j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 1 9 4 e2 0 0

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.JournalofSurgicalResearch.com

Comparison of dexmedetomidine versus propofol

on hemodynamics in surgical critically ill patients

Ya-Fei Chang, BS,a,b,c Anne Chao, MD,d Po-Yuan Shih, MD,d

Yen-Chun Hsu, MD,d Chen-Tse Lee, MD,d Yu-Wen Tien, MD, PhD,b
Yu-Chang Yeh, MD, PhD,d,* and Lee-Wei Chen, MD, PhD,a,e,** behalf of
the NTUH Center of Microcirculation Medical Research (NCMMR)
a
Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C
b
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, R.O.C
c
Department of Nursing, National Taiwan University Hospital, Taipei, Taiwan, R.O.C
d
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C
e
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C

article info abstract

Article history: Background: Sedation with dexmedetomidine and propofol may cause hypotension or
Received 29 December 2017 bradycardia. This study aimed to compare the effects of dexmedetomidine and propofol on
Received in revised form hemodynamics and clinical outcomes in surgical intensive care unit (ICU) patients after
6 March 2018 major abdominal surgery.
Accepted 15 March 2018 Materials and methods: Enrolled patients were randomly allocated to the dexmedetomidine
Available online 11 April 2018 or propofol group. Cardiac index was measured using a continuous noninvasive cardiac
output monitor on the basis of chest bioreactance. Heart rate, blood pressure, opioid
Keywords: requirement, urine output, delirium incidence, ICU length of stay, and total hospital length
Abdominal surgery of stay were compared between the two groups. The incidences of bradycardia, hypoten-
Cardiac index sion, and severe low cardiac index were compared.
Dexmedetomidine Results: We enrolled 60 patients. Heart rate and mean arterial pressure were significantly
Propofol lower in the dexmedetomidine group than in the propofol group. Cardiac index did not
Sedation differ significantly between the two groups (dexmedetomidine group 3.1 L/min/m2, [95%
confidence interval {95% CI} 2.8-3.3] versus propofol group 3.2 L/min/m2 [95% CI 2.9-3.5],
P ¼ 0.578). The incidences of bradycardia, hypotension, and severe low cardiac index did
not differ significantly between the two groups.
Conclusions: Cardiac index did not differ significantly between the dexmedetomidine and
propofol groups in surgical ICU patients after major abdominal surgery.
ª 2018 Elsevier Inc. All rights reserved.

