Journal of Acute Care Physical Therapy REVIEW

ARTICLE

Early Mobilization of
Patients Receiving
Vasoactive Drugs in
Critical Care Units: A
Systematic Review
Downloaded from http://journals.lww.com/jacpt by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60Etgtdnn9T1vLQWJq3kbRMjK/ocE on 12/02/2021

Prasobh Jacob, Praveen Jayaprabha Surendran, Muhamed Aleef E M,

Theodoros Papasavvas, Reshma Praveen, Narasimman Swaminathan, Prasobh Jacob, MBA
Fiona Milligan Department of Cardiac Rehabilitation,
Heart Hospital, Hamad Medical
Corporation, Doha, Qatar.
physioprasobh@gmail.com.
ABSTRACT
Purpose:  Mobilization is feasible, safe, and beneficial to patients Praveen Jayaprabha Surendran, MPT
Department of Cardiac Rehabilita-
admitted to critical care units. Vasoactive therapy appears to be one of
tion, Heart Hospital, Hamad Medical
the most common barriers to early mobilization. Many recent publications Corporation, Doha, Qatar.
have studied the safety and feasibility of mobilizing patients with these
vasoactive drugs. The aim of this review was to synthesize the prevailing Muhamed Aleef E M, BPT
evidence pertaining to mobilizing patients receiving vasoactive drugs. Department of Physiotherapy, Hamad
General Hospital, Hamad Medical
Methods:  The protocol was developed and registered on PROSPERO
Corporation, Doha, Qatar.
(CRD42019127448). A comprehensive literature search was conducted
using PubMed, Physiotherapy Evidence Database (PEDRO), Cochrane Theodoros Papasavvas, PhD
Central, and Embase (through Cochrane) for original research, including Department of Cardiac Rehabilita-
case studies and consensus guidelines. PRISMA guidelines were used to tion, Heart Hospital, Hamad Medical
conduct and report this review. The included articles were appraised using Corporation, Doha, Qatar.
the Newcastle-Ottawa Scale independently and a consensus reached by
3 reviewers. Reshma Praveen, MPT
Department of Physiotherapy, Hamad
Results and Conclusion:  Evidence determining specific doses of General Hospital, Hamad Medical
vasoactive drugs that would allow safe mobilization of patients in critical Corporation, Doha, Qatar.
care is lacking. The criteria that have been used to determine the eligibility
to mobilize patients on vasoactive drugs have not been consistent. Narasimman Swaminathan, MPT
Faculty of Allied Health Sciences,
Sri Ramachandra Institute of Higher
Education and Research, Chennai,
India.
This is an open-access article distributed under the terms of the Creative Commons Attribution-
Fiona Milligan, MN
Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to down-
NHS Ayrshire and Arran, Crosshouse,
load and share the work provided it is properly cited. The work cannot be changed in any way or
Scotland.
used commercially without permission from the journal.
Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the The authors have no conflicts of inter-
Academy of Acute Care Physical Therapy, APTA. est and no source of funding to declare.
DOI: 10.1097/JAT.0000000000000140

JACPT  ■  Volume 12  ■  Number 1  ■  2021 37

Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units

T
he overall mortality of patients admitted to in-
tensive care units (ICUs) has declined due to the
advancement of critical care medicine. However,
the prevalence of morbidity has increased among crit-
ical care survivors.1-8 Previously, patients who were
critically ill and admitted to ICUs were often treated
with sedation and prolonged bed rest9 as a means of
giving rest to the affected organs and reducing energy
consumption.10 However, deleterious effects of bed
rest appear to outweigh its benefits.11-14
Prolonged bed rest in critical care patients con-
tributes to short-term as well as long-term complica-
tions.3,4,8,15,16 Short-term complications include ICU-
acquired weakness and muscle wasting that increases
hospital length of stay and reduces quality of life
(QOL).8,15 Long-term complications include neuro-
muscular weakness, low functional capacity, deficits
in activities of daily living, reduced QOL, hospital
readmission, and death.3,4,16
Several studies have shown that early progres-
sive mobilization is feasible, safe, and beneficial for
most patients admitted to ICUs.2,17-20 Early mobiliza-
tion refers to any form of physical activity within the
first 2 to 5 days of critical illness.21 Early mobilization
has been shown to prevent or minimize ICU-acquired
weakness, improving functional recovery, walking
distance at hospital discharge, and reducing hospital
length of stay.22-25
Although early mobilization is shown to be safe
and feasible,2,17-20 extended periods of bed rest are still
prevalent in ICUs.26-28 The barriers hindering early
mobility in ICUs can be classified as patient-related
(patient symptoms and conditions), structure-related
(human and technical resources), and ICU culture
(staff attitudes) or process (unclear roles and responsi-
bilities).22,23,29,30 The most commonly reported patient-
related barrier is hemodynamic instability requiring
vasoactive drug support.30,31 A multicenter cohort
study of Australian and New Zealand ICUs reported
that vasoactive therapy was the third most common
barrier for early mobilization,32 with several studies
recommending a cautious approach to mobilizing
critically ill patients on vasoactive drugs.2,9,32
Vasoactive drugs are administered to critically
ill patients with severe hemodynamic impairment to
restore adequate tissue perfusion. Vasoactive drugs
consist of inotropes, which increase cardiac out-
put through enhanced myocardial contractility, and
vasopressors, which increase vascular tone.31 Table 1
shows a summary of clinical indications, dose ranges,

