Awake Versus Non-awake Surgery for Brain Surgery

C H A P T E R

15 Awake Versus Non-awake Surgery for Brain Surgery Eva F. Pamias-Portalatin, Andres Ramos-Fresnedo, Karim ReFaey, Alfredo Quinones-Hinojosa Department of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United States

INTRODUCTION The oncologic neurosurgery field is constantly evolving, not only in the new onco-therapeutic options but also in the surgical techniques. New technologies and surgical approaches are constantly being developed with the goal to increase the extent of resection (EOR) and improve the patients’ outcome and survival. In recent years, awake brain surgery has gained attention by the neurosurgical community as an alternative to the asleep craniotomy in order to achieve a better and safer resection. Awake craniotomies (ACs) date back to ancient times when civilizations performed skull trepanations for management of traumatic injuries without efficient anesthetics (Kshettry, Mindea, & Batjer, 2007). After the first anesthetic agents were developed, ACs began to appear for the management of uncontrolled seizures (Liu & Apuzzo, 2002). The primary goal of glioma surgery is to improve overall survival (OS), quality of life (QoL), and maximizing tumor resection (Duffau). However, this principle must be tempered by the potential functional loss

Comprehensive Overview of Modern Surgical Approaches to Intrinsic Brain Tumors https://doi.org/10.1016/B978-0-12-811783-5.00015-X

following a radical removal (Pallud & Dezamis, 2017). Current neurosurgical innovations aim to improve our anatomical, physiological, and functional understanding of the surgical region of interest to prevent potential neurological morbidity during resection. Emerging technologies, as well as state-of the-art intraoperative techniques, can facilitate EOR while minimizing the associated morbidity profile. Recent discoveries suggest that awake procedures for tumor resection can provide better overall outcomes and together with mapping motor and language is possible to achieve a safe resection in some intrinsic brain tumors (Chaichana, Jusue-Torres, Lemos et al., 2014, Chaichana, Cabrera-Aldana et al., 2014; De Benedictis, Moritz-Gasser, & Duffau, 2010; Eseonu, Eguia, ReFaey et al., 2017; Eseonu, ReFaey, Garcia, John et al., 2017; Eseonu, ReFaey, Garcia, Raghuraman, & Qui~ nones-Hinojosa, 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu et al., 2018; Almeida, Chaichana, Rincon-Torroella, & Quinones-Hinojosa, 2015).

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Copyright © 2019 Elsevier Inc. All rights reserved.

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Importantly, despite significant advances in operative techniques and preoperative planning, the effect of EOR in prolonging tumor-free progression and survival remains unclear. Even though it has been correlated with OS (Nitta et al., 2015; Trifiletti et al., 2017), there is lack of level I evidence preventing certainty in the benefits of EOR. Other important values of glioma resection are obtaining tissue diagnosis and decompression of mass effect in order to relive symptomatology. This is of most importance for lesions in areas of eloquences, where close proximity of critical pathways, often related to language and motor function, can present a significant challenge to standard operative strategies. Choosing the appropriate surgical approach for these lesions can be challenging given the controversy that exists regarding the benefits of awake surgery in contrast with surgery performed under general anesthesia (GA) for both low-grade (LGGs) and high-grade gliomas (HGGs). The purpose of this chapter is to gather recent data on the topic and review both awake and asleep techniques to further compare the advantages and disadvantages of each.

AWAKE CRANIOTOMY Back in the 1940s, Dr. Wilder Penfield started working with ACs for cortical brain mapping in order to identify motor and sensory areas of the brain in order to preserve them during lesion resection. He first started working with patients who developed focal seizures after a traumatic brain injuryeinduced scarring tissue within the brain (Bulsara, Johnson, & Villavicencio, 2005; Feindel, 1993). The same principle is now in use for the removal of oncological lesions within eloquent areas of the brain and is now considered the gold standard to obtain a maximum safe resection (Almeida et al., 2015; Eseonu, ReFaey,