* Corresponding author. Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C. Tel.: þ886 2
23562158; fax: þ886 2 23415736.
** Corresponding author. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, and Department of
Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. Tel.: þ886 2 2826 7931; fax: þ886 2 2827 9556.
E-mail addresses: tonyyeh@ntuh.gov.tw (Y.-C. Yeh), chenlw2001@yahoo.com.tw (L.-W. Chen).
0022-4804/$ e see front matter ª 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jss.2018.03.040
 chang et al  dexmedetomidine versus propofol
Introduction
The clinical practice guidelines of the American College of
Critical Care Medicine for the management of pain, agitation,
and delirium have aided clinicians in efficiently managing
patients in adult intensive care unit (ICU) patients.1,2 The
guidelines aim to ameliorate the harmful effects of pain,
agitation, and delirium and to improve clinical outcomes.
They also suggest that dexmedetomidine or propofol may be
preferred over sedation with benzodiazepines to improve
clinical outcomes in critically ill patients receiving mechanical
ventilation.2 Dexmedetomidine is a highly selective a2-adre-
noreceptor agonist3,4 with sedative, anxiolytic, and analgesic
effects.5-7 Dexmedetomidine does not cause respiratory
depression. Bradycardia and hypotension are the most
frequent adverse events with dexmedetomidine.8-11 Propofol
acts on gamma-aminobutyric acid receptors and is commonly
used in the induction of general anesthesia and sedation of
critically ill patients. Bradycardia, hypotension, and respira-
tory depression are the most frequent adverse events with
propofol, and propofol infusion syndrome is a rare but
potentially lethal side effect of propofol.11-13
Several studies have compared the effects of dexmedeto-
midine and propofol on heart rate and blood pressure.9,14,15 To
the best of our knowledge, no study has compared the effects
of dexmedetomidine and propofol on cardiac output in adult
ICU patients. Only one study, however, reported that propofol
infusion, but not dexmedetomidine infusion, can increase
preload dependency and fluid responsiveness in critically ill
patients with circulatory failure.16 Low cardiac output may
cause tissue hypoperfusion and multiorgan dysfunction.
Thus, comparing the effect of dexmedetomidine and propofol
on cardiac output is crucial. With advancements in the bio-
reactance technique,17,18 cardiac output and stroke volume
can be continuously measured using a noninvasive cardiac
output monitor. The present study primarily compared the
effects of dexmedetomidine and propofol on cardiac index in
adult surgical ICU patients after major abdominal surgery.
Furthermore, we compared the effects of dexmedetomidine
and propofol on heart rate, blood pressure, stroke volume
index (SVI), opioid requirement, urine output, delirium inci-
dence, ICU length of stay, total hospital length of stay, and
total hospital cost.
Materials and methods
Study population
This single-blinded, randomized controlled trial was approved
by the Research Ethics Committee of National Taiwan Uni-
versity Hospital (approval number: 201407023MINA) and
registered on the ClinicalTrials.gov protocol registration sys-
tem (ID: NCT02393066). The study was conducted in a surgical
ICU of an Academic Medical Center in Taiwan between
October 2014 and June 2015. Patients aged from 20 to 99 y were
evaluated by the research assistant and consented to partici-
pate in this study before undergoing major abdominal sur-
gery. Exclusion criteria included refractory bradycardia less
195
than 60 beats per minute (bpm), high degree atrioventricular
block (second or third degree), refractory shock despite
resuscitation (mean arterial pressure [MAP] <60 mm Hg), new
onset of myocardial infarction, New York Heart Association
Class IV heart failure, acute physiology and chronic health
evaluation II score >30, severe liver cirrhosis (ChildePugh
class B or C), organ transplantation within 1 y, pregnancy,
known allergic history to dexmedetomidine or propofol,
enrolled in other clinical trial of dexmedetomidine or propofol
within 1 mo, signed consent of do not resuscitate, other con-
ditions determined by surgeon or primary intensivist, and
non-native speaker.
Study protocol
Patients who were transferred to the surgical ICU after surgery
were enrolled and randomly assigned into two groups (dex-
medetomidine or propofol group) on the basis of computer-
generated randomization codes in sealed envelopes. The
principal investigator or research assistant assigned the sed-
atives to the patients, and patients were unaware of their
assigned group. All patients received routine postoperative
care, and the goal of postoperative pain management was to
achieve an 11-point pain intensity numeric rating scale (0 ¼ no
pain and 10 ¼ worst possible pain) of <4. When patients were
arousable and had a Richmond Agitation-Sedation Scale of >0,
dexmedetomidine or propofol was administered by contin-
uous infusion according to their grouping. Patients in the
dexmedetomidine group received continuous intravenous
infusion of dexmedetomidine (Precedex; Hospira) with a
dosage ranging from 0.1 to 0.7 mcg/kg/h. Patients in the pro-
pofol group received continuous intravenous infusion of pro-
pofol (Propofol-Lipuro 1%; B. Braun, Germany) with a dosage
ranging from 0.3 to 1.6 mg/kg/h. The loading dose was omitted
to prevent rapid hemodynamic changes in both groups. An
infusion dosage of 0.1-0.7 mcg/kg/h of dexmedetomidine was
reported to be equivalent to that of 0.3-1.6 mg/kg/h of propo-
fol.19 The infusion rates of dexmedetomidine or propofol were
titrated to achieve a goal of Richmond Agitation-Sedation
Scale of 0 to 2.19,20 The infusion was continued for 24 h as
required. After 24 h, primary intensivists selected the seda-
tives. We recorded the accumulated dose of analgesics, and
the dose of fentanyl was converted into an equivalent dose of
morphine. If the total infusion time of dexmedetomidine or
propofol was <2 h or a severe bradycardia (heart rate <50 bpm
