Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: Lessons learned from recent clinical trials.

Cardiac arrest is a leading contributor to morbidity and mortality in the United States. Survival has been historically dependent on high-quality cardiopulmonary resuscitation (CPR) and rapid defibrillation. However, a large percentage of patients remain in refractory cardiac arrest despite adherence to structured advanced cardiac life support algorithms in which these factors are emphasized. Veno-arterial extracorporeal membrane oxygenation is becoming an increasingly used rescue therapy for patients in refractory cardiac arrest to restore oxygen delivery by extracorporeal CPR (ECPR). Recently published clinical trials have provided new insights into ECPR for patients who sustain an outside hospital cardiac arrest (OHCA). In this narrative review, we summarize the rationale for, results of, and remaining questions from these recently published clinical trials. The existing observational data combined with the latest clinical trials suggest ECPR improves mortality in patients in refractory arrest. However, a mixed methods trial is essential to understand the complexity, context, and effectiveness of implementing an ECPR program.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Disability-Adjusted Life Years Due to Pediatric Out-of-Hospital Cardiac Arrest in the United States: A CARES Surveillance Group Study.

BACKGROUND: Disability-adjusted life years (DALY) are a common public health metric used to estimate disease burden. The DALY due to pediatric out-of-hospital cardiac arrest (OHCA) in the United States is unknown. We aimed to estimate pediatric OHCA DALY and to compare it with the other leading causes of pediatric death and disability in the United States. METHODS: We conducted a retrospective observational analysis of the national Cardiac Arrest Registry to Enhance Survival database. DALY were calculated as the sum of years of life lost and years lived with disability. Years of life lost were calculated using all pediatric (age <18 years) nontraumatic OHCA from the Cardiac Arrest Registry to Enhance Survival from 2016 to 2020. Disability weights based on cerebral performance category scores, an outcome measure of neurologic function, were used to estimate years lived with disability . Data were reported as total, mean, and rate per 100 000 individuals, and were compared with the leading causes of pediatric DALY in the United States published by the Global Burden of Disease study for 2019. RESULTS: Totally 11 177 OHCA met the study inclusion criteria. A modest increase in total OHCA DALY in the United States was observed from 407 500 (years of life lost = 407 435 and years lived with disability =65) in 2016 to 415 113 (years of life lost = 415 055 and years lived with disability =58) in 2020. The DALY rate increased from 553.3 per 100 000 individuals in 2016 to 568.3 per 100 000 individuals in 2020. For 2019, OHCA was the 10th leading cause of pediatric DALY lost behind neonatal disorders, injuries, mental disorders, premature birth, musculoskeletal disorders, congenital birth defects, skin diseases, chronic respiratory diseases, and asthma. CONCLUSIONS: Nontraumatic OHCA is one of the top 10 leading causes of annual pediatric DALY lost in the United States.

Time to Awakening and Self-Fulfilling Prophecies After Cardiac Arrest.

OBJECTIVES: Withdrawal of life-sustaining therapies for perceived poor neurologic prognosis (WLST-N) is common after resuscitation from cardiac arrest and may bias outcome estimates from models trained using observational data. We compared several approaches to outcome prediction with the goal of identifying strategies to quantify and reduce this bias. DESIGN: Retrospective observational cohort study. SETTING: Two academic medical centers ("UPMC" and "University of Alabama Birmingham" [UAB]). PATIENTS: Comatose adults resuscitated from cardiac arrest. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: As potential predictors, we considered clinical, laboratory, imaging, and quantitative electroencephalography data available early after hospital arrival. We followed patients until death, discharge, or awakening from coma. We used penalized Cox regression with a least absolute shrinkage and selection operator penalty and five-fold cross-validation to predict time to awakening in UPMC patients and then externally validated the model in UAB patients. This model censored patients after WLST-N, considering subsequent potential for awakening to be unknown. Next, we developed a penalized logistic model predicting awakening, which treated failure to awaken after WLST-N as a true observed outcome, and a separate logistic model predicting WLST-N. We scaled and centered individual patients' Cox and logistic predictions for awakening to allow direct comparison and then explored the difference in predictions across probabilities of WLST-N. Overall, 1,254 patients were included, and 29% awakened. Cox models performed well (mean area under the curve was 0.93 in the UPMC test sets and 0.83 in external validation). Logistic predictions of awakening were systematically more pessimistic than Cox-based predictions for patients at higher risk of WLST-N, suggesting potential for self-fulfilling prophecies to arise when failure to awaken after WLST-N is considered as the ground truth outcome. CONCLUSIONS: Compared with traditional binary outcome prediction, censoring outcomes after WLST-N may reduce potential for bias and self-fulfilling prophecies.

