Preoperative dobutamine stress echocardiography, intraoperative events, and intraoperative myocardial injury in liver transplantation.

INTRODUCTION: The appropriate method of screening for coronary artery disease in patients who present for liver transplantation is currently uncertain. METHODS: We assessed the utility of a screening protocol using dobutamine stress echocardiography (DSE) in 119 patients who underwent liver transplantation. Patients with cardiac risk factors had DSE performed, and those with positive results were referred for coronary angiography. Outcome was myocardial injury during liver transplantation determined by an elevation of cardiac troponin T measured after transplantation. RESULTS: Seventy-three patients had DSE performed; eight were reported as positive for inducible ischemia. Seven of these patients underwent coronary angiography, and one had significant coronary artery disease. Postoperative troponin elevation occurred in 14 patients. There was no significant difference in the prevalence of troponin elevation in those patients with positive DSE versus those with negative DSE. No significant difference was identified in the prevalence of troponin elevation when comparing those patients with cardiac risk factors who underwent DSE with those patients with no risk factors and no DSE performed. DSE had a sensitivity of 0.2 and a specificity of 0.9 for myocardial injury. The prevalence of intraoperative hemodynamic instability was significantly higher in patients who had evidence of myocardial injury, but hemodynamic instability was no more common in patients who had a positive DSE. CONCLUSION: When used in accordance with our protocol a positive DSE does not reliably identify patients at high cardiac risk during liver transplantation, but a negative DSE is strongly predictive of no myocardial injury.

The effect of in vitro recombinant factor VIIA on coagulation parameters for blood taken during liver transplantation.

Recombinant factor VIIa (rFVIIa) has been utilized in pilot studies in orthotopic liver transplantation (OLT) when administered to patients at doses of 68.37 microg/kg and 80 microg/kg. Although some effectiveness in normalizing measurements of coagulation has been demonstrated, the optimal dose for patients undergoing OLT has not been established. This study evaluated the effects of an in vitro equivalent dose of 120 microg/kg of rFVIIa on coagulation parameters when applied to the blood drawn from patients undergoing OLT. Coagulation function was assessed in 10 patients at four points during OLT. These time points were baseline, 5 minutes prior to reperfusion, 10 minutes after reperfusion, and 70 minutes after reperfusion. These patients did not receive rFVIIa perioperatively. At each of these four time points, a native sample was analyzed for prothrombin time (PT) and thromboelastogram. The rFVIIa (6.1 microg/kg or the approximate equivalent dose of 120 microg/kg for a 70 kg patient) was added to a second sample from the same patient. This second sample was also analyzed for PT and thromboelastogram. There was a statistically significant difference in baseline PT between native versus rFVIIa supplemented samples (15.8 +/- 3.21 vs 13.6 +/- 2.36 seconds, P < .02). The maximum amplitude of the thromboelastogram was larger in the native samples at 5 minutes prior to reperfusion (53.5 mm vs 39 mm, P < .02). No significant differences existed in the variables at any of the other sampling times. This study failed to demonstrate a consistent in vitro effect of rFVIIa on the blood taken from patients during OLT.

Causes and outcome of seizures in liver transplant recipients.

Previous studies found that seizures in orthotopic liver transplantation (OLT) herald a catastrophic neurologic event, but the studies were done of patients who later died and came to autopsy. We studied 630 OLT patients. Laboratory values, electroencephalography, neuroimaging, and levels of cyclosporine or FK506 were reviewed. Neurotoxicity from immunosuppression was considered a trigger for seizures when toxic blood level or increases > or = to 100% were documented, or when white matter lesions or confusional state or tremors were present. Generalized tonic-clonic seizures occurred in 28 of 630 patients (4%). In 7 patients seizures were part of an agonal event (central nervous system infection [n = 3], anoxic encephalopathy [n = 1], cerebral edema with fulminant hepatic failure [n = 1], intracranial hemorrhage [n = 1], and sepsis [n = 1]. In 17 patients cyclosporine (n = 11) or FK506 (n = 6) could be implicated. Remaining causes were acute uremia (n = 1), meningioma (n = 1), and unknown (n = 2). All patients were initially treated with anticonvulsants. Median follow-up of 2 years did not reveal seizure recurrence after discontinuation of anticonvulsants. We conclude that the majority of new-onset seizures after OLT are not indicative of a poor prognosis. Immunosuppression neurotoxicity is the most frequent cause. Anticonvulsant therapy is not necessary for favorable long-term outcome.

