Association of Advanced Airway Insertion Timing and Outcomes After Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. METHODS: We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. RESULTS: Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). CONCLUSION: In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.

The role of lipoprotein(a) in coronavirus disease 2019 (COVID-19) with relation to development of severe acute kidney injury.

Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for correlation with a wide panel of biomarkers. Serum Lp(a) did not significantly differ between COVID-19 patients and sick controls, though its concentration was found to be significantly associated with severity of COVID-19 illness, including acute kidney failure stage (r = 0.380, p = 0.007), admission disease severity (r = 0.355, p = 0.013), and peak severity (r = 0.314; p = 0.03). Lp(a) was also positively correlated with interleukin (IL)-8 (r = 0.308; p = 0.037), fibrinogen (r = 0.344; p = 0.032) and creatinine (r = 0.327; p = 0.027), and negatively correlated with ADAMTS13 activity/VWF:Ag (r = - 0.335; p = 0.021); but not with IL-6 (r = 0.241; p = 0.106). These results would hence suggest that adverse outcomes in patients with COVID-19 may be aggravated by a genetically determined hyper-Lp(a) state rather than any inflammation induced elevations.

Novel Technologies and Techniques for Prehospital Airway Management: An NAEMSP Position Statement and Resource Document.

Novel technologies and techniques can influence airway management execution as well as procedural and clinical outcomes. While conventional wisdom underscores the need for rigorous scientific data as a foundation before implementation, high-quality supporting evidence is frequently not available for the prehospital setting. Therefore, implementation decisions are often based upon preliminary or evolving data, or pragmatic information from clinical use. When considering novel technologies and techniques. NAEMSP recommends:Prior to implementing a novel technology or technique, a thorough assessment using the best available scientific data should be conducted on the technical details of the novel approach, as well as the potential effects on operations and outcomes.The decision and degree of effort to adopt, implement, and monitor a novel technology or technique in the prehospital setting will vary by the quality of the best available scientific and clinical information:• Routine use - Technologies and techniques with ample observational but limited or no interventional clinical trial data, or with strong supporting in-hospital data. These techniques may be reasonably adopted in the prehospital setting. This includes video laryngoscopy and bougie-assisted intubation. • Limited use - Technologies and techniques with ample pragmatic clinical use information but limited supporting scientific data. These techniques may be considered in the prehospital setting. This includes suction-assisted laryngoscopy and airway decontamination and cognitive aids. • Rare use - Technologies and techniques with minimal clinical use information. Use of these techniques should be limited in the prehospital setting until evidence exists from more stable clinical environments. This includes intubation boxes.The use of novel technologies and techniques must be accompanied by systematic collection and assessment of data for the purposes of quality improvement, including linkages to patient clinical outcomes.EMS leaders should clearly identify the pathways needed to generate high-quality supporting scientific evidence for novel technologies and techniques.

Complement levels at admission as a reflection of coronavirus disease 2019 (COVID-19) severity state.

Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.

The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).

OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.

Ventilation in Simulated Out-of-Hospital Cardiac Arrest Resuscitation Rarely Meets Guidelines.