Thoracic point-of-care ultrasound is an accurate diagnostic modality for clinically significant traumatic pneumothorax.

OBJECTIVE: There are conflicting data regarding the accuracy of thoracic point-of-care ultrasound (POCUS) in detecting traumatic pneumothorax (PTX). The purpose of our study was to determine the accuracy of thoracic POCUS performed by emergency physicians for the detection of clinically significant PTX in blunt and penetrating trauma patients. METHODS: We conducted a retrospective institutional review board-approved study of trauma patients 15 years or older presenting to our urban Level I academic trauma center from December 2021 to June 2022. All study patients were imaged with single-view chest radiography (CXR) and thoracic POCUS. The presence or absence of PTX was determined by multidetector computed tomography (CT) or CXR and ultrasound (US) with tube thoracostomy placement. RESULTS: A total of 846 patients were included, with 803 (95%) sustaining blunt trauma. POCUS identified 13/15 clinically significant PTXs (defined as ≥35 mm of pleural separation on a blinded overread or placement of a tube thoracostomy prior to CT) with a sensitivity of 87% (95% confidence interval [CI] 58-97), specificity of 100% (95% CI 99-100), positive predictive value of 81% (95% CI 54%-95%), and negative predictive value of 100% (95% CI 99%-100%). The positive likelihood ratio was 484 and the negative likelihood ratio was 0.1. CXR identified eight (53%) clinically significant PTXs, with a sensitivity of 53% (95% CI 27%-78%) and a specificity of 100%, when correlated with the CT. The most common reason for a missed PTX identified on expert-blinded overread was failure to recognize a lung point sign that was present on US. CONCLUSIONS: Thoracic POCUS accurately identifies the majority of clinically significant PTXs in both blunt and penetrating trauma patients. Common themes for false-negative thoracic US in the expert-blinded overread process identified key gaps in training to inspire US education and medical education research.

External validation of Pittsburgh Cardiac Arrest Category illness severity score.

Early prognostication post-cardiac arrest can help determine appropriate medical management and help evaluate effectiveness of post-arrest interventions. The Pittsburgh Cardiac Arrest Category (PCAC) severity score is a 4-level illness severity score found to strongly predict patient outcomes in both in- (IHCA) and out-of-hospital cardiac arrests (OHCA). We aimed to validate the PCAC severity score in an external cohort of cardiac arrest patients. METHODS: We retrospectively assigned PCAC scores to both IHCA and OHCA patients treated by our hypothermia team from July 1, 2009 to July 1 2016. Our primary outcome was survival to hospital discharge. Secondary outcomes were favorable functional status defined as favorable discharge disposition (home or acute rehabilitation), discharge Cerebral Performance Category (CPC); and discharge modified Rankin Scale (mRS). We tested the association of PCAC and outcomes using a multivariable adjusted logistic regression model. RESULTS: We included 317 subjects in our model. PCAC was strongly associated with survival I Reference; II adjusted odds ratio (OR) 0.20 95% confidence interval (CI) 0.35-0.66, III (OR 0.14 CI 0.3-0.73, p < 0.05); IV (OR 0.05 CI 0.01-0.24, p < 0.01). PCAC was similarly associated with favorable functional outcomes: favorable discharge disposition II (OR 0.12 CI 0.02-0.68), III (OR 0.19 CI 0.05-0.74, p < 0.05) IV (OR 0.05 CI 0.01-0.22, p < 0.01); favorable CPC score II (OR 0.25 CI 0.06-1.03), III (OR 0.14 CI 0.03-0.57, p < 0.01), IV (OR 0.05 CI 0.01-0.20, p < 0.01) and favorable mRS (OR 0.47 CI (0.33-0.68)). CONCLUSION: Early (<6 h post-arrest) PCAC severity scoring strongly predicts patient outcomes from cardiac arrest in both OHCA and IHCA.

