A multicenter, randomized, doubleblind, placebo-controlled trial of amantadine to stimulate awakening in comatose patients resuscitated from cardiac arrest.

OBJECTIVE: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. METHODS: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. RESULTS: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. CONCLUSION: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Duration of cardiopulmonary resuscitation and phenotype of post-cardiac arrest brain injury.

BACKGROUND: Patients resuscitated from cardiac arrest have variable severity of primary hypoxic ischemic brain injury (HIBI). Signatures of primary HIBI on brain imaging and electroencephalography (EEG) include diffuse cerebral edema and burst suppression with identical bursts (BSIB). We hypothesize distinct phenotypes of primary HIBI are associated with increasing cardiopulmonary resuscitation (CPR) duration. METHODS: We identified from our prospective registry of both in-and out-of-hospital CA patients treated between January 2010 to January 2020 for this cohort study. We abstracted CPR duration, neurological examination, initial brain computed tomography gray to white ratio (GWR), and initial EEG pattern. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema (non-malignant coma); BSIB; and cerebral edema (GWR ≤ 1.20). BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We generated predicted probabilities of brain injury phenotype using localized regression. RESULTS: We included 2,440 patients, of whom 545 (23%) were awake, 1,065 (44%) had non-malignant coma, 548 (23%) had BSIB and 438 (18%) had cerebral edema. Only 92 (4%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-13] minutes; non-malignant coma 15 [8-25] minutes; BSIB 21 [13-31] minutes; cerebral edema 32 [22-46] minutes. Predicted probability of phenotype changes over time. CONCLUSIONS: Brain injury phenotype is related to CPR duration, which is a surrogate for severity of HIBI. The sequence of most likely primary HIBI phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema.

Top Ten Tips Palliative Care Clinicians Should Know About Disorders of Consciousness: A Focus on Traumatic and Anoxic Brain Injury.

Palliative care (PC) teams commonly encounter patients with disorders of consciousness (DOC) following anoxic or traumatic brain injury (TBI). Primary teams may consult PC to help surrogates in making treatment choices for these patients. PC clinicians must understand the complexity of predicting neurologic outcomes, address clinical nihilism, and appropriately guide surrogates in making decisions that are concordant with patients' goals. The purpose of this article was to provide PC providers with a better understanding of caring for patients with DOC, specifically following anoxic or TBI. Many of the tips acknowledge the uncertainty of DOC and provide strategies to help tackle this dilemma.

Neurostimulant use is associated with improved survival in comatose patients after cardiac arrest regardless of electroencephalographic substrate.

AIM: Identify EEG patterns that predict or preclude favorable response in comatose post-arrest patients receiving neurostimulants. METHODS: We examined a retrospective cohort of consecutive electroencephalography (EEG)-monitored comatose post-arrest patients. We classified the last day of EEG recording before neurostimulant administration based on continuity (continuous/discontinuous), reactivity (yes/no) and malignant patterns (periodic discharges, suppression burst, myoclonic status epilepticus or seizures; yes/no). In subjects who did not receive neurostimulants, we examined the last 24h of available recording. For our primary analysis, we used logistic regression to identify EEG predictors of favorable response to treatment (awakening). RESULTS: In 585 subjects, mean (SD) age was 57 (17) years and 227 (39%) were female. Forty-seven patients (8%) received a neurostimulant. Neurostimulant administration independently predicted improved survival to hospital discharge in the overall cohort (adjusted odds ratio (aOR) 4.00, 95% CI 1.68-9.52) although functionally favorable survival did not differ. No EEG characteristic predicted favorable response to neurostimulants. In each subgroup of unfavorable EEG characteristics, neurostimulants were associated with increased survival to hospital discharge (discontinuous background: 44% vs 7%, P=0.004; non-reactive background: 56% vs 6%, P<0.001; malignant patterns: 63% vs 5%, P<0.001). CONCLUSION: EEG patterns described as ominous after cardiac arrest did not preclude survival or awakening after neurostimulant administration. These data are limited by their observational nature and potential for selection bias, but suggest that EEG patterns alone should not affect consideration of neurostimulant use.