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1.  Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2) 
Trials  2014;15(1):507.
Background
Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock.
Methods/Design
The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs.
Discussion
The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015.
Trial registration
ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)
doi:10.1186/1745-6215-15-507
PMCID: PMC4307984  PMID: 25539571
Critical illness; Enteral nutrition; Mechanical ventilation; Mortality; Nosocomial infection; Parenteral nutrition; Shock; Vasoactive drugs
2.  Fluid resuscitation should respect the endothelial glycocalyx layer 
Critical Care  2014;18(6):707.
Endothelial glycocalyx degradation induced by fluid overload adds to the concern of a detrimental effect of uncontrolled fluid resuscitation and the risk of unnecessary fluid infusion. As a consequence, the use of new tools for monitoring response to fluids appears promising. From that perspective, the monitoring of plasma concentration of glycocalyx degradation markers could be useful.
doi:10.1186/s13054-014-0707-6
PMCID: PMC4331386  PMID: 25629597
3.  Multiplex PCR performed of bronchoalveolar lavage fluid increases pathogen identification rate in critically ill patients with pneumonia: a pilot study 
Background
In critically ill patients with pneumonia, accurate microorganism identification allows appropriate antibiotic treatment. In patients undergoing bronchoalveolar lavage (BAL), direct examination of the fluid using Gram staining provides prompt information but pathogen identification accuracy is low. Culture of BAL fluid is actually the reference, but it is not available before 24 to 48 h. In addition, pathogen identification rate observed with direct examination and culture is decreased when antibiotic therapy has been given prior to sampling. We therefore assessed, in critically ill patients with suspected pneumonia, the performance of a multiplex PCR (MPCR) to identify pathogens in BAL fluid. This study is a prospective pilot observation.
Methods
We used a MPCR detecting 20 types of microorganisms. Direct examination, culture, and MPCR were performed on BAL fluid of critically ill patients with pneumonia suspicion. The final diagnosis of infective pneumonia was retained after the medical chart was reviewed by two experts. Pathogen identification rate of direct examination, culture, and MPCR in patients with confirmed pneumonia was compared.
Results
Among the 65 patients with pneumonia suspicion, the diagnosis of pneumonia was finally retained in 53 cases. Twenty nine (55%) were community-acquired pneumonia and 24 (45%) were hospital acquired. Pathogen identification rate with MPCR (66%) was greater than with culture (40%) and direct examination (23%) (p =0.01 and p <0.001, respectively). When considering only the microorganisms included in the MPCR panel, the pathogen identification rate provided by MPCR reached 82% and was still higher than with culture (35%, p <0.001) and direct examination (21%, p <0.001). Pathogen identification rate provided by MPCR was not modified in the case of previous antibiotic treatment (66% vs. 64%, NS) and was still better than with culture (23%, p <0.001).
Conclusions
The results of this pilot study suggest that in critically ill patients, MPCR performed on BAL fluid could provide higher identification rate of pathogens involved in pneumonia than direct examination and culture, especially in patients having received antimicrobial treatment.
doi:10.1186/s13613-014-0035-7
PMCID: PMC4273674  PMID: 25593751
Multiplex PCR; SeptiFast®; Bronchoalveolar lavage; Antibiotic therapy; Prior antibiotic treatment; Community-acquired pneumonia; Hospital-acquired pneumonia; Ventilator-acquired pneumonia
5.  Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: a multicentre European cohort study 
Critical Care  2014;18(5):551.
Introduction
The aim of the study was to assess whether adults admitted to hospitals with both Intensive Care Units (ICU) and Intermediate Care Units (IMCU) have lower in-hospital mortality than those admitted to ICUs without an IMCU.
Methods
An observational multinational cohort study performed on patients admitted to participating ICUs during a four-week period. IMCU was defined as any physically and administratively independent unit open 24 hours a day, seven days a week providing a level of care lower than an ICU but higher than a ward. Characteristics of hospitals, ICUs and patients admitted to study ICUs were recorded. The main outcome was all-cause in-hospital mortality until hospital discharge (censored at 90 days).