Intubation of critically ill patients.

Respiratory failure is one of the most common causes for admission to an intensive-care unit. Any patient with loss of central nervous system control of breathing, neuromuscular respiratory failure, or impairment of gas exchange may require tracheal intubation and mechanical ventilation. Tracheal intubation provides a conduit for ventilatory support, maintains the patency of an airway that has potential for obstruction, protects the airway from the contents of the stomach, and allows access to the trachea for pulmonary hygiene. Although the mechanics of intubation are easily learned, many factors must be considered in critically ill patients. Herein we summarize the principles of tracheal intubation in acutely ill patients.

Religious involvement, spirituality, and medicine: implications for clinical practice.

Surveys suggest that most patients have a spiritual life and regard their spiritual health and physical health as equally important. Furthermore, people may have greater spiritual needs during illness. We reviewed published studies, meta-analyses, systematic reviews, and subject reviews that examined the association between religious involvement and spirituality and physical health, mental health, health-related quality of life, and other health outcomes. We also reviewed articles that provided suggestions on how clinicians might assess and support the spiritual needs of patients. Most studies have shown that religious involvement and spirituality are associated with better health outcomes, including greater longevity, coping skills, and health-related quality of life (even during terminal illness) and less anxiety, depression, and suicide. Several studies have shown that addressing the spiritual needs of the patient may enhance recovery from illness. Discerning, acknowledging, and supporting the spiritual needs of patients can be done in a straightforward and noncontroversial manner. Furthermore, many sources of spiritual care (e.g., chaplains) are available to clinicians to address the spiritual needs of patients.

Clinical and radiologic features of cerebral edema in fulminant hepatic failure.

OBJECTIVE: To describe a series of consecutive patients with fulminant hepatic failure (FHF) and to present a new classification system for brain edema, an important cause of mortality in such patients. DESIGN: We reviewed 22 computed tomographic (CT) scans of the brain in 12 patients with FHF and classified the severity of cerebral edema by using predefined criteria. RESULTS: No cerebral edema was detected on CT scans in four patients with stage 1 or 2 hepatic encephalopathy at the time of admission, but it was noted in seven of eight patients with stage 3 or 4 hepatic encephalopathy. The severity of brain edema on CT scans was significantly correlated (P < 0.001) with the stage of hepatic encephalopathy. Three of the four patients who had stage 1 or 2 hepatic encephalopathy at the time of initial assessment ultimately had a good outcome. Of seven patients with stage 3 encephalopathy, two had rapid deterioration to brain death, three died of nonneurologic causes, and two had a good outcome after liver transplantation. One patient with stage 4 hepatic encephalopathy died, and autopsy showed cerebral edema. CONCLUSION: Stage 3 or 4 hepatic encephalopathy is associated with cerebral edema that can be detected on CT scans. The clinical and radiologic signs of cerebral edema in patients who have progression to stage 3 hepatic encephalopathy can be reversed with conventional treatment of increased intracranial pressure. Whether early recognition and treatment of cerebral edema result in increased survival of patients with FHF remains to be determined.

Adverse effects of vancomycin administered in the perioperative period.

Indications for the administration of vancomycin in the perioperative period have expanded in recent years. Used in this situation, vancomycin has caused adverse reactions, the most serious of which is hypotension. We describe five patients who had adverse reactions to vancomycin perioperatively. Vancomycin-induced hypotension usually results from a negative inotropic and vasodilator effect produced in part by a histamine-release phenomenon, which occurs most commonly with rapid intravenous infusion of the drug. Such a release of histamine may also produce an acute urticarial flushing of the upper torso (the "red neck syndrome") and symptoms of pain and muscle spasm in the chest or paraspinal muscles, which may mimic myocardial infarction. These effects usually abate promptly when the infusion of vancomycin is discontinued, and their resolution may be expedited by administration of an antihistamine.

Intensive-care unit experience in the Mayo liver transplantation program: the first 100 cases.

