Alain Combes

Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial

BACKGROUND Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial. In this study, we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome. METHODS Our prospective, randomised, multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France. Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer. 360 patients were randomised, and the primary endpoint was 60-day survival based on an intention-to-treat analysis. FINDINGS Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any other time. INTERPRETATION These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.

Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients.

OBJECTIVES To confirm early, marked decrease in plasma selenium concentrations in patients admitted to a surgical and medical intensive care unit (ICU), and to study this decrease according to the presence or absence of systemic inflammatory response syndrome (SIRS), sepsis, or direct ischemia-reperfusion. DESIGN Prospective, observational study. SETTINGS Collaboration between the adult ICU of a 1,100-bed general hospital and a biochemical research laboratory of a university medical center. PATIENTS One hundred thirty-four consecutive surgical and medical ICU patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS In the first 31 patients, plasma and urine selenium concentrations were measured by electrothermal atomic absorption spectrometry on admission and once weekly during their ICU stay. These values were compared first with severity scores, criteria for SIRS, sepsis, and organ system failure taken on admission, and then with nosocomial infection, organ system failure during ICU stay, and hospital mortality. An early, low mean plasma selenium concentration was observed in these patients compared with selenium laboratory reference values. Plasma selenium, measured on ICU admission, inversely correlated with Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology II scores. Patients with SIRS had lower selenium concentrations than those without SIRS. Mean urine selenium losses were normal in the first 31 patients. Plasma selenium concentration was low in all patients with severe sepsis and septic shock (range 0.20 to 0.72 micromol/L) and in those patients with ischemia-reperfusion from aortic cross-clamping (range 0.34 to 0.68 micromol/L). Despite recommended specific selenium supplementation, plasma selenium concentrations remained low for >2 wks in patients with SIRS. However, there was a slight increase in plasma selenium concentrations in surviving SIRS patients, whereas plasma selenium concentrations decreased in nonsurviving patients. The frequency of ventilator-associated pneumonia, organ system failure, and mortality was three times higher in patients with low plasma selenium concentration at the time of admission (selenium < or =0.70 micromol/L) than for the other patients. CONCLUSIONS In severely ill ICU patients with SIRS, we observed an early 40% decrease in plasma selenium concentrations, reaching values observed in deleterious nutritional selenium deficiency. This prolonged decrease in selenium concentrations could explain the three-fold increase in morbidity and mortality rates in these patients compared with other ICU patients. The efficacy of selenium treatment in SIRS patients with a high gravity index score or hypoperfusion needs further investigation.

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

Morbidity, mortality, and quality-of-life outcomes of patients requiring ≥14 days of mechanical ventilation

ObjectiveTo determine the outcome and health-related quality of life of patients requiring ≥14 days of mechanical ventilation in the intensive care unit (ICU). DesignProspective cohort study with post-ICU, cross-sectional, health-related quality-of-life survey. SettingA 17-bed ICU in a university hospital. PatientsA consecutive cohort of 347 patients receiving mechanical ventilation for ≥14 days. InterventionsNone. Measurements and Main ResultsOf the patients enrolled in the study, 150 (44%) died in the ICU and 197 were discharged (58 of 197 died 1–57 months after discharge). Factors associated with ICU death according to multivariate logistic regression analysis were age ≥65 yrs, preadmission New York Heart Association functional class of ≥3, a preadmission immunocompromised status, septic shock at ICU admission, renal replacement therapy in the ICU, and nosocomial septicemia. Cox proportional hazards multivariate analysis identified age of ≥65, a preadmission immunocompromised status, and duration of mechanical ventilation for >35 days as independent predictors of death after ICU discharge. By contrast, postcardiac surgery patients had a better outcome. Health-related quality of life was evaluated for 87 of the 99 long-term survivors after a median follow-up of 3 yrs by using the Nottingham Health Profile and St. George’s Respiratory questionnaires. Compared with those of a general French population, their scores were significantly worse for each of the Nottingham Health Profile domains, except social isolation. Nottingham Health Profile scores did not significantly differ between postcardiac and nonpostcardiac surgery patients, men and women (except that women felt more socially isolated), and patients with and without acute respiratory distress syndrome (except for more sleep disorders in those with acute respiratory distress syndrome). Finally, pulmonary-specific St. George’s Respiratory Questionnaire global score was worse for acute respiratory distress syndrome survivors. ConclusionsProlonged mechanical ventilation is associated with impaired health-related quality of life compared with that of a matched general population. Despite these handicaps, 99% of the patients evaluated were independent and living at home 3 yrs after ICU discharge. Future studies should focus on physical or psychosocial rehabilitation that could lead to improved management of patients after their ICU stay.

Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

IntroductionSepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients.MethodsA prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded.ResultsSixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups.ConclusionContinuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844.

Pseudomonas aeruginosa Ventilator-Associated Pneumonia: Comparison of Episodes Due to Piperacillin-Resistant versus Piperacillin-Susceptible Organisms

We sought to determine the epidemiological characteristics of patients in an intensive care unit (ICU) who developed ventilator-associated pneumonia (VAP) caused by piperacillin-resistant Pseudomonas aeruginosa (PRPA; n=34) or piperacillin-susceptible P. aeruginosa (PSPA; n=101). According to univariate analysis, the factors associated with the development of PRPA VAP were presence of an underlying fatal medical condition, immunocompromised status, longer previous hospital stay, less-severe illness at the time of ICU admission, duration of mechanical ventilation before onset of VAP, number of classes of antibiotic received, and previous exposure to imipenem or fluoroquinolone. Multivariate logistic regression analysis identified the following significant independent factors: presence of an underlying fatal medical condition (odds ratio [OR], 5.6), previous fluoroquinolone use (OR, 4.6), and initial disease severity (OR, 0.8). We concluded that the clinical characteristics of patients who develop PRPA VAP differ from those of patients who develop PSPA VAP. Restricted fluoroquinolone use is the sole independent risk factor for PRPA VAP that is open to medical intervention.

Extracorporeal membrane oxygenation for respiratory failure in adults

Purpose of reviewThis article reviews case series and trials that evaluated extracorporeal membrane oxygenation (ECMO) for respiratory failure and describes patient and circuit management in the modern era of ECMO support. Recent findingsIn recent years, pivotal progress has been made in the conception and construction of ECMO circuits. They are now simpler, safer, require less anticoagulation and are associated with fewer bleeding complications. The encouraging results of the efficacy and economic assessment of conventional ventilatory support versus ECMO for severe adult respiratory failure (CESAR) trial performed in the United Kingdom and good outcomes of patients who received ECMO as rescue therapy during the recent H1N1 influenza pandemic, in which the latest generation of ECMO technology was used, reignited interest in ECMO for severe acute respiratory distress syndrome (ARDS). SummaryThe latest generation of ECMO systems is more biocompatible, better performing and longer lasting. Although recent studies suggested that veno-venous ECMO might improve the outcomes of patients with ARDS, indications for ECMO use remain uncertain. Future trials of ECMO for severe ARDS should strictly control for standard-of-care mechanical ventilation strategies in the control group and early transportation on ECMO for patients in the intervention arm.

