Abstract
Objective: To assess factors associated with changes in blood pressure during early mobilization protocol for patients with acute ischemic stroke who were treated with mechanical thrombectomy. Design: Retrospective observational study. Method: We analyzed patients with acute ischemic stroke who were treated with mechanical thrombectomy (MT group, n=60) and patients who received conservative medical management (control group, n=60) matched by age and National Institute Health of Stroke Score at admission from April 2009 to July 2014. The proportion of patients with prominent blood pressure change during an early mobilization protocol was compared between the MT group and control group. Factors associated with prominent blood pressure change were also analyzed using multivariable logistic regression analysis. Result: The deviation in blood pressure response was much more significant in the MT than control group (13.3 vs. 1.7%, p<0.016). Logistic regression analysis showed the interval from admission to being able to sit in a wheelchair associated with prominent changes in blood pressure (odds ratio, 1.604; 95% confidence interval, 1.196-2.150; p<0.002). Conclusion: Our results showed that prominent changes in blood pressure during an early mobilization protocol can occur easily in patients with acute ischemic stroke after mechanical thrombectomy.
Keywords: ischemic stroke, mechanical thrombectomy, early mobilization protocol
Intravenous tissue plasminogen activator (IVtPA) therapy for acute ischemic stroke is now widely accepted 1-7). Additionally, mechanical thrombectomy (MT) is considered a primary reperfusion strategy for the treatment of large occluded vessels such as the internal carotid artery (ICA) 8-10). MT is reasonable for patients who have contraindications to the use of IVtPA. Currently, four mechanical clot extraction devices, the Merci retriever (Concentric Medical, Mountain View, CA), the Penumbra system (Penumbra, Alameda, CA), and stent retrievers (Solitaire; Covidien/ev3, Dublin, Ireland or Trevo; Concentric Medical) are cleared for use in Japan for the recanalization of arterial occlusions in patients with ischemic stroke.
Early rehabilitation, and especially early mobilization, is very important in general stroke care. During early mobilization protocol, the evaluation of arterial blood pressure as a dynamic parameter is common and very important. However, there are no suggestions on postoperative blood pressure control after MT, even in the main guidelines such as the American Heart Association guideline 11) and the Japanese Guidelines for the Management of Stroke 2009 12).
In the real clinical scene, postoperative blood pressure management after MT may vary according to individual cases, for example, time to reperfusion, recanalization grade, and postoperative symptoms of cerebral hemorrhage, and little is known about its influence on the progress of early mobilization, especially in terms of changes in blood pressure. The purpose of the present retrospective observational study was to examine the frequency of prominent blood pressure change and to clarify the background factors that influenced prominent blood pressure change during the early mobilization protocol among patients with and without MT matched by age and National Institute of Health Stroke Scale (NIHSS) score.
Method
Patient selection
We began with the analysis of 1120 consecutive cases of patients with ischemic stroke who were admitted to the stroke center of St. Marianna University Toyoko Hospital from April 2009 to July 2014, all of whom underwent an acute rehabilitation program. After the following inclusion criteria were applied, 715 patients remained: 1) hospitalization within 3 days from stroke onset, 2) modified Rankin Scale (mRS) ≤3 before admission, and 3) adoption of our early mobilization protocol. We divided these patients into the MT group and the control group. The MT group included 60 patients who underwent MT using the Merci retriever, Penumbra system, Solitaire or Trevo. Stratified random matching by age and NIHSS score at admission was used to populate the MT group and the control group (n=60), in which the patients received conservative medical management. Finally, 120 patients were eligible for this analysis (Fig. 1). This study was approved by the Institutional Review Board of St. Marianna University of School of Medicine.
Figure 1.
Patient selection
Data collection
The following data were retrospectively collected from patients' medical records: age, sex, mRS (admission, discharge), comorbidity (stroke, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation [Af], ischemic heart disease [IHD], heart failure), etiology of stroke (atherothrombotic infarction, cardioembolic infarction [CEI], lacunar infarction, dissection, paradoxical infarction, undetermined stroke), NIHSS score(at admission, at sitting stress test ), using nicardipine, the interval from admission to starting rehabilitation, the interval from admission to being able to sit in a wheelchair, and changes in blood pressure during mobilization stress test. The vessels occluded (internal carotid artery [ICA], middle cerebral artery [MCA], and basilar artery [BA]) and the instructions provided on blood pressure control after MT were also collected.
