Bettina Fohre and Susanne Konig
Typically in patients with moyamoya disease (MMD), the cerebrovascular reactivity and the cerebral hemodynamic reserve capacity are impaired, causing transient ischemic attack (TIA) or stroke. Therefore the superior aim of anesthetic management for revascularization procedures is to ensure the adequate perfusion and oxygenation of the brain to avoid ischemic episodes.
Special attention is paid to maintain the systolic blood pressure between 120 and 140 mm Hg perioperatively, to avoid hypo- and hypertension and to ensure normoxemia, normocapnia, and normovolemia with crystalloids.
The two concepts of a propofol-based anesthesia and an inhalational anesthesia, either in combination with a short-acting analgesic agent, are both established for surgery in moyamoya patients. The authors favor the total intravenous anesthesia, because of the lower rate of postoperative nausea and vomiting and the better preservation of the regional cortical blood flow in the frontal lobe.
Postoperatively early extubation for an immediate neurological assessment is usually attempted. It demands adequate analgesia and often the use of alpha- or betablocking agents to ensure a smooth, stressless, and hemo- dynamically controlled awakening.
Keywords: impaired hemodynamic reserve capacity, ischemic episodes, normotension, normocapnia, total intravenous anesthesia, early neurological assessment
1.1.1 Basic Physiology of Cerebral Blood Flow
The normal cerebral blood flow (CBF) of 50mL/100g/ min-1 is dependent on cerebral perfusion pressure (CPP), i.e., the difference between mean arterial pressure and intracranial pressure (MAP - ICP).
Three main principles regulate CBF: (1) flow-metabolism coupling, (2) autoregulation, and (3) carbon dioxide (CO2) reactivity. In regions of increased metabolic activity the local CBF is increased by vasodilation of arterioles to deliver more oxygen and glucose, whereas vasoconstriction is encountered in phases of diminished activity.
In healthy adults, cerebral autoregulation keeps CBF constant within blood pressure ranges between 50 and 150 mm Hg, thus preventing cerebral ischemia. Cerebral vessels react to arterial partial pressure of carbon dioxide (PaCO2) by responding to hypercapnia with vasodilation and vice versa.
As described in the Monro-Kellie doctrine, the intracranial volume is the sum of brain tissue, intracranial blood volume, and cerebrospinal fluid and is limited by the non-expandable skull.
The ICP-volume curve is nonlinear and shows the relationship between intracranial volume and ICP. When the initial intracranial volume is low and compensatory mechanisms are not exhausted, an increase in intracranial volume produces a small change in ICP. On the steep part of the curve a similar increase of intracranial volume results in a large increase of ICP, resulting in a decrease of CPP, respectively CBF (Fig. 1.1).
1.1.2 What Is Different in Patients with Moyamoya Disease?
Moyamoya is characterized by chronic progressive stenotic to occlusive changes in the terminal parts of the intracranial internal carotid arteries including the proximal parts of anterior and middle cerebral arteries. A compensatory fine vascular network is developed. Classically, moyamoya disease (MMD) is present bilaterally, but may also develop unilaterally. In these compromised areas, the cerebrovascular reactivity and the cerebral hemodynamic reserve capacity are impaired, causing transient ischemic attacks (TIAs) or strokes.1 The risk of impaired autoregulation may be even higher in pediatric patients.2
Furthermore, the fragile moyamoya vessels are prone to hemorrhage. Typically, CBF shows a paradoxic reactivity to a vasodilatory stimulus in the altered areas. The altered moyamoya vessels are already maximally dilated to provide adequate oxygen supply and perfusion to the brain tissue. These vessels cannot react to a stimulus like hypercapnia the way normal vessels do. Thus, in a hypercapnic state flow will increase in brain areas of preserved normal vasculature and decrease in moyamoya affected vessels, leading to insufficient perfusion. This regional redistribution of blood flow to healthy areas is called “steal phenomenon”3 and might clinically present as a neurologic deficit.
