Caregiver Education for Paralysis Management

(ED-AWARENES II Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Brian Fuller, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Must be taking: Neuromuscular blockers

Disqualifiers: Neurologic injury, Death, Transfer, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The investigators will screen all mechanically ventilated ED patients for study eligibility and will enroll all consecutive patients satisfying inclusion and exclusion criteria. The study design is a pragmatic, multicenter, stepped wedge cluster randomized trial, enrolling at five sites over a 3-year period, divided into six time periods of six months. Prior to the study, each site will be randomized to their position within the design. One site will cross to the intervention period (i.e. succinylcholine as default neuromuscular blocker) every six months from the 2nd to 6th time period. Cluster order will be determined by computer-based randomization. To begin, each site will be exposed to control conditions; by the end of the study, each site will be exposed to intervention conditions. Patients in the control phase will receive usual care, and this phase will be entirely observational. After six months, a site will enter a 2-month transition phase. In this phase, the investigators will implement the intervention, similar to how they have implemented other ED-based interventions for mechanically ventilated patients. The investigators will engage and educate ED clinicians on the importance of AWP prevention and the study objectives. The intervention framework relies on the use of "nudges", without restricting choice. The use of neuromuscular blockers (i.e. "paralytic" medications) is already part of routine care in the ED in order to facilitate endotracheal intubation and initiation of mechanical ventilation for patients with acute respiratory failure. The two most common neuromuscular blockers used in the ED are succinylcholine and rocuronium. The preliminary data show a strong association between rocuronium (a longer-acting neuromuscular blocker) use and AWP. Therefore, this study aims to improve care by educating caregivers on AWP and the use of the neuromuscular blockers, which are already routinely used, and studying that process in a rigorous fashion. The default neuromuscular blocker in the intervention phase will be succinylcholine. Succinylcholine will be the default over rocuronium because: 1) it has safely been the default neuromuscular blocker of choice in the ED for \>40 years ; 2) its 5-minute duration of action greatly reduces AWP risk; 3) the preliminary data regarding an increased risk of AWP with rocuronium and 4) ED rocuronium use has increased despite no patient-centered studies showing benefit over succinylcholine. Passive alerts (i.e. graphics, pocket cards) will also be strategically placed in the ED, and active alerts will be used as reminders before every nursing shift (i.e. "the huddle"). After this transition phase, the site will begin the intervention phase, and patients will again receive clinician-directed care, just after the intervention.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study involves the use of neuromuscular blockers, it's best to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the treatment Education, Educational Intervention, Coping Education, Mental Health Education, Standard neuromuscular blocker practices, Neuromuscular blockers, Paralytic medications, Succinylcholine, Rocuronium?

Research shows that sugammadex can quickly and safely reverse the effects of neuromuscular blockers like rocuronium, which helps in managing muscle relaxation during surgeries. This suggests that using sugammadex in combination with neuromuscular blockers can improve patient outcomes by ensuring rapid recovery from muscle paralysis. ^{1 2 3 4 5}

Is the use of rocuronium and its reversal with sugammadex safe for humans?

Rocuronium, used for muscle relaxation during surgery, is generally safe and well-tolerated in humans, especially when its effects are reversed with sugammadex. Studies show that it does not cause significant adverse effects, even in high-risk patients, and sugammadex effectively reverses its effects without safety concerns. ^{6 7 8 9 10}

How is the drug used in the Caregiver Education for Paralysis Management trial different from other drugs for paralysis?

This treatment uses neuromuscular blockers like rocuronium, which can be rapidly reversed by sugammadex, allowing for quick recovery from paralysis. This is different from older drugs like succinylcholine, which have a longer duration and more side effects. ^{1 3 4 11 12}

Eligibility Criteria

The ED-AWARENESS-2 Trial is for adults over 18 who are receiving mechanical ventilation via an endotracheal tube in the emergency department (ED) and have been treated with neuromuscular blockers. It excludes those with neurological injuries that prevent assessment of awareness during paralysis, patients transferred out, or those who die before extubation.

Inclusion Criteria

I am 18 years old or older.

I am on a breathing machine through a tube in my windpipe.

I have been treated with a muscle relaxant for intubation.

Exclusion Criteria

Transfer to another hospital from the ED

I have a brain condition that makes it hard to assess my pain.

The participant has passed away before being removed from a breathing tube.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Not specified

Control Phase

Patients receive usual care with standard neuromuscular blockers; this phase is entirely observational.

6 months

Transition Phase

Implementation of the intervention with education of ED clinicians on AWP prevention and study objectives.

2 months

Intervention Phase

Patients receive succinylcholine as the default neuromuscular blocker, with passive and active alerts to support the intervention.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for PTSD symptoms, depression, anxiety, and quality of life.

30 days

Treatment Details

Interventions

• Education (Behavioral Intervention)
• Standard neuromuscular blocker practices (Other)

Trial Overview This trial tests whether educating ED clinicians on the use of succinylcholine—a short-acting neuromuscular blocker—over rocuronium can reduce risks associated with prolonged paralysis. The study uses a stepped wedge design across five sites to compare standard practices against this educational intervention.

Participant Groups

Group I: After group Experimental Treatment 1 Intervention

Mechanically ventilated emergency department patients receiving neuromuscular blockers after an educational initiative aimed at improving use of shorter acting neuromuscular blocker practices in the ED.

