Acta Anaesthesiol Scand 2010; 55: 234241
Printed in Singapore. All rights reserved
Heart rate variability may identify patients who will
develop severe bradycardia during spinal anaesthesia
A. CHATZIMICHALI1, A. ZOUMPROULI2, M. METAXARI1, I. APOSTOLAKIS3, T. DARAS3, N. TZANAKIS1 and H. ASKITOPOULOU1
1
Department of Anaesthesiology, University Hospital of Heraklion, Crete, Greece, 2Anaesthesia Department, St Georges Hospital, London, UK
and 3Department of Science, Technical University of Crete, Chania, Crete, Greece
Background and objectives: The reported incidence of cardiac
arrest during spinal anaesthesia is 6.411.2 per 10,000 patients.
Many of these arrests occurred in healthy young patients during
minor surgery. This raises the question of whether some of them
were avoidable. We investigated the value of Heart Rate Varia-
bility (HRV) to identify patients prone to developing severe
bradycardia during spinal anaesthesia.
Methods: Eighty ASA III patients, 2160 years of age,
undergoing elective surgery under spinal anaesthesia were
studied. The HRV was assessed for 25 min before the spinal
block. Two spectral components of HRV were calculated: a
low-frequency (LF) and a high-frequency (HF) component.
Patients were grouped according to whether bradycardia
did or did not develop during spinal anaesthesia.
Results: Nineteen patients developed severe bradycardia
(o45 b.p.m.). The mean value of HF before spinal anaesthesia
A LTHOUGH spinal anaesthesia is considered a
relatively safe technique, there are certain side
effects. Retrospective studies have shown the in-
cidence of bradycardia during spinal anaesthesia to
be as high as 13%.1 The incidence of cardiac arrest
was reported to be 6.4  1.2 per 10,000 spinal
anaesthetics in France, with a fatal outcome in six
out of 26 cardiac arrests (in 40,640 spinal anaes-
thetics). Auroy and colleagues reported that the
risk of deaths after cardiac arrest was significantly
associated with age and ASA physical status class.
The average age of the survivors was 57  20 years,
whereas the average age of non-survivors was
82  7 years.2 In another large retrospective study,
the overall incidence of cardiac arrest during spinal
anaesthesia was reported to be 2.9 per 10,000. The
mean patient age was 66  15 years old. Four of
these arrests occurred in patients younger than 50
years of age.3 In a review of 900 closed insurance
claims for major anaesthetic mishaps, 14 cases of
sudden cardiac arrest in young (36  15 years),
healthy patients (ASA III) who received spinal
234
r 2010 The Authors
Journal compilation r 2010 The Acta Anaesthesiologica Scandinavica Foundation
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2010.02339.x
was significantly increased in the bradycardic group (Po0.05).
The correlation between baseline heart rate (HRbaseline) and
minimum heart rate and LF, HF during spinal anaesthesia was
significant (Po0.01). A receiver operator curve characteristic
analysis showed a sensitivity and specificity of HF and HRbaseline
of 65% and 74%, respectively, to predict bradycardia o45 b.p.m.
after spinal anaesthesia.
Conclusions: The present study shows that HF and clinical
factors such as patients HR baseline could identify patients
prone to developing severe bradycardia during spinal
anaesthesia.
Accepted for publication 23 September 2010
r 2010 The Authors
Journal compilation r 2010 The Acta Anaesthesiologica Scandinavica Foundation
anaesthesia were reported.4 The mechanism of
these events is not well established, particularly
in healthy, young patients. Bradycardia during
spinal anaesthesia is believed to result from at least
two causes: blockade of sympathetic cardio-accel-
erator fibres and decreased venous return to the
heart.5 Carpenter et al.1 have found that patients
classified as ASA physical status I had more than a
threefold increase in the odds of developing bra-
dycardia, when compared with patients of ASA
physical status III or IV. This may result from the
increased vagal tone typically present in young,
healthy patients. Patients with a baseline heart rate
(HRbaseline) of o60 b.p.m. were more likely to
develop severe bradycardia.1 These findings sug-
gest that the balance between the sympathetic and
the parasympathetic tone may play an important
role in the susceptibility of a patient to develop
bradycardia during spinal anaesthesia.
Power spectral analysis of heart rate variability
(HRV) is a useful tool to assess cardiac autonomic
activity.612 Several studies have investigated the

prognostic value of HRV in the obstetric and non-
obstetric population under spinal anaesthesia.
They have used HRV as a tool for predicting those
patients who are at risk of hypotension.1318 There
are no studies investigating the value of HRV in
predicting healthy patients at risk of developing
bradycardia under spinal anaesthesia. We investi-
gated whether pre-operative HRV can identify
patients prone to developing severe bradycardia
during spinal anaesthesia.
Methods
Patients with ASA physical status I and II under-
going elective lower abdominal or lower limb
surgery under spinal anaesthesia were included
in the study. The type of surgery did not require the
use of a tourniquet and the blood loss was minimal.
Patients below 18 and above 60 years of age were
excluded from the study. Patients with a history of
cardiovascular disease, arrhythmia, autonomic ner-
vous system (ANS) disorders such as diabetes
mellitus or use of medication that may affect the
ANS were excluded from the study. Following
approval by the hospitals ethics committee, in-
formed consent was obtained.
Patients did not receive premedication. On arri-
val to the operating room, they were placed in the
supine position and routine monitoring of pulse
oximetry, ECG (lead II and V5), non-invasive blood
pressure and a seven-lead Holter ECG (Syneflash,
Ela Medical, Le Plessis-Robinson, France) was in-
itiated. An intravenous (i.v.) cannula was placed
and pre-hydration with a bolus of 510 ml/kg of
Ringers Lactated solution was started. Spinal
anaesthesia was performed with the patient in the
sitting position using a 25 G spinal needle in the
L3 4 or the L4 5 intervertebral space (according to
access feasibility), and 1012 mg of hyperbaric
bupivacaine 0.5% (5 mg/ml) was injected. The level
of spinal block was evaluated by loss of painful
sensation to pinprick 510 min after the injection.
All patients were kept supine and awake during
the study. No i.v. sedation was administered dur-
ing the operation. Patients were breathing sponta-
neously and directed to breath calmly at a rate of
around 1418 breaths/min as recommended for
HRV measurements.
Severe bradycardia was defined as heart rate
o45 b.p.m. for at least four 15-s consecutive record-
ing epochs.1 HRbaseline was defined as the heart rate
on arrival in the operating room. Ephedrine (5 mg)
HRV and bradycardia during spinal anaesthesia
was given to patients who developed during spinal
anaesthesia o45 b.p.m. accompanied by hypoten-
sion (systolic blood pressure o80 mmHg), and atro-
pine (0.5 mg) to those who developed only severe
bradycardia of o45 b.p.m.
Measurements
Heart rate and blood pressure were recorded every
2 min for 25 min before the spinal injection with the
patient lying quietly in the supine position. A
seven-lead Holter ECG was recorded on a compact
disc. The recorded ECG during the pre-spinal
injection period (25 min) was processed automati-
cally by a Syneflash Holter analyser, which distin-
guishes QRS complexes, systoles outside the sinus
node and technical errors and interference, fol-
lowed by an evaluation by an expert cardiologist.
HRV analysis was performed according to Task
Force of the European Society of Cardiology and
the North American Society of Pacing and Electro-
physiology recommendations.12 Twenty-five-min-
ute recordings of the fast peaks of R waves on
the ECG were acquired with a sampling rate of
1,000 Hz. The beat-to-beat variability of consecutive
R waves of the sinus rhythm was measured con-
tinuously and stored in a computer. Data were
analysed using Fast-Fourier Transformation (FFT).
