Yannick Mallédant - Academia.edu (original) (raw)

Papers by Yannick Mallédant

Research paper thumbnail of Safety of recombinant factor VIIa in patients under extracorporeal membrane oxygenation

European Journal of Cardio-Thoracic Surgery, 2015

To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rat... more To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rate of bleeding control) of recombinant activated coagulation factor VII (rFVIIa) to treat severe bleeding refractory to all surgical and medical treatments in patients under veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support. In a tertiary referral University Cardiothoracic Surgery Centre including three intensive care units, 30 patients received the rFVIIa during ongoing VA or VV ECMO support (8.6% of ECMO activity from 2005 to 2014; N = 347). Early and late clinical results were analysed (retrospective analysis of prospectively collected data). In a substudy, a case-matching procedure was performed among ECMO patients who received (Group A) or did not receive (Group B) rFVIIa treatment. The mediastinum was the most common site of refractory bleeding (after heart transplantation or other cardiac surgery; 90%); 90% (n = 27) of patients were on VA ECMO and the remainder on VV ECMO. The survival rate at ECMO explantation and at the 30th post-implantation day was 67 and 50%, respectively. The final efficacy rate of rFVIIa in stopping bleeding was 93.3%. The rate of thromboembolic events was 3.3% (1 case) and the rate of circuit change was 16.7% (without instances of overt circuit clotting). After case-matching, Group A comprised 23 patients and Group B included 43 patients. No statistically significant differences were observed among groups in terms of thromboembolic events (P = 0.99), circuit change, ventilation time (P = 0.71), infectious complications (P = 06) and survival at both ECMO explantation and the 30th post-implantation day. Late survival was comparable (Kaplan-Meier analysis; P = 0.42). In case of life-threatening bleeding refractory to all conventional therapies, rFVIIa presents an acceptable safety profile in patients under ECMO support. No circuit dysfunctions and limited rates of thromboembolism are observed.

Research paper thumbnail of The accuracy of transcutaneous PCO2 in subjects with severe brain injury: a comparison with end-tidal PCO2

Respiratory care, 2014

In patients suffering from brain injury, end-tidal PCO2 (PETCO2 ) monitoring is controversial, bu... more In patients suffering from brain injury, end-tidal PCO2 (PETCO2 ) monitoring is controversial, but transcutaneous PCO2 (PtcCO2 ), which is noninvasive and utilizes immediate display, may be an alternative method. We hypothesized that PtcCO2 would be more accurate than PETCO2 for monitoring PaCO2 in patients with severe brain injury. A prospective observational study included consecutive mechanically ventilated adult subjects who had acute brain injury and an arterial catheter in place. When an arterial blood gas analysis was required, the PETCO2 and PtcCO2 values were simultaneously recorded. The agreement between the PETCO2 , PtcCO2 , and PaCO2 measurements (reference) was determined using the Bland-Altman method. The number of outliers defined by the formula ([PETCO2 or PtcCO2 ] - PaCO2 ) > ± 4 mm Hg indicated the proportion of measurements that were considered clinically unacceptable. A total of 25 subjects were included in the study, and 85 simultaneous measurements of PaCO2 ...

Research paper thumbnail of Surgical complications and treatment during resection for malignancy of the high bile duct

World journal of surgery, 2001

From January 1968 to January 1997 a series of 50 of 109 patients had undergone resection for high... more From January 1968 to January 1997 a series of 50 of 109 patients had undergone resection for high bile duct cancer in our institution in Rennes, France. The overall operative mortality was 12%, but there were no deaths among those who had only tumor resection or those with hepatectomy with vascular reconstruction. The early complications were biliary fistula (four cases) and subphrenic abscess (three cases), of which two of the biliary fistulas resulted in mortality. There were three gastrointestinal hemorrhages; one was due to gastritis related to hepatorenal insufficiency and was fatal. Two other deaths were due to respiratory failure and ascites associated with hepatic insufficiency. In one patient after liver transplantation with cluster resection, a biliary leak and ileocolic fistula were the cause of postoperative mortality. Another patient suffered a ruptured mycotic aneurysm after pretransplant transtumoral intubation, which emphasizes the risk of infection in an immunosuppr...

Research paper thumbnail of Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane

Biochemical pharmacology, Jan 3, 1994

Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted i... more Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted in the production of reactive intermediate trifluoroacetyl (TFA) halide, capable of covalently binding to hepatocyte proteins. TFA-modified liver proteins can act as antigens and are implicated in the pathogenesis of halothane hepatitis in humans. The aim of this study was to investigate the formation of TFA-neoantigens in halothane-treated primary cultures of adult human hepatocytes and to evaluate the usefulness of this in vitro model for studying immune-mediated halothane hepatotoxicity. Cultured human hepatocytes were incubated with halothane under constant temperature, atmosphere and anaesthetic concentration conditions. The results obtained show that halothane-treated hepatocytes isolated from seven different donors produced TFA-antigens as detected by immunocytochemical and western immunoblot analysis using rabbit anti-TFA antiserum. TFA-adducts were localized mainly in the endopla...

Research paper thumbnail of Factors associated with multidrug-resistant bacteria in secondary peritonitis: impact on antibiotic therapy

Clinical Microbiology and Infection, 2006

Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdomin... more Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdominal infections have a common pathogenesis but some microbiological differences, particularly with respect to the type of bacteria recovered and the level of antimicrobial susceptibility. This report describes a prospective observational study of 93 consecutive patients with secondary peritonitis during an 11-month period. Community-acquired peritonitis accounted for 44 cases and nosocomial peritonitis for 49 cases (post-operative in 35 cases). Fifteen multidrug-resistant (MDR) bacteria were recovered from 14 patients. In univariate analysis, the presence of MDR bacteria was associated significantly with pre-operative and total hospital lengths of stay, previous use of antimicrobial therapy, and post-operative antimicrobial therapy duration and modifications. A 5-day cut-off in length of hospital stay had the best specificity (58%) and sensitivity (93%) for predicting whether MDR bacteria were present. In multivariate analysis, only a composite variable associating pre-operative hospital length of stay and previous use of antimicrobial therapy was a significant independent risk-factor for infection with MDR bacteria. In conclusion, knowledge of these two factors may provide a more rational basis for selecting initial antimicrobial therapy for patients with secondary peritonitis.

Research paper thumbnail of Halothane-induced Cytotoxicity to Rat Centrilobular Hepatocytes in Primary Culture Is Not Increased under Low Oxygen Concentration

Anesthesiology, 1993

Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthet... more Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthetic can induce direct liver injury preferentially localized in centrilobular areas, probably in relation with lower oxygen tension. The reductive pathway has been related to liver damage; however, a correlation between lower oxygen concentration in centrilobular areas, the extent of reductive metabolism of halothane, and the degree of liver injury has not yet been demonstrated. This study was designed to better evaluate the toxicity of the reduced metabolites by using centrilobular and periportal rat hepatocyte subpopulations. Adult rat hepatocytes, either as whole cell preparations or after separation in centrilobular and periportal cell subpopulations, were placed in primary culture and exposed to either 2% or 4% halothane under various oxygen concentrations. The enriched centrilobular hepatocyte subpopulations isolated by the digitonin-collagenase method were characterized by immunolocalization of glutamine synthetase. Three oxygen concentrations were tested: 5%, 20%, and 95%, and the main parameters measured were cell viability and fluoride ion formation. Viability of centrilobular hepatocytes was similar under 5% and 20% O2, but the unpurified hepatocyte population was more susceptible to 5% O2 (P < 0.01). Significantly higher cytochrome P-450 content was found in whole hepatocyte populations under 5% versus 20% oxygen, indicating that centrilobular hepatocytes that contained higher cytochrome P-450 monooxygenase activities were less sensitive to low oxygen concentrations. Halothane toxicity to centrilobular hepatocytes was enhanced under 95% versus 20% O2 (P < 0.05). By contrast, no significant difference was observed when the cells were maintained under 5% O2, although fluoride ions, indicative of reductive metabolism of halothane, were found in much higher amounts in the culture medium. Moreover, under 20% O2, halothane toxicity was significantly greater in centrilobular versus unpurified hepatocytes (P < 0.05). Isolated centrilobular hepatocytes appear to be more sensitive to halothane than their periportal counterparts in vitro. However, the authors' results support the conclusion that increased reductive metabolism of halothane induced by decreasing oxygen concentration is not a critical parameter for the occurrence of liver damage in these cells.

Research paper thumbnail of SURVIVAL, PROLIFERATION, AND FUNCTIONS OF PORCINE HEPATOCYTES ENCAPSULATED IN COATED ALGINATE BEADS: A STEP TOWARD A RELIABLE BIOARTIFICIAL LIVER1

Transplantation, 1997

Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. A... more Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. As an alternative treatment, an efficient extracorporeal bioartificial liver should contain a large yield of functional hepatocytes with an immunoprotective barrier, for providing temporary adequate metabolic support to allow spontaneous liver regeneration or for acting as a bridge toward transplantation. Survival, proliferation, and functions of porcine hepatocytes were evaluated in primary cultures and after embedding in alginate beads, which were subsequently coated with a membrane made by a transacylation reaction between propylene glycol alginate and human serum albumin. Disruption of total pig livers by collagenase perfusion/recirculation allowed the obtention of up to 10(11) hepatocytes with a viability greater than 95%. Hepatocytes in conventional cultures or embedded in coated alginate beads survived for about 10 days, secreted proteins, particularly albumin, and maintained several phase I and II enzymatic activities, namely ethoxyresorufin-O-deethylase, oxidation of nifedipine to pyridine, phenacetin deethylation to paracetamol, glucuroconjugation of paracetamol, and N-acetylation of procainamide. Typical features of mitosis and [3H]thymidine incorporation indicated that porcine hepatocytes proliferated in both conventional cultures and alginate beads. The efficacy of the membrane surrounding alginate beads for protecting cells from immunoglobulins was tested by embedding HLA-typed human lymphocytes, which were subsequently incubated with specific anti-HLA immunoglobulin G and complement. These data show that large yields of porcine hepatocytes that are embedded in coated alginate beads remain functional and are isolated from large molecular weight molecules, such as immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver, containing xenogeneic hepatocytes, to treat acute liver disease in humans.

Research paper thumbnail of Expansion Volemique Neonatale: Quel Volume Faut Il Perfuser?

Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM, 1995

Research paper thumbnail of Lˈinformation au patient en réanimation et à ses proches : le point de vue de la SFAR * * * Texte amendé par le groupe de réflexion éthique (M. Géry Boulard, Elisabeth Balagny, Sadek Beloucif, Yvonnick Blanlœil, Jean–Louis Pourriat, Pierre–Yves Quiviger, Jean–Pierre Tarot) ainsi que le président ...

Cognition, 2001

... 2001 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés. ...

Research paper thumbnail of Use of adult human hepatocytes in primary culture for the study of clometacin-induced immunoallergic hepatitis

Toxicology in Vitro, 1991

To determine whether specific circulating antibodies from patients with drug-induced immunoallerg... more To determine whether specific circulating antibodies from patients with drug-induced immunoallergic hepatitis could be involved in antibody-dependent cell-mediated cytotoxicity, an in vitro model system was set up. Normal human hepatocytes from male kidney transplantation donors were cultured and incubated with clometacin, a drug known to induce immunoallergic hepatitis in humans. After drug exposure and in the presence of lymphoid cells autologous to hepatocytes, addition of sera from patients with clometacin-induced hepatitis consistently resulted in hepatocyte injury characterized by morphological alterations and a decrease in intracellular lactate dehydrogenase and aspartate aminotransferase activities. Sera from patients with hepatitis induced by other drugs, such as cimetidine, halothane or methyldopa, were ineffective and no cytotoxicity occurred in the absence of lymphoid cells or without pre-incubation with clometacin. These results are consistent with the view that clometacin-induced hepatitis has an immunological basis and suggest that human hepatocytes co-cultured with autologous lymphoid cells represent a suitable model to study antibody-dependent cell-mediated cytotoxicity.

Research paper thumbnail of Labeled Granulocyte Scanning for the Diagnosis of Infected Necrosis in Acute Pancreatitis

Pancreas, 1996

Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic com... more Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic complications of pancreatic and peripancreatic necrosis in patients with acute pancreatitis. Confirmation can be obtained only after percutaneous computed tomography (CT)-guided aspiration of the necrotic tissues or fluid collection; although the important role of 99Tc(m)-HMPAO-labeled granulocyte scintigraphy has been recently emphasized. The aim of this study was to determine the sensitivity and specificity of 99m-technetium-hexamethylpropyleneamine oxime (99Tc(m)-HMPAO)- or 111In-oxine-labeled granulocyte scintigraphy for the diagnosis of infection in pancreatic or peripancreatic necrosis to define the ideal label for diagnosis. Thirty-six scintigraphic examinations were performed in 34 consecutive patients (mean age, 58 +/- 2 years) 20 +/- 2 days after the onset of acute pancreatitis (Balthazar classes A-C, n = 7; classes D and E, n = 29). The scintigraphic study included scintigraphic tomography and static acquisition 1 and 3 h, respectively, after reinjection of the autologous 99Tc(m)-labeled granulocytes and static images 3-4 and 24 h after the simultaneous reinjection of 111In-oxine-labeled autologous granulocytes. The diagnosis of infected pancreatic or peripancreatic necrosis was confirmed with percutaneous CT-guided aspiration (14 positive aspirates among 20 performed) and sterile necrosis after negative aspiration (6 negative aspirates) or after a 6 +/- 1-month follow-up free of clinical or biological signs of ongoing sepsis. The sensitivity and specificity were 86 and 73%, respectively, for scintigraphic tomography, 100 and 55% for 3-h 111In images, 93 and 68% for 3-4-h 111In images, and 100 and 64% for 24-h 111In images. The fall in splenic activity between the 3-4 and the 24-h 111In images was 26 +/- 3% in patients with septic pancreatic and peripancreatic necrosis (n = 14) and 16 +/- 3% in those with sterile necrosis (n = 22) (p < 0.01). Labeled granulocyte scintigraphy was thus shown to be an effective tool for the diagnosis of infection in pancreatic and/or peripancreatic necrosis due to acute pancreatitis, especially when the scintiscans are performed early after injection of 99Tc(m) or when the fall in splenic activity over the 24 h following reinjection of 111In is measured in particularly difficult cases. These promising preliminary results should be confirmed by a prospective study.