OBJECTIVE: The American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend ventilation rates of eight to ten breaths per minute or two ventilations every 30 compressions, and tidal volumes between 500-600 ml. However, compliance with these guidelines is mainly unknown. The objective of this study is to estimate the proportion of simulated adult OHCA cases that meet guideline-based ventilation targets. METHODS: We conducted a blinded prospective observational study of standardized simulated cases of EMS-witnessed adult OHCA. During scheduled training sessions, resuscitations were performed by high-quality CPR trained EMS teams composed of four on-duty, full-time EMT/Paramedics from a large urban fire-based EMS agency. A high-fidelity simulation center allowed complete audio and video monitoring from a control room. Rescuers were unaware of the study, or that ventilation practices were being observed. All interventions, including airway and ventilation strategies, were at the discretion of the clinical team. A calibrated Laerdal SimMan 3 G manikin and associated Laerdal Debrief Viewer software recorded ventilation rate, tidal volume, and minute ventilation. Simulations achieving median ventilation rate 7-10 breaths/min, tidal volume 500-600 ml, and minute ventilation 3.5-6 liters/min were considered meeting guideline-based targets. RESULTS: A total of 106 EMS teams were included in the study. Only 3/106 [2.8% (95% CI: 0.6-8.0)] of the EMS teams demonstrated ventilation characteristics meeting all guideline-based targets. The median ventilation rate was 5.8 breaths/min (IQR 4.4-7.7 breaths/min) with 26/106 [24.5% (95% CI: 17.2-33.7)] between 7-10 breaths/min. The median tidal volume was 413.5 ml (IQR 280.5-555.4 ml), with 18/106 [17.0% (95% CI: 10.9-25.5)] between 500-600 ml. The median minute ventilation was 2.4 L/min (IQR 1.2-3.6 L/min) with 16/106 [15.1% (95% CI: 9.4-23.3)] between 3.5-6.0 L/min. CONCLUSION: During simulated adult OHCA resuscitation attempts, ventilation practices rarely met guideline-based targets, despite being performed by well-trained EMS providers. Methods should be developed to monitor and ensure high-quality ventilation during actual OHCA resuscitation attempts.

Serum ACE activity and plasma ACE concentration in patients with SARS-CoV-2 infection.

Significant controversy has arisen over the role of the renin-angiotensin-aldosterone system (RAAS) in COVID-19 pathophysiology. In this prospective, observational study, we evaluated plasma angiotensin converting enzyme (ACE) concentration and serum ACE activity in 52 adults with laboratory-confirmed SARS-CoV-2 infection and 27 non-COVID-19 sick controls. No significant differences were observed in ACE activity in COVID-19 patients versus non-COVID-19 sick controls (41.1 [interquartile range (IQR): 23.0-55.2] vs. 42.9 [IQR 13.6-74.2] U/L, p = .649, respectively). Similarly, no differences were observed in ACE concentration in COVID-19 patients versus non-COVID-19 sick controls (108.4 [IQR: 95.8-142.2] vs. 133.8 [IQR: 100.2-173.7] µg/L, p = .059, respectively). Neither ACE activity (p = .751), nor ACE concentration (p = .283) was associated with COVID-19 severity. Moreover, neither ACE activity, nor ACE concentration was correlated with any inflammatory biomarkers.

Timing of Advanced Airway Placement after Witnessed Out-of-Hospital Cardiac Arrest.

Background: Advanced airways (endotracheal tubes, supraglottic airways) are frequently placed by Emergency Medical Services (EMS) in patients with out-of-hospital cardiac arrest (OHCA). However, if an airway is to be placed, it is unknown whether this should occur early or late in the sequence of resuscitation events. This study evaluated the association between the timing of airway placement and the minute-to-minute probability of achieving return of spontaneous circulation (ROSC). Methods: This secondary analysis of Resuscitation Outcomes Consortium Prehospital Resuscitation using an Impedance Valve and Early versus Delayed (ROC PRIMED) study data included adult, non-traumatic, witnessed OHCA patients with airway placement by EMS before ROSC. The primary exposure variable was time from EMS arrival to advanced airway placement. The outcome was prehospital ROSC. Since resuscitations occur over time, a Cox proportional hazards model was fit to estimate the probability of ROSC as a function of the airway timing, adjusting for Utstein variables. Results: A total of 7,547 patients were included. Time to airway placement was 0-5 minutes in 12% of the cohort, >5-10 (36%), >10-15 (29%), >15-20 (14%), >20-25 (5%), >25-30 (2%), and >30 (2%). ROSC occurred in 43%. Time to airway had a statistically significant impact on ROSC. A negative association between the time to airway placement and the hazard of ROSC was observed, such that increasing intervals between EMS arrival and airway placement were associated with decreasing probabilities of ROSC, regardless of initial cardiac rhythm. Conclusions: EMS advanced airway placement has a time-dependent association with ROSC. In witnessed OHCA patients receiving advanced airways, early airway placement is associated with increased probability of ROSC.

