Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial.

BACKGROUND: Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. METHODS: The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). RESULTS: From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8-7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3). CONCLUSIONS: Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study.

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

Pulmonary embolism-related refractory out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: Prague OHCA study post hoc analysis.

AIMS: Refractory out-of-hospital cardiac arrest (r-OHCA) in patients with pulmonary embolism (PE) is associated with poor outcomes. The role of extracorporeal cardiopulmonary resuscitation (ECPR) in this patient group is uncertain. This study aims to analyse clinical course, outcomes, and the effect of an invasive procedure, including ECPR, in a randomized population. METHODS AND RESULTS: A post hoc analysis of a randomized controlled trial (Prague OHCA study) was conducted to evaluate the effect of ECPR vs. a standard approach in r-OHCA. A subgroup of patients with PE-related r-OHCA was identified, and procedural and outcome characteristics, including favourable neurological survival, organ donation, and complications, were compared to patients without PE. Pulmonary embolism was identified as a cause of r-OHCA in 24 of 256 (9.4%) enrolled patients. Patients with PE were more likely to be women [12/24 (50%) vs. 32/232 (13.8%); P < 0.001] and presented more frequently with an initial non-shockable rhythm [23/24 (95.8%) vs. 77/232 (33.2%); P < 0.001], as well as more severe acidosis at admission [median pH (interquartile range); 6.83 (6.75-6.88) vs. 6.98 (6.82-7.14); P < 0.001]. Their favourable 180-day neurological survival was significantly lower [2/24 (8.3%) vs. 66/232 (28.4%); P = 0.049], but the proportion of accepted organ donors was higher (16.7 vs. 4.7%, P = 0.04). CONCLUSION: Refractory out-of-hospital cardiac arrest due to PE has a different presentation and inferior outcomes compared to other causes but may represent an important source of organ donations. The ECPR method did not improve patient outcomes.

Initial rhythm and survival in refractory out-of-hospital cardiac arrest. Post-hoc analysis of the Prague OHCA randomized trial.

BACKGROUND: The prognosis of refractory out-of-hospital cardiac arrest (OHCA) is generally poor. A recent Prague OHCA study has demonstrated that an invasive approach (including extracorporeal cardiopulmonary resuscitation, ECPR) is a feasible and effective treatment strategy in refractory OHCA. Here we present a post-hoc analysis of the role of initial rhythm on patient outcomes. METHODS: The study enrolled patients who had a witnessed OHCA of presumed cardiac cause without early recovery of spontaneous circulation. The initial rhythm was classified as either a shockable or a non-shockable rhythm. The primary outcome was a composite of 180 day-survival with Cerebral Performance in Category 1 or 2. RESULTS: 256 (median age 58y, 17% females) patients were enrolled. The median (IQR) duration of resuscitation was 52 (33-68) minutes. 156 (61%) and 100 (39%) of patients manifested a shockable and non-shockable rhythm, respectively. The primary outcome was achieved in 63 (40%) patients with a shockable rhythm and in 5 (5%) patients with a non-shockable rhythm (p < 0.001). When patients were analyzed separately based on whether the treatment was invasive (n = 124) or standard (n = 132), the difference in the primary endpoint between shockable and non-shockable initial rhythms remained significant (35/72 (49%) vs 4/52 (8%) in the invasive arm and 28/84 (33%) vs 1/48 (2%) in the standard arm; p < 0.001). CONCLUSION: An initial shockable rhythm and treatment with an invasive approach is associated with a reasonable neurologically favorable survival for 180 days despite refractory OHCA. Non-shockable initial rhythms bear a poor prognosis in refractory OHCA even when ECPR is readily available.

Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial.

BACKGROUND: Survival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes. METHODS: Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan-Meier estimates and Cox proportional hazard model was examined. RESULTS: Among 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5-68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rank p < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14-0.31; P < 0.001). CONCLUSIONS: In this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Coronary angiography and percutaneous coronary intervention in cardiac arrest patients without return of spontaneous circulation.

