Rocuronium Dose Finding Study After Single-shot or Steady-state Propofol Anesthesia

Study Overview
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Brief Summary
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This study is designed to determine the effective-doses ED-50 and ED-95 (the doses required for a 50% and 95% twitch inhibition, respectively) of the non-depolarizing muscle relaxant rocuronium after single-shot or steady-state propofol anesthesia in a clinical setting.

Detailed Description
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Neuromuscular blocking agents are worldwide used as a standard component of a modern balanced anesthesia regime. They are administered to facilitate tracheal intubation, reduce laryngeal trauma and optimize surgical conditions. The dose usually recommended to facilitate tracheal intubation approximates at least two times the drug´s effective dose ED-95 (the dose required for a 95% effect) depending on the choice of the neuromuscular blocking agent. This overdose is administered to induce a very deep paralysis with a fast onset of action providing clinically acceptable intubating conditions. Moreover, our clinical experience has shown that the dose-relationship of a neuromuscular blocking agents estimated during steady-state anesthesia does not necessarily correlate with the dose-response curve of the same drug during anesthetic induction. Therefore, a discrepancy between the applied dose and the clinical outcome measure, the intubating conditions, becomes apparent. This might be related to effects of the co-administered anesthetics at the neuromuscular junction. While inhaled anesthetics augment the paralyzing effects of non-depolarizering muscle relaxants in a dose-dependent fashion and depend on the duration of anesthesia, little is known about the interactions of the intravenous anesthetic propofol with the non-depolarizing blocking agent rocuronium. We hypothesize that the intravenous administration of propofol also influences the potency of rocuronium dependant on the duration of its application. This study, therefore, is designed to determine the dose-response relationship of rocuronium after single-shot or steady-state propofol anesthesia in a clinical setting. The primary endpoints are the ED-50s and ED-95s of rocuronium during anesthetic induction with a single-shot propofol and after 30minutes of steady-state propofol anesthesia. The secondary endpoints are the slopes and the intercepts of the respective dose-response-curves, the onset and duration of muscle paralysis and the recovery from neuromuscular blockade. Materials & Methods We will investigate patients scheduled for elective low-risk surgical procedures under general anesthesia. Patients will be allocated to two experimental groups. After neuromuscular monitoring is established under remifentanil infusion, patients of the group Induction will receive a single-shot propofol followed by injection of rocuronium and endotracheal intubation. Patients of the group Maintenance will be anaesthetized with an induction dose of propofol followed by 30 minutes of total intravenous anesthesia (TIVA: propofol/ remifentanil) before rocuronium is administered. Airway will be managed using a laryngeal mask or tracheal intubation. During surgery, anesthesia will be maintained with TIVA. Onset and duration of neuromuscular blockade and spontaneous recovery will be monitored with electromyography. Postoperatively, patients will be monitored for 60 minutes in our post-anesthesia care unit.

Official Title
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Rocuronium Dose Finding Study After Single-shot or Steady-state Propofol

Conditions
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Neuromuscular Blockade, Anesthesia

Intervention / Treatment
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* Drug: Single-Shot Propofol
* Drug: 30min infusion Propofol
* Drug: Remifentanil infusion
* Drug: Rocuronium (0.07mg/kg/body mass)
* Drug: Rocuronium (0.1mg/kg/body mass)
* Drug: Rocuronium (0.15mg/kg/body mass)
* Drug: Rocuronium (0.2mg/kg/body mass)
* Drug: Rocuronium (0.3mg/kg/body mass)
* Drug: Rocuronium (0.45mg/kg/body mass)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for a low risk-surgical procedure under general anesthesia Patients ASA physical status I-III Patients older than 18years Patients having given informed consent to the study Exclusion Criteria: Patients who decline to give informed consent to the study Known or suspected allergy towards anesthetics or rocuronium Pregnant and breastfeeding women Known or suspected neuromuscular disease Burn injury prior to the investigation Anatomic and functional malformations with expected difficult intubation Anorexia, Bulimia nervosa, Malnutrition Heart failure Use of drugs that interfere with muscle relaxant

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single-shot-Propofol & Remifentanil<br>Induction group: A single-shot propofol induction dose with remifentanil infusion followed by injection of rocuronium (for doses, please see interventions). Airway: tracheal intubation | Drug: Single-Shot Propofol<br>* Single-shot propofol induction dose (1.5-2.5mg/kg body mass)<br>* Other names: 2,6-Diisopropylphenol;Drug: Remifentanil infusion<br>* Remifentanil infusion (0.1-0.2µg/kg/min)<br>* Other names: Ultiva®;Drug: Rocuronium (0.07mg/kg/body mass)<br>* Rocuronium (0.07mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.1mg/kg/body mass)<br>* Rocuronium (0.1mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.15mg/kg/body mass)<br>* Rocuronium (0.15mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.2mg/kg/body mass)<br>* Rocuronium (0.2mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.3mg/kg/body mass)<br>* Rocuronium (0.3mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.45mg/kg/body mass)<br>* Rocuronium (0.45mg/kg/body mass)<br>* Other names: Esmeron;|
| Experimental: 30min infusion Propofol & Remifentanil<br>Maintenance group: 30min of total intravenous anesthesia (TIVA) with propofol and remifentanil before rocuronium (for doses, please see interventions) is administered. Airway: tracheal intubation/laryngeal mask | Drug: 30min infusion Propofol<br>* 30min of propofol infusion (4-6mg/kg/h)<br>* Other names: 2,6-Diisopropylphenol;Drug: Remifentanil infusion<br>* Remifentanil infusion (0.1-0.2µg/kg/min)<br>* Other names: Ultiva®;Drug: Rocuronium (0.07mg/kg/body mass)<br>* Rocuronium (0.07mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.1mg/kg/body mass)<br>* Rocuronium (0.1mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.15mg/kg/body mass)<br>* Rocuronium (0.15mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.2mg/kg/body mass)<br>* Rocuronium (0.2mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.3mg/kg/body mass)<br>* Rocuronium (0.3mg/kg/body mass)<br>* Other names: Esmeron;Drug: Rocuronium (0.45mg/kg/body mass)<br>* Rocuronium (0.45mg/kg/body mass)<br>* Other names: Esmeron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ED-50 of rocuronium | The primary outcome measure is the 1) ED-50 of rocuronium during anesthesia induction with propofol and after steady-state propofol anesthesia | Anesthesia time during their surgical procedure (=arrival in the OR until discharge from the post-anesthesia care unit), ca. 180min | 
| ED-95 of rocuronium | The primary outcome measure is 2) the ED-95 of rocuronium during anesthesia induction with propofol and after steady-state propofol anesthesia | Anesthesia time during their surgical procedure (=arrival in the OR until discharge from the post-anesthesia care unit), ca. 180min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics of rocuronium (composite outcome measure) | The secondary outcome measures are the slopes and the intercepts of the dose-response-curves for rocuronium, the onset and duration of muscle paralysis and the recovery from neuromuscular blockade. | Anesthesia time during their surgical procedure (=arrival in the OR until discharge from the post-anesthesia care unit), ca. 180min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle relaxant, Rocuronium, TIVA, Propofol