Early blood pressure management for endovascular therapy in acute ischemic stroke: A review of the literature

Abstract

The perioperative optimal blood pressure targets during mechanical thrombectomy for acute ischemic stroke are uncertain, and randomized controlled trials addressing this issue are lacking. There is still no consensus on the optimal target for perioperative blood pressure in acute ischemic stroke patients with large vessel occlusion. In addition, there are many confounding factors that can influence the outcome including the patient’s clinical history and stroke characteristics. We review the factors that have an impact on perioperative blood pressure change and discuss the influence of perioperative blood pressure on functional outcome after mechanical thrombectomy. In conclusion, we suggest that blood pressure should be carefully and flexibly managed perioperatively in patient-received mechanical thrombectomy. Blood pressure changes during mechanical thrombectomy were independently correlated with poor prognosis, and blood pressure should be maintained in a normal range perioperatively. Postoperative blood pressure control is associated with recanalization status in which successful recanalization requires normal range blood pressure (systolic blood pressure 120–140 mmHg), while non-recanalization requires higher blood pressure (systolic blood pressure 160–180 mmHg). The preoperative blood pressure targets for mechanical thrombectomy should be tailored based on the patient’s clinical history (systolic blood pressure ≤185 mmHg). Blood pressure should be carefully and flexibly managed intraoperatively (systolic blood pressure 140–180 mmHg) in patient-received endovascular therapy.

Introduction

In the prevention of primary and secondary stroke, hypertension is the most important independent risk factor for stroke, and effective regulation of blood pressure (BP) can significantly reduce the incidence, mortality, and recurrence rate of stroke.¹ Moreover, mechanical thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) in the anterior circulation caused by large vessel occlusion (LVO).^2–5 However, there is no high-level clinical studies have been conducted on BP management in patients receiving endovascular therapy, and there is still no consensus on the optimal target BP control perioperatively and intraoperatively in AIS patients. Therefore, in this study, we review previous published literatures to evaluate the optimal target BP management pre-intra^6–12 and post EVT,^13–15 and we hope that this summary could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in AIS patients in the future.

Cerebral blood flow automatic regulation and pathophysiology

Cerebral perfusion ranges between 50 and 150 mmHg, and normal brain has autoregulation to maintain a constant cerebral blood flow (CBF) at 50 ml/100 g/min by adjusting cerebrovascular resistance and compensating any change in the cerebral perfusion pressure (CPP).¹⁶ This alteration is mainly governed by arteriolar diameter in the small arterioles for normal neuronal functioning. During an acute nervous system emergency, cerebrovascular autoregulation may be impaired, and CBF becomes stress-passive; as a result, CBF follows CPP in a linear manner as well as in chronic stenosis.^17,18 In addition, CO₂ homeostasis also helps to modulate the systemic resistance and BP during this circumstance.^17,19 Therefore, small changes in mean arterial pressure (MAP) can predispose patients to ischemia or cerebral edema, especially in chronic hypertension; thus, strict BP control is essential to prevent further damage.

Multiple mechanisms have been postulated to explain the increase in systemic vascular resistance and BP during acute nervous system emergencies. These include failure to respond to arterial baroreceptors in the brain that regulate cardiovascular function and activation of the neuroendocrine system, including the renin-angiotensin-aldosterone system, the sympathetic autonomic nervous system, and the hypothalamic-pituitary-adrenal axis. Another described mechanism is the Cushing reflex, which causes BP to rise in the case of increased ICP.^17,19–22

Table 1.

Previous study of the influence of baseline blood pressure before EVT to functional outcome.

Author	Year	Patients no	Suggested BP range	Outcome	Study types
Treurniet et al.52	2017	60	No BP targets during the procedure; MAPa, ΔLMAPb	A decrease in MAP during intervention under GA compared with baseline is associated with worse outcome.	A Randomized Clinical Trial IIa B–R
Mistry et al.13	2017	228	No BP targets	Higher peak values of systolic blood pressure correlated with worse 90-day modified Rankin scale and a higher rate of hemorrhagic complications	Retrospective study

BP: blood pressure; GA: general anesthesia; MAP: mean arterial pressure; mRS: modified Rankin Scale.

^aΔMAP: difference between baseline MAP and the average of all MAP values collected during GA at intervals of ≈10 min.

^bΔLMAP: difference between MAP at baseline and the single-lowest MAP during GA.