OBJECTIVES: This study aimed to examine coronary angiography (CAG) findings, percutaneous coronary intervention (PCI) results and outcomes in out-of-hospital cardiac arrest patients (OHCA) without return of spontaneous circulation (ROSC) on admission to hospital. METHODS: We analyzed the OHCA register and compared CAG, PCI, and outcome data in patients with and without ROSC on admission to hospital. RESULTS: Between January 2012 and December 2020, 697 OHCA patients were analyzed. Of these, 163 (23%) did not have ROSC at admission. Patients without ROSC were younger (59 vs. 61 years, p = 0.001) and had a longer resuscitation time (62 vs. 18 minutes, p < 0.001) than patients with ROSC. Significant coronary artery disease was highly prevalent in both groups (65% vs. 68%, p = 0.48). Patients without ROSC had higher rates of acute coronary occlusions (42% vs. 33%, p = 0.046), specifically affecting the left main stem (16% vs. 1%, p < 0.001). PCI was performed in 81 patients (50%) without ROSC and in 295 (55%) with ROSC (p = 0.21). The success rate was 86% in patients without ROSC and 90% in patients with ROSC (p = 0.33). Thirty-day survival was 24% in patients without ROSC and 70% in patients with ROSC. CONCLUSIONS: OHCA patients without ROSC on admission to hospital had higher acute coronary occlusion rates than patients with prehospital ROSC. PCI is feasible with a high success rate in patients without ROSC. Despite prolonged resuscitation times, meaningful survival in patients admitted without ROSC is achievable.

Gender differences and survival after out of hospital cardiac arrest.

BACKGROUND: Published evidence regarding the effect of gender on outcome after out of hospital cardiac arrest (OHCA) is inconsistent. We aimed to investigate the association of gender to outcome and resuscitation characteristics in OHCA patients admitted to the cardiac arrest center. METHODS: In this retrospective analysis of prospective registry data, all patients admitted for OHCA were included. The influence of gender on 30-day survival and good neurological outcome (cerebral performance category of 1 or 2) were examined using Kaplan-Meier estimates and multivariable logistic regression. RESULTS: In total, 932 patients were analysed (239 women, 26%). Women were older (64 vs 60 years, p < 0.001) and less commonly had a shockable rhythm (47% vs 65%, P < 0.001) compared to men. Women were less likely to have a cardiac cause of arrest (54% vs. 75%, p < 0.001), received less therapeutic hypothermia (74% vs 86%, p < 0.001) and coronary angiography (63% vs. 79%, p < 0.001). The overall 30-day survival was lower for women (45% vs. 53%, log-rank p = 0.005) as well as good neurological outcome (37% vs. 46%, p = 0.008). However, according to the multivariate logistic regression, gender was not associated with survival (OR 0.98, 95% CI 0.65-1.50, p = 0.94) nor with good neurological outcome (OR 0.91, 95% CI 0.59-1.40, p = 0.67). CONCLUSION: Women admitted for OHCA to a cardiac center had a different cause of arrest that had a different treatment and outcome compared to men. Survival and good neurological outcome were lower in women, however, after adjusting for baseline characteristics, gender was not associated with survival nor neurological outcome.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

Hypothermic versus Normothermic Temperature Control after Cardiac Arrest.

BACKGROUND: The evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics. METHODS: An individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence). RESULTS: The primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups. CONCLUSIONS: Hypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

Giant cell myocarditis in an older patient - reassessing the threshold for endomyocardial biopsy.

Giant cell myocarditis is a rare form of autoimmune myocarditis with high morbidity and mortality that affects mainly middle-aged adults. We report a case study of a 70-year-old man on chronic immunosuppression who presented with sustained ventricular tachycardia and symptoms of acute systolic heart failure, both with poor response to standard measures. A decision to pursue endomyocardial biopsy established the diagnosis of GCM and lead to initiation of immunosuppressive therapy and a favourable outcome. Our case illustrates that a low threshold for endomyocardial biopsy in new onset heart failure can lead to actionable information even in patients of advanced age.

Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study.

INTRODUCTION: Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy. METHODS AND ANALYSIS: The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05. ETHICS AND DISSEMINATION: The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03029169.

Refractory Ventricle Arrhythmias Alternating with Pulseless Electrical Activity in a Young Woman Rescued by Extracorporeal Cardiopulmonary Resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA). CASE PRESENTATION: The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator. CONCLUSION: Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.

Dysglycemia, Glycemic Variability, and Outcome After Cardiac Arrest and Temperature Management at 33°C and 36°C.

OBJECTIVES: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. DESIGN: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category." SETTING: Thirty-six sites in Europe and Australia. PATIENTS: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. INTERVENTIONS: Targeted temperature management at 33°C or 36°C. MEASUREMENTS AND MAIN RESULTS: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3-5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03-1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. CONCLUSION: Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.

A rationale for early extracorporeal membrane oxygenation in patients with postinfarction ventricular septal rupture complicated by cardiogenic shock.

AIMS: Ventricular septal rupture (VSR) became a rare mechanical complication of myocardial infarction in the era of percutaneous coronary interventions but is associated with extreme mortality in patients who present with cardiogenic shock (CS). Promising outcomes have been reported with the use of circulatory support allowing haemodynamic stabilization, followed by delayed repair. Therefore, we analysed our experience with an early use of Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO) for postinfarction VSR. METHODS AND RESULTS: We conducted a retrospective search of institutional database for patients presenting with postinfarction VSR from January 2007 to June 2016. Data from 31 consecutive patients (mean age 69.5 ± 9.1 years) who were admitted to hospital were analysed. Seven out of 31 patients with VSR who were in refractory CS received V-A ECMO support preoperatively. ECMO improved end-organ perfusion with decreased lactate levels 24 hours after implantation (7.9 mmol/L vs. 1.6 mmol/L, p = 0.01), normalized arterial pH (7.25 vs. 7.40, p < 0.04), improved mean arterial pressure (64 mmHg vs. 83 mmHg, p < 0.01) and lowered heart rate (115/min vs. 68/min, p < 0.01). Mean duration of ECMO support was 12 days, 5 out of 7 patients underwent surgical repair, 4 were weaned from ECMO, 3 survived 30 days and 2 survived more than 1 year. The most frequent complication (5 patients) and the cause of death (3 patients) was bleeding. CONCLUSIONS: Our experience suggests that early V-A ECMO in patients with VSR and refractory CS might prevent irreversible multiorgan failure by improved end-organ perfusion. Bleeding complications remain an important limitation of this approach.

Extra corporeal membrane oxygenation in the therapy of cardiogenic shock (ECMO-CS): rationale and design of the multicenter randomized trial.

AIMS: Extracorporeal membrane oxygenation (ECMO) in veno-arterial configuration represents an increasingly used method for circulatory support. ECMO in cardiogenic shock offers rapid improvement of circulatory status and significant increase in tissue perfusion. Current evidence on the use of ECMO in cardiogenic shock remains insufficient. The aim of the ECMO-CS trial is to compare two recognized therapeutic approaches in the management of severe cardiogenic shock: early conservative therapy and early implantation of veno-arterial ECMO on the background of standard care. METHODS: Eligible patients have either rapidly deteriorating or severe cardiogenic shock, defined using echocardiography, hemodynamic and metabolic criteria. Patients are randomized to the one of two arms: immediate veno-arterial ECMO therapy or early conservative therapy. All other diagnostic and therapeutic procedures are performed as per current standard of care, including other cardiovascular interventions (i.e. percutaneous coronary intervention or cardiac surgery). Follow-up includes visits at 30 days, 6 months and 12 months. Primary endpoint is a composite of death from any cause, resuscitated circulatory arrest, and implantation of another mechanical circulatory support device at 30 days. The sample size of 120 individuals (60 in each arm) provides 80% power to detect 50% reduction of primary endpoint, at alpha = 0.05. Patient recruitment started in October 2014. CONCLUSION: The results of the ECMO-CS trial may significantly influence current practice in the management of patients with severe and rapidly deteriorating cardiogenic shock. ECMO-CS trial registration number is NCT02301819.