Prehospital Triage of Acute Ischemic Stroke Patients to an Intravenous tPA-Ready versus Endovascular-Ready Hospital: A Decision Analysis.

BACKGROUND: American Stroke Association guidelines for prehospital acute ischemic stroke recommend against bypassing an intravenous tPA-ready hospital (IRH), if additional transportation time to an endovascular-ready hospital (ERH) exceeds 15-20 min. However, it is unknown when the benefit of potential endovascular therapy at an ERH outweighs the harm from delaying intravenous therapy at a closer IRH, especially since large vessel occlusion (LVO) status is initially unknown. We hypothesized that current time recommendations for IRH bypass are too short to achieve optimal outcomes for certain patient populations. METHODS: A decision analysis model was constructed using population-based databases, a detailed literature review, and interventional trial data containing time-dependent modified Rankin Scale distributions. The base case was triaged by Emergency Medical Services (EMS) 110 min after stroke onset and had a 23.6% LVO rate. Base case triage choices were (1) transport to the closest IRH (12 min), (2) transport to the ERH (60 min) bypassing the IRH, or (3) apply the Cincinnati Stroke Triage Assessment Tool and transport to the ERH if positive for LVO. Outcomes were assessed using quality-adjusted life years (QALYs). Sensitivity analyses were performed for all major variables, and alternative prehospital stroke scales were assessed. RESULTS: In the base case, transport to the IRH was the optimal choice with an expected outcome of 8.47 QALYs. Sensitivity analyses demonstrated that transport to the ERH was superior until bypass time exceeded 44 additional minutes, or when the onset to EMS triage interval exceeded 99 min. As the probability of LVO increased, ERH transport was optimal at longer onset to EMS triage intervals. The optimal triage strategy was highly dependent on specific interactions between the IRH transportation time, ERH transportation time, and onset to EMS triage interval. CONCLUSIONS: No single time difference between IRH and ERH transportation optimizes triage for all patients. Allowable IRH bypass time should be increased and acute ischemic stroke guidelines should incorporate the onset to EMS triage interval, IRH transportation time, and ERH transportation time.

Developing a standardized measurement of alcohol intoxication.

INTRODUCTION: We assessed multiple examinations and assessment tools to develop a standardized measurement of alcohol intoxication to aid medical decision making in the Emergency Department. METHODS: Volunteers underwent an alcohol challenge. Pre- and post-alcohol challenge, subjects were videotaped performing three standardized clinical examinations: (1) Standardized Field Sobriety Test (SFST) examination, (2) Hack's Impairment Index (HII) examination, and (3) Cincinnati Intoxication Examination (CIE). Emergency clinicians evaluated the level of intoxication using five standardized assessment tools in a blinded and randomized fashion: (1) SFST assessment tool (range 0-18), (2) HII assessment tool (range 0-1), (3) St. Elizabeth Alcohol Intoxication Scale (STE, range 0-17), (4) a Visual Analog Scale (VAS, range 0-100), and (5) a Binary Intoxication Question (BIQ). Construct validity was assessed along with inter- and intra-rater reliability. RESULTS: Median scores pre- and post-alcohol challenge were: SFST 6 (interquartile range 5) and 11 (3), respectively; HII 0 (0.05), 0.1 (0.1); STE 0 (1), 1 (2); VAS 10 (22), 33 (31). For BIQ, 59% and 91% indicated intoxication, respectively. Inter-rater reliability scores were: SFST 0.71 (95% confidence interval 0.48-0.86) to 0.93 (0.88-0.97) depending on examination component; HII 0.90 (0.82-0.95); STE 0.86 (0.75-0.93); VAS 0.92 (0.88-0.94); BIQ 0.3. Intra-rater reliability scores were: SFST 0.74 (0.64-0.82) to 0.87 (0.81-0.91); HII 0.85 (0.79-0.90); STE 0.78 (0.68-0.85); VAS 0.82 (0.74-0.87); BIQ 0.71. VAS reliability was best when paired with the HII and SFST examinations. CONCLUSIONS: HII examination, paired with either a VAS or HII assessment tool, yielded valid and reliable measurements of alcohol intoxication.

