Pre-brief:
We all love Precedex (dexmedetomidine) for its light sedative properties and minimal effects on respiration. But what about its propensity to bring us down through hypotension and bradycardia?
Dexmedetomidine is an α-2 agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects. The sedative and anxiolytic effects are due to the activation of α-2 receptors in the locus coeruleus. The mild analgesic effects are thought to be mediated by α-2 receptor binding in the CNS and the subsequent reduction in substance P and glutamate which are responsible for nociceptive transmission. All of these mechanisms, plus the fact that it causes minimal depression of respiratory function, make dexmedetomidine an attractive option for many patients in the critical care setting.
However, the hemodynamic effects of hypotension and bradycardia (from sympatholysis and baroreflex-mediated parasympathetic activation) can be problematic. These effects are often severe enough to necessitate treatment with vasopressors or atropine, respectively.
How can we predict which patients might experience these issues? And what can be done to address them?
Hypotension:
The incidence of hypotension from dexmedetomidine ranges from 24% – 56%.
One retrospective study conducted by Gerlach and colleagues in 2016 aimed to determine the predictors of dexmedetomidine-associated hypotension in critically ill patients. The study evaluated 283 patients from various ICU settings including medical, surgical, trauma, bone marrow transplant, and cardiothoracic surgery. Patients who were hypotensive at baseline with a MAP < 65 mmHg were excluded. The use of concomitant analgesics and sedatives was similar between groups with fentanyl and midazolam being the most common agents. Loading doses were not permitted. Patients who experienced hypotension compared to those who did not receive similar dosing of dexmedetomidine.
Patients who developed hypotension with dexmedetomidine had the following characteristics:
- Increased age (55.1 yrs vs 50.9 yrs; P=0.03)
- Higher APACHE II scores at the time of drug initiation (22 vs 20; P=0.02)
- History of CAD (32.2% vs 16.0%; P=0.009)
- Lower baseline MAP at time of drug initiation (82 vs 90; P < 0.001)
- On at least 1 vasopressor prior to drug initiation (14.0% vs 2.5%; P<0.001)
Ultimately, increased mortality was seen in the dexmedetomidine associated hypotension group (20.7% vs 9.9%; P=0.016).
The findings of this study are not surprising and though it had obvious limitations due to its retrospective nature and the fact that confounding variables such as volume status were not analyzed, it sheds light on some important factors to keep in mind when using dexmedetomidine.
Bradycardia:
The incidence of bradycardia from dexmedetomidine ranges from 5% – 42%.
The 2016 study by Gerlach and colleagues found that bradycardia occurrence did not differ between patients who experienced dexmedetomidine-associated hypotension vs those who did not (6.6% vs 8.0%; P=0.82).
Elderly patients > 65 years are more likely to experience bradycardia as well as hypotension.
To bolus or not to bolus?
Dexmedetomidine produces a biphasic response as illustrated here:
So what happens when you bolus?
IV boluses produce a temporary high peak plasma concentration resulting in transient hypertension and bradycardia, courtesy of the baroreceptor reflex. Higher maintenance doses also cause high peak plasma concentrations which are sustained with associated hypertension.
A few minutes after bolusing, plasma concentrations decrease and vasodilation occurs due to α-2 receptor activation in vascular endothelial cells. This results in hypotension with a MAP drop of roughly 13-27% from baseline.
Troubleshooting hemodynamic issues:
Helpful tips include avoiding IV boluses, reducing the dose of boluses, or increasing the time over which boluses are delivered (administer them over 20 minutes instead of 10 minutes). For maintenance dosing, titrating the infusion no more frequently than every 30 minutes may also reduce the incidence of hypotension.
These tips are of particular significance for cardiac patients who rely on their heart rate to provide an adequate cardiac output (remember CO = HR x SV); high peak plasma concentrations from IV boluses or high maintenance doses in these patients could be problematic.
The Debrief
- The incidence of hypotension and bradycardia with dexmedetomidine is 24-56% and 5-42% respectively.
- Based on one retrospective study, the predictors of dexmedetomidine-associated hypotension include increased age, higher APACHE II scores, history of CAD, and a lower baseline MAP.
- To reduce the risk of hemodynamic instability, avoid bolusing, particularly in cardiac patients; if you do still choose to bolus, reduce the dose or increase the time over which the bolus is delivered to 20 minutes. Lastly, titrate the infusion no more frequently than every 30 minutes to reduce the risk of hypotension.
References
Weerink M, Struys M, Hannivoort L, et al. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017; 56: 893-913.
Gerlach A, Blais D, Jones G, et al. Predictors of Dexmedetomidine-Associated Hypotension in Critically Ill Patients. Int J Crit Illn Inj Sci. 2016; 6(3): 109-114.
Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com.
