The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–8, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2014.07.029
Selected Topics: Neurological Emergencies
NEUROLOGIC CAUSES OF CARDIAC ARREST AND OUTCOMES Pia Hubner, MD, Giora Meron, MD, Istepan Ku¨rkciyan, MD, Christoph Weiser, MD, Christian Wallmu¨ller, MD, Mathias Sto¨ckl, MD, Andreas Schober, MD, Raphael van Tulder, MD, and Fritz Sterz, MD Department of Emergency Medicine, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria Reprint Address: Istepan Ku¨rkciyan, MD, Department of Emergency Medicine, General Hospital of Vienna, Medical University of Vienna, Austria, Wa¨hringer Gu¨rtel 1820, 1090 Vienna, Austria
, Abstract—Background: Sudden cardiac arrest as a complication of neurologic disorders is rare, occasionally acute neurologic events present with cardiac arrest as initial manifestation. Objective: Our aim was to describe neurologic disorders as a cause of cardiac arrest in order to enable better recognition. Methods: We retrospectively analyzed prospectively collected resuscitation data of all patients treated between 1991 and 2011 at the emergency department after cardiac arrest caused by a neurologic event, including diagnosis, therapy, and outcomes. Results: Over 20 years, 154 patients suffered cardiac arrest as a result of a neurologic event. Out-of-hospital cardiac arrest occurred in 126 (82%) patients, 78 (51%) were male, median age was 51 years (interquartile range 17 to 89 years). As initial electrocardiogram rhythm, pulseless electrical activity was found in 77 (50%) cases, asystole in 61 (40%), and ventricular fibrillation in 16 (10%) cases. The most common cause was subarachnoid hemorrhage in 74 (48%) patients, 33 (21%) patients had intracerebral hemorrhage, 23 (15%) had epileptic seizure, 11 (7%) had ischemic stroke, and 13 (8%) had other neurologic diseases. Return of spontaneous circulation was achieved in 139 (90%) patients. Of these, 22 (14%) were alive at follow-up after 6 months, 14 (9%) with favorable neurologic outcome, 8 of these with epileptic seizure, and most of them with history of epilepsy. Conclusions: Subarachnoidal hemorrhage is the leading neurologic cause of cardiac arrest. Most of the patients with cardiac arrest caused by neurologic disorder have a very poor prognosis. Ó 2014 Elsevier Inc.
INTRODUCTION Sudden cardiac arrest as a complication of neurologic disorders is rare (1,2). Even rarer is the presentation of acute neurologic events with cardiac arrest as initial manifestation (3). We have found descriptions of subarachnoidal hemorrhage (SAH) and sudden unexpected death in epilepsy (SUDEP) in the literature, but there are few publications about intracerebral hemorrhage (ICH) and ischemic stroke as cause of cardiac arrest. SAH is the most common intracranial bleeding leading to sudden cardiac arrest (1,4). We have published a case series of these patients and found that SAH complicated by cardiac arrest is almost always fatal (5). Most deaths after SAH occur almost immediately and are due to initial hemorrhage with cardiorespiratory complications, such as dysrhythmias or respiratory arrest (6,7). Although ICH and ischemic stroke occur far more often than SAH, there are only a few reports describing these as a cause of nontraumatic sudden death (8 10). In contrast, SUDEP is widely recognized and accounts for 7% to 17% of deaths among people with known epilepsy (11 13). Most deaths were associated with convulsive seizures (14,15). Postictal laryngospasm may represent another potential cause of SUDEP (16,17). To enable better recognition of a nontraumatic neurologic disease as cause of cardiac arrest, we retrospectively analyzed cardiac arrest data, diagnosis, therapy, and outcome in these patients.
, Keywords—cardiac arrest; subarachnoid hemorrhage; intracerebral hemorrhage; stroke; cause of death
RECEIVED: 13 December 2013; FINAL SUBMISSION RECEIVED: 5 June 2014; ACCEPTED: 1 July 2014 1
2
P. Hubner et al.
METHODS From July 1, 1991 to December 31, 2011, resuscitation data of all patients admitted to the Department of Emergency Medicine after cardiopulmonary resuscitation, were prospectively documented. The Department of Emergency Medicine is an interdisciplinary emergency department (ED) at the Medical University of Vienna. It is a complete 14-bed intensive care unit (ICU), where patients are routinely treated after resuscitation for up to 24 h and in isolated cases 72 h. Most patients in this study were brought to our ICU by ambulance service after suffering out-of-hospital cardiac arrest. Some patients suffered cardiac arrest at the ED during workup. Another small group of patients suffered cardiac arrest in other places in the hospital and were managed by our code team. The study procedures were in accordance with the ethical standards of the Responsible Committee on Human Experimentation and with the Helsinki Declaration of 1975, as revised in 1983. Cardiac Arrest Registry and Inclusion Criteria Data for all patients were registered according to a specific protocol. Among other details, this includes sex and age of the patients, location of cardiac arrest, whether or not the event was witnessed (the patient was witnessed to suddenly collapse), initial electrocardiogram (ECG) rhythm, and time until restoration of spontaneous circulation (ROSC). Surviving patients were followed up to 6 months after the index event. We retrospectively enriched this registry by adding data, which were helpful to clarify the definitive cause of the cardiac arrest. All patients with neurologic cause of nontraumatic cardiac arrest were enrolled in the study. This included patients who were initially clinically diagnosed with a neurologic cause for their cardiac arrest, as well as patients who were diagnosed by computed tomography (CT) or autopsy later. A tentative diagnosis of the different neurologic events was based on history and clinical examination. This clinical diagnosis was verified in most of the patients by cranial computed tomography (CCT) and further confirmed by autopsy in nonsurvivors. In those patients who had suffered epileptic seizure, there were those without prior known epilepsy, as well as patients with SUDEP. This was defined as sudden, unexpected, nontraumatic, nondrowning death in an individual with epilepsy, witnessed or nonwitnessed, in which postmortem examination did not reveal an anatomic or toxicologic cause for the death (1). In these patients, we tried to rule out other possible causes to sustain the diagnosis of epileptic seizure. Nontraumatic ICH was defined as bleeding into the parenchyma of the brain
that may have extended into the ventricles and, in rare cases, into the subarachnoid space (18). Outcomes The primary outcome was defined as being alive in favorable neurologic condition at 6 months after the index event. Cerebral function was assessed prospectively on arrival and 6 months after ROSC, and was expressed in terms of the Glasgow-Pittsburgh cerebral performance categories (CPC): CPC 1 indicates good capability; CPC 2 indicates slight disability; CPC 3 indicates severe disability, CPC 4 indicates coma or vegetative state; CPC 5 indicates cerebral death. We considered a CPC score of 1 or 2 as favorable and a CPC score of 3, 4, or 5 as unfavorable functional neurological outcome. Study Design and Statistical Methods According to the cause of cardiac arrest, patients were assigned to one of five subgroups: SAH, ICH, ischemic stroke, epileptic seizure, and other neurologic diseases. We evaluated incidence, demographic data, and outcome according to these subgroups. Data are expressed as median and interquartile range (IQR). Percentages were determined for dichotomous variables. RESULTS Over 20 years, 154 patients suffered cardiac arrest with a neurologic cause. Distribution of causes of cardiac arrest is shown in Table 1. Of all patients, 16 (10%) were admitted under ongoing resuscitation. Cardiac arrest occurred out of the hospital in 126 patients, at home in 82 (65%) patients, in a public place in 30 (24%) patients, during transport to the hospital in 12 (9%) patients, and in a physician’s office in 2 (2%) patients. Cardiac arrest occurred in the hospital in 28 patients, at the ED in 14 (50%) patients, in a regular ward in 8 (29%) patients, in the radiology department 4 patients (14%), and in a public area within the hospital in 2 (7%) patients. A cranial computed tomography (CCT) was performed in 123 (80%) of all 154 patients. Overall, autopsy was performed in 72 patients. In 44 patients where the CCT was radiologically diagnostic, autopsy confirmed the radiologic diagnosis. In another 28 (18%) patients without CCT examination, the diagnosis was only established at autopsy. In the remaining 4 (3%) of all patients in whom neither CCT nor autopsy had been performed, we established the cause of cardiac arrest to be of neurologic origin by the patient’s history and clinical presentation. The distribution of diagnoses on the causes of cardiac arrest is presented in Figure 1.
