Continuous vs Bolus Neuromuscular Blockade Regimens in Moderate to Severe Hypoxemic Respiratory Failure and ARDS (COBRA)

Study Title: The Effect of Continuous vs Bolus Neuromuscular Blockade for Patients with Moderate to Severe HRF and ARDS: A Pilot Randomized Controlled Trial

Background:

Acute Respiratory Distress Syndrome (ARDS) affects ~10% of ICU patients and carries high morbidity and mortality. Neuromuscular blockade agents (NMBAs), especially cisatracurium, have historically been administered via continuous infusion to improve oxygenation and reduce ventilator-induced lung injury. However, recent evidence (e.g., ROSE trial) questions this approach, and emerging guidelines suggest intermittent bolus dosing may offer similar benefits with fewer adverse effects. There is a lack of direct comparative data, creating uncertainty in clinical practice.

Hypothesis & Objectives:

The study hypothesizes that a multicenter RCT comparing intermittent bolus vs continuous NMBA infusion in ARDS is feasible and that bolus dosing may show trends toward improved outcomes (e.g., ventilator-free days, fewer adverse events).

Primary objective: Assess feasibility of a definitive trial. Feasibility aims: 1. Recruitment rate (target ≥75%) 2. Protocol adherence (≥85%) 3. Data completeness (≥95%) 4. Safety monitoring of adverse events.

Secondary (exploratory) objectives: Compare 28-day ventilator-free days (VFDs), mortality, ICU/hospital length of stay, and ICU-acquired weakness.

Methods: This is a multicenter, prospective, pilot RCT in Alberta ICUs. 100 adult patients with moderate to severe ARDS will be randomized within 24 hours of diagnosis to either: 1. Intermittent bolus NMBA dosing OR 2. Continuous NMBA infusion (up to 48 hours). Both arms will receive lung-protective ventilation and guideline-based sedation.

Analysis: Feasibility outcomes will be described with 95% confidence intervals. Exploratory clinical outcomes will follow intention-to-treat principles using regression models. Results will inform design and sample size for a full-scale trial.

Risks & Mitigation: Risks such as protocol non-adherence, ICU-acquired weakness, and data loss will be managed via clinician education, adherence monitoring, and real-time data checks. Safety protocols, including allowance for rescue boluses and adherence to sedation best practices, will be enforced.

Team: Led by Drs. Parhar and Doig with a multidisciplinary team of critical care and clinical trial experts, the group has a strong track record in ICU research and implementation.

Significance & Knowledge Translation: This study addresses a critical evidence gap in ARDS care. Findings will inform future guidelines and practice by establishing whether bolus NMBA administration is a feasible, effective, and safer alternative to continuous infusion. Results will be disseminated through academic and clinical networks and will lay the groundwork for a large-scale, definitive RCT.

Inclusion criteria

Age ≥18 years

• Mechanically ventilated and on a controlled ventilation mode
• Diagnosis of moderate to severe ARDS (PaO₂/FiO₂ ≤150 mmHg on PEEP ≥5 cm H₂O)
• Bilateral pulmonary infiltrates consistent with ARDS
• Randomized within 24 hours of meeting ARDS criteria

Exclusion criteria

• Pregnancy
• Known allergy or contraindication to rocuronium
• Neuromuscular disorders (e.g., myasthenia gravis, Guillain-Barré syndrome)
• Brain death or decision for withdrawal of life-sustaining therapy
• Enrollment in a conflicting interventional trial