今日の臨床サポート

心停止後の生存者フォローアップ

概要・推奨   

  1. 心停止後の病態は心停止後症候群(PCAS:post cardiac arrest syndrome)と定義され、①心停止後脳障害、②心停止後心筋障害、③全身虚血再灌流障害、④心停止に至った原疾患、といった病態が複合したものとされている。
  1. 院外心肺停止患者の入院率は23.8%であることや、生存退院率は7.6%であることが知られている[1]
  1. 院外発症の心臓突然死の原因で最も多いのが、虚血性心疾患であり、大部分を占める。診断、予後の改善の両方の視点から、心停止後の生存者に対しては、心臓カテーテル検査での冠動脈疾患の評価を検討する必要がある(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
加藤隆生 : 未申告[2022年]
西﨑祐史 : 特に申告事項無し[2022年]
監修:徳田安春 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを行い、心停止後症候群についての記載を追加した。
  1. 心停止の原因究明は大切なことではあり、短時間で的確な評価が必要となる。そして、神経学的予後を悪化させないことも大切なことである。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 突然死患者の原因を正確に把握することは難しいが、院外発症の突然死の原因の多くは心原性である。
  1. 院外発症の突然死の原因と頻度は、約65~70%が冠動脈疾患、約10%が冠動脈疾患以外の器質的心疾患(心筋炎、肥大型心筋症、不整脈原性右室心筋症など)、約5~10%が器質的心疾患を伴わない致死的不整脈(Brugada syndrome、long QT syndrome、short QT syndrome、catecholaminergic polymorphic VT、Wolff-Parkinson-White syndrome、特発性心室細動など)、約15~35%が非心原性(外傷、出血、薬物中毒、頭蓋内出血、溺水、肺血栓塞栓症、気道閉塞など)と考えられている。
  1. 院外発症の心臓突然死の原因で最も多いのが、冠動脈疾患であり約70%を占めると考えられている。しかし、若年者においてはその限りではない。若年者の心臓突然死を診た場合は冠動脈疾患以外も鑑別の上位に挙げながら診療にあたる必要がある(推奨度2)
  1. 1976年から1985年に院外発症の心臓突然死を生じた40歳未満の若年者162名を対象とした後ろ向き観察研究がある[2]。その研究結果によると、20歳未満では、心筋炎(22%)、肥大型心筋症(22%)が最も多かった。20~29歳では、冠動脈疾患(24%)、心筋炎(22%)、肥大型心筋症(13%)という順序であった。30~39歳では、冠動脈疾患(58%)、心筋炎(11%)と冠動脈疾患が最上位であったが、全年齢で冠動脈疾患が心臓突然死を占める割合と比較すると高い数字ではない。本研究結果から、若年者の心臓突然死を診た場合は冠動脈疾患以外も鑑別の上位に挙げながら診療にあたる必要があると言うことができる。
  1. 心臓突然死患者の約5%は器質的心疾患が明らかでない。心筋症や心筋炎や一過性の電解質異常など不顕性に存在している場合がある。心停止後の生存者をフォローアップするうえで、器質的心疾患の診断においては、病歴聴取、身体診察、血液検査、12誘導心電図、24時間ホルター心電図、運動負荷試験、心エコー、心臓カテーテル検査は最低限必要である(エビデンスレベルG)。
  1. 1997年にThe Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United Statesから、心停止後の生存者のフォローアップにおいて以下の推奨が報告された。器質的心疾患を除外診断するうえで、非侵襲的検査として病歴聴取、身体診察、血液検査、12誘導心電図、24時間ホルター心電図、運動負荷試験、心エコーが、侵襲的検査として心臓カテーテル検査が、最低限必要である。心臓カテーテル検査における、エルゴノビン負荷試験や心筋生検はできれば施行した方がよいが必ず必要とはしない。また、診断がつかないケースでは、注意深く経過を観察し、1年に1回は非侵襲的検査での評価を繰り返すことが好ましいとされている[3]
  1. 心臓突然死の約5%は原因不明であるが、それが、遺伝性心疾患である可能性がある。原因不明の心臓突然死患者の家族は突然死のリスク評価を行うべきである(エビデンスレベルO)。
  1. 2003年に報告された研究では、32人の器質的心疾患のない心臓突然死患者の家族(第1度親族)109人を対象に突然死のリスク評価を行った[4]。その結果、7家族(22%)で遺伝性心疾患が発見された。そのうち、最も多かったのがlong QT症候群で4家族に発見された。その他は、肥大型心筋症、myotonic dystrophyなどであった。原因不明の心臓突然死の原因が遺伝性心疾患である可能性は比較的高く、患者家族の突然死のリスク評価を検討する必要がある。
  1. 心原性疫学研究に基づく正確な情報は揃っていないが、心不全も突然死の原因の1つとして比較的多いと考えられる。
問診・診察のポイント  
  1. 診察により、心臓突然死の原因を同定し可逆的な場合は速やかに治療を開始する。具体的には、家族などからの病歴の聴取(心疾患の既往や治療歴、内服薬の有無やその内容、特に抗不整脈薬が含まれているかどうかを把握する、胸痛の訴えなど虚血性心疾患を示唆する症状の有無など)、身体所見、血液検査(一般的な血算、生化学や動脈血ガス検査にて電解質異常やアシドーシスを評価する)に加え、心臓超音波検査など迅速に施行できる検査を行う。ACLSに含まれる5H5Tの鑑別は基本であり、可逆性の高い緊張性気胸や心タンポナーデなどは確実にこの時点で同定し、治療介入を行う必要がある。ただし、まだ心肺蘇生行為中はその行為の妨げにならない範囲で行う必要がある。

