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Drugs are used during cardiopulmonary resuscitation (CPR) in association with chest compressions and ventilation. The main purpose of drugs during resuscitation is either to improve coronary perfusion pressure and myocardial perfusion in order to achieve return of spontaneous circulation (ROSC). The aim of this up-to-date review is to provide an overview of the main drugs used during cardiac arrest (CA), highlighting their historical context, pharmacology, and the data to support them. Epinephrine remains the only recommended vasopressor. Regardless of the controversy about optimal dosage and interval between doses in recent papers, epinephrine should be administered as early as possible to be the most effective in non-shockable rhythms. Despite inconsistent survival outcomes, amiodarone and lidocaine are the only two recommended antiarrhythmics to treat shockable rhythms after defibrillation. Beta-blockers have also been recently evaluated as antiarrhythmic drugs and show promising results but further evaluation is needed. Calcium, sodium bicarbonate, and magnesium are still widely used during resuscitation but have shown no benefit. Available data may even suggest a harmful effect and they are no longer recommended during routine CPR. In experimental studies, sodium nitroprusside showed an increase in survival and favorable neurological outcome when combined with enhanced CPR, but as of today, no clinical data is available. Finally, we review drug administration in pediatric CA. Epinephrine is recommended in pediatric CA and, although they have not shown any improvement in survival or neurological outcome, antiarrhythmic drugs have a 2b recommendation in the current guidelines for shockable rhythms.
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BACKGROUND/AIMS: The motivating randomized controlled phase I trial evaluates three sodium nitroprusside doses in a novel sodium nitroprusside-enhanced cardiopulmonary resuscitation strategy for improved end-organ perfusion relative to local standard of care. Sodium nitroprusside is a vasodilator with an established safety profile in other indications, whereas the local standard of care uses vasoconstrictors, typically epinephrine. The purpose of the proposed trial is to identify the highest safe dose of sodium nitroprusside in this new context as excessive doses may cause severe hypotension with compromised end-organ perfusion. METHODS: The proposed phase I trial design expands upon traditional dose-finding designs to include a randomized control arm, which is needed to assess safety through the relative increase in serum lactate on hospital admission. For guiding dose escalation, we propose and compare six Bayesian models which characterize expected serum lactate as a function of sodium nitroprusside dose and randomization group. Each model makes a different assumption about the expected change in serum lactate across control cohorts concurrently randomized with each dose. Model selection aims to minimize the expected number of times that a dose is incorrectly classified as safe or unsafe while sample size selection targets an expected number of incorrectly classified doses. Randomization is 1:1 for the initial cohort, and for subsequent cohorts is chosen to maximize the lower confidence bound. RESULTS: The spike-and-slab model minimizes the expected number of times that a dose is incorrectly classified as safe or unsafe under the most scenarios in the motivating three-dose trial, but all six models exhibit relatively similar performance. A 2:1 randomization ratio for the second and third cohorts maximizes the lower confidence bound when using the spike-and-slab model. With the optimal design, on average, 70 individuals will ensure 1 incorrectly classified dose in 6 opportunities. CONCLUSION: We recommend that the motivating trial use the spike-and-slab model with a 1:1 randomization ratio for the initial cohort and 2:1 randomization ratio for subsequent cohorts; however, the simpler fixed effects approaches performed similarly well.
