895502

research-article2019
AOPXXX10.1177/1060028019895502Annals of PharmacotherapyBenken et al

Research Report
Annals of Pharmacotherapy

Hemodynamic Effects of Propofol and

1­–8
© The Author(s) 2019
Article reuse guidelines:
Dexmedetomidine in Septic Patients sagepub.com/journals-permissions
DOI: 10.1177/1060028019895502
https://doi.org/10.1177/1060028019895502

Without Shock journals.sagepub.com/home/aop

Scott Benken, PharmD, BCPS AQ Cardiology, FCCM1,2 ,

Elizabeth Madrzyk, PharmD3, Dan Chen, PharmD4, Jaron Lopez, PharmD1,
Dana Schmelzer, PharmD1, Zack Sessions, PharmD1,
Gourang Patel, PharmD, MSc, FCCM5,6,
and Drayton Hammond, PharmD, MBA, MSc5,6

Abstract
Background: Use of nonbenzodiazepine agents propofol and dexmedetomidine are first line for sedation in the intensive
care unit (ICU). These agents have been implicated in the development of bradycardia and hypotension in critical illness.
Objectives: To compare the development of clinically significant hypotension and/or bradycardia (ie, negative hemodynamic
event) in adults with sepsis yet to require vasopressors receiving either propofol or dexmedetomidine for continuous
sedation. Methods: This was a retrospective multicenter cohort study of adults with non–vasopressor-dependent sepsis
admitted to an ICU at two academic medical centers between July 2013-September 2017. Results: Patients in the propofol
(n = 64) and dexmedetomidine (n = 31) groups developed a clinically significant negative hemodynamic event at statistically
similar frequencies (34.4% vs 16.1%, P = 0.065). Patients receiving propofol developed a larger degree of hypotension (47.3
vs 34.7 mm Hg reduction, P = 0.031). In multivariable logistic regression modeling, independent predictors of a negative
hemodynamic event were a past medical history of chronic kidney disease (odds ratio [OR] = 3.8; 95% CI = 1.17-12.2; P =
0.027) and baseline heart rate (OR = 1.02; 95% CI = 1.00-1.10; P = 0.036). Conclusions and Relevance: A minority of
patients with sepsis who received either propofol or dexmedetomidine experienced an event. Patients with sepsis without
shock receiving continuous infusions of propofol and dexmedetomidine experienced a negative hemodynamic event at
similar frequencies, though the degree of hypotension seen with propofol was greater. The clinical significance of these
adverse effects requires cautious use in sepsis and further investigation.

