Mechanical Ventilation, Neuromuscular Blockade, Respiratory Insufficiency
Conditions
Brief summary
PNEUMA is a preliminary safety and feasibility trial of a novel approach to the titration of neuromuscular blockade (NMB) to safe spontaneous breathing in patients with moderate to severe acute hypoxemic respiratory failure (AHRF) supported with invasive mechanical ventilation.
Detailed description
Controlling respiratory effort in patients with AHRF can be challenging, as they often exhibit a very high respiratory drive despite receiving high doses of sedatives. Consequently, these patients usually receive full neuromuscular blockade, with the goal to avoid such injurious respiratory efforts. Unfortunately, full neuromuscular blockade is not without complications. To address this issue, the use of partial neuromuscular blockade has been proposed as a strategy to maintain respiratory muscle activity while providing lung protective ventilation. The objective of this study is to demonstrate the safety and feasibility of safe spontaneous breathing using partial NMB in moderato to severe AHRF patients supported with invasive mechanical ventilation. Once adequate sedation has been ensured, an infusion of cisatracurium will be started to maintain spontaneous breathing with moderate levels of inspiratory effort, defined by expiratory occlusion pressure (Pocc) between -5 and -15 cmH2O. After establishing a sedation and NMB dosing regimen at which safe spontaneous breathing is achieved, we will document whether these targets can be maintained over a 48-hour period. On December 11 2025, this study has been amended to broaden eligibility criteria from patients with acute respiratory distress syndrome supported on extracorporeal membrane oxygenation (ECMO) to patients with AHRF supported with invasive mechanical ventilation or with venovenous-ECMO. Additionally, the study intervention duration was extended from 24 hours to 48 hours or until hypoxemia is resolved (FiO2 ≤ 40% on PEEP ≤ 8 cmH2O), whichever occurs first. Finally, the study intervention was modified to remove the use of esophageal balloon, and to include sedation and neuromuscular blockade titration targeting Pocc between -5 to -15 cmH2O and according to predefined safety criteria assessed using train of four, respiratory drive and comfort assessments. A total of 15 patients will be enrolled after the amendment, in addition to the 8 patients already enrolled, for a total of 23 patients. Going forward, only patients in whom the intervention is initiated will count toward the study sample size.
Interventions
DRUGCisatracurium
Cisatracurium will be infused to achieve Pocc targets after ensuring adequate sedation. Sedation will be titrated to avoid dyspnea, assessed with P0.1 targets between -1.5 and -3.5 cmH2O and Mechanical Ventilation Respiratory-Distress Observation Scale (MV-RDOS) ≤ 3. If there is no sign of dyspnea or discomfort based on P0.1, MV-RDOS, hemodynamics and the train-of-four ratio is ≥ 60% (compatible with ability to interact using peripheral muscles), sedation will be carefully reduced. After establishing a sedation and NMB strategy at which safe spontaneous breathing is achieved, we will seek to determine whether these targets can be maintained over a 48-hour period or until hypoxemia is resolved (FiO2 ≤ 40% on PEEP ≤ 8 cmH2O), whichever occurs first.
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of patients achieving and maintaining targeted expiratory occlusion pressure (Pocc) | Assessed for 48 hours after study intervention initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of serious adverse events | Assessed for 48 hours after study intervention initiation | — |
| Paralysis Recall | Assessed after 48 hours of the study intervention, as soon as the patient is extubated and oriented. | Evaluted using the modified Brice questionnaire. |
Countries
Canada
Contacts
Primary ContactGlauco M. Plens, MD, PhD
Outcome results
None listed