The first 100 liver transplantations at the Mayo Clinic were performed in 83 patients, who required a total of 917 patient days in the intensive-care unit (ICU). The mean duration of stay in the ICU was 5.91 days after liver transplantation and 6.15 days for patients who subsequently required readmission to the ICU. During the immediate postoperative period, hypothermia and hyperglycemia invariably occurred. Later during the initial admission or on readmission to the ICU, there arose the possibility of infections and renal insufficiency. Prompt diagnosis and treatment are necessary for hypertension, hypokalemia, severe metabolic alkalosis, fever, altered mental status, oliguria, and signs of graft failure in liver transplant patients. In our patient series, selective bowel decontamination minimized the occurrence of gram-negative and fungal sepsis, and use of antihypertensive agents and correction of coagulopathies may have decreased the risk of intracranial bleeding in patients with hypertension and clotting defects. Anticipation of potential conditions postoperatively and early implementation of treatment are key factors in the successful ICU management of patients who have undergone liver transplantation.

Assessment of nutritional status of patients with end-stage liver disease undergoing liver transplantation.

Nutritional assessment factors (including dietary history, anthropometric and biochemical measurements, and evaluation of immunocompetence) were retrospectively reviewed in 74 patients undergoing an initial liver transplantation procedure. The patients were subdivided into four categories on the basis of type of liver disease: chronic active hepatitis (N = 24), primary sclerosing cholangitis (N = 22), primary biliary cirrhosis (N = 20), and acute or subacute hepatitis (N = 8). Our nutritional assessment data indicated that malnutrition was present preoperatively in all liver transplantation groups but that each group had distinct characteristics. The group with primary biliary cirrhosis seemed to have the best hepatic synthetic function despite extreme wasting of muscle and fat. On the basis of all criteria, the group with acute hepatitis was the most malnourished of the various disease groups. Aggressive nutritional support, which includes adequate intake of nutrients and supplementation of vitamins and trace minerals, should be encouraged for all potential liver transplant patients.

Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients.

OBJECTIVE: To characterize the pulmonary hemodynamics and identify predictors of pulmonary hypertension in a group of patients before liver transplantation and to determine whether pulmonary hypertension in these patients is related to survival. MATERIAL AND METHODS: In 362 patients before their first liver transplantation (between 1985 and 1993), the clinical history, laboratory data, and results of pulmonary function tests were recorded. Pulmonary artery (PA) catheterization was performed after induction of anesthesia at the time of transplantation. Monthly follow-up was maintained. RESULTS: A hyperdynamic circulation was often present -- an increased mean cardiac output (7.6 L/min), increased mean PA pressure (20.9 mm Hg), correlation of mean PA pressure with cardiac output (r = 0.25; P<0.001), and decreased mean pulmonary vascular resistance (60 dynes times s/cm5). Mean PA pressures were more than 25 mm Hg in 72 patients (20%). Pulmonary hypertension (defined as mean PA pressure of more than 25 mm Hg and pulmonary vascular resistance in excess of 120 dynes times s/cm5) occurred in 15 patients (4%). Pulmonary function tests revealed obstruction in 7%, restriction in 18%, and low diffusing capacity in 46%. By univariate analysis, lower forced expiratory volume in 1 second, forced vital capacity, and total lung capacity were the only preoperative factors associated with pulmonary hypertension (P<0.05). Survival was significantly lower in patients with acute fulminant hepatitis (P<0.001), the group with the highest mean PA pressure, than in those with other diagnoses. Increased PA pressures or mild to moderate pulmonary hypertension was not found to be associated with a worse survival by univariate or multivariate analysis. CONCLUSION: Increased PA pressure is common in liver transplant patients (20%). "True" pulmonary hypertension occurred in only 4% of our patients and was not associated with an adverse outcome.

Hepatopulmonary syndrome with progressive hypoxemia as an indication for liver transplantation: case reports and literature review.

In the hepatopulmonary syndrome (HPS), a pulmonary vascular complication of liver disease, severe hypoxemia due to pulmonary vascular dilatation can be extremely debilitating. Determining whether patients with advanced liver disease and HPS should be considered for liver transplantation is difficult. We describe three patients with progressive and severe hypoxemia who underwent successful liver transplantation and had resolution of their arterial hypoxemia. In these patients, the progressive pulmonary deterioration accelerated the need and was considered an indication for liver transplantation rather than being considered an absolute or relative contraindication. In addition, we review the literature on 81 pediatric and adult patients with HPS who underwent liver transplantation and specifically highlight mortality, morbidity, syndrome resolution, and prognostic factors. Posttransplantation mortality (16%) was associated with the severity of hypoxemia (mean arterial oxygen tension [PaO2] in 68 survivors was 54.2 +/- 13.2 mm Hg and in 13 nonsurvivors was 44.7 +/- 7.7 mm Hg; P<0.03). Patients with a pretransplantation PaO2 of 50 mm Hg or lower had significantly more frequent mortality (30%) in comparison with those with a PaO2 greater than 50 mm Hg (4%; P<0.02). Pulmonary recommendations that address the severity of hypoxemia and candidacy for liver transplantation are discussed.

