Publications by authors named "Benjamin S Abella"

214 Publications

Frequency of Withdrawal of Life-Sustaining Therapy for Perceived Poor Neurologic Prognosis.

Crit Care Explor 2021 Jul 13;3(7):e0487. Epub 2021 Jul 13.

Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

To measure the frequency of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis among decedents in hospitals of different sizes and teaching statuses.

Design: We performed a multicenter, retrospective cohort study.

Setting: Four large teaching hospitals, four affiliated small teaching hospitals, and nine affiliated nonteaching hospitals in the United States.

Patients: We included a sample of all adult inpatient decedents between August 2017 and August 2019.

Measurements And Main Results: We reviewed inpatient notes and categorized the immediately preceding circumstances as withdrawal of life-sustaining therapy for perceived poor neurologic prognosis, withdrawal of life-sustaining therapy for nonneurologic reasons, limitations or withholding of life support or resuscitation, cardiac death despite full treatment, or brain death. Of 2,100 patients, median age was 71 years (interquartile range, 60-81 yr), median hospital length of stay was 5 days (interquartile range, 2-11 d), and 1,326 (63%) were treated at four large teaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred in 516 patients (25%) and was the sole contributing factor to death in 331 (15%). Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis was common in all hospitals: 30% of deaths at large teaching hospitals, 19% of deaths in small teaching hospitals, and 15% of deaths at nonteaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis happened frequently across all hospital units. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis contributed to one in 12 deaths in patients without a primary neurologic diagnosis. After accounting for patient and hospital characteristics, significant between-hospital variability in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis persisted.

Conclusions: A quarter of inpatient deaths in this cohort occurred after withdrawal of life-sustaining therapy for perceived poor neurologic prognosis. The rate of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred commonly in all type of hospital settings. We observed significant unexplained variation in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis across participating hospitals.
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http://dx.doi.org/10.1097/CCE.0000000000000487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280080PMC
July 2021

Epinephrine plus chest compressions is superior to epinephrine alone in a hypoxia-induced porcine model of pseudo-pulseless electrical activity.

Resusc Plus 2021 Jun 2;6:100110. Epub 2021 Apr 2.

Department of Emergency Medicine, Dartmouth Hitchcock Medical Center, 1 Medical Center Dr #4B, Lebanon, NH 03756, USA.

Aim: Pseudo-pulseless electrical activity (pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG with no clinically detectable pulses. The role of standard external chest compressions (CPR) and its associated intrinsic hemodynamics remains unclear in the setting of pseudo-PEA. We undertook an experimental trial to compare epinephrine alone versus epinephrine with CPR in the treatment of pseudo-PEA.

Methods: Using a porcine model of hypoxic pseudo-PEA, we randomized 12 Yorkshire male swine to resuscitation with epinephrine only (control) (0.0015 mg/kg) versus epinephrine plus standard CPR (intervention). Animals who achieved return of spontaneous circulation (ROSC) were stabilized, fully recovered to hemodynamic and respiratory baseline, and rearrested up to 6 times. Primary outcome was ROSC defined as a sustained systolic blood pressure (SBP) of 60 mmHg for 2 min. Secondary outcomes included time to ROSC, coronary perfusion pressure (CoPP), and end-tidal carbon dioxide (ETCO).

Results: Among 47 events of pseudo-PEA in 12 animals, we observed significantly higher proportion of ROSC when treatment included CPR (14/21 - 67%) compared to epinephrine alone (4/26 - 15%) (p = 0.0007). CoPP, aortic pressures and ETCO were significantly higher, and right atrial pressures were lower in the intervention group.

Conclusions: In a swine model of hypoxia-induced pseudo-PEA, epinephrine plus CPR was associated with improved intra-arrest hemodynamics and higher probability of ROSC. Thus, epinephrine plus CPR may be superior to epinephrine alone in the treatment of patients with pseudo-PEA.
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http://dx.doi.org/10.1016/j.resplu.2021.100110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244467PMC
June 2021

Quantitative characterization of left ventricular function during pulseless electrical activity using echocardiography during out-of-hospital cardiac arrest.

Resuscitation 2021 Jun 1. Epub 2021 Jun 1.

Center for Resuscitation Science, University of Pennsylvania School of Medicine, University of Pennsylvania Blockley Hall, 423 Guardian Drive, Room 414A, Philadelphia, PA 19104, USA.

Background: Several prospective studies have demonstrated that the echocardiographic detection of any myocardial activity during PEA is strongly associated with higher rates of return of spontaneous circulation (ROSC). We hypothesized that PEA represents a spectrum of disease in which not only the presence of myocardial activity, but more specifically that the degree of left ventricular (LV) function would be a predictor of outcomes. The purpose of this study was to retrospectively assess the association between LV function and outcomes in patients with OHCA.

Materials And Methods: Using prospectively obtained data from an observational cohort of patients receiving focused echocardiography during cardiopulmonary resuscitation (CPR) in the Emergency Department (ED) setting, we analyzed 312 consecutive subjects with available echocardiography images with initial rhythm of PEA. We used left ventricular systolic fractional shortening (LVFS), a unidimensional echocardiographic parameter to perform the quantification of LV function during PEA. Regression analyses were performed independently to evaluate for relationships between LVFS and a primary outcome of ROSC and secondary outcome of survival to hospital admission. We analyzed LVFS both as a continuous variable and as a categorial variable using the quartiles and the median to perform multiple different comparisons and to illustrate the relationship of LVFS and outcomes of interest. We performed survival analysis using Cox proportional hazards model to evaluate the hazard corresponding to length of resuscitation.