TABLE 1. Clinical Indications, Dose Range, and Significant Side Effects of the Commonly
Used Vasoactive Drugsa
Drug Clinical Indication Dose Range Major Side Effects
Dopamine Cardiogenic and vasodilatory 2-20 μg/kg/min (maximum Severe hypertension, ventricular
shock, heart failure, 50 μg/kg/min) arrhythmia, cardiac ischemia,
symptomatic bradycardia, tissue ischemia/gangrene (high
unresponsive to atropine or dose)
pacing

Dobutamine Low cardiac output, 2-20 μg/kg/min (maximum Tachycardia, increased ventricular
unresponsive to atropine or 40 μg/kg/min) response rate in patients with atrial
pacing fibrillation, ventricular arrhythmias,
cardiac ischemia, hypertension

Norepinephrine Cardiogenic and vasodilatory 0.01-3 μg/kg/min Arrhythmias, bradycardia,

shock peripheral ischemia, hypertension

Epinephrine Cardiogenic and vasodilatory Infusion Ventricular arrhythmias, severe

shock, cardiac arrest,
bronchospasm/anaphylaxis
symptomatic bradycardia/heart
block unresponsive to atropine
or pacing
0.01-0.10 μg/kg/min hypertension, cardiac ischemia,
sudden cardiac death
Bolus 1 mg IV 3-5 min
(maximum 0.2 mg/kg)
Intramuscular 0.1-0.5 mg

Milrinone Low cardiac output Bolus Ventricular arrhythmias,

50 μg/kg bolus over 10-30 g hypotension, cardiac ischemia
Infusion
0.375-0.75 μg/kg/min
IV, intravenous.
a
Used with permission from Overgaard and Dzavik.33

38 JACPT  ■  Volume 12  ■  Number 1  ■  2021

 Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units

and significant side effects of the most commonly 1. Are patients in critical care units on vasoactive
used vasoactive drugs.33 drugs being mobilized early?
Vasoactive drugs are also used in combinations. 2. Does a relationship exist between dosage of vaso-
Patients who receive multiple vasoactive drugs are active drugs and level of mobility achieved?
categorized into either low, moderate, or high level 3. What are the adverse events reported while mobi-
of support based on the highest level of the individual lizing patients on vasoactive drugs in critical care
medication.34 The dose range classifications of the units?
most commonly used vasoactive drugs are presented
in Table 2.34
Vasoactive agents have been lifesaving drugs, but PICO Details
can cause serious adverse events.35 Reflex bradycar-
Population (P) = Patients admitted in critical care
dia may occur as a compensatory mechanism follow-
  units receiving vasoactive medications.
ing administration of vasoactive drugs, which can
Intervention (I) = Early mobilization.
further induce a reduction in cardiac output.33,36 Vaso-
Comparison (C) = Bed rest or immobilized.
active drug administration can also cause tachycardia,
Outcome (O) = Incidence of mobilization; the level
tachyarrhythmias such as supraventricular arrhyth-
  of maximum mobility achieved, adverse events.
mias, ventricular arrhythmias, and cause myocardial
ischemia.33,37
The use of vasoactive drugs is an independent risk Study Selection Criteria
factor for the development of ICU-acquired weak-
ness, which can be minimized by early mobilization.38 Inclusion Criteria
Several recent publications have discussed the safety
Clinical trials and cohort studies that discuss the
and feasibility of mobilizing patients with vasoactive
mobilization and safety of critically ill patients
drugs.32,34,39-41 These studies have also outlined the
receiving vasoactive drugs (publication date range:
various risks, precautions, contraindications, and bar-
2010-2018).
riers for mobilizing the patients. Understanding these
details continues to be useful for clinicians to imple-
ment early mobility in patients with vasoactive drugs. Exclusion Criteria
The aim of this review was to synthesize the most Studies were excluded if they did not report the num-
recent prevailing evidence pertaining to mobilizing ber of patients receiving vasoactive drugs or the num-
patients receiving vasoactive drugs. ber of mobilization sessions.

