Intra-operative acute isovolemic hemodilution is safe and effective in eliminating allogeneic blood transfusions during right hepatic lobectomy: comparison of living donor versus non-donors.

BACKGROUND: Multiple studies have shown acute isovolemic hemodilution (AIH) to be safe and effective during liver resection to limit the use of banked blood. However, no studies to date have studied AIH in living donor right hepatectomy. Conventional right hepatectomies for living donors is not identical to non-donor right hepatectomies. Since division of the parenchyma is often performed without devascularization of the right lobe, blood loss may be significantly higher. METHODS: Ten consecutive patients undergoing living donor right hepatectomies (LDRH) and ten consecutive patients undergoing non-donor right hepatectomies (NDRH) were compared using AIH. RESULTS: There was no mortality or morbidity related to the use of AIH. No allogeneic blood transfusions were required in either group, intra-operatively or post-operatively. There was no significant difference in post-operative hematocrit, average estimated blood loss, and average fluid replacement. Average hospital length of stay and operating room time were longer for the LDRH. CONCLUSION: AIH can be performed safely and effectively in both LDRH and NDRH without subjecting patients to unnecessary risks of allogeneic blood transfusions.

Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease.

BACKGROUND: Hepapoietin is a naturally occurring cytokine that promotes hepatocyte growth. Animal studies have suggested that hepapoietin and hepatocyte growth factor have a potential role in the prevention and management of liver diseases. However, human studies have been lacking. AIM: To evaluate the safety and pharmacokinetics of single escalating doses of hepapoietin in patients with chronic liver disease. METHODS: An open-label, single escalating dose trial with five different doses of hepapoietin (1, 3, 10, 30 and 100 mg) was performed. Adults with chronic, compensated, non-viral liver disease were included. Liver function tests were obtained before dosing, 24 h after hepapoietin administration and on days 4, 7, 30 and 45. All patients were followed for 45 days. RESULTS: Twenty-five subjects received hepapoietin, with five subjects each at 1, 3, 10, 30 and 100 mg of hepapoietin. Significant decreases occurred in total bilirubin, ammonia, partial thromboplastin time and cholesterol levels overall, and both high-density and low-density lipoprotein cholesterol showed a downward trend. An increase in albumin was observed at the 30 mg dose level. Slight decreases in haemoglobin and red blood cell levels were observed at day 4, but returned to normal levels immediately thereafter. Child-Pugh scores from day 0 to day 7 were improved in 24%, stable in 64% and worse in 12% of patients. Hepatic encephalopathy displayed changes from day 0 to day 45 with improvement in 16%, no change in 80% and worsening in 4%. CONCLUSIONS: Hepapoietin in doses up to 100 mg is safe for use in humans. Potential benefits are suggested by significant decreases in bilirubin, ammonia, partial thromboplastin time and cholesterol levels and an increase in albumin. Further studies with multiple dosing regimens are needed to identify the clinical utility of hepapoietin in the management of chronic liver disease.

Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers.

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus-positive (HCV(+)) donor livers for HCV(+) recipients. This study reviews the clinical outcome of a large series of HCV(+) recipients of HCV(+) liver allografts and compares their course with that of HCV(+) recipients of HCV-negative (HCV(-)) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV(+) transplant recipients were analyzed. Two groups were identified: a group of HCV(+) recipients of HCV(+) donor livers (n = 96), and a group of HCV(+) recipients of HCV(-) donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV(+) allograft (8.3% v 3.1%; P =.01). Patient survival showed a significant difference for the HCV(+) group compared with the HCV(-) group (90% v 77%; P =.01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV(+) group and only 1.3% in the HCV(-) group (P =.04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV(+) recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV(+) donor livers for transplantation in HCV(+) recipients safely and effectively expands the organ donor pool.

Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension is a known complication in the liver transplant candidate. Intravenous epoprostenol has been demonstrated to decrease pulmonary artery pressures and possibly remodel right ventricle geometry. METHODS: In this report, we document the efficacy of inhaled aerosolized epoprostenol in a patient with portopulmonary hypertension. The effect was of rapid onset and offset. RESULTS: After 10 min of delivery, mean pulmonary artery pressure decreased 26%; cardiac output increased by 22%; pulmonary vascular resistance decreased by 42%; and the transpulmonary gradient decreased by 29%. There were no untoward side effects. CONCLUSION: The inhaled route of delivery of epoprostenol is potential alternative for the acute therapy of portpulmonary hypertension.

