Edited by: Osama O. Zaidat, Northeast Ohio Medical University, United States
Reviewed by: Ahmed Mohamed Elhfnawy, Klinik für Neurologie, Uniklinikum Giessen und Marburg, Germany; Mehmet Akif Topçuoǧlu, Hacettepe University, Turkey; Anantha Ramana Vellipuram, Texas Tech University Health Sciences Center El Paso, United States
This article was submitted to Endovascular and Interventional Neurology, a section of the journal Frontiers in Neurology
†These authors have contributed equally to this work
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Malignant cerebral edema (MCE) is one of the serious clinical events in large-vessel occlusion stroke (LVOS), as it can lead to rapid neurologic deterioration (
Blood pressure (BP) management following treatment of LVOS patients with EVT is an important scientific question (
Therefore, in this study, we investigated the association between mean BP level after thrombectomy and the development of MCE in patients treated with EVT. Moreover, determined the best post-EVT maximum BP (BPmax) threshold that predicts the development of MCE. Finally, we evaluated the effect of BP variability (BPV) on the development of MCE.
This study was a retrospective analysis of a prospective registry. We enrolled anterior circulation LVOS patients who underwent EVT at three comprehensive stroke centers (Jinling Hospital between January 2014 and December 2018, Yijishan Hospital between July 2015 and December 2019 and the second affiliated Hospital of Fujian Medical University between January 2016 and December 2019). The study was approved by the local ethics committee.
Patients were included if they fulfilled the following inclusion criteria: (1) age ≥ 18 years; (2) onset to puncture time (OTP) ≤ 480 min; (3) admission NIHSS score ≥ 6, admission Alberta Stroke Program Early CT (ASPECT) score ≥ 6, and pre-stroke modified Rankin Scale (mRS) score <2; and (4) patients with LVOS, including the internal carotid artery (ICA), the middle cerebral artery (MCA) or the anterior cerebral artery (ACA) occlusion. We excluded patients with multiple vessel occlusion (MVO), incomplete BP record, and without post-procedural imaging. Additionally, EVT was performed under local anesthesia in all centers. The flow chart of the inclusion of the study population is displayed in
Flow chart of the study population.
All consecutive patients were prospectively documented. The clinical data included age, sex, medical history of hypertension, diabetes mellitus type 2, admission NIHSS and ASPECT scores, and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification.
BP data were consecutively recorded 24 h after EVT. BP goal was determined by the operator upon the end of thrombectomy or according to institutional protocol. BP was measured by non-invasive BP monitoring devices each hour during the first 24 h after EVT. Mean BP, BPmax, and BPV during the first 24 h were analyzed. BPmax was defined as the highest BP value in 24 h after EVT.
We calculated BPV for both SBP and diastolic BP (DBP) using three statistical methodologies: standard deviation (
In addition, data on the use of continuous intravenous antihypertensive agents were collected for analysis.
The procedural variables were recorded by the operators, including OTP, onset to reperfusion time (OTR), occlusion location, the first thrombectomy approach (stent retriever first, aspiration first, angioplasty, or stent first), bridging therapy, recanalization status, and collateral status.
Recanalization status was evaluated by the modified Thrombolysis in Cerebral Infarction (mTICI) grading system. Successful recanalization was defined as an mTICI score of 2b or 3. Collateral circulation was assessed according to retrograde contrast opacification of vessels within the occluded area on delayed pre-treatment digital subtraction angiography (DSA) images (
For all included patients, the imaging characteristics were assessed by two experienced neurologists/interventionists (ZM Zhou and Q Yang), who were blinded to the clinical data. In the event of discrepancies, the final result was determined by consensus opinion. Referring to previous studies (
Continuous variables are presented as the mean ± standard deviation (
During the study period, 648 anterior circulation LVOS patients who underwent EVT were registered in the three centers. A total of 498 patients were enrolled in the final cohort for analysis after excluding 150 patients due to incomplete BP record (
Of 498 patients, the mean age was 66.9 ± 11.7 years and 290 (58.2%) were male. The median NIHSS and ASPECT scores on admission were 16 (IQR13-20) and 9 (IQR8-10), respectively. The mean OTP time was 262.4 ±79.8 min, and the mean OTR time was 353.3± 93.6 min. Among the included patients, 219 (44%) had 3-month mRS 0–2. The baseline characteristics of the patients are shown in
Demographics and baseline characteristics stratified by MCE.