Research paper thumbnail of Effects of price information on test ordering in an intensive care unit

Intensive Care Medicine, 2002

Objective: To determine if daily information on the price of common laboratory tests and chest X-... more Objective: To determine if daily information on the price of common laboratory tests and chest X-ray could significantly influence test ordering by physicians and decrease the costs. Design: A prospective observational and sequential study. Setting: A 21-bed surgical intensive care unit of a university hospital. Patients: All patients admitted during a 4-month period.

Research paper thumbnail of Effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization

Intensive Care Medicine, 2010

To evaluate the effectiveness of simple daily sensitization of physicians to the duration of cent... more To evaluate the effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization, and impact on infection rates. A prospective, before-after study in a surgical intensive care unit. All consecutive patients who had a central venous catheter (CVC) and/or urinary tract catheter (UTC) were included during two consecutive periods. Period 1 (August 2005 to May 2006) served as the control period. During Period 2 (July 2006 to April 2007), a red square, added to the patient's daily care sheet, questioned the physician about the utility of the CVC and/or UTC. If the response was "No", the CVC and/or the UTC were removed by a nurse. A total of 1,271 patients were analyzed (Period 1, n = 676; Period 2, n = 595). The duration of catheterization (median [interquartile range]) was significantly reduced in Period 2 compared to Period 1 (from (5 [3-9] to 4 [3-7] days, p < 0.001, for CVC, and from 5 [3-11] to 4 [3-8] days, p < 0.001, for UTC). The incidence and density incidence of CVC infection decreased in Period 2 compared to Period 1 (from 1.8% to 0.3%, p = 0.010, and from 2.8 to 0.7/1,000 CVC-days, p = 0.051) whereas UTC infections were not significantly different (4.3 to 3.0%, p = 0.230, and 5.0 to 4.9/1,000 UTC-days, p = 0.938, respectively). A simple daily reminder to physicians on the patients' care sheets decreased the duration of central venous and urinary tract catheterization, and tended to decrease CVC infection rate without affecting UTC infection.

Research paper thumbnail of Hub qualitative blood culture is useful for diagnosis of catheter-related infections in critically ill patients

Intensive Care Medicine, 2005

To assess clinical safety and accuracy of qualitative blood culture drawn through the hub for rul... more To assess clinical safety and accuracy of qualitative blood culture drawn through the hub for ruling out catheter-related infection (CRI). Prospective observational study in a surgical intensive care unit. All patients with sepsis of unknown origin and possibly due to a CRI. Blood culture drawn through a central venous catheter (CVC) just before the catheter was cultured. In 126 patients we investigated 135 cases of sepsis of unknown origin. Using a clinical and bacteriological approach as the reference, the performance of the CVC blood culture was evaluated by the calculation of sensitivity, specificity, and positive and negative predictive values. When CVC blood culture was positive, the time to positivity was considered. Using standard definitions, seven CRIs were diagnosed. CVC blood culture identified five CRIs including the three episodes of catheter-related bacteremia. The method missed two coagulase-negative staphylococcus CRIs without bacteremia. Thirteen false-positive results occurred, including seven bacteremias from a distant source. The CVC blood culture had a sensitivity of 71% (CI 30-95%), specificity of 90% (CI 83-94%), negative predictive value of 98% (CI 93-100%), and positive predictive value of 28% (CI 11-54%). In cases of catheter-related bacteremia the time to positivity of CVC blood culture was 24 h or less. Negative CVC blood culture at 24 h seems useful for management of CVC in selected critically ill surgical patients developing a clinical sepsis. The subsequent risk of catheter-related bacteremia cannot be excluded advocating for an uninterrupted clinical and bacteriological survey.

Research paper thumbnail of Atrial fibrillation in trauma patients requiring intensive care

Intensive Care Medicine, 2006

To evaluate the incidence and risk factors of atrial fibrillation (AF) in trauma patients. Prospe... more To evaluate the incidence and risk factors of atrial fibrillation (AF) in trauma patients. Prospective observational study in a surgical intensive care unit (ICU). All trauma patients admitted in the surgical ICU except those who had AF at admission. AF occurred in 16/293 patients (5.5%). AF patients were older, had a higher number of regions traumatized, and received more fluid therapy, transfusion products, and catecholamines. They more frequently experienced systemic inflammatory response syndrome, sepsis, shock, and acute renal failure and had higher scores of severity (Simplified Acute Physiology Score, SAPS II; Injury Severity Score). ICU length of stay and resources use were also increased. ICU and hospital mortality rates were twice higher in AF patients whereas standardized mortality ratio (observed/expected mortality by SAPS II) was similar in the two groups. We found five independent risk factors of developing AF: catecholamine use (OR = 5.7, 95% CI 1.7-19.1), SAPS II of 30 or higher (OR = 11.6, 95% CI 1.3-103.0), three or more regions traumatized (OR = 6.2, 95% CI 1.8-21.4), age 40 years or higher (OR = 6.3, CI 1.4-28.7), and systemic inflammatory response syndrome (OR = 4.4, 95% CI 1.2-16.1). In addition to age and catecholamine use, inflammation and severity of injury may be involved in the development of AF in trauma patients. Our results suggest that AF could rather be a marker of a higher severity of illness without major effect on mortality.

Research paper thumbnail of Post-Traumatic Course Complicated by Cutaneous Infection with Absidia corymbifera

European Journal of Clinical Microbiology & Infectious Diseases, 1999

Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the c... more Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the case of a young patient with cutaneous mucormycosis due to Absidia corymbifera probably caused by a soil-contaminated wound. Despite daily surgical debridement and amphotericin B therapy, cure could be achieved only by amputation of the lower limb.

