Editorial
General Anesthesia versus Conscious Sedation for the Endovascular Treatment of Acute Ischemic Stroke W. Scott Jellish, MD, PhD, and Steven B. Edelstein, MD
The treatment of acute ischemic stroke is characterized by several standard operating principles, which could affect outcome. The first is that the time from stroke onset to the point of reconciliation should be as short as possible because for every 10 minutes without successful reperfusion, approximately 2 million nerve cells die.1 The second guiding principle is that hemodynamic monitoring is key and avoiding hypotension, large blood pressure variation and extremes of blood pressure are important determinants in patient outcomes. Finally, fluid management and glycemic control may have a definite effect on short and delayed outcomes in stroke patients concerning the size of the infarct and survivability of neurons in the penumbral zone.2 Recently, increased scrutiny has been given to the type of anesthesia used to facilitate the thrombolysis or endovascular procedure to re-establish perfusion.
Make the Case for Sedation Differences in outcomes have been noted in patients receiving general anesthesia or moderate sedation. In many instances, several retrospective studies have determined that outcomes appear worse with the use of general anesthesia compared with monitored anesthesia care or sedation.3,4 Davis et al found the association between general anesthesia and poor outcomes to be high, with 15% of general anesthesia patients having a probability of good outcomes compared with 60% in the local anesthesia sedation group.5 All of these comparative
From the Department of Anesthesiology, Loyola University Medical Center, Maywood, Illinois. Address correspondence to W. Scott Jellish, MD, PhD, Department of Anesthesiology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153. E-mail: [email protected] 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.037
studies are retrospective; and in many instances, the patients receiving general anesthesia had higher National Institutes of Health Stroke Scale scores, were uncooperative, and were generally more debilitated. However, even in studies where patients were propensity matched, the ones who received general anesthesia had significantly higher in-hospital mortality (25% versus 12%) and pneumonia (17.0% versus 9.3%) compared with patients who received conscious sedation.6 Other studies have also documented higher odds of worse functional outcomes when general anesthesia was compared with conscious sedation for endovascular treatment of acute ischemic stroke.7 Investigators point to the fact that there is greater hemodynamic stability with conscious sedation or monitored anesthesia with much less incidences of hypotension compared with general anesthesia. One study had the average lowest recorded blood pressure of 104 6 17 mm Hg, which was significantly lower than that recorded with local anesthesia 134 6 32 mm Hg.5 Many have noted that systolic blood pressure outside the range of 140-180 mm Hg is associated with poor outcomes.8 Others believe that the induction of general anesthesia with the addition of inhalational anesthetics produce arteriolar vasodilation, which could produce prolonged episodes of blood pressure below the optimal levels needed to maintain cerebral perfusion. This vasodilation could also shunt blood away from ischemic maximally vasodilated areas of the brain. Others also point to a time lag that occurs with general anesthesia compared with local or monitored anesthesia care. Some point to the delay that may occur waiting for the availability of the anesthesia care team, especially if these patients present emergently during extremely busy schedules. There is also the inherent time delay to establish general anesthesia and intubation compared with the administration of a local anesthetic to the surgical site and mild sedation. Many, however, have reported no difference in time of treatment between general
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2015: pp 1-4
1
W.S. JELLISH AND S.B. EDELSTEIN
2
anesthesia and local/sedation. There is substantial variability among observations, and it does seem that centers with established protocols of care have the least delay times, regardless of anesthetic technique.9 The ability to monitor the patient’s neurologic status during the procedure is another advantage of moderate conscious sedation not appreciated with general anesthesia. The patient acts as their own monitor to determine the effects of disruption in blood flow and ischemic changes as the endovascular procedure is performed. This would alert the neurointerventionalist to stop the procedure or withdraw the catheter to improve blood flow. It also would produce a timely alert if an intracranial bleed occurred, which would prompt a surgical emergency. Some investigators have noted that patients who received general anesthesia for their endovascular procedure most probably received pharmacologic paralysis. Patients who were paralyzed were reported to have a higher mortality than those receiving sedation.5,10 Neurologic outcome was also reported to be good if patients received conscious sedation rather than heavy sedation or pharmacologic paralysis. There was no difference in the risk of intraprocedural complication between intubated and nonintubated patients. However, the risk of pneumonia, aspiration, and sepsis was higher in intubated patients and may reflect inadequate reversal of neuromuscular blockade or over sedation with general anesthesia and poor airway reflex control with extubation. This would not be as much of a concern with moderate sedation because airway manipulation and muscle relaxant use would be avoided. In many of the studies to date, which show worse outcomes with the use of general anesthesia, the specific anesthetic technique was never described, and it is hard to determine if volatile anesthetics or a total intravenous anesthetic technique was used. Available human data do not recommend one specific anesthetic over another based on neuroprotective properties. However, techniques can be tailored with the use of etomidate or ketamine along with short-acting opioids such as remifentanil to avoid intraoperative hypotension with cerebral hypoperfusion.
