Editorials
Arrhythmias in the ICU
What Do We Know?
Management of arrhythmias is undoubtedly one of the major
problems in emergency and critical care medicine; however,
there are only limited data on the frequency of admissions with
a primary arrhythmia diagnosis and on the incidence and type of
arrhythmia during the intensive care unit (ICU) stay (1–5). In
the ICU setting, an arrhythmia incidence of up to 78% has been
reported (2). However, this retrospective study was too inclu-
sive, including even patients with ventricular or supraventricu-
lar premature beats or bundle branch block, which do not
represent the common perception of a significant, sustained
arrhythmia. Other prospective observational studies reported
an annual incidence of 14.9% (4) and between 15.7 and 19.7%
(3) in a surgical and a medical ICU, respectively.
In the current issue of the Journal (pp. 20–25), the article by
Annane and coworkers (6) examines the incidence of arrhyth-
mias in a general ICU population. The authors did a meticulous
job in collecting data on a large number of patients and used
rigorous criteria for the classification of sustained arrhythmias.
The study confirms previous data on the incidence of arrhyth-
mias and extends existing knowledge in several ways.
Annane and colleagues report in this multicenter 1-month
cohort study a 12% incidence of ventricular plus supraventric-
ular arrhythmias for a general ICU population. This incidence is
in line with the aforementioned data from surgical and medical–
surgical ICUs. When comparing the incidence against previous
studies, it should be recognized that the case mix may not have
been so different when compared with previous work. Only 9
ICUs were mixed, whereas 14 were medical and 3 were surgical
ICUs. Although the majority of patients were admitted for
noncardiac disease (87%), 60% of all patients and 86% in the
arrhythmia group had a cardiovascular history.
Arrhythmia only rarely appears to be a diagnosis for primary
admission to the ICU (1). Rather, arrhythmias occur during the
ICU stay. It is evident that the occurrence of arrhythmia will
depend on an underlying disease and thus on the case mix. It is
therefore interesting that the incidence of arrhythmia is virtually
identical in surgical, medical, and cardiologic ICUs when con-
temporary arrhythmia definitions are used. Moreover, and even
more interesting, the median time to occurrence of specific
arrhythmias in the ‘‘general’’ ICU population of this study was
comparable to the time course of atrial fibrillation (AF) in
noncardiac postoperative patients (7), being around Days 1–2.
Several possible explanations exist for these intriguing findings.
First, the case mix may have been identical in all studies, which is
very unlikely. Second, very different etiologies, such as chronic
obstructive pulmonary disease, acute respiratory distress syn-
drome, pulmonary embolism, and valvular heart disease, may
lead to a final common pathway of arrhythmia as is the case for
AF or flutter. Third, the ICU environment, with interventions
such as mechanical ventilation, vasopressors, and inotropes or
invasive procedures, may be the cause of arrhythmia. Although
sympathetic tone definitely is a trigger for arrhythmias (8) and
sudden cardiac death (9), conflicting data exist as to the influence
Am J Respir Crit Care Med Vol 178. pp 1–6, 2008
Internet address: www.atsjournals.org
of analgesia and sedation. The circadian occurrence of arrhyth-
mia through the 24-hour day does not appear to be influenced by
the presence or absence of sedation (10). Fourth, common
pathophysiologic mechanisms operative in critical illness might
predispose to arrhythmia. One process common to critical illness
and multiorgan failure of different origin is systemic inflamma-
tion. Inflammation has also been suggested to be a possible mech-
anism for AF (11), which is the single most common arrhythmia in
the ICU. However, the occurrence of arrhythmia episodes did not
coincide with a peak in inflammation parameters in an uncon-
trolled study (12). In favor of this fourth possibility, Annane and
colleagues, in the online supplement, report a 5.3% incidence of
supraventricular arrhythmia, mainly AF, when excluding primary
cardiac diagnoses and chronic arrhythmia. Even in trauma pa-
tients with a very different etiology of critical illness, AF was a
predominant arrhythmia (5).
