Dexmedetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol: a randomized controlled trial
Liu et al. Critical Care
Dexmedetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol: a randomized controlled trial
Xu Liu 0
Kai Zhang 0
Wei Wang 0
Guohao Xie 0
Xiangming Fang 0
0 Department of Anesthesiology and Intensive Care Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University , 79 Qingchun Road, 310003 Hangzhou , China
Background: Atrial fibrillation occurs frequently in patients following cardiac surgery and can be a cause of increased morbidity and mortality. The use of dexmedetomidine to prevent atrial fibrillation is unclear. The present study was designed to evaluate the effect of dexmedetomidine sedation on the incidence of atrial fibrillation after cardiac surgery. Methods: Upon arrival to the intensive care unit (ICU), cardiac surgery patients without prior atrial fibrillation or flutter were randomized to receive either dexmedetomidine (0.2-1.5 μg/kg/h) or propofol (0.3-3 mg/kg/h) open-label titrated to a target Richmond agitation-sedation scale of 0 to -3. Our primary endpoint was the incidence of postoperative atrial fibrillation, and the secondary end points were the length of ICU stay, length of hospital stay, and hospital costs. Results: Atrial fibrillation occurred in 6 of 44 patients (13.6 %) in the dexmedetomidine group compared to 16 of 44 patients (36.4 %) in the propofol group (odds ratio = 0.28; 95 % confidence interval, 0.10, 0.80; P = 0.025). The median (interquartile range) length of ICU stay in the dexmedetomidine group was significantly lower than in the propofol group (2.9 (2.4-3.5) vs 3.5 (2.7-4.5 days, P = 0.008), with a trend toward a decrease in median hospital costs (86,367 vs 77,874 Chinese yuan; P = 0.068). The incidence of hypotension was higher in the dexmedetomidine group than in the propofol group (25/44 (56.8 %) vs 13/44 (29.5 %); P = 0.017). Conclusions: Dexmedetomidine sedation reduced the incidence of new-onset postoperative atrial fibrillation and shortened the length of ICU stay in patients after cardiac surgery compared to propofol sedation. Dexmedetomidine treatment was associated with more episodes of hypotension. Trial registration: chictr.org.cn: ChiCTR-IPR-16008231, retrospectively registered: April 6, 2016. This trial was not prospectively registered due to a lack of importance applied to trial registration.
Atrial fibrillation; Cardiac surgery; Dexmedetomidine; Propofol; Sedation
Atrial fibrillation (AF) is the most common complication
and the most common arrhythmia detected following
cardiac surgery [1–4]. The incidence of AF in patients
after cardiac surgery has been reported to range between
15 and 50 % [5–7], with patients undergoing valve
surgery being at the greatest risk . In addition, AF
most commonly occurs within 4 days postoperatively
[5, 8]. Postoperative AF is associated with a prolonged
hospital stay, higher costs, and increased morbidity
and mortality [4–8].
Although a number of prophylactic strategies for the
prevention of postoperative AF have been proposed, they
are not routinely implemented in many clinical centers
[9, 10], including ours. The major reasons for non-use
include a lack of convincing evidence, potential risks
associated with current drug therapies, and complexity
of some prevention regimens [11, 12]. Sedatives and
analgesics are routinely administered to most patients
undergoing cardiac surgery to reduce anxiety and pain
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[13, 14]. Dexmedetomidine has been used as a safe and
efficacious sedative agent in patients undergoing cardiac
surgery [15, 16], without pro-tachyarrhythmic or
negative inotropic effects . Moreover, dexmedetomidine
is associated with decreased incidence of postoperative
supraventricular and ventricular tachyarrhythmia and
has been found to terminate supraventricular tachycardia
in pediatric patients [18–20]. Recently, two retrospective
studies also showed that dexmedetomidine sedation might
decrease atrial arrhythmia in adult patients after
cardiovascular surgery [21, 22]. It appears that dexmedetomidine
sedation would be a good choice for the prevention of
postoperative AF. However, previous studies have been
subject to selection bias and many confounders due to the
observational design. Furthermore, the aforementioned
studies did not directly compare dexmedetomidine with
propofol, which is used in current standard practice for
sedation after cardiac surgery.