Neurologic Causes of Cardiac Arrest
3
Table 1. Neurologic Etiology of Cardiac Arrest (n = 154) Etiology
n (%)
SAH ICH Epileptic seizure Ischemic stroke Other neurologic disorders Amyotrophic lateral sclerosis Subdural hematoma Encephalitis Progressive muscular dystrophy Leukodystrophy Glioblastoma Fungal meningitis, AIDS Hydrocephalus Myasthenia gravis
74 (48) 33 (21) 23 (15) 11 (7) 13 (8) 3 2 2 1 1 1 1 1 1
AIDS = acquired immune-deficiency syndrome; ICH = intracranial hemorrhage; SAH = subarachnoidal hemorrhage.
Outcomes associated with different causes are described in Figure 2. Overall, 14 (9%) of all 154 patients were alive in good neurologic condition at follow-up 6 months after the index event, with a median hospital stay of 55 days (IQR 5 187 days). Neurologic Causes of Cardiac Arrest The resuscitation data of all patients are presented in Table 2.
Figure 1. Diagnostic procedures regarding the cause of cardiac arrest. CT = computed tomography; ICH = intracerebral hemorrhage; SAH = subarachnoidal hemorrhage.
SAH (n = 74 [48%]). Out-of-hospital cardiac arrest occurred in 68 patients, 48 (71%) of these occurred at home, 17 (25%) in public places, 2 (3%) while on transport, and 1 (1%) in a private doctor’s office. In-hospital cardiac arrest occurred in 6 patients, 3 of these at our ED, 1 each at a regular ward, the radiology department, and in a public area of the hospital. In all patients with SAH, the collapse was sudden. Cephalea before cardiac arrest was present in 18 (24%) of 74 patients; in 6 patients, cardiac arrest occurred during sexual intercourse. A CCT was performed and was diagnostic in 64 patients. The site of the ruptured aneurysm causing the SAH was the basilar artery and the middle cerebral artery each in 15, the internal carotid artery in 11, the anterior communicating artery in 6 and the vertebral artery in 2 cases. In 15 patients, the exact location of the source of bleeding was not found. All patients fulfilled the criteria for Hunt-Hess category 5, and all showed cerebral edema. Other findings were loss of gray-white matter differentiation, compression of the fourth ventricle, and effacement of basal cisterns. Herniation was found in 15 patients initially, and in another 10, beginning herniation was present. Neurosurgical intervention was performed in 15 (20%) patients, and 3 of these were alive in good neurologic condition at follow-up 6 months after the index event, with a median hospital stay of 51 days (IQR 23 to 84 days). Another 2 were alive in unfavorable condition, and 10 patients died despite emergent surgical intervention. The remaining 50 patients with CCT-verified diagnosis were not considered to benefit from a neurosurgical procedure, none of them survived. Overall, an autopsy was performed in 40 (54%) of all patients. None of the 7 patients admitted under ongoing resuscitation survived. ICH (n = 33 [21%]). Out-of-hospital cardiac arrest occurred in 23 patients, 13 (56%) were at home, 5 (22%) each were in public places and while on transport. In-hospital cardiac arrest occurred in 10 of 33 patients, 7 of these were at our ED, 2 were at the radiology department, and 1 was in a public area of the hospital. Three patients suffered cardiac arrest after receiving systemic thrombolytic therapy for acute coronary syndrome or pulmonary embolism. Another 2 patients where initially suspected of having suffered cardiac arrest due to pulmonary embolism, and a rescue thrombolysis was performed. At autopsy, neither pulmonary embolism nor any other cause of cardiac arrest except ICH was found. Two other patients had known leukemia. At autopsy or CCT, ruptured cerebral aneurysm was found in 2 patients, an angioma in 2, and an arteriovenous malformation in 1. Of all patients with ICH, 8 presented with headache, 7 were found unconscious before going into cardiac
4
P. Hubner et al.
Figure 2. Outcomes depending on the cause of cardiac arrest. CPC = cerebral performance category; ICH = intracerebral hemorrhage; ROSC = return of spontaneous circulation; SAH = subarachnoidal hemorrhage.
arrest, 3 presented with clouded awareness, 2 with seizures, 3 collapsed suddenly without prior symptoms, and 1 patient presented with nausea before collapse. In 9 patients, the cardiac arrest was not witnessed.
A CCT was performed and was diagnostic in 24 (73%) of the patients. The site of the ICH was the brainstem in 8, frontal lobe in 6, cerebellum in 5, occipital lobe and basal ganglia each in 4, temporal lobe in 2 and thalamus, lateral
Table 2. Resuscitation Data of all Patients After Cardiac Arrest Criteria Male sex n (%) Age (years), median (range) Out-of-hospital CA arrests, n (%) Witnessed CA, n (%) ECG rhythm,* n (%) PEA Asystole VF ROSC (min), median (range) Not resuscitated, n (%) Dead within 6 months, n (%) Alive (CPC 3 4), n (%) Alive (CPC 1 2),† n (%)
Total (n = 154)
SAH (n = 74)
ICH (n = 33)
Seizure (n = 23)
Stroke (n = 11)
Others (n = 13)
78 (51) 51 (17 85) 126 (82) 122 (79)
26 (35) 49 (23 78) 68 (92) 65 (88)
20 (61) 52 (25 79) 23 (70) 24 (73)
19 (83) 48 (18 82) 17 (74) 23 (100)
6 (55) 68 (53 85) 10 (91) 9 (82)
7 (54) 53 (17 74) 8 (62) 8 (62)
77 (50) 61 (40) 16 (10) 18 (0 126) 15 (10) 117 (76) 8 (5) 14 (9)
39 (53) 30 (41) 5 (7) 21 (1 126) 3 (4) 66 (89) 2 (3) 3 (4)
20 (61) 8 (24) 5 (15) 9 (0 42) 7 (21) 23 (70) 1 (3) 2 (6)
10 (43) 11 (48) 2 (9) 14 (1 40) 0 11 (48) 4 (17) 8 (35)
4 (36) 4 (36) 3 (27) 15 (7 94) 4 (36) 7 (64) 0 0
4 (31) 8 (62) 1 (8) 16 (5 32) 1 (8) 10 (77) 1 (8) 1 (8)
CA = cardiac arrest; CCT = cranial computed tomography; CPC = cerebral performance category; ECG = electrocardiogram; ICH = intracranial hemorrhage; PEA = pulseless electric activity; ROSC = return of spontaneous circulation; SAH = subarachnoidal hemorrhage; VF = ventricular fibrillation. * First documented rhythm after cardiac arrest. † Good neurologic outcome.
