Sequential use of midazolam and dexmedetomidine for long-term sedation may reduce weaning time in selected critically ill, mechanically ventilated patients: a randomized controlled study

Yongfang Zhou, Jie Yang, Bo Wang, Peng Wang, Zhen Wang, Yunqin Yang, Guopeng Liang, Xiaorong Jing, Xiaodong Jin, Zhongwei Zhang, Yiyun Deng, Chenggong Hu, Xuelian Liao, Wanhong Yin, Zhihong Tang, Yongming Tian, Liyuan Tao, Yan Kang, Yongfang Zhou, Jie Yang, Bo Wang, Peng Wang, Zhen Wang, Yunqin Yang, Guopeng Liang, Xiaorong Jing, Xiaodong Jin, Zhongwei Zhang, Yiyun Deng, Chenggong Hu, Xuelian Liao, Wanhong Yin, Zhihong Tang, Yongming Tian, Liyuan Tao, Yan Kang

Abstract

Background: Current sedatives have different side effects in long-term sedation. The sequential use of midazolam and dexmedetomidine for prolonged sedation may have distinct advantages. We aimed to evaluate the efficacy and safety of the sequential use of midazolam and either dexmedetomidine or propofol, and the use of midazolam alone in selected critically ill, mechanically ventilated patients.

Methods: This single-center, randomized controlled study was conducted in medical and surgical ICUs in a tertiary, academic medical center. Patients enrolled in this study were critically ill, mechanically ventilated adult patients receiving midazolam, with anticipated mechanical ventilation for ≥ 72 h. They passed the spontaneous breathing trial (SBT) safety screen, underwent a 30-min-SBT without indication for extubation and continued to require sedation. Patients were randomized into group M-D (midazolam was switched to dexmedetomidine), group M-P (midazolam was switched to propofol), and group M (sedation with midazolam alone), and sedatives were titrated to achieve the targeted sedation range (RASS - 2 to 0).

Results: Total 252 patients were enrolled. Patients in group M-D had an earlier recovery, faster extubation, and more percentage of time at the target sedation level than those in group M-P and group M (all P < 0.001). They also experienced less weaning time (25.0 h vs. 49.0 h; HR1.47, 95% CI 1.05 to 2.06; P = 0.025), and a lower incidence of delirium (19.5% vs. 43.8%, P = 0.002) than patients in group M. Recovery (P < 0.001), extubation (P < 0.001), and weaning time (P = 0.048) in group M-P were shorter than in group M, while the acquisition cost of sedative drug was more expensive than other groups (both P < 0.001). There was no significant difference in adverse events among these groups (all P > 0.05).

Conclusions: The sequential use of midazolam and dexmedetomidine was an effective and safe sedation strategy for long-term sedation and could provide clinically relevant benefits for selected critically ill, mechanically ventilated patients.

Trial registration: NCT02528513 . Registered August 19, 2015.

Keywords: Critically ill; Dexmedetomidine; Mechanical ventilation; Midazolam; Propofol; Sequential sedation.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study protocol. SAT spontaneous awakening trial, SBT spontaneous breathing trial
Fig. 2
Fig. 2
Patients screened, enrollment, randomization, and treatment flow diagram. aExtubation failure: patients received reintubation within 48 h after extubation. ITT intention-to-treat analysis, SS safety set analysis, PP per-protocol analysis
Fig. 3
Fig. 3
Weaning time in group M–D, group M–P, and group M

