The Benefit of Prophylactic Anticonvulsant in Post Cardiac Arrest Syndrome With Induced Mild Hypothermia

Cardiac arrest is a leading cause of sudden death, but the survival rate of cardiac arrest is only 5-35%.

Although, the first resuscitation of cardiac arrest patient would be success, the hypoxic brain injury after cardiac arrest is an important cause of the mortality and the morbidity.

For the management of the hypoxic brain injury after cardiac arrest, American Heart Association and European Resuscitation Council recommend induced mild hypothermia therapy. And, ILCOR(International Liaison Committee on Resuscitation) announced the standard treatment of post cardiac arrest syndrome(the success state of first resuscitation of the cardiac arrest patient) included the induced mild hypothermia therapy at September, 2008.

The generalized seizure and myoclonus arise in over 60% of post cardiac arrest syndrome patients and they are very difficult to control. Also, the occurrence of them implies poor prognosis of the patient.

Although, mild hypothermia therapy could be decrease the development and propagation of generalized seizure and myoclonus theologically, the therapy could not prevent the development and propagation of them entirely. Therefore, the use of prophylactic anticonvulsant should be needed. But, there is not randomized control study about the use of prophylactic anticonvulsant.

We hypothesized that the use of prophylactic anticonvulsant to post cardiac arrest syndrome patients would decrease the rate of occurrence of generalized seizure and myoclonus and would improve the neurologic outcome.

We planed that we used two anti-epileptic drugs - valproate, clonazepam - for the prophylactic anticonvulsant. The valproate and clonazepam are in general use for prevention and treatment of generalized seizure and myoclonus and are recommended to treat of generalized seizure and myoclonus to post cardiac arrest syndrome patients by 2008 guideline of ILCOR.

Study Overview

• Status: Unknown
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: Use of prophylactic anticonvulsants (valproate, clonazepam); Drug: Control group

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age : over 18, under 80
• Witnessed arrest
• Successful first resuscitation (ROSC should be last for 20 min.)
• Coma or Semicoma state
• Mean arterial pressure > 60mmHg
• Peripheral Oxygen saturation > 85%
• Expected life span before cardiac arrest > 3 month.
• Performance scale before cardiac arrest > 3 month.

Exclusion Criteria:

• Cause of arrest

  • Sepsis, Progression of malignancy, Trauma, Hemorrhagic shock
• Known Coagulopathy
• Major operation within 7 days
• Previous seizure history
• current use of valproate or clonazepam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; control group	Drug: Control group; Control group
Experimental: Prophylactic group; the group that used prophylactic anticonvulsants (valproate, clonazepam)	Drug: Use of prophylactic anticonvulsants (valproate, clonazepam); start at hypothermia induction valproate : 30mg/kg iv loading - 8hr after - 6mg/kg q 8hr iv till 72hr clonazepam : 1mg po bit via L-tube till 72 hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
electroencephalogram (EEG)	Seizure activity will be measured by EEG EEG will be interpreted by Nerologist	72hr after cardiac arrest

Secondary Outcome Measures

Outcome Measure	Time Frame
CPC score (cerebral performance category) score	1month and 3 month after cardiac arrest

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Min Seob Sim, Master, Dept. of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Publications and helpful links

General Publications

• 1. Willis, C.D., et al., Cardiopulmonary resuscitation after traumatic cardiac arrest is not always futile. Injury, 2006. 37(5): p. 448-54. 2. Eisenberg, M.S., et al., Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med, 1990. 19(2): p. 179-86. 3. Edgren, E., et al., Assessment of neurological prognosis in comatose survivors of cardiac arrest. BRCT I Study Group. Lancet, 1994. 343(8905): p. 1055-9. 4. Nolan, J.P., et al., Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication.Resuscitation, 2008. 79(3): p. 350-79. 5. Neumar, R.W., et al., Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. Circulation, 2008. 118(23): p. 2452-83. 6. Kuboyama, K., et al., Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med, 1993. 21(9): p. 1348-58. 7. Weinrauch, V., et al., Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke, 1992. 23(10): p. 1454-62. 8. Sterz, F., et al., Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med, 1991. 19(3): p. 379-89. 9. Leonov, Y., et al., Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab, 1990. 10(1): p. 57-70. 10. Bernard, S.A., et al., Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med, 2002. 346(8): p. 557-63.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: March 7, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): July 25, 2011
• Last Update Submitted That Met QC Criteria: July 21, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Cardiac arrest; Prophylactic anticonvulsant
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Postoperative Complications; Body Temperature Changes; Brain Injuries; Reperfusion Injury; Heart Arrest; Hypothermia; Post-Cardiac Arrest Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Antimanic Agents; Valproic Acid; Anticonvulsants; Clonazepam
• Other Study ID Numbers: 2009-08-038