Intra-arrest blood-based biomarkers for out-of-hospital cardiac arrest: A scoping review.

Objective: Blood-based biomarkers play a central role in the diagnosis and treatment of critically ill patients, yet none are routinely measured during the intra-arrest phase of out-of-hospital cardiac arrest (OHCA). Our objective was to describe methodological aspects, sources of evidence, and gaps in research surrounding intra-arrest blood-based biomarkers for OHCA. Methods: We used scoping review methodology to summarize existing literature. The protocol was designed a priori following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. Inclusion criteria were peer-reviewed scientific studies on OHCA patients with at least one blood draw intra-arrest. We excluded in-hospital cardiac arrest and animal studies. There were no language, date, or study design exclusions. We conducted an electronic literature search using PubMed and Embase and hand-searched secondary literature. Data charting/synthesis were performed in duplicate using standardized data extraction templates. Results: The search strategy identified 11,834 records, with 118 studies evaluating 105 blood-based biomarkers included. Only eight studies (7%) had complete reporting. The median number of studies per biomarker was 2 (interquartile range 1-4). Most studies were conducted in Asia (63 studies, 53%).  Only 22 studies (19%) had blood samples collected in the prehospital setting, and only six studies (5%) had samples collected by paramedics. Pediatric patients were included in only three studies (3%). Out of eight predefined biomarker categories of use, only two were routinely assessed: prognostic (97/105, 92%) and diagnostic (61/105, 58%). Conclusions: Despite a large body of literature on intra-arrest blood-based biomarkers for OHCA, gaps in methodology and knowledge are widespread.

Statewide implementation of the cardiac arrest registry to enhance survival in Ohio.

Objective: Public health surveillance is essential for improving community health. The Cardiac Arrest Registry to Enhance Survival (CARES) is a surveillance system for out-of-hospital cardiac arrest (OHCA). We describe results of the organized statewide implementation of Ohio CARES. Methods: We performed a retrospective analysis of CARES enactment in Ohio. Key elements included: establishment of statewide leadership, appointment of a dedicated coordinator, conversion to a statewide subscription, statewide dissemination of information, fundraising from internal and external stakeholders, and conduct of resuscitation academies. We identified all adult (≥18 years) OHCA reported in the registry during 2013-2020. We evaluated OHCA characteristics before (2013-2015) and after (2016-2019) statewide implementation using chi-square test. We evaluated trends in OHCA outcomes using the Cochran-Armitage test of trend. Results: Statewide CARES promotion increased participation from 2 (urban) to 136 (129 urban, 7 rural) EMS agencies. Covered population increased from 1.2 M (10% of state) to 4.8 M (41% of state). After statewide implementation, OHCA populations increased male (58.1% vs 60.8%, p < 0.01), white (50.1% vs 63.7%, p < 0.01), bystander witnessed (26.9% vs 32.9%, p < 0.01) OHCAs. Bystander CPR (34.7% vs 33.2%, p = 0.22), bystander AED (13.5% vs 12.3%, p = 0.55) and initial rhythm (shockable 18.0% vs 18.3%, p = 0.32) did not change. From 2013 to 2019 there were temporal increases in ROSC (29.7% to 31.9%, p-trend = 0.028), survival (7.4% to 12.3%, p-trend < 0.001) and survival with good neurologic outcome (5.6% to 8.6%, p-trend = 0.047). Conclusion: The organized statewide implementation of CARES in Ohio was associated with marked increases in community uptake and concurrent observed improvements in patient outcomes. These results highlight key lessons for community-wide fostering of OHCA surveillance.