Baseline BP and clinical prognosis

Hypertension is very common up to 80% in patients with AIS, even patients without previous hypertension.^23,24 This acute hypertension usually spontaneously subside within 10 days of the event.²⁵ However, the role of hypertension either to maintain collateral blood flow to the ischemic penumbra or the area around the edema or a marker of stroke severity is still uncertain.²⁶

Elevated BP at baseline was associated with poor prognosis

Summary analysis of cerebral ischemia test (MERCI) and mechanical embolization removal in multiple MERCI tests showed that higher admission SBP levels were associated with lower likelihood of revascularization.²⁷ Goyal et al.²⁸ reported a potential relation between BP level and functional assessment score in a study of 116 patients with anterior circulation acute large vessel occlusion (ELVO). The results showed that higher SBP admission is an independent predictor of larger infarction volume and provides less benefit in patient-received endovascular treatment.²⁸

This finding was supported by another study by a French multicenter prospective collection database from three comprehensive stroke centers that continuously treated a total of 1332 AIS patients with documented arterial occlusion at three participating centers through intravascular pathways (IV tPA and/or MT prior to IV tPA) between January 2012 and June 2016 (ETIS registry study). They reported that baseline SBP was associated with all-cause mortality and favorable outcomes in patients with AIS treated with MT.⁷ In addition, high mortality was found at both lower and higher baseline SBP values, with favorable outcome rates highest at low SBP values and lowest at high SBP values.^28,29 Strong association of SBP and functional outcome in patient with ischemic stroke was shown in MR CLEAN trial. Their study result showed that the correlation of BP and functional outcome is U-shaped; both low and high baseline systolic BP were associated with poor functional outcome, and higher SBP was associated with increased risk of symptomatic intracranial hemorrhage (adjusted OR: 1.25, 95% CI: 1.09–1.44) in patients with AIS. Despite this strong relation, BP did not influence the safety and efficacy of intra-arterial treatment, and the benefit of IAT was evident for the whole SBP range.⁶

Baseline BP level and collateral compensation

In patients with LVO, BP is important for maintaining the collateral circulation, including leptomeningeal collateral circulation;^30–36 it has an important effect on clinical outcomes,^35,37,38 especially in the treatment of hyperacute stage.³⁹ It has been postulated that improving the collateral flow may lead to slower infarct growth; later, a study conducted by Hong et al.⁴⁰ confirms this theory; they reported that higher baseline BP leads to better collateral flow. This mechanism is reported in previous study, and elevated arterial BP may improve arterial perfusion in AIS, thereby minimizing the final infarct volume.⁴¹ Moreover, elevated arterial BP can also reduce hypoperfusion in AIS.^42,43 However, the relationship between arterial BP and collateral circulation is still uncertain yet.⁴⁴ Another supportive evidence was reported by Jiang et al.,⁴⁵ and they reported that for every 10 mmHg increase in systolic BP, the relative filling time delay decreased by 7%, indicating an improvement in collateral status. Thus, in the hyperacute phase of ischemic stroke, higher arterial BP was associated with an improvement in leptomeningeal collateral circulation.

Table 2.

Previous study of the influence of blood pressure during EVT to functional outcome.

Author	Year	Patients no	Suggested BP range	Outcome	Study types
Petersen et al.46	2019	390	No BP targets	Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes	Retrospective, observational study
Rasmussen et al.67	2018	128	Maintain SBP ≥140 mm Hg and MABP ≥70 mm Hg	No statistically significant association between blood pressure-related parameters during endovascular therapy and neurological outcome	A randomized clinical trial
Pikija et al.11	2018	164	SBP/MAP the reference values ±20% values >120% of the reference to <80% of the reference	A better functional outcome might be achieved by targeting in-procedure BP that exceeds the preprocedure values by more than 20%.	Retrospective study
Maier68	2018	343	No BP targets	PP variability during MT is an independent predictor of worse clinical outcome	Retrospective study
Bennett et al.64	2018	182	No BP targets	The SV is the strongest and most consistent predictor of worse outcomes	Registry study
Whalin et al.12	2016	256	The majority of the patients (88%) had SBP less than the recommended 140mmHg under GA	Mean duration of SBP <100 mm Hg was lower in the good outcome group compared with the poor outcome group (0/0 to 4, 4/1 to 11; P = 0.02). More patients with poor out`come had SBP <100mmHg compared with the patients with good outcome (79% vs. 47%; P = 0.008)	Retrospective study
Hendén et al.10	2015	108	No BP targets during the procedure Periprocedural	Profound intraprocedural hypotension is an independent predictor for poor neurological outcome	Retrospective study
Jagani et al.65	2015	99	No BP targets during the procedure	Patients with acute ischemic stroke undergoing intra-arterial therapy with general anesthesia had lower minimum SBP, DBP, and MAP, greater fluctuations in blood pressure, and less favorable outcomes	Retrospective study

PP (i.e. SBP minus diastolic BP); blood pressure variability was measured as SD, CV, and SV.

