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Cardiac arrest affects millions of people per year worldwide. Although advances in cardiopulmonary resuscitation and intensive care have improved outcomes over time, neurologic impairment and multiple organ dysfunction continue to be associated with a high mortality rate. The pathophysiologic mechanisms underlying the post-resuscitation disease are complex, and a coordinated, evidence-based approach to post-resuscitation care has significant potential to improve survival. Critical care management of patients resuscitated from cardiac arrest focuses on the identification and treatment of the underlying cause(s), hemodynamic and respiratory support, organ protection, and active temperature control. This review provides a state-of-the-art appraisal of critical care management of the post-cardiac arrest patient. [ABSTRACT FROM AUTHOR]

Background: Europe is a patchwork of 47 countries with legal, cultural, religious, and economic differences. A prior study suggested variation in ethical resuscitation/end-of-life practices across Europe. This study aimed to determine whether this variation has evolved, and whether the application of ethical practices is associated with emergency care organisation.Methods: A questionnaire covering four domains of resuscitation ethics was developed based on consensus: (A) Approaches to end-of-life care and family presence during cardiopulmonary resuscitation; (B) Determinants of access to best resuscitation and post-resuscitation care; (C) Diagnosis of death and organ donation (D) Emergency care organisation. The questionnaire was sent to representatives of 32 countries. Responses to 4-choice or 2-choice questions pertained to local legislation and common practice. Positive responses were graded by 1 and negative responses by 0; grades were reconfirmed/corrected by respondents from 31/32 countries (97%). For each resuscitation/end-of-life practice a subcomponent score was calculated by grades' summation. Subcomponent scores' summation resulted in domain total scores.Results: Data from 31 countries were analysed. Domains A, B, and D total scores exhibited substantial variation (respective total score ranges, 1-41, 0-19 and 9-32), suggesting variable interpretation and application of bioethical principles, and particularly of autonomy. Linear regression revealed a significant association between domain A and D total scores (adjusted r(2)=0.42, P<0.001).Conclusions: According to key experts, ethical practices and emergency care still vary across Europe. There is need for harmonised legislation, and improved, education-based interpretation/application of bioethical principles. Better application of ethical practices may be associated with improved emergency care organisation. [ABSTRACT FROM AUTHOR]

Aim Emergency research is necessary to prevent exposure of patients to unvalidated clinical practice (nonmaleficence), and to improve the dismal prognosis of disorders requiring emergent treatment such as cardiac arrest (beneficence). Regulations that govern clinical research should conform to bioethical principles of respect for nonmaleficence, beneficence, autonomy, and justice. Our objectives are to review the evolution of European Union (EU) legislation on emergency research, and to identify potentially remaining problems. Data sources EU legislative sources on clinical research and medical literature describing the impact of EU Regulations on emergency research. Results Article 5 of EU Directive 2001/20/EC required consent before enrolment in a research study to ensure the autonomy of potentially incapacitated research subjects. However, obtaining such consent is often impossible in emergency situations. Directive 2001/20/EC was criticized for potentially preventing emergency research. Several EU Member States addressed this problem by permitting deferred consent. International ethical guidelines supporting deferred consent were also cited by Good Clinical Practice Directive 2005/28/EC. However, Directive 2001/20/EC was not revised to achieve harmonization of EU emergency research, thus resulting in ongoing “ ambiguity” as regards to emergency research legitimacy. This will be definitively addressed by applying EU Regulation No. 536/2014 and repealing Directive 2001/20/EC. The new EU Regulation permits using deferred consent under clearly specified conditions, and may foster emergency research that evaluates interventions posing minimal risk relative to standard practice. Conclusions Legislation related to emergency research in Europe has evolved to increase concordance with bioethical principles so as to increase evidence-based improvements in emergency care. [ABSTRACT FROM AUTHOR]