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文献 

Dion Stub, Stephen Bernard, Stephen J Duffy, David M Kaye
Post cardiac arrest syndrome: a review of therapeutic strategies.
Circulation. 2011 Apr 5;123(13):1428-35. doi: 10.1161/CIRCULATIONAHA.110.988725.
Abstract/Text
PMID 21464058
Y Drory, Y Turetz, Y Hiss, B Lev, E Z Fisman, A Pines, M R Kramer
Sudden unexpected death in persons less than 40 years of age.
Am J Cardiol. 1991 Nov 15;68(13):1388-92.
Abstract/Text This study retrospectively assesses the underlying causes of sudden unexpected death and the occurrence of prodromal symptoms in 162 subjects (aged 9 to 39 years) over a 10-year period (1976 to 1985). Underlying cardiac diseases accounted for sudden death in 73% and noncardiac causes in 15% of subjects. In 12% of subjects, the causes were unidentifiable. Myocarditis (22%), hypertrophic cardiomyopathy (22%) and conduction system abnormalities (13%) were the major causes in 32 subjects aged less than 20 years. Major causes of 46 deaths in subjects 20 to 29 years were atherosclerotic coronary artery disease (24%), myocarditis (22%) and hypertrophic cardiomyopathy (13%). The largest number of deaths in 84 subjects aged greater than or equal to 30 years was attributed to coronary artery disease (58%), followed by myocarditis (11%). Among noncardiac causes of sudden death, intracranial hemorrhage was the most frequent (5%), followed by infectious disease (4%). Prodromal symptoms were reported by 54% of subjects; most frequent were chest pain (25%) in subjects aged greater than or equal to 20 years, and dizziness (16%) in those aged less than 20. Sudden death, which occurred during routine daily activity in 49% and during sleep in 23% of subjects, was related to physical exercise in 23% and emotional upset in 6%. Sudden unexpected death in the young is still an unresolved medical problem. The early recognition of prodromal symptoms could be crucial in the prevention of sudden death, specifically when exercise-related.

PMID 1951130
Abstract/Text BACKGROUND: A wide variety of structural abnormalities are associated with the vast majority of cardiac arrests. However, there is no evidence of structural heart disease in approximately 5% of victims of sudden death, indicating that cardiac arrest in the absence of organic heart disease is more common than previously recognized. The risk of recurrence and the acute and long-term response to therapy are important but unanswered questions. Data from the small series reported so far are of limited value because of the lack of uniform criteria to define and diagnose idiopathic ventricular fibrillation (IVF).
METHODS AND RESULTS: This report originates from a Consensus Conference convened by the Steering Committees of the European (UCARE) and North American (IVF-US) Registries on IVF under the auspices of the Working Group on Arrhythmias of the European Society of Cardiology. Its objective is to provide a unified definition of IVF and to outline the investigations necessary to make this diagnosis. Minimal diagnostic tests for the exclusion of an underlying structural heart disease include non-invasive (blood biochemistry, physical examination and clinical history, ECG, exercise stress test, 24-hour Holter recording, and echocardiogram) and invasive (coronary angiography, right and left ventricular cineangiography, and electrophysiological study) examinations. Programmed electrical stimulation, ventricular biopsy, and ergonovine test during coronary angiography are recommended but not mandatory.
CONCLUSIONS: It is recognized that despite careful evaluation, conditions such as focal cardiomyopathy, myocarditis, or fibrosis and transient electrolyte abnormalities may remain silent. Therefore, patients should undergo careful follow-up, with noninvasive tests repeated every year. The existence of a unified terminology will allow meaningful comparison of data collected by different investigators and will thus contribute to a better understanding of IVF.