METHODS Search Criteria

The 3 overarching review questions, which guided the A literature search was undertaken using PubMed,
process of data analysis, were as follows: Physiotherapy Evidence Database (PEDRO), Cochrane

TABLE 2. Vasoactive Drug Dosage Classificationa

Low Dose, Moderate Dose, High Dose,
Drug Name μg/kg/min μg/kg/min μg/kg/min
Dopamine <3 3-10 >10

Dobutamine <3 3-10 >10

Epinephrine <0.05 0.05-0.2 >0.2

Norepinephrine <0.05 0.05-0.2 >0.2

Vasopressin <0.01 0.02-0.03 0.04

Levosimendan <0.05 0.1 0.2

Milrinone 0-0.15 0.15-0.5 0.5

a
From Boyd et al.
34

JACPT  ■  Volume 12  ■  Number 1  ■  2021 39

Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units
Central, and Embase (through Cochrane) for origi-
nal research, including case studies, cohort studies,
and consensus guidelines published in the English
language. The details of the search terms were pre-
sented in Appendix 1. Three reviewers independently
screened all publications, including titles, abstracts,
and available full-text publications of the literature
searches. The reference lists of the eligible publica-
tions and articles were screened for additional eligible
publications.
Search Outcome
PRISMA guidelines42 were used to conduct and report
this review. A total of 343 articles were retrieved.
Articles related to patients receiving vasoactive drugs
and mobilizations were included for further analysis.
Five articles that specifically discussed the mobiliza-
tion of patients with vasoactive drugs were identified
per the inclusion criteria. Appendix 2 illustrates the
PRISMA flow diagram of this study.
Retrieved articles were reviewed and segregated
based on vasoactive agents used in critical care
patients, their dosage (if reported), criteria for mobi-
lization, percentage of patients who were mobilized,
achieved levels of mobility, and adverse events. This
information was tabulated for the identification of the
variables and drawing conclusions.
The protocol for this systematic review was regis-
tered on PROSPERO International Prospective Reg-
ister of Systematic Reviews (CRD42019127448).
RESULTS
Quality Assessment
Quality assessment of the 5 included studies was con-
ducted independently by 3 reviewers. These articles
were appraised using the Newcastle-Ottawa Scale
for cohort studies.43,44 Any disagreements between
reviewers were resolved by consensus. The risk of
bias assessment for the included studies was summa-
rized in Appendix 3. The segregated results derived
from 5 studies were presented in Table 3. Five stud-
ies,32,34,39-41 comprising of 2 prospective, and 3 retro-
spective cohort studies, were included in this system-
atic review, representing a total of 528 participants.
Two of the 5 studies focused only on patients (166
participants) who received vasoactive medication.32,40
One of these studies included only postcardiothoracic
surgery patients who were not on mechanical ventila-
tors.40 The remaining 3 studies included all patients
admitted in the critical care unit irrespective of the
presence or absence of vasoactive drugs.34,39,41 Two of
the 3 studies reported that 34%39 and 23%41 received
the vasoactive drugs, while the third study reported
40
45%34 of the patients received vasoactive medica-
tions. This study revealed 299 out of 809 mobilization
sessions received during the presence of vasoactive
drugs.
Participants included in this review were admit-
ted in a general, medical or surgical ICU.32,34,39-41 The
patient population was diverse, encompassing cardio-
vascular disorders, sepsis, respiratory diseases, gas-
trointestinal diseases, renal diseases, surgical patients,
patients on extracorporeal membranous oxygenation
(ECMO), and patients requiring mechanical ventila-
tion. Admitting diagnoses of all patients in the studies
were indicative of critical illness, while participants
in 1 study40 were postcardiac surgery. The mean age
of the participants in the studies was 58.6 ± 17 years.
APACHE II (Acute Physiology, Age, Chronic Health
Evaluation II) was used in 3 studies to measure the
severity of diseases.32,39,41 The mean APACHE score
in these studies was 21.97, with a standard deviation
of 7. A score of 25 represents a predicted mortality
of 50% and a score of more than 35 represents a pre-
dicted mortality of 80%.45
Vasoactive Therapy and Early Mobilization
In all 5 included studies, the participants who received
vasoactive drugs were mobilized safely, irrespective
of dose and characteristics of patients.32,34,39-41 Patients
who had compromised heart and lung function requir-
ing life support such as ECMO and vasoactive drugs
were mobilized without serious adverse events.39
The studies underlined that vasoactive medications
should not be considered as a contraindication for
early mobilization.32,34,39-41 One study reported that the
primary barrier for mobilizing the patients receiving
vasoactive drug was the clinician-perceived physi-
ological instability of the patient including hemody-
namic, cardiovascular, respiratory, and neurological
instability.32
Vasoactive Drug Dosage and Level of Mobility
Details of vasoactive drugs and dosages were identi-
fied in all the 5 studies included in this review.32,34,39-41
Activities included in these studies were passive
cycling, range-of-motion exercises, bed mobility
activities, transfers, and ambulation. In all of the stud-
ies, participants who received a low, moderate, and
high dose of vasoactive drugs were mobilized.32,34,39-41
However, only 3 studies identified the level of mobil-
ity achieved by patients with respect to drug dos-
age.32,34,40
The first study reported that patients on low doses
of vasoactive drugs were 5 times more likely to be
mobilized than those on high doses (odds ratio [OR] =
5.50; 95% confidence interval [CI] = 2.23-13.59),32
JACPT  ■  Volume 12  ■  Number 1  ■  2021
 TABLE 3. Segregated Results Derived From 5 Studies
Number of
Patients
Receiving
Study Patient Vasoactive Vasoactive Mobilization Therapeutic
Author Design Characteristics Drugs Drug/Dose Sessions Intervention Adverse Events
Boyd Prospective Mechanically Not mentioned. Both inotropes and 299 In bed exercises = 41 One event of cardiovascular
et al34 cohort study ventilated patients Only session vasopressors used. occasions (15 patients on instability in patients with
of mobilization Low-, moderate-, low dose; 24 moderate and moderate dose during
mentioned. and high-dose 2 on high dose) out-of-bed mobilization
classification
mentioned. Out-of-bed exercises = 114
occasions (67 patients on
low dose; 46 moderate and
1 on high dose)

