Quarterly Journal of Medicine. New Series 83, No. 302, pp.

449-460, June 1992

Haemodynamic Studies During the Management

of Severe Tetanus
FE UDWADIA, JD SUNAVALA, MC JAIN, R D'COSTA, PK JAIN,
A LALL, M SEKHAR, ZF UDWADIA, F KAPADIA, KC KAPUR,
SK MEHTA and RJ KHARAS
From the Intensive Care Unit, Department of Medicine, Breach Candy Hospital,
Bhulabhai Desai Road, Bombay, India

Accepted 9 March 1992

SUMMARY
Detailed invasive haemodynamic studies were performed in 27 of 32 patients with severe

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tetanus. Nineteen had severe uncomplicated tetanus and eight had associated major
complications, chiefly infection and pulmonary complications. The results were compared with
those obtained from 15 healthy male volunteers who served as controls. There were two deaths in
32 patients (mortality 6.25 per cent). Severe tetanus without major complications was
characterized by a high output hyperkinetic circulatory state with tachycardia (heart rate 131
(19.2) beats/minute), increased stroke volume index (43.1 (10.7) ml/m2), increased cardiac
index (5.48 (0.94) l/min/m2) and a normal left ventricular stroke work index (60.5 (15.9)
g/m/m2). Volume loading demonstrated a significant haemodynamic response and increased
vascular capacitance. Even so the maximum percent rise from baseline values of these indices
after volume load was significantly higher in controls (p < 0.001). Autonomic cardiovascular
disturbances affected both sympathetic and parasympathetic activity. Hypertension and
tachycardia alternating with hypotension and bradycardia were related to sudden fluctuations
in systemic vascular resistance. Our studies suggested some degree of myocardial dysfunction in
patients with severe uncomplicated tetanus. The haemodynamics of severe tetanus were masked
and altered by complicating infection, pneumonia, and atelectasis.

INTRODUCTION
Tetanus remains a major public health hazard in India and other developing countries and
still carries a high morbidity and mortality [1, 2]. Changes in cardiovascular physiology are
inherent in severe tetanus, the cardiovascular instability being most marked in those patients
who have severe autonomic disturbances. There is unfortunately a marked paucity of
haemodynamic studies in patients with severe tetanus. This is probably related to the
hazards associated with invasive studies in critically ill individuals and to the fact that the
natural history of severe tetanus is prolonged and invariably complicated by other major
problems, chiefly sepsis, pulmonary infection, pulmonary atelectasis, pulmonary oedema,
and fluid and electrolyte disturbances.- Any one of these complications is capable of
© Oxford University Press 1992
450 FE Udwadia and others
producing its own changes in the circulatory and respiratory systems, masking haemodyna-
mic changes inherent in severe tetanus. Heavy sedation is often used in the management of
severe tetanus, and this, along with the need to administer inotropic drugs to hypotensive
patients, alters the haemodynamic state, adding difficulties to the interpretation of results.
This paper discusses haemodynamic studies and changes in cardiovascular physiology in
the course of management of 27 out of 32 patients with severe tetanus. Haemodynamic
studies guided patient care and we have therefore briefly discussed relevant features in the
management of severe autonomic cardiovascular disturbances in critical tetanus.

METHODS

Subjects
After obtaining institutional approval and informed consent from either the patients or next
of kin, haemodynamic studies were performed in 32 patients with severe tetanus admitted
between 1982 and 1990. Fifteen healthy male volunteers (average age 30 years), gave
informed written consent to serve as controls.
Allowing for minor modifications, the severity of tetanus was graded according to Ablett's
criteria [3, 4]. Grade III (severe tetanus, grade IIIA of Ablett's classification), was
characterized by severe trismus, generalized spasticity, spontaneous prolonged spasms,
respiratory embarrassment with tachypnoea (>40/min), apnoeic spells, dysphagia, tachy-

