BEST

Baillière’s Clinical Anaesthesiology B A I L L I È R E ’ S

Vol. 13, No. 1, pp 1–7, 1999

1 PRACTICE
& RESEARCH

Physiology and pathophysiology of thoracic

sympathetic blockade

Norbert Rolf MD, PhD

Associate Professor of Anaesthesia

Hugo Van Aken MD, PhD, FRCA, FANZCA

Professor of Anaesthesia and Chairman
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster,
Albert Schweitzer-Str. 33, 48149 Münster, Germany

Sympathetic innervation of the heart and lung is mediated by fibres originating from the thoracic
segments T1–4. Sympathetic stimulation in healthy subjects causes coronary vasodilation,
whereas stenotic coronary arteries show vasoconstriction in response to sympathetic
stimulation. Thus, in patients at risk of ischaemia, high thoracic epidural anaesthesia (TEA)
should dilate constricted coronary vessels, decrease heart rate and myocardial metabolism, and
improve cardiac function by reducing pre- and afterload and optimizing oxygen availability. The
pulmonary effects include an improved postoperative diaphragmatic function in lambs and
humans and enhanced respiratory function parameters. Hypoxic pulmonary vasoconstriction, an
important mechanism for the maintenance of adequate oxygenation after induction of general
anaesthesia, is not affected by TEA in dogs. Beneficial effects of epidural sympathetic blockade
on myocardial perfusion and function, and on pulmonary parameters, can only be achieved by a
thoracic blockade, whereas lumbar epidural anaesthesia may exert adverse effects due to a
compensatory increase of thoracic sympathetic activity.

Key words: epidural anaesthesia; sympatholysis; cardiac effects; pulmonary effects.

The thoracic autonomic sympathetic nervous system comprises sympathetic afferents

and efferents which originate from the segments C1–T12 and have their second post-
ganglionic neurone in the sympathetic trunk and the abdominal ganglia. It affects
various organ functions including lacrimation, pupil size, sudation and skin perfusion.
In this review the effects of sympathetic stimulation and blockade on cardiac perfusion
and function and on pulmonary blood flow regulation will be discussed. A detailed
evaluation of the effects on the gastrointestinal tract is presented in Chapter 2 of this
volume by Peter Hodgson and Spencer Liu.
In general, autonomic impulses are transmitted by B- and C-type fibres. The pre-
ganglionic B-fibres are myelinated but thin and transmit with a velocity of 3–15 m/sec-
ond; in contrast, the post-ganglionic C-fibres are thin and unmyelinated. Thus,
autonomic nerve fibres are more susceptible to the effects of local anaesthetics than
sensory Aβ–1 and Aδ-fibres. This explains the fact that the level of sympathetic
blockade after epidural or spinal administration of local anaesthetics lies cephalad to
the level of sensory or motor blockade (Greene, 1958). This zone of differential
1521–6896/99/010001 + 07 $12.00/00 © 1999 Harcourt Publishers Ltd.
2 N. Rolf and H. Van Aken

sympathetic blockade can be as large as six segments in spinal anaesthesia and is less
during epidural anaesthesia owing to an impaired axial and transdural spread of the
local anaesthetic compared with the spinal route of administration (Chamberlain and
Chamberlain, 1986). Sympathetic innervation of the heart and lung is mediated by
fibres originating from the thoracic segments T1–T4. Of note is that the transmission
of anginal pain is also mediated by these sympathetic afferents.

CARDIAC PERFUSION AND FUNCTION

In a resting adult of 70 kg body weight, coronary blood flow (CBF) is approximately

