Neuromuscular Blockade in the Intentive Care Unit, an Observational Study. (CURATIV)

The study Short description of the protocol intended for the lay public. Include a brief statement of the study hypothesis. (Limit: 5000 characters) Neuromuscular blocking agents (NMBAs) are drug capable of inducing a complete paralysis of the muscle. Their use is frequent in the intensive care unit (ICU). Most of the time it is used as a single infusion to facilitate endotracheal intubation, but in the ICU the use of continuous infusion is common in several pathologies: acute distress respiratory syndrome, post-cardiac arrest survivor under hypothermia to prevent shivering, abdominal compartment syndrome, severe traumatic brain injury with uncontrolled intra-cranial pressure and severe asthma among others.

A monitoring of the dose of NMBAs is recommended to guide the depth of paralysis and to guide recovery, but in the ICU, the interest of such a monitoring during continuous infusion is unclear and the level of evidence is low.

The investigators propose to conduct a prospective multicentric observational study to describe the current practice in the use of NMBAs in mechanically ventilated patients in the ICU. As a primary objective we will describe the prevalence of NMBAs use in the ICU. As a secondary objective, the investigators will investigate the impact of protocol and/or monitoring devices of NMBAs on the dose administered and clinical outcome endpoints.

Study Overview

• Status: Completed
• Conditions: Critical Care; Neuromuscular Blockade; Mechanical Ventilation
• Intervention / Treatment: Drug: Neuromuscular Blocking Agents

Detailed Description

Neuromuscular blocking agents (NMBAs) are usually administered during anesthesia for endotracheal tube placement or surgical interventions. But their use is also common in the medical intensive care unit (ICU) (1, 2). Together with sedation and analgesia, they are mainly used in continuous infusion in Acute Respiratory Distress Syndrom (ARDS) (3, 4), but also in post-cardiac arrest survivor under hypothermia to prevent shivering (5), in abdominal compartment syndrome (6), in severe traumatic brain injury with uncontrolled intra-cranial pressure (7) and severe asthma among others.

A monitoring of the treatment is recommended (8) and several monitoring techniques exists: qualitative clinical monitoring is known to be inefficient, qualitative clinical monitoring using scores such as the BSAS (9) or monitoring using peripheral nerve stimulation (train-of-four (TOF) (10)) or other devices such as accelerometry or electromyography.

As opposed to their use in the operating room where the interest of the monitoring is proven, there are discrepancy between studies on whether it is useful to monitor NMBAs in the ICU. For instance, Strange et al. did not observe any advantage of the use of a protocol of NMBAs administration (11), and Baumann et al. came to the same conclusions. However, more recently (12), Hraeich et al. found that the monitoring of NMBAs dosage guided by the TOF allowed to significantly reduce the dose administered during ADRS (13).

Thus, in the ICU, although guidelines recommend to monitor NMBAs administration (8), the level of evidence regarding the interest of monitoring and the device to use for such a monitoring is low.

The investigators propose to conduct a prospective multicentric observational study to describe the current practice in the use of NMBAs in mechanically ventilated patients in the ICU. As a primary objective the investigators will describe the prevalence of NMBAs use in the ICU. As a secondary objective, the investigator will investigate the impact of protocol and/or monitoring devices of NMBAs on the dose administered and clinical outcome endpoints, such as in-ICU mortality, duration of mechanical ventilation or acquired neuromyopathy or other complications of NMBAs.

