Delirium During Critical Illness and Subsequent Change of Treatment in Patients With Cancer: A Mediation Analysis.

OBJECTIVES: To assess whether delirium during ICU stay is associated with subsequent change in treatment of cancer after discharge. DESIGN: Retrospective cohort study. SETTING: A 50-bed ICU in a dedicated cancer center. PATIENTS: Patients greater than or equal to 18 years old with a previous proposal of cancer treatment (chemotherapy, target therapy, hormone therapy, immunotherapy, radiotherapy, oncologic surgery, and bone marrow transplantation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We considered delirium present if Confusion Assessment Method for the ICU was positive. We assessed the association between delirium and modification of the treatment after discharge. We also performed a mediation analysis to assess both the direct and indirect (i.e., mediated by the development of functional dependence after discharge) of delirium on modification of cancer treatment and whether the modification of cancer treatment was associated with mortality at 1 year. We included 1,134 patients, of whom, 189 (16.7%) had delirium. Delirium was associated with the change in cancer treatment (adjusted odds ratio [OR], 3.80; 95% CI, 2.72-5.35). The association between delirium in ICU and change of treatment was both direct and mediated by the development of functional dependence after discharge. The proportion of the total effect of delirium on change of treatment mediated by the development of functional dependence after discharge was 33.0% (95% CI, 21.7-46.0%). Change in treatment was associated with increased mortality at 1 year (adjusted OR, 2.68; 95% CI, 2.01-3.60). CONCLUSIONS: Patients who had delirium during ICU stay had a higher rate of modification of cancer treatment after discharge. The effect of delirium on change in cancer treatment was only partially mediated by the development of functional dependence after discharge. Change in cancer treatment was associated with increased 1-year mortality.

Characteristics and outcomes of autologous hematopoietic stem cell transplant recipients admitted to intensive care units: A multicenter study.

PURPOSE: Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission. METHODS: This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders. RESULTS: We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not. CONCLUSIONS: In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

Trends in clinical profiles, organ support use and outcomes of patients with cancer requiring unplanned ICU admission: a multicenter cohort study.

PURPOSE: To describe trends in outcomes of cancer patients with unplanned admissions to intensive-care units (ICU) according to cancer type, organ support use, and performance status (PS) over an 8-year period. METHODS: We retrospectively analyzed prospectively collected data from all cancer patients admitted to 92 medical-surgical ICUs from July/2011 to June/2019. We assessed trends in mortality through a Bayesian hierarchical model adjusted for relevant clinical confounders and whether there was a reduction in ICU length-of-stay (LOS) over time using a competing risk model. RESULTS: 32,096 patients (8.7% of all ICU admissions; solid tumors, 90%; hematological malignancies, 10%) were studied. Bed/days use by cancer patients increased up to more than 30% during the period. Overall adjusted mortality decreased by 9.2% [95% credible interval (CI), 13.1-5.6%]. The largest reductions in mortality occurred in patients without need for organ support (9.6%) and in those with need for mechanical ventilation (MV) only (11%). Smallest reductions occurred in patients requiring MV, vasopressors, and dialysis (3.9%) simultaneously. Survival gains over time decreased as PS worsened. Lung cancer patients had the lowest decrease in mortality. Each year was associated with a lower sub-hazard for ICU death [SHR 0.93 (0.91-0.94)] and a higher chance of being discharged alive from the ICU earlier [SHR 1.01 (1-1.01)]. CONCLUSION: Outcomes in critically ill cancer patients improved in the past 8 years, with reductions in both mortality and ICU LOS, suggesting improvements in overall care. However, outcomes remained poor in patients with lung cancer, requiring multiple organ support and compromised PS.

Outcomes of Cancer Patients Discharged From ICU After a Decision to Forgo Life-Sustaining Therapies.

OBJECTIVES: Many cancer patients are admitted to an ICU and decisions to forgo life-sustaining therapies are frequent during ICU stay. A significant proportion of these patients are subsequently discharged from ICU, but their outcomes are unknown. DESIGN: Retrospective. SETTING: ICU of oncological hospital. PATIENTS: Adult cancer patients admitted to ICU, then with a decision to forgo life-sustaining therapies and that were discharged from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital mortality, long-term survival, recommencement of cancer treatment, and ICU readmission were recorded. Hospital mortality predictors were evaluated. The propensity score method was used to test the hypothesis that decision to forgo life-sustaining therapies was independently associated with hospital mortality. Among the 16,998 patients that were admitted to ICU, in 1,369 patients (8.1%) a decision to forgo life-sustaining therapies was made during ICU stay. Among the latter group, 507 were discharged from ICU and were examined in this study. The hospital mortality of this group was 80.1% and was independently predicted according to the occurrence of delirium or acute kidney injury during their ICU stay. Six-month and 12-month survival rates were 3.6% and 0.6%. Sixty-four patients (12.6%) resumed cancer treatment and had a longer survival (p < 0.01). Fifty-two patients (10.3%) were readmitted to ICU and had a longer survival (p < 0.01). The decision to forgo life-sustaining therapies was associated with higher hospital mortality (80.0% vs 26.3%, respectively; p < 0.01) and lower rates of survival (p < 0.01). CONCLUSIONS: Approximately 20% of cancer patients discharged from our ICU after a decision to forgo life-sustaining therapies were discharged from hospital. Delirium and acute kidney injury during ICU stay were predictors of hospital mortality. The decision to forgo life-sustaining therapies was independently associated with hospital mortality. Patients readmitted to the ICU and those that resumed cancer treatment had longer survival. Knowledge of these outcomes is important for providing proper therapeutic planning and counseling for patients and their relatives.