Results: We found a positive association between LVFS and the primary outcome of ROSC (OR 1.04, 95%CI 1.01-1.08), but not with the secondary outcome of survival to hospital admission (OR 1.02, 95%CI 0.96-1.08). Given that the relationship was not linear and that we observed a threshold effect in the relationship between LVFS and outcomes, we performed an analysis using quartiles of LVFS. The predicted probability of ROSC was 75% for LVFS between 23.4-96% (fourth quartile) compared to 47% for LVFS between 0-4.7% (first quartile). The hazard of not achieving ROSC was significantly greater for subjects with LVFS below the median (13.1%) compared to the subgroup with LVFS greater than 13.1% (p < 0.05), with the separation of the survival curves occurring at approximately 40 min of resuscitation duration.

Conclusions: Left ventricular function measured by LVFS is positively correlated with higher probability of ROSC and may be associated with higher chances of survival in patients with PEA arrest.
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http://dx.doi.org/10.1016/j.resuscitation.2021.05.016DOI Listing
June 2021

Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons.

Genome Biol 2021 06 3;22(1):169. Epub 2021 Jun 3.

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Background: Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays to allow diagnosis and prevention of transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides a gold standard assay for SARS-CoV-2 RNA, but instrument costs are high and supply chains are potentially fragile, motivating interest in additional assay methods. Reverse transcription and loop-mediated isothermal amplification (RT-LAMP) provides an alternative that uses orthogonal and often less expensive reagents without the need for thermocyclers. The presence of SARS-CoV-2 RNA is typically detected using dyes to report bulk amplification of DNA; however, a common artifact is nonspecific DNA amplification, which complicates detection.

Results: Here we describe the design and testing of molecular beacons, which allow sequence-specific detection of SARS-CoV-2 genomes with improved discrimination in simple reaction mixtures. To optimize beacons for RT-LAMP, multiple locked nucleic acid monomers were incorporated to elevate melting temperatures. We also show how beacons with different fluorescent labels can allow convenient multiplex detection of several amplicons in "single pot" reactions, including incorporation of a human RNA LAMP-BEAC assay to confirm sample integrity. Comparison of LAMP-BEAC and RT-qPCR on clinical saliva samples showed good concordance between assays. To facilitate implementation, we developed custom polymerases for LAMP-BEAC and inexpensive purification procedures, which also facilitates increasing sensitivity by increasing reaction volumes.

Conclusions: LAMP-BEAC thus provides an affordable and simple SARS-CoV-2 RNA assay suitable for population screening; implementation of the assay has allowed robust screening of thousands of saliva samples per week.
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http://dx.doi.org/10.1186/s13059-021-02387-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173101PMC
June 2021

A Multicenter Evaluation of Survival After In-Hospital Cardiac Arrest in Coronavirus Disease 2019 Patients.

Crit Care Explor 2021 May 14;3(5):e0425. Epub 2021 May 14.

Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH.

Importance: In-hospital cardiac arrest survival among coronavirus disease 2019 patients has been reported to range from 0% to 12%. These numbers are significantly lower than reported prepandemic in-hospital cardiac arrest survival rates of approximately 20-25% in the United States for non-coronavirus disease 2019 patients.

Objective: To assess the incidence of in-hospital cardiac arrest survival of coronavirus disease 2019 patients.

Design: A retrospective cohort study of adult patients with coronavirus disease 2019 subsequently found to have in-hospital cardiac arrest and underwent cardiopulmonary resuscitation (cardiopulmonary resuscitation).

Setting: Multiple hospitals of the Cleveland Clinic Health System.

Patients: All adult patients (age ≥ 18 yr) admitted to Cleveland Clinic Health System with a diagnosis of coronavirus disease 2019 who experienced in-hospital cardiac arrest requiring cardiopulmonary resuscitation.

Measurements And Main Results: From March 01, 2020 to October 15, 2020, 3,555 patients with coronavirus disease 2019 were hospitalized; 1,372 were admitted to the ICU; 58 patients had in-hospital cardiac arrest. Median age of this cohort was 66.5 years (interquartile range, 55.0-76.0 yr). Patients were predominantly male (62.5%), White (53.4%), with a median body mass index of 29.7 (interquartile range, 25.8-34.6). Most in-hospital cardiac arrests were in critical care environments (ICU), 51 of 58 (87.9%); seven of 58 (12.1%) were on ward locations. Thirty-four of 58 patients (58.6%) were on mechanical ventilation prior to in-hospital cardiac arrest with a median duration of mechanical ventilation of 9 days (interquartile range, 2-18 d). Twenty-four of 58 patients (44%) were on vasopressors prior to arrest. Initial arrest rhythm was pulseless electrical activity at (63.8%), asystole (29.3%), and pulseless ventricular tachycardia/fibrillation (6.9%). Of the 58 patients, 35 (60.3%) attained return of spontaneous circulation, and 13 of 58 (22.4%) were discharged alive.