for >5 min) developed, the patient was withdrawn from the
study. Within the data safety monitoring plan, an interim
analysis was conducted when 30 participants were enrolled to
determine the safety and adequacy. If the incidence of
adverse events or survival rate was significantly different be-
tween the two groups, the decision of continuance, suspen-
sion, or termination of study would be discussed and decided.
Study outcomes
The primary outcome of this study was the difference in
cardiac index between the dexmedetomidine and propofol
groups. Under the condition of a cardiac index of 3.0 L/min/m2
with a standard deviation of 0.7 L/min/m2, one side a ¼ 0.05,
196 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 1 9 4 e2 0 0
and b ¼ 0.2, 30 patients in each group have the power to detect
a difference of 0.5 L/min/m2 of cardiac index between the two
groups. The secondary outcomes of this study were differ-
ences in heart rate, blood pressure, SVI after infusion of sed-
atives; opioid requirement, urine output, incidence of
delirium at 24 h; ICU length of stay, and total hospital length of
stay. We also compared the incidences of that patients who
had one or more episodes of bradycardia (heart rate <60 bpm),
hypotension (MAP <60 mm Hg), and severe low cardiac index
(cardiac index <2.0 L/min/m2) between the two groups. Car-
diac index and SVI were continuously monitored using a
noninvasive cardiac output monitor on the basis of chest
bioreactance (NICOM; Cheetah Medical Inc, Portland, OR).18,21-
23
Systolic blood pressure, diastolic blood pressure, and MAP
were continuously monitored using a radial artery catheter.
Opioid requirement was defined as the morphine equivalent
dose. Delirium was diagnosed using the confusion assess-
ment method for the ICU.24
Statistical analysis
All data were analyzed using SPSS, version 20 (IBM SPSS,
Chicago, IL). Continuous data are described as
mean  standard deviation and were tested by Student’s t-test
or as the median (interquartile range) and were tested by
ManneWhitney U-test, where appropriate. Categorical vari-
ables are described as percentage and were compared using
the chi-square or Fisher exact test, where appropriate. Mean
difference at different time points were investigated using
two-way repeated measures analysis of variance (with time
and group factors), the means of which were described as the
mean with 95% confidence interval (95% CI). A P value of <0.05
was considered statistically significant.
Results
We screened 131 eligible patients, and 60 patients were
enrolled and randomized (Fig. 1). The baseline characteristics
did not differ significantly between the two groups (Table 1).
The mean infusion rate of dexmedetomidine and propofol
Fig. 1 e Consort study flow chart. The flow of patients
through the randomized clinical trial.
was 0.17  0.06 mcg/kg/h and 0.42  0.08 mg/kg/h, respec-
tively. The mean infusion time of dexmedetomidine and
propofol was 22  4 h and 22  3 h, respectively. At 12 and 24 h,
the net fluid balance did not differ significantly between
dexmedetomidine and propofol groups, respectively
(1089  650 mL versus 930  797 mL, P ¼ 0.398; 1919  902 mL
versus 1634  1080 mL; P ¼ 0.271).
Hemodynamic parameters
Results of repeated measures analysis of variance revealed
that the cardiac index did not differ significantly throughout
the first 12 h of infusion (dexmedetomidine group 3.1 L/min/
m2 [95% CI 2.8-3.3] versus propofol group 3.2 L/min/m2 [95% CI
2.9-3.5], P ¼ 0.578) (Fig. 2) nor did the incidence of severe low
cardiac index (dexmedetomidine group 23% versus propofol
group 14%, P ¼ 0.614) or the SVI. Heart rate, systolic blood
pressure, diastolic pressure, and MAP are presented in
Figure 3. The mean heart rate was lower in the dexmedeto-
midine group (78 bpm [95% CI 73-82]) than in the propofol
group (87 bpm [95% CI 83-92], P ¼ 0.003). The incidence of
bradycardia did not differ significantly between the two
groups (dexmedetomidine group 13% versus propofol group
7%; P ¼ 0.672). MAP was lower in the dexmedetomidine group
(81 mm Hg [95% CI 78-84]) than in the propofol group (91 mm
Hg [95% CI 87-94], P <0.001). The incidence of hypotension did
not differ significantly between the two groups (dexmedeto-
midine group 7% versus propofol group 3%; P ¼ 1.000). Two
patients in the dexmedetomidine group required continuous
infusion of norepinephrine. One of them was a 60-y-old male
patient, with a medical history of hypertension and hepatitis
B, who received atypical hepatectomy. His lactate level was
3.3 mmol/L before enrollment. His condition improved within
23 h after lowering the infusion rate of dexmedetomidine to
0.1 mcg/kg/h and supplementing fluids; the highest infusion
rate of norepinephrine was 0.04 mcg/kg/min. The lowest
cardiac index was 4.5 L/min/m2 at 2 h. The other patient was
an 82-y-old male patient, with a medical history of hyper-
tension, coronary arterial disease, and chronic obstructive
pulmonary disease. This patient had received colorectal sur-
gery. His lactate level was 2.6 mmol/L before enrollment. The
highest infusion rate of norepinephrine was 0.17 mcg/kg/min,
and the lowest cardiac index was 2.1 L/min/m2 at 6 h. His
hypotension resolved after 12 h without sequela, and his
cardiac index was 2.9 L/min/m2 at 24 h.
Opioid requirement, urine output, and clinical outcomes
At 24 h, the opioid requirement did not differ significantly
between the two groups (dexmedetomidine group: 33 [21-48]
mg versus propofol group: 30 [19-43] mg; P ¼ 0.459) nor did
urine output (dexmedetomidine group: 1530 [1260-1970] mL
versus propofol group: 1850 [1180-2200] mL; P ¼ 0.387). No
patient experienced delirium in both groups within 24 h after
surgery. The Median ICU length of stay was not significantly
different between the two groups. The median total hospital
length of stay was shorter in the dexmedetomidine group
than in the propofol group (18 [13-27] d versus 25 [16-32] d;
P ¼ 0.042). The comparisons of investigating effects between
the two study medications are summarized in Table 2.
 chang et al  dexmedetomidine versus propofol 197

