Impact of the Depth of Neuromuscular Blockade on Respiratory Mechanics in Moderate to Severe ARDS Patients

The Depth of Neuromuscular Blockade is Not Related to Expiratory Transpulmonary Pressure and Respiratory Mechanics in Moderate to Severe ARDS Patients. A Prospective Cohort Study

Neuromuscular blockade (NMB) is proposed in patients with moderate to severe acute respiratory distress syndrome (ARDS). The supposed benefit of these muscle relaxants could be partly linked to their effects on respiratory mechanics by reducing ventilator induced lung injuries (VILI), especially the so called atelectrauma. Although its monitoring is recommended in clinical practice, data about the depth of NMB necessary for an effective relaxation of the thoracic and diaphragmatic muscles and, therefore, the reduction of the chest wall elastance, are scarce. The investigators hypothesised that complete versus partial NMB can modify respiratory mechanics and its partitioning.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Ventilator-Induced Lung Injury
• Intervention / Treatment: Other: Modulation of the depth of the neuromuscular blockade

Detailed Description

The investigators conducted a prospective study to compare the respiratory mechanics of patients with moderate to severe ARDS according to the NMB depth, using an oesophageal pressure catheter (NutriVent®, Sidam) for transpulmonary pressure (PL) assessment, and facial train of four (TOF) for neuromuscular blockade monitoring. The oesophageal balloon was calibrated according to the method recently described to estimate the individual target volume which is assumed to be more adequate. Each patient was analysed at two different times: deep NMB (TOF = 0) and intermediate to light NMB (TOF > 0). The mechanical ventilation parameters were identical for these two measurements. The primary endpoint was the proportion of patients with expiratory transpulmonary pressure (PLexp) greater than or equal to 0 according to the NMB level, in order to assess the risk of region-dependent atelectasis and alveolar opening/closing injury (atelectrauma). Secondary endpoints included: the impact of the depth of NMB on other partition parameters of respiratory mechanics, and the variability of results according to the type of oesophageal balloon calibration.

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• France
  • Brittany
    • Saint-Brieuc, Brittany, France, 22000
      • Centre Hospitalier de Saint Brieuc

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The population includes mainly pulmonary ARDS with a predominance of SARS-CoV2 pneumonia

Description

Inclusion Criteria:

• Moderate to severe ARDS patients with PaO2/FiO2 ratio < 150 mmHg
• Mechanical ventilation, deep sedation and neuromuscular blockade with continuous infusion of cisatracurium for more than 24 hours
• Presence of an oesophageal catheter
• Written informed consent

Exclusion Criteria:

• contraindication of oesophageal catheter

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Moderate to severe ARDS adult patients under mechanical ventilation and neuromuscular blockade; no intervention	Other: Modulation of the depth of the neuromuscular blockade; Analysis of the respiratory mechanics at two times: Facial train of four = 0, indicating a deep neuromuscular blockade; Facial train of four > 0, indicating a intermediate to light neuromuscular blockade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with expiratory transpulmonary pressure greater than or equal to 0	Proportion of patients with expiratory transpulmonary pressure greater than or equal to 0 according to the level of neuromuscular blockade (%)	one day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inspiratory transpulmonary pressure	Inspiratory transpulmonary pressure according to the level of neuromuscular blockade (cmH20)	one day
Respiratory system compliance	Respiratory system compliance according to the level of neuromuscular blockade (ml/cmH20)	one day
Chest wall elastance	Chest wall elastance according to the level of neuromuscular blockade (cmH2O/l)	one day
Pulmonary elastance	Pulmonary elastance according to the level of neuromuscular blockade (cmH2O/l)	one day
Driving pressure	Driving pressure according to the level of neuromuscular blockade (cmH20)	one day
Transpulmonary driving pressure	Transpulmonary driving pressure according to the level of neuromuscular blockade (cmH20)	one day
Plateau pressure	Plateau pressure according to the level of neuromuscular blockade (cmH20)	one day
Oesophageal balloon calibration	Proportion of patients with expiratory transpulmonary pressure greater than or equal to 0 according to the oesophageal balloon calibration volume (%)	one day

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Saint-Brieuc
• Investigators: Principal Investigator: Nicolas BARBAROT, MD, Centre Hospitalier Saint Brieuc

Publications and helpful links

General Publications

• Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, Guerin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP, Pesenti A, Tobin M, Mancebo J, Brochard L; PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine). The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014 Mar 1;189(5):520-31. doi: 10.1164/rccm.201312-2193CI.
• Alhazzani W, Belley-Cote E, Moller MH, Angus DC, Papazian L, Arabi YM, Citerio G, Connolly B, Denehy L, Fox-Robichaud A, Hough CL, Laake JH, Machado FR, Ostermann M, Piraino T, Sharif S, Szczeklik W, Young PJ, Gouskos A, Kiedrowski K, Burns KEA. Neuromuscular blockade in patients with ARDS: a rapid practice guideline. Intensive Care Med. 2020 Nov;46(11):1977-1986. doi: 10.1007/s00134-020-06227-8. Epub 2020 Oct 26.
• Guervilly C, Bisbal M, Forel JM, Mechati M, Lehingue S, Bourenne J, Perrin G, Rambaud R, Adda M, Hraiech S, Marchi E, Roch A, Gainnier M, Papazian L. Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome. Intensive Care Med. 2017 Mar;43(3):408-418. doi: 10.1007/s00134-016-4653-4. Epub 2016 Dec 24.
• Baedorf Kassis E, Train S, MacNeil B, Loring SH, Talmor D. Monitoring of neuromuscular blockade: a comparison of train-of-four and the Campbell diagram. Intensive Care Med. 2018 Dec;44(12):2305-2306. doi: 10.1007/s00134-018-5420-5. Epub 2018 Oct 22. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 21, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Train of four; Oesophageal pressure; Transpulmonary pressure; Neuromuscular blockade
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: 2023-A00165-40

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