François Gouin

Epidemiology, management, and risk factors for death of invasive candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006)

Objective:To describe the evolving epidemiology, management, and risk factors for death of invasive Candida infections in intensive care units (ICUs). Design:Prospective, observational, national, multicenter study. Setting:One hundred eighty ICUs in France. Patients:Between October 2005 and May 2006, 300 adult patients with proven invasive Candida infection who received systemic antifungal therapy were included. Interventions:None. Measurements and Main Results:One hundred seven patients (39.5%) with isolated candidemia, 87 (32.1%) with invasive candidiasis without documented candidemia, and 77 (28.4%) with invasive candidiasis and candidemia were eligible. In 37% of the cases, candidemia occurred within the first 5 days after ICU admission. C. albicans accounted for 57.0% of the isolates, followed by C. glabrata (16.7%), C. parapsilosis (7.5%), C. krusei (5.2%), and C. tropicalis (4.9%). In 17.1% of the isolates, the causative Candida was less susceptible or resistant to fluconazole. Fluconazole was the empirical treatment most commonly introduced (65.7%), followed by caspofungin (18.1%), voriconazole (5.5%), and amphotericin B (3.7%). After identification of the causative species and susceptibility testing results, treatment was modified in 86 patients (31.7%). The case fatality ratio in ICU was 45.9% and did not differ significantly according to the type of episode. Multivariate analysis showed that factors independently associated with death in ICU were type 1 diabetes mellitus (odds ratio [OR] 4.51; 95% confidence interval [CI] 1.72–11.79; p = 0.002), immunosuppression (OR 2.63; 95% CI 1.35–5.11; p = 0.0045), mechanical ventilation (OR 2.54; 95% CI 1.33–4.82; p = 0.0045), and body temperature >38.2°C (reference, 36.5–38.2°C; OR 0.36; 95% CI 0.17–0.77; p = 0.008). Conclusions:More than two thirds of patients with invasive candidiasis in ICU present with candidemia. Non-albicans Candida species reach almost half of the Candida isolates. Reduced susceptibility to fluconazole is observed in 17.1% of Candida isolates. Mortality of invasive candidiasis in ICU remains high.

Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia.

Background: Dynamic action of anesthetic agents was compared at cortical and subcortical levels during induction of anesthesia. Unconsciousness involved the cortical brain but suppression of movement in response to noxious stimuli was mediated through subcortical structures. Methods: Twenty-five patients with Parkinson disease, previously implanted with a deep-brain stimulation electrode, were enrolled during the implantation of the definitive pulse generator. During induction of anesthesia with propofol (n = 13) or sevoflurane (n = 12) alone, cortical (EEG) and subcortical (ESCoG) electrogenesis were obtained, respectively, from a frontal montage (F3–C3) and through the deep-brain electrode (p0–p3). In EEG and ESCoG spectral analysis, spectral edge (90%) frequency, median power frequency, and nonlinear analysis dimensional activation calculations were determined. Results: Sevoflurane and propofol decreased EEG and ESCoG activity in a dose-related fashion. EEG values decreased dramatically at loss of consciousness, whereas there was little change in ESCoG values. Quantitative parameters derived from EEG but not from ESCoG were able to predict consciousness versus unconsciousness. Conversely, quantitative parameters derived from ESCoG but not from EEG were able to predict movement in response to laryngoscopy. Conclusion: These data suggest that in humans, unconsciousness mainly involves the cortical brain, but that suppression of movement in response to noxious stimuli is mediated through the effect of anesthetic agents on subcortical structures.

Development and validation of a perioperative satisfaction questionnaire.

Background:Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vécu de l’Anesthésie Générale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia. Methods:Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item–dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach α coefficients and by test–retest. Results:Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown. Conclusion:The EVAN-G adds important information oriented toward patients’ perceptions. The authors’ approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.

Neuroprotective Effects of Propofol in a Model of Ischemic Cortical Cell Cultures Role of Glutamate and Its Transporters

Background During cerebral ischemia, excess of glutamate release and dysfunction of its high affinity transport induce an accumulation of extracellular glutamate, which plays an important role in neuronal death. The authors studied the relationship among propofol neuroprotection, glutamate extracellular concentrations, and glutamate transporter activity in a model of ischemic cortical cell cultures. Methods Thirteen-day-old primary cortical neuronal-glial cultures were exposed to a 90-min combined oxygen–glucose deprivation (OGD) in an anaerobic chamber, followed by reoxygenation. Propofol was added only during the OGD period, and its effect was compared to that of the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801). Twenty-four hours after the injury, cell death was quantified by lactate dehydrogenase release and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Extracellular concentrations of glutamate in culture supernatants and glutamate uptake were performed at the end of OGD period by high-performance liquid chromatography and incorporation of l-[3H]glutamate into cells, respectively. Results At clinically relevant concentrations (0.05–10 &mgr;m), propofol offered protection equivalent to that of MK-801. It significantly reduced lactate dehydrogenase release and increased the reduction of MTT. At the end of the ischemic injury, propofol was able to reverse the OGD-induced increase in glutamate extracellular concentrations and decrease of glutamate uptake. The inhibition of the glial GLT1 transporter by 3-methyl-glutamate did not further modify the effect of propofol on glutamate uptake, suggesting that GLT1 was not the major target of propofol. Conclusion Propofol showed a neuroprotective effect in this in vitro model of OGD, which was apparently mediated by a GLT1-independent restoration of the glutamate uptake impaired during the injury.