Table 1 e Baseline characteristics of the study population.

Baseline characteristics Dexmedetomidine (n ¼ 31) Propofol (n ¼ 29) P
Age (y/o) 71  12 70  10 0.64
Gender (male/female) 19/12 16/13 0.79
Height (cm) 161  10 159  9 0.55
Weight (kg) 61  17 60  9 0.70
Heart rate (beats/min) 76  10 75  9 0.74
Systolic blood pressure (mm Hg) 131  14 131  10 0.97
Diastolic blood pressure (mm Hg) 74  11 74  8 0.96
Mean arterial pressure (mm Hg) 93  11 93  8 0.85
APACHE II score 13  4 13  3 0.46
Medical history, n (%)
Atrial fibrillation 1 (3) 5 (17) 0.07
Coronary artery disease 7 (23) 5 (17) 0.61
Hypertension 22 (71) 18 (59) 0.33
Diabetes mellitus 9 (29) 10 (35) 0.66
COPD/asthma 3 (10) 1 (3) 0.34
Duodenal/gastric ulcers 5 (16) 5 (17) 0.91
Types of surgery, n (%)
Pancreatic or duodenal surgery 13 (42) 13 (45) 0.82
Gastric surgery 6 (19) 7 (24) 0.66
Intestinal surgery 6 (19) 7 (24) 0.66
Hepatic or cholecystic surgery 6 (19) 2 (7) 0.16

Data are presented as mean  standard deviation or n (%).

APACHE II ¼ acute physiology and chronic health evaluation II; COPD ¼ chronic obstructive pulmonary disease.

might have some potential clinical benefit for patients with

Discussion coronary heart diseases. Moreover, in our previous animal
study, we reported that surgical stress and pain contribute to
Our results revealed that although the heart rate and MAP tachycardia and hypertension, and it might result in an in-
were lower in the dexmedetomidine group than in the pro- testinal microcirculatory dysfunction.27 We found that dex-
pofol group, cardiac index did not differ significantly between medetomidine improves tachycardia, hypertension, and
the two groups. In addition, the incidence of hypotension and intestinal microcirculation.27 Further studies are warranted to
bradycardia did not differ between the two groups. We also investigate the potential benefit of dexmedetomidine on
observed that the median total hospital length of stay was microcirculation in surgical patients. The physiologic effects
shorter in the dexmedetomidine group than in the propofol of the two medications are shown in Figure 4.
group. The average age of our patients was 70 y, and our re-
sults reveal that low infusion rates of both drugs could provide
light-level sedation and prevent severe complications.
Maintaining adequate cardiac output is crucial for
providing adequate tissue perfusion to prevent multiple organ
dysfunction. Our results demonstrate that although MAP and
heart rate were lower in the dexmedetomidine group, cardiac
index and urine output did not differ significantly between the
two groups. Moreover, the 95% CI of mean heart rate, MAP,
and cardiac index in the dexmedetomidine group was >73
bpm, >78 mm Hg, and >2.8 L/min/m2, respectively; all pa-
rameters were in the normal range. Dexmedetomidine may
have a clinical benefit of preventing postoperative tachycardia
and hypertension, and two studies have reported that dex- Fig. 2 e Cardiac index (A) and stroke volume index (B). The
medetomidine provides a hemodynamic stabilization effect error bars represent 95% CIs of the means (n [ 31 in the
and reduces postoperative cardiovascular complications.25,26 dexmedetomidine group and n [ 29 in the propofol group).
In this study, a mean reduction of heart rate of 9 bpm seems Cardiac index and stroke volume index did not differ
clinically insignificant. However, for a 12-h period of obser- significantly between the two groups, as determined using
vation, it represents a total reduction of 6480 heart beats. This two-way repeated measures ANOVA.
198 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 1 9 4 e2 0 0

