Single versus continuous sustained inflations during chest compressions and physiological-based cord clamping in asystolic lambs

BackgroundThe feasibility and benefits of continuous sustained inflations (SIs) during chest compressions (CCs) during delayed cord clamping (physiological-based cord clamping; PBCC) are not known. We aimed to determine whether continuous SIs during CCs would reduce the time to return of spontaneous circulation (ROSC) and improve post-asphyxial blood pressures and flows in asystolic newborn lambs.MethodsFetal sheep were surgically instrumented immediately prior to delivery at ~139 days’ gestation and asphyxia induced until lambs reached asystole. Lambs were randomised to either immediate cord clamping (ICC) or PBCC. Lambs then received a single SI (SIsing; 30 s at 30 cmH2O) followed by intermittent positive pressure ventilation, or continuous SIs (SIcont: 30 s duration with 1 s break). We thus examined 4 groups: ICC +SIsing, ICC +SIcont, PBCC +SIsing, and PBCC +SIcont. Chest compressions and epinephrine administration followed international guidelines. PBCC lambs underwent cord clamping 10 min after ROSC. Physiological and oxygenation variables were measured throughout.ResultsThe time taken to achieve ROSC was not different between groups (mean (SD) 4.3±2.9 min). Mean and diastolic blood pressure was higher during chest compressions in PBCC lambs compared with ICC lambs, but no effect of SIs was observed. SIcont significantly reduced pulmonary blood flow, diastolic blood pressure and oxygenation after ROSC compared with SIsing.ConclusionWe found no significant benefit of SIcont over SIsing during CPR on the time to ROSC or on post-ROSC haemodynamics, but did demonstrate the feasibility of continuous SIs during advanced CPR on an intact umbilical cord. Longer-term studies are recommended before this technique is used routinely in clinical practice.

Abstract 8875: Early Compared to Late Administration of Epinephrine in Adults With Shockable Initial Rhythm Out-of-Hospital Cardiac Arrest

Introduction: The optimal timing of epinephrine administration in shockable initial rhythm out-of-hospital cardiac arrest (OHCA) is unclear. Hypothesis: Early compared to late epinephrine following first electrical defibrillation attempt is associated with better outcomes in shockable initial rhythm OHCA. Methods: We conducted a retrospective study in adults with shockable initial rhythm OHCA from 2011-2015 in North America. We used multivariable logistic regression to assess associations between timing of epinephrine and prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and hospital discharge with favorable neurological outcome (modified Rankin Scale score≤3). We used propensity-score-matching and subgroup analyses to assess robustness of associations. Results: Of 6416 patients, median age was 64 (IQR: 54-74) years, 5136 (80%) were men, 2226 (35%) received epinephrine within four minutes after first defibrillation, 5119 (80%), 1237 (19%), and 996 (16%) had prehospital ROSC, survival to hospital discharge, and favorable neurological outcome at discharge respectively. Adjusted for confounders, we observed lower odds of prehospital ROSC (OR=0.95, 95%CI 0.94-0.96; p<0.001), survival to hospital discharge (OR=0.91, 95%CI 0.89-0.92; p<0.001), and favorable neurological outcomes at discharge (OR=0.92, 95%CI 0.90-0.93; p<0.001) per minute later epinephrine administration. Compared to epinephrine administration within four minutes following first defibrillation attempt, later epinephrine was associated with lower odds of prehospital ROSC (OR=0.58, 95%CI 0.51-0.68; p<0.001), survival to hospital discharge (OR=0.50, 95%CI 0.43-0.58; p<0.001), and favorable neurological outcome at discharge (OR=0.51, 95%CI 0.43-0.59; p<0.001). Associations remained significant in a well-balanced propensity score matched cohort and subgroup analyses by witness status, EMS response time, and total epinephrine dose. Conclusion: In shockable initial rhythm OHCA, early compared to late epinephrine administration following first defibrillation attempt was associated with better odds of prehospital ROSC, survival to hospital discharge, and hospital discharge with favorable neurological outcome.

Abstract 11112: Impact of Changes in Clinical Practice Guidelines on Survival Outcomes After Traumatic Out-of-Hospital Cardiac Arrest

