Hypertension in Acute Intracerebral Haemorrhage and Ischaemic Stroke: When and When not to Treat.

Review Article

Hypertension in Acute Intracerebral Haemorrhage and Ischaemic Stroke: When and When not to Treat.

  • Chris Isles 1*
  • Ritesh Malik 2

*Corresponding Author: Chris Isles, Medical Unit of Dumfries and Galloway Royal Infirmary, Dumfries DG2 8RX, UK.

Citation: : Chris Isles, Ritesh Malik, (2024), Hypertension in Acute Intracerebral Haemorrhage and Ischaemic Stroke: When and When not to Treat., Clinical Medical Reviews and Reports, 6(4); DOI:10.31579/2690-8794/211

Copyright: © 2024, Chris Isles. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 28 April 2024 | Accepted: 10 May 2024 | Published: 23 May 2024

Keywords: acute intracerebral haemorrhage; acute ischaemic stroke; hypertension; treatment

Abstract

The most common forms of hypertensive crisis in developed countries are pulmonary oedema/heart failure, acute coronary syndrome, acute intracerebral haemorrhage and acute ischaemic stroke.  Hypertension can be both cause and consequence of stroke and is associated with poor functional outcome and increased mortality.  It does not necessarily follow that lowering of blood pressure acutely will confer benefit, so the question that arises is when and when not to treat?  Current recommendations are to consider patients with acute spontaneous intracerebral haemorrhage with a SBP of 150-220 mmHg for urgent treatment within 6 hours of symptom onset, using a locally agreed protocol for BP lowering, aiming to achieve a systolic BP between 130-139 mmHg within one hour and sustained for at least 7 days.   By contrast the only certainty for BP lowering after acute ischaemic stroke is a BP target <185/110mmHg for thrombolysis.  The many randomised trials in acute ischaemic stroke are inconclusive about stopping or continuing antihypertensive drugs, or specific BP targets, in almost all other settings. 

Introduction

The management of hypertensive crisis has been the subject of many recent reviews [1-3].  These have tended to draw on recommendations of the AHA [4], ESC [5-6] and NICE [7] and are based on expert opinion rather than randomised treatment trials, given the lack of the latter in this particular field of medicine.  In this review, we will examine in more detail the evidence relating to the management of one particular hypertensive crisis, namely that of hypertension in acute stroke.  To our knowledge, acute stroke is the only hypertensive crisis that has been subjected to randomised trials. Our review will concentrate on three large randomised trials in stroke due to intracerebral haemorrhage (ICH) [8-10], and one recently published large trial in acute ischaemic stroke [11].   For additional analyses of these and several smaller trials, see the reviews by [12-13].

Literature Review

Intracerebral haemorrhage

INTERACT-2 (Investigators in the second Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) was a randomised controlled trial in 2,839 patients with ICH and elevated systolic BP (SBP) 150–220 mm Hg who were allocated to receive intensive (target SBP <140 P=0.06). P=0.04).  P=0.002)>

INTERACT-3 was a randomized controlled trial in 7036 patients, with ICH and SBP 140mmHg or greater, who were allocated to early intensive BP reduction as part of a bundle of hyperacute care incorporating protocols for hyperglycaemia, pyrexia and abnormal anticoagulation, or to usual care [10].  Target systolic blood pressure in the care bundle group was less than 140 mm Hg within one hour of the initiation of treatment, with a systolic blood pressure of 130 mm Hg being the threshold for the cessation of treatment.  An intravenous agent, commonly urapidil, sodium nitroprusside, labetalol or nicardipine, was prescribed in 78.9% of those allocated to intensive treatment and to 70.9% of controls.  The primary outcome was functional recovery measured by the modified Rankin scale at 6 months. The likelihood of a poor functional outcome was lower in the care bundle group (odds ratio 0·86; 95% CI 0·76 to 0·97; p=0·015) [10].   There was no significant difference in the combined end point of death or disability (modified Rankin scores 3–6) at 6 months (odds ratio 0·89; 95% CI 0·78–1·02; p=0·10).

ATACH-2 (Antihypertensive Treatment of Acute Cerebral Haemorrhage) randomised 1000 patients with acute ICH and hypertension to the same two systolic BP targets as INTERACT-2 (ie, <140>5 ml/hr) who received treatment within 2 hours after symptom onset, intensive BP lowering was associated with improved functional independence (odds ratio 1.98, 95% CI 1.06–3.69; p = 0.031) [11].

In summary, three large randomised trials of antihypertensive therapy in patients with ICH have shown no reduction in a combined end-point of death or disability.  Two reported small but significant improvements in disability and quality of life scores, while the third didn’t.   Although target systolic BP was the same, there were differences in trial design and execution.  INTERACT-2 and ATACH-2 were trials purely of early BP reduction whereas INTERACT-3 tested a package of hyperacute care of which early BP reduction was but one component.  BP lowering had to start within 6 hours of presentation in both INTERACT trials and within 4.5 hours in ATACH-2.  The choice of drug and the route of administration in INTERACT-2 and INTERACT-3 were at the discretion of the trial physician while all patients in ATACH-2 were to receive intravenous nicardipine as first line therapy.   BP reduction was faster and more pronounced in ATACH-2 (average SBP over the first 24 hours was 120-130 mmHg in ATACH-2 compared to 135-145 mmHg in INTERACT-2 and INTERACT-3).  It is conceivable therefore that this degree of reduction may have been excessive in ATACH-2 [15], though it has recently been suggested that a subgroup of ‘fast bleeding’ patients who receive intravenous antihypertensive therapy within two hours may benefit [11].   Importantly, all three trials excluded patients who had an underlying structural cause eg tumour, arteriovenous malformation or aneurysm; or Glasgow Coma Scale below 6; or early neurosurgery to evacuate the haematoma; or a massive haematoma with a poor expected prognosis [8-10].

