Periprocedure Management of Blood Pressure After Acute Ischemic Stroke : Journal of Neurosurgical Anesthesiology

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Focused Review

Periprocedure Management of Blood Pressure After Acute Ischemic Stroke

Sharma, Deepak MBBS, MD, DM

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Journal of Neurosurgical Anesthesiology 35(1):p 4-9, January 2023. | DOI: 10.1097/ANA.0000000000000891
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Abstract

KEY POINTS

  • Acute ischemic stroke is among the leading causes of mortality and long-term disability worldwide. Mechanical thrombectomy is the most effective treatment for acute ischemic stroke due to large vessel occlusions in appropriately selected patients.
  • The U-shaped relationship between blood pressure and outcome in acute ischemic stroke patients is well known; both high and low blood pressure are associated with poor outcomes, likely due to increased rates of cerebral edema in patients with high blood pressure and increased coronary events in those with low blood pressure.
  • Cerebral autoregulation may be impaired early after acute ischemic stroke.
  • Hypotension before recanalization is associated with compromised collateral flow, larger infarct volumes, and worse functional outcomes in patients with large vessel occlusion stroke, whereas hypertension following the restoration of blood flow may lead to hyper-perfusion syndrome and cerebral hemorrhage.
  • Evidence to support specific hemodynamic targets during and around mechanical thrombectomy is limited; guidelines for hemodynamic management around thrombectomy are primarily extrapolated from intravenous tissue plasminogen activator (t-PA) trials and retrospective analyses.
  • There is growing interest in exploring autoregulation-based blood pressure goals for individualized management using near-infrared spectroscopy and transcranial Doppler ultrasonography, although data are currently limited.
  • Early efforts have demonstrated the potential for machine learning techniques to provide a better decision-making approach for blood pressure management in acute ischemic stroke.
  • More direct evidence is needed to identify specific hemodynamic goals, treatment thresholds, and pharmacological strategies in stroke patients undergoing mechanical thrombectomy.

INTRODUCTION

Mechanical thrombectomy (MT) is the most effective treatment for acute ischemic stroke (AIS) due to large vessel occlusions in appropriately selected patients, with a number needed to treat 2.6 for improved functional outcomes and reduced mortality.1 The indications for MT have expanded with the extension of the eligibility time window up to 24 hours for selected patients.2,3 In fact, the treatment paradigm of AIS with large vessel occlusion is rapidly moving from “timed window” to “tissue window.”4 While the superiority of general anesthesia or monitored anesthesia care for MT continues to be debated, there is no disagreement that periprocedural optimization of blood pressure (BP) is critical irrespective of anesthetic technique.4,5 Yet, direct evidence to support specific hemodynamic targets is limited; guidelines for hemodynamic management before, during and after MT are primarily extrapolated from intravenous t-PA trials and retrospective analyses.6 This focused review aims to provide an update on recent evidence around periprocedural BP management after AIS, highlighting the implications for clinical practice and identifying gaps in current literature. Other important aspects of periprocedural management, such as management of oxygenation, ventilation, glycemia, and complications, are not discussed here.

CURRENT EVIDENCE

Collateral Flow and Blood Pressure in Acute Ischemic Stroke

Optimizing BP to support collateral flow is crucial, while revascularization is accomplished with MT. Since dynamic cerebral autoregulation (CA) is impaired early after AIS,7,8 blood flow within the ischemic penumbra is BP-dependent. In a recent study examining the collateral status of leptomeningeal vessels in patients with anterior circulation stroke, the investigators found that for every 10 mm Hg increase in systolic blood pressure (SBP), relative filling time delay decreased by 7%, indicating improved collateral status.9 In an analysis of hemodynamic data from the GOLIATH trial, mean arterial pressure (MAP) <70 mm Hg (odds ratio, 0.35 P=0.048) and baseline infarct volume (odds ratio, 0.96 P=0.003) were the most significant predictors of worse collateral circulation in patients undergoing MT.10 Curiously, the most significant predictors of infarct growth at 24 hours included phenylephrine dose (regression beta estimate, 6.78 P=0.014).10 These data further demonstrate that sedation/anesthesia-induced BP drop has deleterious effects on cerebral collateral circulation during MT, which may not be reversed by vasopressor administration. Although comorbidities such as chronic hypertension can impact collateral flow,11 avoidance of hypotension during MT appears critical for preserving collaterals and minimizing infarct growth.

Hypotension before recanalization is associated with compromised collateral flow, larger infarct volumes, and worse functional outcomes in patients with large vessel occlusion stroke.12 At the same time, hypertension following revascularization may lead to hyper-perfusion syndrome and cerebral hemorrhage.13 Importantly, microvascular resistance within the ischemic territory may remain elevated in some patients despite successful recanalization, leading to post MT microvascular hypoperfusion.14 This phenomenon of “no-reflow” with persistent oligemia may be due to capillary dysfunction with microvascular occlusion, microthrombi clogging, astrocyte swelling, or pericyte constriction.14 Persistent elevation of the pulsatility index on transcranial Doppler (TCD) has recently been proposed as a clinical marker of the no-reflow phenomenon.14

The relationship between BP and outcome in AIS patients is a U-shaped curve with both high and low BP prognosticating poor outcome, likely due to cerebral edema in patients with high BP and risk of worsening cerebral ischemia and increased risk of coronary events in those with low BP. The MR CLEAN trial confirmed the U-shaped relation of baseline SBP with good functional outcome (modified Rankin scale 0–2) and death at 90 days, with the SBP nadir around 120 mm Hg.15 Similar results were found in the Endovascular Treatment in Ischemic Stroke registry with a 3.78-times and 1.81-times greater risk of mortality with SBP < 110 mm Hg and >180 mm Hg, respectively, compared with SBP 150 mm Hg.16 Besides severe hypertension and hypotension, dynamic fluctuations in BP are also detrimental, likely due to impaired CA causing worsening hypoperfusion with infarction or hyper-perfusion with cerebral edema.17

Myocardial Dysfunction in Acute Ischemic Stroke

Electrocardiographic morphologic abnormalities, cardiac arrhythmias, elevated serum cardiac troponin-T, and depressed cardiac function have been well described in patients with AIS. Recent data demonstrate the association of Takotsubo cardiomyopathy (stress-induced transient ballooning of the left ventricle) in patients with ischemic lesions in the right anterior circulation, insula, and peri-insular areas.18 Sympathetic surge, hypothalamic-pituitary axis activation and hypothalamic paraventricular nucleus output also contribute to cardiac arrhythmias and impaired myocardial contractility.19 The acute impairment of cardiac function has implications for pharmacological choices and hemodynamic management during the periprocedural period.

Blood Pressure Management Before and During Recanalization With Mechanical Thrombectomy

Before successful reperfusion, it is important to ensure that collateral pathways continue to perfuse brain regions at risk of worsening ischemia. Hypotension and hypovolemia should be corrected to maintain systemic perfusion levels, though optimal preprocedure BP for best outcomes is unknown.6 Data on optimal fluid management strategies in AIS are also limited; a systematic analysis of 12 studies comparing colloids and crystalloids found no difference in the odds of death or dependence.20 Fluid choice should be at the physician's discretion, depending on individual patient characteristics.

The lowest SBP >140 mm Hg during MT predicts good neurological outcome after AIS.21 Even in patients undergoing MT with monitored anesthesia care, a ≥10% decrease in MAP from baseline has an odds ratio of 4.38 for poor outcome, and MAP <85 mm Hg before reperfusion has an odds ratio for poor outcome of 2.22.22 While early studies noted that hypotension was common during MT with general anesthesia and potentially contributed to worse neurological outcomes,21 subsequent randomized controlled trials comparing general anesthesia to conscious sedation/monitored anesthesia care for MT did not find a difference in neurological outcomes when SBP was maintained >140 mm Hg.23–25 These data highlight the importance of avoiding BP reductions during MT before revascularization, irrespective of anesthetic technique. Hypotension during anesthesia, especially during induction of general anesthesia, is multifactorial, and anesthesiologists should use clinical judgment to select appropriate pharmacological agent(s) based on patient characteristics. Anesthetic-induced impairment of CA, which can render the brain further susceptible to the risk of worsening ischemia, is undesirable; hence, the dose of anesthetic agents should be carefully titrated. Although the usefulness of drug-induced hypertension in patients with AIS is not well established,6 it is reasonable to correct BP reductions associated with the administration of anesthetic/sedative agents.26 Despite its widespread use, there may be a possible association between BP correction with phenylephrine and infarct growth.10 Data on systemic and cerebral effects of vasopressors/inotropes, particularly in setting of AIS and MT, are limited and insufficient to make specific recommendations.