Annual and lifetime economic productivity loss due to adult out-of-hospital cardiac arrest in the United States: A study for the CARES Surveillance Group.

OBJECTIVE: To estimate the annual and lifetime economic productivity loss due to adult out-of-hospital cardiac arrest (OHCA) in the United States (U.S.). METHODS: All adult (age ≥ 18 years) non-traumatic EMS-treated OHCA with complete data for age, sex, race, and survival outcomes from the CARES database for 2013-2018 were included. Annual and lifetime labor productivity values, based on age and gender, were obtained from previously published national economic data. Productivity losses for OHCA events were calculated by year in U.S. dollars. Productivity losses for survivors were assigned by cerebral performance category score (CPC): CPC 1 and 2 = 0% productivity loss; CPC 3-5 = 100% productivity loss. Sensitivity analyses were performed assigning CPC 2 varying productivity losses (0-100%) based on CPC score and discharge location. Lifetime productivity values assumed 1% annual growth and 3% discount rate and were adjusted for inflation based on 2016 values. Results were extrapolated to annual U.S. population estimates for the study period. RESULTS: A total of 338,492 (96.5%) cases met inclusion criteria. The mean annual and lifetime productivity losses per OHCA in 2018 were $48,224 and $638,947 respectively. The total annual economic productivity loss due to OHCA in the U.S. increased from $7.4B in 2013 to $11.3B in 2018. Lifetime economic productivity loss increased from $95.2B in 2013 to $150.2B in 2018. Sensitivity analyses yielded similar findings. Per annual death, OHCA ranked third ($10.2B) in annual economic productivity loss in the U.S. behind cancer ($22.9B) and heart disease ($20.3B) in 2018. CONCLUSION: Adult non-traumatic OHCA events are associated with significant annual and lifetime economic productivity losses and should be the focus of public health resources to improve preventative measures and survival outcomes.

Clinical ultrasonography in patients who inject drugs (the CUPID protocol): an illustrated case series.

In 2017, there were ≈47,600 opioid overdose-related deaths in the United States. US emergency department (ED) visits for suspected opioid overdose increased by 30% between July 2016 and September 2017.2 The current US opioid epidemic makes it critical for emergency physicians to be aware of common and uncommon infectious and non-infectious complications of injection drug use. Point-of-care ultrasound has become a widely available, non-invasive diagnostic tool in EDs across the United States and worldwide. The increasing population of injection drug use patients is at risk for serious morbidity and mortality from an array of disease states amenable to ultrasound-based diagnosis. We propose a protocol for clinical ultrasonography in patients who inject drugs (the CUPID protocol), a focused, 3-system point-of-care ultrasound approach emphasizing cardiovascular, thoracic, and musculoskeletal imaging. The protocol is a screening tool, designed to detect high risk infectious and noninfectious complications of injection drug use.

Time to Reevaluate the Away Rotation: Improving Return on Investment for Students and Schools.