Intraoperative use of inhaled PGI(2) for acute pulmonary hypertension and right ventricular failure.

Inhaled prostacyclin (PGI(2)) can be used as an effective pulmonary vasodilator intraoperatively to treat pulmonary hypertension and impending right ventricular failure.

Outcomes of laparoscopic donor nephrectomy in obese patients.

The applicability of laparoscopic donor nephrectomy (LDN) has not been assessed in the obese donor. We hypothesized that obesity is not a technical contraindication to LDN. From May 1998 to February 1999, 40 patients underwent LDN at the Georgetown Transplant Institute with the transperitoneal technique. Prophylaxis against deep venous thrombosis consisted of venous compression stockings, low-molecular weight heparin in obese patients, and early ambulation. The following variables were examined: donor sex, age, weight, height, related versus nonrelated donation, body mass index (BMI; wt/ht2), operating room time, estimated blood loss, length of stay, time out of work, and complications. BMI>31 indicates morbid obesity, BMI>27 indicates >20% over ideal body weight, and normal BMI is 25. The patients were divided into nonobese (BMI< or =31) and obese groups (BMI>31). The two groups do not differ in outcome after LDN. Our data indicate that obesity is not associated with increased morbidity or mortality after LDN.

Portopulmonary hypertension and the liver transplant candidate.

The management of the liver transplant (OLT) candidate with portopulmonary hypertension (PPHTN) has dramatically changed in the past 3 years. Careful preoperative evaluation with functional characterization of right ventricular function plays a critical role. The pulmonary vascular response to epoprostenol infusion serves as a deciding factor for OLT candidacy. Careful perioperative attention to avoid right ventricular failure from acutely elevated pulmonary artery pressures or sudden increases in right ventricular preload is a key physiologic tenet of management. With increased surgical expertise, anesthetic sophistication, and availability of epoprostenol, PPHTN is no longer considered an absolute contraindication for OLT.

Transesophageal echocardiographic detection of gas embolism and cardiac valvular dysfunction during laparoscopic nephrectomy.

UNLABELLED: We used transesophageal echocardiography (TEE) to monitor venous gas embolism, cardiac performance, and the hemodynamic effects of positioning and pneumoperitoneum in 16 healthy kidney donors undergoing laparoscopic nephrectomy. A four-chamber view was used continuously, except at predetermined intervals, when a complete TEE examination for cardiac function was performed. Other clinical variables recorded include systolic, diastolic, and mean arterial blood pressure; heart rate (HR), pulse oximetric saturations; and end-tidal CO2. Baseline valvular incompetence was seen in 13 of the 16 patients when supine and asleep. After positioning for surgery and induction of pneumoperitoneum, TEE revealed valvular incompetence with regurgitation more pronounced from baseline in 15 of the 16 patients. In one patient, during renal vein dissection, gas entered the right atrium from the inferior vena cava, worsening tricuspid regurgitation. Hemodynamic variables and ejection fraction were tested by using repeated-measures analysis of variance for significance (P < 0.05). Pneumoperitoneum increased (P < 0.05) systolic blood pressure (from 102.8 +/- 3.89 to 120.8 +/- 3.88 mm Hg) and HR (from 68.9 +/- 3.19 to 75.6 +/- 2.62). Ejection fraction was unchanged. The high incidence of valvular incompetence indicates that further studies are needed to assess these effects during laparoscopic nephrectomy with cardiac disease. IMPLICATIONS: Laparoscopic surgery has gained popularity as a procedure for the removal of donated kidneys. Although the insufflation of gas necessary for this relatively simple approach poses a low risk of venous air embolism, it may increase the risk of changes in valvular competency.

Transverse hepatectomy for symptomatic polycystic liver disease.

