1. Principles of cerebral vasospasm prevention and treatment
The following main evidence-based evidence for the prevention and treatment of cerebral vasospasm mostly comes from aneurysmal subarachnoid hemorrhage (aSAH), other cerebral vasospasm can take this as a reference and be handled according to the patient’s condition as appropriate.
Once cerebral vasospasm occurs, the danger is serious, there are no specific clinical signs and symptoms, and various as long as the auxiliary examination means, such as DSA, TCD, CTA, etc. also have their own limitations, while cerebral vasospasm shows inconsistency in clinical symptoms and angiographic effects. In addition, delayed cerebral vasospasm mostly occurs on day 3-5 after SAH and lasts for 2-3 weeks. Therefore, the principles of prevention and treatment for cerebral vasospasm should include four aspects, including etiological treatment, prevention-oriented, full treatment, and prevention and control of complications.
(1) Angiography or TCD suggests cerebral vasospasm and the patient has clinical symptoms: early treatment is needed, as well as dynamic monitoring.
(2) Patients with angiography or TCD suggesting cerebrovascular spasm without clinical symptoms: prophylactic treatment is recommended, along with dynamic monitoring, and timely adjustment of treatment plan if clinical symptoms appear.
(3) If angiography or TCD does not reveal cerebrovascular spasm, but the patient has clinical symptoms, treatment and dynamic monitoring are also required.
(4) For patients with high-risk factors for cerebral vasospasm, such as spontaneous aSAH, traumatic SAH and after perivascular surgery, although the patient has no clinical symptoms temporarily, it is still necessary to strengthen the monitoring of the condition and give preventive treatment.
(5) The principles of specific therapeutic measures include: improving hemodynamic parameters, restoring cerebrovascular autoregulation mechanism, maintaining effective blood volume, maintaining effective cerebral perfusion, controlling intracranial pressure, and preventing cerebral edema.
(6) The two core aspects of general prevention and control measures are blood pressure and fluid (blood volume and electrolyte balance) management.
2.Etiological treatment
Early etiological treatment for patients with spontaneous SAH is the key to successful treatment. Cerebral angiography or CTA should be performed as soon as possible after the patient is seen, and once the rupture of intracranial aneurysm is confirmed, aneurysm clamping or endovascular intervention embolization should be performed as soon as possible depending on the patient’s condition. This can significantly reduce the risk of rebleeding from the aneurysm and create conditions for the removal of the draining SAH. If the patient comes to the hospital is beyond the best time for treatment, the decision should be based on the patient’s condition.
Early removal of as much blood as possible from the subarachnoid space is an effective means of preventing cerebral vasospasm after SAH. After treatment of the aneurysm and other etiology, cerebrospinal fluid drainage can remove the blood accumulation in the subarachnoid space and reduce other spasmogenic substances, lower the intracranial pressure and prevent hydrocephalus. Commonly used methods include repeated lumbar punctures for drainage of bloody cerebrospinal fluid, continuous drainage of the brain pool or ventricles, and continuous drainage by lumbar puncture placement.
In general cranial surgery and endovascular interventional embolization treatment operations, it is also important to consider reducing local vascular irritation and injury as much as possible to avoid bleeding into the subarachnoid space during surgery and inducing cerebral vasospasm.
3.Drug treatment
(1) Calcium antagonists
It is the most commonly used method to prevent and treat cerebral vasospasm by blocking the abnormal calcium inward flow of vascular smoothness and cells to reduce the incidence and severity of cerebral vasospasm. Several evidence-based medical studies at home and abroad have confirmed that calcium antagonists can reduce the ischemic neurological impairment caused by vasospasm, decrease the mortality rate of patients and improve the prognosis.
Among the various calcium antagonists, the main clinical recommendation is currently nimodipine. It is a second-generation dihydropyridine calcium antagonist with a high degree of intracranial vascular selectivity and a weak vasodilatory effect on other than intracranial vessels. Nimodipine is also currently the drug of choice recommended in many national and regional SAH guidelines, including those of the American Heart Association, Canada and Italy, to prevent and treat cerebral vasospasm after SAH.
Following the principles of early, full, adequate and safe administration, the recommended dosage of nimodipine is as follows.
Early: Nimodipine should be given to patients with spontaneous SAH as soon as possible after admission, and intravenous infusion is recommended.
