The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation.

INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Impact of an intensive care unit diary on psychological distress in patients and relatives*.

OBJECTIVE: To assess the impact of an intensive care unit diary on the psychological well-being of patients and relatives 3 and 12 months after intensive care unit discharge. DESIGN: Prospective single-center study with an intervention period between two control periods. SETTING: Medical-surgical intensive care unit in a 460-bed tertiary hospital. PATIENTS: Consecutive patients from May 2008 to November 2009 and their relatives. Study inclusion occurred after the fourth day in the intensive care unit. INTERVENTIONS: A diary written by both the patient's relatives and the intensive care unit staff. MEASUREMENTS AND MAIN RESULTS: Patients and relatives completed the Hospital Anxiety and Depression Scale and Peritraumatic Dissociative Experiences Questionnaire 3 months after intensive care unit discharge, and completed the Impact of Events Scale assessing posttraumatic stress-related symptoms 12 months after intensive care unit discharge. Of the 378 patients admitted during the study period, 143 were included (48 in the prediary period, 49 in the diary period, and 46 in the postdiary period). In relatives, severe posttraumatic stress-related symptoms after 12 months varied significantly across periods (prediary 80%, diary 31.7%, postdiary 67.6%; p<.0001). Similar results were obtained in the posttraumatic stress-related symptom score after 12 months in the surviving patients (prediary 34.6 ± 15.9, diary 21 ± 12.2, and postdiary 29.8 ± 15.9; p = .02). CONCLUSIONS: The intensive care unit diary significantly affected posttraumatic stress-related symptoms in relatives and surviving patients 12 months after intensive care unit discharge.

Diagnostic accuracy of procalcitonin in critically ill immunocompromised patients.

BACKGROUND: Recognizing infection is crucial in immunocompromised patients with organ dysfunction. Our objective was to assess the diagnostic accuracy of procalcitonin (PCT) in critically ill immunocompromised patients. METHODS: This prospective, observational study included patients with suspected sepsis. Patients were classified into one of three diagnostic groups: no infection, bacterial sepsis, and nonbacterial sepsis. RESULTS: We included 119 patients with a median age of 54 years (interquartile range [IQR], 42-68 years). The general severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7) and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of immunodepression were hematological disorders (64 patients, 53.8%), HIV infection (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52 patients (43.7%) had no infection. PCT concentrations on the first ICU day were higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26] ng/ml in patients without bacterial infection, P < 0.0001). PCT concentrations on day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for diagnosing bacterial sepsis. The area under the receiver operating characteristic (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations > 0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95% confidence interval, 2.53-29.3; P = 0.0006). PCT concentrations were not significantly correlated with hospital mortality. CONCLUSION: Despite limited specificity in critically ill immunocompromised patients, PCT concentrations may help to rule out bacterial infection.

Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era.

INTRODUCTION: The widespread use of highly active antiretroviral therapy (ART) has reduced HIV-related life-threatening infectious complications. Our objective was to assess whether highly active ART was associated with improved survival in critically ill HIV-infected patients. METHODS: A retrospective study from 1996 to 2005 was performed in a medical intensive care unit (ICU) in a university hospital specialized in the management of immunocompromised patients. A total of 284 critically ill HIV-infected patients were included. Differences were sought across four time periods. Risk factors for death were identified by multivariable logistic regression. RESULTS: Among the 233 (82%) patients with known HIV infection before ICU admission, 64% were on highly active ART. Annual admissions increased over time, with no differences in reasons for admission: proportions of patients with newly diagnosed HIV, previous opportunistic infection, CD4 counts, viral load, or acute disease severity. ICU and 90-day mortality rates decreased steadily: 25% and 37.5% in 1996 to 1997, 17.1% and 17.1% in 1998 to 2000, 13.2% and 13.2% in 2001 to 2003, and 8.6% in 2004 to 2005. Five factors were independently associated with increased ICU mortality: delayed ICU admission (odds ratio (OR), 3.04; 95% confidence interval (CI), 1.29 to 7.17), acute renal failure (OR, 4.21; 95% CI, 1.63 to 10.92), hepatic cirrhosis (OR, 3.78; 95% CI, 1.21 to 11.84), ICU admission for coma (OR, 2.73; 95% CI, 1.16 to 6.46), and severe sepsis (OR, 3.67; 95% CI, 1.53 to 8.80). Admission to the ICU in the most recent period was independently associated with increased survival: admission from 2001 to 2003 (OR, 0.28; 95% CI, 0.08 to 0.99), and between 2004 and 2005 (OR, 0.13; 95% CI, 0.03 to 0.53). CONCLUSIONS: ICU survival increased significantly in the highly active ART era, although disease severity remained unchanged. Co-morbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Earlier ICU admission from the hospital ward might improve survival.

Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure.

