Dexmedetomidine, almost as many uses as there are letters
- Mar 6th, 2023
- Gage A. Stuntz
Author: Gage A. Stuntz, MD (Critical Care Fellow, Cooper University Hospital) // Reviewed by: Mark Ramzy, DO (@MRamzyDO); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)
Dexmedetomidine (Dex) is an alpha 2-adrenergic agonist which causes sedation, amnesia, and mild anesthetic properties. Uniquely, it causes deep sedation with maintained arousability without the dreaded side effect of respiratory depression.1 This medication has found its way into multiple applications in the ED setting from pediatric procedures to helping facilitate much needed imaging. Its sedative properties have even found a role in adults receiving non-invasive ventilation and even in our most critically ill patients on mechanical ventilation.
Commonly encountered side effects following the administration of Dex include hypotension, bradycardia, and less commonly, constipation. Given Dex’s mechanism of action, bradycardia is a commonly countered side effect, and a common rationale for discontinuation, despite there being limited evidence of increased morbidity or mortality.1
Dex has been used in several cases of acute agitation both with and without substance use as the presumed source. The central sympatholytic mechanism of the drug has been shown to be effective in reducing agitation and the requirement for additional medication administration, however larger studies are lacking in this area.2 Dex in two acutely agitated patients who were started on Dex infusions after receiving multiple doses of IV benzodiazepines and were ultimately able to be weaned off the drip. The lowest recorded HR was 65 and MAP was 69 and both resolved without intervention.2
The effect of Dex on heart rate and blood pressure was tested in healthy subjects who were given medical grade cocaine and then a dose of Dex. Subjects had heart rate and BP elevations shortly after the administration of cocaine. The effects of both resolved within several minutes after administration of Dex.2 This effect was used in clinical practice in a case report of a patient with acute Type B aortic dissection with recent crack cocaine use.3 The patient’s hypertension was refractory to esmolol, labetalol, nitroglycerine, and lorazepam administration. Dex was used as an ancillary medication and had such a strong sympatholytic effect that the other vasoactive medications were weaned off quickly.
Dex has also been studied and was shown to be effective ancillary treatment in several other acute toxidromic scenarios including alcohol withdrawal, acute agitation and cocaine ingestion in adolescents.4 Though Dex does have efficacy in assisting with symptom control and agitation in alcohol withdrawal, it is not appropriate as monotherapy, only as adjunctive treatment.
Noninvasive Ventilation (NIV)
Approximately 9% of patients on NIV with acute respiratory failure will need to be intubated. Sedative choice in these patients has been very frequently studied with midazolam and fentanyl both having well established safety.5,6 Dex has been shown to be both equally effective as versed in maintaining compliance with NIV in COPD and acute pulmonary edema in a comparison study.5 Dex was shown to have several benefits over versed in decreased duration of NIV and decreased rates of intubation as well.6
Patients with a history of cardiac disease, specifically diastolic heart failure have been speculated to be at risk for decompensation with Dex administration. This literature centers around cardiac surgical patients in the OR.15 Given that none of these studies were on undifferentiated ED patients, and a well-established safety profile for the drug in all comers, these concerns need further study.15
Dex has shown efficacy in intubated patients as first line therapy for post intubation sedation, and is actually recommended above benzodiazepines.5 Dex and propofol have both been shown to decrease ventilator days, morbidity and mortality.7 Early Dex has been studied in the immediate post intubation setting with the result that Dex had no difference in 90 day all-cause mortality, although did show an increase in adverse events which did not cause any additional morbidity. Comparators in this study involved propofol, midazolam and other sedatives.8
Although no evidence was found for the use of Dex in extubating patients in the emergency department, there is evidence supporting its use in ICU extubations. While this is not directly transferrable to the ED setting, it has been shown to be effective in extubating agitated ICU patients and is favored for its lack of respiratory depressant effects.8
Dex has emerged, especially now that it is generic and less expensive, as an option for procedural and imaging (CT and MRI) sedation in children in the ER. In a large retrospective analysis comparing Dex to propofol for non-invasive procedures, both agents allowed successful completion of the procedure 98% of the time. The main differences in the two medications were that propofol had a 9.7% airway intervention rate compared to Dex’s 2.2%, at the cost of longer recovery rates in the dex group.9
Dex has been compared to other sedative drugs such as Midazolam and Ketamine in the intranasal route. Dex was shown to be equivalent to these agents with no increased adverse effects. In fact, some of the patients receiving Dex had decreased risk of nausea. On a separate note, the use of Dex has been shown to decrease the risk of pre-procedure anxiety associated with laceration repairs.10,11,12
Dex has also been studied in children with autism. One small case series showed efficacy with intramuscular administration for the purpose of obtaining imaging studies, however ketamine and midazolam have also shown similar efficacy and new trials appear to be ongoing.16