Results
One hundred and sixty-seven ICUs from 17 European countries enrolled 5,834 patients. Overall, 1,113 (19.1%) patients died in the ICU and 1,397 died in hospital, with a total of 1,397 (23.9%) deaths. The illness severity was higher for patients in ICUs with an IMCU (median Simplified Acute Physiology Score (SAPS) II: 37) than for patients in ICUs without an IMCU (median SAPS II: 29, P <0.001). After adjustment for patient characteristics at admission such as illness severity, and ICU and hospital characteristics, the odds ratio of mortality was 0.63 (95% CI 0.45 to 0.88, P = 0.007) in favour of the presence of IMCU. The protective effect of the IMCU was absent in patients who were admitted for basic observation, for example, after surgery (odds ratio 1.15, 95% CI 0.65 to 2.03, P = 0.630) but was strong in patients admitted to an ICU for other reasons (odds ratio 0.54, 95% CI 0.37 to 0.80, P = 0.002).
Conclusions
The presence of an IMCU in the hospital is associated with significantly reduced adjusted hospital mortality for adults admitted to the ICU. This effect is relevant for the patients requiring full intensive treatment.
Trial registration
Clinicaltrials.gov NCT01422070. Registered 19 August 2011.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0551-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-014-0551-8
PMCID: PMC4261690
6.  Sex and severe sepsis 
Critical Care  2013;17(3):144.
Epidemiological studies document that males are more prone than females to develop severe sepsis and this is confirmed by Sakr and colleagues in the previous issue of Critical Care. However, the impact of gender on prognosis of severe sepsis is a matter of debate. Sakr and colleagues report a higher mortality in septic females than in males. This puzzling result might be explained by confounding factors such as age, nosocomial infections, follow-up period, and case mix. The impact of sexual hormones in older females is less relevant. Treatments aimed at modifying sexual hormone profile are promising but need to be tested in future trials.
doi:10.1186/cc12690
PMCID: PMC3672659  PMID: 23680409
7.  Mechanical ventilation and clinical practice heterogeneity in intensive care units: a multicenter case-vignette study 
Background
Observational studies on mechanical ventilation (MV) show practice variations across ICUs. We sought to determine, with a case-vignette study, the heterogeneity of processes of care in ICUs focusing on mechanical ventilation procedures, and whether organizational patterns or physician characteristics influence practice variations.
Methods
We conducted a cross-sectional multicenter study using the case-vignette methodology. Descriptive analyses were calculated for each organizational pattern and respondent characteristics. An Index of Qualitative Variation (IQV, from 0, no heterogeneity, to a maximum of 1) was calculated.
Results
Forty ICUs from France (N = 33) and Switzerland (N = 7) participated; 396 physicians answered our case-vignettes. There was major heterogeneity of management processes related to MV within and across centers (mean IQV per center 0.51, SD 0.09). We observed the lowest variability (mean IQV per question < 0.4) for questions related to intubation procedure, ventilation of acute respiratory distress syndrome and the use of the semirecumbent position. We observed a high variability (mean IQV per question > 0.6) for questions related to management of endotracheal tube or suctioning, management of sedation and analgesia, and respect of autonomy. Heterogeneity was independent of respondent characteristics and of the presence of written procedures. There was a correlation between the processes associated with the highest variability (mean IQV per question > 0.6) and the annual volume of ICU admission (r = 0.32 (0.01 to 0.58)) and MV (r = 0.38 (0.07 to 0.63)). Within ICUs there was a large heterogeneity regarding knowledge of a local written procedure.
Conclusions
Large clinical practice variations were found among ICUs. High volume centers were more likely to have heterogeneous practices. The presence of a local written procedure or respondent characteristics did not influence practice variation.
doi:10.1186/2110-5820-4-2
PMCID: PMC3922080  PMID: 24484902
Mechanical ventilation; Clinical practice; Volume-outcome; Protocols
8.  How is intensive care reimbursed? A review of eight European countries 
Reimbursement schemes in intensive care are more complex than in other areas of healthcare, due to special procedures and high care needs. Knowledge regarding the principles of functioning in other countries can lead to increased understanding and awareness of potential for improvement. This can be achieved through mutual exchange of solutions found in other countries. In this review, experts from eight European countries explain their respective intensive care unit reimbursement schemes. Important conclusions include the apparent differences in the countries’ reimbursement schemes-despite all of them originating from a DRG system-, the high degree of complexity found, and the difficulties faced in several countries when collecting the data for this collaborative work. This review has been designed to assist the intensivist clinician and researcher in understanding neighbouring countries’ approaches and in putting research into the context of a European perspective. In addition, steering committees and decision makers might find this a valuable source to compare different reimbursement schemes.
