Neuromuscular Blockade for Post-Cardiac Arrest Care

Out-of-hospital cardiac arrest (OHCA) occurs in more than 300,000 patients in the United
States each year with an estimated mortality of greater than 90%. Unfortunately, we currently
have little to offer in terms of treatment other than supportive care for the post-cardiac
arrest patient. Neuromuscular blockade (NMB) is sometimes utilized in post-arrest patients
particularly for the prevention of shivering. However, usage of NMB remains controversial and
current American Heart Association recommendations are to minimize utilization. Recent
prospective randomized trials in patients with acute respiratory distress syndrome suggest a
mortality benefit from NMB and an excellent safety profile. Furthermore, observational trials
in both sepsis and post-cardiac arrest show that the use of NMB is associated with improved
survival. Given this, we hypothesize that continuous NMB will be beneficial in post-arrest
patients. In order to test this hypothesis, we propose a multi-center, randomized,
open-label, phase II trial in post-CA patients comparing sustained NMB administration for 24
hours to standard of care after ROSC. We will enroll adult, comatose OHCA patients with
return of spontaneous circulation and will utilize an already existing clinical trials
network for the completion of the study. Patients will be randomized to receive either
rocuronium for 24 hours or to receive placebo with usual care. Previous data from our group
has suggested that lactate levels in the post-arrest patient are a good surrogate marker for
mortality. We have therefore chosen to utilize lactate levels at 24 hours as the primary
endpoint for the current trial. Secondarily we will evaluate clinical endpoints including
length of stay, in-hospital mortality, and good neurological outcome. We will perform at
sub-study of inflammatory markers and oxygen consumption.

Inclusion Criteria:

- Adult (≥ 18 years)

- Cardiac arrest with sustained return of spontaneous circulation (ROSC)

- Comatose (i.e., not following commands) following ROSC

- Undergoing targeted temperature management

- Time of enrollment ≤ 6 hours from initiation of targeted temperature management

- Serum Lactate ≥2

Exclusion Criteria:

- Pre-existing dementia, severe brain injury, or dependence on others for activities of
daily living (i.e. a modified Rankin scale score of 4 or higher)

- Traumatic etiology of the cardiac arrest

- Protected population (pregnant, prisoner)