Attributable mortality of ICU-acquired bloodstream infections: Impact of the source, causative micro-organism, resistance profile and antimicrobial therapy.

OBJECTIVES: ICU-acquired bloodstream infection (ICUBSI) in Intensive Care unit (ICU) is still associated with a high mortality rate. The increase of antimicrobial drug resistance makes its treatment increasingly challenging. METHODS: We analyzed 571 ICU-BSI occurring amongst 10,734 patients who were prospectively included in the Outcomerea Database and who stayed at least 4 days in ICU. The hazard ratio of death associated with ICU-BSI was estimated using a multivariate Cox model adjusted on case mix, patient severity and daily SOFA. RESULTS: ICU-BSI was associated with increased mortality (HR, 1.40; 95% CI, 1.16-1.69; p = 0.0004). The relative increase in the risk of death was 130% (HR, 2.3; 95% CI, 1.8-3.0) when initial antimicrobial agents within a day of ICU-BSI onset were not adequate, versus only 20% (HR, 1.2; 95% CI, 0.9-1.5) when an adequate therapy was started within a day. The adjusted hazard ratio of death was significant overall, and even higher when the ICU-BSI source was pneumonia or unknown origin. When treated with appropriate antimicrobial agents, the death risk increase was similar for ICU-BSI due to multidrug resistant pathogens or susceptible ones. Interestingly, combination therapy with a fluoroquinolone was associated with more favorable outcome than monotherapy, whereas combination with aminoglycoside was associated with similar mortality than monotherapy. CONCLUSIONS: ICU-BSI was associated with a 40% increase in the risk of 30-day mortality, particularly if the early antimicrobial therapy was not adequate. Adequacy of antimicrobial therapy, but not pathogen resistance pattern, impacted attributable mortality.

Continuous renal replacement therapy versus intermittent hemodialysis in intensive care patients: impact on mortality and renal recovery.

PURPOSE: The best renal replacement therapy (RRT) modality remains controversial. We compared mortality and short- and long-term renal recovery between patients treated with continuous RRT and intermittent hemodialysis. METHODS: Patients of the prospective observational multicenter cohort database OUTCOMEREA™ were included if they underwent at least one RRT session between 2004 and 2014. Differences in patients' baseline and daily characteristics between treatment groups were taken into account by using a marginal structural Cox model, allowing one to substantially reduce the bias resulting from confounding factors in observational longitudinal data analysis. The composite primary endpoint was 30-day mortality and dialysis dependency. RESULTS: Among 1360 included patients with RRT, 544 (40.0 %) and 816 (60.0 %) were initially treated by continuous RRT and intermittent hemodialysis, respectively. At day 30, 39.6 % patients were dead. Among survivors, 23.8 % still required RRT. There was no difference between groups for the primary endpoint in global population (HR 1.00, 95 % CI 0.77-1.29; p = 0.97). In patients with higher weight gain at RRT initiation, mortality and dialysis dependency were significantly lower with continuous RRT (HR 0.54, 95 % CI 0.29-0.99; p = 0.05). Conversely, this technique appeared to be deleterious in patients without shock (HR 2.24, 95 % CI 1.24-4.04; p = 0.01). Six-month mortality and persistent renal dysfunction were not influenced by the RRT modality in patients with dialysis dependence at ICU discharge. CONCLUSION: Continuous RRT did not appear to improve 30-day and 6-month patient outcomes. It seems beneficial for patients with fluid overload, but might be deleterious in the absence of hemodynamic failure.

Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall.

Treatment intensity and outcome of nonagenarians selected for admission in ICUs: a multicenter study of the Outcomerea Research Group.