1.2.1 Choice of Anesthesia Technique
The superior aim of anesthesia for revascularization procedures is to ensure adequate perfusion and oxygenation of the brain and to avoid ischemic episodes. The ideal anesthetic agent should deliver smooth and hemody- namically stable anesthesia, good operating conditions (“slack brain”), and a smooth and rapid emergence to allow early neurological assessment. Cerebral perfusion pressure should be maintained, autoregulation and CO2 reactivity should be preserved.
There are some studies that have investigated propofol- maintained versus inhalational-maintained anesthesia in adult patients undergoing elective craniotomy. Both strategies were associated with similar brain relaxation, although mean ICP values were lower and CPP values higher with propofol-maintained anesthesia. The recovery profiles, e.g., eye opening, tracheal extubation, obeying verbal commands, and orientation varied only in the range of minutes without clinical significance. Also the incidence of postoperative pain, seizures, and agitation were similar with both techniques. Nevertheless, the incidence of postoperative nausea and vomiting (PONV) was significantly lower during propofol-maintained anesthesia.4
Concerning moyamoya patients, both anesthetic concepts are established and no significant differences in patient outcome were noted. Rather the carefully titrated induction drugs and good control of blood pressure, oxygenation, and stability of CO2 level are determinative.5
In authors’ opinion, there are some important arguments in favor of total intravenous anesthesia: the lower rate of PONV,6 the better preservation of the regional cortical blood flow in the frontal lobe in comparison to sevoflurane,7 the occurrence of steal phenomenon with inhalational anesthesia,8 and finally, a positive practical experience with this technique for intracranial surgery over the past 20 years in their center.
1.2.2 Preoperative Evaluation and Premedication
Patients with MMD often present with many other medical conditions, which may impact anesthetic management. Therefore, a profound preoperative anesthetic assessment is necessary and special attention should be paid to the preexisting neurologic deficits and the neurologic physical status. Motor deficits or epilepsy are signals of chronic ischemia. A history of frequent TIAs, prolonged intermittent neurologic deficits, or stroke should draw attention to an already impaired cerebral blood supply in these patients, and has been identified as a significant risk factor for perioperative complications.9 Preoperative evaluation must also include the determination of the individual baseline blood pressure, which involves several measurements before the day of surgery. A comparative blood pressure measurement on both arms is recommended to exclude falsely low blood pressure measurement intrao- peratively due to, for example, subclavian artery stenosis.
Hypertension is found in some patients as a compensatory mechanism for cerebral vascular insufficiency. Caution is necessary when attempting to treat an elevated blood pressure in these patients.
Special attention has to be paid to the patient’s chronic medication. Anticonvulsive and antihypertensive medication should be continued until the day of surgery.
Regarding the antiplatelet-medication in MMD patients, the practice of continuing the medication varies among centers. The perioperative application of aspirin and the postoperative antiplatelet therapy have become controversial. Some centers are giving antiplatelet-medication while others have abandoned them. In our center we determine the effectiveness of aspirin in each patient through a platelet-function test. Thereby detected aspirin nonresponders receive alternative antiplatelet agents.10
Premedication should be prescribed carefully. Anxioly- sis may be necessary and beneficial in children with MMD, as crying should be strictly avoided, because the resultant hyperventilation may lead to hypocapnia and consecutively to cerebral vasoconstriction, resulting in cerebral ischemia. Vice versa oversedation followed by hypoventilation should also be avoided.
Midazolam is most often used for premedication, but other drugs can also be used.11
The American Society of Anesthesiologists (ASA) standard monitoring should be extended to invasive arterial blood pressure monitoring and urine output measurement. Anesthesiologists should consider placing the arterial line prior to induction, especially if preexisting medical conditions prompt it, and if the procedure is not considered too stressful for the patient.
Continuous arterial blood pressure monitoring intra- and postoperatively is the key for keeping the blood pressure within a predefined range (see Chapter 1.2.4).
Adequate venous access is essential and can be established by two “well-running” intravenous lines. A central venous catheter is not mandatory but should be considered in patients with very poor venous access or severe coexisting medical conditions.
