Association of Personalized Blood Pressure Targets With Hemorrhagic Transformation and Functional Outcome After Endovascular Stroke Therapy

The loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to changes in blood pressure (BP),¹ potentially resulting in additional injury from relative hypoperfusion or hyperperfusion. We have shown that near-infrared spectroscopy can be used to identify and track the BP range in individual patients at which autoregulation is optimally functioning.² Such an autoregulation-derived, personalized BP range may provide a favorable physiologic environment for the injured brain. In this study, we used a novel approach to define and trend limits of autoregulation (LA) to determine patient-specific, dynamic BP targets. The aim of this study was to assess the feasibility of determining personalized BP targets as well as the association of deviating from these targets with radiographic and clinical outcomes.

We conducted a single-center prospective cohort study of patients with large-vessel occlusion ischemic stroke undergoing endovascular therapy (ET). Approval for the study was obtained from the Yale University human investigations committee. All patients or their legally authorized representatives provided written informed consents. Autoregulatory function was continuously measured for 24 hours following thrombectomy by interrogating changes in near-infrared spectroscopy–derived tissue oxygenation, a surrogate for cerebral blood flow, in response to changes in mean arterial pressure (MAP) using time-correlation analysis (Figure 1). The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved, as previously described.³ The percentage of time that MAP exceeded the upper LA (ULA) was calculated for each patient and its association with outcomes on the modified Rankin scale was assessed using a multivariable ordinal logistic regression. All statistics were computed using SPSS, version 24 (IBM Corp), and statistical significance was set at 2-tailed P < .05.

We enrolled 65 patients (mean [SD] age, 71.6 [16.5] years; 30 women [46%]; mean [SD] National Institutes of Health Stroke Scale score, 14.3 [6.2]; mean [SD] monitoring time, 25.6 [16.5] hours). Optimal BP and LA were calculated for 86.3% of the total monitoring period. Adjusting for age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT score, and the degree of reperfusion, the percentage of time above the ULA (% time > ULA) was independently associated with higher (worse) modified Rankin scale scores at discharge (adjusted odds ratio [OR] per 10% time >ULA, 1.6; 95% CI, 1.1-2.5, P = .03) and 90 days (adjusted OR per 10% time >ULA, 2.4; 95% CI, 1.4-4.1, P = .001; Figure 2A and B).

Hemorrhagic transformation (HT) was seen in 30 patients (46.1%) and was overall associated with poor outcomes. We observed a progressive increase in the percentage of time above the ULA with worsening grades of HT (9% for no HT, 13.5% for hemorrhagic infarction 1 and 2, and 20.9% for parenchymal hematoma 1 and 2; P = .01; Figure 2C). In addition, patients who developed symptomatic intracerebral hemorrhage spent significantly more time above the ULA compared with patients without symptomatic intracerebral hemorrhage (11% vs 24.6%; P = 0.01). In a binary logistic regression, the percentage of time above the ULA was significantly associated with HT (OR, 1.75; 95% CI, 1.11-2.78; P = .02).

We showed that a continuous, noninvasive estimation of personalized BP targets is feasible and that exceeding individualized thresholds of autoregulation is associated with HT and worse functional outcomes even after adjusting for prognostic covariates. To our knowledge, there are no randomized clinical trials of optimal BP management after ET and data to guide treatment approaches are limited. Most patients enrolled in thrombectomy trials also received intravenous tissue plasminogen activator and were treated according to current guidelines of a BP of less than 180/105 mm Hg for 24 hours. However, recanalization rates with ET are much higher, and it remains unclear if the same BP target applies. Once recanalization is achieved, BP management above the ULA may lead to reperfusion injury with consequent development of cerebral edema and hemorrhage. This phenomenon is well described after carotid revascularization^4,5 but may also occur in acute stroke.⁶ Accordingly, several thrombectomy trials aimed for lower BP targets if successful reperfusion was achieved. However, the optimal BP range after ET is likely associated with numerous factors, and stratifying by reperfusion status alone may not be sufficient. Further research is needed to test autoregulation-based treatment strategies, including tailored pharmacologic BP augmentation and lowering therapies based on patients’ real-time autoregulatory status.

Accepted for Publication: May 24, 2019.

Corresponding Author: Nils H. Petersen, MD, Department of Neurology, Yale Medical School, 15 York St, New Haven, CT 06510 (nils.petersen@yale.edu).

Published Online: July 29, 2019. doi:10.1001/jamaneurol.2019.2120

Author Contributions: Dr Petersen and Mr Silverman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Petersen and Mr Silverman contributed equally to the manuscript.

Concept and design: Petersen, Sheth.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Petersen, Silverman.

Critical revision of the manuscript for important intellectual content: Wang, Strander, Kodali, Matouk, Sheth.

Statistical analysis: Petersen, Silverman, Wang, Strander, Kodali.

Obtained funding: Petersen, Sheth.

Administrative, technical, or material support: Strander, Sheth.

Supervision: Petersen, Wang, Matouk, Sheth.

Conflict of Interest Disclosures: Dr Petersen reported grants from National Center for Advancing Translational Science (NCATS) of the National Institutes of Health (NIH) and the American Heart Association (AHA) during the conduct of the study. Dr Sheth reported grants from Biogen, Bard, Hyperfine, and the NIH outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by AHA grant 17MCPRP33460188/Nils Petersen/2017 and Clinical and Translational Science Awards grant KL2 TR001862 from NCATS.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of AHA or NIH.

Additional Contributions: We thank the following individuals who contributed a critical review of our article: Lauren Sansing, MD, Joseph Schindler, MD, Guido Falcone, MD, Emily Gilmore, MD, and Adam Jasne, MD (Department of Neurology, Yale School of Medicine), Branden Cord, MD, and Ryan Hebert, MD (Department of Neurosurgery, Yale School of Medicine), and Michele Johnson, MD (Department of Radiology, Yale School of Medicine). None of these individuals were compensated for their contributions.