Long-term Dexmedetomidine versus Midazolam in Patients Under Mechanical Ventilation: A Double-blinded Randomized Clinical Trial Long-term dexmedetomidine for sedation in ICU.
Journal of Cellular & Molecular Anesthesia,
Vol. 6 No. 3 (2021),
7 September 2021
,
Page 259-268
https://doi.org/10.22037/jcma.v6i3.33104
Abstract
Background: Dexmedetomidine has been approved for short-term analgesia and sedation of patients in the intensive care unit (ICU). Longer duration of sedation with Dexmedetomidine is off-label and its safety has not yet been tested. This study aims to examine the safety profile for long-term use of Dexmedetomidine and compare it to midazolam (MID) based sedation in the ICU.
Methods: One hundred and one patients on mechanical ventilation were randomized to receive either Dexmedetomidine 0.2-1.0 µg/kg/h or MID 20- 40 µg/kg/h in a double-blinded fashion to reach the target of -2 to 1 on the Richmond Agitation-Sedation Scale (RASS). Duration of mechanical ventilation was the primary endpoint; secondary endpoints included the occurrences of composite cardiac adverse event (CCAE), bradycardia, hypotension, significant dysrhythmias, heart failure myocardial infarction or death within 28 days, ICU length of stay, need for additive analgesic, time spent at target sedation, and delirium.
Results: The duration of mechanical ventilation and ICU stay were almost 2 days shorter in the DEXMEDETOMIDINE group (P= 0.002 and 0.001, respectively), but regarding CCAE, sinus bradycardia occurred more frequently (P= 0.399 ) and mortality was similar in both groups (P=0.378).
Conclusion: Our results confirmed the results of previous trials showing that long-term Dexmedetomidine was comparable to benzodiazepines for the frequency of major complications in critically ill patients. Although Dexmedetomidine is capable to reduce the duration of mechanical ventilation and ICU stay, physicians should weigh these benefits against the occurrence of significant bradycardia and hypotension.
- Dexmedetomidine
- Long term sedation
- Critical Care
- Mechanical ventilation
How to Cite
References
Nasraway SA, Jr., Jacobi J, Murray MJ, Lumb PD. Sedation, analgesia, and neuromuscular blockade of the critically ill adult: revised clinical practice guidelines for 2002. Crit Care Med. 2002;30(1):117-8.
Mirkheshti A. Dexmedetomidine or Clonidine: Action Expresses Priorities. J Cell Mol Anesth. 2021;5(4).
Hamishehkar H, Beigmohammadi MT, Abdollahi M, Ahmadi A, Mahmoodpour A, Mirjalili MR, et al. Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation. Daru. 2010;18(3):155-62.
Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308(19):1985-92.
Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, et al. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology. 2001;95(2):324-33.
Swart EL, de Jongh J, Zuideveld KP, Danhof M, Thijs LG, Strack van Schijndel RJ. Population pharmacokinetics of lorazepam and midazolam and their metabolites in intensive care patients on continuous venovenous hemofiltration. Am J Kidney Dis. 2005;45(2):360-71.
Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1):119-41.
González-Gil A, Picazo RA, de Bruyn P, Illera JC. Corticoadrenal and Cardiorespiratory Responses to Administration of Propofol Combined with Dexmedetomidine or Ketamine in Rabbits. J Am Assoc Lab Anim Sci. 2018;57(3):278-81.
Behnaz F, Karbalaeifar R, Chegini A, Mohseni G, Valizadeh S. Effect of Dexmedetomidine on Transcription Factors and Inflammatory Cytokines in Elective Aortic Aneurysm Repair Surgery. J Cell Mol Anesth. 2020;5(3):131-42.
Hosseini B, Dabbagh A, Mosaffa F, Dabir S, Moshari M, Seyed Alshohadaei S, et al. The effects of Ropivacaine and its Combination with Dexmedetomidine and Dexamethasone on Neural Apoptosis. J Cell Mol Anesth. 2020;5(2):143-9.
Szumita PM, Baroletti SA, Anger KE, Wechsler ME. Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine. Am J Health Syst Pharm. 2007;64(1):37-44.
Biccard BM, Goga S, de Beurs J. Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials. Anaesthesia. 2008;63(1):4-14.
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):1151-60.
Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, et al. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009;111(5):1075-84.
