Expert Consensus on Neurosurgery for the Prevention and Treatment of Cerebral Vascular Spasm
Preface
Cerebral vasospasm is a common clinical problem in neurosurgery, and its basic and clinical research is one of the hot issues in the field of neurosurgery at home and abroad, especially aneurysmal subarachnoid hemorrhage (aSAH) is an important cause of death and disability. Currently, cerebral vasospasm caused by aSAH has attracted widespread attention from clinicians, while post-traumatic cerebral vasospasm may occur after craniocerebral injury, and other craniocerebral surgeries and endovascular interventions may also cause secondary cerebral vasospasm, and these aspects also need sufficient clinical attention. The Neurosurgery Section of the Chinese Medical Association invited famous experts in domestic neurosurgery to reach a consensus after several discussions, and proposed the “Expert Consensus on Prevention and Treatment of Cerebrovascular Spasm in Neurosurgery”, aiming to promote a more comprehensive understanding of cerebrovascular spasm among domestic neurosurgeons and to solve the problem of standardization of diagnosis, prevention and treatment of cerebrovascular spasm for the benefit of the majority of patients.
Definition and epidemiology of cerebral vasospasm
1.Definition of cerebral vasospasm
In 1927, Moniz performed the first human cerebral angiography, in 1937, Dandy performed the first craniotomy to clamp intracranial aneurysm, and in 1951, Ecker made the first diagnosis of cerebral vasospasm based on cerebral angiography. According to the definition of authoritative neurosurgical monographs at home and abroad, cerebral vasospasm is “a state of persistent constriction of intracranial arteries”. The diagnosis of cerebral vasospasm is mainly based on clinical symptoms, signs and cerebral angiographic images of the patient. ischemic neurological deficits (DIND).
2. Epidemiology of cerebral vasospasm
The incidence of spontaneous subarachnoid hemorrhage (SAH) varies among countries and regions, with an overall incidence of about 10/100,000 people per year. It is presumed from this. The predominant cause of SAH is ruptured intracranial aneurysms, which account for approximately 85% of all cases. The remaining cases may result from other rare causes, such as cerebrovascular malformations, periaqueductal non-aneurysmal subarachnoid hemorrhage (PNSH), dural arteriovenous fistulas, spinal cord vascular lesions, smog, disorders of coagulation mechanisms, neoplastic hemorrhage, hypertension, and cocaine abuse. Due to different diagnostic methods and regional and ethnic differences, the incidence of cerebral vasospasm after aSAH reported in different literature varies widely, ranging from 20% to 80%, with symptomatic cerebral vasospasm occurring in approximately 10% to 50% of cases.
The incidence of cerebral vasospasm after craniocerebral injury SAH is approximately 27% to 50%, especially in younger patients and in patients with low GCS scores on admission1.
During interventional treatment of cerebrovascular disease, the incidence of cerebral vasospasm is reported in the literature to be between 17% and 60%.2-6 In general neurosurgical craniotomy, cerebral vasospasm may also occur after surgery, with an incidence of approximately 22% to 49%, which may lead to delayed cerebral ischemia and seriously affect the efficacy of surgery if not diagnosed and treated in a timely manner.7-10
Etiology, pathophysiology and classification of cerebral vasospasm
1. Etiology of cerebral vasospasm
Rupture of intracranial aneurysms located around the ring of Willis artery at the base of the brain often leads to extensive SAH. The blood flowing into the subarachnoid space and its degradation products are the most important cause of cerebral vasospasm. The incidence and severity of cerebral vasospasm are mostly closely related to the amount of blood accumulation in the subarachnoid space. Injury, compression and traction of blood vessels during cranial injury, cranial surgery or endovascular intervention, mechanical stimulation during intravascular manipulation, chemicals such as contrast agents, and bleeding into the subarachnoid space during surgery can also lead to cerebral vasospasm.
According to reports in the literature, cerebral vasospasm may also be induced in other conditions, such as tuberculous and septic meningitis, migraine, and hypertensive encephalopathy.
1.Pathophysiological mechanism of cerebral vasospasm
According to the existing research results, the pathophysiological mechanisms of cerebral vasospasm occurrence are related to the following factors.
(1) Mechanical stimulation of blood and surgical instruments on the vessel wall;
(2) Structural destruction of the vessel wall due to clot compression and nutritional disorders of the vessel wall;
(3) damage caused by oxidation of oxyhemoglobin to methemoglobin and release of oxygen radicals;
(4) vasoactive substances, such as 5-HT, catecholamines, hemoglobin and arachidonic acid metabolites of the vasoconstrictor effect;
(5) Increased intracranial pressure, excessive dehydration treatment without timely blood volume replacement;
(6) inflammation and immune response of the vessel wall.
