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| Name | Class |
|---|---|
| Baxter Healthcare Corporation | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sevoflurane | Active Comparator | Patients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
|
| Desflurane | Active Comparator | Patients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sevoflurane | Drug | Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water |
|
| 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). |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Helen Diller Cancer Center | San Francisco | California | 94115 | United States | ||
| UCSF Moffitt-Long Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10754616 | Background | Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84. doi: 10.1097/00000542-200004000-00014. | |
| 11684981 |
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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.
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
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| ID | Title | Description |
|---|---|---|
| FG000 | Sevoflurane | Patients received sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
| FG001 | Desflurane | Patients received Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Desflurane | Drug | Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water |
|
| Rocuronium | Drug |
|
| Neostigmine | Drug |
|
| Glycopyrrolate | Drug |
|
| 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 |
| San Francisco |
| California |
| 94143 |
| United States |
| Sundman E, Witt H, Sandin R, Kuylenstierna R, Boden K, Ekberg O, Eriksson LI. Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology. 2001 Nov;95(5):1125-32. doi: 10.1097/00000542-200111000-00016. |
| 15728054 | Background | Mckay RE, Large MJC, Balea MC, Mckay WR. Airway reflexes return more rapidly after desflurane anesthesia than after sevoflurane anesthesia. Anesth Analg. 2005 Mar;100(3):697-700. doi: 10.1213/01.ANE.0000146514.65070.AE. |
| 20037150 | Background | McKay RE, Malhotra A, Cakmakkaya OS, Hall KT, McKay WR, Apfel CC. Effect of increased body mass index and anaesthetic duration on recovery of protective airway reflexes after sevoflurane vs desflurane. Br J Anaesth. 2010 Feb;104(2):175-82. doi: 10.1093/bja/aep374. Epub 2009 Dec 26. |
| 18635478 | Background | Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268. |
| 1449405 | Background | DePippo KL, Holas MA, Reding MJ. Validation of the 3-oz water swallow test for aspiration following stroke. Arch Neurol. 1992 Dec;49(12):1259-61. doi: 10.1001/archneur.1992.00530360057018. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sevoflurane | Patients received sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
| BG001 | Desflurane | Patients received Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Only participants judged by the clinician as able to take the test (n=57) | Posted | Number | participants | At 2 minutes after response to command (T1). |
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| 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. | Posted | Mean | Full Range | seconds | Up to 1 hour post-operative |
|
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| 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 | Only participants able to respond at time of assessment | Posted | Mean | Full Range | units on a scale | 30 minutes after T1 |
|
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| 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 | Only patients able to respond at time of assessment | Posted | Mean | Full Range | units on a scale | 60 minutes after T1 |
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| 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. | Posted | Mean | Full Range | Seconds | up to 60 minutes after T1 |
|
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1-2 hours postoperatively
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sevoflurane | Patients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) Sevoflurane: Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water | 0 | 41 | 0 | 41 | ||
| EG001 | Desflurane | Patients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) Desflurane: Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water | 0 | 40 | 0 | 40 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rachel Eshima McKay | University of California, San Francisco | 415-502-1715 | eshimar@anesthesia.ucsf.edu |
| ID | Term |
|---|---|
| D005683 | Gagging |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000077149 | Sevoflurane |
| D000077335 | Desflurane |
| D000077123 | Rocuronium |
| D009388 | Neostigmine |
| D006024 | Glycopyrrolate |
| ID | Term |
|---|---|
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| D009930 | Organic Chemicals |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D005019 | Ethyl Ethers |
| D000732 | Androstanols |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D050338 | Phenylammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009861 | Onium Compounds |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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