Conclusions: We report a 22% survival to discharge after in-hospital cardiac arrest in coronavirus disease 2019 patients, a survival rate similar to before the coronavirus disease 2019 pandemic.
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http://dx.doi.org/10.1097/CCE.0000000000000425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133239PMC
May 2021

Cerebrovascular pressure reactivity and intracranial pressure are associated with neurologic outcome after hypoxic-ischemic brain injury.

Resuscitation 2021 07 27;164:114-121. Epub 2021 Apr 27.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, USA.

Aim: We evaluated the association of physiological parameters measured by intracranial multimodality neuromonitoring with neurologic outcome in a consecutive series of patients with hypoxic-ischemic brain injury (HIBI).

Methods: We retrospectively identified all patients with HIBI who underwent combined invasive intracranial pressure (ICP) and brain tissue oxygen (PO) monitoring over a 3 year period. Cerebrovascular pressure reactivity index (PRx) was calculated continuously as a surrogate of cerebral autoregulation. Favorable outcome was defined as recovery of consciousness (Glasgow Coma Scale motor score = 6). Differences in mean ICP, PRx and PO for the entire monitoring period across outcomes were measured. Logistic regression and area under receiver operating characteristic (AUROC) curve were used to assess the association of each monitoring parameter with neurologic outcome.

Results: We analyzed data from 36 patients. Most (89%) had an antecedent sudden cardiac arrest. Favorable outcome occurred in 8 (22%) patients. ICP and PRx were higher in patients with unfavorable outcome (ICP: 26 ± 4.1 mmHg vs 7.5 ± 2 mmHg, p = 0.0002; PRx: 0.51 ± 0.05 vs 0.11 ± 0.05, p < 0.0001). There was no significant difference in PO between groups (unfavorable: 20 ± 2.4 mmHg vs favorable: 25 ± 1.5 mmHg, p = 0.12). Both ICP (AUROC 0.84, 95%CI 0.72-0.98, p = 0.003) and PRx (AUROC 0.94, 95%CI 0.85-1, p = 0.0002) discriminated between favorable and unfavorable outcome, in contrast to PO, (AUROC 0.59, 95%CI 0.39-0.78, p = 0.52). ICP > 15 mmHg, PRx > 0.2, and PO < 18 mmHg had sensitivity/specificity of 68%/100%, 89%/88%, and 40%/100% respectively for discriminating outcomes.

Conclusion: Cerebrovascular pressure reactivity and intracranial pressure appear to be associated with neurologic outcome in patients with HIBI.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.023DOI Listing
July 2021

Staying on Target: Maintaining a Balanced Resuscitation During Damage Control Resuscitation Improves Survival.

J Trauma Acute Care Surg 2021 Apr 24. Epub 2021 Apr 24.

Division of Traumatology, Surgical Critical Care & Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Penn Acute Research Collaboration (PARC), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA Center for Translational Injury Research, Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA Arcos, Inc., Missouri City, TX, USA Center for Resuscitation Science, Department of Emergency Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Division of Trauma, Critical Care, and Burn, Department of Surgery, The Ohio State University, Columbus, OH, USA Department of Nursing, Penn Presbyterian Medical Center, Philadelphia, PA, USA Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Background: Damage control resuscitation (DCR) improves survival in severely bleeding patients. However, deviating from balanced transfusion ratios during a resuscitation may limit this benefit. We hypothesize that maintaining a balanced resuscitation during DCR is independently associated with improved survival.

Methods: This was a secondary analysis of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients receiving ≥3 units packed red blood cells (PRBC) in one-hour over the first 6-hours and surviving beyond 30-minutes were included. Linear regression assessed the effect of percent time in a high-ratio range on 24-hour survival. We identified an optimal ratio and percent of time above the target ratio threshold by Youden's index. We compared patients with a 6-hour ratio above the target and above the percent time threshold (On-Target) with all others (Off-Target). Kaplan-Meier analysis assessed the combined effect of blood product ratio and percent time over the target ratio on 24-hour and 30-day survival. Multivariable logistic regression identified factors independently associated with 24-hour and 30-day survival.

Results: Of 1,245 PROMMTT patients, 524 met inclusion criteria. Optimal targets were plasma:PRBC and platelet:PRBC of 0.75 and ≥40% time spent over this threshold. For plasma:PRBC, On-Target (n=213) vs Off-Target (n=311) patients were younger (median 31-years, interquartile range [22, 50] vs 40 [25, 54], p=0.002) with similar injury burdens and presenting physiology. Similar patterns were observed for platelet:PRBC On-Target (n=116) and Off-Target (n=408) patients. After adjusting for differences, On-Target plasma:PRBC patients had significantly improved 24-hour (OR 2.25, 95% CI, 1.20-4.23) and 30-day (OR 1.97, 95% CI 1.14-3.41) survival while On-Target platelet:PRBC patients did not.

Conclusion: Maintaining a high ratio of plasma:PRBC during damage control resuscitation is independently associated with improved survival. Performance improvement efforts and prospective studies should capture time spent in a high-ratio range.

Level Of Evidence: Epidemiologic/prognostic study, Level II.
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http://dx.doi.org/10.1097/TA.0000000000003245DOI Listing
April 2021

Studies Utilizing Therapeutic Hypothermia and Targeted Temperature Management.

Ther Hypothermia Temp Manag 2021 Jun 22;11(2):71-75. Epub 2021 Apr 22.