• Study Type: Observational
• Enrollment (Actual): 282

Contacts and Locations

Study Locations

• France
  • Argenteuil, France, 95100
    • CH D'argenteuil
  • Le Chesnay, France, 78157
    • CH de Versailles
  • Le Kremlin-Bicêtre, France, 94270
    • CHU Kremlin-Bicêtre
  • Le Mans, France, 72037
    • CH Le mans
  • Nantes, France, 44000
    • CHU Nantes
  • Nîmes, France
    • CHU Nîmes
  • Orléans, France
    • CHR Orléans
  • Paris, France
    • Chu La Pitie Salpetriere
  • Pontoise, France, 95303
    • CH de Pontoise
  • Tours, France, 37044
    • CHRU Bretonneau
  • la Roche sur Yon, France, 85925
    • CHD Les Oudairies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized in ICU and under mechanical ventilation

Description

• Inclusion criteria

  • Adult Patients hospitalized in an intensive care unit
  • Patient under invasive mechanical ventilation
  • Administration of at least a single dose of neuromuscular blocking agent

• Exclusion criteria :

  • Administration of a single dose of Succinylcholine or Rocuronium for a rapid-sequence intubation
  • Moribund patient whose life expectancy is less than 24 hours
  • Patient under 18 years old
  • Patient under legal guardianship.
  • Pregnant women
  • Patient already included previously in the study
  • Absence of health insurance in France
  • Neuromuscular blocking agent administered outside the ICU (i.e. in the operating room)

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
Neuromuscular blockade; Patients who will receive neuromuscular blockade during their ICU length stay will be follow until day 28 or their hospital discharge.	Drug: Neuromuscular Blocking Agents; Patient who will receive neuromuscular blockade will be follow during their ICU lenght stay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who receive neuromuscular blockade	Proportion between patients who receive neuromuscular blockade and patients hospitalized in ICU and under mechanical ventilation	ICU Length stay (usually 7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indications of neuromuscular blockade	Description of indications for neuromuscular blockade	ICU Length stay (usually 7 days)
Monitoring of neuromuscular blockade	Proportion of patients in whom neuromuscular blockade was monitored	ICU Discharge (usually 7 days)
Neuromuscular blocking agents administered dose	Total dose and duration of NMBAs	ICU Discharge (usually 7 days)
Tolerance of neuromuscular blocking agents	Acquired ICU weakness, pressure ulcer, ventilator associated pneumonia, other potential side effects neuromuscular blocking agents	ICU Discharge (usually 7 days)
Number of tracheostomy	Proportion of patients who received tracheostomy during their ICU stay	ICU Discharge (usually 7 days)
Duration of ICU stay	Duration of ICU stay	ICU Discharge (usually 7 days)
Duration of mechanical ventilation	Duration of mechanical ventilation	Time from intubation to successfull extubation (usually 5 days)
ICU Mortality	Proportion of patients dead during their ICU length stay	Time of ICU discharge (usually 7 days)

Collaborators and Investigators

• Sponsor: French Society for Intensive Care

Publications and helpful links

General Publications

• Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
• Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
• Arroliga A, Frutos-Vivar F, Hall J, Esteban A, Apezteguia C, Soto L, Anzueto A; International Mechanical Ventilation Study Group. Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest. 2005 Aug;128(2):496-506. doi: 10.1378/chest.128.2.496.
• Arroliga AC, Thompson BT, Ancukiewicz M, Gonzales JP, Guntupalli KK, Park PK, Wiedemann HP, Anzueto A; Acute Respiratory Distress Syndrome Network. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2008 Apr;36(4):1083-8. doi: 10.1097/CCM.0B013E3181653895.
• Lascarrou JB, Le Gouge A, Dimet J, Lacherade JC, Martin-Lefevre L, Fiancette M, Vinatier I, Lebert C, Bachoumas K, Yehia A, Lagarrigue MH, Colin G, Reignier J. Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: observational study of neurological and infectious outcomes. Resuscitation. 2014 Sep;85(9):1257-62. doi: 10.1016/j.resuscitation.2014.05.017. Epub 2014 Jun 2.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2019
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: July 18, 2019
• First Submitted That Met QC Criteria: July 18, 2019
• First Posted (Actual): July 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Blocking Agents
• Other Study ID Numbers: 2019-A01378-49

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: IPD can be obtained from PI after careful evaluation of request by clinical research committee of the French Intensive Care Society

Drug and device information, study documents

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