There was a decreasing trend for new-onset atrial fibrillation incidence with higher cumulative doses of dexmedetomidine.
Results from a recent cohort study have found that treatment with dexmedetomidine was associated with a decreased risk of new-onset atrial fibrillation in patients with critical illness, suggesting that it may be warranted to evaluate this association in future studies.
Atrial fibrillation is the most common type of arrhythmia in patients with critical illness, with reported incidence ranging from 10% to 44% in patients with sepsis. In the intensive care unit (ICU), new-onset atrial fibrillation is characterized by rapid structural remodeling due to inflammation that provides an arrhythmogenic atrial substrate and is trigged by potentially reversible factors, such as proarrhythmic drugs, electrolyte imbalance, and volume overload.
Dexmedetomidine is a highly selective a2 receptor agonist widely used for sedation in patients with critical illness. It targets receptors within the locus coeruleus and exerts an analgesic effect via receptors in the spinal cord. The dose-dependent sedative effect is well understood and does not result in clinically significant respiratory depression.
Furthermore, dexmedetomidine may benefit patients with critical illness via its sympatholytic activity that is associated with reduced heart rate and depressed sinus node and atrial ventricular node conduction. Studies have also found that dexmedetomidine was associated with cytokine transcription and inhibited inflammation, suggesting that it may be a potential treatment associated with decreased risk of new-onset atrial fibrillation.
In their study, investigators used the Medical Information Mart for Intensive Care (MIMIC)-IV database for primary analysis. The analysis focused on patients who started treatment with dexmedetomidine early after ICU admission and excluded patients who started dexmedetomidine 48 hours after ICU admission. Eligible patients were divided into 2 groups: those who received dexmedetomidine within 48 hours of ICU admission and those who never received dexmedetomidine.
New-onset atrial fibrillation occurred in 371 patients (17.6%) in the dexmedetomidine group compared with 1323 patients (22.4%) in the no dexmedetomidine group. Administration of dexmedetomidine was associated with reduced risk of new-onset atrial fibrillation and this association remained in sensitivity analyses.
To evaluate the dose-dependent association of dexmedetomidine with new-onset atrial fibrillation, the cumulative dose of dexmedetomidine from ICU admission to day 7 in the ICU was stratified into 4 groups. The investigators found that there was a decreasing trend for new-onset atrial fibrillation incidence with higher cumulative doses.
Among patients who developed new-onset atrial fibrillation, the median time from ICU admission to atrial fibrillation onset was significantly longer in the dexmedetomidine group than the no dexmedetomidine group, at 2.1 days and 1.3 days, respectively. No significant differences were observed in the use of medications for rate control, rhythm control, or electrical cardioversion.
Patients in the dexmedetomidine group had a longer median length of stay in the ICU and hospital than the non-dexmedetomidine group. However, in-hospital mortality was significantly lower in the dexmedetomidine group, with 132 patients (6.3%) versus 758 (12.8%), respectively.
This finding suggests that when patients developed new-onset atrial fibrillation without administration of dexmedetomidine, there was an additional risk of mortality beyond the combined risk of no dexmedetomidine and new-onset atrial fibrillation development. Although the underlying biological mechanisms are unclear, the authors said a potential explanation may be that the pleiotropic effect of dexmedetomidine on immunomodulation, sympatholytic activity, and hemodynamics is synergistic in the presence of new-onset atrial fibrillation.
Song MJ, Jang Y, Lee JH, Yoon JH, Kim DJ, Jung SY, et al. Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness. JAMA Netw Open. 2023;6(4):e239955. doi:10.1001/jamanetworkopen.2023.9955.