Department of Emergency Medicine, University of Michigan, SIREN Emergency Clinical Trials Network and Neurological Emergencies Treatment, TrialsClinical Coordinating Centers, Ann Arbor, Michigan, USA.

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http://dx.doi.org/10.1089/ther.2021.29092.njbDOI Listing
June 2021

Rapid response system adaptations at 40 US hospitals during the COVID-19 pandemic.

Resusc Plus 2021 Jun 12;6:100121. Epub 2021 Apr 12.

Center for Resuscitation Science, University of Pennsylvania, United States.

Background: Management of patients with acute deterioration from novel coronavirus disease of 2019 (COVID-19) has posed a particular challenge for rapid response systems (RRSs) due to increased hospital strain and direct risk of infection to RRS team members.

Objective: We sought to characterize RRS structure and protocols adaptions during the COVID-19 pandemic.

Design Setting And Participants: Internet-based cross-sectional survey of RRS leaders, physicians, and researchers across the United States.

Results: Clinicians from 46 hospitals were surveyed, 40 completed a baseline survey (87%), and 19 also completed a follow-up qualitative survey. Most reported an increase in emergency team resources during the COVID-19 pandemic. The number of sites performing simulation training sessions decreased from 88% before COVID-19 to 53% during the pandemic.

Conclusions: Most RRSs reported pandemic-related adjustments, most commonly through increasing resources and implementation of protocol changes. There was a reduction in the number of sites that performed simulation training.
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http://dx.doi.org/10.1016/j.resplu.2021.100121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041183PMC
June 2021

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Nat Commun 2021 04 15;12(1):2349. Epub 2021 Apr 15.

Infectious and Tropical Diseases Department, Angers University Hospital, Angers, France.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
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http://dx.doi.org/10.1038/s41467-021-22446-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050319PMC
April 2021

Optimizing a decision support system for damage-control resuscitation using mixed methods human factors analysis.

J Trauma Acute Care Surg 2021 Aug;91(2S Suppl 2):S154-S161

From the Division of Traumatology, Surgical Critical Care & Emergency Surgery (D.S., K.Q., J.W.C.), Penn Acute Research Collaboration (PARC) (D.S., B.S.A., J.W.C.), Perelman School of Medicine at the University of Pennsylvania; Department of Nursing (P.Z.C., S.H., A.H.), Penn Presbyterian Medical Center, Penn Medicine; University of Pennsylvania School of Nursing Philadelphia (P.Z.C.); Leonard Davis Institute of Health Economics (P.Z.C., J.W.C.), University of Pennsylvania, Philadelphia, Pennsylvania; Arcos, Inc. (C.M.), Missouri City, Texas; Department of Emergency Medicine (B.S.A.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Surgery (J.W.C.), Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Background: Damage-control resuscitation (DCR) improves trauma survival; however, consistent adherence to DCR principles through multiple phases of care has proven challenging. Clinical decision support may improve adherence to DCR principles. In this study, we designed and evaluated a DCR decision support system using an iterative development and human factors testing approach.

Methods: The phases of analysis included initial needs assessment and prototype design (Phase 0), testing in a multidimensional simulation (Phase 1), and testing during initial clinical use (Phase 2). Phase 1 and Phase 2 included hands-on use of the decision support system in the trauma bay, operating room, and intensive care unit. Participants included trauma surgeons, trauma fellows, anesthesia providers, and trauma bay and intensive care unit nurses who provided both qualitative and quantitative feedback on the initial prototype and all subsequent iterations.

Results: In Phase 0, 14 (87.5%) of 16 participants noted that they would use the decisions support system in a clinical setting. Twenty-four trauma team members then participated in simulated resuscitations with decision support where 178 (78.1%) of 228 of tasks were passed and 27 (11.8%) were passed with difficulty. Twenty-three (95.8%) completed a postsimulation survey. Following iterative improvements in system design, Phase 2 evaluation included 21 trauma team members during multiple real-world trauma resuscitations. Of these, 15 (71.4%) completed a formal postresuscitation survey. Device-level feedback on a Likert scale (range, 0-4) confirmed overall ease of use (median score, 4; interquartile range, 4-4) and indicated the system integrated well into their workflow (median score, 3; interquartile range, 2-4). Final refinements were then completed in preparation for a pilot clinical study using the decision support system.

Conclusions: An iterative development and human factors testing approach resulted in a clinically useable DCR decision support system. Further analysis will determine its applicability in military and civilian trauma care.

Level Of Evidence: Therapeutic/Care Management, Level V.
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http://dx.doi.org/10.1097/TA.0000000000003224DOI Listing
August 2021

ST-Elevation Myocardial Infarction Track.

Ther Hypothermia Temp Manag 2021 Jun 5;11(2):65-70. Epub 2021 Apr 5.

ICON plc., North Wales, Pennsylvania, USA.

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http://dx.doi.org/10.1089/ther.2021.29091.babDOI Listing
June 2021

Cardiopulmonary Resuscitation in Coronavirus Disease 2019: Far from Futile.

Crit Care Med 2021 08;49(8):e797-e798

Center for Resuscitation Science, University of Pennsylvania, Philadelphia, PA.

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http://dx.doi.org/10.1097/CCM.0000000000005000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277040PMC
August 2021

Delays in antibiotic redosing: Association with inpatient mortality and risk factors for delay.