Group II: Before group Active Control 1 Intervention

Mechanically ventilated emergency department patients receiving standard neuromuscular blockers prior to an educational initiative on the importance of ED-based targeted shorter acting neuromuscular blocker.

Standard neuromuscular blocker practices is already approved in United States, United States, European Union, European Union for the following indications:

🇺🇸 Approved in United States as Succinylcholine for:

• Facilitation of endotracheal intubation
• Initiation of mechanical ventilation for acute respiratory failure

🇺🇸 Approved in United States as Rocuronium for:

• Facilitation of endotracheal intubation
• Initiation of mechanical ventilation for acute respiratory failure

🇪🇺 Approved in European Union as Succinylcholine for:

• Facilitation of endotracheal intubation
• Initiation of mechanical ventilation for acute respiratory failure

🇪🇺 Approved in European Union as Rocuronium for:

• Facilitation of endotracheal intubation
• Initiation of mechanical ventilation for acute respiratory failure

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cooper University Hospital/Cooper Medical School of Rowan University Camden, NJ

Hennepin Healthcare Minneapolis, MN

Roy J. and Lucille A. Carver College of Medicine Iowa City, IA

University of Washington School of Medicine Seattle, WA

Who Is Running the Clinical Trial?

Washington University School of Medicine Lead Sponsor

National Heart, Lung, and Blood Institute (NHLBI) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical implications of new neuromuscular concepts and agents: so long, neostigmine! So long, sux! [2022] Although antiquated and long targeted for obsolescence, neostigmine and succinylcholine still serve the anesthesia community, decades after their inferior pharmacological profiles have been recognized. The need to quickly establish a good intubation condition with a relaxant that will recover rapidly is fundamental to safe anesthesia practice. So is the need to restore muscle power safely and quickly at the end of surgery, by reversing a residual neuromuscular block. Recent data have shown that sugammadex can safely and rapidly reverse profound neuromuscular block established by rocuronium and vecuronium. This allows for use of rocuronium to establish a good intubation condition, and use of sugammadex to terminate the neuromuscular block at will. The present article assesses the clinical implications of such therapeutic regimen, and provides an educated guess on how the clinical neuromuscular practice might change, if and when sugammadex becomes clinically available.

2. Brazil pubmed.ncbi.nlm.nih.gov

Use of neuromuscular blockers in Brazil. [2022] The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers, focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of neuromuscular blockers. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main neuromuscular blockers used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to neuromuscular blockers were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to neuromuscular blockers. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice.

3. United States pubmed.ncbi.nlm.nih.gov

Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to Small Doses of Sugammadex between Elderly and Nonelderly Patients. [2019] WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients.

4. Italy pubmed.ncbi.nlm.nih.gov

Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: a randomized controlled study. [2019] This randomized controlled study compared the recovery times of sugammadex and neostigmine as antagonists of moderate rocuronium-induced neuromuscular block in patients with liver cirrhosis and controls undergoing liver resection.

5. England pubmed.ncbi.nlm.nih.gov

Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. [2021] Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.

6. Spain pubmed.ncbi.nlm.nih.gov

[Rocuronium]. [2018] Rocuronium is a new nondepolarizing neuromuscular blocking agent (NDNMBA) that has recently been introduced for clinical use. Its main advantage over other such agents is its rapid onset of action, which may lead to its use as the relaxant of choice when rapid intubation is required. An additional advantage is that, unlike other amino-steroidal NDNMBAs, rocuronium does not produce active metabolites. The potency of rocuronium is five times lower than that of vecuronium and its half life at its place of effect is shorter. Selectivity for the laryngeal muscle system is greater, possibly explaining the rapid onset observed. Hemodynamic stability, along with the absence of histamine release even at doses as high as 4 to 5 ED95, allow it to be used in high risk patients. Successful use has been reported in emergency surgery in patients with full stomachs, in cesarean deliveries, in cardiovascular surgery, and in liver, kidney and other transplants. Rocuronium administered in repeated doses or in continuous infusion provides adequate muscle relaxation over the required period, with predictable reversibility of effects.

7. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial. [2018] Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

8. England pubmed.ncbi.nlm.nih.gov

Neuromuscular block. [2018] Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built-in self-destruct mechanism that makes them specially useful in kidney or liver failure, and the vecuronium group, which are specially free from unwanted side effects. Of this latter group, the compound rocuronium is of special interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors.

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study. [2022] Sugammadex facilitates rapid reversal of rocuronium- and vecuronium-induced neuromuscular blockade. This study aimed to evaluate the safety, tolerability and pharmacokinetics of high doses of sugammadex (up to 96 mg/kg) in healthy subjects.

10. England pubmed.ncbi.nlm.nih.gov

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1). [2022] Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved and no adverse events or other safety concerns were reported.

11. France pubmed.ncbi.nlm.nih.gov

Reduced-dose rocuronium for day-case tonsillectomy in children where volatile anaesthetics are not used: operating room time saving. [2018] Mivacurium, rocuronium, and vecuronium are neuromuscular blocking agents (NMB) commonly used in pediatric day-case anesthesia. Mivacurium is the most appropriate NMB for short surgical procedures where NMB drugs were required but is not available in all countries.

12. Brazil pubmed.ncbi.nlm.nih.gov

Prophylactic use of pregabalin for prevention of succinylcholine-induced fasciculation and myalgia: a randomized, double-blinded, placebo-controlled study. [2017] Succinylcholine is commonly used to achieve profound neuromuscular blockade of rapid onset and short duration.