Craniotomy for Subarachnoid Hemorrhage (SAH) Secondary to Cerebral Aneurysm
Author: Ryan Pong, MD

Case: A 46 year-old female has been brought to the Emergency Department (ED) by paramedics. She was in her usual state of health at work when she had a sudden onset of headache and nausea and lost consciousness and collapsed. 911 was called and she was transported immediately to the ED with one bout of emesis en route.

PMH: Hypertension, tobacco use with 25 pack year history of smoking, migraine headaches

Medications: Lisinopril 10 mg PO daily. Excedrin as needed.

Physical Examination: She is obtunded and resting in the gurney with her eyes closed, which do not open in response to any stimulation. Upon attempts at arousal she grunts. She does withdraw from painful stimulation on the left but no movement on the right side. Her pupils are reactive and equal.

Vital signs: Blood pressure 210/115, pulse rate 48, respiratory rate 14, temperature 36.8^oC, SpO₂ 93 % on 6 liters delivered by face mask.

Habitus: 64 kg. 164 cm. BMI 24.

Heart: Bradycardia noted with a possible 3^rd heart sound after S2
Lungs: Rales at bilateral bases
Airway: C-spine collar is in place, Mallampati score is unable to be evaluated due to patient inability to participate with the exam. She appears to have regular and solid dentition with a slightly less than three fingerbreadth mental hyoid distance.

Laboratory Studies: Na 130 mmol/L K 3.1 mmol/L Glucose 213 mg/dL WBC 22 x 10⁹/L Hgb 35 g/dL and Plt 258 x10⁹/L

Key Questions:

1. When evaluating a patient with subarachnoid hemorrhage, what are the clinical findings associated with a poor outcome? How do those translate into clinical care preoperatively?
2. What are the cardiopulmonary sequelae that can impact intraoperative management? What clues does her physical exam lend to the status of her cardiopulmonary status? What work up is necessary to further evaluate?
3. How does one decide between open craniotomy for aneurysm surgery and endovascular therapy?

Case Continued: A CT angiogram was completed and the neurosurgeon, who does both endovascular coiling as well as open clipping favors open craniotomy for this patient given the geometry of the aneurysm (wide neck) as well as proximity to nearby vessels.

4. What is the time frame that leads to the best patient outcome for securing intracranial aneurysms?
5. Describe the considerations to achieve induction of anesthesia for craniotomy as safely as possible.
6. What anesthetic agents should be used for the maintenance phase of anesthesia? Do neuromonitoring requirements alter the anesthetic plan?
7. Would therapeutic hypothermia be indicated during clipping of this aneurysm?

Case Continued: Induction of anesthesia and securing the airway was accomplished uneventfully. The bone flap has been removed, dura opened and dissection is ongoing. Abruptly the surgeon notes that the aneurysm has ruptured and that a temporary clip will need to be placed.

8. What are the conditions where burst suppression may be warranted? How could it be performed? How would you monitor for burst suppression? What is temporary clipping? How is it performed? What tactics should be employed during temporary clipping to improve patient outcomes?
9. How is the secured aneurysm evaluated intraoperatively? What is the role of micro Doppler? Of indocyanin green (ICG)? Of intraoperative angiography?
10. How do you decide whether to allow patient emergence after aneurysm clipping? What considerations prevail?
11. What are the risks to the patient in the immediate post-operative period? Where should a patient be monitored and how?

Case Continued: The patient is in the neurointesive care unit (NICU) on post-operative day 4 extubated and seemingly stable. She does respond to voice by opening her eyes and does squeeze her left hand when asked to. Early in the evening, she is noted to no longer respond to voice or verbal command.

12. How does delayed cerebral ischemia present? How is it detected? How is it treated?

Discussion:

• The anesthetic management of a ruptured cerebral aneurysm requires applying the cerebral pathophysiology of the pressure volume relationship of the cranial vault, maximizing cerebral perfusion while aspiring to minimize the risk of rerupture and subsequent rebleeding.
• There are interactions between other organ systems (for example the heart and lungs) that may complicate the care of a ruptured cerebral aneurysm patient and need consideration.
• Treatment of the aneurysm can be via endovascular treatment with coils or open clipping.¹ Complex anatomy and center preference still play a large role in determining who are deemed operative or endovascular candidates.
• Delayed cerebral ischemia can manifest after a successful operation for securing the aneurysm and patients at risk require monitoring for this complication in the post-operative period.