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Reanimação Cardiopulmonar , Humanos , Nitroprussiato/uso terapêutico , Teorema de Bayes , Projetos de Pesquisa , LactatosAssuntos
Cateterismo Cardíaco/normas , Cardiologia/normas , Parada Cardíaca Extra-Hospitalar/terapia , Intervenção Coronária Percutânea/normas , Algoritmos , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/mortalidade , Tomada de Decisão Clínica , Consenso , Angiografia Coronária/normas , Técnicas de Apoio para a Decisão , Coração Auxiliar/normas , Hemodinâmica , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Determining whether to pursue or terminate resuscitation efforts remains one of the biggest challenges of cardiopulmonary resuscitation (CPR). No ideal cut-off duration has been recommended and the association between CPR duration and survival is still unclear for out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the association between CPR duration and 30-day survival after OHCA with favorable neurological outcomes according to initial rhythm. METHODS: This was an observational, retrospective analysis of the French national multicentric registry on cardiac arrest, RéAC. The primary endpoint was neurologically intact 30-day survival according to initial rhythm. RESULTS: 20,628 patients were included. For non-shockable rhythms, the dynamic probability of 30-day survival with a Cerebral Performance Category (CPC) of 1 or 2 was less than 1% after 25 min of CPR. CPR duration over 10 min was not associated with 30-day survival with CPC of 1 or 2 (adjusted OR: 1.67; CI 95% 0.95-2.94). For shockable rhythms, the dynamic probability of 30-day survival with a CPC score of 1 or 2, was less than 1% after 54 min of CPR. CPR duration of 21-25 min was still associated with 30-day survival and 30-day survival with a CPC of 1 or 2 (adjusted OR: 2.77; CI 95% 2.16-3.57 and adjusted OR: 1.82; CI 95% 1.06-3.13, respectively). CONCLUSIONS: Survival decreased rapidly with increasing CPR duration, especially for non-shockable rhythms. Pursuing CPR after 25 min may be futile for patients presenting a non-shockable rhythm. On the other hand, shockable rhythms might benefit from prolonged CPR.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Estudos Retrospectivos , Parada Cardíaca Extra-Hospitalar/terapia , Sistema de Registros , França/epidemiologiaRESUMO
Expanded use of exercise heart rate recovery (HRR) has renewed interest in the pathophysiology of heart rate control. This study uses basic physiologic principles to construct a unique model capable of describing the full time course of sympathetic and parasympathetic activity during HRR. The model is tested in a new study of 22 diverse subjects undergoing both maximal and submaximal treadmill exercise. Based on this analysis, prolongation of HRR involves changes within the sinus node, changes in sympathetic function, in parasympathetic function, and in the central mechanisms regulating autonomic balance. The methods may provide unique insight into alterations in autonomic control in health and disease.
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Sistema Nervoso Autônomo/fisiopatologia , Exercício Físico , Frequência Cardíaca , Recuperação de Função Fisiológica , Teste de Esforço , HumanosRESUMO
AIM: To assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. METHODS: VF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) - ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. RESULTS: MAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. CONCLUSION: HUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.
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Reanimação Cardiopulmonar , Parada Cardíaca , Animais , Suínos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Hemodinâmica/fisiologia , Pressão Arterial , Circulação Cerebrovascular/fisiologiaRESUMO
AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising resuscitation strategy for select patients suffering from refractory out-of-hospital cardiac arrest (OHCA), though limited data exist regarding the best practices for ECPR initiation after OHCA. METHODS: We utilized a modified Delphi process consisting of two survey rounds and a virtual consensus meeting to systematically identify detailed best practices for ECPR initiation following adult non-traumatic OHCA. A modified Delphi process builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Consensus was achieved when items reached a high level of agreement, defined as greater than 80% responses for a particular item rated a 4 or 5 on a 5-point Likert scale. RESULTS: Snowball sampling generated a panel of 14 content experts, composed of physicians from four continents and five primary specialties. Seven existing institutional protocols for ECPR cannulation following OHCA were identified and merged into a single comprehensive list of 207 items. The panel reached consensus on 101 items meeting final criteria for inclusion: Prior to Patient Arrival (13 items), Inclusion Criteria (8), Exclusion Criteria (7), Patient Arrival (8), ECPR Cannulation (21), Go On Pump (18), and Post-Cannulation (26). CONCLUSION: We present a list of items for ECPR initiation following adult nontraumatic OHCA, generated using a modified Delphi process from an international panel of content experts. These findings may benefit centers currently performing ECPR in quality assurance and serve as a template for new ECPR programs.