[ Contemporary Reviews in Critical Care Medicine ]

Atrial Fibrillation in the ICU

Nicholas A. Bosch, MD; Jonathan Cimini, BS; and Allan J. Walkey, MD

Atrial fibrillation (AF) is the most common arrhythmia encountered in the ICU. Preexisting AF is
highly prevalent among older patients with chronic conditions who are at risk for critical illness,
whereas new-onset AF can be triggered by accelerated atrial remodeling and arrhythmogenic
triggers encountered during critical illness. The acute loss of atrial systole and onset of rapid
ventricular rates that characterize new-onset AF often lead to decreased cardiac output and
hemodynamic compromise. Thus, new-onset AF is both a marker of disease severity as well as a
likely contributor to poor outcomes, similar to other manifestations of organ dysfunction during
critical illness. Evaluating immediate hemodynamic effects of new-onset AF during critical
illness is an important component of rapid clinical assessment aimed at identifying patients in
need of urgent direct current cardioversion, treatment of reversible inciting factors, and
identification of patients who may benefit from pharmacologic rate or rhythm control. In
addition to acute hemodynamic effects, new-onset AF during critical illness is associated with
both short- and long-term increases in the risk of stroke, heart failure, and death, with AF
recurrence rates of approximately 50% within 1 year following hospital discharge. In the
absence of a strong evidence base, there is substantial practice variation in the choice of
strategies for management of new-onset AF during critical illness. We describe acute and long-
term evaluation and management strategies based on current evidence and propose future
avenues of investigation to fill large knowledge gaps in the management of patients with AF
during critical illness. CHEST 2018; 154(6):1424-1434

KEY WORDS: atrial fibrillation; critical illness; sepsis

Atrial fibrillation (AF) is the most common physicians. Thus, clinicians encounter either
sustained cardiac arrhythmia, with a lifetime prevalent (preexisting) or incident (new-
risk in the community of 25%1 and onset) AF among nearly one in three
associated complications of heart failure, critically ill patients.6
stroke, and death.2-4 As a comorbidity of
aging, preexisting AF is common among The present review discusses the clinical
patients presenting to the ICU. As a frequent impact of, and evidence-based approaches
complication of critical illness,5 new-onset to, AF in critically ill patients, with specific
AF is also a problem familiar to ICU consideration of risk factors,

ABBREVIATIONS: AF = atrial fibrillation; AV = atrioventricular; BB = for Implementation and Improvement Sciences (Dr Walkey), Boston
beta-blocker; CCB = calcium channel blocker; CHA2DS2VASc = University School of Medicine, Boston, MA.
congestive heart failure, hypertension, age $ 75 years, diabetes, pre- FUNDING/SUPPORT: Dr Walkey is supported by the National Heart,
vious stroke/transient ischemic attack, vascular disease, age 65 to 74 Lung, and Blood Institute [Grants 5K01HL116768-03 and
years, sex category; DCCV = direct current cardioversion; RVR = rapid 1R01HL136660-01].
ventricular response; SR = sinus rhythm CORRESPONDENCE TO: Allan J. Walkey, MD, The Pulmonary Center,
AFFILIATIONS: From the Department of Medicine (Drs Bosch and 72 E Concord St, R-304, Boston, MA 02118; e-mail: alwalkey@bu.edu
Walkey), The Pulmonary Center, Boston University School of Medi- Copyright Ó 2018 American College of Chest Physicians. Published by
cine, Boston, MA; Massachusetts College of Pharmacy and Health Elsevier Inc. All rights reserved.
Sciences (Mr Cimini), Worcester Campus, Boston, MA; and the Center
DOI: https://doi.org/10.1016/j.chest.2018.03.040

1424 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]
pathophysiology, treatments, and outcomes of new- produce a susceptible atrial substrate, providing fertile
onset AF during critical illness. ground for the development of sustained AF in response
to the myriad arrhythmogenic triggers of critical illness.

