Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation.

Large doses of aprotinin (1,000,000-2,000,000 kallikrein inhibitor units [KIU] initial dose and a 500,000 KIU/h infusion) have been used during orthotopic liver transplantation (OLT) to reduce the incidence and severity of fibrinolysis. This double-blinded study was designed to investigate whether a small-dose infusion of aprotinin (200,000 KIU/h) would control fibrinolysis. A controlled study was undertaken to compare small-dose aprotinin with a placebo in patients undergoing OLT with veno-venous bypass. Forty-four patients were randomized either to the aprotinin group (n = 21), which received an intravenous infusion of 200,000 KIU/h without an initial dose, or to a control group (n = 23), which received normal saline. Coagulation variables, thrombelastograms, and postoperative blood drainage were measured. Blood levels of fibrin degradation products (FDP) were significantly higher in the control group (95% > 20 micrograms/mL) at the end of surgery compared to the aprotinin group (53% > 20 micrograms/mL, P < 0.01). The transfusion of cryoprecipitate units was more in the control group versus the aprotinin (12.6 +/- 12.8 vs 5.7 +/- 7.5; P < 0.04), as was the number of fresh frozen plasma units (6.6 +/- 3.5 vs 3.6 +/- 6.1; P < 0.05). We conclude that an infusion of a small dose of aprotinin can safely control fibrinolysis during liver transplantation with a concomitant reduction in transfusion of blood products.

Danger of amiodarone therapy and elevated inspired oxygen concentrations in mice.

Our study showed a statistically significant incidence of pulmonary edema in mice receiving amiodarone and 100% oxygen. This finding, together with a variety of clinical reports, indicates that in patients receiving amiodarone therapy, FiO2 should be maintained at the lowest possible level, consistent with adequate oxygenation.

Oral transmucosal fentanyl citrate for premedication in adults.

This study was designed to assess the efficacy of oral transmucosal fentanyl citrate (OTFC) for premedication in an adult population and to determine its effects on anxiety, sedation, gastric volume, and gastric fluid acidity. The fentanyl citrate is incorporated in a lozenge mounted on a handle (oralet). The effects of OTFC, placebo oralet, and no premedication were compared in a prospective, double-blind study on 90 adult ASA physical status I and II patients undergoing same-day admission surgery. Patients were randomly assigned to one of three groups: OTFC group (n = 30), placebo group (n = 30), and control group (n = 30). Arterial blood pressure, heart rate, respiratory frequency, and oxygen saturation determined by pulse oximetry were recorded before any premedication was given, and then every 10 min until the patient was taken to the operating room. Baseline anxiety and sedation levels were assessed to ensure group similarity immediately before premedication was given and at the more anxiety-provoking phase upon entering the operating room. Anxiety levels were rated using the Spielberger State-Trait Anxiety Inventory short form and sedation levels were assessed with the Ramsay scale. Side effects, as reported by the patients, were also recorded. Gastric contents were aspirated via an orogastric tube after induction of anesthesia and were measured for volume and pH. No significant differences were found among the three groups in mean arterial pressure, heart rate, or respiratory frequency. Initial oxygen saturation levels in all groups decreased after 30 min but not less than 96% except for one patient in the OTFC group, who decreased to 88%. On entering the operating room, the OTFC group demonstrated significantly higher levels of anxiolysis than the control group, but no significant differences were seen between the OTFC and the placebo groups or the placebo and control groups. Mean gastric volumes (OTFC, 29 mL; placebo, 26 mL; control, 24 mL) and pH (OTFC, 2.0; placebo, 1.8; control, 2.1) were similar in all groups. There were no significant differences among the groups in levels of sedation achieved. Mild dizziness or light-headedness was the most commonly reported side effect in 23% of the OTFC group. In the OTFC group, 71.4% like the premedicant effect as compared to 46.4% of the placebo group. Most of the groups found the oralet method of premedicant delivery very acceptable. This study demonstrates that the OTFC oralet is an effective anxiolytic in adults. It has minimal side effects and is prepared in an acceptable format. There was no measurable increase in gastric contents or acidity in the oralet groups, compared to those patients who were given nothing by mouth.

