- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00452062
Dexamethasone and the Prevention of Post-Extubation Airway Obstruction in Adults
Mackay Memorial Hospital
Laryngotracheal injury related to intubation may cause narrowing of the airway due to edema of the glottis. Post-extubation airway frequently necessitating re-intubation and resulting in the prolongation of intensive care. Factors correlating with the development of post-extubation stridor include age, female gender, an elevated Acute Physiologic and Chronic Health Evaluation II, trauma related to endotracheal intubation, excessive ETT size, unnecessary tube mobility, increased cuff pressure, frequent tracheal aspirations, infection, arterial hypotension, and a prolonged intubation period. Because the presence of an endotracheal tube (ETT) precludes direct visualization of the upper airway, recognition of edema due to laryngotracheal injury is often difficult. However, upper airway patency may be measured indirectly in the intubated patient by documentation of a leak around the ETT upon deflation of the sealing balloon cuff encircling the ETT. Controversy currently exists regarding the effectiveness of prophylactic steroid therapy for patients considered at high risk for post-extubation stridor. Only a limited number of prospective trials involving adults and evaluating the benefits of corticosteroid therapy prior to extubation have been conducted.
Studies regarding the efficacy of prophylactic corticosteroids for intubated patients have yielded conflicting results due to differences in the number of doses or types of corticosteroids administered.
The present study was conducted to evaluate the effects of prophylactic dexamethasone therapy for a subset of high-risk patients who had been intubated for > 48 hours and who were undergoing their first elective extubation in an ICU setting. The specific objectives were to determine whether multiple doses of dexamethasone are effective in the reduction or prevention of post-extubation airway obstruction in patients with a cuff leak volume (CLV) < 110 mL and to ascertain whether an aftereffect follows the discontinuation of dexamethasone.
Study Overview
Detailed Description
Materials and methods Patients The current study included patients admitted to the adult medical ICU of the Mackay Memorial Medical Center from 1 October 2004 and 1 July 2007 and who met the inclusion criteria described below. Informed consent was obtained from the patients or their relatives prior to entering the trial. This study was approved by the Institutional Research Ethics Board. The cuff-leak test was therefore administered to patients requiring mechanical ventilation for more than 48 hours. All patients were > 18 years of age and met the following weaning criteria: 1) temperature ≤ 38°C for > 8 hours, 2) discontinuous use of sedatives, 3) heart rate ≥ 70 and ≤ 130 /min, 4) systolic blood pressure (SBP) ≥ 80 mm Hg in the absence of vasopressors, 5) fraction of inspired oxygen (FiO2) ≤ 0.6, PaO2 ≥ 60, and partial pressure of oxygen (PaO2)/FiO2 ratio > 200, 6) positive end-expiratory pressure (PEEP) ≤ 5 cm H2O, 7) rapid and shallow ratio of frequency to tidal volume (f/VT ≤ 105), 8) minute ventilation ≤ 15 L/min, and 9) pH ≥ 7.3. Supplemental oxygen was continued to maintain an oxygen saturation > 95% as measured by a pulse oximeter.
Exclusion criteria were: 1) the need for more than one tracheal intubation during the hospital stay, 2) unstable hemodynamics (i.e., a mean SBP < 90 mm Hg, a SBP decrease > 40 mm Hg, or a mean arterial pressure [MAP] < 70 mm Hg), 3) profound recalcitrant hypoxemia (i.e., PaO2 < 60 mm Hg with a FiO2 > 0.50), or 4) administration of corticosteroids 7 days prior to extubation. All patients were intubated with a high-volume, low-pressure cuffed ETT. Patients exhibiting excessive movement were sedated or paralyzed during mechanical ventilation. Routine nursing care included ETT suctioning every 2 hours or as needed to maintain a patent airway. Patients were mechanically ventilated in the volume-assisted control mode with a tidal volume of 10 mL/kg of ideal body weight, a respiratory rate of 20 breaths/minute, and a zero PEEP during CLV measurement. The operator-selected inspiratory tidal volume of 10 mL per kilogram of ideal body weight, displayed as an expiratory tidal volume, was recorded. The balloon cuff was deflated, the expiratory tidal volume was recorded over the 6 subsequent respiratory cycles, and the average of the lowest 3 values was utilized for subsequent analyses. The CLV was determined as the difference in the actual tidal volume before and after cuff deflation.