New-onset AF During Critical Illness: Risk Critical Illness and Atrial Remodeling
Factors and Mechanisms Accelerated cardiac structural and electrical remodeling
Mechanisms of new-onset AF during critical illness are can occur due to infection and inflammation that are
only partially elucidated. To better grasp the common during critical illness. Murine and primate
mechanisms and risk factors of AF during critical illness, models of pneumonia show that bacteria deposit within
we first review the current understanding of the the myocardium and result in development of atrial
mechanisms of AF in the community setting. fibrosis and an arrhythmogenic substrate, despite
Sustained AF is believed to occur through a two-step treatment with antibiotics.15-17 Bacteria can also alter
process that includes the following: 1) the formation of calcium ion channel gene expression through toxin
an arrhythmogenic atrial substrate as fertile ground for release, resulting in a shortened atrial-effective refractory
the development of AF, and 2) the “seed” that initiates period which produces electrical remodeling that further
AF through an arrhythmogenic trigger. Remodeling of predisposes to AF during sepsis.18
atria into a proarrhythmic substrate is most often due to Inflammation, regardless of the presence of infection, may
the development of atrial fibrosis. Chronic heart failure, also play a role in the development of AF. Elevated
hypertension, valve disease, and myocardial infarction inflammatory markers in patients with sepsis and
result in multiple, common pathways of inflammation, postoperative patients are associated with an increased risk
renin-angiotensin system activation, and generation of of developing AF.19 Inflammation may predispose to
reactive oxygen species that produce atrial fibrosis.7 In arrhythmia development as a result of direct inflammatory
addition to atrial fibrosis, persistent tachycardia can cell infiltration and oxidative damage to atrial myocytes.20,21
produce electrical remodeling that leads to an atrial Inflammation and oxidative damage may also help explain
substrate susceptible to AF through changes in associations between obesity and new-onset AF, both in the
intracellular calcium ion handling and ion channel community and during critical illness.19,22 In turn, early
expression.8 AF may be initially triggered through reports suggest that anti-inflammatory agents such as
multiple factors that perturb normal electrical glucocorticoids and statins may decrease the incidence of
conduction such as hypokalemia, hypomagnesemia, AF; these agents warrant further study.23
hypovolemia, and alterations in parasympathetic and
sympathetic activity, leading atrial foci to develop AF Triggers During Critical Illness
abnormal automaticity, self-sustaining action potentials,
In the ICU, AF is more frequent among patients
or re-entrant circuits.7,9-12 When arrhythmogenic
receiving vasopressor agents, in patients with electrolyte
triggers occur in the absence of an arrhythmogenic
derangements, and in patients with greater disease
substrate, AF is generally fleeting and self-terminating.
severity.24-26 For example, hypokalemia and changes in
However, when arrhythmogenic triggers combine with
the balance of autonomic activity as a result of
atrial fibrosis or electrical remodeling, AF can be
vasopressors may alter ion channel activity and cell
sustained and becomes increasingly difficult to terminate
automaticity that predispose to AF.9,27 Dopamine and
through further electrical remodeling.13
epinephrine in particular have chronotropic effects that
Although critical illness-induced AF also likely follows can lead to increased atrial ectopic discharges triggering
the development of a susceptible atrial substrate new AF.27 Greater illness severity is also associated with
combined with a triggering event, the specific factors the risk of new AF development, which may be a
that contribute to the arrhythmogenic substrate and the consequence of increased release of catecholamines and
specific triggers may differ from community-acquired progressive autonomic dysfunction.19,25,28 Lastly, atrial
AF. For example, traditional risk factors associated with size on echocardiography is associated with new-onset
AF in the community setting (ie, structural and valvular AF in the ICU, suggesting that iatrogenic atrial pressure/
heart disease) have not been consistently linked to new- volume overload may also be important in the
onset AF during critical illness.14 Rather, emerging development of AF in the critically ill.29 Figure 1
evidence suggests that acute events during critical illness summarizes proposed mechanisms for AF development
accelerate cardiac remodeling and fibrosis to rapidly in patients who are critically ill.

chestjournal.org 1425
 Pre-Critical Illness
Altered ion
channel
Normal Atria
Age Tachycardia
Diabetes activity
CHF
CKD

