Download Type of Anesthesia and Differences in Clinical Outcome After Intra

Type of Anesthesia and Differences in Clinical Outcome
After Intra-Arterial Treatment for Ischemic Stroke
Lucie A. van den Berg, MD; Diederik L.H. Koelman, BSc; Olvert A. Berkhemer, MD; Anouk D.
Rozeman, MD; Puck S.S. Fransen, MD; Debbie Beumer, MD; Diederik W. Dippel, MD, PhD;
Aad van der Lugt, MD, PhD; Robert J. van Oostenbrugge, MD, PhD; Wim H. van Zwam, MD, PhD;
Patrick A. Brouwer, MD; Sjoerd Jenniskens, MD; Jelis Boiten, MD, PhD;
Geert A. Lycklama à Nijeholt, MD, PhD; Jan Albert Vos, MD, PhD; Wouter J. Schonewille, MD, PhD;
Charles B.L.M. Majoie, MD, PhD; Yvo B.W.E.M. Roos, MD, PhD; for the MR CLEAN
pretrial study group*
Downloaded from http://stroke.ahajournals.org/ by guest on July 28, 2017
Background and Purpose—Intra-arterial treatment (IAT) in patients with acute ischemic stroke (AIS) can be performed with
or without general anesthesia (GA). Previous studies suggested that IAT without the use of GA (non-GA) is associated
with better clinical outcome. Nevertheless, no consensus exists about the anesthetic management during IAT of AIS
patients. This study investigates the association between type of anesthesia and clinical outcome in a large cohort of
patients with AIS treated with IAT.
Methods—All consecutive patients with AIS of the anterior circulation who received IAT between 2002 and 2013 in 16
Dutch hospitals were included in the study. Primary outcome was functional outcome on the modified Rankin Scale at
discharge. Difference in primary outcome between GA and non-GA was estimated using multiple ordinal regression
analysis, adjusting for age, stroke severity, occlusion of the internal carotid artery terminus, previous stroke, atrial
fibrillation, and diabetes mellitus.
Results—Three hundred forty-eight patients were included in the analysis; 70 patients received GA and 278 patients did
not receive GA. Non-GA was significantly associated with good clinical outcome (odds ratio 2.1, 95% confidence
interval 1.02–4.31). After adjusting for prespecified prognostic factors, the point estimate remained similar; statistical
significance, however, was lost (odds ratio 1.9, 95% confidence interval 0.89–4.24).
Conclusions—Our study suggests that patients with AIS of the anterior circulation undergoing IAT without GA have
a higher probability of good clinical outcome compared with patients treated with general anesthesia. (Stroke.
2015;46:1257-1262. DOI: 10.1161/STROKEAHA.115.008699.)
Key Words: acute stroke ◼ anesthesia ◼ conscious sedation ◼ thrombectomy ◼ thrombolytic therapy
I
ntra-arterial treatment (IAT) has been proven effective
and safe for patients with acute ischemic stroke (AIS).1–3
Numerous studies have evaluated the effect of different
thrombolytic agents and devices.4,5 However, less is known
about the effect of anesthesia during IAT. During intervention, patients receive either general anesthesia (GA) or no
GA (non-GA), referring to local anesthesia at groin puncture
site with or without conscious sedation (CS). Recent retrospective studies suggest that non-GA is as feasible as GA
and that GA may be associated with a lower rate of successful recanalization and worse clinical outcome.6–10 Several
factors could contribute to these findings. Induction and
recovery phases in GA are stressful and could lead to cardiac arrhythmias and cardiac ischemia. Furthermore, inhaled
and intravenous anesthetic agents are known to alter blood
carbon dioxide (CO2) and can cause blood pressure shifts
that could lead to changes in cerebral autoregulation with
decreased cerebral perfusion.11
Received January 29, 2015; final revision received March 5, 2015; accepted March 9, 2015.
From the Departments of Neurology (L.A.v.d.B., D.L.H.K., Y.B.W.E.M.R.) and Radiology (O.A.B., C.B.L.M.M.), Academic Medical Center,
Amsterdam, The Netherlands; Departments of Neurology (A.D.R., J.B.) and Radiology (G.A.L.à.N.), Medical Center Haaglanden, The Hague, The
Netherlands; Departments of Neurology (P.S.S.F., D.W.D.) and Radiology (P.S.S.F., A.v.d.L., P.A.B.), Erasmus University Medical Center, Rotterdam, The
Netherlands; Departments of Neurology (D.B., R.J.v.O.) and Radiology (W.H.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands;
Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands (S.J.); and Department of Neurology (J.A.V.) and
Radiology (W.J.S.), Sint Antonius Hospital, Nieuwegein, The Netherlands.
*A full list of the MR CLEAN pretrial study group is given in the Appendix.
Presented in part at the World Stroke Conference, Istanbul, October 2014.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
115.008699/-/DC1.
Correspondence to Y.B.W.E.M. Roos, MD, PhD, Department of Neurology, the Academic Medical Center, Meibergdreef 9, 1100 DD, PO Box 22660,
Amsterdam, The Netherlands. E-mail [email protected]
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.008699
1257
1258 Stroke May 2015
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Currently, no consensus exists about the optimal anesthetic
management of AIS patients during IAT. Previous studies
had several methodological limitations that prevent to draw
definite conclusions.12 Most important was the imbalance in
stroke severity at baseline in most studies, resulting in more
severe strokes in the GA group as compared with the non-GA
group. Furthermore, the majority of studies had small numbers of patients. In the absence of definite evidence, current
practice is largely based on local protocols and preferences
of the neurointerventionalists.13 Possible advantages of GA
are (1) immobilization of the patient to prevent wire-induced
vessel injury and to facilitate navigation with a quicker
recanalization; (2) adequate ventilation and airway protection; and (3) limiting patient discomfort. On the other hand,
a non-GA approach (1) may reduce time to treatment initiation; (2) allow neurological assessments during and after
the procedure, (3) does not induce blood pressure lowering,
and (4) does not require intubation. Nonetheless, when using
a non-GA approach, there is a chance of a need to convert
acutely to GA accompanied by emergency intubation, which
is associated with a higher rate of aspiration pneumonia and
poor outcome.14
In this retrospective study among 16 Dutch hospitals, we
aimed to evaluate the relation between anesthetic management during IAT and clinical outcome. In most intervention
centers in the Netherlands, a standard strategy regarding anesthetic management for acute stroke interventions is applied,
thereby limiting bias through patient selection by baseline
stroke severity in this study. We hypothesized that a non-GA
approach during IAT in patients with AIS of the anterior circulation is associated with a better clinical outcome compared
with GA based on a potentially shorter time from onset to
treatment initiation, avoidance of potentially harmful blood
pressure changes, and quicker recovery without the use of GA.
Methods
We conducted a retrospective cohort study in patients from the pretrial
cohort of the Multicenter Randomized Clinical Trial of Endovascular
Treatment for Acute Ischemic Stroke in The Netherlands (MR
CLEAN), which consists of all consecutive patients with AIS treated
with IAT in 16 stroke centers in The Netherlands. Information concerning procedures and treated patients was gathered to assess pretrial experience in centers that were committed to participate in the
MR CLEAN trial.15 The registry started in October 2002 and continued until a center started participation in the trial. The institutional
review board from the coordinating institution approved registration
and use of the data. We only included patients with an anterior circulation stroke in our analysis. Patients were treated intra-arterially
with a thrombolytic agent, a dedicated clot retriever or a retrievable
stent. The method of IAT was left to the discretion of the treating
neurointerventionalists.
Study Procedures
All centers kept a prospective registry of patients who received IAT.
Data collection itself was largely retrospective. Demographic variables, premorbid stroke risk factors, National Institutes of Health
Stroke Scale (NIHSS) score at baseline, use of intravenous tissuetype plasminogen activator, timing of baseline and treatment procedures, treatment type (intra-arterial thrombolytics, mechanical
treatment, or both), and type of anesthesia (GA or non-GA) were obtained from medical charts and intervention reports by trained medical researchers. When necessary and possible, NIHSS at baseline was
reconstructed from clinical data with a modified algorithm.16 When
missing, IAT time points were reconstructed using angiogram times:
for start of IAT, time of first scan minus 5 minutes; for end of IAT,
time of last scan plus 5 minutes.
Outcomes
Modified Rankin Scale (mRS) for functional outcome at discharge
was assessed by a certified neurologist or neurology fellow.17 Good
clinical outcome was defined as mRS of ≤2. Grade of recanalization
was assessed with the modified Thrombolysis in Cerebral Infarction
score (mTICI).18 Recanalization was defined as mTICI score 2b or 3
on Digital Subtraction Angiography imaging at the end of the procedure. Three experienced observers from a center that was not involved in the treatment assessed all Digital Subtraction Angiography
runs. Observers were blinded for baseline data of the patient and for
intervention center. All periprocedural and postprocedural complications, including conversion from local to GA, were recorded from
intervention and imaging reports and patient records. Symptomatic
intracranial hemorrhage (SICH) was defined as parenchymal hemorrhage at any site in the brain on the CT-scan, being compatible
with documented neurological deterioration. Asymptomatic intracranial hemorrhage was defined as parenchymal hemorrhaged at any
site of the brain found on follow-up CT-scan without neurological
deterioration.
Statistical Analysis
Analyses were based on the intention to treat principle. Conversions
from non-GA to GA were therefore counted in the non-GA arm of
the study. Descriptive statistics was expressed as means with standard
deviation or medians with interquartile range (IQR). Groups (nonGA versus GA) were compared by the chi-square test for categorical
variables and the Student-t test or, in case of a non-normal distribution, the Mann–Whitney U test for continuous variables. Univariable
logistic analysis was performed to determine an association between
type of anesthesia and good clinical outcome. Multivariable logistic regression was performed to adjust for predefined prognostic
variables: age, stroke severity (NIHSS) at baseline, occlusion of the
internal carotid artery terminus, history of previous stroke, atrial
fibrillation, and diabetes mellitus. Additionally, we performed multivariable ordinal logistic regression analysis to assess the adjusted
common odds ratio for a shift in direction of a better outcome on the
mRS, adjusted for the aforementioned variables. Statistical analyses
were performed using SPSS version 22.0.
Results
We identified 369 patients with an anterior circulation stroke
and available information on anesthetic management during IAT and functional outcome at discharge. Of these 369
patients, we excluded 21 patients for multiple reasons, for
example, patients already under GA for other procedures, lack
of information on timing of procedures, or cross over to no
IAT (see online-only Data Supplement for patient flow-chart).
Three hundred forty-eight patients were used for the analysis;
278 patients were treated without GA and 70 patients with
GA. Information on the use of CS and specific agents were
not available in most of the cases. Patients received non-GA
based on standard strategy in 274 cases. In 4 cases, procedure
was started without GA, despite the local standard strategy
indicating GA. The majority of patients (N=63) received GA
as initial treatment modality, based on the local standard strategy. Seven patients received GA because of agitation, respiratory insufficiency, or decreased level of consciousness before
start of the treatment, whereas they would normally be treated
without GA.
van den Berg et al Type of Anesthesia During Intra-Arterial Treatment 1259
Ten patients (10/278 [4%]) in the non-GA group converted
to GA during treatment. In 9 patients, reason for conversion
was agitation and patient movement. One patient had respiratory insufficiency during treatment initiation. These converted
cases were included in the non-GA group based on the intention to treat principle.
