Treatment and Therapy of Stroke Acute Phase

Treatment and Therapy of Stroke Acute Phase
       Therapy is divided into two phases, namely the acute and post-acute phase. Acute phase (0-14 days after onset of disease). Treatment goal is to rescue neurons that had not to die, and that other pathological processes that accompany not disturb / threatening brain function. Actions and drugs given should ensure perfusion of blood to the brain remained adequate, it does not reduce.So that needs to be maintained optimal function of respiration, heart, blood pressure, blood is maintained at optimal levels, control blood sugar levels (high blood sugar levels are not lowered drastically), when severe fluid balance, electrolyte, and acid-base should continue to be monitored.

      Prompt and appropriate treatment is expected to suppress mortality and reduce disability. The main goal of treatment is to improve blood flow to the brain as quickly as possible and protect neurons by cutting the ischemic cascade. Management of acute stroke patients can be basically divided in:
1. General management, guideline 5 B
A Breathing
B Blood
C Brain
D Bladder
E Bowel

2. Management based on the cause
A Ischemic Stroke
  • Improving blood flow to the brain (reperfusion)
  • Prevention of the occurrence of thrombosis (anticoagulan)
  • Protection of neuronal / cytoprotection
B Haemorrhagic Stroke
  • Management of conservative
  • intra-cerebral hemorrhage
  • Sub-arachnoid haemorrhage
  • Management of operative

1. General management, guideline 5 B
A Breathing: airway must be open relief, suction mucus and slam to prevent lack of oxygen with all the consequences. Kept both oxygenation and ventilation, to prevent aspiration (false teeth opened). Intubation in patients with a GCS <8. In approximately 10% of patients with pneumonia (pneumonia) is the leading cause of death in week 2-4 after a brain attack. The patient should lie on his side left-right alternating every 2 hours. And if there is inflammation or asthma treated quickly.

B. Blood: Blood pressure in the early stages, should not be immediately taken down, because it can make things worse, unless the systolic blood pressure > 220 mmHg and or diastolic > 120 mmHg (ischemic stroke), systolic > 180 mmHg and or diastolic> 100 mmHg (stroke hemorrhagic). Maximal blood pressure reduction of 20%.
Drugs that can be used Nicardipin (0.5 - 6 µg / kg / min continuous infusion), diltiazem (5-40 µg / kg / min drip), nitroprusside (0.25 to 10 µg / kg / min continuous infusion) , nitroglycerin (5-10 µg / min continuous infusion), labetolol 20 -80 mg IV bolus every 10 minutes, captopril 6.25 to 25 mg oral / sub lingual. Fluid and electrolyte balance should be supervised.
Blood sugar levels (Blood Glucose) is too high, as evidenced worsen outcomes for stroke patients, regular insulin by sliding scale doses GD> 150-200 mg / dL 2 units, each increase of 50 mg / dL, the dose was increased up to 2 units of insulin levels GD> 400 mg / dL dose of insulin 12 units.

C. Brain: When obtained an increase of intra-cranial pressure with signs of headache, projectile vomiting and relative bradycardia should eradicate, the drug is commonly used mannitol 20% from 1 to 1.5 g / kg followed by 6 x 100 cc (0.5 g / kg), within 15-20 minutes with monitoring of osmolality between 300-320 mOsm, another advantage of the use of mannitol is destroying free radicals.
Increased body temperature should be avoided due to multiply excitatory neurotransmitter release, free radicals, BBB damage and damage recovery of energy metabolism and increase the inhibition of protein kinase. Mild hypothermia 30 degree Celcius or 33 degree Celcius has a neuroprotective effect. When a seizure dont give anticonvulsant diazepam iv because it will aggravate the blood perfusion to the brain tissue

D. Bladder: Avoid a urinary tract infection urine should be retained in case of intermittent catheter. If there is urinary incontinence, in pairs, male condom catheter, the catheter female pairs.
E. Bowel: The need for fluids and calories to note, avoid obstipation, Keep the regular defecation, when the tide NGT obtained difficulty swallowing food. Noteworthy albumin deficiency because it can aggravate brain edema.