Structural Electrical
remodeling remodeling

TGF-B1
Renin-angiotensin
Inflammation/ROS

Arrhythmogenic
Normal Atria
Atria
Critical Illness

Sustained
Glucocorticoids ?
tachycardia
Statins ? – Structural Electrical
remodeling remodeling
Bacterial
Surgery Inflammation
Altered ion Toxins
channel
expression
Bacterial Accelerated Thyroid
Infection fibrosis Storm
Altered
intracellular
Volume Arrhythmogenic ion handling Anti-
Atrial Atria
overload Stretch arrhythmics

Uremic
Vasopressors Trigger Myocyte Toxins
Beta-blockers ? trauma/injury
–
Myocardial
Sepsis
Altered ischemia
Excessive
adrenergic intracellular
Beta- stimulation ion handling Right heart
agonists catheterization

Ventilator
Atrial Fibrillation Electrolyte
dyssynchrony derangements

Figure 1 – Proposed mechanisms and risk factors for new-onset AF during critical illness. AF develops through a two-step process: creation of an
arrhythmogenic substrate followed by a triggering event. During critical illness, both acute (dark blue boxes) and chronic risk factors (light blue boxes)
have roles in the development of AF. Prior to critical illness, chronic risk factors for AF may alter the normal atrial myocardium into an arrhyth-
mogenic substrate predisposing to AF during critical illness. During critical illness, patients with both normal and arrhythmogenic atria can develop
new-onset AF in the setting of acute risk factors. Risk factors potentially lead to accelerated structural and electrical remodeling and may then trigger
AF through multiple mechanisms, including adrenergic stimulation. Proposed pathways by which these risk factors lead to AF may be optimal targets
for future preventative strategies. AF ¼ atrial fibrillation; CHF ¼ congestive heart failure; CKD ¼ chronic kidney disease; ROS ¼ reactive oxygen
species; TGF ¼ transforming growth factor.

Prediction of New-onset AF During Critical Illness Klouwenberg et al19 recently developed a prediction tool
Tools that identify patients at high risk for new-onset AF for new-onset AF based on clinical factors, including
during critical illness may inform mechanisms of AF, time since admission, age, obesity, immunocompromise,
identify potential targets for intervention, and enrich elevation of inflammatory markers, shock, renal failure,
future trials studying AF preventative strategies. Klein potassium level, and FIO2. This tool can identify the risk