We designed and implemented a prospective
randomized controlled trial (RCT) to determine whether
dexmedetomidine reduces the incidence of
postoperative AF while effectively sedating mechanically
ventilated patients after cardiac surgery, when compared
to propofol sedation.
This prospective randomized controlled clinical trial was
approved by the Ethics Committee of the First Affiliated
Hospital of Zhejiang University and registered at
chictr.org.cn (ChiCTR-IPR-16008231). This study was
conducted in the First Affiliated Hospital of Zhejiang
University between January 2015 and December 2015.
Written informed consent was obtained from the patient
or next of kin before enrollment. The inclusion criteria
were as follows: age ≥18 years, elective cardiac surgery
with cardiopulmonary bypass (CPB), admitted to
intensive care unit (ICU) while intubated and ventilated, and
lack of prior AF or flutter before receiving sedation in
the ICU. Patients were excluded when they had at least
one of the following characteristics at arrival in the ICU:
heart rate <50 beats per minute, atrioventricular
conduction block of grade II or III (unless a pacemaker had
been installed), mean arterial pressure (MAP) <55 mmHg
(despite appropriate intravenous volume replacement
and vasopressor treatment), acute severe neurological
disorder, propofol or dexmedetomidine allergy or other
contraindications. In addition, patients who had received
two or more sedatives within 24 h postoperatively were
Randomization, masking and intervention
Patients received standard anesthesia including
induction with midazolam and sufentanil and paralysis with
cisatracurium and maintenance with sevoflurane, propofol
and sufentanil. During CPB, the administration of
sevoflurane was stopped. The bypass circuit was primed with
1000 mL of lactated Ringer solution, 100 mL of 5 % sodium
bicarbonate and 200 mL of 20 % mannitol. Prior to aortic
cannulation, heparin was adjusted to maintain an activated
clotting time longer than 450 seconds. The pump flow rates
ranged from 1.8 to 2.4 L/min/m2. The core temperature
was controlled at 32 to 34 °C using a heat exchanger in the
bypass circuit. After surgery, the patients were transferred
to the ICU. Upon arrival at the ICU, the patient’s blood
pressure, electrocardiograms and oxygen saturation were
monitored. The patients were randomized in a 1:1 ratio to
receive sedation with either propofol (control) or
dexmedetomidine according to the random number table.
Dexmedetomidine or propofol was continuously
infused without a loading dose. Sedation levels were
evaluated with the Richmond agitation-sedation scale (RASS),
which ranges from −5 (unarousable) to 4 (combative).
An assessment of RASS was performed every 2 h or
more often if required (e.g., if the patient’s condition
changed). The intravenous infusion speed of
dexmedetomidine (≤1.5 μg/kg/h) or propofol (≤3 mg/kg/h) was
adjusted to maintain RASS values between 0 and -3
[23, 24]. When hypotension (MAP <65 mmHg) and/or
bradycardia (heart rate <60 beats/minute) lasted longer
than 5 minutes, the infusion of the sedative was stopped
until the patient exhibited blood pressure and heart rate
within an acceptable range. The infusion of the sedative
was stopped before extubation at the discretion of the
Sufentanil was continuously infused (usually at a rate
of 0.06 μg/kg/h) for intravenous analgesia and
discontinued until a total dose of 200 μg had been administered.
Pain was assessed using the visual analog scale (VAS)
(range 0 (no pain) to 10 (maximal pain)). If the VAS
score was >3 , additional analgesia (morphine or
tramadol) was provided.
The primary outcome was the incidence of AF within
96 h of surgery. Postoperative AF was defined as no
consistent P waves before each QRS complex and an
irregular ventricular rate . Each patient underwent
continuous electrocardiographic monitoring for at least
96 h after surgery. The investigators recorded the time
of AF onset when they detected AF on the
electrocardiogram displayed on the bedside monitor, and a
twelvelead electrocardiographic recording was performed to
confirm the rhythm if necessary. AF episodes lasting
longer than 5 minutes were recorded .
Adverse events recorded during the ICU stay included:
bradycardia (heart rate <60 beats/minute for >5 minutes
), hypotension (MAP <65 mmHg for >3 minutes),
and postoperative nausea/vomiting and delirium
(identified with a confusion assessment method for the ICU).