Polycystic liver disease can result in massive enlargement of the liver with resultant debilitating symptoms of abdominal pain, chronic fatigue, and severely compromised functional status. Fenestration of hepatic cysts has been advocated as a treatment for polycystic disease. However, in patients with predominant small cyst replacement, fenestration alone often results in limited hepatic volume reduction without improvement in patient functional status. Liver transplantation has also been previously advocated for polycystic liver disease with predominant small cyst replacement, but, with the severe shortage of donor organs, alternative treatment should be considered. In this report we present a case of massive enlargement of the liver with severe clinical debilitation due to polycystic liver disease. Transverse hepatectomy provided a safe and effective alternative to fenestration or liver transplantation.

Acute pancreatitis and fulminant hepatic failure.

BACKGROUND: The association of acute pancreatitis with fulminant hepatic failure (FHF) was first recognized in 1973. Since then, few studies have described the clinical profile of the FHF patient with acute pancreatitis. Identification of the distinguishing attributes of pancreatitis in combination with FHF will provide a more sound basis for clinical management. The purposes of this study were to identify distinguishing clinical characteristics of acute pancreatitis in FHF and to compare outcomes with those of patients with acutely decompensated chronic liver disease and acute pancreatitis (DECOMP). STUDY DESIGN: This was a retrospective survey of 30 patients with FHF and 30 with DECOMP admitted during the period July 1995 to July 1997. RESULTS: The prevalence of acute pancreatitis in FHF and DECOMP was 33% and 23%, respectively. Acute pancreatitis was associated with severe hepatocellular synthetic dysfunction, renal insufficiency, requirement for endotracheal intubation, increased acuity of illness at the time of ICU admission, more rapid decompensation during the disease, and significantly greater mortality in both the FHF and DECOMP groups. CONCLUSIONS: In both FHF and DECOMP, acute pancreatitis increases disease acuity and mortality. Acute pancreatitis does not occur with significantly greater frequency in FHF. Implementation of orthotopic liver transplantation may not be warranted in this setting.

The clinical implications of hypophosphatemia following major hepatic resection or cryosurgery.

OBJECTIVES: To determine the incidence and predisposing factors leading to postoperative hypophosphatemia after major hepatic surgery and the consequences of this electrolyte abnormality. DESIGN: A retrospective study. SETTING: A university tertiary care referral center. PATIENTS AND METHODS: Thirty-five consecutive patients undergoing either major hepatic resections or cryosurgery from July 1994 through January 1997 were retrospectively reviewed for the occurrence of hypophosphatemia and postoperative complications. MAIN OUTCOME MEASURES: Prolonged ventilatory support, intensive care unit and hospital stays, and the incidence of postoperative complications. RESULTS: The overall incidence of hypophosphatemia in our series was 21 (67%) of 35 with a mortality rate of 1 (2.8%) in 35. Mean operative time, estimated blood loss, partial vascular occlusion time, and transfusion requirements were similar between the hypophosphatemic and the nonhypophosphatemic groups. The presence of postoperative complications was significantly greater in the hypophosphatemic group (17 [80%] of 21) vs the nonhypophosphatemic group (4 [28%] of 14) (P<.05). The incidence of antacid use in the hypophosphatemic group (14 [66%] of 21) was significantly higher than the use in the nonhypophosphatemic group (2 [14%] of 14) (P<.05). CONCLUSIONS: Hypophosphatemia commonly occurs in major hepatic procedures. The presence of moderate hypophosphatemia is associated with the use of antacid therapy but no other perioperative or operative variables. The occurrence of hypophosphatemia correlates with an increased incidence of postoperative complications. Awareness of this entity can direct aggressive replacement of phosphates and avert the occurrence of severe hypophosphatemia and associated complications.

Dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation.

This study attempts to evaluate the efficacy of dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation. Two hundred twenty consecutively submitted patients were evaluated in preparation for orthotopic liver transplantation. Dobutamine stress echocardiography was performed in 80 patients with known or suspected coronary artery disease. Follow-up information was available in 40 patients in the form of cardiac catheterization and/or outcome from liver transplantation to validate the dobutamine stress echo findings. The prevalence of coronary artery disease in this cohort was 5% and was closely associated with the presence of diabetes mellitus. Dobutamine stress echocardiography, when interpreted as abnormal in the presence of wall motion abnormalities only, is associated with a sensitivity, specificity, and positive and negative predictive value of 100%. Dobutamine stress echocardiography is highly efficacious and should be the screening study of choice to detect coronary artery disease in patients undergoing orthotopic liver transplantation.