Making the Case for General Anesthesia There are several proponents that support the utilization of general anesthesia for the endovascular management of acute ischemic strokes. Many perceived benefits exist including patient immobility, potential neuroprotection from inhaled anesthetics, blood pressure manipulation, and control of ventilation/airway. Immobility is extremely important when using small catheters in very complex locations such as the brainstem. It also allows for better mapping by the neuroradiologists
and eliminates variations in image caused by spontaneous respirations.
Neuroprotection of Inhaled Anesthetics General anesthesia is usually provided with the utilization of inhaled anesthetic agents. Most of the commercially available agents are fluorocarbons that have the ability to render amnesia, analgesia, and muscle relaxation. In the United States, 3 agents are predominantly used: isoflurane, desflurane, and sevoflurane. The neuroprotective effects of inhaled agents have been investigated for years and, to date, there are still no consensus data regarding effectiveness. An extensive review of the potential neuroprotective effects of inhaled anesthetics was performed by Kitano et al.11 Although most studies were performed in rat models and limited to solitary agents (typically general anesthesia is provided with a variety of pharmaceuticals), it appears that ‘‘dose, timing, and duration of inhalational anesthetic administration, in addition to the severity of ischemic brain injury, are critical to outcome and may provide a possible explanation for the lack of benefit seen in clinical studies.’’ Mechanisms of neuroprotection are numerous and include: potentiation of GABAergic neurotransmission, glutamatergic neurotransmission antagonism, attenuation of ischemia-induced intracellular calcium increases, reduction of cerebral metabolic oxygen consumption, and inhibition of glutamate release, thus limiting excitotoxicity.12-15 In addition, it has been noted by Wilson et al16 that there is a potential role for ‘‘free radical scavenging’’ of ischemia-induced reactive oxidative species by inhalational agents. This ultimately leads to a reduction in lipid peroxidation of neuronal cells. As is evident, more clinical trials are required to determine the ultimately neuroprotective effects of inhaled agents, but these can be difficult to perform due to confounding variables.
Blood Pressure Control Another perceived benefit of general anesthesia during endovascular management of acute ischemic stroke is the maintenance of blood pressure control. It is well known that inhalational agents cause a dose-dependent decrease in blood pressure because of multiple mechanisms. These include vasodilation, decreases in systemic vascular resistance with compensatory increases in heart rate (reflex tachycardia), and decreases in myocardial contractility. There is also a well-known uncoupling of cerebral blood flow to cerebral metabolic oxygen consumption, which given the right circumstances, may lead to an increase in intracranial pressure. However, during general anesthesia, sympathetic stimulation elicited by pain, stress, anxiety, and so forth
ANESTHESIA EFFECT ON TREATMENT OUTCOME FOR AIS
is controlled, thus leading to a decrease in circulating catecholamines. This attenuation allows the anesthesia provider the ability to quickly control blood pressure with the utilization of exogenous vasodilatory or vasopressor agents. It has been established that excessive blood pressure (220/120) is a contraindication to thrombolytic therapy in acute ischemic stroke. However, the minimum baseline pressure is also unclear. The International Stroke Trial proposed that both high and low blood pressures were detrimental to the acute stroke patient and consisted as a U-shaped curve. The low end of systolic blood pressure was determined to be around 140-150 mm Hg.5,8 The concern, however, may be that many stroke patients have pre-existing hypertension and shifts in autoregulation. In addition, during stroke there is a disruption of autoregulation and as such, areas of ischemia are more sensitive to pressure changes, especially in areas of the ischemic penumbra.17 Therefore, even brief decreases in blood pressure (as seen with the induction of general anesthesia) may be detrimental to the patient.
