Cardiovascular Complications of the Guillain-Barr Syndrome

Siddharth Mukerji, MDa, Feras Aloka, MDa, Muhammad U. Farooq, MDb,

Mounzer Y. Kassab, MDb, and George S. Abela, MDa,c,*
The Guillain-Barr syndrome (GBS) is the most common cause of acute flaccid paralysis
in young adults and the elderly and an important cause of admission to intensive care units.
Manifestations of the GBS vary from monoparesis to life-threatening paralysis of the
respiratory muscles. The latter is often punctuated by the presence of cardiac involvement.
This ranges from variations in blood pressure to involvement of the myocardium and
potentially fatal arrhythmias. This review addresses some of the common cardiovascular
complications of the GBS, with their myriad presentations and therapeutic options, as well as
potential preventive measures that can be helpful in the management of patients admitted to
intensive care units. In conclusion, it is necessary to recognize the potentially fatal cardiovas-
cular complications associated with the GBS and treat them accordingly. 2009 Elsevier Inc.
All rights reserved. (Am J Cardiol 2009;104:14521455)

The Guillain-Barr syndrome (GBS), also known as tomegalovirus, Epstein-Barr virus, and human immunode-
acute inflammatory demyelinating polyneuropathy, can be ficiency virus infection have also been associated with the
acute or subacute in presentation. It affects the peripheral GBS.11,12 Anecdotal reports suggest that a small percentage
nerves and is characterized by symmetrical progressive as- of patients develop the GBS after events such as immuni-
cending weakness with areflexia and variable sensory com- zation, especially with meningococcal and influenza vac-
plaints. It can affect motor, sensory, and autonomic fibers cines; surgery; trauma; bone marrow transplantation; and
and is believed to be the most frequent cause of acute even tumor necrosis factor antagonist therapy.13,14
neuromuscular paralysis and ventilatory failure.1,2 The GBS Different degrees of affliction of the autonomic nervous
is presumed to be caused by an aberrant immune response system can be seen in up to 70% of patients with the GBS.15
against peripheral nerves by cross-reacting antibodies.3,4 Current data suggest sympathetic overactivity rather than
The incidence of the GBS is estimated at 1 to 2 per 100,000 parasympathetic hypoactivity in such patients.16 Autonomic
per year. An increased incidence after 50 years of age, with dysfunction has been commonly reported in the acute de-
a preponderance in women, has been reported.5,6 Morbidity myelinating subtype and is accompanied by elevated levels
and eventual mortality in patients with the GBS are associ- of epinephrine and norepinephrine in the plasma and in-
ated with cardiopulmonary instability, including blood pres- creased 24-hour urine levels of vanilmandelic acid.17,18 It is
sure (BP) fluctuations, potentially fatal tachyarrhythmia, postulated that a failure of catecholamine uptake in the
bradyarrhythmia, and myocarditis. Hence, these patients irritated peripheral nerves may be responsible for these
need to be monitored in intensive care settings. In this elevations. Also, the denervated organs have been noted to
review, we describe the common cardiovascular complica- be increasingly sensitive to catecholamines, resulting in
tions (Table 1) and management associated with the GBS. denervation hypersensitivity. Cardiovascular disturbances
are believed to be secondary to a combination of this entity
Pathogenesis in addition to impairment of the carotid sinus reflex.19 By
pathology, various patterns of lymphocytic infiltration and
The GBS is often preceded by an infection that is be- macrophage-mediated demyelination coincide with the
lieved to evoke an immune response. This leads to a cross- symptoms. Recovery is typically associated with remyeli-
reaction with peripheral nerve components because of nation.
shared epitopes resulting in acute polyneuropathy.7 This is
further supported by the identification of various antigan-
glioside antibodies noted in necropsy and animal models Clinical Variants
that cross-react with the ganglioside surface molecules of The GBS is a heterogenous syndrome with several vari-
peripheral nerves.7,8 Also, this phenomenon may explain ant forms and distinguishing features. Acute inflammatory
the potential involvement of the heart, which possesses demyelinating polyneuropathy is the most common form
lactose-containing gangliosides. The most commonly iden- seen in the United States and Europe (85% to 90%). A
tified precipitant is Campylobacter jejuni infection.9,10 Cy- clinical variant, Miller Fisher syndrome, characterized by
ophthalmoplegia, ataxia, and areflexia, occurs in 5% of
a cases in the United States and 25% of cases in Japan.20
Department of Medicine, bDepartment of Neurology, Division of
Cerebrovascular Disorders, and cDivision of Cardiology, Michigan State Acute motor axonal neuropathy and acute sensorimotor
University, East Lansing, Michigan. Manuscript received May 6, 2009; axonal neuropathy are primary axonal forms of the GBS.
revised manuscript received and accepted June 28, 2009. These forms are frequently observed in China, Japan, and
*Corresponding author: Tel: 517-353-4830; fax: 517-353-4978. Mexico but constitute only an estimated 5% to 10% of the
E-mail address: george.abela@hc.msu.edu (G.S. Abela). GBS cases in the United States.21 Other rare variants of the

