Determinants of hospital and one-year mortality among older patients admitted to intensive care units: results from the multicentric SENIOREA cohort.

BACKGROUND: Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population. METHODS: We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit. RESULTS: 501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients' place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors. CONCLUSIONS: The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care. Clinical trial registration NCT01679171.

Correction to: Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

The members of the Palurea Study Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

PURPOSE: Prospective data on potential factors associated with severity of imported Plasmodium falciparum malaria are lacking. We evaluated whether several host- and parasite-related biomarkers may improve early severity evaluation. METHODS: Prospective multicenter observational study comparing uncomplicated and severe imported falciparum malaria in adults conducted in France in 52 units, from 2007 to 2010. Association of several host- and parasite-related biomarkers with severity of malaria was tested using univariate and multivariate analyses. RESULTS: Of 295 patients, 140 had uncomplicated malaria and 155 severe malaria (including very severe and less severe cases according to predefined criteria). Curative intravenous quinine treatment was used in 154/155 patients with severe malaria and atovaquone/proguanil in 74 % of patients with uncomplicated malaria. Hospital mortality was 5.2 % (8 patients), all in the severe malaria group. Among host-related biomarkers, CRP, procalcitonin, and sTREM-1 were significantly higher and albumin was significantly lower in severe versus uncomplicated malaria; only the last three biomarkers also differed significantly between the very and less severe malaria groups. Among parasite-related biomarkers, only plasma PfHRP2 was significantly higher in severe versus uncomplicated malaria and in very severe versus less severe malaria; parasitemia did not differ between very and less severe malaria. By multivariate analysis, only lower plasma albumin and higher sTREM-1 were associated with greater severity, with intermediate accuracies. CONCLUSIONS: During imported malaria, the most useful biomarkers associated with severity seem to be plasma albumin and sTREM-1; and among parasite-related parameters, PfHRP2 was more strongly associated with severity than parasitemia was.

Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study.

INTRODUCTION: Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. METHODS: Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. RESULTS: One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. CONCLUSIONS: We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.

High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial.

PURPOSE: Intubation of hypoxemic patients is associated with life-threatening adverse events. High-flow therapy by nasal cannula (HFNC) for preoxygenation before intubation has never been assessed by randomized study. Our objective was to evaluate the efficiency of HFNC for preoxygenation, compared to high fraction-inspired oxygen facial mask (HFFM). METHODS: Multicenter, randomized, open-labelled, controlled PREOXYFLOW trial (NCT 01747109) in six French intensive care units. Acute hypoxemic adults requiring intubation were randomly allocated to HFNC or HFFM. Patients were eligible if PaO2/FiO2 ratio was below 300 mmHg, respiratory rate at least 30/min and if they required FiO2 50% or more to obtain at least 90% oxygen saturation. HFNC was maintained throughout the procedure, whereas HFFM was removed at the end of general anaesthesia induction. Primary outcome was the lowest saturation throughout intubation procedure. Secondary outcomes included adverse events related to intubation, duration of mechanical ventilation and death. RESULTS: A total of 124 patients were randomized. In the intent-to-treat analysis, including 119 patients (HFNC n = 62; HFFM n = 57), the median (interquartile range) lowest saturation was 91.5% (80-96) for HFNC and 89.5% (81-95) for the HFFM group (p = 0.44). There was no difference for difficult intubation (p = 0.18), intubation difficulty scale, ventilation-free days (p = 0.09), intubation-related adverse events including desaturation <80% or mortality (p = 0.46). CONCLUSIONS: Compared to HFFM, HFNC as a preoxygenation device did not reduce the lowest level of desaturation.

Investigation and management of multidrug-resistant Acinetobacter baumannii spread in a French medical intensive care unit: one outbreak may hide another.

An outbreak in a medical intensive care unit was due to an OXA-23-producing Acinetobacter baumannii strain imported from a repatriate hospitalized in Singapore. This outbreak revealed another multidrug resistant epidemic strain that had been present in the hospital for 2 years. Both outbreaks were controlled after 9 months of an extensive infection control program.

Contribution of the ethics committee of the French Intensive Care Society to describing a scenario for implementing organ donation after Maastricht type III cardiocirculatory death in France.

French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit).

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis.

PURPOSE: The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established. METHODS: We investigated the time course of plasma sEPCR over the 5 first days (D) of severe sepsis in 40 patients. RESULTS: No significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetics profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or little critical influence on the sEPCR profile. However, we found that sEPCR kinetics was clearly associated with patient's outcome (D28 survival). We demonstrate that a significant but moderate (<15% of basal level) and transient increase in sEPCR level at D2 is associated with poor outcome at D28. CONCLUSION: Severe sepsis, at the onset, only triggers moderate quantitative changes in plasma sEPCR levels. Our findings suggest that in severe sepsis, an early (at D2), transient but significant increase in circulating sEPCR may be detrimental suggesting that sEPCR could provide an early biological marker of sepsis outcome.

Propofol Infusion syndrome during refractory status epilepticus in a young adult: successful ECMO resuscitation.

