Suffredini Dante A, Cui Xizhong, Jaswal Dharmvir, Remy Kenneth E, Li Yan, Sun Junfeng, Solomon Steven B, Fitz Yvonne, Moayeri Mahtab, Leppla Stephen, Eichacker Peter Q
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Rm 2C145, Bethesda, MD, 20892, USA.
Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Intensive Care Med Exp. 2017 Oct 23;5(1):48. doi: 10.1186/s40635-017-0159-9.
Although anthrax immune globulin (AIG) improved survival in antibiotic-treated Bacillus anthracis-challenged animal models, whether it adds to the benefit of conventional hemodynamic support for B. anthracis toxin-associated shock is unknown.
We therefore tested AIG in sedated, mechanically ventilated canines challenged with 24-h B. anthracis lethal and edema toxin infusions and supported for 96 h with a previously demonstrated protective regimen of titrated normal saline and norepinephrine.
Compared to controls, proportional survival (%) was increased with AIG treatment started 4 h before (33 vs. 100%, n = 6 each) or 2 h (17 vs. 86%, n = 6 and 7 respectively) or 5 h (0 vs. 67%, n = 3 each) after the start of toxin (p ≤ 0.05) and overall [3 survivors of 15 controls (20%) vs. 14 of 16 AIG animals (88%); p = 0.006]. Averaged across treatment times, AIG increased blood pressure at 48 h and decreased norepinephrine requirements at 72 h (p ≤ 0.02), increased left ventricular ejection fraction at 48 and 72 h (p ≤ 0.02), and increased urine output and decreased net fluid balance at 72 and 96 h (p ≤ 0.04). AIG also reduced acidosis and renal and hepatic injury markers between 24 and 96 h.
These findings further support AIG's potential benefit for patients with B. anthracis infection and developing toxin-associated shock.
尽管炭疽免疫球蛋白(AIG)在抗生素治疗的炭疽芽孢杆菌攻击动物模型中提高了生存率,但对于它是否能增加传统血流动力学支持对炭疽芽孢杆菌毒素相关休克的益处尚不清楚。
因此,我们在经镇静、机械通气的犬类中进行了试验,这些犬类接受了24小时的炭疽芽孢杆菌致死毒素和水肿毒素输注,并采用先前证明具有保护作用的滴定生理盐水和去甲肾上腺素方案进行了96小时的支持治疗。
与对照组相比,在毒素开始前4小时(33%对100%,每组n = 6)或2小时(17%对86%,分别为n = 6和7)或5小时(0对67%,每组n = 3)开始AIG治疗时,比例生存率(%)有所提高(p≤0.05),总体而言[15只对照组中有3只存活(20%),而16只接受AIG治疗的动物中有14只存活(88%);p = 0.006]。在各治疗时间点进行平均后,AIG在48小时时升高了血压,在72小时时降低了去甲肾上腺素需求量(p≤0.02),在48小时和72小时时提高了左心室射血分数(p≤0.02),并在72小时和96小时时增加了尿量并减少了净液体平衡(p≤0.04)。AIG还在24至96小时之间减轻了酸中毒以及肾脏和肝脏损伤标志物。
这些发现进一步支持了AIG对炭疽芽孢杆菌感染和发生毒素相关休克患者的潜在益处。