Citations

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.

Abstract RATIONALE: Clinical practice guidelines recommend that mechanically ventilated patients (MVPs) receiving sedative therapy achieve a target goal of ‘awake and calm’ when medically possible. However, ICU sedation practices rely on clinicians’ administration of medications based on observations of patients’ arousal/motor activity that are not consistently based on symptom assessments nor consider patients’ preferences. We hypothesized that MVPs would safely self-manage sedative therapy (SMST) base on individual needs and perceived anxiety while experiencing less sedative exposure and delirium. METHODS: A two-group randomized clinical trial conducted in two Midwestern academic medical centers enrolled 161 MVPs willing and able to depress a medication delivery push-button device who remained on protocol for 7 days or until extubated, withdrew or died. Control group (CG) patients (n=81) received sedative medications administered by ICU nurses per unit protocols. Experimental SMST group patients (n=80) received a basal infusion of dexmedetomidine (0.2 mcg/kg/hr titrated per algorithm) + self-administered bolus doses (0.25 mcg/kg up to 3/hour). Primary outcomes were anxiety ratings using a 100-mm visual analog scale (VAS-A), sedation intensity score (aggregate summary of 9 intravenous sedative/opioid medications received range 0-36), and incidence of delirium using the CAM-ICU. Analyses were descriptive and parametric statistics and Generalized Estimating Equations. RESULTS: Patients were predominantly White (93%) females (55%), mean age 58.9+15.1 years receiving mechanical ventilation for respiratory failure (60%) with mean APACHE III of 84.5 + 32.5. Anxiety was highly variable over time wherein patients in both groups endorsed the full range from 0-100. VAS-A over time between groups was -0.06 (p=0.98) indicating that anxiety was 0.06 units lower for SMST patients versus CG. Median sedation intensity in SMST group 11.8 + 9.6, compared to CG 12.7 + 9.6 (p = 0.55) over 7 days. 10.2% of SMST patients had one or more incident delirium events compared to 8.5% of CG (p =.97). Hypotension was experienced equally between groups: 22 in SMST, 23 in CG (p = 1.0) as were device disruptions: 2 in SMST versus 3 in CG (p = 1.0). 82% of SMST were satisfied/very satisfied with ability to self-administer dexmedetomidine; 70% were satisfied/very satisfied with ability to control anxiety; 68% were satisfied/very satisfied with the level of relaxation experienced. CONCLUSIONS: Although there were no significant differences between groups on the primary outcomes, the experimental SMST intervention was safe with high patient-reported satisfaction. SMST may be a viable new paradigm for sedative therapy administration among select ICU patients.

Abstract Objective: Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments. Design: Retrospective cohort study. Methods: The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results: MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation. Conclusions: The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.

Importance Anemia is a common complication of surgery and acute illness that is associated with adverse clinical outcomes. The role of anemia prevention and treatment strategies in this setting remains unclear. Objective To evaluate the effect of a multifaceted anemia management bundle vs standard care on posthospitalization hemoglobin recovery and multidimensional functional outcomes in survivors of acute illness. Design, Setting, and Participants This parallel group randomized clinical trial, known as the Practical Anemia Bundle for Sustained Blood Recovery, was conducted at postsurgical and medical intensive care units at a large US medical center. Critically ill patients (aged ≥18 years) with moderate to severe anemia (hemoglobin concentration <10 g/dL) were enrolled between March 2022 and November 2023. Participants were randomly assigned 1:1 to the intervention or standard care group. Intention-to-treat analyses were performed between July 2024 and January 2025. Intervention The intervention bundle was delivered throughout the duration of hospitalization and included optimized phlebotomy practices, clinical decision support, and pharmacological anemia treatment with intravenous iron. Main Outcomes and Measures The primary outcome was the mean difference in hemoglobin concentration at 1 month after hospital discharge. Results A total of 100 patients (median [IQR] age, 68 [61-72] years; 57 men [57.0%]; 65 [65.0%] with postsurgical admission to the intensive care unit) were enrolled during acute illness. Forty-nine patients (49.0%) were assigned to receive the intervention, and 51 (51.0%) were assigned to receive standard care. Hemoglobin concentration at 1 month after discharge was greater in patients receiving the intervention vs standard care (median [IQR], 12.2 [11.8-13.0] g/dL vs 11.5 [10.2-12.6] g/dL; adjusted mean difference, 0.69 [95% CI, 0.13-1.20] g/dL; P = .02). Conclusions and Relevance This randomized clinical trial found that a multifaceted anemia prevention and treatment bundle was feasible, was well tolerated, and improved posthospitalization hemoglobin concentrations up to 3 months in critically ill adults. These findings can inform the design of future trials. Trial Registration ClinicalTrials.gov Identifier: NCT05167734

