Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke
Preliminary Results From a Retrospective, Multicenter Study
Background and Purpose— Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT.
Methods— A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death.
Results— The mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63–3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23–2.30; P<0.0001) compared with conscious sedation.
Conclusions— Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.
Endovascular therapy (also known as intra-arterial therapy, or IAT) for severe acute ischemic stroke (AIS) has been proven effective for middle cerebral artery occlusion in a randomized trial.1 The effect of devices and pharmacologic agents on vessel recanalization and clinical outcomes has been reported in several clinical registries.2–9 Intraprocedural techniques including the use of sedatives have not been rigorously studied. General anesthesia (GA) is often used to (1) sedate and immobilize the patient to prevent wire-induced vessel injury; (2) facilitate blood pressure control; (3) provide adequate patient ventilation and airway protection; and (4) make the procedure tolerable for patients. Conscious sedation (CS) may reduce delays to treatment and allow neurologic assessments during the procedure, which may reveal imminent or developing vascular complications as well as improvement or resolution of symptoms that may influence the rest of the procedure. The optimal modality of sedation during IAT for AIS has not been defined. We sought to determine whether there were safety concerns with the use of CS as well as differences in clinical outcomes between the 2 groups in a retrospective study among 12 stroke centers in the United States.
After approval from the institutional review board from each institution as well as the coordinating institution, a retrospective study was constructed at 12 stroke centers (Table 1) to assess predictors of poor outcomes after IAT for AIS. A data-collection form consisting of demographic variables (de-identified), National Institutes of Health Stroke Scale (NIHSS) score, intravenous tissue-type plasminogen activator use, use of GA, time to groin puncture, location of thrombus (including tandem occlusions), technical aspects of the procedure (devices and pharmacologic agents used), recanalization grade, time to recanalization, postprocedural hemorrhage, and 90-day outcomes were recorded by each site. Inclusion criteria for this study were patients with anterior circulation AIS who were treated with endovascular therapy between 2005 and 2009 at each institution with 90-day clinical follow-up. Patients with posterior circulation strokes (owing to their frequent need for airway support) and those in whom no intervention was performed (spontaneous recanalization) were not included in this analysis. A total of 1079 patients met the inclusion criteria, 980 of whom had 90-day follow-up data and were therefore included in the analysis.
Given the retrospective nature of this multicenter study, the data were collected from each center’s internal database and were sent to the coordinating center for analysis. Recanalization was graded according to the Thrombolysis In Myocardial Infarction score. Patients with a Thrombolysis In Myocardial Infarction score of 2 or 3 were defined as those with successful recanalization.10 Hemorrhages were classified as parenchymal hematoma or hemorrhagic infarction, based on previously published guidelines.11 Patients with parenchymal hematoma 1– or parenchymal hematoma 2–type hemorrhages were classified as symptomatic hemorrhages, whereas hemorrhagic infarction 1 or hemorrhagic infarction 2 hemorrhages were classified as asymptomatic hemorrhages. Good outcomes were defined as a modified Rankin Score of ≤2. Recanalization grades and hemorrhages were classified by the individual centers. Because of the retrospective nature of this study, we were unable to assess the reason for intubation in each case. In many cases, however, this was determined on the basis of operator-specific preferences.
SPSS version 10.0 was used to analyze the data. A univariate analysis was performed with Fisher’s exact test for categorical variables and Student t test for continuous variables in comparing patients placed under GA versus CS. Additionally, a univariate analysis was performed in a similar fashion for comparing patients with a good outcome with those with a poor outcome as well as for mortality. A binary logistic regression was then constructed with variables with a probability value <0.10 to determine independent predictors of poor outcome and mortality. A similar separate analysis was performed with patients who presented with an isolated M1 middle cerebral artery occlusion to remove clot location as a potential confounder from the analysis.
A total of 1079 patients met the inclusion criterion from 12 centers in this study. Of these patients, 980 (91%) patients had clinical follow-up at 90 days and were analyzed. The mean age for the entire cohort was 66±15 years with a median NIHSS score of 17 (interquartile range, 13 to 20). Successful recanalization was achieved in 68% of patients, with 37% of patients achieving a good outcome. The overall mortality rate was 31% with a symptomatic hemorrhage rate of 9.2% and an asymptomatic hemorrhage rate of 24.7%. Table 1 summarizes the number of patients recruited for the study by each institution. A total of 428 (44%) patients were placed under GA before the procedure. Patients who were placed under GA were more likely to have carotid terminus occlusions (25% versus 15%, P<0.01) and higher baseline NIHSS scores (17±5 versus 16±6, P<0.01) than the CS patients, but there were no differences in the time to treatment (306±133 versus 296±172 minutes, P<0.09), the rates of asymptomatic hemorrhage (27% versus 24%, P<0.22), or the rates of symptomatic hemorrhage (9.3% versus 9.1%, P<0.82), respectively.
