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Intravascular and/or intracardiac thrombus formation followed by pulmonary thromboembolism with right ventricular dysfunction immediately after graft reperfusion during orthotopic liver transplantation (OLT) is described in 7 patients. This complication may have been related to excessive activation of the coagulation system by graft reperfusion, which overwhelmed anticoagulation mechanisms and was disproportionate to fibrinolysis. Activation of the coagulation system may be more pronounced in patients who receive less than optimal grafts, require massive transfusion, or have septic complications at the time of OLT. It is unclear whether antifibrinolytic therapy during the anhepatic stage had a role. Transesophageal echocardiography was useful in diagnosing and managing intracardiac thrombus and pulmonary thromboembolism. (Liver Transpl 2001;7:783-789.) P ulmonary air embolism or thromboembolism may occur during major vascular surgery. However, this complication is expected to be more common during orthotopic liver transplantation (OLT) because of several factors inherent to the procedure: excessive activation of the coagulation system secondary to injury to a large capillary bed, venous stasis during clamping of the portal vein and inferior vena cava (IVC), ischemic insult to the intestines, activators released from the grafted liver, and massive blood transfusion.A few case reports have documented intravascular and/or intracardiac thrombus formation during the dissection or anhepatic stage of OLT. 1-6 However, to date, the occurrence of intravascular and/or intracardiac thrombus formation within the first few minutes after reperfusion, followed by clinically significant pulmonary thromboembolism, has not been documented. In the 7 patients presented here, hemodynamic instability within minutes after graft reperfusion was associated with clinical signs of pulmonary embolism, evidenced by dramatic increases in pulmonary artery (PAP) and central venous pressures (CVP), as well as right ventricular (RV) dysfunction on transesophageal echocardiography (TEE), evidenced by acute right atrial and RV dilatation and hypokinesia, severe tricuspid regurgitation, and leftward shift of the interatrial and interventricular septa. These changes coincided with the observation of blood clots in the right atrium (RA) and pulmonary artery (PA) by TEE. These cases were encountered over a period of 2.5 years, during which time 577 OLTs were performed at the University of Pittsburgh (Pittsburgh, PA). During this period, coagulation management in the operating room was guided by thromboelastography and platelet count. Thromboelastography was performed on native blood and blood samples with the in vitro addition of ⑀-aminocaproic acid (EACA; 0.1% solution) and protamine (0.01% solution) for differential diagnosis of fibrinolysis and heparin effect, respectively.Transfusion and coagulation management guidelines of the liver transplant program were as follows. 7 Hemoglobin level was maintained at 8 to 10 g/dL; approximately an equal numbe...

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F < 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with ε-aminocaproic acid (0.09%) and an untreated sample. Blood treated with ε-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of ε-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, ε-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with ε-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 ± 29.5% to 94.8 ± 7.4% (mean ± SD, P < 0.001). None of the treated patients had hemorrhagic or thrombotic complications. In patients undergoing liver transplantation, the judicious use of a small dose of ε-aminocaproic acid, when its efficacy was confirmed in vitro, effectively treated the severe fibrinolysis without clinical thrombotic complications. KeywordsBlood; coagulation; fibrinolysis; Liver; transplantation; Measurement techniques; thrombelastography; Pharmacology; ε-aminocaproic acid Orthotopic liver transplantation is frequently associated with surgical bleeding that requires massive blood transfusion. 1 The surgical bleeding is compounded by preexisting coagulopathy, dilutional coagulopathy, fibrinolysis, and, possibly, disseminated intravascular In a recent series of patients undergoing liver transplantation, the degree of coagulopathy and volume of transfusion decreased with the introduction of replacement therapy guided by the frequent thrombelastographic monitoring of the coagulation system and the use of heparin-coated veno-venous bypass. 3,4 However, active fibrinolysis, manifest as generalized oozing from a previously dry surgical field and unresponsive to replacement therapy, has been a major difficulty in the intraoperative management of liver transplantation.Since the early experience in hepatic transplantation, activation of the fibrinolytic system has been recognized, 5,6 and, although antifibrinolytic treatment appears beneficial, it has been used only sporadically. Vo...

