Mechanical thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) in patients with large vessel occlusions.1,2 Numerous factors are known to affect outcomes after MT for AIS, including the anesthetic techniques used during the procedures.1,3–5 Also blood pressure (BP) control during AIS management has been shown to play an important role in patient outcomes as there is loss of autoregulation in patients with AIS.6,7
The choice of anesthetic technique depends on local preferences, mainly based on the availability and experience of anesthesiologists, preference of neurointerventionists, and clinical status of the patient. Current anesthetic approaches for MT include general anesthesia (GA), conscious sedation (CS), and no sedation (NS). With increasing numbers of patients presenting for MT, anesthesia coverage is a problem in many centers, especially out of hours. Further, in centers where CS or NS is the primary anesthetic technique for MT, the involvement of anesthesiologists is often limited to patients who are unstable or require GA.7,8
Early observational studies reported that GA was associated with lower rates of successful recanalization,9 higher mortality7,9,10 and worse neurological outcomes compared with CS or NS.11,12 Hemodynamic instability during GA was one of the important factors for these poor outcomes.13,14 However, recent randomized controlled trials (RCT) have shown that GA and CS have similar outcomes, especially when hemodynamic stability is maintained in both groups.15,16 Perioperative hemodynamic stability is essential during MT, as both hypotension and hypertension are associated with poorer outcomes.7,17,18 In contrast to many reports focusing on the hemodynamic management of patients undergoing MT with GA,19,20 there is a paucity of literature on the management of perioperative hemodynamics in patients managed with CS or NS.
The aim of our study was to review the hemodynamic management by anesthesiologists and clinical outcomes, in patients undergoing MT under CS. We hypothesized that hemodynamic interventions are frequently required during MT under CS.
Institutional ethics review board approval was obtained and the requirement of informed consent was waived before data collection (UHN REB #16-5415 BE, May 2016). We performed a retrospective cohort study evaluating the role of anesthesiologists in hemodynamic management during MT for AIS under CS.
The inclusion criteria were all adult patients who had undergone endovascular revascularization of the anterior circulation in our institution from January 1, 2012 to March 31, 2016. We excluded patients undergoing revascularization in the posterior circulation due to the substantially different risks and management approaches in this population.21
In our center, anesthesiologists are routinely involved in the management of MT for AIS. The anesthesia team is contacted as soon as a decision to perform endovascular treatment is made in order to ensure that an anesthesiologist is present when the patient arrives at the neuroradiology suite. Our usual anesthetic preference is CS, defined as the administration of sedative and/or analgesic medications, maintaining spontaneous ventilation and without invasive airway support. NS consists of monitored anesthesia care, without administration of any sedative or analgesic drugs. The choice between CS and NS is based on the clinical indication in individual patients. Conversely, patients are administered GA if they have a Glasgow Coma Score of 8 or lower, are agitated or unable to lie still, and if they are already intubated upon arrival at the neuroradiology suite. Conversion to GA is defined as the emergent induction of GA during the procedure due to failure of an initial CS or NS, or due to an intraoperative complication. The choice of anesthetic drugs administered is at the discretion of the attending anesthesiologist. Standard monitoring includes 5-lead electrocardiogram, oxygen saturation, capnography, noninvasive BP every 2.5 minutes and temperature. Invasive BP monitoring (ie, arterial line) is used on an individual basis as determined by the anesthesiologist. All awake or sedated patients receive supplementary oxygen via nasal prongs or facemask. BP management is at the discretion of the anesthesiologist, although, in general, our institutional practice is to maintain systolic BP >140 mm Hg. However, individual targets are set in discussion between anesthesiologist, neurologist and interventional neuroradiologist. Hemodynamic interventions are instituted when there is persisting (lasting >5 min) hypotension or hypertension, or when deemed clinically indicated by the attending anesthesiologist. Choice of agents used for hemodynamic intervention is also at the discretion of the anesthesiologist.
Two research assistants (A.M. and J.M.) independently retrieved data from the patients’ electronic medical records, including neuroradiology, nursing and operative records. An anesthesiologist (G.A.) reviewed the anesthetic charts of all eligible patients and verified the collected data to ensure good quality. Patients with incomplete data were excluded from the study.
Data collected included patient demographics, medical comorbidities (hypertension, diabetes, dyslipidemia, atrial fibrillation, coronary artery disease, congestive heart failure, prior stroke, smoking history, and concurrent antiplatelet and/or anticoagulation treatment), stroke-related data (National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, tissue plasminogen activator administration, location of the occlusion and endovascular device used) and anesthetic data (anesthetic technique, drugs used and their doses, use of vasoactive agents, and perioperative hemodynamics).