Research paper thumbnail of Current aspects of extracorporeal membrane oxygenation in a tertiary referral centre: determinants of survival at follow-up

European Journal of Cardio-Thoracic Surgery, 2014

To describe the clinical results (both early and at follow-up) of patients currently receiving ex... more To describe the clinical results (both early and at follow-up) of patients currently receiving extracorporeal membrane oxygenation (ECMO) therapy for cardiac and/or pulmonary failure. To assess the effect of indications, clinical presentations and ECMO modalities on early/late clinical outcomes. To identify baseline factors associated with worse survival at follow-up. We reviewed the prospectively collected data of 325 patients receiving ECMO therapy at a tertiary referral centre during the 2005-2013 period. Follow-up was prospectively conducted by dedicated personnel (average: 84 ± 86 days, 100% complete). Survival was analysed by stratified Kaplan-Meier curves. Veno-arterial (VA) ECMO was employed in 80% of cases (due to early graft failure (EGF) in 13% of cases, post-cardiotomy in 29%, primary cardiogenic shock in 42% for miscellaneous aetiologies, other indications in 15.4%) and veno-venous (VV) ECMO in the remainders (adult respiratory distress syndrome). In the VA and VV groups, weaning rates were 59 and 53%, survival at 30th postimplantation day was 44 and 45% and survival at the end of the follow-up was 41 and 45%, respectively. Implantation under advanced life support (ALS) occurred in 15% of cases (26% survival at 30 days). VA patients had a higher rate of thrombotic/haemorrhagic complications and of transfusion of blood products and shorter ventilation time. Worse early and follow-up survival were observed among patients aged ≥65 years, having pH ≤ 7, lactates >12 mmol/l, creatinine >200 μmol/l at implantation or receiving ECMO under ALS. No difference in survival was noted among VA vs VV patients. Patients receiving ECMO for EGF displayed better early and late survival (64% at 30 days and 53% at 6 months) than post-cardiotomy (36 and 34%, respectively), post-acute myocardial infarction (48 and 40%) and the remaining patients (46 and 45%). Despite most critical baseline conditions, ECMO therapy is confirmed useful for the treatment of patients with acute cardiopulmonary failure refractory to conventional treatments. The ECMO modality (VA vs VV), as well as indications to support, identifies different patient profiles and dissimilar outcomes. Preimplantation markers of gravity and end-organ damage are useful in the stratification of expected survival. These may facilitate clinical decision-making and appropriate allocation of hospital resources.

Research paper thumbnail of Steady-state pharmacokinetics of dopamine in adult patients

Critical Care Medicine, 1993

To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. Prospective c... more To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. Prospective clinical study. University hospital intensive care unit. Fourteen patients (aged 43 to 73 yrs) recovering from esophageal surgery. Dopamine was infused and blood samples were collected. Plasma dopamine concentrations were measured at steady state and subsequently at the end of the dopamine infusion using high-performance liquid chromatography. Clearances, volume of distribution, mean residence times, half-lives, and elimination and distribution rate constants were derived. The clearances were independent of the infusion rate at 1, 3, and 6 micrograms/kg/min, and ranged between 0.050 and 0.056 L/min/kg. A two-compartment open model was fitted to the postinfusion plasma concentration data obtained at 3 and 6 micrograms/kg/min. On average, the steady-state volume of distribution and the apparent terminal elimination half-life increased with the dose: 0.78 to 1.58 L/kg, respectively, and 22.1 to 37.9 mins, respectively, for the rates of 3 and 6 micrograms/kg/min. The rate constant associated with the uptake of dopamine into the peripheral compartment (K12) was on average four to five times higher than the rate constant associated with the reverse process (K21). The redistribution of dopamine into the central compartment could be the main factor involved in the apparent terminal elimination of dopamine from plasma. Due to the relative rates of distribution and elimination, the attainment of a steady-state plasma concentration of dopamine should only depend on the terminal half-life. These results, which remain to be validated in a greater number of patients, indicate that the attainment of 90% of the plateau (i.e., in 3.3 half-lives) would require 70 to 125 mins, depending on the infusion rate.

Research paper thumbnail of Diagnostic and therapeutic management of nosocomial pneumonia in surgical patients: Results of the Eole study

Critical Care Medicine, 2002

To assess clinical, microbiological, and therapeutic features of nosocomial pneumonias in surgica... more To assess clinical, microbiological, and therapeutic features of nosocomial pneumonias in surgical patients. Prospective (October 1997 through May 1998), consecutive case series analysis of patients suspected of having pneumonia during the fortnight after a surgical procedure or trauma and receiving antibiotic therapy prescribed by the attending physician for this diagnosis. A total of 230 study centers in teaching (n = 66) and nonteaching hospitals (n = 164) (surgical wards and intensive care units). A total of 837 evaluable patients (mean age 61 +/- 18 yrs) including 629 intensive care unit patients. None. The diagnostic and therapeutic procedures followed were based on guidelines. Antibiotics and any changes of therapy and duration of treatment were decided by the attending physician. The charts were reviewed by a panel of experts that classified the cases according to clinical, radiologic, and microbiological criteria (when available). The efficacy of treatment was evaluated over a 30-day period following the index episode. The patients were classified into three groups: definite pneumonia (n = 261), possible pneumonia (n = 392), or low-probability pneumonia (n = 184). Ventilator-acquired pneumonia was reported in 303 patients. Early onset pneumonia was reported in 512 cases. Microbiological sampling was performed in 718 patients, by bronchoscopy in 367 cases, recovering 450 organisms in 328 patients, including 94 polymicrobial specimens. High proportions of Gram-negative bacteria and staphylococci were cultured, even in early onset pneumonias. Antibiotic therapy was administered for 13 +/- 4 days, using monotherapy in 254 cases. Changes in the initial antibiotic therapy (135 monotherapies) were decided in 517 patients (including clinical failure or persistent infection, n = 171; organisms resistant to initial therapy, n = 177; pulmonary superinfection, n = 68). Death occurred in 180 patients, related to pneumonia in 53 cases. Nosocomial pneumonias in surgical patients are characterized by high frequency of early onset pneumonia, high proportion of nosocomial organisms even in these early onset pneumonias, and moderate mortality rate.

Research paper thumbnail of Catecholamines induce an inflammatory response in human hepatocytes

Critical Care Medicine, 2008

The liver is an early target organ in sepsis, severe sepsis, and septic shock, contributing to mu... more The liver is an early target organ in sepsis, severe sepsis, and septic shock, contributing to multiple organ failure, and both lipopolysaccharide and gut-derived catecholamines are implicated in the occurrence of hepatocellular dysfunction. Treatment of septic shock involves administration of vasoactive agents such as exogenous catecholamines or vasopressin in order to reestablish blood pressure. As a prelude to clinical application, we tested the hypothesis that catecholamines could modulate the lipopolysaccharide-induced inflammatory response and function in human liver.

