Partial neuromuscular blockade to enable safe spontaneous breathing in acute hypoxemic respiratory failure

Partial Neuromuscular Blockade in Acute Hypoxemic Respiratory Failure

This tests whether a low-dose infusion of the muscle-paralyzing drug cisatracurium can let people with moderate to severe low-oxygen respiratory failure on mechanical ventilation or venovenous ECMO breathe safely on their own while protecting their lungs.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT04524585 on ClinicalTrials.gov

What this trial studies

PNEUMA is a preliminary safety and feasibility effort that uses a titrated infusion of cisatracurium to achieve partial neuromuscular blockade permitting controlled spontaneous breathing in patients with moderate to severe acute hypoxemic respiratory failure. After ensuring adequate sedation, investigators adjust the drug infusion to target an expiratory occlusion pressure (Pocc) between −5 and −15 cmH2O, a range intended to preserve moderate inspiratory effort while avoiding injurious efforts. Once targets are achieved, the protocol documents whether those sedation and dosing targets can be maintained over a 48-hour period. Eligibility was broadened from ARDS on ECMO to patients with AHRF supported with invasive mechanical ventilation or venovenous-ECMO at the enrolling center.

Who should consider this trial

Good fit: Adults with moderate to severe acute hypoxemic respiratory failure supported on invasive mechanical ventilation or venovenous-ECMO (PaO2/FiO2 <150 or FiO2 ≥60% with SpO2 ≤97%) who have no contraindication to neuromuscular blockade or ulnar nerve stimulation and no known neuromuscular disorder.

Not a fit: Patients with contraindications to neuromuscular blockers (for example allergy or malignant hyperthermia), bilateral ulnar neuropathy or wrist burns, or pre-existing neuromuscular disorders are not eligible and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce complications of full paralysis while keeping lung-protective ventilation and allowing some patient-initiated breathing.

How similar studies have performed: Full neuromuscular blockade has been used in ARDS, but partial neuromuscular blockade is a relatively novel approach with limited prior clinical trial data on safety and efficacy.

Eligibility criteria

Inclusion Criteria:

Patients supported on invasive mechanical ventilation for moderate to severe AHRF (PaO2/FiO2 \< 150 mm Hg or FiO2 ≥ 60% with an SpO2 ≤ 97% or receiving venovenous extracorporeal membrane oxygenation)

Exclusion Criteria:

1. Contraindication to neuromuscular blockade (allergy, history of malignant hyperthermia)
2. Contraindication to ulnar nerve stimulation (bilateral peripheral neuropathy, skin burns on both wrists)
3. Previous history of a formally diagnosed neuromuscular disorder

Where this trial is running

Toronto, Ontario

• University Health Network — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Ewan Goligher, MD, PhD — University Health Network, Toronto
• Study coordinator: Glauco M. Plens, MD, PhD

Conditions Respiratory Insufficiency; Neuromuscular Blockade; Mechanical Ventilation