2. Management based on the cause
A. Ischemic Stroke
- Improving blood flow to the brain (reperfusion)
         Remove the blockage causes a stroke is the most ideal effort, thrombolytic drug that has been approved by the FDA is the rt-PA (tissue plasminogen activator recombinan) at a dose of 0.9 mg / kg up to 90 mg (10% bolus and the remainder given continuous infusion in 60 min). Unfortunately, that treatment with these drugs should have requirements for less than 3 hours, so that only patients admitted to hospital with early onset and completion of blood tests, CT scans of the head and informed consent were fast can receive this drug.
     Another way to improve blood flow such as by improving hemorheologi like pentoxifillin that the drug reduces blood viscosity by increasing red blood cell deformability with a dose of 15 mg / kg / day. Other drugs that also improves the circulation is naftidrofuril by improving blood flow through the cellular elements of the blood dose of 600 mg / day iv for 10 days, followed by oral 300 mg / day.

- Prevention of the occurrence of thrombosis (anticoagulation)
     To avoid further thrombus are two classes of treatments available are anti-coagulants and anti-platelet aggregation. Anti-coagulants given to stroke patients who are at risk for brain embolism occurs as patients with congenital heart non-valvular atrial fibrillation, mural thrombus in the left ventricle, myocardial infarction new and artificial heart valves. Drugs that can be given is a starting dose of heparin 1000 U / hour check APTT 6 hours later to achieve 1.5 to 2.5 times the control day 3 replaced oral anti-coagulants, low molecular weight heparin LWMH) dose of 2 x 0.4 cc subcutaneous platelet monitor day 1 & 3 if number <100,000 not supplied), Warfarin dose = 8 mg the first day, second day = 6 mg, Day 3th dose adjustment by looking at the patient's INR.
        Patients with severe paresis, which long lay-risk occurred venous thrombosis and pulmonary emboli given heparin for prevention of 2 x 5,000 units of sub cutan or LMWH 2 x 0.3 cc for 7-10 days.
        Anti-platelet aggregation has many options including dose aspirin 80-1200 mg / day of the mechanism of action by inhibiting the cyclooxygenase pathway, dipiridamol combined with aspirin, aspirin 25 mg + dipiridamol SR 200 mg twice daily by inhibiting the cyclooxygenase pathway, phosphodiesterase and adenosine re-uptake, cilostazol dose of 2 x 50 mg mechanism of action of inhibiting phosphodiesterase III activity, ticlopidin dose of 2 x 250 mg with adenosine diphosphate receptor menginhibisi and thyenopyridine and clopidogrel dose of 1 x 75 mg adenosine diphosphate receptor menginhibisi and thyenopyridine.

- Protection of neuronal / cytoprotection
          It is interesting to observe the drugs in this group because it is expected to be able to cut the ischemic cascade so as to prevent further damage neurons. These medicines include:
o CDP-Choline works with repair cell membranes by adding phospatidylcholine synthesis, inhibiting the formation of free radicals and also increases the synthesis of acetylcholine is a neurotransmitter for cognitive function. Meta-analysis Group Cohcrane Riview Stroke Study (Saver 2002) 7 study 1963 patients with ischemic stroke and bleeding, the dose of 500-2000 mg daily for 14 days showed reduced mortality and significant disability. Therapeutic Windows 2-14 days.
o Piracetam, ways of working are certainly not unknown, is expected to improve the integrity of the cells, improve membrane fluidity and normalize the function of the membrane. 12 g IV bolus dose followed 4 x 3 g iv until day four, day five was continued 3 x 4 g orally until week four, week five to week 12 were given 2 x 2.4 g by mouth,. Therapeutic Windows 7-12 hours.
o Statins, used for anti-lipid diklinik, has neuroprotective properties for cerebral ischemia and stroke. Has the effect of anti-oxidants "downstream and upstream". Downstream effects are stabilizing atherosclerotic plaque, thereby reducing the release of artery to artery thromboembolism. Effect "upstream" is to improve the setting of eNOS endothelial Nitric Oxide 'synthesis, has anti thrombus, vasodilatory and anti-inflammatory), inhibited iNOS inducible Nitric Oxide' synthesis, properties against eNOS), anti-inflammatory and anti-oxidant.
o Cerebrolisin, a brain protein fat free with the anti calpain, caspase inhibitors and neurotrophic dose as 30-50 cc for 21 days showed significant improvement in motor function.