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cardia ( > 120/min), excessive perspiration and increased salivation. Grade IV (very severe
tetanus, grade IIIB of Ablett's classification) was characterized by features of Grade III with
autonomic dysfunction involving the cardiovascular system: sustained hypertension (blood
pressure > 160/100 mmHg), sustained hypotension (systolic blood pressure < 90 mmHg) or
episodic hypertension often followed by hypotensive spells.
Of the 32 patients, 18 had grade 111 and 14 had grade IV tetanus. The male to female ratio
was 13:3 and the average age was 32 years (10-67 years). Haemodynamic studies from five
patients (three grade III; two grade IV tetanus), though invaluable for patient management,
are excluded from discussion as these patients were receiving inotropic support. Of the
remaining 27 patients, 15 had grade III and 12 had grade IV tetanus. The male to female ratio
in these patients was 8:1 and the average age was 30 years (10-55 years). These 27 patients
were divided into two groups. Group A comprised 19 patients, 12 with grade III and seven
with grade IV tetanus which was without major complications at the time of haemodynamic
study. These patients had no clinical or laboratory evidence of septicaemia, sepsis,
pulmonary infection, atelectasis, pneumonia, bronchopneumonia, or other major complica-
tions.
Group B comprised eight patients, three with grade III and five with grade IV tetanus, who
had major complications at the time of haemodynamic study. Three patients had
bronchopneumonia, four had gram-negative sepsis with major pulmonary atelectasis, and
one was admitted with progressively severe adult respiratory distress syndrome.

Protocol
All patients on admission received 10000 units i.v. of tetanus antiserum and adequate
attention to any injury or wound. A tracheostomy was performed immediately and the
patient was paralysed with pancuranium (2-6 mg i.v.) to allow controlled ventilation using a
volume cycled Servo 900C or Bennett MA2 ventilator. No patient was on positive end-
expiratory pressure at the time of study. The dose of pancuranium was tailored to each
 Haemodynamic Studies in Severe Tetanus 451
patient's needs; it was generally required every 1-3 hours, depending on the severity and
frequency of spasms. The paralytic drug was stopped when spasms disappeared—generally
4-7 weeks after admission, and the patient was then weaned off the ventilator. Each patient
was sedated with i.v. diazepam 30-40 mg/day, which was continued until the cessation of
ventilator support. Rectal temperature, heart rate and electrocardiograph, were conti-
nuously monitored and blood pressure was recorded continuously via a radial artery
catheter in the forearm. The clinical features, circulatory, respiratory and other parameters
were charted daily, as for our usual intensive care unit protocol. Complications, as and when
they occurred, were recorded and treated appropriately. Chest radiography, blood count,
appropriate cultures, biochemical and other relevant investigations were performed
periodically. Drugs altering circulatory haemodynamics, such as propranolol, nifedipine,
dopamine and dobutamine, were used sparingly and only when absolutely necessary and
under close continuous haemodynamic monitoring. Patients remained under critical care
throughout their hospital stay.

Haemodynamic Calculations
Within 48-72 h of admission, a 7.5 F quadruple-lumen balloon-flotation thermodilution
catheter (Swan-Ganz; American Edwards Laboratories) was introduced percutaneously
via the subclavian vein into the pulmonary artery. All haemodynamic recordings and

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calculations were done using a Hewlett-Packard 78534C Monitor/Terminal to which were
attached 78551A and 78552B Modules. The haemodynamic recordings included heart rate
(HR), mean arterial blood pressure (ABPm), peak systolic pressure, central venous
pressure (CVP), mean pulmonary artery pressure, (PAP), pulmonary capillary wedge
pressure (PCWP) and cardiac output (CO). The cardiac output was measured at end-
expiration in triplicate by the thermodilution technique and the average computed: the
printout of the thermodilution curve for each measurement was reviewed for quality
control. The variables listed were calculated by the standard formulae: cardiac index
(CI) = CO/BSA 1/min.m2; stroke volume index (SVI) = CI/HR ml/m2; systemic vascular
resistance index (SVRI) = 80x(ABPm — CVP)/CI dynes-sec/cm5.m2; pulmonary vascular
resistance index (PVRI) = 80 x (PAPm - PCWP)/CI dynes-sec/cm5.m2; left ventricular
stroke work index (LVSWI) = SVI x ABPm x 0.0136 g.m/m2; right ventricular stroke work
index (RVSWI) = SVI x PAPm x 0.0136 g.m/m2.

Haemodynamic Protocol
Group A. Our emphasis, for obvious reasons, was on this large group. All haemodynamic
'sets' of studies in this group were performed with the patient on a volume cycled ventilator,
on afixedtidal volume and respiratory rate and on inspired oxygen concentration (FiO2) of
40 per cent. The patient was not receiving inotropic drugs and was haemodynamically stable
with reference to temperature, pulse rate, blood pressure, for at least 2 h before
measurements were made. The following 'sets' of haemodynamic studies were performed.
First, initial studies were made in each of the 19 patients, within 48-72 h of admission and
at the height of the disease. These measurements were made at a time when the patients were
not fully under the effect of pancuranium (i.e. not optimally paralysed) and yet not
frequently convulsing (i.e. not free from the drug's effect). The haemodynamic measure-
ments were immediately repeated in this group after volume loading with approximately
2200 ml normal saline (at the rate of 50 ml/kg/h). Cardiac output and other haemodynamic
452 FE Udwadia and others

