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

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

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.

Study Overview

• Status: Completed
• Conditions: Airway Reflexes, Protective; Recovery After Neuromuscular Block; Anesthetic Recovery
• Intervention / Treatment: Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate; Drug: Sevoflurane; Drug: Desflurane

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Moffitt-Long Hospital
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Baxter Healthcare Corporation

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: August 23, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (ESTIMATE): September 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Anesthetics, Inhalation; Reflex, Pharyngeal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Adjuvants, Anesthesia; Anesthetics, Inhalation; Neuromuscular Agents; Cholinesterase Inhibitors; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Parasympathomimetics; Desflurane; Sevoflurane; Glycopyrrolate; Rocuronium; Neostigmine
• Other Study ID Numbers: H10722-35629-01