Am J Emerg Med 2021 Mar 1;46:63-69. Epub 2021 Mar 1.

Department of Emergency Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA. Electronic address:

Objective: Although timely administration of antibiotics has an established benefit in serious bacterial infection, the majority of studies evaluating antibiotic delay focus only on the first dose. Recent evidence suggests that delays in redosing may also be associated with worse clinical outcome. In light of the increasing burden of boarding in Emergency Departments (ED) and subsequent need to redose antibiotic in the ED, we examined the association between delayed second antibiotic dose administration and mortality among patients admitted from the ED with a broad array of infections and characterized risk factors associated with delayed second dose administration.

Methods: We performed a retrospective cohort study of patients admitted through five EDs in a single healthcare system from 1/2018 through 12/2018. Our study included all patients, aged 18 years or older, who received two intravenous antibiotic doses within a 30-h period, with the first dose administered in the ED. Patients with end stage renal disease, cirrhosis and extremes of weight were excluded due to a lack of consensus on antibiotic dosing intervals for these populations. Delay was defined as administration of the second dose at a time-point greater than 125% of the recommended interval. The primary outcome was in-hospital mortality.

Results: A total of 5605 second antibiotic doses, occurring during 4904 visits, met study criteria. Delayed administration of the second dose occurred during 21.1% of visits. After adjustment for patient characteristics, delayed second dose administration was associated with increased odds of in-hospital mortality (OR 1.50, 95%CI 1.05-2.13). Regarding risk factors for delay, every one-hour increase in allowable compliance time was associated with a 18% decrease in odds of delay (OR 0.82 95%CI 0.75-0.88). Other risk factors for delay included ED boarding more than 4 h (OR 1.47, 95%CI 1.27-1.71) or a high acuity presentation as defined by emergency severity index (ESI) (OR 1.54, 95%CI 1.30-1.81 for ESI 1-2 versus 3-5).

Conclusions: Delays in second antibiotic dose administration were frequent in the ED and early hospital course, and were associated with increased odds of in-hospital mortality. Several risk factors associated with delays in second dose administration, including ED boarding, were identified.
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http://dx.doi.org/10.1016/j.ajem.2021.02.058DOI Listing
March 2021

In-hospital cardiac arrest in patients with coronavirus 2019.

Resuscitation 2021 03 27;160:72-78. Epub 2021 Jan 27.

Center for Resuscitation Science, University of Pennsylvania, United States; Department of Emergency Medicine, University of Pennsylvania, United States.

Background: Coronavirus Disease 2019 (COVID-19) has caused over 1 200 000 deaths worldwide as of November 2020. However, little is known about the clinical outcomes among hospitalized patients with active COVID-19 after in-hospital cardiac arrest (IHCA).

Aim: We aimed to characterize outcomes from IHCA in patients with COVID-19 and to identify patient- and hospital-level variables associated with 30-day survival.

Methods: We conducted a multicentre retrospective cohort study across 11 academic medical centres in the U.S. Adult patients who received cardiopulmonary resuscitation and/or defibrillation for IHCA between March 1, 2020 and May 31, 2020 who had a documented positive test for Severe Acute Respiratory Syndrome Coronavirus 2 were included. The primary outcome was 30-day survival after IHCA.

Results: There were 260 IHCAs among COVID-19 patients during the study period. The median age was 69 years (interquartile range 60-77), 71.5% were male, 49.6% were White, 16.9% were Black, and 16.2% were Hispanic. The most common presenting rhythms were pulseless electrical activity (45.0%) and asystole (44.6%). ROSC occurred in 58 patients (22.3%), 31 (11.9%) survived to hospital discharge, and 32 (12.3%) survived to 30 days. Rates of ROSC and 30-day survival in the two hospitals with the highest volume of IHCA over the study period compared to the remaining hospitals were considerably lower (10.8% vs. 64.3% and 5.9% vs. 35.7% respectively, p < 0.001 for both).

Conclusions: We found rates of ROSC and 30-day survival of 22.3% and 12.3% respectively. There were large variations in centre-level outcomes, which may explain the poor survival in prior studies.
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http://dx.doi.org/10.1016/j.resuscitation.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839632PMC
March 2021

Low Microcirculatory Perfused Vessel Density and High Heterogeneity are Associated With Increased Intensity and Duration of Lactic Acidosis After Cardiac Surgery with Cardiopulmonary Bypass.

Shock 2021 Aug;56(2):245-254

Department of Emergency Medicine, Center for Resuscitation Science, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Introduction: Lactic acidosis after cardiac surgery with cardiopulmonary bypass is common and associated with an increase in postoperative morbidity and mortality. A number of potential causes for an elevated lactate after cardiopulmonary bypass include cellular hypoxia, impaired tissue perfusion, ischemic-reperfusion injury, aerobic glycolysis, catecholamine infusions, and systemic inflammatory response after exposure to the artificial cardiopulmonary bypass circuit. Our goal was to examine the relationship between early abnormalities in microcirculatory convective blood flow and diffusive capacity and lactate kinetics during early resuscitation in the intensive care unit. We hypothesized that patients with impaired microcirculation after cardiac surgery would have a more severe postoperative hyperlactatemia, represented by the lactate time-integral of an arterial blood lactate concentration greater than 2.0 mmol/L.