Table 2 summarizes the univariate analysis comparing predictors of outcome after endovascular therapy for acute stroke. Older patients with a higher NIHSS score and a thrombus in the more proximal intracranial vasculature were more likely to have a poor outcome. The use of a stent was associated with a higher probability of a good outcome, whereas the use of the Merci retrieval system (Concentric Medical, Mountain View, Calif) was associated with a poor outcome in univariate analysis. Table 3 summarizes the binary logistic-regression model for independent predictors of a poor outcome. The use of GA was found to have an independent association with poor clinical outcomes. The use of a stent was associated with good outcomes. As expected, lack of recanalization, older age, higher initial NIHSS score, and postprocedural asymptomatic or symptomatic hemorrhage were associated with a poor clinical outcome. A similar analysis was performed to determine predictors of mortality as summarized in Table 4,and patients in whom GA was used were at a higher risk of mortality.
Owing to the imbalance of patients with carotid terminus occlusions and higher NIHSS scores in the GA group, a separate analysis was performed for patients presenting with isolated M1 middle cerebral artery occlusions to remove clot location as a potential confounder. A total of 494 patients were analyzed, and the mean NIHSS score was balanced between the GA and CS groups (17±4 versus 16±5, P=0.11). In binary logistic-regression modeling, when controlling for age, NIHSS score, time to groin puncture, time to recanalization, recanalization status, and presence of hemorrhage, patients placed under GA were at a significantly higher risk of a poor outcome (odds ratio=2.46; 95% CI, 1.54 to 3.92; P<0.0001).
The type of sedation used in acute stroke interventions varies on the basis of operator and/or institutional protocols. Recent registries of devices for acute stroke intervention have not stipulated the type of anesthesia to be used as part of the protocol.8,9 Individual endovascular specialists use GA or CS on the basis of experience and comfort. There are limited safety data, however, on the use of CS for neurointerventional procedures.12,13 This multicenter study of patients treated with endovascular therapy for anterior circulation AIS demonstrates that CS appears to be as safe as GA with respect to posttreatment intracranial hemorrhage. Furthermore, IAT patients undergoing CS may have improved outcomes and lower mortality compared with patients undergoing GA.
The induction and recovery phases of anesthesia are extremely stressful and frequently associated with hemodynamic perturbations (ie, tachycardia, hypotension, and hypertension) and catecholamine release, which may be associated with cardiac dysrhythmias and ischemia.14 Postanesthesia shivering is often associated with severe patient discomfort and pain and a significant increase in oxygen consumption, which can theoretically impede peripheral oxygen delivery.15 Additionally, there are changes in cerebral autoregulation due to responses to carbon dioxide and blood pressure shifts that are altered by inhaled and intravenous anesthetic agents. These changes may profoundly impact cerebral blood flow, leading to extension of ischemic injury.16 Along with changes in cerebral blood flow there can be increases in intracranial pressure with some agents (eg, isoflurane).16 The effects of all of these changes are unknown, especially in the acutely ischemic brain, but in combination they may result in decreased cerebral perfusion, potentiation of ischemic injury, and possibly direct neuronal toxicity.16 Although some anesthetic agents (eg, barbiturates) may have some neuroprotective effect, the most commonly used agents for GA have very short half-lives, and it is unknown what effect their withdrawal will have on reperfusion injury, especially after recanalization.16 We were unable to collect information on the specific types of anesthetic agents used and hemodynamic perturbations during the procedures, owing to the retrospective nature of this study, but despite this limitation, the currently used protocols for GA for acute stroke interventions may have deleterious effects on outcomes. Further study is required to determine whether these potentially harmful effects are due to hemodynamic alterations, anesthetic agents, changes in autoregulation, or other factors.
CS patients can be monitored for new or worsening neurologic deficits, which can indicate decreases in regional cerebral blood flow due to inadvertent embolization, thrombus formation, progression of ischemia, or the development of an expanding hematoma and mass effect; the operator can thus reassess the angiographic images to find the possible cause and take corrective measures if possible. Another theoretical benefit of CS is that continuous neurologic assessments may also enable the operator to determine the end point of treatment based on clinical improvement as opposed to angiographic recanalization.17 The potential benefit of this approach is that patients will be exposed to a lower risk of complications when fewer endovascular interventions are performed and procedures are shorter in duration. These data were not recorded in our study but may be 1 of the factors accounting for outcome differences in this cohort.
Although there were no significant differences in the time to treatment or time to recanalization between CS and GA patients, delays related to GA may still account for some of the differences in outcome. The time intervals in this study were determined from the time of symptom onset, which is the standard approach in stroke studies. However, it has been demonstrated that for patients who are selected for IAT by advanced neuroimaging (eg, diffusion-weighted/perfusion weighted magnetic resonance imaging or computed tomography perfusion), the time from imaging to recanalization may be a more clinically relevant parameter than the time from onset.18 Owing to the retrospective nature of the study, we could not account for this time interval. It is likely that this time would be longer in patients undergoing GA.
The main argument against CS has been that patient movement can result in procedural complications and disrupt the IAT procedure. Awake stroke patients may be agitated because of the stroke or discomfort caused by the intracranial endovascular intervention owing to innervation of the cerebral vessels.13 Patient agitation along with increased respiration can cause significant head movement that affects both fluoroscopy and digital subtraction angiography. This motion can make the interpretation of angiographic images more difficult and often makes fluoroscopic navigation to the site of occlusion challenging. The result may be longer procedural times, increased patient exposure to contrast and fluoroscopy, and delayed time to recanalization. In addition, patient discomfort may lead to hypertension and tachycardia, but these effects of CS are treatable, unlike the most dreaded complications, movement-induced wire perforation and consequent hemorrhage, which are, for the most part, not treatable.