Age, mean (SD), y | 66.9 (11.7) | 67 (10.9) | 66.9 (11.8) | 0.995 |
Male, |
290 (58.2) | 55 (56.7) | 235 (58.6) | 0.733 |
No. of BP measurements per patient, mean (SD) | 22 (4.5) | 22 (3.7) | 21 (4.6) | 0.878 |
Hypertension | 335 (67.3) | 75 (77.3) | 260 (64.8) | 0.019 |
Diabetes mellitus | 101 (20.3) | 23 (23.7) | 78 (19.5) | 0.349 |
AF | 236 (47.4) | 47 (48.5) | 189 (47.1) | 0.815 |
Baseline SBP, mmHg | 145 (128–160) | 150 (132–160) | 143 (128–160) | 0.085 |
Baseline DBP, mmHg | 80 (72–91) | 83 (70–95) | 80 (74–90) | 0.558 |
Admission NIHSS scores | 16 (13–20) | 18 (15–21) | 15 (12–19) | <0.001 |
Admission ASPECT scores | 9 (8–10) | 8 (7–9) | 9 (8–10) | <0.001 |
0.113 | ||||
LAA | 169 (33.9) | 27 (27.8) | 142 (35.4) | |
Cardioembolic | 277 (55.6) | 58 (59.8) | 219 (54.6) | |
Undetermined or others | 52 (10.5) | 12 (12.4) | 40 (10) | |
0.001 | ||||
ICA | 209 (42) | 64 (66) | 145 (36.2) | |
MCA/ACA (M1/A1) | 254 (51) | 28 (28.9) | 226 (56.4) | |
MCA/ACA (M2/A2) | 35 (7) | 5 (5.2) | 30 (7.5) | |
OTP, mean (SD), min | 262.4 (79.8) | 259.5 (76.1) | 263.1 (80.8) | 0.679 |
OTR, mean (SD), min | 353.3 (93.6) | 377.9 (90.8) | 347.3 (93.4) | <0.001 |
<0.001 | ||||
Grade 0 | 92 (18.5) | 37 (38.1) | 55 (13.7) | |
Grade 1 | 197 (39.6) | 41 (42.3) | 156 (38.9) | |
Grade 2 | 209 (42) | 19 (19.6) | 190 (47.4) | |
Bridging treatment, |
119 (23.9) | 30 (30.9) | 89 (22.2) | 0.070 |
0.194 | ||||
Stent retriever first | 389 (78.2) | 79 (81.4) | 310 (77.3) | |
Aspiration first | 59 (11.8) | 13 (13.4) | 46 (11.5) | |
Angioplasty or stent first | 50 (10) | 5 (5.2) | 45 (11.2) | |
Continuous intravenous antihypertensive agents, |
306 (61.4) | 61 (62.9) | 245 (61.1) | 0.745 |
mTICI, 2b/3, |
364 (73.1) | 51 (52.6) | 313 (78.1) | <0.001 |
90-day mRS 0–2, |
219 (44) | 8 (8.2) | 211 (52.6) | <0.001 |
Among the enrolled patients, 97 (19.5%) patients developed MCE. We did not find differences in baseline BP between the patients with MCE and without MCE. However, patients with MCE had significantly higher mean SBP (128 mmHg vs. 123 mmHg,
Additionally, a significant association was observed between BP serial measurements after thrombectomy and MCE (
Serial SBP levels plotted according to the development of MCE.
After adjusting the admission NIHSS and ASPECT scores, the history of hypertension, baseline BP, OTR, occlusion location, bridging treatment, collateral circulation and mTICI, higher BPmax (OR, 1.021; 95% CI, 1.006–1.036;
Distribution of CED in patients with a SBPmax of ≤ 165 mm Hg and >165 mmHg during the first 24 h after EVT.
In subgroup analyses, no heterogeneity in the effect of SBPmax >165 mm Hg on the development of MCE was observed according to subgroups of patients based on history of hypertension, collateral status, continuous intravenous antihypertensive agents, bridge therapy, occlusion site and recanalization status after correction for multiplicity (
Subgroup analysis for heterogeneity of effect of SBPmax >165 mmHg on the development of MCE. The odds of developing MCE for each subgroup is depicted with a square and a line, representing a 95% CI on the forest plot on the right.
We further evaluated the effect of BPV on the development of MCE. In the multivariate logistic regression models, increases in SBPSD (OR, 1.061; 95% CI, 1.003–1.123;
Association of blood pressure parameters with the development of MCE.
