Anne-Sylvie Dumenil

Association between hypernatraemia acquired in the ICU and mortality: a cohort study

BACKGROUND The aim of this study is to describe the prevalence and outcomes of intensive care unit (ICU)-acquired hypernatraemia (IAH). METHODS A retrospective analysis was performed on a prospectively collected database fed by 12 ICUs. Subjects are unselected patients with ICU stay >48 h. Mild and moderate to severe hypernatraemia were defined as serum sodium >145 and >150 mmol/L, respectively. IAH was hypernatraemia occurring >or=24 h after ICU admission in patients with normal serum sodium at ICU admission. RESULTS Of the 8441 patients, 301 were excluded because they had hypernatraemia at ICU admission. Of the remaining 8140 patients, 901 (11.1%) experienced mild hypernatraemia, and 344 (4.2%) experienced moderate to severe hypernatraemia. Factors independently associated with IAH were male gender, severity at admission as assessed by the Simplified Acute Physiology Score version II (SAPS II), and organ failure or life-supporting treatment at ICU admission. Unadjusted hospital mortality was 15.2% in patients without hypernatraemia compared to 29.5% in patients with mild IAH and 46.2% in those with moderate to severe IAH (P < 0.0001). When any degree of IAH was handled as a time-dependent variable in a subdistribution hazard model, the subdistribution hazard ratio (SHR) for ICU mortality was 4.26 [95% confidence interval (CI), 3.74-4.84]. After stratification by centre and adjustment for confounders, both mild IAH and moderate to severe IAH were independently associated with mortality [SHR 2.03 (95% CI 1.73-2.39) and 2.67 (95% CI 2.19-3.26), respectively]. CONCLUSION IAH is frequent and associated with mortality after adjustment on severity at ICU admission.

Impact of adverse events on outcomes in intensive care unit patients.

Objective:To examine the association between predefined adverse events (AE) (including nosocomial infections) and intensive care unit (ICU) mortality, controlling for multiple adverse events in the same patient and confounding variables. Design:Prospective observational cohort study of the French OUTCOMEREA multicenter database. Setting:Twelve medical or surgical ICUs. Patients:Unselected patients hospitalized for ≥48 hrs enrolled between 1997 and 2003. Interventions:None. Measurements and Main Results:Of the 3,611 patients included, 1415 (39.2%) experienced one or more AEs and 821 (22.7%) had two or more AEs. Mean number of AEs per patient was 2.8 (range, 1–26). Six AEs were associated with death: primary or catheter-related bloodstream infection (BSI) (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.6–5.32), BSI from other sources (OR, 5.7; 95% CI, 2.66–12.05), nonbacteremic pneumonia (OR, 1.69; 95% CI, 1.17–2.44), deep and organ/space surgical site infection without BSI (OR, 3; 95% CI, 1.3–6.8), pneumothorax (OR, 3.1; 95% CI, 1.5–6.3), and gastrointestinal bleeding (OR, 2.6; 95% CI, 1.4–4.9). The results were not changed when the analysis was confined to patients with mechanical ventilation on day 1, intermediate severity of illness (Simplified Acute Physiology Score II between 35 and 55), no treatment-limitation decisions, or no cardiac arrest in the ICU. Conclusions:AEs were common and often occurred in combination in individual patients. Several AEs independently contributed to death. Creating a safe ICU environment is a challenging task that deserves careful attention from ICU physicians.

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

IntroductionTo 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.MethodsObservational 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.ResultsA 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.ConclusionsOne-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.

Pseudomonas Aeruginosa Ventilator-Associated Pneumonia: Predictive Factors of Treatment Failure.

