No abstract

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...

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)

The purpose of this retrospective study was to examine the potential role of cerebral hemodynamic and metabolic factors in the outcome of patients with fulminant hepatic failure (FHF). Based on the literature, a hypothetical model was proposed in which physiologic changes progress sequentially in five phases, as defined by intracranial pressure (ICP) and cerebral blood flow (CBF) measurements. Seventy-six cerebral physiologic profiles were obtained in 26 patients (2 to 5 studies each) within 6 days of FHF diagnosis. ICP was continuously measured by an extradural fiber optic monitor. Global CBF estimates were obtained by xenon clearance techniques. Jugular venous and peripheral artery catheters permitted calculation of cerebral arteriovenous oxygen differences (AVDO 2 ), from which cerebral metabolic rate for oxygen (CMRO 2 ) was derived. A depressed CMRO 2 was found in all patients. There was no evidence of cerebral ischemia as indicated by elevated AVDO 2 s. Instead, over 65% of the patients revealed cerebral hyperemia. Eight of the 26 patients underwent orthotopic liver transplantation-all recovered neurologically, including 6 with elevated ICPs. Of the 18 patients receiving medical treatment only, all 7 with increased ICP died in contrast to 9 survivors whose ICP remained normal (P < 0.004). Hyperemia, per se, was not related to outcome, although it occurred more frequently at the time of ICP elevations. Six patients were studied during brain death. All 6 revealed malignant intracranial hypertension, preceded by hyperemia. In conclusion, the above findings are consistent with the hypothetical model proposed. Prospective longitudinal studies are recommended to determine the precise evolution of the pathophysiologic changes. (Liver Transpl 2005;11:1353-1360.)