Ventilation Control Another perceived benefit from general anesthesia is the ability to have a secured airway and to control arterial carbon dioxide levels (PaCO2) via manipulation of ventilation. General anesthesia reduces the production of carbon dioxide by a reduction in global oxygen consumption. In addition, inhalation anesthesia with spontaneous ventilation leads to an increase in respiratory rate and a decrease in tidal volume. If the patient’s ventilation is not mechanically controlled, resultant hypercarbia may occur. It is well known that hypercarbia leads to increases in cerebral blood flow, whereas decreases in carbon dioxide lead to a vasoconstriction of cerebral vessels in the presence of preserved autoregulation. As mentioned before, during ischemic strokes, autoregulation may be disrupted and excessive hypocapnia may adversely affect blood flow in regions that have preserved function. In a review by Curley et al,18 it was noted that in addition to reductions in cerebral blood flow, hypocapnia may aggravate cerebral ischemia by increasing cerebral demand via enhanced neuronal excitability and by alterations in the oxygendissociation curve leading to increased affinity of oxygen to hemoglobin. Maintenance of normocapnia appears to be of value, yet spontaneously ventilating patients receiving most forms of sedation, whether it be inhalational anesthetics or opioids, will be at risk for hypercarbia. This is a result of the fact that because these agents shift the respiratory curve to the right resulting in a higher resting PaCO2 required to maintain ventilation. No matter what anesthetic technique is used for the endovascular procedure, many investigators have pointed out that outcomes are assuredly better and safer
3
for the patient when an expert in anesthesia is responsible for hemodynamic management and control of sedation. The neurointerventionalist is fully focused on the procedure and in many instances, inadequately directing the sedation by the nurse.19 The anesthesia team is better equipped to handle procedural complications, hemodynamic control, and airway emergencies that could occur during these endovascular procedures in critically ill patients. Given the emergent and usually complex nature of the interventional procedure in the acute ischemic patient and the hemodynamic control necessary, an anesthesiologist or anesthesia care team should be present to provide sedation, deep sedation, or general anesthesia. Hemodynamic control and airway management, including appropriate ventilation, is imperative for a successful outcome.
References 1. Saver JL. Time is brain-quantified. Stroke 2006;37:263-266. 2. Els T, Klisch J, Orszagh M, et al. Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis influence on clinical outcomes and infarct size. Cerebrovasc Dis 2002;13:89-94. 3. Gupta R. Local is better than general anesthesia during endovascular acute stroke intervention. Stroke 2010; 41:2718-2719. 4. Molina CA, Selim MH. General or local anesthesia during endovascular procedures: sailing quiet in the darkness or fast under a daylight storm. Stroke 2010;41:2720-2721. 5. Davis MJ, Menon BK, Baghirzada LB. Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology 2012;116:396-405. 6. McDonald JS, Brinjiki W, Rabinstein AA, et al. Conscious sedation versus general anaesthesia during mechanical thrombectomy for stroke: a propensity score analysis. J Neurointerv Surg 2014;1-6. 7. Brinjiki W, Mural MH, Rabinstein AA, et al. Conscious sedation versus general anesthesia during endovascular acute ischemic stroke treatment: a systematic review and meta-analysis. AJNR Am J Neuroradiol 2015;36:525-529. 8. Leonardi-Bee J, Bath PM. Blood pressure and clinical outcomes in the international stroke trial. Stroke 2002; 33:1315-1320. 9. Anastasian ZH. Anaesthetic management of the patient with acute ischaemic stroke. Br J Anaesth 2014;113:9-16. 10. Abou-Chebl A, Lin R, Hussain MS, et al. Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multi-center study. Stroke 2010;41:1175-1179. 11. Kitano H, Kirsch JR, Hurn PD. Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J Cereb Blood Flow Metab 2007; 27:348-355. 12. Warner DS. Anesthetics provide limited but real protection against brain injury. J Neurosurg Anesthesiol 2004; 16:303-307. 13. Kawaguchi M, Furuya H, Patel PM. Neuroprotective effects of anesthetic agents. J Anesth 2005;19:150-156. 14. Baughman VL. Brain protection during neurosurgery. Anesthesiol Clin North America 2002;20:315-327. 15. Danton GH, Dietrich WD. The search for neuroprotective strategies in stroke. AJNR 2004;25:181-194.
4 16. Wilson JX, Gelb AW. Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol 2002;14:66-79. 17. Koenig MA, Geocadin RG, de Grouchy M, et al. Safety of induced hypertension therapy in patients with acute ischemic stroke. Neurocrit Care 2006;4:3-7.
W.S. JELLISH AND S.B. EDELSTEIN 18. Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured brain: more harm than benefit. Crit Care Med 2010;38:1348-1359. 19. Grise EM, Adeoye O. Blood pressure control for acute ischemic and hemorrhagic stroke. Curr Opin Crit Care 2012;18:132-138.