PMID 8994445
E Behr, D A Wood, M Wright, P Syrris, M N Sheppard, A Casey, M J Davies, W McKenna, Sudden Arrhythmic Death Syndrome Steering Group
Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.
Lancet. 2003 Nov 1;362(9394):1457-9.
Abstract/Text 4.1% of sudden cardiac deaths in the 16-64 age-group are unexplained. In this group, cardiac pathological findings are normal and toxicological tests are negative; termed sudden arrhythmic death syndrome (SADS). We searched for evidence of inherited cardiac disease in cases of SADS. Of 147 first-degree relatives of 32 people who died of SADS, 109 (74%) underwent cardiological assessment. Seven (22%) of the 32 families were diagnosed with inherited cardiac disease: four with long QT syndrome; one with non-structural cardiac electrophysiological disease; one with myotonic dystrophy; and one with hypertrophic cardiomyopathy. Families of people who die of SADS should be offered assessment in centres with experience of inherited cardiac disease.

PMID 14602442
S Viskin, B Belhassen
Idiopathic ventricular fibrillation.
Am Heart J. 1990 Sep;120(3):661-71.
Abstract/Text A review of the literature dealing with sudden death revealed 19 articles in which ostensibly healthy patients with documented VF unrelated to any known cardiac or noncardiac etiology are reported. Fifty-four patients fulfilling the criteria for idiopathic VF, including 14 patients investigated at our institution, are described. The mean age of patients for studies that reported age data was 36 years, with a male-to-female ratio of 2.5 to 1. Over 90% of the patients required resuscitation, while syncope due to nonsustained VF occurred in the rest. Diagnosis of VF was preceded by syncope in one fourth of the patients. Holter monitoring and exercise stress tests were often unrewarding. Available electrophysiologic data revealed a 69% inducibility rate of sustained ventricular tachyarrhythmias using nonaggressive protocols of ventricular stimulation in most cases. Induced tachyarrhythmias were poorly tolerated, and were mostly of polymorphic configuration. Class IA antiarrhythmic agents were highly effective in preventing reinduction of these arrhythmias. Available figures suggest an 11% rate of sudden death within 1 year of diagnosis. Appropriate antiarrhythmic therapy appears to improve prognosis. Reviewed data suggest that idiopathic VF represents an underestimated cause of sudden cardiac death in ostensibly healthy patients. An international registry of patients with idiopathic VF is warranted.

PMID 2202193
Andrew D Krahn, Michael Gollob, Raymond Yee, Lorne J Gula, Allan C Skanes, Bruce D Walker, George J Klein
Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion.
Circulation. 2005 Oct 11;112(15):2228-34. doi: 10.1161/CIRCULATIONAHA.105.552166. Epub 2005 Oct 3.
Abstract/Text BACKGROUND: Cardiac arrest with preserved left ventricular function may be caused by uncommon genetic conditions. Although these may be evident on the ECG, long-term monitoring or provocative testing is often necessary to unmask latent primary electrical disease.
METHODS AND RESULTS: Patients with unexplained cardiac arrest and no evident cardiac disease (normal left ventricular function, coronary arteries, and resting corrected QT) underwent pharmacological challenge with adrenaline and procainamide infusions to unmask subclinical primary electrical disease. Family members underwent noninvasive screening and directed provocative testing on the basis of findings in the proband. Eighteen patients (mean+/-SD age, 41+/-17 years; 11 female) with unexplained cardiac arrest were assessed. The final diagnosis was catecholaminergic ventricular tachycardia (CPVT) in 10 patients (56%), Brugada syndrome in 2 patients (11%), and unexplained (idiopathic ventricular fibrillation) in 6 patients (33%). Of 55 family members (mean+/-SD age, 27+/-17 years; 33 female), 9 additional affected family members were detected from 2 families, with a single Brugada syndrome patient and 8 CPVT patients.
CONCLUSIONS: Provocative testing with adrenaline and procainamide infusions is useful in unmasking the etiology of apparent unexplained cardiac arrest. This approach helps to diagnose primary electrical disease, such as CPVT and Brugada syndrome, and provides the opportunity for therapeutic intervention in identified, asymptomatic family members who harbor the same disease.