Garcia, John et al., 2017; Hervey-Jumper & Berger, 2016; Hervey-Jumper et al., 2015). The awake craniotomy surgical technique allows intraoperative localization and protection of cortical and subcortical motor and language pathways while having real-time feedback from the patient. This allows the surgeon to reduce the risk of morbidity and permanent severe postoperative neurological deficits caused by resecting and/or injuring eloquent areas (Almeida et al., 2015; Eseonu, Eguia, ReFaey et al., 2017; Hervey-Jumper & Berger, 2016; Hervey-Jumper et al., 2015; Magill, Han, Li, & Berger, 2017; Sanai & Berger, 2018; Snyder et al., 2014; Wang et al., 2017).

Awake Craniotomy: Advantages Accurate Motor and Speech Mapping Tumor location might influence the choice of anesthesia technique between awake or asleep procedures. Lesions in eloquent areas of the brain that control motor or language, as the one shown in Fig. 15.1, may cause eloquent areas to be inadvertently damaged during resection while having the patient asleep. It is imperative for the patient to be awake during language mapping and motor mapping of fine highly specialized movements as an alternative to monitoring with peripheral motor evoked potentials (MEPs) and/or asleep mapping. Asleep brain mapping does not acquire the same sensitivity and specificity as awake brain mapping, in the identification of eloquent brain areas; which leads to an increase in the stimulation threshold and thus limits the EOR. (Duffau et al., 2003). However, some may prefer asleep mapping because it may be more sensitive (Duffau et al., 2003). Therefore, craniotomies under local anesthesia are recommended to make sure that adequate motor and language responses are preserved, aided with mapping of these areas (Fig. 15.2) (Hervey-Jumper et al., 2015).

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279

(A)

(B) FIGURE 15.2 Intraoperative brain mapping markers. Intraoperative image of an awake craniotomy showing eloquent brain cortex on the left temporal lobe with sterile numbered markers identifying eloquent areas found during cortical stimulation. Patient presented with anomia on marked areas during stimulation.

FIGURE 15.1

Brain MRI showing a glioblastoma (WHO grade IV) within the motor cortex. Brain MRI showing a glioblastoma (WHO grade IV) within the motor cortex on the right hemisphere. (A) Axial T1-weighted sequence with contrast showing a contrast-enhancing lesion in the posterior right frontal lobe with central necrosis. (B) Axial T2-weighted sequence without contrast showing a hyperintense lesion in the posterior frontal lobe with associated vasogenic edema.

Increase Extent of Resection Surgical removal of gliomas is one of the key components to the treatment of this disease. In the past, tumors within eloquent areas were deemed inoperable, but technology such as navigation system, intraoperative imaging, and brain mapping now allow safer removal of these lesions while maximizing the EOR. This can translate into longer periods of OS (Almeida

et al., 2015; Awad et al., 2017; Chaichana, Jusue-Torres, Navarro-Ramirez et al., 2014; Duffau, 2015; Eseonu, Eguia, ReFaey et al., 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Hervey-Jumper & Berger, 2016; Lau, Hervey-Jumper, Han, & Berger, 2017; Magill et al., 2017; Noorani & Sanai, 2017; Oppenlander et al., 2014; Sanai & Berger, 2009, 2018; Snyder et al., 2014; Wang et al., 2017), progression-free survival (PFS) (Almeida et al., 2015; Chaichana, Jusue-Torres, NavarroRamirez et al., 2014; Eseonu, Eguia, ReFaey et al., 2017; Eseonu, ReFaey, Garcia, John et al., 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Hervey-Jumper & Berger, 2016; Lau et al., 2017; Sanai & Berger, 2009, 2018; Snyder et al., 2014; Wang et al., 2017), and malignant progressionefree survival (Eseonu, Eguia, ReFaey et al., 2017; Eseonu, ReFaey, Garcia, John et al., 2017; Hervey-Jumper & Berger, 2016; Sanai & Berger, 2018).

