Michael F.X. Glynn

Treatment of primary liver graft nonfunction with prostaglandin E1

Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.

Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation

Background Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis. Methods Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay. Results Patients receiving transexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving transexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving transexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation. Conclusions High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial.

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.

Prevention of postbypass bleeding with tranexamic acid and ϵ-aminocaproic acid

Abstract In this institution, two antifibrinolytic agents have been in routine use before cardiopulmonary bypass (CPB) to prevent bleeding due to fibrinolysis; ϵ-aminocaproic acid (EACA) or tranexamic acid (TA) are administered as intravenous infusions over 2 hours, from the time of anesthetic induction until the onset of CPB. TA is 10 times more potent and binds more strongly to plasminogen than EACA. Data were collected retrospectively on 411 patients undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass who had received one of four therapy regimens: 10 g of EACA (65 patients), 15 g of EACA (60 patients), 6 g of TA (100 patients), or 10 g of TA (75 patients). Patients who did not receive any drug (91) served as controls. Anesthestic technique and the heparin/protamine protocol did not differ. Blood collected by mediastinal and pleural tubes was auto transfused up to 6 hours postoperatively. Both TA and EACA reduced post-CPB bleeding in the first 24 hours. Ten grams of TA was the most effective, resulting in a 52% and 36% reduction in blood loss over controls at 6 and 24 hours, respectively. Although 10 g of TA was more effective than 6 g of TA in blood loss control for the first 6 hours, the difference was not significant at 24 hours. A significantly lower number of patients in the 10 g TA group received blood products than in control (28% v 49%) patients (P = 0.02). Pretreatment with 10 g of TA prevented excessive (over 750 mL in 6 hours) bleeding after CPB.

Complications after peritoneovenous shunting for ascites

The results and complications in our first 23 consecutive patients receiving the peritoneovenous shunt for intractiable hepatic ascites are presented. A good initial diuretic effect was obtained in 20 of the 23 patients, with reversal of hepatorenal failure in 3 of 5 patients. The postoperative complication rate was high (74 percent). Infection, coagulopathy and complication of the underlying liver disease contributed to a mortality rate of 26 percent. Late complications were related to the primary liver disease. The 6 month survival rate was 58 percent and the 1 hear survival rate 52 percent with five patients followed up for more than 2 years. Because of the significant morbidity and mortality associated with the peritoneovenous shunt, we recommend it only for patients with massive intractable hepatic ascites whose condition is refractory to maximal medical therapy.

Ancrod (arvin®) as an Alternative to Heparin Anticoagulation for Cardiopulmonary Bypass

Heparin is the anticoagulant used during cardiopulmonary bypass (CPB). Both the use of heparin and the reversal of its effect with protamine have well-documented complications. Ancrod is a defibrinogenating enzyme that has been used as an anticoagulant in humans, but its use as an anticoagulant for CPB has been limited to studies in animals. Twenty patients for elective aortocoronary bypass surgery were anticoagulated by means of an intravenous infusion of ancrod pre-operatively. Target plasma fibrinogen concentrations of 0.40-0.80 g/l were achieved within 13.3 +/- 2.5 h using an average dose of ancrod of 1.65 +/- 0.55 U/g. All perfusions were without incident. Postoperative blood loss (2286 +/- 1311 cc) was compared to that of 20 matched controls (1737 +/- 973 cc), as was blood product use; 4.1 +/- 2.1 U of packed cells versus 2.5 +/- 2.3 U (P less than 0.05) and 5.6 +/- 3.1 U of plasma versus 2.6 +/- 2.9 U (P less than 0.05) in the ancrod and heparin-treated groups, respectively. There were no differences in the postoperative courses or recovery periods of the ancrod-treated and control patients. This study confirms the efficacy and feasibility of ancrod as an alternative form of anticoagulation for CPB.

