Neurologic Prognosis after Cardiac Arrest REPLY

Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
New England Journal of Medicine (Impact Factor: 55.87). 09/2009; 361(6):605-11. DOI: 10.1056/NEJMcp0903466
Source: PubMed


A 55-year-old man collapses while jogging through the park. A bystander finds him unconscious and without a pulse and initiates cardiopulmonary resuscitation (CPR) while an ambulance is summoned. On arrival in the emergency room, the patient is in ventricular fibrillation; the partial pressure of oxygen in arterial blood is 200 mm Hg, the pH is 7.25, and the bicarbonate level is 18 mmol per liter. Spontaneous circulation is reestablished, but he remains comatose with absent pupillary reflexes. He is then treated with hypothermia, achieving a core temperature of 34 degrees C in 4 hours, which is maintained for 24 hours, after which he remains unconscious. What would you advise regarding his neurologic prognosis?

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    • "Yet the outcome from global ischemia is often diffuse damage to the higher brain with sparing of the hypothalamus and brainstem. As a result, over several weeks many afflicted patients transition from coma to a persistent vegetative state [3]–[5], [12], [13], [47]. Neocortex, striatum, hippocampus and cerebellar cortex are particularly vulnerable to ischemia [17], [48]–[51]. "
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    ABSTRACT: Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a ‘persistent vegetative state’ where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD) causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by ‘higher’ hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT) imaging in response to 10 minutes of oxygen/glucose deprivation (OGD) revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1–10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival of lower brain regions that maintain vital functions will support the persistent vegetative state.
    PLoS ONE 05/2014; 9(5):e96585. DOI:10.1371/journal.pone.0096585 · 3.23 Impact Factor
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    • "There is a well recognized but poorly understood caudal-to-rostral increase in the brain`s vulnerability to neuronal injury caused by metabolic stress [1][2][3] [4]. Global brain ischemia caused by heart attack or near-drowning can leave a functional brainstem while `higher` regions are severely compromised [4], leading to the persistent vegetative state (PVS). Maintained brainstem function with minimal higher brain activity in PVS patients is confirmed by case studies of global ischemia using MR imaging [5][6][7] as well as numerous studies measuring regional metabolism [8]. "
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    ABSTRACT: Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na(+)/K(+) pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K(+)]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.
    PLoS ONE 11/2013; 8(11):e79589. DOI:10.1371/journal.pone.0079589 · 3.23 Impact Factor
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    • "Therapeutic hypothermia (TH) improves outcome in comatose survivors of cardiac arrest (CA) [1-3]. TH also alters the predictive value of neurologic prognostication in patients with postanoxic coma [4]. We and others recently demonstrated that, compared with previous studies performed before the introduction of TH [5], neurologic examination performed at 72 hours may be unreliable to predict outcome after CA, and that standard EEG may significantly improve prognostication at this time [6,7]. "
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    ABSTRACT: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.
    Critical care (London, England) 09/2010; 14(5):R173. DOI:10.1186/cc9276 · 4.48 Impact Factor
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