Study protocol Patients requiring mechanical ventilation for > 48 hours and exhibiting a CLV < 110 mL were therefore included in the trial. The study was prospective, randomized, double-blind, and placebo-controlled. The randomization procedure was performed by a respiratory therapist not involved in patient care using blocked randomization. Patients were randomized to receive intravenous dexamethasone 5 mg per injection, or intravenous normal saline at an equivalent volume. Dexamethasone or normal saline (placebo) was administered every 6 hours for a total of 4 doses. Cuff leak tests were measured one hour after each injection and 24 hours after the 4th injection of dexamethasone or placebo. Both the physician and the staff who administered the treatment were blinded. The ICU physicians were not apprised of the measurements obtained by the respiratory therapist. Extubation was carried out 24 hours after the last injection of intervention fluid. After extubation, the presence of an audible, high-pitched wheeze was an indication for the inhalation of racemic epinephrine.
Patients meeting at least two of the following criteria were assigned to take non-invasive positive-pressure ventilation by face mask: 1) respiratory acidosis (defined as an arterial pH < 7.35 with a partial pressure of arterial carbon dioxide > 45 mm Hg), 2) clinical signs suggestive of respiratory-muscle fatigue or increased respiratory effort (i.e., use of accessory muscles, intercostal retraction, or paradoxical motion of the abdomen), 3) a respiratory rate > 25 breaths per minute for 2 consecutive hours, and 4) hypoxemia (defined as an arterial oxygen saturation of < 90 % or a PaO2 of < 80 mm Hg with a FiO2 > 0.50). Patients were re-intubated with mechanical ventilation support if they met at least one of the following criteria: 1) pH < 7.3 with a partial pressure of carbon dioxide increase > 15 mm Hg, 2) a change in mental status rendering the patient unable to tolerate non-invasive ventilation, 3) a decrease in the oxygen saturation to < 85% despite the use of a high fraction of inspired oxygen (a PaO2 < 50 mm Hg with a FiO2 > 70 %), 4) lack of improvement in signs of respiratory-muscle fatigue, 5) hypotension with a SBP < 80 mm Hg for more than 30 minutes despite adequate volume challenge, 6) a diastolic blood pressure drop > 20 mm Hg, and 7) copious secretions that could not be adequately cleared or that were associated with acidosis, hypoxemia, or changes in mental status (somnolence, agitation, or diaphoresis).
Study Type
Enrollment
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Taipei, Taiwan, 104
- Recruiting
- Mackay Memorial Hospital
-
Contact:
- Wan-Ting Chen, Ms
- Phone Number: 2003 +886-2-25433535
- Email: wanting.b352@ms1.mmh.org.tw
-
Principal Investigator:
- Chao-Hsien Lee, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
All patients were > 18 years of age and met the following weaning criteria:
- Temperature ≤ 38°C for > 8 hours,
- Discontinuous use of sedatives,
- Heart rate ≥ 70 and ≤ 130 /min,
- Systolic blood pressure (SBP) ≥ 80 mm Hg in the absence of vasopressors,
- Fraction of inspired oxygen (FiO2) ≤ 0.6, PaO2 ≥ 60, and partial pressure of oxygen (PaO2)/FiO2 ratio > 200,
- Positive end-expiratory pressure (PEEP) ≤ 5 cm H2O,
- Rapid and shallow ratio of frequency to tidal volume (f/VT ≤ 105),
- Minute ventilation ≤ 15 L/min, and
- pH ≥ 7.3. Supplemental oxygen was continued to maintain an oxygen saturation > 95% as measured by a pulse oximeter.
