Recommendation For Thrombolytic Treatment of Acute Ischemic Stroke in Patients Width Covid-19

ABBREVIATIONS IN THIS GUIDANCE

AIS: acute ischemic stroke

COVID-19: coronavirus disease

CT: computed tomographic

CTA: computed tomographic angiography

ICU: intensive care unit

mRS: modified rankin score

SARS-CoV-2: severe acute respiratory syndrome coronavirus 2

INTRODUCTION

In Chile, as in the rest of the world, the severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2) pandemic has substantially modified the functioning of health systems focusing attention in how to handle the coronavirus infections^1,2,3. In this context, health systems are facing three challenges: face the pandemic; ensure the attention to other pathologies not related to coronavirus disease (COVID-19), which will maintain their prevalence; and the attention of new and complex medical situations, such as those in which COVID-19 positive  patients present complications of the disease and/or derived from other diseases, leading to high mortality scenarios^4,5,6.

In the case of acute ischemic stroke (AIS) and COVID-19, patients can: develop a stroke while being a contact of a COVID-19 positive patient; have an infection from COVID-19 and a concomitant stroke; or developing a stroke as a possible complication of the COVID-19 infection, which occurs more frequently in patients with a more severe infection^7,8. It should be taken in consideration that patients with COVID 19 have a significant burden of cardiovascular risk factors, especially those hospitalized in intensive care unit⁹.

This recommendation aims to develop an acute treatment protocol for patients with an AIS and a suspicion or confirmation of a COVID-19 infection¹⁰. It is important to emphasize that this recommendation is transitory and does not replace the recommended current guidelines for AIS treatment published in the Ministry of Health protocols^11,12. The application time of his recommendation will be determined by the duration of the pandemic, and after it, the need to maintain this protocol in patients with COVID-19 infection, will be assessed.

ESSENTIAL POINTS OF THE RECOMMENDATION

1. Objective:
   1. To develop a protocol for the thrombolytic treatment of AIS in patients with a suspected or confirmed COVID-19 infection.
2. Target population.
   1. Patients with suspicion of AIS in time window, both in emergency service and in case of hospitalization. Two groups in relation to COVID-19 infection have to be considered:
      1. Group one: asymptomatic patient. This refers to patients with no history of contact, travel, fever and / or respiratory symptoms.
      2. Group two: suspected infection with SARS-CoV-2 or COVID-19 (+) (for more details check references)¹³.

         In case a reliable anamnesis is not available, due to the absence of a family member or witness, incomplete information and / or inability to communicate with the patient, the patient has to be considered as potentially infected.

3. Personal protective equipment (for more details check references)^{14,15,16,17,18}.
   1. Asymptomatic patient: surgical mask.
   2. COVID 19 (+) patient and / or possible COVID 19 (+): a long-sleeved disposable fluid repellent gown with rear opening, surgical facemask (or respirators when work environments and procedures have a risk of aerosolised transmission), disposable gloves, coats that cover the cuffs, and eye protection (full-face shield or visor, polycarbonate safety spectacles or equivalent).
      1. For thrombectomy consider local protocol of operating room.
4. Define the COVID-19 severity before the AIS reperfusion therapy, in order to exclude patients with a high probability of poor outcome and / or mortality, as a consequence of their respiratory and neurological symptoms^{5,6,11,18,19,20}. The following are factors of that can lead to a bad outcome:
   1. Age > 80 years .
   2. Pre-neurological condition: modified rankin score (mRS) >
   3. COVID-19 clinical and laboratory severity criteria that suspect a bad outcome:
      1. Refractory hypotension.
      2. Respiratory failure which is non-responsive to oxygen supplementation.
      3. Invasive ventilation is required.
      4. PaO2/FiO2 <250 (arterial gas).

   These factors should not be used in an individual or absolute way. These require an assessment in conjunction with the patient´s treating team, to define whether or not the situation is safe or not to performing a AIS reperfusion therapy. In addition, it should be considered that the patient´s serious clinical condition may change after medical treatment and that it needs to be redefined.