Fig. 3 e Heart rate (A), mean arterial pressure (B), systolic blood pressure (C), and diastolic blood pressure (D). The error bars
represent 95% CIs of the means (n [ 31 in the dexmedetomidine group and n [ 29 in the propofol group). Heart rate, MAP,
systolic blood pressure, and diastolic blood pressure were lower in the dexmedetomidine group than in the propofol group,
as determined using two-way repeated measures ANOVA.

In the present study, the median total hospital length of

stay was shorter in the dexmedetomidine group than in the
propofol group. This finding is consistent with that of Curtis
et al.28 that the mean hospital length of stay was shorter in the
Table 2 e Summary of effects of the two study
dexmedetomidine group than in the propofol group. Several
medications.
clinical benefits of dexmedetomidine may potentially
Effects Dexmedetomidine
contribute to shortening the hospital length of stay. These
versus propofol
clinical benefits may include reduction of postoperative ar-
rhythmias,29,30 lower incidence of delirium,29,31 being more Heart rate Slower
arousable and cooperative,15 and improved patient-ventilator Systolic blood pressure Lower
synchrony.32 By contrast, a retrospective study at an Aca- Diastolic blood pressure Lower
demic Medical Center reported that the use of dexmedeto- Mean arterial pressure Lower
midine was associated with longer ICU and hospital lengths of Cardiac index NS
stay.33 Because of the limited sample size of this study, we
Stroke volume index NS
cannot differentiate whether short hospital stay is due to
Incidences of
beneficial effects of dexmedetomidine or patients’ factors. In
Bradycardia (heart rate <60 beats NS
addition, several studies have reported that ICU or hospital
per minute)
costs were lower in the dexmedetomidine groups than in the
Hypotension (mean arterial NS
propofol groups.28,34,35
pressure <60 mm Hg)
Our study has several limitations. First, the research ethics
Severe low cardiac index (cardiac NS
committee of our hospital approved a maximum infusion
index <2 L/min/m2)
period of only 24 h for dexmedetomidine, and 18 patients were
12 h fluid balance NS
discharged (eight in the dexmedetomidine group and 10 in the
propofol group) before 24 h after admission to ICU. We did not 24 h fluid balance NS

compare the hemodynamic effects at 24 h after the infusion of 24 h opioid requirement NS