0002-9149/09/$ see front matter 2009 Elsevier Inc. All rights reserved. www.AJConline.org
doi:10.1016/j.amjcard.2009.06.069
 Review/CVS Complications in the GBS 1453

Table 1 ing short-term heart rate variability, carotid pressure, and

Common cardiovascular complications of the Guillain-Barr syndrome modified Valsalva maneuvers, are not very useful in
Rhythm abnormalities 1. Bradyarrhythmias predicting serious bradyarrhythmias.23,28 Hence, Flache-
2. Sustained sinus tachycardia necker et al23 recommended simple bedside tests such as
3. Atrial and ventricular arrhythmias eyeball pressure testing. Furthermore, those investigators
Blood pressure variability 1. Hypotension recommended heart rate power spectrum analysis as ad-
2. Hypertension junct testing to assess the risk for possible life-threaten-
Myocardial involvement 1. Myocarditis
ing arrhythmias.23,28,31 This is a highly specialized non-
2. Neurogenic stunned myocardium
3. Heart failure
invasive method of investigating the neural mechanisms
Acute coronary syndromes 1. ST elevation myocardial infarction of cardiovascular regulation using beat-to-beat interval
Electrocardiographic changes 1. Giant T waves (RR interval) variability.28 Aggressive correction of as-
2. Prolonged QT intervals sociated factors such as hypoxia, medication side effects,
3. ST-T changes and metabolic abnormalities as well as awareness of
4. U waves tracheal suctioning as a cause may help prevent arrhyth-
5. Atrioventricular block mias.32 It thus appears that currently, there is no definite
6. Bradycardia and tachycardia recommendation for the modality of therapy. The concept
of long-term temporary pacing to allow time for recovery
may be compared with permanent pacing in documented
GBS have been reported, including acute pandysautonomia, symptomatic asystole and is very much a judgment
with symptoms including diarrhea, vomiting, dizziness, ab- call. This might vary on the basis of the clinical ap-
dominal pain, ileus, orthostatic hypotension, urinary reten- proach of the treating physician. Transcutaneous pacing
tion, pupillary abnormalities, an invariant heart rate, de- is another viable option if needed for a short-term
creased sweating, salivation, and lacrimation. Reflexes are period.33
absent or diminished, and sensory symptoms may be
present. It may respond to intravenous immunoglobulin BP variability: BP variability can be attributed to dis-
therapy.22 turbances in the baroreceptor reflex pathway as well as
changes in the catecholamine levels. The dysregulation of
Cardiovascular Complications the parasympathetic and sympathetic systems is responsible
for alterations in venomotor tone and peripheral vascular
Cardiovascular abnormalities in the GBS are attributed resistance, most often causing transient or in some cases
to autonomic neuropathy and are seen variably in 2/3 of persistent hypotension. Fluctuations in BP are common and
affected patients.23 However, pathologic changes at autopsy are thought to be characteristic of the GBS, helping differ-
in some patients who died from the GBS have not consis- entiate it from critical illness neuropathy.34 Increases and
tently demonstrated these changes.24,25 This suggests vary- decreases in BP have been documented and can occur in the
ing degrees of autonomic nervous system impairment, es- same patient during the course of the illness. This is espe-
pecially in the efferent fibers of the vagus nerves.24 Heart cially observed in patients on mechanical ventilators.35 In
rate variability, BP variability, cardiomyopathy, and elec- the study by Pfeiffer et al,16 significant BP decreases were
trocardiographic changes are some of the well-described noted in 75% of the subjects, although none reported any
entities.26,27 In this review, we focus on the more commonly orthostatic symptoms, while other studies suggest an in-
occurring complications. creased frequency of hypertension as well. This was par-
Rhythm abnormalities: Sustained sinus tachycardia is tially consistent with previously reported data.1 Although
the most common abnormality. Because of its transient Pfeiffer et al16 postulated that these episodes of BP devia-
nature, it usually does not require treatment.28 In a study by tion were related to mechanical ventilation, analgesia, and
Pfeiffer et al,16 an increase in the mean heart rate to 125 sedation, they could not account for 13 of 36 patients who
beats/min was documented in only 25% of the subjects. This developed hypotension despite being off sedation. They
was believed to be due to sympathetic hyperactivity. How- ultimately concluded that an increased daily systolic BP
ever, treatment with blockers or other antihypertensive variation of 85 mm Hg was a sensitive indicator of dys-
medications should be held, because this may aggravate autonomia. Patients with BP fluctuations and high diurnal
incipient bradycardia and hypotension. Therapy is indicated heart rates have been identified as at high risk for arrhyth-
only in older patients with coronary artery disease.16 Other mias as well.35 Hence, patients with labile BP should un-
tachyarrhythmias, including atrial and ventricular arrhyth- dergo prolonged cardiovascular monitoring, preferably in
mias, may occur. Treatment is often temporary and is an intensive care unit. Intra-arterial BP monitoring is rec-
recommended only in life-threatening situations. Vagal ommended for all patients with BP fluctuations. In patients
overactivity caused by afferent baroreceptors reflex fail- with hypotension, a fluid challenge is advocated before
ure is believed to be instrumental in causing bradycardia starting low-dose vasopressor therapy. Presently, there are
(Figure 1).29 Bradyarrhythmias can occur in up to 50% of no specific recommendations for target mean arterial pres-
patients with the GBS, and potentially serious events sure. For hypertension, the judicious use of antihypertensive
necessitating the administration of atropine or pacemaker therapy and/or vasodepressors is warranted. Patients with
placement, including atrioventricular block and asystole, mean arterial pressure 125 mm Hg may be treated with
have been reported in 7% to 34% of patients.16,30 Unfor- intravenous labetalol, esmolol, or nitroprusside. Ventilated
tunately, standardized autonomic function tests, includ- patients on sedation should also be closely monitored for
1454 The American Journal of Cardiology (www.AJConline.org)

