectomia radicale.

The results of anesthesia and perioperative assistance on a series of 84 patients who underwent since 1982 to 1990 a one-stage radical cystectomy and urinary diversion are reported. Reduction of the high risk of operation is particularly dependent on preoperative preparation, use of a safe anesthesia technique with continuous evaluation of vital signs, control of blood loss and use of low dose of heparin for prevention of venous thromboembolism. The complication rate was low, 7.1% for the early one, 16.6% for late one. General mortality of 5.9% is dependent on the high average age of the patients and on the fact all the cases were deeply invasive cancer.