Research paper thumbnail of Safety of recombinant factor VIIa in patients under extracorporeal membrane oxygenation

European Journal of Cardio-Thoracic Surgery, 2015

To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rat... more To address the safety (rate of thromboembolic events and circuit complications) and efficacy (rate of bleeding control) of recombinant activated coagulation factor VII (rFVIIa) to treat severe bleeding refractory to all surgical and medical treatments in patients under veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support. In a tertiary referral University Cardiothoracic Surgery Centre including three intensive care units, 30 patients received the rFVIIa during ongoing VA or VV ECMO support (8.6% of ECMO activity from 2005 to 2014; N = 347). Early and late clinical results were analysed (retrospective analysis of prospectively collected data). In a substudy, a case-matching procedure was performed among ECMO patients who received (Group A) or did not receive (Group B) rFVIIa treatment. The mediastinum was the most common site of refractory bleeding (after heart transplantation or other cardiac surgery; 90%); 90% (n = 27) of patients were on VA ECMO and the remainder on VV ECMO. The survival rate at ECMO explantation and at the 30th post-implantation day was 67 and 50%, respectively. The final efficacy rate of rFVIIa in stopping bleeding was 93.3%. The rate of thromboembolic events was 3.3% (1 case) and the rate of circuit change was 16.7% (without instances of overt circuit clotting). After case-matching, Group A comprised 23 patients and Group B included 43 patients. No statistically significant differences were observed among groups in terms of thromboembolic events (P = 0.99), circuit change, ventilation time (P = 0.71), infectious complications (P = 06) and survival at both ECMO explantation and the 30th post-implantation day. Late survival was comparable (Kaplan-Meier analysis; P = 0.42). In case of life-threatening bleeding refractory to all conventional therapies, rFVIIa presents an acceptable safety profile in patients under ECMO support. No circuit dysfunctions and limited rates of thromboembolism are observed.

Research paper thumbnail of The accuracy of transcutaneous PCO2 in subjects with severe brain injury: a comparison with end-tidal PCO2

Respiratory care, 2014

In patients suffering from brain injury, end-tidal PCO2 (PETCO2 ) monitoring is controversial, bu... more In patients suffering from brain injury, end-tidal PCO2 (PETCO2 ) monitoring is controversial, but transcutaneous PCO2 (PtcCO2 ), which is noninvasive and utilizes immediate display, may be an alternative method. We hypothesized that PtcCO2 would be more accurate than PETCO2 for monitoring PaCO2 in patients with severe brain injury. A prospective observational study included consecutive mechanically ventilated adult subjects who had acute brain injury and an arterial catheter in place. When an arterial blood gas analysis was required, the PETCO2 and PtcCO2 values were simultaneously recorded. The agreement between the PETCO2 , PtcCO2 , and PaCO2 measurements (reference) was determined using the Bland-Altman method. The number of outliers defined by the formula ([PETCO2 or PtcCO2 ] - PaCO2 ) > ± 4 mm Hg indicated the proportion of measurements that were considered clinically unacceptable. A total of 25 subjects were included in the study, and 85 simultaneous measurements of PaCO2 ...

Research paper thumbnail of Surgical complications and treatment during resection for malignancy of the high bile duct

World journal of surgery, 2001

From January 1968 to January 1997 a series of 50 of 109 patients had undergone resection for high... more From January 1968 to January 1997 a series of 50 of 109 patients had undergone resection for high bile duct cancer in our institution in Rennes, France. The overall operative mortality was 12%, but there were no deaths among those who had only tumor resection or those with hepatectomy with vascular reconstruction. The early complications were biliary fistula (four cases) and subphrenic abscess (three cases), of which two of the biliary fistulas resulted in mortality. There were three gastrointestinal hemorrhages; one was due to gastritis related to hepatorenal insufficiency and was fatal. Two other deaths were due to respiratory failure and ascites associated with hepatic insufficiency. In one patient after liver transplantation with cluster resection, a biliary leak and ileocolic fistula were the cause of postoperative mortality. Another patient suffered a ruptured mycotic aneurysm after pretransplant transtumoral intubation, which emphasizes the risk of infection in an immunosuppr...

Research paper thumbnail of Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane

Biochemical pharmacology, Jan 3, 1994

Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted i... more Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted in the production of reactive intermediate trifluoroacetyl (TFA) halide, capable of covalently binding to hepatocyte proteins. TFA-modified liver proteins can act as antigens and are implicated in the pathogenesis of halothane hepatitis in humans. The aim of this study was to investigate the formation of TFA-neoantigens in halothane-treated primary cultures of adult human hepatocytes and to evaluate the usefulness of this in vitro model for studying immune-mediated halothane hepatotoxicity. Cultured human hepatocytes were incubated with halothane under constant temperature, atmosphere and anaesthetic concentration conditions. The results obtained show that halothane-treated hepatocytes isolated from seven different donors produced TFA-antigens as detected by immunocytochemical and western immunoblot analysis using rabbit anti-TFA antiserum. TFA-adducts were localized mainly in the endopla...

Research paper thumbnail of Factors associated with multidrug-resistant bacteria in secondary peritonitis: impact on antibiotic therapy

Clinical Microbiology and Infection, 2006

Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdomin... more Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdominal infections have a common pathogenesis but some microbiological differences, particularly with respect to the type of bacteria recovered and the level of antimicrobial susceptibility. This report describes a prospective observational study of 93 consecutive patients with secondary peritonitis during an 11-month period. Community-acquired peritonitis accounted for 44 cases and nosocomial peritonitis for 49 cases (post-operative in 35 cases). Fifteen multidrug-resistant (MDR) bacteria were recovered from 14 patients. In univariate analysis, the presence of MDR bacteria was associated significantly with pre-operative and total hospital lengths of stay, previous use of antimicrobial therapy, and post-operative antimicrobial therapy duration and modifications. A 5-day cut-off in length of hospital stay had the best specificity (58%) and sensitivity (93%) for predicting whether MDR bacteria were present. In multivariate analysis, only a composite variable associating pre-operative hospital length of stay and previous use of antimicrobial therapy was a significant independent risk-factor for infection with MDR bacteria. In conclusion, knowledge of these two factors may provide a more rational basis for selecting initial antimicrobial therapy for patients with secondary peritonitis.

