All-cause mortality in cancer patients treated for sepsis in intensive care units: a systematic review and meta-analysis.

PURPOSE: Sepsis is a common complication in patients with cancer, but studies evaluating the outcomes of critically ill cancer patients with sepsis on a global scale are limited. We aimed to summarize the existing evidence on mortality rates in this patient population. METHODS: Prospective and retrospective observational studies evaluating critically ill adult cancer patients with sepsis, severe sepsis, and/or septic shock were included. Studies published from January 2010 to September 2021 that reported at least one mortality outcome were retrieved from MEDLINE (Ovid), Embase (Ovid), and Cochrane databases. Study selection, bias assessment, and data collection were performed independently by two reviewers, and any discrepancies were resolved by a third reviewer. The risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled intensive care unit (ICU), hospital, and 28/30-day mortality rates. The heterogeneity of the data was tested using the chi-square test, with a P value < 0.10 indicating significant heterogeneity. RESULTS: A total of 5464 citations were reviewed, of which 10 studies met the inclusion criteria; these studies included 6605 patients. All studies had a Newcastle-Ottawa scale score of 7 or higher. The mean patient age ranged from 51.4 to 64.9 years. The pooled ICU, hospital, and 28/30 day mortality rates were 48% (95% CI, 43- 53%; I2 = 80.6%), 62% (95% CI, 58-67%; I2 = 0%), and 50% (95% CI, 38- 62%; I2 = 98%), respectively. Substantial between-study heterogeneity was observed. CONCLUSION: Critically ill cancer patients with sepsis had poor survival, with a hospital mortality rate of about two-thirds. The substantial observed heterogeneity among studies could be attributed to variability in the criteria used to define sepsis as well as variability in treatment, the severity of illness, and care across settings. Our results are a call to action to identify strategies that improve outcomes for cancer patients with sepsis.

A Systematic Review and Meta-Analysis Evaluating Geographical Variation in Outcomes of Cancer Patients Treated in ICUs.

The reported mortality rates of cancer patients admitted to ICUs vary widely. In addition, there are no studies that examined the outcomes of critically ill cancer patients based on the geographical regions. Therefore, we aimed to evaluate the mortality rates among critically ill cancer patients and provide a comparison based on geography. DATA SOURCES: PubMed, EMBASE, and Web of Science. STUDY SELECTION: We included observational studies evaluating adult patients with cancer treated in ICUs. We excluded non-English studies, those with greater than 30% hematopoietic stem cell transplant or postsurgical patients, and those that evaluated a specific type of critical illness, stage of malignancy, or age group. DATA EXTRACTION: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Studies were classified based on the continent in which they were conducted. Primary outcomes were ICU and hospital mortality. We pooled effect sizes by geographical region. DATA SYNTHESIS: Forty-six studies were included (n = 110,366). The overall quality of studies was moderate. Most of the published literature was from Europe (n = 22), followed by North America (n = 9), Asia (n = 8), South America (n = 5), and Oceania (n = 2). Pooled ICU mortality rate was 38% (95% CI, 33-43%); the lowest mortality rate was in Oceania (26%; 95% CI, 22-30%) and highest in Asia (51%; 95% CI, 44-57%). Pooled hospital mortality rate was 45% (95% CI, 41-49%), with the lowest in North America (37%; 95% CI, 31-43%) and highest in Asia (54%; 95% CI, 37-71%). CONCLUSIONS: More than half of cancer patients admitted to ICUs survived hospitalization. However, there was wide variability in the mortality rates, as well as the number of available studies among geographical regions. This variability suggests an opportunity to improve outcomes worldwide, through optimizing practice and research.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Iatrogenic Toxicities in the Intensive Care Unit.

Drug-induced iatrogenic toxicities are common in critically ill patients and have been associated with increased morbidity and mortality. Early recognition and management of iatrogenic toxicities is essential; however, the diagnosis is usually complicated by the underlying critical illness, comorbidities, and administration of multiple medications. This article reviews several types of iatrogenic toxicities associated with medications that are commonly used in critically ill patients. The mechanism of the iatrogenic toxicities, clinical presentation, and diagnosis, as well as management are discussed.