BP values at hospital admission and arrival at the neuroradiology suite were collected, the latter considered the baseline BP. Intraprocedural hypotension or hypertension were defined as systolic BP <140 and >180 mm Hg, respectively, as per the guidelines from the Society for Neuroscience in Anesthesiology and Critical Care.22 The important time points collected included start of anesthesia, start of the procedure, revascularization, and completion of the procedure. Revascularization time was defined as the time of the first angiographic run showing a reperfusion score of Thrombolysis in Cerebral Infarction >2.
The primary outcome was hemodynamic intervention, defined as the administration of either vasopressor/inotropes or antihypertensive agents to maintain systolic BP between 140 and 180 mm Hg. The secondary outcome was poor hemodynamic control, defined as the presence of intraprocedure systolic hypotension (<140 mm Hg) or hypertension (>180 mm Hg) for a period longer than 15 minutes in spite of hemodynamic intervention. Hemodynamic interventions were measured in terms of both number of doses and total amount of vasoactive agents administered. The dose units were standardized as follows: ephedrine 5 mg, phenylephrine 40 mcg, labetalol 5 mg, esmolol 20 mg, hydralazine 5 mg, metoprolol 1 mg. The administration of 1 standard dose of any of these agents was considered 1 hemodynamic intervention.
Other clinical outcomes studied included successful revascularization, in-hospital death, neurological status at discharge, and complications. Successful revascularization was defined as a Thrombolysis in Cerebral Infarction score ≥2b, corresponding to reperfusion of at least 50% of the affected territory. A favorable neurological outcome was defined as a modified Rankin Scale (mRS) score ≤2 at hospital discharge. Complications included intracranial hemorrhage confirmed by computerized tomogram (symptomatic or asymptomatic), respiratory complications (pneumonia and/or respiratory failure), and vascular complications (femoral hematoma).
The baseline demographics, stroke, and endovascular therapy data were summarized as mean±SD or medians (interquartile range [IQR]) or frequency (%) as indicated. Student test was used for parametric data, Mann-Whitney test for nonparametric data, and χ2 test for categorical data. Predictors for hemodynamic intervention and failed hemodynamic control were explored by univariate and multivariate logistic regression analysis. The analyses were performed using STATA (version 14) software (StataCorp, TX).
A total of 178 patients underwent MT for AIS between January 2012 and May 2016, from which 29 patients were excluded due to involvement of the posterior circulation and 6 because of incomplete data. Subsequently, 17 patients who had GA were also excluded of which 9 patients were primary GA and the remained intraoperative conversion to GA after failed CS. A final cohort of 126 patients was analyzed (Fig. 1). The median age was 75 years (IQR, 85 to 82) and 59.5% were female. Demographic data and stroke characteristics are shown in Table 1.
An anesthesiologist was present for 124 (98.4%) of the procedures. The remaining 2 patients were managed by neuroradiology nurses, under the supervision of the neuroradiologist. The anesthetic approach was CS in 116 (92.1%) patients and NS in 10 (7.9%). The mean (±SD) doses of anesthetic agents used were: midazolam 1.5 (±0.8) mg, propofol 133.9 (±120.7) mg, fentanyl 73.3 (±45.7) mcg, and remifentanil 271.4 (±256.1) mcg.
The median (IQR) hospital admission-to-anesthesia start and anesthesia start-to-revascularization times were 95 (70 to 129) and 80 (55 to 110) minutes, respectively. The median (IQR) anesthesia-to-procedure start time was 5 (0 to 15) minutes.
Mean (±SD) systolic and diastolic BP on hospital admission was 143.63 (±24.76) and 79.34 (±13.22) mm Hg, respectively. The mean (±SD) systolic and diastolic baseline BP on arrival at the neuroradiology suite was 148.31 (± 23.1) and 77.35 (±12.4) mm Hg, respectively. The baseline systolic BP was <140 mm Hg in 30.2% of the patients and >180 mm Hg in 14.3%. Invasive BP monitoring was performed in 5 (3.9%) patients, via the radial artery in all cases.