Methods: We measured sublingual microcirculation using incident darkfield video microscopy in 50 subjects on intensive care unit admission after cardiac surgery. Serial measurements of systemic hemodynamics, blood gas, lactate, and catecholamine infusions were recorded each hour for the first 6 h after surgery. Lactate area under the curve (AUC) was calculated over the first 6 h. The lactate AUC was compared between subjects with normal and low perfused vessel density (PVD < 18 mm/mm2), high microcirculatory heterogeneity index (MHI > 0.4), and low vessel-by-vessel microvascular flow index (MFIv < 2.6).

Results: Thirteen (26%) patients had a low postoperative PVD, 20 patients (40%) had a high MHI, and 26 (52%) patients had a low MFIv. Patients with low perfused vessel density had higher lactate AUC compared with subjects with a normal PVD (22.3 [9.4-31.0] vs. 2.6 [0-8.8]; P < 0.0001). Patients with high microcirculatory heterogeneity had a higher lactate AUC compared with those with a normal MHI (2.5 [0.1-8.2] vs. 13.1 [3.7-31.1]; P < 0.001). We did not find a difference in lactate AUC when comparing high and low MFIv.

Conclusion: Low perfused vessel density and high microcirculatory heterogeneity are associated with an increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass.
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http://dx.doi.org/10.1097/SHK.0000000000001713DOI Listing
August 2021

A conceptual framework for Emergency department design in a pandemic.

Scand J Trauma Resusc Emerg Med 2020 Dec 17;28(1):118. Epub 2020 Dec 17.

Department of Emergency Medicine, Singapore General Hospital, 1 Outram Road, Singapore City, 169608, Singapore.

Background: The current COVID-19 pandemic is highlighting gaps around the world in the design and workflow of Emergency Departments (ED). These gaps have an impact on both patient care and staff safety and represent a risk to public health. There is a need for a conceptual framework to guide ED design and workflow to address these challenges. Such a framework is important as the ED environment will always remain vulnerable to infectious diseases outbreaks in the future.

Aims: This paper aims to address issues and principles around ED design and workflow amidst the COVID-19 pandemic. We propose a conceptual framework and checklist for EDs to be prepared for future outbreaks as well.

Methods: A scoping literature review was conducted, of the experiences of EDs in managing outbreaks such as SARS, H1N1 and COVID-19. The combined experiences of the authors and the experiences from the literature were grouped under common themes to develop the conceptual framework.

Results: Four key principles were derived- (1) situational awareness, surveillance and perimeter defence, (2) ED staff protection, (3) surge capacity management and (4) ED recovery. The findings were integrated in a proposed conceptual framework to guide ED design in response to an infectious disease outbreak. There are various elements which need to be considered at ED input, throughput and output. These elements can be categorised into (1) system (workflow, protocols and communication), (2) staff (human resources), (3) space (infrastructure), and (4) supply (logistics) and are placed in a checklist for pragmatic use.

Conclusion: The ED needs to be in a constant state of preparedness. A framework can be useful to guide ED design and workflow to achieve this. As all ED systems are different with varying capabilities, our framework may help EDs across the world prepare for infectious disease outbreaks.
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http://dx.doi.org/10.1186/s13049-020-00809-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745175PMC
December 2020

Fever management in COVID-19 patients.

Minerva Anestesiol 2021 01 24;87(1):1-3. Epub 2020 Nov 24.

Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

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http://dx.doi.org/10.23736/S0375-9393.20.15195-2DOI Listing
January 2021

Practical considerations for postarrest targeted temperature management.

Turk J Emerg Med 2020 Oct-Dec;20(4):157-162. Epub 2020 Oct 7.

Department of Emergency Medicine, The Center for Resuscitation Science, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Out-of-hospital cardiac arrest remains a major challenge worldwide, with survival to discharge rates of <20% in the great majority of countries. Advancements in prehospital care, including increasing deployment of automated external defibrillators and improvements in bystander cardiopulmonary resuscitation, have led to more victims achieving return of spontaneous circulation (ROSC), yet the majority of patients with ROSC suffer in-hospital mortality or significant neurologic injuries that persist after discharge. This postarrest morbidity and mortality is largely due to a complex syndrome of mitochondrial dysfunction, inflammatory cascades and cellular injuries known as the postcardiac arrest syndrome (PCAS). The management of PCAS represents a formidable task for emergency and critical care providers. A cornerstone of PCAS treatment is the use of aggressive core body temperature control using thermostatically controlled devices, known as targeted temperature management (TTM). This therapy, demonstrated to be effective in improving both survival and neurologic recovery by several randomized controlled trials nearly 20 years ago, remains a major topic of clinical investigation. Important practical questions about TTM remain: How soon must providers initiate the therapy? What TTM goal temperature maximizes benefit while limiting potential adverse effects? How long should TTM therapy be continued in patients following resuscitation? In this review, we will address these issues and summarize clinical research over the past decade that has added to our fund of knowledge surrounding this important treatment of patients following cardiac arrest.
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http://dx.doi.org/10.4103/2452-2473.297466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549514PMC
October 2020

Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.

JAMA Intern Med 2021 02;181(2):195-202

Abramson Cancer Center and Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia.

Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.

Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.

Design, Setting, And Participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.

Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.

Main Outcomes And Measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants.

Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.

Conclusions And Relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.

