Inhalative Sedation in ICU With Sevoflurane Via Anaesthetic Conserving Device Compared to Propofol

Study Overview
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Brief Summary
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The evaluation of the presented study will work on the practicability of inhalative sedation on the ICU, potential benefits and limitations of the ACD system in a postoperative sedated patient population in comparison to a standard intravenous sedation regimen with propofol, and focus on renal and hepatic function, cardioprotection and pharmacoeconomics

Detailed Description
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A goal-oriented sedation complies the ability to sedate the patient as deeply as necessary, and allow a modern ventilation regimen with early spontaneous breathing and a pain-free cooperative patient. The ideal sedative agent - with a short duration of action, predictable wake-up times, low drug toxicity, haemodynamic stability and less side effects, and a rational pharmacoeconomic impact nowadays - has still to be found. Inhalative anaesthetics show these properties, but until the introduction of AnaConDa© (Anesthetic Conserving Device, ACD) in 2005, the use of volatile anaesthetics on the intensive care unit (ICU) required specific evaporating devices or scavenging systems. The ACD, a modified heat- moisture filter, is connected to the breathing circuit of conventional ICU ventilators and a syringe pump delivers the volatile anaesthetic to the ACD where it is vaporized through a rod. Most of the exhaled gas is absorbed in a charcoal filter's membrane and reflected to the patient in the following inspiration. Randomised, controlled and comparative studies to the use of volatile anaesthetics in ICU via this innovative device are still missing. Isoflurane has been studied in small patient populations and in comparison to midazolam, while Sevoflurane - a newer volatile agent with short action, brief elimination time, and low hepatic biodegradation - has only been studied intraoperatively and in short-term sedation. This is the first prospective, randomised, clinical study on the feasibility of sevoflurane via the ACD for sedation in ICU patients until 72 hours in comparison to a standard intravenous sedation with propofol. The investigation will work on potential benefits and limitations of the use of volatile agents on the ICU, the quality of sedation (Richmond Agitation Sedation Scale, BIS), infusion rate stability of sevoflurane and respiratory parameters, short-term recovery (time from discontinuation of infusion until following verbal commands and extubation), haemodynamics, renal and hepatic function and adverse side effects.

Conditions
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Recovery From Sedation, Sevoflurane Consumption, Renal Function, Hepatic Function, Cardioprotection

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years elective operative procedure, and indication for admission to the ICU for postoperative sedation ASA I-III weight 50-120 kg Haemoglobin > 10 g/dl ability and acceptance to agree to the study participation Exclusion Criteria: malignant hyperthermia muscle diseases or weakness liver insufficiency (ASAT, ALAT > 40 U/min) pancreas insufficiency emergencies women in child bearing age and missing negative pregnancy test, pregnancy or lactation diseases from the central nervous system (such as M. Parkinson and multiple sclerosis) increased intracranial pressure, head trauma pre-existing delirium, agitation and psychiatric derangements alcohol and drug abuse (including opioid abuse) allergy to any of the study agents refusal from the patient to participate in the study participation in another study project.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1-Sevo<br>Sevoflurane/ACD group (n=60) | Drug: Sevoflurane<br>* Sevoflurane sedation, 0.5-1 Vol%, continuously via syringe pump, up to 72 hours in ICU<br>* Other names: Sevorane (Abbott GmbH, Wiesbaden, Germany);|
| 2-Propofol<br>Propofol group (n=60) | Drug: Propofol<br>* Propofol, 1.5-3 mg/kgBW/h, continuously via syringe pump, up to 72 hours<br>* Other names: disoprivan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extubation time |  | Termination of sedation to extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consumption of anaesthetics |  | until discharge from hospital | 
| Renal function |  | until discharge from hospital | 
| Hepatic function |  | until discharge from hospital | 
| Cardioprotection |  | until discharge from hospital | 
| Costs |  | until discharge from hospital | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation, Volatile anaesthetic, Sevoflurane, Propofol, Recovery