Research paper thumbnail of Halothane-induced Cytotoxicity to Rat Centrilobular Hepatocytes in Primary Culture Is Not Increased under Low Oxygen Concentration

Anesthesiology, 1993

Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthet... more Halothane can be metabolized by both oxidative and reductive pathways in the liver. This anesthetic can induce direct liver injury preferentially localized in centrilobular areas, probably in relation with lower oxygen tension. The reductive pathway has been related to liver damage; however, a correlation between lower oxygen concentration in centrilobular areas, the extent of reductive metabolism of halothane, and the degree of liver injury has not yet been demonstrated. This study was designed to better evaluate the toxicity of the reduced metabolites by using centrilobular and periportal rat hepatocyte subpopulations. Adult rat hepatocytes, either as whole cell preparations or after separation in centrilobular and periportal cell subpopulations, were placed in primary culture and exposed to either 2% or 4% halothane under various oxygen concentrations. The enriched centrilobular hepatocyte subpopulations isolated by the digitonin-collagenase method were characterized by immunolocalization of glutamine synthetase. Three oxygen concentrations were tested: 5%, 20%, and 95%, and the main parameters measured were cell viability and fluoride ion formation. Viability of centrilobular hepatocytes was similar under 5% and 20% O2, but the unpurified hepatocyte population was more susceptible to 5% O2 (P < 0.01). Significantly higher cytochrome P-450 content was found in whole hepatocyte populations under 5% versus 20% oxygen, indicating that centrilobular hepatocytes that contained higher cytochrome P-450 monooxygenase activities were less sensitive to low oxygen concentrations. Halothane toxicity to centrilobular hepatocytes was enhanced under 95% versus 20% O2 (P < 0.05). By contrast, no significant difference was observed when the cells were maintained under 5% O2, although fluoride ions, indicative of reductive metabolism of halothane, were found in much higher amounts in the culture medium. Moreover, under 20% O2, halothane toxicity was significantly greater in centrilobular versus unpurified hepatocytes (P < 0.05). Isolated centrilobular hepatocytes appear to be more sensitive to halothane than their periportal counterparts in vitro. However, the authors' results support the conclusion that increased reductive metabolism of halothane induced by decreasing oxygen concentration is not a critical parameter for the occurrence of liver damage in these cells.

Research paper thumbnail of SURVIVAL, PROLIFERATION, AND FUNCTIONS OF PORCINE HEPATOCYTES ENCAPSULATED IN COATED ALGINATE BEADS: A STEP TOWARD A RELIABLE BIOARTIFICIAL LIVER1

Transplantation, 1997

Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. A... more Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. As an alternative treatment, an efficient extracorporeal bioartificial liver should contain a large yield of functional hepatocytes with an immunoprotective barrier, for providing temporary adequate metabolic support to allow spontaneous liver regeneration or for acting as a bridge toward transplantation. Survival, proliferation, and functions of porcine hepatocytes were evaluated in primary cultures and after embedding in alginate beads, which were subsequently coated with a membrane made by a transacylation reaction between propylene glycol alginate and human serum albumin. Disruption of total pig livers by collagenase perfusion/recirculation allowed the obtention of up to 10(11) hepatocytes with a viability greater than 95%. Hepatocytes in conventional cultures or embedded in coated alginate beads survived for about 10 days, secreted proteins, particularly albumin, and maintained several phase I and II enzymatic activities, namely ethoxyresorufin-O-deethylase, oxidation of nifedipine to pyridine, phenacetin deethylation to paracetamol, glucuroconjugation of paracetamol, and N-acetylation of procainamide. Typical features of mitosis and [3H]thymidine incorporation indicated that porcine hepatocytes proliferated in both conventional cultures and alginate beads. The efficacy of the membrane surrounding alginate beads for protecting cells from immunoglobulins was tested by embedding HLA-typed human lymphocytes, which were subsequently incubated with specific anti-HLA immunoglobulin G and complement. These data show that large yields of porcine hepatocytes that are embedded in coated alginate beads remain functional and are isolated from large molecular weight molecules, such as immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver, containing xenogeneic hepatocytes, to treat acute liver disease in humans.

Research paper thumbnail of Expansion Volemique Neonatale: Quel Volume Faut Il Perfuser?

Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM, 1995

Research paper thumbnail of Lˈinformation au patient en réanimation et à ses proches : le point de vue de la SFAR * * * Texte amendé par le groupe de réflexion éthique (M. Géry Boulard, Elisabeth Balagny, Sadek Beloucif, Yvonnick Blanlœil, Jean–Louis Pourriat, Pierre–Yves Quiviger, Jean–Pierre Tarot) ainsi que le président ...

Cognition, 2001

... 2001 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés. ...

Research paper thumbnail of Use of adult human hepatocytes in primary culture for the study of clometacin-induced immunoallergic hepatitis

Toxicology in Vitro, 1991

To determine whether specific circulating antibodies from patients with drug-induced immunoallerg... more To determine whether specific circulating antibodies from patients with drug-induced immunoallergic hepatitis could be involved in antibody-dependent cell-mediated cytotoxicity, an in vitro model system was set up. Normal human hepatocytes from male kidney transplantation donors were cultured and incubated with clometacin, a drug known to induce immunoallergic hepatitis in humans. After drug exposure and in the presence of lymphoid cells autologous to hepatocytes, addition of sera from patients with clometacin-induced hepatitis consistently resulted in hepatocyte injury characterized by morphological alterations and a decrease in intracellular lactate dehydrogenase and aspartate aminotransferase activities. Sera from patients with hepatitis induced by other drugs, such as cimetidine, halothane or methyldopa, were ineffective and no cytotoxicity occurred in the absence of lymphoid cells or without pre-incubation with clometacin. These results are consistent with the view that clometacin-induced hepatitis has an immunological basis and suggest that human hepatocytes co-cultured with autologous lymphoid cells represent a suitable model to study antibody-dependent cell-mediated cytotoxicity.

Research paper thumbnail of Labeled Granulocyte Scanning for the Diagnosis of Infected Necrosis in Acute Pancreatitis

Pancreas, 1996

Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic com... more Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic complications of pancreatic and peripancreatic necrosis in patients with acute pancreatitis. Confirmation can be obtained only after percutaneous computed tomography (CT)-guided aspiration of the necrotic tissues or fluid collection; although the important role of 99Tc(m)-HMPAO-labeled granulocyte scintigraphy has been recently emphasized. The aim of this study was to determine the sensitivity and specificity of 99m-technetium-hexamethylpropyleneamine oxime (99Tc(m)-HMPAO)- or 111In-oxine-labeled granulocyte scintigraphy for the diagnosis of infection in pancreatic or peripancreatic necrosis to define the ideal label for diagnosis. Thirty-six scintigraphic examinations were performed in 34 consecutive patients (mean age, 58 +/- 2 years) 20 +/- 2 days after the onset of acute pancreatitis (Balthazar classes A-C, n = 7; classes D and E, n = 29). The scintigraphic study included scintigraphic tomography and static acquisition 1 and 3 h, respectively, after reinjection of the autologous 99Tc(m)-labeled granulocytes and static images 3-4 and 24 h after the simultaneous reinjection of 111In-oxine-labeled autologous granulocytes. The diagnosis of infected pancreatic or peripancreatic necrosis was confirmed with percutaneous CT-guided aspiration (14 positive aspirates among 20 performed) and sterile necrosis after negative aspiration (6 negative aspirates) or after a 6 +/- 1-month follow-up free of clinical or biological signs of ongoing sepsis. The sensitivity and specificity were 86 and 73%, respectively, for scintigraphic tomography, 100 and 55% for 3-h 111In images, 93 and 68% for 3-4-h 111In images, and 100 and 64% for 24-h 111In images. The fall in splenic activity between the 3-4 and the 24-h 111In images was 26 +/- 3% in patients with septic pancreatic and peripancreatic necrosis (n = 14) and 16 +/- 3% in those with sterile necrosis (n = 22) (p < 0.01). Labeled granulocyte scintigraphy was thus shown to be an effective tool for the diagnosis of infection in pancreatic and/or peripancreatic necrosis due to acute pancreatitis, especially when the scintiscans are performed early after injection of 99Tc(m) or when the fall in splenic activity over the 24 h following reinjection of 111In is measured in particularly difficult cases. These promising preliminary results should be confirmed by a prospective study.