JACPT  ■  Volume 12  ■  Number 1  ■  2021

Rebel Retrospective Mechanically 119 Dose classification 195 Low-intensity mobilization: Hypotension in 14
et al32 cohort study ventilated and available for IMS 1-2 in 43 patients patients and new onset of
nonmechanically dysrhythmia in 1 patient
ventilated patients Noradrenaline Moderate-intensity
mobilization: IMS 3-5 in
Dobutamine 71 patients
Vasopressin High-intensity
Adrenaline mobilization: IMS 6-10 in
25 patients
Levosimendan
Milrinone
Metaraminol

Abrams Retrospective Patients receiving 18 Dose classification Not mentioned The intervention ranges There were no patient-
et al39 cohort study ECMO for refractory available for from active assisted ROM related or circuit-related
respiratory or sitting in bed, sitting complications as a result of
cardiac failure Norepinephrine at the edge of the bed, physical therapy treatment
in the medical and vasopressin standing and ambulation sessions in any of the
intensive care unit patients

Nievera Retrospective Postcardiac surgery 47 Dose classification Not mentioned Most patients (56%) were 13% of patients experienced
et al40 cohort study patients who are available for able to ambulate 50 ft a decrease in mean arterial
not on mechanical (15 m) pressure
ventilators or VADs Norepinephrine

(continues)

41
Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units
Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units

while patients on moderate doses were twice as likely

to be mobilized than those on high doses (OR = 2.50;

Adverse Events
95% CI = 0.95-6.59).32 The second study34 reported
similar conclusions; the study revealed that 59% of

hypertension and 3
mobilized patients received a low dose of vasoactive

2 hypotension; 2
drugs, 40% received a moderate dose, and 0.87%
received a high dose.34 Contrary to the above find-

mobilization; in-bed passive tachycardia

ings, the third study found no relationship between
vasoactive drug dose and achieved level of mobility.40
According to the authors, the achieved level of mobil-
leg press, in chair sitting, in- ity might have been related to other factors, such as
chair passive mobilization; comorbid conditions and baseline physical fitness.40
in-chair passive and active
cycling; in-chair leg press;
and active cycling; in-bed
Intervention includes in-