Two spectral components of HRV were calculated:
a low frequency (LF) of 0.060.15 Hz and a high-
frequency (HF) component of 0.150.4 Hz. In order
to cancel out the influence of the parasympathetic
activity on the LF spectral power, the LF/HF ratio
was also calculated. This ratio provides a measure of
the sympatho-vagal balance. An increase in the LF/
HF ratio reflects a predominance of sympathetic
over parasympathetic activity.12 As FFT analysis
requires stationary collection of the data, patients
were asked to lie calmly in a supine position.
Patients were classified into two groups according
to the heart rate developed during spinal anaesthe-
sia. Patients with a minimum heart rate (HRmin)
445 b.p.m. were included in the non-bradycardic
group and those with HRmino45 b.p.m. in the bra-
dycardic group.
Statistical analysis
Data were analysed using the statistical package of
SPSS 16. All numeric data were checked for normal
distribution using the KolmogorovSmirnov test.
The w2-test was used for testing independence
between all variables. The t-test (for normally
235
A. Chatzimichali et al.

distributed data) or the MannWhitney test (non- Table 1

normally distributed data) was used to examine Demographic data, level of sensory block, dose of local anaes-
differences between the groups for variables. The thetic administered and pre-hydration in the two groups of
Pearson correlation was used to demonstrate cor- patients.
relation between variables. Bradycardic Non- P
For the assessment of the accuracy of each para- group bradycardic
(n 5 19) group (n 5 61)
meter in discriminating bradycardic from non-
Age (years)
bradycardic patients, we performed receiver op- Mean 38  9 39  10 o0.67
erator characteristic curve (ROC) analysis. A ROC Median 39 40
curve is the plot of a tests true-positive rate Range 32 38
Minimummaximum 2456 2260
(sensitivity) vs. its false-positive rate (1 specifi- Weight (kg)
city). The area under the ROC curve (AUC) is a Mean 80.5  19 75  16 o0.25
quantitative measure of selectivity (1.0 best selec- Median 75 75
Range 70 87
tivity, 0.5 worst selectivity). The value for the AUC Minimummaximum 50120 48135
can be interpreted as follows: an area of 0.75, for Height (m)
example, means that a randomly selected indivi- Mean 1.69  0.09 1.68  0.09 o0.67
Median 1.7 1.68
dual from the positive group has a test value larger Range 0.3 0.3
than that of a randomly chosen individual from the Minimummaximum 1.61.9 1.61.9
BMI
negative group 75% of the time. When the variable Mean 27.7  5.3 26.2  3.9 o0.27
under study cannot distinguish between the two Median 27.7 25.4
groups, the area will be equal to 0.5 (the ROC curve Range 17.5 22.5
Minimummaximum 18.7836.28 18.6441.20
will coincide with the diagonal). The 95% confi- ASA status (I/II) 11 / 8 37 / 24
dence interval for the area can be used to test the Pre-hydration (ml)
hypothesis that the theoretical area is 0.5. If the Mean 537  198 462  156 o0.13
Median 500 500
confidence interval does not include the 0.5 value, Range 900 700
there is evidence that the test does have an ability Minimummaximum 1001000 100800
to distinguish between the two groups.19,20 ROC Local anaesthetic (mg)
Mean 11.44  1.14 11.30  1.74 o0.59
analysis was performed to evaluate the sensitivity Median 12 11
and specificity of LF/HF, LF, HF and HRbaseline to Range 3 10.5
detect patients who showed an HR lower than Minimummaximum 1013 7.518
Upper T sensory block 72 72
45 b.p.m. P values o0.05 were considered statisti-
cally significant. Values are mean  SD, median and range.
BMI, body mass index; T, thoracic level.

Results
Eighty patients (47 women and 33 men) were en-
rolled, 2160 years old, ASA physical status III.
During spinal anaesthesia, 19 patients developed
bradycardia (HRo45 b.p.m.) and were included in
the bradycardic group, while 61 patients did not
developed bradycardia and formed the non-brady-
cardic group. Within the bradycardic group, eight
patients had HRbaseline  60 b.p.m. and seven
patients had an upper sensory blockade to T5.