Exclusion Criteria:
- The need for more than one tracheal intubation during the hospital stay,
- Unstable hemodynamics (i.e., a mean SBP < 90 mm Hg, a SBP decrease > 40 mm Hg, or a mean arterial pressure [MAP] < 70 mm Hg),
- Profound recalcitrant hypoxemia (i.e., PaO2 < 60 mm Hg with a FiO2 > 0.50), or
- Administration of corticosteroids 7 days prior to extubation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
The purpose of this study was to ascertain whether administration of multiple doses of dexamethasone to critically ill intubated patients reduces or prevents the occurrence of post-extubation airway obstruction.
|
Secondary Outcome Measures
Outcome Measure |
---|
The secondary purpose of this study was to ascertain whether administration of multiple doses of dexamethasone to critically ill intubated patients reduces or prevents the occurrence of noninvasive ventilation or re-intubation.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chao-Hsien Lee, MD, Mackay Memorial Hospital
Publications and helpful links
General Publications
- Cheng KC, Hou CC, Huang HC, Lin SC, Zhang H. Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients. Crit Care Med. 2006 May;34(5):1345-50. doi: 10.1097/01.CCM.0000214678.92134.BD. Erratum In: Crit Care Med. 2007 May;35(5):1454.
- Anene O, Meert KL, Uy H, Simpson P, Sarnaik AP. Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med. 1996 Oct;24(10):1666-9. doi: 10.1097/00003246-199610000-00011.
- Chung YH, Chao TY, Chiu CT, Lin MC. The cuff-leak test is a simple tool to verify severe laryngeal edema in patients undergoing long-term mechanical ventilation. Crit Care Med. 2006 Feb;34(2):409-14. doi: 10.1097/01.ccm.0000198105.65413.85.
- Lee CH, Peng MJ, Wu CL. Dexamethasone to prevent postextubation airway obstruction in adults: a prospective, randomized, double-blind, placebo-controlled study. Crit Care. 2007;11(4):R72. doi: 10.1186/cc5957.
Study record dates
Study Major Dates
Study Start
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Respiration Disorders
- Respiratory Insufficiency
- Airway Obstruction
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
Other Study ID Numbers
- MMH-I-S-106
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Airway Obstruction
-
Beth Israel Deaconess Medical CenterMedWaves, IncRecruitingAirway Obstruction | Central Airway ObstructionUnited States
-
McMurray Medical Group, LLCCompletedUpper Airway ObstructionUnited States
-
Massachusetts General HospitalCompletedUpper Airway ObstructionUnited States
-
Rigshospitalet, DenmarkCompletedUpper Airway ObstructionDenmark
-
Zhongda HospitalUnknownMalignant Airway ObstructionChina
-
Assistance Publique - Hôpitaux de ParisRecruitingRespiratory Distress | Upper Airway ObstructionFrance
-
ResMedCompletedRespiratory Failure | Respiratory Insufficiency | Upper Airway ObstructionUnited States
-
Aerin MedicalOhio State UniversityCompletedNasal ObstructionUnited States
-
Massachusetts General HospitalCompletedMechanical Ventilation Complication | Upper Airway ObstructionUnited States
-
University of RochesterCompletedUpper Airway ObstructionUnited States
Clinical Trials on Dexamethasone
-
Ottawa Hospital Research InstituteCompletedPain Syndrome | Early-stage Breast CancerCanada
-
Universitätsklinikum Hamburg-EppendorfGemeinsamer Bundesausschuss (G-BA); Staburo GmbHRecruiting
-
Centre hospitalier de l'Université de Montréal...CompletedPrevention of Hypersensitivity Reactions to PaclitaxelCanada
-
Universidade Federal de PernambucoCompletedDiabetic Macular EdemaBrazil
-
Vanderbilt University Medical CenterTerminatedAsthma | CroupUnited States
-
Dr. Stephen ChoiThe Physicians' Services Incorporated FoundationCompletedShoulder Surgery | Nerve BlockCanada
-
Shanghai Jiao Tong University Affiliated Sixth...CompletedAnalgesia | Time | Brachial Plexus Block | Shoulder Surgery | Dexamethasone | Intravenous Drug UsageChina
-
Poznan University of Medical SciencesRecruitingWrist Injuries | Hand Injuries | Hand Injuries and Disorders | Hand Disease | Wrist DiseasePoland
-
University of California, San FranciscoCompletedOral Lichen Planus | Pemphigus Vulgaris | Mucous Membrane Pemphigoid | Chronic Graft-versus-host-diseaseUnited States
-
University of BelgradeCompleted