measurements were made at the height of the volume load, and also at 15 min, 30 min and 1 h
after stopping the infusion.
Haemodynamic measurements were repeated in 11 patients 5-6 days after admission
during increased muscle activity (just before a dose of pancuranium was due) and also
during utmost relaxation (at the height of action of pancuranium).
Haemodynamic studies were repeated in eight patients when they were recovering and
were ready to be weaned off the ventilator.
Haemodynamic studies were also performed in four patients with grade IV tetanus during
a time of severe autonomic disturbances involving the cardiovascular system. Three of these
patients had wide fluctuations in blood pressure occurring over 4-6 h, ranging from
markedly hypertensive to hypotensive values. Haemodynamic measurements and calcula-
tions of the usual haemodynamic variables were made daily for 3 days in each of these three
patients during periods of hypotension and hypertension and mean values (with S.D.) of
each variable were noted. The fourth patient, who had sustained hypertension of 210/120
mmHg for 3 days, underwent haemodynamic studies on the second day of his sustained
hypertension. None of these patients were on drugs that could affect haemodynamic
measurements at the time of study.

Group B. Haemodynamic measurements similar to those in the previous group were made
only at the time of admission. These patients were extremely ill and hence measurements
were not made following volume load or during increased muscle activity and during the

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phase of relaxation.

Control subjects. Haemodynamic studies were made during a basal state and following a
volume load with normal saline as in the 19 patients in group A. The percentage increase
(from the basal state) in pulmonary capillary wedge pressure, stroke volume index, cardiac
index, systemic and pulmonary vascular resistance indices and left and right ventricular
stroke work indices following a volume load was noted and was compared to that observed
in the 19 patients of group A.
Arterial pH, partial pressure of arterial oxygen {PaOi)> partial pressure of arterial carbon
dioxide (PaCO2) and the partial pressure of mixed venous oxygen {PgOi} were measured
(using the Radiometer Model ABL4) at the time of initial haemodynamic measurements;
these measurements were repeated frequently during the patients' stay in the intensive care
unit. Arterial oxygen saturation (SaC>2) and the mixed venous oxygen saturation {SgOi) were
measured and recorded by an Oximeter (Hemoximeter OSM2). The oxygen content of
arterial blood (CaO2) and the oxygen content of mixed venous blood (QO2) were calculated
using standard formulae [5].

Statistical Analysis.
Haemodynamic values are expressed as means with standard deviation (SD) The paired / test
was used to compare the differences in mean values between groups of patients. All p values
< 0.05 were considered to indicate statistical significance.

RESULTS
There were just two deaths in the 32 patients with severe tetanus, both in our study group of
27 patients. One death in group B was due to severe adult respiratory distress syndrome in a
patient with grade III tetanus; she was admitted with this complication and it was our
 Haemodynamic Studies in Severe Tetanus 453
TABLE 1. Cardiovascular complications in severe
tetanus

No. of
patients
Sustained tachycardia (> 150/min) 19
Hypotension (systolic BP<90 mmHg) 5
Hypertension
(a) Moderate (diastolic BP> 105 mmHg) 7
(b) Severe (diastolic BP> 115 mmHg) 2
Episodic labile hypertension (hypertension and
tachycardia, alternating with hypotension and
bradycardia) 8
Sudden death 1
Sudden cardiac arrest with successful resuscitation 3
Severe sweating 24
Severe vasoconstriction 1
Hyperpyrexia 11
Cardiac arrhythmias
Supraventricular tachycardia 7
Ventricular extrasystolies 24
Nodal rhythm 3
Short runs of spontaneous 3

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Reversible ventricular tachycardia
Idioventricular rhythm 1
Myocardial infarction 1
Hypothermia 1

surmise that the respiratory distress was due to tetanus per se. The other death (in group A)
was sudden and occurred in a patient with grade IV tetanus, 25 days after admission. ECG
monitoring showed the development of a sudden slow idioventricular rhythm which did not
respond to atropine, isoprenaline or dopamine. After 10 min there was further widening and
slowing of the ventricular complexes followed by cardiac arrest and death. All other patients
made a complete recovery. The duration of ventilator support in those that recovered varied
from 4 to 7 weeks. The overall clinical course of these patients was stormy, with frequent and
varied complications which are outside the scope of this paper. However, cardiovascular
complications chiefly related to autonomic disturbances and to arrhythmias have been listed
in Table 1.