BACKGROUND: Outcome of very elderly patients admitted in intensive care unit (ICU) was most often reported for octogenarians. ICU admission demands for nonagenarians are increasing. The primary objective was to compare outcome and intensity of treatment of octogenarians and nonagenarians. METHODS: We performed an observational study in 12 ICUs of the Outcomerea™ network which prospectively upload data into the Outcomerea™ database. Patients >90 years old (case patients) were matched with patients 80-90 years old (control patients). Matching criteria were severity of illness at admission, center, and year of admission. RESULTS: A total of 2419 patients aged 80 or older and admitted from September 1997 to September 2013 were included. Among them, 179 (7.9 %) were >90 years old. Matching was performed for 176 nonagenarian patients. Compared with control patients, case patients were more often hospitalized for unscheduled surgery [54 (30.7 %) vs. 42 (23.9 %), p < 0.01] and had less often arterial monitoring for blood pressure [37 (21 %) vs. 53 (30.1 %), p = 0.04] and renal replacement therapy [5 (2.8 %) vs. 14 (8 %), p = 0.05] than control patients. ICU [44 (25 %) vs. 36 (20.5 %), p = 0.28] or hospital mortality [70 (39.8 %) vs. 64 (36.4 %), p = 0.46] and limitation of life-sustaining therapies were not significantly different in case versus control patients, respectively. Only 16/176 (14 %) of case patients were transferred to a geriatric unit. CONCLUSION: This multicenter study reported that nonagenarians represented a small fraction of ICU patients. When admitted, these highly selected patients received similar life-sustaining treatments, except RRT, than octogenarians. ICU and hospital mortality were similar between the two groups.

Colonization and infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure?

OBJECTIVES: It remains uncertain whether colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-PE) affect the outcomes for ICU patients. Our objectives were to measure the effects of ESBL-PE carriage and infection on mortality, ICU length of stay (LOS) and carbapenem exposure in this population. METHODS: A cause-specific hazard model based on prospectively collected data was built to assess the impact of ESBL-PE colonization and infection on competing risks of death and ICU discharge at day 28 in a multicentre cohort of ICU patients. Carbapenem exposure during the ICU stay was compared between infected carriers, uninfected carriers and non-carriers. RESULTS: Among the 16,734 included patients, 594 (3.5%) were ESBL-PE carriers, including 98 (16.4%) with one or more ESBL-PE infections during the ICU stay. After adjustment for baseline and time-dependent confounders, ESBL-PE infections increased the probability of death at day 28 [adjusted cause-specific hazard ratio (aCSHR), 1.825, 95% CI 1.235-2.699, P = 0.0026] and the ICU LOS (aCSHR for discharge alive at day 28, 0.563, 95% CI 0.432-0.733, P < 0.0001). ESBL-PE carriage without infection extended the LOS (aCSHR, 0.623, 95% CI, 0.553-0.702, P < 0.0001), without affecting mortality (aCSHR, 0.906, 95% CI, 0.722-1.136, P = 0.3916). Carbapenem exposure increased in both infected and uninfected carriers when compared with non-carriers (627, 241 and 69 carbapenem days per 1000 patient days, respectively, P < 0.001). CONCLUSIONS: ESBL-PE infections increased carbapenem consumption, LOS and day 28 mortality. ESBL-PE infections were rather infrequent in carriers; however, even ESBL-PE carriage without infection increased carbapenem exposure and delayed discharge, thereby amplifying the selective pressure and the colonization pressure in the ICU.

Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study.

INTRODUCTION: Whether diabetes mellitus increases the risk of acute kidney injury (AKI) during sepsis is controversial. MATERIALS AND METHODS: We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT), and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009. RESULTS: First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes) to 746 matched controls (without diabetes). Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05]) or RRT (HR, 1.09; P = 0.6). However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02), had higher serum creatinine values (134 vs. 103 µmoL/L; P<0.001) and had less often recovered a creatinine level less than 1.25 fold the basal creatinine (41.1% vs. 60.5%; P<0.001). CONCLUSIONS: In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay.

Impact of early nutrition and feeding route on outcomes of mechanically ventilated patients with shock: a post hoc marginal structural model study.