Keywords
sedatives, sepsis, hemodynamics, critical care, adverse drug reactions

Background syndrome’s pathophysiology, particularly the decreased

Use of nonbenzodiazepine agents preferentially to benzodi-
azepines to provide light sedation in patients experiencing
or at risk for agitation in the intensive care unit (ICU) is
recommended in the most recent guidelines for the manage-
ment of pain, agitation, delirium, immobilization, and
sleep.1 The guidelines provide a conditional recommenda-
tion for either propofol or dexmedetomidine as agents of
choice for sedation of critically ill patients.1 Propofol and
dexmedetomidine have been implicated in the development
of bradycardia and hypotension though the extent to which
these adverse effects occur in specific subpopulations of
critical illness remains understudied.2-12 In many patient
populations, these adverse effects can be managed without
causing patient harm. However, patients with sepsis may be
at increased risk for these adverse effects because of the
systemic vascular resistance seen, which results from the
body’s systemic inflammatory response.11 Although pre-
venting or not adding to hemodynamic instability in all
critically ill patients is vital to prevent illness progression,
in patients already in shock on vasopressors, these effects
1
University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA
2
University of Illinois Health, Chicago, IL, USA
3
Loyola University Medical Center, Maywood, IL, USA
4
Mayo Clinic Health System—Eau Claire, WI, USA
5
Rush University Medical Center, Chicago, IL, USA
6
Rush Medical College, Chicago, IL, USA
Corresponding Author:
Scott Benken, Department of Pharmacy Practice, University of Illinois at
Chicago College of Pharmacy, 833 S Wood St, Chicago, IL 60612, USA.
Email: benken@uic.edu
2 Annals of Pharmacotherapy 00(0)
may carry less relevance. Thus, it is particularly crucial to
study negative hemodynamic effects in patients without a
vasopressor requirement given the complex and sometimes
unpredictable nature of the condition and the known, unfa-
vorable outcomes in patients who require vasopressors
associated with sepsis.13
Recent studies comparing adverse effects from propofol
and dexmedetomidine have included patients in septic shock
already requiring vasopressors.9,11 Nelson et al11 performed
a retrospective cohort study of septic shock patients ­requiring
sedation and found these agents to have a similar incidence
of negative hemodynamic events (propofol 31.4% vs dex-
medetomidine 29.7%; P = 0.99). Morelli et al9 performed a
prospective, open-labeled crossover study in deeply sedated
septic shock patients on mechanical ventilation and found a
decrease in background vasopressors (propofol before dex-
medetomidine norepinephrine dose equivalents = 0.69 µg/
kg/min vs during dexmedetomidine norepinephrine dose
equivalents = 0.3 µg/kg/min, P < 0.05) when patients had a
short (4-hour) exposure to dexmedetomidine compared with
propofol, but the clinical significance of these findings
remains unclear. Marler et al10 evaluated propofol compared
with nonpropofol sedation (primarily fentanyl and mid-
azolam [~80%]; only ~7% received dexmedetomidine) in
primarily severe sepsis patients and found no difference in
vasopressor initiation for hypotension. Additionally, the pro-
spective, multicenter Dexmedetomidine for Sepsis in
Intensive Care Unit Randomized Evaluation (DESIRE) trial
evaluated the use of dexmedetomidine compared with non-
dexmedetomidine sedative agents (eg, fentanyl, propofol,
and midazolam) in patients with sepsis.12 Approximately
two-thirds of patients were in septic shock. Development
of hypotension was not reported, though the incidence of
bradycardia was similar between the dexmedetomidine
and nondexmedetomidine groups (7% vs 2%; P = 0.1).
Approximately 40% of the nondexmedetomidine compar-
ator arm received propofol, and adjunctive propofol
was allowed in the dexmedetomidine group per the trial
protocol.
Despite these recent investigations into septic shock
patients, there are no investigations comparing these 2 first-
line agents head-to-head in patients with sepsis without
shock. The rationale for further research and analysis
regarding negative hemodynamic events with clinical out-
comes with the comparison of propofol versus dexmedeto-
midine was to determine that the hemodynamic-related
events were not iatrogenic but rather a progressive physio-
logical process secondary to sepsis.
Objectives
The purpose of this study was to compare the development
of clinically significant hypotension and bradycardia in
adult patients with sepsis without shock receiving either
propofol or dexmedetomidine and, additionally, to identify
risk factors in this patient group for developing negative
hemodynamic events.
Methods
Design
This was a retrospective, observational, cohort study of
adult patients with sepsis admitted to a medical ICU at 2
academic medical centers between July 1, 2013, and
September 30, 2017. The study period was chosen to pro-
vide an adequate cohort size to draw conclusions regarding
these effects while still reflecting current sedation practices.
The protocol was approved by each institution’s investiga-
tional review board.
Participants
Patients who were eligible for inclusion were at least 18
years of age, admitted to an ICU for greater than 48 hours,
and mechanically ventilated and sedated with either propo-
fol of dexmedetomidine and met the Sepsis-3 definition of
sepsis while receiving their sedatives.14 Patients eligible for
inclusion were excluded if they received propofol and dex-
medetomidine concurrently or if they were on vasopressors
at the time of sedative initiation. Additionally, patients were
excluded if they crossed-over and, thus, received both pro-
pofol and dexmedetomidine as their sedatives. All patients
had an initial target mean arterial pressure (MAP) of at least
65 mm Hg. Institutional policies to guide propofol and dex-
medetomidine use were in place during the study period and
similar between institutions. Recommendations were to ini-
tiate propofol at 5 to 10 µg/kg/min and titrate by 5 to 10 µg/
kg/min every 5 to 10 minutes up to a maximum dosage of
75 to 80 µg/kg/min to achieve a target sedation score and to
initiate dexmedetomidine at 0.2 µg/kg/h and titrate by 0.1
µg/kg/h every 30 minutes up to a maximum dosage of 1.4
µg/kg/h to achieve a target sedation score. All patients had
an initial target Richmond Agitation Sedation Scale
(RASS) score of light sedation, which translated to a goal
RASS of either +1 to −1 or 0 to −2.15 Patients receiving
these medications had continuous hemodynamic monitor-
ing. Adjunctive sedative agents were defined as another
agent (eg, benzodiazepine) used as an intermittent bolus,
and adjunctive analgesic agents were defined as another
agent (eg, opioid analgesic) given as an intermittent bolus
or continuous infusion. A convenience sample of all patients
during the study period that met the study inclusion criteria
was used.
Outcomes
The primary outcome was development of a clinically
significant negative hemodynamic event. This negative
Benken et al 3
Figure 1.  Patient screening and inclusion.
hemodynamic event was defined as either clinically sig-
nificant hypotension (defined as a decrease in MAP by at
least 20%, initiation of vasopressor support, decrease in
baseline systolic blood pressure [SBP] by at least 30 mm
Hg) or clinically significant bradycardia (heart rate [HR]
< 50 beats/min [bpm]) that resulted in a clinical interven-
tion being provided (ie, fluid challenge, initiation of vaso-
pressor support, and/or discontinuation of propofol or
dexmedetomidine).8,11 Secondary outcomes were mortal-
ity at 28 days, ICU length of stay, hospital length of stay,
mechanical ventilation duration, absolute decrease in
blood pressure (ie, hypotension) in millimeters of mer-
cury if hypotension occurred, and absolute decrease in
HR (ie, bradycardia; in bpm) if bradycardia occurred.
Outcome Analysis
Primary and secondary outcomes were analyzed via the
Student t-test for continuous data, Mann-Whitney U for
nonparametric data, and Pearson χ2 or Fisher exact test, as
appropriate, for categorical data. All analyses were per-
formed using SPSS.v25 ©. Based on the data distribution,
the mean and SD or median and interquartile ranges were
used to report the analyses of baseline characteristics, and
primary and secondary outcomes. A P value of 0.05 was
used when determining statistical significance between
treatment groups. Bivariate analyses were assessed for cor-
relations between independent variables and dependent out-
comes of clinically significant bradycardia and hypotension
as well as either qualifying as a negative hemodynamic
event. Variables resulting in a P <0.1 via univariate analy-
sis were included in multivariable logistic regression mod-
eling to investigate factors associated with the development
of these events. Variables demonstrating collinearity were
not included in multivariable modeling.
Results
Participants
Of 274 patients screened, 95 were included, with 64 patients
in the propofol group and 31 patients in the dexmedetomi-
dine group (Figure 1). Many baseline and clinical character-
istics were similar between the 2 treatment groups (Table 1).
Patients receiving propofol were less frequently patients with
cirrhosis (4.7% vs 29%, P = 0.002) with a lower average
total bilirubin (1.4 [1.7] vs 5.5 [6.8] mg/dL, P < 0.001), had
a lower total SOFA score (5.7 [3.4] vs 8.9 [4.9], P < 0.001),
and had a higher baseline MAP (104 [22.3] vs 89 [12.3] mm
Hg, P < 0.001). The most common source of infection was
pulmonary in both groups, and patients receiving dexmedeto-
midine were more often on stress dose steroids (Table 2).
Patients receiving propofol had a shorter duration of sedation
4 Annals of Pharmacotherapy 00(0)