Patient demographics were similar in both
groups, as well as the level of sensory block,
quantity of the local anaesthetic, pre-hydration
(Table 1), baseline BP (BPbaseline), LF and LF/HF
(Table 2). The only statistically significant differ-
ences between the groups were HRbaseline and HF
(Table 2). The w2-test showed that the development
of bradycardia was independent of sex (w2 5 2.293,
P 5 0.130), age (2140, 4160) (w2 5 1.813, P 5 0.178)
and BMI (17.527.5 and 27.637.5) (w2 5 3.787,
P 5 0.052). The variables HF, pre-hydration and
the quantity of local anaesthetic did not show a
normal distribution. Only HF and HRbaseline were
statistically different between the two groups
(P 5 0.049 according to the MannWhitney test
and P 5 0.02 according to the t-test, respectively).
Pearsons linear correlation showed HRmin to be
significantly correlated to HRbaseline (r 5 0.537,
P 5 0.00) (Fig. 1). According to the non-parametric
Spearman coefficient, both HRbaseline and HRmin
were significantly correlated with the mean value
of HF (r 5 0.339, P 5 0.002 and r 5 0.320,
P 5 0.004) (Fig. 2) and the mean value of LF
(r 5 0.317, P 5 0.04 and r 5 0.303, P 5 0.006).
ROC analysis revealed that HF at rest and
HRbaseline were specific to detect patients at risk

236
 HRV and bradycardia during spinal anaesthesia

Table 2
Data of pre-spinal LF, HF and LF/HF ratio, BPbaseline and
HRbaseline in two groups.
Bradycardic Non- P
group bradycardic
(n 5 19) group (n 5 61)
LF
Mean  SD 1913  1764 1262  1069 o0.14
Median 1368.40 1020.80
Range 6810.80 4308
Minimummaximum 356.67167.4 82.204390.2
HF
Mean  SD 1061  1301 696  1378 o0.049
Median 456.3 308.4
Range 4686.80 9586.5
Minimummaximum 111.24798 22.49608.9
LF/HF
Mean  SD 3  1.6 3.5  2 o0.37
Median 3.33 3.12
Range 5.73 13.37 Fig. 1. Correlation of baseline heart rate and minimum heart rate
Minimummaximum 0.466.19 0.513.87 during spinal anaesthesia.
BPbaseline (mmHg)
Mean  SD 130  24 131  16 o0.87
Median 128 132
Range 82 68
Minimummaximum 100182 97165 component of HRV before spinal anaesthesia de-
HRbaseline (b.p.m.)
Mean  SD 66  13 78  14 o0.02 veloped severe bradycardia following sympathetic
Median 65 76 blockade. This probably indicates increased para-
Range 44 62 sympathetic activity in these patients. However,
Minimummaximum 5094 60122
BPmin (mmHg) the sensitivity and specificity of HF was not high
Mean  SD 104  16 108  11 o0.35 enough to distinguish these patients. ROC analysis
Median 97 105 of HF demonstrated a medium sensitivity (65%)
Range 55 48
Minimummaximum 90145 87135 and specificity in contrast to the LF and LF/HF
HRmin (b.p.m.) ratio, which did not have a predictive value. HF
Mean  SD 41  4 58  10 o0.00
Median 41 56
and vagal activity seem to be more clearly asso-
Range 19 50 ciated than LF and sympathetic activity.2125 It has
Minimummaximum 3554 4595 been demonstrated that patients with impaired
Values are mean  SD, median and range. ANS regulation were at a high risk of hypotension
LF, low frequency; HF, high frequency; LF/HF, ratio of low to after induction of general anaesthesia.