Combination of histopathological and electromyographic patterns can help to evaluate functional outcome of critical ill patients with neuromuscular weakness syndromes

IntroductionThe aim of the study was to describe patterns of neuromuscular weakness using a combination of electromyography and histology, and to evaluate functional outcome in patients following complicated cardiovascular surgery.MethodsFifteen adults requiring long-term mechanical ventilation (>15 days) following cardiovascular surgery associated with postoperative complications were prospectively included. Electrophysiological and histological analyses (muscle and nerve) were performed when failure to wean from mechanical ventilation associated with peripheral neuromuscular weakness was noticed. Functional disability was evaluated 12 months after surgery.ResultsSix patients had a predominantly axonal neuropathy, six presented with myopathy, and three patients had a combination of axonal neuropathy and myopathy. All of them presented with acute tetraparesis and failure to wean from mechanical ventilation. All of the study patients who received corticosteroids exhibited a myopathic pattern (with or without axonopathic changes) but never an axonopathic pattern only. Only two of the eight survivors at 12 months were not ambulatory. These two patients had no detectable compound muscle action potential on electrophysiological examination.ConclusionThe combination of electromyographic evaluation and neuromuscular histological abnormalities could help to identify the type and severity of neuromuscular weakness, in turn helping to evaluate the patients potential functional prognosis.

Sevoflurane Protects Rat Mixed Cerebrocortical Neuronal–glial Cell Cultures against Transient Oxygen–glucose Deprivation: Involvement of Glutamate Uptake and Reactive Oxygen Species

Background:The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia–reoxygenation. Methods:Mature mixed cerebrocortical neuronal–glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen–glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase. Extracellular concentrations of glutamate and glutamate uptake were assessed at the end of the ischemic injury by high-performance liquid chromatography and incorporation of L-[3H]glutamate into cells, respectively. Free radical generation in cells was assessed 6 h after OGD during the reoxygenation period using 2′,7′-dichlorofluorescin diacetate, which reacts with intracellular radicals to be converted to its fluorescent product, 2′,7′-dichlorofluorescin, in cell cytosol. Results:Twenty-four hours after OGD, sevoflurane, in a concentration-dependent manner, significantly reduced lactate dehydrogenase release and increased cell viability. At the end of OGD, sevoflurane was able to reduce the OGD-induced decrease in glutamate uptake. This effect was impaired in the presence of threo-3-methyl glutamate, a specific inhibitor of the glial transporter GLT1. Sevoflurane counteracted the increase in extracellular level of glutamate during OGD and the generation of reactive oxygen species during reoxygenation. Conclusion:Sevoflurane had a neuroprotective effect in this in vitro model of ischemia–reoxygenation. This beneficial effect may be explained, at least in part, by sevoflurane-induced antiexcitotoxic properties during OGD, probably depending on GLT1, and by sevoflurane-induced decrease of reactive oxygen species generation during reoxygenation.

Early anesthetic preconditioning in mixed cortical neuronal-glial cell cultures subjected to oxygen-glucose deprivation: the role of adenosine triphosphate dependent potassium channels and reactive oxygen species in sevoflurane-induced neuroprotection.