Cerebral function can be monitored in various ways. Most reliable techniques are the combined transcranial motor-evoked potentials (MEP) and sensory-evoked potentials (SEP) monitoring. Cerebral function monitoring is of crucial importance especially in pediatric patients and in unstable adult patients, because they may experience strokes even after short-term blood pressure drops. Electroencephalography can help identify focal slowing, indicating a compromise CBF. Although nearinfrared spectroscopy (NIRS) is only validated for measurement of cerebral oxygen saturation on the forehead, it has been shown that a sustained drop in regional oxygen saturation is closely related to the occurrence of neuro
logical events following surgery,12 and thus NIRS may provide useful information intraoperatively.
1.2.4 Targets of Anesthesia
Hemodynamics: What Is the Optimal Blood Pressure?
It is very important to have appropriate hemodynamic conditions throughout the perioperative period. Reduction in CBF is poorly tolerated, especially in children because they have a diminished autoregulatory response and a higher cerebral metabolic rate.5
Hypotension may cause ischemia or threaten the graft patency because of developing thrombosis. Hypertension may lead to bleeding or cause a hyperperfusion syndrome with clinical symptoms such as an ischemic attack (see also Chapter 1.4.2).
There is not the one optimal blood pressure for all MMD patients. Generally it is recommended to maintain the blood pressure normotensive or to keep it within 10 to 20% of the preoperatively established baseline.11'13 Some MMD patients induce hypertension and are dependent on higher systolic blood pressure levels. Therefore, the systolic blood pressure target should be determined for the individual MMD patient between the surgeon and the anesthesiologist. It is of tremendous importance to maintain the blood pressure stable perioperatively within the defined limits. According to our experience, in case of hypertensive adult MMD patients, we suggest to keep the systolic blood pressure 20% above the individual baseline systolic blood pressure. For normotensive adult patients, we suggest to keep the systolic blood pressure at 140 mm Hg. The individual baseline systolic blood pressure can function as the lower threshold for the systolic blood pressure.
Careful and smooth titration of anesthetic drugs for induction, maintenance of anesthesia as well as anticipating cardiovascular responses to surgical stimuli is very important for blood pressure control. Episodes of hypotension should be treated immediately with vasoactive drugs, e.g., norepinephrine or phenylephedrine.
The postoperative goal for blood pressure maintenance should be consented with the surgeon. The target blood pressure depends on the quality and diameter (which determines also the flow) of the bypass. It is also to be taken into consideration if additional indirect techniques have been performed, for example, encephalo-myo-synangiosis. Hyperperfusion of the brain has to be strictly avoided as well as insufficient flow and hypoperfusion. Thus, no general rule can be given.5 An appropriate analgesic management has to be established before emergence from anesthesia and during the postoperative period to prevent hypertensive episodes. Vasodilating drugs such as urapidil or labetalol should be kept handy.
How to Ventilate the Patient?
Normocapnia should be the target of ventilation, regardless of the ventilator mode chosen. The arterial pCO2 should range between 39 and 43 mm Hg, because the cortical blood flow is maximal in this range.14,15 A retrospective analysis of 124 children undergoing surgery for MMD showed that those patients who suffered from postoperative ischemic complications had intraopera- tively PaCO2 levels significantly above 45 mm Hg. If additional risk factors (preoperative TIA) were present, the incidence of postoperative ischemic complications was even higher.9 This is consistent with a recent investigation of adult MMD patients. It has been demonstrated that hemodynamically unstable Berlin Moyamoya Grade 3 patients (severe MMD) have the highest risk for perioperative ischemia.16
The collateral network of vessels in patients with MMD is in a state of maximal vasodilation. When healthy vessels dilate in response to hypercapnia, they steal the blood from the hemodynamically compromised areas (of maximal vasodilation).5,8 See Chapter 1.1.2.
1.2.5 Induction and Maintenance
The major aim of anesthesia induction in MMD patients is to perform a smooth induction, not to allow blood pressure to swing between hypertension and hypotension, as well as to avoid hyperventilation, hypoventilation, and hypoxemia.
