Abstract
Emergence from general anesthesia and tracheal extubation is frequently associated with an intense physiologic and metabolic response. These reactions may lead to homeostasis alterations, especially in patients with comorbidities. Neurosurgical patients are at higher risk to develop complications during the emergence from anesthesia resulting in significant morbidity and mortality. Early awakening and extubation under respiratory and cardiovascular stability are the main goals during emergence from anesthesia in a neurosurgical patient. Nevertheless, rapid emergence may impose an increased risk in some patients. Intracranial hemorrhage, hematomas, and cerebral edema with consequent cerebral hypoperfusion are the most concerning complications after an intracranial surgery. Blood pressure changes, hypoxia, and hypercapnia are some of the main factors associated with these events. Coughing and bucking after surgery also trigger an important sympathetic stimulation with concomitant increased venous pressure. Prolonged emergence or delayed arousal from anesthesia after neurosurgery is a concern for both, surgeon and anesthesiologist. Anesthesia technique, area of the brain affected by surgery or trauma, size of the lesion, and preoperative medications are the variables influencing both the emergence and arousal stages.
Keywords
Emergence, Extubation, General anesthesia, Hemodynamic changes, Neurological surgery, Prolonged emergence
Outline
Introduction 247
Neurophysiological Response During Emergence in Neurosurgical Patients 248
Specific Perioperative Considerations 248
Surgical Site and Lesion Location 248
Anesthetic Techniques 248
Balanced Anesthesia 249
Total Intravenous Anesthesia 249
Anesthetic Technique and Recovery of Cognitive Function 249
Dexmedetomidine 249
Delayed Emergence and Arousal 250
Complications 251
Intracranial Hemorrhage or Hematoma 251
Hypertension and Cerebral Hyperperfusion 251
Postoperative Nausea and Vomiting 252
Conclusion 252
References 252
Introduction
Multiple historical factors may be related directly or indirectly with the emergence from anesthesia. William Harvey’s statement in Exercitatio anatomica de motu cordis et sanguinis in animalibus ( On the Movement of the Heart and Blood in Animals ) regarding the blood circulating around the body (1628) took down Galenic dogma (130 BC) about blood circulatory mechanism and created the basis of physiological and pharmacological principles. In 1846, William T. Morton performed the first successful administration of anesthesia but little was known about emergence from anesthesia and patients’ reaction after ether administration. Prior to this successful experience, Morton tried couple of times to anesthetize a patient with unexpected reactions: agitation and disorganized speech.
Cerebral autoregulation and physiological adaptation in the immediate postoperative period are linked to intraoperative efforts to maintain homeostasis. Induced hypocapnia, use of osmotic fluids, and placement of drains are examples of perioperative variables with an important impact in outcomes during the emergence from anesthesia.
An increasing body of evidence regarding anesthesia management supports different techniques based on physicians and institutions’ preferences such as total intravenous anesthesia (TIVA), balanced anesthesia, local anesthesia, or use of adjuvants and their combinations.
Postoperative stress response during extubation may entail increased catecholamine response, oxygen consumption (VO 2 ), blood pressure, and heart rate due to laryngeal stimulation, although other mechanisms are described. Variations in metabolism, hemodynamic parameters, cerebral blood flow (CBF), and intracranial pressure may be developed as a result of shivering or pain with consequent impairment in patients’ outcomes.
Neurological examination should be carried out in the operating room during emergence to identify a potential neurological deficit or emergence delirium. Some patients undergoing complex procedures involving eloquent areas of the brain may be suitable for a planned delay in emergence from anesthesia, avoiding life-threatening complications such as intracranial hemorrhage (ICH), respiratory impairment, and aspiration due to unprotected airway.
Neurophysiological Response During Emergence in Neurosurgical Patients
Several physiological changes take place during the emergence from anesthesia including metabolic variations and those affecting brain homeostasis. Even with slightly normal PaCO 2 levels, bicarbonate levels in the cerebrospinal fluid (CSF) may decrease significantly. Therefore, consequent pH reduction in brain perivascular areas will lead to vasodilation and hyperemia.