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Perhaps, gross total resection (GTR) should be the ultimate objective for glioma surgery (Lau et al., 2017; Wang et al., 2017), as recent findings suggest a benefit from it. Recent literature based on surgeons’ experience has demonstrated that ACs provide an advantage over asleep craniotomies (Hervey-Jumper et al., 2015). ACs can be a challenging procedure for the neurosurgeon, as a certain amount of experience, along with a specialized team, is needed to successfully perform these operations. It is, however, a benefit that should be offered to the patient if an experienced surgeon and multidisciplinary team are available. Comparison between awake and asleep surgeries have shown that a higher quantity of total resections can be obtained through AC (Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017). Unfortunately, it is not always possible to achieve this in all glioma patients. Chaichana, Jusue-Torres, Navarro-Ramirez et al. (2014) explored the minimum threshold of EOR that provides a benefit to the patient. The authors found that both EOR and residual volume (RV) are significantly associated with survival and recurrence where the thresholds are 70% and 5 cubic cm, respectively. These data have been supported by other studies in the literature (Grabowski et al., 2014; Lacroix et al., 2001; Orringer et al., 2012; Sanai, Polley, McDermott, Parsa, & Berger, 2011). These findings may help guide surgical and adjuvant therapies aimed at optimizing outcomes for glioblastoma patients (Chaichana, Jusue-Torres, NavarroRamirez et al., 2014) (Table 15.1). Preservation of functionality is of vital importance in the outcome for glioma patients. Preserving a 1 cm margin between the resection and the eloquent areas has been generally recommended to avoid damaging functional tracts, mainly because of the lack of reliability with these imaging modalities (Hervey-Jumper & Berger, 2016; Sanai & Berger, 2009). Currently, preoperative and intraoperative techniques allow the surgeon to identify and preserve

cortical and subcortical tracts. This allows extending the resection further from the recommended margin. Experimental studies have discovered glioma cells farther than imagingobservable limits, suggesting their presence as far as 2 cm away from the lesion (Duffau, 2015; Hervey-Jumper et al., 2015; Snyder et al., 2014). To be able to attempt a complete resection, including nonobservable cells, supramarginal resection can be attempted if feasible as long as avoiding deficits. This is reliant on the ability to detect eloquent tissue. Resection of MRIobservable nontumoral brain seems to provide further improvement of the patient if compared with only a total resection (Awad et al., 2017; Duffau, 2016; Hervey-Jumper et al., 2015). Although maximizing the EOR is a key component of glioma surgery, a balance with functional preservation must be met, as it is not recommended to sacrifice functionality to achieve survival. In the 1930s, Walter E. Dandy reported a series of five cases in which he performed hemispherectomies on glioma-affected hemispheres, reporting a recurrence on the other hemisphere (Dandy, 1928). Better Postoperative Seizure Control Given the high morbidity and mortality in glioma patients, the purpose of resection is to provide better disease outcomes and QoL. Unfortunately, seizures add a high morbidity to the patient. In fact, seizures are the most common presenting symptom for patients with LGG, with various studies reporting an incidence higher than 80% (Pallud et al., 2014). HGG on the other hand, only tend to present with seizures in 25% of the cases (Flanigan et al., 2017). Seizures have a direct impact on the functionality and cognitive functions of the patient, contributing to a lower QoL (Pallud et al., 2014; Wang et al., 2017). The first 72 postoperative hours are critical for management of seizures, as postoperative changes have been associated with epileptogenic discharges. In addition, the electrical stimulus provided during brain

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TABLE 15.1 Minimum Percent of Resection Needed to Improve Outcomes From Five Different Studies Study Lacroix et al. (2001)

N value

Extent of Resection

Mean Survival (months)

Univariate Analysis

Multivariate Analysis

416

<98% >98%

8.8 13

<0.0001

<0.0001

Conclusions

Limitations

98% of resection was associated with increased survival.

Before temozolomide was a standard in the treatment. Retrospective study carried in a single institution. Recurrent and newly diagnosed glioblastomas were included.

