10.1.1 Inhaled Anesthetics

Inhaled volatile anesthetics (sevoflurane, desflurane, and isoflurane) are the most commonly used maintenance agents for general anesthesia (GA) due to their ease of delivery and reliable, dose-dependent amnesia, hypnosis, and akinesia. ¹ Volatile anesthetics have no single site of activity and are agents of mass action and globally depress activity in the brain and spinal cord. The primary hypnotic effect involves gamma-aminobutyric acid (GABA) type A receptors; however, there are many other sites of action such as ion channels, nicotinic, serotonin type 3, glycerin, and glutamate receptors. ² These agents hinder brain-mapping techniques in a dose-dependent fashion either by depressing epileptogenic foci or hindering their locations by paradoxical neuroexcitatory properties. At high concentrations, sevoflurane can cause burst suppression and reduce electrocorticography (ECoG) spike activity. ³ However, seizure-like activity and electroencephalography (EEG)-recorded seizures have been described with volatile anesthetics, and they are thought to be due to excitatory neuronal foci stimulated by the global inhibition of the central nervous system. ⁴ Despite this finding, in general, this neuronal stimulation is unreliable when seeking to identify ECoG spike activity during epileptic surgery. ⁵ For these reasons, although some authors will describe the use of volatile anesthetics as a way to potentially stimulate epileptogenic foci during ECoG while under GA, it is most common to limit these agents to 0.5 MAC with higher doses of opioids as an adjunct to the anesthetic, as the effect on ECoG recording is negligible. ⁶

Similarly, nitrous oxide has also been used in the neurosurgical population and has been shown to attenuate the frequency of spike in epileptic patients, ⁷ but is thought to not interfere with ECoG when combined with high doses of opioids alone. ⁶ Nitrous oxide is significantly less potent when compared to volatile anesthetics during GA and has several limitations, such as expansion of gas-filled spaces (i.e., potential for pneumocephalus ⁸ ) and diffusion hypoxia. ⁹ Nitrous oxide/opioid technique can be associated with a higher risk of nausea and vomiting, which has resulted in its decreased popularity over the years and replacement with intravenous (IV) anesthetic techniques.

The neuroinhibitory effects of vapor anesthetics can also significantly hinder cerebral mapping using direct electrical stimulation (DES) of the motor cortex. As inhaled anesthetics are used only under GA with a secured airway, DES is the only type of cortical mapping that can be performed in this setting, typically with an observer looking for motor movement in the face and extremities. Moreover, even low concentrations of inhaled anesthetic of 0.5 MAC can result in inadequate or failed mapping. ^{10 ,​ 11} Because of these reasons, vapor anesthetics are often replaced by IV anesthetic agents in cases where motor evoked potentials are used intraoperatively, and it is thought to be due to less interference of alpha motor neurons from IV agents. ¹²

10.1.2 Intravenous Hypnotic and Analgesic Agents

Intravenous anesthetic agents (propofol, dexmedetomidine, ketamine, remifentanil, and sufentanil) are often utilized as an adjunct to inhaled anesthetics or as part of a total intravenous anesthesia (TIVA) technique with the intent of minimizing interference with cortical mapping and, in some situations, enhancing it.

Propofol is the most commonly used induction and IV maintenance agent in GA cases under TIVA. Low doses of propofol are also titrated to achieve moderated sedation in surgical procedures under a nerve block or local anesthetic infiltration with special care in maintaining the patient’s natural airway. It is also a preferred anesthetic in ambulatory settings due to its rapid emergence and decreased risk of postoperative nausea and vomiting (PONV). Propofol has significant dose-dependent anxiolytic, hypnotic, and antiepileptic effects due primarily to it being a GABA type A receptor agonist. ¹³ Similar to inhaled anesthetics, propofol causes a dose-dependent initial increase in EEG activity with low doses, but progresses to inhibition of epileptic foci, burst suppression, and isoelectricity with higher doses. ¹⁴ In the setting of epileptic surgery, ECoG recording can be a challenge when propofol is used in general anesthetic doses. However, because of rapid metabolism and redistribution, reliable ECoG recording can be obtained within 20 to 30 minutes after the discontinuation of the infusion. ^{15 ,​ 16}