PURPOSE: Few data are available about optimal nutrition modalities in mechanically ventilated patients with shock. Our objective was to assess associations linking early nutrition (<48 h after intubation), feeding route and calorie intake to mortality and risk of ventilator-associated pneumonia (VAP) in patients with invasive mechanical ventilation (IMV) and shock. METHODS: In the prospective OutcomeRea database, we identified adults with IMV >72 h and shock (arterial systolic pressure <90 mmHg) within 48 h after intubation. A marginal structural Cox model was used to create a pseudo-population in which treatment was unconfounded by subject-specific characteristics. RESULTS: We included 3,032 patients. Early nutrition was associated with lower day-28 mortality [HR 0.89, 95 % confidence interval (CI) 0.81-0.98, P = 0.01] and day-7 mortality (HR 0.76, CI 0.66-0.87, P < 0.001) but not with lower day-7 to day-28 mortality (HR 1.00, CI 0.89-1.12, P = 0.98). Early nutrition increased VAP risk over the 28 days (HR 1.08, CI 1.00-1.17, P = 0.046) and until day 7 (HR 7.17, CI 6.27-8.19, P < 0.001) but decreased VAP risk from days 7 to 28 (HR 0.85, CI 0.78-0.92, P < 0.001). Compared to parenteral feeding, enteral feeding was associated with a slightly increased VAP risk (HR 1.11, CI 1.00-1.22, P = 0.04) but not with mortality. Neither mortality nor VAP risk differed between early calorie intakes of ≥20 and <20 kcal/kg/day. CONCLUSION: In mechanically ventilated patients with shock, early nutrition was associated with reduced mortality. Neither feeding route nor early calorie intake was associated with mortality. Early nutrition and enteral feeding were associated with increased VAP risk.

Initiation of nutritional support is delayed in critically ill obese patients: a multicenter cohort study.

BACKGROUND: A high catabolic rate characterizes the acute phase of critical illness. Guidelines recommend an early nutritional support, regardless of the previous nutritional status. OBJECTIVE: We aimed to assess whether the nutritional status of patients, which was defined by the body mass index (BMI) at admission in an intensive care unit (ICU), affected the time of nutritional support initiation. DESIGN: We conducted a cohort study that reported a retrospective analysis of a multicenter ICU database (OUTCOMEREA) by using data prospectively entered from January 1997 to October 2012. Patients who needed orotracheal intubation within the first 72 h and >3 d were included. RESULTS: Data from 3257 ICU stays were analyzed. The delay before feeding was different according to BMI groups (P = 0.035). The delay was longer in obese patients [BMI (in kg/m²) ≥30; n = 663] than in other patients with either low weight (BMI <20; n = 501), normal weight (BMI ≥20 and <25; n = 1135), or overweight (BMI ≥25 and <30; n = 958). The association between nutritional status and a delay in nutrition initiation was independent of potential confounding factors such as age, sex, and diabetes or other chronic diseases. In comparison with normal weight, the adjusted RR (95% CI) associated with a delayed nutrition initiation was 0.92 (0.86, 0.98) for patients with low weight, 1.00 (0.94, 1.05) for overweight patients, and 1.06 (1.00, 1.12) for obese patients (P = 0.004). CONCLUSIONS: The initiation of nutritional support was delayed in obese ICU patients. Randomized controlled trials that address consequences of early compared with delayed beginnings of nutritional support in critically ill obese patients are needed.

ICU physician-based determinants of life-sustaining therapy during nights and weekends: French multicenter study from the Outcomerea Research Group.

OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used.

Acute respiratory distress syndrome and risk of AKI among critically ill patients.

BACKGROUND AND OBJECTIVES: Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded. RESULTS: This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001). CONCLUSIONS: ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.

Influence of early dysnatremia correction on survival of critically ill patients.

Increasing evidence suggests that dysnatremia at intensive care unit (ICU) admission may predict mortality. Little information is available, however, on the potential effect of dysnatremia correction. This is an observational multicenter cohort study in patients admitted between 2005 and 2012 to 18 French ICUs. Hyponatremia and hypernatremia were defined as serum sodium concentration less than 135 and more than 145 mmol/L, respectively. We assessed the influence on day 28 mortality of dysnatremia correction by day 3 and of the dysnatremia correction rate. Of 7,067 included patients, 1,830 (25.9%) had hyponatremia and 634 (9.0%) had hypernatremia at ICU admission (day 1). By day 3, hyponatremia had been corrected in 1,019 (1,019/1,830; 55.7%) and hypernatremia in 393 (393/634; 62.0%) patients. After adjustment for confounders, persistent hyponatremia or hypernatremia on day 3 was independently associated with higher day 28 mortality (odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.06 - 1.61; and OR, 1.86; 95% CI, 1.37 - 2.54; respectively). Hyponatremia corrected by day 3, hypernatremia corrected by day 3, and ICU-acquired hyponatremia were not associated with day 28 mortality. Median correction rate from days 1 to 3 was 2.58 mmol/L per day (interquartile range, 0.67 - 4.55). Higher natremia correction rate was associated with lower crude and adjusted day 28 mortality rates (OR per mmol/L per day, 0.97; 95% CI, 0.94 - 1.00; P = 0.04; and OR per mmol/L per day, 0.93; 95% CI, 0.90 - 0.97; P = 0.0003, respectively). Our results indicate that dysnatremia correction is independently associated with survival, with the effect being greater with faster correction rates of up to 12 mmol/L per day.

Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial.

IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear. OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012. INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay. MAIN OUTCOMES AND MEASURES: The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy. RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03). CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00318942.

Safety of intrahospital transport in ventilated critically ill patients: a multicenter cohort study*.

OBJECTIVES: To describe intrahospital transport complications in critically ill patients receiving invasive mechanical ventilation. DESIGN: Prospective multicenter cohort study. SETTING: Twelve French ICUs belonging to the OUTCOMEREA study group. PATIENTS: Patients older than or equal to 18 years old admitted in the ICU and requiring invasive mechanical ventilation between April 2000 and November 2010 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six thousand two hundred forty-two patients on invasive mechanical ventilation were identified in the OUTCOMEREA database. The statistical analysis included a description of demographic and clinical characteristics of the cohort, identification of risk factors for intrahospital transport and construction of an intrahospital transport propensity score, and an exposed/unexposed study to compare complication of intrahospital transport (excluding transport to the operating room) after adjustment on the propensity score, length of stay, and confounding factors on the day before intrahospital transport. Three thousand and six intrahospital transports occurred in 1,782 patients (28.6%) (1-17 intrahospital transports/patient). Transported patients had higher admission Simplified Acute Physiology Score II values (median [interquartile range], 51 [39-65] vs 46 [33-62], p < 10) and longer ICU stay lengths (12 [6-23] vs 5 [3-11] d, p < 10). Post-intrahospital transport complications were recorded in 621 patients (37.4%). We matched 1,659 intrahospital transport patients to 3,344 nonintrahospital transport patients according to the intrahospital transport propensity score and previous ICU stay length. After adjustment, intrahospital transport patients were at higher risk for various complications (odds ratio = 1.9; 95% CI, 1.7-2.2; p < 10), including pneumothorax, atelectasis, ventilator-associated pneumonia, hypoglycemia, hyperglycemia, and hypernatremia. Intrahospital transport was associated with a longer ICU length of stay but had no significant impact on mortality. CONCLUSIONS: Intrahospital transport increases the risk of complications in ventilated critically ill patients. Continuous quality improvement programs should include specific procedures to minimize intrahospital transport-related risks.

Incidence and outcome of contrast-associated acute kidney injury in a mixed medical-surgical ICU population: a retrospective study.

BACKGROUND: Contrast-enhanced radiographic examinations carry the risk of contrast-associated acute kidney injury (CA-AKI). While CA-AKI is a well-known complication outside the intensive care unit (ICU) setting, data on CA-AKI in ICU patients are scarce. Our aim was to assess the incidence and short-term outcome of CA-AKI in a mixed medical-surgical ICU population. METHODS: We conducted a single-center retrospective analysis between September 2006 and December 2008 on adult patients who underwent a contrast-enhanced computed tomography for urgent diagnostic purposes. CA-AKI was defined as either a relative increment in serum creatinine of ≥ 25% or an absolute increment in serum creatinine of ≥ 0.3 mg/dL within 48 hrs after contrast administration. ICU mortality rates of patients with and without CA-AKI were compared in univariate and multivariate analyses. The need for renal replacement therapy (RRT) was also recorded. RESULTS: CA-AKI occurred in 24/143 (16.8%) patients. Coexisting risk factors for kidney injury, such as sepsis, nephrotoxic drugs and hemodynamic failure were commonly observed in patients who developed CA-AKI. ICU mortality was significantly higher in patients with than in those without CA-AKI (50% vs 21%, p = 0.004). In multivariate logistic regression, CA-AKI remained associated with ICU mortality (odds ratio: 3.48, 95% confidence interval: 1.10-11.46, p = 0.04). RRT was required in 7 (29.2%) patients with CA-AKI. CONCLUSIONS: In our cohort, CA-AKI was a frequent complication. It was associated with a poor short-term outcome and seemed to occur mainly when multiple risk factors for kidney injury were present. Administration of ICM should be considered as a potential high-risk procedure and not as a routine innocuous practice in ICU patients.

Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial.

OBJECTIVE: Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen. We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis. DESIGN: This multicentre, randomised, controlled, single-blind trial was performed in two parallel groups. SETTING: Eight intensive care units in France. PARTICIPANTS: Adults with the phenotype of severe sepsis and no overt source of infection, negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission. INTERVENTION: The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians' clinical judgement without reference to procalcitonin values in the control arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of patients on antibiotics on day 5 postrandomisation. RESULTS: Over a 3-year period, 62/1250 screened patients were eligible for the study, of whom 31 were randomised to each arm; 4 later withdrew their consent. At day 5, 18/27 (67%) survivors were on antibiotics in the experimental arm, versus 21/26 (81%) controls (p=0.24; relative risk=0.83, 95% CI: 0.60 to 1.14). Only 8/58 patients (13%) had baseline procalcitonin <0.25 µg/l; in these patients, physician complied poorly with the algorithm. CONCLUSIONS: In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen, the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure. However, the premature termination of the trial may not allow definitive conclusions.

Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change.

INTRODUCTION: To assess the prevalence of dysnatremia, including borderline changes in serum sodium concentration, and to estimate the impact of these dysnatremia on mortality after adjustment for confounders. METHODS: Observational study on a prospective database fed by 13 intensive care units (ICUs). Unselected patients with ICU stay longer than 48 h were enrolled over a 14-year period were included in this study. Mild to severe hyponatremia were defined as serum sodium concentration < 135, < 130, and < 125 mmol/L respectively. Mild to severe hypernatremia were defined as serum sodium concentration > 145, > 150, and > 155 mmol/L respectively. Borderline hyponatremia and hypernatremia were defined as serum sodium concentration between 135 and 137 mmol/L or 143 and 145 respectively. RESULTS: A total of 11,125 patients were included in this study. Among these patients, 3,047 (27.4%) had mild to severe hyponatremia at ICU admission, 2,258 (20.3%) had borderline hyponatremia at ICU admission, 1,078 (9.7%) had borderline hypernatremia and 877 (7.9%) had mild to severe hypernatremia. After adjustment for confounder, both moderate and severe hyponatremia (subdistribution hazard ratio (sHR) 1.82, 95% CI 1.002 to 1.395 and 1.27, 95% CI 1.01 to 1.60 respectively) were associated with day-30 mortality. Similarly, mild, moderate and severe hypernatremia (sHR 1.34, 95% CI 1.14 to 1.57; 1.51, 95% CI 1.15 to 1.99; and 2.64, 95% CI 2.00 to 3.81 respectively) were independently associated with day-30 mortality. CONCLUSIONS: One-third of critically ill patients had a mild to moderate dysnatremia at ICU admission. Dysnatremia, including mild changes in serum sodium concentration, is an independent risk factor for hospital mortality and should not be neglected.

Efficacy of renal replacement therapy in critically ill patients: a propensity analysis.

INTRODUCTION: Although renal replacement therapy (RRT) is a common procedure in critically ill patients with acute kidney injury (AKI), its efficacy remains uncertain. Patients who receive RRT usually have higher mortality rates than those who do not. However, many differences exist in severity patterns between patients with and those without RRT and available results are further confounded by treatment selection bias since no consensus on indications for RRT has been reached so far. Our aim was to account for these biases to accurately assess RRT efficacy, with special attention to RRT timing. METHODS: We performed a propensity analysis using data of the French longitudinal prospective multicenter Outcomerea database. Two propensity scores for RRT were built to match patients who received RRT to controls who did not despite having a close probability of receiving the procedure. AKI was defined according to RIFLE criteria. The association between RRT and hospital mortality was examined through multivariate conditional logistic regression analyses to control for residual confounding. Sensitivity analyses were conducted to examine the impact of RRT timing. RESULTS: Among the 2846 study patients, 545 (19%) received RRT. Crude mortality rates were higher in patients with than in those without RRT (38% vs 17.5%, P < 0.001). After matching and adjustment, RRT was not associated with a reduced hospital mortality. The two propensity models yielded concordant results. CONCLUSIONS: In our study population, RRT failed to reduce hospital mortality. This result emphasizes the need for randomized studies comparing RRT to conservative management in selected ICU patients, with special focus on RRT timing.