Research paper thumbnail of Effects of price information on test ordering in an intensive care unit

Intensive Care Medicine, 2002

Objective: To determine if daily information on the price of common laboratory tests and chest X-... more Objective: To determine if daily information on the price of common laboratory tests and chest X-ray could significantly influence test ordering by physicians and decrease the costs. Design: A prospective observational and sequential study. Setting: A 21-bed surgical intensive care unit of a university hospital. Patients: All patients admitted during a 4-month period.

Research paper thumbnail of Effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization

Intensive Care Medicine, 2010

To evaluate the effectiveness of simple daily sensitization of physicians to the duration of cent... more To evaluate the effectiveness of simple daily sensitization of physicians to the duration of central venous and urinary tract catheterization, and impact on infection rates. A prospective, before-after study in a surgical intensive care unit. All consecutive patients who had a central venous catheter (CVC) and/or urinary tract catheter (UTC) were included during two consecutive periods. Period 1 (August 2005 to May 2006) served as the control period. During Period 2 (July 2006 to April 2007), a red square, added to the patient's daily care sheet, questioned the physician about the utility of the CVC and/or UTC. If the response was "No", the CVC and/or the UTC were removed by a nurse. A total of 1,271 patients were analyzed (Period 1, n = 676; Period 2, n = 595). The duration of catheterization (median [interquartile range]) was significantly reduced in Period 2 compared to Period 1 (from (5 [3-9] to 4 [3-7] days, p < 0.001, for CVC, and from 5 [3-11] to 4 [3-8] days, p < 0.001, for UTC). The incidence and density incidence of CVC infection decreased in Period 2 compared to Period 1 (from 1.8% to 0.3%, p = 0.010, and from 2.8 to 0.7/1,000 CVC-days, p = 0.051) whereas UTC infections were not significantly different (4.3 to 3.0%, p = 0.230, and 5.0 to 4.9/1,000 UTC-days, p = 0.938, respectively). A simple daily reminder to physicians on the patients' care sheets decreased the duration of central venous and urinary tract catheterization, and tended to decrease CVC infection rate without affecting UTC infection.

Research paper thumbnail of Hub qualitative blood culture is useful for diagnosis of catheter-related infections in critically ill patients

Intensive Care Medicine, 2005

To assess clinical safety and accuracy of qualitative blood culture drawn through the hub for rul... more To assess clinical safety and accuracy of qualitative blood culture drawn through the hub for ruling out catheter-related infection (CRI). Prospective observational study in a surgical intensive care unit. All patients with sepsis of unknown origin and possibly due to a CRI. Blood culture drawn through a central venous catheter (CVC) just before the catheter was cultured. In 126 patients we investigated 135 cases of sepsis of unknown origin. Using a clinical and bacteriological approach as the reference, the performance of the CVC blood culture was evaluated by the calculation of sensitivity, specificity, and positive and negative predictive values. When CVC blood culture was positive, the time to positivity was considered. Using standard definitions, seven CRIs were diagnosed. CVC blood culture identified five CRIs including the three episodes of catheter-related bacteremia. The method missed two coagulase-negative staphylococcus CRIs without bacteremia. Thirteen false-positive results occurred, including seven bacteremias from a distant source. The CVC blood culture had a sensitivity of 71% (CI 30-95%), specificity of 90% (CI 83-94%), negative predictive value of 98% (CI 93-100%), and positive predictive value of 28% (CI 11-54%). In cases of catheter-related bacteremia the time to positivity of CVC blood culture was 24 h or less. Negative CVC blood culture at 24 h seems useful for management of CVC in selected critically ill surgical patients developing a clinical sepsis. The subsequent risk of catheter-related bacteremia cannot be excluded advocating for an uninterrupted clinical and bacteriological survey.

Research paper thumbnail of Atrial fibrillation in trauma patients requiring intensive care

Intensive Care Medicine, 2006

To evaluate the incidence and risk factors of atrial fibrillation (AF) in trauma patients. Prospe... more To evaluate the incidence and risk factors of atrial fibrillation (AF) in trauma patients. Prospective observational study in a surgical intensive care unit (ICU). All trauma patients admitted in the surgical ICU except those who had AF at admission. AF occurred in 16/293 patients (5.5%). AF patients were older, had a higher number of regions traumatized, and received more fluid therapy, transfusion products, and catecholamines. They more frequently experienced systemic inflammatory response syndrome, sepsis, shock, and acute renal failure and had higher scores of severity (Simplified Acute Physiology Score, SAPS II; Injury Severity Score). ICU length of stay and resources use were also increased. ICU and hospital mortality rates were twice higher in AF patients whereas standardized mortality ratio (observed/expected mortality by SAPS II) was similar in the two groups. We found five independent risk factors of developing AF: catecholamine use (OR = 5.7, 95% CI 1.7-19.1), SAPS II of 30 or higher (OR = 11.6, 95% CI 1.3-103.0), three or more regions traumatized (OR = 6.2, 95% CI 1.8-21.4), age 40 years or higher (OR = 6.3, CI 1.4-28.7), and systemic inflammatory response syndrome (OR = 4.4, 95% CI 1.2-16.1). In addition to age and catecholamine use, inflammation and severity of injury may be involved in the development of AF in trauma patients. Our results suggest that AF could rather be a marker of a higher severity of illness without major effect on mortality.

Research paper thumbnail of Post-Traumatic Course Complicated by Cutaneous Infection with Absidia corymbifera

European Journal of Clinical Microbiology & Infectious Diseases, 1999

Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the c... more Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the case of a young patient with cutaneous mucormycosis due to Absidia corymbifera probably caused by a soil-contaminated wound. Despite daily surgical debridement and amphotericin B therapy, cure could be achieved only by amputation of the lower limb.

