Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Management of respiratory failure in immune checkpoint inhibitors-induced overlap syndrome: a case series and review of the literature.

BACKGROUND: Checkpoint inhibitor-induced overlap syndrome ([OS] myocarditis, and myositis with or without myasthenia gravis) is rare but life-threatening. CASES PRESENTATION: Here we present a case series of four cancer patients that developed OS. High troponinemia raised the concern for myocarditis in all the cases. However, the predominant clinical feature differed among the cases. Two patients showed marked myocarditis with a shorter hospital stay. The other two patients had a prolonged ICU stay due to severe neuromuscular involvement secondary to myositis and myasthenia gravis. Treatment was based on steroids, plasmapheresis, intravenous immunoglobulin, and immunosuppressive biological agents. CONCLUSION: The management of respiratory failure is challenging, particularly in those patients with predominant MG. Along with intensive clinical monitoring, bedside respiratory mechanics can guide the decision-making process of selecting a respiratory support method, the timing of elective intubation and extubation.

Clinical Characteristics and Cause of Death Among Hospitalized Decedents With Cancer and COVID-19.

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among nonsurvivors, 31 (51%) patients had hematologic cancers, and 29 (48%) had undergone cancer-directed chemotherapy within 3 months before admission. The median time to death was 15 days (95% confidence interval [CI], 11.8 to 18.2). There were no differences in time to death by cancer category or cancer treatment intent. The majority of decedents (84%) had full code status at admission; however, 53 (87%) had do-not-resuscitate orders at the time of death. Most deaths were deemed to be COVID-19 related (88.5%). The concordance between the reviewers for the cause of death was 78.7%. In contrast to the belief that COVID-19 decedents die because of their comorbidities, in our study only 1 of every 10 patients died of cancer-related causes. Full-scale interventions were offered to all patients irrespective of oncologic treatment intent. However, most decedents in this population preferred care with nonresuscitative measures rather than full support at the end of life.

Sepsis-Related Outcomes of Patients with Philadelphia-Negative Myeloproliferative Neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than nonseptic patients (7.5% vs 1.8%; p < .001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

Sepsis-related outcomes of patients with Philadelphia-negative myeloproliferative neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than non-septic patients (7.5% vs 1.8%; P<.001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

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.

Outcomes and Predictors of 28-Day Mortality in Patients With Solid Tumors and Septic Shock Defined by Third International Consensus Definitions for Sepsis and Septic Shock Criteria.

BACKGROUND: Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce. RESEARCH QUESTION: What are the independent predictors of 28-day mortality in critically ill adults with solid tumors and septic shock? STUDY DESIGN AND METHODS: Cohort of solid tumor patients admitted to the ICU with septic shock. Demographic and clinical characteristics were gathered from the electronic health records. We developed a reduced multivariate logistics regression model to identify independent predictors of 28-day mortality and used Kaplan-Meier plots to assess survival. RESULTS: A total of 271 patients were included. The median age was 62 years (range, 19-94 years); 57.2% were men and 53.5% were White. The most common underlying malignancies were lung (19.2%), breast (7.7%), pancreatic (7.7%), and colorectal (7.4%) cancers. Most patients (84.5%) harbored metastatic disease. Twenty-eight days after ICU admission, 188 patients (69.4%) had died. Nonsurvivors showed a higher rate of advanced cancer, longer hospital stays before ICU admission, and higher Sequential Organ Failure Assessment scores at admission and throughout the ICU stay (P < .001 for all). The multivariate analysis identified metastatic disease (OR, 3.17; 95% CI, 1.43-7.03), respiratory failure (OR, 2.34; 95% CI, 1.15-4.74), elevated lactate levels (OR, 3.19; 95% CI, 1.90-5.36), and Eastern Cooperative Oncology Group performance scores of 3 or 4 (OR, 2.72; 95% CI, 1.33-5.57) as independent predictors of 28-day mortality. Only 38 patients (14%) were discharged home without medical assistance. INTERPRETATION: The 28-day mortality rate of patients with solid tumors and septic shock was considerably high. Factors associated with worse survival included advanced oncologic disease, poor performance status, high lactate level, and concomitant acute respiratory failure. Early goals-of-care discussions should be considered for frail patients with septic shock and advanced metastatic disease without denying access to the appropriate level of care.