Sanai et al. (2011)

46

>77% >79% >89% >100%

<90% >90%

12.5 12.8 13.8 16

N/A 16

<0.0001

0.005

0.004

0.005

78% of resection increased survival

Before temozolomide was a standard in the treatment.

Better survival correlating with better resection

Retrospective study carried in a single institution.

90% of resection significantly increased survival

Small sample. Semiautomatic volumetric analysis

AWAKE CRANIOTOMY

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Orringer et al. (2012)

500

Retrospective study carried in a single institution Chaichana, Jusue-Torres, NavarroRamirez et al. (2014)

259

Grabowski et al. (2014)

128

<70% >70%

<98% >98%

14 16

0.0007

0.05

0.0006

0.03

EOR of 70% and 5 cm3 of RV was associated with better survival

Semiautomatic volumetric analysis

EOR and RV were significantly associated with better survival

Semiautomatic volumetric analysis

Residual tumor in imaging was the strongest predictor for survival

Retrospective study carried in a single institution

Retrospective study carried in a single institution

281

EOR, end of resection; RV, residual volume.

10.5 14.4

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15. AWAKE VERSUS NON-AWAKE SURGERY FOR BRAIN SURGERY

stimulation increases the risk of intra- and postoperative seizures (Eseonu, Eguia, Garcia, Kaplan, Qui~ nones-Hinojosa, 2017) (Fig. 15.3). In both LGG and HGG, maximizing tumor resection has been proven useful for postoperative seizure control, with data presenting a higher rate of patients being seizure free after

(A)

(B)

FIGURE 15.3 Brain electrocorticography and mapping. Images of a left-sided frontal craniotomy showing intraoperative brain mapping during an awake craniotomy. (A) Electrocorticography with a high-density grid to identify cortical epileptogenic discharges. Patients are monitored during 6e8 min (B) electrocorticography for continuous monitoring along with cortical stimulation with the Ojemann stimulator for brain mapping to identify eloquent areas of the brain.

gross total resection, compared with patients where subtotal resection was achieved (Duffau, 2015; Hervey-Jumper & Berger, 2016; Pallud et al., 2014; Sanai & Berger, 2018; Wang et al., 2017; Xu et al., 2017). In a study, J. Pallud et al. (2014) showed that following treatment, patients in which a higher EOR was achieved correlated with a higher incidence of seizure control, even in patients who did not receive prophylaxis with antiepileptic drugs. Data from this study suggest that seizure control correlates with the volume of tumor resected. Improve Postoperative Outcomes We have previously described how a minimum threshold of EOR has an impact on overall outcomes (Chaichana, Jusue-Torres, NavarroRamirez et al., 2014; Grabowski et al., 2014; Lacroix et al., 2001; Sanai et al., 2011; Orringer et al., 2012). Likewise, the minimum threshold of EOR suggested for seizure control correlates with the values established for overall outcomes (Xu et al., 2017). This means that the same thresholds could potentially be used to predict postoperative seizure control. Currently, the objective of oncological treatment for gliomas is to improve PFS and the patient’s QoL. More importantly, it is possible to improve QoL if a GTR is achieved (Chaichana, Jusue-Torres, Navarro-Ramirez et al., 2014). Higher scores in the Karnofsky Performance Scale (KPS) (Table 15.2) (Osho et al., 2018) have been reported for patients who undergo an AC for maximization of tumor resection. Additionally, analyses from AC patients demonstrate a trend of KPS score improvement during the first 6 postoperative months, as compared with lower KPS scores in patients who undergo procedures under GA (Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017). Indeed, QoL seems to also be benefited from the low rate of neurological deficits reported during ACs (Eseonu, RinconTorroella, ReFaey, & Qui~ nones-Hinojosa, 2017) (Table 15.3).