225 ml/minute, which is about 4–5% of cardiac output. In the autoregulatory range,
CBF is nearly constant over a wide range of perfusion pressures. At a constant
myocardial oxygen consumption, a decrease in coronary perfusion pressure causes
autoregulatory vasodilation, coronary vascular resistance being adjusted to maintain
constant myocardial perfusion. The major variables influencing coronary flow are
perfusion pressure, myocardial systolic compression, metabolic control and neuro-
humoral factors. Beyond the autoregulatory range, coronary perfusion is proportion-
ally related to coronary perfusion pressure and inversely dependent on coronary
vascular resistance. Under these circumstances, changes in mean arterial pressure
(MAP) are usually followed by a proportional change in CBF. Coronary perfusion
pressure is commonly defined as the difference between MAP and left ventricular end-
diastolic pressure. Because nearly 70% of CBF occurs during diastole and increases in
heart rate are accompanied by a shortening of the duration of diastole, heart rate is
also an important determinant of CBF. Neural effects on cardiac performance and
rhythm are mediated via α- and β-adrenergic receptors. Sympathetic α-adrenergic
stimulation leads to a vasoconstrictive influence on epicardial vessels, where α-
receptors dominate. Moreover, this vasconstrictive activity limits vasodilation in the
subepicardial vessels and prevents epicardial steal. In healthy subjects, this stimulation
does not necessarily lead to an increase in coronary vascular resistance as metabolic
counterregulation may mobilize substantial vasodilatory reserve, especially in the
subendocardial tissue.
Intramyocardial and subendocardial coronary arteries are dominated by β1-
adrenergic receptors (Feigl, 1983). The effect of β-adrenergic stimulation of coronary
vessels is not clearly defined as multiple effects are mediated by β-receptors in vivo.
β-Stimulation causes positive inotropy and chronotropy leading to increased myo-
cardial metabolism and oxygen consumption. Because perfusion and contraction are
coupled, an increased myocardial metabolism is followed by an increase in CBF via
metabolic regulation. The exact mechanism of metabolic regulation remains
controversial; adenosine triphosphate (ATP) sensitive K+-channel openers (Katsuda et
al, 1996), adenosine (Cason et al, 1994), prostaglandins (Nakhostine and Lamontagne,
1994), neuropeptides (Gutterman and Morgan, 1995) and nitric oxide (Goodson et
al, 1994) are involved. However, in contrast to the previously held assumption that
post-stenotic coronary segments are maximally dilated as a result of the above-
mentioned metabolic control, it is now clear that sympathetic stimulation may over-
ride local metabolic control (Brown, 1985). Thus, also in subjects with coronary
stenoses there is a vasodilatory reserve which may be ‘mobilized’ by sympathetic
blockade. A more detailed overview of some of these mechanisms is provided in
Chapter 4 of this issue.
 Physiology and pathophysiology of thoracic sympathetic blockade 3

The effects of sympathetic stimulation in patients with coronary artery disease differ
from those in healthy subjects. Nabel et al (1988) have demonstrated a constriction of
atherosclerotic arteries induced by the cold pressor test, while smooth segments
dilated. This effect of sympathetic activation is in concordance with the finding in
patients with classic angina that the diameter of the atherosclerotic artery decreased
during exercise (Gage et al, 1986). Activation of sympathetic influences also has the
potential to override local metabolic vasodilation, which has been shown for adenosine
infusion or stress, induced by the cold pressor test. This might be caused by activation
of α-receptors restricting the metabolically related flow increase by about 30%.
As well as sympathetic reflexes, the endothelium plays an important role in the tone
of coronary arteries (Furchgott and Jothianandan, 1991). In animal studies it has been
demonstrated that, after removal of the endothelium, the relaxing effects of β-
adrenergic agonists are reduced and the constrictive effects of α-adrenergic agonists
are enhanced (Miller and Vanhoutte, 1984; Rubanyi and Vanhoutte, 1985). Therefore,
a malfunction of the endothelium can have further deleterious effects in the mediation
of sympathetic activity.
Sympathetic blockade by high thoracic epidural anaesthesia (TEA) has the potential
for blocking cardiac afferent and efferent fibres, which originate from the first to fifth
thoracic levels (T1–T5). The perception of cardiac pain and angina is mediated via
sympathetic afferent nerves. Stimulation of sympathetic efferents leads to an increase
of inotropy, cardiac output and systemic vascular resistance. Epidurally applied
anaesthetics targeted to the T1–T5 segments produce sensory blockade, motor
blockade (depending on concentration) and blockade of the cardiac sympathetic fibres.
It has been reported that TEA leads to a reduction in heart rate, cardiac output and
systemic vascular resistance and may therefore decrease myocardial oxygen demand
(Blomberg et al, 1989; Saada et al, 1992). However, others reported increased heart
rates with reduced cardiac output (Reiz et al, 1979) or no change in either value
(Sjögren and Wright, 1972; Hasenbos et al, 1988). The effect of TEA on left ventricular
contractility has been the subject of several animal and clinical studies, but it still
remains controversial. Contractility has been reported to be unchanged (Ottesen et
al, 1978; Rolf et al, 1996), reduced (Hotvedt et al, 1984; Davis et al, 1986; Lundberg et
al, 1987) or improved (Blomberg et al, 1990; Kock et al, 1990). The variability of these
results might be due to different types of anaesthetics used, whether or not
epinephrine was added, the differing number of segments blocked and species differ-
ences. Various parameters have been used to measure left ventricular function, includ-
ing isovolumetric and ejection phase indices such as dP/dtmax, stroke volume, systolic
time intervals or ejection fractions. All these parameters are highly dependent on
cardiac loading conditions (Robotham et al, 1991). In conclusion, positive effects of
TEA cannot simply be deduced from these investigations and differences in patient
populations have to be taken in account when studies of TEA are evaluated. Ideally, in
patients at risk of ischaemia, TEA should dilate constricted coronary vessels, decrease
heart rate and myocardial metabolism and improve cardiac function by reducing pre-
and afterload and optimizing oxygen availability.