Mobilization protocol
We use our mobilization protocol for standardization and management of risks during early mobilization (Fig. 2). This mobilization protocol is composed of 4 stages: bed rest, elevation of the head of the bed to 30° and to 60°, and sitting in a wheelchair. The protocol provided criteria for 1) excluding the patient from the mobilization protocol on doctor's orders, 2) evaluating the patient's general condition and assessing whether the conduction of a stress test is acceptable, 3) conducting a stress test while checking blood pressure and heart rate response, 4) advancing patient mobilization along the stages of the protocol, and 5) documenting mobility status.
Figure 2.
Mobilization protocol and stress test criteria
When the patient passes the stress test criteria for their current stage of the protocol, the mobility level rises to the next stage. Criteria for cancellation of the protocol include i) deterioration of neurological symptoms, ii) prominent changes in blood pressure (rise in systolic blood pressure [SBP] >220 mmHg or in diastolic blood pressure [DBP] >120 mmHg; drop in SBP >30 mmHg [if main artery occlusion: >20 mmHg]) and heart rate (maximum heart rate >150 bpm; new arrhythmia: paroxysmal Af, Lown Grade ≥IVb, Mobitz type II block). This protocol is used by all staff, including doctors, nurses, and physical therapists in the stroke care unit and intensive care unit.
In this study, we defined the patients with prominent changes in blood pressure as those who could not clear the test cancelation criteria due to a prominent change in blood pressure during each stress test, i.e., bed angles of 30° and 60° and sitting in a wheelchair.
Statistical analysis
Quantitative variables are described as mean and standard deviation, and qualitative data is described as number and percentage. Differences between groups were assessed with chi-square test and Mann-Whitney test. A multivariable binary logistic regression analysis was performed to analyze the relationship between the deviation in blood pressure response and background variables. A p value <0.05 was considered significant. Statistical analysis was carried out with SPSS 12.0 for Windows (SPSS Inc., Chicago, IL, USA).
Result
The 60 patients with acute ischemic stroke in the MT group were treated with the Merci retriever (n=13), Merci retriever + Penumbra system (n=9), Penumbra system (n=31), Solitaire (n=2), Trevo (n=3), Trevo + Penumbra system (n=1), and Trevo + Solitaire (n=1). Occluded vessels in the MT group included the ICA (n=21), MCA (n=35), and BA (n=4). Control of postoperative SBP after MT was necessary for a wide range of SBP, from ≤140 mmHg to ≥200 mmHg (Table 1).
Table 1.
Postoperative blood pressure management
| Target systolic blood pressure (mmHg) | n | (%) |
|---|---|---|
| ≦140 | 15 | 25.1 |
| ≦160 | 21 | 35.0 |
| ≦185 | 16 | 26.7 |
| ≦200 | 8 | 13.3 |
In a comparison between the MT group (34 men and 26 women; mean age 74.9±13.3 years) and the control group (32 men and 28 women; 75.1±13.7 years), prominent changes in blood pressure occurred only during the wheelchair stress test, and these changes occurred at a significantly higher frequency in the MT group than control group (13.3 vs 1.7%, p=0.016) (Table 2). The ratio of patients with CEI as the etiology of stroke (70.0 vs. 50.0%, p=0.051) and that with Af (71.7 vs. 48.3%, p=0.008) were higher in the MT group. The proportion of patients with a mRS indicating good outcome at discharge differed between the two groups, but it was better in the MT group. The interval from admission to starting rehabilitation (2.6±1.9 vs. 1.6±1.3 days, p<0.000) and to being able to sit in a wheelchair (4.7±3.6 vs. 3.6±2.0 days, p=0.019) were longer in the MT group (Table 3).
Table 2.
The proportion of the prominent blood pressure change
| All patients n=120 |
Control group n=60 |
MT group n=60 |
p value | |
|---|---|---|---|---|
| Blood pressure deviation, n (%) | 9 (7.5) | 1 (1.7) | 8 (13.3) | 0.016 |
| Rise | 1 (0.8) | 0 (0.0) | 1 (1.7) | |
| Drop | 8 (6.7) | 1 (1.7) | 7 (11.7) |
Table 3.
