The Effect of Propofol and Remifentanil Sequence on ED50 and ED95 of Rocuronium in Rapid Sequence Induction Anesthesia

Study Overview
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Brief Summary
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Rapid sequence induction (RSI) is a well-known procedure to maintain a safe and rapid airway in patients especially at risk of aspiration. Propofol and rocuronium are generally used agents for RSI. However, the difficult airway scenarios are always valid for these patients, even without predictive signs of difficult airway. Therefore, it is important to decrease the rocuronium dose used in RSI to achieve a rapid recovery of a neuromuscular conduction with the aid of a reversal agent in case of difficult airway. The short acting opioids such as remifentanil may be helpful to reduce the dose of rocuronium in RSI.

Detailed Description
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Rapid sequence induction is a widely used anesthesia technique to achieve a safe airway control. However, the difficult airway may be expected in these patients as in the others. In the difficult airway situation, cholinesterase inhibitors and sugammadex may be used for the reversal. However, sugammadex is not always available due to its cost in every hospital. In addition to this, it is well-known that cholinesterase inhibitors do not work well in case of deep neuromuscular block. In consideration of these informations, the recovery of the neuromuscular block gain an importance in patients undergoing RSI with difficult airway. Therefore, decreasing the dosage of non-depolarizing neuromuscular agent may be helpful in case of the difficult airway situations. With the aim of decreasing the neuromuscular blocker dosage, opioid analgesics especially remifentanil is preferred combined with propofol to decrease the hemodynamic response to laryngoscopy and intubation. A recent study demonstrated that after induction of anesthesia with remifentanil and propofol, ED50 of rocuronium for acceptable intubation conditions was 0.20 mg/kg. In another study, the authors showed that the administration sequence of propofol and remifentanil for target controlled anesthesia affect the onset time of rocuronium due to change in cardiac output. The authors concluded that the prior administration of remifentanil decreased the cardiac output and delayed the onset time of rocuronium. The investigators hypothesized that prior administration of remifentanil compared to propofol may increase the ED50 and ED95 of rocuronium for acceptable intubation conditions in RSI.

Official Title
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Does the Choice of Administration Sequence of Propofol and Remifentanil Affect the ED50 and ED95 of Rocuronium for Rapid Sequence Induction of Anesthesia?

Conditions
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Anesthesia, Neuromuscular Blockade

Intervention / Treatment
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* Drug: Propofol
* Drug: Remifentanil
* Drug: Rocuronium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) physical status I-II patients patients scheduled for elective surgery Exclusion Criteria: suspected or known difficult airway a significant renal or hepatic dysfunction a known neuromuscular disease hypertension a known allergy to one of the drugs used in general anesthesia a body mass index lower than 18.5 kg/m2 or higher than 30 kg/m2 intake of any medication that might interact with rocuronium patient refusal

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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: propofol<br>Propofol arm includes patients that induction of general anesthesia started with propofol and followed by remifentanil and rocuronium administration | Drug: Propofol<br>* Propofol will be used in either two arms. The injection sequence will be changed. In propofol arm of the study, general anesthesia will be started with 2 mg/kg propofol administered within 15 seconds. And, then remifentanil will be given. In remifentanil arm of the study, 2 mg/kg propofol will be applied within 15 seconds following remifentanil injection.<br>Drug: Remifentanil<br>* Remifentanil will be used in either two arms. The injection sequence will be changed. In remifentanil arm, general anesthesia will be started with 2 μg/kg remifentanil administered within 30 seconds. And then propofol will be given. In propofol arm of the study the same dose will be applied within 30 seconds following propofol administration.<br>* Other names: Ultiva;Drug: Rocuronium<br>* Rocuronium will be used for either two study arms. Rocuronium will be given in a 0.8 mg/kg dosage in the first study subject. And then, if the intubation condition is acceptable, the dose of the rocuronium will be decreased by 0.1 mg/kg for the next patient. Otherwise, if the intubation condition is not acceptable, the rocuronium dosage will be increased by 0.1 mg/kg for the next patient. This will be continue for ten crossover points (the point that turn from unsuccessful intubation to successful intubation).<br>* Other names: Esmeron;|
| Active Comparator: remifentanil<br>Remifentanil arm include patients that induction of general anesthesia started with remifentanil and followed by propofol and rocuronium administration | Drug: Propofol<br>* Propofol will be used in either two arms. The injection sequence will be changed. In propofol arm of the study, general anesthesia will be started with 2 mg/kg propofol administered within 15 seconds. And, then remifentanil will be given. In remifentanil arm of the study, 2 mg/kg propofol will be applied within 15 seconds following remifentanil injection.<br>Drug: Remifentanil<br>* Remifentanil will be used in either two arms. The injection sequence will be changed. In remifentanil arm, general anesthesia will be started with 2 μg/kg remifentanil administered within 30 seconds. And then propofol will be given. In propofol arm of the study the same dose will be applied within 30 seconds following propofol administration.<br>* Other names: Ultiva;Drug: Rocuronium<br>* Rocuronium will be used for either two study arms. Rocuronium will be given in a 0.8 mg/kg dosage in the first study subject. And then, if the intubation condition is acceptable, the dose of the rocuronium will be decreased by 0.1 mg/kg for the next patient. Otherwise, if the intubation condition is not acceptable, the rocuronium dosage will be increased by 0.1 mg/kg for the next patient. This will be continue for ten crossover points (the point that turn from unsuccessful intubation to successful intubation).<br>* Other names: Esmeron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ED50 of rocuronium | ED50 of rocuronium means the dose of rocuronium that is required for providing acceptable intubation conditions in the 50% of patients undergoing intubation. Each individual dose that allow or not allow an acceptable intubation condition will determine the next patient rocuronium dose. At the end, ED50 of rocuronium will be calculated as means of drug dosage that providing acceptable intubation condition. | One minute after rocuronium injection | 
| ED95 of rocuronium | ED595 of rocuronium means the dose of rocuronium that is required for providing acceptable intubation conditions in the 95% of patients undergoing intubation. Each individual dose that allow or not allow an acceptable intubation condition will determine the next patient rocuronium dose. At the end, ED95 of rocuronium will be estimated by using statistical tools such as pava estimator or R code. | One minute after rocuronium injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean arterial blood pressure | the effect of propofol and remifentanil administration sequence on mean arterial blood pressure will be evaluated. | before and after 10 minutes of induction of anesthesia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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propofol, remifentanil, rocuronium