Clinical trial NCT04524585: Partial Neuromuscular Blockade in Acute Respiratory Distress Syndrome
Official title: Partial Neuromuscular Blockade in Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Respiratory Insufficiency
Extracorporeal Membrane Oxygenation Complication
Neuromuscular Blockade
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO).

Detailed description: Controlling respiratory effort in patients with ARDS 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 severe ARDS patients supported on VV-ECMO.

An esophageal balloon and a catheter will be placed. Once adequate sedation has been ensured, small boluses of cisatracurium will be administered. Then, an infusion of cisatracurium will be started to maintain spontaneous breathing at esophageal pressure swings (Pes) of 3-10 cm H2O or selected diaphragm electrical activity (Edi) targets. 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 24-hour period.

Eligibility criteria: Inclusion Criteria:

1. Potentially injurious respiratory efforts as defined by esophageal pressure swings or occlusion pressure swing AND Riker Sedation-Agitation Scale (SAS) ≤2 (if the clinical team has elected to sedate to that depth).
2. The medical team has undertaken a trial of discontinuing neuromuscular blockade and determined that the patient requires reinstitution of neuromuscular blockade to ensure toleration of ECMO and they are willing for the patient undergo a trial of partial neuromuscular blockade
3. The patient is receiving neuromuscular blockade with no plan to discontinue neuromuscular blockade until the next day and the medical team is willing for the patient to undergo a trial of partial neuromuscular blockade

Exclusion Criteria:

1. Decannulation from VV-ECMO is anticipated within 24 hours
2. Contraindication to esophageal catheterization
3. Contraindication to neuromuscular blockade (allergy, history of malignant hyperthermia)
4. Patient has a condition deemed by the medical team to require complete NMB

Primary outcomes:
measure: Rate of patients achieving and maintaining targeted esophageal pressure swings
timeFrame: Assessed after achievement of Pes targets for 24 hours
Secondary outcomes:
measure: Rates of serious adverse events
timeFrame: Assessed maintenance 24 hours phase
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Ewan Goligher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: