Why coma after cardiac arrest

Regional that is, the occipital and temporal lobes , spatial that is, widespread and diffuse lesions or temporal that is, absence of resolution in FLAIR abnormalities MRI findings may provide better insight into the degree and mechanisms of hypoxic—ischemic brain injury, and hence better predict outcome in comatose survivors, including those treated with TH [ 73 - 75 ].

Bilateral hippocampal hyperintense signals on DWI and FLAIR also appear to be specific imaging indicators of poor prognosis in patients who suffer global hypoxic—ischemic injury [ 76 ]. However, one should emphasize that most studies of neuroimaging for CA patients are limited by their retrospective nature, heterogeneous populations for example, not all patients were comatose , and the self-fulfilling prophecy of early withdrawal of life-sustaining therapy that is, the falsely pessimistic interpretation of prognostic variables concurrently used to forgo life support [ 77 ].

Additionally, the prediction of good outcome remains even more uncertain than that of poor outcome, and both CT and MRI need to be further evaluated in well-conducted prospective studies in the CA population. Previous studies have suggested some benefits of a multimodal approach. Combination of the neurological examination, EEG findings, SSEPs and two serum biomarkers improved prognostic value with no false positives for death [ 79 ].

Importantly, the precise multimodal approach will vary among centers depending on the availability of electrophysiological monitoring, technical expertise and laboratory facilities, and the use of several prognostic tools does increase costs. Also, self-fulfilling prophecy should be avoided and considerable efforts have to be addressed to combine the different variables to accurately predict neurological outcome.

Finally, decisions to withdraw life support should also require good education and training, should require good communication between the ICU team, and should be based on the ethical principles of autonomy, beneficence, nonmaleficence and justice. Taking into account all of the previous referenced studies, we thus propose a combination of several prognostic tools to improve the accuracy of predicting good and poor outcomes after HIE and TH Figure 5. After initial neurological examination at hospital admission and before sedation and muscular paralysis to induce TH, whenever possible , continuous or repeated standard EEG monitoring should be started already during TH to identify the presence of early seizures, of malignant EEG patterns and of EEG reactivity.

Evidence of reactive EEG or continuous background activity indicates a high probability of good neurological recovery, and these patients usually wake up rapidly after rewarming and discontinuation of sedation. In contrast, malignant patterns — including burst suppression, generalized periodic epileptiform discharges and cerebral inactivity that is, a flat EEG or unreactive background — are associated with poor outcome.

Immediate initiation and prolonged therapy should be considered for post-anoxic status epilepticus, especially if it occurs in the rewarming phase in the absence of other signs of extensive brain injury; in contrast, early nonconvulsive seizures are often associated with a poor outcome, especially if associated with an unreactive EEG and nonresponse to anti-epileptic treatment.

The effect of treatment on this kind of seizures is uncertain. Multimodal prognostication of coma after cardiac arrest and therapeutic hypothermia.

Summary of the suggested timing after cardiac arrest of all available tools that are used to predict poor outcome or neurological recovery from coma. This algorithm suggests that poor prognosis or neurological recovery should be considered when specific findings are present but this does not necessarily mean that withdrawal of care should be initiated, because this approach has not been validated.

Dashed lines, lack of strong evidence to support the suggestion. High biomarker levels did not relate to a specific cutoff value because of several limitations affecting their measurements and accuracy see text. Importantly, no EEG finding should be used alone to predict poor outcome, and these negative EEG patterns need to be correlated with neurological examination at 48 to 72 hours after the end of TH, when sedation has been withheld for at least 24 hours. If patients have generalized persistent status myoclonus during the first 24 hours, poor outcome can be predicted if it is associated with bilateral absence of N20 after rewarming.

If SSEPs are not available, a malignant EEG pattern increases the likelihood of poor prognosis but further diagnostic work-up including brain imaging and biomarkers should be considered.

However, prognostic accuracy is increased if these signs are associated with an unreactive EEG or malignant patterns. In other comatose patients, bilateral absence of N20 potentials 48 to 72 hours after CA indicates irreversible brain damage.

If these findings that is, malignant EEG, poor clinical findings and bilateral absence of N20 potentials are absent, prognostication becomes more difficult.

Because these methods have some limitations, they should not be used to make final decisions on treatment levels. Rather, a prolonged observation period 1 to 2 weeks should be considered to allow for delayed neurological recovery.