Haemodynamic Results in Group A

The mean values (with SD) of haemodynamic measurements and the calculated haemodyna-
mic variables in our initial study on 19 patients with severe uncomplicated tetanus are shown
in Table 2. These patients at the height of their disease were noted to have a high output
hyperkinetic circulation characterized by marked tachycardia, an increase in mean arterial
blood pressure and an increase in the stroke volume index and cardiac index. The systemic
vascular resistance index was on the low side of normal and the filling pressures of the left
and right heart were normal. The arteriovenous oxygen difference (CaOj— CcOi) was
normal. This hyperkinetic state was exaggerated during periods of increased muscle activity
and lessened significantly (/?<0.01) during periods of relaxation (Table 3).
The recovery phase was associated with a significantly lower cardiac index (3.88 vs. 5.891/
454 FE Udwadia and others

TABLE 2. Haemodynamic observations in patients with severe uncomplicated tetanus during

basal state and after fluid challenge*

Basal within 2-3 After fluid challenge p values

days of admission (n=19) „
(n=19)

Temperature °C 37.84 (0.62) 37.84 (0.64) 0.97

Heart rate (/min) 131.00 (19.20) 130.00 (18.40) 0.74
ABP mean (mmHg) 103.00 (13.50) 109.00 (10.20) 0.029
CVP(mmHg) 3.40 (2.00) 4.60 (3.30) 0.064
CI (1/min.m2) 5.48 (0.94) 6.71 (1.23) < 0.001
SVI (ml/m2) 43.10 (10.70) 53.00 (12.40) <0.001
PAP mean (mmHg) 10.70 (3.70) 17.60 (5.50) <0.001
PCWP(mmHg) 6.90 (3.20) 12.70 (3.90) <0.001
SVRI (dynes.sec/cm'.m2) 1508.00 (390.10) 1275.00 (306.00) <0.001
PVRI (dynes.sec/cm5.m2) 84.60 (39.30) 93.60 (41.40) 0.17
LVSWI (gm.m/m2) 60.50 (15.90) 76.90 (20.00) <0.001
RVSWI (gm.m/m2) 6.12 (2.44) 12.29 (4.35) <0.001
P.Ot (mmHg) 76.20 (10.00) 75.10 (9.60) 0.23
PaCO2 (mmHg) 34.40 (4.60) 34.80 (4.70) 0.28
pH 7.44 (0.058) 7.44 (0.063) 0.39
GOi-G-CMml/dl) 4.60 (0.83)

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•Values represent means with SD in parenthesis. The significance of observations after fluid
challenge is in relation to the basal state: ABP, arterial blood pressure; CVP, central venous pressure;
CI, cardiac index; SVI, stroke volume index; PAP, pulmonary artery pressure; PCWP, pulmonary
capillary wedge pressure; SVRI, systemic vascular resistance index; PVRI, pulmonary vascular
resistance index; LVSWI, left ventricular stroke work index; RVSWI, right ventricular stroke work
index; PaO2 = partial pressure of arterial oxygen; PaCC>2 = partial pressure of arterial carbon dioxide;
CCC>2 = oxygen content of arterial blood; C5O2 = oxygen content of mixed venous blood.

min.m2; p = 0.001), and a significantly higher systemic vascular resistance index (1794 vs.,
1298 dynes.sec/cm5.m2; p = 0.004), as compared to these values obtained soon after
admission. There was a trend during recovery towards a lower heart rate (113 vs. 135/min;
p = 0A2) and mean arterial blood pressure (90 vs. 98 mmHg; p = 0.058), but this did not
achieve clinical significance, possibly due to a small sample size.
A study of the response to volume load in these patients showed a significant rise in the
mean pulmonary artery pressure, pulmonary capillary wedge pressure, stroke volume index,
cardiac index and in left and right ventricular stroke work indices at the height of the volume
load (p < 0.001) (Table 2). The rise in the above values could not be sustained. Within 15 min
the pulmonary artery pressure and the pulmonary capillary wedge pressure had fallen to
preload levels; the cardiac index, stroke volume index and left ventricular stroke work index
started to fall within 15 min and returned to preload levels 1 h after fluid challenge.
The results following volume load in the 12 patients with grade III disease were essentially
the same as those in the seven grade IV patients, except in relation to the left ventricular
stroke work index: in the 12 grade III patients this rose on volume load from 60 (15.2) to 81
(18.4) g.m/m2, the rise being clearly significant (p < 0.01), while in the seven grade IV patients
it rose from 60 (9.92) to 74 (16) g.m/m2. This rise was not as significant (p = 0.\).
A comparison of the effects of volume loading in 19 patients with severe uncomplicated
tetanus at the height of the disease with 15 normal controls is shown in Fig. 1. Two features
 Haemodynamic Studies in Severe Tetanus 455

