Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest

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

Conditions
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Hypothermia, Cardiac Arrest With Successful Resuscitation, Skeletal Muscle Relaxant Overdose

Intervention / Treatment
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* Drug: rocuronium
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rocuronium<br>Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia | Drug: rocuronium<br>* continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)<br>* Other names: Esmeron;|
| Placebo Comparator: Placebo<br>Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded) | Other: placebo<br>* continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)<br>* Other names: sodium-chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elapsed time to target temperature |  | Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation | 
| Dissipated energy to reach the target temperature |  | Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation | 
| Changes in basal metabolism due to shivering or elevated stress levels |  | during the first 72 hours after cardiac arrest | 
| 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 | 
| Changes in serum levels of midazolam, fentanyl and rocuronium |  | within the first 48 hours of treatment | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac arrest, therapeutic hypothermia, skeletal muscle paralysis, shivering, serum drug levels, basal metabolism