Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest (RELAX)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Cardiac Arrest With Successful Resuscitation Hypothermia Skeletal Muscle Relaxant Overdose |
Drug: rocuronium Other: placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Requirement of Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest - a Pilot Study |
- Number of shivering episodes [ Time Frame: 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 ] [ Designated as safety issue: No ]Shivering episodes will be detected according to the Shivering Assessment Scale
- Elapsed time to target temperature [ Time Frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation ] [ Designated as safety issue: No ]
- Dissipated energy to reach the target temperature [ Time Frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation ] [ Designated as safety issue: No ]
- Changes in basal metabolism due to shivering or elevated stress levels [ Time Frame: during the first 72 hours after cardiac arrest ] [ Designated as safety issue: No ]
- Depth of relaxation [ Time Frame: during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling ] [ Designated as safety issue: Yes ]via train of four measurement
- Changes in serum levels of midazolam, fentanyl and rocuronium [ Time Frame: within the first 48 hours of treatment ] [ Designated as safety issue: Yes ]
- Number of necessary boli of rocuronium [ Time Frame: 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 ] [ Designated as safety issue: Yes ]In case of a shivering episode, a bolus of rocuronium will be administered (0,25mg/kg)
| Estimated Enrollment: | 60 |
| Study Start Date: | November 2010 |
| Estimated Study Completion Date: | July 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Rocuronium
Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia
|
Drug: rocuronium
continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)
Other Name: Esmeron
|
|
Placebo Comparator: Placebo
Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded)
|
Other: placebo
continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)
Other Name: sodium-chloride
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Heidrun Losert, MD | 00431404001964 | heidrun.losert@meduniwien.ac.at |
| Contact: Mathias Stöckl, MD | 00431404001964 | mathias.stoeckl@meduniwien.ac.at |
| Austria | |
| Medical University of Vienna, Department of Emergency Medicine | Recruiting |
| Vienna, Austria, 1190 | |
| Contact: Heidrun Losert, MD 00431404001964 heidrun.losert@meduniwien.ac.at | |
| Contact: Mathias Stöckl, MD 00431404001964 mathias.stoeckl@meduniwien.ac.at | |
| Principal Investigator: | Heidrun Losert, MD | Medical University Vienna, Department of Emergency Medicine |
More Information
No publications provided
| Responsible Party: | Heidrun Losert, Priv. Doz. Dr. Heidrun Losert, Medical University of Vienna |
| ClinicalTrials.gov Identifier: | NCT01719770 History of Changes |
| Other Study ID Numbers: | RELAX1 |
| Study First Received: | July 6, 2011 |
| Last Updated: | October 30, 2012 |
| Health Authority: | Austria: Ethikkommission |
Keywords provided by Medical University of Vienna:
|
cardiac arrest therapeutic hypothermia skeletal muscle paralysis |
shivering serum drug levels basal metabolism |
Additional relevant MeSH terms:
|
Hypothermia Heart Arrest Muscle Hypotonia Overdose Paralysis Heart Diseases Cardiovascular Diseases Body Temperature Changes Signs and Symptoms Neuromuscular Manifestations Neurologic Manifestations |
Nervous System Diseases Poisoning Substance-Related Disorders Rocuronium Neuromuscular Nondepolarizing Agents Neuromuscular Blocking Agents Neuromuscular Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013