high frequency; BP, blood pressure; HR, heart rate. Especially, impaired parasympathetic activity,
reflected by HF, indicated a high risk of haemody-
namic instability.24,25
of developing bradycardia during spinal anaesthe- Identification of the factors that increase the risk
sia. The AUC was found to be significantly differ- of bradycardia during spinal anaesthesia should
ent from 0.5 (95% CI 5 0.5160.783 and 0.5960.883, help to prevent the development of cardiac arrest
respectively) (Figs 3 and 4). HF presented a med- in these patients. The prospective study of Carpen-
ium sensitivity and specificity to detect bradycar- ter et al.1 showed that the strongest predictors for
dic patients (65%). However, HRbaseline showed a the development of bradycardia during spinal
better sensitivity and specificity (74%). anaesthesia were a HRbaselineo60 b.p.m., pre-
operative administration of b adrenoreceptor an-
tagonists and the ASA physical status. Pollard26
reviewed all reported cases of asystole or severe
Discussion
bradycardia during spinal anaesthesia and also the
This is a pilot study that investigated whether pre- underlying mechanisms. The clinical factors that
operative HRV is a useful tool to predict those predicted moderate bradycardia (defined as a heart
patients who are prone to developing severe rate below 50 b.p.m.) were HRbaselineo60 b.p.m.,
bradycardia during spinal anaesthesia. It did de- ASA physical status I (vs. ASA physical status
monstrate that patients with an increased HF IIIIV), use of b-blocking drugs, sensory level

237
A. Chatzimichali et al.
A B
C D
above T6, age less than 50 years and a prolonged PR
interval on the ECG.26
The importance of heart rate at rest before spinal
anaesthesia was confirmed by the present study.
ROC analysis revealed a high sensitivity and spe-
cificity (74%) of HRbaseline for the prediction of
severe bradycardia during spinal anaesthesia.
Analysis of HRV is a non-invasive, indirect
measurement of autonomic regulation. ANS is
modulated by the baroreceptors, vasomotor centre,
respiratory centre, arterial blood pressure and re-
spiratory movements. Frequency domain measure-
ments of HRV provide information on the degree
of autonomic modulation rather than the level of
autonomic tone. The HF component primarily
reflects respiration-driven vagal modulation of si-
nus arrhythmia. There is consensus that vagal
activity is the major modulator of HF.27 The physio-
logical correlate of the LF component of HRV is not
clear. There are studies showing that a normalized
value of the LF component is modulated by sympa-
thetic efferent activity while some other studies
demonstrate that the LF power is modulated by
both vagal and sympathetic efferent activity. Pre-
vious studies suggest that the LF/HF ratio is a better
indicator of the relationship between the sympa-
thetic and the parasympathetic nervous system.27
The only studies that have studied the usefulness
of HRV before spinal anaesthesia are those in
238
Fig. 2. Correlations of Heart Rate Varia-
bility parameters and minimum and
baseline heart rate. (A) Correlation of
mean value of high frequency (HF) and
minimum heart rate during spinal
anaesthesia. (B) Correlation of mean va-
lue of low frequency (LF) and minimum
heart rate during spinal anaesthesia. (C)
Correlation of mean value of HF and
baseline heart rate. (D) Correlation of
mean value of LF and baseline heart rate.
relation to hypotension. Studies by Hanss and
colleagues have shown that a high LF/HF ratio
could identify ASA III patients at risk of develop-
ing severe hypotension during spinal anaesthesia
for prostate surgery or caesarean delivery. ROC
analysis revealed 85% sensitivity and 85% specifi-
city of the LF/HF ratio above 2.5 to predict a
systolic blood pressure decrease of more than
20% of baseline during spinal anaesthesia.
Our results are different from these data prob-
ably because of the different populations (pregnant
women and patients older than 60 years) and the
different aims of the studies. They hypothesized
that HRV, as an indirect measure of autonomic
control, may predict hypotension after spinal
anaesthesia. During pregnancy, ANS regulation is
generally modified. Sympathetic outflow is in-
creased in healthy pregnant women, pregnant
women with pre-eclampsia and pregnant women
hospitalized for other complications.