Table 1. Baseline Characteristics
Baseline
Age in years, mean (SD)
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Patients treated under GA were significantly younger (57 years
versus 62 years) and less often had atrial fibrillation (9/70 [29%]
versus 40/278 [16%]). Furthermore, patients in the GA group
had a longer time from onset of symptoms to start of IAT of
00:20 hours (median 04:01; interquartile range 01:53 hours versus 03:40; interquartile range 01:41) and were more frequently
treated with mechanical thrombectomy only (32/70 [46%] versus 61/278 [22%]). The distribution of baseline stroke severity
(NIHSS), pretreatment with intravenous tissue-type plasminogen
activator, and occlusion site was similar in both groups (Table 1).
Clinical Outcome
A total of 82 (82/348 [24%]) patients were functionally independent (mRS 0–2) at discharge. Good clinical outcome was
seen in 26% (72 /278) of patients in the non-GA group and in
14% (10/70) of patients in the GA group. A higher mortality
rate was seen in the GA group (15/70 [21%]) compared with
the non-GA group (46/278 [17%]); however, this difference
was not statistically significant (Table 2). The distribution of
the mRS in both treatment groups is presented in Figure.
In unadjusted logistic regression analysis, non-GA was significantly associated with good clinical outcome (odds ratio
2.1, 95% confidence interval 1.02–4.31). After adjusting for
prespecified prognostic factors, the point estimate remained
positive and, however, did not reach statistically significance
(odds ratio 1.9, 95% confidence interval 0.89–4.24). The
additional multivariable ordinal regression analysis showed a
shift in distribution on the mRS in favor of the non-GA group
(adjusted common odds ratio 1.6, 95% confidence interval
0.98–2.54). This also was not statistically significant.
Periprocedural Complications
Vessel perforation was seen in 4 patients (4/278 [1%]) treated
without GA and did not occur in patients treated under GA.
Two of these 4 patients had an accompanying SICH with an
outcome of respectively 4 and 5 on the mRS at discharge. From
one patient, neither SICH nor asymptomatic intracranial hemorrhage was reported and had an mRS of 3 at discharge, and
one patient had an asymptomatic intracranial hemorrhage with
mRS 4 at discharge. Dissection of the internal carotid artery
during treatment was seen in both groups (non-GA: 12/278
[4%] versus GA: 2/70 [3%]), as well as device-related complications (non-GA: 6/278 [2%] versus GA: 3/70 [4%]). These
included failure to deploy the retrievable stent, a broken guidewire, a broken stent, and a part of device unable to retrieve.
Postprocedural Complications
Postprocedural complications are summarized in Table 2.
There was no difference in occurrence of SICH or asymptomatic intracranial hemorrhage between the 2 treatment groups.
No General
Anesthesia
(n=278)
General
Anesthesia
(n=70)
P Value
Demographics
Men, n (%)
149 (53.6)
35 (50.0)
0.59
62 (14.0)
57 (17.7)
0.03
Medical history and risk factors
Diabetes mellitus, n (%)
Hypertension, n (%)
40 (14.8)
9 (13.4)
0.77
130 (51.7)
37 (44.8)
0.31
Atrial fibrillation, n (%)
79 (29.3)
11 (16.4)
0.03
Hypercholesterolemia or statin
use, n (%)
63 (23.4)
22 (32.8)
0.07
Prior stroke or TIA, n (%)
38 (14.1)
8 (11.9)
0.65
Ischemic heart disease, n (%)
43 (15.9)
16 (23.9)
0.13
15 (7)
16 (5)
0.76
Clinical
Baseline NIHSS, median, (IQR)
Time from symptom onset to start
IAT (hours), median (IQR)
03:40 (01:41) 04:01 (01:53) 0.02
Intravenous thrombolysis with
r-tPA, n (%)
211 (75.9)
45 (65.2)
0.07
M1 MCA, total n (%)
184 (66.2)
49 (70.0)
0.54
M2 MCA, total n (%)
62 (22.3)
9 (12.9)
0.08
M3 MCA, total n (%)
1 (0.4)
0
0.62
Most proximal site of occlusion as
assessed on angiography
ICA, total n (%)
ICA-T, total n (%)
8 (2.9)
3 (4.3)
0.55
23 (8.3)
9 (12.9)
0.24
Procedure
Mechanical IA therapy only, n (%)
61 (21.9)
IA thrombolysis only, n (%)
81 (29.1)
9 (12.9)
0.01
136 (48.9)
29 (41.4)
0.26
Combination of IA thrombolysis
and mechanical IA therapy, n (%)
10 (3.7)
Conversion from non-GA
to GA, n (%)
32 (45.7) <0.001
NA
…
GA indicates general anesthesia; IA, intra-arterial; IAT, intra-arterial
treatment; ICA, internal carotid artery; IQR, interquartile range; MCA, middle
cerebral artery; NA, not applicable; NIHSS, National Institutes of Health Stroke
Scale; r-tPA, recombinant tissue-type plasminogen activator; SD, standard
deviation; and TIA, transient ischemic attack.
Progression of ischemic stroke and seizures was seen more
often in the GA group. Pneumonia and other infections were
more frequent in the non-GA group. However, these differences were not statistically significant.
Angiographic Reperfusion
mTICI scores were not available for 13 patients in the nonGA group. Of the available scores, full recanalization (mTICI
2b/3) was reached in 113/265 (43%) of patients in the non-GA
group versus 34/70 (49%) in the non-GA group. All scores on
the mTICI are summarized in Table 2.