Outcomes and Predictors of 28-Day Mortality in Patients With Hematologic Malignancies and Septic Shock Defined by Sepsis-3 Criteria.

BACKGROUND: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. METHODS: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. RESULTS: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18-89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03-1.20), respiratory failure (OR, 3.12; 95% CI, 1.49-6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10-1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26-0.69), serum albumin (OR, 0.51; 95% CI, 0.31-0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24-0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. CONCLUSIONS: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.

Humanizing the intensive care unit experience in a comprehensive cancer center: A patient- and family-centered improvement study.

OBJECTIVES: Improving family-centered outcomes is a priority in oncologic critical care. As part of the Intensive Care Unit (ICU) Patient-Centered Outcomes Research Collaborative, we implemented patient- and family-centered initiatives in a comprehensive cancer center. METHODS: A multidisciplinary team was created to implement the initiatives. We instituted an open visitation policy (OVP) that revamped the use of the two-way communication boards and enhanced the waiting room experience by hosting ICU family-centered events. To assess the initiatives' effects, we carried out pre-intervention (PRE) and post-intervention (POST) family/caregiver and ICU practitioner surveys. RESULTS: A total of 159 (PRE = 79, POST = 80) family members and 147 (PRE = 95, POST = 52) ICU practitioners participated. Regarding the decision-making process, family members felt more included (40.5% vs. 68.8%, p < 0.001) and more supported (29.1% vs. 48.8%, p = 0.011) after the implementation of the initiatives. The caregivers also felt more control over the decision-making process in the POST survey (34.2% vs. 56.3%, p = 0.005). Although 33% of the ICU staff considered OVP was beneficial for the ICU, 41% disagreed and 26% were neutral. Only half of them responded that OVP was beneficial for patients and 63% agreed that OVP was beneficial for families. Half of the practitioners agreed that OVP resulted in additional work for staff. SIGNIFICANCE OF RESULTS: Our project effectively promoted patient- and family-centered care. The families expressed satisfaction with the communication of information and the decision-making process. However, the ICU staff felt that the initiatives increased their work load. Further research is needed to understand whether making this project universal or introducing additional novel practices would significantly benefit patients admitted to the ICU and their family.

Pain management during the withholding and withdrawal of life support in critically ill patients at the end-of-life: a systematic review and meta-analysis.

PURPOSE: To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the intensive care unit. METHODS: We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Virtual Health Library from inception through March 2019. We considered any study evaluating pharmaceutical interventions for pain management during the withholding or withdrawing of life support in adult critically ill patients at the end-of-life. Two independent investigators performed the screening and data extraction. We pooled data on utilization rate of analgesic and sedative drugs and summarized the dosing between the moment prior to withholding or withdrawal of life support and the moment before death. RESULTS: Thirteen studies met inclusion criteria. Studies were conducted in the United States (38%), Canada (31%), and the Netherlands (31%). Eleven studies were single-cohort and twelve had a Newcastle-Ottawa Scale score of less than 7. The mean age of the patients ranged from 59 to 71 years, 59-100% were mechanically ventilated, and 47-100% of the patients underwent life support withdrawal. The most commonly used opioid and sedative were morphine [utilization rate 60% (95% CI 48-71%)] and midazolam [utilization rate 28% (95% CI 23-32%)], respectively. Doses increased during the end-of-life process (pooled mean increase in the dose of morphine: 2.6 mg/h, 95% CI 1.2-4). CONCLUSIONS: Pain control is centered on opioids and adjunctive benzodiazepines, with dosages exceeding those recommended by guidelines. Despite consistency among guidelines, there is significant heterogeneity among practices in end-of-life care.

Critical Care Admission of an HIV Patient with Diabetic Ketoacidosis Secondary to Pembrolizumab.