Neurologic Causes of Cardiac Arrest
ventricle, and fourth ventricle each in 1 case. In 1 patient, the site could not be determined. Surgical intervention was performed in 5 (15%) patients, 2 of them were alive at follow-up 6 months after the cardiac arrest with good neurologic outcomes. Another patient was alive in unfavorable condition, 2 patients died despite emergent surgical intervention. The remaining 20 patients with CCT-verified diagnosis were not considered to benefit from a neurosurgical procedure, none of them survived. Overall, an autopsy was performed in 13 (39%) of all patients, in 9 of these 13 patients in whom no CCT was performed, it was diagnostic. In those 5 patients admitted under ongoing resuscitation, no ROSC could be established at any time. Epileptic seizure (n = 23 [15%]). Out-of-hospital cardiac arrest occurred in 17 of 23 patients, 10 (59%) were at home, 6 (35%) were in a public place, and 1 (6%) was while on transport. In-hospital cardiac arrest occurred in 6 of 23 patients, 3 of these were at our ED, 2 were at a regular ward, and 1 was in a public area of the hospital. Patients with epileptic seizure suffered cardiac arrest during ongoing convulsions. Overall, a CCT was performed in 21 (91%) patients and an autopsy in 4 patients. Of all patients, 13 had SUDEP, 4 had a malignant cerebral disease, 4 had a seizure associated with alcohol or drug abuse, 1 had hydrocephalus, and in 1 it occurred after dialysis. All patients with SUDEP underwent CCT, and this showed 5 with cerebral edema, 1 with leukencephalopathy, 1 with lacunary lesion, and in 6 patients no radiologic changes could be found. In all 4 patients with a malignancy, the tumor and local edema were present. In addition, in 4 patients with alcohol or drug-associated epileptic seizure, CCT was performed in 3 and showed cerebral edema in 1 case. Of all patients with epileptic seizure, 8 survived with favorable neurologic outcomes (35%), 6 patients with SUDEP, 1 with astrocytoma, and 1 with chronic renal failure and dialysis. The median duration of the patients’ stay at the hospital was 54 days (IQR 5 187 days). Ischemic stroke (n = 11 [7%]).Out-of-hospital cardiac arrest occurred in 10 of 11 (90%) patients, 4 of these were at home, 4 were while on transport, and 1 each in a regular ward and in a public place. In-hospital cardiac arrest occurred at our ED in 1 patient. The site of the ischemic stroke was the cerebellum in 3 patients, medial (temporal) lobe in 3 patients, parietal lobe in 2 patients, and occipital lobe and complete left hemisphere in 1 patient each. In 1 patient, the site could not be determined. Of all patients with stroke, 5 patients presented with progressing dyspnea, eventually leading to respiratory failure, 3 collapsed suddenly without prior symptoms
5
and 1 patient presented with clouded awareness before collapse. One patient suffered from impaired speech and hemiparesis in the days leading up to their cardiac arrest. In 2 patients, cardiac arrest was not witnessed. Of all patients with ischemic stroke, 4 did not achieve ROSC at any time, and the remaining 7 died after a median of 2 days (IQR 1 6 days). Other neurologic diseases (n = 13 [8%]). Details are shown in Table 1. Out-of-hospital cardiac arrest occurred in 8 of 13 patients, 7 of these were at home, and 1 was in a public place. In-hospital cardiac arrest occurred in 5 patients, all at a regular ward. One patient with myasthenia gravis, who had been resuscitated, survived, and was discharged after 49 days in favorable neurologic condition. Another patient with amyotrophic lateral sclerosis (ie, Lou Gehrig’s disease), who presumably had cardiac arrest due to respiratory arrest from muscle failure, achieved ROSC, was alive 6 months after the index event, but due to the underlying motor-neuron disease was in an unfavorable neurologic condition. One patient with encephalitis associated with acquired immune-deficiency syndrome was admitted to the ED under ongoing resuscitation but did not achieve ROSC. All other patients achieved ROSC, but died within a median of 1 day (IQR 1 1.5 days). DISCUSSION Data of patients who had been treated at the ED after cardiac arrest due to neurologic etiologies showed SAH in almost half of our study cohort. Ischemic stroke, although a very common occurrence, led to sudden cardiac arrest only rarely. While almost all patients suffering from SAH or epileptic seizure achieved ROSC, the ROSC rate in patients with ICH or ischemic stroke was much lower. Survival with good neurologic outcome was found mainly in patients with seizure. Because cardiac causes of sudden cardiac death are much more common, the diagnostic pathway is more apparent. The key to diagnosing a neurologic event as cause of cardiac arrest is to keep this possibility in mind even in the absence of obvious neurologic features. Signs like sudden and severe headache before collapse may be indicative of SAH (8). The description of generalized seizure by bystanders may point to SUDEP as cause of cardiac arrest (11). If a neurologic event is suspected, or if no other obvious cause of cardiac arrest can be found, a CCT should be performed (4,5). However, if there is the possibility of an acute coronary event, CCT should not delay possible angiography. Initial ECG rhythms were pulseless electric activity and asystole in most of our patients, which are unspecific rhythms. Ventricular fibrillation as initial ECG rhythm,
6
which occurred in 16 patients, might be misleading and the cardiac arrest might be erroneously thought to be due to a cardiac cause, especially without prior knowledge of a neurologic event. We have previously reported the poor prognosis for patients with cardiac arrest due to SAH, and have not found any improvement (5). Of 74 patients in our study population, only 3 could be discharged in good neurologic condition. Mitsuma et al. also observed a high ROSC rate, but no patient survived to hospital discharge (19). Initial cardiac rhythm revealed no ventricular fibrillation. In patients with out-of-hospital cardiac arrest, SAH was found in about 6%, and in about 15% of resuscitated patients. Inamasu et al. found no survivors of 23 patients with SAH after cardiac arrest (4). Kuisma and Alaspaa found no survivors in 18 patients with intracranial processes (3). This is in stark contrast to the report of Toussaint et al., who found that 11 (3.6%) of their 307 patients with SAH suffered cardiac arrest, but 54% of these 11 patients survived (20). This can probably be explained by the short duration of cardiac arrest (mean 6.5 min) compared with our study, where the mean time to ROSC was 21 min (IQR 1 126 min) (20). We believe that the poor outcomes in our study can be ascribed mainly to the large and irreversible morphologic cerebral damage, which we found on inspection of the CCT scans and in autopsy. Broderick et al., who reported in 1994 that most deaths after SAH occur very rapidly and are due to the initial hemorrhage as well as to its size, confirm this observation (6). The mechanisms leading to cardiac arrest in patients with underlying neurologic condition are controversial. We believe that either mechanical herniation of the brainstem, due to the sudden increase of intracranial pressure, or respiratory arrest followed by hypoxic cardiac arrest, due to compression of brainstem centers, might be the main mechanisms. In 1984, Hijdra et al. described that respiratory arrest was found in 37 patients with SAH, while 2 had ventricular fibrillation (7). Nontraumatic ICH is caused primarily by spontaneous rupture of small vessels damaged by chronic hypertension or amyloid angiopathy. Epidemiologically, ICH is more than twice as common as SAH. It is more likely to result in death than ischemic cerebral infarction or SAH (21). However, there are few reports in the literature describing sudden cardiac arrest as complication or initial presentation of ICH (21,22). Inamasu et al. reported only 2 patients with ICH vs. 10 patients with SAH (8). This may be due to the comparatively slower rise of intracranial pressure than in SAH. Therefore, even in large ICH, the respiratory function usually remains intact. In our study population, ICH was the second most common cause of neurologic cardiac arrest after SAH. Phillips et al. found even more patients with ICH than