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AWAKE CRANIOTOMY

TABLE 15.2

Karnofsky Performance Status Scale (Osho et al., 2018) Functional Status Class (KPS Designation)

Score

Clinical Characteristics

100

Normal activity and work: Normal to no complaints

90

Normal activity and work: Minor signs and symptoms of disease

80

Normal activity and work: Performs with some effort. Some signs or symptoms of disease

70

Unable to carry on normal activity or work: cares for self

60

Unable to carry on normal activity or work: requires occasional assistance but able to care for most of personal needs

50

Unable to carry on normal activity or work: requires considerable assistance and frequent medical care

40

Disabled: Requires special care and assistance

30

Disabled: severe disability. Hospital admission likely indicated

20

Disabled: very sick. Hospital admission necessary. Active supportive treatment necessary

10

Disabled: moribund. Fatal process progressing rapidly

0

Dead

Independent

Partially dependent

Disabled

Dead

Lower Hospital Cost and Length of Hospital Stay Offering surgical management to a patient can result in excessive health expenditures. A study performed by Zygourakis et al. (2017) analyzed the cost of craniotomies across the United States using a national database. They show that the cost has been increasing for the last 20 years. In this study, the average cost of a craniotomy ranged between 27,744 (1078) and 36,058 (1684), but cost may vary depending on the location of the hospital. Cost also tends to inflate for the most prestigious institutions across the country. Another important factor affecting costs are the different levels of complexity for each surgical case. It is said that ACs further increase the cost of surgery due to increased complexity, which requires a specialized team and equipment. Nevertheless, inpatient cost analysis suggests that the total average cost of an AC is

lower, as extra care and monitoring from GA and the secondary effects that cause craniotomy price to inflate are avoided by having the patient awake (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, RinconTorroella, ReFaey, Lee et al., 2017). On the other hand, due to postoperative changes and secondary effects of GA, strict monitoring, ICU stay and supplementary studies may be required, further increasing costs and length of hospital stay (LoS). LoS is a major contributing factor to direct inpatient costs. Fortunately, AC seems to shorten the time spent at the hospital (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nonesHinojosa, 2017). Studies have reported a mean LoS of 7 days for procedures performed under GA, compared with 4 days for AC (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Zygourakis et al., 2017). Postoperative GA effects might be a major contributor to the increase in hospital stay, as they have been

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284 TABLE 15.3

15. AWAKE VERSUS NON-AWAKE SURGERY FOR BRAIN SURGERY

Potential Advantages and Disadvantages for Awake and Asleep Craniotomies Awake Craniotomy

Advantages

Disadvantages

Asleep Craniotomy 1. Avoid emotional distress 2. Reduce discomfort during prolonged procedures 3. Alternative for failed awake craniotomies 4. Viable option for positions with extreme head turns (e.g., park bench or prone)

1. Reduced morbidity 2. Reduction of severe postoperative neurological deficits 3. Accurate brain mapping 4. Better probability to increase extent of resection 5. Higher rates of gross total resection 6. Better postoperative seizure control 7. Better postoperative KPS score 8. Improved postoperative quality of life 9. Reduction in hospital LoS 10. Reduction in overall health-care costs 1. Need of a highly trained multidisciplinary team 2. Unable to control breath rate and CO2 resulting in brain swelling 3. Patient discomfort 4. Not recommended with certain surgical positions

1. Unable to perform speech mapping 2. Lower accuracy for motor mapping as only MEPs can be performed 3. Evaluation for neurological deficits can only be performed after the patient is completely awake 4. Lower probability to achieve a favorable extent of resection 5. Worse overall survival 6. Lower overall KPS score 7. Poorer postoperative neurological outcomes 8. Slower rate of recovery 9. Higher overall health-care costs 10. Longer hospital LoS 11. Higher readmission rates with shorter time for readmission 12. Worse postoperative seizure control

KPS, Karnofsky Performance Scale; LoS, length of hospital stay; MEPs, motor evoked potentials.

shown to increase nausea, vomiting, and lethargy (Eseonu, Rincon-Torroella, ReFaey, & Qui~ ones-Hinojosa, 2017; Eseonu, Rincon-Torroella, n ReFaey, Lee et al., 2017). In addition, ictal events, which are more frequent with procedures performed under GA, also need extra imaging and observation, adding additional costs and days spent at the hospital (Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Eseonu, Eguia, Garcia et al., 2017). All of the abovementioned contribute to a shorter LoS and less readmission rates in the AC patients avoiding extra expenditure (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, Eguia, Garcia et al., 2017).

