Airway Reflexes, Protective, Anesthetic Recovery, Recovery After Neuromuscular Block
Conditions
Keywords
Reflex, Pharyngeal, Anesthetics, Inhalation
Brief summary
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.
Interventions
DRUGSevoflurane
Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water
DRUGDesflurane
Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water
DRUGRocuronium
DRUGNeostigmine
DRUGGlycopyrrolate
Sponsors
Baxter Healthcare Corporation
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | At 2 minutes after response to command (T1). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1) | Up to 1 hour post-operative | 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. |
| Nausea and Vomiting | 30 minutes after T1 | 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 |
| Time From Anesthetic Discontinuation to First Ability to Swallow | up to 60 minutes after T1 | 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. |
Countries
United States
Participant flow
Recruitment details
At one U.S. clinical site, patients scheduled to undergo surgery requiring general anesthesia lasting approximately 1.5 - 3.0 hours requiring tracheal intubation and paralysis during surgery were invited to participate
Pre-assignment details
Participation of the first 26 enrollees was considered a pilot to determine the feasibility of measuring the primary outcome at T1+5 minutes. The majority of participants were alert, and no meaningful analyses could be made. The study was modified to assess the primary outcome at T1 + 2 minutes, and 81 additional participants were recruited.
Participants by arm
| Arm | Count |
|---|---|
| Sevoflurane Patients received sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) | 41 |
| Desflurane Patients received Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) | 40 |
| Total | 81 |
Baseline characteristics
| Characteristic | Sevoflurane | Desflurane | Total |
|---|---|---|---|
| Age, Continuous | 45.3 years | 43.3 years | 44.3 years |
| Region of Enrollment United States | 41 participants | 40 participants | 81 participants |
| Sex: Female, Male Female | 41 Participants | 36 Participants | 77 Participants |
| Sex: Female, Male Male | 0 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 41 | 0 / 40 |
| serious Total, serious adverse events | 0 / 41 | 0 / 40 |
Outcome results
Primary
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.
Time frame: At 2 minutes after response to command (T1).
Population: Only participants judged by the clinician as able to take the test (n=57)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sevoflurane | Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | able to swallow at T1+2 minutes | 16 participants |
| Sevoflurane | Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | unable to swallow at T1+2 minutes | 10 participants |
| Desflurane | Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | able to swallow at T1+2 minutes | 25 participants |
| Desflurane | Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. | unable to swallow at T1+2 minutes | 6 participants |
p-value: 0.11Chi-squared
Secondary
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
Time frame: 30 minutes after T1
Population: Only participants able to respond at time of assessment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sevoflurane | Nausea and Vomiting | Nausea | 0.385 units on a scale |
| Sevoflurane | Nausea and Vomiting | Vomiting | 0 units on a scale |
| Desflurane | Nausea and Vomiting | Nausea | 1.359 units on a scale |
| Desflurane | Nausea and Vomiting | Vomiting | 0 units on a scale |
Secondary
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
Time frame: 60 minutes after T1
Population: Only patients able to respond at time of assessment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sevoflurane | Nausea and Vomiting | Nausea | 0.263 units on a scale |
| Sevoflurane | Nausea and Vomiting | Vomiting | 0 units on a scale |
| Desflurane | Nausea and Vomiting | Nausea | 1.333 units on a scale |
| Desflurane | Nausea and Vomiting | Vomiting | 0.026 units on a scale |
Secondary
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.
Time frame: up to 60 minutes after T1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sevoflurane | Time From Anesthetic Discontinuation to First Ability to Swallow | 1275 Seconds |
| Desflurane | Time From Anesthetic Discontinuation to First Ability to Swallow | 718 Seconds |
Secondary
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.
Time frame: Up to 1 hour post-operative
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sevoflurane | Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1) | 623 seconds |
| Desflurane | Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1) | 343 seconds |