Table 1.  Baseline Characteristics.

Dexmedetomidine (n = 31) Propofol (n = 64) P Value

Male, n (%) 14 (45.2) 39 (60.9) 0.147
Age in years, average (SD) 55.3 (14.5) 57.4 (15.4) 0.529
Actual body weight in kilograms, average (SD) 80.3 (19.7) 85.5 (28.4) 0.355
Height in centimeters, average (SD) 167.4 (12.3) 164.2 (20.7) 0.427
PMH HTN, n (%) 22 (71) 40 (62.5) 0.416
PMH HF, n (%) 5 (16.1) 7 (10.9) 0.475
PMH AF, n (%) 3 (9.7) 5 (7.8) 0.518
PMH CAD, n (%) 4 (12.9) 8 (12.5) 0.596
PMH CKD, n (%) 6 (19.4) 15 (23.4) 0.653
PMH ESLD/cirrhosis, n (%) 9 (29) 3 (4.7) 0.002
Baseline MAP before sedation (mm Hg), average (SD) 88.5 (12.3) 104.4 (22.3) <0.001
Baseline HR before sedation (bpm), average (SD) 107.3 (17.6) 104.4 (28.1) 0.603
SOFA total, average (SD) 8.87 (4.9) 5.7 (3.4) <0.001
Baseline PaO2:FiO2, average (SD) 214.2 (140.6) 234.4 (162.4) 0.585
Baseline platelets ×103, average (SD) 159.3 (168.2) 172.5 (126.8) 0.683
Baseline total bilirubin (mg/dL), average (SD) 5.5 (6.8) 1.4 (1.7) <0.001
Baseline SCr (mg/dL), average (SD) 2.6 (1.8) 3.2 (4.2) 0.448
Baseline GCS, average (SD) 9.6 (3.9) 10.2 (3.9) 0.588