Another factor that might have contributed to these

Intervention

bed passive and active

Therapeutic

standing and walking

inconsistent findings may be the functional status of
the participants. In the first 2 studies the participants
were patients who required mechanical ventilation,
whereas in this study40 the participants did not require
mechanical ventilation and, consequently, had higher
functional status than the participants of the first 2
ECMO, extracorporeal membrane oxygenation; IMS, ICU mobility scale; ROM, range of motion; VAD, ventricular assistive device.

studies.
Only 1 study19 quantified the level of mobility
Mobilization
Sessions

achieved by using a validated scale, namely the ICU

149 sessions

mobility scale (IMS).46,47 However, the data assessor

converted the mobilization descriptions from the doc-
umentation to the IMS score. This study showed 31%
of the patients achieved an IMS score of 1 to 2, 51%
achieved an IMS score of 3 to 5, and 18% achieved an
Dose classification

IMS score of 6 to 10.32

TABLE 3. Segregated Results Derived From 5 Studies (Continued)

Vasoactive
Drug/Dose

Noradrenaline
available for

Adverse Events
Serious adverse events were defined as a fall to the
ground, cardiac arrest, unplanned extubation, new
onset of cardiac dysrhythmias, removal of invasive
lines and tubes, loss of consciousness, hypoten-
Number of

Vasoactive
Receiving
Patients

sion necessitating escalation of medical therapy (as

Drugs
58

determined by the treating clinicians, rather than an

absolute threshold), and death.23,29,32,48 None of the
included studies reported any serious adverse events
associated with early mobilization.32,34,39-41 Overall,
Critically ill patients
Characteristics

the most commonly cited adverse event was revers-

ible hypotension.32,34,41
Patient

One study34 followed a standard traffic light system

recommended by an international multidisciplinary
expert consensus group9 for predicting the adverse
events while mobilizing patients. Green indicates a
low risk of an adverse event, yellow indicates a poten-
tial risk of an adverse event, and significant potential
cohort study

risk of an adverse event is categorized as red.9 In this

Design
Hickmann Prospective
Study

study, no adverse events were reported during in-bed

exercise sessions, whereas 1 minor adverse event,
without any clinical significance, was reported during
the out-of-bed exercise sessions.34 The adverse event
reported was cardiovascular instability in a patient
Author