1426 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]
for AF in patients with sepsis with a C statistic of 0.81 measures (eg, Sequential Organ Failure Assessment) and
(https://safescore.shinyapps.io/safe). may represent an underrecognized sepsis-defining organ
dysfunction.34
Clinical Consequences of AF during Critical Among survivors of critical illness, new-onset AF
Illness frequently resolves prior to discharge,35 and thus
AF may lead to clinical decompensation through “secondary AF” has long been thought of as a self-
interrelated mechanisms. During AF, the coordinated limited event36 in patients in whom the AF trigger is
depolarization and contraction of the heart is disrupted transient. However, emerging evidence suggests that AF
by innumerable, disorganized atrial electrical impulses following critical illness often reoccurs after resolution of
leading to erratic contraction and loss of the “atrial kick” the critical illness and that long-term outcomes
that assists with ventricular filling during diastole. following critical illness may be associated with
Patients with diastolic dysfunction may be prone to arrhythmia persistence or reoccurrence. For example, in
hemodynamic decompensation during episodes of AF a large observational study, 55% of patients with new-
because of the increased reliance on the “atrial kick” onset AF who survived a sepsis hospitalization had AF
during left ventricular filling. Loss of atrial systole may occurrence within 5 years compared with 16% of
be particularly important in critical illnesses such as patients who did not have AF during a sepsis
sepsis, during which approximately one half of patients hospitalization.37 Interestingly, patients with new-onset
have impaired ventricular relaxation.30 In critical illness, AF during sepsis had higher 5-year risks of ischemic
excess sympathetic tone can also alter the depolarizing stroke, heart failure, and death compared with patients
properties of conducting fibers in the atrioventricular with no AF but a reduced risk compared with patients
(AV) node, allowing increased conduction of atrial with preexisting AF. These data suggest a potential
impulses to the ventricles and rapid ventricular pathway in which new-onset AF during critical illness
responses (RVRs) that further impair cardiac output.31 increases the risk of recurrent AF following critical
In one study evaluating hemodynamic consequences of illness, which then increases the risk of long-term poor
new-onset AF during critical illness, 37% of critically ill outcomes. Thus, AF during sepsis may contribute to the
patients with new-onset AF developed immediate development of the “post-ICU syndrome” and may
hemodynamic instability, 25% had heart rates > 150 represent an opportunity for intervention to improve
beats/min, and 11% exhibited new signs of cardiac long-term outcomes following critical illness.
ischemia and heart failure.32 Thus, although AF during
critical illness often presents during times of high disease Acute Management
severity, it also seems to increase the severity of the
Breaking the self-propagating cycles of AF and disease
disease itself.
progression represents a potential target to improve
outcomes during and following critical illness. The
Outcomes of AF During and After Critical treatment priorities of AF in the ICU depend on
Illness multiple factors, including the goals of care of the
Because development of AF during critical illness is patient, inciting events/reversible triggers, comorbid
associated with more severe illness prior to onset, as well disease, hemodynamic effects, and the risks of potential
as clinical worsening following onset, ascertaining the therapeutic agents. Within this context, we recommend
causal role of AF in patient outcomes is difficult. In one a multifaceted approach to the management of acute AF
study of 1,782 patients admitted to the ICU with sepsis, in critical illness based on current physiological
418 (23%) developed new-onset AF; the new-onset AF understanding and observational evidence. Therefore, a
was associated with increased hospital mortality after general approach to AF in the ICU setting includes the
accounting for competing risks and multiple, time- following: (1) assessment for potential hemodynamic
varying cofounding variables (subdistribution hazard effects and mechanisms of hemodynamic change likely
ratio, 2.10 [95% CI, 1.61-2.73]).19 Multiple other studies attributable to AF, (2) removal of offending agents that
have identified associations between new-onset AF and increase the risk for AF (ie, beta-agonists) and/or
increased risk of death during sepsis and critical correction of reversible arrhythmogenic triggers
illness.5,25,29,33 Thus, new-onset AF is a dysfunctional (electrolyte imbalances, airway obstruction, and atrial
cardiac response to infection with strong prognostic stretch), and (3) choice of an initial treatment strategy
implications beyond traditional organ dysfunction that maximizes potential benefit and minimizes risk

chestjournal.org 1427
when AF seems to be causing harm. Considerations for AF during critical illness (outlined in the following
initial pharmacologic strategies include rate control sections).
when adverse effects of AF seem due to an elevated heart
rate, or rhythm control when adverse effects of AF may Direct Current Cardioversion
be due to loss of atrial systole, or where a rate control In hemodynamically unstable patients with AF with
strategy is ineffective or has unacceptable side effects. In RVR or when AF with RVR contributes to ongoing
the event of precipitous hemodynamic compromise due myocardial ischemia, the American Heart Association,
to AF, urgent direct current cardioversion (DCCV) the American College of Cardiology, and the Heart
should be used. Finally, patients should be assessed for Rhythm Society 2014 guidelines make a strong
candidacy for arterial thromboembolism prophylaxis. recommendation, based on limited evidence, for
Figure 2 summarizes treatment priorities of new-onset DCCV.38 Despite this recommendation, the success

New AF

Rapid Clinical Assessment

1. Hemodynamic
DCCV
compromise?
• Discontinue beta-
agonists and anti-
arrhythmics if possible
2. Offending agent
• Change
vasopressors if
present?
using dopamine
• Correct electrolytes
or epinephrine
• Correct ventilator
3. Reversible inciting dyssynchrony
factors? • Treat myocardial
ischemia
• Optimize volume status
• Treat underlying infection

4. Is AF still present and

causing adverse effects
despite above measures?