Acute kidney injury was diagnosed according to Acute
Kidney Injury Network (AKIN) criteria: an absolute
increase in serum creatinine ≥26.4 μmol/L, percentage
increase in serum creatinine ≥50 % (1.5-fold from
baseline), or urine output <0.5 ml/kg/h for >6 h within 48 h
after surgery . The intubation time (time from ICU
admission to the time of extubation), length of ICU stay,
length of (postoperative) hospital stay and hospital fees
were also recorded.
Sample size determination was based on an expected
35 % occurrence of postoperative AF in the propofol
group and an expected 10 % occurrence of AF in the
dexmedetomidine group [11, 22, 28]. At a significance
level of 0.05 with a power of 0.80, the resulting sample
size was 40 patients in each group. Anticipating a
dropout rate of approximately 10 %, a sample size of 45
patients in each group was considered to be appropriate.
Data were described using descriptive statistics and
presented as the median (interquartile range) unless
indicated otherwise. All continuous variables were analyzed
using the Mann-Whitney U test due to the relatively
small numbers. Categorical variables were compared
using the Fisher exact test. Kaplan-Meier curves were
generated for postoperative AF. SPSS (SPSS 16.0 for
Windows; SPSS, Chicago, IL, USA) and GraphPad Prism
5.04 (GraphPad Software, La Jolla, CA, USA) were used
for statistical analyses. A P value <0.05 (two-sided) was
regarded as statistically significant.
A total of 479 patients were assessed for eligibility after
cardiac surgery with CPB (Fig. 1). After 389 patients
were excluded, 90 patients were randomly assigned to
two groups: 45 patients received propofol and 45
patients received dexmedetomidine. One patient in each
group was also infused with the other sedative within
24 h after surgery. Therefore, 44 patients in each group
were included in the analysis. There were no differences
between the groups in baseline demographic and
surgical characteristics (Table 1).
There were 22 patients who had AF during the first
96 h after cardiac surgery with CPB. Patients assigned to
receive dexmedetomidine were significantly less likely to
have AF than patients assigned to receive propofol (6
(13.6 %) vs 16 (36.4 %); odds ratio, 0.28; 95 % confidence
interval, 0.10, 0.80; P = 0.025; number needed to treat,
4.4) (Table 2). The relative risk reduction was 62.6 %.
The Kaplan-Meier incidence of postoperative AF in the
dexmedetomidine group and propofol group is shown in
Fig. 2. In patients who had received dexmedetomidine,
the median onset of AF tended to be delayed compared
with control patients (Table 2).
One patient in the propofol group died on the second
postoperative day due to cardiac failure. There were no
statistically significant differences between the groups in
peak postoperative cardiac troponin I (cTnI),
bradycardia, nausea and vomiting, mechanical ventilation ≥24 h,
acute kidney injury, or delirium (Table 2). However, the
incidence of hypotension was significantly higher in the
dexmedetomidine group than in the propofol group
(Table 2). Patients with hypotension recovered quickly
Fig. 1 Consort flow diagram of the study participants
Body mass index, kg/m2
New York Heart
Type of operation
Mitral valve surgery
Aortic valve surgery
CABG+ valve surgery
Other cardiac surgery
47.3 (36.6–67.1) 50.7 (34.2–62.4)
Data are presented as the median (interquartile range) or number (%).
aVentricular pacing. CABG coronary artery bypass graft
after intravenous fluid replacement and/or adjusting the
infusion speed of vasoactive drugs. The details of
sedation and analgesia are reflected in Table 3.
Medical resource utilization is also reported in Table 2.
Although the intubation time, length of hospital stay
and postoperative hospital days were similar in the two
groups, the length of ICU stay was significantly shorter
in the dexmedetomidine group than in the propofol
group (2.9 (2.4–3.5) vs 3.5 (2.7–4.5 days, P = 0.008), with
a trend toward a decrease in median hospital fees
(86,367 vs 77,874 Chinese yuan, P = 0.068). Patients who
experienced postoperative AF were significantly older
65.0 (57.0–71.0) 65.0 (56.8–71.0)
Acute kidney injury
Intubation time, h
25.5 (19.5–36.4) 40.4 (19.3–53.1)
Table 2 Postoperative characteristics and resource utilization of
Length of ICU stay, days
Postoperative hospital days
21.2 (17.0–22.8) 21.0 (16.9–22.5)
14.0 (11.0–17.0) 13.5 (11.3–17.0)
8.64 (7.32–9.63) 7.79 (6.72–9.05)
Data are presented as the number (%) or median (interquartile range).