Discussion
Our study suggests that patients with anterior circulation
AIS treated with IAT, who did not receive GA, have a higher
1260 Stroke May 2015
Table 2. Clinical, Radiographic, and Safety Outcomes
No General
Anesthesia
(n=278)
General
Anesthesia
(n=70)
P Value
Clinical outcome
mRS 0–2, n (%)
72 (25.9)
10 (14.3)
0.04
Mortality, n (%)
46 (16.5)
15 (21.4)
0.34
0, n (%)
36 (13.6)
11 (15.7)
0.55
1, n (%)
19 (7.2)
6 (8.6)
0.62
2a, n (%)
97 (36.6)
19 (27.1)
0.22
2b, n (%)
35 (13.2)
14 (20.0)
0.11
mTICI score post treatment*
3, n (%)
Full recanalization (TICI 2b/3)
78 (29.5)
20 (28.6)
0.93
113 (42.6)
34 (48.6)
0.37
50 (18)
9 (12.9)
0.31
0 (0)
0.31
Procedural complications
Total complications, n (%)
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Vessel perforation, n (%)
Dissection, n (%)
4 (1.4)
12 (4.3)
2 (2.9)
0.58
Device-related complications, n (%)
6 (2.2)
3 (4.3)
0.32
Hemodynamic and airway
complications, n (%)
2 (0.7)
0 (0)
0.48
1 (0.4)
0 (0)
0.62
4 (5.7)
0.42
Reperfusion syndrome, n (%)
Migration of thrombus,
microthrombi, or restenosis, n (%)
Seizures during treatment, n (%)
10 (3.6)
3 (1.1)
0 (0)
0.38
12 (4.3)
0 (0)
0.08
SICH, n (%)
33 (11.9)
8 (11.4)
0.92
AICH, n (%)
32 (11.5)
9 (12.9)
0.76
Progression of stroke†, n (%)
28 (10.1)
12 (17.1)
0.15
Pneumonia, n (%)
41 (14.7)
9 (12.9)
0.69
Other infection, n (%)
23 (8.3)
3 (4.3)
0.26
Groin hematoma, n (%)
Postprocedural complications
Cardiac arrythmias‡, n (%)
6 (2.2)
0 (0)
0.38
Myocardial infarction, n (%)
1 (0.4)
0 (0)
0.62
Decompensated heart failure, n (%)
2 (0.7)
1 (1.4)
0.57
Major extracranial hemorrhage,
n (%)
4 (1.4)
2 (2.9)
0.42
PE/DVT, n (%)
2 (0.7)
1 (1.4)
0.57
Seizures, n (%)
10 (3.6)
5 (7.1)
0.19
AICH indicates asymptomatic intracranial hemorrhage; DVT, deep venous
thrombosis; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in
Cerebral Infarction; PE, pulmonary embolism; SICH, symptomatic intracranial
hemorrhage; and TIA, transient ischemic attack.
*mTICI scores were not available for 13 patients in the non-GA group.
†Progression of stroke was defined as symptomatic (malignant) brain edema
seen on noncontrast CT that could have required hemicraniectomy.
‡Cardiac arrhythmias did not include atrial fibrillation; atrial fibrillation
seen on electrocardiography during admission was considered present before
admission for stroke.
probability of good clinical outcome compared with patients
who received GA. Furthermore, we observed that IAT was
initiated sooner after symptom onset in patients treated
without GA as compared with GA. We did not find major
differences with regard to safety parameters between the 2
treatment modalities.
Our findings are consistent with earlier findings in both
terms of clinical and safety outcomes between the 2 treatment
types. However, previous studies reported an imbalance in
baseline NIHSS in favor of non-GA-treated patients, which
could have influenced outcome. In contrast, our study had
equal scores on baseline NIHSS. Hence, difference in baseline
stroke severity is not the reason for improved clinical outcome
after non-GA patients in our cohort.
How can we explain improved outcome in patients treated
without the use of GA? First of all, it is known that inhaled
or intravenous anesthetic agents can alter blood CO2 levels
and blood pressure shifts, which can lead to changes in cerebral autoregulation and consequently in decrease of cerebral
bloodflow, leading to extension of ischemic injury. Use of
propofol and induction dosages of fentanyl predicted postinduction hypotension in a study of Reich and colleagues.19
Furthermore, some anesthetic gases might act as a vasodilatator, resulting in the reverse Robin Hood syndrome, with steal
from blood flow of the affected vascular territories toward
unaffected territories, further compromising flow in the ischemic area.20 There are data that support these findings in AIS
patients treated with IAT. Davis et al found that lower blood
pressures were associated with worse outcomes in patients
undergoing CS or GA, and the mean systolic blood pressure
in patients undergoing CS was 135 mm Hg compared with 104
mm Hg in patients with GA.21 Additionally, in a retrospective
study of 126 patients with a middle cerebral artery stroke
treated with IAT, Jumaa et al showed that final infarct volume
was significantly larger in intubated patients versus nonintubated patients (mean infarct volume [cm3] 147 versus 80.2,
P=0.002).7 In our study, we were unable to collect adequate
information on type of anesthetic agents, blood pressure, CO2,
and cerebral bloodflow during treatment nor final infarct volumes to confirm these data.
Another reason often suggested for the difference in outcome could be a higher rate of aspiration and pneumonia in
intubated patients and contribution of pneumonia to poor outcome.9 However, we found a lower rate of pneumonia in the
GA group, and therefore, this phenomenon cannot explain the
differences in clinical outcome in our study. Conversely, lack
of airway protection by the absence of intubation could lead
to higher rates of pulmonary aspiration in non-GA patients.
