Impact of Anesthetic Choice (Sevoflurane Versus Desflurane) on Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block

Study Overview
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Brief Summary
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Protective airway reflexes may be impaired in the postoperative period, creating the potential for aspiration of gastric contents, even after a patient exhibits appropriate response to command. Because assessment of airway reflex recovery is not possible in an intubated patient, the clinician must make an empiric decision as to when a patient is safe to extubate, and choose a combination of techniques least likely to result in pharyngeal impairment. Adequacy of reversal of neuromuscular block by cholinesterase inhibitors (e.g., neostigmine) is unpredictable, especially in the presence of profound paralysis, and tactile assessment of train-of four and sustained tetanus has shown poor correlation with objective assessments. Protective airway reflexes may also be impaired during early recovery by the anesthetics themselves, even when muscle relaxant has been avoided. In the absence of muscle relaxant the investigators previously demonstrated that patients receiving an anesthetic with higher tissue solubility, sevoflurane showed significantly greater impairment of swallowing up to 14 minutes after response to command compared to patients receiving an anesthetic with lower tissue solubility, desflurane. Therefore, we ask whether the combination of the more soluble anesthetic and the presence of neuromuscular block antagonized by neostigmine may create a multiplicative effect that might further prolong pharyngeal recovery. We plan to randomly assign 100 patients scheduled to undergo surgery with general anesthesia to a standardized anesthetic that includes 1) sevoflurane, rocuronium with 70 µg/kg neostigmine + 14 µg/kg glycopyrrolate antagonism (group S); or 2) desflurane, rocuronium with 70 µg/kg neostigmine + 14 µg/kg glycopyrrolate antagonism (group D). Airway reflex recovery will be judged as adequate by the patient's ability to swallow 20 mL of water without coughing or drooling 5, 10, 15, 20, 30 and 60 minutes after response to command. Anesthetic (sevoflurane or desflurane) will be discontinued after administration of reversal agent and recovery to TOF (train-of-four) ratio of 0.7.

Official Title
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Effect of Anesthetic Choice (Sevoflurane Versus Desflurane) on Speed and Sustained Nature of Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block

Conditions
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Airway Reflexes, Protective, Recovery After Neuromuscular Block, Anesthetic Recovery

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Desflurane
* Drug: Rocuronium
* Drug: Neostigmine
* Drug: Glycopyrrolate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA 1-2 patients Age 18-65 years body mass index (BMI) ≤ 35kg/m2 Planned surgery requiring general anesthesia lasting approximately 1.5-3.0 hours Surgery requires or benefits from skeletal muscle relaxation All must pass the baseline 20 mL water swallowing test as previously described. Exclusion Criteria: Pre-existing neuromuscular or central nervous system disorder Known condition interfering with gastric emptying Planned surgical procedure on the head or neck Known liver disease Serum creatinine > 1.5 mg/dL Concurrent use of neuroleptic medications Contraindication or previous adverse response to any of the study drugs Active asthma or reactive airways disease Surgery where upright position or brief cough would be contraindicated Inability to provide informed consent

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sevoflurane<br>Patients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) | Drug: Sevoflurane<br>* Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water<br>Drug: Rocuronium<br> <br> Drug: Neostigmine<br> <br> Drug: Glycopyrrolate<br> <br> |
| Active Comparator: Desflurane<br>Patients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) | Drug: Desflurane<br>* Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water<br>Drug: Rocuronium<br> <br> Drug: Neostigmine<br> <br> Drug: Glycopyrrolate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | The patient is judged by the primary anesthetist to be awake at time T1. At 2 minutes after T1, the patient was asked to swallow 20mL of water from a paper cup, and a blinded observer judged the ability to swallow based on transit of water to the posterior pharynx (absence of pooling or drooling) and absence of cough or gag. | At 2 minutes after response to command (T1). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1) | At the conclusion of surgery, after the patient's potent inhaled anesthetic was discontinued, the commands open your eyes and squeeze my hand were given at 30-second intervals. The time at which patient first appropriately response to both commands was noted as T1. | Up to 1 hour post-operative | 
| Nausea and Vomiting | Patients were asked to rate their experience of nausea and vomiting on a 0-10 verbal analog scale, with 0 being absence and 10 being the worst imaginable | 30 minutes after T1 | 
| Nausea and Vomiting | Patients were asked to rate their experience of nausea and vomiting on a 0-10 verbal analog scale, with 0 being absence and 10 being the worst imaginable | 60 minutes after T1 | 
| Time From Anesthetic Discontinuation to First Ability to Swallow | At 2 minutes after first response to command (T1), the patient was asked to swallow 20 mL of water from a paper cup, and an observer blinded to anesthetic assignment assessed the ability to swallow based on transit of water to the posterior pharynx (absence of pooling or drooling) and absence of cough or gag (indicating misdirection of the water bolus into the laryngeal inlet). This test was repeated at 6, 14, 22, 30 and 60 minutes after the time of first response to command. | up to 60 minutes after T1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reflex, Pharyngeal, Anesthetics, Inhalation