Dose Escalation Trial of Desulfated Heparin (ODSH) in Septic Peritonitis.
Dose Escalation Trial of Desulfated Heparin (ODSH) in Septic Peritonitis.
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DOI：
10.3389/fvets.2022.862308
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发表时间：
2022
影响因子：
3.2
通讯作者：
Otto, Cynthia M.
中科院分区：
文献类型：
--
作者：
Mauro, Katie D.;Lambert, Michele P.;Kowalska, M. Anna;Thawley, Vincent J.;Poncz, Mortimer;Otto, Cynthia M.
败血症腹膜炎与严重的发病率和死亡率有关。作为一种治疗脓毒症的潜在药物，2-O，3-O硫代肝素(ODSH)可降低小鼠脓毒症模型中组蛋白和血小板第4因子(PF4)的含量。这项先导性临床试验评估了ODSH在客户拥有的感染性腹膜炎犬中的安全性和有效性。在一项IACUC批准的、开放标签的、前瞻性的、剂量递增的临床试验中，在6只患有自发性化脓性腹膜炎的狗身上，在手术探索之后开始给予ODSH，以实现源头控制。记录入院时的急性患者生理和实验室评估(APPLEfast和APPLEFULL)评分、感染性腹膜炎的来源、血管升压剂的需求、血液产品的给药以及出院时的存活时间。在每次ODSH剂量时检测血小板计数、游离DNA(CfDNA)浓度和血小板因子4(PF4)浓度。根据预先确定的升级方案，每8小时给药一次，共4次(最大总剂量为75毫克/公斤)。给药后，患者在ICU中接受监测，以寻找临床出血的证据。入院时APPLEfast和APPLE满分分别为22+/-6和32+/-10。4只犬静脉注射4剂ODSH，2只犬静脉注射3剂ODSH。研究期间平均总剂量为48.3+/-21.6 mg/kg。没有狗需要降低剂量，也没有任何出血的证据。四只狗活了下来，出院了。在感染性腹膜炎的狗身上，没有记录使用ODSH的不良反应。一项随机对照试验是必要的，以评估ODSH作为一种治疗感染性腹膜炎的新疗法。
Septic peritonitis is associated with significant morbidity and mortality. As a potential therapeutic agent in the treatment of sepsis, 2-O, 3-O desulfated heparin (ODSH) reduces histones and platelet factor 4 (PF4) in mouse sepsis models. This pilot clinical trial evaluated the safety and effect of ODSH in client-owned dogs with septic peritonitis. In an IACUC-approved, open-label, prospective, dose-escalation clinical trial in 6 dogs with spontaneous septic peritonitis, ODSH administration was initiated following surgical explore to achieve source control. Acute patient physiology and laboratory evaluation (APPLEfast and APPLEfull) scores on admission, source of septic peritonitis, requirement for vasopressors, the administration of blood products, and survival to discharge were recorded. Platelet count, cell free DNA (cfDNA) concentration, and platelet factor 4 (PF4) concentrations were measured at the time of each ODSH dosage. A dose of ODSH was administered every 8 hs for a total of 4 doses (maximum total dosage 75 mg/kg) based on a pre-determined escalation protocol. Patients were monitored in the ICU following administration for evidence of clinical hemorrhage. The mean APPLEfast and APPLEfull scores on admission were 22 +/- 6 and 32 +/-10, respectively. Four dogs received 4 total dosages of ODSH and 2 dogs received 3 total dosages of ODSH intravenously. The mean total dosage of ODSH administered during the study period was 48.3 +/- 21.6 mg/kg. No dog required dose de-escalation or had any evidence of bleeding. Four dogs survived to discharge. No adverse effects of ODSH administration were documented in dogs with septic peritonitis. A randomized controlled trial is necessary to evaluate ODSH as a novel therapeutic in the treatment of septic peritonitis.
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DOI：
10.1161/atvbaha.113.302236
发表时间：
2014-01-01
影响因子：
8.7
作者：
Kowalska, M. Anna;Zhao, Guohua;Poncz, Mortimer
通讯作者：
Poncz, Mortimer
影响因子：
6.7
作者：
Joglekar MV;Quintana Diez PM;Marcus S;Qi R;Espinasse B;Wiesner MR;Pempe E;Liu J;Monroe DM;Arepally GM
通讯作者：
Arepally GM
影响因子：
1.3
作者：
Llewellyn, Efa A.;Todd, Jeffrey M.;Rendahl, Aaron
通讯作者：
Rendahl, Aaron
影响因子：
4.6
作者：
Wang Y;Luo L;Braun OÖ;Westman J;Madhi R;Herwald H;Mörgelin M;Thorlacius H
通讯作者：
Thorlacius H
影响因子：
1.3
作者：
Letendre, Jo-Annie;Goggs, Robert
通讯作者：
Goggs, Robert