Clinical trial NCT01719770: Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest
Official title: Requirement of Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Arrest With Successful Resuscitation
Hypothermia
Skeletal Muscle Relaxant Overdose
Keywords: cardiac arrest
therapeutic hypothermia
skeletal muscle paralysis
shivering
serum drug levels
basal metabolism
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2012-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Number of shivering episodes
timeFrame: during cooling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours
Secondary outcomes:
measure: Elapsed time to target temperature
timeFrame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation
measure: Dissipated energy to reach the target temperature
timeFrame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation
measure: Changes in basal metabolism due to shivering or elevated stress levels
timeFrame: during the first 72 hours after cardiac arrest
measure: Depth of relaxation
timeFrame: during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling
measure: Changes in serum levels of midazolam, fentanyl and rocuronium
timeFrame: within the first 48 hours of treatment
measure: Number of necessary boli of rocuronium
timeFrame: during colling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Emergency Medicine
Study officials:
affiliation: Medical University Vienna, Department of Emergency Medicine
name: Heidrun Losert, MD
role: PRINCIPAL_INVESTIGATOR
References: