Seizure Detection Using SEDline During Therapeutic Hypothermia in Cardiac Arrest Victims

• Sponsor: Gil Joon Suh (Other)
• Overall Status: Completed
• CT.gov ID: NCT01946802
• Collaborator: Masimo Corporation (Industry), Humed Co., Ltd (Other)
• Enrollment: 39
• Location: 1
• Duration (Months): 22
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Current guidelines recommend the use of sedatives and neuromuscular blocking agents to avoid shivering during therapeutic hypothermia in cardiac arrest victims. Therefore, it is difficult to detect seizure and the frequent or continuous EEG monitoring is recommended. However, it is difficult to follow this recommendation in most clinical situations due to the lack of specialized devices and persons. The purpose of this study is whether SEDline (frontal 4-channel EEG device) has a diagnostic value to detect seizure during therapeutic hypothermia in cardiac arrest victims.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Device: Frontal 4 channel EEG

Detailed Description

1. Treatment of cardiac arrest victims Enrolled patients receive basic and advanced cardiac life support according to the 2010 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC).

After acquiring sustained return of spontaneous circulation (ROSC), the patients are immediately admitted to the ICU and are provided postresuscitation care including mild therapeutic hypothermia for 24 hours post-ROSC.

During therapeutic hypothermia, their core temperatures are maintained from 32 to 34°C.

Then rewarming is conducted (< 0.25°C/hour) till core temperature 36.5°C. To avoid shivering, we use sedatives and neuromuscular blocking agents during the therapeutic hypothermia.

1. Conventional EEG Conventional EEG is conducted for 30 minutes at

1. During therapeutic hypothermia and rewarming (within 72 hours after cardiac arrest) Then, the results are interpreted by a neurologist for the presence of seizure.

1. SEDline SEDline is monitored during the simultaneous period with the conventional EEG. Data retrieved from the SEDline are blindly interpreted by 3 investigators to determine the presence of seizure activity.

The presence of seizure activity in SEDline is determined by the definition

1. Electrographic seizure: rhythmic discharge or spike and wave pattern with definite evolution in frequency, location, or morphology lasting several seconds.

2. Spike: Transient, clearly distinguishable from background activity, with pointed peak at conventional paper speeds and a duration of 20 to less than 70 ms

3. Anti-epileptic drug The use of anti-epileptic drugs is guided by the results of conventional EEG or the presence of clinically seizure-like movement

4. Gold standard The presence of Seizure identified in conventional EEG.

5. Primary outcome The diagnostic performance of SEDline to detect seizure will be tested: Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under receiver operating characteristics curve (AUC).

Study Design

• Study Type: Observational
• Actual Enrollment: 39 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Trial of Device for Seizure Detection Using SEDline During Therapeutic Hypothermia in Cardiac Arrest Victims
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Frontal 4 channel EEG Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.	Device: Frontal 4 channel EEG; Simultaneous conventional EEG and SEDline monitoring for 30 minutes during and after therapeutic hypothermia; Other Names: SEDline, Masimo corporation

Outcome Measures

Primary Outcome Measures

1. Percentage of Seizure-positive and Seizure-negative That Were Correctly Classified by the SEDline in All Evaluated Cases [Within 72 hours after cardiac arrest]

   Conventional EEG (gold standard for seizure detection) and SEDline monitoring will be conducted simultaneously for 30 minutes at During therapeutic hypothermia and rewarming (12 ~ 72 hours after cardiac arrest). Then, data retrieved from the conventional EEG and SEDline will be interpreted and analyzed for the presence of seizure.

Secondary Outcome Measures

1. Sensitivity of SEDline for Seizure Detection [Within 72 hours after cardiac arrest]

   Sensitivity measured the percentage of seizures identified by the SEDline in cases those were identified as seizures by the conventional EEG.

2. Specificity [Within 72 hours after cardiac arrest]

   Specificity measured the percentage of seizure-negative identified by the SEDline in cases those were identified as seizure-negative by the conventional EEG.

3. Positive Predictive Value [Within 72 hours after cardiac arrest]

   Positive predictive value measured the percentage of seizures identified by the conventional EEG in cases those were identified as seizures by the SEDline.

4. Negative Predictive Value [Within 72 hours after cardiac arrest]

   Negative predictive value measured the percentage of seizure-negative identified by the conventional EEG in cases those were identified as seizure-negative by the SEDline.

5. Area Under Receiver Operating Characteristics Curve (AUC) of SEDline for Seizure Detection [Within 72 hours after cardiac arrest]

   The Area under receiver operating characteristics curve (AUC) of SEDline represents the accuracy of the SEDline to detect seizures compared with the conventional EEG.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.

• Cardiac arrest is defined as cessation of cardiac mechanical activity, confirmed by the absence of a detectable pulse, unresponsiveness, and apnea.

Exclusion Criteria:

• Age < 18 years old

• Contraindication to therapeutic hypothermia: active life-threatening bleeding, septic shock, or refractory fatal arrhythmia..

