Alternative Sedation During Bronchoscopy (DEX)

A Randomized, Placebo-controlled, Concealed Allocation Comparison of Respiratory Depression and Coughing During Bronchoscopy With Dexmedetomidine-ketamine as an Adjunct to Fentanyl-midazolam Sedation

This protocol hopes to determine whether the use of dexmedetomidine-ketamine can reduce the use of standard of care fentanyl-midazolam sedation during bronchoscopy. This may result in less respiratory depression while providing better compliance with the procedure.

Study Overview

• Status: Completed
• Conditions: Sedation
• Intervention / Treatment: Drug: Midazolam load; Drug: Fentanyl load; Drug: Midazolam demand; Drug: Fentanyl demand; Drug: Benadryl demand; Drug: Dexmedetomidine load; Drug: Ketamine load; Drug: Dexmedetomidine maintenance; Drug: Ketamine maintenance

Detailed Description

All patients enrolled in the study will be undergoing bronchoscopy, which is typically performed with sedation. All procedural sedation carries some risk. Several features of the study may lower the risk of sedation relative to that of conventional sedation. An anesthesiologist will be present throughout the procedure. Continuous monitoring of respiration with RIP will be employed. Administration of sedation will be via a volumetric syringe pump. Benefits specific to dexmedetomidine-ketamine include the lack of respiratory depression and greater hemodynamic stability.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults over the age of 18 scheduled for elective flexible bronchoscopy in the endoscopy suite or OR of HUP

Exclusion Criteria:

• History of inability to complete bronchoscopy attributable to inadequate sedation
• Requiring more than 2 LPM supplemental oxygen to maintain SaO2 > 90%
• History of allergy to study medications
• Pregnancy
• A history of psychosis
• Any condition deemed likely by the pulmonologist or anesthesiologist to pose a significant risk due to elevation of blood pressure, including cerebral/aortic aneurysm, and or ischemic cardiovascular disease
• Bradydysrhythmia deemed significant by the anesthesiologist or pulmonologist
• A diagnosis of significant renal or hepatic impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; midazolam load fentanyl load midazolam demand fentanyl demand benadryl demand	Drug: Midazolam load; 2 mg bolus prior to bronchoscopy; Other Names: Versed; Drug: Fentanyl load; 50 µg bolus prior to bronchoscopy; Other Names: Abstral; Actiq; Fentora; Onsolis; Drug: Midazolam demand; 0.5 mg demand bolus at discretion of pulmonologist; Other Names: Versed; Drug: Fentanyl demand; 12.5 µg demand bolus at discretion of pulmonologist; Other Names: Abstral; Actiq; Fentora; Onsolis; Drug: Benadryl demand; 25 mg bolus after 6th and 13th demand midazolam/fentanyl bolus; Other Names: Diphenhydramine Hcl; Aler-Dryl; Banophen; Ben Tann; Bromanate AF; Diphen; Diphenadryl; Diphenhist; Dytan; Unisom; Sominex; Silphen; Siladryl
Active Comparator: dexmedetomidine and ketamine; dexmedetomidine load ketamine load dexmedetomidine maintenance ketamine maintenance midazolam demand fentanyl demand benadryl demand	Drug: Midazolam demand; 0.5 mg demand bolus at discretion of pulmonologist; Other Names: Versed; Drug: Fentanyl demand; 12.5 µg demand bolus at discretion of pulmonologist; Other Names: Abstral; Actiq; Fentora; Onsolis; Drug: Benadryl demand; 25 mg bolus after 6th and 13th demand midazolam/fentanyl bolus; Other Names: Diphenhydramine Hcl; Aler-Dryl; Banophen; Ben Tann; Bromanate AF; Diphen; Diphenadryl; Diphenhist; Dytan; Unisom; Sominex; Silphen; Siladryl; Drug: Dexmedetomidine load; Dexmedetomidine 1 µg/kg prior to bronchoscopy; Other Names: Precedex; Dexmedetomidine Hydrochloride; Drug: Ketamine load; Ketamine 30 mg bolus prior to bronchoscopy; Other Names: Ketalar; Calypsol; Ketamin; Ketaminol; Ketanest; Tekam; Vetalar; Drug: Dexmedetomidine maintenance; 0.5 µg/kg/hour for the duration of bronchoscopy (58.5 minutes average); Other Names: Precedex; Dexmedetomidine Hydrochloride; Drug: Ketamine maintenance; 8 µg/kg/min for the duration of bronchoscopy (58.5 minutes average); Other Names: Ketalar; Calypsol; Ketamin; Ketaminol; Ketanest; Tekam; Vetalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decreased Minute Ventilation	An initial baseline minute ventilation estimate was obtained via calibrated respiratory impedance plethysmography bands. Subsequent minute ventilation was normalized to this value. Values exceeding 100% were excluded from analysis, as these typically reflected a period of hyperpnea subsequent to relief of airway obstruction by chin lift or jaw thrust.	During the bronchoscopy procedure only, 58.5 minutes average
Total Fentanyl	Total fentanyl dose delivered during the procedure	During the bronchoscopy procedure only, 58.5 minutes average
Total Midazolam	Total midazolam delivered during procedure	Duration of procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desaturation (Cumulative)	Cumulative time below saturation of 90% - the total number of seconds that the pulse oximeter reported a saturation below 90%	During the bronchoscopy procedure only, 58.5 minutes average
Desaturation (Longest)	Longest time below saturation of 90% (the number of seconds elapsed between the start of a period in which the pulse oximeter saturation fell below 90% and the return above 90%)	During the bronchoscopy procedure only, 58.5 minutes average
Conversion to General Anesthesia	Patients in which the procedure could not be completed without conversion to general anesthesia	During the bronchoscopy procedure only, 58.5 minutes average
Patient Satisfaction	Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied)	After the bronchoscopy procedure only
Endoscopist Satisfaction	Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied)	After the bronchoscopy procedure only

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Jeff E Mandel, MD MS, University of Pennsylvania

Publications and helpful links

General Publications

• Yarmus LB, Akulian JA, Gilbert C, Mathai SC, Sathiyamoorthy S, Sahetya S, Harris K, Gillespie C, Haas A, Feller-Kopman D, Sterman D, Lee HJ. Comparison of moderate versus deep sedation for endobronchial ultrasound transbronchial needle aspiration. Ann Am Thorac Soc. 2013 Apr;10(2):121-6. doi: 10.1513/AnnalsATS.201209-074OC.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: July 7, 2010
• First Posted (Estimate): July 8, 2010

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: bronchoscopy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Ketamine; Fentanyl; Midazolam; Dexmedetomidine; Diphenhydramine
• Other Study ID Numbers: 810981