Accuracy of SOFA, qSOFA, and SIRS scores for mortality in cancer patients admitted to an intensive care unit with suspected infection.

PURPOSE: To compare the prognostic accuracy of Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) with systemic inflammatory response syndrome (SIRS) criteria in critically ill cancer patients with suspected infection. METHODS: Data for 450 cancer patients admitted to an intensive care unit (ICU) in 2014 with a suspected infection were retrospectively analyzed. Sensitivity, specificity, and area under the receiver operating curve (AUC) values for SOFA, qSOFA, and SIRS criteria for ICU and hospital mortalities were calculated. Mortalities according to Sepsis-2 stratification (e.g., sepsis, severe sepsis, and septic shock) and Sepsis-3 stratification (e.g., infection, sepsis, and septic shock) were also compared. RESULTS: SOFA outperformed SIRS in predicting mortalities for ICU [(AUC, 0.76; 95% confidence interval (CI) 95%, 0.71-0.81) vs. (AUC, 0.62; 95% CI, 0.56-0.67), p < .01] and hospital [(AUC, 0.69; 95% CI, 0.65-0.74) vs. (AUC, 0.58; 95% CI, 0.52-0.63), p < .01)] patients. Similarly, qSOFA outperformed SIRS for both settings [(AUC, 0.71; 95% CI, 0.65-0.76, p = .02) vs. (AUC, 0.69; 95% CI, 0.64-0.74; p < .01), respectively]. CONCLUSIONS: SOFA and qSOFA were more sensitive and accurate than SIRS in predicting ICU and hospital mortality for critically ill cancer patients with suspected infection.

Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis.

INTRODUCTION: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required. METHODS: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest. RESULTS: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive. CONCLUSIONS: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted. TRIAL REGISTRATION NUMBER: CRD42014009116 . Registered 29 March 2014.

Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study.

INTRODUCTION: Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU). METHODS: In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure. RESULTS: Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30). CONCLUSIONS: Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT01268410.

Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials.

INTRODUCTION: Catecholamines are the most used vasopressors in vasodilatory shock. However, the development of adrenergic hyposensitivity and the subsequent loss of catecholamine pressor activity necessitate the search for other options. Our aim was to evaluate the effects of vasopressin and its analog terlipressin compared with catecholamine infusion alone in vasodilatory shock. METHODS: A systematic review and meta-analysis of publications between 1966 and 2011 was performed. The Medline and CENTRAL databases were searched for studies on vasopressin and terlipressin in critically ill patients. The meta-analysis was limited to randomized controlled trials evaluating the use of vasopressin and/or terlipressin compared with catecholamine in adult patients with vasodilatory shock. The assessed outcomes were: overall survival, changes in the hemodynamic and biochemical variables, a decrease of catecholamine requirements, and adverse events. RESULTS: Nine trials covering 998 participants were included. A meta-analysis using a fixed-effect model showed a reduction in norepinephrine requirement among patients receiving terlipressin or vasopressin infusion compared with control (standardized mean difference, -1.58 (95% confidence interval, -1.73 to -1.44); P < 0.0001). Overall, vasopressin and terlipressin, as compared with norepinephrine, reduced mortality (relative risk (RR), 0.87 (0.77 to 0.99); P = 0.04). Vasopressin compared with norepinephrine decreased mortality in adult patients (RR, 0.87 (0.76 to 1.00); P = 0.05) and in patients with septic shock (42.5% vs. 49.2%, respectively; RR, 0.87 (0.75 to 1.00); P = 0.05; number needed to treat, 1 to 15). There was no difference in adverse events between the vasopressin and control groups (RR, 0.98 (0.65 to 1.47); P = 0.92). CONCLUSIONS: Vasopressin use in vasodilatory shock is safe, associated with reduced mortality, and facilitates weaning of catecholamines. In patients with septic shock, use of vasopressin compared with norepinephrine may also decrease mortality.

Delirium screening in critically ill patients: a systematic review and meta-analysis.

OBJECTIVE: Despite its frequency and impact, delirium in critically ill patients is poorly recognized. Our aim was to systematically review the accuracy of delirium screening instruments in critically ill patients. DATA SOURCE: Systematic review and meta-analysis of publications between 1966 and 2011. The Medline and Embase databases were searched for studies on delirium in critically ill patients. STUDY SELECTION: The meta-analysis was limited to studies in critically ill patients in intensive care units, surgical wards, or emergency rooms. The delirium screening tool had to be feasible in a clinical setting for use by a nonexpert. As the gold standard, delirium had to be diagnosed based on appropriate criteria by a delirium expert. DATA EXTRACTION: The outcomes assessed were sensitivity, specificity, likelihood ratios, and summary receiver operating characteristics curves. DATA SYNTHESIS: Sixteen studies covering 1,523 participants and five screening tools were included in the systematic review. The pooled sensitivities and specificities of Confusion Assessment Method for the Intensive Care Unit for detection of delirium in critically ill patients were 75.5% and 95.8%, and for Intensive Care Delirium Screening Checklist 80.1% and 74.6%, respectively. All but one study was performed in a research setting, and that one study suggested that with routine use of the Confusion Assessment Method for the Intensive Care Unit, half of the patients with delirium were not detected. CONCLUSIONS: The Confusion Assessment Method for the Intensive Care Unit was the most specific bedside tool for the assessment of delirium in critically ill patients. However, there was significant heterogeneity of the results. These findings were largely obtained in research settings, and the low sensitivity of the Confusion Assessment Method for the Intensive Care Unit in routine, daily practice may limit its use as a screening test.