Backgrounds comparison between the MT group and the control group
| All patients n=120 |
Control group n=60 |
MT group n=60 |
p value | |||||
|---|---|---|---|---|---|---|---|---|
| Age (year), mean ±SD | 75.0±13.5 | 75.1±13.7 | 74.9±13.3 | 0.427 | ||||
| Sex, n (%) | 0.977 | |||||||
| Male | 66 | (55.0) | 32 | (53.3) | 34 | (56.7) | ||
| Female | 54 | (45.0) | 28 | (46.7) | 26 | (43.3) | ||
| modified Rankin Scale before admission, n (%) | 0.087 | |||||||
| 0 | 96 | (80.0) | 46 | (76.7) | 50 | (83.3) | ||
| 1 | 5 | (4.2) | 4 | (6.7) | 1 | (1.7) | ||
| 2 | 6 | (5.0) | 1 | (1.7) | 5 | (8.3) | ||
| 3 | 13 | (10.8) | 9 | (15.0) | 4 | (6.7) | ||
| modified Rankin Scale at discharge, n (%) | 0.021 | |||||||
| 0 | 4 | (3.3) | 0 | (0.0) | 4 | (6.7) | ||
| 1 | 14 | (11.7) | 3 | (5.0) | 11 | (18.3) | ||
| 2 | 14 | (11.7) | 9 | (15.0) | 5 | (8.3) | ||
| 3 | 25 | (20.8) | 13 | (21.7) | 12 | (20.0) | ||
| 4 | 50 | (41.7) | 31 | (51.7) | 19 | (31.7) | ||
| 5 | 12 | (10.0) | 4 | (6.7) | 8 | (13.3) | ||
| 6 | 1 | (0.8) | 0 | (0.0) | 1 | (1.7) | ||
| Etiology of stroke, n (%) | 0.051 | |||||||
| ATBI | 34 | (28.3) | 23 | (38.3) | 11 | (18.3) | ||
| CEI | 72 | (60.0) | 30 | (50.0) | 42 | (70.0) | ||
| Undetermined | 9 | (7.5) | 4 | (6.7) | 5 | (8.3) | ||
| Dissection | 2 | (1.7) | 1 | (1.7) | 1 | (1.7) | ||
| Lacunar | 2 | (1.7) | 2 | (3.3) | 0 | (0.0) | ||
| Paradoxical | 1 | (0.8) | 0 | (0.0) | 1 | (1.7) | ||
| Comorbidity, n (%) | ||||||||
| Stroke | 19 | (15.8) | 10 | (16.7) | 9 | (15.0) | 0.500 | |
| Hypertension | 74 | (61.7) | 41 | (68.3) | 33 | (55.0) | 0.094 | |
| Dyslipidemia | 30 | (25.0) | 14 | (23.3) | 16 | (26.7) | 0.417 | |
| Diabetes mellitus | 31 | (25.8) | 13 | (21.7) | 18 | (30.0) | 0.202 | |
| Atrial fibrillation | 72 | (60.0) | 29 | (48.3) | 43 | (71.7) | 0.008 | |
| IHD | 6 | (5.0) | 2 | (3.3) | 4 | (6.7) | 0.340 | |
| Heart Failur | 10 | (8.3) | 6 | (10.0) | 4 | (6.7) | 0.372 | |
| Occluded vessel | ||||||||
| ICA | - | - | - | - | 21 | (35.0) | ||
| MCA | - | - | - | - | 35 | (58.3) | ||
| BA | - | - | - | - | 4 | (6.7) | ||
| NIHSS, mean±SD | ||||||||
| at admission | 17.3±6.5 | 16.9±6.5 | 17.8±6.5 | 0.429 | ||||
| at sitting stress test | 11.1±7.1 | 11.1±6.7 | 11.5±7.5 | 0.960 | ||||
| Interval from admission (days), mean±SD | ||||||||
| to starting rehabilitation | 2.1±1.7 | 1.6±1.3 | 2.6±1.9 | 0.000 | ||||
| to being able to sit a wheelcahir | 4.1±2.9 | 3.6±2.0 | 4.7±3.6 | 0.019 | ||||
| Use of nicardipine, n (%) | 31 | (25.8) | 1 | (1.7) | 30 | (50.0) | <0.001 | |
MT: mechanical thrombectomy, ATBI: atherothrombotic, CEI: cardioembolic infarction, IHD: ischemic heart failure
ICA: internal carotid artery, MCA: middle cerebral artery, BA: basilar artery, NIHSS: national institute of health stroke scale
Multivariable binary logistic regression was used to examine the association between the prominent changes in blood pressure and the background variables after controlling simultaneously for potential confounders from the univariate analysis. Variables considered in the models were age, NIHSS score, CEI, HT, Af, use of nicardipine, interval from admission to starting rehabilitation, and interval from admission to being able to sit in a wheelchair. Only the interval from admission to being able to sit in a wheelchair was shown by the stepwise regression method to be a factor associated with prominent changes in blood pressure (odds ratio, 1.604; 95% confidence interval, 1.196-2.150; p=0.002) (Table 4).