In patients undergoing MT who have not received intravenous t-PA, the current recommendation from the American Heart Association/American Stroke Association is to maintain BP≤185/110 mm Hg before the procedure.6 Notably, this recommendation is based on the fact that the vast majority of patients enrolled in the randomized controlled trials demonstrating benefits of MT with stent retrievers had preprocedural BP managed below 185/110 mm Hg. Pharmacological options to carefully reduce elevated BP include labetalol, nicardipine, and clevidipine in titrated doses, though hydralazine and enalaprilat may also be considered.6 Caution is warranted against aggressive BP lowering; a post hoc analysis of 3 randomized controlled clinical trials identified MAP reductions below 70 mm Hg or reductions>20% from baseline as thresholds for increased risk of worse functional outcome.27 A 15 percent reduction in BP may be reasonable before MT in patients with BP >185/110 mm Hg.6 During MT, it is advisable to follow the recommendations from the Society for Neuroscience in Anesthesiology and Critical Care and maintain SBP between 140 and 180 mm Hg.26

Blood Pressure Management after Mechanical Thrombectomy

Recanalization is achieved in up to 70% to 80% of patients after MT.28,29 The immediate concern after successful reperfusion is the prevention of ischemia-reperfusion injury and hemorrhagic conversion (Fig. 1). At the same time, it is important to continue to avoid hypotension.6 The course of elevated BP after MT may be inversely associated with the degree of vessel recanalization. Nevertheless, high BP after MT is a risk factor for intracranial hemorrhage and worse functional outcomes, regardless of recanalization status.30 Goyal et al30 demonstrated that a 10mm Hg increment in maximum SBP in the first 24 hours after MT was independently associated with a lower likelihood of 3-month functional independence and higher odds of 3-month mortality. These authors also found that BP<160/90 mm Hg during the first 24 hours following MT was independently associated with a lower likelihood of 3-month mortality compared with permissive hypertension. In the DAWN trial, maintaining SBP<140 mm Hg and MAP>70 mm Hg after achieving thrombolysis in cerebral infarction score of 2b/3 ensured sufficient perfusion while mitigating risks of hemorrhagic transformation.31 Interestingly, the BP-TARGET trial found that intensive SBP control to 100 to 129 mm Hg after successful MT for anterior circulation AIS did not reduce radiographic intraparenchymal hemorrhage rates at 24 to 36 hours in comparison with a standard care SBP target of 130 to 185 mm Hg.32 Clinicians should follow current guidelines, which recommend maintaining BP≤180/105 mm Hg during and for 24 hours after the procedure in patients who undergo MT, including those with successful reperfusion.6,33

F1
FIGURE 1:
Computed tomographic scans of a patient with left carotid terminus occlusion showing post-thrombectomy hemorrhagic conversion. A, Arrow shows carotid terminus occlusion. B, Preprocedure CT scan. C, CT scan immediately after mechanical thrombectomy. D, CT scan 24 hours later showing hemorrhagic conversion (arrow). CT indicates computed tomography.

Individualized Blood Pressure Management

There is growing interest in exploring autoregulation-based BP goals for individualized patient management after AIS rather than population-based goals. Near-infrared spectroscopy monitoring is a convenient, noninvasive option to identify and track the BP range where CA is effective; importantly, this BP range may change over time.34 In a single-center, prospective cohort study, Petersen et al35 computed the tissue oxygenation autoregulatory index as a moving correlation coefficient between MAP and tissue oxygenation index measured by near-infrared spectroscopy to determine the optimal MAP to maintain cerebral oxygenation; they demonstrated that the limits of autoregulation are not stable, but change over time and vary among patients.35 Also, spending more time outside the individualized upper limit of autoregulation was independently associated with worse discharge and 90-day outcomes.35 Similarly, TCD-guided BP management after MT has recently been shown to improve prognosis. In patients presenting with blood flow velocity deceleration or features of intracranial hypertension, BP manipulation under TCD guidance successfully reduced early neurological deterioration and improved final functional outcomes.36 While these novel approaches offer the potential for the identification of precise therapeutic goals, their wider clinical application will require additional evidence.

UNANSWERED QUESTIONS AND FUTURE RESEARCH

Recommendations for periprocedural BP management in AIS patients are primarily extrapolated from intravenous t-PA trials and retrospective analyses. Further research is needed to identify specific BP targets, thresholds for intervention and optimal pharmacological choices for BP management in patients undergoing MT. Prospective trials are also required to identify patients who will benefit from BP augmentation before MT. There is considerable variability in BP monitoring (invasive vs. noninvasive, site of monitoring, etc.), and a consensus in monitoring approaches is also highly desirable. The currently ongoing BEST-II (NCT 04116112) and OPTIMAL-BP (NCT 04205305) trials aim to evaluate the safety of lowering SBP targets to 140 to 180 mm Hg after AIS. The ENCHANTED 2 trial (NCT 04140110), which aimed to examine the effect of SBP <120 mm Hg in patients with complete reperfusion after EVT has been suspended due to safety concerns. Whether BP targets should vary by anesthetic technique or not is unknown and will need to be determined.

The advent of personalized, CA-based approaches to hemodynamic management is attractive, but further research is needed to test such autoregulation-based treatment strategies, including tailored pharmacologic BP adjustments based on real-time autoregulatory status. Early efforts have demonstrated the potential for machine learning techniques to provide a better decision-making approach for BP management in AIS patients.37 For example, diastolic BP appears to be the main variable in predicting the probability of BP reduction in the first 24 hours after AIS. In patients receiving t-PA/MT, labetalol and amlodipine were effective treatments in cases where SBP was >180 mm Hg but DBP was <120 mm Hg.37 With further advancements, there is potential for the development of systems to predict hypotension and hypertension that could alert clinicians before the hemodynamic perturbation occurs.38 Such systems have been successfully shown to reduce the burden of intraoperative hypotension in other settings.39

CONCLUSIONS

Periprocedural BP in AIS patients undergoing MT impacts short- and long-term outcomes. Table 1 summarizes the BP recommendations based on the current guideline. Direct evidence to make specific recommendations on treatment goals, intervention thresholds, and pharmacological options is limited. However, there is a gradually increasing body of evidence to inform BP management after AIS, including interest in innovative, individualized hemodynamic management approaches. If sedation/anesthesia is provided for MT according to protocols that strictly avoid BP extremes, existing evidence suggests that periinterventional BP drops may not be associated with either early neurological improvement or long-term functional outcomes.40 While further evidence is awaited, guidelines from the American Heart Association/American Stroke Association6 and the Society for Neuroscience in Anesthesiology and Critical Care26 provide a useful, practical framework for clinical management.

TABLE 1 - Recommendations for Periprocedural Blood Pressure Management During Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Based on American Heart Association/American Stroke Association Guidelines6
Blood Pressure Goal Class of Recommendation* Level of Evidence
Pre MT, without t-PA ≤185/110 IIa B-NR
Pre MT, after t-PA <180/105 I B-R
During MT, without t-PA ≤180/105 IIa B-NR
During MT, after t-PA <180/105 I B-R
Post MT, without t-PA and TICI 0-2a ≤180/105 IIa B-NR
Post MT, after t-PA or TICI 2b-3 <180/105 IIb B-NR
The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) recommends maintaining systolic blood pressure 140 to 180 mm Hg during MT and diastolic blood pressure <105 mm Hg (Class IIa, Level of evidence B) and readjusting blood pressure goals after successful recanalization (Class IIb, Level of evidence C).26
*Class of Recommendation: I, Strong; IIa, Moderate; IIb, Weak.
B-R, evidence level B, randomized trial; B-NR, evidence level B, nonrandomized trial.
MT indicates mechanical thrombectomy; TICI, thrombolysis in cerebral infarction scale; t-PA, tissue plasminogen activator.

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Keywords:

acute ischemic stroke; mechanical thrombectomy; blood pressure; cerebral autoregulation; outcomes

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