Thrombolysis of a massive intracardiac thrombus during resuscitation: documentation by transoesophageal echocardiography

Acute pulmonary embolism is a frequent potentially reversible cause of sudden cardiac arrest. The early diagnosis is challenging but essential for further treatment. New therapeutic options in resuscitation, such as extracorporeal resuscitation, are leading to frequent transports of patients to emergency rooms with ongoing resuscitation. A transoesophageal echo performed during resuscitation can give hints for reversible causes for the cardiac arrest. We present a case of a 40-year-old female patient who was transferred to our department with ongoing resuscitation and received a transoesophageal echo immediately on arrival. The examination showed a massive intracardiac thrombus. The subsequent thrombolysis and following resuscitation were observed and documented via transoesophageal echo.

Abstract 264: Traumatic and Hemorrhagic Complications After Extracorporeal Cardiopulmonary Resuscitation for Out-of-hospital Cardiac Arrest

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is a rescue therapy for treatment of refractory out-of-hospital cardiac arrests (OHCA). We describe the incidence of traumatic and hemorrhagic complications among patients undergoing ECPR for OHCA and the association between CPR duration and ECPR-related injuries or bleeding. Methods: We examined prospectively collected data from the Extracorporeal Resuscitation Outcomes Database (EROD), which includes ECPR-treated OHCAs from participating hospitals (Oct 2014 - Aug 2019). The primary outcome was traumatic or hemorrhagic complications, defined as injury to the chest, abdomen, or vasculature, or bleeding requiring transfusion or surgery. The primary exposure was the cardiac arrest to ECPR initiation interval (CA-ECPR interval), measured as the time from arrest to initiation of ECPR. Descriptive statistics were used to compare demographic, cardiac arrest, and ECPR characteristics among patients with and without CPR-related traumatic or bleeding complications. Multivariable logistic regression was used to examine the association between CPR duration and traumatic or bleeding complications. Results: A total of 68 patients from 4 hospitals received ECPR for OHCA were entered into EROD and met inclusion criteria. Median age was 51 (IQR 38-58), 81% were male, 40% had BMI > 30, and 70% had pre-existing medical comorbidities. A total of 65% had an initial shockable cardiac rhythm, mechanical CPR was utilized in at least 29% of patients, and 27% were discharged alive. A total of 37% experienced a traumatic or bleeding complication, with major bleeding (32%), vascular injury (18%), and cannula site bleeding (15%) being the most common. Compared to patients with shorter CPR times, patients with a 10 minute longer CA-ECPR interval had 18% (95% CI -2-42%) higher odds of suffering a mechanical or bleeding complication, but this did not reach statistical significance (p=0.08). Conclusions: Traumatic injuries and bleeding complications are common among patients undergoing ECPR. Further study is needed to investigate the relation between arrest duration and complications. Clinicians performing ECPR should anticipate and assess for injuries and bleeding in this high-risk population.

Evaluating the potential impact of an emergency department extracorporeal resuscitation (ECPR) program: a health records review

ABSTRACTObjectivesExtracorporeal cardiopulmonary resuscitation in refractory cardiac arrest (ECPR) is an emerging resuscitative therapy that has shown promising results for selected patients who may not otherwise survive. We sought to identify the characteristics of cardiac arrest patients presenting to our institution to begin assessing the feasibility of an ECPR program.MethodsThis retrospective health records review included patients aged 18–75 years old presenting to our academic teaching hospital campuses with refractory nontraumatic out-of-hospital or in-emergency department (ED) cardiac arrest over a 2-year period. Based on a scoping review of the literature, both “liberal” and “restrictive” ECPR criteria were defined and applied to our cohort.ResultsA total of 179 patients met inclusion criteria. Median age was 60 years, and patients were predominantly male (72.6%). The initial rhythm was ventricular tachycardia/ventricular fibrillation in 49.2%. The majority of arrests were witnessed (69.3%), with immediate bystander CPR performed on 53.1% and an additional 12% receiving CPR within 10 minutes of collapse. Median prehospital time was 40 minutes (interquartile range, 31–53.3). Two-thirds of patients (65.9%) were identified as having a reversible cause of arrest and favorable premorbid status was identified in nearly three quarters (74.3%). Our two sets of ECPR inclusion criteria revealed that 33 and 5 patients (liberal and restrictive criteria, respectively), would have been candidates for ECPR.ConclusionAt our institution, we estimate between 6% and 40% of ED refractory cardiac arrest patients would be candidates for ECPR. These findings suggest that the implementation of an ECPR program should be explored.