Adverse effects of AF
Adverse effects of AF
are due primarily to
are due primarily to
elevated HR or of
loss of atrial systole
unknown cause

First line
Beta-blocker (esmolol) First line
Rate control Magnesium infusion
Second line
Nondihydropyridine ineffective Second line
calcium channel blocker Amiodarone
Digoxin

Figure 2 – Acute management priorities in new-onset AF during critical illness. Identification of new-onset AF during critical illness should prompt a
four-step rapid clinical assessment: (1) assessment for hemodynamic compromise requiring urgent DCCV, (2) removal of potential offending agents, (3)
reversal of inciting acute factors, and (4) treatment to reduce rate or convert to sinus if AF persists and is associated with adverse effects. DCCV ¼ direct
current cardioversion; HR ¼ heart rate. See Figure 1 legend for expansion of other abbreviation.

1428 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]
rates of attempted cardioversion of AF during critical associations between digoxin use and increased
illness are low: in postoperative patients who developed mortality, especially in patients with underlying heart
AF, attempted cardioversion resulted in immediate failure with serum digoxin levels > 1.2 ng/ml. In
conversion to sinus rhythm (SR) in 71% of patients, but addition, the vagomimetic effects of digoxin may be less
after 1 h, only 43% patients remained in SR, and after 24 effective during critical illnesses characterized by high
h, only 23% patients remained in SR.39 Thus, in critically catecholamine states.41-43 Magnesium affects ion
ill patients in whom cardioversion is attempted, channel activity to decrease cardiac automaticity and
concurrent administration of rate or rhythm control prolong AV node refractoriness, which may improve
therapy should be considered given the high likelihood rate control and lead to SR conversion without
of AF recurrence soon after a successful cardioversion substantial negative inotropic activity.44 Amiodarone
attempt. When DCCV is used during critical illness, inhibits adrenergic stimulation and blocks the delayed
there is often inadequate time or patient stability to rectifier current, which can lead to conversion to SR as
assess for left atrial thrombus. In addition, comorbid well as prolonged AV node refractoriness slowing AV
disease (ie, coagulation defects, recent stroke) is often conduction. A main advantage of amiodarone, unlike
present, which increases the risk of instituting several other antiarrhythmic agents, is that it is not
anticoagulation. It is unknown if administering contraindicated in patients with structural or coronary
anticoagulation in critically ill patients prior to DCCV heart disease.45 Potential disadvantages to amiodarone
decreases the risk of thromboembolic events or if there is are hypotension during IV infusion and pro-arrhythmic
an optimal timing of anticoagulation prior to DCCV. and organ toxicity effects, including an increased risk of
Thus, we recommend that the decision to administer chronic interstitial pneumonitis and organizing
periprocedural anticoagulation be informed by the pneumonia. Acutely, amiodarone lung toxicity can
urgency of DCCV and relative or absolute mimic ARDS.46-48
contraindication to such therapy.
There is significant practice variability regarding initial
Medication Options for Rate and Rhythm Control medication choice for AF during critical illness. In the
United States, CCBs are administered as initial
In critically ill patients without severe hemodynamic
treatment most frequently (36%) for patients with AF
decompensation resulting from AF, clinicians have a
and sepsis, followed by BBs (28%), digoxin (20%). and
range of medical therapies to consider for rate or rhythm
amiodarone (16%). Practices also vary according to
control. Frequently chosen rate control medications are
country: a survey of intensivists in the United Kingdom
nondihydropyridine calcium channel blockers (CCBs),
found that > 80% would choose amiodarone as first-line
beta-blockers (BBs), and cardiac glycosides such as
treatment, whereas 12% chose BBs.49 Despite being a
digoxin. Medications selected for rhythm control most
less commonly used initial treatment, preliminary BB
often include magnesium and amiodarone, both of
use for AF was associated with a lower risk of in-hospital
which have rhythm- and rate-controlling properties.
mortality compared with CCBs, digoxin, or amiodarone
CCBs, such as verapamil and diltiazem, inhibit voltage-
in an observational analysis among patients with
gated calcium channels, decreasing depolarization of the
sepsis.50 In addition, a study using granular ICU data
AV node and slowing heart rate; however, these agents
showed that initial use of metoprolol for AF with RVR
also have vasodilatory and negative inotropic effects and
was associated with lower need for administration of a
are contraindicated in patients with acute heart failure.
second agent compared with amiodarone and better rate
BBs have rate-controlling, negative inotropic and
control at 4 h compared with diltiazem.51 Other studies
vasodilatory effects similar to CCBs, but they function as
suggest that use of esmolol during sepsis enhances
sympatholytic agents through antagonism of the beta1-
arterial elastance and ventricular-arterial coupling,52
receptor, leading to decreased conduction through the
which may improve cardiovascular efficiency and reduce
AV node and reduced effects of catecholamines on the
mortality.53 Thus, use of BBs to treat arrhythmias during
myocardium. A distinct pharmacokinetic advantage of
critical illness is a promising area of investigation.
BBs is the ultra-short-acting preparation esmolol, which
allows rapid titration and discontinuation with fast Two small randomized trials comparing rate vs rhythm
recovery from potential drug-related hypotension.40 control medications in AF with RVR in the acute (but
Digoxin slows heart rate by increasing vagal tone; it is non-ICU) setting supplement observational studies
associated with low rates of hypotension but has a during critical illness. In a single-center study of 150
narrow therapeutic index. Observational studies show patients with uncomplicated acute symptomatic AF with