References

    1. Sessler CN, Wilhelm W. Analgesia and sedation in the intensive care unit: an overview of the issues. Crit Care. 2008;12 Suppl 3(Suppl 3):S1. doi: 10.1186/cc6147.
    1. Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, 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. doi: 10.1097/CCM.0000000000003299.
    1. Pearson SD, Patel BK, Pearson SD. Evolving targets for sedation during mechanical ventilation. Curr Opin Crit Car. 2020;26(1):47–52. doi: 10.1097/MCC.0000000000000687.
    1. Gommers D, Bakker J. Medications for analgesia and sedation in the intensive care unit: an overview. Crit Care. 2008;12(Suppl 3):S4. doi: 10.1186/cc6150.
    1. Soliman HM, Mélot C, Vincent JL. Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth. 2001;87:186–192. doi: 10.1093/bja/87.2.186.
    1. Wunsch H, Kahn JM, Kramer AA, Rubenfeld GD. Use of intravenous infusion sedation among mechanically ventilated patients in the United States. Crit Care Med. 2009;37:3031–3039. doi: 10.1097/CCM.0b013e3181b02eff.
    1. Aragón RE, Proaño A, Mongilardi N, de Ferrari A, Herrera P, Roldan R, et al. Sedation practices and clinical outcomes in mechanically ventilated patients in a prospective multicenter cohort. Crit Care. 2019;23(1):130.8. doi: 10.1186/s13054-019-2394-9.
    1. Hall RI, Sandham D, Cardinal P, Tweeddale M, Moher D, Wang X, et al. Propofol vs midazolam for ICU sedation, a Canadian multicenter randomized trial. Chest. 2001;119:1151–1159. doi: 10.1378/chest.119.4.1151.
    1. Carrasco G, Molina R, Costa J, Soler JM, Cabré L. Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients, a cost–benefit analysis. Chest. 1993;103:557–564. doi: 10.1378/chest.103.2.557.
    1. Bauer TM, Ritz R, Haberthür C, Ha HR, Hunkeler W, Sleight AJ, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet. 1995;346:145–147. doi: 10.1016/S0140-6736(95)91209-6.
    1. Barrientos-Vega R, Mar Sánchez-Soria M, Morales-García C, Robas-Gómez A, Cuena-Boy R, Ayensa-Rincon A. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med. 1997;25:33–40. doi: 10.1097/00003246-199701000-00009.
    1. Fraser GL, Devlin JW, Worby CP, Alhazzani W, Barr J, Dasta JF, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013;41(9 Suppl 1):S30–S38. doi: 10.1097/CCM.0b013e3182a16898.
    1. Weinbroum AA, Halpern P, Rudick V, Sorkine P, Freedman M, Geller E. Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison. Intensive Care Med. 1997;23:1258–1263. doi: 10.1007/s001340050495.
    1. Nimmo GR, Mackenzie SJ, Grant IS. Haemodynamic and oxygen transport effects of propofol infusion in critically ill adults. Anaesthesia. 1994;4:485–489. doi: 10.1111/j.1365-2044.1994.tb03517.x.
    1. Krajčová A, Waldauf P, Anděl M, et al. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015;12(19):398. doi: 10.1186/s13054-015-1112-5.
    1. Romagnoli S, Amigoni A, Blangetti I, Casella G, Chelazzi C, Forfori F, et al. Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients. Miner Anestesiol. 2018;84(6):731–746.
    1. Gerlach AT, Dasta JF. Dexmedetomidine: an updated review. Ann Pharmacother. 2007;41:245–252. doi: 10.1345/aph.1H314.
    1. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small dose dexmedetomidine infusions. Anesth Analg. 2000;90:699–705. doi: 10.1097/00000539-200003000-00035.
    1. Venn M, Newman J, Grounds M. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. 2003;29(2):201–207. doi: 10.1007/s00134-002-1579-9.
    1. Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, et al. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009;35(2):282–290. doi: 10.1007/s00134-008-1296-0.
    1. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, 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(22):2644–2653. doi: 10.1001/jama.298.22.2644.
    1. Ng KT, Shubash CJ, Chong JS. The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis. Anaesthesia. 2019;74(3):380–392. doi: 10.1111/anae.14472.
    1. Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489–499. doi: 10.1001/jama.2009.56.
    1. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151–1160. doi: 10.1001/jama.2012.304.
    1. Gupta S, Singh D, Sood D, Kathuria S. Role of dexmedetomidine in early extubation of the intensive care unit patients. J Anaesthesiol Clin Pharmacol. 2015;31(1):92–98. doi: 10.4103/0970-9185.150554.
    1. Constantin JM, Momon A, Mantz J, Payen JF, De Jonghe B, Perbet S, et al. Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth Crit Care Pain Med. 2016;35(1):7–15. doi: 10.1016/j.accpm.2015.06.012.
    1. Lachaine J, Beauchemin C. Economic evaluation of dexmedetomidine relative to midazolam for sedation in the intensive care unit. Can J Hosp Pharm. 2012;65(2):103–110.
    1. Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506–2517. doi: 10.1056/NEJMoa1904710.
    1. Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75(10):1119–1130. doi: 10.1007/s40265-015-0419-5.
    1. Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263–306. doi: 10.1097/CCM.0b013e3182783b72.
    1. Olsen HT, Nedergaard HK, Strøm T, Jakob O, Wian K-A, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103–1111. doi: 10.1056/NEJMoa1906759.
    1. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, et al. An official American thoracic society/European society of intensive care medicine/society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195(9):1253–1263. doi: 10.1164/rccm.201703-0548ST.
    1. Zhou Y, Jin X, Kang Y, Liang G, Liu T, Deng Ni. Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study. Crit Care. 2014;18(3):R122. doi: 10.1186/cc13922.
    1. Gélinas C, Fillion L, Puntillo KA, et al. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care. 2006;15:420–427. doi: 10.4037/ajcc2006.15.4.420.
    1. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126–134. doi: 10.1016/S0140-6736(08)60105-1.
    1. Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;29:1033–1056. doi: 10.1183/09031936.00010206.
    1. Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–1344. doi: 10.1164/rccm.2107138.
    1. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, 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(21):2703–2710. doi: 10.1001/jama.286.21.2703.
    1. Senoglu N, Oksuz H, Dogan Z, Yildiz H, Demirkiran H, Ekerbicer H. Sedation during noninvasive mechanical ventilation with dexmedetomidine or midazolam: a randomized, double-blind, prospective study. Curr Ther Res Clin Exp. 2010;71(3):141–153. doi: 10.1016/j.curtheres.2010.06.003.
    1. Cavallazzi R, Saad M, Marik PE. Delirium in the ICU: an overview. Ann Intensive Care. 2012;2(1):49. doi: 10.1186/2110-5820-2-49.
    1. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–1762. doi: 10.1001/jama.291.14.1753.

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