Over the past 10 years, brain surgery in awake patients has become an increasingly frequent procedure, even in patients of young age . Indications have extended from lesions located in eloquent brain areas and epilepsy surgery to other procedures necessitating precise functional or electrophysiological testing, and to less specific procedures with no functional goal, in an attempt to reduce the side effects of general anaesthesia [2,3], facilitate early postoperative neurological evaluation, hasten recovery, and shorten hospital stay . This technique has several specific objectives and can be achieved through various means . Success requires rigorous patient selection and meticulous preparation. All these aspects will be reviewed in this paper.
Current indications of awake craniotomies
Classically, an awake craniotomy is indicated when patient's cooperation is needed during the neurosurgical procedure to allow functional testing. Since the introduction of awake craniotomy by Horsley at the end of the 19th century and its later use by Penfield for the surgical treatment of intractable epilepsy [6,7], its indications have enlarged and can be classified into four categories . The first category encloses the procedures necessitating electrocorticographic mapping or precise electrophysiological recordings, while avoiding any interference between anaesthesia and those recordings. Examples of surgeries entering this first category are epilepsy surgery and deep brain stimulation for Parkinson's disease . The second category includes the resection of lesions located close to or into functionally essential motor, cognitive, or sensory cortical areas. The third one refers to those procedures necessitating the obliteration or resection of vascular lesions that are essential for the vascularization of functionally important territories. Finally, the fourth category has no functional goal and encompasses minor intracranial procedures, hence allowing faster recovery and earlier discharge . These last procedures include, for example, ventriculostomy, stereotactic biopsy, brain endoscopy, and resection of small brain lesions. In this last case, additional arguments to promote awake procedures have been advocated by some authors that include reduced oxidative and emotional stress for the patient, and lower postoperative pain .
The decision to perform an awake craniotomy relies on surgical and patient considerations (Table 1). The first element participating into the decision is a surgical dilemma: generous resection of brain tissue lessens the probability of lesion recurrence and increases survival, whereas limited resection decreases the risk of major functional deficits that may severely impede the patient's quality of life . Although intraoperative motor or sensory-evoked responses , as well as neuronavigation may help in preserving neurological functionality, they do not outperform direct awake functional testing in circumscribing the tissue to be removed . The potential advantage of an earlier recovery and closer neurological follow-up also enters the decision process. The third surgical element that influences the decision is the necessity of precise functional testing and/or electrophysiological recording during the procedure.
The risk–benefit balance of awake craniotomy depends also on risks associated with the patients themselves, that may compromise surgery or even be life-threatening: airway conformation and risk of obstructive apnoea, severity and frequency of seizures, propensity for nausea and vomiting, raised intracranial pressure (ICP), propensity for bleeding, patients' willingness to collaborate, anxiety and discomfort associated with the procedure, and presence of abnormal movements and cognitive deficits that may impede comprehension and collaboration.
Picht et al.  have recently proposed with success a decision algorithm based on patients' neuroanatomical data and language functional mapping, and on eventual anaesthetic, surgical, or neuropsychological risks associated with the performance of an awake craniotomy, to decide whether a given patient should undergo an awake procedure or a general anaesthesia. They propose to perform awake procedures in patients having adequate neuroanatomical and functional data available, and with a nonincreased operative risk. Awake procedures associated with functional testing should be used in patients with limited functional data and nonincreased operative risk. General anaesthesia associated with neuronavigation should be restricted to patients with adequate functional data and increased operative risk. Finally, patients with limited functional data and increased operative risk should benefit from an awake procedure associated with functional testing as needed. Although limited to the resection of brain lesions located close to, or into eloquent cortical areas, this kind of decision algorithm may be of great help to the multidisciplinary team in deciding on the type of management.
Specific objectives of anaesthetic management
In order to optimize the benefits of awake craniotomy, the objectives of anaesthetic management must be three-fold : allow patient's cooperation, preserve general homeostasis, and limit the interference between anaesthetic agents and quality of electrophysiological recordings. Patient's cooperation necessitates optimal analgesia, anxiolysis and sedation adapted to surgical events, prevention of any discomfort related to position, or length of procedure, prevention of nausea and vomiting, as well as prevention of seizures. Maintenance of homeostasis involves the preservation of patent airway and adequate ventilation, haemodynamic stability, and brain relaxation. A good evaluation and preparation of the patient will orient the choice of the best suited anaesthetic technique and hence facilitate the achievement of these goals.