AF atrial fibrillation, cTnI cardiac troponin I, ICU intensive care unit
Fig. 2 Kaplan-Meier incidence of postoperative atrial fibrillation
according to treatment group
Table 3 Details of sedation and analgesia in propofol and
Propofol (n = 44) Dexmedetomidine P value
(n = 44)
889 (645 to 1000) 870 (725 to 1019)
Data are presented as the median (interquartile range) or n (%). aNumber of
patients who received extra analgesic treatment within 24 h after surgery.
RASS Richmond agitation-sedation scale, VAS visual analog scale
and had a longer ICU stay, more postoperative hospital
days and higher hospital fees compared to patients
without postoperative AF (Table 4).
To our knowledge, the current study is the first
prospective randomized trial confirming that
dexmedetomidine sedation reduces new-onset postoperative AF
and shortens the length of ICU stay with a trend toward
a decrease in hospital costs, compared to propofol
sedation. The absolute risk reduction for AF was 22.8 % in
patients following cardiac surgery, with a number
needed to treat of 4.4, suggesting that dexmedetomidine
administration during the early postoperative period
could prevent one case of AF for every five patients.
In addition, our results also demonstrated that
postoperative AF was associated with a longer stay in the
ICU, more postoperative hospital days and increased
Dexmedetomidine is an α2 adrenergic receptor agonist
that induces sedative, anxiolytic and analgesic effects
without causing respiratory depression [18, 29] and has
been increasingly used for sedation in cardiac surgery
patients [16, 29]. A small retrospective study (n = 45)
reported that patients undergoing cardiovascular surgery
who received dexmedetomidine were less likely to have
new-onset AF than patients who did not receive any
sedative drugs , which supports the results of the
current study. However, a recent meta-analysis showed
that dexmedetomidine was not associated with a
decrease in the incidence of postoperative AF in patients
undergoing cardiac surgery . The potential reasons
for this inconsistency may be the fact that postoperative
AF was not the primary outcome, an explicit and
consistent definition of AF was lacking, different
observation periods were used for detecting AF, a large variety
of types of surgery and drug regimens were included in
those studies [31–36], and patients with prior AF were
not excluded in most studies [31–35]. Some patients
had a history of chronic, recurrent AF that was resistant
to chemical cardioversion . Consequently, the
inclusion of patients with prior AF in the study may have
concealed the efficacy of dexmedetomidine to reduce
Several potential factors could contribute to the effect
of dexmedetomidine on preventing new-onset
postoperative AF. First, dexmedetomidine could reduce myocardial
ischemia-reperfusion injury and improve the perfusion of
the myocardium in patients undergoing cardiac surgery
[16, 36]. Second, the inflammatory response induced by
cardiac surgery and bypass can alter atrial
electrophysiology and structural substrates, leading to increased
vulnerability to AF [14, 37]. Dexmedetomidine has been
shown to inhibit the inflammatory response in animal
models [38, 39] and in clinical trials [40, 41]. Tasdogan
et al.  found that postoperative patients who received
dexmedetomidine had significantly lower levels of tumor
necrosis factor-alpha, interleukin-1 and interleukin-6 than
those who received propofol. Third, increased adrenergic
tone plays a role in the development of postoperative AF
Table 4 Comparison of patients with and without atrial fibrillation (AF) or flutter
Patients with AF (n = 22)
Patients without AF (n = 66)
Female gender, n (%)
Body mass index, kg/m2
Cardiopulmonary bypass time, minutes
Cross-clamp time, minutes
Intubation time, h
Length of ICU stay, days
Length of hospital stay, days
Postoperative hospital days
Hospital fees, Chinese yuan, ×104
Data are presented as the median (interquartile range) unless otherwise stated. ICU intensive care unit
. Dexmedetomidine can decrease catecholamines 
and inhibit the arrhythmogenic effect of epinephrine .
