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

NCT01199237 | Completed Phase 4 Results

• 1 other identifier: H10722-35629-01
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Reflex, Pharyngeal; Anesthetics, Inhalation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1)

  Up to 1 hour post-operative

• Nausea and Vomiting

  30 minutes after T1

• Nausea and Vomiting

  60 minutes after T1

• Time From Anesthetic Discontinuation to First Ability to Swallow

  up to 60 minutes after T1

Study Arms (2)

Sevoflurane

ACTIVE COMPARATOR

Patients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg)

Drug: Sevoflurane; Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate

Desflurane

ACTIVE COMPARATOR

Patients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg)

Drug: Desflurane; Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate

Interventions

Sevoflurane DRUG

Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water

Sevoflurane

Desflurane DRUG

Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water

Desflurane

Rocuronium DRUG

Desflurane; Sevoflurane

Neostigmine DRUG

Desflurane; Sevoflurane

Glycopyrrolate DRUG

Desflurane; Sevoflurane

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Baxter Healthcare Corporation: collaborator

Study Sites (2)

UCSF Helen Diller Cancer Center

San Francisco, California, 94115, United States

Location

UCSF Moffitt-Long Hospital

San Francisco, California, 94143, United States

Location

Related Publications (6)

• 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.

  PMID: 10754616 BACKGROUND

• 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.

  PMID: 11684981 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.

  PMID: 15728054 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.

  PMID: 20037150 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.

  PMID: 18635478 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.

  PMID: 1449405 BACKGROUND

MeSH Terms

Conditions

Gagging; Respiratory Aspiration

Interventions

Sevoflurane; Desflurane; Rocuronium; Neostigmine; Glycopyrrolate

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Ethyl Ethers; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rachel Eshima McKay
• Organization: University of California, San Francisco

eshimar@anesthesia.ucsf.edu

415-502-1715

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2010
• First Posted: September 10, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2013
• Last Updated: May 16, 2014
• Results First Posted: May 8, 2014

Record last verified: 2014-05

Locations

US (2)