B. Haemorrhagic Stroke
- Conservative Management of Intra Cerebral Hemorrhage
         Giving anti-bleeding: Epsilon aminocaproat 30-36 g / day of tranexamic acid 6 x 1 g to prevent blood clot lysis whice is formed by tissue plasminogen. Evaluation of coagulation status as granting protamin 1 mg heparin in patients receiving 100 mg and 10 mg of vitamin K intravenously in patients receiving warfarin with elongated prothrombine time.
        To reduce the damage of ischemic tissue surrounding the hematoma may be given medicines that have neuroprotectan properties.

- Conservative Management of Bleeding Sub Arahnoid
o Bed rest for 3 weeks in total with a calm, conscious patients, the use of morphine 15 mg IM in general needed to relieve headache pain in conscious patients.
o vasospasm occurs in 30% of patients, Calcium Channel Blockers can be administered at a dose of 60-90 mg orally every 4 hours for 21 days or 15-30 mg / kg / hr for 7 days, followed by oral 360 mg / day for 14 days , effective to prevent vasospasm usually occurs on day 7 after iktus which continued until the second week after iktus. If there is a positive balance vasospasm do liquid 1-2 Liter cultivated pulmonary artery pressure 18-20 mmHg and 10 mmHg Central venous pressure, if it fails also sought an increase in systolic blood pressure to 180-220 mmHg using dopamine.

- Surgical Management
Surgical management objectives are: Spending a blood clot, cerebrospinal fluid distribution and micro-vascular surgery.
Many important than the results of the CT scan and arteriography is the state / condition of the patient's own:
Factors influencing factors:
1. Age
- Over 70 years old --> no surgery
- 60-70 years old --> more rigorous consideration of surgical
- Less than 60 years -->  Surgery can be performed more safely
2. Level of consciousness
- Commas / sopor  --> no surgery
- Aware / somnolence --> no surgery except consciousness or neurologic state  is decreased
- Cerebellar Hemorrhage: sometimes the surgery results are satisfactory even consciousness is coma
3. Topis lesions
• Lobar Hematoma (cortical and Subcortical)
  - If ICP (Intra-Cranial Pressure) is not rising -->  no surgery
  - When ICP rising with herniation signs accompanied --> Surgery
• Bleeding putamen
  - When a small or moderate hematoma -->  no surgery
  - If more than 3 cm hematoma  --> no surgery, except consciousness or worsening  deficit neurologic
• Bleeding thalamus
  - In general, surgery is not only aimed at hyidrocephalus with VP shunt due to bleeding when possible.
• Bleeding cerebellum
   - If the bleeding is more than 3 cm in the first week --> surgery
   - When neurologic clinical is stable, medicinal treated with control
   - If the hematoma is small but with signs of brain stem suppression --> surgerys
4. Sectional hematoma volume
   - When you cross over 3 cm hematoma volume of more than 50 cc then surgery
   - When a small cross section, diminishing awareness and neurologic state and signs of emphasis the brain stem --> surgery
5. The right time for surgery
   - Recommended for surgery as soon as possible 6-7 hours after the attack before the onset of brain edema, if not possible, should be postponed until 5-15 days later.

Indications of surgery patients were patients with grade PSA Hunt & Hest Scale of 1 to 3, the surgery can be immediate (<72 hours) or later (after 14 days). Surgery patients with Hunt & Hest PSA Scale 4-5 shows a high mortality rate (75%).


MEDICAL BOOKS ABOUT STROKE




Resources:
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 http://www.hospitalpharmacyeurope.com/default.asp?title=Tenecteplase_challenges_alteplase_after_stroke&page=article.display&article.id=28396&category.id=589

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