Aim: In this study, we examine the impact of a trauma-based resuscitation protocol on survival outcomes following emergency medical services (EMS) witnessed traumatic out-of-hospital cardiac arrest (OHCA). Methods: We included EMS-witnessed OHCAs arising from trauma and occurring between 2008 and 2019. In December 2016, a new resuscitation protocol for traumatic OHCA was introduced prioritizing the treatment of potentially reversible causes before conventional cardiopulmonary resuscitation. The effect of the new protocol on survival outcomes was assessed using adjusted multivariable logistic regression models. Results: Paramedics attempted resuscitation on 490 patients, with 341 (69.6%) and 149 (30.4%) occurring during the control and intervention periods, respectively. A reduction in the proportion of cases receiving cardiopulmonary resuscitation and epinephrine administration were found in the intervention period compared to the control period, whereas trauma-based interventions increased significantly, including blood administration (pre-arrest: 17.9% vs 3.7%; intra-arrest: 24.1% vs 2.7%), splinting (pre-arrest: 38.6% vs 17.1%; intra-arrest: 20.7% vs 5.2%), and finger thoracostomy (pre-arrest: 13.1% vs 0.6%; intra-arrest: 22.8% vs 0.9%), respectively, with p-values <0.001 for all comparisons. After adjustment, the trauma-based resuscitation protocol was not associated with an improvement in survival to hospital discharge (AOR 1.29, 95% CI: 0.51-3.23), event survival (AOR 0.72, 95% CI: 0.41-1.28) or prehospital return of spontaneous circulation (AOR 0.63, 95% CI: 0.39-1.03). Conclusion: In our region, the introduction of a trauma-based resuscitation protocol led to an increase in the delivery of almost all trauma interventions; however, this did not translate into better survival outcomes following EMS-witnessed traumatic OHCA.

Paradoxical refractory hypotension following adrenaline administration in a patient taking clozapine

Clozapine is a potent antipsychotic commonly used for refractory schizophrenia. Adverse effects are well recognised including constipation, intestinal obstruction, agranulocytosis and cardiomyopathy. We present a case of paradoxical refractory hypotension following epinephrine administration in a patient taking clozapine. A psychiatric inpatient who had been taking clozapine for many years developed paralytic ileus and obstruction requiring surgical intervention. Following initiation of epinephrine administration intraoperatively he developed refractory hypotension which improved only when epinephrine was weaned off. This effect is likely due to uninterrupted β2-agonist activity in the presence of clozapine-induced α-blockade. Clinicians need to have greater awareness of this serious interaction and avoid the use of epinephrine in patients taking clozapine.

Risk factors and prognosis in very low birth weight infants treated for hypotension during the first postnatal week from the Korean Neonatal Network

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks’ gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life.

27 ECG monitoring during NRP: A false sense of security?

Primary Subject area Neonatal-Perinatal Medicine Background During neonatal resuscitation, use of an electrocardiogram (ECG) provides a more reliable measurement of heart rate than auscultation or pulse oximetry. Having an ECG monitor may, however, provide a false sense of security in the unlikely scenario of a newborn with pulseless rhythms. This could delay critical resuscitative steps during neonatal resuscitation. Objectives The aim of this study is to evaluate whether the presence of ECG monitoring has an impact on the resuscitative steps of neonatal resuscitation providers. Design/Methods We conducted a prospective crossover randomized controlled trial, which took place at Sainte-Justine University Health Center in Montreal, Quebec, Canada. Residents, fellows, attending physicians, transport nurses, and respiratory therapists were recruited in teams of three. They participated in two simulation scenarios (pulseless electrical activity [PEA] with and without ECG monitoring). Teams were randomized to one of the scenarios and then crossed over. A debriefing session followed the two scenarios. All sessions were video-recorded. The primary outcome was the time to pulse check once the simulated mannequin was programmed to become pulseless. Secondary outcomes were the number of pulse checks, time to intubation, time to start of chest compressions, and time to administration of epinephrine. Results Preliminary results (n=5 groups, 10 scenarios) showed that the time to check the pulse once the mannequin was pulseless was longer when ECG electrodes were used (98.0 vs 55.6 sec, p = 0.07). There was a statistically significant decreased number of pulse checks with the ECG compared to without (2.4 vs 5.6, p = 0.004). Time to start of positive pressure ventilation (31.3 vs 27 sec), intubation (182.4 vs 179.2 sec), chest compressions (235.2 vs 227.6 sec), and epinephrine administration (340.8 vs 241.5 sec), were all increased in the presence ECG monitoring, but the difference between groups was not statistically significant. Conclusion ECG monitoring may alter the behaviour of individuals and delay recognition of a pulseless state, but preliminary data suggest that clinical endpoints are not affected.