P. Hubner et al.
with SAH (2). In the beginning of the era of systemic thrombolytic therapy in acute coronary syndromes, we had some patients who developed massive ICH and sudden cardiac arrest as a complication of the cerebral bleeding. None of these patients survived. SUDEP as cause of sudden cardiac death is a well described and published disease entity (11,13 15,23). It is frequently unwitnessed, and this is consistent with many studies. Among those situations that are witnessed, however, the majority are associated with convulsions, suggesting that seizures are directly and causally related to SUDEP (12). The rate of survival with good neurologic outcomes in the patients with epileptic seizure was high. This might possibly be explained by the fact that an epileptic seizure is not characterized by acute morphologic cerebral changes. In these patients, the cardiac arrest was most likely caused by respiratory failure due to prolonged seizures. Other causes, such as intracranial tumor and alcohol or drug abuse, had unfavorable outcomes. However, we realize that the number of patients with epileptic seizure as cause for cardiac arrest is too small to draw a final conclusion about outcomes. Ischemic stroke is a rare cause of sudden cardiac arrest and there are few reports describing these patients (2,10). In our study population, during a study period of 20 years, we only found 11 patients, all but 1 suffered an out-of-hospital cardiac arrest. In all of these patients, structural cerebral damage, as described in CCTor autopsy, was exceptionally large and outcomes were dismal, as no patient was alive at 6 months. Patients with cardiac arrest caused by stroke did not have typical symptoms (eg, hemiparesis) before they collapsed. Collapse was sudden in all of these cases. Most of these patients could be diagnosed in autopsy. It is interesting to observe that ventricular fibrillation was the first recorded ECG rhythm in 3 of these patients. So¨ro¨s and Hachinski suggest that sudden death in these patients may be ascribed to a complex interaction between cardiovascular and neurologic causes, with a resulting autonomic imbalance (9). Silver et al. describe two mechanisms for sudden cardiac arrest, which may be either due to life-threatening dysrhythmias or acute transtentorial herniation (24). Limitations Data for this study were analyzed retrospectively, which can be considered a limitation, however, it was collected prospectively. CONCLUSIONS SAH was the leading cause of cardiac arrest and was found in almost half of our patients. Most of the patients
Neurologic Causes of Cardiac Arrest
with SAH, ICH, or ischemic stroke had very poor prognoses. Although rare, neurologic causes should be considered in patients with cardiac arrest. REFERENCES 1. Skrifvars MB, Parr MJ. Incidence, predisposing factors, management and survival following cardiac arrest due to subarachnoid haemorrhage: a review of the literature. Scand J Trauma Resusc Emerg Med 2012;20:75. 2. Phillips LH, Whisnant JP, Reagan TJ. Sudden death from stroke. Stroke 1977;8:392–5. 3. Kuisma M, Alaspaa A. Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997;18:1122–8. 4. Inamasu J, Miyatake S, Tomioka H, et al. Subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest: a prospective computed tomography study. Resuscitation 2009;80:977–80. 5. Kurkciyan I, Meron G, Sterz F, et al. Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest. Resuscitation 2001;51:27–32. 6. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 1994;25:1342–7. 7. Hijdra A, Vermeulen M, van Gijn J, van Crevel H. Respiratory arrest in subarachnoid hemorrhage. Neurology 1984;34:1501–3. 8. Inamasu J, Miyatake S, Tomioka H, et al. Headache, cardiac arrest, and intracranial hemorrhage. J Headache Pain 2009;10:357–60. 9. So¨ro¨s P, Hachinski V. Cardiovascular and neurological causes of sudden death after ischaemic stroke. Lancet Neurol 2012;11:179–88. 10. Tokgo¨zoglu SL, Batur MK, Topcuoglu MA, Saribas O, Kes S, Oto A. Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke 1999;30:1307–11. 11. Nashef L, Garner S, Sander JW, Fish DR, Shorvon SD. Circumstances of death in sudden death in epilepsy: interviews of bereaved relatives. J Neurol Neurosurg Psychiatry 1998;64:349–52.
7 12. Lhatoo SD, Sander JW. Cause-specific mortality in epilepsy. Epilepsia 2005;46:36–9. 13. Johnston A, Smith P. Sudden unexpected death in epilepsy. Expert Rev Neurother 2007;7:1751–61. 14. Langan Y, Nashef L, Sander JW. Sudden unexpected death in epilepsy: a series of witnessed deaths. J Neurol Neurosurg Psychiatry 2000;68:211–3. 15. Dasheiff RM. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death. J Clin Neurophysiol 1991;8: 216–22. 16. Tavee J, Morris H 3rd. Severe postictal laryngospasm as a potential mechanism for sudden unexpected death in epilepsy: a near-miss in an EMU. Epilepsia 2008;49:2113–7. 17. Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997;38(11 Suppl):S6–8. 18. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med 2001;344:1450–60. 19. Mitsuma W, Ito M, Kodama M, et al. Clinical and cardiac features of patients with subarachnoid haemorrhage presenting with out-ofhospital cardiac arrest. Resuscitation 2011;82:1294–7. 20. Toussaint LG 3rd, Friedman JA, Wijdicks EF, et al. Survival of cardiac arrest after aneurysmal subarachnoid hemorrhage. Neurosurgery 2005;57:25–31. 21. Broderick JP, Adams HP Jr, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30:905–15. 22. Broderick JP, Brott T, Tomsick T, Miller R, Huster G. Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 1993;78:188–91. 23. Langan Y. Sudden unexpected death in epilepsy (SUDEP): risk factors and case control studies. Seizure 2000;9:179–83. 24. Silver FL, Norris JW, Lewis AJ, Hachinski VC. Early mortality following stroke: a prospective review. Stroke 1984;15:492–6.