chestjournal.org 1429
RVR requiring hospital admission, randomization to There are currently no anticoagulation guidelines for AF
diltiazem was associated with a higher percentage of during sepsis; further studies are direly needed to clarify
sustained ventricular rate control (90%) compared with potential benefits/harms prior to standardized treatment
digoxin (74%) and amiodarone (74%) (BBs were not being recommended. Given the lack of clear benefit and
evaluated).54 In a single-center study of 60 ICU patients the potential for harm, in critically ill patients with new-
with supraventricular tachycardia (AF: n ¼ 57; atrial onset AF during sepsis who do not have planned
flutter: n ¼ 2; atrial tachycardia: n ¼ 1), randomization cardioversion, we do not currently recommend routinely
to diltiazem compared with two dosing strategies of initiating parenteral anticoagulation for arterial
amiodarone did not seem to result in different rates of thromboembolism prophylaxis during the acute phases
adequate heart rate control within 4 h (70% for diltiazem of critical illness.
vs 55% for amiodarone load vs 75% for amiodarone load
and maintenance); however, diltiazem was associated Approaches to Long-term Management
with an increased rate of drug discontinuation due to
Following critical illness, decisions to initiate
hypotension (30% vs 0% vs 5%, respectively).46 Given
anticoagulation to reduce thromboembolic risk depend
the observational findings of decreased mortality,
on the persistence of arrhythmia, thromboembolic and
improved heart rate control, better ventriculo-arterial
bleeding risks, and goals of care. AF during critical
coupling, and pharmacokinetic advantages, it is
illness frequently resolves prior to discharge
reasonable to use esmolol as a first-line treatment for
(86% resolution in a single-center study of patients with
hemodynamically significant AF during critical illness if
septic shock), but long-term thromboembolic risk of
no contraindications exist. If additional control is
patients with new AF during critical illness seems to
needed, second-line agents may include magnesium,
remain relatively high.35 Among survivors who
diltiazem, and amiodarone, with digoxin reserved for
developed new-onset AF during sepsis and who
situations in which other agents are ineffective or
experience an ischemic stroke following the sepsis
contraindicated. The strong safety profile of magnesium
hospitalization, one half did not have another AF
and similar rate of conversion to SR compared with
diagnosis recorded prior to the stroke.37 Thus, among
amiodarone make magnesium a reasonable choice prior
patients with new-onset AF during the critical illness
to amiodarone if rhythm control strategy is chosen.55
that seems to be “resolved,” there may be opportunity to
Table 1 summarizes AF treatment strategies.56-68
reduce post-critical illness stroke events through
increased AF surveillance following hospital discharge.
Subacute Management In patients without contraindications to anticoagulation
After rate and rhythm management of AF during critical whose AF persists following hospital discharge,
illness, the next clinical dilemma is often the decision to thromboembolism prophylaxis should be initiated in
start arterial thromboembolism prophylaxis with those not at low risk (as determined by using
anticoagulation. Patients with critical illness and AF CHA2DS2VASc [congestive heart failure, hypertension,
have a twofold increased risk of in-hospital ischemic age $ 75 years, diabetes, previous stroke/transient
stroke compared with those without AF,25 but they also ischemic attack, vascular disease, age 65 to 74 years, sex
have higher bleeding risk and often require invasive category] score).70 Once the decision is made to initiate
procedures that may necessitate interruption of anticoagulation, we agree with the 2014 guideline
anticoagulation; decisions regarding anticoagulation of recommendations of the American Heart Association,
critically ill patients are complex. In a nationwide study the American College of Cardiology, and the Heart
of patients with AF and sepsis in the United States, Rhythm Society regarding choice of anticoagulant
35.3% received parenteral anticoagulant agents. In medication.38 The timing of prophylaxis initiation
propensity score-matched patients, there was no should be informed according to the patient’s goals of
difference in rate of in-hospital ischemic stroke between care, renal function, bleeding risk, and medication
patients who received or did not receive parental interactions.71 For patients who have no evidence of AF
anticoagulant agents; however, there was an increase in persistence following critical illness, measures should be
clinically significant bleeding (8.6% vs 7.2%) in the instituted to facilitate detection of subclinical AF.
patients who received parenteral anticoagulation.69 It is Specifically, outpatient cardiac monitoring should be
unknown if similar associations exist for nonsepsis considered in patients without AF persistence but with
causes of critical illness. elevated CHA2DS2VASc scores to identify patients who

