Bayesian methods: a potential path forward for sepsis trials.

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

Effect of a Rapid Response Team on the Incidence of In-Hospital Mortality.

BACKGROUND: Approximately half of the life-limiting events, such as cardiopulmonary arrests or cardiac arrhythmias occurring in hospitals, are considered preventable. These critical events are usually preceded by clinical deterioration. Rapid response teams (RRTs) were introduced to intervene early in the course of clinical deterioration and possibly prevent progression to an event. An RRT was introduced at the Cleveland Clinic in 2009 and transitioned to an anesthesiologist-led system in 2012. We evaluated the association between in-hospital mortality and: (1) the introduction of the RRT in 2009 (primary analysis), and (2) introduction of the anesthesiologist-led system in 2012 and other policy changes in 2014 (secondary analyses). METHODS: We conducted a single-center, retrospective analysis using the medical records of overnight hospitalizations from March 1, 2005, to December 31, 2018, at the Cleveland Clinic. We assessed the association between the introduction of the RRT in 2009 and in-hospital mortality using segmented regression in a generalized estimating equation model to account for within-subject correlation across repeated visits. Baseline potential confounders (demographic factors and surgery type) were controlled for using inverse probability of treatment weighting on the propensity score. We assessed whether in-hospital mortality changed at the start of the intervention and whether the temporal trend (slope) differed from before to after initiation. Analogous models were used for the secondary outcomes. RESULTS: Of 628,533 hospitalizations in our data set, 177,755 occurred before and 450,778 after introduction of our RRT program. Introduction of the RRT was associated with a slight initial increase in in-hospital mortality (odds ratio [95% confidence interval {CI}], 1.17 [1.09-1.25]; P < .001). However, while the pre-RRT slope in in-hospital mortality over time was flat (odds ratio [95% CI] per year, 1.01 [0.98-1.04]; P = .60), the post-RRT slope decreased over time, with an odds ratio per additional year of 0.961 (0.955-0.968). This represented a significant improvement (P < .001) from the pre-RRT slope. CONCLUSIONS: We found a gradual decrease in mortality over a 9-year period after introduction of an RRT program. Although mechanisms underlying this decrease are unclear, possibilities include optimization of RRT implementation, anesthesiology department leadership of the RRT program, and overall improvements in health care delivery over the study period. Our findings suggest that improvements in outcome after RRT introduction may take years to manifest. Further work is needed to better understand the effects of RRT implementation on in-hospital mortality.

Chest pain in patients recovering from noncardiac surgery: A retrospective analysis.

STUDY OBJECTIVE: Chest pain is relatively common postoperatively. Myocardial infarction (MI) is one cause of chest pain after surgery, but chest pain also results from less severe conditions. Because of its potential severity, chest pain usually prompts the activation of Rapid Response Systems (RRS). While chest pain is a cardinal symptom of myocardial ischemia in the non-surgical setting, the significance and relevance of chest pain after noncardiac surgery remains unclear. DESIGN: We conducted a retrospective analysis of noncardiac surgical inpatients for whom postoperative chest pain triggered our multidisciplinary RRS. SETTING: Surgical wards at Cleveland Clinic, Cleveland, OH. PATIENTS: Postsurgical patients after noncardiac surgery in whom the RSS system was activated for chest pain. INTERVENTIONS: RRS specified interventions like ECG readings, troponin measurements, transfer to ICU. MEASUREMENTS: Our primary outcome was MI. Secondary outcomes included the proportion of patients who had an ECG performed, troponin measurements, echocardiography, cardiac catheterization, and were admitted to the Intensive Care Unit (ICU). MAIN RESULTS: 5850 surgical patients experienced postoperative chest pain and triggered an RRS activation between 2009 and 2019. A total of 3110 patients had troponin T measured within 6 h after RRS activation, and 538 of them (17%) had elevated troponin, meeting the Fourth Universal Definition criteria for MI. Additionally, 2 patients had ST-segment elevation infarction (STEMI) without troponin measurement. Among the 540 patients with MI, only 19 (3.5%) were diagnosed with a STEMI by ECG, 388 (72%) had echocardiography, 43 patients (8%) had cardiac catheterization, 8 patients (1.5%) required emergent cardiac surgery, and 424 (79%) were admitted to an ICU. CONCLUSION: Chest pain is a serious clinical sign, often indicating a postoperative myocardial infarction, and therefore should be taken seriously. Troponin screening should be routinely considered in postsurgical patients who report chest pain.

