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.

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.

Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: a prospective, randomized, double-blind study.

The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P =.0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.

Liver transplantation for massive hepatic haemangiomatosis causing restrictive lung disease.

A 34-yr-old man with hepatic haemangiomatosis presented for orthotopic liver transplantation. His massively distended abdomen caused thoracic compression and severe restrictive lung disease. Respiratory failure was the principal indication for transplantation. Increased airway pressures, pulmonary hypertension, systemic hypotension caused by aorto-caval compression, and blood loss, complicated the intra-operative anaesthetic management. Weaning from mechanical ventilation was impaired by acute and chronic metabolic alkalosis, and diaphragmatic laxity.

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.

Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

Several studies have demonstrated increased morbidity and mortality in patients with cirrhosis undergoing anesthesia and surgery. Cirrhosis is a chronic liver disease, which may affect all body systems. The severity of the disease, assessed by the Child-Pugh classification, has a substantial effect on patient outcome. The extent of surgery and co-morbid conditions also have a major impact. In the past few years, changes have been made in the diagnosis, preoperative preparation, surgical and anesthetic management and perioperative care of patients with liver disease. The aim of this review is to examine whether these changes have resulted in improved perioperative outcomes.

Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation.

In the setting of moderate to severe pulmonary artery hypertension, orthotopic liver transplantation (OLT) may be complicated by pulmonary hemodynamic instability and cardiopulmonary mortality. We retrospectively studied the relationship between cardiopulmonary-related mortality and initial (untreated) pre-OLT pulmonary hemodynamics in 43 patients with portopulmonary hypertension who underwent attempted OLT. Thirty-six patients were reported in 18 peer-reviewed studies, and 7 patients underwent OLT at our institution since 1996. Transplantation procedure outcome, mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), cardiac output, pulmonary capillary wedge pressure, and transpulmonary gradient (TPG) are summarized. Overall mortality was reported in 15 of 43 patients (35%). Fourteen of the 15 deaths (93%) were primarily related to cardiopulmonary dysfunction. Two deaths were intraoperative, 8 deaths occurred during the transplantation hospitalization, and 4 patients died of cardiopulmonary deterioration posthospitalization. In 4 patients, the transplantation procedure could not be successfully completed. Cardiopulmonary mortality was associated with greater pre-OLT MPAP (49 +/- 14 v 36 +/- 7 mm Hg; P <.005), PVR (441 +/- 173 v 261 +/- 156 dynes.s.cm(-5); P <.005), and TPG (37 +/- 13 v 22 +/- 10 mm Hg; P <.005). MPAP of 50 mm Hg or greater was associated with 100% cardiopulmonary mortality. In patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater, the mortality rate was 50%. No mortality was reported in patients with a pre-OLT MPAP less than 35 mm Hg or TPG less than 15 mm Hg. Cardiopulmonary-related mortality in OLT patients with portopulmonary hypertension was frequent and associated with significantly increased pre-OLT MPAP, PVR, and TPG compared with survivors. Treated or untreated, we recommend intraoperative cancellation or advise against proceeding to OLT for an MPAP of 50 mm Hg or greater. Patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater appear to be at high risk for cardiopulmonary-related mortality after OLT. A prospective study is needed to define optimal pretransplantation treatments and pulmonary hemodynamic criteria that minimize OLT mortality associated with portopulmonary hypertension.

Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.

Pulmonary hypertension has been associated with poor outcome after liver transplantation. We assessed the diagnostic accuracy of Doppler echocardiography in detecting significant pulmonary hypertension. Seventy-four potential liver transplant candidates underwent Doppler echocardiography in which the systolic right ventricular pressure (RVsys) was used to estimate the systolic pulmonary artery pressure (PAsys). Group 1 included 39 consecutive patients with RVsys >/=50 mm Hg who underwent elective right heart catheterization. Group 2 consisted of 35 patients with RVsys <50 mm Hg in whom pulmonary artery pressures were measured at the beginning of the transplantation procedure. The accuracy of the estimates by Doppler echocardiography was assessed against measurements made by direct catheterization. Patients in groups 1 and 2 were comparable in their demographic and liver disease characteristics. There was a strong correlation between RVsys by Doppler echocardiography and PAsys by right heart catheterization (r =.78, P <.01). Of the 39 patients in group 1, 29 (72%) had at least moderate pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg), including 12 (30%) with severe pulmonary hypertension (MPAP >/=50 mm Hg). Only 1 of the group 2 patients had MPAP >/=35 mm Hg. Thus, in the diagnosis of moderate to severe pulmonary hypertension, the sensitivity of echocardiography was 97% and specificity was 77%. Doppler echocardiography is an accurate screening test to detect moderate to severe pulmonary hypertension. We advise that liver transplant candidates with RVsys >/=50 mm Hg undergo right heart catheterization to fully characterize pulmonary hemodynamics.

Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension.

Patients with end-stage liver failure, portal hypertension, and associated pulmonary artery hypertension (portopulmonary hypertension [PPHTN]) have a high mortality when undergoing liver transplantation. Successful transplantation in these patients may depend on efforts to reduce pulmonary artery pressure (PAP). To this end, a number of centers are using a continuous intravenous (IV) infusion of epoprostenol, which has been shown to improve symptoms, extend life span, and reduce PAP in patients with primary pulmonary hypertension. We report four cases in which treatment of patients with PPHTN with continuous IV epoprostenol was followed by the development of progressive splenomegaly, with worsening thrombocytopenia and leukopenia. This finding may limit the usefulness of epoprostenol in PPHTN and influence the timing of transplantation in such patients.

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension.

Pulmonary artery hypertension in association with liver failure (portopulmonary hypertension [PPHTN]) is a significant barrier to liver transplantation because patients with this condition have a very high mortality when transplantation is undertaken. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, reduces pulmonary artery pressure (PAP) in some patients with primary pulmonary hypertension, but its effect in patients with PPHTN is controversial. We investigated the hemodynamic effects of inhaled NO in 6 patients with PPHTN. Five of 6 patients responded to NO inhalation with decreases in PAP and pulmonary vascular resistance of greater than 10%; these decreases were statistically significant at NO concentrations of 10 and 30 ppm. Cardiac output did not significantly change. We conclude that inhalation of NO reduces PAPs in some patients with PPHTN.

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.

Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

BACKGROUND: Patients with cirrhosis have a reduced life expectancy. Anesthesia and surgery have been associated with clinical decompensation in patients with cirrhosis. METHODS: The authors retrospectively reviewed the records of all patients with the diagnosis of cirrhosis who underwent any surgical procedure under anesthesia at their institution between January 1980 and January 1991 (n = 733). Univariate and multivariate analyses were used to identify the variables associated with perioperative complications and short- and long-term survival. RESULTS: The perioperative mortality rate (within 30 days of surgery) was 11.6%. The perioperative complication rate was 30.1%. Postoperative pneumonia was the most frequent complication. Multivariate factors that were associated with perioperative complications and mortality included male gender, a high Child-Pugh score, the presence of ascites, a diagnosis of cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine concentration, the diagnosis of chronic obstructive pulmonary disease, preoperative infection, preoperative upper gastrointestinal bleeding, a high American Society of Anesthesiologists physical status rating, a high surgical severity score, surgery on the respiratory system, and the presence of intraoperative hypotension. CONCLUSION: Risk factors have been identified for patients with cirrhosis who undergo anesthesia and surgery.

Post-liver transplantation myocardial dysfunction.

Patients with end-stage liver disease usually show a hyperdynamic circulatory state. It has previously been reported that patients who develop myocardial depression in the early post-liver transplantation period are more prone to organ failure and death. We reviewed the records of 754 adult patients undergoing liver transplantation at our institution and identified 7 patients who initially showed hyperdynamic circulation, but then developed reversible dilated cardiomyopathy in the early posttransplantation period. All identifiable causes of cardiac dysfunction, such as myocardial ischemia, thyroid dysfunction, and electrolyte imbalances, were excluded. Left ventricular ejection fraction decreased from a preoperative median baseline of 60% to 20% (P = .02), with four-chamber dilatation on echocardiogram. All these patients required supportive care, including mechanical ventilation, afterload reduction, inotropic support, and monitoring in the intensive care unit. Cardiac function subsequently improved in all patients, with ejection fraction increasing to a median of 50%. All patients were discharged from the hospital. At a median follow-up of 15 months, there was no recurrence of heart failure. The increased peripheral resistance seen after successful liver transplantation may be an important causative factor.