All of the above physicochemical factors can lead to changes in smooth muscle cell membrane permeability of the vascular wall and increased inward flow of calcium ions, as well as increased release of intracellular calcium depots, which eventually leads to increased intracellular calcium ion concentration in smooth muscle cells, prompting abnormal contraction of vascular smooth muscle and leading to vasospasm. Therefore, calcium ion overload is now recognized as the most important link in the development of vasospasm.
After the occurrence of cerebral vasospasm, the intracranial circulatory system becomes hemodynamically impaired, resulting in local or diffuse cerebral blood perfusion deficit and brain tissue in a hypoxic state, which may result in a series of clinical symptoms if not corrected in time. Therefore, paying attention to the protection of neurological function at the same time is beneficial to improve the adverse consequences of cerebrovascular spasm.
2, classification of cerebral vasospasm
According to the etiology, it can be divided into 4 categories: ① spontaneous SAH; ② craniocerebral injury SAH; ③ some medical factors, such as craniocerebral surgery, cerebral angiography, and intravascular intervention operations; ④ less common causes, such as tuberculosis and septic meningitis.
(1) Diffuse cerebral vasospasm, which may involve multiple major intracranial vessels such as the internal carotid artery, the vertebral basilar artery, the middle cerebral artery, and the proximal segment of the anterior cerebral artery at the same time, and the angiogram shows that each vessel is poorly visualized and linear; (2) multisegmental cerebral vasospasm, which shows that one or several intracranial arteries are unevenly thick and thin with salami-like or bamboo-like spasm; (3) focal cerebral vasospasm, which is mainly a limited spasm of the aneurysm-carrying artery where the ruptured aneurysm is located.
According to the degree of lumen narrowing on angiography, cerebral vasospasm can be classified into 3 grades: severe, with lumen narrowing of 50% or more; moderate, with lumen narrowing of 25% to 50%; and mild, with lumen narrowing of less than 25%.
The disease can be divided into early-onset cerebral vasospasm and chronic cerebral vasospasm, the latter is also called late-onset cerebral vasospasm.
Early-onset cerebral vasospasm occurs mostly within 24 hours after hemorrhage and can be detected on emergency angiography, mostly as unilateral focal vasospasm near the ruptured aneurysm. Conventional cerebral angiography usually only detects vasospasm in large intracranial vessels.
In a 2003 study, segmental microvascular spasm was found to occur in more than 50% of patients early after SAH (before clamping), with a reduction in vessel diameter of up to 75%, resulting in a range of clinical symptoms and ultimately affecting clinical outcome.11 Therefore, the clinical outcome of SAH can be influenced by the use of orthogonal polarization spectral imaging. Therefore, timely detection of microvascular spasm and early prevention is one of the keys to improve the outcome of cerebral vasospasm.
The typical delayed cerebral vasospasm begins to appear on day 3-5 after SAH, peaks on day 7-10, and continues for 2-3 weeks before gradually resolving12.
Diagnosis of cerebral vasospasm
1. Clinical manifestations
1.1 History: clear intracranial aneurysm rupture leading to SAH, and the patient has a typical history of severe headache attacks. Other conditions include history of cranial injury, endovascular intervention, cranial surgery or other cranial diseases.
1.2 Typical symptoms: Cerebral vasospasm itself does not have typical specific clinical manifestations. Generally, 3-5 days after SAH, if there is a deterioration of consciousness, even accompanied by newly appeared focal localization signs, such as hemiparesis, hemianesthesia, aphasia, and manifestations of increased intracranial pressure, such as headache and vomiting, clinical except electrolyte disorders (hypernatremia), CT examination except secondary hydrocephalus and The possibility of cerebral vasospasm should be highly suspected after CT examination excluding secondary hydrocephalus and intracranial hematoma, etc. Unexplained increase in body temperature and leukocytosis also need to be taken into account clinically, and the possibility of cerebral vasospasm exists.
2.Clinical classification
For aSAH, Hunt and Hess grading and the International Federation of Neurological Surgeons (WFNS) scale are commonly used to determine the severity of the disease (Table 1).
3. Auxiliary examination
3.1 Digital subtraction angiography (DSA)
Cerebral angiography (digital subtraction angiography) is the “gold standard” for the diagnosis of cerebral vasospasm, with a high positive detection rate for aneurysms and cerebrovascular malformations, and can clearly show the branches of cerebral vessels at all levels. The disadvantage is that it is inconvenient to repeat the examination several times after SAH. When available, angiography can be considered for those suspected of having vasospasm15.