The Effect of Three Different Doses of Tranexamic Acid on Blood Loss After Cardiac Surgery With Mild Systemic Hypothermia (32°C)

Abstract Objective: Prophylactic administration of tranexamic acid (TA), an antifibrinolytic agent, decreases bleeding after cardiac surgery with systemic hypothermia (25°C to 29°C). Warmer systemic temperatures during cardiopulmonary bypass (CPB) may reduce bleeding and thus alter the requirement for TA. The effect of three different doses of TA on bleeding after cardiac surgery with mild systemic hypothermia (32°C) is evaluated. Design: Double-blind, prospective, randomized study. Setting: University hospital. Participants: One hundred fifty adult patients undergoing aortocoronary bypass or valvular cardiac surgery. Interventions: Patients received TA, 50 (n = 50), 100 (n = 50), or 150 (n = 50) mg/kg intravenously before CPB with mild systemic hypothermia. Measurements and Main Results: Blood loss through chest drains over 6, 12, and 24 hours after surgery and total hemoglobin loss were measured. Autotransfused blood, transfused banked blood and blood products, and coagulation profiles were measured. Analysis of variance on log-transformed data for blood loss and confidence intervals (Cis) of 0.95 were calculated and transformed to milliliters of blood. No patient was re-explored for bleeding. Blood loss at 6 hours was statistically greater in the 50-mg/kg group compared with the other two groups (p = 0.03; p = 0.02). Total hemoglobin loss was statistically greater in the 50-mg/kg group compared with the 150-mg/kg group (p = 0.04). There was no statistical difference in blood transfusion rate or coagulation profiles among the three groups. However, preoperative hemoglobin level was statistically lower in the 150-mg/kg group compared with the other two groups (p = 0.01). Conclusion: Of the three doses of TA studied, the most efficacious and cost-effective dose to reduce bleeding after cardiac surgery with mild hypothermic systemic perfusion is 100 mg/kg.

Blood Conservation with Membrane Oxygenators and Dipyridamole

Cardiopulmonary bypass induces platelet activation and dysfunction, which result in platelet deposition and depletion. Reduced platelet numbers and abnormal platelet function may contribute to postoperative bleeding. A membrane oxygenator may preserve platelets and reduce bleeding more than a bubble oxygenator, and the antiplatelet agent dipyridamole may protect platelets intraoperatively and reduce bleeding postoperatively. A prospective randomized trial was performed in 44 patients undergoing elective coronary artery bypass grafting to assess the effects of the membrane oxygenator and dipyridamole on platelet counts, platelet activation products, and postoperative bleeding. Patients who were randomized to receive a bubble oxygenator and no dipyridamole had the lowest postoperative platelet counts, the greatest blood loss, and the most blood products transfused. Platelet counts were highest and blood loss was least in patients randomized to receive a membrane oxygenator and dipyridamole (p less than .05). A bubble oxygenator with dipyridamole and a membrane oxygenator without dipyridamole resulted in intermediate postoperative platelet counts and blood loss. Arterial thromboxane B2 and platelet factor 4 concentrations were elevated on cardiopulmonary bypass in all groups. Both the membrane oxygenator and dipyridamole were independently effective (by multivariate analysis) in preserving platelets. Optimal blood conservation was achieved with a membrane oxygenator and dipyridamole.

Successful treatment of massive pulmonary embolism after coronary artery bypass grafting due to heparin-induced thrombocytopenia

Massive pulmonary embolism is a rare complication in patients undergoing coronary artery bypass grafting. Frequently patients have had exposure to heparin before the operation. In this article we report a patient who 6 days after a cardiac operation suffered a massive pulmonary embolism. The patient was later discovered to have heparin-associated thrombocytopenia with serum heparin antibody. We recommend patients receiving heparin have frequent platelet counts and those with induced thrombocytopenia undergo sensitivity testing.

Elevated liver enzymes and thrombocytopenia in the third trimester of pregnancy: An unusual case report and a review of the literature

A woman presented in the third trimester of pregnancy with epigastric pain, elevated liver enzymes, and thrombocytopenia. The frozen-section liver biopsy findings were compatible with acute fatty liver of pregnancy. The light and electron microscopic findings were those of preeclampsia. All clinical and laboratory abnormalities resolved before delivery.