Neurological prognostication after cardiac arrest—Recommendations from the Swedish Resuscitation Council☆
Introduction
In Sweden, 10,000 people suffer sudden and unexpected, out-of-hospital cardiac arrest every year. In approximately 5000 of these, cardiopulmonary resuscitation (CPR) is initiated.1, 2 Due to improved pre-hospital care, an increasing number of patients regain spontaneous circulation and are hospitalized for continued treatment.2 In hospitals, attitudes towards unconscious cardiac arrest patients have undergone a dramatic change. Underlying coronary artery disease is now frequently treated in its acute phase. Moreover, most patients receive adequate intensive care, which often involves hypothermia treatment.3 Thanks to these improvements, the proportion of patients who survive has increased, although there may be significant differences between hospitals.4, 5 Despite improvements, registration data indicate that the long-term survival rate after out-of-hospital cardiac arrest in Sweden amounts to no more than 10 percent.1, 2
Once cardiac function has been stabilized, the neurological prognosis depends mainly on the length of time without circulation to the brain. It is estimated that ischaemic brain injury is responsible for 70 percent or more of mortality in patients treated following cardiac arrest.6, 7, 8 Induced hypothermia has been shown to protect the brain in experimental cardiac arrest models.9 It has become a recommended treatment10, 11 since clinical studies have shown that cooling to 32–34 °C during a 12- to 24-h period decreased mortality and improved neurological function.12, 13 In Sweden, hypothermia treatment is used at most hospitals but it is recognized that the optimal target temperature and duration of treatment are not yet known.14 Hypothermia treatment is typically continued for 24 h and as a consequence, the patient is sedated and mechanically ventilated, sometimes for several days after normal body temperature has been restored. Patients who regain consciousness spontaneously shortly after the cardiac arrest, as well as those who wake up while sedation is being phased out after completed hypothermia treatment, have a favourable neurological prognosis. These patients are usually able to resume an independent life, although minor cognitive difficulties are common.15 In patients who do not regain consciousness, the prognosis deteriorates with the duration of unconsciousness or coma.16 A structured neurological prognostication is crucial as a foundation for informing relatives, prioritizing intensive care resources and avoiding futile care in cases where a vegetative state or death can be anticipated.
Neurological prognostication should be founded on available, evidence-based methods. Written local routines should be available at all hospitals treating cardiac arrest patients. US guidelines for prognostication after cardiac arrest, published in 2006 by the American Academy of Neurology (AAN), have had a great impact worldwide.17 Current international10 and AAN guidelines have the disadvantage of being primarily based on earlier studies on patients not treated with hypothermia. Thus, these guidelines have limited applicability for the majority of cardiac arrest patients in Sweden. The Swedish Resuscitation Council has commissioned the task force on post resuscitation care to develop national recommendations for neurological prognostication. Members of the task force (TC, HF, SR) have, together with an expert panel (MB, LJL, IR, CR), carried out non-systematized literature reviews within their respective areas of expertise. The final results have been formulated during consensus meetings. It has not been the intention of the group to cover all aspects of available prognostication methods. Our aim has rather been to present a simple, safe and, as far as possible, evidence-based model that can be applied to patients who have or have not received hypothermia treatment after cardiac arrest. This document has been circulated for consideration and comment to the respective Swedish specialist associations for neurology, anaesthesia and intensive care, neurophysiology, and cardiology. The recommendations have previously been published in Swedish in Läkartidningen, the Journal of the Swedish Medical Association18 and are aimed at all hospital personnel involved in cardiac arrest care and treatment.
Section snippets
When should neurological prognostication be carried out?
After just a few minutes of circulatory arrest, all brain functions cease. If circulation is restored, the nervous system will make a gradual recovery. Brainstem reflexes return first, then the motor response to pain and, finally, cortical activity and consciousness.19 Prolonged circulatory arrest results in more delayed and incomplete recovery. In consequence, non-recovered brainstem reflexes and stereotypic or absent pain reactions in patients with continued unconsciousness gradually become
What is the prognostic significance of factual circumstances?
Several circumstances related to the cardiac arrest have a clear statistical association with the prognosis. In a nationwide Swedish dataset involving more than 30,000 patients,20 the following factors were found to be associated with a favourable prognosis (here listed in order of importance): (1) ventricular fibrillation as the first registered rhythm, (2) short wait for an ambulance, (3) cardiac arrest outside the patient's home, (4) witnessed cardiac arrest, (5) cardiopulmonary
Clinical and electrographic seizures
Seizures usually take the form of myoclonic muscle twitches in the face, the trunk or the extremities.37, 38 However, generalized tonic-clonic and focal epileptic seizures also occur. Sedatives routinely administered during hypothermia treatment have a suppressive effect on myoclonus and other manifestations of epilepsy. Pronounced and generalized myoclonus appearing during the first 24 h after cardiac arrest is usually,23, 27 but not always,25, 35, 39 a sign of severe brain damage and an
Diagnostic imaging (CT/MRI)
Injuries arising as a consequence of cardiac arrest affect both the cortex and white matter of the brain. However, they appear more prominent in certain central areas such as the basal ganglia and thalami. In CT imaging, ischaemic injuries appear as blurred boundaries, i.e. decreased differentiation, between grey and white matter. This can be observed within 24 h of the cardiac arrest.44, 45, 46, 47, 48, 49 Brain swelling may be present and may lead to brain-stem herniation in some cases. Using
Biochemical markers
The most thoroughly studied biomarkers of cardiac arrest are S-100B and neuron-specific enolase (NSE),56, 57, 58 the latter being included in the AAN recommendations.17 The release profile of these biomarkers in plasma differs. At least two samples should be analysed to reduce the risk of error and to evaluate the trend. The reliability of using biomarkers in prognostication following hypothermia treatment has been called into question.30, 57, 59, 60, 61 However, the correlation between NSE
Recommended routine for prognostication
Intensive care measures following cardiac arrest follow the same priorities as other intensive care, i.e. they are prioritized based on the function and prognosis of all vital organs. In this patient group, however, the neurological outcome is decisive in most cases. Daily clinical examination is the most important instrument for assessing the extent of brain injury. Level of consciousness is assessed using a validated coma scale such as the GCS taking the possible effects of sedatives,
Summary
Modern treatment methods have improved the survival rate following cardiac arrest, but neurological prognostication has become more complicated by the increasingly advanced and complex care. Although the risk of extensive hypoxic brain injury increases with each day the unsedated patient does not wake up, good recovery may still occur and will require an extended period of treatment. It is important to identify patients with a poor prognosis in order to spare them and their next-of-kin
Conflict of interest statement
Tobias Cronberg (TC) and Hans Friberg (HF) are members of the steering committee for Target Temperature Management Trial (TTM, ClinicalTrials.gov Identifier: NCT01020916). HF has received lecturing fees from Care Fusion and Bard Medical. TC participates in a sub-study for TTM that receives support from Care Fusion. Lars Johan Liedholm, Ingmar Rosén, Sten Rubertsson and Christian Rylander have no conflicts to declare.
Acknowledgement
We have received permission from Läkartidningen for translation and publication in Resuscitation.
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.01.019