PULMONARY FUNCTION AND BLOOD FLOW

An in-depth evaluation of the effects of TEA on the respiratory system is provided by

Thomas Hachenberg and Birgit Pfeiffer in Chapter 5 of this volume. Impaired
ventilatory function as reflected by reduced vital capacity occurs after abdominal as
4 N. Rolf and H. Van Aken

well as after thoracic surgery (Ford et al, 1983; Road et al, 1984; Dureuil et al, 1986;
Easton et al, 1989). Periods of hypoxaemia occur post-operatively, especially during
sleep (Catley et al, 1985; Beydon et al, 1992; Rosenberg et al, 1994) and are associated
with myocardial ischaemia. Impairment of lung function starts with induction of general
anaesthesia and lasts for 1–2 weeks post-operatively.
The inhibition of diaphragmatic function despite profound analgesia plays an
important role in ventilatory impairment (Simonneau et al, 1983). The precise
mechanism of diaphragmatic dysfunction is unknown; one hypothesis suggests that
stimulation of afferent nerves in the chest and abdominal walls, viscera and the
diaphragm leads to an inhibition of phrenic motor drive (Dureuil et al, 1986). TEA has
been shown to improve post-operative diaphragmatic function in lambs (Polaner et al,
1993) and humans (Mankikian et al, 1988) and to improve respiratory function
parameters (Fratacci et al, 1993).
In contrast to these beneficial effects, TEA has potentially negative effects resulting
from paralysis of the thoracic muscles (Polaner et al, 1993). The denervation of the
musculature of the rib cage theoretically alters lung volumes. Measurements of
functional residual capacity (FRC) before and after induction of TEA in subjects with-
out lung disease did not reveal any changes in this muscle-tone-dependent lung volume
(Lundh et al, 1983). In elderly patients, Sakura et al (1996) found a significant decrease
of 13% in minute ventilation and a 14% decrease in tidal volume after induction of TEA
but no impairment in the response to hypercapnia or hypoxia. When TEA is extended
to high thoracic levels (T1), FRC is significantly increased (Warner et al, 1996) and
associated with a reduction in intrathoracic blood volume after peripheral vasodilation.
As with effects on cardiac function, the number of segments blocked seems to play an
important role in the effects of epidural anaesthesia on lung function.
The pulmonary vasculature is innervated by the autonomic nervous system, and
hypoxic pulmonary vasoconstriction may be influenced by sympathetic neural
blockade. Hypoxic pulmonary vasoconstriction, an important mechanism for
maintenance of adequate oxygenation after induction of general anaesthesia (Theissen
and Meissner, 1996), is not affected by TEA in dogs (Ishibe et al, 1996).

LUMBAR VERSUS THORACIC BLOCKADE

An important question is whether beneficial effects can be achieved by lumbar epidural

anaesthesia (LEA) instead of TEA. Sympathetic block leads to numerous effects on the
vascular bed. Measurement of sympathetic impulses in post-ganglionic fibres to skin
and muscle of the legs has shown a complete block of either spontaneous or induced
sympathetic activity during epidural anaesthesia (Lundin et al, 1989). Epidural blockade
of lumbar segments resulted in an increased sympathetic activity in splanchnic nerves
due to baroreceptor drive, but only TEA produces near total ablation of splanchnic
activity (Hogan et al, 1993, 1995).
However, both techniques have an inherent risk of cardiovascular depression and
hypotension. The most frequent cardiovascular complications, for example vasovagal
syncope and arterial vasodilation, are usually treated successfully with atropine and
intravenous volume replacement, as well as vasopressor drugs when indicated.
Bradycardia due to the Bezold–Jarisch reflex is commonly refractory to atropine
treatment and the administration of potent vasopressors. These patients experience
hypotension and profound bradycardia, associated with venous blood pooling and
heightened cardiac contractility (Mark, 1983). This results in reflex arterial dilation and
 Physiology and pathophysiology of thoracic sympathetic blockade 5

vagally mediated bradycardia. Owing to the extent of the sympathetic block and
vasodilation, this reflex occurs more often with LEA than with TEA.
In an experimental setting in swine, the injection of bupivacaine for LEA with
blockade to the thoracic level induced a severe reduction of myocardial blood flow
distal to a coronary artery stenosis (Mergner et al, 1994). The reduction in oxygen
supply due to hypotension during LEA is not followed by a concomitant reduction in
demand (Saada et al, 1992). This might even be aggravated by an enhanced sympathetic
reactivity in sympathetically intact areas (Baron et al, 1988), which has recently been
demonstrated for LEA and TEA in cats (Taniguchi et al, 1997). During TEA the lower
CBF seems to be compensated by a decrease in myocardial oxygen demand and
cardiac work (Saada et al, 1992). Similar reductions in mean arterial pressure are not
followed by segmental wall motion disturbances during TEA (Saada et al, 1992) but
during LEA (Saada et al, 1989). Kock et al (1990) found an improved cardiac perform-
ance during exercise under TEA than during control exercise. Ischaemia-induced left
ventricular global and regional wall motion abnormalities were improved under TEA,
associated with less pronounced ST segment depression. In conclusion, TEA has more
favourable effects than LEA in the patient with coronary artery disease.

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 Physiology and pathophysiology of thoracic sympathetic blockade 7

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