Trial Registration: ClinicalTrials.gov Identifier: NCT04329923.
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http://dx.doi.org/10.1001/jamainternmed.2020.6319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527945PMC
February 2021

Predicting cardiac arrest in the emergency department.

J Am Coll Emerg Physicians Open 2020 Aug 3;1(4):321-326. Epub 2020 Feb 3.

Department of Emergency Medicine and the Center for Resuscitation Science University of Pennsylvania School of Medicine Philadelphia Pennsylvania.

In-hospital cardiac arrest remains a leading cause of death: roughly 300,000 in-hospital cardiac arrests occur each year in the United States, ≈10% of which occur in the emergency department. ED-based cardiac arrest may represent a subset of in-hospital cardiac arrest with a higher proportion of reversible etiologies and a higher potential for neurologically intact survival. Patients presenting to the ED have become increasingly complex, have a high burden of critical illness, and face crowded departments with thinly stretched resources. As a result, patients in the ED are vulnerable to unrecognized clinical deterioration that may lead to ED-based cardiac arrest. Efforts to identify patients who may progress to ED-based cardiac arrest have traditionally been approached through identification of critically ill patients at triage and the identification of patients who unexpectedly deteriorate during their stay in the ED. Interventions to facilitate appropriate triage and resource allocation, as well as earlier identification of patients at risk of deterioration in the ED, could potentially allow for both prevention of cardiac arrest and optimization of outcomes from ED-based cardiac arrest. This review will discuss the epidemiology of ED-based cardiac arrest, as well as commonly used approaches to predict ED-based cardiac arrest and highlight areas that require further research to improve outcomes for this population.
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http://dx.doi.org/10.1002/emp2.12015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493514PMC
August 2020

What gaps in chest compressions tell us about gaps in CPR knowledge.

Resuscitation 2020 09 22;154:119-120. Epub 2020 Jul 22.

Center for Resuscitation Science and Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, US. Electronic address:

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http://dx.doi.org/10.1016/j.resuscitation.2020.07.013DOI Listing
September 2020

Association of an Emergency Department-embedded Critical Care Unit with Hospital Outcomes and Intensive Care Unit Use.

Ann Am Thorac Soc 2020 12;17(12):1599-1609

Department of Emergency Medicine.

A small but growing number of hospitals are experimenting with emergency department-embedded critical care units (CCUs) in an effort to improve the quality of care for critically ill patients with sepsis and acute respiratory failure (ARF). To evaluate the potential impact of an emergency department-embedded CCU at the Hospital of the University of Pennsylvania among patients with sepsis and ARF admitted from the emergency department to a medical ward or intensive care unit (ICU) from January 2016 to December 2017. The exposure was eligibility for admission to the emergency department-embedded CCU, which was defined as meeting a clinical definition for sepsis or ARF and admission to the emergency department during the intervention period on a weekday. The primary outcome was hospital length of stay (LOS); secondary outcomes included total emergency department plus ICU LOS, hospital survival, direct admission to the ICU, and unplanned ICU admission. Primary interrupted time series analyses were performed using ordinary least squares regression comparing monthly means. Secondary retrospective cohort and before-after analyses used multivariable Cox proportional hazard and logistic regression. In the baseline and intervention periods, 3,897 patients met the inclusion criteria for sepsis and 1,865 patients met the criteria for ARF. Among patients admitted with sepsis, opening of the emergency department-embedded CCU was not associated with hospital LOS (β = -1.82 d; 95% confidence interval [CI], -4.50 to 0.87;  = 0.17 for the first month after emergency department-embedded CCU opening compared with baseline; β = -0.26 d; 95% CI, -0.58 to 0.06;  = 0.10 for subsequent months). Among patients admitted with ARF, the emergency department-embedded CCU was not associated with a significant change in hospital LOS for the first month after emergency department-embedded CCU opening (β = -3.25 d; 95% CI, -7.86 to 1.36;  = 0.15) but was associated with a 0.64 d/mo shorter hospital LOS for subsequent months (β = -0.64 d; 95% CI, -1.12 to -0.17;  = 0.01). This result persisted among higher acuity patients requiring ventilatory support but was not supported by alternative analytic approaches. Among patients admitted with sepsis who did not require mechanical ventilation or vasopressors in the emergency department, the emergency department-embedded CCU was associated with an initial 9.9% reduction in direct ICU admissions in the first month (β = -0.099; 95% CI, -0.153 to -0.044;  = 0.002), followed by a 1.1% per month increase back toward baseline in subsequent months (β = 0.011; 95% CI, 0.003-0.019;  = 0.009). This relationship was supported by alternative analytic approaches and was not seen in ARF. No associations with emergency department plus ICU LOS, hospital survival, or unplanned ICU admission were observed among patients with sepsis or ARF. The emergency department-embedded CCU was not associated with clinical outcomes among patients admitted with sepsis or ARF. Among less sick patients with sepsis, the emergency department-embedded CCU was initially associated with reduced rates of direct ICU admission from the emergency department. Additional research is necessary to further evaluate the impact and utility of the emergency department-embedded CCU model.
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http://dx.doi.org/10.1513/AnnalsATS.201912-912OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706601PMC
December 2020

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial.

Ann Emerg Med 2020 10 9;76(4):489-500. Epub 2020 Jul 9.

