The geriatric surgical patient: stress, anesthetics, and functional outcomes

老年外科患者：压力、麻醉和功能结果

• 批准号: 8313907
• 负责人: Stacie Deiner
• 金额: $ 8.48万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313907
• 关键词: Age; Aging; Anesthesia procedures; Anesthetics; Award; Biological Markers; Caring; Cells; Clinical Trials; Comorbidity; Data; Defect; Delirium; Dendritic Cells; Development; Elderly; Epinephrine; Ethers; Exhibits; Gases; General Anesthesia; Genes; Geriatrics; Goals; Grant; Guidelines; Hospital Costs; Hydrocortisone; Immunologics; Immunosuppression; Impaired cognition; Incidence; Infection; Intravenous; Intravenous Anesthesia; Isoflurane; Laboratories; Length of Stay; Medical; Medicare/Medicaid; Messenger RNA; Morbidity - disease rate; Nature; Neurobiology; Norepinephrine; Operative Surgical Procedures; Outcome; Oxidative Stress; Pathologic; Patient Readmission; Patients; Perioperative; Perioperative complication; Pharmaceutical Preparations; Physiological; Pilot Projects; Plasma; Population; Postoperative Complications; Postoperative Period; Predisposition; Principal Investigator; Procedures; Propofol; Publishing; Relative (related person); Research; Research Personnel; Risk; Risk Factors; Serum; Societies; Somatotropin; Stress; Sympathetic Nervous System; Techniques; Work; base; biological adaptation to stress; career; comparative effectiveness; effectiveness trial; experience; functional outcomes; heart rate variability; improved; innovation; macrophage; monocyte; mortality; neurotoxic; neutrophil; older patient; oxidative damage; prospective; response; sevoflurane

DESCRIPTION (provided by applicant): Older age (>70) is an independent risk factor for postoperative complications and mortality. However the nature of age's contribution to postsurgical complications remains unclear. One hypothesis is that older patients are more susceptible to the sequelae of pathologic stress. Published data suggest that a relatively new anesthesia technique is associated with superior control of the stress response. This technique eschews the traditional use of inhalational gas (e.g. ether, isoflurane, sevoflurane) in favor of intravenous medications (total intravenous anesthesia, TIVA). This has only been possible in the past several years when the development of improved medications (e.g. propofol) has made it possible to conduct an anesthetic without gas. It is well established that TIVA is associated with a lesser activation of the stress response as evidenced by serum cortisol, lower plasma levels of norepinephrine (NE), epinephrine (E), and growth hormone (GH), and lesser heart rate variability (HRV). If the use of TIVA effectively suppresses the stress response in older adults, then anesthesiologists will leverage this effect to produce better postoperative outcomes. In the context of a GEMSSTAR award, we propose a prospective pilot study to clarify the relationship between anesthetic technique, postsurgical outcomes and a unique set of mRNA markers of perioperative stress in patients >70 years old undergoing TIVA vs. those who are exposed to gas. From published data and experience through my research group's current clinical trial, we have evidence to suggest that TIVA may be a superior technique in older patients. In addition our group has worked closely with the Neurobiology of Aging laboratory at Mount Sinai to identify 9 oxidative stress genes that completely discriminate between immediate pre- and postsurgical patients. We suggest that the mRNA of these genes may be specific biomarkers of patients who are particularly at-risk of perioperative complications. Our hypotheses: 1) Patients undergoing general anesthesia with TIVA will have better outcomes than patients who receive inhalational anesthesia. 2) Patients undergoing general anesthesia with TIVA will have less stress, induction of the oxidative damage response, and immunosuppression than patients who receive inhalational anesthesia. This project is significant because it utilizes innovative biomarkers of stress and is the first study to propose a comparison of an alternative to potentially neurotoxic gas anesthesia in the elderly. The results from this study will form the basis for larger comparative effectiveness trials of anesthetic technique and outcomes in the elderly.

描述（由申请人提供）：年龄（> 70）是术后并发症和死亡率的独立风险因素。但是，年龄对术后并发症的贡献的性质尚不清楚。一种假设是，老年患者更容易受到病理应激的后遗症的影响。已发布的数据表明，一种相对较新的麻醉技术与对压力反应的高分控制有关。这项技术避免了吸入气体（例如乙醚，异氟烷，七氟苯烷）的传统用途，而有利于静脉内药物（总静脉麻醉，TIVA）。这只有在过去几年中，当改良药物的开发（例如丙泊酚）的发展使得没有气体的麻醉剂成为可能。众所周知，TIVA与血清皮质醇，较低血浆去甲肾上腺素（NE），肾上腺素（E）和生长激素（GH）（GH）以及较小的心脏率变异性（HRV）所证明的TIVA与应激反应的激活相关。如果使用TIVA可以有效抑制老年人的压力反应，那么麻醉师将利用这种作用来产生更好的术后结局。在GEMSSTAR奖的背景下，我们提出了一项前瞻性试点研究，以阐明麻醉技术，术后结果和一组独特的围手术胁迫的mRNA标记，> 70岁的患者与暴露于天然气的患者与那些暴露于天然气的患者之间的关系。从我的研究小组当前的临床试验中发布的数据和经验，我们有证据表明TIVA可能是老年患者的卓越技术。此外，我们的小组还与西奈山的衰老实验室的神经生物学紧密合作，以鉴定9种氧化应激基因，这些氧化应激基因完全区分了立即的前和术后患者。我们建议这些基因的mRNA可能是特别是围手术期并发症患者的特定生物标志物。我们的假设：1）与接受吸入性麻醉的患者相比，接受全身麻醉的患者的结局更好。 2）与接受吸入性麻醉的患者相比，患有TIVA的全身麻醉的患者的压力较小，氧化损伤反应的诱导和免疫抑制。该项目之所以重要，是因为它利用了压力的创新生物标志物，并且是首次提出对老年人潜在神经毒性气体麻醉替代方案进行比较的研究。这项研究的结果将构成对麻醉技术和老年人结果的更大比较有效性试验的基础。