Considering the limits of the neurological examination, certain electrophysiological tests have been proposed. A simplified EEG method with a limited number of EEG electrodes, in combination with amplitude-integrated EEG, could be used in comatose survivors of CA, and may provide relevant and rapid bedside information that could be evaluated also by non-neurologists [ 35 , 37 ]. Functional deficiency of the auditory—frontal cortex network of auditory discrimination is a common finding shared by different neurological disorders with cognitive impairment [ 80 ].

This deficiency can be measured with the so-called mismatch negativity, an EEG finding that is elicited during a specific auditory stimulus using sounds that differ in pitch, duration or loudness. Mismatch negativity has been shown to better predict awakening than SSEPs in patients remaining comatose several days after CA [ 81 ].

In a study by Tzovara and colleagues, all nonsurvivors showed deterioration in mismatch negativity between two measurements, whereas all those patients who had an early improvement in auditory discrimination regained consciousness [ 82 ].

Finally, long latency evoked potentials, such as P70 and P, have been correlated with neurological status in CA survivors after 3 and 6 months; however, these potentials are difficult to perform in the early phase and do not provide additional predictive value to the available electrophysiological tests [ 9 , 83 ].

Analysis of the time course of biomarkers could also improve their predictive value. Preliminary studies have shown that other blood biomarkers, including glial fibrillary acidic protein, neurofilaments or tau protein, may represent alternative biomarkers [ 84 - 86 ].

Also, because the post-CA syndrome activates a systemic inflammatory response syndrome similar to that of sepsis [ 2 ], C-reactive protein, copeptin and especially procalcitonin could be considered adjunctive tools to assess prognosis [ 87 - 89 ]. The combination of such molecules with biomarkers of heart injury, such as cardiac troponins and brain natriuretic peptide, along with novel biomarkers, including circulating cell-free DNA and micro-RNAs, could create a multipanel of biomarkers to incorporate into the prognostication process of CA patients [ 58 ].

Advanced MRI techniques could provide interesting information, although their usefulness is less clear than conventional neuroimaging techniques. Some of the newer techniques include diffusion tensor imaging, fractional anisotropy, functional MRI including resting-state and task-specific functional MRI using blood oxygen level-dependent contrast, and high angular resolution diffusion imaging tractography.

These imaging techniques can evaluate brain oxygenation, regional activation in response to external stimuli, neuronal structure and axonal myelination, and all these findings may give new insight into the investigation of post-anoxic brain injury. Accurate prognostication of comatose patients suffering from HIE and treated with TH can be obtained only 72 to 96 hours after CA and requires a multimodal approach.

The neurological examination remains the gold standard; however, motor responses may be delayed up to 5 days in patients undergoing TH and neurological examination is not sufficient to accurately predict prognosis.

The addition of EEG could improve prognostic accuracy, in particular the presence of an early within 24 hours from CA reactive EEG pattern as a finding suggestive of good prognosis, whereas a nonreactive or burst-suppressed EEG pattern is associated with a poor outcome. Bilateral absence of N20 at 48 to 72 hours is almost invariably associated with a poor prognosis. Findings from MRI investigations could potentially help to identify patients with extensive hypoxic—ischemic brain injury.

Additional tools are under investigation to further improve the quality of prognosis assessment in this population. The remaining authors declare that they have no competing interests.

FST planned and drafted the manuscript. All the authors contributed to literature research, data interpretation and critical revision of the manuscript. All authors read and approved the final manuscript. The authors would like to dedicate this article to Dr CA Wijman whose research contributed hugely to the assessment of prognosis of comatose patients after cardiac arrest. They would like to express gratitude to designer Vincenzo Ciffo vinciffo alice.

National Center for Biotechnology Information , U. Journal List Crit Care v. Crit Care. Published online Jan Author information Copyright and License information Disclaimer. Corresponding author. Fabio Silvio Taccone: eb. This article has been cited by other articles in PMC. Abstract The prognosis of patients who are admitted in a comatose state following successful resuscitation after cardiac arrest remains uncertain.

Review Clinical scenario A year old woman collapsed on the street and underwent bystander cardiopulmonary resuscitation. How to predict neurological outcomes in hypoxic—ischemic encephalopathy Prognostication in hypoxic—ischemic encephalopathy HIE is a particular challenge because decisions to withdraw life-sustaining therapies largely depend on predicted prognosis [ 4 ].

Open in a separate window. Figure 1. Clinical examination Clinical manifestations after CA depend on the susceptibility of different brain regions to anoxia for example, the cerebral cortex, thalamus and cerebellum are more susceptible than subcortical areas and the brainstem.