Apparently, these events occur regardless of the anesthetic agent used during maintenance. Bruder et al. reported a significant increment of 60% from baseline in CBF velocity during extubation and within the first hour after neurosurgery, with no relation found between these values and the surgery or anesthesia techniques.
Increased catecholamine blood levels have been reported after neurological surgery. However, this condition by itself may interfere with the CBF only in the presence of a defective blood–brain barrier or when autoregulation is compromised. Different options are available to treat catecholamine hemodynamic effects such as β-blocker use (e.g., esmolol) and hypothermia prevention.
On the other hand, sympathetic activation may play a crucial role on the central nervous system (CNS) responses during emergence from anesthesia. Reuptake inhibition of dopamine and norepinephrine by methylphenidate administration will trigger several mechanisms within the CNS leading to a faster recovery after isoflurane and propofol exposure.
Surgery and anesthesia may also increase the incidence of emesis during the emergence. The “emesis center” includes the area postrema (AP), nucleus tractus solitarius, and the dorsal motor nucleus of the vagus nerve. No less than 17 neurotransmitters exert their action on this center throughout the interaction with several receptors such as dopamine, substance P/neurokinin-1, cannabinoid, histamine, among others. The aforementioned responses may be generated during extubation as a result of the autonomic nervous system activation.
Specific Perioperative Considerations
Diagnosis of potential postoperative complications may be delayed due to a slow return to consciousness making neurological examination difficult to perform after neurosurgery. Postanesthesia arousal is a variable considered when assessing anesthesia quality. Preoperative neurologic status, location and size of the lesion, and anesthesia technique are some of the variables interfering with the early postoperative recovery of cognition, hemodynamics, and nociception during emergence.
Surgical Site and Lesion Location
Brain herniation, ischemia, and poor surgical field are the expected consequences of increased intracranial volume. These events have been associated with delayed arousal after intracranial surgery. Predictive factors for delayed postsurgical emergence are the following: mass effect of space-occupying lesion (over 30 mm size), cerebral structures shifting from midline >3 mm with perilesional edema, and prolonged retraction pressure needed to expose the surgical field during tumor resection.
Anesthetic Techniques
Definitive criteria for quality of recovery related to the anesthesia technique during neurosurgical procedures have not been established. However, a targeted and neurological evaluation is performed at the end of surgery to assess outcomes.
The Short Orientation Memory Concentration Test (SOMCT) and the Aldrete score are commonly used when comparing the time and quality of recovery of patients undergoing supratentorial craniotomy, either under balanced or TIVA technique.
TIVA based on propofol–remifentanil has shown slightly shorter extubation time, faster return to consciousness, and faster recovery in comparison with balanced anesthesia. However, most of the studies have demonstrated no statistical significance in quality of recovery among patients either when TIVA or balanced anesthesia was performed.
The NeuroMorfeo Study was carried out in 411 patients reporting no difference in time after extubation to achieve an Aldrete score ≥9 between both balanced and TIVA groups. Hemodynamics and brain surgical conditions were also similar among groups. Nevertheless, a reduced endocrine response to surgical stress was linked to propofol/remifentanil combination.
Balanced Anesthesia
Desflurane provides shorter extubation and recovery time than sevoflurane in patients undergoing craniotomy under balanced anesthesia. Magni et al. compared the effects of sevoflurane (1.5–2%) and desflurane (6–7%) on emergence analyzing the data collected from 120 neurosurgical patients. No significant difference was found regarding the time for emergence (12.2 ± 4.9 min versus 10.8 ± 7.2 min), recorded as the time when eye opening occurred since the inhaled agent administration was suspended. On the other hand, the sevoflurane group needed more time for tracheal extubation in contrast to the desflurane group (18.2 ± 2.3 min versus 11.3 ± 3.9 min). Similarly, the time of recovery (defined in this study as the time that patients’ consciousness allowed them to repeat their name and date of birth) was longer in the sevoflurane group (12.4 ± 7.7 min versus 1.3 ± 3.9 min). The characteristic of the surgical field, such as state of the brain tissue and the intracranial pressure (ICP) and postoperative cognitive function are also comparable between both inhaled anesthetics during supratentorial surgeries. Cognitive impairment commonly occurs in both groups within the first 15 min after extubation or after Aldrete score was ≥9, usually returning to baseline during the next 30 min.
