Patients with FHF are admitted to a surgical intensive care unit for management, as discussed in a previous section of the monograph. In addition to aggressive ICU care, transplant surgeons and hepatologists have to assess the patient's overall condition, attempt to determine the underlying etiology of the disease, predict the chances of spontaneous recovery and complete an emergency evaluation for liver transplantation. At our center, the King's College criteria are used as a guideline to predict outcome without liver transplantation. In addition, we follow the general trend in the severity of encephalopathy and elevation of ICP, the degree of coagulopathy, metabolic acidosis and renal failure. Once the initial assessment is made, an emergency evaluation for liver transplantation is completed, usually within 12-24 hours. This evaluation is similar to evaluation of patients with chronic liver disease, with a few exceptions. Patients with FHF usually are not known to have underlying liver disease and the evaluation work-up must reveal the cause for liver failure. As discussed earlier, the differential diagnosis includes:
1. Drug induced hepatotoxicity;
2. Viral hepatitis;
3. Exposure to environmental toxins;
4. Miscellaneous causes; and
5. Indeterminate (cryptogenic) etiology.
In the United States, the most common etiology of FHF remains indeterminate, or non-A, non-B viral hepatitis, which constitutes 45% of all cases in several combined series.32 Table 6.2 summarizes the laboratory and diagnostic work-up of patients with FHF. In addition to this work-up, patients are seen by various consultants to assess their overall condition and to rule out any absolute contraindication to liver transplantation, as summarized in Table 6.3.
Unlike chronic liver disease, cerebral edema and intracranial hypertension develop rapidly and represent the leading cause of death in this patient population. Neurologic complications resulting in irreversible brain damage or brain-stem herniation are the leading contraindications to liver transplantation in this setting.33 The cornerstone of patient management in FHF is prevention, early recognition and prompt treatment of cerebral edema. Cerebral edema occurs in later stages of hepatic encephalopathy related to FHF and can be determined by clinical, radiological or invasive methods. Clinical findings include decerebrate posturing, myoclonus, spastic rigidity, seizure activity, systemic hypertension, bradycardia, hyperventilation and mydriasis with diminished pupillary response. Initially, the findings of cerebral edema are paroxysmal, but later on become persistent. Papilledema is a late finding and commonly not present, even in the advanced stages of the disease.34 Noninvasive diagnostic modalities, including computerized tomographic scanning, EEG monitoring and transcranial doppler flow measurement, have not been proven helpful in early detection or management of cerebral edema.35-38 Cerebral edema in infants may be diagnosed by cranial ultrasonography to detect lateral ventricle effacement. In older children and adults, CAT scanning can detect cerebral edema, but there is a latent period between its actual onset and radiographic appearance.36 Magnetic resonance angiography (MRA) is logistically not readily available to critically ill individuals.
Currently, intracranial pressure (ICP) monitoring is the best means of monitoring intracranial hypertension and is recommended for patients with stage 3 or 4 encephalopa-thy to guide treatment. ICP can be measured using an epidural, subdural or intraventricular fiberoptic catheters. In a large comparative study, data from 262 patients with FHF were
Table 6.2. Liver transplant evaluation for FHF and SFHF
CBC and Differential Chemistry panel Coagulation profile 24-h Cr Clearance Urinalysis ABGs
ANA, AMA, ceruloplasmin, urine copper, a1-antitrypsin
Thyroid function tests Alcohol and drug toxicology screen Viral Serologies
Bacterial, fungal and viral cultures Blood Sputum Urine Ascites 12 lead EKG CXR
Pulmonary function tests Abdominal ultrasound with doppler Head CT scan
Table 6.3. Contraindications to liver transplantation in FHF
Severe irreversible brain damage HIV infection Extrahepatic malignancy Uncontrolled sepsis
Severe pulmonary hypertension and advanced cardiopulmonary disease Active substance abuse or major psychosocial problems Relative Contraindications
Elevated ICP or reduced CPP Multiorgan system failure Hemodynamic instability Advanced age
Portal vein thrombosis except when secondary to hepatocellular carcinoma analyzed for incidence of bleeding or other complications. Although slightly less sensitive to ICP changes, epidural catheters had the lowest complication rate (3.8%) and lowest rate of fatal hemorrhage (1%).39 The goal of invasive monitoring is to maintain ICP at levels below 15 mmHg, if possible, while maintaining a cerebral perfusion pressure (CPP) above 50 mmHg. CPP is calculated using the formula: CPP = MAP - ICP; MAP stands for calculated mean arterial pressure. ICP monitoring allows aggressive management of cerebral edema; the same is true for measurement of CPP, which appears to be a better predictor of outcome than ICP alone.40 Experience with ICP monitoring using a Ladd monitor at the University of Nebraska Medical Center was summarized by Inagaki et al.41 Data from 61 patients were analyzed in a two part study, initially retrospectively (n = 30) and then prospectively (n = 31); CPP less than 40 mmHg for 2 hours or more was a contraindication to OLT due to the high incidence of irreversible brain damage. Another study, however, of 37 patients with FHF (including 14 patients with adverse parameters, i.e., ICP > 25 mmHg and CPP < 40 mmHg), showed no significant differences in peak ICP, number of ICP surges or lowest CPP among survivors, nonsurvivors and survivors with transplantation.42 In the same series, 6 out of 14 patients with adverse parameters survived, 2 following liver transplantation. The effect of high ICP, or low CPP, on outcome following liver transplantation, has not been studied in a randomized, controlled fashion. However, it appears that elevated ICP secondary to severe cerebral edema is associated with increased risk of development of irreversible brain damage and a grave outcome following liver transplantation. Therefore, patients with grade III or IV encephalopathy require aggressive and attentive support to prevent development of massive cerebral edema, as delineated in previous sections. Accurate implementation of supportive measures can delay onset of massive cerebral edema. Patients who fail to respond could be placed in a barbiturate coma, as discussed earlier. Thiopental infusion has been shown to decrease cerebral metabolic activity, lower central nervous system oxygen demand and protect the brain from ischemic injury secondary to decreased cerebral blood flow. Thiopental infusion lowered ICP and reduced mortality from FHF in a retrospective, nonrandomized study.43 In general, however, we find the effect of Thiopental infusion on ICP transient and unpredictable.
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