BACKGROUND: Propofol infusion syndrome (PRIS) is a rare but serious complication of propofol administration consisting of metabolic disorder with acidosis, often leading to fatal cardiovascular collapse. METHODS: A case of PRIS is described in a 17-year-old female with refractory status epilepticus (RSE) who was receiving high-dose propofol for seizure control and sedation. RESULTS: Metabolic syndrome was observed with renal failure, severe metabolic acidosis, and rhabdomyolysis after 58 h of propofol infusion at a maximum dose of 8.8 mg/kg/h. It was not initially associated with circulatory failure. Propofol was stopped immediately, and brief bradycardia was observed. The patient was started on continuous hemofiltration resulting in correction of the metabolic disorder. However, cardiocirculatory failure occurred a few hours later. Her clinical evolution and biological assessments were typical of PRIS. Extracorporeal membrane oxygenation (ECMO) was initiated despite the presence of cardiocirculatory arrest. Cardiocirculatory function improved rapidly, and the patient was weaned off ECMO after 5 days. No severe neurologic effects were observed, and she left the intensive care unit after 36 days, returning home after 2 months. CONCLUSIONS: Careful consideration should be given before prescribing propofol as first-line therapy for RSE, and this drug should be avoided altogether if high doses are required. Close biochemical monitoring is needed if propofol is used for more than a few hours, so that PRIS can be recognized promptly. Immediate discontinuation of propofol is essential, and early hemofiltration should be initiated. ECMO should be considered in cases of cardiocirculatory failure.

Efficacy of doripenem in the treatment of Pseudomonas aeruginosa experimental pneumonia versus imipenem and meropenem.

OBJECTIVES: The aim of this study was to compare doripenem with imipenem and meropenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia and then to compare different doripenem doses and methods of intravenous administration. METHODS: Using a rabbit experimental model of pneumonia, efficacy was assessed following 2 days of treatment by colony counts of different tissues (lung, spleen and blood culture). RESULTS: Mean pulmonary bacterial loads were 3.17 ± 0.53, 3.42 ± 0.61 and 2.75 ± 0.59 log(10) cfu/g for imipenem, doripenem (0.5 g three times daily) and meropenem, respectively, compared with 7.57 ± 0.99 cfu/g for control animals. At a higher dose (1 g three times daily), doripenem showed significantly better efficacy (2.70 ± 0.65 log(10) cfu/g) than the standard regimen of doripenem. Sterilization of spleen cultures was achieved with standard regimens of imipenem (1 g three times daily) and a higher dose of doripenem. CONCLUSIONS: In this model of P. aeruginosa pneumonia, doripenem had an efficacy equivalent to that of meropenem and imipenem at a high dose of 1 g three times a day and lower efficacy at a standard dose (0.5 g three times daily) than the other two agents in terms of bacteria cultivated from spleens. Doripenem is a new drug that offers new therapeutic options, especially for difficult-to-treat infections such as pneumonia due to non-fermenting Gram-negative bacteria.

A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock.

INTRODUCTION: We aimed to establish whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during evolving bacterial community-acquired infection in adults is associated with severe sepsis or septic shock. METHODS: We conducted a multicentre case-control study in eight intensive care units. Cases were all adult patients admitted for severe sepsis or septic shock due to a bacterial community-acquired infection. Control individuals were patients hospitalized with a mild community-acquired infection. Each case was matched to one control for age, presence of diabetes and site of infection. RESULTS: The main outcome measures were the proportions of cases and controls exposed to NSAIDs or aspirin during the period of observation. In all, 152 matched pairs were analyzed. The use of NSAIDs or aspirin during the observation period did not differ between cases and controls (27% versus 28; odds ratio = 0.93, 95% confidence interval [CI] = 0.52 to 1.64). If aspirin was not considered or if a distinction was made between acute and chronic drug treatment, there remained no difference between groups. However, the median time to prescription of effective antibiotic therapy was longer for NSAID users (6 days, 95% CI = 3 to 7 days) than for nonusers (3 days, 95% CI = 2 to 3 days; P = 0.02). CONCLUSIONS: In this study, the use of NSAIDs or aspirin during evolving bacterial infection was frequent and occurred in one-quarter of the patients with such infection. Although the use of NSAIDs by patients with severe sepsis or septic shock did not differ from their use by those with mild infection at the same infected site, we observed a longer median time to prescription of effective antibiotic therapy in NSAID users.

Fatal coinfection with Legionella pneumophila serogroup 8 and Aspergillus fumigatus.

Legionella pneumophila is an important cause of community-acquired and nosocomial pneumonia. We report on a patient who simultaneously developed L. pneumophila serogroup 8 pneumonia and Aspergillus fumigatus lung abscesses. Despite appropriate treatments, Aspergillus disease progressed with metastasis. Coinfections caused by L. pneumophila and A. fumigatus remain exceptional. In apparently immunocompetent patients, corticosteroid therapy is a key risk factor for aspergillosis.

Effect of brain-dead donor resuscitation on delayed graft function: results of a monocentric analysis.