Objectives There is substantial practice variation in the management strategies for atrial fibrillation (AF) with rapid ventricular rate (RVR) and hemodynamic instability in critically ill patients. This study aimed to evaluate the use and effectiveness of direct current cardioversion (DCCV) for unstable AF RVR in the intensive care unit (ICU). Design Multicenter retrospective cohort study. Setting Non-cardiac/cardiovascular surgery ICUs of the Mayo Clinic Hospitals in Minnesota, Wisconsin, Florida, and Arizona. Patients Adult patients who developed paroxysmal AF RVR with hemodynamic instability (heart rate ≥ 130 beats per minute and a documented SBP ≤ 90 mmHg or the need for vasopressors) during ICU stay. Interventions Emergency DCCV. Measurements and Main Results Primary outcomes were in-hospital mortality, hospital-, ICU-, and organ support-free days. Secondary outcomes were return to sinus rhythm rate before and after discharge. Among 691 patients eligible for inclusion, 47 (6.8%) received emergent DCCV in the ICU. The frequency of DCCV was higher for patients located in surgical ICUs (14.5% vs 6.1%, P = .04). Patients were 1:2 propensity-score matched. The comparative analyses were conducted on 141 patients. Those who underwent DCCV were more likely to restore sinus rhythm (odds ratio [95% confidence interval], 5.2 [1.30 20.8]). However, DCCV was not associated with increased odds of having sinus rhythm at discharge, lower mortality, or higher number of ICU-, or hospital-free days. The number of organ support-free days was significantly lower in the DCCV group (estimate ± standard error, −5.0 ± 2.0, P = .012). Conclusions Emergency DCCV is rarely used to treat unstable AF in non-cardiac ICUs. Despite increased likelihood of immediate sinus rhythm restoration, DCCV was not associated with improvement in patient-centered outcomes. Prospective studies are warranted to evaluate harms and benefits of DCCV in non-cardiac critically ill patients with unstable AF where the driver of hemodynamic instability is often an underlying condition rather than arrhythmia per se.

OBJECTIVES: Estimated glomerular filtration rate is more accurate with combined creatinine and cystatin C equations (eGFRcr-cys) than creatinine alone. This study created and evaluated a cefepime dosing nomogram based on eGFRcr-cys for initial dosing in the critically ill. DESIGN: Pharmacokinetic modeling and simulation study. SETTING: Academic medical center. PATIENTS: Critically ill adults treated with cefepime. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 120 patients with baseline cystatin C and follow-up cefepime levels were used to develop a nomogram based on eGFRcr-cys and weight for initial cefepime dosing. The predicted proportion of patients who achieved a free cefepime concentration above the minimum inhibitory concentration of the organism for 100% of the dosing interval in the first 24 hours (100% ƒT > MIC at 24 hr) was compared between administered doses and those predicted by the nomogram doses. Overall drug exposure was estimated with the free area under the concentration time curve from 0 to 24 hours (ƒAUC0–24) and compared between administered and nomogram doses. Achievement of 100% ƒT > MIC at 24 hours was predicted to be significantly better with the nomogram compared with the administered dose (76% vs. 38%; p < 0.001). The median ƒAUC0–24 as predicted by the nomogram (666 mg·hr/L) was slightly higher than the actual ƒAUC0–24 with administered doses (612 mg·hr/L; p = 0.01), but the nomogram led to fewer ƒAUC0–24 values which were either too high (> 900) or too low (< 300) (7% vs. 20%; p = 0.004). CONCLUSIONS: Use of a cystatin C-inclusive dosing nomogram for cefepime could improve target attainment without increasing the risk of potentially toxic levels in the critically ill.