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1.  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 
Critical Care  2013;17(6):R273.
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).
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.
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).
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.
PMCID: PMC4056532  PMID: 24238574
2.  Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance 
Critical Care  2013;17(6):R265.
Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.
This is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010.
Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics.
Initial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups.
Initial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria.
PMCID: PMC4056004  PMID: 24200097
3.  Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study 
Critical Care  2013;17(2):R56.
Urinary indices have limited effectiveness in separating transient acute kidney injury (AKI) from persistent AKI in ICU patients. Their time-course may vary with the mechanism of AKI. The primary objective of this study was to evaluate the diagnostic value of changes over time of the usual urinary indices in separating transient AKI from persistent AKI.
An observational prospective multicenter study was performed in six ICUs involving 244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93 with persistent AKI. Urinary sodium, urea and creatinine were measured at ICU admission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12, H18, and H24). Transient AKI was defined as AKI with a cause for renal hypoperfusion and reversal within 3 days.
Significant increases from H0 to H24 were noted in fractional excretion of urea (median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P < 0.0001), urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P < 0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29 to 104), P = 0.01). Fractional excretion of sodium did not change significantly during the first 24 hours in the ICU (P = 0.13). Neither urinary index values at ICU admission nor changes in urinary indices between H0 and H24 performed sufficiently well to recommend their use in clinical setting (area under the receiver-operating characteristic curve ≤0.65).
Although urinary indices at H24 performed slightly better than those at H0 in differentiating transient AKI from persistent AKI, they remain insufficiently reliable to be clinically relevant.
PMCID: PMC3733426  PMID: 23531299
4.  Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change 
Critical Care  2013;17(1):R12.
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.
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.
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.
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.
PMCID: PMC4056804  PMID: 23336363
5.  Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study 
Critical Care  2011;15(4):R178.
Several factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea.
We conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges).
A total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar.
FeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.
PMCID: PMC3387621  PMID: 21794161
acute kidney failure; ICU; fractional excretion of sodium; acute tubular necrosis; diuretics; sensitivity and specificity
6.  Acute respiratory distress syndrome during neutropenia recovery 
Critical Care  2010;14(1):114.
Acute respiratory failure is a life-threatening complication in cancer patients. During neutropenia, patients are at high risk for bacterial pneumonia or invasive fungal infections, when neutropenia is prolonged. A high proportion of patients in whom neutropenia had been complicated by pneumonia will present with substantial respiratory deterioration during neutropenia recovery. Patients with fungal pneumonia and those receiving granulocyte colony-stimulating factor to shorten neutropenia duration may be at higher risk for this acute lung injury/acute respiratory distress syndrome during neutropenia recovery. Routine screening of patient's risk factors is crucial since first symptoms of acute respiratory distress syndrome may occur before biological leukocyte recovery.
PMCID: PMC2875486  PMID: 20236481
7.  Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study 
Critical Care  2008;12(6):R137.
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.
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.
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 (ρ = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (ρ = -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).
NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.
PMCID: PMC2646347  PMID: 18990203
8.  Clinical review: Specific aspects of acute renal failure in cancer patients 
Critical Care  2006;10(2):211.
Acute renal failure (ARF) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, ARF may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic or immunological mechanisms. This article reviews specific renal disease in cancer patients, providing a comprehensive overview of the causes of ARF in this setting, such as treatment toxicity, acute renal failure in the setting of myeloma or bone marrow transplantation.
PMCID: PMC1550893  PMID: 16677413

Results 1-8 (8)