Research paper thumbnail of Current aspects of extracorporeal membrane oxygenation in a tertiary referral centre: determinants of survival at follow-up

European Journal of Cardio-Thoracic Surgery, 2014

To describe the clinical results (both early and at follow-up) of patients currently receiving ex... more To describe the clinical results (both early and at follow-up) of patients currently receiving extracorporeal membrane oxygenation (ECMO) therapy for cardiac and/or pulmonary failure. To assess the effect of indications, clinical presentations and ECMO modalities on early/late clinical outcomes. To identify baseline factors associated with worse survival at follow-up. We reviewed the prospectively collected data of 325 patients receiving ECMO therapy at a tertiary referral centre during the 2005-2013 period. Follow-up was prospectively conducted by dedicated personnel (average: 84 ± 86 days, 100% complete). Survival was analysed by stratified Kaplan-Meier curves. Veno-arterial (VA) ECMO was employed in 80% of cases (due to early graft failure (EGF) in 13% of cases, post-cardiotomy in 29%, primary cardiogenic shock in 42% for miscellaneous aetiologies, other indications in 15.4%) and veno-venous (VV) ECMO in the remainders (adult respiratory distress syndrome). In the VA and VV groups, weaning rates were 59 and 53%, survival at 30th postimplantation day was 44 and 45% and survival at the end of the follow-up was 41 and 45%, respectively. Implantation under advanced life support (ALS) occurred in 15% of cases (26% survival at 30 days). VA patients had a higher rate of thrombotic/haemorrhagic complications and of transfusion of blood products and shorter ventilation time. Worse early and follow-up survival were observed among patients aged ≥65 years, having pH ≤ 7, lactates >12 mmol/l, creatinine >200 μmol/l at implantation or receiving ECMO under ALS. No difference in survival was noted among VA vs VV patients. Patients receiving ECMO for EGF displayed better early and late survival (64% at 30 days and 53% at 6 months) than post-cardiotomy (36 and 34%, respectively), post-acute myocardial infarction (48 and 40%) and the remaining patients (46 and 45%). Despite most critical baseline conditions, ECMO therapy is confirmed useful for the treatment of patients with acute cardiopulmonary failure refractory to conventional treatments. The ECMO modality (VA vs VV), as well as indications to support, identifies different patient profiles and dissimilar outcomes. Preimplantation markers of gravity and end-organ damage are useful in the stratification of expected survival. These may facilitate clinical decision-making and appropriate allocation of hospital resources.

Research paper thumbnail of Steady-state pharmacokinetics of dopamine in adult patients

Critical Care Medicine, 1993

To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. Prospective c... more To study the pharmacokinetics of dopamine in hemodynamically stable adult patients. Prospective clinical study. University hospital intensive care unit. Fourteen patients (aged 43 to 73 yrs) recovering from esophageal surgery. Dopamine was infused and blood samples were collected. Plasma dopamine concentrations were measured at steady state and subsequently at the end of the dopamine infusion using high-performance liquid chromatography. Clearances, volume of distribution, mean residence times, half-lives, and elimination and distribution rate constants were derived. The clearances were independent of the infusion rate at 1, 3, and 6 micrograms/kg/min, and ranged between 0.050 and 0.056 L/min/kg. A two-compartment open model was fitted to the postinfusion plasma concentration data obtained at 3 and 6 micrograms/kg/min. On average, the steady-state volume of distribution and the apparent terminal elimination half-life increased with the dose: 0.78 to 1.58 L/kg, respectively, and 22.1 to 37.9 mins, respectively, for the rates of 3 and 6 micrograms/kg/min. The rate constant associated with the uptake of dopamine into the peripheral compartment (K12) was on average four to five times higher than the rate constant associated with the reverse process (K21). The redistribution of dopamine into the central compartment could be the main factor involved in the apparent terminal elimination of dopamine from plasma. Due to the relative rates of distribution and elimination, the attainment of a steady-state plasma concentration of dopamine should only depend on the terminal half-life. These results, which remain to be validated in a greater number of patients, indicate that the attainment of 90% of the plateau (i.e., in 3.3 half-lives) would require 70 to 125 mins, depending on the infusion rate.

Research paper thumbnail of Diagnostic and therapeutic management of nosocomial pneumonia in surgical patients: Results of the Eole study

Critical Care Medicine, 2002

To assess clinical, microbiological, and therapeutic features of nosocomial pneumonias in surgica... more To assess clinical, microbiological, and therapeutic features of nosocomial pneumonias in surgical patients. Prospective (October 1997 through May 1998), consecutive case series analysis of patients suspected of having pneumonia during the fortnight after a surgical procedure or trauma and receiving antibiotic therapy prescribed by the attending physician for this diagnosis. A total of 230 study centers in teaching (n = 66) and nonteaching hospitals (n = 164) (surgical wards and intensive care units). A total of 837 evaluable patients (mean age 61 +/- 18 yrs) including 629 intensive care unit patients. None. The diagnostic and therapeutic procedures followed were based on guidelines. Antibiotics and any changes of therapy and duration of treatment were decided by the attending physician. The charts were reviewed by a panel of experts that classified the cases according to clinical, radiologic, and microbiological criteria (when available). The efficacy of treatment was evaluated over a 30-day period following the index episode. The patients were classified into three groups: definite pneumonia (n = 261), possible pneumonia (n = 392), or low-probability pneumonia (n = 184). Ventilator-acquired pneumonia was reported in 303 patients. Early onset pneumonia was reported in 512 cases. Microbiological sampling was performed in 718 patients, by bronchoscopy in 367 cases, recovering 450 organisms in 328 patients, including 94 polymicrobial specimens. High proportions of Gram-negative bacteria and staphylococci were cultured, even in early onset pneumonias. Antibiotic therapy was administered for 13 +/- 4 days, using monotherapy in 254 cases. Changes in the initial antibiotic therapy (135 monotherapies) were decided in 517 patients (including clinical failure or persistent infection, n = 171; organisms resistant to initial therapy, n = 177; pulmonary superinfection, n = 68). Death occurred in 180 patients, related to pneumonia in 53 cases. Nosocomial pneumonias in surgical patients are characterized by high frequency of early onset pneumonia, high proportion of nosocomial organisms even in these early onset pneumonias, and moderate mortality rate.

Research paper thumbnail of Catecholamines induce an inflammatory response in human hepatocytes

Critical Care Medicine, 2008

The liver is an early target organ in sepsis, severe sepsis, and septic shock, contributing to mu... more The liver is an early target organ in sepsis, severe sepsis, and septic shock, contributing to multiple organ failure, and both lipopolysaccharide and gut-derived catecholamines are implicated in the occurrence of hepatocellular dysfunction. Treatment of septic shock involves administration of vasoactive agents such as exogenous catecholamines or vasopressin in order to reestablish blood pressure. As a prelude to clinical application, we tested the hypothesis that catecholamines could modulate the lipopolysaccharide-induced inflammatory response and function in human liver.