Corinne Vezinet

Dose-response curves of inhaled nitric oxide with and without intravenous almitrine in nitric oxide-responding patients with acute respiratory distress syndrome

Background Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50–60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide.

Hemodynamic and hormonal responses to the sudden interruption of caval flow: insights from a prospective study of hepatic vascular exclusion during major liver resections.

Hepatic vascular exclusion (HVE) combines portal triad clamping and occlusion of the inferior vena cava. Although HVE has been performed for major liver resections during the last 2 decades, little is known about the mechanisms that explain its satisfactory hemodynamic tolerance. Consequently, we performed a comprehensive study of both hemodynamic and hormone responses to HVE. Twenty-two patients who underwent liver resection for secondary tumors developed in noncirrhotic livers were prospectively studied. Heart rate, arterial blood pressure, pulmonary artery pressure, mixed venous saturation, cardiac output, and left ventricular dimensions determined by transesophageal echocardiography were monitored in HVE patients. Blood concentrations of arginine vasopressin (AVP), epinephrine, norepinephrine, dopamine, and atrial natriuretic peptide and plasma renin activity (PRA) were measured before clamping; 5, 15, and 30 min after clamping; and 15 min after unclamping. Hemodynamic response to HVE was characterized by a significant (P < 0.05) decrease in left ventricular dimensions, fractional area change, and pulmonary artery pressure. We also observed a marked decrease in cardiac output (50%) and an increase in heart rate and systemic vascular resistance. After unclamping, there was peripheral vasodilation, assessed by a significant decrease in systemic vascular resistance from the preclamping value to unclamping. An acute and sustained increase in AVP and norepinephrine that returned to baseline after unclamping and the absence of modification in PRA concentrations were noted. The marked decrease in venous return that characterizes HVE is compensated for by an increase in vascular resistance secondary to an important activation of the AVP and sympathetic systems. The PRA system does not play an important role in maintaining arterial blood pressure during HVE.

Extracorporeal membrane oxygenation as a bridge to liver transplantation for acute respiratory distress syndrome-induced life- threatening hypoxaemia aggravated by hepatopulmonary syndrome

IntroductionCombined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease.MethodsThe case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described.ResultsA 51-year-old man with a five-year history of alcoholic cirrhosis was admitted for acute respiratory failure, platypnoea and severe hypoxaemia requiring emergency tracheal intubation. Following mechanical ventilation, hypoxaemia remained refractory to positive end-expiratory pressure, 100% of inspired oxygen and inhaled nitric oxide. Two-dimensional contrast-enhanced (agitated saline) transthoracic echocardiography disclosed a massive right-to-left extracardiac shunt, without patent foramen ovale. Contrast computed tomography (CT) of the thorax using quantitative analysis and colour encoding system established the diagnosis of acute respiratory distress syndrome aggravated by hepatopulmonary syndrome. According to the severity of the respiratory condition, a veno-venous extracorporeal membrane oxygenation was implemented and the patient was listed for emergency liver transplantation. Orthotopic liver transplantation was performed at Day 13. At the end of the surgical procedure, the improvement in oxygenation allowed removal of extracorporeal membrane oxygenation (Day 5). The patient was discharged from hospital at Day 48. Three months after hospital discharge, the patient recovered a correct physical autonomy status without supplemental O2.ConclusionsIn a cirrhotic patient, acute respiratory distress syndrome was aggravated by hepatopulmonary syndrome causing life-threatening hypoxaemia not controlled by standard supportive measures. The use of extracorporeal membrane oxygenation, by controlling gas exchange, allowed the performing of a successful liver transplantation and final recovery.

Nonalcoholic Fatty Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Alcohol-Associated Cirrhosis Awaiting Liver Transplants

BACKGROUND & AIMS Many patients with alcohol-associated cirrhosis also have diabetes, obesity, or insulin resistance-mediated steatosis, but little is known about how these disorders affect the severity of liver disease. We analyzed the prevalence and prognostic implications of metabolic risk factors (MRFs) such as overweight, diabetes, dyslipidemia, and hypertension in patients with alcohol-associated cirrhosis awaiting liver transplants. METHODS We performed a retrospective study of 110 patients with alcohol-associated cirrhosis (77% male; mean age, 55 y; 71% with >6 mo of abstinence) who received liver transplants at a single center in Paris, France, from 2000 through 2013. We collected data on previous exposure to MRFs, steatosis (>10% in the explant), and histologically confirmed hepatocellular carcinoma (HCC). RESULTS HCC was detected in explants from 29 patients (26%). Steatosis was detected in explants from 47 patients (70% were abstinent for ≥6 mo); 50% had a history of overweight or type 2 diabetes. Fifty-two patients (47%) had a history of MRFs and therefore were at risk for nonalcoholic fatty liver disease. A higher proportion of patients with MRF had HCC than those without MRF (46% vs 9%; P < .001). A previous history of overweight or type 2 diabetes significantly increased the risk for HCC (odds ratio, 6.23; 95% confidence interval [CI], 2.47-15.76, and odds ratio, 4.63; 95% CI, 1.87-11.47, respectively; P < .001). MRF, but not steatosis, was associated with the development of HCC (odds ratio, 11.76; 95% CI, 2.60-53; P = .001) independent of age, sex, amount of alcohol intake, or severity of liver disease. CONCLUSIONS Patients with alcohol-associated cirrhosis who received transplants frequently also had nonalcoholic fatty liver disease. MRFs, particularly overweight, obesity, and type 2 diabetes, significantly increase the risk of HCC.

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

IntroductionTo date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications.MethodsPCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction.ResultsIn the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest.ConclusionPCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.

Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial.

Background:Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. Methods:This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and &agr;-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. Results:Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. Conclusion:For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration.

Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month

This prospective observational study was designed to analyze platelet functions across time in 50 patients scheduled for liver transplantation (LT) secondary to decompensated cirrhosis or hepatocellular carcinoma. Platelet functions were assessed before LT (pre-LT), one week (D7) and 1 month (D28) after LT. Platelet count significantly increased from pre-LT time to day 28 as well as circulating CD34+hematopoietic stem cells. To avoid any influence of platelet count on assays, platelet function was evaluated on platelet-rich-plasma adjusted to pre-LT platelet count. Although platelet secretion potential did not differ between time-points, as evaluated by the expression of CD62P upon strong activation, platelet aggregation in response to various agonists significantly increased along time, however with no concomitant increase of circulating markers of platelet activation: platelet microvesicles, platelet-leukocyte complexes, soluble CD40L and soluble CD62P. In the multivariate analysis, hepatic function was associated with platelet count and function. A lower platelet aggregation recovery was correlated with Child C score. History of thrombosis or bleeding was associated with respective higher or lower values of platelet aggregation. This longitudinal analysis of platelet functions in LT patients showed an improvement of platelet functions along time together with platelet count increase, with no evidence of platelet hyperactivation at any time-point.

Influence of diluent volume of colistimethate sodium on aerosol characteristics and pharmacokinetics in ventilator-associated pneumonia caused by MDR bacteria

Objectives Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS. Methods A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed. Results The mass median aerodynamic diameters were 1.4 ± 0.2 versus 0.9 ± 0.2 μm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) μg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume. Conclusions Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.