Dexamethasone and the Prevention of Post-Extubation Airway Obstruction in Adults

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).