Patients with AIS of large cerebral artery may have a degree
of dysphagia and are unlikely to have been fasted before intervention. The urgent need for conversion to GA may occur,
accompanied by a higher risk of aspiration. Most previous
studies did not examine the rate of conversion from non-GA to
GA. In our study, only 10 patients in the non-GA group were
converted to GA. No effect on clinical outcome was seen in
these patients. The small number of converted patients in our
study demonstrates that in current medical practice, the risk
of conversion to GA is relatively small, thereby not clearly
influencing clinical outcome in the non-GA group.
The most important factor leading to poor outcome could be
that GA may lead to treatment delay resulting in a prolonged
onset to recanalization time and therefore reduce the chance
of good clinical outcome. However, 2 previous studies that
investigated this perception found no difference in time to treatment between GA and non-GA and between intubated and
van den Berg et al Type of Anesthesia During Intra-Arterial Treatment 1261
GA
non-GA
2,9 4,3
4,7
7,1
6,9
mRS 0
15,7
14,5
mRS 1
37,1
19,2
mRS 2
11,4
25,7
mRS 3
21,4
12,3
mRS 4
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nonintubated state, respectively.6,7 In our cohort, IAT in patients
treated under GA was started 20 minutes later than in patients
treated without GA. Because time from stroke onset to treatment is an important factor for outcome after acute stroke treatment, this may account for difference in clinical outcome. To
our knowledge, this is the first study to demonstrate a difference
in time to treatment between GA and non-GA. Future studies
need to confirm this and should use specific time points to provide insight into the point at which most time is lost.
The main reason for neurointerventionalists to use GA
is to minimize patient movement. Awake patients could be
agitated during treatment, resulting in head movements that
affect Digital Subtraction Angiography images. As a result,
longer times to recanalization may occur. Major concern, of
course, is increasing risk of procedural complications, such
as vessel perforation or dissection and subsequent intracranial
hemorrhage. In our group of non-GA patients, rate of vessel
perforation was low and SICH was seen as often as in patients
treated under GA. Other studies showed similar safety result,
indicating that a non-GA approach seems to be a safe choice.
As we know from previous studies, higher recanalization leads
to better clinical outcome.22 In a meta-analysis from Brinjikji et
al, which included all available studies on anesthesia and IAT of
AIS, a significant difference was found in recanalization grades
in favor of non-GA.10 In our study, full recanalization was reached
in similar percentages of patients in both treatment groups. So,
we can conclude that higher recanalization may not account for
better outcomes in the non-GA group in our cohort of patients.
The effect of anesthesia on clinical outcome in AIS patients
remains a black box, containing several factors that could influence outcome. Our study did not answer the question which
individual parameters are responsible for worse clinical outcome in patients treated under GA. Faster initiation of treatment
from stroke onset could be one of the major factors in this study.
Limitations
Our study does have several limitations. One of the major
limitations is the retrospective and nonrandomized nature.
Choice of anesthesia was based on standard local strategy
or preference of the neurointerventionalist. The latter could
have led to selection bias or confounding by indication or
center, although a standard strategy regarding anesthetic
management for acute stroke interventions is applied in most
centers. Also the majority of centers and operators preferred
not to use GA; therefore, group sizes were unequal. Optimal
method would include randomization between GA and nonGA. Currently, the ANSTROKE (Sedation Versus General
Anesthesia for Endovascular Therapy in Acute Stroke—Impact
on Neurological Outcome) trial is randomizing AIS patients
16,7
mRS 5
Figure. Distribution of outcomes on the
modified Rankin Scale (mRS) in percentages in patients who received general
anesthesia (GA; n=70) or no GA (non-GA;
n=278). mRS 0 to 1 indicate excellent
outcome; mRS 2 to 3, moderate disability;
mRS 4 to 5, severe disability; and mRS 6,
dead.
mRS 6
between GA and sedation only.23 Furthermore, mRS scores
were only available at discharge. It is preferable to assess the
effect of anesthesia on clinical outcome over a longer period
of time.
Conclusions
Overall, the results of our study are in line with previous
studies and show that patients who do not receive GA have a
higher probability of good clinical outcome and do not have
higher complication rates than patients who undergo GA.
Local anesthesia, with the possible use of CS, during IAT for
AIS seems a good strategy if possible.
Appendix
The MR CLEAN pretrial study group.
Participating centers with local investigators in order of
enrollment (N):
Department of Neurology and Radiology, Sint Antonius
Hospital, Nieuwegein, the Netherlands (136), Wouter
Schonewille, MD, PhD, Jan Albert Vos, MD, PhD;
Department of Neurology and Radiology, Medical Center
Haaglanden, the Hague, the Netherlands (108), Jelis Boiten,
MD, PhD, Geert Lycklama à Nijeholt, MD, PhD; Department
of Neurology and Radiology, HAGA Hospital, the Hague,
the Netherlands (44) Sebastiaan de Bruijn, MD, PhD, Lukas
van Dijk, MD; Department of Neurology and Radiology,
Maastricht University Medical Center and Cardiovascular
Research Institute Maastricht, the Netherlands (34), Robert
van Oostenbrugge, MD, PhD, Wim van Zwam, MD, PhD;
Department of Neurology and Radiology, Erasmus MC
University Medical Center Rotterdam, the Netherlands (34),
Diederik Dippel, MD, PhD, Aad van der Lugt, MD, PhD;
Department of Neurology and Radiology, University Medical
Center Utrecht, the Netherlands (30), Jaap Kappelle, MD,
PhD, Rob Lo, MD; Department of Neurology and Radiology,
Academic Medical Center Amsterdam, the Netherlands (26),
Yvo Roos, MD, PhD, Charles Majoie, MD, PhD; Department
of Neurology and Radiology, Sint Elisabeth Hospital, Tilburg,
the Netherlands (24), Paul de Kort, MD, PhD, Willem Jan van
Rooij, MD, PhD; Department of Neurology and Radiology,
Rijnstate Hospital, Arnhem, the Netherlands (23), Jeannette
Hofmeijer, MD, PhD, Jacques van Oostayen, MD, PhD;
Department of Neurology and Neurosurgery, Radboud
University Medical Center, Nijmegen, the Netherlands
(15) Ewoud van Dijk, MD, PhD, Joost de Vries, MD, PhD;
Department of Neurology and Radiology, Atrium Medical
Center, Heerlen, the Netherlands (13), Tobien Schreuder,
MD, Roel Heijboer, MD; Department of Neurology and
Radiology, University Medical Center Groningen, the
1262 Stroke May 2015
Netherlands (10), Patrick Vroomen, MD, PhD, Omid Eshghi,
MD; Department of Neurology and Radiology, Reinier de
Graaf Gasthuis, Delft, the Netherlands (8), Leo Aerden,
MD, PhD, René Dallinga, MD; Department of Neurology
and Radiology, Isala Klinieken, Zwolle, the Netherlands (6)
Jan van den Berg, MD, PhD, Boudewijn van Hasselt, MD;
Department of Neurology and Radiology, Medical Spectrum
Twente, Enschede, the Netherlands (2), Heleen den Hertog,
MD, PhD, Alexander Tielbeek, MD, PhD; Department of
Neurology and Radiology, Leiden University Medical Center,
the Netherlands (1), Marieke Wermer, MD, PhD, Marianne
van Walderveen, MD, PhD.
Disclosures
Dr Majoie’s institution received fees for his role as a consultant for
Stryker (speakers bureau/lecture fees). Dr Boiten has received honoraria for his role as a consultant for Boehringer Ingelheim. The other
authors report no conflicts.
Downloaded from http://stroke.ahajournals.org/ by guest on July 28, 2017
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Type of Anesthesia and Differences in Clinical Outcome After Intra-Arterial Treatment
for Ischemic Stroke
Lucie A. van den Berg, Diederik L.H. Koelman, Olvert A. Berkhemer, Anouk D. Rozeman,
Puck S.S. Fransen, Debbie Beumer, Diederik W. Dippel, Aad van der Lugt, Robert J. van
Oostenbrugge, Wim H. van Zwam, Patrick A. Brouwer, Sjoerd Jenniskens, Jelis Boiten, Geert
A. Lycklama à Nijeholt, Jan Albert Vos, Wouter J. Schonewille, Charles B.L.M. Majoie and
Yvo B.W.E.M. Roos
for the MR CLEAN pretrial study group
Stroke. 2015;46:1257-1262; originally published online April 7, 2015;
doi: 10.1161/STROKEAHA.115.008699
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2015 American Heart Association, Inc. All rights reserved.
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World Wide Web at:
http://stroke.ahajournals.org/content/46/5/1257
Data Supplement (unedited) at:
http://stroke.ahajournals.org/content/suppl/2015/04/07/STROKEAHA.115.008699.DC1
http://stroke.ahajournals.org/content/suppl/2016/04/07/STROKEAHA.115.008699.DC2
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SUPPLEMENTAL MATERIAL
Patient flow-chart
369 IA treated patients with
AIS of the anterior
circulation
11 patients who received
IAT during elective
procedure
5 patients who eventually
did not receive IAT
4 patients with missing
information
1 patient who received
thrombectomy for cerebral
venous thrombosis
348 patients used for the
analysis
IA indicates intra-arterial; AIS, acute ischemic stroke, IAT, intra-arterial treatment
1
the 3 collateral scores were each significant predictors within
their respective models (P<0.05 for all 3 models), whereas
the effect of type of treatment (intravenous tPA alone versus
endovascular therapy) was significant using scores 1 and 2
were significant predictors of 90-day mRS (P<0.05), but
there was no significant interaction between them (P=0.34).
Collateral status and type of treatment remained significant
when adjusted for age, baseline NIHSS, and time from stroke
31
Figure. Ninety-day modified Rankin Scale (mRS) distribution for endovascular therapy vs intravenous tissue-type plasminogen activator
in the Interventional Management of Stroke 3 trial stratified by good, intermediate, and poor collateral status as per the 3 collateral scores.
Black lines indicate shifts in mRS 0 to 1 and mRS 0 to 2, across treatment types. tPA indicates tissue-type plasminogen activator.
Abstract 9
마취 방법에 따른 허혈뇌졸중의 동맥내 치료 이후 임상 결과의 차이
Type of Anesthesia and Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic
Stroke
Lucie A. van den Berg, MD; Diederik L.H. Koelman, BSc; Olvert A. Berkhemer, MD; Anouk D. Rozeman, MD; Puck S.S. Fransen, MD; Debbie Beumer, MD;
Diederik W. Dippel, MD, PhD; Aad van der Lugt, MD, PhD; Robert J. van Oostenbrugge, MD, PhD; Wim H. van Zwam, MD, PhD; Patrick A. Brouwer, MD;
Sjoerd Jenniskens, MD; Jelis Boiten, MD, PhD; Geert A. Lycklama à Nijeholt, MD, PhD; Jan Albert Vos, MD, PhD; Wouter J. Schonewille, MD, PhD; Charles
B.L.M. Majoie, MD, PhD; Yvo B.W.E.M. Roos, MD, PhD; for the MR CLEAN pretrial study group*
(Stroke. 2015;46:1257-1262.)