PMID 16203906
Barry J Maron, Kevin P Carney, Harry M Lever, Jannet F Lewis, Ivan Barac, Susan A Casey, Mark V Sherrid
Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy.
J Am Coll Cardiol. 2003 Mar 19;41(6):974-80.
Abstract/Text OBJECTIVES: The goal of this study was to determine the impact of race on identification of hypertrophic cardiomyopathy (HCM).
BACKGROUND: Sudden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. These catastrophes have become an important issue for African Americans, although HCM has been previously regarded as rare in this segment of the U.S. population.
METHODS: We studied the relationship of race to the prevalence of CVDs causing sudden death in our national athlete registry, and compared these findings with a representative multicenter hospital-based cohort of patients with HCM.
RESULTS: Of 584 athlete deaths, 286 were documented to be due to CVD at ages 17 +/- 3 years; 156 (55%) were white, and 120 (42%) were African American. Most were male (90%), and 67% participated in basketball and football. Among the 286 cardiovascular deaths, most were due to HCM (n = 102; 36%) or anomalous coronary artery of wrong sinus origin (n = 37; 13%). Of the athletes who died of HCM, 42 (41%) were white, but 56 (55%) were African American. In contrast, of 1,986 clinically identified HCM patients, only 158 (8%) were African American (p < 0.001).
CONCLUSIONS: In this autopsy series, HCM represented a common cause of sudden death in young and previously undiagnosed African American male athletes, in sharp contrast with the infrequent clinical identification of HCM in a hospital-based population (i.e., by seven-fold). This discrepancy suggests that many HCM cases go unrecognized in the African American community, underscoring the need for enhanced clinical recognition of HCM to create the opportunity for preventive measures to be employed in high-risk patients with this complex disease.

PMID 12651044
C M Spaulding, L M Joly, A Rosenberg, M Monchi, S N Weber, J F Dhainaut, P Carli
Immediate coronary angiography in survivors of out-of-hospital cardiac arrest.
N Engl J Med. 1997 Jun 5;336(23):1629-33. doi: 10.1056/NEJM199706053362302.
Abstract/Text BACKGROUND: The incidence of acute coronary-artery occlusion among patients with sudden cardiac arrest outside of the hospital is unknown, and the role of reperfusion therapy has not been determined. We therefore performed immediate coronary angiography and angioplasty when indicated in survivors of out-of-hospital cardiac arrest.
METHODS: Between September 1994 and August 1996, coronary angiography was performed in 84 consecutive patients between the ages of 30 and 75 years who had no obvious noncardiac cause of cardiac arrest.
RESULTS: Sixty of the 84 patients had clinically significant coronary disease on angiography, 40 of whom had coronary-artery occlusion (48 percent). Angioplasty was attempted in 37 patients and was technically successful in 28. Clinical and electrocardiographic findings, such as the occurrence of chest pain and the presence of ST-segment elevation, were poor predictors of acute coronary-artery occlusion. The in-hospital survival rate was 38 percent. Multivariate logistic-regression analysis revealed that successful angioplasty was an independent predictor of survival (odds ratio, 5.2; 95 percent confidence interval, 1.1 to 24.5; P=0.04).
CONCLUSIONS: Acute coronary-artery occlusion is frequent in survivors of out-of-hospital cardiac arrest and is predicted poorly by clinical and electrocardiographic findings. Accurate diagnosis by immediate coronary angiography can be followed in suitable candidates by coronary angioplasty, which seems to improve survival.

PMID 9171064
Tanveer Rab, Karl B Kern, Jacqueline E Tamis-Holland, Timothy D Henry, Michael McDaniel, Neal W Dickert, Joaquin E Cigarroa, Matthew Keadey, Stephen Ramee, Interventional Council, American College of Cardiology
Cardiac Arrest: A Treatment Algorithm for Emergent Invasive Cardiac Procedures in the Resuscitated Comatose Patient.
J Am Coll Cardiol. 2015 Jul 7;66(1):62-73. doi: 10.1016/j.jacc.2015.05.009.
Abstract/Text Patients who are comatose after cardiac arrest continue to be a challenge, with high mortality. Although there is an American College of Cardiology Foundation/American Heart Association Class I recommendation for performing immediate angiography and percutaneous coronary intervention (when indicated) in patients with ST-segment elevation myocardial infarction, no guidelines exist for patients without ST-segment elevation. Early introduction of mild therapeutic hypothermia is an established treatment goal. However, there are no established guidelines for risk stratification of patients for cardiac catheterization and possible percutaneous coronary intervention, particularly in patients who have unfavorable clinical features in whom procedures may be futile and affect public reporting of mortality. An algorithm is presented to improve the risk stratification of these severely ill patients with an emphasis on consultation and evaluation of patients prior to activation of the cardiac catheterization laboratory.