Figure 2. Figure 3. Biomarkers Biomarkers are quantifiable biological substances, usually peptides, which can be easily measured in peripheral blood. Imaging Current guidelines state that available data are insufficient to support the use of computed tomography CT imaging in neuro-prognostication of comatose CA survivors [ 61 ].

Figure 4. Multimodal prognostic algorithm Previous studies have suggested some benefits of a multimodal approach. Figure 5. Perspectives and areas for future clinical investigation Considering the limits of the neurological examination, certain electrophysiological tests have been proposed. Conclusions Accurate prognostication of comatose patients suffering from HIE and treated with TH can be obtained only 72 to 96 hours after CA and requires a multimodal approach.

Acknowledgements The authors would like to dedicate this article to Dr CA Wijman whose research contributed hugely to the assessment of prognosis of comatose patients after cardiac arrest. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med. Post cardiac arrest syndrome: a review of therapeutic strategies. Predicting neurological outcome after cardiac arrest. Curr Opin Crit Care. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest.

Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation an evidence-based review : report of the Quality Standards Subcommittee of the American Academy of Neurology. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Does therapeutic hypothermia affect time to awakening in cardiac arrest survivors? Serum neuron-specific enolase and SB protein in cardiac arrest patients treated with hypothermia.

Cognitive and neurophysiological outcome of cardiac arrest survivors treated with therapeutic hypothermia. Prognosis in nontraumatic coma. Ann Intern Med. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P enzyme system. Crit Care Med. Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia.

Neurocrit Care. But when this occurs, the sudden rush of blood to areas of damaged tissues can cause injury. It may seem counterintuitive because restarting the flow of blood is the critical goal. But the lack of oxygen and nutrients during the time of cardiac arrest means that when blood flow is restored, it places oxidative stress on the brain as toxins flood already-damaged tissues.

The inflammation and nerve injury this causes can trigger a cascade of symptoms, including:. The severity of these symptoms is closely linked to how long the person went without oxygen. Other factors include any pre-existing conditions affecting the brain and cardiovascular system. When the heart stops, so does the flow of blood that's pumped throughout the body.

Brain damage will begin in a matter of minutes because of the lack of oxygen carried by the blood cells. Cardiac arrest is usually fatal outside of a hospital setting, but even those who are revived may have severe and lasting impacts.

It's important to act quickly to restart the heart and limit these catastrophic effects. All brain activity is thought to cease by around three to four minutes from the moment the heart stops. Thus, every second counts if someone suddenly collapses in front of you and stops breathing.

Rather than wasting time putting the victim in the car and rushing to the hospital, call and start hands-only CPR immediately.

You may buy enough time until the paramedics arrive to restart the heart. Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life.

Heart disease and stroke statistics update: a report from the American Heart Association. Association of neighborhood characteristics with incidence of out-of-hospital cardiac arrest and rates of bystander-initiated CPR: implications for community-based education intervention. Wellbourn C, Efstathiou N. How does the length of cardiopulmonary resuscitation affect brain damage in patients surviving cardiac arrest? A systematic review.

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We and our partners process data to: Actively scan device characteristics for identification. I Accept Show Purposes. Was this page helpful? Thanks for your feedback! Sign Up. What are your concerns? Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Corresponding author. Donald W Marion: moc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

You may not use this work for commercial purposes. This article has been cited by other articles in PMC. Introduction and context Cardiac arrest results in the cessation of spontaneous circulation, which causes hypoxic-ischemic encephalopathy, the severity of which is primarily related to the time from arrest to restoration of spontaneous circulation.

Recent advances Prognosis Clinical risk factors associated with poor outcome after cardiac arrest continue to be extensively studied in the search for one or a combination of features with high enough specificity and sensitivity to be clinically reliable. Table 1.

Open in a separate window. Molecular biomarkers Cardiac arrest and loss of spontaneous circulation causes global cerebral ischemia. Imaging biomarkers The relationship between the clinical manifestations of hypoxic-ischemic encephalopathy following cardiac arrest, and anatomic brain injury, is not entirely clear. Treatment of comatose cardiac arrest patients Therapeutic hypothermia is now considered standard of care for patients with OHCA and ventricular fibrillation as the initial rhythm, though clinical trials continue to be conducted to better define the benefits of the therapy, treatment parameters, and duration of effect.

Implications for clinical practice During the past years several studies have better defined the clinical characteristics, and molecular and electrophysiologic biomarkers that can be reliably used to predict poor long-term outcomes for those who survive OHCA.

Notes Competing interests The author declares that he has no competing interests. References 1. Khot S, Tirschwell DL. Long-term neurological complications after hypoxic-ischemic encephalopathy. Semin Neurol.

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