Partial Neuromuscular Blockade in Acute Respiratory Distress Syndrome (PNEUMA)

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).

Study Overview

• Status: Terminated
• Conditions: Respiratory Insufficiency; Neuromuscular Blockade; Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Drug: Neuromuscular blockade

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Partial NMB

Drug: Neuromuscular blockade; Cisatracurium will be infused to achieve esophageal pressure targets and maintain a Riker Sedation-Agitation Scale (SAS) score of 1-2. Additional boluses of cisatracurium will be delivered as required and adjustment of continuous infusion rate. 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 24-hour period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of patients achieving and maintaining targeted esophageal pressure swings	Assessed after achievement of Pes targets for 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Rates of serious adverse events	Assessed maintenance 24 hours phase

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 19-5975

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No