doi:10.1186/2110-5820-3-37
PMCID: PMC3843541  PMID: 24216146
Intensive care unit; Intensive care economics; Reimbursement; DRG system
9.  Alteration of skin perfusion in mottling area during septic shock 
Background
Mottling score has been reported to be a strong predictive factor during septic shock. However, the pathophysiology of mottling remains unclear.
Methods
In patients admitted in ICU for septic shock, we measured on the same area the mean skin perfusion by laser Doppler, the mottling score, and variations of both indices between T1 (6 hours after vasopressors were started) and T2 (24 hours later).
Results
Fourteen patients were included, SAPS II was 56 [37–71] and SOFA score at T1 was 10 [7–12]. The mean skin surface area analyzed was 4108 ± 740 mm2; 1184 ± 141 measurements were performed over each defined skin surface area. Skin perfusion was significantly different according to mottling score and decreased from 37 [31–42] perfusion units (PUs) for a mottling score of [0–1] to 22 [20–32] PUs for a mottling score of [2–3] and 23 [16–28] for a score of [4–5] (Kruskal-Wallis test, P = 0.05). We analyzed skin perfusion changes during resuscitation in each patient and together with mottling score variations between T1 and T2 using a Wilcoxon signed-rank test. Among the 14 patients included, mottling score increased (worsened) in 5 patients, decreased (improved) in 5 patients, and remained stable in 4 patients. Baseline skin perfusion at T1 was arbitrarily scored 100%. Mean skin perfusion significantly decreased in all the patients whose mottling score worsened from 100% baseline to 63.2 ± 10.7% (P = 0.001), mean skin perfusion significantly increased in all patients whose mottling score improved from 100% baseline to 172.6 ± 46.8% (P = 0.001), and remained stable in patients whose mottling score did not change (100.5 ± 6.8%, P = 0.95).
Conclusions
We have shown that mottling score variations and skin perfusion changes during septic shock resuscitation were correlated, providing additional evidence that mottling reflects skin hypoperfusion.
doi:10.1186/2110-5820-3-31
PMCID: PMC3848827  PMID: 24040941
Septic shock; Microcirculation; Mottling; Intensive care medicine
10.  Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement 
Critical Care  2013;17(4):R166.
Introduction
Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.
Methods
We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.
Results
Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).
Conclusions
The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.
doi:10.1186/cc12845
PMCID: PMC4056523  PMID: 23890518
11.  Are clinical trials dealing with severe infection fitting routine practices? Insights from a large registry 
Critical Care  2013;17(3):R89.
Introduction
Guidelines dealing with severe sepsis and septic shock mostly rely on randomized controlled trials (RCTs) to ensure the best standards of care for patients. However, patients included in high-quality studies may differ from the routine population and alter external validity of recommendations. We aimed to determine to what extent non-inclusion criteria of RCTs dealing with severe sepsis and septic shock may affect application of their conclusions in routine care.
Methods
In a first step, the MEDLINE database was searched for RCTs treating severe sepsis and septic shock patients between 1992 and 2008, and non-inclusion criteria for these studies were abstracted. Two reviewers independently evaluated the articles, which were checked by a third reviewer. We extracted data on the study design, main intervention, primary endpoint, criteria for inclusion, and criteria for non-inclusion. In a second step, the distribution of the non-inclusion criteria was observed in a prospective multicenter cohort of severe sepsis and septic shock patients (Cub-Rea network, 1992 to 2008).
Results
We identified 96 articles out of 7,012 citations that met the screening criteria. Congestive heart failure (35%) and cancer (30%) were frequent exclusion criteria in selected studies, as well as other frequent disorders such as gastrointestinal and liver diseases and all causes of immune suppression. Of the 67,717 patients with severe sepsis and septic shock in the Cub-Rea database, 40,325 (60%) experienced at least one of the main exclusion criteria, including 11% of congestive heart failure patients and 11% of cancer patients. In addition, we observed a significant trend for increasing number of patients with these criteria along time.
Conclusion
Current exclusion criteria for RCTs dealing with severe sepsis and septic shock excluded most patients encountered in daily practice and limit external validity of the results of high-quality studies.
doi:10.1186/cc12734
PMCID: PMC3706971  PMID: 23705948
sepsis; septic shock; randomized controlled trial; exclusion criteria; co-morbidity; cohort
12.  Specific antioxidant properties of human serum albumin 
Human serum albumin (HSA) has been used for a long time as a resuscitation fluid in critically ill patients. It is known to exert several important physiological and pharmacological functions. Among them, the antioxidant properties seem to be of paramount importance as they may be implied in the potential beneficial effects that have been observed in the critical care and hepatological settings. The specific antioxidant functions of the protein are closely related to its structure. Indeed, they are due to its multiple ligand-binding capacities and free radical-trapping properties. The HSA molecule can undergo various structural changes modifying its conformation and hence its binding properties and redox state. Such chemical modifications can occur during bioprocesses and storage conditions of the commercial HSA solutions, resulting in heterogeneous solutions for infusion. In this review, we explore the mechanisms that are responsible for the specific antioxidant properties of HSA in its native form, chemically modified forms, and commercial formulations. To conclude, we discuss the implication of this recent literature for future clinical trials using albumin as a drug and for elucidating the effects of HSA infusion in critically ill patients.
doi:10.1186/2110-5820-3-4
PMCID: PMC3577569  PMID: 23414610
Human serum albumin; Antioxidant force; Oxidized albumin; Critically ill patients
13.  Climate and cultural aspects in intensive care units 
Critical Care  2011;15(6):312.
Research carried out in the field of work and organisational psychology shows that work unit climate and culture are important determinants of work unit performance. We briefly summarise what we have learnt about the climate-performance relationship in work units distinct from ICUs. Then, we show how the ICU culture can be measured, and summarise research on the culture-performance relationship in ICUs.
doi:10.1186/cc10361
PMCID: PMC3388710  PMID: 22188718
14.  Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders 
Critical Care  2012;16(4):R148.
Introduction
The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship.
Methods
Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots.
Results
Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal.
Conclusions
The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.
doi:10.1186/cc11462
PMCID: PMC3580737  PMID: 22871090
16.  Comparison of superior vena cava and femoroiliac vein pressure according to intra-abdominal pressure 
Background
Previous studies have shown a good agreement between central venous pressure (CVP) measurements from catheters placed in superior vena cava and catheters placed in the abdominal cava/common iliac vein. However, the influence of intra-abdominal pressure on such measurements remains unknown.
Methods
We conducted a prospective, observational study in a tertiary teaching hospital. We enrolled patients who had indwelling catheters in both superior vena cava (double lumen catheter) and femoroiliac veins (dialysis catheter) and into the bladder. Pressures were measured from all the sites, CVP, femoroiliac venous pressure (FIVP), and intra-abdominal pressure.
Results
A total of 30 patients were enrolled (age 62 ± 14 years; SAPS II 62 (52–76)). Fifty complete sets of measurements were performed. All of the studied patients were mechanically ventilated (PEP 3 cmH20 (2–5)). We observed that the concordance between CVP and FIVP decreased when intra-abdominal pressure increased. We identified 14 mmHg as the best intra-abdominal pressure cutoff, and we found that CVP and FIVP were significantly more in agreement below this threshold than above (94% versus 50%, P = 0.002).
Conclusions
We reported that intra-abdominal pressure affected agreement between CVP measurements from catheter placed in superior vena cava and catheters placed in the femoroiliac vein. Agreement was excellent when intra-abdominal pressure was below 14 mmHg.
doi:10.1186/2110-5820-2-21
PMCID: PMC3424143  PMID: 22742667
Intensive unit care; Central venous pressure; Superior vena cava; Femoroiliac vena; Intra-abdominal pressure
17.  Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study 
Background
We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device.
Methods
We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin].
Results
Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71–48.8; p < 0.001).
Conclusions
The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.
doi:10.1186/2110-5820-2-16
PMCID: PMC3409028  PMID: 22697362
Hypoglycemia; Intensive care unit; Infusion tubing; Central venous catheter; Intensive insulin therapy
18.  Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study 
Critical Care  2012;16(3):R94.
