Dose Finding Study for Effective Reversal of a Deep Rocuronium-induced Neuromuscular Block With Sugammadex in Morbidly Obese Patients

Study Overview
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Brief Summary
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During laparoscopic bariatric surgery, adequate muscle relaxation is important to maintain good surgical conditions. To achieve this muscle relaxation, neuromuscular transmission blocking agents, such as rocuronium (Esmeron®) are used. It sometimes happens that there is still some neuromuscular blocking activity left in the patient on awakening from anesthesia. This is called residual curarization and is known to cause postoperative complications such as impairment of respiratory function. Sugammadex (Bridion®) is a novel drug which selectively binds rocuronium (Esmeron®). It allows for reversing of neuromuscular transmission blocking activity. Until now, all studies with sugammadex were performed in non-obese patients. Obese patient have a high risk to suffer from post-operative respiratory failure. Therefore it is vital to avoid residual curarization. Sugammadex might be an important factor. Obese patients have a large total body weight different from ideal body weight. Recent research demonstrated that the dose for the neuromuscular blocking agent rocuronium (Esmeron®) needs to be calculated on the patients' Ideal Body Weight rather than on Total Body Weight. At this moment no data is available on the dose-response relationship of sugammadex in morbidly obese patients. We hypothesize that in morbidly obese patients sugammadex should be dosed on ideal bodyweight, instead of total bodyweight.

Detailed Description
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Flowchart : 72 participants Stratification BMI<50 BMI >50 Randomization Randomization TBW IBW TBW IBW 2mg/kg n=9 2mg/kg n=9 2mg/kg n=9 2mg/kg n=9 4mg/kg n=9 4mg/kg n=9 4mg/kg n=9 4mg/kg n=9 TBW : Total Body Weight IBW : Ideal Body Weight

Official Title
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Dose Finding Study for Effective Reversal of a Deep Rocuronium-induced Neuromuscular Block With Sugammadex in Morbidly Obese Patients.

Conditions
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Morbidly Obese Patients

Intervention / Treatment
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* Drug: Sugammadex 2 mg/kg
* Drug: Sugammadex. 4 mg/kg
* Procedure: Neuromuscular monitoring.
* Procedure: Clinical evaluation of residual curarization .


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : ASA I-II-III Age 18 - 65 year Male or female BMI > 30 Exclusion criteria : Renal failure Liver dysfunction Breastfeeding female patients, or female patients without reliable contraception Neuromuscular disease Malignant hyperthermia or a family history of malignant hyperthermia Allergy for neuromuscular blocking agents or other medications used during general anesthesia Infectious disease or patients with fever Patients who already received rocuronium or sugammadex on the day of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: BMI < 50, Total Body Weight (TBW), 2mg/kg<br>Patients with a BMI < 50, who will be dosed according to total body weight. | Drug: Sugammadex 2 mg/kg<br>* Patients receive 2 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI < 50, TBW, 4 mg/kg<br>Patients with a BMI < 50, who will be dosed according to total body weight. | Drug: Sugammadex. 4 mg/kg<br>* Patients receive 4 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI < 50, Ideal Body Weight (IBW), 2 mg/kg<br>Patients with a BMI < 50, who will be dosed according to ideal body weight. | Drug: Sugammadex 2 mg/kg<br>* Patients receive 2 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI < 50, IBW, 4 mg/kg<br>Patients with a BMI < 50, who will be dosed according to ideal body weight. | Drug: Sugammadex. 4 mg/kg<br>* Patients receive 4 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI > 50, TBW, 2mg/kg<br>Patients with a BMI > 50, who will be dosed according to total body weight. | Drug: Sugammadex 2 mg/kg<br>* Patients receive 2 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI > 50, TBW, 4mg/kg<br>Patients with a BMI > 50, who will be dosed according to total body weight. | Drug: Sugammadex. 4 mg/kg<br>* Patients receive 4 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI >50, IBW, 2 mg/kg<br>Patients with a BMI > 50, who will be dosed according to ideal body weight. | Drug: Sugammadex 2 mg/kg<br>* Patients receive 2 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|
| Experimental: BMI >50, IBW, 4 mg/kg<br>Patients with a BMI > 50, who will be dosed according to ideal body weight. | Drug: Sugammadex. 4 mg/kg<br>* Patients receive 4 mg/kg Sugammadex.<br>Procedure: Neuromuscular monitoring.<br>* Neuromuscular monitoring using a TOF watch SX (Organon).<br>Procedure: Clinical evaluation of residual curarization .<br>* Every 30 min, during the first 2 hours after the end of the surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete recovery of muscle relaxation, 30 minutes after end of surgery. | Measured with TOF Watch SX (TOF ratio > 0.9); clinical evaluation (eg head lift) of residual curarization in the Post Anesthetic Care. | 30 minutes after end of surgery. | 
| Time to complete recovery of muscle relaxation, 1 hour after the end of surgery. | Measured with TOF Watch SX (TOF ratio > 0.9); clinical evaluation (eg head lift) of residual curarization in the Post Anesthetic Care. | 1hour after end of surgery. | 
| Time to complete recovery of muscle relaxation, 1 hour 30 minutes after the end of surgery. | Measured with TOF Watch SX (TOF ratio > 0.9); clinical evaluation (eg head lift) of residual curarization in the Post Anesthetic Care. | 1hour 30 minutes after end of surgery. | 
| Time to complete recovery of muscle relaxation, 2 hours after the end of surgery. | Measured with TOF Watch SX (TOF ratio > 0.9); clinical evaluation (eg head lift) of residual curarization in the Post Anesthetic Care. | 2 hours after end of surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need/use of rescue medication at the end of surgery | Additional administration of sugammadex 2 mg/kg Total Body Weight) at the end of surgery. | The hours following the end of surgery. |