Evaluation of the Patient with SAH:

• There are two main ways to describe the preoperative clinical condition of patients with subarachnoid hemorrhage.
  1. Hunt and Hess²
     

     Score	Mentation	Motor Deficits
     I	Normal	None
     II	Normal	None +/- cranial nerve deficits
     III	Drowsy	Focal
     IV	Stupor	Hemiparesis
     V	Coma	Decerebrate

     1. The morbidity inflection point is between II and III; when mentation is affected, the patient’s risk of morbidity is increased dramatically. ³
     2. The mortality inflection point is between III and IV; when major neurologic deficits are detected, the risk of mortality is increased.³
• Our patient is minimally responsive—grunting to arousal and hemiparetic on one side. This would place her in a Hunt Huss Grade IV with both increased morbidity and mortality risk.
  1. ii. The World Federation of Neurologic Surgeons (WFNS) is a similar scale utilizing the Glasgow Coma Scale Score and the presence or absence of motor deficits.⁴
• Utilizing a clinical grading system is important for both prognostication but also to help inform the level of impairment during the perioperative period. There is a direct correlation with clinical grade and risk of vasospasm, elevated ICP, impaired autoregulation, vasomotor reactivity (the cerebrovascular response to p_aCO₂), as well as myocardial abnormalities.⁵
• Given that our patient is a Hunt Hess Grade IV, one would expect to see all of the above sequelae and associated derangements in cerebral physiology.
• A review of the patient’s computed tomography (CT) scan should be done. The presence and degree of edema, degree of sulcal effacement and the presence of hydrocephalus can be determined. Also the blood burden helps prognostication of outcome as well as the risk of delayed cerebral ischemia. The Fisher scale has been used for this purpose with the thicker the layers of blood correlating to increased risk of vasospasm.⁶

Cardiopulmonary Considerations:

• Subarachnoid hemorrhage can be associated with abnormalities with the heart secondary to a neurogenically stressed myocardium. 40-100% of those with aneurysmal subarachnoid hemorrhage have coincident EKG changes ranging from T wave inversions to ST segment depression and dysrhythmias including atrial fibrillation and flutter.⁷ A troponin leak can also accompany these EKG findings.⁸ If an echocardiogram is performed, wall motion abnormalities can be found in about 13-18% of patients. Takotsubo cardiomyopathy can be seen in up to 10% of those with SAH.⁹
• Myocardial dysfunction can complicate perioperative management. If cardiac output is diminished, manipulating blood pressure may have to rely on both vasoconstriction (e.g. phenylephrine) as well as increasing ionotropy (e.g. epinephrine). This patient has evidence of coronary compromise, given the S3 heart sound, indicating volume overload as well as the pulmonary edema. Pulmonary edema is observed in 8-28% of patients with SAH.¹⁰ There are three etiologies possible: 1) poor myocardial function with subsequent pulmonary congestion, 2) direct sympathetically mediated edema or 3) inflammatory mediated.
• Our patient has signs of myocardial dysfunction given the S3, likely indicating a poor myocardial functional state. An EKG, troponin measures and a transthoracic echocardiogram may provide additional information that could inform perioperative management. As most ruptured cerebral aneurysm surgeries are urgent but not emergent, there is usually time to obtain these studies prior to the surgical event.

Open Craniotomy Versus Endovascular Therapy for SAH:

• Open craniotomy and clipping of the aneurysm or endovascular therapy with coils may be considered.¹ Data suggest that while there are less morbidity and dependency after coiling, there is an increased risk of rebleeding.¹¹ A general approach would be to consider coiling as the primary intervention unless unfavorable geometry exist that precludes coiling or in young patients with a ruptured anterior circulation aneurysm.¹² There is likely to be significant variability between medical centers.