Introduction
Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients.
Methods
In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units.
Results
174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation.
Conclusion
Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups.
ClinicalTrials.gov
NCT00464204
doi:10.1186/cc11358
PMCID: PMC3580640  PMID: 22624531
19.  Variability of Intensive Care Admission Decisions for the Very Elderly 
PLoS ONE  2012;7(4):e34387.
Although increasing numbers of very elderly patients are requiring intensive care, few large sample studies have investigated ICU admission of very elderly patients. Data on pre triage by physicians from other specialities is limited. This observational cohort study aims at examining inter-hospital variability of ICU admission rates and its association with patients' outcomes. All patients over 80 years possibly qualifying for ICU admission who presented to the emergency departments (ED) of 15 hospitals in the Paris (France) area during a one-year period were prospectively included in the study. Main outcome measures were ICU eligibility, as assessed by the ED and ICU physicians; in-hospital mortality; and vital and functional status 6 months after the ED visit. 2646 patients (median age 86; interquartile range 83–91) were included in the study. 94% of participants completed follow-up (n = 2495). 12.4% (n = 329) of participants were deemed eligible for ICU admission by ED physicians and intensivists. The overall in-hospital and 6-month mortality rates were respectively 27.2% (n = 717) and 50.7% (n = 1264). At six months, 57.5% (n = 1433) of patients had died or had a functional deterioration. Rates of patients deemed eligible for ICU admission ranged from 5.6% to 38.8% across the participating centers, and this variability persisted after adjustment for patients' characteristics. Despite this variability, we found no association between level of ICU eligibility and either in-hospital death or six-month death or functional deterioration. In France, the likelihood that a very elderly person will be admitted to an ICU varies widely from one hospital to another. Influence of intensive care admission on patients' outcome remains unclear.
Trial Registration
ClinicalTrials.gov NCT00912600
doi:10.1371/journal.pone.0034387
PMCID: PMC3324496  PMID: 22509296
20.  A balanced view of balanced solutions 
Critical Care  2010;14(5):325.
The present review of fluid therapy studies using balanced solutions versus isotonic saline fluids (both crystalloids and colloids) aims to address recent controversy in this topic. The change to the acid-base equilibrium based on fluid selection is described. Key terms such as dilutional-hyperchloraemic acidosis (correctly used instead of dilutional acidosis or hyperchloraemic metabolic acidosis to account for both the Henderson-Hasselbalch and Stewart equations), isotonic saline and balanced solutions are defined. The review concludes that dilutional-hyperchloraemic acidosis is a side effect, mainly observed after the administration of large volumes of isotonic saline as a crystalloid. Its effect is moderate and relatively transient, and is minimised by limiting crystalloid administration through the use of colloids (in any carrier). Convincing evidence for clinically relevant adverse effects of dilutional-hyperchloraemic acidosis on renal function, coagulation, blood loss, the need for transfusion, gastrointestinal function or mortality cannot be found. In view of the long-term use of isotonic saline either as a crystalloid or as a colloid carrier, the paucity of data documenting detrimental effects of dilutional-hyperchloraemic acidosis and the limited published information on the effects of balanced solutions on outcome, we cannot currently recommend changing fluid therapy to the use of a balanced colloid preparation.
doi:10.1186/cc9230
PMCID: PMC3219243  PMID: 21067552
21.  The challenge of admitting the very elderly to intensive care 
The aging of the population has increased the demand for healthcare resources. The number of patients aged 80 years and older admitted to the intensive care unit (ICU) increased during the past decade, as has the intensity of care for such patients. Yet, many physicians remain reluctant to admit the oldest, arguing a "squandering" of societal resources, that ICU care could be deleterious, or that ICU care may not actually be what the patient or family wants in this instance. Other ICU physicians are strong advocates for admission of a selected elderly population. These discrepant opinions may partly be explained by the current lack of validated criteria to select accurately the patients (of any age) who will benefit most from ICU hospitalization. This review describes the epidemiology of the elderly aged 80 years and older admitted in the ICU, their long-term outcomes, and to discuss some of the solutions to cope with the burden of an aging population receiving acute care hospitalization.
doi:10.1186/2110-5820-1-29
PMCID: PMC3224497  PMID: 21906383
22.  Should fresh blood be recommended for intensive care patients? 
Critical Care  2010;14(3):158.