Preoperative patient evaluation and preparation
In addition to classical preanaesthetic evaluation, attention should be paid to register elements that may influence the risk–benefit balance of the procedure. Specific preoperative evaluation of patients scheduled for an awake craniotomy is as follows:
- Upper airway
- Difficult intubation signs (mouth opening, Mallampaty score, large tongue, cervical stiffness, teeth, neck diameter, prognatia, retrognatia)
- Obstructive apnoea (obesity, sleep apnoea)
- Current treatment
- Plasma levels
- Type, number, and frequency of episodes
- Nausea and vomiting
- Past history following anaesthesia
- History of motion sickness
- Type and size of lesion
- Indirect neuroimaging signs and clinical signs of elevated ICP
- Type and localization of lesion
- Current medications (antiplatelets, nonsteroidal anti-inflammatory medications)
- Personal and family past history
- Patient collaboration
- Neurological problems (dysphasia, abnormal movements).
As far as good oxygenation and CO2 elimination must be maintained throughout the procedure despite possible episodes of unprotected spontaneous ventilation, careful evaluation of the risk of obstructive apnoea is mandatory. Examination of the upper airway conformation and search for signs of possible difficult intubation, neck stiffness, large tongue, Mallampaty score, prognatia, and retrognatia must be performed. Because they are at high risk of obstructive apnoea, patients possibly suffering from obstructive sleep apnoea should be identified. A quick and simple score, the Snoring – Tiredness during day time – Observed apnea – High blood pressure - Body mass index – Age – Neck circumference – Gender (STOP-BANG) score, may be used to screen for this lesion and eventually orient patients towards a more precise evaluation . Seizures during the procedure may be uneasy to manage. Hence, the adequacy of treatment, plasma levels of medications, and occurrence and frequency in daily life must be checked. A history of nausea and vomiting following a previous anaesthesia and a history of motion sickness must incite to take prophylactic measures. Brain relaxation may be uneasy to obtain in a spontaneously breathing sedated patient, particularly if ICP is already high before the procedure. An indirect estimation of ICP is therefore necessary, based on clinical signs or neuroimaging. The bleeding risk must also be evaluated through the past medical and family history of the patient and through the enumeration of current medications that may facilitate bleeding such as antiplatelet agents. Finally, such a stressful procedure necessitates a psychological preparation of the patient by the surgeon and the anaesthesiologist. The reasons for performing the procedure awake must be explained, as well as the sequence of events, the expected length and possible discomfort, the associated risks, and the means used to limit inconvenience. The patient must be reassured and eventually trained to the functional test that will be performed during surgery . Such a preparation certainly helps in ameliorating patients' tolerance and general satisfaction about the procedure .
Premedication may be helpful in reducing patients' anxiety but may favour respiratory depression and impede cooperation. Habits vary between teams, ranging from small doses of benzodiazepines  or clonidine  to no premedication at all . Atropine-like medications are sometimes used but may provoke very uncomfortable mouth dryness. Corticoids reduce brain oedema and prevent nausea. They are sometimes associated with serotonin antagonists or metoclopramide to further reduce the incidence of nausea and vomiting, as well as to ranitidine to reduce gastric acidity . Antiepileptic medications should be given on the morning of surgery to prevent the occurrence of seizures .
Intraoperative anaesthetic management
The main challenge of intraoperative anaesthetic management during awake craniotomy relies on the ability of rapidly adjusting the level of sedation and analgesia according to the sequence of surgical events, while ensuring haemodynamic stability and adequate ventilation. Depth of anaesthesia must be tightly controlled, permitting episodes of full consciousness when needed and smooth transitions between anaesthetic stages, while maintaining patients' comfort and immobility. The choice of anaesthetic agents, as well as the anaesthetic technique is determinant for success.
As far as flexibility is mandatory, short-acting medications should be preferred. The combination of propofol and remifentanil is often chosen [18,19,23–25], although no advantage of remifentanil over longer acting opioids has been demonstrated in terms of intraoperative complications and patients' satisfaction . The use of remifentanil as a single agent may also be associated with acute opioid tolerance . Propofol is easy to titrate but may induce respiratory depression, particularly if used in conjunction with opioids . At subanaesthetic concentrations, it may induce motor restlessness and abnormal movements . Hence, target-controlled infusions, which allow tight control of concentrations, will be the preferred mode of administration. Tight control can be completed by the use of depth of the hypnotic component of anaesthesia monitors [18,30]. Additional advantages of propofol are its antiemetic properties and nonprolonged influence on electrocorticographic recordings [31,32]. Neuroleptic derivatives should not be used because of a higher incidence of seizures  and as they facilitate respiratory depression when used in combination with opioids  (Table 2).