General Anesthesia versus Conscious Sedation for the Endovascular Treatment of Acute Ischemic Stroke W. Scott Jellish, MD, PhD, and Steven B. Edelstein, MD
The treatment of acute ischemic stroke is characterized by several standard operating principles, which could affect outcome. The first is that the time from stroke onset to the point of reconciliation should be as short as possible because for every 10 minutes without successful reperfusion, approximately 2 million nerve cells die.1 The second guiding principle is that hemodynamic monitoring is key and avoiding hypotension, large blood pressure variation and extremes of blood pressure are important determinants in patient outcomes. Finally, fluid management and glycemic control may have a definite effect on short and delayed outcomes in stroke patients concerning the size of the infarct and survivability of neurons in the penumbral zone.2 Recently, increased scrutiny has been given to the type of anesthesia used to facilitate the thrombolysis or endovascular procedure to re-establish perfusion.
Make the Case for Sedation Differences in outcomes have been noted in patients receiving general anesthesia or moderate sedation. In many instances, several retrospective studies have determined that outcomes appear worse with the use of general anesthesia compared with monitored anesthesia care or sedation.3,4 Davis et al found the association between general anesthesia and poor outcomes to be high, with 15% of general anesthesia patients having a probability of good outcomes compared with 60% in the local anesthesia sedation group.5 All of these comparative
From the Department of Anesthesiology, Loyola University Medical Center, Maywood, Illinois. Address correspondence to W. Scott Jellish, MD, PhD, Department of Anesthesiology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL 60153. E-mail: [email protected] 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.037
studies are retrospective; and in many instances, the patients receiving general anesthesia had higher National Institutes of Health Stroke Scale scores, were uncooperative, and were generally more debilitated. However, even in studies where patients were propensity matched, the ones who received general anesthesia had significantly higher in-hospital mortality (25% versus 12%) and pneumonia (17.0% versus 9.3%) compared with patients who received conscious sedation.6 Other studies have also documented higher odds of worse functional outcomes when general anesthesia was compared with conscious sedation for endovascular treatment of acute ischemic stroke.7 Investigators point to the fact that there is greater hemodynamic stability with conscious sedation or monitored anesthesia with much less incidences of hypotension compared with general anesthesia. One study had the average lowest recorded blood pressure of 104 6 17 mm Hg, which was significantly lower than that recorded with local anesthesia 134 6 32 mm Hg.5 Many have noted that systolic blood pressure outside the range of 140-180 mm Hg is associated with poor outcomes.8 Others believe that the induction of general anesthesia with the addition of inhalational anesthetics produce arteriolar vasodilation, which could produce prolonged episodes of blood pressure below the optimal levels needed to maintain cerebral perfusion. This vasodilation could also shunt blood away from ischemic maximally vasodilated areas of the brain. Others also point to a time lag that occurs with general anesthesia compared with local or monitored anesthesia care. Some point to the delay that may occur waiting for the availability of the anesthesia care team, especially if these patients present emergently during extremely busy schedules. There is also the inherent time delay to establish general anesthesia and intubation compared with the administration of a local anesthetic to the surgical site and mild sedation. Many, however, have reported no difference in time of treatment between general
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2015: pp 1-4
1
W.S. JELLISH AND S.B. EDELSTEIN
2
anesthesia and local/sedation. There is substantial variability among observations, and it does seem that centers with established protocols of care have the least delay times, regardless of anesthetic technique.9 The ability to monitor the patient’s neurologic status during the procedure is another advantage of moderate conscious sedation not appreciated with general anesthesia. The patient acts as their own monitor to determine the effects of disruption in blood flow and ischemic changes as the endovascular procedure is performed. This would alert the neurointerventionalist to stop the procedure or withdraw the catheter to improve blood flow. It also would produce a timely alert if an intracranial bleed occurred, which would prompt a surgical emergency. Some investigators have noted that patients who received general anesthesia for their endovascular procedure most probably received pharmacologic paralysis. Patients who were paralyzed were reported to have a higher mortality than those receiving sedation.5,10 Neurologic outcome was also reported to be good if patients received conscious sedation rather than heavy sedation or pharmacologic paralysis. There was no difference in the risk of intraprocedural complication between intubated and nonintubated patients. However, the risk of pneumonia, aspiration, and sepsis was higher in intubated patients and may reflect inadequate reversal of neuromuscular blockade or over sedation with general anesthesia and poor airway reflex control with extubation. This would not be as much of a concern with moderate sedation because airway manipulation and muscle relaxant use would be avoided. In many of the studies to date, which show worse outcomes with the use of general anesthesia, the specific anesthetic technique was never described, and it is hard to determine if volatile anesthetics or a total intravenous anesthetic technique was used. Available human data do not recommend one specific anesthetic over another based on neuroprotective properties. However, techniques can be tailored with the use of etomidate or ketamine along with short-acting opioids such as remifentanil to avoid intraoperative hypotension with cerebral hypoperfusion.