TerSera Therapeutics, Deerfield, IL.

Study Objective: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial.

Methods: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded.

Results: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%).

Conclusion: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.
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http://dx.doi.org/10.1016/j.annemergmed.2020.05.025DOI Listing
October 2020

COVID-19 and cardiac arrhythmias.

Heart Rhythm 2020 Sep 22;17(9):1439-1444. Epub 2020 Jun 22.

Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.

Objectives: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.

Methods: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.

Results: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.

Conclusion: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307518PMC
September 2020

Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial.

Intensive Care Med 2020 Jul 8;46(7):1361-1370. Epub 2020 Jun 8.

Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.

Purpose: To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest.

Methods: A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1-2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes.

Results: In total, 300 patients were analyzed and the proportion with CPC 1-2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95-3.85, p = .07. In patients with shockable rhythm, CPC 1-2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06-9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12-4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55-18.3, p = .008.

Conclusions: In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.
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http://dx.doi.org/10.1007/s00134-020-06024-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334260PMC
July 2020

Severe Impairment of Microcirculatory Perfused Vessel Density Is Associated With Postoperative Lactate and Acute Organ Injury After Cardiac Surgery.

J Cardiothorac Vasc Anesth 2021 Jan 14;35(1):106-115. Epub 2020 May 14.

Department of Emergency Medicine, Center for Resuscitation Science, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Objective: Resuscitation after cardiac surgery needs to address multiple pathophysiological processes that are associated with significant morbidity and mortality. Functional microcirculatory derangements despite normal systemic hemodynamics have been previously described but must be tied to clinical outcomes. The authors hypothesized that microcirculatory dysfunction after cardiac surgery would include impaired capillary blood flow and impaired diffusive capacity and that subjects with the lowest quartile of perfused vessel density would have an increased postoperative lactate level and acute organ injury scores.

Design: Prospective, observational study.

Setting: A single, tertiary university cardiovascular surgical intensive care unit.

Participants: 25 adults undergoing elective cardiac surgery requiring cardiopulmonary bypass.

Intervention: Sublingual microcirculation was imaged using incident dark field microscopy before and 2 to 4 hours after surgery in the intensive care unit.

Measurements And Main Results: Compared with baseline measurements, postoperative vessel-by-vessel microvascular flow index (2.9 [2.8-2.9] v 2.5 [2.4-2.7], p < 0.0001) and perfused vessel density were significantly impaired (20.7 [19.3-22.9] v 16.3 [12.8-17.9], p < 0.0001). The lowest quartile of perfused vessel density (<12.8 mm/mm) was associated with a significantly increased postoperative lactate level (6.0 ± 2.9 v 1.8 ± 1.2, p < 0.05), peak lactate level (7.6 ± 2.8 v 2.8 ± 1.5, p = 0.03), and sequential organ failure assessment (SOFA) score at 24 and 48 hours.

Conclusion: In patients undergoing cardiac surgery, there was a significant decrease in postoperative microcirculatory convective blood flow and diffusive capacity during early postoperative resuscitation. Severely impaired perfused vessel density, represented by the lowest quartile of distribution, is significantly related to hyperlactatemia and early organ injury.
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http://dx.doi.org/10.1053/j.jvca.2020.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666105PMC
January 2021

Factors affecting the course of resuscitation from cardiac arrest with pulseless electrical activity in children and adolescents.

Resuscitation 2020 07 17;152:116-122. Epub 2020 May 17.

Department of Mathematics and Physics, University of Stavanger, Norway.

Background: Although in-hospital pediatric cardiac arrests and cardiopulmonary resuscitation occur >15,000/year in the US, few studies have assessed which factors affect the course of resuscitation in these patients. We investigated transitions from Pulseless Electrical Activity (PEA) to Ventricular Fibrillation/pulseless Ventricular Tachycardia (VF/pVT), Return of Spontaneous Circulation (ROSC) and recurrences from ROSC to PEA in children and adolescents with in-hospital cardiac arrest.

Methods: Episodes of cardiac arrest at the Children's Hospital of Philadelphia were prospectively registered. Defibrillators that recorded chest compression depth/rate and ventilation rate were applied. CPR variables, patient characteristics and etiology, and dynamic factors (e.g. the proportion of time spent in PEA or ROSC) were entered as time-varying covariates for the transition intensities under study.

Results: In 67 episodes of CPR in 59 patients (median age 15 years) with cardiac arrest, there were 52 transitions from PEA to ROSC, 22 transitions from PEA to VF/pVT, and 23 recurrences of PEA from ROSC. Except for a nearly significant effect of mean compression depth beyond a threshold of 5.7 cm, only dynamic factors that evolved during CPR favored a transition from PEA to ROSC. The latter included a lower proportion of PEA over the last 5 min and a higher proportion of ROSC over the last 5 min. Factors associated with PEA to VF/pVT development were age, weight, the proportion spent in VF/pVT or PEA the last 5 min, and the general transition intensity, while PEA recurrence from ROSC only depended on the general transition intensity.

Conclusion: The clinical course during pediatric cardiac arrest was mainly influenced by dynamic factors associated with time in PEA and ROSC. Transitions from PEA to ROSC seemed to be favored by deeper compressions.
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http://dx.doi.org/10.1016/j.resuscitation.2020.05.013DOI Listing
July 2020
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