If angiography confirms the presence of severe cerebral vasospasm, simultaneous endovascular intervention or direct intravascular balloon dilation at the site of spasm can also be considered.
3.2 Transcranial Doppler ultrasound (TCD) blood flow detection
TCD is a common method for detecting cerebral vascular spasm. If TCD reveals increased blood flow velocity in local cerebral vessels, it suggests the presence of vascular stenosis due to vascular spasm. The current common diagnostic criteria are peak middle cerebral artery flow velocity greater than 200 cm/s and/or mean flow velocity greater than 120 cm/s. This index is generally consistent with angiographic evidence of severe vasospasm.
The main advantage of TCD is that it is non-invasive, can be repeated multiple times in a row, and can be used to dynamically detect the course of vasospasm as well as to evaluate the effectiveness of treatment. It should be noted that the specificity of the TCD test is high and the sensitivity is relatively low. The accuracy of the measured values depends on the experience and skill of the physician in charge of the test, and due to the limitations of the skull thickness, only certain specific intracranial vascular segments can be measured.
During craniotomy, ultrasound technology can also be used to directly detect the flow velocity of intracranial vessels under direct vision to understand whether there is cerebral vasospasm and to take timely targeted therapeutic measures, such as local irrigation with poppies or nimodipine.
3.3 CT
CT has a high diagnostic accuracy for acute SAH occurring within 12 hours, and the site of intracranial aneurysm can be indirectly inferred according to the site of SAH intracranially shown by CT. However, it should be noted that the detection rate of SAH is related to the time after bleeding to the time of receiving CT examination, the amount and location of bleeding, and the longer the time of CT examination from the onset, the lower the sensitivity. If CT examination is performed 7 days after bleeding, the positive rate decreases to only about 50%. A small amount of bleeding can result in false negatives due to deviations in the CT level range, and also in patients with anemia (erythrocyte pressure volume less than 30%), CT examinations can also show false negative results.
The risk of cerebral vasospasm, a modified Fisher classification16 (Table 2), can be inferred based on the amount of bleeding shown on CT within 24 hours after SAH.
3.4 CTA, MRA
CT and magnetic resonance angiography are now increasingly sophisticated. High-resolution CT angiography (CTA) CT perfusion imaging can accurately diagnose severe vasospasm in major intracranial vessels, such as the internal carotid artery, middle cerebral artery, A1 segment of the anterior cerebral artery, and basilar artery, but has limitations for diagnosing vasospasm in small arteries and for identifying mild and moderate spasm.
Table 1 Clinical grading of aneurysmal subarachnoid hemorrhage
Grading
Hunt and Hess grading method13*
WFNS scale14
I
Asymptomatic or with mild headache, cervical tonicity
Glasgow coma score 15, no motor deficits
Ⅱ
Moderate to severe headache, cervical stiffness, cranial nerve palsy
Glasgow coma score 13~14, no motor deficits
III
Mild focal neurological deficit, drowsiness or confusion
Glasgow coma score 13-14, with motor deficits
IV
Coma, moderate to severe hemiparesis, early decerebrate cerebral tonicity
Glasgow coma score 7-12, with or without motor deficits
V
Deep coma, decerebrate, near death
Glasgow coma score 3-6, with or without motor deficits
*Note: ①Add 1 grade for those with severe systemic diseases (such as atherosclerosis, hypertension, etc.) or angiographically confirmed severe cerebral vasospasm;
②The unruptured aneurysm can be classified as grade 0, and those with only cranial nerve palsy without acute meningeal irritation signs are classified as grade Ia.
Table 2 Modified Fisher’s grading
Grading
CT performance
Risk of cerebral vasospasm (%)
0
No hemorrhage seen
3
1
Only basal pool hemorrhage seen
14
2
Peripheral brain pool or lateral fissure pool hemorrhage
38
3
Extensive SAH with intracerebral parenchymal hematoma
57
4
Thicker blood accumulation in the basal and peripheral brain pools and lateral fissure pool
57
Prevention and treatment of cerebral vasospasm
1. Principles of prevention and treatment of cerebral vasospasm
The following main evidence-based evidence on the prevention and treatment of cerebral vasospasm is mostly from aSAH, and other types of cerebral vasospasm can be used as reference and handled according to the patient’s condition.
