Burst Suppression Therapy for Seizures after Cardiac Arrest

(RESTORE Trial)

Overseen By Kevin Bao

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Disqualifiers: Acute cerebral hemorrhage, pregnancy, prisoners

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24-48 hours

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Burst Suppression EEG Target Intravenous Anesthesia for seizures after cardiac arrest?

Research indicates that burst suppression, an EEG pattern used during anesthesia, is associated with outcomes in patients with refractory status epilepticus (a severe form of seizures). This suggests that using burst suppression as a treatment may help manage seizures, although the specific effectiveness for seizures after cardiac arrest is not directly addressed. ^{1 2 3 4 5}

Is Burst Suppression Therapy generally safe for humans?

Burst Suppression Therapy, often used during anesthesia, has been studied for safety in various settings, including surgery and intensive care. While it is used to manage severe seizures and other conditions, it can sometimes indicate deeper anesthesia or potential brain issues, so careful monitoring is essential. ^{1 2 3 4 5}

How is Burst Suppression EEG Target Intravenous Anesthesia different from other treatments for seizures after cardiac arrest?

This treatment is unique because it uses a specific EEG pattern called burst suppression to guide the depth of anesthesia, aiming to control seizures by alternating between high and low brain activity. This approach is different from standard treatments as it involves continuous monitoring and adjustment of brain activity through intravenous anesthesia, which is not commonly used for seizures after cardiac arrest. ^{1 2 3 5 6}

What is the purpose of this trial?

RESTORE is a randomized clinical trial investigating the safety and feasibility of using EEG treatment targets (burst suppression vs. seizure suppression) for post-cardiac arrest refractory status epilepticus treatment.

Research Team

Edilberto Amorim, MD

Principal Investigator

Assistant Professor of Neurology

Eligibility Criteria

This trial is for adults over 18 who've had a non-traumatic, out-of-hospital cardiac arrest and are now in a coma with refractory status epilepticus confirmed by EEG. They must have regained circulation within 45 minutes and be admitted to the ICU. It's not for those with acute brain bleeding or stroke, pregnant women, or prisoners.

Inclusion Criteria

I had a sudden heart stoppage outside of a hospital without injury.

I was diagnosed with a severe seizure condition after a heart attack, confirmed by EEG.

Your heart starts beating again on its own within 45 minutes.

Exclusion Criteria

I have had a recent stroke or brain bleed.

Pregnancy

Prisoners

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive anesthetic treatment targeting burst suppression or seizure suppression on EEG for 24 hours. Intervention may be repeated once in case of PCARSE recurrence.

24-48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment, including seizure recurrence and neurological function at discharge and up to 180 days.

180 days

Treatment Details

Interventions

• Burst Suppression EEG Target Intravenous Anesthesia
• Seizure Suppression EEG Target Intravenous Anesthesia

Trial Overview The RESTORE trial is comparing two types of intravenous anesthesia based on EEG targets: one aiming for burst suppression (reducing brain activity) and the other for seizure suppression (stopping seizures), to see which is safer and more feasible after cardiac arrest.

Participant Groups

Group I: Seizure Suppression EEG Target Experimental Treatment 1 Intervention

Anesthetic will be titrated to achieve seizure suppression on continuous EEG for 24 hours.

Group II: Burst Suppression EEG Target Experimental Treatment 1 Intervention

Anesthetic will be titrated to achieve burst suppression on continuous EEG (50-99% attenuation/suppression) for 24 hours.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

The ZOLL Foundation

Collaborator

Trials

1

Recruited

30+

Findings from Research

In a study of 147 adult patients with refractory status epilepticus treated with continuous IV anesthesia, complete burst suppression (≥50% suppression) was achieved in 21% of patients, but this was not linked to better outcomes like seizure termination or survival.

However, in patients with cerebral anoxia, burst suppression was associated with improved outcomes, showing that 72% of those without burst suppression achieved persistent seizure termination compared to only 29% with burst suppression, and survival rates were also higher (50% vs 14%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Induced Burst Suppression and Clinical Outcomes in Patients With Refractory Status Epilepticus: A 9-Year Cohort Study. Fisch, U., Jünger, AL., Baumann, SM., et al.[2023]

Burst suppression (BS) is a unique EEG pattern characterized by alternating high-voltage slow waves and low-voltage periods, commonly observed during surgery or in ICU settings.

BS can indicate either increased anesthetic depth or potential cerebral damage, serving as a critical marker for clinicians to assess brain function and therapeutic endpoints in patients with severe neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does electroencephalographic burst suppression still play a role in the perioperative setting? Lobo, FA., Vacas, S., Rossetti, AO., et al.[2022]

Burst-suppression is an electroencephalographic pattern caused by various factors, including metabolic suppression from anesthetic medications, indicating its complex physiological mechanisms.

The review discusses both supporting and opposing evidence for using burst-suppression as a therapeutic measure in perioperative settings, highlighting its potential clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroencephalographic Burst-Suppression, Perioperative Neuroprotection, Postoperative Cognitive Function, and Mortality: A Focused Narrative Review of the Literature. Ma, K., Bebawy, JF.[2023]

Burst suppression is an EEG pattern that can occur due to various conditions, including general anesthesia, and is characterized by alternating high and low amplitude brain activity.

Our study found distinct electrophysiological differences in burst suppression patterns between the anesthetics sevoflurane and propofol, suggesting that they may work through different circuit mechanisms in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propofol and sevoflurane induce distinct burst suppression patterns in rats. Kenny, JD., Westover, MB., Ching, S., et al.[2020]

In two children undergoing barbiturate anesthesia for severe epilepsy, EEG monitoring revealed epileptiform discharges during periods of burst suppression, highlighting the complexity of interpreting EEG patterns in this context.

The study emphasizes the need to differentiate between true electrocerebral silence and EEG suppression, as well as between epileptiform discharges and burst patterns, to effectively manage anesthesia depth during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epileptic EEG discharges during burst suppression. Jäntti, V., Eriksson, K., Hartikainen, K., et al.[2008]

Burst-suppression EEG patterns, which show alternating high-power oscillations and periods of inactivity, are observed during conditions like general anesthesia and coma, suggesting they may have protective effects on the brain.

Recent advances in understanding burst-suppression patterns indicate that while they can be used therapeutically, there is ongoing debate about their association with negative clinical outcomes, highlighting the need for careful monitoring and control during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etiology of Burst Suppression EEG Patterns. Shanker, A., Abel, JH., Schamberg, G., et al.[2021]

References

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

Association Between Induced Burst Suppression and Clinical Outcomes in Patients With Refractory Status Epilepticus: A 9-Year Cohort Study. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Does electroencephalographic burst suppression still play a role in the perioperative setting? [2022]

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

Electroencephalographic Burst-Suppression, Perioperative Neuroprotection, Postoperative Cognitive Function, and Mortality: A Focused Narrative Review of the Literature. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Propofol and sevoflurane induce distinct burst suppression patterns in rats. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Epileptic EEG discharges during burst suppression. [2008]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Etiology of Burst Suppression EEG Patterns. [2021]