Background Research in an emergency setting such as that with an acute cardiovascular event is challenging because the window of opportunity to treat may be short and may preclude time to obtain informed consent from the patient or their representative. Some perceive that requiring informed consent in emergency situations has limited improvements in care. Vulnerable populations including minorities or residents of low-income countries are at greatest risk of need for resuscitation. Lack of enrollment of such patients would increase uncertainties in treatment benefit or harm in those at greater risk of need for resuscitation. We sought to assess international variation in policies and procedures related to exception from informed consent (EFIC) or deferred consent for emergency research. Methods A brief survey instrument was developed and modified by consensus among the investigators. Included were multiple choice and open-ended responses. The survey included an illustrative example of a hypothetical randomized study. Elicited information included the possibility of conducting such a study in the respondent's country, as well as approvals required to conduct the study. The population of interest was emergency physicians or other practitioners of acute cardiovascular event research. Results Usable responses were obtained from 44 countries (76% of surveyed). Community opposition to EFIC was noted in 6 (14%) countries. Emergency Medical Services (EMS) providers in 8 (20%) countries were judged unable or unwilling to participate. A majority of countries (36, 82%) required approval by a Research Ethics Committee or similar. Government approval was required in 25 (57%) countries. Conclusion There is international variation in practices and polices related to consent for emergency research. There is an ongoing need to converge regulations based on the usefulness of multinational emergency research to benefit both affluent and disadvantaged populations. [ABSTRACT FROM AUTHOR]

Cardiac arrest requires immediate treatment, in order to prevent patient death. Cardiac arrest outcomes still remain very poor, especially when the patient requires vasopressor treatment. Vasopressors have been advocated, in order to increase the coronary and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR). Recent data suggest an epinephrine-related benefit with respect to short- and long-term outcomes, only when epinephrine is administered within the first 10 min of collapse. Also, increasing the epinephrine dosing interval from 3-5 to 6-10 min during CPR may be associated with improved long-term outcomes. In the in-hospital setting, the combination of vasopressin, epinephrine, and corticosteroid supplementation during and after CPR (in the presence of post-resuscitation shock) may be superior to epinephrine alone during CPR. The use of new formulations of amiodarone, potentially devoid of serious hypotensive effects, may contribute to increased rates of sustained return of spontaneous circulation in patients with ventricular fibrillation/ pulseless ventricular tachycardia cardiac arrest. Encouraging preliminary results have been reported on the use of beta blockers in patients with shockable cardiac arrest. Other potentially promising pharmacological interventions include the use of cariporide, nitrates (and particularly inhaled nitric oxide), noble gases, levosimendan, and erythropoietin. The purpose of the current paper is to review the clinical and laboratory evidence that support new and potentially useful pharmacological interventions during CPR. [ABSTRACT FROM AUTHOR]

Cardiac arrest constitutes an extremely life-threatening condition that inevitably and promptly results in death if left untreated. Cardiac arrest outcomes still remain very poor, especially when the presenting cardiac rhythm is nonshockable. Important, recent, clinical research has focused on the quality of cardiopulmonary resuscitation (CPR), the mechanical augmentation of the circulation during CPR, CPR drugs, and therapeutic hypothermia. Chest compression depth of at least 51 mm increases the probability of neurologically favorable survival. Despite initially promising results, a large effectiveness study failed to confirm the efficacy of the mechanical augmentation of the circulation. Epinephrine has finally been shown to slightly improve functional outcome after out-of-hospital cardiac arrest, especially when given early. In a recent, in-hospital study of 268 patients, the addition of vasopressin and methylprednisolone during CPR and the administration of hydrocortisone in postresuscitation shock improved functional outcome after vasopressor-requiring cardiac arrest; however, corticosteroid efficacy still needs to be separately confirmed in a large, international trial. Lastly, preliminary human data may support the conduct of high quality trials evaluating the efficacy of beta adrenergic antagonists in shockable cardiac arrest, and nitrates may warrant evaluation in the clinical setting. The purpose of this paper is to review these potentially important advances in the management of cardiac arrest. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination. OBJECTIVE: To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring. in-hospital cardiac arrest. DESIGN, SETTING AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1,2008, to October 1,2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). DESIGN, SETTING AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1,2008, to October 1,2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). MAIN OUTCOMES AND MEASURES: Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2. RESULTS: Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups. CONCLUSION AND RELEVANCE: Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status. TRIAL REGISTRATION: dinicaltrials.gov Identifier: NCT00729794 [ABSTRACT FROM AUTHOR]