Extracorporeal resuscitation with carbon monoxide improves renal function by targeting inflammatory pathways in cardiac arrest in pigs

Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesized that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest. Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional [cardiopulmonary resuscitation (CPR)], an extracorporeal (E-CPR), or a CO-assisted extracorporeal (CO-E-CPR) protocol. CO was applied using a membrane-controlled releasing system. Markers of renal injury were measured, and histopathological analyses were carried out. We investigated renal pathways involving inflammation as well as apoptotic cell death. No differences in serum neutrophil gelatinase-associated lipocalin (NGAL) were detected after CO treatment compared with Sham animals (Sham 71 ± 7 and CO-E-CPR 95 ± 6 ng/mL), while NGAL was increased in CPR and E-CPR groups (CPR 135 ± 11 and E-CPR 124 ± 5 ng/mL; P < 0.05). Evidence for histopathological damage was abrogated after CO application. CO increased renal heat shock protein 70 expression and reduced inducible cyclooxygenase 2 (CPR: 60 ± 8; E-CPR 56 ± 8; CO-E-CPR 31 ± 3 µg/mL; P < 0.05). Caspase 3 activity was decreased (CPR 1,469 ± 276; E-CPR 1,670 ± 225; CO-E-CPR 755 ± 83 pg/mL; P < 0.05). Furthermore, we found a reduction in renal inflammatory signaling upon CO treatment. Our data demonstrate improved renal function by extracorporeal CO treatment in a porcine model of cardiac arrest. CO reduced proinflammatory and proapoptotic signaling, characterizing beneficial aspects of a novel treatment option to overcome high mortality.

Carbon monoxide improves haemodynamics during extracorporeal resuscitation in pigs

Aims Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism. Methods and results In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P &lt; 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P &lt; 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P &lt; 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response. Conclusions CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.

Phosphodiesterase-4 inhibition reduces ECLS-induced vascular permeability and improves microcirculation in a rodent model of extracorporeal resuscitation

Extracorporeal circulation can be accompanied by increased vascular permeability leading to pathological fluid balance and organ dysfunction. The second messenger cAMP is involved in capillary permeability and maintains endothelial integrity. The aim of the present study was to evaluate the effect of phosphodiesterase-4 (PDE4) inhibition with rolipram on extracorporeal circulation-induced capillary leakage, microcirculatory dysfunction, and organ injury in rodents. Rats were randomly allocated to the following groups: sham ( n = 5), venoarterial extracorporeal circulation [extracorporeal life support (ECLS), n = 7], ECLS + rolipram ( n = 7), extracorporeal resuscitation (ECPR; n = 7), and ECPR + rolipram ( n = 7). In the groups that underwent ECPR, ECLS-based cardiopulmonary resuscitation (ECPR) was performed after the induction of hypoxic cardiac arrest. Upon return of spontaneous circulation, rolipram was administered intravenously. The mesenteric microcirculation was studied using intravital microscopy, and organ specimens were harvested upon completion of the study. ECLS and ECPR induced a proinflammatory response (cytokines IL-1β, IL-6, and TNF-α). Although PDE4 expression was upregulated in vascular tissue, PDE4 inhibition abrogated impaired microcirculation and capillary leak (albumin extravasation of the sham group: 1 ± 0.03-fold, ECLS group: 1.2 ± 0.05-fold, ECLS + rolipram group: 0.99 ± 0.04-fold, ECPR group: 1.6 ± 0.04-fold, and ECPR + rolipram group: 1.06 ± 0.02-fold from the sham group, P < 0.05). PDE4 inhibition led to stabilization of vascular cAMP levels but did not affect cytokine levels. Capillary leak was reduced, as demonstrated by the decrease of the systemic biomarkers soluble vascular-endothelial cadherin and activated complement 3. Histological analysis revealed reduced injury to the lungs and kidneys after PDE4 inhibition, with a significant decrease in systemic renal damage markers. Our findings demonstrate that extracorporeal circulation causes an inflammatory reaction associated with decreased vascular cAMP levels, increased vascular permeability, and impaired microcirculation. PDE4 inhibition proved to be capable of reducing these side effects in ECLS and ECPR, leading to reduced microcirculatory, renal, and pulmonary injury. NEW & NOTEWORTHY Various complications are common after extracorporeal circulation. Among these, endothelial injury may cause impaired microcirculation and capillary leak. Here, we report that phosphodiesterase-4 inhibition targeting endothelial cAMP is capable of reducing microvascular complications in a rodent model of extracorporeal resuscitation. Microcirculation and vascular permeability are influenced without targeting extracorporeal circulation-induced inflammation. Thus, pulmonary and renal organ protection may be conferred.