Abstract 10911: Amplitude Spectral Area to Guide Shock and Epinephrine Delivery in a Swine Model of Ventricular Fibrillation and Closed-Chest Resuscitation

Introduction: VF accounts for ~30% of all sudden cardiac arrest episodes. VF signal analysis in the frequency domain - calculating the amplitude spectral area (AMSA) - can inform on the probability that an electrical shock could terminate VF followed by return of spontaneous circulation (ROSC). BLS guidelines require delivery of shocks every 2 min and epinephrine every 4 min. Yet, shocks often do not terminate VF and may injure the myocardium. We have previously reported that guiding the timing of shock delivery based on AMSA reduces myocardial injury and improves outcome. Epinephrine is given to increase the coronary perfusion pressure (CPP) and therefore myocardial blood flow but has detrimental effects on post-resuscitation myocardial function and possibly on neurological outcome. Hypothesis: Monitoring AMSA during CPR could be used not only to guide shock delivery but also to avoid administering epinephrine when AMSA predicts a high probability of shock success, reserving epinephrine when AMSA predicts a low probability of shock success and additional CPP increase might be helpful. Methods: In a swine model of electrically induced VF and mechanical chest compressions, two resuscitation protocols were compared in 8 pigs each: (1) A guidelines-driven (GD), delivering shocks and epinephrine guided by the current BLS protocol and (2) An AMSA-driven, delivering shocks and epinephrine guided by AMSA (ADSE). VF was untreated for 10 min and pigs that achieved ROSC were monitored for 240 min. Results: Compared to GD, ADSE was associated with a shorter time to ROSC (400±80 vs 569±16 sec, p=0.034) and higher survival rate at 240 minutes with borderline statistical significance (7/8 vs 3/8, p=0.059). ADSE required fewer shocks (3±2 vs 5±2, p=0.026) and received fewer doses of epinephrine (median [interquartile range], 1[1-1] vs 2[1.3-3], p=0.038). Conclusions: Resuscitation with the ADSE protocol was superior to the GD protocol resulting in a shorter time to ROSC with improved survival requiring fewer shocks and fewer epinephrine doses. The ADSE protocol represents a more tailored approach to resuscitation enabling delivery of resuscitation interventions with higher precision and consequently minimizing their associated adverse effects.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis

Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Mechanism and Potential Treatment of the 'No Reflow' Phenomenon After Acute Myocardial Infarction: Role of Pericytes and GPR39

The 'no reflow' phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow, and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, prior to reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared to controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39 knockout and VC43 treated mice compared to controls. We conclude that GPR39 mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI, and that smaller no reflow zones in GPR39 knockout and VC43 treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI as well as providing a therapeutic pathway for the condition.

Standard CPR versus interposed abdominal compression CPR in shunted single ventricle patients: comparison using a lumped parameter mathematical model

Introduction: Cardiopulmonary resuscitation (CPR) in the shunted single-ventricle population is associated with poor outcomes. Interposed abdominal compression-cardiopulmonary resuscitation, or IAC-CPR, is an adjunct to standard CPR in which pressure is applied to the abdomen during the recoil phase of chest compressions. Methods: A lumped parameter model that represents heart chambers and blood vessels as resistors and capacitors was used to simulate blood flow in both Blalock-Taussig-Thomas and Sano circulations. For standard CPR, a prescribed external pressure waveform was applied to the heart chambers and great vessels to simulate chest compressions. IAC-CPR was modelled by adding phasic compression pressure to the abdominal aorta. Differential equations for the model were solved by a Runge-Kutta method. Results: In the Blalock-Taussig-Thomas model, mean pulmonary blood flow during IAC-CPR was 30% higher than during standard CPR; cardiac output increased 21%, diastolic blood pressure 16%, systolic blood pressure 8%, coronary perfusion pressure 17%, and coronary blood flow 17%. In the Sano model, pulmonary blood flow during IAC-CPR increased 150%, whereas cardiac output was improved by 13%, diastolic blood pressure 18%, systolic blood pressure 8%, coronary perfusion pressure 15%, and coronary blood flow 14%. Conclusions: In this model, IAC-CPR confers significant advantage over standard CPR with respect to pulmonary blood flow, cardiac output, blood pressure, coronary perfusion pressure, and coronary blood flow. These results support the notion that single-ventricle paediatric patients may benefit from adjunctive resuscitation techniques, and underscores the need for an in-vivo trial of IAC-CPR in children.