Emergency circulatory support in refractory cardiogenic shock patients in remote institutions: a pilot study (the cardiac-RESCUE program)

AIMS Temporary circulatory support with extracorporeal membrane oxygenation (ECMO) is often the only alternative for supporting patients with refractory cardiogenic shock (RCS). In practice, this strategy is limited to a small minority of patients hospitalized in tertiary-care centres with ECMO programs. The cardiac-RESCUE program was designed to test the feasibility of providing circulatory support distant from specialized ECMO centres, for RCS patients in remote locations. METHODS AND RESULTS From January 2005 to December 2009, hospitals without ECMO facilities throughout the Greater Paris area were invited to participate. One hundred and four RCS cases were assessed and 87 consecutively eligible patients (mean age 46 ± 15 years, 41% following cardiac arrest) had ECMO support instituted locally and were enrolled into the program. Local initiation of ECMO support allowed successful transfer to the tertiary-care centre in 75 patients. Of these, 32 patients survived to hospital discharge [overall survival rate 36.8%, 95% confidence interval (CI) 27.4-46.2]. Independent predictors for in-hospital mortality included initiation of ECMO during cardiopulmonary resuscitation [hazard ratio (HR) = 4.81, 95% CI 2.25-10.30, P < 0.001] and oligo-anuria (HR = 2.48, 95% CI 1.29-4.76, P = 0.006). After adjusting for other confounding factors, in-hospital mortality was not statistically different from that of 123 consecutive patients who received ECMO at our institution during the same period (odds ratio 1.48, 95% CI 0.72-3.00, P = 0.29). CONCLUSION Offering local ECMO support appears feasible in a majority of RCS patients hospitalized in remote hospitals. In this otherwise lethal situation, our pilot experience suggests that over one-third of such patients can survive to hospital discharge.

Early Percutaneous Tracheotomy Versus Prolonged Intubation of Mechanically Ventilated Patients After Cardiac Surgery: A Randomized Trial

BACKGROUND Whether early percutaneous tracheotomy in patients who require prolonged mechanical ventilation can shorten mechanical ventilation duration and lower mortality remains controversial. OBJECTIVE To compare the outcomes of severely ill patients who require prolonged mechanical ventilation randomly assigned to early percutaneous tracheotomy or prolonged intubation. DESIGN Prospective, randomized, controlled, single-center trial (ClinicalTrials.gov registration number: NCT00347321). SETTING Academic center. PATIENTS 216 adults requiring mechanical ventilation 4 or more days after cardiac surgery. INTERVENTION Immediate early percutaneous tracheotomy or prolonged intubation with tracheotomy 15 days after randomization. MEASUREMENTS The primary end point was the number of ventilator-free days during the first 60 days after randomization. Secondary outcomes included 28-, 60-, or 90-day mortality rates; durations of mechanical ventilation, intensive care unit stay, and hospitalization; sedative, analgesic, and neuroleptic use; ventilator-associated pneumonia rate; unscheduled extubations; comfort and ease of care; and long-term health-related quality of life (HRQoL) and psychosocial evaluations. RESULTS There was no difference in ventilator-free days during the first 60 days after randomization between early percutaneous tracheotomy and prolonged intubation groups (mean, 30.4 days [SD, 22.4] vs. 28.3 days [SD, 23.7], respectively; absolute difference, 2.1 days [95% CI, -4.1 to 8.3 days]) nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, and 30% vs. 30%, respectively). The durations of mechanical ventilation and hospitalization, as well as frequencies of ventilator-associated pneumonia and other severe infections, were also similar. However, early percutaneous tracheotomy was associated with less intravenous sedation; less time of heavy sedation; less haloperidol use for agitation, delirium, or both; fewer unscheduled extubations; better comfort and ease of care; and earlier resumption of oral nutrition. After a median follow-up of 873 days, between-group survival, psychosocial evaluations, and HRQoL were similar. LIMITATION The prolonged intubation group had more ventilator-free days during days 1 to 60 than what was hypothesized (mean, 23.0 days [SD, 17.0]). CONCLUSION Early tracheotomy provided no benefit in terms of mechanical ventilation and length of hospital stay, rates of mortality or infectious complications, and long-term HRQoL for patients who require prolonged mechanical ventilation after cardiac surgery. However, the well-tolerated procedure was associated with less sedation, better comfort, and earlier resumption of autonomy. PRIMARY FUNDING SOURCE French Ministry of Health.