Abbreviations: AF, atrial fibrillation; CAD, coronary artery disease; CKD, chronic kidney disease; ESLD, end-stage liver disease; FiO2, fraction of
inspired oxygen; GCS, Glasgow Coma Scale; HF, heart failure; HR, heart rate; HTN, hypertension; MAP, mean arterial pressure; PaO2, partial pressure
of arterial oxygen; PMH, past medical history; SCr, serum creatinine; SOFA, sequential organ failure assessment.

Table 2.  Sepsis Characteristics.

Dexmedetomidine (n = 31) Propofol (n = 64) P Value

Source of infection 0.135
  CNS, n (%) 1 (3.2) 1 (1.6) —
  Pulmonary, n (%) 10 (32.3) 31 (49.2) —
  Intraabdominal, n (%) 7 (22.6) 5 (7.9) —
  Renal/GU, n (%) 6 (19.4) 5 (7.9) —
  SSTI/CLABSI, n (%) 2 (6.5) 9 (12.7) —
Unknown/Other/Multiple 5 (16.1) 13 (20.6) —
Stress dose steroids 8 (25.8) 1 (1.6) <0.001

Abbreviations: CLABSI, central line–associated blood stream infections; CNS, central nervous system; GU, genitourinary; SSTI, skin and soft-tissue
infections.

and longer duration of mechanical ventilation though neither
of these reached statistical significance (Table 3). Patients
receiving dexmedetomidine demonstrated a higher number
of dosage titrations of both their primary sedative (8.8 [11.5]
vs 4.5 [3.5], P = 0.007) and adjunctive continuous infusion
fentanyl (10.5 [8.8] vs 5.5 [4.1], P = 0.001). Patients receiv-
ing propofol received more frequent administrations of
adjunctive intravenous push sedatives and analgesics (Table
3). The maximum dose of continuous infusion fentanyl and
the duration of continuous infusion fentanyl were similar
between groups (Table 3). These agents were given in close
proximity (within 15 minutes) to the negative hemodynamic
event at similar frequencies in the propofol and dexmedeto-
midine groups (12.5% vs 9.7%, P > 0.99).
Outcomes and Safety
Patients in the propofol and dexmedetomidine groups had
statistically similar percentage of clinically significant neg-
ative hemodynamic events (34.4% vs 16.1%; odds ratio
[OR] = 2.23; 95% CI = 0.92-8.08; P = 0.065). The inci-
dence of each component of clinically significant negative
hemodynamic events were similar (bradycardia [4.7% vs
6.5%, P = 0.66] and hypotension [32.8% vs 19.4%, P =
0.173]). When clinically significant hypotension devel-
oped, the degree of hypotension (a decrease of SBP) was
greater in patients who received propofol (47.3 [22.7] vs
34.7 [14.6] mm Hg, P = 0.031). Other outcomes were simi-
lar between groups (Table 4).
Benken et al 5

Table 3.  Intubation, Sedation, and Mechanical Ventilation Characteristics.

