Effect of Different Depths of Neuromuscular Blockade on Respiratory Mechanics in Patients With Moderate-severe Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse alveolar injury caused by a variety of pulmonary and extrapulmonary factors, leading to refractory hypoxemia. It has high incidence and mortality rates. Neuromuscular blocking agents (NMBAs) play a crucial role as adjunctive therapy for ARDS, aiding in lung-protective ventilation by inhibiting excessive spontaneous breathing, improving patient-ventilator synchrony, and reducing barotrauma.

Determining the appropriate depth of muscle relaxation in moderate to severe ARDS patients receiving NMBAs remains a clinical challenge. Research has shown that partial neuromuscular blockade is feasible in certain ARDS patients. However, large randomized controlled trials (RCTs) and clinical practices often use higher doses of NMBAs to ensure complete cessation of spontaneous breathing. This indicates an ongoing debate regarding the optimal depth of neuromuscular blockade necessary for lung-protective ventilation in ARDS patients. It also raises the question of whether the optimal depth of neuromuscular blockade varies among patients with different severities of ARDS.

This study aims to investigate changes in respiratory mechanics and other physiological parameters in moderate to severe ARDS patients under different depths of neuromuscular blockade. The investigators will evaluate the impact of targeted neuromuscular blockade depth on lung protection in these patients.

Study Overview

• Status: Recruiting
• Conditions: ARDS; Lung Protective Ventilation
• Intervention / Treatment: Drug: cisatracurium

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lihong Xu; Phone Number: +86 18551696812; Email: 220223899@seu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhongda Hospital, Affiliated to Southeast University
      • Contact: Yingzi Huang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with moderate to severe ARDS requiring the use of NMBAs, as assessed by clinicians (Berlin definition 2012: PaO2/FiO2 < 150 mmHg, PEEP ≥ 5).
2. Age: 18-85 years.
3. Signed informed consent.

Exclusion Criteria:

1. History of allergy to NMBAs.
2. Open chest or abdominal injuries.
3. Patients with pulmonary masses, lung transplantation, or lung resection.
4. Contraindications to esophageal catheter placement.
5. Pregnant patients.
6. Contraindications to TOF measurement (e.g., history of neuromuscular disease, presence of a cardiac pacemaker).
7. Severe dysfunction of other organs with an expected short-term mortality (within 7 days) or palliative care.
8. Previous inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Moderate-Severe ARDS patients; The dose of cisatracurium was gradually adjusted to achieve different depth of muscle relaxation

Drug: cisatracurium; The initial bolus dose of cisatracurium injection is 0.05-0.1mg/kg, followed by a continuous infusion of 1ug/kg/min of cisatracurium, with data on vital signs, respiratory mechanics, TOF response, etc. recorded after a 15-minute wait. The maintenance infusion dose of cisatracurium is then gradually increased in a gradient of 0.5ug/kg/min, with data collection after a 15-minute wait after each increase. If the patient's spontaneous breathing completely disappears, the infusion dose of cisatracurium will no longer be increased, and the titration will end.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
transpulmonary pressure (PL)	At baseline and 15 minutes after each adjustment of the cisatracurium dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
esophageal pressure swing（∆Pes）	At baseline and 15 minutes after each adjustment of the cisatracurium dose.
train train of four count (TOF-count)	At baseline and 15 minutes after each adjustment of the cisatracurium dose.

Collaborators and Investigators

• Sponsor: Southeast University, China

Publications and helpful links

General Publications

• 1. Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS: Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012, 307(23):2526-2533. 2. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116. 3. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116. 4. Doorduin J, Nollet JL, Roesthuis LH, et al. Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes. Am J Respir Crit Care Med. 2017;195(8):1033-1042. doi:10.1164/rccm.201605-1016OC 5. Guervilly C, Bisbal M, Forel JM et al (2017) Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome. Intensive Care Med 43:408-418.17. Bouju P, Tadié JM, Barbarot N, et al. Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study. Ann Intensive Care. 2017;7(1):10. 6. Thompson Bastin ML, Smith RR, Bissell BD, et al. Comparison of fixed dose versus train-of-four titration of cisatracurium in acute respiratory distress syndrome. J Crit Care. 2021;65:86-90. 7. Hraiech S, Forel JM, Guervilly C, et al. How to reduce cisatracurium consumption in ARDS patients: the TOF-ARDS study. Ann Intensive Care. 2017;7(1):79.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 21, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 21, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: respiratory mechanics; ARDS; lung protective ventilation; neuromuscular blockade
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Blocking Agents; Cisatracurium
• Other Study ID Numbers: ARDS-NMBAs study 2024-07-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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