8
P. Hubner et al.
ARTICLE SUMMARY 1. Why is this topic important? Since they are rare, neurologic causes for cardiac arrest are often not, or not soon enough, considered in the management of emergencies. 2. What does this study attempt to show? We review the epidemiology of patients with neurologic emergencies. 3. What are the key findings? Patients with neurologic emergencies usually have poor outcomes. Outcomes vary between patients with large structural damage and patients with epileptic seizure as reason for cardiac arrest. 4. How is patient care impacted? Consideration of neurologic causes of cardiac arrest may lead to faster recognition and diagnosis.
http://dx.doi.org/10.1016/j.jemermed.2014.07.029
Selected Topics: Neurological Emergencies
NEUROLOGIC CAUSES OF CARDIAC ARREST AND OUTCOMES Pia Hubner, MD, Giora Meron, MD, Istepan Ku¨rkciyan, MD, Christoph Weiser, MD, Christian Wallmu¨ller, MD, Mathias Sto¨ckl, MD, Andreas Schober, MD, Raphael van Tulder, MD, and Fritz Sterz, MD Department of Emergency Medicine, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria Reprint Address: Istepan Ku¨rkciyan, MD, Department of Emergency Medicine, General Hospital of Vienna, Medical University of Vienna, Austria, Wa¨hringer Gu¨rtel 1820, 1090 Vienna, Austria
, Abstract—Background: Sudden cardiac arrest as a complication of neurologic disorders is rare, occasionally acute neurologic events present with cardiac arrest as initial manifestation. Objective: Our aim was to describe neurologic disorders as a cause of cardiac arrest in order to enable better recognition. Methods: We retrospectively analyzed prospectively collected resuscitation data of all patients treated between 1991 and 2011 at the emergency department after cardiac arrest caused by a neurologic event, including diagnosis, therapy, and outcomes. Results: Over 20 years, 154 patients suffered cardiac arrest as a result of a neurologic event. Out-of-hospital cardiac arrest occurred in 126 (82%) patients, 78 (51%) were male, median age was 51 years (interquartile range 17 to 89 years). As initial electrocardiogram rhythm, pulseless electrical activity was found in 77 (50%) cases, asystole in 61 (40%), and ventricular fibrillation in 16 (10%) cases. The most common cause was subarachnoid hemorrhage in 74 (48%) patients, 33 (21%) patients had intracerebral hemorrhage, 23 (15%) had epileptic seizure, 11 (7%) had ischemic stroke, and 13 (8%) had other neurologic diseases. Return of spontaneous circulation was achieved in 139 (90%) patients. Of these, 22 (14%) were alive at follow-up after 6 months, 14 (9%) with favorable neurologic outcome, 8 of these with epileptic seizure, and most of them with history of epilepsy. Conclusions: Subarachnoidal hemorrhage is the leading neurologic cause of cardiac arrest. Most of the patients with cardiac arrest caused by neurologic disorder have a very poor prognosis. Ó 2014 Elsevier Inc.
INTRODUCTION Sudden cardiac arrest as a complication of neurologic disorders is rare (1,2). Even rarer is the presentation of acute neurologic events with cardiac arrest as initial manifestation (3). We have found descriptions of subarachnoidal hemorrhage (SAH) and sudden unexpected death in epilepsy (SUDEP) in the literature, but there are few publications about intracerebral hemorrhage (ICH) and ischemic stroke as cause of cardiac arrest. SAH is the most common intracranial bleeding leading to sudden cardiac arrest (1,4). We have published a case series of these patients and found that SAH complicated by cardiac arrest is almost always fatal (5). Most deaths after SAH occur almost immediately and are due to initial hemorrhage with cardiorespiratory complications, such as dysrhythmias or respiratory arrest (6,7). Although ICH and ischemic stroke occur far more often than SAH, there are only a few reports describing these as a cause of nontraumatic sudden death (8 10). In contrast, SUDEP is widely recognized and accounts for 7% to 17% of deaths among people with known epilepsy (11 13). Most deaths were associated with convulsive seizures (14,15). Postictal laryngospasm may represent another potential cause of SUDEP (16,17). To enable better recognition of a nontraumatic neurologic disease as cause of cardiac arrest, we retrospectively analyzed cardiac arrest data, diagnosis, therapy, and outcome in these patients.
, Keywords—cardiac arrest; subarachnoid hemorrhage; intracerebral hemorrhage; stroke; cause of death
RECEIVED: 13 December 2013; FINAL SUBMISSION RECEIVED: 5 June 2014; ACCEPTED: 1 July 2014 1
2
P. Hubner et al.
METHODS From July 1, 1991 to December 31, 2011, resuscitation data of all patients admitted to the Department of Emergency Medicine after cardiopulmonary resuscitation, were prospectively documented. The Department of Emergency Medicine is an interdisciplinary emergency department (ED) at the Medical University of Vienna. It is a complete 14-bed intensive care unit (ICU), where patients are routinely treated after resuscitation for up to 24 h and in isolated cases 72 h. Most patients in this study were brought to our ICU by ambulance service after suffering out-of-hospital cardiac arrest. Some patients suffered cardiac arrest at the ED during workup. Another small group of patients suffered cardiac arrest in other places in the hospital and were managed by our code team. The study procedures were in accordance with the ethical standards of the Responsible Committee on Human Experimentation and with the Helsinki Declaration of 1975, as revised in 1983. Cardiac Arrest Registry and Inclusion Criteria Data for all patients were registered according to a specific protocol. Among other details, this includes sex and age of the patients, location of cardiac arrest, whether or not the event was witnessed (the patient was witnessed to suddenly collapse), initial electrocardiogram (ECG) rhythm, and time until restoration of spontaneous circulation (ROSC). Surviving patients were followed up to 6 months after the index event. We retrospectively enriched this registry by adding data, which were helpful to clarify the definitive cause of the cardiac arrest. All patients with neurologic cause of nontraumatic cardiac arrest were enrolled in the study. This included patients who were initially clinically diagnosed with a neurologic cause for their cardiac arrest, as well as patients who were diagnosed by computed tomography (CT) or autopsy later. A tentative diagnosis of the different neurologic events was based on history and clinical examination. This clinical diagnosis was verified in most of the patients by cranial computed tomography (CCT) and further confirmed by autopsy in nonsurvivors. In those patients who had suffered epileptic seizure, there were those without prior known epilepsy, as well as patients with SUDEP. This was defined as sudden, unexpected, nontraumatic, nondrowning death in an individual with epilepsy, witnessed or nonwitnessed, in which postmortem examination did not reveal an anatomic or toxicologic cause for the death (1). In these patients, we tried to rule out other possible causes to sustain the diagnosis of epileptic seizure. Nontraumatic ICH was defined as bleeding into the parenchyma of the brain
that may have extended into the ventricles and, in rare cases, into the subarachnoid space (18). Outcomes The primary outcome was defined as being alive in favorable neurologic condition at 6 months after the index event. Cerebral function was assessed prospectively on arrival and 6 months after ROSC, and was expressed in terms of the Glasgow-Pittsburgh cerebral performance categories (CPC): CPC 1 indicates good capability; CPC 2 indicates slight disability; CPC 3 indicates severe disability, CPC 4 indicates coma or vegetative state; CPC 5 indicates cerebral death. We considered a CPC score of 1 or 2 as favorable and a CPC score of 3, 4, or 5 as unfavorable functional neurological outcome. Study Design and Statistical Methods According to the cause of cardiac arrest, patients were assigned to one of five subgroups: SAH, ICH, ischemic stroke, epileptic seizure, and other neurologic diseases. We evaluated incidence, demographic data, and outcome according to these subgroups. Data are expressed as median and interquartile range (IQR). Percentages were determined for dichotomous variables. RESULTS Over 20 years, 154 patients suffered cardiac arrest with a neurologic cause. Distribution of causes of cardiac arrest is shown in Table 1. Of all patients, 16 (10%) were admitted under ongoing resuscitation. Cardiac arrest occurred out of the hospital in 126 patients, at home in 82 (65%) patients, in a public place in 30 (24%) patients, during transport to the hospital in 12 (9%) patients, and in a physician’s office in 2 (2%) patients. Cardiac arrest occurred in the hospital in 28 patients, at the ED in 14 (50%) patients, in a regular ward in 8 (29%) patients, in the radiology department 4 patients (14%), and in a public area within the hospital in 2 (7%) patients. A cranial computed tomography (CCT) was performed in 123 (80%) of all 154 patients. Overall, autopsy was performed in 72 patients. In 44 patients where the CCT was radiologically diagnostic, autopsy confirmed the radiologic diagnosis. In another 28 (18%) patients without CCT examination, the diagnosis was only established at autopsy. In the remaining 4 (3%) of all patients in whom neither CCT nor autopsy had been performed, we established the cause of cardiac arrest to be of neurologic origin by the patient’s history and clinical presentation. The distribution of diagnoses on the causes of cardiac arrest is presented in Figure 1.
