Development of a Mechanically Ventilated and Sedated Model of Canine Septic Shoc

犬败血性休克机械通气和镇静模型的开发

• 批准号: 7733595
• 负责人: Charles Natanson
• 金额: $ 15.12万
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7733595
• 关键词: Acute; Algorithms; Alveolar; Analgesics; Animal Model; Animals; Antibiotics; Blood Platelets; Canis familiaris; Cardiopulmonary; Case Study; Cell Count; Development; Ensure; Enzymes; Event; Fentanyl; Goals; Hospitals; Human; Incidence; Interleukin-1; Kidney; Leukocytes; Liquid substance; Liver; Lung; Masks; Mechanical ventilation; Mechanics; Medetomidine; Metabolic; Midazolam; Modeling; Output; Oxygen; Pain management; Patients; Pneumonia; Protocols documentation; Pulmonary artery structure; Purpose; Rate; Research; Sedation procedure; Sepsis; Septic Shock; Serum; Severities; Shock; Sodium; Staphylococcus aureus; Survival Rate; Survivors; Time; Treatment Protocols; Unconscious State; Urine; Vasoconstrictor Agents; base; cytokine; design; dosage; falls; hemodynamics; lung injury; mortality; novel therapeutics; pressure; sedative; septic

A shock canine pneumonia model that permitted relief of discomfort using objective criteria was developed and validated. After intrabronchial S. aureus challenge, mechanical ventilation, antibiotics, fluids, vasopressors, sedatives and analgesics were titrated based on algorithms for 96 h. Increasing S. aureus (1 to 8 x 10(9) cfu/kg) produced decreasing survival rates (p = 0.04). From 4 to 96 h, changes in arterial-alveolar oxygen gradients, mean pulmonary artery pressures, interleukin-1, serum sodium levels, mechanical ventilation and vasopressor support were ordered based on survival time acute nonsurvivors (</=24 h, n = 8) >/=subacute nonsurvivors (24 to 96 h, n = 8) >/= survivors (>/=96 h, n = 22) (all p < 0.05). In the first 12 h, increases in lactate and renal abnormalities were greatest in acute nonsurvivors (all p < 0.05). Compared to survivors, subacute nonsurvivors had greater rises in cytokines, liver enzymes and greater falls in platelets, white cell counts, pH, and urine output from 24 to 96 h (all p < 0.05). Importantly, these changes were not attributable to dosages of sedation which decreased in nonsurvivors (survivors: 5.0 +/- 1.0 vs. nonsurvivors: 3.8 +/-0.7 ml/h/(fentanyl/midazolam/medetomidine); p = 0.02). In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis. The integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsis.

一个休克犬肺炎模型，允许缓解不适使用客观标准被开发和验证。支气管内金黄色葡萄球菌攻击后，根据算法滴定机械通气、抗生素、液体、血管加压剂、镇静剂和镇痛药96小时。金黄色葡萄球菌增加（1 ~ 8 × 10(9) cfu/kg）导致存活率下降（p = 0.04）。从4到96小时，动脉-肺泡氧梯度、平均肺动脉压、白细胞介素-1、血清钠水平、机械通气和血管加压剂支持的变化根据生存时间排序：急性非幸存者（</=24小时，n = 8）、bb0 /=亚急性非幸存者（24至96小时，n = 8）、>/=幸存者（>/=96小时，n = 22）（均p < 0.05）。在前12小时，急性非幸存者的乳酸和肾脏异常增加最多（均p < 0.05）。与幸存者相比，亚急性非幸存者在24至96小时内细胞因子、肝酶升高更大，血小板、白细胞计数、pH值和尿量下降更大（均p < 0.05）。重要的是，这些变化不是由于非幸存者镇静剂量的减少(幸存者：5.0 +/- 1.0 vs非幸存者：3.8 +/-0.7 ml/h/（芬太尼/咪达唑仑/美托咪定）；P = 0.02)。在这个模型中，疼痛控制方案并没有掩盖代谢功能和肺损伤的变化，也没有掩盖与脓毒症严重程度增加相关的更多血液动力学和肺支持的需要。将常规用于脓毒症患者的特异性和支持性滴定治疗整合到该模型中，可能为评估脓毒症治疗提供更现实的环境。