Nutritional support for liver transplantation: identifying caloric and protein requirements.

OBJECTIVE: To characterize the caloric and protein requirements of patients with end-stage liver disease before and for 28 days after liver transplantation. DESIGN: We prospectively assessed 16 adult patients who were scheduled to undergo liver transplantation between December 1989 and September 1990. MATERIAL AND METHODS: Nitrogen balance, 24-hour urinary creatinine, 3-methylhistidine, and resting energy expenditure were determined before transplantation and on days 1, 3, 5, 14, and 28 after transplantation. The investigators were unaware of the results of these measurements, and patients were fed in accordance with a previously established clinical protocol. RESULTS: Resting energy expenditure did not increase from preoperative values; however, urinary nitrogen and 3-methylhistidine increased significantly after liver transplantation, an indication of protein catabolism from a myofibrillar source. A negative nitrogen balance persisted for 28 days post-operatively. CONCLUSION: We recommend that caloric intake be determined by using the formulation provided by the Harris-Benedict equation at ideal body weight plus 20%. We also recommend that intake of protein be adjusted on the basis of preoperative nutritional assessment, perioperative hepatic and renal function, and results of tests used to measure the adequacy of administered protein. Parenterally or enterally administered protein of more than 1.2 g/kg daily should be well tolerated in most patients who have undergone liver transplantation.

Acute hepatic failure: the emerging role of orthotopic liver transplantation.

From 1985 through 1987, we diagnosed acute hepatic failure in 13 patients. Spontaneous recovery occurred in three of these patients. Eight patients underwent liver transplantation, five of whom survived and three of whom died. In addition, two patients died before undergoing transplantation. The survival rate of 62% was better than that among our previous series of similar patients. This improvement seems to be related to the use of orthotopic liver transplantation as a therapeutic alternative among these patients. One of the three patients who died after liver transplantation had normal liver function, but respiratory failure caused by Pneumocystis carinii developed 4 months after the transplantation. The surgical procedure was less difficult in patients with acute fulminant hepatitis than in those with chronic liver disease because fewer problems arose from adhesions, venous collaterals, and ascites. The emerging role of orthotopic liver transplantation in patients with acute hepatic failure is demonstrated by the improvement of survival rates observed by various groups, including ours, when this therapeutic modality is available.

Comparison of analgesic requirements after liver transplantation and cholecystectomy.

In a prospective study of 10 patients who underwent liver transplantation and 10 patients who underwent cholecystectomy, we analyzed the postoperative analgesic requirements and the resultant plasma morphine concentrations. Analgesia was more intense, with less medication, and the plasma morphine concentration was significantly lower in the liver transplant group than in the cholecystectomy group. This finding is most likely attributable to endogenous factors rather than to altered morphine pharmacokinetics.

Pulmonary complications of orthotopic liver transplantation.

We retrospectively reviewed the pulmonary complications and associated morbidity and mortality of 44 consecutive patients who underwent 52 orthotopic liver transplantations (OLTs) at the Mayo Clinic during 1987. All survivors participated in follow-up for 1 year after OLT. Of the five deaths in the study group, three were associated with pulmonary infections. On postoperative chest roentgenograms, 24 cases of pulmonary infiltrates were noted; 12 were caused by infections. Ten opportunistic pulmonary infections developed in nine patients: four cytomegalovirus, three Pneumocystis carinii pneumonia, and one each of Cryptococcus, Aspergillus, and Candida. All except one of the opportunistic infections were diagnosed after the sixth postoperative week. Fiberoptic bronchoscopy was helpful for diagnosing opportunistic pulmonary infections in six patients. One Aspergillus pulmonary infection was diagnosed by transthoracic needle aspiration. Bacterial pneumonia occurred in five patients. Preoperative pulmonary function tests, performed in 40 patients, revealed a restrictive ventilatory defect in 28% and impaired gas transfer in 52%. Pleural effusion was present in 18% of patients preoperatively and in 77% during the first week after OLT. Preoperative severity of liver disease and results of arterial blood gas determinations, pulmonary function tests, and chest roentgenography were not associated with postoperative mortality and pulmonary infections. Infectious and noninfectious pulmonary complications are common in liver transplant recipients. Attempts to decrease the frequency and severity of pulmonary complications by early diagnosis and effective treatment may diminish the morbidity and mortality associated with OLT.

