Development of a rapid, scalable, and deployable point-of-care blood volume diagnostic for monitoring postpartum and trauma-related hemorrhage

摘要 产后出血（Postpartum hemorrhage，PPH）是全球孕产妇死亡的主要原因，占孕产妇死亡总数的1/4 分娩相关死亡。PPH被描述为累积失血1 L或以上，症状为 产后24小时内出现低血容量症。最近，有报道表明，约53-93%的PPH- 如果及时进行医疗和干预，相关死亡本来是可以预防的。 目前，OB-GYN使用失血和患者状况的主观视觉评估或半客观评估， 评估浸血的垫，窗帘，和其他材料，也吸收羊水，尿液，和其他 分娩时沿着血液排出。我们当然可以做得更好：这代表着一个巨大的未满足和关键的 需要考虑到目前没有评估血容量或失血的定量方法来识别和 直接PPH治疗决策和干预措施。为了满足这一需求，并直接响应NOT-EB- 21-001，QuantiPort正在开发一种新的快速，可扩展，可部署，易于使用和廉价的点- 用于测量该NIH产后和创伤相关出血BV的护理前BV诊断设备 SBIR第一阶段应用。为了测量BV，我们的团队开发了一种独特的方法， 成像超声换能器定位在皮肤上，在主要血管上，其将量化 注射的微泡（MB）示踪剂（Sonazoid®，GE Healthcare）的血管内浓度 静脉注射可以在3分钟内获得实际血容量结果， 每20分钟重复一次，以提供随时间推移的定量测量，从而确定失血速率 或评估治疗干预的功效。由于系统设计简单而笨重， 轻型设备可以很容易地适应现有的临床工作流程。申报的MB示踪剂是安全的、非放射性标记的， 具有与红细胞相似的流变性，可消除体积误差，在室温下稳定 几个月到几年为执行建议的研究，我们的目标包括：1）建立一个 手动非成像超声系统，并使用体外血管- 流动体模，以及2）在日本猕猴体内进行BV诊断的概念验证测试， 俄勒冈州国家灵长类动物研究中心这些研究的成功执行将导致 开发一种独特的新型超声系统，以快速、便携和低成本的方式准确测量BV， 是PPH和创伤护理有效方法。我们的目标是确保QuantiPort的设备能够及时有效地引导 和可行的干预措施，以改善产妇发病率和死亡率由于PPH，这是一个关键的意图， NOT-EB-21-001。

ABSTRACT Postpartum hemorrhage (PPH) is the leading cause of maternal mortality globally, accounting for 1/4th of all delivery-associated deaths. PPH is described as the cumulative blood loss of 1L or more with symptoms of hypovolemia within 24 hours after giving birth. Recently, reports have demonstrated that about 53-93% of PPH- related deaths could have been prevented by administering timely medical treatments and interventions. Currently, OB-GYNs use subjective visual assessments of blood loss and patient condition or semi-objective assessments of blood-soaked pads, drapes, and other materials that also absorb amniotic fluid, urine, and other excretions along with blood at delivery. We can certainly do better: This represents a great unmet and critical need given there is currently no quantitative method of assessing blood volume, or blood loss, to identify and direct PPH treatment decisions and interventions. To address this need and in direct response to NOT-EB- 21-001, QuantiPort is developing a novel rapid, scalable, deployable, easy-to-use, and inexpensive point- of-care BV diagnostic device to measure BV for postpartum and trauma-related hemorrhage in this NIH SBIR Phase I application. To measure BV, our team has developed a unique approach comprised of a non- imaging ultrasound transducer positioned on the skin, over a major blood vessel, which will quantify the intravascular concentration of a microbubble (MB) tracer agent (Sonazoid®, GE Healthcare) injected intravenously. The actual blood volume result can be obtained in under 3 minutes and assessments may be repeated every 20 minutes to provide quantitative measurements over time to determine the rate of blood loss or to assess the efficacy of therapeutic interventions. As the system design is simple and unwieldy, this small, lightweight device can easily fit into existing clinical workflows. The proposed MB tracer is safe, non-radiolabeled, has similar rheology to red blood cells to eliminate volumetric inaccuracies, and is stable at room temperature for months to years. To execute the proposed studies, our objectives for this application include: 1) building a manual non-imaging ultrasound system and optimizing the detection MB tracer agent using an in vitro vascular- flow phantom, and 2) performing proof-of-concept testing of the BV diagnostic in vivo in Japanese macaques at the Oregon National Primate Research Center. Successful execution of these studies will result in the development of a unique and novel ultrasound system to accurately measure BV in a rapid, portable, and cost- effective way for PPH and trauma care. Our goal is to ensure that QuantiPort’s device can effectively guide timely and actionable interventions to improve maternal morbidity and mortality due to PPH, which is a key intention of NOT-EB-21-001.