Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseases.

Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years.

Association of Time to Rapid Response Team Activation With Patient Outcomes Using a Range of Physiologic Deterioration Thresholds.

Clinical deterioration of hospitalized patients is common and can lead to critical illness and death. Rapid response teams (RRTs) assess and treat high-risk patients with signs of clinical deterioration to prevent further worsening and subsequent adverse outcomes. Whether activation of the RRT early in the course of clinical deterioration impacts outcomes, however, remains unclear. We sought to characterize the relationship between increasing time to RRT activation after physiologic deterioration and short-term patient outcomes. DESIGN: Retrospective multicenter cohort study. SETTING: Three academic hospitals in Pennsylvania. PATIENTS: We included the RRT activation of a hospitalization for non-ICU inpatients greater than or equal to 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was time to RRT activation after physiologic deterioration. We selected four Cardiac Arrest Risk Triage (CART) score thresholds a priori from which to measure time to RRT activation (CART score ≥ 12, ≥ 16, ≥ 20, and ≥ 24). The primary outcome was 7-day mortality-death or discharge to hospice care within 7 days of RRT activation. For each CART threshold, we modeled the association of time to RRT activation duration with 7-day mortality using multivariable fractional polynomial regression. Increased time from clinical decompensation to RRT activation was associated with higher risk of 7-day mortality. This relationship was nonlinear, with odds of mortality increasing rapidly as time to RRT activation increased from 0 to 4 hours and then plateauing. This pattern was observed across several thresholds of physiologic derangement. CONCLUSIONS: Increasing time to RRT activation was associated in a nonlinear fashion with increased 7-day mortality. This relationship appeared most marked when using a CART score greater than 20 threshold from which to measure time to RRT activation. We suggest that these empirical findings could be used to inform RRT delay definitions in further studies to determine the clinical impact of interventions focused on timely RRT activation.

Impact of COVID-19 on inpatient clinical emergencies: A single-center experience.

AIM: Determine changes in rapid response team (RRT) activations and describe institutional adaptations made during a surge in hospitalizations for coronavirus disease 2019 (COVID-19). METHODS: Using prospectively collected data, we compared characteristics of RRT calls at our academic hospital from March 7 through May 31, 2020 (COVID-19 era) versus those from January 1 through March 6, 2020 (pre-COVID-19 era). We used negative binomial regression to test differences in RRT activation rates normalized to floor (non-ICU) inpatient census between pre-COVID-19 and COVID-19 eras, including the sub-era of rapid COVID-19 census surge and plateau (March 28 through May 2, 2020). RESULTS: RRT activations for respiratory distress rose substantially during the rapid COVID-19 surge and plateau (2.38 (95% CI 1.39-3.36) activations per 1000 floor patient-days v. 1.27 (0.82-1.71) during the pre-COVID-19 era; p = 0.02); all-cause RRT rates were not significantly different (5.40 (95% CI 3.94-6.85) v. 4.83 (3.86-5.80) activations per 1000 floor patient-days, respectively; p = 0.52). Throughout the COVID-19 era, respiratory distress accounted for a higher percentage of RRT activations in COVID-19 versus non-COVID-19 patients (57% vs. 28%, respectively; p = 0.001). During the surge, we adapted RRT guidelines to reduce in-room personnel and standardize personal protective equipment based on COVID-19 status and risk to providers, created decision-support pathways for respiratory emergencies that accounted for COVID-19 status uncertainty, and expanded critical care consultative support to floor teams. CONCLUSION: Increased frequency and complexity of RRT activations for respiratory distress during the COVID-19 surge prompted the creation of clinical tools and strategies that could be applied to other hospitals.

Understanding Debriefing: A Qualitative Study of Event Reconstruction at an Academic Medical Center.

