Gmehlin, Cameron G.

Abstract Rationale Critically ill lung cancer patients are a growing, high-risk population. However, prognostic tools to guide intensive care unit (ICU) decision-making are limited. Objectives To identify oncologic and critical illness factors associated with 90-day mortality following ICU admission in patients with lung cancer. Methods We conducted a retrospective cohort study of lung cancer patients admitted to the ICU across Mayo Clinic Health System between 2018 and 2024. The primary outcome was 90-day mortality. Two complementary Cox proportional hazards models were developed: a focused model including cancer-specific variables (stage, time since diagnosis, time since last systemic therapy, prior thoracotomy, Eastern Cooperative Oncology Group [ECOG] performance status prior to admission, body mass index, cause of critical illness, code status at admission) and a full model that added broader clinical factors (age and Sequential Organ Failure Assessment [SOFA] score). We also evaluated discharge disposition and transitions in code status. Results Among 528 patients, 90-day mortality was 58.7%. In the focused model (C-index 0.67), independent predictors of mortality included late-stage disease, cancer-specific reason for ICU admission, limitations in resuscitation orders, and ECOG >1. In the full model (C-index 0.95), only age and SOFA score remained significant. Among early-stage patients, recent targeted or combination therapy was associated with higher mortality, though this association may reflect underlying disease characteristics or treatment selection rather than direct treatment effects. Patients who changed code status during admission had high mortality (83%) and a low rate of discharge home (11%). Conclusion Lung cancer patients admitted to ICU experience high short-term mortality, with outcomes shaped by both oncologic status and the severity of acute illness. A dual-model approach suggests a risk hierarchy: Cancer-specific factors inform baseline mortality risk with an ICU admission, but age and physiologic derangement are the dominant drivers of survival once critical illness develops. These findings support dynamic, multidisciplinary prognostication and underscore the need to integrate oncology and critical care expertise in ICU decision-making.

This systematic review examined multicenter randomized controlled trials (RCTs) conducted during the Sepsis-3 era that evaluated pharmaceutical and mechanistic interventions in adult patients with sepsis or septic shock, with a focus on identifying interventions that demonstrated mortality benefit. A comprehensive search was performed across Ovid MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, WHO ICTRP, and Web of Science for trials published since 2016. Studies were included if they enrolled adult patients with sepsis or septic shock using Sepsis-3 criteria and reported mortality as either a primary or secondary outcome. Data were extracted by two independent reviewers and included trial design characteristics, funding source, randomization methods, and reported outcomes. Among the 31 eligible multicenter RCTs enrolling over 7,000 patients across 550 centers, only four trials showed a mortality benefit. These included three studies from China—two evaluating herbal anti-inflammatory compounds and one evaluating aminophylline—and one European study assessing corticosteroid therapy in vasopressor-dependent septic shock. The remaining 27 trials reported no mortality benefit, and substantial heterogeneity was observed in patient populations, sepsis definitions, and outcome reporting. Median mortality in control arms was 31.6% (IQR 24.1–45.5), and 35.4% (IQR 25.7–49.6) in intervention arms. These findings suggest that despite extensive efforts, most interventions have not reduced mortality in multicenter sepsis trials. Future research should focus on optimizing trial design, refining patient selection, and incorporating patient-centered outcomes beyond mortality.