TABLE 3. Haemodynamic observations in patients with severe uncomplicated

tetanus during relaxation (at the peak of pancuranium action) and during
increased muscle activity (just before the next dose of pancuranium was due) *

Relaxation (n= 11) Increased muscle p values

activity
("=11)

Temperature °C 37.80 (0.68) 37.80 (0.83) 0.60

Heart rate/min 130.0 (15.00) 147.00 (19.30) 0.002
ABP mean (mmHg) 97.00 (13.80) 114.00 (17.40) 0.004
CVP (mmHg) 3.70 (3.20) 7.00 (5-40) 0.007
CI (1/min.m2) 4.72 (1.17) 6.97 (1.74) <0.001
SVI (ml/m2) 36.50 (9.20) 48.10 (14.40) 0.001
PAP mean (mmHg) 11.00 (4.20) 18.20 (6.50) 0.001
PCWP (mmHg) 8.00 (3.60) 13.10 (5.20) 0.002
SVRI (dynes.sec/cm5.m2) 1692.00 (578.60) 1293.00 (339.30) 0.003
PVRI (dynes.sec/cm^m2) 93.80 (46.60) 116.00 (37.10) 0.09
LVSWI (gm.m/m2) 47.20 (9.80) 74.00 (20.00) < 0.001
RVSWI (gm.m/m2) 5.24 (1.78) 12.06 (6.72) 0.003
P0O2 (mmHg) 72.60 (2.40) 67.60 (1.40) <0.001
PaCO2 (mmHg) 30.00 (3.00) 35.50 (1.90) <0.001
pH 7.40 (0.021) 7.37 (0.024) 0.02

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Abbreviations as Table 2.

are worthy of note. First, at the height of the volume load the percentage rise from baseline
values in the pulmonary capillary wedge pressure was similar in both groups. However, the
percentage rise in the central venous pressure, mean pulmonary artery pressure, cardiac
index, stroke volume index, and left and right ventricular stroke work indices was
significantly greater in the controls (p < 0.001). Second, the significant rise in the above
values persisted in the controls at 1 h after the volume load, as compared to patients with
severe tetanus.
Haemodynamic results obtained from four patients with grade IV tetanus during periods
of severe autonomic cardiovascular disturbances are shown in Table 4.
Three patients had marked lability in blood pressure readings. The hypertensive peaks
(which varied from 180/100 mmHg to 210/120 mmHg) were characterized by a significant
rise in central venous pressure (p<0.01), systemic vascular resistance index (/?<0.01) and
heart rate (130-190/min; p <0.0l). Hypotensive episodes (70-85/30-50 mmHg) were
associated with a significant fall in central venous pressure (p<0.0\), systemic vascular
resistance index (p<0.0l) and heart rate (50-90/min; p <0.01). Labile blood pressure was
not associated with changes in left heart filling pressure or in cardiac output or left
ventricular stroke work index, but chiefly resulted from sudden alterations in the systemic
vascular resistance.
The fourth patient had sustained severe hypertension with a blood pressure of 210/120
mmHg and a heart rate of 120/min for 3 days. His studies showed a mean arterial blood
pressure of 130 mmHg, cardiac index 2.2 1/min.m2 and systemic vascular resistance of 4620
dynes.sec/cm5. He was given propranolol 10 mg thrice daily and nifedipine 20 mg twice daily.
The haemodynamic study repeated one day later showed a heart rate of 96/min, mean
arterial blood pressure 90 mmHg, cardiac index 4.5 1/min.m2 and a systemic vascular
resistance of 1500 dynes.sec/cm5.
456 FE Udwadia and others
240

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* TIME IN HOURS-

CONTROLS ° o SEVERE TETANUS **» P<OOO1

FIG. I. Percentage change (mean ± SEM) from baseline after volume load, in central venous pressure
(CVP, Panel A), mean pulmonary artery pressure (PAPmean, Panel B), pulmonary capillary wedge
pressure (PCWP, Panel C), cardiac index (Cl, Panel D), stroke volume index (SVI, Panel E), systemic
vascular resistance index (SVRI, Panel F), left ventricular stroke work index (LVSWI, Panel G) and
right ventricular stroke work index (RVSWI, Panel H). FC denotes fluid challenge. Values of patients
with severe tetanus were compared with the corresponding values of the controls and wherever
significant the difference is marked on the figure thus: ***/>< 0.001.