Away rotations are common among senior medical students preparing to apply for residency. For competitive specialties, multiple away rotations may be viewed as a de facto requirement for a strong application. Although away rotations are often valuable learning experiences, a variety of noneducational factors motivate students to enroll, including the need for letters of recommendation, students' uncertainty regarding their strength as applicants, perceived competitiveness of residency applications, and conflicting guidance from advisors.Students who enroll in away rotations often benefit from a novel educational environment, opportunities for career exploration, and the chance to assess "fit" with a program. Yet away rotations also come at a significant cost. Students must deal with the time and expenses of rotating at multiple institutions. The application process for away rotations is expensive, disjointed, and inefficient. Students must work hard to make an impression on host institution faculty, and risk hurting their residency applications with a negative letter of recommendation.To reduce the burden of away rotations, future research should assess the impact of multiple away rotations on success in the Match. Allowing students limited access to letters of recommendation content would allow students and advisors to make informed decisions regarding additional rotations. Students would benefit from greater standardization of the application process for away rotations, with uniform dates, timely acceptances and rejections, and a cap for the number of applications per student. Students can maximize their returns by targeting away rotations that provide the most diverse educational experiences and valuable letters of recommendation.

Modified breast cancer model for preclinical immunotherapy studies.

BACKGROUND: Interest in immunotherapy for breast cancer is rapidly emerging, and applicable animal models that mimic human cancer are urgently needed for preclinical studies. This study aimed to improve a technique for orthotopic inoculation of syngeneic breast cancer cells to be used as a preclinical animal model for immunotherapy. MATERIALS AND METHODS: We used our previously reported murine model of orthotopic cancer cell inoculation under direct vision and compared the efficiency of tumorigenesis with tumor cells suspended in either phosphate-buffered saline or Matrigel containing varying numbers of cells. As a model for immune rejection, murine BALB/c-derived 4T1-luc2 breast cancer cells were inoculated orthotopically into both BALB/c and C57BL/6 mice. RESULTS: Matrigel-suspended cells formed larger tumors with higher efficiency than phosphate-buffered saline-suspended cells. The maximum volume of Matrigel that could be inoculated without spillage was 20 µL and 30 µL in the #2 and #4 mammary fat pads, respectively. Tumor take rates increased as the injected cell number increased. In this immune rejection model, there were no significant differences in tumor weight between the strains up to day 7, after which tumor weight decreased in C57BL/6 mice. Bioluminescence in C57BL/6 mice was also significantly less than that in BALB/c mice and increased up to day 7, then swiftly decreased thereafter. CONCLUSIONS: This improved technique of innoculating murine breast cancer cells using bioluminescence technology may be useful in evaluating the efficacy of tumor regression mediated by immune responses, as shown by an allogeneic response in C57BL/6 mice.

Live animals for preclinical medical student surgical training.

AIMS: The use of live animals for surgical training is a well-known, deliberated topic. However, medical students who use live animals rate the experience high not only in improving their surgical techniques, but also positively influencing their confidence levels in the operating room later in their careers. Therefore, we hypothesized that the use of live animal models is a unique and influential component of preclinical medical education. MATERIALS AND METHODS: Medical student performed the following surgical procedures using mice; surgical orthotopic implantation of cancer cells into fat pad and subsequently a radical mastectomy. The improvement of skill was then analyzed. RESULTS: All cancer cell inoculations were performed successfully. Improvement of surgical skills during the radical mastectomy procedure was documented in all parameters. All wounds healed without breakdown or dehiscence. The appropriate interval between interrupted sutures was ascertained after fifth wound closure. The speed of interrupted sutures was doubled by last wound closure. The time required to complete a radical mastectomy decreased by almost half. A single animal died immediately following the operation due to inappropriate anesthesia, which was attributed to the lack of understanding of the overall operative management. CONCLUSION: Surgical training using live animals for preclinical medical students provides a unique learning experience, not only in improving surgical skills but also and arguably most importantly, to introduce the student to the complexities of the perioperative environment in a way that most closely resembles the stress and responsibility that the operating room demands.