Fourth, dexmedetomidine can enhance vagal activity,
leading to alterations in Ca2+ currents across the myocyte
cell membrane, which in turn could result in prolonged
repolarization and an increased effective refractory period
. Based on the combination of organ-protective,
antiinflammatory, sympatholytic and parasympathomimetic
effects, it is not surprising that the use of
dexmedetomidine during the early postoperative period could be
beneficial in preventing AF after cardiac surgery.
An increased risk of bradycardia and hypotension can
be a concern of dexmedetomidine [23, 24]. In this study,
hypotension was more common among
dexmedetomidinetreated patients despite the similar levels of sedation
attained by patients treated with dexmedetomidine
and propofol. However, hypotension was quickly
rectified after intravenous fluid replacement and/or
adjusting the infusion speed of the vasoactive or sedative
drug, which rarely necessitated stopping the study in
This study has several limitations. Fist, there was no
blinding of the propofol and dexmedetomidine infusions
in our study. However, the diagnosis of AF was made by
continuous electrocardiogram (ECG) monitoring and/or
12-lead ECG, and the practitioners who identified AF
were not aware of the study objectives.
Second, routine prophylactic strategies for
postoperative AF, such as the perioperative use of β-blockers, were
not implemented in our study. The choice of
antiarrhythmic medications was left to the discretion of the
attending physicians, but physicians chose drugs
according to local guidelines. For example, digitalis was usually
used to slow the ventricular rate during AF in our ICU.
Furthermore, the attending physicians were also unaware
of the study objectives. More patients received digitalis in
the propofol group than in the dexmedetomidine group
(see Additional file 1), which is mostly due to a greater
number of postoperative AF incidents among patients
Third, although the elderly patients were more likely to
have postoperative AF, the patients in this study were
younger than those in most other studies (mean age, 54 vs
approximately 65 years) [1, 3, 31]. Moreover, only 16
patients in our study (18.2 %) were ≥65 years old. Therefore,
additional studies are needed to investigate the effects of
dexmedetomidine on the prevention of postoperative AF
in elderly patients after cardiac surgery.
Fourth, tests about the secondary end points (e.g., the
length of ICU stay) and the incidence of adverse events
(e.g., hypotension) were performed without adjusting for
multiple testing in this study. Therefore, these results are
explorative and confirmatory studies are needed. However,
our primary endpoint, the incidence of postoperative AF,
was a single primary endpoint and therefore no
adjustments are needed .
Our results demonstrated that the use of
dexmedetomidine might be efficacious in the prevention of
postoperative AF and could be beneficial in reducing medical
resource utilization in patients after cardiac surgery.
Larger RCTs are needed to confirm our findings.
Patients with new onset postoperative AF were
significantly older and had a longer ICU stay, more
postoperative hospital days and increased hospital
Dexmedetomidine sedation reduced new-onset
postoperative AF and shortened the ICU stay in
patients after cardiac surgery compared to propofol
The administration of dexmedetomidine during the
early postoperative period could prevent one case of
AF for every five patients undergoing cardiac
Additional file 1: Table S1. Postoperative medication use of the
patients in propofol and dexmedetomidine groups. Description of data:
medications were used within 96 h after cardiac surgery (DOCX 13 kb)
AF: Atrial fibrillation; AKIN: Acute Kidney Injury Network; BMI: Body mass
index; CK-MB: Creatine kinase-MB; COPD: Chronic obstructive pulmonary
disease; CPB: Cardiopulmonary bypass; cTnI: Cardiac troponin I;
ECG: Electrocardiogram; ICU: Intensive care unit; LVEF: Left ventricular
ejection fraction; MAP: Mean arterial pressure; NYHA: New York Heart
Association; RASS: Richmond agitation-sedation scale; RCT: Randomized
controlled trial; VAS: visual analog scale
XL participated in the design of the study, collected the data, performed the
statistical analysis and drafted the manuscript. KZ participated in the design
of the study, collected the data and helped to draft the manuscript. WW
participated in the design of the study, collected the data and helped to
revise the manuscript. GHX performed the statistical analysis and revised the
manuscript. XMF conceived of the study, and participated in its design and
coordination and revised the manuscript. All authors read and approved the
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
The trial was approved by the Ethics Committee of the First Affiliated Hospital
of Zhejiang University and registered at chictr.org.cn (ChiCTR-IPR-16008231).
Written informed consent was obtained from the patient or next of kin
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