OBJECTIVES: The current trend to manage critically ill hematologic patients admitted with acute respiratory failure is to perform noninvasive ventilation to avoid endotracheal intubation. However, failure of noninvasive ventilation may lead to an increased mortality. DESIGN: Retrospective study to determine the frequency of noninvasive ventilation failure and identify its determinants. SETTING: Medical intensive care unit in a University hospital. PATIENTS: All consecutive patients with hematologic malignancies admitted to the intensive care unit over a 10-yr period who received noninvasive ventilation. RESULTS: A total of 99 patients were studied. Simplified Acute Physiology Score II at admission was 49 (median, interquartile range, 39-57). Fifty-three patients (54%) failed noninvasive ventilation and required endotracheal intubation. Their PaO2/FiO2 ratio was significantly lower (175 [101-236] vs. 248 [134-337]) and their respiratory rate under noninvasive ventilation was significantly higher (32 breaths/min [30-36] vs. 28 [27-30]). Forty-seven patients (89%) who failed noninvasive ventilation required vasopressors. Hospital mortality was 79% in those who failed noninvasive ventilation, and 41% in those who succeeded. Patients who failed noninvasive ventilation had a significantly longer intensive care unit stay (13 days [8-23] vs. 5 [2-8]) and a significantly higher rate of intensive care unit-acquired infections (32% compared with 7%). Factors independently associated with noninvasive ventilation failure by multivariate analysis were respiratory rate under noninvasive ventilation, longer delay between admission and noninvasive ventilation first use, need for vasopressors or renal replacement therapy, and acute respiratory distress syndrome. CONCLUSIONS: Failure of noninvasive ventilation occurs in half the critically ill hematologic patients and is associated with an increased mortality. Predictors of noninvasive ventilation failure might be used to guide decisions regarding intubation.

Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study.

INTRODUCTION: The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients. METHODS: We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography. RESULTS: Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (rho = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (rho = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90). CONCLUSIONS: NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.

Formal Academic Training on Ethics May Address Junior Physicians' Needs.

BACKGROUND: Surveys have highlighted perceived deficiencies among ICU residents in end-of-life care, symptom control, and confidence in dealing with dying patients. Lack of formal training may contribute to the failure to meet the needs of dying patients and their families. The objective of this study was to evaluate junior intensivists' perceptions of triage and of the quality of the dying process before and after formal academic training. METHODS: Formal training on ethics was implemented as a part of resident training between 2007 and 2012. A cross-sectional survey was performed before (2007) and after (2012) this implementation. This study included 430 junior intensivists who were interviewed during these periods. RESULTS: More responders attended a dedicated training course on ethics and palliative care during 2012 (38.5%) than during 2007 (17.4%; P < .0001). During 2012, respondents reported less discomfort and fewer uncertainties regarding decisions about limiting life-sustaining treatment (17.7% vs 39.1% in 2007; P < .0001) or the triage process (48.5% vs 69.4% in 2007; P < .0001). Factors independently associated with positive perceptions of the dying process were physician's age (OR, 1.19 per year; 95% CI, 1.09-1.25) and male sex (OR, 1.61; 95% CI, 1.05-2.47). Conversely, anxiety about family members' reactions (OR, 0.58; 95% CI, 0.0.37-0.87) and lack of training (OR, 0.29; 95% CI, 0.17-0.50) were associated with negative perceptions of this process. CONCLUSIONS: Formal training dedicated to ethics and palliative care was associated with a more comfortable perception of the dying process. This training may decrease the uncertainty and discomfort of junior intensivists in these situations.

Determinants of recovery from severe posterior reversible encephalopathy syndrome.

OBJECTIVE: Few outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES. DESIGN: 70 patients with severe PRES admitted to 24 ICUs in 2001-2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90. MAIN RESULTS: Consciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105-143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3-5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02-1.45, p = 0.03) and time to causative-factor control (OR, 3.3; 95%CI, 1.04-10.46, p = 0.04), whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia) (OR, 0.06; 95%CI, 0.01-0.38, p = 0.003). CONCLUSIONS: By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.

Opinions of families, staff, and patients about family participation in care in intensive care units.

PURPOSE: The aims of the study were to assess opinions of caregivers, families, and patients about involvement of families in the care of intensive care unit (ICU) patients; to evaluate the prevalence of symptoms of anxiety and depression in family members; and to measure family satisfaction with care. MATERIALS AND METHODS: Between days 3 and 5, perceptions by families and ICU staff of family involvement in care were collected prospectively at a single center. Family members completed the Hospital Anxiety and Depression Scale (HADS) and a satisfaction scale (Critical Care Family Needs Inventory). Nurses recorded care provided spontaneously by families. Characteristics of patient-relative pairs (n = 101) and ICU staff (n = 45) were collected. Patients described their perceptions of family participation in care during a telephone interview, 206 ± 147 days after hospital discharge. RESULTS: The numbers of patient-relative pairs for whom ICU staff reported favorable perceptions were 101 (100%) of 101 for physicians, 91 (90%) for nurses, and 95 (94%) for nursing assistants. Only 4 (3.9%) of 101 families refused participation in care. Only 14 (13.8%) of 101 families provided care spontaneously. The HADS score showed symptoms of anxiety in 58 (58.5%) of 99 and of depression in 26 (26.2%) of 99 family members. The satisfaction score was high (11.0 ± 1.25). Among patients, 34 (77.2%) of 44 had a favorable perception of family participation in care. CONCLUSIONS: Families and ICU staff were very supportive of family participation in care. Most patients were also favorable to care by family members.