As mentioned earlier, cerebral vasospasm, once it occurs, is a serious hazard with no specific clinical signs and symptoms, and various major adjunctive examinations, such as DSA, TCD, and CTA, have their own limitations, and cerebral vasospasm often shows inconsistency in clinical symptoms and angiographic images. In addition, delayed cerebral vasospasm mostly occurs on the 3rd to 5th day after SAH and lasts for 2 to 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) Angiography or TCD suggesting cerebrovascular spasm, but the patient does not have clinical symptoms: prophylactic treatment is recommended, along with dynamic monitoring, and timely adjustment of the treatment plan if clinical symptoms appear.
(3) Angiography or TCD does not reveal cerebrovascular spasm, but the patient has clinical symptoms, treatment should be given and monitored dynamically
(4) For patients with high-risk factors for cerebral vasospasm, such as spontaneous aSAH, traumatic SAH and after perivascular surgery, even though 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 control measures are blood pressure and fluid (blood volume and electrolyte balance) management.
2. Etiological treatment
For patients with spontaneous SAH, early etiological treatment 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, craniotomy and aneurysm neck clamping surgery 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 beyond the optimal time for treatment, the decision should be made according to 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 aneurysms and other etiologies, cerebrospinal fluid drainage can remove blood accumulation in the subarachnoid space and reduce other spasmogenic substances, lower 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 interventions, it is also necessary to consider reducing local vascular irritation and injury as much as possible, avoiding bleeding into the subarachnoid space during surgery and inducing cerebral vasospasm.
3.Drug treatment
3.1 Calcium antagonists
To reduce the incidence and severity of cerebral vasospasm by blocking the abnormal calcium inward flow of vascular smooth muscle cells is the most common method to prevent and treat cerebral vasospasm in clinical practice. The results of several evidence-based medical studies at home and abroad have confirmed that calcium antagonists can reduce ischemic neurological impairment caused by vasospasm, reduce patient mortality and improve prognosis.
Among various calcium antagonists, nimodipine is currently the main clinical recommendation. It is a 2nd generation dihydropyridine calcium antagonist with high selectivity for intracranial vasculature and weak vasodilator effect on other than intracranial vasculature.
A 2007 Cochrane Centre meta-analysis showed that nimodipine significantly reduced secondary ischemic symptoms after SAH, resulting in a significant reduction in the relative risk of both death and disability due to cerebral vasospasm17.
Nimodipine is also currently the drug of choice recommended for the prevention and treatment of cerebral vasospasm after SAH in several national and regional guidelines for the management of SAH, including those of the American Heart Association (AHA)18, Canada19 and Italy20.
Following the principles of early, full, adequate, and safe administration, the recommended use and dosage of nimodipine are as follows: (1) Early: nimodipine should be started as soon as possible after admission of a patient with spontaneous SAH, and intravenous infusion is recommended. j
A meta-analysis published in Neurosurg demonstrated that prophylactic application of nimodipine in patients with aSAH after detection of hemorrhage significantly reduced neurological injury and death due to cerebral vasospasm.21 A 2006 Neurosurg Rev review of cerebral vasospasm prevention and treatment showed that nimodipine was used as prophylactic treatment for cerebral vasospasm in most patients with aSAH.22 For patients with auditory neuro tumor surgery, a randomized controlled clinical trial published in Neurosurgery in 2007 showed that prophylactic use of nimodipine injection starting 1 day before craniotomy was significantly more effective in preventing postoperative neurological deficits than starting intraoperatively.23
(2) Throughout: Cerebral vasospasm can persist for 2 to 3 weeks after SAH, so nimodipine maintenance therapy is required for at least 14 to 21 days. Youmans Neurosurgery (Youmans
Neurological
Surgery), 5th edition, clearly states that an important principle in the management of cerebral vasospasm in patients with subarachnoid hemorrhage is the use of nimodipine for a course of 21 days.24 It is recommended that nimodipine be administered intravenously for 14 days, followed by a change to oral sequential therapy.
(3) Adequate dose: The dose of intravenous infusion of nimodipine depends on body weight. Patients with body weight below 70 kg or unstable blood pressure: the starting dose is 0,5 mg/h, if well tolerated, it can be increased to 1 mg/h after 2 h. Patients with body weight above 70 kg: the starting dose is 1 mg/h, if well tolerated, it can be increased to 2 mg/h after 2 h. The daily intravenous dose is 24~48 mg.
The half-life of nimodipine is about 1.5 h. Intravenous administration is recommended by infusion pump to maintain a stable blood concentration. The recommended oral dose is 60 mg every 4 hours.