Making the Case for General Anesthesia There are several proponents that support the utilization of general anesthesia for the endovascular management of acute ischemic strokes. Many perceived benefits exist including patient immobility, potential neuroprotection from inhaled anesthetics, blood pressure manipulation, and control of ventilation/airway. Immobility is extremely important when using small catheters in very complex locations such as the brainstem. It also allows for better mapping by the neuroradiologists
and eliminates variations in image caused by spontaneous respirations.
Neuroprotection of Inhaled Anesthetics General anesthesia is usually provided with the utilization of inhaled anesthetic agents. Most of the commercially available agents are fluorocarbons that have the ability to render amnesia, analgesia, and muscle relaxation. In the United States, 3 agents are predominantly used: isoflurane, desflurane, and sevoflurane. The neuroprotective effects of inhaled agents have been investigated for years and, to date, there are still no consensus data regarding effectiveness. An extensive review of the potential neuroprotective effects of inhaled anesthetics was performed by Kitano et al.11 Although most studies were performed in rat models and limited to solitary agents (typically general anesthesia is provided with a variety of pharmaceuticals), it appears that ‘‘dose, timing, and duration of inhalational anesthetic administration, in addition to the severity of ischemic brain injury, are critical to outcome and may provide a possible explanation for the lack of benefit seen in clinical studies.’’ Mechanisms of neuroprotection are numerous and include: potentiation of GABAergic neurotransmission, glutamatergic neurotransmission antagonism, attenuation of ischemia-induced intracellular calcium increases, reduction of cerebral metabolic oxygen consumption, and inhibition of glutamate release, thus limiting excitotoxicity.12-15 In addition, it has been noted by Wilson et al16 that there is a potential role for ‘‘free radical scavenging’’ of ischemia-induced reactive oxidative species by inhalational agents. This ultimately leads to a reduction in lipid peroxidation of neuronal cells. As is evident, more clinical trials are required to determine the ultimately neuroprotective effects of inhaled agents, but these can be difficult to perform due to confounding variables.
Blood Pressure Control Another perceived benefit of general anesthesia during endovascular management of acute ischemic stroke is the maintenance of blood pressure control. It is well known that inhalational agents cause a dose-dependent decrease in blood pressure because of multiple mechanisms. These include vasodilation, decreases in systemic vascular resistance with compensatory increases in heart rate (reflex tachycardia), and decreases in myocardial contractility. There is also a well-known uncoupling of cerebral blood flow to cerebral metabolic oxygen consumption, which given the right circumstances, may lead to an increase in intracranial pressure. However, during general anesthesia, sympathetic stimulation elicited by pain, stress, anxiety, and so forth
ANESTHESIA EFFECT ON TREATMENT OUTCOME FOR AIS
is controlled, thus leading to a decrease in circulating catecholamines. This attenuation allows the anesthesia provider the ability to quickly control blood pressure with the utilization of exogenous vasodilatory or vasopressor agents. It has been established that excessive blood pressure (220/120) is a contraindication to thrombolytic therapy in acute ischemic stroke. However, the minimum baseline pressure is also unclear. The International Stroke Trial proposed that both high and low blood pressures were detrimental to the acute stroke patient and consisted as a U-shaped curve. The low end of systolic blood pressure was determined to be around 140-150 mm Hg.5,8 The concern, however, may be that many stroke patients have pre-existing hypertension and shifts in autoregulation. In addition, during stroke there is a disruption of autoregulation and as such, areas of ischemia are more sensitive to pressure changes, especially in areas of the ischemic penumbra.17 Therefore, even brief decreases in blood pressure (as seen with the induction of general anesthesia) may be detrimental to the patient.