Effect of Pulsatility on Microcirculation in Patients Treated with Extracorporeal Cardiopulmonary Resuscitation: A Pilot Study.

The effect of pulsatile blood flow on microcirculation during extracorporeal cardiopulmonary resuscitation (ECPR) is not elucidated; therefore, we designed an observational study comparing sublingual microcirculation in patients with refractory cardiac arrest (CA) with spontaneously pulsatile or low/nonpulsatile blood flow after treatment with ECPR. Microcirculation was assessed with Sidestream Dark Field technology in 12 patients with CA who were treated with ECPR and 12 healthy control subjects. Microcirculatory images were analyzed offline in a blinded fashion, and consensual parameters were determined for the vessels ≤20 µm. The patients' data, including actual hemodynamic parameters, were documented. Pulsatile blood flow was defined by a pulse pressure (PP) ≥ 15 mm Hg. Compared with the healthy volunteers, the patients who were treated with ECPR exhibited a significantly lower proportion of perfused capillaries (PPC); other microcirculatory parameters did not differ. The groups of patients with pulsatile (n = 7) versus low/nonpulsatile (n = 5) blood flow did not differ in regards to the collected data and hemodynamic variables (except for the PP and ejection fraction of the left ventricle) as well as microcirculatory parameters. In conclusion, microcirculation appeared to be effectively supported by ECPR in our group of patients with CA with the exception of the PPC. We found only nonsignificant contribution of spontaneous pulsatility to extracorporeal membrane oxygenation-generated microcirculatory blood flow.

Safety, feasibility, and outcomes of induced hypothermia therapy following in-hospital cardiac arrest-evaluation of a large prospective registry*.

OBJECTIVES: Despite a lack of randomized trials, practice guidelines recommend that mild induced hypothermia be considered for comatose survivors of in-hospital cardiac arrest. This study describes the safety, feasibility, and outcomes of mild induced hypothermia treatment following in-hospital cardiac arrest. DESIGN: Prospective, observational, registry-based study. SETTING: Forty-six critical care facilities in eight countries in Europe and the United States reporting in the Hypothermia Network Registry and the International Cardiac Arrest Registry. PATIENTS: A total of 663 patients with in-hospital cardiac arrest and treated with mild induced hypothermia were included between January 2004 and February 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A cerebral performance category of 1 or 2 was considered a good outcome. At hospital discharge 41% of patients had a good outcome. At median 6-month follow-up, 34% had a good outcome. Among in-hospital deaths, 52% were of cardiac causes and 44% of cerebral cause. A higher initial body temperature was associated with reduced odds of a good outcome (odds ratio, 0.79; 95% CI, 0.68-0.92). Adverse events were common; bleeding requiring transfusion (odds ratio, 0.56; 95% CI, 0.31-1.00) and sepsis (odds ratio, 0.52; 95% CI, 0.30-0.91) were associated with reduced odds for a good outcome. CONCLUSIONS: In this registry study of an in-hospital cardiac arrest population treated with mild induced hypothermia, we found a 41% good outcome at hospital discharge and 34% at follow-up. Infectious complications occurred in 43% of cases, and 11% of patients required a transfusion for bleeding. The majority of deaths were of cardiac origin.

Targeted temperature management at 33°C versus 36°C after cardiac arrest.

BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. CONCLUSIONS: In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).

Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal. "Prague OHCA study".

BACKGROUND: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. METHODS: This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. PRIMARY OUTCOME: 6 months survival with good neurological outcome (Cerebral Performance Category 1-2). Secondary outcomes will include 30 day neurological and cardiac recovery. DISCUSSION: Authors introduce and offer a protocol of a proposed randomized study comparing a combined "hyperinvasive approach" to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future. ETHICS AND REGISTRATION: The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.