Acute ischaemic stroke

CATIS-2 (China Antihypertensive Trial in acute Ischaemic Stroke) was a multicentre, randomised open label trial of early versus delayed antihypertensive treatment in 4810 patients with acute ischaemic stroke and elevated SBP 140-220mmHg [11].   Patients were allocated to receive antihypertensive treatment within 24-48 hours of stroke onset (target 10-20% SBP reduction within 24 hours and SBP <140 P=0.08). >

Discussion

Intracerebral haemorrhage

We have summarised current recommendations for control of hypertension in acute ICH in Table 1 [7, 16-18].  There is a general consensus that patients in whom treatment can be started within 6 hours of symptom onset and whose SBP lies between 150 and 220mmHg, will benefit from blood pressure lowering.  There are slight differences in recommended blood pressure targets (Table 1).


 

 

Table 1: Recommendations for BP reduction in acute ICH


 

Acute ischaemic stroke

CATIS-2 is the latest study to have concluded that early treatment of hypertension in ischaemic stroke does not confer benefit, and may possibly be harmful (CATIS-2). The only certainty for BP lowering after acute ischaemic stroke is a BP target <185>


 

Schematic cerebral auto regulatory curve showing the relation between cerebral blood flow and mean arterial pressure.   This is shifted to the right in chronic hypertension.  Cerebral blood flow becomes pressure dependent for a time after acute stroke.[21]


 

There are a few exceptions to the general rule that it is best not to lower BP too quickly in acute ischaemic stroke (apart from the recommendation to lower BP for thrombolysis above).   If BP is >220/120mmHg in the acute phase then it is considered reasonable to lower MAP by no more than 15% over 24 hours to maintain perfusion of the penumbra [18-19], Early treatment of hypertension is also indicated in acute ischaemic stroke if this is associated with one or more hypertensive emergencies, namely hypertensive encephalopathy, hypertensive nephropathy, hypertensive heart failure, aortic dissection or pre-eclampsia/eclampsia [7,19]

Choice of Medication 

Although the AHA [4] and the ESC [5] provide dosing schedules for no fewer than 12 intravenous antihypertensives, we feel it is unlikely that clinicians will have experience of more than a few of these, given that hypertensive emergencies are uncommon and the indications for their intravenous use infrequent [3].  Labetalol, nitroglycerin and nicardipine have all been used intravenously for control of hypertension acutely in intracerebral haemorrhage (Table 2).  Of note, intravenous nicardipine is not stocked in all UK hospitals [3].   There remains uncertainty about the best time to start antihypertensive therapy in ischaemic stroke.  The National Clinical Guideline for Stroke states that antihypertensive medication should generally be initiated prior to the transfer of care out of hospital or at 2 weeks, whichever is the soonest, or at the first clinic visit for people not admitted [7], by which time oral calcium channel blocker, ACE inhibitor or angiotensin receptor blocker would all be acceptable choices.


 

 

IV Labetalol
  • To reconstitute, dilute 200mg in 200ml 5

    Conclusion

    Current recommendations for the management of hypertension in acute stroke reflect the need for a tailored approach.  The evidence in favour of treating hypertension acutely in intracerebral haemorrhage is not as strong as we would wish, but is probably strong enough to consider those with a SBP of 150-220 mmHg for urgent treatment within 6 hours of symptom onset, using a locally agreed protocol for BP lowering, aiming to achieve a systolic BP between 130-139 mmHg within one hour and sustained for at least 7 days [7] (Figure 2).  By contrast the only certainty for BP lowering after acute ischaemic stroke is a BP target <185>

    Flowchart for treatment of hypertension in acute ischaemic stroke

     

    Flowchart for treatment of hypertension in acute haemorrhagic stroke

    References

    Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

    img

    Virginia E. Koenig

    Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

    img

    Delcio G Silva Junior

    Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

    img

    Ziemlé Clément Méda

    Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

    img

    Mina Sherif Soliman Georgy

    We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

    img

    Layla Shojaie

    The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

    img

    Sing-yung Wu

    Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

    img

    Orlando Villarreal

    Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

    img

    Katarzyna Byczkowska

    Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

    img

    Anthony Kodzo-Grey Venyo

    Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

    img

    Pedro Marques Gomes

    Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

    img

    Bernard Terkimbi Utoo

    This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

    img

    Prof Sherif W Mansour

    Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

    img

    Hao Jiang

    As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

    img

    Dr Shiming Tang

    Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

    img

    Raed Mualem

    International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

    img

    Andreas Filippaios

    Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

    img

    Dr Suramya Dhamija

    Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

    img

    Bruno Chauffert

    I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

    img

    Baheci Selen

    "We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

    img

    Jesus Simal-Gandara

    I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

    img

    Douglas Miyazaki

    We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

    img

    Dr Griffith

    I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

    img

    Dr Tong Ming Liu

    I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

    img

    Husain Taha Radhi

    I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

    img

    S Munshi

    Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

    img

    Tania Munoz

    “The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

    img

    George Varvatsoulias

    Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

    img

    Rui Tao

    Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

    img

    Khurram Arshad

    Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

    img

    Gomez Barriga Maria Dolores

    The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

    img

    Lin Shaw Chin

    Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

    img

    Maria Dolores Gomez Barriga