dexmedetomidine or propofol. Additional studies are required 24 h urine output NS
to compare the long-term effects of dexmedetomidine and Median hospital length of stay Shorter
propofol on hemodynamics. Second, the enhanced recovery
NS ¼ nonsignificant difference.
after surgery strategy was performed by surgical teams and
 chang et al  dexmedetomidine versus propofol
Fig. 4 e Physiologic effects of dexmedetomidine and propofol. GABA [ gamma-aminobutyric acid; M [ muscarinic;
SVR [ systemic vascular resistance. (Color version of figure is available online.)
anesthesiologists in our surgical patients, and 14 (45%) pa-
tients and 16 (55%) patients in the dexmedetomidine and
propofol group, respectively, were tracheally extubated in the
operation room. Thus, we did not compare the tracheal
extubation time between the two groups. Third, this study
excluded patients with severe heart failure and refractory
shock. Additional studies are warranted to investigate the
effect on cardiac index between dexmedetomidine and pro-
pofol in patients with limited cardiac output.
Conclusion
In conclusion, our results indicate that cardiac index did not
differ significantly between the dexmedetomidine and pro-
pofol groups during the 12-h infusion of sedatives in surgical
ICU patients after major abdominal surgery. Additional
studies may be warranted to determine the effects of lower
heart rate and other clinical benefits of dexmedetomidine on
patient’s outcomes and the hospital length of stay.
Acknowledgment
The authors thank Roger Lien (B.S.E., MicroStar Instruments
CO, Ltd, Taiwan) for providing technical assistance with
noninvasive cardiac output monitoring. The authors also
thank all participants of NTUH Center of Microcirculation
Medical Research (NCMMR).
Authors’ contributions: Y-.F.C. participated in the study
design, patient enrollment, interpreted the data, and drafted
the article. A.C. participated in revising the article. P-.Y.S. and
Y-.C.H. participated in patient enrollment and revised the
article. C-.T.L. interpreted the data and drafted the article. Y-
.W.T. participated in the study design and interpreted the
199
data. Y-.C.Y. and L-.W.C. participated in the study design,
interpreted the data, and drafted the article. All authors have
read and approved the final article.
Disclosure
There was neither financial nor other potential conflict of in-
terest for all authors.
references
1. Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice
guidelines for the sustained use of sedatives and analgesics in
the critically ill adult. Crit Care Med. 2002;30:119e141.
2. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines
for the management of pain, agitation, and delirium in adult
patients in the intensive care unit. Crit Care Med.
2013;41:263e306.
3. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline
receptor agonists. Their pharmacology and therapeutic role.
Anaesthesia. 1999;54:146e165.
4. Sanders RD, Maze M. Alpha2-adrenoceptor agonists. Curr Opin
Investig Drugs. 2007;8:25e33.
5. Arcangeli A, D’Alo C, Gaspari R. Dexmedetomidine use in
general anaesthesia. Curr Drug Targets. 2009;10:687e695.
6. Martin E, Ramsay G, Mantz J, Sum-Ping ST. The role of the
alpha2-adrenoceptor agonist dexmedetomidine in
postsurgical sedation in the intensive care unit. J Intensive
Care Med. 2003;18:29e41.
7. 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;64:37e44.
8. Ahmed S, Murugan R. Dexmedetomidine use in the ICU: are
we there yet? Crit Care. 2013;17:320.
9. Erdman MJ, Doepker BA, Gerlach AT, Phillips GS, Elijovich L,
Jones GM. A comparison of severe hemodynamic
disturbances between dexmedetomidine and propofol for
200 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 1 9 4 e2 0 0
sedation in neurocritical care patients. Crit Care Med.
2014;42:1696e1702.
10. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation
with dexmedetomidine vs lorazepam on acute brain
dysfunction in mechanically ventilated patients: the MENDS
randomized controlled trial. JAMA. 2007;298:2644e2653.
11. Ruokonen E, Parviainen I, Jakob SM, et al. Dexmedetomidine
for continuous sedation I: dexmedetomidine versus propofol/
midazolam for long-term sedation during mechanical
ventilation. Intensive Care Med. 2009;35:282e290.
12. Fong JJ, Kanji S, Dasta JF, Garpestad E, Devlin JW. Propofol
associated with a shorter duration of mechanical ventilation
than scheduled intermittent lorazepam: a database analysis