Temperature corrected thrombelastography in hypothermic patients.

Thrombelastograms and other coagulation studies are performed at 37 degrees C, regardless of the patient's body temperature. This prospective study of 45 patients undergoing orthotopic liver transplantation was conducted to evaluate the effect on the thrombelastogram performed at the patient's actual body temperature compared with a control thrombelastogram heated in the standard fashion to 37 degrees C. Thrombelastograms were obtained after the induction of anesthesia and at various times throughout the operation when clinically indicated. A freshly drawn sample of the patient's blood was divided into two aliquots and run simultaneously on two thrombelastographs; one thrombelastograph was modified with a thermostat to perform the test at the patient's body temperature and the other was unmodified to serve as a control. The temperature of the patients in this study ranged from 36.9 degrees C to 32 degrees C. The variables of the thrombelastogram measured were: r (reaction time in minutes), r + K (coagulation time in minutes), alpha (coagulation rate in degrees), and MA (maximum amplitude in millimeters). Whenever the patient's body temperature was less than 37 degrees C, statistically significant prolongation of the reaction time, coagulation time, and decrease in the clot formation rate occurred compared with control variables at 37 degrees C. Overall means were as follows: r for control, 8.24 +/- 0.28 min; r for temperature corrected, 9.32 +/- 0.27 min; r + K for control, 15.4 +/- 0.65 min; r + K for temperature corrected, 17.5 +/- 0.81 min; and alpha for control, 39.8 +/- 1.22 degrees; alpha for temperature corrected, 37.7 +/- 1.23 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Duration of vecuronium-induced neuromuscular block as a predictor of liver allograft dysfunction.

The major causes of liver graft failure are acute rejection, technical failure, and primary nonfunction (PNF). This study was undertaken to determine whether delayed return of neuromuscular function correlates with allograft primary dysfunction in humans given vecuronium. Twenty-two adult patients undergoing orthotopic liver transplantation were given an initial dose of vecuronium, 0.1 mg/kg intravenously (i.v.). All patients recovered from vecuronium-induced neuromuscular block prior to explantation. No additional neuromuscular blocker was given until the liver graft was implanted and reperfused. Fifteen minutes after reperfusion another 0.1 mg/kg vecuronium was given IV and recovery time from attaining complete neuromuscular block to return of the fourth twitch of a train-of-four was recorded. Patients were divided into three groups according to postoperative liver function. Group I consisted of 17 patients with immediate normal liver graft function. Group II consisted of four patients with primary dysfunction (PDF) [peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2000 U/L, prothrombin time > 16 s, and poor quality and quantity of bile within 3 days postoperatively] which eventually recovered normal function. Group III consisted of one patient with PNF (uncorrectable coagulopathy, severe metabolic acidosis, rising AST and ALT, and minimal or no bile output), whose graft never recovered. Recovery time in Groups II and III was prolonged compared to Group I (P < 0.05). Recovery time in Group III was prolonged compared to Group II (P < 0.05). A test based on these results using a recovery time of > 135 min as a predictor of PDF has a sensitivity and specificity of 80% and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood transfusion in orthotopic liver transplantation: six-year experience.

Patients undergoing orthotopic liver transplantation (OLT) are susceptible to massive blood loss and require transfusion. Possible reasons for increased transfusion demands include platelet abnormalities, thrombocytopenia secondary to hypersplenism, clotting factor deficiencies, fibrinolysis, increased surgical blood loss associated with portal hypertension and previous surgical procedures, and hypothermia. The purpose of this study was to review trends in blood product usage during our first 6 years of experience performing OLT.

Effect of intraoperative low-dose dopamine on renal function in liver transplant recipients.

