Safety and Efficacy of Inhaled Sedation in Management of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Detailed Description: Acute exacerbations of chronic obstructive pulmonary disease (COPD) often lead to too much carbon dioxide in the blood and difficulty breathing. Non-invasive ventilation (NIV) can help avoid a breathing tube, but many patients become agitated or uncomfortable with the mask, limiting its success. Traditional sedatives may worsen breathing or build up in the body. Isoflurane is an inhaled anesthetic with bronchodilator properties that can be given in small, quickly adjustable doses using the AnaConDa® device in-line with an NIV circuit. This study will test whether light isoflurane sedation can safely improve NIV tolerance and reduce the need for intubation in COPD flare-ups. The study investigators will enroll 20 adults (age ≥ 18) admitted with a confirmed COPD exacerbation and hypercapnic respiratory failure who meet medical criteria for BiPAP-mode NIV. After obtaining informed consent, each participant will receive isoflurane delivered at 1.5 mL/hour via a syringe pump connected to the AnaConDa® device placed between the ventilator's Y-piece and the patient's mask. The fresh gas flow will be set equal to each patient's minute ventilation plus 0.5 L/min. NIV settings will be adjusted for comfort and gas exchange: pressure support 8-20 cm H₂O (target 10 mL/kg ideal body weight), PEEP 4-6 cm H₂O, respiratory rate 12-16 breaths/min (I:E ratio 1:3-1:4), and FiO₂ 30-40% to maintain SpO₂ 88-94%. Sedation will be titrated to a light level (Richmond Agitation Sedation Scale \[RASS\] -1 to -2). If a patient becomes overly sedated (RASS ≤ -3) or requires endotracheal intubation within 24 hours, this will be recorded as an intervention failure and isoflurane will be stopped immediately. Continuous monitoring will include pulse oximetry, electrocardiogram, and non-invasive blood pressure (every 15 minutes for the first hour, then hourly). Arterial blood gases will be drawn at baseline and at 2, 6, 12, and 24 hours. At each time point we will also record RASS score and ask the patient to rate comfort on a 0-10 visual analogue scale (VAS). The primary outcome is the proportion of patients experiencing intervention failure (intubation or excessive sedation) within 24 hours. Secondary outcomes are changes over time in vital signs (heart rate, blood pressure, respiratory rate), arterial blood gas values (pH, PaCO₂, PaO₂), sedation depth (RASS), patient comfort (VAS), and safety events (hypotension, bradycardia, respiratory depression, serious adverse events). We will follow participants until hospital discharge or intubation. An interim analysis after the first 10 patients will assess safety and futility. The trial will be halted early if more than 50% of participants meet failure criteria or if the serious adverse event rate exceeds 20%. Data will be analyzed on both an intent-to-treat and per-protocol basis. Continuous measures will be compared using paired t-tests or nonparametric equivalents; categorical outcomes will use Chi-square or Fisher's exact tests; time-to-intubation will be analyzed with Kaplan-Meier methods. This study is approved by the Institutional Ethics Committee (BREC 23/121) and will follow ICH-GCP and Declaration of Helsinki guidelines. All participant data will be anonymized and stored in a secure electronic database. Participation is voluntary, and patients may withdraw at any time without affecting their standard medical care.