• Intracranial pathology including hemorrhage or tumor

• Visible generalized seizure before the study enrollment

• Advanced directives to withdraw life-sustaining treatment

• No informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Emergency Medicine, Seoul National University Hospital	Seoul		Korea, Republic of	110-744

Sponsors and Collaborators

• Gil Joon Suh
• Masimo Corporation
• Humed Co., Ltd

Investigators

• Study Director: Gil Joon Suh, Prof, Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Crepeau AZ, Rabinstein AA, Fugate JE, Mandrekar J, Wijdicks EF, White RD, Britton JW. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology. 2013 Jan 22;80(4):339-44. doi: 10.1212/WNL.0b013e31827f089d. Epub 2013 Jan 2.
• HOCKADAY JM, POTTS F, EPSTEIN E, BONAZZI A, SCHWAB RS. ELECTROENCEPHALOGRAPHIC CHANGES IN ACUTE CEREBRAL ANOXIA FROM CARDIAC OR RESPIRATORY ARREST. Electroencephalogr Clin Neurophysiol. 1965 May;18:575-86.
• Rossetti AO, Urbano LA, Delodder F, Kaplan PW, Oddo M. Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest. Crit Care. 2010;14(5):R173. doi: 10.1186/cc9276. Epub 2010 Sep 29.

• Responsible Party: Gil Joon Suh, Professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT01946802
• Other Study ID Numbers: H-1303-013-470
• First Posted: Sep 20, 2013
• Last Update Posted: Mar 23, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Gil Joon Suh, Professor, Seoul National University Hospital: Heart arrest; Cardiopulmonary resuscitation; Hypothermia induced; Seizures; Electroencephalography
• Additional relevant MeSH terms: Seizures; Heart Arrest; Hypothermia

Study Results

Participant Flow

Recruitment Details	Form 31/12/2014 to 19/08/2016 In the Emergency Intensive Care Unit of Seoul National University Hospital
Pre-assignment Detail	53 were screened for eligibility. 9 were excluded (4 Advanced directives to withhold or withdraw life-sustaining treatment, 3 No informed consent, 1 Known intracranial pathology, and 1 Visible generalized seizure). 44 provided informed consents. 5 were withdrawn(see baseline characteristics). Finally 39 patients were enrolled.

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic cardiac arrest.
Period Title: Overall Study
STARTED	44
COMPLETED	39
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest. Frontal 4 channel EEG: Simultaneous conventional EEG and SEDline monitoring for 30 minutes during and after therapeutic hypothermia
Overall Participants	39
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 53.8%
>=65 years	18 46.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	14 35.9%
Male	25 64.1%
Region of Enrollment (participants) [Number]
Korea, Republic of	39 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Seizure-positive and Seizure-negative That Were Correctly Classified by the SEDline in All Evaluated Cases
Description	Conventional EEG (gold standard for seizure detection) and SEDline monitoring will be conducted simultaneously for 30 minutes at During therapeutic hypothermia and rewarming (12 ~ 72 hours after cardiac arrest). Then, data retrieved from the conventional EEG and SEDline will be interpreted and analyzed for the presence of seizure.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

44 provided informed consents. Among them 5 were withdrawn. 1 death before EEG, 2 relative withdrew patient, 1 combined septic shock, and 1 patient did not perform EEG within 72 hours. Finally 39 patients were enrolled in this study. Conventional EEG (gold standard for seizure detection) and SEDline monitoring were conducted simultaneously for 30 minutes at During therapeutic hypothermia and rewarming.

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [percentage of seizures]	100

2. Secondary Outcome

Title	Sensitivity of SEDline for Seizure Detection
Description	Sensitivity measured the percentage of seizures identified by the SEDline in cases those were identified as seizures by the conventional EEG.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [percentage of seizure (+)]	100

3. Secondary Outcome

Title	Specificity
Description	Specificity measured the percentage of seizure-negative identified by the SEDline in cases those were identified as seizure-negative by the conventional EEG.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [percentage of seizure (-)]	100

4. Secondary Outcome

Title	Positive Predictive Value
Description	Positive predictive value measured the percentage of seizures identified by the conventional EEG in cases those were identified as seizures by the SEDline.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [percentage of seizure (+)]	100

5. Secondary Outcome

Title	Negative Predictive Value
Description	Negative predictive value measured the percentage of seizure-negative identified by the conventional EEG in cases those were identified as seizure-negative by the SEDline.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [percentage of seizure (-)]	100

6. Secondary Outcome

Title	Area Under Receiver Operating Characteristics Curve (AUC) of SEDline for Seizure Detection
Description	The Area under receiver operating characteristics curve (AUC) of SEDline represents the accuracy of the SEDline to detect seizures compared with the conventional EEG.
Time Frame	Within 72 hours after cardiac arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest.
Measure Participants	39
Number [probability]	1.00

Adverse Events

Time Frame	30 days
Arm/Group Title	Frontal 4 Channel EEG
Arm/Group Description	Consecutive comatose patients admitted to the emergency ICU for postresuscitation care following successful cardiopulmonary resuscitation after nontraumatic out-of-hospital and in-hospital cardiac arrest. Frontal 4 channel EEG: Simultaneous conventional EEG and SEDline monitoring for 30 minutes during and after therapeutic hypothermia
All Cause Mortality
	Frontal 4 Channel EEG
	Affected / at Risk (%)	# Events
Total	17/39 (43.6%)
Serious Adverse Events
	Frontal 4 Channel EEG
	Affected / at Risk (%)	# Events
Total	0/39 (0%)
Other (Not Including Serious) Adverse Events
	Frontal 4 Channel EEG
	Affected / at Risk (%)	# Events
Total	0/39 (0%)

Limitations/Caveats

Since the SEDline system provides 4-channel-processed EEG monitoring in the frontal area, focal seizures could not be detected and spatial localization of the seizure might be difficult.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.