Similar to previous data, AF was the single most frequent
arrhythmia in the current study. AF carries a two- to six-fold
risk of stroke, and the rate of ischemic stroke in nonvalvular AF
averages 5% per year (13). The stroke rate secondary to new
onset AF in critically ill patients in the ICU is essentially un-
known. For the first time in a prospective study, data on
neurological consequences of true AF in the ICU are reported
by Annane and coworkers. The authors identified 4 of 87
patients with focal neurological deficits accounting for a rate
of 4.6% during their 1-month observation period. This is in line
with data on AF in the non–critically ill population. Thus,
the current study presents important data on the stroke risk in
the ICU, but certainly requires confirmation in a larger number
of patients.
Some studies suggested that supraventricular arrhythmias
are associated with higher mortality (2, 14). It has been unclear
so far whether this association merely reflected an association of
arrhythmias with a higher severity of disease. The current study
adds a new aspect to this discussion by adjusting for a variety of
important covariates, among which were age and the Simplified
Acute Physiology (SAPS) II score. The authors found that
supraventricular arrhythmias were no longer associated with a
poorer hospital/90-day survival after covariate adjustment and
after propensity score matching. This finding shows that AF and
supraventricular tachycardia are associated with higher comor-
bidity and are indicators of sicker patients but not necessarily a
harbinger of a poorer outcome.
Conflict of Interest Statement: G.H. has no financial relationship with any
commercial entity that has interest in the subject of this manuscript.
GOTTFRIED HEINZ, M.D.
Universitätsklinik für Innere Medizin II
Vienna, Austria
References
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Hirschl MM, Laggner AN. Sustained ventricular tachycardia in the
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3. Reinelt P, Delle Karth G, Geppert A, Heinz G. Incidence and type of
cardiac arrhythmias in critically ill patients: a single center experience
in a medical-cardiologic ICU. Intensive Care Med 2001;27:1466–1473.
4. Knotzer H, Mayr A, Ulmer H, Lederer W, Schobersberger W, Mutz N,
Hasibeder W. Tachyarrhythmias in a surgical intensive care unit: case-
controlled epidemiologic study. Intensive Care Med 2000;26:908–914.
5. Seguin P, Laviolle B, Maurice A, Lecqulerc C, Malledant Y. Atrial
fibrillation in trauma patients requiring intensive care. Intensive Care
Med 2006;32:398–404.
6. Annane D, Sébille V, Duboc D, Le Heuzey J-Y, Sadoul N, Bouvier E,
Bellissant E. Incidence and prognosis of sustained arrhythmias in
critically ill patients. Am J Respir Crit Care Med 2008;178:20–25.
7. Brathwaite D, Weissmann C. The new onset of atrial arrhythmias
following major noncardiothoracic surgery is associated with increased
mortality. Chest 1998;114:462–468.
8. Lampert R, Jain D, Burg M, Batsford W, McPherson CA. Destabilizing
effects of mental stress on ventricular arrhythmias in patients with
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9. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an
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10. Delle Karth G, Reinelt P, Buberl A, Geppert A, Hülsmann M, Berger R,
Heinz G. Circadian variation in ventricular tachycardia and atrial fibrilla-
tion in a medical-cardiological ICU. Intensive Care Med 2003;29:963–968.
Reduced Lung Function in Cystic Fibrosis
A Primary or Secondary Phenotype?
During the past decade, advances in the early assessment of cystic
fibrosis (CF) lung disease have led to an improved understanding
of its pathophysiology, but many questions still remain unan-
swered (1). The earliest airway abnormalities of focal, distal
mucous plugging leading to peripheral airway dilatation (2) have
been difficult to detect with the current armentarium of clinical
tests. Recently, objective measures have been developed dem-
onstrating that CF lung disease begins early, often prior to clinical
manifestations (3–5). Diminished physiologic measurements (3–
5), increased airway inflammation, and early infection (6–8) as
well as developing bronchiectasis (9, 10) have been demonstrated
during early infancy. Longitudinal data during infancy have also
shown that this reduction in lung function does not ‘‘catch up,’’ even
after initiation of treatment (3). Despite these advances, the trig-
gering factor for the cascade of events leading to early airway in-
fection, inflammation, and flow limitation has not been entirely clear.