Timing of Therapy:

• The timing of surgery has created two thought processes: 1) operating on a newly inflamed and injured brain can only increase the secondary neuronal damage. 2) Operating early will allow a reduction of rebleeding risk and vigorous treatment of vasospasm. Aneurysmal clipping is rarely an emergent surgery while most centers tend to secure aneurysms with earlier surgery in an urgent fashion. The worst time to operate is between 7 and 10 days post rupture, when the risk of vasospasm is at its greatest.¹³

Considerations for Induction of Anesthesia:

• There are two major forces in effect that need to be considered when caring for a patient with a cerebral aneurysm at risk:
  1. Transmural pressure (TMP) is the pressure across the aneurysmal dome, this is the force that acts to rupture the aneurysm. TMP is defined as mean arterial pressure (MAP) which is the force that causes rupture minus the intracranial pressure (ICP) which acts as a force to keep the lid on the dome of the aneurysm. Ideally, the transmural pressure would be as minimal as possible.
  2. Cerebral perfusion pressure (CPP) is the pressure available to make substrates of metabolism available to the brain. It is defined as the MAP (forward moving energy) minus the ICP (energy that resists forward movement).
• Note that TMP and CPP are mathematically defined by the same variables. Thus as one seeks to perfuse and nourish the brain, the risk of rupture is increased. As one seeks to reduce the risk of rupture, the risk of underperfusing the brain is increased. Knowing the patient’s baseline pressure can serve as a starting point, however, the choice of blood pressure target must consider each unique patient scenario and the risk of rupture versus hypoperfusion.
• The choice of succinylcholine versus other neuromuscular blocking drugs such as rocuronium or cisatracurium requires consideration of effect on ICP, rapidity to which a secure airway is required, time course of neurological deficits and conditions desired for neuromonitoring. While succinylcholine has been found to increase intracranial pressure,¹⁴ as long as the brain is well anesthetized and pCO₂ controlled, the effects should be negligible.¹⁵ While caution should always be used when utilizing succinylcholine with regards to hyperkalemia, it has not been found to significantly raise potassium in either early or delayed surgery.¹⁶ Requirements for motor evoked potential (MEP) monitoring may suggest that rocuronium or cisatracurium be avoided. However, the time from tracheal intubation to the time MEP signals are needed is usually sufficient to allow for both to exist satisfactorily in one anesthetic. The one caveat is the institutional practice regarding when baseline values are obtained, however, since positioning should not impact signals as in spine surgery, the need for baseline MEP signals early in the case is questionable.

Maintenance of Anesthesia:

• Neurophysiologic monitoring, including somatosensory evoked potentials (SSEP) and MEPs have seen an increase in utilization.¹⁷ If these modalities are used, a total intravenous anesthetic (e.g. propofol and narcotic) usually affords the least attenuation of signals. If burst suppression is utilized, avoiding a troubling false positive loss of signals is important, as the increased dosage of propofol used to induce burst suppression can attenuate SSEP and MEP signals. If possible, a second set of baseline values should be obtained after burst suppression has been achieved.
• Anesthesia for maintenance can be performed with an inhaled agent¹⁸ or TIVA with propofol depending on the neuromonitoring requirements addressed earlier. While several studies do show improved operating conditions with TIVA, outcome studies are lacking.¹⁹

Therapeutic Hypothermia:

• Hypothermia can also protect from ischemia secondary to hypoperfusion. As discussed above, 60% of the CRMO₂ is from neuronal function as indicated by EEG, the remaining 40% of the CRMO₂ is from the basal metabolic activity of the brain cells. This 40% is not affected by burst suppression, but both the 60% from electrical activity and 40% from the basal metabolic requirements are reduced with hypothermia. The Intraoperative Hypothermia during Aneurysm Surgery Trial (IHAST) was a large (n=1001) trial of good grade (WFNS I, II or III) ruptured aneurysms, and failed to show improve outcomes at targets of 33^oC vs 36.5^o20 Some centers may still utilize hypothermia, especially in more complex aneurysm surgery or worse clinical grade patients. Hyperthermia should be avoided because the CMRO₂ increases when the tissue is warmed, which can exacerbate ischemic injury.