Haemodynamic Results in Group B

The results in these eight severely ill patients (three with grade III and five with grade IV
tetanus) represent haemodynamic alterations produced not only by tetanus but also by the
major complications of sepsis, septicaemia, pulmonary infection, atelectasis, and adult
respiratory distress syndrome. The following mean haemodynamic (SD) values were
obtained in these patients: heart rate 112 (19.5) beats/min; mean arterial blood pressure 97
(10.3) mmHg; central venous pressure 4 (2.25) mmHg; mean pulmonary artery pressure 16
(5.24) mmHg; pulmonary capillary wedge pressure 12 (4.8) mmHg; cardiac output 4.6 (0.58)
1/min; cardiac index 3.2 (0.38) 1/min.m2; stroke volume index 29 (5.73) ml/m2; systemic
vascular resistance index 2323 (378.1) dynes.sec/cm5.m2; pulmonary vascular resistance
index 184 (115.3) dynes.sec/cm5.m2; left ventricular stroke work index 42 (12.6) g.m/m2; right
ventricular stroke work index 6.2 (2.2) g.m/m2.
The mean cardiac index was significantly lower (/xO.01) and the systemic vascular
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Haemc
TABLE 4. Observations during hypertensive and hypotensive spells in patients with grade IV tetanus*

Patient 1 Patient 2 Patient 3 f

Hypertension Hypotension Hypertension Hypotension Hypertension Hypotension I<v

Studies in Severe Tetanus

Heart rate (min) 180.0(3.5) 70.0 (2.3)t 166.0(5.4) 63.0(1.8) 167.0(1.8) 83.0 (6.6)f
ABP mean (mmHg) 143.0 (4.7) 60.0 (5.3)t 135.0(5.6) 63.0 (3.4)f 130.0(2.5) 52.0 (6.2)f
CVP (mmHg) 6.0 (0.6) 1.3(0.3)t 6.3 (0.3) 1.7(0.3) 5.3 (0.7) 1.7(0.3)f
SVRI (dynes.sec/cm5. m2) 2237.0 (99.5) 952.0 (75.9)t 2274.0 (74.0) 1117.0(55.2)1 2324.0(61.2) 961.0 (85.4)f

* Values represent means with SD (in parenthesis) of studies performed on three consecutive days. The significance of
observations between hypotensive and hypertensive spells is compared in eachi patient.
Abbreviations as Table 2.
f/7<0.01.
458 FE Udwadia and others
resistance index, pulmonary vascular resistance index and mean pulmonary artery pressure
were significantly higher (/><0.01) in this group compared to the 19 patients in group A.

DISCUSSION
There are very few data on the haemodynamics of severe uncomplicated tetanus in world
literature. Montero et al. [6] reported haemodynamic studies in 24 patients, but their
observations were blurred and bedevilled by major pulmonary lesions and complications
that in themselves produce cardiorespiratory changes. James and Manson [7] reported on
the use of IV magnesium sulphate in severe tetanus and noted a high cardiac index in six
patients. Our observations are unique not only because they were made on a large group of
patients but because in 19 out of 27 patients these haemodynamic measurements reflect the
state of the cardiovascular system in uncomplicated severe tetanus at the height of the
disease. In the remaining eight patients the haemodynamic measurements were vitiated by
major complications associated with severe tetanus. We found it impossible to interpret
these measurements, other than to note that they were significantly different from those
observed in severe uncomplicated tetanus.
The high output hyperdynamic circulatory state observed in severe uncomplicated tetanus
was, in our opinion, chiefly due to excessive muscular contractions, increased sympathetic
tone, and to a rise in the core temperature. Frequent convulsive seizures and increased
muscle tone produce an increase in tissue metabolism and an increased oxygen demand.