Outcomes Associated with ICU Telemedicine and Other Risk Factors in a Multi-Hospital Critical Care System: A Retrospective, Cohort Study for 30-Day In-Hospital Mortality.

Introduction: Intensive care unit telemedicine (ICU-TM) is expanding due to increasing demands for critical care, but impact on outcomes remains controversial. This study evaluated the association of ICU-TM and other clinical factors with 30-day, in-hospital mortality. Methods: This retrospective, cohort study included 151,780 consecutive ICU patients admitted to nine hospitals in the Cleveland Clinic Health System from 2010 to 2020. Patients were identified from an institutional datamart and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) registry. Primary outcome was 30-day in-hospital mortality. Analyses included multivariate logistic regression modeling, and survival analysis. Results: Overall, unadjusted 30-day, in-hospital mortality incidence was significantly different with (5.6%) or without ICU-TM (7.2%), and risk ratio was 0.78 (95% confidence interval [CI] 0.75-0.81) (p < 0.0001). Mortality rate for ICU-TM and no ICU-TM was 2.4/1,000 versus 3.2/1,000 patient days, respectively (p < 0.0001). Multivariate logistic regression showed that ICU-TM was associated with reduced 30-day mortality (odds ratio 0.78, 95% CI 0.72-0.83). Increased risk was seen with cardiac arrest admissions, males, acute stroke, weekend admission, emergency admission, race (non-white), sepsis, APACHE IV score, ICU length of stay (LOS), and the interaction term, emergency surgical admissions. Reduced risk was associated with hospital LOS, surgical admission, and the interaction terms (weekend admissions with ICU-TM and after-hour admissions with ICU-TM). The model c-statistic was 0.77. Median ICU and hospital lengths of stay were significantly reduced with ICU-TM, with no difference in 48-h mortality or 48-h mortality rate. Conclusion: ICU telemedicine exposure appears to be one of several operational and clinical factors associated with reduced 30-day, in-hospital mortality.

Intracranial hemorrhage surgery on patients on mechanical circulatory support: a case series.

BACKGROUND: Cardiac disease is the leading cause of death in the United States and late-stage heart failure is associated with a high level of morbidity and mortality. The ventricular assist devices and extracorporeal membrane oxygenators are the mainstay of mechanical circulatory support devices for the patients with extremely low cardiac output. However, they come at a price of significant risk factors, including intracranial hemorrhage. The incidence of intracranial hemorrhage on extracorporeal membrane oxygenators and on ventricular assist devices is 37% and 13% to 14%, respectively. METHODS/RESULTS: The cases in this series focus on the risks of ICH and the decompressive craniotomies that were carried out on patients while they were on mechanical circulatory support. The intraoperative anesthetic management for patients on mechanical circulatory support for the noncardiothoracic anesthesiologist is highlighted. CONCLUSIONS: The results of recent cardiothoracic surgery trials have led to an increase of surgical management instead of medical management in the treatment of heart failure. Although most agree with the immediate reversal of anticoagulation and antiplatelet therapy, there is no standard protocol for restarting anticoagulation or antiplatelet therapy after craniotomy in this population. The standard practices of resuscitation and ACLS including inotropes, vasopressors, and vasodilators (with the exception of chest compressions that can dislodge the devices), can be used as needed. The identification of cardiothoracic surgeons and perfusionists who are available for immediate assistance as and when required during the surgery and transportation is an important factor.