BACKGROUND: We have previously shown that a delayed graft function (DGF) longer than 6 days was a crucial threshold for long-term graft outcome. The aim of this study was to analyze the correlation of DGF >or=6 days with brain-dead donor variables, including those related to resuscitation, in a population of 262 consecutive brain-dead donors from 1990 to 2003. METHODS: We used a marginal logistic model in which DGF was considered as a binary variable with a cutoff of 6 days. RESULTS: Monovariate analysis of donor parameters showed that male, age above 35 years, primary history of hypertension, hydroxyethyl starch (HES) fluid greater than 1500 mL or epinephrine infusion during resuscitation were risk factors for prolonged DGF. The multivariate logistic regression model showed that epinephrine use during donor resuscitation (P<0.001, odds ratio [OR]=4.35), cold ischemia time (CIT) >or=16 hr (P=0.01, OR=2.16), and recipient age >55 years (P=0.003, OR=2.75), were associated with a risk of prolonged DGF. A long stay (>40 hr) in intensive care and a large volume of colloids (>1250 mL, except HES) correlated with a lower risk of DGF. CONCLUSION: Our study shows an impact for only a limited number of brain dead donor resuscitation parameters on DGF duration. We also show that CIT has a much lower threshold (<16 hr) for DGF risk than previously described. Importantly, we show that recipient age is clearly a major independent risk factor for prolonged DGF, whereas donor age seems to act mostly as a dependent risk factor.

Helicobacter pylori infection is not associated with an increased hemorrhagic risk in patients in the intensive care unit.

INTRODUCTION: The potential role of Helicobacter pylori in acute stress ulcer in patients in an intensive care unit (ICU) is controversial. The aim of this study was to determine the frequency of H. pylori infection in ICU patients by antigen detection on rectal swabs, and to analyze the potential relationship between the presence of H. pylori and the risk of digestive gastrointestinal bleeding. METHODS: In this prospective, multicenter, epidemiological study, the inclusion criteria were as follows: patients admitted to the 12 participating ICU for at least two days, who were free of hemorrhagic shock and did not receive more than four units of red blood cells during the day before or the first 48 hours after admission to the ICU. Rectal swabs were obtained within the first 24 hours of admission to the ICU and were tested for H. pylori antigens with the ImmunoCard STAT! HpSA kit. The following events were analyzed according to H. pylori status: gastrointestinal bleeding, unexplained decline in hematocrit, and the number of red cell transfusions. RESULTS: The study involved 1,776 patients. Forty-nine patients (2.8%) had clinical evidence of upper digestive bleeding. Esophagogastroduodenoscopy was performed in 7.6% of patients. Five hundred patients (28.2%) required blood transfusion. H. pylori antigen was detected in 6.3% of patients (95% confidence interval 5.2 to 7.5). H. pylori antigen positivity was associated with female sex (p < 0.05) and with a higher Simplified Acute Physiology Score II (SAPS II; p < 0.05). H. pylori antigen status was not associated with the use of fiber-optic gastroscopy, the need for red cell transfusions, or the number of red cell units infused. CONCLUSION: This large study reported a small percentage of H. pylori infection detected with rectal swab sampling in ICU patients and showed that the patients infected with H. pylori had no additional risk of gastrointestinal bleeding. Thus H. pylori does not seem to have a major role in the pathogenesis of acute stress ulcer in ICU patients.

Mortality prediction using SAPS II: an update for French intensive care units.

INTRODUCTION: The standardized mortality ratio (SMR) is commonly used for benchmarking intensive care units (ICUs). Available mortality prediction models are outdated and must be adapted to current populations of interest. The objective of this study was to improve the Simplified Acute Physiology Score (SAPS) II for mortality prediction in ICUs, thereby improving SMR estimates. METHOD: A retrospective data base study was conducted in patients hospitalized in 106 French ICUs between 1 January 1998 and 31 December 1999. A total of 77,490 evaluable admissions were split into a training set and a validation set. Calibration and discrimination were determined for the original SAPS II, a customized SAPS II and an expanded SAPS II developed in the training set by adding six admission variables: age, sex, length of pre-ICU hospital stay, patient location before ICU, clinical category and whether drug overdose was present. The training set was used for internal validation and the validation set for external validation. RESULTS: With the original SAPS II calibration was poor, with marked underestimation of observed mortality, whereas discrimination was good (area under the receiver operating characteristic curve 0.858). Customization improved calibration but had poor uniformity of fit; discrimination was unchanged. The expanded SAPS II exhibited good calibration, good uniformity of fit and better discrimination (area under the receiver operating characteristic curve 0.879). The SMR in the validation set was 1.007 (confidence interval 0.985-1.028). Some ICUs had better and others worse performance with the expanded SAPS II than with the customized SAPS II. CONCLUSION: The original SAPS II model did not perform sufficiently well to be useful for benchmarking in France. Customization improved the statistical qualities of the model but gave poor uniformity of fit. Adding simple variables to create an expanded SAPS II model led to better calibration, discrimination and uniformity of fit, producing a tool suitable for benchmarking.