Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of oral Nimodipine and IV milrinone combination therapy for management of cerebral spasm after aneurysmal subarachnoid hemorrhage.

Detailed Description
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after being informed about the study and potential risks. All patients giving written consent will be randomized by double-blind manner into 2groups each one containing 15 patients. Group 1(n =15 ):the patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube In group 2(n =15 ): the patients will receive Oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone.

Official Title
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Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy of Oral Nimodipine and Intravenous Milrinone: Randomized Clinical Trial

Conditions
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Oral Nimodipine, Milrinone, Vascular Spasm After Traumatic Subarachnoidhaemorrhage

Intervention / Treatment
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* Drug: nimodipine
* Drug: Oral Nimodipine and milrinone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients admitted to our surgical ICU aged between (18-60) years old World Federation of Neurological Surgeons grades 1-3 Grades Exclusion Criteria: Aneurysmal SAH SAH with Fisher Grade I and IV, World Federation of Neurological Surgeons grade IV & V No informed consent, peripheral vascular disease Cardiac disease (heart block, severe valvular stenosis, cardiomyopathothy , ejection fraction<40%), Renal impairment (serum creatinine ≥ 1.4 mg.L-1), Hemodynamic instability

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: triple H group<br>The patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube from the first day of admission, then after the diagnosis of vasospasm is confirmed, Triple H therapy (hypertension, hypervolemia and hemodilution) will be started. norepnnephrine (0.01-0.2ug/kg/min) to mentain main arterial blood pressure >100mmhg and hypervolemia to maintain the CVP around 12---14 mmHg and hemodilution to maintain the haematocrit between 30% and 33%. | Drug: nimodipine<br>* (60 mg/4 hours) orally or via nasogastric tube<br>|
| Active Comparator: Milrinone group<br>The patients will receive oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone bolus of 0.1-0.2 mg/kg followed by 0.75mcg/k/min, if no response after 30min increase the infusion to 1-25mcg/kg/min with maintaining CVP 5:8. Norepinephrine (0.01-0.2ug/kg/min) is used only to restore the mean arterial pressure (MAP) to its previous values If there was no recurrence of symptoms after 72 h, we decreased the milrinone infusion by 0.25 mcg/kg/min every 24 or 48 h until discontinuation. If there are any recurrent of symptoms of vasospasm, the patients are placed back on the dose they were previously receiving. If required, another Milrinone bolus is administered if the patient's deficits do not revert12. | Drug: Oral Nimodipine and milrinone<br>* Oral Nimodipine then after the diagnosis of vasospasm is confirmed, start milrinone bolus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of transcutaneous cerebral mixed oxygen saturation | by forehead bilateral interconnected adhesive probes | every 24 hours up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants having cerebral infarction (cerebral infarction incidence) | detected by computed tomography | every 48 hours up to 1 week | 
| Number of participants restore of the previous conscious level and motor state(Percentage of drug success) | restore of the previous conscious level and motor state | 1 hour after administration of milrinone and 2 hours after administration of triple H therapy | 
| value of Glasgow coma scale | with minimum scale vlue of 3 is the worst and maximum value of 16 indicate better outcome | every 24 hours up to total days of ICU and hospital stay | 
| Number of participants develop one of adverse events | hypotension ,bradycardia,hypotesion | after administration of the study drugs up to 30 days | 
| Total ICU and hospital stay |  | up to 30 days after administration of the study drugs | 
| mortality rate | Number of participants died within 30 day after administration of the study drugs | 30 day after administration of the study drugs | 
| value of Modified Rankin scale | Level 0: no symptoms Level 1: no significant disability, despite symptoms; able to perform all usual duties and activities Level 2: slight disability unable to perform all previous activities but able to look after own affairs without assistance Level 3: moderate disability; requires some help, but able to walk without assistance. Level 4: moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Level 5: sever disability; bedridden, incontinent and requires nursing care and attention | 3,6,12 monthes after drug administration | 
| Glasgow Outcome Scale | 1. Dead: As a direct result of brain trauma, or … due to secondary complications or other complications 2. Vegetative State: Patients who remain unresponsive and speechless…. 3. Severe Disability: The The patient is conscious but needs the assistance of another person for some activities of daily living every day.…. 4. Moderate Disability: Such a patient is able to look after himself at home, to get out and about to the shops and to travel by public transport. However, some previous activities, either at work or in social life, are now no longer possible by reason of either physical or mental deficit…. 5. Good Recovery: This indicates the capacity to resume normal occupational and social activities, although there may be minor physical or mental deficits…social outcome should be included in the assessment here, such as leisure activities and family relationships.. | 3,6,12 monthes after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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milrinone Oral Nimodipine