Patients undergoing orthotopic liver transplantation frequently receive dopamine infusions to preserve renal function. To test the benefit of such infusions on renal function, 48 nonanuric patients presenting for OLT were entered into a randomized double-blind protocol. After exclusion of 1 patient for intraoperative nephrectomy, 22 patients received dopamine at a rate of 3 micrograms.kg-1.min-1 during surgery and the first postoperative 48 h, and a control group of 25 patients received saline. Venovenous bypass was used in 45 of 47 patients. During the hepatic vascular anastomoses, the donor liver was flushed with cold saline. In 7 patients, the flush contained mannitol (50 g) as part of a surgical protocol to investigate its role as a potential free radical scavenger. Initially, it appeared that there was an increase in urine output during the neohepatic phase in those patients receiving dopamine versus controls (4.20 +/- 3.3 vs 2.10 +/- 1.3 ml.kg-1.h-1, respectively). Upon further statistical analysis, this increase was associated with inclusion of mannitol in the liver flush of 5 patients in the dopamine group. After excluding all patients receiving flush containing mannitol, there was no significant difference in urine output during the neohepatic phase between the dopamine group and controls (2.94 +/- 0.45 and 2.10 +/- 0.28 ml.kg-1.h-1, respectively). The glomerular filtration rates at 1 month after surgery were similar and decreased approximately 40% in each group. Although a beneficial effect of dopamine in all situations cannot be ruled out the authors conclude that routine perioperative use of dopamine is of little value in nonanuric patients presenting for orthotopic liver transplantation.

Perioperative renal function in patients undergoing orthotopic liver transplantation. A randomized trial of the effects of verapamil.

Patients who undergo orthotopic liver transplantation often experience a significant drop in GFR postoperatively. Postulated mechanisms include intraoperative hemodynamic changes, suboptimal renal perfusion during the anhepatic stage, and cyclosporine administration. We undertook a prospective double-blind study to investigate these factors, as well as to determine the protective effects of verapamil on perioperative renal function. Twenty-five patients with normal renal function undergoing OLT received either placebo (n = 13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was administered until after reperfusion of the graft liver, and venovenous bypass (VVB) was utilized in all cases. Patients completing six weeks of the study experienced 61% and 48% decreases in GFR within the placebo and verapamil groups respectively. A significant decrease in GFR occurred in the placebo group between one and six weeks post-OLT, and a significant drop in GFR occurred in the verapamil group by one week post-OLT. Differences between the groups were not significant, however. Systemic, renal, and hepatic hemodynamics were similar at all times between groups, and renal hemodynamics and urine output were unchanged during VVB. We conclude that (1) perioperative factors do not contribute to renal dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics during the anhepatic phase; (3) CsA is the most likely causative agent for post-OLT renal dysfunction; and (4) intraoperative verapamil serves no protective role, as administered in this study.

Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters.

Desmopressin acetate (DDAVP) has been advocated as efficacious in reducing mediastinal bleeding following cardiopulmonary bypass (CPB), and has been shown to ameliorate platelet dysfunction; however, this has not been evaluated during routine coronary artery bypass grafting (CABG). In the present study, this therapy was evaluated utilizing the thromboelastograph (TEG), a rapid, on-line means of diagnosing a coagulopathy. During elective CABG, 20 patients received either DDAVP, 0.3 microgram/kg, intravenously, following heparin reversal after CPB, or a placebo infusion, in a randomized, double-blind fashion. Hemostasis was monitored with both the TEG and conventional coagulation tests. No significant differences between the two groups were found at induction, postprotamine, post-"study infusion," or 2 hours postoperatively, with the exception of the postoperative PTT (31.1 +/- 3.2 v 36.5 +/- 5.9 seconds for DDAVP v placebo, P = 0.03). Total blood products transfused intraoperatively, and in the first 8, 16, 24, or 48 postoperative hours, were also similar between the groups. No manifestations of hypercoagulability were seen, but hypotension during the infusion was noted in four patients receiving DDAVP, and in none of the controls. It is concluded that the expense and potential complications of DDAVP therapy do not justify its routine use in CABG.