Etiologies and outcome of acute respiratory failure in HIV-infected patients.

OBJECTIVE: To assess the etiologies and outcome of acute respiratory failure (ARF) in HIV-infected patients over the first decade of combination antiretroviral therapy (ART) use. METHODS: Retrospective study of all HIV-infected patients (n = 147) admitted to a single intensive care unit (ICU) for ARF between 1996 and 2006. RESULTS: ARF revealed the diagnosis of HIV infection in 43 (29.2%) patients. Causes of ARF were bacterial pneumonia (n = 74), Pneumocystis jirovecii pneumonia (PCP, n = 52), other opportunistic infections (n = 19), and noninfectious pulmonary disease (n = 33); the distribution of causes did not change over the 10-year study period. Two or more causes were identified in 33 patients. The 43 patients on ART more frequently had bacterial pneumonia and less frequently had opportunistic infections (P = 0.02). Noninvasive ventilation was needed in 49 patients and endotracheal intubation in 42. Hospital mortality was 19.7%. Factors independently associated with mortality were mechanical ventilation [odds ratio (OR) = 8.48, P < 0.0001], vasopressor use (OR, 4.48; P = 0.03), time from hospital admission to ICU admission (OR, 1.05 per day; P = 0.01), and number of causes (OR, 3.19; P = 0.02). HIV-related variables (CD4 count, viral load, and ART) were not associated with mortality. CONCLUSION: Bacterial pneumonia and PCP remain the leading causes of ARF in HIV-infected patients in the ART era. Hospital survival has improved, and depends on the extent of organ dysfunction rather than on HIV-related characteristics.

Is There a Correlation between Vitamin C Status and Catecholamines Concentrations in Hemodialysis Patients?

It is well established that there is a high incidence of cardiovascular diseases in hemodialysis patients, and involvement of oxidative stress has been hypothesised in these phenomena. Plasma norepinephrine is an independent predictor of many causes of mortality in general, and high norepinephrine levels predict cardiovascular complications in end stage renal disease. The aim of our study was to evaluate the potential link between vitamin C status, a marker of oxidative stress, and catecholamine concentrations before and after hemodialysis sessions. In a prospective study of 16 chronic hemodialysis patients, ascorbyl free radical levels were directly measured using electron spin resonance spectroscopy. These values were expressed with respect to vitamin C concentrations to obtain a direct index of oxidative stress. Vitamin C, epinephrine and norepinephrine were measured by high performance liquid chromatography. The data were examined for correlations between these compounds and clinical parameters including blood pressure and heart rates. In hemodialysis patients, ascorbyl free radical/vitamin C ratios increased significantly after dialysis. No differences were observed for catecholamine concentrations during hemodialysis sessions. In multivariate analysis, the ascorbyl free radical/vitamin C ratio did not correlate with epinephrine or norepinephrine levels. In our study, plasma norepinephrine and ascorbyl free radical/vitamin C ratios were not related among patients with end-stage renal disease. From these findings, we conclude that although these two factors are likely to be involved in the same causal pathway leading to cardiovascular events, it is likely that they seem to be independent.

Influence of ischemia on heart-rate variability in chronic hemodialysis patients.

BACKGROUND: Sudden cardiac death occurring in patients with end-stage renal disease (ESRD) may be related to poor autonomic function with a significant decreased heart-rate variability (HRV). In addition, coronary artery disease has a high prevalence in this population and accounts for 50% of deaths. In the present study, relationships between HRV and myocardial ischemic abnormalities revealed by myocardial scintigraphy (MS) were evaluated in 32 chronic hemodialysis patients. METHODS: We prospectively studied 32 chronic hemodialysis patients. Each underwent MS and 24 h electrocardiography at baseline for analysis of time and frequency domain the day of dialysis. Three periods were analyzed: during dialysis session, the morning after (nondialytic period), and in a 24 h period. Patients were included in group 1 (seven women, 11 men; mean age: 62+/-19 years) when MS revealed no ischemia, whereas patients were included in group 2 (seven women, seven men; mean age: 63.1+/-20 years) when MS revealed ischemic lesions. RESULTS: A student+/-test revealed that during the nondialytic period, two important markers of HRV, percentage of delta RR>50 ms (pNN50) (4.5+/-4.04 in group 1 versus 1.7+/-1.4 in group 2), and root mean square of delta RR (rMSSD) (27.7+/-13.4 versus 19.7+/-6.8) were significantly reduced in group 2 compared with values in group 1. No significant difference appears between the two groups for standard deviation of normal to normal intervals (SDNN), mean heart rate, and spectral analysis. CONCLUSION: Patients with ESRD and myocardial ischemia revealed by MS have reduced parasympathetic activity during the nondialytic period. Correlations between parameters of HRV and ischemic lesions revealed by MS have been shown for the first time.