Neurologic Causes of Cardiac Arrest
3
Table 1. Neurologic Etiology of Cardiac Arrest (n = 154) Etiology
n (%)
SAH ICH Epileptic seizure Ischemic stroke Other neurologic disorders Amyotrophic lateral sclerosis Subdural hematoma Encephalitis Progressive muscular dystrophy Leukodystrophy Glioblastoma Fungal meningitis, AIDS Hydrocephalus Myasthenia gravis
74 (48) 33 (21) 23 (15) 11 (7) 13 (8) 3 2 2 1 1 1 1 1 1
AIDS = acquired immune-deficiency syndrome; ICH = intracranial hemorrhage; SAH = subarachnoidal hemorrhage.
Outcomes associated with different causes are described in Figure 2. Overall, 14 (9%) of all 154 patients were alive in good neurologic condition at follow-up 6 months after the index event, with a median hospital stay of 55 days (IQR 5 187 days). Neurologic Causes of Cardiac Arrest The resuscitation data of all patients are presented in Table 2.
Figure 1. Diagnostic procedures regarding the cause of cardiac arrest. CT = computed tomography; ICH = intracerebral hemorrhage; SAH = subarachnoidal hemorrhage.
SAH (n = 74 [48%]). Out-of-hospital cardiac arrest occurred in 68 patients, 48 (71%) of these occurred at home, 17 (25%) in public places, 2 (3%) while on transport, and 1 (1%) in a private doctor’s office. In-hospital cardiac arrest occurred in 6 patients, 3 of these at our ED, 1 each at a regular ward, the radiology department, and in a public area of the hospital. In all patients with SAH, the collapse was sudden. Cephalea before cardiac arrest was present in 18 (24%) of 74 patients; in 6 patients, cardiac arrest occurred during sexual intercourse. A CCT was performed and was diagnostic in 64 patients. The site of the ruptured aneurysm causing the SAH was the basilar artery and the middle cerebral artery each in 15, the internal carotid artery in 11, the anterior communicating artery in 6 and the vertebral artery in 2 cases. In 15 patients, the exact location of the source of bleeding was not found. All patients fulfilled the criteria for Hunt-Hess category 5, and all showed cerebral edema. Other findings were loss of gray-white matter differentiation, compression of the fourth ventricle, and effacement of basal cisterns. Herniation was found in 15 patients initially, and in another 10, beginning herniation was present. Neurosurgical intervention was performed in 15 (20%) patients, and 3 of these were alive in good neurologic condition at follow-up 6 months after the index event, with a median hospital stay of 51 days (IQR 23 to 84 days). Another 2 were alive in unfavorable condition, and 10 patients died despite emergent surgical intervention. The remaining 50 patients with CCT-verified diagnosis were not considered to benefit from a neurosurgical procedure, none of them survived. Overall, an autopsy was performed in 40 (54%) of all patients. None of the 7 patients admitted under ongoing resuscitation survived. ICH (n = 33 [21%]). Out-of-hospital cardiac arrest occurred in 23 patients, 13 (56%) were at home, 5 (22%) each were in public places and while on transport. In-hospital cardiac arrest occurred in 10 of 33 patients, 7 of these were at our ED, 2 were at the radiology department, and 1 was in a public area of the hospital. Three patients suffered cardiac arrest after receiving systemic thrombolytic therapy for acute coronary syndrome or pulmonary embolism. Another 2 patients where initially suspected of having suffered cardiac arrest due to pulmonary embolism, and a rescue thrombolysis was performed. At autopsy, neither pulmonary embolism nor any other cause of cardiac arrest except ICH was found. Two other patients had known leukemia. At autopsy or CCT, ruptured cerebral aneurysm was found in 2 patients, an angioma in 2, and an arteriovenous malformation in 1. Of all patients with ICH, 8 presented with headache, 7 were found unconscious before going into cardiac
4
P. Hubner et al.
Figure 2. Outcomes depending on the cause of cardiac arrest. CPC = cerebral performance category; ICH = intracerebral hemorrhage; ROSC = return of spontaneous circulation; SAH = subarachnoidal hemorrhage.
arrest, 3 presented with clouded awareness, 2 with seizures, 3 collapsed suddenly without prior symptoms, and 1 patient presented with nausea before collapse. In 9 patients, the cardiac arrest was not witnessed.
A CCT was performed and was diagnostic in 24 (73%) of the patients. The site of the ICH was the brainstem in 8, frontal lobe in 6, cerebellum in 5, occipital lobe and basal ganglia each in 4, temporal lobe in 2 and thalamus, lateral
Table 2. Resuscitation Data of all Patients After Cardiac Arrest Criteria Male sex n (%) Age (years), median (range) Out-of-hospital CA arrests, n (%) Witnessed CA, n (%) ECG rhythm,* n (%) PEA Asystole VF ROSC (min), median (range) Not resuscitated, n (%) Dead within 6 months, n (%) Alive (CPC 3 4), n (%) Alive (CPC 1 2),† n (%)
Total (n = 154)
SAH (n = 74)
ICH (n = 33)
Seizure (n = 23)
Stroke (n = 11)
Others (n = 13)
78 (51) 51 (17 85) 126 (82) 122 (79)
26 (35) 49 (23 78) 68 (92) 65 (88)
20 (61) 52 (25 79) 23 (70) 24 (73)
19 (83) 48 (18 82) 17 (74) 23 (100)
6 (55) 68 (53 85) 10 (91) 9 (82)
7 (54) 53 (17 74) 8 (62) 8 (62)
77 (50) 61 (40) 16 (10) 18 (0 126) 15 (10) 117 (76) 8 (5) 14 (9)
39 (53) 30 (41) 5 (7) 21 (1 126) 3 (4) 66 (89) 2 (3) 3 (4)
20 (61) 8 (24) 5 (15) 9 (0 42) 7 (21) 23 (70) 1 (3) 2 (6)
10 (43) 11 (48) 2 (9) 14 (1 40) 0 11 (48) 4 (17) 8 (35)
4 (36) 4 (36) 3 (27) 15 (7 94) 4 (36) 7 (64) 0 0
4 (31) 8 (62) 1 (8) 16 (5 32) 1 (8) 10 (77) 1 (8) 1 (8)
CA = cardiac arrest; CCT = cranial computed tomography; CPC = cerebral performance category; ECG = electrocardiogram; ICH = intracranial hemorrhage; PEA = pulseless electric activity; ROSC = return of spontaneous circulation; SAH = subarachnoidal hemorrhage; VF = ventricular fibrillation. * First documented rhythm after cardiac arrest. † Good neurologic outcome.