IMPORTANCE: Patients admitted to the ICU often experience gastrointestinal complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become increasingly prevalent in the treatment of type 2 diabetes mellitus and obesity, and there is evidence that their use may be associated with an increased risk of clinically significant gastrointestinal events. However, their impact on critically ill patients admitted to the medical ICU is unknown. OBJECTIVES: This study examined whether pre-ICU use of GLP-1RAs was associated with increased incidence of gastrointestinal complications and hospitalization outcomes. DESIGN, SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of critically ill patients admitted to academic and community hospitals of Mayo Clinic Health System from January 1, 2018, to December 31, 2023. Patients who were admitted to surgical ICUs and those who were exposed to GLP-1RA medications before but did not have an active prescription within 30 days of admission were excluded. Patients exposed to GLP-1RA were matched with those nonexposed in a 1:1 fashion based on demographic factors, factors affecting gastrointestinal motility, overall illness burden, and clinical acuity. MAIN OUTCOMES AND MEASURES: Outcomes of interest were the development of gastrointestinal dysfunction, ICU- and hospital-free days, and mortality. RESULTS: A total of 31,327 patients with diabetes or obesity were identified of whom these, 631 were exposed to GLP-1RA before admission. In the matched cohort of 1262 patients, baseline variables were evenly distributed between the two groups. There were no significant differences in the odds of developing nausea/vomiting, constipation, ileus, obstruction, impaction, or aspiration pneumonia between the GLP-1RA exposed and unexposed groups. Similarly, ICU and hospital mortality rates were comparable across the two groups. However, GLP-1RA exposed patients had significantly more hospital-free days compared with unexposed patients (estimate, 1.19; 95% CI, 0.38–2.0; p = 0.004). CONCLUSIONS AND RELEVANCE: GLP-1RA exposure was not associated with increased odds of clinically significant gastrointestinal complications in nonsurgical critically ill patients. Increased hospital-free days observed among GLP-1RA exposed patients requires further study.

Abstract RATIONALE: Critical illness has been shown to disrupt gastrointestinal function, and patients admitted to the intensive care unit (ICU) often experience constipation, aspiration, ileus, and small bowel obstruction. Glucagon-like peptide 1 receptor agonists (GLP-1RA) have become increasingly prevalent in the treatment of type 2 diabetes mellitus and obesity. Pharmacovigilance studies suggest that use of GLP-1RAs may be associated with increased risk of clinically significant gastrointestinal effects. In this study, we assessed whether pre-ICU use of GLP-1RA for either diabetes or obesity was associated with adverse gastrointestinal outcomes. METHODS: This was a retrospective matched cohort study of patients with underlying obesity or diabetes admitted to a Mayo Clinic Medical ICU from 9/1/2018-12/31/2023. Patients who started GLP-1RA within <30 days or stopped them >30 days before admission were excluded. Out of 33,104 eligible patients, we identified 1,549 GLP-1RA exposed patients and matched these to three controls each based on age (±10), sex, body mass index (±5), presence of obesity, diabetes and complications, comorbidities associated with decreased motility, smoking status, alcoholism, abdominal surgeries, Apache score (±20), and Charlson comorbidity index (CCI). Development of gastrointestinal dysfunction (determined by ICD codes) and hospital- and ICU- free days were the outcomes. Conditional logistic regression and mixed linear models were used for the analyses. RESULTS: The final, matched cohort included 6,196 patients. Most patients were male (56.3%), the median age was 66 years (IQR 58-74), 69.9% had a diagnosis of obesity, and 97.5% had a diagnosis of diabetes. Of the patients, 22.9% had a history of abdominal surgery during their lifetime and 30% had surgery within 30 days of admission. When comparing GLP-1RA exposed and non-exposed patients, significant differences were noted in use of motility altering medications (p=0.001, OR 6.75, CI 2.11-21.56), BMI (p<0.001, estimate=0.6, CI 0.47-0.72), and APACHE score (p<0.001, estimate=14.75, CI14.45 – 15.06). Univariable analysis showed that rates of constipation, impaction, and nausea/vomiting were significantly higher among GLP-1RA exposed patients admitted to the ICU, while rates of obstruction were significantly lower (Table 1). After adjusting for APACHE score, only nausea/vomiting remained statistically significant. After controlling for APACHE, GLP-1RA use was associated with an increased number of hospital free days (Table 1). CONCLUSIONS: Our research suggests that in the medical ICU population, GLP-1RA use is unlikely to be associated with adverse GI outcomes. Furthermore, GLP-1RA may be associated with overall hospital length of stay but not ICU length of stay.