Dexmedetomidine (n = 31) Propofol (n = 64) P Value

Propofol maximum dose (µg/kg/min), average (SD) — 44.9 (22.3) —
Dexmedetomidine maximum dose (µg/kg/h), average (SD) 0.8 (0.5) — —
Duration of sedative in hours, average (SD) 76.7 (97) 46.9 (55.6) 0.061
Number of sedative dose titrations, average (SD) 8.8 (11.5) 4.5 (3.5) 0.007
Fentanyl maximum dose (µg/h), average (SD) 155.6 (80.7) 169.6 (126.9) 0.612
Duration of fentanyl use (hours), average (SD) 92 (67.2) 73.9 (58.2) 0.228
Number of fentanyl dose titrations, average (SD) 10.5 (8.8) 5.5 (4.1) 0.001
Duration of mechanical ventilation (hours), average (SD) 134.9 (146) 191.3 (271.1) 0.282
Propofol giving duration intubation, n (%) 20 (64.5) 42 (67.7) 0.756
Etomidate given duration intubation, n (%) 2 (6.5) 4 (6.5) >0.99
Intravenous push fentanyl given, n (%) 13 (41.9) 48 (75) 0.002
Intravenous push morphine given, n (%) 7 (22.6) 10 (15.6) 0.407
Intravenous push hydromorphone given, n (%) 2 (6.5) 16 (25) 0.025
Intravenous push midazolam given, n (%) 13 (41.9) 34 (53.1) 0.306
Intravenous push lorazepam given, n (%) 5 (16.1) 29 (45.3) 0.005

Table 4.  Negative Hemodynamic Effects and Outcomes.

Dexmedetomidine (n = 31) Propofol (n = 64) P Value

Either bradycardia or hypotension, n (%) 5 (16.1) 22 (34.4) 0.065
Significant bradycardia, n (%) 2 (6.5) 3 (4.7) 0.66
Degree of bradycardia (in bpm) decrease, average (SD) 36.8 (12.9) 35.8 (4.4) 0.877
Significant hypotension, n (%) 6 (19.4) 21 (32.8) 0.173
Degree of hypotension (in mm Hg) decrease, average (SD) 34.7 (14.6) 47.3 (22.7) 0.031
Mortality, n (%) 11 (35.5) 25 (39.1) 0.736
Hospital LOS in days, average (SD) 33.48 (68.5) 19.53 (15.29) 0.122
ICU LOS in days, average (SD) 15.19 (14.11) 12.87 (10.65) 0.374

Abbreviations: ICU, intensive care unit; LOS, length of stay.