1430 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]
chestjournal.org

TABLE 1 ] AF Rate and Rhythm Control Treatment Strategies During Critical Illness
Intervention and Dose Class and Mechanism Expected Efficacya Onset of Effect Contraindications Potential Adverse Effects
Esmolol: Load 500 mg/kg IV Beta-blocker: blocks binding of Noncritical illness SVT with RVR: 5 min56 Bradycardia; Bradyarrhythmia
(may repeat); followed by catecholamines to beta1- mean decrease in heart rate of decompensated hypotension; heart
50-300 mg/kg/min56 receptors, decreases AV node 39 beats/min57 heart failure; 2nd or block; hyperkalemia;
conduction, reduces 3rd degree heart hypoglycemia;
arrhythmia induction and block; sick sinus bronchospasm (rare
inotropy syndrome; AF with with beta1-
an accessory antagonist)56,58
pathway56,58
Metoprolol tartrate: 2.5- Same as above Noncritical illness SVT: mean 20 min58 Same as above Same as above
5 mg IV every 2 to 5 min58 decrease in heart rate of 28
beats/min59
Diltiazem: Load 0.25 mg/kg Nondihydropyridine calcium Critical illness SVT with RVR: 3 min60 Bradycardia; Bradyarrhythmia
IV, followed by 5-15 mg/h60 channel blocker: inhibits mean decrease in heart rate of decompensated peripheral edema;
L-type voltage-gated calcium 44 beats/min after 4 h46 heart failure; 2nd or hypotension;
channels, decreases AV node 3rd degree heart constipation60,61
conduction, reduces inotropy block; sick sinus
syndrome; AF with
an accessory
pathway60,61
Verapamil: Load 0.075- Same as above Noncritical illness AF or atrial 10 min61 Same as above Same as above
0.15 mg/kg IV, followed flutter with RVR: mean
by 0.005 mg/kg/min61 decrease in heart rate of 45
beats/min57
Digoxin: Load 0.25 mg IV, Cardiac glycoside: inhibits Na-K Noncritical illness AF with RVR: 5-30 min62 Ventricular fibrillation62 Digoxin toxicity (monitor
followed by repeat dosing ATPase increasing mean decrease in heart rate of levels); dysrhythmias;
(maximum 1.5 mg/24 h).62 intracellular sodium and approximately 30 beats/min increased myocardial
Dose lower in renal failure calcium, vagomimetic within 6 h of administration54 oxygen demand62
Amiodarone: Load 150 mg Class 3 antiarrhythmic: blocks Critical illness AF or atrial flutter 8 h (mean Bradycardia; Bradyarrhythmia
IV over 10 min, followed adrenergic signaling and ion with RVR: mean decrease in time to Cardiogenic shock, ventricular
by 1 mg/min for 6 h, flow, extends refractory heart rate of 37 beats/min64 SR)65 2nd or 3rd degree arrhythmias;
followed by 0.5 mg/min period, decreases AV node Noncritical illness AF: heart block; severe hypotension (IV
for 18 h63 conduction, reduces restoration of SR in 83% 20 h sinus node formulation); organ
membrane excitability after administration65 disorders63 toxicity (liver, thyroid,
skin, and lung)63

