提示: 手机请竖屏浏览!

右美托咪定和丙泊酚用于机械通气成人脓毒症患者镇静的比较
Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis


Christopher G. Hughes ... 其他 • 2021.04.15
相关阅读
• 右美托咪定用于危重患者的早期镇静 • 对危重机械通气患者采取非镇静或浅镇静的比较

摘要


背景

现行指南建议应用右美托咪定或异丙酚对机械通气的成人患者实施浅镇静。这两种镇静剂在唤醒能力、免疫性和炎症方面存在差异。对于采用浅镇静的机械通气成人脓毒症患者,两种镇静剂对结局的影响是否有差异尚不清楚。

 

方法

在一项多中心、双盲试验中,我们将机械通气的成人脓毒症患者随机分组,两组分别接受右美托咪定(每小时0.2~1.5 μg/kg)或丙泊酚(每分钟5~50 μg/kg),由床旁护士调整剂量,达到临床医师根据里士满激越-镇静量表(RASS,评分范围为-5分[无应答]至+4分[好斗])设定的镇静目标。主要终点是14天干预期间无谵妄且无昏迷的生存天数。次要终点包括28日时不使用呼吸机的天数、90日时的死亡率以及6个月时年龄校正的认知功能电话问卷(Telephone Interview for Cognitive Status,TICS-T;评分范围为0~100分,均值为50±10分,评分较低表示认知能力较差)总分。

 

结果

在接受随机分组的432例患者中,422例被分配接受一种试验药物并被纳入分析,其中214例患者接受了中位剂量为每小时0.27 μg/kg的右美托咪定,208例接受了中位剂量为每分钟10.21 μg/kg的丙泊酚。接受试验药物的中位持续时间为3.0天(四分位距,2.0~6.0),中位RASS评分为-2.0分(四分位距,-3.0~-1.0)。在无谵妄且无昏迷的生存天数(校正的中位数,10.7天vs. 10.8天;比值比,0.96;95%置信区间[CI],0.74~1.26)、不使用呼吸机的天数(校正的中位数,23.7天vs. 24.0天;比值比,0.98;95% CI,0.63~1.51)、90日时的死亡率(38% vs. 39%;风险比,1.06;95% CI,0.74~1.52)或6个月时的TICS-T评分(校正的中位评分,40.9分vs. 41.4分;比值比,0.94;95% CI,0.66~1.33)方面,右美托咪定和丙泊酚之间未发现差异。两组的安全性终点相似。

 

结论

在采用建议的浅镇静治疗的机械通气成人脓毒症患者中,右美托咪定组患者和丙泊酚组患者的结局无差异(由美国国立卫生研究院资助;在ClinicalTrials.gov注册号为NCT01739933)。





作者信息

Christopher G. Hughes, M.D., M.S.C.R., Patrick T. Mailloux, D.O., John W. Devlin, Pharm.D., Joshua T. Swan, Pharm.D., M.P.H., Robert D. Sanders, M.D., Antonio Anzueto, M.D., James C. Jackson, Psy.D., Aimee S. Hoskins, B.S.N., R.N., Brenda T. Pun, D.N.P., R.N., Onur M. Orun, M.S., Rameela Raman, Ph.D., Joanna L. Stollings, Pharm.D., Amy L. Kiehl, M.A., Matthew S. Duprey, Pharm.D., Ph.D., Lan N. Bui, Pharm.D., M.P.H., Hollis R. O’Neal, Jr., M.D., Allison Snyder, M.S.N., A.P.R.N., Michael A. Gropper, M.D., Ph.D., Kalpalatha K. Guntupalli, M.D., Gregg J. Stashenko, M.D., Mayur B. Patel, M.D., M.P.H., Nathan E. Brummel, M.D., M.S.C.I., Timothy D. Girard, M.D., M.S.C.I., Robert S. Dittus, M.D., M.P.H., Gordon R. Bernard, M.D., E. Wesley Ely, M.D., M.P.H., and Pratik P. Pandharipande, M.D., M.S.C.I. for the MENDS2 Study Investigators*
From the Critical Illness, Brain Dysfunction, and Survivorship Center (C.G.H., J.C.J., A.S.H., B.T.P., O.M.O., R.R., J.L.S., A.L.K, M.B.P., N.E.B., T.D.G., R.S.D., G.R.B., E.W.E., P.P.P.), the Center for Health Services Research (C.G.H., J.C.J., R.R., M.B.P., T.D.G., R.S.D., E.W.E., P.P.P.), the Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology (C.G.H., P.P.P.), the Division of Allergy, Pulmonary, and Critical Care Medicine (J.C.J., B.T.P., G.R.B., E.W.E.), and the Division of General Internal Medicine and Public Health (R.S.D.), Department of Medicine, the Departments of Biostatistics (O.M.O., R.R.) and Pharmaceutical Services (J.L.S.), and Division of Trauma and Surgical Critical Care, Department of Surgery (M.B.P.), Vanderbilt University Medical Center, and the Anesthesia Service (C.G.H., P.P.P.), Research Service (J.C.J.), Surgical Service (M.B.P.), and Geriatric Research, Education and Clinical Center (R.S.D., E.W.E.), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System — both in Nashville; the Neuroscience Institute and Department of Critical Care Medicine, Maine Medical Center, Portland (P.T.M.); the Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston (J.W.D., M.S.D.); the Departments of Pharmacy (J.T.S., L.N.B.) and Surgery (J.T.S.) and the Center for Outcomes Research (J.T.S.), Houston Methodist, and the Pulmonary, Critical Care and Sleep Medicine Section, Ben Taub Hospital, Baylor College of Medicine (K.K.G.), Houston; the Division of Pulmonary/Critical Care Medicine, University of Texas Health, and the South Texas Veterans Health Care System, San Antonio (A.A.); and Texas Health Harris Methodist Hospital Fort Worth, Fort Worth (A.S.) — all in Texas; the University of Sydney, and the Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney, and the Department of Anesthesiology, University of Wisconsin, Madison (R.D.S.); Pulmonary and Critical Care Medicine, Baton Rouge General Medical Center and Our Lady of the Lake Regional Medical Center, Baton Rouge, LA (H.R.O.); the Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco (M.A.G.); Pulmonary and Critical Care, Mission Hospital, Asheville, NC (G.J.S.); the Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus (N.E.B.); and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh (T.D.G.). Address reprint requests to Dr. Hughes at 1211 21st Ave. S., 422 MAB, Nashville, TN 37212, or at christopher.hughes@vumc.org. *The MENDS2 Study Investigators are listed in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis: current estimates and limitations. Am J Respir Crit Care Med 2016;193:259-272.