In children, it is recommended to carefully guide the separation from the parents before anesthesia to prevent crying and thus an increase of ICP or hyperventilation. Intubation should be performed in a deeply anesthetized patient to avoid any hemodynamic effect.
For intravenous induction the choice of agents includes propofol, thiopental, or etomidate.
Also in children, intravenous induction has some advantage over inhalational induction. For the latter, sevoflurane is the agent of choice. Intravenous opioids are recommended to attenuate the response to laryngoscopy and tracheal intubation. The authors prefer the shortacting remifentanil. Administration may be started at a low dose before the induction agent is applied (e.g., remifentanil 0.1pg/kg BW/min for 5 minutes) and then continued and increased in dosage (e.g., 0.2-0.3pg/kg BW/min) throughout the procedure as part of the total intravenous anesthesia (TIVA). Bolus administration of fentanyl (e.g., 3- 3.5pg/kg BW) for induction and repetitive doses throughout surgery is another option.
The ideal choice for muscle relaxation is a nondepolarizing agent, unlikely to cause hemodynamic changes or histamine release.11,13,17
Body temperature should be monitored throughout the procedure and measures should be taken to maintain normal body temperature. The proposed beneficial effect of mild hypothermia reduces the cerebral metabolic rate and thus protects the brain against hypoxia and ischemia to some degree. However, as to date, no randomized controlled trial has been conducted to show the benefit of hypothermia for vascular patients in neurosurgery.
Moreover, hypothermia bears the risk of increased bleeding by compromising coagulation and may further precipitate postoperative shivering, and thus increase cerebral metabolic rate.
Anesthesiologists might be asked to administer an intravenous bolus of indocyanine green (ICG) during bypass surgery. ICG video-angiography visualizes the patency of a bypass graft. Technically the angiography requires a microscope with an integrated ICG camera that applies near-infrared light on the surgical field.
ICG is delivered as a powder (25 mg) that has to be diluted in 5 cc of distilled water. Usually the applied dose ranges between 5 and 25 mg. Following the intravenous ICG injection, a short period of “falsely low” pulse oximetry values has to be anticipated due to the dye. ICG is administered in close communication with the surgeon either through a well running intravenous line or a central line, which is immediately flushed with a bolus of 20 cc sodium chloride.
ICG is generally a safe drug, nevertheless, cases have been reported of patients who showed adverse reaction to the ICG injection, especially hypotension.18
Perioperative fluid management should aim at maintaining normovolemia.
The holding of packed red blood cells or fresh frozen plasma for the surgical procedure should be agreed upon with the surgeon in each institution, depending on the average need for transfusion for the procedure. Intraoperatively, it is crucial to check hemoglobin and hematocrit values regularly. Severe anemia should be treated. There is no ideal hematocrit or hemoglobin level for all MMD patients, but polycythemia should be avoided as much as pronounced hemodilution, because both can lead to cerebral ischemia, the latter by reducing the oxygen-carrying capacity of the blood.5,13
The major target at emergence is a smooth and hemodynamically controlled awakening. Extubation may be performed in the operating room (OR) if feasible, to allow for immediate neurological assessment. At the end of surgery an individual blood pressure range should be agreed upon between surgeon and anesthesiologist individualized for each patient, and any deviations should be treated immediately. Usually, the range for systolic blood pressure in adult patients will be set between 120 and 140 mm Hg. Blood pressure increases may occur during patient awakening and should be carefully treated with a well-controllable antihypertensive agent, e.g., with a beta-blocking agent (e.g., esmolol) or alpha-blocking agent urapidil (the latter is not available in United States and Canada). It is also crucial to prevent coughing or shivering and to administer sufficient pain relief.
Sufficient spontaneous ventilation will aid to maintain normocapnia, which should be regularly controlled via PaCO2 measurement through blood gas analysis. Adequate oxygen supply may be assured through oxygen insufflation via a nasal line. An oxygen mask should be avoided, since the straps put direct pressure on the side of the head where bypass surgery had just been performed.