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 26139060
Christopher M Booth, Robert H Boone, George Tomlinson, Allan S Detsky
Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest.
JAMA. 2004 Feb 18;291(7):870-9. doi: 10.1001/jama.291.7.870.
Abstract/Text CONTEXT: Most survivors of cardiac arrest are comatose after resuscitation, and meaningful neurological recovery occurs in a small proportion of cases. Treatment can be lengthy, expensive, and often difficult for families and caregivers. Physical examination is potentially useful in this clinical scenario, and the information obtained may help physicians and families make accurate decisions about treatment and/or withdrawal of care.
OBJECTIVE: To determine the precision and accuracy of the clinical examination in predicting poor outcome in post-cardiac arrest coma.
DATA SOURCES AND STUDY SELECTION: We searched MEDLINE for English-language articles (1966-2003) using the terms coma, cardiac arrest, prognosis, physical examination, sensitivity and specificity, and observer variation. Other sources came from bibliographies of retrieved articles and physical examination textbooks. Studies were included if they assessed the precision and accuracy of the clinical examination in prognosis of post-cardiac arrest coma in adults. Eleven studies, involving 1914 patients, met our inclusion criteria.
DATA EXTRACTION: Two authors independently reviewed each study to determine eligibility, abstract data, and classify methodological quality using predetermined criteria. Disagreement was resolved by consensus.
DATA SYNTHESIS: Summary likelihood ratios (LRs) were calculated from random effects models. Five clinical signs were found to strongly predict death or poor neurological outcome: absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7), absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6), absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8), no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0), and no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4). The proportion of individuals' dying or having a poor neurological outcome was calculated by pooling the outcome data from the 11 studies (n = 1914) and used as an estimate of the pretest probability of poor outcome. The random effects estimate of poor outcome was 77% (95% CI, 72%-80%). The highest LR increases the pretest probability of 77% to a posttest probability of 97% (95% CI, 87%-100%). No clinical findings were found to have LRs that strongly predicted good neurological outcome.
CONCLUSIONS: Simple physical examination maneuvers strongly predict death or poor outcome in comatose survivors of cardiac arrest. The most useful signs occur at 24 hours after cardiac arrest, and earlier prognosis should not be made by clinical examination alone. These data provide prognostic information, rather than treatment recommendations, which must be made on an individual basis incorporating many other variables.

PMID 14970067
Toshikazu Abe, Shigeyuki Watanabe, Atsushi Mizuno, Masahiro Toyama, Vicken Y Totten, Yasuharu Tokuda
A model for predicting angiographically normal coronary arteries in survivors of out-of-hospital cardiac arrest.
J Intensive Care. 2015;3(1):32. doi: 10.1186/s40560-015-0099-y. Epub 2015 Jul 15.
Abstract/Text BACKGROUND: It has been recommended that all survivors of out-of-hospital cardiac arrest (OHCA) have immediate coronary angiography (CAG), even though it has been reported that half of the survivors have normal coronary arteries. Our aim was to develop a model which might identify those who have angiographically normal coronary arteries. Reliable prediction would reduce unnecessary CAG.
METHODS: A retrospective, observational, cohort study was conducted on 47 consecutive adult survivors who received immediate CAG after resuscitation from OHCA, between June 1, 2006 and March 31, 2011. We analyzed the clinical and electrocardiographic characteristics of the survivors with and without normal coronary arteries.
RESULTS: All subjects had CAG. Normal coronary arteries were found in 25/47. These persons did not have diabetes mellitus (p = 0.0069) or a history of acute coronary syndrome (ACS) (p = 0.0069). Any abnormality of the ST segment or ST segment elevation on electrocardiogram (ECG) was strongly related to abnormal coronary arteries (p = 0.0045 and p = 0.0200, respectively). The partitioning model for predicting angiographically normal coronary arteries showed that all patients (8/8) with no ST segment change on their ECG had normal coronary arteries. Eight out of ten patients with ST segment abnormalities also had normal coronary arteries with a history of arrhythmia without a history of ACS.
CONCLUSIONS: Survivors of OHCA who have no history of diabetes mellitus, who have no past history of ACS, and who present with no ST segment abnormalities may not require urgent/emergent CAG. Further studies are needed to guide clinicians in the determination of emergent cardiac catheterization following resuscitation of OHCA.