Awake Craniotomy: Disadvantages Increased Risk of Brain Swelling and Hypoperfusion The AC procedure imparts important benefits to specific patients as previously discussed. However, it also has disadvantages, making the procedure challenging for the surgeon and the patient. Although studies have shown that ACs with intraoperative brain mapping have proven to result in a lower rate of intra- and postoperative complications and neurological function (De Benedictis et al., 2010; Eseonu, RinconTorroella, ReFaey, & Qui~ nones-Hinojosa, 2017;

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AWAKE CRANIOTOMY

Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Lau et al., 2017; Sanai & Berger, 2009), it is important to note that, even after a great resection was performed, patients can present with postoperative complications due to surgical effects (e.g., edema and direct injury to cortical and subcortical tracts). Postoperative neurological deficits can appear and even worsen during the first 72 h. However, due to brain plasticity, these deficits tend to disappear during the first three postoperative months. Due to the differences in behavior of different grade gliomas, the appearance of severe permanent deficits differs between both LGGs and HGGs. Permanent deficits occur less than 5% (Eseonu, Eguia, ReFaey et al., 2017; Eseonu, ReFaey, Garcia, John et al., 2017) and up to 11.3% for LGGs and HGGs, respectively (Magill et al., 2017). Injury to microvasculature and intraoperative hypoperfusion can happen during surgery and contribute greatly to these deficits (Chaichana, Jusue-Torres, Navarro-Ramirez et al., 2014; Eseonu, RinconTorroella, ReFaey, Lee et al., 2017; Magill et al., 2017; ). Unfortunately, vascular injury, brain edema, and hypoperfusion may even be worse in ACs, as having the patient awake with less constant control of respiratory rate and end tidal CO2 can worsen the risk of brain edema and most specially if the patient has a seizure. It is important to have antiedema and antiseizure medications available, as well as preparation in case intubation is needed. Patient and Surgeon Discomfort Another important factor is patient positioning. Prolonged surgeries may cause the patient to be uncomfortable and to not tolerate the procedure required to convert the AC into an asleep one (Au, Bharadwaj, Venkatraghavan, Bernstein, 2016). It is also extremely important to include a well-trained neuroanesthesia team in the operation to maintain a comfortable environment for both the patient and the surgeon.

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Asleep Craniotomy Before the use of local anesthetics were introduced to the neurosurgical field, craniotomies were performed under GA (Bulsara et al., 2005). Of course, this technique provides advantages and disadvantages if compared with the awake technique. This section will address the advantages and disadvantages of GA for glioma resection.

Asleep Craniotomy: Advantages Patient Comfort Asleep craniotomies have proven to be beneficial under certain circumstances. One of the advantages relies on our ability to remove emotional distress from the patient by providing deep sedation. Indeed, GA provides deep comfort to the patient during the surgical event, especially in prolonged procedures (Au et al., 2016). Most of the time the team can identify in advance when the patient will not be able to tolerate an awake procedure. In these cases an asleep craniotomy might be advantageous (Au et al., 2016). As an Alternative for Failed Awake Craniotomy Failed ACs happen when the patient for any reason is unable to tolerate being awake at any point during the procedure. If the patient has been properly screened and received an adequate scalp block by the anesthesia team, it is uncommon that these procedure needs to be converted to an asleep craniotomy. However, there is a narrow possibility for the surgeon to encounter these situations, and the team should have all the necessary equipment to expeditiously convert the case to GA, and it is one of the instances where GA is beneficial for the patient. Conversion from local to GA has been reported in as low as 0.5% (Hervey-Jumper et al., 2015). Of course, this value varies