5. Clinical evaluation.
   1. Limit the number of members and the contact time of the healthcare team with the COVID-19 (+) patient.
6. Diagnostic Imaging.
   1. Perform neuroimaging protocols according to local availability.
   2. Maintain local neuroimaging protocols, avoiding transfers and images unnecessary and incomplete.
   3. Perform computed tomographic angiography (CTA) of vessels of the neck and brain in the same study (a single exposition).
   4. In case of performing a chest computed tomographic (CT) on the group two of patients (see point I.A), do it in conjunction with brain and neck imaging (a single exposure) and without delay the cerebral perfusion therapy^21,22.
7. Treatment:
   1. Maintain treatment algorithms according to predefined local protocols.
   2. During the first 24 hours and the treatment, perform only strictly necessary clinical controls in order to decrease the exposure of healthcare team²³.
   3. In case tenecteplase is available, consider using it, since it requires a shorter time of administration^24,25.
8. Hospitalization:
   1. Hospitalization in the COVID-19 unit in charge of intensive care unit (ICU) and neurology.
   2. During hospitalization, carry out strictly necessary clinical controls, in order to decrease exposure of health personnel

PROTOCOL: Thrombolytic treatment of patients with AIS and with suspicion or confirmation of SARS-CoV-2 infection.

REFERENCES

1. Ministerio de salud. Subsecretaría de Salud Pública. Decreto número 10, de 2020.- Modifica decreto Nº 4, de 2020, que decreta alerta sanitaria por el período que se señala y otorga facultades extraordinarias que indica por Emergencia de Salud Pública de Importancia Internacional por brote del nuevo coronavirus (2019-NCOV). https://www.diariooficial.interior.gob.cl/publicaciones/2020/03/25/42614/01/1745010.pdf
2. Lewnard JA, Lo NC. Scientific and ethical basis for social-distancing interventions against COVID-19. Lancet Infect Dis 2020. DOI: https://doi.org/10.1016/S1473-3099(20)30190-0.
3. Parnet WE, Sinha MS. Covid-19 — The Law and Limits of Quarantine. NEJM 2020. DOI: 10.1056/NEJMp2004211.
4. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.
5. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu, Wang Y, Pan S, Zou X, Yuan S, Shang Y, Clinical Course and Outcomes of Critically Ill Patients With SARS-CoV-2 Pneumonia in Wuhan, China: A Single-Centered, Retrospective, Observational Study. Lancet Respir Med 2020. DOI: 10.1016/S2213-2600(20)30079-5.
6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, We L, Li H, Wu X, Xu J, Tu S, Zhan Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020. DOI: 10.1016/S0140-6736(20)30566-3.
7. Li, Yanan and Wang, Mengdie and Zhou, Yifan and Chang, Jiang and Xian, Ying and Mao, Ling and Hong, Candong and Chen, Shengcai and Wang, Yong and Wang, Hailing and Li, Man and Jin, Huijuan and Hu, Bo, Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study (3/3/2020). Available at SSRN: https://ssrn.com/abstract=3550025 or http://dx.doi.org/10.2139/ssrn.3550025.
8. Mao, Ling and Wang, Mengdie and Chen, Shengcai and He, Quanwei and Chang, Jiang and Hong, Candong and Zhou, Yifan and Wang, David and Miao, Xiaoping and Hu, Yu and Li, Yanan and Jin, Huijuan and Hu, Bo, Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study (February 24, 2020). Available at SSRN: https://ssrn.com/abstract=3544840 or http://dx.doi.org/10.2139/ssrn.3544840.
9. Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China, Clin Res Cardiol 2020;10.1007/s00392-020-01626-9. doi:10.1007/s00392-020-01626-9.