Tabeefar H, Beigmohammadi MT, Javadi MR, Abdollahi M, Mahmoodpoor A, Ahmadi A, et al. Effects of Pantoprazole on Systemic and Gastric Pro- and Anti-inflammatory Cytokines in Critically Ill Patients. Iran J Pharm Res. 2012;11(4):1051-8.
Spapen HD, Diltoer MW, Nguyen DN, Hendrickx I, Huyghens LP. Effects of N-acetylcysteine on microalbuminuria and organ failure in acute severe sepsis: results of a pilot study. Chest. 2005;127(4):1413-9.
Chen X, Li L, Hu J, Zhang C, Pan Y, Tian D, et al. Anti-inflammatory effect of dexmedetomidine combined with hypothermia on acute respiratory distress syndrome in rats. J Surg Res. 2017;216:179-84.
Piazza O, Staiano RI, De Robertis E, Conti G, Di Crescenzo V, Loffredo S, et al. Effect Of α2-Adrenergic Agonists And Antagonists On Cytokine Release From Human Lung Macrophages Cultured In Vitro. Transl Med UniSa. 2016;15:67-73.
Kunisawa T. Dexmedetomidine hydrochloride as a long-term sedative. Ther Clin Risk Manag. 2011;7:291-9.
Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018;197(9):1147-56.
Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats. BMC Anesthesiol. 2015;15:68.
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, 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):1338-44.
Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, 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(13):1321-8.
Baron R, Binder A, Biniek R, Braune S, Buerkle H, Dall P, et al. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015;13:Doc19.
Holliday SF, Kane-Gill SL, Empey PE, Buckley MS, Smithburger PL. Interpatient variability in dexmedetomidine response: a survey of the literature. ScientificWorldJournal. 2014;2014:805013.
Salarian S, Taherkhanchi B, Dabbagh A, Darban M, Bagheri B. Dexmedetomidine Mechanism of Action: an update. J Cell Mol Anesth. 2016;1(2):91-4.
Pasin L, Greco T, Feltracco P, Vittorio A, Neto CN, Cabrini L, et al. Dexmedetomidine as a sedative agent in critically ill patients: a meta-analysis of randomized controlled trials. PLoS One. 2013;8(12):e82913.
Zamani MM, Keshavarz-Fathi M, Fakhri-Bafghi MS, Hirbod-Mobarakeh A, Rezaei N, Bahrami A, et al. Survival benefits of dexmedetomidine used for sedating septic patients in intensive care setting: A systematic review. J Crit Care. 2016;32:93-100.
Abuhasna S, Al Jundi A, Abdelatty W, Urrahman M. Evaluation of long-term infusion of dexmedetomidine in critically ill patients: A retrospective analysis. Int J Crit Illn Inj Sci. 2012;2(2):70-4.
Ozaki M, Takeda J, Tanaka K, Shiokawa Y, Nishi S, Matsuda K, et al. Safety and efficacy of dexmedetomidine for long-term sedation in critically ill patients. J Anesth. 2014;28(1):38-50.
Zhang Z, Chen K, Ni H, Zhang X, Fan H. Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis. Sci Rep. 2017;7:44979.
Shah PN, Dongre V, Patil V, Pandya S, Mungantiwar A, Choulwar A. Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population. Indian J Crit Care Med. 2014;18(5):291-6.
Paliwal B, Rai P, Kamal M, Singariya G, Singhal M, Gupta P, et al. Comparison Between Dexmedetomidine and Propofol with Validation of Bispectral Index For Sedation in Mechanically Ventilated Intensive Care Patients. J Clin Diagn Res. 2015;9(7):Uc01-5.
Anger KE. Dexmedetomidine: a review of its use for the management of pain, agitation, and delirium in the intensive care unit. Curr Pharm Des. 2013;19(22):4003-13.
Chen K, Lu Z, Xin YC, Cai Y, Chen Y, Pan SM. Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients. The Cochrane database of systematic reviews. 2015;1(1):Cd010269.
Dasta JF, Kane-Gill SL, Pencina M, Shehabi Y, Bokesch PM, Wisemandle W, et al. A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med. 2010;38(2):497-503.
Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, 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(2):R38.
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):489-99.
Turunen H, Jakob SM, Ruokonen E, Kaukonen KM, Sarapohja T, Apajasalo M, et al. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015;19(1):67.
Lee S. Dexmedetomidine: present and future directions. Korean J Anesthesiol. 2019;72(4):323-30.
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