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15. AWAKE VERSUS NON-AWAKE SURGERY FOR BRAIN SURGERY

depending on the center and the surgeon’s experience. Among the most common causes for intraoperative conversion include uncontrollable seizures and inability to map due to communication issues with the patient (Nossek et al., 2013). Other causes include patient exhaustion and severe neurological deficits (Eseonu, ReFaey, Garcia, John et al., 2017). Freedom to Position Patient for Challenging Approaches Tumor location and patient positioning also influences the decision of anesthesia care for craniotomies (Au et al., 2016). Posterior approaches, generally used for gliomas located in the posterior fossa or posterior parietal or occipital lobe may be uncomfortable for the patient as the patient is generally in prone or park bench positioning with extreme head turns. On the other hand, neck positioning can be challenging for these approaches and might cause muscular discomfort, which might be easily avoided with deep sedation. Both, the surgeons’ and patient’s comfort are very important factors to consider as this provides an accurate and safer resection. The previously discussed situations are documented advantages of GA for brain tumor surgery. However, each patient has to be studied properly in order to personalize each case and evaluate the reasons that might favor the use of deep sedation over an awake procedure.

Asleep Craniotomy: Disadvantages It is necessary to assess every case individually to ensure an adequate management of the patient under GA. Even though it might be beneficial in some cases as mentioned earlier, outcomes are generally poorer when compared with those cases performed using local anesthesia. Less Accurate Brain Mapping Cortical and subcortical stimulation are essential components to increase the EOR particularly

in gliomas located within eloquent areas, as it is the gold standard for a maximum and safe resection (Almeida et al., 2015; Eseonu, ReFaey, Garcia, John et al., 2017; Hervey-Jumper & Berger, 2016; Hervey-Jumper et al., 2015). Unfortunately, speech mapping is not possible when the patient is under deep sedation. This can result in higher risk of deficit and less EOR for tumors located within the speech cortex. On the other hand, motor mapping can be performed under GA by measuring MEPs on peripheral muscles. New evidence suggests that MEPs performed under deep sedation are not as effective as perioperative motor movement during awake mapping (Eseonu, RinconTorroella, ReFaey, Lee et al., 2017). Potentially Worse Overall Outcomes EXTENT OF RESECTION AND OVERALL SURVIVAL

Limitations in brain mapping during asleep procedures will directly impact overall postoperative outcomes and EOR. Recent studies have reported minimal differences between both techniques, but interventions under GA trend toward a lower percentage of resection (Eseonu, RinconTorroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Magill et al., 2017). Indeed, EOR has an impact on the patient’s overall survival. Hence, it would not be surprising to identify decreased survival in patients who undergo asleep craniotomies. FUNCTIONAL OUTCOMES AND KARNOFSKY PERFORMANCE SCALE

Immediate and long-term functional outcomes tend to be suboptimal in patients who undergo glioma resection under GA. Immediately after surgery and through the first month, patients who undergo craniotomy for glioma resection with any anesthesia technique tend to demonstrate new or worsened functional deficits. These may be due to surgical effects and

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AWAKE CRANIOTOMY

edema on brain parenchyma (Eseonu, RinconTorroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017). This is reflected by the effect on the KPS, which tends to be equal between both anesthesia techniques. As recovery continues and surgical effects on brain parenchyma diminish, patients tend to demonstrate significant improvement over the course of 3e6 months. However, patients operated on under GA tend to show a slower-paced improvement and a higher rate of permanent deficits, resulting in a lower definitive KPS (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017). These permanent deficits can be explained by damage to neurological tracts and vasculature (Chaichana, Jusue-Torres, Navarro-Ramirez et al., 2014; Magill et al., 2017) or due to the poor known secondary effect of neuroanesthesia medications on the brain. Higher Overall Health-Care Costs and Increased Length of Hospital Stay The cost of craniotomy has risen over the past 20 years (Zygourakis et al., 2017), probably due to advances in neurosurgery where higher specialization and technology needs to be used to provide better outcomes. In addition, medical expenses for these cases tend to increase if the procedure was performed under GA (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017). Short-term costs are generally not high but tend to increase in the long term (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, RinconTorroella, ReFaey, Lee et al., 2017). Higher costs correlate with the functional outcomes of the patient, as nonoptimal outcomes require extra medical care and health expenditures. Immediate postoperative anesthesia effects are also major contributors to increased cost. Among the reported symptomatology presented immediately after GA are nausea, vomiting, and