Some prefer the option of longer acting agents deprived of respiratory depression properties. Among them, α2-agonists offer good analgesia, anxiolysis, and sedation while keeping patients easily arousable . Clonidine is usable but dexmedetomidine has the best pharmacokinetic profile. It has been successfully used by several authors in this indication [34,35], even in adolescent  and paediatric patients , and it allows accurate mapping of epileptic foci .
Volatile anaesthetic agents are not suitable for the management of awake craniotomy, as they are not easily administered in patients whose ventilation is not controlled. Psychotropic effects of ketamine, as well as its effect on ICP preclude its use at anaesthetic concentrations in this indication. However, small doses in association with other medications could allow benefitting from its excellent antinociceptive properties with poor respiratory depression. This combination remains to be evaluated in a properly designed study.
The tricky aspect of an awake craniotomy resides in the contrast between one or more awake phases of functional testing and electrophysiological recordings in which any device controlling the upper airway may be highly uncomfortable, and prolonged phases in which anaesthesia can be deepened to ensure patient comfort and when upper airway and ventilation must be controlled. To overcome this problem, several anaesthetic techniques have been proposed.
Monitored conscious sedation is the most frequently used technique, particularly for minimally invasive procedures such as ventriculostomy, brain endoscopy, cerebral biopsy, and deep brain stimulation for Parkinson's disease. Spontaneous ventilation is maintained throughout the procedure, while giving supplementary oxygen through a plastic face mask [18,20,25]. This noninvasive technique provides good comfort to the patient, but may be at high risk of obstructive apnoea in susceptible patients. Close monitoring of respiratory rate and expired carbon dioxide is highly recommended to prevent those apnoeic episodes. As illustrated in Fig. 1, the insertion of the sampling catheter for gas monitoring into the face mask allows detecting the absence of expired carbon dioxide and hence apnoea. Several well tolerated devices may help preventing obstructive apnoea such as nasopharyngeal canula or intraoral devices used to advance the mandible . A simple Mayo canula is usually not well tolerated. Other authors use laryngeal masks (LMA) [22,40] or noninvasive positive pressure ventilation through a nasal mask [41,42].
Another option is the asleep-awake-asleep technique or one of its variants: the first part of the procedure is performed under general anaesthesia and controlled mechanical ventilation, spontaneous ventilation is allowed during the awake phase of functional or electrophysiological testing, and general anaesthesia is induced back under controlled mechanical ventilation for the third phase. Controlled ventilation may be achieved using a LMA  or an endotracheal tube inserted in the awake patient under fibreoptic control, removed during the awake phase, and inserted back using the same technique at the time of the second asleep phase . Proper local anaesthesia of the upper airway is mandatory in this case. A variant approach consists of a two-phase technique, the asleep-awake technique, which overcomes the problem of controlling back patient ventilation once testing has been performed .
Analgesia must be optimal the whole procedure long to improve patient tolerance. In addition to intravenous analgesia, local and locoregional analgesia are of great help. Scalp block using epinephrine containing local anaesthetic agent solutions is often used. Doses of ropivacaine or levobupivacaine up to 3.6 and 2.5 mg kg−1, respectively, have been demonstrated to be well tolerated [46,47]. However, a more selective approach, that is the selective block of six nerves on each side of the scalp (the auriculotemporal, the supratrochlear, the zigomaticotemporal, the auriculotemporal, and the greater and lesser temporal nerves)  or a superficial cervical plexus block may help reducing doses and improving efficiency. Gebhard et al.  have also proposed selective blocks of the arm or leg to prevent involuntary movements during the procedure.
In addition to classical anaesthetic monitoring, the invasive monitoring of arterial blood pressure is recommended. End-tidal CO2 is easy to measure when the upper airway is equipped with an endotracheal tube or a LMA. Through a facial mask, as mentioned above, a trend of end-tidal CO2 can be obtained (Fig. 1). It will only serve to detect obstructive apnoea. In this case, the arterial line will particularly be interesting to control arterial blood gases.