PP: pulse pressure; SD: standard deviation; CV: coefficient of variation; SV: successive variation; BP: blood pressure; CS: conscious sedation; DBP: diastolic blood pressure; GA: general anesthesia; LMAP: lowest mean arterial pressure; MABP: mean arterial blood pressure; MAP: mean arterial pressure; mRS: modified Rankin Scale; MT: mechanical thrombectomy; SBP: systolic blood pressure; IV: intravenous; LVO: large vessel occlusion; FIV: final infarct volume; FFO: favorable functional outcome; ELVO: emergent large vessel occlusion; EVT: endovascular treatment.

Table 3.

Previous study of the influence of blood pressure after EVT to functional outcome.

Author	Year	Patient no	Suggested BP range	Outcome	Study types
Goyal et al.15	2017	217	Post-MT achieved BP goals: 140/90 mm Hg (intensive), 160/90 mm Hg (moderate), and, 220/110 mm Hg or, 180/105 mm Hg when pretreated with IV thrombolysis (permissive hypertension).	High maximum SBP levels following MT are independently associated with increased likelihood of three-month mortality and functional dependence in LVO patients. Moderate BP control is also related to lower odds of three-month mortality in comparison to permissive hypertension.	Retrospective study
Cernik et al.58	2019	703	Median of SBP <140 mm Hg	Lowering of BP within the first 24 h after MT may have a positive impact	Retrospective bi-center study
Schönenberger et al.54	2018	150	Maintain SBP between 140–160 mm Hg for GA and CS	Peri-interventional BP drops were not associated with either early neurological improvement or long-term functional outcome	A monocentric randomized trial

MT: mechanical thrombectomy; SBP: systolic blood pressure; IV: intravenous; LVO: large vessel occlusion; BP: blood pressure; CS: conscious sedation; GA: general anesthesia; MT: mechanical thrombectomy; SBP: systolic blood pressure.

Intraoperative BP and clinical prognosis

From 2014 to 2018, an observational study was conducted by Petersen et al.,⁴⁶ and they reported that lower BP during EVT may increase the infarct volume and is associated with poor prognosis.⁴⁶ Compensatory vasodilatory failure at the distal end of occluded vessels and the failure of intrinsic self-regulatory function of ischemic tissue lead to pressure passivity; as a result, patients become more susceptible to changes in BP.^47,48 In this circumstance, a decrease in systemic BP may result in a corresponding decrease in CBF to ischemic tissue, which may lead to infarction progression and poorer prognosis.⁴⁹ Another study by Pikija et al.¹¹ showed that patients whose BP was controlled within the recommended range (<120 mmHg) for EVT therapy, better functional outcomes could be achieved by targeting intraoperative BP that exceeded 20% of the preoperative value.¹¹

Local or general anesthesia (GA) is generally applied during EVT. However, the use of GA has been reported by previous studies that it has less benefit in terms of functional outcome, mortality, and recanalization rates.^12,50–53 In contrast, SIESTA (sedation vs. intubation for Endovascular stroke treatment)⁵⁴ and GOLIATH (intra-arterial therapy under general or local anesthesia) trial⁵⁵ reported that no significant differences were found between patients treated with GA or local anesthesia with regard to the primary outcome or early neurological improvement. The BP was lower in GA group in GOLIATH trial, which is quite different with three recent anesthesia trials, which maintain the SBP according to recent consensus recommendations (greater than or equal to 140 mmHg).⁵⁵ Consistent with GOLIATH trial, the AnStroke trial also showed similar results. This result might be attributed due to the adjustment of the intraoperative BP (MAP was maintained at a considerably higher level 91 ± 8 mmHg in the GA group compared with their previous study (78 ± 8 mmHg)). As their previous investigation, they found that intraprocedural fall in MAP >40% was an independent factor for poor neurological outcome.^55,56 However, further study is still needed for verification, because GA in particular is well known to be associated with a substantial drop in BP during induction and maintenance of anesthesia. Even fluctuations in BP may be disadvantageous in the acute phase of stroke. Moreover, during thrombectomy, GA was often associated with hypotension and related with worse clinical outcomes.