Key Words: acute stroke ■ anesthesia ■ conscious sedation ■ thrombectomy ■ thrombolytic therapy
배경과 목적
급성 허혈뇌졸중(acute ischemic stroke, AIS) 환자에서 동맥내
치료(intra-arterial treatment, IAT)는 전신마취(general
anesthesia, GA)로 또는 이것 없이 수행될 수 있다. 이전 연구에
서는 GA 없이 시행한 IAT (non-GA)가 더 좋은 임상 결과를 보
이는 것을 시사하였다. 그럼에도 불구하고, AIS 환자에서 IAT 동
안 마취 관리에 대한 합의는 이루어지지 않았다. 본 연구는 IAT
로 치료받은 AIS 환자 대규모 코호트에서 마취 방법과 임상 결과
사이의 연관성을 조사하였다.
방법
16개의 네덜란드 병원에서 2002년에서 2013년 사이에 IAT를 받
은 전체 연속적인 앞순환 AIS 환자들을 대상으로 하였다. 주요
결과는 퇴원 시 수정Rankin척도(mRS)의 기능적 결과였다. GA
와 non-GA 사이의 일차 결과의 차이는 연령, 뇌졸중 중증도,
내경동맥 말단의 폐색, 뇌졸중 병력, 심방세동, 당뇨병 등을 보정
한 다중순서회귀분석(multiple ordinal regression analysis)을
사용하여 측정하였다.
결과
348명의 환자들이 분석에 포함되었다; 70명은 GA를 받았고,
278명은 GA를 받지 않았다. non–GA가 좋은 임상 결과(OR
2.1, 95% CI 1.02-4.31)와 유의한 관련이 있었다. 미리 정한
예후인자를 보정한 이후, 점추정치(point estimate)는 유사하였다;
하지만, 통계적 유의성은 사라졌다(OR 1.9, 95% CI 0.89-4.24).
결론
본 연구는 GA 없이 IAT를 받은 앞순환 AIS 환자가 GA로 치료받
은 환자에 비해 좋은 임상 결과의 확률이 높을 것임을 시사한다.
van den
Berg
al et al Type
of Anesthesia
Treatment 12611261
van
den et
Berg
Type
of AnesthesiaDuring
During Intra-Arterial
Intra-Arterial Treatment
32
GA
Stroke 한국어판 Vol. 8, No. 3
2,9 4,3
GA
7,1
non-GA
non-GA
4,7
6,9
2,9 4,3
4,7
7,1
15,7
6,9
14,5
mRS 0
mRS 0
mRS 1
15,7
14,5
37,1
37,1
11,4
19,2
25,7
19,2
mRS 1
mRS 2
11,4
12,3
25,7
mRS 2
mRS 3
21,4
21,4
16,7
12,3
mRS 3
mRS 4
mRS 4
16,7
mRS 5
mRS 5
mRS 6
Figure. Distribution
outcomes
on the
Figure.
Distributionofof
outcomes
on the
modified Rankin
(mRS)
in percentmodified
RankinScale
Scale
(mRS)
in percentages in patients who received general
ages
in patients who received general
anesthesia (GA; n=70) or no GA (non-GA;
anesthesia
or no
GA (non-GA;
n=278). mRS(GA;
0 to n=70)
1 indicate
excellent
n=278).
outcome;mRS
mRS02to
to 1
3,indicate
moderateexcellent
disability;
outcome;
mRS
2 to
3, moderate
disability;
mRS 4 to 5,
severe
disability;
and mRS
6,
dead.4 to 5, severe disability; and mRS 6,
mRS
dead.
mRS 6
between GA and sedation only.23 Furthermore, mRS scores
nonintubated state, respectively.6,7 In our cohort, IAT in patients
were
at discharge.
treated
under
GA
was
started
20
minutes
later
than
in
patients
23 is preferable to assess the
betweenonly
GAavailable
and sedation
only.It
nonintubated state, respectively.6,7 In our cohort, IAT in patients
Furthermore, mRS scores
effect of anesthesia on clinical outcome over a longer period
treated without GA. Because time from stroke onset to treatwere
only
available
at
discharge.
It
is preferable to assess the
treated under
GA
was
started
20
minutes
later
than
in
patients
of time.
ment is an important factor for outcome after acute stroke treateffect
of
anesthesia
on
clinical
outcome
over a longer period
treated without
GA.
Because
time
from
stroke
onset
to
treatment, this may account for difference in clinical outcome. To
ment is an important
factorthis
forisoutcome
aftertoacute
strokeatreatour knowledge,
the first study
demonstrate
difference of time.
Conclusions
ment, this may
account
for difference
in clinical
outcome.
in time
to treatment
between GA
and non-GA.
Future To
studies
Overall, the results of our study are in line with previous
needthis
to confirm
this and
should
use specific time
points to pro- Conclusions
our knowledge,
is the first
study
to demonstrate
a difference
studies and show that patients who do not receive GA have a
vide insight
into the point
at which
most time
is lost.
higher the
probability
and do
not previous
have
in time to treatment
between
GA and
non-GA.
Future
studies
Overall,
resultsofofgood
ourclinical
study outcome
are in line
with
The
to prouse GA
higher complication rates than patients who undergo GA.
need to confirm
thismain
and reason
shouldfor
useneurointerventionalists
specific time points to
studies and show that patients who do not receive GA have a
is to minimize patient movement. Awake patients
could be
Local
anesthesia,
with the possible use of CS, during IAT for
말아야
하나?
vide insight agitated
into theduring
point at
which most time is lost. 너무 낮게는 가지
probability
of good clinical outcome and do not have
treatment, resulting in head movements that higher
AIS seems a good strategy if possible.
The mainaffect
reason
forSubtraction
neurointerventionalists
to use
Digital
Angiography images.
As GA
a result, higher complication rates than patients who undergo GA.
is to minimize
movement.