In this issue of the Journal (pp. 42–49), Kozlowska and col-
leagues (11) eloquently describe the evolution of lung function
from infancy through the preschool years in children with CF
compared with healthy control subjects. The longitudinal mea-
sures were performed using the raised-volume rapid thoraco-
abdominal compression technique and incentive spirometry
and were carefully conducted based on standardized, published
guidelines (12). The prospective inclusion of a parallel control
group strengthens the findings in this study and is unique, given
the difficulty of assessing sedated lung function during infancy in a
healthy population. These novel results better define the specific
physiologic measures that identify early lung disease throughout
the first years of life. While diminished values of forced expiratory
volume at 0.75 second (FEV0.75) and forced expiratory flows be-
tween 25 and 75% of forced vital capacity (FEF25–75) were docu-
mented across all ages, FEV at 0.5 second (FEV0.5) only differ-
entiated children with CF from healthy controls during infancy,
not during preschool years. This interesting finding likely reflects
the predominance of the central airway component in the mea-
sure of FEV0.5. Because early CF lung disease is located in the
distal airways, identifying longitudinal physiologic markers that
best represent peripheral airway mucous plugging is critical for
future therapeutic trials conducted in this young age group.
2008
11. Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA,
Bauer JA, Tchou PJ, Niebauer MJ, Natale A, et al. C-reactive protein
elevation in patients with atrial arrhythmias: inflammatory mechanisms
and persistence of atrial fibrillation. Circulation 2001;104:2886–2891.
12. Koreny M, Reinelt P, Meyer B, Delle Karth G, Geppert A, Hülsmann
M, Priglinger U, Berger R, Heinz G. Dynamics of inflammation
parameters prior to tachyarrhythmias in critically ill patients. Wien
Klin Wochenschr 2005;117:342–347.
13. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL,
Halperin JL, Kay GN, Klein WW, Levy S, et al. ACC/AHA/ESC
guidelines for the management of patients with atrial fibrillation:
executive summary a report of the ACC/AHA Task Force on Practice
Guidelines and the ESC Committee for Practice Guidelines and Policy
Conferences (Committee to Develop Guidelines for the Management
of Patients with Atrial Fibrillation) developed in collaboration with the
North American Society of Pacing and Electrophysiology. Circulation
2001;104:2118–2150.
14. Goodman S, Shirov T, Weissmann C. Supraventricular arrhythmias in
intensive care unit patients: short and long-term consequences. Anesth
Analg 2007;104:880–886.
DOI: 10.1164/rccm.200804-554ED
Newborn screening was not available in London during the
time period when this study was conducted and infants were diag-
nosed on the basis of clinical symptoms. The question of whether
the reduction in lung function represents a primary rather than
secondary abnormality can therefore not be answered by this
study. Autopsy specimens (13) obtained immediately after birth
have revealed lungs without evidence of morphologic damage,
but the methodology in these studies may have been inadequate
to detect subtle abnormalities in lung growth as well as functional
changes induced by alterations in smooth muscle tone. Therefore,
the pertinent question of when physiologic abnormalities truly
begin, in utero, at birth or later, is still unresolved. The imple-
mentation of newborn screening offers the opportunity to study
infants prior to the development of clinical signs and symptoms
and will allow researchers to address this issue more effectively.
Longitudinal evaluation of the infant with CF, diagnosed by
newborn screening, from birth through the school-age years is
important in linking structural damage, physiologic findings, and
the presence of lower airway inflammation and/or infection.
Whereas it has been difficult in the past to evaluate CF lung
disease adequately in the youngest children, measures such as the
raised-volume rapid thoracoabdominal compression technique,
controlled breathing chest computed tomography scans, and
bronchoalveolar lavage are now available, which will help tackle
these important research questions (1).
While demarcating the physiologic markers of early CF pe-
ripheral airway disease remains important, discovering the etiol-
ogy of diminished lung function is of equal significance. Outlining
the cause of reduced lung function helps to monitor and guide
future modes of early CF management. If the CF lungs are normal
at birth, what is triggering the cascade of events leading to chronic
inflammation and infection? Kozlowska and colleagues (11) report
that the presence of Pseudomonas aeruginosa infection, wheezing,
and recent cough was independently associated with reduced lung
function. In fact, lung function remained decreased even in those
children with apparent eradication of P. aeruginosa. Despite these
significant associations, P. aeruginosa may not be the cause of the
reduced lung function but simply a marker of more significant lung
disease in this subpopulation. Because these infants were diag-