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.

Eligibility of out-of-hospital cardiac arrest patients for extracorporeal cardiopulmonary resuscitation in the United States: A geographic information system model.

BACKGROUND: Recent evidence suggest that extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers. METHODS: We constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. The combined model was used to estimate the total number of ECPR candidates. RESULTS: There were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were deemed eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model. CONCLUSIONS: Less than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.

Complement Levels at Admission Reflecting Progression to Severe Acute Kidney Injury (AKI) in Coronavirus Disease 2019 (COVID-19): A Multicenter Prospective Cohort Study.

Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients. Materials and Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers. The primary endpoint was development of severe AKI defined by KDIGO stage 2+3 criteria, while the secondary endpoint was need for renal replacement therapy (RRT). Complement markers with significant associations with endpoints were then correlated with a panel of inflammatory and thrombotic biomarkers and assessed for independent association with outcome measures using logistic regression. Results: A total of 131 hospitalized COVID-19 patients (median age 66 [IQR, 54-75] years; 54.2% males) were enrolled, 33 from the US, and 98 from Hungary. There was a greater prevalence of complement over-activation and consumption in those who developed severe AKI and need for RRT during hospitalization. C3a/C3 ratio was increased in groups developing severe AKI (3.29 vs. 1.71; p < 0.001) and requiring RRT (3.42 vs. 1.79; p < 0.001) in each cohort. Decrease in alternative and classical pathway activity, and consumption of C4 below reference range, as well as elevation of complement activation marker C3a above the normal was more common in patients progressing to severe AKI. In the Hungarian cohort, each standard deviation increase in C3a (SD = 210.1) was independently associated with 89.7% increased odds of developing severe AKI (95% CI, 7.6-234.5%). Complement was extensively correlated with an array of inflammatory biomarkers and a prothrombotic state. Conclusion: Consumption and dysregulation of complement system is associated with development of severe AKI in COVID-19 patients and could represent a promising therapeutic target for reducing thrombotic microangiopathy in SARS-CoV-2 infection.

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.

Early prediction of COVID-19-associated acute kidney injury: Are serum NGAL and serum Cystatin C levels better than serum creatinine?

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with a high risk of acute kidney injury (AKI), often requiring renal replacement therapy (RRT). Serum Cystatin C (sCysC) and serum Neutrophil Gelatinase-Associated Lipocalin (sNGAL) are emerging biomarkers for kidney injury, and were suggested to be superior to serum creatinine (sCr) in several clinical settings. Moreover, elevated sCysC is associated with disease severity and mortality in COVID-19. We aimed to assess the utility of sCysC and sNGAL for predicting COVID-19-associated AKI, need for RRT, and need for intensive care unit (ICU) admission, when measured at presentation to the emergency department (ED). METHODS: Patients presenting to the ED with laboratory-confirmed COVID-19 were included. The primary outcome was development of COVID-19-associated AKI, while the secondary outcomes were need for RRT and ICU admission. RESULTS: Among 52 COVID-19 patients, 22 (42.3%) developed AKI with 8/22 (36.4%) requiring RRT. Both sCr and sCysC demonstrated excellent performance for predicting AKI (AUC, 0.86 and 0.87, respectively) and need for RRT (AUC, 0.94 and 0.95, respectively). sNGAL displayed acceptable performance for predicting AKI (AUC, 0.81) and need for RRT (AUC, 0.87). CONCLUSIONS: SCr and sCysC measured at ED presentation are both highly accurate predictors of AKI and need for RRT, whereas sNGAL demonstrated adequate diagnostic performance. While sCyC was previously shown to be superior to sCr as a diagnostic biomarker of kidney injury in certain etiologies, our findings demonstrate that sCr is comparable to sCyC in the context of predicting COVID-19-associated AKI. Given the high sensitivity of these biomarkers for predicting the need for RRT, and as sCysC is associated with mortality in COVID-19 patients, we recommend their measurement for enabling risk stratification and early intervention.