Goldilocks in cardiac arrest: A scoping review of invasive hemodynamic monitoring in the pre-hospital setting for getting adrenaline dosing just right

Introduction A one-size-fits-all approach to adrenaline dosing is likely to be sub-optimal for out-of-hospital cardiac arrest given the diverse nature of patient age, bodyweight, frailty and intra-arrest coronary perfusion pressure. An individualised adrenaline dosing approach to cardiac arrest using invasive blood pressure monitoring has been shown to increase rates of return of spontaneous circulation in the hospital setting, but evidence for this approach has not yet been reviewed in the pre-hospital setting. Methods A scoping review was undertaken using Science Direct, ProQuest, PubMed, CINAHL Complete and GALE Health and Wellness databases with the search terms ‘arterial line’, ‘pre-hospital’, ‘cardiac arrest’ and similar derivatives. Subject matter experts and authors of articles meeting inclusion criteria were also consulted to help identify further relevant studies. Articles were included if they pertained to the use of arterial lines in cardiac arrest in the pre-hospital field, and excluded if they related to traumatic cardiac arrest, in a language other than English, Dutch or French, or not retrievable as a full text. Results A total of 1408 articles were identified using the search method, of which three remained after de-duplication, use of inclusion and exclusion criteria, and full text appraisal. The current pre-hospital literature is lacking and avenues for further research to improve the evidence for hemodynamic guided resuscitation were identified. Conclusion Paramedic-initiated invasive arterial monitoring presents a new, but as yet unproven, intervention for improving cardiac arrest outcomes.

Esmolol during cardiopulmonary resuscitation reduces neurological injury in a porcine model of cardiac arrest

Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (2[1–3] vs. 21[16–52] ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

A case report: adenosine triggered myocardial infarction during myocardial perfusion stress test imaging in a diabetic patient

Background Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) can in general be used safely in daily clinical practice. However, under the right circumstances, it can lead to serious complications. Case summary A 68-year-old female patient with diabetes and a history of inferior ST-elevation myocardial infarction 8 years earlier, visited our outpatient clinic with atypical chest discomfort. In order to assess whether this is due to myocardial ischaemia, MPI-SPECT was ordered. As it was suspected she would not achieve sufficient exercise levels, pharmacologic stress using adenosine was arranged. During the scan, she developed acute myocardial infarction. Subsequent urgent coronary angiography demonstrated a subtotal stenosis in the proximal left anterior descending coronary artery which was successfully stented. She was still free from angina 4 months later. Discussion The combination of a reduced systemic and coronary perfusion pressure in the presence of an exhausted coronary autoregulation, may be a starting point for local geometrical changes that initiate the classic cascade of thrombus formation and acute occlusion of coronary arteries during MPI-SPECT. This illustrates the need for continuous patient and electrocardiogram monitoring.

Esmolol during Cardiopulmonary Resuscitation Reduces Neurological Injury in a Porcine Model of Cardiac Arrest

Background. Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Methods. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 36 pigs and left untreated for 12min. During CPR, animals were randomized to receive epinephrine (30µg/kg) with either esmolol (0.5mg/kg) or saline (control). Pigs were then observed up to 96h. Results. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (p<0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (p<0.05) and hippocampal microglial activation (p<0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (p<0.01). Conclusions. In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

Cardiac arrest complicating cardiogenic shock: from pathophysiological insights to Impella-assisted cardiopulmonary resuscitation in a pheochromocytoma-induced Takotsubo cardiomyopathy—a case report

Background A ‘catecholamine storm’ in a case of pheochromocytoma can lead to a transient left ventricular dysfunction similar to Takotsubo cardiomyopathy. A cardiogenic shock can thus develop, with high left ventricular end-diastolic pressure and a reduction in coronary perfusion pressure. This scenario can ultimately lead to a cardiac arrest, in which unloading the left ventricle with a peripheral left ventricular assist device (Impella®) could help in achieving the return of spontaneous circulation (ROSC). Case summary A patient affected by Takotsubo cardiomyopathy caused by a pheochromocytoma presented with cardiogenic shock that finally evolved into refractory cardiac arrest. Cardiopulmonary resuscitation was performed but ROSC was achieved only after Impella® placement. Discussion In the clinical scenario of Takotsubo cardiomyopathy due to pheochromocytoma, when cardiogenic shock develops treatment is difficult because exogenous catecholamines, required to maintain organ perfusion, could exacerbate hypertension and deteriorate the cardiomyopathy. Moreover, as the coronary perfusion pressure is critically reduced, refractory cardiac arrest could develop. Although veno-arterial extra-corporeal membrane oxygenation (va-ECMO) has been advocated as the treatment of choice for in-hospital refractory cardiac arrest, in the presence of left ventricular overload a device like Impella®, which carries fewer complications as compared to ECMO, could be effective in obtaining the ROSC by unloading the left ventricle.