Table 4.
Result of multivariable logistic regression concerned with deviation of blood pressure response
| variable | partial regression coefficient | p value | odds ratio | 95% confidence interval |
|---|---|---|---|---|
| Interval from admission to be able to sit a wheelchair | 0.472 | 0.002 | 1.604 | 1.196-2.15 |
Model chai square test: p<0.01
Hosmer and Lemeshow test: p=0.659
Predictive value: 93.3%
Discussion
We found that the frequency of prominent changes in blood pressure occurring during the use of our early mobilization protocol was significantly higher in the MT group than control group and was significantly associated with the interval from admission to being able to sit in a wheelchair.
In many cases, the instruction of postoperative blood pressure control provided by doctor was lower than guidelines 11,12). Blood pressure control after MT is usually decided on the basis of the acute treatment procedure and postoperative conditions, for example, use of t-PA, time to reperfusion, recanalization grade, and postoperative symptoms of cerebral hemorrhage. So before conducting a mobilization protocol for patients with MT, adequate information on such factors is absolutely necessary.
In the analysis of the relationship between changes in blood pressure and the background variables, only the interval from admission to being able to sit in a wheelchair was significantly associated with prominent changes in blood pressure, and it was longer in the MT group. Postoperative bed rest was extended as a therapeutically needed bed rest in patients with MT for the following reasons: i) MT is used in main arteries that cause cerebral infarction, so it is necessary to mobilize the patient carefully, and ii) MT usually requires postoperative sedation to avoid postoperative complications, especially post-ischemic hyperperfusion syndrome and cerebral hemorrhage. Bed rest causes a reduction in total blood volume that reduces cardiac stroke volume and maximum cardiac output. Such cardiac atrophy can be detected with as little as 2 weeks of bed rest 13,14), so the longer bed rest of the patients in the MT group may have had an influence on the prominent changes in blood pressure seen in these patients, even though the portion of blood pressure deviation was lower than a precedent study 15).
The prevalence of Af and the portion of CEI in the MT group was higher than those of the control group, but both of them were not associated with prominent blood pressure changes by a multivariable binary logistic regression. Previous study showed cardiac arrhythmia including Af was a factor influencing hemodynamics 16). In the present study, however, there was no cases with manifestation of new arrhythmia during a stress test, so it was considered that the influence on hemodynamics was minimized.
Use of nicardipine by intravenous injection, which is not usually used for patients with ischemic stroke, is specifically blood pressure management to prevent postoperative symptoms of cerebral hemorrhage after MT. The portion of using nicardipine in the MT group was also higher, but it was not associated with prominent blood pressure changes. A previous study showed that use of antihypertensive drugs in the early period poststroke is not detrimental to postural blood pressure regulation 17), and the result of present study was similar to the study.
The proportion of good outcomes (mRS: 0-2) at discharge in the MT group, however, was better than that of the control group. Nowadays, MT's ability to improve patient outcomes has reported 18) and many variables are concerned with outcomes (e.g. age, severity of stroke, start timing and intensity of rehabilitation), thus, the longer bed rest in the MT group did not appear to have a large influence on outcomes.
Our study had limitations. The number of patients was small, and it was a retrospective study. Thus, it was thought that the results were more likely to reflect the characteristics of our facility only. Further research is warranted to analyze the progress of rehabilitation after MT.
Conclusion
The present retrospective study showed that prominent changes in blood pressure can occur easily during the use of an early mobilization protocol in patients with acute ischemic stroke after MT.
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