Awake
patients
could
be of Local
the
possible
Systolic
Blood
Pressure
and anesthesia,
Mortalitywith
After
Stroke use of CS, during IAT for
longerpatient
times to
recanalization
may occur.
Major
concern,
Appendix
agitated during
treatment,
resulting
head movements
thatsuch AISThe
course,
is increasing
risk of in
procedural
complications,
seems
a
good
strategy
if possible.
MR CLEAN pretrial study
group.
Too Low, No Go?
as vessel
perforation
or dissectionimages.
and subsequent
intracranial
affect Digital
Subtraction
Angiography
As a result,
Participating centers with local investigators in order of
In our
group
non-GA
patients,
rate
ofof
vessel
longer timeshemorrhage.
to recanalization
may
occur.
concern,
enrollment
(N): Markovic,Appendix
Michelle
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Department of Neurology and Radiology, Sint Antonius
course, is increasing
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The
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treated under GA. Other studies showed similar safety(Stroke.
result, 2015;46:1307-1313.)
Hospital, Nieuwegein, the Netherlands (136), Wouter
as vessel perforation or dissection and subsequent intracranial
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기저 혈압
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수축기 혈압과 higher
심혈관 사건 사이에 J형
곡선의 Department
in similar
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ofmeta-analysis
patients in bothfrom
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van Dijk, MD;
Department
of Neurology(108),
and Radiology,
to better
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outcome.
In
a
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제시한다.
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Maastricht University Medical Center and Cardiovascular
al, which included all available studies on anesthesia and IAT of
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better outcomes
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뇌졸중 후 MD,
Research
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Maastricht,
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(34), Robert
AIS, a significant
difference
was found
in recanalization
grades
of Neurology
and
Radiology,
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The
effect
of
anesthesia
on
clinical
outcome
in
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patients
van 교할
Oostenbrugge,
MD, 수치였다.
PhD, Wim비슷한
van Zwam,
MD,
때
가장
높은
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Academic Medical Center Amsterdam, the Netherlands (26),
ence outcome.
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come in patients
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of treatment
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Choice
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the Netherlands
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사망률의
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have led
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Radiology,
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Medical
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Amsterdam,
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management for acute stroke interventions is applied in most
Department of Neurology and Neurosurgery, Radboud
결과 does have several limitations. One of the major
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University Medical Center, Nijmegen, the Netherlands
limitations
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Pressure
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de
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local strategy
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Kort,
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Jan van
method would
include
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Neurology
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Atrium
Medical
4. Crude and Adjusted Hazard Ratios of All-Cause Mortality or Vascular Mortality by SBP
or preference
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Schreuder,
All-Cause Mortality
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Endovascular
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MD,
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Heijboer,
MD; Department
of Neurology
and
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selectionforbias
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indication
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Hospital,
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(n=130
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University
Medical
Center
Groningen,
on Neurological
Outcome)
trial regarding
is randomizing
AIS patients
center, although
a standard
strategy
anesthetic
HR (95%
CI) Radiology,
P Value MD,
HR PhD,
(95% CI)
P Value
Hofmeijer,
Jacques
van
Oostayen,
MD,thePhD;
Abstract 10
수축기 혈압과 뇌졸중 후 사망률
Crudeis applied in most
management for acute stroke interventions
Department of Neurology and Neurosurgery, Radboud
SBP 120–139 mm Hg
Ref
…
Ref
…
centers. Also the majority of centers and operators
preferred
University
Center,
SBP <120 mm Hg
0.86 (0.46–1.59)
0.627 Medical
0.74 (0.30–1.85)
0.521 Nijmegen, the Netherlands
≥140 mm Hg
0.834
(0.61–2.69)MD, 0.514
not to use GA; therefore, group sizes wereSBPunequal.
Optimal 1.05 (0.66–1.67)
(15) Ewoud
van1.28Dijk,
PhD, Joost de Vries, MD, PhD;
Adjusted*
method would include randomization between
GA
and
nonDepartment
of
Neurology
and
Radiology, Atrium Medical
SBP 120–139 mm Hg
Ref
…
Ref
…
GA. Currently, the ANSTROKE (Sedation
Versus
General 1.43 (0.82–2.50)
Center, 0.208
Heerlen,
the Netherlands
(13), Tobien Schreuder,
SBP <120
mm Hg
1.71 (0.75–3.90)
0.203
SBP ≥140 mm Hg
0.194
0.82 (0.41–1.62)
Anesthesia for Endovascular Therapy in Acute
Stroke—Impact 0.73 (0.45–1.18)
MD, Roel
Heijboer,
MD; 0.569
Department of Neurology and
SBP <120 mm Hg vs ≥140 mm Hg
1.96 (1.13–3.39)
0.017
2.08 (0.93–4.68)
0.075
Radiology, University Medical Center Groningen, the
on Neurological Outcome) trial is randomizing
AIS patients
CI indicates confidence interval; HR, hazard ratio; and SBP, systolic blood pressure.
*Adjusting for age, sex, race/ethnicity, poverty income ratio, hypertension, total serum cholesterol >200 mg/dL,
coronary artery disease, angina, congestive heart failure, body mass index, use antihypertensive medication(s), smoking.
hypercholesterolemia; and to use antihypertensive medications. They were less likely to be obese or to smoke (Table 1).
Mortality assessment was at a mean follow-up of 4.1 years
(2.6–5.7 years). At 2 years, patients in the low to normal SBP
group tended to have higher cumulative all-cause mortality
for covariates (Figure [A]). Both low SBP and high SBP
(approximately >180 mm Hg) were associated with greater
risk of mortality compared with SBP in the normal or moderately high range (Figure [A]). Similar patterns were seen with
cardiovascular mortality but were not as robust (P=0.12 for