Multivariable logistic regression analysis identified no
variables that were associated with developing bradycardia.
Variables included in the model for developing clinically
significant hypotension included the following: etomidate
during intubation, intravenous hydromorphone given, past
medical history of chronic kidney disease (CKD), and base-
line HR. Receiving intravenous push hydromorphone and
having a past medical history of CKD were the only vari-
ables significantly associated with increased odds of devel-
oping clinically significant hypotension (OR = 3.6, 95% CI
= 1.14-11.2, P = 0.029, and OR = 3.2, 95% CI = 1.10-
9.60, P = 0.037, respectively). Variables included in the
model for developing a negative hemodynamic event
included the following: sedation group, etomidate during
intubation, intravenous hydromorphone given, past medical
history of CKD, and baseline HR. Past medical history of
CKD (OR = 3.8; 95% CI = 1.17-12.2; P = 0.027) and base-
line HR (OR = 1.02; 95% CI = 1.00-1.10; P = 0.036) were
associated with the development of a negative hemodynamic
event. Of note, doses of agents were not associated with
negative hemodynamic events (OR = 1.004, 95% CI =
0.98-1.02, P = 0.727, and OR = 1.36, 95% 0.35-5.24, P =
0.657, for propofol and dexmedetomidine, respectively).
Discussion
This was the first study to compare the incidence and degree
of negative hemodynamic effects from propofol and dex-
medetomidine in mechanically ventilated adult patients
experiencing sepsis without shock. A total of 28% of
patients experienced a negative hemodynamic event that
likely was precipitated by propofol or dexmedetomidine
infusions. Patients with sepsis who received a continuous
infusion of propofol experienced a larger percentage of
negative hemodynamic events, though in our investigation,
this did not reach significance. Furthermore, those receiv-
ing propofol who experienced clinically significant hypo-
tension had a greater decrease in SBP than those receiving
dexmedetomidine. Understanding the impact of these nega-
tive sequalae and factors that affect their development can
support their appropriate use.
6 Annals of Pharmacotherapy 00(0)
Patients experiencing sepsis frequently develop impaired
endothelium function, increased capillary leak, and
increased venous capacitance that result in a decrease in
venous return to the heart.16 Additionally, cytokines released
as a result of the host response to endotoxins decrease sys-
temic vascular resistance, resulting in systemic arterial
hypotension. Concurrently, reflex sinus tachycardia com-
monly arises to increase cardiac output and microcircula-
tory perfusion.16 Propofol may exacerbate arterial
hypotension through inhibition of peripheral sympathetic
vasoconstrictor nerve activity and reduce arterial blood
pressure and HR through reduction in plasma catechol-
amine concentrations.17 Dexmedetomidine may inhibit cen-
tral norepinephrine release from sympathetic nerves without
activating compensatory changes in the renin-angiotensin-
aldosterone or vasopressin biological pathways, which may
predispose a patient with sepsis to hypotension and brady-
cardia.18 In patients without the physiological impairments
from sepsis, these mechanisms of hemodynamic compro-
mise may be easily overcome; however, sepsis appears to
affect response to these effects. In our investigation, it
appears that though this mechanism is present, it exists in
only a minority of patients.
An additional variable identified via regression analysis
affecting occurrence of a negative hemodynamic event
while receiving a sedative infusion was the presence of pre-
existing CKD. Traditionally, providers are more likely to
provide overall lower total fluid resuscitation amounts in
patients with a past medical history of CKD. A study by
Lowe et al19 provided some insight because investigators
stated that the phenomena could be secondary to a combina-
tion of decreased fluid resuscitation and plasma hormones
when compared with non-CKD patients. The decreased
fluid resuscitation could also predispose the patients with
CKD to a negative hemodynamic event.
One strategy to overcome a negative hemodynamic
event would be implementing a slower titration of infusions
and, when possible, avoiding bolus doses of other opioid
therapies (eg, morphine and hydromorphone) that were
observed and have been reported in the literature.20,21 Acute
administration of opioids can lead to vasodilation and
decreased sympathetic tone.20 Morphine and hydromor-
phone can lead to histamine release and, as a result, can
cause significant decreases in systemic vascular resistance
and blood pressure. These effects are rarely the result of
sole opioid administration, and when combined with other
medications that share this effect, these results may be
compounded.22
The baseline BP was not associated with a negative hemo-
dynamic event, so it would be appropriate to initiate either
infusion for sedation in mechanically ventilated patients
regardless of the BP. However, one baseline variable that did
appear to affect the observation of a negative hemodynamic
event was baseline HR. Therefore, clinicians should exercise
caution within the initiation of a sedative infusion. The clini-
cal impact of relative bradycardia, either intrinsic or iatro-
genic, in sepsis is not entirely understood because it may be
protective in some patients or represent myocardial dysfunc-
tion and portend a worse outcome in patients.23,24
The rates of hypotension in our investigation are compa-
rable to those in previously published literature in some but
not all critically ill patients.2,5,10,12,25-27 Patients in the
Propofol with Dexmedetomidine (PRODEX) trial experi-
enced clinically significant hypotension in both the propo-
fol (13.4%) and dexmedetomidine (13%) groups less
frequently than in this study.5 Almost 50% of the patients
were declared as being infected, though it is unclear if these
patients were septic. In a multicenter, retrospective cohort
pilot study of patients with “sepsis or severe sepsis,” half of
the patients who received a propofol infusion progressed to
requiring vasopressor support, with approximately 60%
having at least a 20 mm Hg decrease in MAP.10 This higher
percentage may not represent the actual incidence of hypo-
