ประสิทธิผลของแนวทางการให้ยา Nicardipine แบบเร่งรัด ในการควบคุมความดันโลหิตในผู้ป่วยโรคหลอดเลือดสมองตีบหรืออุดตันเฉียบพลันที่ได้รับยาละลายลิ่มเลือด

Supitchaya Kornjirakasemsan

Authors

Supitchaya Kornjirakasemsan Pharmacy Department, Nakornping Hospital

Keywords:

acute ischemic stroke, nicardipine, rapid titration, door-to-needle time, clinical outcomes

Abstract

Background: Hypertension is a major barrier leading to delays in door-to-needle (DTN) time among patients with acute ischemic stroke (AIS).

Objective: To evaluate the effectiveness and safety of a Rapid Titration Protocol (RTP/NIPPONS) compared with a Slow Titration Protocol (STP) for nicardipine administration in managing blood pressure among AIS patients receiving intravenous thrombolysis.

Methods: This retrospective cohort study was conducted at Nakornping Hospital between January 1, 2020, and September 30, 2025. The study included AIS patients requiring blood pressure control prior to thrombolytic therapy using either the RTP/NIPPONS or the STP. The primary outcome was nicardipine-to-rtPA (NRT) time.

Results: A total of 218 patients were analyzed, consisting of 137 in the STP group (62.84%) and 81 in the RTP/NIPPONS group (37.16%). The RTP/NIPPONS group demonstrated a significantly shorter NRT time with a median of 18 minutes (IQR 11–32), compared to 37 minutes (IQR 20–70) in the STP group (p < 0.001). The median DTN time was 49 minutes (IQR 39–63) in the RTP/NIPPONS group and 53 minutes (IQR 43–64) in the STP group, which was not statistically significant. Notably, despite higher baseline stroke severity in the RTP/NIPPONS group, after adjusting for confounding factors, this group had 3.17 times higher odds of achieving functional independence (aOR 3.17; 95% CI: 1.63–6.16; p = 0.001). There was no significant difference in the incidence of symptomatic intracerebral hemorrhage between the two groups.

Conclusion: The rapid nicardipine titration protocol (RTP/NIPPONS) effectively reduces the duration to control of blood pressure prior to thrombolysis and significantly improves clinical outcomes without increasing the risk of symptomatic intracerebral hemorrhage.

References

Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-418. doi: 10.1161/STR.0000000000000211.

Kunz A, Ebinger M, Geisler F, Rozanski M, Waldschmidt C, Weber JE, et al. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol. 2016;15(10):1035-43. doi: 10.1016/S1474-4422(16)30129-6.

Peacock F 4th, Varon J, Ebrahimi R, Dunbar L, Pollack CV Jr. Clevidipine for severe hypertension in acute heart failure: a VELOCITY trial analysis. Congest Heart Fail. 2010;16(2):55-9. doi: 10.1111/j.1751-7133.2009.00133.x.

Liu-Deryke X, Janisse J, Coplin WM, Parker D Jr, Norris G, Rhoney DH. A comparison of nicardipine and labetalol for acute hypertension management following stroke. Neurocrit Care. 2008;9(2):167-76. doi: 10.1007/s12028-008-9057-z.

Ahmed N, Wahlgren N, Brainin M, Castillo J, Ford GA, Kaste M, et al. Relationship of blood pressure, antihypertensive therapy, and outcome in ischemic stroke treated with intravenous thrombolysis: retrospective analysis from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). Stroke. 2009;40(7):2442-9. doi: 10.1161/STROKEAHA.109.548602.

Gasecki D, Kwarciany M, Kowalczyk K, Narkiewicz K, Karaszewski B. Blood Pressure Management in Acute Ischemic Stroke. Curr Hypertens Rep. 2020;23(1):3. doi: 10.1007/s11906-020-01120-7.

Anderson CS, Huang Y, Lindley RI, Chen X, Arima H, Chen G, et al. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019;393(10174):877-88. doi: 10.1016/S0140-6736(19)30038-8.

Grise EM, Adeoye O, Lindsell C, Alwell K, Moomaw C, Kissela B, et al. Emergency department adherence to American Heart Association guidelines for blood pressure management in acute ischemic stroke. Stroke. 2012;43(2):557-9. doi: 10.1161/STROKEAHA.111.637983.