PURPOSE: This qualitative study sought to characterize the role of debriefing after real critical events among anesthesia residents at the Hospital of the University of Pennsylvania. METHOD: From October 2016 to June 2017 and February to April 2018, the authors conducted 25 semistructured interviews with 24 anesthesia residents after they were involved in 25 unique critical events. Interviews focused on the experience of the event and the interactions that occurred thereafter. A codebook was generated through annotation, then used by 3 researchers in an iterative process to code interview transcripts. An explanatory model was developed using an abductive approach. RESULTS: In the aftermath of events, residents underwent a multistage process by which the nature of critical events and the role of residents in them were continuously reconstructed. Debriefing-if it occurred-was 1 stage in this process, which also included stages of internal dialogue, event documentation, and lessons learned. Negotiated in each stage were residents' culpability, reputation, and the appropriateness of their affective response to events. CONCLUSIONS: Debriefing is one of several stages of interaction that occur after a critical event; all stages play a role in shaping how the event is interpreted and remembered. Because of its dynamic role in constituting the nature of events and residents' role in them, debriefing can be a high-stakes interaction for residents, which can contribute to their reluctance to engage in it. The function and quality of debriefing can be assessed in more insightful fashion by understanding its relation to the other stages of event reconstruction.

Failure to Debrief after Critical Events in Anesthesia Is Associated with Failures in Communication during the Event.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Debriefing after an actual critical event is an established good practice in medicine, but a gap exists between principle and implementation. WHAT THIS ARTICLE TELLS US THAT IS NEW: Failure to debrief after critical events is common among anesthesia trainees and likely anesthesia teams. Communication breakdowns are associated with a high rate of the failure to debrief. BACKGROUND: Debriefing after an actual critical event is an established good practice in medicine, but a gap exists between principle and implementation. The authors' objective was to understand barriers to debriefing, characterize quantifiable patterns and qualitative themes, and learn potential solutions through a mixed-methods study of actual critical events experienced by anesthesia personnel. METHODS: At a large academic medical center, anesthesiology residents and a small number of attending anesthesiologists were audited and/or interviewed for the occurrence and patterns of debriefing after critical events during their recent shift, including operating room crises and disruptive behavior. Patterns of the events, including event locations and event types, were quantified. A comparison was done of the proportion of cases debriefed based on whether the event contained a critical communication breakdown. Qualitative analysis, using an abductive approach, was performed on the interviews to add insight to quantitative findings. RESULTS: During a 1-yr period, 89 critical events were identified. The overall debriefing rate was 49% (44 of 89). Nearly half of events occurred outside the operating room. Events included crisis events (e.g., cardiac arrest, difficult airway requiring an urgent surgical airway), disruptive behavior, and critical communication breakdowns. Events containing critical communication breakdowns were strongly associated with not being debriefed (64.4% [29 of 45] not debriefed in events with a communication breakdown vs. 36.4% [16 of 44] not debriefed in cases without a communication breakdown; P = 0.008). Interview responses qualitatively demonstrated that lapses in communication were associated with enduring confusion that could inhibit or shape the content of discussions between involved providers. CONCLUSIONS: Despite the value of proximal debriefing to reducing provider burnout and improving wellness and learning, failure to debrief after critical events can be common among anesthesia trainees and perhaps anesthesia teams. Modifiable interpersonal factors, such as communication breakdowns, were associated with the failure to debrief.

Quality Improvement in Anesthesiology - Leveraging Data and Analytics to Optimize Outcomes.

Quality improvement is at the heart of practice of anesthesiology. Objective data are critical for any quality improvement initiative; when possible, a combination of process, outcome, and balancing metrics should be evaluated to gauge the value of an intervention. Quality improvement is an ongoing process; iterative reevaluation of data is required to maintain interventions, ensure continued effectiveness, and continually improve. Dashboards can facilitate rapid analysis of data and drive decision making. Large data sets can be useful to establish benchmarks and compare performance against other providers, practices, or institutions. Audit and feedback strategies are effective in facilitating positive change.

Improving Providers' Role Definitions to Decrease Overcrowding and Improve In-Hospital Cardiac Arrest Response.