Full course: Cerebral vasospasm can last for 2-3 weeks after SAH, so nimodipine maintenance therapy is needed for at least 14-21 days. It is recommended to switch to oral sequential therapy after 14 days of intravenous infusion of nimodipine.
Adequate dose: The dose of nimodipine intravenous infusion is dependent on body weight. Patients with weight below 70 kg or unstable blood pressure: the starting dose is 0.5 mg/h and can be increased to 1 mg/h after 2 h if well tolerated; patients with weight above 70 kg: the starting dose is 1 mg/h and can be increased to 2 mg/h after 2 h if well tolerated. 24-48 mg of intravenous dose is administered daily. The infusion pump is recommended for continuous administration. The recommended dose for oral administration is 60 mg every 4 hours.
Safety: Studies have shown that nimodipine does not increase the incidence of rebleeding after aSAH. The effect of nimodipine on intracranial pressure is similar to that of placebo.
Intraoperative local irrigation: The configured dilution of nimodipine (1:19 nimodipine injection/Ringer’s solution) is warmed to the same temperature as the blood and then dripped in the intraoperative brain pool.
(2) Magnesium agent
Some clinical studies at home and abroad have confirmed that magnesium sulfate has a certain effect on the prevention and treatment of cerebral vascular spasm. The starting dose is 10mg/kg body weight intravenous drip, the maintenance dose is 30mg/(kg.d).
(3) poppy bases
Poppy base is a vasodilator, local application can be highly selective action on spastic arteries, the disadvantage is the short duration of action, the vasodilator effect on elderly patients decreased. Usage: 100ml of 0.3% poppyine solution is infused intra-arterially at a rate of 0.1ml/s. It can be used for intra-arterial perfusion during endovascular intervention or local irrigation during craniotomy.
(4) Other drugs
Fasudil is a protease inhibitor, which mainly reduces the sensitivity of vascular smooth muscle cells to increased intracellular calcium ion concentration by inhibiting Rho kinase activity. To avoid the risk of inducing re-rupture of the aneurysm, it should be started after the intracranial aneurysm causing SAH has been clamped or embolized. Also, the duration of administration should not exceed 2 weeks. The recommended use of fasudil is 30 mg IV over 30 minutes 2-3 times daily.
Clinical trials on endothelin receptor antagonists have confirmed its tendency to reduce the severity of vasospasm and decrease the incidence of cerebral ischemia.
Some clinical trials on stroke suggest that statins can also reduce the incidence of cerebral vasospasm and improve prognosis, which are still in clinical trials.
4.Endovascular treatment
There are two methods of endovascular treatment for cerebral vasospasm: balloon angioplasty and direct infusion of intra-arterial vasodilator drugs. Both can be used alone or in combination.
5.Hemodynamic treatment
Elevated blood pressure, volume expansion, and hemodilution are collectively called 3H therapy. It is a commonly used clinical method. If used, there must be enhanced monitoring measures, i.e., corresponding dynamic monitoring means of arterial pressure, central venous pressure, blood routine, biochemistry, etc.
(1) Elevating arterial pressure should be started after successful intracranial aneurysm surgery or embolization treatment, and systolic pressure can be maintained at 140-200 mmHg level and adjusted according to the degree of improvement of clinical symptoms. Dopamine, dobutamine or epinephrine may also be considered as commonly used drugs to raise blood pressure.
(2) The central venous pressure must be monitored and maintained at 8-10 mmHg, i.e. 100-130 cmH2O.
(3) Hemodilution therapy can be used to reduce the erythrocyte pressure product to 30%-35% with colloidal solution.
When using triple H treatment, attention should be paid to the corresponding complications, such as elevated blood pressure may increase myocardial workload and lead to myocardial ischemia; increased circulating volume may lead to pulmonary edema, vasogenic cerebral edema, hyponatremia, decreased blood viscosity, and reduced platelet aggregation ability may induce bleeding.
Contraindications: ruptured aneurysm has not been clamped or embolized; CT shows severe cerebral infarction; significantly increased intracranial pressure, combined with cerebral edema; patients combined with severe primary cardiac and renal diseases, etc.
Warm tip: Please combine the specific medication with the clinical situation and be guided by the doctor’s interview.