Hypotension / Complications
Dex is frequently derided for its well-known adverse effects of bradycardia and hypotension which stem from its sympatholytic and alpha 2 agonist properties. These side effects, which include bradycardia and hypotension, have been extensively studied most recently in a 2021 issue of the Western Journal of EM. A retrospective study of 103 emergency department patients receiving Dex found 54% experiencing an adverse effect. This was defined as a 30% decrease in their blood pressure or bradycardia with HR under 60 BPM. Patients who had those adverse events had no increase of in-hospital mortality at 28 days.13
The effect of blood pressure in patients with sepsis in the ICU was also studied in a 2019 crossover trial of 38 patients in the journal of critical care medicine. Patients were switched from propofol after they were stabilized and on steady vasopressor requirement, to Dex for 4 hours and then back to propofol for 4 more hours. All 38 cases that used Dex were associated with a decrease in vasopressor dosage, followed by a subsequent increase when propofol was started again after 4 hours of Dex. No other adverse events recorded and no increase in mortality were associated with the switch to Dex. While this topic needs further study and this was a small study of only 38 patients, it provides some initial look into the safety profile of Dex in septic patients.14
A systematic review published in Academic Emergency Medicine in March 2023 included 35 studies (903 patients) on use of Dex. Authors found modest evidence that Dex may assist with medical imaging but mixed and limited evidence concerning its use for procedural sedation and sedation for nonintubated and intubated patients. They found infrequent adverse events, though bradycardia, hypotension, and respiratory depression were most commonly seen with IV administration and higher doses. There were a number of limitations with significant heterogeneity, and authors state further studies are needed. Interestingly, they did discuss the use of intranasal and sublingual administration.
Baumgartner K, Groff V, Yaeger LH, Fuller BM. The use of dexmedetomidine in the emergency department: A systematic review. Acad Emerg Med. 2023 Mar;30(3):196-208. doi: 10.1111/acem.14636. Epub 2022 Dec 19. PMID: 36448276.
- There is literature to support the use of dexmedetomidine in patients with sympathomimetic toxidrome. It may be a reasonable approach to utilize Dex, with or without a bolus, while closely monitoring these patients in an ED setting.
- In patients having difficulty tolerating non-invasive ventilation, Dex may assist in promoting compliance and possibly decreasing the rate of intubation when compared to benzodiazepines.
- Dex has a well-established role in sedation in the post-extubation setting, and may have a role in ED extubations, although this has not been studied.
- In pediatric patients, Dex promotes compliance with procedural and imaging sedation with a longer onset of action and longer duration of action compared to propofol and benzodiazepines. Dex is associated with a decreased risk of requirement of airway intervention compared to propofol.
- Although bradycardia and hypotension are common reasons for not using Dex, this has been consistently shown across multiple indications to rarely affect the choice of sedation and have not been shown to cause increased morbidity and mortality. Propofol has similar rates of hypotension and bradycardia in comparable large studies.
 Carollo DS, et al. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. Aug 2008 PMID: 18660652
 Menon DV, et al. Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol. 2007. PMID: 17692748
 Javed F, et al. Dexmedetomidine use in the setting of cocaine-induced hypertensive emergency and aortic dissection: a novel indication. Case Rep Med. 2011. PMID: 21961011
 Tobias JD. Dexmedetomidine to control agitation and delirium from toxic ingestions in adolescents. J Pediatr Pharmacol Ther. 2010. PMID: 22477792
 Huang Z, et al. Dexmedetomidine versus midazolam for the sedation of patients with non-invasive ventilation failure. Intern Med. 2012. PMID: 22975538
 Senoglu N, et al. Sedation during noninvasive mechanical ventilation with dexmedetomidine or midazolam: A randomized, double-blind, prospective study. Curr Ther Res Clin Exp. 2010. PMID: 24683260
 Fraser GL, 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. PMID: 23989093
 Shehabi Y, et al. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019. PMID: 33686482
 Schacherer NM, et al. Propofol Versus Dexmedetomidine for Procedural Sedation in a Pediatric Population. South Med J. 2019. PMID: 31050796
 Neville DN, et al. Double-blind Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department. Acad Emerg Med. 2016. PMID: 27129606
 Fantacci C, et al. Intranasal drug administration for procedural sedation in children admitted to pediatric Emergency Room. Eur Rev Med Pharmacol Sci. 2018. PMID: 29364490
 Poonai N, et al. Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review. Pediatrics. 2020. PMID: 31862730
 Sinnott J, et al. The Use of Dexmedetomidine in the Emergency Department: A Cohort Study. West J Emerg Med. 2021;22(5):1202-1209. Published 2021. PMID: 34546899
 Morelli A, et al. The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial. Crit Care Med. 2019. PMID: 30394918
 Wang G, et al. The efficacy and safety of dexmedetomidine in cardiac surgery patients: A systematic review and meta-analysis. PLoS One. 2018. PMID: 30231052
 Mason KP, et al. Intramuscular dexmedetomidine sedation for pediatric MRI and CT. AJR Am J Roentgenol. 2011. PMID: 21862817
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