Clinical trial NCT06514209: Effect of Different Depths of Neuromuscular Blockade on Respiratory Mechanics in Patients With Moderate-severe Acute Respiratory Distress Syndrome
Official title: Effect of Different Depths of Neuromuscular Blockade on Respiratory Mechanics in Patients With Moderate-severe Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ARDS
Lung Protective Ventilation
Keywords: ARDS
lung protective ventilation
neuromuscular blockade
respiratory mechanics
Lead sponsor: Southeast University, China
Sponsor class: OTHER
First posted: 2024-07-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: transpulmonary pressure (PL)
timeFrame: At baseline and 15 minutes after each adjustment of the cisatracurium dose.
Secondary outcomes:
measure: esophageal pressure swing（∆Pes）
timeFrame: At baseline and 15 minutes after each adjustment of the cisatracurium dose.
measure: train train of four count (TOF-count)
timeFrame: At baseline and 15 minutes after each adjustment of the cisatracurium dose.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital, Affiliated to Southeast University
state: Jiangsu
Study officials:
References:
citation: 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.