PMID 26175896
Abstract/Text BACKGROUND: We conducted a prospective, multicenter, randomized comparison of implantable cardioverter-defibrillator (ICD) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias.
METHODS AND RESULTS: From 1987, eligible patients were randomized to an ICD, amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents randomization ratio 1:3). Assignment to propafenone was discontinued in March 1992, after an interim analysis conducted in 58 patients showed a 61% higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months. The study continued to recruit 288 patients in the remaining 3 study groups; of these, 99 were assigned to ICDs, 92 to amiodarone, and 97 to metoprolol. The primary end point was all-cause mortality. The study was terminated in March 1998, when all patients had concluded a minimum 2-year follow-up. Over a mean follow-up of 57+/-34 months, the crude death rates were 36.4% (95% CI 26.9% to 46.6%) in the ICD and 44.4% (95% CI 37.2% to 51.8%) in the amiodarone/metoprolol arm. Overall survival was higher, though not significantly, in patients assigned to ICD than in those assigned to drug therapy (1-sided P=0.081, hazard ratio 0.766, [97.5% CI upper bound 1.112]). In ICD patients, the percent reductions in all-cause mortality were 41.9%, 39.3%, 28. 4%, 27.7%, 22.8%, 11.4%, 9.1%, 10.6%, and 24.7% at years 1 to 9 of follow-up.
CONCLUSIONS: During long-term follow-up of cardiac arrest survivors, therapy with an ICD is associated with a 23% (nonsignificant) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol. The benefit of ICD therapy is more evident during the first 5 years after the index event.

PMID 10942742
S J Connolly, M Gent, R S Roberts, P Dorian, D Roy, R S Sheldon, L B Mitchell, M S Green, G J Klein, B O'Brien
Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone.
Circulation. 2000 Mar 21;101(11):1297-302.
Abstract/Text BACKGROUND: Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone.
METHODS AND RESULTS: A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094).
CONCLUSIONS: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.

PMID 10725290
Abstract/Text BACKGROUND: Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias. They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs, but the relative efficacy of these two treatment strategies is unknown.
METHODS: To address this issue, we conducted a randomized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia. Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms, along with a left ventricular ejection fraction of 0.40 or less. One group of patients was treated with implantation of a cardioverter-defibrillator; the other received class III antiarrhythmic drugs, primarily amiodarone at empirically determined doses. Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years. Of 1016 patients (45 percent of whom had ventricular fibrillation, and 55 percent ventricular tachycardia), 507 were randomly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy. The primary end point was overall mortality.
RESULTS: Follow-up was complete for 1013 patients (99.7 percent). Overall survival was greater with the implantable defibrillator, with unadjusted estimates of 89.3 percent, as compared with 82.3 percent in the antiarrhythmic-drug group at one year, 81.6 percent versus 74.7 percent at two years, and 75.4 percent versus 64.1 percent at three years (P<0.02). The corresponding reductions in mortality (with 95 percent confidence limits) with the implantable defibrillator were 39+/-20 percent, 27+/-21 percent, and 31+/-21 percent
CONCLUSIONS: Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms, the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival.

PMID 9411221
S J Connolly, A P Hallstrom, R Cappato, E B Schron, K H Kuck, D P Zipes, H L Greene, S Boczor, M Domanski, D Follmann, M Gent, R S Roberts
Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg . Canadian Implantable Defibrillator Study.
Eur Heart J. 2000 Dec;21(24):2071-8. doi: 10.1053/euhj.2000.2476.
Abstract/Text AIMS: Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia.
METHODS AND RESULTS: Individual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect meta-analysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0.306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0.72 (95% confidence interval 0.60, 0.87;P=0.0006). For the outcome of arrhythmic death, the hazard ratio was 0.50 (95% confidence interval 0.37, 0.67;P<0.0001). Survival was extended by a mean of 4.4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction < or = 35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the non-thoracotomy era.
CONCLUSION: Results from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.

