Léa Fialkow

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

IntroductionApoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS.MethodsA prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys.ResultsIn medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001).ConclusionIn medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of sepsis in this population.

Pulse pressure variation and prediction of fluid responsiveness in patients ventilated with low tidal volumes

OBJECTIVE: To determine the utility of pulse pressure variation (ΔRESPPP) in predicting fluid responsiveness in patients ventilated with low tidal volumes (VT) and to investigate whether a lower ΔRESPPP cut-off value should be used when patients are ventilated with low tidal volumes. METHOD: This cross-sectional observational study included 37 critically ill patients with acute circulatory failure who required fluid challenge. The patients were sedated and mechanically ventilated with a VT of 6-7 ml/kg ideal body weight, which was monitored with a pulmonary artery catheter and an arterial line. The mechanical ventilation and hemodynamic parameters, including ΔRESPPP, were measured before and after fluid challenge with 1,000 ml crystalloids or 500 ml colloids. Fluid responsiveness was defined as an increase in the cardiac index of at least 15%. ClinicalTrial.gov: NCT01569308. RESULTS: A total of 17 patients were classified as responders. Analysis of the area under the ROC curve (AUC) showed that the optimal cut-off point for ΔRESPPP to predict fluid responsiveness was 10% (AUC = 0.74). Adjustment of the ΔRESPPP to account for driving pressure did not improve the accuracy (AUC = 0.76). A ΔRESPPP≥10% was a better predictor of fluid responsiveness than central venous pressure (AUC = 0.57) or pulmonary wedge pressure (AUC = 051). Of the 37 patients, 25 were in septic shock. The AUC for ΔRESPPP≥10% to predict responsiveness in patients with septic shock was 0.84 (sensitivity, 78%; specificity, 93%). CONCLUSION: The parameter ΔRESPPP has limited value in predicting fluid responsiveness in patients who are ventilated with low tidal volumes, but a ΔRESPPP>10% is a significant improvement over static parameters. A ΔRESPPP≥10% may be particularly useful for identifying responders in patients with septic shock.

Characteristics of chronically critically ill patients: comparing two definitions

Approximately 80% of the patients admitted into intensive care units survive the acute event, and most remain in this unit briefly.1 However, a subgroup does not recover sufficiently quickly to become independent and from then they recover slowly.2 These patients are called chronically critically ill (CCI) patients, and, depending on the definition criteria, comprise 5 to 10% of the patients admitted into intensive care units.3-5 There is a great deal of controversy regarding the definition of a CCI patient. The two most commonly used definitions are the duration of mechanical ventilation (MV) and tracheostomy.2 The advantage of the latter is that the patients are identified by a code, simplifying the extraction of information from a secondary database.2 However, the great variability in the indication of tracheostomy and its tendency to be performed increasingly early may contribute to the selection of patients with different evolutions than those of chronic patients.6,7 MV varies from 4 to 29 days across different studies.2 A recent consensus conference defined patients with cases of prolonged MV as those who need invasive MV for at least 21 days.8 Regardless of the definition, the main characteristics of this population are repeated episodes of shock and infection during their stays in the Intensive Care Unit (ICU).9 It is clear that a chronic critical illness is not simply an extension of an acute critical illness but, rather, is a complex syndrome characterized by metabolic, neuroendocrine, neuropsychiatric and immunological changes.10 This study aims to compare the two definitions of CCI patients: tracheostomy (Tracheo group) and MV ≥ 21 days (MV group). In addition, we described the clinical, epidemiological and outcome characteristics of the CCI patients and tried to identify the factors that predispose patients to the evolution to chronic critical illness.

Mechanical ventilation in patients in the intensive care unit of a general university hospital in southern Brazil : an epidemiological study

OBJECTIVES: To determine the characteristics, the frequency and the mortality rates of patients needing mechanical ventilation and to identify the risk factors associated with mortality in the intensive care unit (ICU) of a general university hospital in southern Brazil. METHOD: Prospective cohort study in patients admitted to the ICU who needed mechanical ventilation for at least 24 hours between March 2004 and April 2007. RESULTS: A total of 1,115 patients admitted to the ICU needed mechanical ventilation. The mortality rate was 51%. The mean age (± standard deviation) was 57±18 years, and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.6±8.3. The variables independently associated with mortality were (i) conditions present at the beginning of mechanical ventilation, age (hazard ratio: 1.01; p<0.001); the APACHE II score (hazard ratio: 1.01; p<0.005); acute lung injury/acute respiratory distress syndrome (hazard ratio: 1.38; p=0.009), sepsis (hazard ratio: 1.33; p=0.003), chronic obstructive pulmonary disease (hazard ratio: 0.58; p=0.042), and pneumonia (hazard ratio: 0.78; p=0.013) as causes of mechanical ventilation; and renal (hazard ratio: 1.29; p=0.011) and neurological (hazard ratio: 1.25; p=0.024) failure, and (ii) conditions occurring during the course of mechanical ventilation, acute lung injuri/acute respiratory distress syndrome (hazard ratio: 1.31; p<0.010); sepsis (hazard ratio: 1.53; p<0.001); and renal (hazard ratio: 1.75; p<0.001), cardiovascular (hazard ratio: 1.32; p≤0.009), and hepatic (hazard ratio: 1.67; p≤0.001) failure. CONCLUSIONS: This large cohort study provides a comprehensive profile of mechanical ventilation patients in South America. The mortality rate of patients who required mechanical ventilation was higher, which may have been related to the severity of illness of the patients admitted to our ICU. Risk factors for hospital mortality included conditions present at the start of mechanical ventilation conditions that occurred during mechanical support.