Ventilation rates measured by capnography during out-of-hospital cardiac arrest resuscitations and their association with return of spontaneous circulation.

BACKGROUND: Clinical guidelines for adult out-of-hospital cardiac arrest (OHCA) recommend a ventilation rate of 8-10 per minute yet acknowledge that few data exist to guide recommendations. The goal of this study was to evaluate the utility of continuous capnography to measure ventilation rates and the association with return of spontaneous circulation (ROSC). METHODS: This was a retrospective observational cohort study. We included all OHCA during a two-year period and excluded traumatic and pediatric patients. Ventilations were recorded using non-invasive continuous capnography. Blinded medically trained team members manually annotated all ventilations. Four techniques were used to analyze ventilation rate. The primary outcome was sustained prehospital ROSC. Secondary outcomes were vital status at the end of prehospital care and survival to hospital admission. Univariable and multivariable logistic regression models were constructed. RESULTS: A total of 790 OHCA were analyzed. Only 386 (49%) had useable capnography data. After applying inclusion and exclusion criteria, the final study cohort was 314 patients. The median ventilation rate per minute was 7 (IQR 5.4-8.5). Only 70 (22%) received a guideline-compliant ventilation rate of 8-10 per minute. Sixty-two (20%) achieved the primary outcome. No statistically significant associations were observed between any of the ventilation parameters and patient outcomes in both univariable and multivariable logistic regression models. CONCLUSIONS: We failed to detect an association between intra-arrest ventilation rates measured by continuous capnography and proximal patient outcomes after OHCA. Capnography has poor reliability as a measure of ventilation rate. Achieving guideline-compliant ventilation rates remains challenging.

Hemodynamic changes as a diagnostic tool in acute heart failure--a pilot study.

OBJECTIVES: To examine whether posturally induced changes in cardiac output differentiate patients presenting with dyspnea to the emergency department (ED) with acute heart failure (AHF) from other causes. METHODS: This was an observational study of patients presenting to the ED with dyspnea. Exclusion criteria included ischemic chest pain, electrocardiographic changes diagnostic of acute myocardial infarction, pericardial effusion or chest wall deformities causing dyspnea, or heart transplant. Hemodynamic variables of cardiac index (CI), total peripheral resistance index, and thoracic fluid content (TFC) were determined in upright seated and supine positions 3 minutes apart using bioreactance technology (Cheetah Medical Inc, Portland, Ore). Acute heart failure was defined as either B-type natriuretic peptide 100 to 500 pg/mL and discharge diagnosis of AHF or a B-type natriuretic peptide greater than 500 pg/mL. RESULTS: Of 92 patients, 25 had AHF, 23 had asthma/chronic obstructive pulmonary disease (COPD), and 44 had dyspnea related to other conditions; 41 (44.1%) were male, 56 (60.2%) were African American, and the mean age was 58 ± 15.0 years. Mean baseline TFC was higher in AHF vs asthma/COPD (59.3 ± 26.0 vs 39.7 ± 14.8 1/kW, P = .003) and trended higher compared to other patients with dyspnea (49.2 ± 22.0, P = .10). Postural changes in mean CI were lower in AHF (-0.20 ± 0.84 L min(-1) m(-2)) vs asthma/COPD (1.20 ± 1.23 L min(-1) m(-2); P = .002) and other dyspnea patients (0.82 ± 0.91 L min(-1) m(-2); P = .007). CONCLUSION: Patients with AHF have greater TFC but lower CI responses to postural changes compared to patients with asthma and COPD. Knowledge of these changes may help rapidly differentiate AHF from asthma and COPD in the ED.