雾化吸入普通肝素治疗COVID-19住院患者：98例患者的多中心病例系列研究

Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients.

作者信息

van Haren Frank M P, van Loon Lex M, Steins Anne, Smoot Thomas L, Sas Caitlin, Staas Sabrina, Vilaseca Alicia B, Barbera Ruben A, Vidmar Gustavo, Beccari Hugo, Popilevsky Frida, Daribayeva Eleonora, Venkatesan Bhuvaneshwari, Mozes Susan, Postel Rachel, Popilevski Natalie, Webb Andrew, Nunes Quentin, Laffey John G, Artigas Antonio, Smith Roger, Dixon Barry, Richardson Alice, Yoon Hwan-Jin, Page Clive

机构信息

Australian National University, College of Health and Medicine, Canberra, Australia.

Intensive Care Unit, Saint George Hospital, Sydney, Australia.

出版信息

Br J Clin Pharmacol. 2022 Jun;88(6):2802-2813. doi: 10.1111/bcp.15212. Epub 2022 Jan 19.

DOI:10.1111/bcp.15212

PMID:34984714

Abstract

AIMS

To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19.

METHODS

Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO ) and FiO , and the World Health Organisation modified ordinal clinical scale.

RESULTS

There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO ratio and the FiO worsened before and improved after commencement of inhaled UFH (change in slope, P < .001).

CONCLUSION

Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.

摘要

目的

确定雾化吸入普通肝素（UFH）治疗住院COVID-19患者的安全性和潜在疗效。

方法

对实验室确诊的住院COVID-19患者进行回顾性、非对照、多中心单臂病例系列研究，采用雾化吸入UFH（5000 IU每8小时一次、10000 IU每4小时一次或25000 IU每6小时一次）治疗6±3（平均±标准差）天。观察指标为治疗前（基线）和治疗期间最高水平（峰值）的活化部分凝血活酶时间（APTT），以及包括出血在内的不良事件。探索性疗效指标为氧合，通过氧饱和度与吸入氧分数（FiO₂）的比值以及FiO₂进行评估，还有世界卫生组织修订的序贯临床量表。

结果

共纳入98例患者。在接受稳定的预防性或治疗性全身抗凝治疗但未接受治疗性UFH输注的患者中，APTT水平从基线的34±10秒升至峰值38±11秒（P<.0001）。在3例接受治疗性UFH输注的患者中，APTT水平从基线的72±20秒升至峰值84±28秒，无显著升高（P=.17）。2例患者发生严重不良事件：1例胃溃疡出血需输血，1例大腿血肿；二者均接受治疗性抗凝。16例患者发生轻微出血，其中13例接受治疗性抗凝。吸入UFH开始前氧饱和度/FiO₂比值及FiO₂恶化，开始后改善（斜率变化，P<.001）。