Patients are transferred under continuous monitoring and care from the OR to an intensive care or postanesthesia care unit, where they are monitored overnight. Discharge to the normal ward should be decided the next morning, after neurologic examination and depending on the patient’s well-being.
Blood pressure, oxygen saturation, hematocrit, volume status, and urine output should be closely monitored in the postoperative period. Maintaining normovolemia and avoiding blood pressure exaggeration is crucial. Neurologic examination has to be performed frequently to identify ischemia at an early state.13
1.3.2 Pain Control
Good analgesia is an important factor in reducing the risk of postoperative cerebral ischemia or infarction. In children, pain relief can also help avoid crying and associated negative effects of hyperventilation and hypocapnia. Pain management can be performed according to the institution’s standards. Early after surgery, opioids will usually be part of the regimen. There are several options, e.g., pir- itramid (which is not approved in the United States), morphine, or fentanyl, which can be applied by titrating intravenous doses or by continuous infusion, the latter only if the patient is permanently monitored for signs of ventilatory suppression. Of note, when anesthesia was performed with a short-acting agent such as remifentanil, adequate additional analgesia, e.g., with an opioid such as morphine, has to be applied before emergence.
Reduced cerebral hemodynamic reserve capacity
Attention to previous transient ischemic attacks (TIAs), preexisting neurologic deficits
Stage of hemodynamic failure (see Chapter 1.2.2)
Antiplatelet and anticoagulation management of your center
Adequate cerebral perfusion
Normotension, within 10-20% of baseline blood
Normoxia, elevate fraction of inspired oxygen (FiO2) to
1.0 during temporary occlusion
Prefer propofol and a short-acting opioid
Sufficient analgesia intra- and postoperatively
Prevent hypo- and hypertension, hypo- and
Electrocardiogram, pulse oximetry, noninvasive blood
Arterial line for invasive BP
Central venous catheter if required by concomitant
Urine output, body temperature
Near-infrared spectroscopy (NIRS)
Transfer to intensive care unit
BP control within set limits
Ensure graft perfusion (antiplatelet or anticoagulation)
Additionally a peripherally acting analgesic should be applied before emergence, such as paracetamol or metamizol.
Placement of a skull block may be a useful addition to anesthesia in MMD patients. It has been shown to be helpful in children during encephalo-duro-arterio-myo synagiosis (EDAMS) surgery, providing calm awakening and lower analgesic requirements postoperatively.19
Prevention of any deterioration of cerebral perfusion is pivotal in the care of MMD patients.
1.4.1 Ischemic Stroke and Transient Ischemic Attacks
Transitory ischemic attacks can occur as a result of inappropriate cerebral perfusion and cannot be reliably detected while the patient is under anesthesia. Alternatively, a graft thrombosis may be the cause. As pointed out previously, hypotension or suboptimal blood pressure control has to be strictly avoided intra- and postopera- tively. Generally, the controlled mild hypertension is of greatest relevance to prevent ischemic events in MMD patients. Clinicians should keep in mind the increased risk for ischemic complications in patients with a history of TIAs (see also Chapter 1.2.2). Patients undergoing indirect revascularization procedures will have a persistent risk for cerebral ischemia until the neovascularization has been completed, which may require months.
Intraoperatively bypass patency should be assessed directly and/or with ICG spectroscopy by the surgeon. Postoperatively, transcranial Doppler evaluation or perfusion CT/MRI are valuable diagnostic tools.
1.4.2 Cerebral Hyperperfusion Syndrome
Typically in moyamoya patients the diseased vessels are already maximally vasodilated and show little autoregu- latory capacity. The low-flow superficial temporal artery to middle cerebral artery (STA-MCA) bypass might lead to cerebral hyperperfusion in a previously poorly perfused cerebral vascular bed, often presenting as a transient neurological deterioration or an ischemic attack.
Furthermore, cerebral hyperperfusion may lead to intracranial hemorrhage with potentially fatal outcome, thus underlining the emphasis which has to be put onto a strict blood pressure control.