Granulocyte accumulation in the transplanted liver does not correlate with clinical and histologic evidence of dysfunction.

RATIONALE AND OBJECTIVES: To evaluate the role of granulocytes in reperfusion injury after liver transplantation. The authors injected radiolabeled granulocytes to determine if human liver graft outcome could be correlated with granulocyte accumulation. MATERIALS AND METHODS: Pure granulocyte suspension was prepared from eight patients 12 to 24 hours after orthotopic liver transplantation. The granulocytes were labeled with indium-111 (111In) oxine and reinjected. Total body radionuclide images were performed. Liver uptake of granulocytes was compared with biochemical and histologic evidence of liver injury. RESULTS: No correlation was found between liver uptake of granulocytes, as measured by geometric mean counts, and the biochemical or histologic measures of liver injury. Liver uptake of 111In was 9.6% for the patient who had liver dysfunction and 10.4% mean of the study group. This technique did not detect early signs of liver dysfunction. CONCLUSIONS: This investigation supports the premise that granulocytes do not play a major role in reperfusion injury of the newly transplanted liver graft.

Hyperdynamic circulatory state after liver transplantation.

HCS is common pre-LT (69% of our patients) and frequently develops in NHCS patients during LT. There is a trend toward normalization of HCS after LT. Despite the increased requirement for postoperative blood transfusion in those patients with HCS, it may be prudent to avoid treatment of HCS with cardiodepressants and await its spontaneous reversal.

Thrombocytopenia after liver transplantation.

Thrombocytopenia occurs in postoperative liver transplant patients, with platelet counts reaching a nadir on the third postoperative day. Significant bleeding episodes are not uncommon during the first five days postoperatively when platelet counts are low. This thrombocytopenia may be the result of platelet sequestration in the newly grafted liver. The sequestration phenomenon does not appear to be on the basis of antiplatelet antibody activity. Further work defining the time course of this organ sequestration and evaluating the possible release of previously sequestered platelets back into the circulation need to be done. Also, it may be productive to study medications known to inhibit platelet activation (ie, cyclooxygenase inhibitors, prostacyclin, and calcium channel blockers) with the intent of interrupting platelet adhesiveness-sequestration at the time of recirculation of the newly grafted liver.

Serum vasopressin concentrations during orthotopic liver transplantation.

BACKGROUND: We report measurements of the temporal response of serum vasopressin concentrations in the period after reperfusion of the liver graft during orthotopic liver transplantation (OLT). METHODS: Vasopressin concentrations were determined in 11 adult patients undergoing OLT by radioimmunoassay of samples collected after induction, at 5 minutes prior to reperfusion, and at 10, 20, 30, 40, 50, 60, 90, and 120 minutes after reperfusion. RESULTS: Pre-incision vasopressin concentrations ranged from <0.5 to 2.6 pg/mL (reference serum vasopressin, <1.7 pg/mL). Overall, levels increased before reperfusion, but fell thereafter. Individual patients manifested elevated levels during the period after reperfusion. Values immediately before reperfusion exhibited most variability, ranging from 0.8 to 40 pg/mL (median, 15; interquartile range [IQR], 4-29) Median vasopressin concentrations 10 minutes postreperfusion were 7.6 pg/mL (IQR, 3-27). Only 3 of the 11 patients failed to generate vasopressin levels >20 pg/mL. In each of these patients, hemodynamics were satisfactory without the need for additional pressor infusion. Maximum vasopressin concentration measured in any patient was 85 pg/mL. There was no correlation between vasopressin concentration and mean blood pressure or systemic vascular resistance index. CONCLUSION: Vasopressin concentrations during OLT vary widely and are elevated periodically during the anhepatic and postreperfusion stages, with no apparent relationship between vasopressin concentrations and blood pressure. Although vasopressin concentrations were not as high as those measured during some other clinical situations, these data suggest that a relative vasopressin deficiency is not a direct cause of hypotension during OLT.