tension from propofol because many of these patients could
have progressed to septic shock because it was only a
48-hour observation window, making it hard to differentiate
hypotension attributable to a rapidly deteriorating sepsis
clinical course versus an observation of a true medication
adverse effect. Additionally, this percentage did not differ
from the comparator arm, which primarily utilized mid-
azolam infusions, raising the suspicion that the hypotension
was observed as a result of the clinical course.10 In a neuro-
critical care cohort of patients, 34% vs 28% of patients on
propofol and dexmedetomidine, respectively, experienced
clinically significant hypotension.28 Although this patient
population is distinctly different from the sepsis population,
less than 5% of these patients were on a vasoactive agent
when sedation was initiated and less than 10% had a MAP
less than 70 mm Hg, suggesting that systemic vasodilation
at the time of sedation initiation was not present in most
patients, similar to our study population. In our patient pop-
ulation, no patient was on vasoactive agents, and the aver-
age baseline MAP was 99 mm Hg. Finally, a recent
investigation of propofol and dexmedetomidine in post–
cardiac surgery patients found hypotension in 23% to 46%
of patients.27 Although this patient population has many dif-
ferences when compared with ours, post–cardiac surgery
patients share many clinical features similar to the systemic
inflammatory response syndrome seen in sepsis patients.29
Therefore, the current investigation provides clinical insight
into the incidence of negative hemodynamic events in
patients who are not in septic shock.
Another hemodynamic variable analyzed was the
­occurrence of bradycardia. In the following investigation, a
HR <50 bpm was utilized to categorize bradycardia. The
incidence of bradycardia in the dexmedetomidine group
was 6.5% and in the propofol group was 4.7%. Because the
2 sedative agents exhibit different pharmacological
Benken et al 7
mechanisms of action, a direct dose comparison was not
performed at the time of the event. To our knowledge, this
investigation is one of the first to describe the difference in
bradycardia between 2 sedative infusions for patients not
already in septic shock on vasoactive infusions. Beesley
et al23 performed a retrospective review of 1554 septic
shock patients. Of the total sample reviewed, 44% (686
patients) met criteria and were included in the analysis and
had a relative bradycardia episode, defined as a HR <80
bpm. Investigators did perform a propensity score analysis
to balance the groups and concluded that there was a differ-
ence in patient outcome in those patients who did experi-
ence a relative bradycardic event. Although overall
negative hemodynamic events were statistically similar in
our study population, numerical differences exist. These
differences seem to be driven by the development of clini-
cally significant hypotension as opposed to bradycardia.
Limitations
The results of this study must be considered in light of its
limitations. There are several factors that have the potential
to influence hemodynamics that were not controlled for
within our study. Assessment of fluid resuscitation during
sepsis management was not assessed within our population.
This may have an effect on the hemodynamics of patients,
but in a retrospective analysis, it is hard to accurately collect
these data. Furthermore, the timing of administration of
other potentially hemodynamically active medications (eg,
fentanyl, morphine, and benzodiazepines) was not exactly
captured though the frequencies of close proximity (within
15 minutes) to the negative hemodynamic events were sim-
ilar in studied groups. Also, though the maximum dose and
duration of the most common concurrent analgesic (con-
tinuous infusion fentanyl) was similar, the total exposure to
this agent was not captured and, in theory, could have been
skewed between groups carrying hemodynamic conse-
quence. Additionally, though the incidence of stress dose
steroids was captured and was not an independent predictor
of negative hemodynamic events, the rationale and indica-
tion for this therapy are unclear. Again, this could poten-
tially confound our hemodynamic interpretation of our
patients’ baseline hemodynamic status because the best lit-
erature surrounding stress dose steroids use in sepsis deals
with patients on vasopressor agents already. It also could
signify that there was a severity of illness not captured in
the variables collected or baseline adrenal function deficits
that led clinicians to opt for this therapy outside of the tradi-
tional context. Additionally, the retrospective, observational
design of our study may allow for differences in baseline
characteristics, and the potential for selection bias with sed-
ative agent selection based off provider preferences or other
patient characteristics does exist. This may be of particular
importance because baseline HR was associated with
negative hemodynamic events, and perhaps other aspects of
myocardial function (eg, echocardiographic findings) not
collected were guiding sedation selection. Finally, the study
period includes a time before and after the most recent defi-
nitions of sepsis. In an effort to ameliorate this limitation,
our investigation included only patients with the most
recent definition of sepsis.
Conclusions and Relevance
When determining whether to initiate propofol, dexmedeto-
midine, or another agent in an adult patient with sepsis,
adverse event development is a component of the decision-
making process alongside clinical efficacy.
Overall, a minority of patients with sepsis who received
either propofol or dexmedetomidine experienced a negative
hemodynamic event. Patients with sepsis without shock
receiving continuous infusions of propofol and dexmedeto-
midine experienced statistically similar frequencies of neg-
ative hemodynamic events, though when these events
occurred, they were more pronounced with propofol. The
clinical significance of these adverse effects requires fur-
ther investigation.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iDs
Scott Benken https://orcid.org/0000-0002-8811-2458
Drayton Hammond https://orcid.org/0000-0002-9056-5560
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