BACKGROUND: How nontechnical factors such as inadequate role definition and overcrowding affect outcomes of in-hospital cardiac arrest (IHCA) is unknown. Using a bundled intervention, we sought to improve providers' role definitions and decrease overcrowding during IHCA events. OBJECTIVES: To determine if a bundled intervention consisting of a nurse/physician leadership dyad, visual cues for provider roles, and a "role check" would lead to reductions in crowding and improve perceptions of communication and team leadership. METHODS: Baseline data on the number and type of IHCA providers were collected. Providers were asked to complete a postevent survey rating communication and leadership. A bundled intervention was then introduced. Data were then obtained for the subsequent IHCA events. RESULTS: Twenty ICHA events were captured before and 34 after the intervention. The number of physicians present at pulse checks 2 (median [interquartile range]: 6 [5-8] before vs 5 [3-6] after, P = .02) and 3 (7 [5-9] vs 4 [4-5], P = .004) decreased significantly after the intervention. The overall number of providers at the third pulse check (18 [14-22] before vs 14 [12-16] after, P = .04) also decreased after the intervention. On a 10-point Likert scale, ratings of communication (8 [7-8]) and physician leadership (8 [7-9]) did not differ significantly from before to after the intervention. Both the physician leads (90%) and patients' primary nurses (97%) were able to identify clear nurse leaders. CONCLUSION: A bundled intervention targeted at improving IHCA response led to a decrease in overcrowding at ICHA events without substantial changes in the perceptions of communication or physician leadership.

Interdisciplinary rounds in the postanesthesia care unit: a new perioperative paradigm.

Patients in the perioperative and postanesthesia care unit (PACU) experience several transitions in patient care at the same time that the majority of major morbidities will arise. The transitions for these patients are at the critical juncture between surgery and a steady sustained recovery. Historically these important medical problems have been addressed as a nonformalized process. The authors have introduced a formalized process, based on interdisciplinary rounding strategies used in intensive care units, to attend patients and address problems.

Optical reversal of halothane-induced immobility in C. elegans.

Volatile anesthetics (VAs) cause profound neurological effects, including reversible loss of consciousness and immobility. Despite their widespread use, the mechanism of action of VAs remains one of the unsolved puzzles of neuroscience [1, 2]. Genetic studies in Caenorhabditis elegans [3, 4], Drosophila [3, 5], and mice [6-9] indicate that ion channels controlling the neuronal resting membrane potential (RMP) also control anesthetic sensitivity. Leak channels selective for K(+) [10-13] or permeable to Na(+) [14] are critical for establishing RMP. We hypothesized that halothane, a VA, caused immobility by altering the neuronal RMP. In C. elegans, halothane-induced immobility is acutely and completely reversed by channelrhodopsin-2 based depolarization of the RMP when expressed specifically in cholinergic neurons. Furthermore, hyperpolarizing cholinergic neurons via halorhodopsin activation increases sensitivity to halothane. The sensitivity of C. elegans to halothane can be altered by 25-fold by either manipulation of membrane conductance with optogenetic methods or generation of mutations in leak channels that set the RMP. Immobility induced by another VA, isoflurane, is not affected by these treatments, thereby excluding the possibility of nonspecific hyperactivity. The sum of our data indicates that leak channels and the RMP are important determinants of halothane-induced general anesthesia.

Anesthetic considerations for the patient undergoing therapy for advanced heart failure.

PURPOSE OF REVIEW: Advanced heart failure (AHF) affects a growing percentage of our population. The anesthesiologist must be cognizant of the perioperative considerations of patients undergoing state-of-the-art therapy for AHF. These therapies include classic and novel agents to improve systolic function, neurohormonal modulators, heart rhythm and synchronization management and mechanical support of the circulation. The perioperative considerations and recommendations may range from invasive hemodynamic monitoring, management of proper inotropic support to maintain left ventricular and right ventricular systolic function, isolation from electromagnetic interference in patients with rhythm management devices, maintenance of appropriate systemic and pulmonary vascular resistance, and surgical planning and anticoagulant management. RECENT FINDINGS: Studies of the efficacy and hemodynamic changes of patients on inotropic therapy (milrinone, levosimendan, and istaroxime) and neuropeptide (nesiritide) therapy will be reviewed. Perioperative considerations of patients on mechanical circulatory support will be discussed. The need for implementation of temporary mechanical support for noncardiac surgery will be discussed. SUMMARY: A working knowledge of AHF treatments and perioperative considerations is necessary for all anesthesiologists as more patients receiving therapy will be presenting for all types of surgical procedures.