Movement may not be the primary factor for vessel perforation because rates of wire perforation are low during percutaneous interventions for acute myocardial infarction, during which the heart is continuously beating.19 Most IAT-related intracranial hemorrhages may be directly attributed to either thrombolytic effect, infarct size, or device-vessel incompatibility rather than patient movement.20,21 Intracranial angioplasty and stenting have been safely performed in awake patients and reported in a single-center study.13 Similarly, a single-center study comparing CS with GA in patients undergoing coil embolization for intracranial aneurysms found no differences in complications between the 2 approaches.12 In that study, 150 procedures were performed with CS (92 for unruptured aneurysms and 58 for ruptured aneurysms) and 43 procedures were performed with GA. Only 3 patients were converted from CS to GA. Device-induced discomfort may indicate severe vasospasm, dissection, or imminent vessel perforation, thus alerting the operator to more closely inspect the fluoroscopic/angiographic images and alter the endovascular technique. The latter can consist of less-aggressive device manipulation, device repositioning, or even removal.13 This may offset the potential risks of movement-induced wire perforation. Although we were unable to assess rates of perforation in this study, CS patients did not have a higher incidence of intracranial hemorrhagic complications compared with patients under GA.
When pain and discomfort become severe, analgesics can often alleviate this discomfort. Fortunately, most patients tolerate these procedures well, but it is difficult to account for any psychological distress or recollection of the procedure for patients in this emergency setting. The current database did not include quality-of-life measures, and in future clinical trials, quality of life and psychological distress can be measured.
Another concern with CS is the possible need for emergency intubation for airway protection and an increased risk of intraprocedural aspiration due to vomiting, which is not infrequent during IAT. Emergency intubation may lead to further complications, particularly with catheters in the intracranial circulation. Our study did not address this issue because we could not separate which patients were intubated “electively” as part of the IAT protocol and which were intubated emergently during the procedure. We did not collect data on the incidence of aspiration with GA or CS, but it is known that intubation of a patient in an emergency setting, as is often the case for AIS patients, is associated with a higher risk of aspiration.14 More data are needed to determine whether the risk of aspiration is greater with planned intubation for GA or with CS (with or without intraoperative emergency intubation). Given that the overall outcomes were better with CS, if there were higher rates of aspiration or pneumonia in the CS group, it did not appear to affect clinical outcomes.
In addition to the limitations highlighted in the preceding paragraphs, the major limitation of this study is the nonprospective and nonrandomized nature. Patient comorbidities, clinical status, and endovascular techniques used could not be controlled for and may have had an impact on clinical outcomes. Additionally, we do not have data on what percentage of patients who died were due to family-requested end-of-life care as opposed to progression of the disease. It is likely that some patients died owing to withdrawal of care. Despite these limitations, we provide a large real-world experience with regard to predictors of outcomes after IAT.
In conclusion, CS appears to be as safe as GA during IAT for anterior circulation AIS and appears to be associated with a higher probability of a good clinical outcome. A future prospective study will further our understanding of the effects of CS and GA on clinical outcomes in patients undergoing IAT for AIS.
Source of Funding
David Liebeskind has received significant research support from the National Institutes of Health.
Alex Abou-Chebl, MD; Ridwan Lin, MD; Muhammad Shazam Hussain, MD; Daniel P. Hsu, MD; Sabareesh K. Natarajan, MD, MS; Ashish Nanda, MD; Melissa Tian, RN; Qing Hao, MD, PhD; Junaid S. Kalia, MD; and Thanh N. Nguyen, MD, have no relevant conflicts of interest to disclose. Albert J. Yoo has research support from Penumbra Corp. Tudor G. Jovin, MD, is on the consultant/scientific advisory boards for CoAxia Medical and Concentric Medical and is a consultant for EV3. Elad I. Levy, MD, has received a research grant from Boston Scientific Corp; research support from Micrus Endovascular, Abbott Vascular, and EV3; has received honoraria from Intratech Medical Ltd; has an ownership interest in Mynx/Access Closure and TheraSyn Sensors, Inc; and is on the consultant/advisory boards for Cordis Neurovascular and Micrus Endovascular. Marilyn M. Rymer, MD, is a speaker for Concentric Medical and a consultant for Genentech. Ashis H. Tayal, MD, is a speaker for Genentech and Boehringer Ingelheim. David S. Liebskind, MD, and Raul G. Nogueira, MD, are consultants to and on the advisory boards for Concentric Medical, EV3, and CoAxia. Osama Zaidat, MD, is on the consultant/scientific advisory board for Boston Scientific Corp. Michael Chen, MD, is a speaker for Concentric Medical. Rishi Gupta, MD, is on the consultant/scientific advisory boards for Concentric Medical and CoAxia.
- Received November 24, 2009.
- Accepted January 11, 2010.
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