Clinical trial NCT01199237: Impact of Anesthetic Choice (Sevoflurane Versus Desflurane) on Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block
Official title: Effect of Anesthetic Choice (Sevoflurane Versus Desflurane) on Speed and Sustained Nature of Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Airway Reflexes, Protective
Recovery After Neuromuscular Block
Anesthetic Recovery
Keywords: Reflex, Pharyngeal
Anesthetics, Inhalation
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2010-09-10
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis.
timeFrame: At 2 minutes after response to command (T1).
Secondary outcomes:
measure: Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1)
timeFrame: Up to 1 hour post-operative
measure: Nausea and Vomiting
timeFrame: 30 minutes after T1
measure: Nausea and Vomiting
timeFrame: 60 minutes after T1
measure: Time From Anesthetic Discontinuation to First Ability to Swallow
timeFrame: up to 60 minutes after T1
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Moffitt-Long Hospital
state: California
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.