Effect of hydrocortisone versus methylprednisolone on clinical outcomes in oncology patients with septic shock.

BACKGROUND: Corticosteroids are used as adjunctive treatment of critical illness-related corticosteroid insufficiency in patients with septic shock. This study aims to compare the impact of hydrocortisone versus methylprednisolone on duration of septic shock in critically ill oncology patients. METHODS: Single-center, retrospective cohort study of adult patients receiving hydrocortisone ≥200 mg/day or methylprednisolone ≥40 mg/day with septic shock. The primary outcome was time to shock reversal defined as time to systolic blood pressure ≥90 mmHg without vasopressors for ≥24 h. RESULTS: Eighty-eight patients were included, 49 patients received hydrocortisone and 39 patients received methylprednisolone. Solid tumor malignancy was more common in the hydrocortisone group, while hematological malignancy was more common in the methylprednisolone group (p = 0.009). Time to shock reversal was similar between hydrocortisone and methylprednisolone groups (72.4 versus 70.4 h; p = 0.825). Intensive care unit mortality occurred in 51.02% versus 53.85% of patients in hydrocortisone versus methylprednisolone, respectively (p = 0.792). Patients who received methylprednisolone had higher rates of mechanical ventilation (89.74% versus 55.1%, p < 0.001) and longer intensive care unit and hospital lengths of stay (4.2 versus 11.4 days and 14.3 versus 25.7 days; p < 0.001) compared to hydrocortisone. No differences were seen in incidence of steroid-related adverse effects between groups. CONCLUSIONS: In oncology patients with septic shock, the use of hydrocortisone versus methylprednisolone does not appear to affect time to shock reversal.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

The chimeric antigen receptor-intensive care unit (CAR-ICU) initiative: Surveying intensive care unit practices in the management of CAR T-cell associated toxicities.

PURPOSE: A task force of experts from 11 United States (US) centers, sought to describe practices for managing chimeric antigen receptor (CAR) T-cell toxicity in the intensive care unit (ICU). MATERIALS AND METHODS: Between June-July 2019, a survey was electronically distributed to 11 centers. The survey addressed: CAR products, toxicities, targeted treatments, management practices and interventions in the ICU. RESULTS: Most centers (82%) had experience with commercial and non-FDA approved CAR products. Criteria for ICU admission varied between centers for patients with Cytokine Release Syndrome (CRS) but were similar for Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Practices for vasopressor support, neurotoxicity and electroencephalogram monitoring, use of prophylactic anti-epileptic drugs and tocilizumab were comparable. In contrast, fluid resuscitation, respiratory support, methods of surveillance and management of cerebral edema, use of corticosteroid and other anti-cytokine therapies varied between centers. CONCLUSIONS: This survey identified areas of investigation that could improve outcomes in CAR T-cell recipients such as fluid and vasopressor selection in CRS, management of respiratory failure, and less common complications such as hemophagocytic lymphohistiocytosis, infections and stroke. The variability in specific treatments for CAR T-cell toxicities, needs to be considered when designing future outcome studies of critically ill CAR T-cell patients.

Carbapenem versus Cefepime or Piperacillin-Tazobactam for Empiric Treatment of Bacteremia Due to Extended-Spectrum-ß-Lactamase-Producing Escherichia coli in Patients with Hematologic Malignancy.

Infections with extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL-producing E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single-center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL-producing E. coli bacteremia. No association between increased 14-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to that with carbapenems (19%) was observed (P = 0.19 and P = 0.04, respectively). This observation was consistent in multivariate Cox proportional hazards models adjusted for confounding and an inverse probability of treatment-weighted (IPTW) Cox proportional hazards model. Both fever and persistent bacteremia were more common in patients treated empirically with cefepime or piperacillin-tazobactam. Empiric treatment with cefepime or piperacillin-tazobactam did not result in increased mortality relative to that with treatment with carbapenems in patients with hematologic malignancy and ESBL-producing E. coli bacteremia, although most patients were changed to carbapenems early in treatment. However, due to prolonged fever and persistent bacteremia, their role may be limited in this patient population.