who received a moderate dose of a vasoactive drug

et al41

while using a tilt table, but the type of cardiovascular

42 JACPT  ■  Volume 12  ■  Number 1  ■  2021

 Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units
instability was not reported.34 They identified that a
holistic clinical assessment including patient’s age,
level of exercise tolerance, functional independence
prior to ICU admission, current hemodynamic status,
and the amount of ventilatory and cardiac support
required minimized the risk of an adverse event.32,34,49
A study that included solely patients who received
vasoactive drugs reported an adverse event rate of
7.8%, but none of these was life-threatening.32 Early
cessation of mobilization occurred in 5.1% of the
patients as a result of transient physiological changes
(ie, desaturation, hypotension, bradycardia, and nau-
sea). The adverse events were more likely to be expe-
rienced in patients with lower mean arterial pressure
(OR = 0.72; 95% CI = 0.58-0.88) and higher FiO2
(OR = 1.38; 95% CI = 1.10-1.72).32 The other 2
studies did not report any significant adverse events
during mobilization.39,40 Another study provided lim-
ited data regarding adverse events specific to patients
with vasoactive drugs, including only the statement
that hypotension occurred in 2 patients receiving low-
dose vasopressors, hypertension in 2, and tachycardia
in 3.41
DISCUSSION
Currently, several reviews and studies have addressed
early mobilization of the patients in critical
care.2,8,9,17,30,48-51 This systematic review focused spe-
cifically on patients receiving vasoactive drugs and
explored the early mobilization practices, the rela-
tionship between drug dosage and the achieved level
of mobility, and the reported adverse events associ-
ated with early mobilization.
Vasoactive Therapy and Early Mobilization
Overall, the studies included in this review indicated
that mobilization of critically ill patients receiving
vasoactive drugs with stable hemodynamics could be
safely conducted without serious adverse events. Even
patients on mechanical ventilators, ECMO, and renal
replacement therapy were mobilized safely.32,34,39,41
The most common barrier to mobilizing the
patients were clinician-perceived hemodynamic insta-
bility and lack of multidisciplinary approach.32,50 A
study in medical ICUs found that 43% of physicians,
59% of nurses, and 42% of physiotherapists disagreed
with the mobilization of a patient on vasopressor
agents.50 The reluctance to embrace new mobilization
practices, lack of collaborative approach, reduced
knowledge regarding the appropriateness of mobili-
zation, and absence of guidelines were the major bar-
riers reported for early mobilization.50 The study con-
cluded that even though the majority of the critical
care clinicians were knowledgeable about the benefits
JACPT  ■  Volume 12  ■  Number 1  ■  2021
of early mobilization, most of them disagreed with
mobilizing patients on vasoactive drugs.50
Some of the published expert-driven protocols
recommended that the presence of a high dose of
vasoactive drugs was a contraindication for mobiliza-
tion.52-54 McWilliams et al52,53 in their 2 studies con-
sidered high doses of vasoactive agents (>0.2 μg/kg/
min noradrenaline or equivalent) as exclusion criteria,
and a low dose of vasoactive agents (0.01-0.02 μg/
kg/min noradrenaline, or equivalent) as a restriction
to sitting at the edge of bed. Sommers et al54 in their
evidence-based, expert-driven practical statement,
and rehabilitation recommendation considered dopa-
mine ≥10 μg/kg/min and nor/adrenaline ≥0.1 μg/kg/
min as an absolute contraindication for mobilization.
This review revealed that a team-based,
protocol-driven approach made mobilization feasible
to patients with vasoactive drugs, irrespective of the
dosage.41,55 A detailed assessment by an interprofes-
sional team was useful to determine the readiness
for exercise/mobilization of patients with vasoactive
drugs.26,39-41
Vasoactive Drug Dosage and Level of Mobility
The relationship between dosage of vasoactive drugs
and achieved level of mobility was inconsistently doc-
umented across studies included in this review.32,34,39-41
This review was not able to synthesize the correlation
between vasoactive drug dosage and level of mobility
because of the lack of standard outcome measures.
One important finding of this review was that, as a
general practice, patients on high and moderate doses
were less likely mobilized, compared with patients on
a low dose. Conversely, the evidence demonstrates
that many patients on high and moderate doses were
mobilized without serious adverse events.32,34,40
A case series of sedated mechanical ventilated
patients concluded that passive cycling was safe
even with a high dose of norepinephrine (maximum
concentration was 0.47 μg/kg/min).56 The important
component that influences the clinical decision to ini-
tiate mobilization was the hemodynamic stability of
the patient, not the dosage, or the number of vasoac-
tive drugs.32,40
This review’s findings were consistent with an
expert consensus statement,9 which reported that the
presence of vasoactive drugs was not an absolute con-
traindication to mobilization.
Adverse Events
The description of adverse events during mobiliza-
tion varied widely among the included studies.32,34,39-41
The incidence of adverse events associated with early
mobilization of patients receiving vasoactive drugs
43
Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units
was low, and most of them were not serious.32,34,39-41
One study identified that adverse events were more
likely to occur in patients with higher peripheral cap-
illary oxygen saturation (SpO2), a higher fraction
of inspired oxygen (FiO2), and lower mean arterial
pressure during mobilization.32 They reported that
clinicians were more likely to attempt mobilization
of patients with higher SpO2, presuming they have
adequate respiratory reserve. According to their
study, the mean arterial pressure was more clinically
significant in predicting the adverse events than SpO2
and FiO2.32 These hemodynamic parameters need to
be considered in predicting the adverse events during
mobilization.32
The consensus recommendation of 23 multidis-
ciplinary experts outlining safety consideration was
and will be a valuable tool in guiding the exercise
rehabilitation or early mobilization of patients.9 In
conjunction with a thorough assessment, this tool
was and will be useful to avoid adverse events during
mobilization.9,34
Clinical Implications
This review covers a broad spectrum of patients who
received different doses of vasoactive drugs; there-
fore, this could be useful for clinicians working in all
ICUs. The presence of vasoactive drugs should not be
considered as an independent factor to determine the
early mobilization of critically ill patients. The deci-
sion to mobilize a patient receiving vasoactive drugs
should depend on the clinical status of the patient at
the time of the planned mobilization and the direction
of trends in the past hours, rather than the dose of
vasoactive drugs. A cautious approach with slow pro-
gressive mobilization would help to achieve higher
levels of mobility, even with a higher dose of vasoac-
tive drugs.
LIMITATIONS
This review has several limitations. First, the method-
ological quality of the included studies was variable.
Second, the mobility achieved by the patients was
not assessed using validated tools. Third, the optimal
dose of vasoactive drugs for safe mobilization could
not be determined due to lack of data.
CONCLUSION
This review concludes that mobilizing patients in crit-
ical care units who are on vasoactive drugs appears to
be safe for most patients. Expert consensus is lack-
ing regarding the dose of vasoactive drugs that would
allow safe mobilization of patients and the highest
level of mobility that could be achieved in critical
44
care. The criteria that have been used to determine the
eligibility and progression of mobilization of patients
on vasoactive drugs were not consistent. Current
available studies indicate no serious adverse events
associated with mobilization. However, a holistic
approach remains vital to reduce or avoid any adverse
events.
Future multicenter prospective cohort studies
with large patient samples, diverse clinical diagnosis,
and utilizing appropriate outcome measure will be
essential to determine the optimal dose of vasoactive
drugs for safe mobilization and the level of mobility
achieved.
ACKNOWLEDGMENTS
The authors are grateful to Dr Steve Milanese for his
valuable inputs and guidance throughout this review.
They are also thankful to Pramod Divakar Shenoy and
Sheena Maria John for their valuable suggestions for
this review.
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 Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units