As far as it determines patient tolerance to the procedure, installation on the operating table must be optimal. The mattress must be comfortable, and, ideally, be designed to prevent bedsores. Knees should be supported, as well as arms and shoulders. The position of the head should be checked after placement of the pin head holder to ensure for comfort and ease of spontaneous ventilation. Bladder catheterization is also necessary. Temperature should be monitored and warming blankets used accordingly.
Complications and outcome
When the procedure is well prepared, complications are rare (Table 3). The most frequent intraoperative complications are obstructive apnoea, nausea and vomiting, seizures, and loss of patient cooperation. Other complications are episodes of high blood pressure, bradycardia associated with a trigeminocardiac reflex, and air embolism. Those complications may compromise success and necessitate conversion into general anaesthesia. Experienced anaesthesiologists are less prone to encounter complications than inexperienced ones .
Obstructive apnoea and hypoventilation prevention are cornerstones of the anaesthetic management. Hypoxaemia and hypercarbia may result from these events, with consequences on ICP. Prevention begins during the preoperative evaluation of the risk of obstructive apnoea. If the risk is high, the use of noninvasive positive pressure ventilation devices may be an option, as is the choice of an asleep-awake-asleep anaesthetic technique. In case of spontaneous ventilation through a facial mask, the monitoring of expired CO2 is mandatory and sedation should be tightly titrated. Caution should also be paid to head positioning of the patient to facilitate ventilation and permit access at all times  (Fig. 2).
Nausea and vomiting have been reported to occur in as much as 8% of patients . Prevention includes good psychological preparation to reduce stress, prophylactic administration of serotonin antagonists or metoclopramide in patients at risk of developing such a complication, corticoid administration, propofol use, and limitation of opioids.
Partial or generalized seizures are more frequent during surgical treatment of intractable epilepsy. Prevention also begins during the preoperative evaluation of patients. At that time, the introduction of antiepileptic medications if not already present or the adjustment of dosage may be necessary. Electrical cortical stimulations, when needed, should be single stimulations as opposed to trains of stimulations. Indeed, trains of stimulation may be associated with an incidence of seizures as high as 20% . Epilepsy may cause ventilation problems, not only during the seizure itself but also during the postictal period.
Loss of patient cooperation is associated with agitation, restlessness, and movements. It greatly compromises functional testing. Good psychological preparation, adequate titration of sedation, good analgesia, comfortable installation on tray, and efforts to shorten the procedure as much as possible help preventing this loss of cooperation.
Hypertensive and tachycardic episodes are more frequent during awake craniotomies than during general anaesthesia . They can be prevented by adequate analgesia and, eventually, vasodilators or β-blocking agents. Severe bradycardia may occur at the time of dura mater stimulation through a trigeminocardiac reflex, which may be prevented by topical anaesthesia of the dura. If encountered, removal of the stimulus and administration of atropine should be considered.
Air embolism may occur during awake craniotomies as in any neurosurgical procedure . Prevention and treatment of this event are not different when occurring during an awake procedure.
Bleeding may be favoured by hypertensive episodes and any cause of increased cephalic venous pressure, such as obstructive apnoea. It may cause an increase in ICP and brain herniation, and embarrassment of the surgeon. Preoperative screening of bleeding disorders is necessary, as well as precautions to keep cephalic venous pressure at an acceptable level.
Studies comparing outcomes between awake and general anaesthesia craniotomies are scarce. Most series report satisfactory results of awake procedures in terms of tumour cytoreduction, neurological improvement or incidence of postoperative neurological deficit, wound complications, haematomas, and death . To our knowledge, only one team has performed a prospective comparison for resection of lesions located in eloquent cortex , with better results in the general anaesthesia group than in the awake group.
The anaesthetic management of awake craniotomies is challenging. Success is the result of well prepared teamwork and necessitates the intervention of skilled individuals. The experience of the practitioners is also determinant for the choice of the technique used. Throughout the procedure, complications must be anticipated and managed according to predefined guidelines. Choosing one or the other therapeutic option may not be easy with respect to the evaluation of patient cooperation capacity. Furthermore, there is a crucial need for prospective randomized clinical trials to improve the safety and efficacy of this technique, as well as to validate it in comparison to more conventional procedures.
The present work was supported by the Department of Anaesthesia and Intensive Care Medicine, CHU Liege, Liege, Belgium. It was presented as a refresher course at the Euroanaesthesia 2009 meeting, held on 6–9 June in Milan, Italy.
There are no conflicts of interest.
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