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.

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.

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.

Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2-Priming Protease TMPRSS2.

BACKGROUND: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry. METHODS: We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems. RESULTS: We identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity. CONCLUSIONS: Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.

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.

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.

Alterations in the lipid profile associate with a dysregulated inflammatory, prothrombotic, anti-fibrinolytic state and development of severe acute kidney injury in coronavirus disease 2019 (COVID-19): A study from Cincinnati, USA.

BACKGROUND AND AIMS: Reduction of atherogenic lipoproteins is often the ultimate goal of nutritional interventions, however this is complicated given that hypolipidemia is frequently observed in coronavirus disease 2019 (COVID-19) patients. We aimed to explore the association of hypolipidemia with patient outcomes in terms of immunothrombosis and multiorgan injury, focusing on specialized apolipoproteins apo A1 and apo B. METHODS: Lipid profiles of 50 COVID-19 patients and 30 sick controls presenting to the Emergency Department (ED) were measured in this prospective observational study. The primary outcome was development of severe acute kidney injury (AKI). Need for hospitalization and ICU admission were secondary outcomes. Lipoproteins were analyzed for independent association with serum creatinine (SCr) increase ratio and correlated with a wide panel of biomarkers. RESULTS: COVID-19 cohort had significantly lower apo A1 (p = 0.006), and higher apo B/apo A1 ratio (p = 0.041). Patients developing severe AKI had significantly lower LDL-C (p = 0.021). Apo B/apo A1 was associated with 2.25-fold decrease in serum SCr increase ratio, while LDL-C with a 1.5% decrease. Hypolipidemia correlated with low plasminogen, ADAMTS13 activity/VWF:Ag, and high inflammatory biomarkers (CRP, IL-6, IL-8, IL-10), plasminogen activator inhibitor-1 (PAI-1), ED creatinine, and SCr increase ratio. CONCLUSION: Although favored in dietetics, findings of a low LDL-C in COVID-19 patients should be alarming in light of our observations. Low apo B/apo A1 ratio and LDL-C are predictive of renal deterioration in COVID-19 patients, and low LDL-C in particular may potentially serve to indicate COVID-19 related AKI driven by disrupted fibrinolysis and a secondary thrombotic microangiopathy-like process.

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.

Duration of exposure to a prehospital advanced airway and neurological outcome for out-of-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) studies have focused on the benefits and harms of placing an intra-arrest advanced airway, but few studies have evaluated the benefits and harms after successful placement. We hypothesize that increased time in the tumultuous prehospital environment after intra-arrest advanced airway placement results in reduced patient survival. METHODS: This was a secondary analysis of adult, non-traumatic, OHCA patients with an advanced airway placed in the PRIMED trial. The exposure variable was the time interval between successful advanced airway placement and Emergency Department (ED) arrival. The outcome was cerebral performance category (CPC) 1 or 2 at hospital discharge. Multivariable logistic regression, adjusted for Utstein variables and resuscitation-associated time intervals, was used to estimate adjusted odds ratios (aOR). RESULTS: The cohort of complete cases included 4779 patients. The median time exposed to a prehospital advanced airway was 27 min (IQR 20-35). The total prehospital time was 39.4 min (IQR 32.3-48.1). An advanced airway was placed intra-arrest in 3830 cases (80.1%) and post-return of spontaneous circulation (post-ROSC) in 949 cases (19.9%). Overall, 486 (10.2%) of the cohort achieved the CPC outcome, but this was higher in the post-ROSC (21.7%) versus intra-arrest (7.5%) cohort. CPC was not associated with the time interval from advanced airway placement to ED arrival in the intra-arrest airway cohort (aOR 0.98, 95%CI 0.94-1.01). CONCLUSIONS: In OHCA patients who receive an intra-arrest advanced airway, longer time intervals exposed to a prehospital advanced airway are not associated with reduced patient survival.

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.