Abstract: Background: Prior meta-analyses-reported results of randomised controlled trials (RCTs) published between 1997 and 2004 failed to show any vasopressin-related benefit in cardiac arrest. Based on new RCT-data and a hypothesis of a potentially increased vasoconstricting efficacy of vasopressin, we sought to determine whether the cumulative, current evidence supports or refutes an overall and/or selective benefit for vasopressin regarding sustained restoration of spontaneous circulation (ROSC), long-term survival, and neurological outcome. Methods: Two reviewers independently searched PubMed, EMBASE, and Cochrane Database for RCTs assigning adults with cardiac arrest to treatment with a vasopressin-containing regimen (vasopressin-group) vs adrenaline (epinephrine) alone (control-group) and reporting on long-term outcomes. Data from 4475 patients in 6 high-methodological quality RCTs were analyzed. Subgroup analyses were conducted according to initial cardiac rhythm and time from collapse to drug administration (T DRUG)<20min. Results: Vasopressin vs. control did not improve overall rates of sustained ROSC, long-term survival, or favourable neurological outcome. However, in asystole, vasopressin vs. control was associated with higher long-term survival {odds ratio (OR)=1.80, 95% confidence interval (CI)=1.04–3.12, P =0.04}. In asystolic patients of RCTs with average T DRUG <20min, vasopressin vs. control increased the rates of sustained ROSC (data available from 2 RCTs; OR=1.70, 95% CI=1.17–2.47, P =0.005) and long-term survival (data available from 3 RCTs; OR=2.84, 95% CI=1.19–6.79, P =0.02). Conclusions: Vasopressin use in the resuscitation of cardiac arrest patients is not associated with any overall benefit or harm. However, vasopressin may improve the long-term survival of asystolic patients, especially when average T DRUG is <20min. [Copyright &y& Elsevier]

The article discusses a study on cardiac arrest which showed improved long-term survival with combined vasopressin-epinephrine. It hypothesizes that combined vasopressin-epinephrine and corticosteroid supplementation during and after resuscitation may improve survival in refractory in-hospital cardiac arrest. The findings of the study constitute the first evidence of increased efficacy of adding vasopressin and methylprednisolone to epinephrine during CPR and treating postresuscitation shock with stress-dose hydrocortisone.

Aim: To perform a systematic review and individual participant data meta-analysis of vasopressin and glucocorticoids for the treatment of cardiac arrest.Methods: The PRISMA-IPD guidelines were followed. We searched Medline, Embase, and the Cochrane Library for randomized trials comparing vasopressin and glucocorticoids to placebo during cardiac arrest. The population included adults with cardiac arrest in any setting. Pairs of investigators reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were conducted using individual participant data. A Bayesian framework was used to estimate posterior treatment effects assuming various prior beliefs. The certainty of evidence was evaluated using GRADE.Results: Three trials were identified including adult in-hospital cardiac arrests only. Individual participant data were obtained from all trials yielding a total of 869 patients. There was some heterogeneity in post-cardiac arrest interventions between the trials. The results favored vasopressin and glucocorticoids for return of spontaneous circulation (odds ratio: 2.09, 95%CI: 1.54 to 2.84, moderate certainty). Estimates for survival at discharge (odds ratio: 1.39, 95%CI: 0.90 to 2.14, low certainty) and favorable neurological outcome (odds ratio: 1.64, 95%CI, 0.99 to 2.72, low certainty) were more uncertain. The Bayesian estimates for return of spontaneous circulation were consistent with the primary analyses, whereas the estimates for survival at discharge and favorable neurological outcome were more dependent on the prior belief.Conclusions: Among adults with in-hospital cardiac arrest, vasopressin and glucocorticoids compared to placebo, improved return of spontaneous circulation. Larger trials are needed to determine whether there is an effect on longer-term outcomes. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "β-Adrenergic Receptor-Mediated Cardiac Contractility Is Inhibited Via Vasopressin Type 1A-Receptor-Dependent Signaling" in a previous issue is presented.