Apoptosis and hepatic allograft reperfusion injury.

Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death. Until recently, investigators have focused upon necrosis as the sine qua non of lethal cell injury. Specifically, within the realm of liver transplantation, preservation strategies dealing with ischemia/reperfusion injury have concentrated upon minimizing the biochemical and histologic correlates associated with necrosis. Little is known of the role of apoptosis in reperfusion injury in human liver transplantation. Post-reperfusion liver biopsies from 35 patients were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was identified histologically and using a chromogenic technique of in situ labeling of fragmented DNA. The number of apoptotic cells increased in parallel with the necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic cells. The recipient peak serum transaminase values were also noted to increase with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: 1) apoptosis occurs in the setting of reperfusion injury during human orthotopic liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel with pathologic and biochemical parameters of reperfusion injury. Given the distinct nature of apoptosis and the highly regulated and conserved pathway for its initiation, inhibition of apoptosis with specific molecular targets, may serve to decrease allograft reperfusion injury.

Effects of split torso positioning and laparoscopic surgery for donor nephrectomy on respiratory mechanics.

STUDY OBJECTIVE: To test whether split torso positioning, abdominal insufflation, and other procedures performed during laparoscopic nephrectomy would affect mechanical impedances to inflation [i.e., elastance (E) and resistance (R) of the total respiratory system (Ers, and Rrs), lungs (EL and RL), and chest wall (Ecw and Rcw)] differently from previously studied laparoscopic procedures. DESIGN: Unblinded study, each patient serving as own control. SETTING: University hospital. PATIENTS: 12 ASA physical status I and II patients scheduled for laparoscopic donor nephrectomy, all without cardiopulmonary disease. INTERVENTIONS: Patients were anesthetized and paralyzed, tracheally intubated and mechanically ventilated at 10, 20, and 30 breaths/minute and at tidal volumes of 250, 500, and 800 ml. Measurements were made in the following positions: supine, split torso, abdominal insufflation (Pab = 15 mmHg), and supine after deflation. MEASUREMENTS AND MAIN RESULTS: Airway flow and pressure and esophageal pressure were measured. Discrete Fourier transformation was used to calculate E and R. These were analyzed with repeated measures, linear multiple regression with accepted level of significance at p < 0.05. Ers, Ecw, and Rcw increased (p < 0.05) while EL decreased (p < 0.05) when patients changed from supine to split torso. During Pab = 15 mmHg, Ers, Ecw, and Rcw increased further and Rrs and RL increased (p < 0.05). Following abdominal deflation, Ecw and Ers remained elevated (p < 0.05). The changes in Ecw caused by laparoscopy and surgery were greater than we have previously measured in other laparoscopic procedures, while the changes in EL were less. CONCLUSIONS: Laparoscopic nephrectomy affects lung and chest wall mechanical properties differently from other laparoscopic procedures. This finding could be due to the split torso positioning, and the effects of abdominal swelling on the chest wall caused by administration of more perioperative fluids with laparoscopic nephrectomy.

Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension, defined as mean pulmonary artery pressure >25 mmHg in the presence of a normal pulmonary capillary wedge pressure and portal hypertension, is a known complication of end-stage liver disease that has been associated with high morbidity and mortality at the time of liver transplantation. We have recently reported the successful treatment of portopulmonary hypertension with chronic intravenous epoprostenol and now report the first patient with severe portopulmonary hypertension successfully treated with epoprostenol who subsequently underwent successful liver transplantation. METHODS: A patient with severe portopulmonary hypertension was treated with intravenous epoprostenol, 23 ng/kg/min, for a 4-month period, after which the portopulmonary hypertension resolved and the patient underwent successful liver transplantation. RESULTS: The patient was discharged, continues to do well, and at 3 months is off epoprostenol with near normal pulmonary artery pressures. CONCLUSIONS: Chronic epoprostenol, in conjunction with a multidisciplinary, well-planned perioperative evaluation and treatment plan, may be the answer to a heretofore untreatable disease.