Postoperative BP and clinical prognosis

The American Heart Association/American Stroke Association guidelines recommended to lower BP below 180/105 after successful revascularization (defined as TICI 2b or 3) in patients undergoing MT.⁵⁷ To avoid reperfusion injury, the DAWN trial suggested lower BP than the guidelines, and they used an SBP target >140 mm Hg during the first 24 h, followed by the REVASCAT trial which maintained patient’s BP below 160/90 mm Hg.⁵ A retrospective dual-center study by Cernik et al.⁵⁸ also suggests that BP reduction within 24 h after MT treatment may have a positive effect on clinical outcomes in treated patients. Moreover, a recent survey conducted at centers in the United States tended to lower BP levels in the majority of patients who were successfully recanalized, while higher BP levels were maintained in the majority of patients who were not recanalized.¹³ In contrast, Anadani et al.⁵⁹ suggested that the elevation of SBP in the acute phase after MT was associated with functional deterioration. Goyal et al.¹⁴ compared the three BP targets 24 h after MT. The highest level of high SBP after MT was independently related to the three-month mortality and increased functional dependence in LVO patients, while moderate BP control was associated with a three-month mortality reduction.¹⁴ Consistent with that, Martins et al.⁶⁰ studied the correlation between mean BP and prognosis after revascularization by intravenous thrombolysis and intra-arterial therapy. They found a J-shaped relationship between BP and prognosis in patients without recanalization and a linear relationship in patients with recanalization.⁶⁰ They concluded that both high and low-admission BP-values are associated with higher early and late mortality.

BP variability and clinical prognosis

The definition of BP was various in different studies; however, the main hemodynamic parameters measured are SBP and MAP.⁶¹ BP is primarily assessed within the first 24 h, rather than before recanalization, during which time, it may seriously affect ischemic penumbra survival and clinical outcomes.⁶² Pulse pressure (PP) may be a better parameter to describe BP variability than SBP because of its relative accuracy to describe the fluctuating components of BP. A study regarding BP variability influence the patient’s prognosis was conducted by Delgado et al.⁶³ They compared the effects of BP variability in recanalized and non-recanalized patients and reported an association between BP variability (estimated by mean SD) and DWI lesion growth and three-month prognosis in recanalized patients, but not in recanalized patients. Another study by Whalin et al.¹² studied BP variability in MT treated patients with BP decline, and they reported that a decrease of ≥10% in MAP from baseline in AIS patients with postoperative recanalization was associated with poor prognosis.¹² Subsequently, in patients treated with MT under GA, an average arterial BP drop of >40% was an independent predictor of poor neurological outcomes.¹⁰ In addition, Bennett et al.⁶⁴ suggested that the successive variation (the square root of the average difference in BP between successive measurements (BP calculated over three time intervals: 0–24, 0–72, and 0–120 h)) is the strongest and the most consistent predictor of worse outcomes.⁶⁴ Consistent with that, Jagani et al.⁶⁵ demonstrated that patients with AIS undergoing intra-arterial therapy with GA had lower minimum SBP, DBP, and MAP lead to greater fluctuations in BP and less favorable outcomes.⁶⁵

Meta-analysis of antihypertensive therapy

Recent meta-analysis including nine studies with a total of 1037 patients evaluated the effect of perioperative BP on functional outcomes. Results from five studies showed that there are three types of BP decline that associated with a three-month poor functional outcomes: first, decrease of the MAP >40% from baseline will increase the risk of poor prognosis for 1.8-fold (OR = 2.8; 95%CI [1.09–7.19]; P = 0.032); second, the lowest MAP before recanalization below 100 mmHg will increase the risk of poor prognosis for 0.28-fold in every 10 mmHg decrease (OR = 1.28; 95%CI [1.01–1.62]; P = 0.04); third, a decrease of MAP >10% will increase the risk of poor prognosis for 3.38-fold (OR = 4.38; 95%CI [1.53–12.6]; P >0.01). While, four studies did not show an association between BP and functional outcomes during MT, including three rigorous studies of perioperative systolic BP targets (within 140–180 mm Hg).⁶⁶

Conclusions

In patients with hyperacute cerebral infarction requiring MT, both hypertension and hypotension appear to be associated with deterioration of neurological function. Determining the optimal BP range may improve prognosis and reduce complications such as hemorrhagic transformation. The current guidelines recommend that BP should be at least <180–185/105–110 mmHg, and no association between BP and functional outcome was found with strict intraoperative BP control. The specific target value of BP has not yet been determined. BP fluctuation and variability were independently correlated with poor prognosis, and maintaining stable BP was crucial in the perioperative management. Postoperative BP control seems to be determined according to recanalization status in which successful recanalization requires lower BP, while non-recanalization requires higher BP.

In summary, we believe that the preoperative BP targets for MT should be tailored based on the patient’s clinical history (hypertension, diabetes, other medical history, etc.) and stroke characteristics (occlusions, collateral status, ASPECTS, sedation, etc.) although the basic management should be based on the recommended current guidelines. Further study is needed to optimal the perioperative management of BP. At last, several unanswered questions such as whether hypertension should be treated, what is the optimal BP target value or target range, what is the most suitable drugs to use, and when to begin the antihypertensive therapy still need to be solved in the future study. At the moment, we suggest that BP should be carefully and flexibly managed perioperatively in patient-received MT.