Partial Neuromuscular Blockade in Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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Partial Neuromuscular Blockade in Acute Respiratory Distress Syndrome

Conditions
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Respiratory Insufficiency, Extracorporeal Membrane Oxygenation Complication, Neuromuscular Blockade

Intervention / Treatment
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* Drug: Neuromuscular blockade


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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Partial NMB<br> | Drug: Neuromuscular blockade<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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