Evaluating mortality in intensive care units: contribution of competing risks analyses

INTRODUCTION: Kaplan–Meier curves and logistic models are widely used to describe and explain the variability of survival in intensive care unit (ICU) patients. The Kaplan–Meier approach considers that patients discharged alive from hospital are 'non-informatively' censored (for instance, representative of all other individuals who have survived to that time but are still in hospital); this is probably wrong. Logistic models are adapted to this so-called 'competing risks' setting but fail to take into account censoring and differences in exposure time. To address these issues, we exemplified the usefulness of standard competing risks methods; namely, cumulative incidence function (CIF) curves and the Fine and Gray model. METHODS: We studied 203 mechanically ventilated cancer patients with acute respiratory failure consecutively admitted over a five-year period to a teaching hospital medical ICU. Among these patients, 97 died before hospital discharge. After estimating the CIF of hospital death, we used Fine and Gray models and logistic models to explain variability hospital mortality. RESULTS: The CIF of hospital death was 35.5% on day 14 and was 47.8% on day 60 (97/203); there were no further deaths. Univariate models, either the Fine and Gray model or the logistic model, selected the same eight variables as carrying independent information on hospital mortality at the 5% level. Results of multivariate were close, with four variables selected by both models: autologous stem cell transplantation, absence of congestive heart failure, neurological impairment, and acute respiratory distress syndrome. Two additional variables, clinically documented pneumonia and the logistic organ dysfunction, were selected by the Fine and Gray model. CONCLUSION: The Fine and Gray model appears of interest when predicting mortality in ICU patients. It is closely related to the logistic model, through direct modeling of times to death, and can be easily extended to model non-fatal outcomes

Direct admission to the intensive care unit from the emergency department and mortality in critically ill hematology patients

Background: The aim of this study was to assess the benefit of direct ICU admission from the emergency department (ED) compared to admission from wards, in patients with hematological malignancies requiring critical care. Methods: Post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICU in Belgium and France from January 2010 to May 2011. The variable of interest was a direct ICU admission from the ED and the outcome was in-hospital mortality. The association between the variable of interest and the outcome was assessed by multivariable logistic regression after multiple imputation of missing data. Several sensitivity analyses were performed: complete case analysis, propensity score matching and multivariable Cox proportional-hazards analysis of 90-day survival. Results: Direct ICU admission from the ED occurred in 266 (26.4%) cases, 84 of whom (31.6%) died in the hospital versus 311/742 (41.9%) in those who did not. After adjustment, direct ICU admission from the ED was associated with a decreased in-hospital mortality (adjusted OR: 0.63; 95% CI 0.45-0.88). This was confirmed in the complete cases analysis (adjusted OR: 0.64; 95% CI 0.45-0.92) as well as in terms of hazard of death within the 90 days after admission (adjusted HR: 0.77; 95% CI 0.60-0.99). By contrast, in the propensity score-matched sample of 402 patients, direct admission was not associated with in-hospital mortality (adjusted OR: 0.92; 95% CI 0.84-1.01). Conclusions: In this study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. Assessment of early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation

Acute respiratory failure in patients with hematological malignancies : outcomes according to initial ventilation strategy : a Groupe de recherche respiratoire en réanimation onco-hématologique (Grrr-OH) study

Background: In patients with hematological malignancies and acute respiratory failure (ARF), noninvasive ventilation was associated with a decreased mortality in older studies. However, mortality of intubated patients decreased in the last years. In this study, we assess outcomes in those patients according to the initial ventilation strategy. Methods: We performed a post hoc analysis of a prospective multicentre study of critically ill hematology patients, in 17 intensive care units in France and Belgium. Patients with hematological malignancies admitted for ARF in 2010 and 2011 and who were not intubated at admission were included in the study. A propensity score-based approach was used to assess the impact of NIV compared to oxygen only on hospital mortality. Results: Among 1011 patients admitted to ICU during the study period, 380 met inclusion criteria. Underlying diseases included lymphoid (n = 162, 42.6 %) or myeloid (n = 141, 37.1 %) diseases. ARF etiologies were pulmonary infections (n = 161, 43 %), malignant infiltration (n = 65, 17 %) or cardiac pulmonary edema (n = 40, 10 %). Mechanical ventilation was ultimately needed in 94 (24.7 %) patients, within 3 [2-5] days of ICU admission. Hospital mortality was 32 % (123 deaths). At ICU admission, 142 patients received first-line noninvasive ventilation (NIV), whereas 238 received oxygen only. Fifty-five patients in each group (NIV or oxygen only) were matched according the propensity score. NIV was not associated with decreased hospital mortality [OR 1.5 (0.62-3.65)]. Conclusions: In hematology patients with acute respiratory failure, initial treatment with NIV did not improve survival compared to oxygen only

Safety of hyperbaric oxygen therapy in mechanically ventilated patients

Background: To evaluate the epidemiology of patients who require mechanical ventilation during hyperbaric oxygen therapy. Materials and methods: One-hundred-fifty patients who required mechanical ventilation during hyperbaric oxygen therapy were prospectively studied during a 6-year period in a French university hyperbaric centre. We analysed the indication of hyperbaric oxygen therapy, agent used for sedation, presence of a chest tube, need for vasopressor agents and tolerance and appearance of side effects. Finally, we compared the outcomes of patients according to the presence or absence of acute respiratory distress syndrome (ARDS). Results: Eleven children and 139 adult patients were included (n = 150) in the study. In both populations, carbon monoxide poisoning (51%) and iatrogenic gas embolism (33%) were the two main causes of intubation and mechanical ventilation. The combination of midazolam and sufentanil was used in 85 (67%) patients. All of the patients were given a bolus of a neuromuscular blocker during the hyperbaric session, despite the presence of ARDS in 35 patients. Patient-ventilator asynchrony was the most frequent side effect in 6 (5%) patients and was often the consequence of suboptimal sedation. Mortality was higher in the group with ARDS (23%). Conclusions: Carbon monoxide poisoning and iatrogenic gas embolism are the two main diseases of the patients who required mechanical ventilation during hyperbaric oxygen therapy in this study. Mechanical ventilation is a safe method for patients during hyperbaric oxygen therapy. Sedation needs to be perfected to avoid patient-ventilator asynchrony.

Quality assessment of phase I dose-finding cancer trials: proposal of a checklist

Qualitative checklists for phase III trials have been proposed, to improve the reporting of such trials and to assess the validity of their results

Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D

International audienceBackgroundType 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.MethodsWe reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.ResultsA total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24–38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20–40]. Median maximal inspiratory pressure (MIP) was 31 cmH2O [IQR 20.25–39.75]. Median maximal expiratory pressure (MEP) was 30 cm H2O [20–36]. Median left ventricular ejection fraction (LVEF) was 55% [45–64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.ConclusionIn our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality