Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest

Condition(s) targeted: Cardiac Arrest With Successful Resuscitation; Hypothermia; Skeletal Muscle Relaxant Overdose

Intervention: rocuronium (Drug); placebo (Other)

Phase: Phase 3

Status: Completed

Sponsored by: Medical University of Vienna

Official(s) and/or principal investigator(s):
Heidrun Losert, MD, Principal Investigator, Affiliation: Medical University Vienna, Department of Emergency Medicine

Mild hypothermia improves neurological outcome after cardiac arrest. Neuromuscular blockers are in use, together with analgesia and sedation, during the cooling process in many centers to prevent shivering. Since neuromuscular blockers are accused to be associated with various side effects causing serious harm and/or leading to prolong ICU stay. So economical use seems to be reasonable. Furthermore, the use of neuromuscular blockers may mask epileptic activity. Therefore, post hypoxic seizures might remain undetected. Aim of this study is to investigate if a continuous application of neuromuscular blockers is necessary to prevent shivering and thereby avoid the counter regulation to achieve the target temperature as soon as possible in mild hypothermic therapy after cardiac arrest. A single center (university hospital) study. Randomized, double blinded, double dummy study design. Eligible are all adult patients after successful resuscitation due to cardiac arrest of presumed cardiac origin. All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed cardiopulmonary origin will be included. Patients <18 years, cardiac arrest >6 hours before admittance at the hospital, patients with known or clinically apparent pregnancy, patients who reach our hospital with a body temperature below 35°C, patients with known allergic reactions against rocuronium, patients with a history of myasthenia gravis, patients with obvious intoxication, wards of the state/prisoners and patients with known epileptic disease will be excluded. Primary outcome: Shivering episodes will be scored with the Shivering Assessment Scale. Secondary outcome: Total doses of rocuronium, time to target core temperature of 33°C, dissipated energy and total energy needed during the cooling period will be compared between the two groups. Changes in basal metabolism and depth of relaxation will be ascertained. Furthermore, serum levels of midazolam, fentanyl, rocuronium and stress hormones will be measured. Train-of-four will be performed to assess the depth of relaxation. Sedation will be monitored via bispectral index; measurement of metabolic activity will be evaluated using indirect calorimetry. Additionally, EEG will be performed to detect epileptiform activities. Blood will be drawn to measure levels of midazolam, fentanyl and rocuronium.

Official title: Requirement of Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest - a Pilot Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Number of shivering episodes

Secondary outcome:

Elapsed time to target temperature

Dissipated energy to reach the target temperature

Changes in basal metabolism due to shivering or elevated stress levels

Depth of relaxation

Changes in serum levels of midazolam, fentanyl and rocuronium

Number of necessary boli of rocuronium

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- all patients receiving mild therapeutic hypothermia after cardiac arrest

- cardiac arrest due to cardiopulmonary origin

Exclusion Criteria:

- patients younger than 18 years

- traumatic cardiac arrest

- cardiac arrest due to exsanguination, strangulation, smoke inhalation, drug overdose,

electrocution, hanging or drowning

- known or clinically apparent pregnancy

- no treatment with mild therapeutic hypothermia because of an AND order

- terminal illness

- a body core temperature below 35°C at hospital admission

- known allergic reaction against rocuronium

- history of myasthenia gravis

- obvious intoxication

- ward of the state or prisoner

- known epileptic disease

- cardiac arrest >6 hours prior to hospital admission

Medical University of Vienna, Department of Emergency Medicine, Vienna 1190, Austria

Starting date: November 2010
Last updated: April 30, 2015