2. Dhital R, Basnet S, Poudel DR. Predictors and outcome of invasive mechanical ventilation in hospitalized patients with sepsis: data from National Inpatient Sample. J Community Hosp Intern Med Perspect 2018;8:49-52.

3. Vincent J-L, Marshall JC, Namendys-Silva SA, et al. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med 2014;2:380-386.

4. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911-922.

5. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-1762.

6. Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311-2318.

7. Pisani MA, Kong SYJ, Kasl SV, Murphy TE, Araujo KLB, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009;180:1092-1097.

8. Schuler A, Wulf DA, Lu Y, et al. The impact of acute organ dysfunction on long-term survival in sepsis. Crit Care Med 2018;46:843-849.

9. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306-1316.

10. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med 2012;367:30-39.

11. Helmy SA, Al-Attiyah RJ. The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients. Anaesthesia 2001;56:4-8.

12. Wang X, Cheng Y, Liu X, Yang J, Munoz D, Zhang C. Unexpected pro-injury effect of propofol on vascular smooth muscle cells with increased oxidative stress. Crit Care Med 2011;39:738-745.

13. Kelbel I, Koch T, Weber A, Schiefer HG, van Ackern K, Neuhof H. Alterations of bacterial clearance induced by propofol. Acta Anaesthesiol Scand 1999;43:71-76.

14. Memiş D, Hekimoğlu S, Vatan I, Yandim T, Yüksel M, Süt N. Effects of midazolam and dexmedetomidine on inflammatory responses and gastric intramucosal pH to sepsis, in critically ill patients. Br J Anaesth 2007;98:550-552.

15. Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth 2001;86:650-656.

16. Qiao H, Sanders RD, Ma D, Wu X, Maze M. Sedation improves early outcome in severely septic Sprague Dawley rats. Crit Care 2009;13:R136-R136.

17. Nishina K, Akamatsu H, Mikawa K, et al. The effects of clonidine and dexmedetomidine on human neutrophil functions. Anesth Analg 1999;88:452-458.

18. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644-2653.

19. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301:489-499.

20. Pandharipande PP, Sanders RD, Girard TD, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care 2010;14:R38-R38.

21. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012;307:1151-1160.

22. Kawazoe Y, Miyamoto K, Morimoto T, et al. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial. JAMA 2017;317:1321-1328.

23. Shehabi Y, Howe BD, Bellomo R, et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 2019;380:2506-2517.

24. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018;46(9):e825-e873.

25. Chandrasekhar R, Hughes CG, Pun BT, Orun OM, Ely EW, Pandharipande PP. Statistical analysis plan for the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure trial. Crit Care Resusc 2020;22:63-71.

26. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338-1344.

27. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 2017;45:486-552.

28. Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6,064 patients. Crit Care Med 2017;45:171-178.

29. Pun BT, Balas MC, Barnes-Daly MA, et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU Liberation Collaborative in over 15,000 adults. Crit Care Med 2019;47:3-14.

30. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-2710.31. Gélinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the Critical-Care Pain Observation Tool in adult patients. Am J Crit Care 2006;15:420-427.

32. Brandt J, Spencer M, Folstein MF. The telephone interview for cognitive status. Neuropsychiatry Neuropsychol Behav Neurol 1988;1:111-117.

33. Christie JD, Plotkin Biester RC, Taichman DB, et al. Formation and validation of a telephone battery to assess cognitive function in acute respiratory distress syndrome survivors. J Crit Care 2006;21:125-132.

34. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged — the Index of Adl: a standardized measure of biological and psychosocial function. JAMA 1963;185:914-919.

35. Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.

36. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001;33:337-343.

37. Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. Psychol Med 1994;24:145-153.

38. Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375:475-480.

39. Olsen HT, Nedergaard HK, Strøm T, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med 2020;382:1103-1111.

40. Djaiani G, Silverton N, Fedorko L, et al. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial. Anesthesiology 2016;124:362-368.

服务条款 | 隐私政策 | 联系我们