Influence of Skeletal Muscle Paralysis on Metabolism in Hypothermic Patients After Cardiac Arrest

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of muscle relaxing drugs on the energy rate during hypothermia after cardiac arrest.

Detailed Description
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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. However, neuromuscular blockers are accused to be associated with various side effects causing serious harm and/or leading to prolonged ICU stay. Furthermore, the use of neuromuscular blockers may mask epileptic activity. Therefore, the advantages and disadvantages of neuromuscular blockers during therapeutic hypothermia need to be re-evaluated. Aim of this study is to investigate if continuous application of neuromuscular blockers is necessary to prevent shivering and thereby avoiding an increase in energy expenditure in patients during therapeutic hypothermia and rewarming after cardiac arrest (initial 72h).

Official Title
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Influence of Skeletal Muscle Paralysis on Metabolism in Hypothermic Patients After Cardiac Arrest

Conditions
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Critical Illness, Cardiac Arrest

Intervention / Treatment
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* Drug: Rocuronium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed cardiopulmonary origin Exclusion Criteria: age < 18 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 patients with known epileptic disease

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Neuromuscular blocker group<br>Continuous application of neuromuscular blockers during therapeutic hypothermia. Bolus application of placebo in case of shivering. | Drug: Rocuronium<br>* Continuous application of Rocuronium (0.5 mg/kg body weight/hour). Bolus application of placebo in case of shivering.<br>|
| Placebo Comparator: Placebo group<br>Continuous application of placebo during therapeutic hypothermia. Bolus application of neuromuscular blockers in case of shivering. | Drug: Placebo<br>* Continuous application of placebo during therapeutic hypothermia. Bolus application of Rocuronium (0.5 mg/kg body weight) in case of shivering.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of resting energy expenditure compared to baseline at 33C° | resting energy expenditure will be assessed with indirect calorimetry at different measurement time points: 12-24 h after initiation of mild hypothermia (33C°) during warming up (at 34.5°C) during warming up (at 36°C) during warming up (at 36.5°C - 37.5°C) normal Temperature, after 48 - 72 h after initiation of mild hypothermia | initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of substrate oxidation rate (protein, fat and glucose) compared to baseline at 33C° | substrate oxidation rates will be assessed with indirect calorimetry at different measurement time points: 12-24 h after initiation of mild hypothermia (33C°) during warming up (at 34.5°C) during warming up (at 36°C) during warming up (at 36.5°C - 37.5°C) at normal Temperature, after 48 - 72 h after initiation of mild hypothermia | initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h |