Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest

Hypothermia Clinical Trial

— RELAX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01719770
• Other study ID #: RELAX1
• Status: Completed
• Phase: Phase 3
• First received: July 6, 2011
• Last updated: April 30, 2015
• Start date: November 2010
• Est. completion date: April 2015

Study information

• Verified date: April 2015
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2015
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cardiac Arrest With Successful Resuscitation
• Heart Arrest
• Hypothermia
• Muscle Hypotonia
• Paralysis
• Skeletal Muscle Relaxant Overdose

Intervention

Drug:
• rocuronium
continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)

Other:
• placebo
continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Emergency Medicine	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of shivering episodes	Shivering episodes will be detected according to the Shivering Assessment Scale	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	No
Secondary	Elapsed time to target temperature		Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation	No
Secondary	Dissipated energy to reach the target temperature		Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation	No
Secondary	Changes in basal metabolism due to shivering or elevated stress levels		during the first 72 hours after cardiac arrest	No
Secondary	Depth of relaxation	via train of four measurement	during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling	Yes
Secondary	Changes in serum levels of midazolam, fentanyl and rocuronium		within the first 48 hours of treatment	Yes
Secondary	Number of necessary boli of rocuronium	In case of a shivering episode, a bolus of rocuronium will be administered (0,25mg/kg)	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	Yes