Moreover, when compared with opioids such as fentanyl, alfentanil, and sufentanil in combination with isoflurane showed no clinical relevance regarding the time for obtaining a satisfactory neurological evaluation after surgery.
Total Intravenous Anesthesia
Despite the advantages of propofol use in neurosurgery such as reduction of cerebral metabolic rate of oxygen and ICP, increase of cerebral perfusion pressure (CPP), and antiemetic effect, adverse events like shivering, high blood pressure, and postoperative nausea and vomiting (PONV) are not uncommon.
The effects and outcomes of several combinations of opioids and propofol infusions have been compared during neurosurgery with different results. Gerlach et al. compared propofol/remifentanil versus propofol/sufentanil in supratentorial surgeries and reported a reduced time for extubation in the remifentanil group (6.4 min vs. 14.3 min). When remifentanil/propofol combination was used, SOMCT and Rancho Los Amigos Scale scores are comparable to baseline sooner than the interval of time reported by sufentanil/propofol group. Nevertheless, Djian et al. showed similar results among groups regarding extubation time and reported an increase in costs in the remifentanil group when compared to the sufentanil group.
On the other hand, remifentanil is characterized by a faster onset in reducing cardiovascular responses during intubation when compared with fentanyl. However, hemodynamic parameters, ICP, and CPP levels are similar during the maintenance of anesthesia with both, remifentanil and fentanyl, whereas naloxone administration after neurosurgery is importantly increased in patients who received fentanyl.
Moreover, remifentanil/propofol seems to be a common option for transsphenoidal procedures as it may offer a reduced incidence of postoperative coughing during and after extubation by providing an ideal emergence.
In fact, these studies provide more evidence on the convenience of using opioid drips in neuroanesthesia as discontinuation at an appropriate time will result in a shorter extubation and recovery.
Anesthetic Technique and Recovery of Cognitive Function
Recovery of cognitive functions after surgery has become one of the major concerns among neuroanesthesiologists and also an important parameter when comparing different anesthetic techniques in neurosurgical patients. In fact, a connection between the pathogenesis of neurodegenerative diseases and the development of postoperative cognitive dysfunction has been described.
Dexmedetomidine
Some adjuvants such as the alpha-2 adrenoreceptor agonist dexmedetomidine have been widely used in neuroanesthesia with potential intra- and postoperative advantages. Dexmedetomidine produces dose-dependent sedation, anxiolysis, and analgesia without any concomitant respiratory depression along with decreased anesthetic requirements (hypnotics and opioids). These characteristics make dexmedetomidine a suitable drug for neuroanesthesia.
Smoother arousal and recovery after neurological surgery has been reported with the use of dexmedetomidine as an adjunct during neuroanesthesia. Bekker et al. carried out a prospective, randomized, double-blinded study and concluded that dexmedetomidine use during sevoflurane/remifentanil general anesthesia was associated with less perioperative antihypertensive drugs administration, when compared with placebo (43% vs. 86%).
Dexmedetomidine is also associated with a reduction in CBV, leading to minimization of intraoperative brain retraction, optimization of oxygen supply/demand relation, and inhibition of hypercapnia-induced cerebral vasodilation.
Delayed Emergence and Arousal
Agitation During Emergence From Anesthesia
Agitation during and after emergence is a clinical situation commonly seen in neurosurgical patients (up to 30% of incidence) and usually described within the first hours after intensive care unit admission. The sedation-agitation scale (SAS) and the Richmond Agitation-Sedation Scale are useful clinical assessing tools for both physicians and nurses, to detect a potential postoperative agitation or delirium event. Around 80% of neurosurgical patients who experienced agitation during the emergence received a score of ≥6 based on SAS classification (very agitated or dangerous agitation).
Systemic high blood pressure, increased ICP, hemorrhage, and PONV are the most relevant postoperative complications associated with a fast emergence from anesthesia in neurosurgical patients. In addition, extremely agitated patients may unintentionally pull out their catheters or even the endotracheal tube.
Randomized controlled trials have compared the influence of different anesthetics on emergence agitation after intracranial surgery, revealing that the incidence of agitation during the early phase of recovery varied from 2.5% to 13.3%. Chen et al. identified several independent factors associated with emergence agitation after craniotomy under general anesthesia such as patient-related factors (male gender or patients taking antidepressant drugs or benzodiazepines), anesthesia-related factors (anesthesia management, time exposed to anesthesia, and existence of endotracheal tube), and surgery-related factors (frontal approach).
Surgery and anesthesia time, pain, and anesthesia management have been also reported as relevant predictors for delirium and agitation during emergence in nonneurosurgical patients. In this patient setting, TIVA using propofol seems to decrease the incidence of agitation during the emergence from anesthesia.
In summary, preemptive techniques and pharmacological interventions could be applied to decrease the onset of agitation during the emergence or within the first postoperative hours.
Delayed Emergence
Early neurological assessments after surgery entail a fast recovery from the moment of emergence from general anesthesia. Nevertheless, rapid emergence is not an adequate option for every patient. Baseline assessed neurological status, surgical concerns and prognosis, hemodynamics, and respiratory support, among other factors, may play an important role on delaying emergence (planned or unexpected). Hypothermia or pain may contribute to the postoperative physiologic stress responses to emergence.
Delayed emergence is considered when patients failed to awake being unable to respond to simple verbal commands. The time when a delayed emergence should be diagnosed is 15 min after anesthesia discontinuation, although up to 30 min has also been considered.
Planned Delayed Emergence
In patients with compromised clinical conditions, risks of early extubation may outweigh the benefits. Impaired baseline level of consciousness, poor airway control, prolonged (>6 h) or complicated surgery, unstable intraoperative hemodynamics or ventilation difficulties, and increased brain swelling are some of the clinical situations in which planned delayed recovery should be considered. Other considerations may include surgery involving eloquent areas of the brain, significant brain ischemia, and posterior fossa lesions.
Cai et al. reported a 49.8% rate of delayed extubation after intracranial surgery (398 out of 800 patients). Although data may be limited, the criteria for delayed extubation have been described in reviews and observational prospective studies.
If a planned emergence delay has been decided, the possibility of a brief awakening to perform a short neurological assessment is a common practice among physicians. Complementary options to an early neurologic evaluation are postoperative computed tomography or ICP monitoring.
In patients undergoing posterior fossa or infratentorial surgery, the feasibility of postoperative extubation will be determined by (but not limited to) the location of the lesion, the extent of surgery (especially if the brainstem is involved), and brain edema. PONV is also more frequent in posterior fossa surgery. Unprotected airway combined with PONV may result in life-threatening situations such as aspiration of gastric content, increased ICP, among others.
Surgical positioning may also interfere with patient outcomes during emergence. Macroglossia and consequent upper airway obstruction is usually related with the sitting and prone position probably due to a regional disruption in venous and lymphatic drainage. Some authors suggest that patients undergoing posterior fossa surgery should be extubated at least 1–2 h after they are considered to be fully recovered from anesthesia. However, increased incidence of pneumonia coexisting with other comorbidities, higher incidence of tracheostomy, prolonged hospital admission, and increased costs have been associated with delayed emergence after neurosurgery.
Causes of Delayed Emergence
Scientific evidence incriminates multiple factors in delayed emergence such as perioperative opiate analgesia, hypothermia, anxiolytics, metabolic or electrolyte disturbances, drug clearance impairment, stroke, pneumocephalus, CSF hypotension, and seizures.
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