Elsevier

Resuscitation

Volume 49, Issue 2, May 2001, Pages 183-191
Resuscitation

Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest

https://doi.org/10.1016/S0300-9572(00)00348-8Get rights and content

Abstract

Background and purpose: patients with cardiac arrest have a high mortality and the long-term outcome is doubtful. The prognosis is mainly dependent on clinical parameters. S-100 and neurone specific enolase (NSE) are established biochemical markers of central nervous system (CNS) injury. The purpose of this study was to validate the use of serum determinations of S-100 and NSE with neurological investigations in regard to brain damage and long-term outcome after cardiac arrest. Methods: neurological examinations were performed on 66 patients after cardiac arrest. Serum levels of S-100 and NSE were determined during the first 3 days of post arrest, using commercial luminescent immunoassays (LIAs). The main outcome variable was the Glasgow Outcome Scale (GOS), while secondary variables were the activity of daily living (ADL) index and mini mental state examination (MMSE). Outcome was determined at 1 year. Results: the serum levels of S-100 and NSE were increased during the first 3 days after the arrest and were related to coma depth, time of anoxia and abnormal brain stem reflexes. High levels predicted a poor outcome, according to the GOS (death, vegetative state and severe disability). The prognostic value of the brain damage markers was comparable with that of traditional clinical parameters. None of the secondary outcome variables (ADL and MMSE) was strongly associated with S-100 or NSE. Discussion: the serum levels of S-100 and NSE increased after cardiac arrest due to the anoxic brain damage. The determination of S-100 and NSE can be used as an adjunct to predict long-term outcome after cardiac arrest.

Zusammenfassung

Objectivos: Os doentes vitimas de paragem cardiorespiratória (PCR) têm mortalidade elevada e prognóstico a longo prazo mau. O prognóstico é definido essencialmente por critérios clı́nicos. A S-100 e a enolase especı́fica do neurónio (NSE) são marcadores bioquı́micos de lesão do Sistema Nervoso Central (SNC). O objectivo deste estudo é validar o uso do nı́veis séricos das proteı́nas S-100 e NSE como indicadores da dimensão da lesão e do prognóstico pós PCR. Métodos: Foi feito exame neurológico em 66 doentes pós PCR. Determinaram-se os nı́veis de S-100 e NSE nos primeiros 3 dias usando um método de imunoensaio luminescente (LIAs). A principal variável estudada foi a Escala de Coma de Glasgow (ECGlasgow) e as variáveis secundárias foram o “ Activity of Daily Living Index” (ADL) o Minimal Mental State Examination (MMSE). O resultado foi avaliado ao ano. Resultados: Os nı́veis séricos de S-100 e NSE estavam aumentados nos 3 primeiros dias pós PCR e relacionaram-se com a profundidade do coma, tempo de anóxia e com as alterações dos reflexos do tronco cerebral. Nı́veis elevados foram indicativos de mau prognóstico de acordo com o Glasgow (morte, estado vegetativo e gravidade da incapacidade). O valor prognóstico destes marcadores de lesão cerebral foi comparável ao dos parâmetros clı́nicos tradicionais. Não foi possı́vel correlacionar o ADL e MMSE com os nı́veis de S-100 e NSE. Discussão: Os nı́veis de S-100 e NSE aumentam pós PCR devido à lesão cerebral anóxica. A sua determinação pode ser uma ajuda para prever o resultado neurológico pós PCR a longo prazo.

Introduction

Out-of-hospital cardiac arrest is a life-threatening situation, which calls for distinct, fast action by bystanders and the emergency rescue team [1]. Many patients bear clinical signs of brain damage and the ensuing mortality is very high [2]. For a valued prognosis, the extent of the brain damage needs to be evaluated. Deep coma and pathological brain stem reflexes indicate an advanced brain injury. Despite progress in diagnosis, there is still difficulty in evaluating brain damage suffered during the period without circulation. Lumbar punctures with analyses of CSF-neurone specific enolase (NSE) have been used to measure the degree of brain injury and high CSF-levels of NSE post-arrest are predictors of an unfavourable outcome [3]. However, lumbar punctures are impractical in the routine situation. Computed tomography (CT) scans provide little information about brain damage, except in cases with pronounced oedema, and the investigation can be difficult to perform in mechanically ventilated patients [4]. Similarly, EEG is not sensitive enough to detect patients with an unfavourable outcome, except in cases with very extensive damage.

We have shown previously that measurement of serum S-100 was useful in order to evaluate the short-term outcome in this patient group [5]. This protein is a sensitive marker of astroglial cell damage. NSE is a protein located in neurones [6]. It has been shown that both S-100 and NSE increase in serum during the first days after an acute cerebral infarction [7]. Recent reports have shown the value of serum-NSE sampling in relation to prolonged coma after cardiac arrest [8], [9].

We have studied 66 out-of-hospital cardiac arrest patients and followed them for 1 year. We measured serum S-100 protein and NSE during the first 3 days after the collapse. The main purpose was to explore the possible use of these serum markers of brain damage as prognostic tools in long-term outcome and to determine whether there is an association between the levels of these markers and the outcome 1 year after resuscitation as measured by the Glasgow Outcome Scale (GOS), [10] activity of daily living (ADL) [11] and mini mental state examination (MMSE) [12]. The second aim was to compare the prognostic value of these biochemical markers with traditional clinical signs of brain damage.

Section snippets

Patients and methods

In this study, we included 66 consecutive patients with out-of-hospital cardiac arrest. After successful resuscitation at the scene of the collapse, patients were transferred to the emergency department at Sahlgrens University Hospital in Göteborg, Sweden. Patients with a fatal outcome within 24 h were not included in the study. (17 patients with cardiac arrests were not included for technical reasons.) The study started in October 1994 and the last patient was included in January 1997.

Blood

Clinical variables

During the time of the survey 598 patients suffered out-of-hospital cardiac arrest with attempted resuscitation. Among them 178 were admitted for hospital alive and 130 were alive 24 h after admission. The 1-year mortality among these 130 patients was 66%. This study deals with 66 of these 130 patients, who were admitted to one of the two city hospitals, Sahlgrens University Hospital in the community of Göteborg.

In this study population, the mean age was 67.6±1.8 years (S.E.) (range 21–89

Discussion

Our study sample appears to be representative for resuscitated patients in the community of Goteborg. The main outcome variable was good or poor outcome, according to the GOS. Good outcome included good recovery and moderate disability, while poor outcome meant severe disability, permanent vegetative state and death. About 35% of the patients in our study population had a good outcome, which agrees well with previous studies [16], [17]. A total of 30 patients (45%) died with anoxic brain damage

Acknowledgements

This study was supported by the John and Brit Wennerström Foundation, the Rune and Ulla Amlôv Foundation, the Hjalmar Svensson Foundation, the Laerdal Foundation for Acute Medicine, the Heart-Lung Foundation, Göteborg Foundation for Neurological Research, the Edit Jacobson Foundation and the Göteborg Medical Society.

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