Elevated intracranial pressure (ICP) leads to loss of cerebral perfusion, cerebral herniation, and irreversible brain damage in patients with acute liver failure (ALF). Conventional techniques for monitoring ICP can be complicated by hemorrhage and infection. Transcranial doppler ultrasonography (TCD) is a noninvasive device which can continuously measure cerebral blood flow velocity, producing a velocity-time waveform that indirectly monitors changes in cerebral hemodynamics, including ICP. The primary goal of this study was to determine whether TCD waveform features could be used to differentiate ALF patients with respect to ICP or, equally important, cerebral perfusion pressure (CPP) levels. A retrospective study of 16 ALF subjects with simultaneous TCD, ICP, and CPP measurements yielded a total of 209 coupled ICP-CPP-TCD observations. The TCD waveforms were digitally scanned and seven points corresponding to a simplified linear waveform were identified. TCD waveform features including velocity, pulsatility index, resistive index, fraction of the cycle in systole, slopes, and angles associated with changes in the slope in each region, were calculated from the simplified waveform data. Paired ICP-TCD observations were divided into three groups (ICP Ͻ 20 mmHg, n ϭ 102; 20 Յ ICP Ͻ 30 mmHg, n ϭ 74; and ICP Ն 30 mmHg, n ϭ 33). Paired CPP-TCD observations were also divided into three groups (CPP Ն 80 mmHg, n ϭ 42; 80 Ͼ CPP Ն 60 mmHg, n ϭ 111; and CPP Ͻ 60 mmHg, n ϭ 56). Stepwise linear discriminant analysis was used to identify TCD waveform features that discriminate between ICP groups and CPP groups. Four primary features were found to discriminate between ICP groups: the blood velocity at the start of the Windkessel effect, the slope of the Windkessel upstroke, the angle between the end systolic downstroke and start diastolic upstroke, and the fraction of time spent in systole. Likewise, 4 features were found to discriminate between the CPP groups: the slope of the Windkessel upstroke, the slope of the Windkessel downstroke, the slope of the diastolic downstroke, and the angle between the end systolic downstroke and start diastolic upstroke. The TCD waveform captures the cerebral hemodynamic state and can be used to predict dynamic changes in ICP or CPP in patients with ALF. The mean TCD waveforms for corresponding, correctly classified ICP and CPP groups are remarkably similar. However, this approach to predicting intracranial hypertension and CPP needs to be further refined and developed before clinical application is feasible. Liver Transpl 14: 1048-1057, 2008. © 2008 AASLD. Received November 21, 2007 accepted January 22, 2008. Abbreviations: ␣ ED , end diastole angle; ␣ PS , peak systole angle; ␣ PW , peak Windkessel angle; ␣ PS , peak systole angle; ␣ SD , start diastole angle; ␣ SW , start Windkessel angle; ALF, acute liver failure; CBFV, cerebral blood flow velocity; CPP, cerebral perfusion pressure; HR, heart rate; ICP, intracranial pressure; MAP, mean arterial pressure; PaCO 2 , CO 2 partial pressur...

The purpose of this retrospective study was to determine cerebral hemodynamic and metabolic changes in comatose patients with fulminant hepatic failure. Computerized tomography of the brain and cerebral blood flow measurements by the xenon-computerized tomography scan or intravenous xenon-133 methods were obtained in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients, arteriojugular venous oxygen content difference and cerebral metabolic rate for oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral blood flow and arteriojugular venous oxygen content difference were adjusted to the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52% of the patients had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas 24% had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher adjusted cerebral blood flows showed cerebral swelling on computerized tomography scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p < 0.002). The adjusted arteriojugular venous oxygen content difference was negatively correlated with adjusted cerebral blood flow (r = -0.61, p < 0.002). The majority of patients with reduced adjusted cerebral blood flows had low adjusted arteriojugular venous oxygen content differences (less than 5 vol%), indicating hyperemia rather than ischemia. The average cerebral metabolic rate for oxygen was 50% of normal (1.6 +/- 0.4 ml/100 gm/min); even patients with low cerebral metabolic rates for oxygen recovered neurologically.(ABSTRACT TRUNCATED AT 250 WORDS)

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Thirty-two patients with coronary artery disease who underwent liver transplantation between 1990 and 1994 were identified. Coronary artery disease was managed medically (n = 9), by angioplasty (n = l), or surgically (n = 22) prior to liver transplantation. Two patients underwent simultaneous coronary artery bypass gralting and liver transplantation. Complete preoperative cardiac evaluation was performed in all patients. Perioperative and postoperative morbidity and mortality were retrospectively determined. Overall mortality was 50%, whereas morbidity was 81 %. Follow-up was between 1 and 3 years after liver transplantation.Subgroup analysis revealed that medically managed patients had a 56% mortality and a 100% morbidity. The patient who underwent angioplasty survived without morbidity. One patient who underwent simultaneous coronary artery bypass grafting and liver transplantation died intraoperatively. The second patient survived but required pacerthotopic liver transplantation (OLT) has be-