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Since the arteriovenous difference in oxygen content was normal this increased oxygen
demand can only be translated into an increased oxygen supply and consumption through
peripheral vasodilatation, increased venous return and an increased cardiac output.
Increased sympathetic activity contributed to an increase in cardiac output and it was
manifested by marked tachycardia (130-190/min), which was disproportionate to the rise in
core temperature and which persisted during curare-induced relaxation, and by severe
sweating unrelated to fluctuations in body temperature. These features occurred in all
patients, even in the absence of abruptfluctuationsin blood pressure and heart rate. A slight
rise in core temperature at the time of the study was a minor contributory factor to the
hyperkinetic circulatory state.
Volume loading patients with severe but uncomplicated tetanus highlighted important
features in circulatory haemodynamics. The inability to sustain the peak rise in pulmonary
capillary wedge pressure and cardiac output for more than 10-15 min after volume challenge
was, in our view, largely related to an increase in the vascular capacitance of a highly
compliant vascular system produced by arteriolar, capillary and venous dilatation, chiefly in
skeletal muscles. Myocardial function was also suspect, particularly in grade IV tetanus.
Thus though volume challenge produced a significant rise in stroke volume index, cardiac
index and in left and right ventricular stroke work indices, the percentage increase from
baseline in these values was significantly greater in our controls; also the degree ofrisein the
left ventricular stroke work index in patients with grade IV tetanus was not as significant as
that in patients with grade III tetanus. A more accurate assessment of left ventricular
function by radionuclide methods was not possible as transport of critically ill patients to
distant departments was hazardous and impractical.
Haemodynamic studies during severe tetanus with autonomic cardiovascular distur-
bances have been reported earlier as individual case reports, and results have been attributed
chiefly to sympathetic overactivity [8-15]. We however feel that both sympathetic and
parasympathetic disturbances are involved in the cardiovascular autonomic disturbances of
severe tetanus. Our study showed that sympathetic disturbances could take the form of
 Haemodynamic Studies in Severe Tetanus 459
either a sustained increase in sympathetic tone or a seizure-like discharge from the
sympathetic nervous system. The former produced tachycardia, and an increase in the
systemic vascular resistance which led to sustained hypertension with cold peripheries. A
seizure-like discharge could lead to sudden tachycardia, an increase in the central venous
pressure and a sudden sharp increase in the systemic vascular resistance with spikes of
hypertension. The cessation of this seizure-like discharge led to hypotension and bradycar-
dia and was associated with a sharp fall in the systemic vascular resistance and a fall in the
central venous pressure. The cardiac index and the left heartfillingpressures were unaltered
during these episodes of fluctuating sympathetic activity. Haemodynamic studies with
similar results have been reported by Corbett et al. [14]. The failure of the left ventricular
stroke work index to rise significantly during hypertensive spells again suggested an
impairment of myocardial function. Whether this impairment is related to the tetanus toxin
or to excessive catecholamine levels in blood is a matter of conjecture. Parasympathetic
activity also plays an important role in the autonomic cardiovascular disturbances, as
hypotension, bradycardia and even 'arrest' can be accentuated by increased parasympathe-
tic tone. Evidence for increased parasympathetic activity in patients with both grade III and
rv tetanus was evinced by the presence of excessive salivation, excessive tracheobronchial
secretion, sudden bradycardia and cardiac arrest occasionally observed following tracheal
suction, and the spontaneous occurrence of transient junctional rhythms. Cardiac arrest is
the most dreaded complication of severe tetanus and is often related to autonomic
disturbances: we have observed this following sudden hypotension, following a bradyr-

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hythm induced by tracheal suction and following a sudden paroxysmal rise in core
temperature above 42.2°C [4]. The one patient in our study who suffered sudden death was
unusual in that cardiac arrest was preceded by a sudden onset of slow idioventricular
rhythm, suggesting a conduction defect below the atrioventricular junction, probably at the
level of the bundle branches of His. This disturbance in conduction preceding arrest and
death was in our opinion more due to the direct effect of tetanus toxin on conducting tissue
rather than to excessive parasympathetic activity.
A number of methods have been tried to control autonomic cardiovascular disturbances
in tetanus, including /?-adrenergic blockade [ 12], heavy sedation [7,12, 16], and labetalol [11,
17]. Even so the mortality in such patients was over 50 per cent [7, 15, 18]. More recently
James and Manson [7] reported two deaths in 10 patients treated with i.v. infusions of
magnesium sulphate and Sutton et al. [19] reported the successful use of i.v. clonidine in one
patient. We attribute our low mortality to good overall critical care, to efficient
cardiorespiratory support and to the avoidance of drugs that strongly depress either the
central or autonomic nervous system. Drugs acting on the cardiovascular system were used
sparingly under constant haemodynamic monitoring, and only when it was deemed
absolutely necessary to alter grossly deranged haemodynamic function or parameters. Our
haemodynamic monitoring and studies were indeed of great relevance and help, in that they
enabled us to adhere to the above principles. Thus hypotensive episodes were treated with a
volume load. If the latter was contraindicated or was ineffective, we used dopamine or
dobutamine titrated to maintain the systolic pressure just above 100-110 mmHg.
Hypertensive episodes with systolic blood pressure above 200 mmHg or a diastolic blood
pressure above 100 mmHg were treated with a small dose of oral propranolol (5-10 mg) or
sublingual nifedipine (5 mg), to which these patients were generally exquisitely sensitive.
Bradyrhythms were treated with i.v. atropine and sinus tachyrhythms beyond 190/min with
oral verapamil 40 mg twice or thrice daily, or with a small dose of propranolol. Above all we
did not use more than 30-40 mg diazepam i.v./day. This is in striking contrast to large doses
of diazepam 200-300 mg/day that form the cornerstone of treatment in almost all tetanus
460 FE Udwadia and others
units both in this country and in the West. We feel that sedatives and drugs used in a dose that
markedly depress the central and autonomic nervous systems have inherent dangers and
may well predispose to cardiac arrest (particularly following periods of acute hypotension or
severe bradyrhythms) and render resuscitation more difficult. Our principles of management
stand vindicated by the low mortality of our patients.