BACKGROUND: The purpose of the present study, on mixed cortical neuronal-glial cell cultures subjected to transient oxygen-glucose deprivation (OGD) was: i) to compare the neuroprotection afforded by sevoflurane added either before (preconditioning) or during (direct neuroprotection) the OGD and ii) to explore the possible involvement of adenosine triphosphate-sensitive potassium (KATP) channels and intracellular reactive oxygen species (ROS) levels in the mechanism of the early preconditioning effect of sevoflurane. METHODS: Mature mixed cortical neuronal-glial cell cultures were exposed to 90-min OGD in an anaerobic chamber followed by reoxygenation. Sevoflurane (0.03–3.4 mM) was randomly administered for 90 min and discontinued 60 min before OGD (early preconditioning) or during the 90-min OGD (direct neuroprotection). Cell death was quantified 24 h after the OGD by lactate dehydrogenase release into the bathing medium. Intracellular ROS generation was assessed at the end of sevoflurane preconditioning using 2′,7′-dichlorofluorescin diacetate. RESULTS: Sevoflurane preconditioning elicited a potent threshold-dependent neuroprotective effect at concentrations higher than 0.07 mM and sevoflurane added during OGD elicited a dose dependent neuroprotective effect. Blockers of KATP channels (glibenclamide 0.3 &mgr;M and 5 hydroxydecanoic acid 50 &mgr;M), or ROS-scavengers (N-2-mercaptopropionyl glycine 100 &mgr;M and N-acetylcysteine 50 &mgr;M), although they did not affect cell viability, counteracted the neuroprotection produced by early sevoflurane preconditioning. Sevoflurane exposure during preconditioning induced a significant increase in ROS levels which was prevented by both ROS scavengers and blockers of KATP channels. CONCLUSION: Early sevoflurane preconditioning induced a threshold-dependent protection of mixed cortical neuronal-glial cell cultures against OGD by mechanisms that seem to involve opening KATP channels, thereby leading to generation of ROS.

Role of endogenous adenosine as a predictive marker of vasoplegia during cardiopulmonary bypass and postoperative severe systemic inflammatory response.

Objective:Systemic inflammatory response (SIRS) and severe SIRS (SIRS with organ dysfunction) occurring after cardiopulmonary bypass (CPB) are common causes of morbidity and mortality among cardiac surgical patients. These syndromes are often preceded by a profound vasodilation, characterized by vasoplegia occurring during surgery. Many substances have been implicated in their pathophysiology. Adenosine is a strong endogenous vasodilating agent released by endothelial cells and myocytes under metabolic stress and may be involved in blood pressure failure during CPB induced by severe SIRS. Design:A prospective comparative observational study. Setting:The operating room and intensive care unit of a tertiary care university hospital. Patients:Adenosine plasma levels (mean ± sd; APLs) were measured before (baseline), during, and immediately after surgery in 35 patients who underwent aortic valve replacement involving CPB. APLs were correlated to operative and postoperative clinical courses. Measurements and Main Results:APLs were significantly higher in seven patients with vasoplegia and postoperative severe SIRS (1.6 &mgr;mol·L−1 [0.2–2.6] vs. 0.4 &mgr;mol·L−1 [0.1–1.0]) at baseline and during surgery. The duration of mechanical ventilation and stay in the intensive care unit were significantly longer for patients with higher APLs. Mean arterial pressure was inversely correlated with mean arterial APLs (Pearson’s correlation coefficient: R = −0.66; p < .001). Conclusions:High APLs were found in patients with operative vasoplegia and postoperative severe SIRS occurring after cardiopulmonary bypass. This suggests that adenosine release is involved in vasoplegia that occurs during the systemic inflammatory response to cardiac surgery. Further studies are needed to clarify the association between cytokine production and adenosine release in severe SIRS following cardiac surgery.

Candidoses invasives en réanimation : analyse des traitements antifongiques au cours de l’enquête française AmarCand

OBJECTIVE Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines. STUDY DESIGN Prospective, observational, French multicenter study (October 2005-May 2006). PATIENTS AND METHODS Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis. RESULTS One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida. CONCLUSION The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

Postoperative Treatment With Angiotensin-Converting Enzyme Inhibitors in Patients With Preoperative Reduced Left Ventricular Systolic Function

OBJECTIVE The utility of angiotensin-converting enzyme inhibitors (ACE-Is) as early substitutes for dobutamine was studied after cardiac surgery in patients with preoperative left ventricular ejection fraction (LVEF) </=0.4. DESIGN Randomized, prospective study. SETTINGS University hospital. PARTICIPANTS Thirty-four patients with preoperative LVEF </=0.4 undergoing elective cardiac surgery. INTERVENTIONS Patients were prospectively randomized into 2 groups before the operation. Group R patients treated with ACE-Is received ramipril, 1.25 mg twice a day, from the day after the operation (D(2)), and group C did not receive ACE-Is. In both groups, the withdrawal from dobutamine started at D(3). MEASUREMENTS AND MAIN RESULTS NT-BNP levels were determined before (T(0)), immediately after surgery (T(1)), and on the next 4 days (T(2), T(3), T(4), and T(5)). Creatinine values were recorded before surgery, at the second day, and at the discharge from the intensive care unit. In both groups, baseline NT-BNP levels were high, although not significantly different, and increased postoperatively until T(5). This increase was more pronounced in group C (p = 0.037 and 0.008 at T(3) and T(4)(,) respectively). ACE-Is were well tolerated in all patients in group R. CONCLUSIONS ACE-Is can be used as a dobutamine substitute as early as the first postoperative day after cardiac surgery without renal consequences. Ramipril was beneficial in patients with left ventricular dysfunction as shown by NT-BNP levels that were lower in group R.