Neurologic Causes of Cardiac Arrest
ventricle, and fourth ventricle each in 1 case. In 1 patient, the site could not be determined. Surgical intervention was performed in 5 (15%) patients, 2 of them were alive at follow-up 6 months after the cardiac arrest with good neurologic outcomes. Another patient was alive in unfavorable condition, 2 patients died despite emergent surgical intervention. The remaining 20 patients with CCT-verified diagnosis were not considered to benefit from a neurosurgical procedure, none of them survived. Overall, an autopsy was performed in 13 (39%) of all patients, in 9 of these 13 patients in whom no CCT was performed, it was diagnostic. In those 5 patients admitted under ongoing resuscitation, no ROSC could be established at any time. Epileptic seizure (n = 23 [15%]). Out-of-hospital cardiac arrest occurred in 17 of 23 patients, 10 (59%) were at home, 6 (35%) were in a public place, and 1 (6%) was while on transport. In-hospital cardiac arrest occurred in 6 of 23 patients, 3 of these were at our ED, 2 were at a regular ward, and 1 was in a public area of the hospital. Patients with epileptic seizure suffered cardiac arrest during ongoing convulsions. Overall, a CCT was performed in 21 (91%) patients and an autopsy in 4 patients. Of all patients, 13 had SUDEP, 4 had a malignant cerebral disease, 4 had a seizure associated with alcohol or drug abuse, 1 had hydrocephalus, and in 1 it occurred after dialysis. All patients with SUDEP underwent CCT, and this showed 5 with cerebral edema, 1 with leukencephalopathy, 1 with lacunary lesion, and in 6 patients no radiologic changes could be found. In all 4 patients with a malignancy, the tumor and local edema were present. In addition, in 4 patients with alcohol or drug-associated epileptic seizure, CCT was performed in 3 and showed cerebral edema in 1 case. Of all patients with epileptic seizure, 8 survived with favorable neurologic outcomes (35%), 6 patients with SUDEP, 1 with astrocytoma, and 1 with chronic renal failure and dialysis. The median duration of the patients’ stay at the hospital was 54 days (IQR 5 187 days). Ischemic stroke (n = 11 [7%]).Out-of-hospital cardiac arrest occurred in 10 of 11 (90%) patients, 4 of these were at home, 4 were while on transport, and 1 each in a regular ward and in a public place. In-hospital cardiac arrest occurred at our ED in 1 patient. The site of the ischemic stroke was the cerebellum in 3 patients, medial (temporal) lobe in 3 patients, parietal lobe in 2 patients, and occipital lobe and complete left hemisphere in 1 patient each. In 1 patient, the site could not be determined. Of all patients with stroke, 5 patients presented with progressing dyspnea, eventually leading to respiratory failure, 3 collapsed suddenly without prior symptoms
5
and 1 patient presented with clouded awareness before collapse. One patient suffered from impaired speech and hemiparesis in the days leading up to their cardiac arrest. In 2 patients, cardiac arrest was not witnessed. Of all patients with ischemic stroke, 4 did not achieve ROSC at any time, and the remaining 7 died after a median of 2 days (IQR 1 6 days). Other neurologic diseases (n = 13 [8%]). Details are shown in Table 1. Out-of-hospital cardiac arrest occurred in 8 of 13 patients, 7 of these were at home, and 1 was in a public place. In-hospital cardiac arrest occurred in 5 patients, all at a regular ward. One patient with myasthenia gravis, who had been resuscitated, survived, and was discharged after 49 days in favorable neurologic condition. Another patient with amyotrophic lateral sclerosis (ie, Lou Gehrig’s disease), who presumably had cardiac arrest due to respiratory arrest from muscle failure, achieved ROSC, was alive 6 months after the index event, but due to the underlying motor-neuron disease was in an unfavorable neurologic condition. One patient with encephalitis associated with acquired immune-deficiency syndrome was admitted to the ED under ongoing resuscitation but did not achieve ROSC. All other patients achieved ROSC, but died within a median of 1 day (IQR 1 1.5 days). DISCUSSION Data of patients who had been treated at the ED after cardiac arrest due to neurologic etiologies showed SAH in almost half of our study cohort. Ischemic stroke, although a very common occurrence, led to sudden cardiac arrest only rarely. While almost all patients suffering from SAH or epileptic seizure achieved ROSC, the ROSC rate in patients with ICH or ischemic stroke was much lower. Survival with good neurologic outcome was found mainly in patients with seizure. Because cardiac causes of sudden cardiac death are much more common, the diagnostic pathway is more apparent. The key to diagnosing a neurologic event as cause of cardiac arrest is to keep this possibility in mind even in the absence of obvious neurologic features. Signs like sudden and severe headache before collapse may be indicative of SAH (8). The description of generalized seizure by bystanders may point to SUDEP as cause of cardiac arrest (11). If a neurologic event is suspected, or if no other obvious cause of cardiac arrest can be found, a CCT should be performed (4,5). However, if there is the possibility of an acute coronary event, CCT should not delay possible angiography. Initial ECG rhythms were pulseless electric activity and asystole in most of our patients, which are unspecific rhythms. Ventricular fibrillation as initial ECG rhythm,
6
which occurred in 16 patients, might be misleading and the cardiac arrest might be erroneously thought to be due to a cardiac cause, especially without prior knowledge of a neurologic event. We have previously reported the poor prognosis for patients with cardiac arrest due to SAH, and have not found any improvement (5). Of 74 patients in our study population, only 3 could be discharged in good neurologic condition. Mitsuma et al. also observed a high ROSC rate, but no patient survived to hospital discharge (19). Initial cardiac rhythm revealed no ventricular fibrillation. In patients with out-of-hospital cardiac arrest, SAH was found in about 6%, and in about 15% of resuscitated patients. Inamasu et al. found no survivors of 23 patients with SAH after cardiac arrest (4). Kuisma and Alaspaa found no survivors in 18 patients with intracranial processes (3). This is in stark contrast to the report of Toussaint et al., who found that 11 (3.6%) of their 307 patients with SAH suffered cardiac arrest, but 54% of these 11 patients survived (20). This can probably be explained by the short duration of cardiac arrest (mean 6.5 min) compared with our study, where the mean time to ROSC was 21 min (IQR 1 126 min) (20). We believe that the poor outcomes in our study can be ascribed mainly to the large and irreversible morphologic cerebral damage, which we found on inspection of the CCT scans and in autopsy. Broderick et al., who reported in 1994 that most deaths after SAH occur very rapidly and are due to the initial hemorrhage as well as to its size, confirm this observation (6). The mechanisms leading to cardiac arrest in patients with underlying neurologic condition are controversial. We believe that either mechanical herniation of the brainstem, due to the sudden increase of intracranial pressure, or respiratory arrest followed by hypoxic cardiac arrest, due to compression of brainstem centers, might be the main mechanisms. In 1984, Hijdra et al. described that respiratory arrest was found in 37 patients with SAH, while 2 had ventricular fibrillation (7). Nontraumatic ICH is caused primarily by spontaneous rupture of small vessels damaged by chronic hypertension or amyloid angiopathy. Epidemiologically, ICH is more than twice as common as SAH. It is more likely to result in death than ischemic cerebral infarction or SAH (21). However, there are few reports in the literature describing sudden cardiac arrest as complication or initial presentation of ICH (21,22). Inamasu et al. reported only 2 patients with ICH vs. 10 patients with SAH (8). This may be due to the comparatively slower rise of intracranial pressure than in SAH. Therefore, even in large ICH, the respiratory function usually remains intact. In our study population, ICH was the second most common cause of neurologic cardiac arrest after SAH. Phillips et al. found even more patients with ICH than