10. Sociedad española de neurología. Adaptación temporal de los protocolos de tratamiento endovascular de la Comunidad Valenciana en pacientes con ictus isquémico agudo y sospecha o confirmación de Covid19 (20 de Marzo de 2020). https://www.svneurologia.org/wordpress/wp-content/uploads/2020/03/criterios-ictus-covid-1.pdf.
11. Ministerio de Salud. Problema de Salud AUGE N°37. Ataque Cerebrovascular Isquémico en personas de 15 años y más. https://diprece.minsal.cl/garantias-explicitas-en-salud-auge-o-ges/guias-de-practica-clinica/ataque-cerebrovascular-isquemico-en-personas-de-15-anos-y-mas/recomendaciones-2/
12. Ministerio de salud. Código ACV para servicio de urgencia 2018. https://www.enfermeriaaps.com/portal/codigo-acv-servicios-urgencia-minsal-chile-2018
13. Ministerio de salud. Actualización de definición de caso sospechoso para vigilancia epidemiológica ante brote de COVID-19 en China, Ordinario B51 N° 895. https://www.minsal.cl/nuevo-coronavirus-2019-ncov/informe-tecnico/
14. Ministerio de salud. Protocolo de referencia para correcto uso de Equipo de Protección Personal en pacientes sospechosos o confirmados de COVID-19. Circular C37 Nº1. https://www.minsal.cl/wp-content/uploads/2020/03/PROTOCOLO-DE-USO-DE-EQUIPOS-DE-PROTECCI%C3%93N-PERSONAL-EN-LA-PREVENCI%C3%93N-DE-TRANSMISI%C3%93N-COVID19-versi%C3%B3n-24-03-2020-corregido-%C3%BAltima-p%C3%A1gina.pdf  
15. Zunt JR. Invited Commentary: Neurology during the COVID-19 pandemic: Lessons learned at the initial U.S. epicenter. https://blogs.neurology.org/covid-19-coronavirus/invited-commentary-neurology-during-the-coronavirus-2019-covid-19-pandemic-lessons-learned-at-the-initial-u-s-epicenter/?fbclid=IwAR3SmExFYJL4xXHrrEclW8zoKucAiLiOrIaJV2vPNf3HfcH1mwK7Fd6gQVk.
16. Fraser JF, Arthur A, Chen M, Levitt M, Mocco J, Albuquerque F, Ansari SA, Dabus G, Jayaraman MV, Mack WJ0, Milburn JM1, Mokin M, Narayanan S3, Puri AS, Siddiqui AH, Tsai JP, Klucznik RP. Society of NeuroInterventional Surgery recommendations for the care of emergent neurointerventional patients in the setting of COVID-19.
17. Ministerio de salud. Precauciones estándares para control de infecciones en la atención de salud y algunas consideraciones sobre aislamiento de pacientes. https://www.minsal.cl/portal/url/item/d8615b8fdab6c48fe04001016401183d.pdf
18. SOCHIMI 2020. RECOMENDACIONES PARA EL MANEJO DE LA INSUFICIENCIA RESPIRATORIA AGUDA EN PACIENTES CON NEUMONIA POR CORONAVIRUS V. 1.0. https://www.medicina-intensiva.cl/reco/RECOMENDACIONES_MANEJO_INSUFICIENCIA_RESPIRATORIA2020.pdf.
19. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) - China CCDC, February 17 2020.
20. Zhou Z, Guo D, Li C, et al. Coronavirus disease 2019: initial chest CT findings [published online ahead of print, 2020 Mar 24]. Eur Radiol. 2020;10.1007/s00330-020-06816-7. doi:10.1007/s00330-020-06816-7
21. Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases [published online ahead of print, 2020 Feb 26]. 2020;200642. doi:10.1148/radiol.2020200642.
22. Faigle R, Butler J, Carhuapoma JR, Johnson B, Zink EK, Shakes T, Rosenblum M, Saheed M, Urrutia VC. Safety Trial of Low-Intensity Monitoring After Thrombolysis: Optimal Post Tpa-Iv Monitoring in Ischemic STroke (OPTIMIST). Neurohospitalist 2020;10(1):11-15. DOI: 10.1177/1941874419845229 journals.sagepub.com/home/NHO.
23. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012;366(12):1099–1107. doi:10.1056/NEJMoa1109842
24. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573–1582. doi:10.1056/NEJMoa1716405.