Methylphenidate and amantadine to stimulate reawakening in comatose patients resuscitated from cardiac arrest

Abstract

Background: Despite critical-care packages including therapeutic hypothermia (TH), neurologic injury is common after cardiac arrest (CA) resuscitation. Methylphenidate and amantadine have treated coma in traumatically-brain-injured patients with mixed success, but have not been explored in post-arrest patients.

Objective: Compare the outcome of comatose post-arrest patients treated with neurostimulants to a matched cohort.

Methods: Retrospective cohort study from 6/2008 to 12/2011 in a tertiary university hospital. We included adult patients treated with methylphenidate or amantadine after resuscitation from in-hospital or out-of-hospital CA (OHCA) of any rhythm, excluding patients with traumatic/surgical etiology of arrest, terminal re-arrest within 6h, or withdrawal of care by family within 6h. Primary outcome was following commands; secondary outcomes included survival to hospital discharge, cerebral performance category (CPC), and modified Rankin scale (mRS). We compared characteristics and outcomes to a control cohort matched on TH and 72 h FOUR score ± 1.

Results: Of 588 patients, 8 received methylphenidate, 6 received amantadine, and 2 both. Most were female suffering OHCA with median age 61 years. All received TH and a multi-modal neurological evaluation. Initial exam revealed median GCS 6 and FOUR 7, which was unchanged at 72 h. Six patients (38%) followed commands prior to discharge at median 2.5 days (range: 1-18 days) after treatment. Patients receiving neurostimulants trended toward improved rate of following commands, survival to hospital discharge, and distribution of CPC and mRS scores.

Conclusions: Neurostimulants may be considered to stimulate wakefulness in selected post-cardiac arrest patients, but a prospective trial is needed to evaluate this therapy.