 Kuwabara Y, Ichiya Y, Sasaki M, et al. Response to hypercapnia in moyamoya disease. Cerebrovascular response to hypercapnia in pediatric and adult patients with moyamoya disease. Stroke. 1997; 28(4):701-707
 Lee JK, Williams M, Jennings JM, et al. Cerebrovascular autoregulation in pediatric moyamoya disease. PaediatrAnaesth. 2013; 23(6):547-556
 Han JS, Abou-Hamden A, Mandell DM, et al. Impact of extracranial- intracranial bypass on cerebrovascular reactivity and clinical outcome in patients with symptomatic moyamoya vasculopathy. Stroke. 2011; 42(11):3047-3054
 Chui J, Mariappan R, Mehta J, Manninen P, Venkatraghavan L. Comparison of propofol and volatile agents for maintenance of anesthesia during elective craniotomy procedures: systematic review and metaanalysis. Can J Anaesth. 2014; 61(4):347-356
 Chui J, Manninen P, Sacho RH, Venkatraghavan L. Anesthetic management of patients undergoing intracranial bypass procedures. Anesth Analg. 2015; 120(1):193-203
 Sneyd JR, Andrews CJ, Tsubokawa T. Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery. BrJ Anaesth. 2005; 94(6):778-783
 Kikuta K, Takagi Y, Nozaki K, et al. Effects of intravenous anesthesia with propofol on regional cortical blood flow and intracranial pressure in surgery for moyamoya disease. Surg Neurol. 2007; 68(4): 421-424
 Sato K, Shirane R, Kato M, Yoshimoto T. Effect of inhalational anesthesia on cerebral circulation in Moyamoya disease. J Neurosurg Anesthesiol. 1999; 11(1):25-30
 Iwama T, Hashimoto N, Yonekawa Y. The relevance of hemodynamic factors to perioperative ischemic complications in childhood moya- moya disease. Neurosurgery. 1996; 38(6):1120-1125, discussion 1125-1126
 Smith ER, Scott RM. Surgical management of moyamoya syndrome. Skull Base. 2005; 15(1):15-26
 Baykan N, Ozgen S, Ustalar ZS, Dag^inar A, Ozek MM. Moyamoya disease and anesthesia. Paediatr Anaesth. 2005; 15(12):1111-1115
 Orihashi K, Sueda T, Okada K, Imai K. Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion. Eur J Cardiothorac Surg. 2004; 26(5):907-911
 Parray T, Martin TW, Siddiqui S. Moyamoya disease: a review of the disease and anesthetic management. J Neurosurg Anesthesiol. 2011; 23(2):100-109
 Kurehara K, Ohnishi H, Touho H, Furuya H, Okuda T. Cortical blood flow response to hypercapnia during anaesthesia in Moyamoya disease. CanJ Anaesth. 1993; 40(8):709-713
 Yusa T, Yamashiro K. Local cortical cerebral blood flow and response to carbon dioxide during anesthesia in patients with moyamoya disease. J Anesth. 1999; 13(3):131-135
 Czabanka M, Boschi A, Acker G, et al. Grading of moyamoya disease allows stratification for postoperative ischemia in bilateral revascularization surgery. Acta Neurochir. 2016; 158:1895-1900
 Brown SC, Lam AM. Moyamoya disease-a review of clinical experience and anaesthetic management. Can J Anaesth. 1987; 34(1):71-75
 Bjerregaard J, Pandia MP, Jaffe RA. Occurrence of severe hypotension after indocyanine green injection during the intraoperative period. A A Case Rep. 2013; 1(1):26-30
 Ahn HJ, Kim JA, Lee JJ, et al. Effect of preoperative skull block on pediatric moyamoya disease. J Neurosurg Pediatr. 2008; 2(1):37-41 Suggested Readings
ChuiJ, Manninen P, Sacho RH, Venkatraghavan L. Anesthetic management of patients undergoing intracranial bypass procedures. Anesth Analg. 2015; 120(1):193-203
Parray T, Martin TW, Siddiqui S. Moyamoya disease: a review of the disease and anesthetic management. J Neurosurg Anesthesiol. 2011; 23(2):100- 109