Alexander A. Vitin

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.

Anesthetic management of acute mesenteric ischemia in elderly patients.

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

Ischemic insult to the splanchnic vasculature can jeopardize bowel viability and lead to devastating consequences, including bowel necrosis and gangrene. Although acute mesenteric ischemia (AMI) may occur at any age, the elderly are most commonly affected due to their higher incidence of underlying systemic pathology, most notably atherosclerotic cardiovascular disease. Treatment options include pharmacology-based actions, endovascular, and surgical interventions. AMI remains a life-threatening condition with a mortality rate of 60% to 80%, especially if intestinal infarction has occurred and surgical intervention becomes emergent. Early recognition and an aggressive therapeutic approach are essential if the usually poor outcome is to be improved. Anesthetic management is complex and must account for comorbid disease as well as the patients presumptive acute deterioration. Blood pressure support typically involves careful, but often massive, fluid resuscitation and may also additionally require pharmacologic support.

Effects of Fibrinogen Levels and Platelet Counts on Viscoelastic Testing in Cirrhotic Patients

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.

Severe Austrian Syndrome in an Immunocompromised Adult Patient – A Case Report

Abstract Introduction. Cirrhotic patients have been considered for decades to have a pro-haemorrhagic pattern and were treated as such based on the results from standard coagulation tests. The aim of our study was to determine the effects of platelet count and fibrinogen levels on rotational thromboelastometry (ROTEM) parameters. Methods. We prospectively included 176 patients with End-Stage Liver Disease (ESLD) admitted to our Intensive Care Unit prior to liver transplantation. Collected data consisted of severity scores, liver, renal and standard coagulation tests, fibrinogen levels, platelet counts and ROTEM parameters. Four ROTEM assays were performed (ExTEM, InTEM, ApTEM and FibTEM) and the following parameters included: CT – clotting time, CFT – clot formation time, MCF – maximum clot firmness, ML – maximum lysis, alpha angle, TPI – thrombin potential index, MaxV - maximum velocity of clot formation (MaxV), MaxVt - time to MaxV, MCE - maximum clot elasticity and AUC - area under the curve. Results. Statistical analysis demonstrated a linear correlation between platelet counts and ExTEM TPI (R2 linear =0.494), ExTEM MaxV (R2 linear =0.253), ExTEM MCE (R2 linear = 0.351) and ExTEM MCF (R2 cubic = 0.498). Fibrinogen levels correlated linearly with ExTEM MCF (R2 linear = 0.426), ExTEM TPI (R2 linear = 0.544), ExTEM MaxV (R2 linear = 0.332), ExTEM MCE (R2 linear = 0.395) and non-linearly with ExTEM CFT (R2 cubic = 0.475). Conclusion. Fibrinogen levels and platelet counts had an important effect on both standard and derived ROTEM parameters. Further analysis is required in order to determine clinically oriented cut-off values below which severe coagulopathy would develop.

Perioperative Stress-Induced (Takotsubo) Cardiomyopathy in Liver Transplant Recipients

Abstract Background: Known also as Osler’s triad, Austrian syndrome is a complex pathology which consists of pneumonia, meningitis and endocarditis, all caused by the haematogenous dissemination of Streptococcus pneumoniae. The multivalvular lesions are responsible for a severe and potential lethal outcome. Case report: The case of a 51-year-old female patient, with a past medical history of splenectomy, is presented. She developed bronchopneumonia, acute meningitis and infective endocarditis as a result of Streptococcus pneumoniae infection and subsequently developed multiple organ dysfunction syndromes which led to a fatal outcome. Bacteriological tests did not reveal the etiological agent. The histopathological examination showed a severe multivalvular endocarditis, while a PCR based molecular analysis from formalin fixed valvular tissue identified Streptococcus pneumoniae as the etiologic agent. Conclusions: The presented case shows a rare syndrome with a high risk of morbidity and mortality. Following the broad-spectrum treatment and intensive therapeutic support, the patient made unfavourable progress which raised differential diagnosis problems. In this case, the post-mortem diagnosis demonstrated multiple valvular lesions occurred as a result of endocarditis.

The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

Abstract A comprehensive analysis of published cases of Takotsubo cardiomyopathy, occurred in liver transplant recipients in the perioperative period, has been attempted in this review. Predisposing factors, precipitating events, potential physiological mechanisms, acute and post-event management have been discussed.

Review. Perioperative Management of Lactic Acidosis in End-Stage Liver Disease Patient

Abstract Sepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs) of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.