RATIONALE The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain. OBJECTIVES To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP. METHODS From the multicenter OUTCOMEREA database (1997-2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence. MEASUREMENTS AND MAIN RESULTS A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3-0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4-1.0]; P = 0.048). CONCLUSIONS Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Ventilator-Associated Events: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia

Objectives:Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events, comprising ventilator-associated conditions and infection-related ventilator-associated complications. We assess 1) the current epidemiology of ventilator-associated event, 2) the relationship between ventilator-associated event and ventilator-associated pneumonia, and 3) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration. Design:Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1996-2012). Patients:Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode, using slightly modified Centers for Disease Control and Prevention definitions. Intervention:None. Measurements and Main Results:Among the 3,028 patients, 2,331 patients (77%) had at least one ventilator-associated condition, and 869 patients (29%) had one infection-related ventilator-associated complication episode. Multiple causes, or the lack of identified cause, were frequent. The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%). Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection-related ventilator-associated complication, respectively. A good correlation was observed between ventilator-associated condition and infection-related ventilator-associated complication episodes, and ventilator-associated pneumonia occurrence: R2 = 0.69 and 0.82 (p < 0.0001). The median number of days alive without antibiotics and mechanical ventilation at day 28 was significantly higher in patients without any ventilator-associated event (p < 0.05). Ventilator-associated condition and infection-related ventilator-associated complication rates were closely correlated with antibiotic use within each ICU: R2 = 0.987 and 0.99, respectively (p < 0.0001). Conclusions:Ventilator-associated event is very common in a population at risk and more importantly highly related to antimicrobial consumption and may serve as surrogate quality indicator for improvement programs.

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 < 10–4) and longer ICU stay lengths (12 [6–23] vs 5 [3–11] d, p < 10–4). 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 < 10–4), 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.

Renal perfusion assessment by renal Doppler during fluid challenge in sepsis.

Objectives:To assess renal resistive index variations in response to fluid challenge. Design:Prospective cohort study. Setting:Three ICUs in French teaching hospitals. Patients:Consecutive patients receiving mechanical ventilation and requiring a fluid challenge. Intervention:Resistive index measurement before and after fluid challenge. Measurements and Main Results:Renal Doppler was used to measure resistive index and esophageal Doppler to monitor aortic blood flow. Of the 35 included patients, 17 (49%) met our definition for fluid challenge responsiveness, that is, had at least a 10% increase in aortic blood flow. After fluid challenge, mean arterial pressure increased from 73 mm Hg (interquartile range 68–79) to 80 mm Hg (75–86; p < 0.0001) and stroke volume from 50 mL (30–77) to 55 mL (39–84; p < 0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (–1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67–0.75] before and 0.71 [0.67–0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65–0.75] before and 0.72 [0.68–0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r2 = 0.04, p = 0.25), in fluid challenge responders (r2 = –0.02, p = 0.61), or in fluid challenge nonresponders (r2 = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury (AKIN definition), with transient acute kidney injury, or with persistent acute kidney injury. Conclusion:Systemic hemodynamic changes induced by fluid challenge do not translate into resistive index variations in patients without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.

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

IntroductionAlthough 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.MethodsWe 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.ResultsAmong 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.ConclusionsIn 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.

Severe Hypothermia Increases the Risk for Intensive Care Unit–Acquired Infection

BACKGROUND Although hypothermia is widely accepted as a risk factor for subsequent infection in surgical patients, it has not been well defined in medical patients. We sought to assess the risk of acquiring intensive care unit (ICU)--acquired infection after hypothermia among medical ICU patients. METHODS Adults (≥18 years) admitted to French ICUs for at least 2 days between April 2000 and November 2010 were included. Surgical patients were excluded. Patient were classified as having had mild hypothermia (35.0°C-35.9°C), moderate hypothermia (32°C-34.9°C), or severe hypothermia (<32°C), and were followed for the development of pneumonia or bloodstream infection until ICU discharge. RESULTS A total of 6237 patients were included. Within the first day of admission, 648 (10%) patients had mild hypothermia, 288 (5%) patients had moderate hypothermia, and 45 (1%) patients had severe hypothermia. Among the 5256 patients who did not have any hypothermia at day 1, subsequent hypothermia developed in 868 (17%), of which 673 (13%), 176 (3%), and 19 (<1%) patients had lowest temperatures of 35.0°C-35.9°C, 32.0°C-34.9°C, and <32°C, respectively. During the course of ICU admission, 320 (5%) patients developed ICU-acquired bloodstream infection and 724 (12%) patients developed ICU-acquired pneumonia. After controlling for confounding variables in multivariable analyses, severe hypothermia was found to increase the risk for subsequent ICU-acquired infection, particularly in patients who did not present with severe sepsis or septic shock. CONCLUSIONS The presence of severe hypothermia is a risk factor for development of ICU-acquired infection in medical patients.

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.