Gregory Dembo

A Randomized Clinical Trial Testing the Anti-Inflammatory Effects of Preemptive Inhaled Nitric Oxide in Human Liver Transplantation

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were

Treatment of severe lactic acidosis during the pre-anhepatic stage of liver transplant surgery with intraoperative hemodialysis

1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.

Effects of vasoactive agents on blood loss and transfusion requirements during pre-reperfusion stages of the orthotopic liver transplantation

Severe uncompensated lactic acidosis manifesting during the pre-anhepatic stage of orthotopic liver transplant surgery is an uncommon event, but it poses serious concern because of the additional lactate production and impaired elimination by the liver that develops during the anhepatic and allograft reperfusion stages of the procedure. A man with end-stage liver disease secondary to hepatitis C and hemochromatosis and normal renal function, who developed severe lactic acidosis in the pre-anhepatic stage of liver transplantation, was treated successfully with intraoperative, continuous venovenous hemodialysis. Hemodialysis effectively corrected the patients lactic acidosis and removed lactate, which contributed to hemodynamic stability during the anhepatic and graft reperfusion stages of his liver transplant surgery.

Surgical management of hepatocellular carcinoma after Fontan procedure

Objective: To evaluate the effects of vasoactive drugs, specifi cally low-dose vasopressin and phenylephrine infusions, on blood loss / transfusion requirements during dissection and anhepatic (pre-reperfusion) stages of orthotopic liver transplantations. Methods: A retrospective analysis of 110 orthotopic liver transplantation (OLT) cases was performed. The variables studied were: blood loss before and after reperfusion of the liver graft; blood volumes returned by cell-saver and amounts of transfused blood products; amounts of infused colloids and crystalloids; hemodynamic parameters such as MABP, MPAP, CO/CI, SVR; dosage of vasoactive drugs. Short – and long-term outcome measures included length-of stay (LOS), ICU LOS, 48 –hours return to the OR rate, incidence of the primary non-function of the liver graft, amounts of fresh frozen plasma (FFP) and cryoprecipitate, administered in the ICU, and 1-year mortality. The study subjects were allocated in two groups. Study group consisted of 15 patients that received a low-dose (0.04U/min) vasopressin infusion alongside with other vasoactive agents, such as phenylephrine and epinephrine, during the dissection and anhepatic stages of the procedure. Control group consisted of 95 patients, that received the same vasoactive agents except a lowdose vasopressin infusion. Anesthetic and transfusion management in both groups were otherwise identical. Results: The estimated blood loss before reperfusion of the liver graft was in 50.2% lower (p=0.0094) and total blood loss was in 38.8% lower ( p=0.0548) in the vasopressin group in comparison with control group of subjects of the same age, sex and with the same MELD score. No statistically signifi cant differences neither in hemodynamic parameters between the two groups, nor in transfusion requirements and volumes of crystalloid and colloids infused, were detected. No differences were found also in long-term outcome parameters. Conclusions: The decrease in blood loss in the vasopressin group may be attributed to the use of a vasopressin infusion. A low-dose (0.04U/min) vasopressin infusion may be an effective technique for blood loss reduction during the pre-reperfusion stages in orthotopic liver transplantation.

Anesthetic implications of the new anticoagulant and antiplatelet drugs

The Fontan operation has successfully prolonged the lives of patients born with single-ventricle physiology. A long-term consequence of post-Fontan elevation in systemic venous pressure and low cardiac output is chronic liver inflammation and cirrhosis, which lead to an increased risk of hepatocellular carcinoma (HCC). Surgical management of patients with post-Fontan physiology and HCC is challenging, as the requirement for adequate preload in order to sustain cardiac output conflicts with the low central venous pressure (CVP) that minimizes blood loss during hepatectomy. Consequently, liver resection is rarely performed, and most reports describe nonsurgical treatments for locoregional control of the tumors in these patients. Here, we present a multidisciplinary approach to a successful surgical resection of a HCC in a patient with Fontan physiology.

Conflicting Hemodynamic Goals in an Adult Patient With Fontan Physiology Presenting for Resection of a Hepatocellular Carcinoma.

In this review, we discuss the anesthetic implications of the new anticoagulant and antiplatelet drugs, focusing our discussion mainly on neuroaxial/regional anesthesia and central catheter placement issues. We offer practical recommendations for their use.

Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature

THE FONTAN PROCEDURE is used to treat children with congenital heart disease resulting in a single functional ventricle. Caval flow is directed to the pulmonary arteries without the aid of a subpulmonic ventricle. The absence of a right ventricle requires chronically elevated central venous pressure (CVP), which must be maintained at a sufficient level to drive pulmonary blood flow and maintain cardiac output. This pressure is transmitted to the liver, causing chronic hepatic congestion, which may be exacerbated by lower mean arterial perfusion pressures and chronic hypoxemia. These factors contribute to the increased rates of liver inflammation, gastroesophageal varices, liver nodules, and increasing reports of hepatocellular carcinoma (HCC) in these patients. In patients with Fontan circulation, a precipitous drop in preload can result in low cardiac output and hypotension. In patients requiring liver resection, elevated CVP is transmitted via the hepatic veins in the surgical bed, resulting in increased intraoperative bleeding. This leads to the practice of targeting CVP of less than 5 mmHg for major hepatectomy. These conflicting hemodynamic goals are examined in this case report.

Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature: Perioperative care in MRCD

Vater Y, Dembo G, Martay K, Klein Y, Vitin A, Weinbroum AA. Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01203.x
© 2010 John Wiley & Sons A/S.

Drug management in emergent liver transplantation of mitochondrial disorder carriers

Vater Y, Dembo G, Martay K, Klein Y, Vitin A, Weinbroum AA. Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01203.x
© 2010 John Wiley & Sons A/S.

Intraoperative epoprostenol and nitric oxide for severe pulmonary hypertension during orthotopic liver transplantation: a case report and review of the literature.

Vater Y, Dembo G, Martay K, Klein Y, Vitin A, Weinbroum AA. Drug management in emergent liver transplantation of mitochondrial disorder carriers: review of the literature.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01203.x
© 2010 John Wiley & Sons A/S.