Mean | 128 (120–136) | 123 (116–131) | <0.001 | 1.035 | 1.006–1.065 | 0.017 |
Max | 148 (139–161) | 158 (144–175) | <0.001 | 1.021 | 1.006–1.036 | 0.007 |
CV | 9.05 (7.19–11.73) | 10.02 (8.39–14.30) | <0.001 | 1.065 | 0.981–1.018 | 0.948 |
SV | 12.32 (9.66–15.64) | 14.73 (11.68–18.99) | <0.001 | 1.031 | 0.989–1.075 | 0.149 |
SD | 11.19 (8.81–14.23) | 13.31 (10.36–18.71) | <0.001 | 1.061 | 1.003–1.123 | 0.039 |
Mean | 73 (66–79) | 70 (65–76) | 0.071 | 0.990 | 0.954–1.028 | 0.606 |
Max | 89 (81–98) | 95 (84–101) | 0.001 | 1.012 | 0.989–1.036 | 0.313 |
CV | 11.95 (9.56–14.87) | 13.45 (11.17–15.89) | 0.002 | 0.999 | 0.927–1.078 | 0.987 |
SV | 9.56 (7.58–12.02) | 10.66 (8.88–13.80) | 0.001 | 1.015 | 0.939–1.098 | 0.708 |
SD | 8.42 (6.61–10.62) | 9.44 (8.08–11.45) | <0.001 | 1.009 | 0.907–1.122 | 0.872 |
In this multicenter observational study, the main findings were as follows: First, patients with a higher mean SBP during the first 24 h after EVT were more likely to develop MCE. Moreover, the serial SBP measurements demonstrated that patients with MCE had significantly higher SBP values than those without MCE. Second, the best SBPmax threshold that predicted the development of MCE was 165 mmHg. Furthermore, subgroup analyses also revealed similar direction and size for the effect of post-EVT SBPmax >165 mm Hg on the development of MCE. Third, BPV, as evaluated by SBPSD, was associated with the development of MCE in EVT-treated patients.
MCE is the leading cause of neurologic deterioration or death within the first days after ischemic stroke (
BP management following EVT in LVOS patients is increasingly being taken seriously (
In the present study, we found that LVOS patients with a higher mean SBP during the first 24 h after EVT were more likely to develop MCE. This result is in accordance with previous studies (
A possible explanation of our findings is that elevated SBP during the first 24 h after EVT causes BBB disruption and facilitates brain edema formation (
Another interesting finding of this study was the pattern of SBP trends in the 24 h post-EVT. After EVT, there was a decline in SBP. The results were similar to those of recent studies. For example, Cho et al. found that SBP decreased steeply during the first 5–7 h after EVT and then achieved a plateau for 24 h (
In addition, in the subgroup analyses, we revealed a similar direction and size for the effect of post-EVT SBPmax >165 mm Hg on the development of MCE. However, the adjusted OR were not significant for patients with successful recanalization, without history of hypertension, without intravenous antihypertensive agent and ICA occlusion. A possible explanation is that patients with successful recanalization have a lower rate of MCE [14% (51/364) vs. 34.3% (46/134)]. Additionally, the lack of association in patients without a history of hypertension or intravenous antihypertensive agents may be due to having a normal BP after EVT in these patients. Collateral circulation may be the main impact factor for the insignificant effect of BP on MCE in patients with ICA occlusion.
Notably, in addition to the mean SBP and SBPmax, we also found that BP variability (SBPSD) was associated with the development of MCE. This result were in line with the findings of Skalidi et al.' study (
There are some limitations to this study. First, this was a retrospective study with a modest sample size, and we did not unify the protocol for post-thrombectomy BP management. Hence, the results should be interpreted with caution. Second, intraoperative BP is also an important parameter affecting the clinical outcome after EVT. Unfortunately, the intraprocedural BP was not analyzed. Third, we did not exclude patients with parenchymal hemorrhage, which may affect the assessment of MCE. However, such patients are rare. To our knowledge, we are the first group to investigate the association of post-procedural BP with the course of MCE in patients treated with EVT. Our study further expanded our understanding of the management of BP in patients with EVT.
In conclusion, higher mean SBP during the first 24 h after EVT is associated with the development of MCE in LVOS patients. Having an SBPmax >165 mm Hg was prospectively identified to best discriminate the development of MCE. Moreover, increasing BPV may pose a higher risk of developing MCE. These findings suggest that continuous BP monitoring after EVT could be used as a non-invasive predictor for clinical deterioration due to MCE. Randomized clinical studies are warranted to address BP goal after thrombectomy.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The study was approved by the Ethics Committee of the First Affiliated Hospital of Wannan Medical College (201900039). The patients/participants provided their written informed consent to participate in this study.
All authors have contributed to the theoretical formalism, designing the study, data collection, data analysis, and writing the manuscript.
This work was supported by the National Natural Science Foundation of China (Nos. 81870946 and 81530038), National Key Research and Development Program (No. 2017YFC1307901), and the Fundamental Research Funds for the Central Universities (No. WK9110000056).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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