Episodes of both intraprocedural hypotension and hypertension were common, with 77.8% and 19.1% patients having at least 1 episode of hypotension (systolic BP <140 mm Hg) or hypertension (systolic BP >180 mm Hg), respectively (Table 2). The majority of these episodes were self-limiting. The incidence of intraprocedural hypotension was higher among patients who received sedation compared to no sedation (80.2% vs. 50%, P=0.043). Hemodynamic intervention was required in 38.9% (49/126) of patients; in 15.1% (19/126) for hypotension and in 19.8% (25/126) for hypertension. Five patients required intervention for both hypotension and hypertension. The details of the hemodynamic interventions are shown in Table 3, and the vasoactive agents used and their dosages in Table 4. In the multivariate analysis, systolic BP at hospital admission was a predictor of hemodynamic intervention (Table 5), with lower BP values being associated with a higher risk of intervention (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.04; P=0.019).
Poor hemodynamic control of hypotension (minimum systolic BP below 140 mm Hg lasting >15 min despite intervention) occurred in 12.7% (16/126) of patients, whereas no patient had poor control of hypertension (maximum systolic BP above 180 mm Hg lasting >15 min). In the multivariate analysis, baseline systolic BP was a predictor for poor hemodynamic control, with lower baseline systolic BP associated with a higher risk of intraprocedural hypotension (OR, 0. 92; 95% CI, 0.89-0.96; P<0.001) (Table 6).
Successful revascularization was achieved in 73.7% (84/126) of patients, and 29.6% (37/126) had a favorable functional neurological outcome at discharge. The incidence of inhospital mortality was 18% (23/126). The mean (IQR) length of hospital stay was 6.3 days (3.0 to 9.9 d). Periprocedure complications included intracranial hemorrhage in 21.4% (27), respiratory complications in 13.6% (17) and puncture site-hematoma in 20% (25) of patients.
This study presents a detailed description of the hemodynamic management of patients undergoing MT under CS for anterior circulation AIS. Anesthesiologists participated in the care of 98.4% of all patients, and the majority (92%) received CS. The main findings of our study are that episodes of both hypotension and hypertension were common during MT, with 77.8% and 19.1% of patients having at least 1 episode of hypotension (systolic BP <140 mm Hg) or hypertension (systolic BP >180 mm Hg), respectively, at some point during the procedure. Hemodynamic interventions were frequent (38.9%) and indicated for treating both hypotension (15.1%) and hypertension (19.8%). However, prolonged (>15 min) episodes of hypotension were seen in only 12.7% of the patients, and no patient had prolonged hypertension. These findings suggest that the need for careful hemodynamic management is not confined to GA but also required during CS, and that the routine presence of anesthesiologists during MT might be helpful in maintaining hemodynamic stability as well as for the rapid treatment of emergent complications irrespective of anesthesia technique. Finally, our cohort represents a real life scenario where all patients presenting for MT were included. This is in contrast to RCTs where patients are preselected according to specific inclusion criteria, and some excluded if there is deviation from study protocol.
Numerous factors are known to affect procedure times, revascularization results and patient outcomes after MT, including anesthetic technique and hemodynamic stability.1,3,5–7 Although earlier studies showed poor outcomes in patients undergoing GA, recent RCTs have failed to confirm these findings.15,16 One of the important determinants of the differences in outcomes between previous observational studies and recent RCTs is the maintenance of perioperative hemodynamic stability.
Tight hemodynamic control has been recommended for patients with AIS (class IIa, level of evidence B), with a target systolic BP between 140 and 180 mm Hg.22 This recommendation was based on a retrospective study by Leonardi-Bee et al,23 who described a U-shaped relationship systolic BP and outcomes in patients with AIS. Subsequently, many studies have supported a relationship between hypotension and poor outcomes after AIS.7,17 Until recently, most studies investigating hemodynamic management during MT included patients undergoing the procedure under GA, and very few presented a detailed description of hemodynamic management under CS.24,25 Although GA might lead to a higher incidence of hemodynamic interventions during MT, our results confirm that other anesthetic approaches are not exempt from such a requirement.
In our study hemodynamic intervention was required in more than one-third of patients during CS, and these findings are similar to those of a recent retrospective study on patients undergoing thrombectomy under sedation.25 Similarly, in the hemodynamic analysis from the GOLIATH (General or Local anesthesia in Intra Arterial Therapy) trial, 57% of patients in the local anesthesia/conscious sedation group required vasopressors to maintain systolic BP >140 mm Hg compared with 98% in the GA group.26
Our study also showed that hemodynamic intervention was required equally for the treatment of both hypotension and hypertension. This finding should raise awareness about the importance of avoiding not only hypotension but also hypertension; the later has been shown to be associated with a higher risk of hyperperfusion following revascularization as well as with hemorrhagic conversion of the stroke.22 In addition, a recent study has shown that higher admission systolic BP is an independent predictor of poor outcome after MT for AIS.18
It has been suggested that the use of vasoactive drugs may be associated with worse outcomes. For example, Mundiyanapurath et al20 showed that the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. In our cohort, none of the patients received norepinephrine during MT. The extent to which vasoactive drugs per se are more harmful than the underlying hypotension that triggered their use is difficult to ascertain. However, the potential deleterious effect of prolonged vasoconstriction in the setting of an ischemic process should not be ignored.
