A randomized clinical trial of calcium entry blocker administration to comatose survivors of cardiac arrest: Design, methods, and patient characteristics

doi:10.1016/0197-2456(91)90011-A

Controlled Clinical Trials

Volume 12, Issue 4, August 1991, Pages 525-545

https://doi.org/10.1016/0197-2456(91)90011-A Get rights and content

Abstract

The Brain Resuscitation Clinical Trial (BRCT) II was a double-masked, randomized controlled clinical study of cardiopulmonary-cerebral resuscitation (CPCR) designed to test therapy for the amelioration of brain damage after cardiac arrest. Lidoflazine, a calcium entry blocker, was chosen for investigation because of its beneficial effects on postischemic encephalopathy in animals, its minimal cardiovascular depressant effects, and its protective actions in myocardial ischemia in patients. Twenty-four hospitals in eight countries participated. Over 4 years, 520 patients were recruited, of whom 4 were subsequently lost to follow-up. Patients age averaged 63 years and 62% were men. Cardiac arrest occurred prior to hospitalization in 63%. All patients received basic and advanced life support until circulation was restored, and then standardized extracerebral organ support. After restoration of spontaneous circulation with normal blood pressure, patients who failed to awaken were randomly assigned to receive IV administration of either lidoflazine or placebo. In each patient, outcome was evaluated by cerebral performance during a 6-month follow-up period. Periodic safety monitoring was carried out to assure that no excess of mortality or complications occurred in the lidoflazine-treated group compared with the placebo-treated group.

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Cited by (106)

Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement
2023, Canadian Journal of Cardiology
Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.
L’arrêt cardiaque (AC) est associé à un faible taux de survie sans atteinte neurologique. La cause de décès la plus fréquente à la suite d’une réanimation après un AC est l’interruption des mesures visant à prolonger la vie en raison du sombre pronostic neurologique découlant des lésions cérébrales hypoxiques ischémiques sous-jacentes. La neuropronostication est une composante importante du parcours thérapeutique dans le cas des patients hospitalisés ayant subi un AC, mais elle est complexe, difficile à réaliser et souvent fondée sur des données fragmentaires. Après avoir évalué, à l’aide du système GRADE (Grading of Recommendations Assessment, Development, and Evaluation), les facteurs sous-jacents et les modalités diagnostiques sur lesquels repose le pronostic, nous avons formulé des recommandations portant sur les points suivants : 1) circonstances suivant immédiatement l’AC; 2) examen neurologique ciblé; 3) myoclonies et convulsions; 4) biomarqueurs sérologiques; 5) neuro-imagerie; 6) examens neurophysiologiques; et 7) neuropronostication multimodale. Cet énoncé de position se veut un guide pratique pour améliorer les soins prodigués en milieu hospitalier aux patients ayant subi un AC et souligne l’importance d’adopter une approche de neuropronostication systématique et multimodale. Il met également en lumière le manque de données probantes.
Cardiac arrest survivors lost to follow-up after 3-Months, 6-Months and 1-Year
2020, Resuscitation
Long-term assessment of global functional outcomes in cardiac arrest (CA) survivors allows for evaluation of acute care practices and referral to rehabilitation services. Given that many post-CA patients are lost to follow-up (LTFU), we explored whether these patients are systematically different from those who complete follow-up based on demographic, resuscitation and outcome characteristics.
We conducted a prospective cohort study of 168 English-speaking CA survivors between 9/25/2016 and 5/31/2018. We measured demographic data and global functional outcomes using Modified Rankin Scale (mRS), and Cerebral Performance Category (CPC) in-person at hospital discharge, and via telephone at 3-, 6-months, and 1-year. We compared patients LTFU (e.g., failure to contact or refused to follow-up) with those contacted. Patients who were hospitalized, in a rehabilitation facility, missed by the research team, or dead were considered not eligible for follow-up.
Of the 116 patients eligible for follow-up at 3-months, the majority completed follow-up (n = 69; 59.5%) and 47 (40.5%) were LTFU. Conversely, at 6-months and 1-year, fewer subjects were assessed (42% and 47%) compared to those who were LTFU (58% and 53%), respectively. At 3-months, LTFU patients were younger, unmarried, and had longer ICU stay. At 6-months and 1-year, LTFU patients were primarily male, had a non-shockable primary rhythm, and non-cardiac arrest etiologies.
Over one-third of patients are LTFU during the first year after CA, and differences emerged for demographics and characteristics of the event. Future research should account for the informative, non-random distribution of patients LTFU.
Effects of Shenfu injection on survival and neurological outcome after out-of-hospital cardiac arrest: A randomised controlled trial
2020, Resuscitation
We aimed to assess the effects of Shenfu injection (SFI) in combination with epinephrine during cardiac arrest on survival and neurological outcome after out-of-hospital cardiac arrest (OHCA).
In this randomised, assessor-blind controlled trial, Utstein-style data were collected from 1233 OHCA patients treated at the Beijing Emergency Medical Center between January 2013 and June 2016. The patients were randomised into either a treatment group that received a combination of SFI and standard treatment with epinephrine or a control group that received standard treatment with epinephrine alone. The primary outcome was survival to hospital admission. The secondary outcomes were return of spontaneous circulation (ROSC), survival to hospital discharge, favourable neurological outcome at discharge, survival to one year, and favourable neurological outcome at one-year survival.
In both groups, the survival to hospital admission, ROSC, survival to hospital discharge, and one-year survival rate after discharge from the hospital did not differ significantly. However, SFI achieved favourable neurological outcome at discharge in comparison with the standard treatment with an odds ratio (OR) of 2.72 at a 95% confidence interval (CI; 1.00–8.53). Meanwhile, unlike with epinephrine alone, the combination of SFI and epinephrine achieved a better cerebral performance category (CPC) score (1–2) after one-year survival (OR: 5.08, 95% CI: 1.07–47.80).
The combination of SFI and epinephrine had favourable neurological outcomes after OHCA compared with those with epinephrine alone, whereas the survival to admission was not significantly altered.
Effect of cancer history on post-resuscitation treatments in out-of-hospital cardiac arrest
2019, Resuscitation
There is growing evidence that optimal post-resuscitation treatment is a significant factor for overall survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA). However, there is also growing evidence of disparities in treatments in vulnerable populations such as elderly individuals or patients with underlying diseases, including cancer.
The aim of this study was to evaluate the influence of cancer status on post-resuscitation therapies among OHCA patients.
This was a cross-sectional observational study based on a nationwide prospective OHCA registry database of Korea. All adult OHCA patients with presumed cardiac etiology and sustained return of spontaneous circulation (ROSC) from 2009 to 2016 were included in this study. Main exposure was history of cancer and primary outcome was post-resuscitation care, including percutaneous coronary intervention (PCI) and targeted temperature management (TTM). Multivariable logistic regression was used to analyze the association between cancer and post-resuscitation treatments.
A total of 33,760 patients were included for final analysis. Multivariable logistic analysis showed that cancer patients were significantly less likely to receive PCI and TTM compared to those without history of cancer with adjusted odds ratios of 0.29 (95% CI: 0.24–0.37) and 0.66 (0.58–0.77), respectively.
The results of this study suggest that a prior history of cancer may be associated with lower probability to receive potentially beneficial post-resuscitation treatments.
Multidisciplinary Management of the Post–Cardiac Arrest Patient
2018, Cardiology Clinics
Short ECG segments predict defibrillation outcome using quantitative waveform measures
2016, Resuscitation
Quantitative waveform measures of the ventricular fibrillation (VF) electrocardiogram (ECG) predict defibrillation outcome. Calculation requires an ECG epoch without chest compression artifact. However, pauses in CPR can adversely affect survival. Thus the potential use of waveform measures is limited by the need to pause CPR. We sought to characterize the relationship between the length of the CPR-free epoch and the ability to predict outcome.
We conducted a retrospective investigation using the CPR-free ECG prior to first shock among out-of-hospital VF cardiac arrest patients in a large metropolitan region (n = 442). Amplitude Spectrum Area (AMSA) and Median Slope (MS) were calculated using ECG epochs ranging from 5 s to 0.2 s. The relative ability of the measures to predict return of organized rhythm (ROR) and neurologically-intact survival was evaluated at different epoch lengths by calculating the area under the receiver operating characteristic curve (AUC) using the 5-s epoch as the referent group.
Compared to the 5-s epoch, AMSA performance declined significantly only after reducing epoch length to 0.2 s for ROR (AUC 0.77–0.74, p = 0.03) and with epochs of ≤0.6 s for neurologically-intact survival (AUC 0.72–0.70, p = 0.04). MS performance declined significantly with epochs of ≤0.8 s for ROR (AUC 0.78–0.77, p = 0.04) and with epochs ≤1.6 s for neurologically-intact survival (AUC 0.72–0.71, p = 0.04).
Waveform measures predict defibrillation outcome using very brief ECG epochs, a quality that may enable their use in current resuscitation algorithms designed to limit CPR interruption.

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^∗: See Appendix for participants.

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A randomized clinical trial of calcium entry blocker administration to comatose survivors of cardiac arrest: Design, methods, and patient characteristics

Abstract

Lancet

Controlled Clin Trials

Collaborative randomized clinical study of cardiopulmonary-cerebral resuscitation

Crit Care Med

Randomized clinical study of cardiopulmonary-cerebral resuscitation: design, methods and patient characteristics

Am J Emerg Med

Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest

N Engl J Med

Cardioprotective effects of lidoflazine during 1-hour normothermic global ischemia

Circulation

Possible role of calcium blockers in cerebral resuscitation: A review of the literature and synthesis for future studies

Crit Care Med

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs

Crit Care Med

Myocardial protection in open-heart surgery

Informed consent in resuscitation research

JAMA