Copyright 2000 The European Society of Cardiology.
PMID 11102258
K A Hossmann, B Grosse Ophoff
Recovery of monkey brain after prolonged ischemia. I. Electrophysiology and brain electrolytes.
J Cereb Blood Flow Metab. 1986 Feb;6(1):15-21. doi: 10.1038/jcbfm.1986.3.
Abstract/Text Adult normothermic monkeys were submitted to 1 h of total cerebral ischemia, followed by blood recirculation for 1.5-24 h. During ischemia EEG and evoked potentials were suppressed within 12 s and 3 min, respectively. Upon recirculation, high-voltage EEG bursts began to reappear after 82-125 min, followed by gradual return of continuous background activity and near normalization of EEG frequency pattern within 24 h. Somatically evoked potentials, in contrast, exhibited only partial recovery, and consciousness did not return during the observation period. At the end of the experiments, tissue contents of sodium, potassium, calcium, and magnesium were measured in the gray and white matter of parietal lobe by atomic absorption spectroscopy. Gray matter sodium content gradually increased by approximately 50% from 41.0 to 59.8 mumol/g wet wt during 24 h of recirculation. The other electrolytes including calcium did not change during the observation period. Postischemic recovery reported in this and the accompanying article is attributed to careful control of postischemic general physiological state and prevention or treatment of postischemic complicating side effects such as postischemic brain edema, hypotension, acidosis, pulmonary distress, and anuria. No specific drug treatment such as application of calcium antagonists or metabolic inhibitors was necessary to achieve this effect.

PMID 3944213
Fabio Silvio Taccone, Edoardo Picetti, Jean-Louis Vincent
High Quality Targeted Temperature Management (TTM) After Cardiac Arrest.
Crit Care. 2020 Jan 6;24(1):6. doi: 10.1186/s13054-019-2721-1. Epub 2020 Jan 6.
Abstract/Text Targeted temperature management (TTM) is a complex intervention used with the aim of minimizing post-anoxic injury and improving neurological outcome after cardiac arrest. There is large variability in the devices used to achieve cooling and in protocols (e.g., for induction, target temperature, maintenance, rewarming, sedation, management of post-TTM fever). This variability can explain the limited benefits of TTM that have sometimes been reported. We therefore propose the concept of "high-quality TTM" as a way to increase the effectiveness of TTM and standardize its use in future interventional studies.

PMID 31907075
K B Kern, R W Hilwig, K H Rhee, R A Berg
Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning.
J Am Coll Cardiol. 1996 Jul;28(1):232-40.
Abstract/Text OBJECTIVES: This study investigated the effect of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on left ventricular systolic and diastolic function.
BACKGROUND: Cardiac arrest from ventricular fibrillation results in cessation of forward blood flow, including myocardial blood flow. During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal. Once the heart is defibrillated and successful resuscitation achieved, reversible myocardial dysfunction, or "stunning," may occur. The magnitude and time course of myocardial stunning from cardiac arrest is unknown.
METHODS: Twenty-eight domestic swine (26 +/- 1 kg) were studied with both invasive and noninvasive measurements of ventricular function before and after 10 or 15 min of untreated cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac output, isovolumetric relaxation time (tau) and transthoracic Doppler-echocardiographic studies were obtained.
RESULTS: Twenty-three of 28 animals were successfully resuscitated and postresuscitation data obtained. Left ventricular ejection fraction showed a significant reduction 30 min after resuscitation (p < 0.05). Regional wall motion analysis revealed diffuse, global left ventricular systolic dysfunction. Left ventricular end-diastolic pressure increased significantly in the postresuscitation period (p < 0.05). Isovolumetric relaxation time (tau) was significantly increased over baseline by 2 h after resuscitation (p < 0.05). Similar findings were noted with the Doppler-echocardiographic analysis, including a reduction in fractional shortening (p < 0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase in left ventricular isovolumetric relaxation time at 5 h after resuscitation (p < 0.05> By 24 h, these invasive and noninvasive variables of systolic and diastolic left ventricular function had begun to improve. At 48 h, all measures of left ventricular function had returned to baseline levels.
CONCLUSIONS: Myocardial systolic and diastolic dysfunction is severe after 10 to 15 min of untreated cardiac arrest and successful resuscitation. Full recovery of this postresuscitation myocardial stunning is seen by 48 h in this experimental model of ventricular fibrillation cardiac arrest.

PMID 8752819

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