Hypotension due to a central neuroxial block is
mainly a result of pre-ganglionic sympathetic fi-
bres. Differences in the regulation of the ANS
among patients may explain the haemodynamic
differences in response to spinal anaesthesia. Sym-
patholysis due to spinal anaesthesia was reflected
by a significant decrease of LF/HF as well as LF
and a significant increase of HF in the course of
spinal anaesthesia. Frequency domain analysis,

Fig. 3. Receiver operator characteristic curve (ROC) analysis for
high frequency demonstrated 65 % sensitivity and specificity to
predict bradycardia during spinal anaesthesia. Area under the
curve 5 0.65 and Po0.05.
Fig. 4. Receiver operator characteristic curve (ROC) analysis for
beseline heart rate demonstrated 74 % sensitivity and specificity to
predict bradycardia during spinal anaesthesia. Area under the
curve 5 0.74 and Po0.05.
HRV and bradycardia during spinal anaesthesia
especially the LF/HF ratio, may be more sensitive
for the prediction of post-spinal hypotension com-
pared with parameters solely reflecting parasym-
pathetic control (HF).1417
In our study, a significant correlation was demon-
strated, confirming the view that human cardiac
function is mainly controlled via vagal regulation.
Probably, an increased vagal activity can occur dur-
ing spinal anaesthesia and patients with a strong
resting vagal tone should be at an increased risk
for bradycardia. The term vagotonic describes the
clinical condition of resting bradycardia, atrioventri-
cular block or complete atrioventricular dissociation
that is present in 7% of the population. In vagotonic
patients, cardiac arrest can occur when procedures
that increase vagal activity are performed.26 How-
ever, ROC analysis of the HR baseline demonstrated
better sensitivity and specificity compared with ROC
analysis of HF.
These findings suggest that pre-operative deter-
mination of ANS control might provide a useful
tool to detect patients at risk of severe haemody-
namic impairment during spinal anaesthesia.1417
HRV as a clinical diagnostic instrument for perio-
perative patients shows promise, although a more
basic physiological study as well as clinical experi-
ence are needed for further validation of HRV before
it can be recommended as a standard part of our
diagnostic or monitoring armamentarium.28
The incidence of bradycardia in the present study
was extremely high (24%) in comparison with the
recent literature.1 Carpenter and colleagues found a
lower incidence of bradycardia in a different popu-
lation. However, he showed a threefold increase in
the odds of developing bradycardia of ASA I com-
pared with ASA III or IV patients. There are no
relevant studies on the incidence of bradycardia in
ASA I and II patients during spinal anaesthesia.
Limitations
Some limitations of our study should be pointed
out. First, HRV is a non-invasive, indirect measure
of autonomic activity. Second, artefacts during
HRV data recording due to patients movements
were inevitable. However, artefacts were elimi-
nated by computer-based artefact detection, fol-
lowed by an evaluation by an expert. Third, HRV
recording on the day of surgery, the nothing peros
state, stress and anxiety (patients without preme-
dication) may influence the HRV parameters.
In conclusion, the present study demonstrated a
significant correlation between HRbaseline and the
239
A. Chatzimichali et al.
development of bradycardia as well as a high
sensitivity and specificity for the prediction of
bradycardia during spinal anaesthesia. HRV and
more specific HF as a predictor of vagal activity
may help to identify patients who will develop
severe bradycardia during spinal anaesthesia. The
use of HRV and HRbaseline in the pre-operative
period could be useful in identifying the significant
percentage of young, healthy patients who are
likely to develop severe bradycardia or even asys-
tole during spinal anaesthesia. The optimum goal
is to significantly reduce the incidence of sudden
cardiac arrest in a healthy population. These find-
ings encourage further investigation of the prog-
nostic value of HRV.
Acknowledgements
Conflict of interest: There is no conflict of interest related to the
study.
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