Clinical significance of early echocardiography after out-of-hospital cardiac arrest on arrival to a heart attack centre

Background Left ventricular systolic dysfunction (LVSD) is common after out of hospital cardiac arrest (OOHCA) and can manifest as global or regional change. Purpose We evaluated the extent of global and regional LVSD and its association with coronary artery disease (CAD) and outcome in those undergoing coronary angiography after OOHCA. Methods 619 patients with OOHCA were admitted at our centre between 1st May 2012 and 31st December 2017. 398 patients were included. Rates of cardiogenic shock and extent of CAD, as classified by the SYNTAX score were measured. The primary endpoint was 12-month mortality. Patients with incomplete data were excluded from the analysis. Results Two hundred and sixty-six patients (median age 62 [53–71] 76.3% male) underwent both trans-thoracic echocardiography andcoronary angiography on arrival and were included in the final analysis. 81.6% had ventricular fibrillation, 83.5% were witnessed and 51.9% occurred at residence. Ninety-six patients (36%) had significant LVSD (Left Ventricular Ejection Fraction [LVEF] &lt;40%) and 139 (52.2%) patients had regional wall motion abnormalities (RWMAs) on arrival. Patients were classified into 4 groups (Group A: LVEF &lt;40%/Global, Group B: LVEF &lt;40%/RWMA, Group C: LVEF ≥40%/Global and Group D: LVEF ≥40%/RWMA) with frequencies of 10.9%, 25.2%, 41.4% and 22.6%). Patients in Group D had the shortest low-flow times and lowest rates of epinephrine administration, with most favourable metabolic status on arrival, based on lactate and creatinine values. In Groups B and D (RWMAs), patients were significantly more likely to have a post-ROSC ECG demonstrating ST elevation/LBBB and absence of epinephrine administration during resuscitation with shorter low flow times. Extent of CAD was similar between the four groups. From patients with LVEF ≥40%, patients in Group C had substantially lower SYNTAX scores than compared with Group D (0.5 vs 13.5, p&lt;0.001). However, both Group B and C (RWMA) groups had highest rates of culprit lesions compared with matched global groups which was reflected in higher PCI rates (Figure 1). The primary endpoint of 12-month mortality was lowest in Group D and highest in the Group A group. A similar effect was observed for poor neurological outcome and 30-day mortality. Patients with regional LVSD had significantly improved survival at 12 months compared with those with global LVSD (70.5% vs 48.3%, p&lt;0.001) vs 51). Those in Group D had highest survival at 12 months, while this was similar for Groups B and C and lowest in Group A (Figure 2). Cardiac aetiology death was significantly higher in those with LVEF &lt;40% compared to those with LVEF ≥40% (70.5% vs 48.3%, p&lt;0.001). Conclusions Patients with significant LVEF &lt;40% have higher rates of cardiogenic shock and mortality which was driven by cardiac aetiology death, while presence of RWMAs are associated with a higher rate of culprit coronary lesions and improved outcome FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Abstract P348: Pathophysiological Basis Of A Compound Variant In Calcium And Sarcomere Regulation Causing Cardiac Arrhythmias And Hypertrophic Cardiomyopathy

Rationale: Hypertrophic cardiomyopathy (HCM) is common inheritable heart disease. HCM is highly associated with arrhythmias and/or sudden death. Studies show that molecular defects in calcium handling impairing the cardiomyocyte contractility is a predominant cause. However, the pathophysiology underlying HCM with arrhythmias is not well understood, hindering the identification of novel therapies. Objective: To investigate the pathophysiological consequences of compound variants, consisting of Histidine Rich Calcium Binding Protein gene ( HRC S96A ) and an intronic 25bp deletion in cardiac myosin binding protein-C ( MYBPC3 Δ25bp ). Methods and Results: Clinical data revealed that co-segregation of HRC S96A and MYBPC3 ΔInt32 results in cardiac arrhythmia, heart failure, and sudden cardiac death in South Asians. To determine the cellular/molecular trigger underlying the pathophysiology of this dual variant, we used humanized, knock-in, heterozygous mouse models, including HRC S81A (equivalent to HRC S96A ) MYBPC3 Δ25bp , HRC S81A / MYBPC3 Δ25bp (double variant, DV), and wild-type controls. Echocardiography revealed a significant decrease in the percentage of ejection fraction and fractional shortening in DV mice, as well as the presence of diastolic dysfunction, at 12 weeks of age, compared to single-variant and wild-type mice. Electrocardiogram tracing of DV mice showed the presence of stress-induced arrhythmias, such as ventricular tachycardia after caffeine and epinephrine administration. Using isolated cardiomyocytes in vitro , Calcium transient experiments indicated a significant decrease in fractional shortening, Ca 2+ transient amplitude, and a higher number of after-contractions in cardiomyocytes from DV mice. DV mouse hearts showed increased phosphorylation of CaMKII and SR Ca 2+ leak by cardiomyocytes. Inclusion of the CaMKII inhibitor KN-93 rescued the increases in SR Ca 2+ leak and in aftercontractions. Conclusion: Impaired Ca 2+ -handling, owing to the HRC S96A variant, aggravates SR Ca 2+ leak and aftercontractions in MYBPC3 Δ25bp cardiomyocytes, subsequently triggering cardiac arrhythmias and sudden death in vivo .