Despite current consensus guidelines recommending a target systolic BP between 140 and 180 mm Hg,22 recent studies have suggested alternative BP goals during MT.15,25 In the SIESTA trial, systolic BP was maintained in the range of 120 to 185 mm Hg.15 Recently, Whalin et al25 showed that a ≥10% mean arterial pressure reduction from baseline was a strong risk factor for poor outcomes in a homogenous population of patients with stroke undergoing thrombectomy under sedation. These authors suggested that this threshold could guide hemodynamic management of patients during sedation and GA during MT. Chasing specific BP targets can lead to relative hypertension or hypotension in some patients, especially if their baseline systolic BP values were <140 or >180 mm Hg. In fact, in the GOLIATH trial 62% of patients in the CS group and 94% in GA group had systolic BP <140 mm Hg. However, this study did not find a statistically significant association between BP-related variables and neurological outcome.26 In our cohort, almost 30% of patients had baseline systolic BP <140 mm Hg on arrival at the neuroradiology suite, and 77.8% had an episode of intraoperative systolic BP <140 mm Hg but not all received an intervention (19.1%). This could be explained by a large number of such episodes being self-limiting, and resolving without the need for active intervention. More importantly this suggests that BP management during AIS should not follow a one-size-fits-all approach, and that optimal BP targets should be tailored toward an individual patient’s baseline BP, preexisting comorbidities, severity and duration of the neurological insult, and risk of hemorrhagic transformation. An individualized target BP should be decided after discussion between anesthesiologist, neurologist, and interventional neuroradiologist.
In our study favorable functional neurological outcome at discharge (mRS ≤2) was lower (29.6%) than in the majority of published RCTs. This may be due to several reasons. First, the mRS score was recorded at discharge in our study, rather than at 90 days as is the case in majority of RCTs assessing MT outcomes.1,9,27 However, when outcomes at discharge are compared, our results are comparable with recent studies by Van der Berg et al11 (24%) and Athiraman et al (22%).19 Secondly, our cohort represents a real world patient population as opposed to an RCT population where inclusion criteria for MT are much more specific and restricted.
Previous studies have reported on the beneficial effect of an integrated stroke unit,28 and of incorporating neurointensivists into the stroke team.29 Recently, it has been suggested that it is the anesthesiologist, rather than anesthesia itself, which may influence outcomes following MT for AIS.30 However, the involvement and the role of the anesthesiologists in this setting has remained poorly defined and often not specified in clinical studies.9–11,27,31 Our experience suggests that the routine inclusion of anesthesiologists in the multidisciplinary stroke team greatly facilitates the transition of care from hospital admission to reperfusion, and has ensured a rapid and effective management of intraprocedural complications.
This retrospective study was inherently subjected to selection and information bias, despite our data being obtained from prospectively collected databases and standard anesthetic records. The analysis was mainly focused on hemodynamic control and mode of anesthesia, but other perioperative issues such as fluid management, and temperature and glycemic control, might constitute important elements where anesthesiologists could also deliver important interventions. However, in the absence of a control group managed by nonanesthesiologists, the net effect or impact of the presence of an anesthesiologist during MT for AIS remains difficult to ascertain. Finally, power analysis was not performed and this might have negatively impacted our secondary outcomes and subgroup analyses.
The requirement for hemodynamic intervention is frequent during MT performed under CS, and not exclusive to GA. Careful hemodynamic management is therefore warranted during MT regardless of the anesthetic technique. The routine presence of anesthesiologists during MT may be helpful in ensuring hemodynamic stability, and for rapid treatment of emergent complications. A shift toward a more individualized approach with tailored hemodynamic targets is needed during management of patients undergoing MT for AIS.
The authors are deeply grateful to the research assistants, Abigail Mukubvu (AM) and Jigesh Mehta (JM), for their dedication and perseverance with the data collection for this manuscript.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
anesthesia; blood pressure; hemodynamic management; mechanical thrombectomy; stroke