Burst Suppression:

• Burst suppression is utilized to decrease the metabolism of brain tissue that will have its blood supply attenuated for a period of time. Roughly 60% of the cerebral oxygen requirement (CMRO₂) is due to the electrical activity of the brain. By reducing the electrical activity via burst suppression, it is thought that the safe ischemic time may be increased. Ischemic time usually occurs due to the utilization of a temporary clip either to facilitate permanent clip placement or to control blood loss after the aneurysm has ruptured intraoperatively. There is no good evidence to suggest that utilizing burst suppression affects outcomes.²¹
• Burst suppression can be induced with any hypnotic agent, traditionally with sodium thiopental. Because of the difficulty in obtaining sodium thiopental, propofol has become an alternative choice to induce burst suppression.²² An increase in the infusion rate with or without an initial bolus prior to the temporary clip placement can induce periods of isoelectricity on the EEG which can be monitored with any type of EEG recorder such as the BIS²³, Sedline or other systems (space on the forehead may not be accessible depending on surgical approach). If burst suppression is attempted for cerebral protection, the importance of suppressing the brain prior to temporary clip placement cannot be overstated—while the rest of the brain will enter burst suppression with propofol dosing after the clip is placed, the brain at risk is likely to receive little to no protection.

Intraoperative Evaluation of the Secured Aneurysm:

• After a clip is placed, an assessment needs to be made if 1) the aneurysm is completely secured and 2) no surrounding vessels were inadvertently occluded. Microdoppler is a technique that is employed by the surgeon to evaluate for absence of flow in the aneurysmal sac and persistence of flow in surrounding vessels.²⁴
• Traditional intraoperative angiography can be utilized to evaluate clip placement. This involves setting up a C-arm in the OR suite and cannulation of the patient’s groin and performing traditional digital subtraction angiography. While this is the gold standard, it is time consuming, involves risk of damaging vessels and resource intensive and may not allow for the timely repositioning of the permanent clip should a vessel be inadvertently occluded.
• Indocyanin green (ICG) video angiography has largely supplanted intraoperative angiography. Injecting a fluorescent molecule that is then detected by a special filter built into the surgical microscope allows almost instantaneous evaluation of clip placement.²⁵ ICG needs to be mixed prior to injection and is stable for about 6 hours. ICG does interfere with pulse oximetry momentarily. There are case reports of anaphylaxis following the injection of ICG likely related to the iodine additive or the dye itself.

Emergence Considerations:

• Emergence from anesthesia should be considered on a case by case basis. Factors that should be considered include preoperative condition (Hunt Hess grades 1-2 should likely be able to be extubated immediately following surgery) and intraoperative events (aneurysmal rupture or prolonged temporary clip utilization or hemodynamic instability may be indicators for continued sedation and mechanical ventilation). A rapid emergence in order to facilitate a neurologic exam is helpful and continued neurologic exams on a frequent basis should be utilized in the immediate post-operative period.

Postoperative Considerations:

• Most patients who have a ruptured cerebral aneurysm clipped are monitored in a neurointensive care unit. The normal concerns surrounding a post-operative craniotomy exist: monitoring physiologic parameters as well as mental status both surveilling for signs of intracranial bleeding or swelling.

Delayed Cerebral Ischemia:

• One added risk to a subarachnoid hemorrhage patient is the risk of delayed cerebral ischemia associated with cerebral vasospasm. Vasospasm by angiography occurs in 40-60% of patients and is associated with symptoms about 20-30% of the time. The peak incidence of this complication is between post bleed day 3 and 7.
• Detecting vasospasm includes serial neurologic exam, transcranial doppler flow velocity surveillance²⁶, SPECT scans or CT or MR perfusion studies. Digital subtraction angiography remains the gold standard and also allows for therapeutic interventions such as angioplasty or injection of vasodilators.²⁷
• Treatment of vasospasm prior to angioplasty used to involve the institution of Triple H therapy: Hypervolemia, Hypertension, and Hemodilution. With data lacking to support all arms of the triad, hypertension to allow adequate perfusion is the mainstay in therapy. While hypervolemia may improve cardiac output and hence cerebral perfusion, it has been associated with an increased risk in pulmonary dysfunction.²⁸

---

References:

1. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360: 1267-74.
2. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968;28: 14-20.
3. Cottrell and Young’s Neuroanesthesia. Philadelphia, PA: Elsevier; 2010.
4. Report of World Federation of Neurological Surgeons Committee on a Universal Subarachnoid Hemorrhage Grading Scale. J Neurosurg 1988;68: 985-6.
5. Priebe HJ. Aneurysmal subarachnoid haemorrhage and the anaesthetist. Br J Anaesth 2007;99: 102-18.
6. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6: 1-9.
7. Sakr YL, Ghosn I, Vincent JL. Cardiac manifestations after subarachnoid hemorrhage: a systematic review of the literature. Prog Cardiovasc Dis 2002;45: 67-80.
8. Naidech AM, Kreiter KT, Janjua N, et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 2005;112: 2851-6.
9. Lee VH, Connolly HM, Fulgham JR, et al. Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an underappreciated ventricular dysfunction. J Neurosurg 2006;105: 264-70.
10. Muroi C, Keller M, Pangalu A, et al. Neurogenic pulmonary edema in patients with subarachnoid hemorrhage. J Neurosurg Anesthesiol 2008;20: 188-92.
11. Molyneux AJ, Birks J, Clarke A, et al. The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 2015;385: 691-7.
12. Lanzino G, Murad MH, d’Urso PI, et al. Coil embolization versus clipping for ruptured intracranial aneurysms: a meta-analysis of prospective controlled published studies. AJNR Am J Neuroradiol 2013;34: 1764-8.
13. Kassell NF, Torner JC, Jane JA, et al. The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results. J Neurosurg 1990;73: 37-47.
14. Lanier WL, Milde JH, Michenfelder JD. Cerebral stimulation following succinylcholine in dogs. Anesthesiology 1986;64: 551-9.
15. Kovarik WD, Mayberg TS, Lam AM, et al. Succinylcholine does not change intracranial pressure, cerebral blood flow velocity, or the electroencephalogram in patients with neurologic injury. Anesth Analg 1994;78: 469-73.
16. Manninen PH, Mahendran B, Gelb AW, et al. Succinylcholine does not increase serum potassium levels in patients with acutely ruptured cerebral aneurysms. Anesth Analg 1990;70: 172-5.
17. Szelenyi A, Langer D, Kothbauer K, et al. Monitoring of muscle motor evoked potentials during cerebral aneurysm surgery: intraoperative changes and postoperative outcome. J Neurosurg 2006;105: 675-81.
18. Engelhard K, Werner C. Inhalational or intravenous anesthetics for craniotomies? Pro inhalational. Curr Opin Anaesthesiol 2006;19: 504-8.
19. Chui J, Mariappan R, Mehta J, et al. Comparison of propofol and volatile agents for maintenance of anesthesia during elective craniotomy procedures: systematic review and meta-analysis. Can J Anaesth 2014;61: 347-56.
20. Todd MM, Hindman BJ, Clarke WR, et al. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 2005;352: 135-45.
21. Hindman BJ, Bayman EO, Pfisterer WK, et al. No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial. Anesthesiology 2010;112: 86-101.
22. Ravussin P, de Tribolet N. Total intravenous anesthesia with propofol for burst suppression in cerebral aneurysm surgery: preliminary report of 42 patients. Neurosurgery 1993;32: 236-40 discussion 240.
23. Pauls RJ, Dickson TJ, Kaufmann AM, et al. A comparison of the ability of the EEGo and BIS monitors to assess emergence following neurosurgery. Can J Anaesth 2009;56: 366-73.
24. Siasios I, Kapsalaki EZ, Fountas KN. The role of intraoperative micro-Doppler ultrasound in verifying proper clip placement in intracranial aneurysm surgery. Neuroradiology 2012;54: 1109-18.
25. Roessler K, Krawagna M, Dorfler A, et al. Essentials in intraoperative indocyanine green videoangiography assessment for intracranial aneurysm surgery: conclusions from 295 consecutively clipped aneurysms and review of the literature. Neurosurg Focus 2014;36: E7.
26. Seiler RW, Grolimund P, Aaslid R, et al. Cerebral vasospasm evaluated by transcranial ultrasound correlated with clinical grade and CT-visualized subarachnoid hemorrhage. J Neurosurg 1986;64: 594-600.
27. Schmidt U, Bittner E, Pivi S, et al. Hemodynamic management and outcome of patients treated for cerebral vasospasm with intraarterial nicardipine and/or milrinone. Anesth Analg 2010;110: 895-902.
28. Treggiari MM, Participants in the International Multi-disciplinary Consensus Conference on the Critical Care Management of Subarachnoid H. Hemodynamic management of subarachnoid hemorrhage. Neurocrit Care 2011;15: 329-35.