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cognitive deficits, and patients are most likely to complain about these symptoms after recovering from sedation (Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017). Another factor affecting immediate postoperative costs is hospital LoS. Several studies have evaluated the mean hospital LoS after brain tumor resection (Eseonu, ReFaey, Garcia, John et al., 2017; Eseonu, ReFaey, Garcia et al., 2017; Eseonu, Rincon-Torroella, ReFaey, Lee et al., 2017; Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Flanigan et al., 2017; Hervey-Jumper et al., 2015; Zygourakis et al., 2017). Mean stay for craniotomies under GA has been reported to range between 7 and 8 days (Eseonu, Rincon-Torroella, ReFaey, & Qui~ nones-Hinojosa, 2017; Eseonu, RinconTorroella, ReFaey, Lee et al., 2017). Disease expenditure cost tends to increase with a lengthened hospital stay. Generally, patients who stay admitted in the hospital for a longer time frame, postoperative outcomes need to be more closely monitored for a longer period of time. This means extra resources need to be allocated to the patient. Moreover, lengthened hospital stays seem to be affected by lower rates of GTR, GA effects, and increased rates of complications. Increase in long-term health expenditure correlates with long-term recovery and functionality. Slower recoveries and worse functional outcomes tend to increase readmission rates. Certainly, readmission rate added to the extra care are needed given the worse outcomes that it carries, and this will have a significant increase in these costs. Factors such as seizures (Eseonu, Eguia, Garcia et al., 2017) and worse neurological outcomes (Dewan, White-Dzuro, Brinson, Thompson, Chambless, 2016) have been associated with a higher readmission rate. One of the major disease burdens of gliomas is seizure events, and probably due to a lower EOR, patients who undergo GA tend to present a higher incidence of postoperative seizure events (Awad et al., 2017; Bonney et al., 2017).

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CONCLUSIONS Through the last 20 years, new evidence suggest that ACs are, to date, the most viable surgical pathway for management of gliomas. Compared with other available technology, brain mapping seems to be the most beneficial for overall patient outcomes. Furthermore, compared with asleep surgery, awake procedures allows for the most accurate cortical and subcortical brain mapping for identification of motor and speech areas of the brain. Intra- and postoperative complications can also be significantly reduced if the patient undergoes awake brain mapping. It is also important to note how a higher EOR can be obtained after awake mapping. Better overall outcomes are highly correlated with the extent of tumor resection, so much so that supramarginal resections can benefit the patient even more. Awake brain mapping has shown to increase the amount of resected tumoral volume, adding more weight to the value of awake procedures for glioma management. Preserving a patient’s functional status is a priority for glioma surgery, and it is not surprising that maximizing EOR can help maintain and even improve functional status. Of course, establishing a correlation between better functional outcomes and ACs is needed. One of the most weighing factors on functional status of the patient is the development of seizures. Interestingly, a higher number of patients have been reported to reach a seizurefree status after an AC, highlighting the importance of this surgical technique for epilepsy management. Furthermore, patients tend to remain for shorter periods of hospitalization after an AC, contributing to a better immediate postsurgical outcome. Cost is also affected by length of hospitalization; by reducing LoS, hospitalization cost can also be reduced. In addition, the multidisciplinary approach of an AC tends to elevate the immediate cost of surgery while

compared with GA procedures, but this cost is then inverted in the long run by the reduction in postoperative complications and preservation of functionality.

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