Fresh blood has many potential advantages over older blood, but there is no evidence that these properties translate into clinical benefit for intensive care patients. The observational multicenter study by Karam and colleagues provides some evidence suggesting that blood stored for less than 14 days is better than older blood in terms of new organ failure and reduction in length of stay in pediatric intensive care units. Though in favor of using young blood, this study suffers from several limitations. As a consequence, it is ethical and certainly pertinent to conduct a randomized clinical trial in order to test the hypothesis that fresh blood might reduce mortality. The rationale is strong and the potential benefit of fresh blood is substantial.
doi:10.1186/cc9011
PMCID: PMC2911714  PMID: 20565831
23.  An integrated approach for prescribing fewer chest x-rays in the ICU 
Chest x-rays (CXRs) are the main imaging tool in intensive care units (ICUs). CXRs also are associated with concerns inherent to their use, considering both healthcare organization and patient perspectives. In recent years, several studies have focussed on the feasibility of lowering the number of bedside CXRs performed in the ICU. Such a decrease may result from two independent and complementary processes: a raw reduction of CXRs due to the elimination of unnecessary investigations, and replacement of the CXR by an alternative technique. The goal of this review is to outline emblematic examples corresponding to these two processes. The first part of the review concerns the accumulation of evidence-based data for abandoning daily routine CXRs in mechanically ventilated patients and adopting an on-demand prescription strategy. The second part of the review addresses the use of alternative techniques to CXRs. This part begins with the presentation of ultrasonography or capnography combined with epigastric auscultation for ensuring the correct position of enteral feeding tubes. Ultrasonography is then also presented as an alternative to CXR for diagnosing and monitoring pneumothoraces, as well as a valuable post-procedural technique after central venous catheter insertion. The combination of the emblematic examples presented in this review supports an integrated global approach for decreasing the number of CXRs ordered in the ICU.
doi:10.1186/2110-5820-1-4
PMCID: PMC3159900  PMID: 21906323
24.  Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience 
PLoS ONE  2010;5(4):e10208.
Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
doi:10.1371/journal.pone.0010208
PMCID: PMC2859048  PMID: 20436664
25.  Does nonadherence to local recommendations for empirical antibiotic therapy on admission to the intensive care unit have an impact on in-hospital mortality? 
Objective
1/ To evaluate if empirical antibiotic prescription on admission to our intensive care unit (ICU) respects the local recommendations for antibiotic prescription and to identify predictors of nonadherence to these guidelines. 2/ To assess whether nonadherence to the guidelines is associated with increased in-hospital mortality due to the initial infection.
Materials and methods
This was a prospective six-month observational study performed in a 14-bed medical ICU. Patients were included if they received curative antibiotic therapy on admission. Respect of the local treatment recommendations was evaluated according to adherence to the local empirical guidelines defined in a 80-page booklet which is given in our hospital to every physician.
Results
Among 132 antibiotic prescriptions, 21 (16%) were unjustified (absence of infection), 17 (13%) were microbiologically documented at admission, and nine (7%) were given for infections from unknown origin. Among the 85 (64%) empirical prescriptions that could be evaluated for adherence to local recommendations, nine (11%) were inappropriate and 76 (89%) appropriate. In univariate analysis hospital-acquired infection was the sole predictor of inappropriate treatment (p = 0.0475). Independent predictors of in-hospital mortality due to the initial infection were inappropriate empirical treatment (odds ratio [OR] = 14.64, 95% confidence interval [CI]: 2.17–98.97; p = 0.006), prescription of fluoroquinolones (OR = 8.22, 95% CI: 1.88–35.95; p = 0.005) and a higher Simplified Acute Physiology Score II score (per one-point increment (OR = 1.04, 95% CI: 1.01–1.07; p = 0.02).
Conclusion
Nonadherence to local empirical antibiotic therapy guidelines was associated with increased in-hospital mortality due to the initial infection.
PMCID: PMC2710381  PMID: 19707259
antimicrobial therapy; appropriateness; mortality; intensive care unit

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