ACKNOWLEDGEMENTS
We are indebted to Sister S Amaria (ICU Superintendent), other staff of the Intensive Care
Unit, the Pathology and Physiotherapy Departments and the resident doctors of the Breach
Candy Hospital for their assistance in this study. We are also grateful to Ms KF Irani and Mr
A Khopkar for their help in preparing this manuscript, and to Mr A Kannappan for his help
in the statistical analysis. We are also indebted to Mr D Chandriani for his assistance in this
study.

REFERENCES
1. Vadivale VM, Phaneendra Rao RS, Krishna Rao TS, Chakledar BK. A study of tetanus cases in a
hospital at Manipal, South Kanara District, Karnataka. Indian J Public Health 1985; 29: 29-35.
2. Bildhaya CS. A study of tetanus in a hospital at Ahmedabad. J Indian Med Assoc 1983; 80: 21-25.
3. Ablett JJL. In: Ellis M (ed). Symposium on tetanus in Great Britain, Leeds United Hospitals. 1967.

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4. Udwadia FE, Lall A, Udwadia ZF, Sekhar M, Vora A. Tetanus and its complications: intensive
care and management experience in 150 Indian patients. Epidem Infect 1987; 99: 675-84.
5. Shapiro BA, Harrison RA, Walton JR. Clinical Application of Blood Gases. 3rd ed. Chicago-
London: Year Book Medical Publishers Inc, 1982.
6. Montero Benzo, Santatecla V. Estudio de la alteraciones hemodinamicas en el tetanos grave.
(Hemodynamic changes in severe tetanus). Rev Esp Anestesiol Rean 1984; 31: 234-37.
7. James MF, Manson ED. The use of magnesium sulphate infusions in the management of very
severe tetanus. Intensive Care Med 1985; 11: 5-12.
8. De Michele DJ, Taviera Da Silva AM. Cardiovascular findings in a patient with severe tetanus.
Crit Care Med 1983; 11: 828-29.
9. Kerr JH, Travis KW, O'Rouke RA, el al. Autonomic complications in a case of severe tetanus. Am
JMed 1974; 57: 303-09.
10. Rie MA, Wilson RS. Morphine therapy controls autonomic hyperactivity in severe tetanus. Ann
Intern Med 1978; 88: 653-54.
11. Wesley AG, Hariprasad D, Pather M, Rocke DA. Labetalol in tetanus. Anaesthesia 1983; 38: 243-
49.
12. Prys Roberts C, Corbett JL, Kerr JH, Smith AC, Spalding JM. Treatment of sympathetic
overactivity in tetanus. Lancet 1969; i: 542-45.
13. Corbett JL, Spalding JM, Harris PJ. Hypotension in tetanus. Br Med J 1973; 3: 423-28.
14. Corbett JL, Kerr JH, Prys Roberts C, Smith AC, Spalding JM. Cardiovascular disturbances in
severe tetanus due to overactivity of the sympathetic nervous system. Anaesthesia 1969; 24: 198-
212.
15. Kerr JH. Current topics in tetanus. Intensive Care Med 1979; 5: 105-10.
16. Cole LB, Youngman HR. Treatment of tetanus. Lancet 1969; i: 1017-29.
17. Dundee JW, Morrow WFK. Labetalol in severe tetanus. Br Med J 1979; 1: 1121-22.
18. Trujillo MH, Castillo A, EspanaJ, MenzoH.Zefra R. Import of intensive care management in the
prognosis of tetanus: analysis of 641 patients. Chest 1987; 92: 63-65.
19. Sutton DN, Trenlitt MB, Woodcock TE, Nielsen MS. Management of autonomic dysfunction in
severe tetanus: the use of magnesium sulphate and clonidine. Intensive Care Med 1990; 16: 75-80.