Anadani M, Arthur AS, Tsivgoulis G, Simpson KN, Alawieh A, Orabi Y, et al. Blood Pressure Goals and Clinical Outcomes after Successful Endovascular Therapy: A Multicenter Study. Ann Neurol. 2020;87(6):830-9. doi: 10.1002/ana.25716.

de Havenon A, Petersen N, Sultan-Qurraie A, Alexander M, Yaghi S, Park M, et al. Blood Pressure Management Before, During, and After Endovascular Thrombectomy for Acute Ischemic Stroke. Semin Neurol. 2021;41(1):46-53. doi: 10.1055/s-0040-1722721.

Goyal N, Tsivgoulis G, Pandhi A, Chang JJ, Dillard K, Ishfaq MF, et al. Blood pressure levels post mechanical thrombectomy and outcomes in large vessel occlusion strokes. Neurology. 2017;89(6):540-7. doi: 10.1212/WNL.0000000000004184.

Hecht JP, Richards PG. Continuous-Infusion Labetalol vs Nicardipine for Hypertension Management in Stroke Patients. J Stroke Cerebrovasc Dis. 2018;27(2):460-5. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.023.

Huang X, Guo H, Yuan L, Cai Q, Zhang M, Zhang Y, et al. Blood pressure variability and outcomes after mechanical thrombectomy based on the recanalization and collateral status. Ther Adv Neurol Disord. 2021;14:1756286421997383. doi: 10.1177/1756286421997383.

Jiang S, Zhou Y, Zhou Y, Huang G. Intensive blood pressure management for ischemic stroke patients following endovascular thrombectomy: a meta-analysis of randomized controlled trials. BMC Neurol. 2024;24(1):469. doi: 10.1186/s12883-024-03976-7.

Malhotra K, Goyal N, Katsanos AH, Filippatou A, Mistry EA, Khatri P, et al. Association of Blood Pressure With Outcomes in Acute Stroke Thrombectomy. Hypertension. 2020;75(3):730-9. doi: 10.1161/HYPERTENSIONAHA.119.14230.

Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016;375(11):1033-43. doi: 10.1056/NEJMoa1603460.

Cook AM, Morgan Jones G, Hawryluk GWJ, Mailloux P, McLaughlin D, Papangelou A, et al. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocrit Care. 2020;32(3):647-66. doi: 10.1007/s12028-020-00959-7.

Li Y, Liang M, Jiang C, Wang G, Li J, Zhang Y, et al. Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease. Nephrol Dial Transplant. 2018;33(3):409-17. doi: 10.1093/ndt/gfx267.

Tsivgoulis G, Katsanos AH, Butcher KS, Boviatsis E, Triantafyllou N, Rizos I, et al. Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis. Neurology. 2014;83(17):1523-9. doi: 10.1212/WNL.0000000000000917.

Cook E, Clifton GG, Vargas R, Bienvenu G, Williams R, Sambol N, et al. Pharmacokinetics, pharmacodynamics, and minimum effective clinical dose of intravenous nicardipine. Clin Pharmacol Ther. 1990;47(6):706-18. doi: 10.1038/clpt.1990.97.

Curran MP, Robinson DM, Keating GM. Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indications. Drugs. 2006;66(13):1755-82. doi: 10.2165/00003495-200666130-00010.

Promkamtan P. External Validation of The Symptomatic Intracranial Hemorrhage ScorePredicts Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke Patients at Nakornping Hospital. Journal of Nakornping Hospital. 2018;9(1):12-22. [In Thai]

Yuan G, Xia H, Xu J, Long C, Liu L, Huang F, et al. Reducing intravenous thrombolysis delay in acute ischemic stroke through a quality improvement program in the emergency department. Front Neurol. 2022;13:931193. doi: 10.3389/fneur.2022.931193.

Jung S, Rosini JM, Nomura JT, Caplan RJ, Raser-Schramm J. Even Faster Door-to-Alteplase Times and Associated Outcomes in Acute Ischemic Stroke. J Stroke Cerebrovasc Dis. 2019;28(12):104329. doi: 10.1016/j.jstrokecerebrovasdis.2019.104329.