Ketamine and dexmedetomidine are unique, as they produce hypnosis via non-GABA mechanism of action and have analgesic properties. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and is useful in procedure sedation, as it provides hypnosis and dissociative analgesia but with less respiratory depression. Although the medication functions by inhibiting glutamatergic neurotransmission, it also increases the release of excitatory amino acids such as glutamate and aspartate. ¹⁷ Therefore, ketamine has the potential to enhance EEG recording and motor cortex excitability, making it a useful anesthetic in ECoG and DES for motor mapping. A significant drawback of using ketamine, especially with conscious sedation or in an awake craniotomy, is that the anesthetic can cause psychosis-like side effects. ¹⁸ Thus, dexmedetomidine has largely replaced the use of ketamine for procedure sedation in the neurosurgical population. Dexmedetomidine is a selective α2-adrenergic agonist which indirectly increases activation of GABA neurons and produces sedation mirroring physiological sleep. ¹⁹ When combined as an analgesic adjunct to GA, dexmedetomidine has minimal effect to ECoG and adequate mapping can take place without discontinuing the infusion. ²⁰ A significant advantage of dexmedetomidine at low doses is that it causes minimal respiratory depression and maintains a relaxed but a cooperative patient, making it ideal for awake craniotomies. ²¹

Opioids play a unique and vital role in neuroanesthesia particularly during cerebral mapping. During GA, maintenance anesthetics, such as propofol or inhaled anesthetics, are reduced to minimal amnestic doses in order to prevent interference with cerebral mapping. Therefore, high doses of opioids are used to avoid patient discomfort and movement, such as coughing on the endotracheal tube. Opioids generally do not interfere with EEG recording, ECoG, DES, or microelectrode recording (MER). Short-acting opioids, such as sufentanil or remifentanil infusions, are commonly used, as they are easily titratable and allow for a rapid emergence upon their discontinuation. Remifentanil infusion can also be titrated with conscious sedation in awake craniotomy as an analgesic adjunct, ²¹ and respiratory depression can be quickly reversed with its discontinuation due to rapid breakdown of remifentanil in the plasma. ²² However, opioids have a few unique considerations in this surgical population. A rapid bolus of fentanyl can cause centrally mediated muscle rigidity that is not epileptic in nature. ²³ High doses of opioids can also stimulate EEG seizure activity and this property has been utilized intraoperatively to facilitate ECoG recording. ^{24 ,​ 25 ,​ 26} It is important to consider that high doses and prolonged infusions of short-acting opioids can lead to postoperative hyperalgesia and poor pain management, as made evident in both animal models ²⁷ and clinical practice. ^{28 ,​ 29}

10.2.1 General Anesthesia—“Asleep”

General anesthesia is the most common anesthetic technique as it maximizes patient comfort, immobilization, and surgical exposure. Since the patient’s airway is secured prior to the surgery, GA offers the ideal conditions for airway management, oxygenation, and ventilation during surgery. However, as previously discussed in the chapter, anesthetics administered during GA have the greatest interference with cerebral mapping. The following guidelines can help overcome common interferences:

1. 
   

   Avoid benzodiazepines preoperatively.

   
   
2. 
   

   Titration of an opioid infusion to avoid movement or “bucking” on the ventilator.

   
   
   
   
   1. 
      

      Sufentanil 0.2–0.5 μg/kg/h or

      
      
   2. 
      

      Remifentanil 0.1–0.5 μg/kg/h.

   
   
3. 
   

   Prior to cerebral mapping, decrease the maintenance anesthetic dose to amnestic doses.

   
   
   
   
   1. 
      

      Volatile anesthetic at less than 0.5 MAC or

      
      
   2. 
      

      Propofol 100–150 μg/kg/min.

   
   
4. 
   

   Add dexmedetomidine at 0.5–1.0 μg/hg/h to supplement analgesia and hypnosis as it has minimal effect on ECoG. ²⁰

   
   
5. 
   

   Other pharmacologic agents for enhancing ECoG recording include nitrous oxide, ⁷ etomidate, ³⁰ methohexital, ³¹ alfentanil, ²⁵ and remifentanil. ²⁶

   
   
6. 
   

   During mapping of the motor cortex via DES, neuromuscular blockers and volatile anesthetics are to be avoided.

Performing a “scalp block” as an adjunct to GA is recommended as it improves intraoperative hemodynamic stability, reduces anesthetics requirements, reduces the risk for PONV, and provides postoperative analgesia for up to 24 hours. ^{32 ,​ 33 ,​ 34} A detailed technical description of a scalp block and local anesthetic infiltration during craniotomies is to follow.