Ventilation Control Another perceived benefit from general anesthesia is the ability to have a secured airway and to control arterial carbon dioxide levels (PaCO2) via manipulation of ventilation. General anesthesia reduces the production of carbon dioxide by a reduction in global oxygen consumption. In addition, inhalation anesthesia with spontaneous ventilation leads to an increase in respiratory rate and a decrease in tidal volume. If the patient’s ventilation is not mechanically controlled, resultant hypercarbia may occur. It is well known that hypercarbia leads to increases in cerebral blood flow, whereas decreases in carbon dioxide lead to a vasoconstriction of cerebral vessels in the presence of preserved autoregulation. As mentioned before, during ischemic strokes, autoregulation may be disrupted and excessive hypocapnia may adversely affect blood flow in regions that have preserved function. In a review by Curley et al,18 it was noted that in addition to reductions in cerebral blood flow, hypocapnia may aggravate cerebral ischemia by increasing cerebral demand via enhanced neuronal excitability and by alterations in the oxygendissociation curve leading to increased affinity of oxygen to hemoglobin. Maintenance of normocapnia appears to be of value, yet spontaneously ventilating patients receiving most forms of sedation, whether it be inhalational anesthetics or opioids, will be at risk for hypercarbia. This is a result of the fact that because these agents shift the respiratory curve to the right resulting in a higher resting PaCO2 required to maintain ventilation. No matter what anesthetic technique is used for the endovascular procedure, many investigators have pointed out that outcomes are assuredly better and safer
3
for the patient when an expert in anesthesia is responsible for hemodynamic management and control of sedation. The neurointerventionalist is fully focused on the procedure and in many instances, inadequately directing the sedation by the nurse.19 The anesthesia team is better equipped to handle procedural complications, hemodynamic control, and airway emergencies that could occur during these endovascular procedures in critically ill patients. Given the emergent and usually complex nature of the interventional procedure in the acute ischemic patient and the hemodynamic control necessary, an anesthesiologist or anesthesia care team should be present to provide sedation, deep sedation, or general anesthesia. Hemodynamic control and airway management, including appropriate ventilation, is imperative for a successful outcome.
References 1. Saver JL. Time is brain-quantified. Stroke 2006;37:263-266. 2. Els T, Klisch J, Orszagh M, et al. Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis influence on clinical outcomes and infarct size. Cerebrovasc Dis 2002;13:89-94. 3. Gupta R. Local is better than general anesthesia during endovascular acute stroke intervention. Stroke 2010; 41:2718-2719. 4. Molina CA, Selim MH. General or local anesthesia during endovascular procedures: sailing quiet in the darkness or fast under a daylight storm. Stroke 2010;41:2720-2721. 5. Davis MJ, Menon BK, Baghirzada LB. Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology 2012;116:396-405. 6. McDonald JS, Brinjiki W, Rabinstein AA, et al. Conscious sedation versus general anaesthesia during mechanical thrombectomy for stroke: a propensity score analysis. J Neurointerv Surg 2014;1-6. 7. Brinjiki W, Mural MH, Rabinstein AA, et al. Conscious sedation versus general anesthesia during endovascular acute ischemic stroke treatment: a systematic review and meta-analysis. AJNR Am J Neuroradiol 2015;36:525-529. 8. Leonardi-Bee J, Bath PM. Blood pressure and clinical outcomes in the international stroke trial. Stroke 2002; 33:1315-1320. 9. Anastasian ZH. Anaesthetic management of the patient with acute ischaemic stroke. Br J Anaesth 2014;113:9-16. 10. Abou-Chebl A, Lin R, Hussain MS, et al. Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multi-center study. Stroke 2010;41:1175-1179. 11. Kitano H, Kirsch JR, Hurn PD. Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J Cereb Blood Flow Metab 2007; 27:348-355. 12. Warner DS. Anesthetics provide limited but real protection against brain injury. J Neurosurg Anesthesiol 2004; 16:303-307. 13. Kawaguchi M, Furuya H, Patel PM. Neuroprotective effects of anesthetic agents. J Anesth 2005;19:150-156. 14. Baughman VL. Brain protection during neurosurgery. Anesthesiol Clin North America 2002;20:315-327. 15. Danton GH, Dietrich WD. The search for neuroprotective strategies in stroke. AJNR 2004;25:181-194.
4 16. Wilson JX, Gelb AW. Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol 2002;14:66-79. 17. Koenig MA, Geocadin RG, de Grouchy M, et al. Safety of induced hypertension therapy in patients with acute ischemic stroke. Neurocrit Care 2006;4:3-7.
W.S. JELLISH AND S.B. EDELSTEIN 18. Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured brain: more harm than benefit. Crit Care Med 2010;38:1348-1359. 19. Grise EM, Adeoye O. Blood pressure control for acute ischemic and hemorrhagic stroke. Curr Opin Crit Care 2012;18:132-138.