(Continued)
1431
 may benefit from anticoagulation, a strategy that has

Studies of treatment efficacy of AF during critical illness are limited. Thus, inclusion of arrhythmia type (AF, atrial flutter, and SVT) and context (critical illness, noncritical illness, or postoperative) are included.
Embolic stroke, pain, skin
shown promise in patients following cryptogenic

Potential Adverse Effects

burns, arrhythmias68
stroke.72

hypotension; CNS

hyporeflexia;

depression67
depression;
Prevention of AF

respiratory
Heart block;
Prevention of new-onset AF in the ICU is an appealing
strategy to potentially improve outcomes and mitigate
the often-difficult short- and long-term management
of critically ill patients who have AF with RVR. To
date, few studies have analyzed prevention of AF in the
Contraindications
2nd or 3rd degree

general ICU setting. In a recent, prospective

Digitalis toxicity
heart block67

nonrandomized study, the administration of

hydrocortisone in patients with septic shock was
associated with lower rates of new-onset AF following
propensity score matching.73 Randomized trials have
AF ¼ atrial fibrillation; AV ¼ atrioventricular; HR ¼ heart rate; RVR ¼ rapid ventricular rate; SR ¼ sinus rhythm; SVT ¼ supraventricular tachycardia.

shown lower rates of new-onset AF following cardiac

surgery in patients administered magnesium infusions,
Onset of Effect

glucocorticoids, and BBs23,55,74; it is unknown whether

Within 30
min66

Instant

these strategies are of benefit in a general ICU

population. Specific therapies to reduce AF during
critical illness cannot be recommended at this time.
conversion to SR, 23% in SR
RVR: 21.4% have resolution

Postoperative AF: 71% initial

Future Considerations
noncritical illness AF with
Expected Efficacya

Future studies of AF in the ICU will help guide our

Combined critical and

ability to predict, prevent, and manage this frequent

and potentially devastating arrhythmia. Improvements
after 24 h39

in technology to identify the timing and duration of

of RVR66

AF in the ICU using automated detection algorithms

and mining of large ICU electronic medical records
will help us to understand the temporal association
between risk factors and AF and potentially inform
mechanisms (projectreporter.nih.gov [1R01HL136660-
channels and activates Na-K
ATPase promoting resting

01]). Long-term AF detection techniques may also

Electrolyte: blocks calcium

Electrical shock: electrical

Class and Mechanism

help to identify patients following ICU hospitalizations

energy depolarizes all
excitable membranes

who are most likely to benefit from thromboembolism

prophylaxis. Randomized trials to address gaps in our
polarization67

knowledge of acute rate and rhythm control therapies

in the critically ill are ongoing, assessing the effect of
magnesium infusions on AF with RVR in the ICU75
and specific dosing strategies of amiodarone for AF
during sepsis.76 Further randomized trials are needed
to identify the optimal rate or rhythm strategy for
over 10 min; repeat if no

synchronized 120-200 J
Magnesium sulfate: 1-3 g

patients in the ICU and to clarify the differences, if

response in 15 min66
] (Continued)

present, between specific medications within these

Direct current cardio-

biphasic or 200 J
Intervention and Dose

strategies.
version: QRS

monophasic

Acknowledgments
Financial/nonfinancial disclosures: None declared.
TABLE 1

Role of sponsors: The sponsor had no role in the design of the study,
the collection and analysis of the data, or the preparation of the
manuscript.
a

1432 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]
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1434 Contemporary Reviews in Critical Care Medicine [ 154#6 CHEST DECEMBER 2018 ]