APPENDIX 1
Search terms:
The following are the details of the search terms used.
#1 “critical ill patient*” OR “intensive care unit*” OR “ICU”
#2 “vasoactive drug*” OR “vasoactive agent*” OR Dopamine OR Noradrenaline OR inotrope* OR vasopressor
OR adrenaline OR epinephrine OR norepinephrine OR dobutamine OR milrinone OR “vasoactive medicine*”
OR “vasoactive medication*”
#3 “early mobilization” OR “early mobilisation” OR “early ambulation” OR “early walking” OR ambulation
OR walking OR “active transfer” OR “passive transfer” OR “passive mobilization”
#1 and #2 and #3

APPENDIX 2

PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) flow diagram showing the
inclusion of studies.

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48
APPENDIX 3. Newcastle–Ottawa Quality Assessment Scale for Cohort Studies43,44
Quality Assessment
Criteria Rebel et al32 Boyd et al34 Nievera et al40 Abrams et al39 Hickmann et al41
Selection

Representativeness of the • Somewhat representative • Somewhat representative • Somewhat • Somewhat • Somewhat

exposed cohort of the average in the of the average in the representative of representative of representative of
community community the average in the the average in the the average in the
Selection of the
community community community
nonexposed cohort No description of the No description of the
derivation of the derivation of the No description of the No description of the No description of the
Ascertainment of exposure
nonexposed cohort nonexposed cohort derivation of the derivation of the derivation of the
Demonstration that nonexposed cohort nonexposed cohort nonexposed cohort
• Secure record (medical • Secure record (medical
outcome of interest was
record) record) • Secure record (medical • Secure record • Secure record (medical
not present at start of
record) (medical record) record)
study • Yes • Yes
No No No

Comparability

Comparability of cohorts • • • • •
on the basis of the
design or analysis

Outcome

Assessment of outcome No description No description No description No description • Independent blind

assessment
Was follow-up long enough • Yes, adequate follow-up • Yes, adequate follow-up • Yes, adequate follow-up • Yes, adequate 100
Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units

for outcomes to occur period for outcome of period for outcome of period for outcome of patients • Yes, adequate period
interest interest interest December 1, 2014, to
Adequacy of follow-up of No dropout mentioned
January 31, 2015
cohorts October 2016 to February 2015 to November 2010 to July
December 2016 December 2016 2011 No dropout mentioned
• Complete follow-up (no • Complete follow-up (no • Complete follow-up (no
dropout mentioned in this dropouts mentioned in dropout mentioned in
study) this study) this study
Note: A study can be awarded a maximum of 1 star for each numbered item within the Selection and Outcome categories. A maximum of 2 stars can be
given for Comparability (each asterisk represents if individual criterion with in the subsection was fulfilled).

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