using project IMPACT. Ann Pharmacother. 2007;41:1986e1991.
13. Roberts RJ, Barletta JF, Fong JJ, et al. Incidence of propofol-
related infusion syndrome in critically ill adults: a
prospective, multicenter study. Crit Care. 2009;13:R169.
14. Torbic H, Papadopoulos S, Manjourides J, Devlin JW. Impact of
a protocol advocating dexmedetomidine over propofol
sedation after robotic-assisted direct coronary artery bypass
surgery on duration of mechanical ventilation and patient
safety. Ann Pharmacother. 2013;47:441e446.
15. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine
for long-term sedation I: dexmedetomidine vs midazolam or
propofol for sedation during prolonged mechanical
ventilation: two randomized controlled trials. JAMA.
2012;307:1151e1160.
16. Yu T, Huang Y, Guo F, Yang Y, Teboul JL, Qiu H. The effects of
propofol and dexmedetomidine infusion on fluid
responsiveness in critically ill patients. J Surg Res.
2013;185:763e773.
17. Squara P, Denjean D, Estagnasie P, Brusset A, Dib JC, Dubois C.
Noninvasive cardiac output monitoring (NICOM): a clinical
validation. Intensive Care Med. 2007;33:1191e1194.
18. Marque S, Cariou A, Chiche JD, Squara P. Comparison
between Flotrac-Vigileo and Bioreactance, a totally
noninvasive method for cardiac output monitoring. Crit Care.
2009;13:R73.
19. Iirola T, Aantaa R, Laitio R, et al. Pharmacokinetics of
prolonged infusion of high-dose dexmedetomidine in
critically ill patients. Crit Care. 2011;15:R257.
20. Gerlach AT, Dasta JF, Steinberg S, Martin LC, Cook CH. A new
dosing protocol reduces dexmedetomidine-associated
hypotension in critically ill surgical patients. J Crit Care.
2009;24:568e574.
21. Keren H, Burkhoff D, Squara P. Evaluation of a noninvasive
continuous cardiac output monitoring system based on
thoracic bioreactance. Am J Physiol Heart Circ Physiol.
2007;293:H583eH589.
22. Marik PE. Noninvasive cardiac output monitors: a state-of
the-art review. J Cardiothorac Vasc Anesth. 2013;27:121e134.
23. Rich JD, Archer SL, Rich S. Noninvasive cardiac output
measurements in patients with pulmonary hypertension. Eur
Respir J. 2013;42:125e133.
24. Ely EW, Inouye SK, Bernard GR, et al. Delirium in
mechanically ventilated patients: validity and reliability of
the confusion assessment method for the intensive care unit
(CAM-ICU). JAMA. 2001;286:2703e2710.
25. Ji F, Li Z, Nguyen H, et al. Perioperative dexmedetomidine
improves outcomes of cardiac surgery. Circulation.
2013;127:1576e1584.
26. Biccard BM, Goga S, de Beurs J. Dexmedetomidine and cardiac
protection for non-cardiac surgery: a meta-analysis of
randomised controlled trials. Anaesthesia. 2008;63:4e14.
27. Yeh YC, Sun WZ, Ko WJ, et al. Dexmedetomidine prevents
alterations of intestinal microcirculation that are induced by
surgical stress and pain in a novel rat model. Anesth Analg.
2012;115:46e53.
28. Curtis JA, Hollinger MK, Jain HB. Propofol-based versus
dexmedetomidine-based sedation in cardiac surgery
patients. J Cardiothorac Vasc Anesth. 2013;27:1289e1294.
29. Geng J, Qian J, Cheng H, Ji F, Liu H. The influence of
perioperative dexmedetomidine on patients undergoing
cardiac surgery: a meta-analysis. PLoS One. 2016;11:e0152829.
30. Narisawa A, Nakane M, Kano T, et al. Dexmedetomidine
sedation during the nighttime reduced the incidence of
postoperative atrial fibrillation in cardiovascular surgery
patients after tracheal extubation. J Intensive Care. 2015;3:26.
31. Djaiani G, Silverton N, Fedorko L, et al. Dexmedetomidine
versus propofol sedation reduces delirium after cardiac
surgery: a randomized controlled trial. Anesthesiology.
2016;124:362e368.
32. Conti G, Ranieri VM, Costa R, et al. Effects of
dexmedetomidine and propofol on patient-ventilator
interaction in difficult-to-wean, mechanically ventilated
patients: a prospective, open-label, randomised, multicentre
study. Crit Care. 2016;20:206.
33. Patanwala AE, Erstad BL. Comparison of dexmedetomidine
versus propofol on hospital costs and length of stay. J Intensive
Care Med. 2016;31:466e470.
34. Turunen H, Jakob SM, Ruokonen E, et al. Dexmedetomidine
versus standard care sedation with propofol or midazolam in
intensive care: an economic evaluation. Crit Care. 2015;19:67.
35. Thoma BN, Li J, McDaniel CM, Wordell CJ, Cavarocchi N,
Pizzi LT. Clinical and economic impact of substituting
dexmedetomidine for propofol due to a US drug shortage:
examination of coronary artery bypass graft patients at an
urban medical centre. Pharmacoeconomics. 2014;32:149e157.