Figure 1. Electrocardiogram of a patient with GBS demonstrating severe bradyarrhythmias and prolonged asystole (5.4 seconds) revealing a blocked P wave
(arrows) and peaked T waves. Note the different P-wave morphology before and immediately after the asystole.29

graphic studies should be considered in patients with pro-

longed episodes of tachycardia, labile BP, cardiac enzyme
abnormalities, and abnormal results on electrocardiography.
Because most of these cases are reversible, supportive man-
agement is indicated.
Acute coronary syndromes: A review of the published
research reveals anecdotal reports of acute coronary syn-
dromes, including ST-segment elevation myocardial infarc-
tion occurring during therapy for the GBS with intravenous
immunoglobulins.40 In other reported cases, cardiac cathe-
terization has demonstrated normal coronary artery mor-
phology in such patients, while 1 report suggested coronary
spasm.41,42 In the former study,41 intracoronary Doppler
flow measurements revealed an elevated baseline coronary
flow velocity with a decreased coronary flow reserve in the
left circumflex artery, probably secondary to a catechol-
Figure 2. High-power image of myocytes indicating myocarditis. There are amine surge. Thus, treating physicians should always be
lymphocytic infiltrates in the cardiac tissue (hematoxylin and eosin stain- aware of this very rare phenomenon.
ing, 250). Reproduced from http://commons.wikimedia.org/wiki/File:
Viral_myocarditis_(1).JPG. Electrocardiographic changes: Although electrocar-
diographic changes do not constitute a specific pathology,
we review some of the commonly occurring changes. A
sudden decreases in BP as well, especially given that the wide spectrum of electrocardiographic changes have been
possibility of denervation hypersensitivity is high.36,37 With demonstrated, including giant T waves, prolonged QT in-
labile BP, other contributing conditions, such as pulmo- tervals, ST-T changes, U waves, and atrioventricular blocks,
nary thromboembolism, hypoxemia, sepsis, gastrointes- in addition to bradycardia and tachycardia as described
tinal bleeding, and metabolic abnormalities, need to be previously.43 These changes are believed to be secondary to
considered.15 associated myocardial involvement. Hence, patients mani-
Myocardial involvement: This ranges from asymptom- festing with bizarre electrocardiographic results should be
atic myocarditis to neurogenic stunned myocardium and investigated for underlying cardiomyopathy. Along with
heart failure. It can be reasonably argued that these effects 2-dimensional echocardiographic studies, other modalities
arise from the activation of the sympathetic nervous system, to demonstrate cardiac involvement may be an option.
caused by catecholamine-associated myocardial injury.38 Scans such as iodine-123 meta-iodobenzylguanidine myo-
However, infectious agents incriminated in the cause of the cardial scintigraphy, which is used to estimate local myo-
GBS, in addition to certain chemicals and hypersensitivity cardial sympathetic nerve damage, autonomic nerve distur-
to medications, can also account for myocarditis39 (Figure 2). bance in neuropathy, and disturbance of the autonomic
The occurrence of this abnormality is not as high as heart nervous system in neurodegenerative disease, may be con-
rate or BP fluctuations. This could be due partly to not sidered.43 Imaging techniques such as carbon-11 hy-
performing 2-dimensional echocardiography on patients droxyephedrine positron emission tomography can also be
with the GBS routinely. Hence, 2-dimensional echocardio- used to study sympathetic innervation of myocardium.44
 Review/CVS Complications in the GBS 1455

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