(4) Safety: The results of the 2007 Cochrane Centre meta-analysis demonstrated that nimodipine does not increase the incidence of rebleeding after aSAH.17 International large-scale clinical trials have demonstrated that the effect of nimodipine on intracranial pressure is similar to that of placebo.25
(5) Intraoperative local irrigation26, 27, 28: A newly configured dilution of nimodipine (1:19 nimodipine injection/Ringer’s solution) was warmed to the same temperature as blood and then dripped in the intraoperative brain pool.
3.2 Magnesium agent
Some clinical studies at home and abroad have confirmed that MgSO4, i.e. magnesium sulfate, has a certain effect on cerebrovascular spasm. The starting dose is 10
The starting dose is 10 mg/kg body weight intravenous drip, the maintenance dose is 30mg/(kg・d) 29. currently magnesium agent to prevent cerebrovascular spasm has not been recommended by other guidelines.
3.3 Poppy bases
Poppyrine is a vasodilator, and local application can act highly selectively on spastic arteries, with the disadvantage of short duration of action and reduced vasodilatory effect in elderly patients30.
Usage: 100 ml of 0,3% poppyine solution is infused intra-arterially at a rate of 0,1 ml/s. It can be used for intra-arterial perfusion during endovascular intervention or local irrigation during craniotomy. Please refer to the drug instructions for the specific use method.
3.4 Other drugs
Fasudil is a protein kinase inhibitor that reduces the sensitivity of vascular smooth muscle cells to increased intracellular calcium ion concentrations, mainly by inhibiting Rho kinase activity. A randomized clinical trial in Japan (275 patients with SAH) confirmed that fasudil reduced the occurrence of cerebral vasospasm. According to its instructions for use, to avoid the risk of inducing re-rupture and bleeding of the aneurysm, it should be started after the intracranial aneurysm causing SAH has been clamped or embolized, and should not be administered for more than 2 weeks in an intravenous formulation.31 The recommended use of fasudil is 30 mg intravenously over 30 minutes 2 to 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 common methods for endovascular treatment of cerebral vasospasm: balloon angioplasty and direct infusion of intra-arterial vasodilator drugs. Both can be used alone or in combination.
Some studies have shown that for severe segmental cerebral vasospasm, within a few hours after balloon vasodilatation, 60% to 80% of patients have significant improvement in clinical symptoms.
Complications of balloon dilation techniques are operationally related and include causing acute arterial entrapment and displacement of aneurysm clips. It is generally indicated only for limited spasm of large intracranial arteries.
5.Hemodynamic treatment
Elevated blood pressure, volume expansion and hemodilution are collectively referred to as 3H therapy, which is a more commonly used clinical approach. If used, there must be enhanced monitoring measures, namely the corresponding arterial pressure, central venous pressure, blood routine, biochemistry and other dynamic monitoring means. The specific measures generally used at present are.
(1) Elevating arterial pressure should be started after successful intracranial aneurysm surgery or embolization treatment, and systolic blood pressure can be maintained at the level of 140-200 mmHg and adjusted according to the degree of improvement of clinical symptoms. The common drug used to raise blood pressure is dopamine, and dobutamine or epinephrine may also be considered.
(2) Volume expansion therapy must monitor central venous pressure and maintain it at 8-10 mmHg, i.e., 100-130 cmH2O.
(3) Hemodilution therapy can be used with colloidal solution to reduce the red blood cell pressure volume to 30%~35%.
When using 3H therapy, 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, and decreased blood viscosity; reduced platelet aggregation capacity may induce bleeding, etc. Contraindications: ruptured aneurysm not yet clamped or embolized; CT showing already severe cerebral infarction; significantly increased intracranial pressure, combined with severe cerebral edema; patient combined with severe primary cardiac and renal disease, etc.32
Summary
Cerebral vasospasm is one of the common problems in neurosurgery and is closely related to spontaneous SAH, craniocerebral injury, craniotomy, and endovascular interventions, which should attract extensive attention from the general practitioners.
Early diagnosis and early adoption of effective preventive and therapeutic measures are key to reduce the occurrence of cerebral vasospasm and improve the prognosis.
However, the mechanism of cerebral vasospasm is complex, and once it occurs, the prognosis is poor and the death and disability rates are high, so it should be given full attention in clinical practice.
This consensus is only an academic consensus of experts, the implementation of which still depends on the specific condition of the patient, and the relevant product instructions should be consulted before taking various preventive and therapeutic measures. With the continuous progress of medicine, the content of this consensus will be updated accordingly.