P. Hubner et al.
with SAH (2). In the beginning of the era of systemic thrombolytic therapy in acute coronary syndromes, we had some patients who developed massive ICH and sudden cardiac arrest as a complication of the cerebral bleeding. None of these patients survived. SUDEP as cause of sudden cardiac death is a well described and published disease entity (11,13 15,23). It is frequently unwitnessed, and this is consistent with many studies. Among those situations that are witnessed, however, the majority are associated with convulsions, suggesting that seizures are directly and causally related to SUDEP (12). The rate of survival with good neurologic outcomes in the patients with epileptic seizure was high. This might possibly be explained by the fact that an epileptic seizure is not characterized by acute morphologic cerebral changes. In these patients, the cardiac arrest was most likely caused by respiratory failure due to prolonged seizures. Other causes, such as intracranial tumor and alcohol or drug abuse, had unfavorable outcomes. However, we realize that the number of patients with epileptic seizure as cause for cardiac arrest is too small to draw a final conclusion about outcomes. Ischemic stroke is a rare cause of sudden cardiac arrest and there are few reports describing these patients (2,10). In our study population, during a study period of 20 years, we only found 11 patients, all but 1 suffered an out-of-hospital cardiac arrest. In all of these patients, structural cerebral damage, as described in CCTor autopsy, was exceptionally large and outcomes were dismal, as no patient was alive at 6 months. Patients with cardiac arrest caused by stroke did not have typical symptoms (eg, hemiparesis) before they collapsed. Collapse was sudden in all of these cases. Most of these patients could be diagnosed in autopsy. It is interesting to observe that ventricular fibrillation was the first recorded ECG rhythm in 3 of these patients. So¨ro¨s and Hachinski suggest that sudden death in these patients may be ascribed to a complex interaction between cardiovascular and neurologic causes, with a resulting autonomic imbalance (9). Silver et al. describe two mechanisms for sudden cardiac arrest, which may be either due to life-threatening dysrhythmias or acute transtentorial herniation (24). Limitations Data for this study were analyzed retrospectively, which can be considered a limitation, however, it was collected prospectively. CONCLUSIONS SAH was the leading cause of cardiac arrest and was found in almost half of our patients. Most of the patients
Neurologic Causes of Cardiac Arrest
with SAH, ICH, or ischemic stroke had very poor prognoses. Although rare, neurologic causes should be considered in patients with cardiac arrest. REFERENCES 1. Skrifvars MB, Parr MJ. Incidence, predisposing factors, management and survival following cardiac arrest due to subarachnoid haemorrhage: a review of the literature. Scand J Trauma Resusc Emerg Med 2012;20:75. 2. Phillips LH, Whisnant JP, Reagan TJ. Sudden death from stroke. Stroke 1977;8:392–5. 3. Kuisma M, Alaspaa A. Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997;18:1122–8. 4. Inamasu J, Miyatake S, Tomioka H, et al. Subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest: a prospective computed tomography study. Resuscitation 2009;80:977–80. 5. Kurkciyan I, Meron G, Sterz F, et al. Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest. Resuscitation 2001;51:27–32. 6. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 1994;25:1342–7. 7. Hijdra A, Vermeulen M, van Gijn J, van Crevel H. Respiratory arrest in subarachnoid hemorrhage. Neurology 1984;34:1501–3. 8. Inamasu J, Miyatake S, Tomioka H, et al. Headache, cardiac arrest, and intracranial hemorrhage. J Headache Pain 2009;10:357–60. 9. So¨ro¨s P, Hachinski V. Cardiovascular and neurological causes of sudden death after ischaemic stroke. Lancet Neurol 2012;11:179–88. 10. Tokgo¨zoglu SL, Batur MK, Topcuoglu MA, Saribas O, Kes S, Oto A. Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke 1999;30:1307–11. 11. Nashef L, Garner S, Sander JW, Fish DR, Shorvon SD. Circumstances of death in sudden death in epilepsy: interviews of bereaved relatives. J Neurol Neurosurg Psychiatry 1998;64:349–52.
7 12. Lhatoo SD, Sander JW. Cause-specific mortality in epilepsy. Epilepsia 2005;46:36–9. 13. Johnston A, Smith P. Sudden unexpected death in epilepsy. Expert Rev Neurother 2007;7:1751–61. 14. Langan Y, Nashef L, Sander JW. Sudden unexpected death in epilepsy: a series of witnessed deaths. J Neurol Neurosurg Psychiatry 2000;68:211–3. 15. Dasheiff RM. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death. J Clin Neurophysiol 1991;8: 216–22. 16. Tavee J, Morris H 3rd. Severe postictal laryngospasm as a potential mechanism for sudden unexpected death in epilepsy: a near-miss in an EMU. Epilepsia 2008;49:2113–7. 17. Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997;38(11 Suppl):S6–8. 18. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med 2001;344:1450–60. 19. Mitsuma W, Ito M, Kodama M, et al. Clinical and cardiac features of patients with subarachnoid haemorrhage presenting with out-ofhospital cardiac arrest. Resuscitation 2011;82:1294–7. 20. Toussaint LG 3rd, Friedman JA, Wijdicks EF, et al. Survival of cardiac arrest after aneurysmal subarachnoid hemorrhage. Neurosurgery 2005;57:25–31. 21. Broderick JP, Adams HP Jr, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30:905–15. 22. Broderick JP, Brott T, Tomsick T, Miller R, Huster G. Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 1993;78:188–91. 23. Langan Y. Sudden unexpected death in epilepsy (SUDEP): risk factors and case control studies. Seizure 2000;9:179–83. 24. Silver FL, Norris JW, Lewis AJ, Hachinski VC. Early mortality following stroke: a prospective review. Stroke 1984;15:492–6.
8
P. Hubner et al.
ARTICLE SUMMARY 1. Why is this topic important? Since they are rare, neurologic causes for cardiac arrest are often not, or not soon enough, considered in the management of emergencies. 2. What does this study attempt to show? We review the epidemiology of patients with neurologic emergencies. 3. What are the key findings? Patients with neurologic emergencies usually have poor outcomes. Outcomes vary between patients with large structural damage and patients with epileptic seizure as reason for cardiac arrest. 4. How is patient care impacted? Consideration of neurologic causes of cardiac arrest may lead to faster recognition and diagnosis.