BACKGROUND: Pembrolizumab is a checkpoint inhibitor that targets the programmed cell death-1 receptor (PD-1) and has shown to be effective against several malignancies, including lung cancer. However, life-threatening immune-related adverse events can result from these immunotherapy treatments. Case presentation. A 62-year-old man with HIV, metastatic adenocarcinoma of the lung, and no previous history of diabetes presented to the emergency department with new-onset nausea, vomiting, and generalized weakness. Glucose was 1191 mg/dl, hemoglobin A1c 11%, and potassium 6.9 mEq/L. He had metabolic acidosis with a lactate of 6.6 mmol/L and anion gap of 38 mEq/L, and ketones were detected on the urinalysis. Severe diabetic ketoacidosis was diagnosed, and the patient was admitted to the intensive care unit. Additional investigations showed low C-peptide and negative anti-glutamic acid decarboxylase antibody, anti-insulin antibody, and anti-islet-antigen 2Ab antibody. After ruling out other possible etiologies, pembrolizumab was considered to be the cause of the diabetes and ketoacidosis. CONCLUSIONS: Life-threatening adverse drug events associated with checkpoint inhibitors such as pembrolizumab are on the rise. We recommend to closely follow and monitor patients receiving these immunotherapies. This strategy could lead to early detection and prevention, as well as reduction of more serious life-threatening complications requiring intensive care.

Hemorrhagic Shock Secondary to Aortoesophageal Fistula as a Complication of Esophageal Cancer.

Although aortoesophageal fistulas are rare, they can present as life-threatening emergencies. This condition can develop secondary to an aneurysm, foreign bodies, infiltrating tumors, and radiotherapy. We report a patient with hemorrhagic shock secondary to an aortoesophageal fistula. A 69-year-old male with squamous cell carcinoma of the esophagus treated with chemoradiation and metallic stent placement was admitted to the intensive care unit (ICU) after an episode of hematemesis. The patient was hemodynamically unstable, requiring fluid resuscitation, blood transfusions, and respiratory and vasopressor support. The patient developed electric pulseless activity, and cardiopulmonary resuscitation was performed for 40 minutes. An upper endoscopy showed the esophageal tumor infiltrating into the stent, and computed tomography (CT) angiogram showed leakage of contrast from the thoracic aorta to the esophagus. The diagnosis of aortoesophageal fistula was made. The patient underwent endovascular management for the fistula. However, his critical condition did not improve, and the patient perished.

Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-Life Patients: A Systematic Review.

OBJECTIVES: To identify and synthesize available recommendations from scientific societies and experts on pain management at the end-of-life in the ICU. DATA SOURCES: We conducted a systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their inception until March 28, 2019. STUDY SELECTION: We included all clinical practice guidelines, consensus statements, and benchmarks for quality. DATA EXTRACTION: Study selection, methodological quality, and data extraction were performed independently by two investigators. A quality assessment was performed by four investigators using the Appraisal of Guidelines for Research and Evaluation II instrument. The recommendations were then synthesized and categorized. DATA SYNTHESIS: Ten publications were included. The Appraisal of Guidelines for Research and Evaluation II statement showed low scores in various quality domains, especially in the applicability and rigor of development. Most documents were in agreement on five topics: 1) using a quantitative tool for pain assessment; 2) administering narcotics for pain relief and benzodiazepines for anxiety relief; 3) against prescribing neuromuscular blockers during withdrawal of life support to assess pain; 4) endorsing the use of high doses of opioids and sedatives for pain control, regardless of the risk that they will hasten death; and 5) using quality indicators to improve pain management during end-of-life in the ICU. CONCLUSIONS: In spite of the lack of high-quality evidence, recommendations for pain management at the end-of-life in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Considering the growing demand for the involvement of palliative care teams in the management of the dying patients in the ICU, there is a need to clearly define their early involvement and to further develop comprehensive evidence-based pain management strategies. Based on the study findings, we propose a management algorithm to improve the overall care of dying critically ill patients.

Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. OBJECTIVE: To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. METHODS: We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). RESULTS: Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). CONCLUSIONS: Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.