McMullin Neil R, Hedner Ulla, Ezban Mirella, Lauritzen Brian, Prince M Dale, Holcomb John B, Sondeen Jill L
US Army Institute of Surgical Research, San Antonio, Texas, USA.
Shock. 2008 Jun;29(6):703-8. doi: 10.1097/SHK.0b013e31815dbcbf.
Noncompressible hemorrhage requires hypotensive resuscitation until definitive measures can be taken to prevent rebleeding by sustaining blood pressure at subphysiological levels. Previous studies have demonstrated that a 180- or 720-microg kg(-1) dose of recombinant factor VIIa (rFVIIa) increases the MAP at which rebleeding occurs in a swine aortotomy model. The purpose of the current study was to determine the efficacy of a lower dose of 90 microg kg(-1) given prophylactically to prevent or reduce rebleeding in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation. Fourteen female 40-kg Yorkshire-cross pigs were splenectomized and instrumented with venous and arterial catheters. The infrarenal aorta was exposed, and suction catheters were placed along the right and left paracolic gutters. After a 10-min baseline, 90 microg kg(-1) (i.v.) of either rFVIIa (n = 6) or vehicle (n = 8) was administered. Five minutes later, an aortotomy was created using a 2.5-mm biopsy punch. The weight of the shed blood was continuously recorded. Lactated Ringer's was given (100 mL kg(-1) min(-1)) 10 min after aortotomy until rebleeding occurred. The MAP at rebleed and the subsequent rebleed hemorrhage volume was recorded over the 2-h study period. After rebleed occurred, lactated Ringer's sufficient to maintain MAP at baseline levels was given. Initial hemorrhage volume and rebleed MAP (P = 0.31) did not differ significantly between groups. Rebleed hemorrhage volume was reduced by 54% in the rFVIIa group from 79 +/- 4 mL kg(-1) in the vehicle group to 43 +/- 6 mL kg(-1) in the rFVIIa group (mean +/- SEM; P < 0.005). The MAP at which rebleed occurred was not different between the groups, 71 +/- 4 mmHg in the rFVIIa group versus 59 +/- 5 in the vehicle group. Prophylactic administration of rFVIIa at 90 microg kg(-1), a dose similar to the recommended dose in hemophilia patients with inhibitors, reduced rebleed hemorrhage volume, suggesting that this dose is effective in this swine aortotomy model.
对于不可压缩性出血，需要进行低血压复苏，直到能够采取确定性措施，通过将血压维持在低于生理水平来防止再次出血。先前的研究表明，在猪主动脉切开术模型中，180微克/千克或720微克/千克剂量的重组因子VIIa（rFVIIa）会提高再次出血时的平均动脉压（MAP）。本研究的目的是在一项前瞻性、随机、双盲研究中，使用猪失血性休克和复苏模型，确定预防性给予90微克/千克较低剂量的rFVIIa预防或减少再次出血的疗效。14只体重40千克的雌性约克夏杂交猪接受脾切除术，并植入静脉和动脉导管。暴露肾下主动脉，在左右结肠旁沟放置吸引导管。在10分钟的基线期后，静脉注射给予90微克/千克的rFVIIa（n = 6）或赋形剂（n = 8）。5分钟后，用2.5毫米活检打孔器进行主动脉切开术。持续记录失血量。主动脉切开术后10分钟给予乳酸林格氏液（100毫升/千克/分钟），直到再次出血发生。在2小时的研究期间记录再次出血时的MAP和随后的再次出血出血量。再次出血发生后，给予足以将MAP维持在基线水平的乳酸林格氏液。两组之间的初始出血量和再次出血时的MAP（P = 0.31）无显著差异。rFVIIa组的再次出血出血量从赋形剂组的79±4毫升/千克减少了54%，降至rFVIIa组的43±6毫升/千克（平均值±标准误；P < 0.005）。两组再次出血时的MAP无差异，rFVIIa组为71±4毫米汞柱，赋形剂组为59±5毫米汞柱。预防性给予90微克/千克的rFVIIa，该剂量与有抑制剂的血友病患者的推荐剂量相似，可减少再次出血出血量，表明该剂量在该猪主动脉切开术模型中有效。
