The Magnesium Web Site received the
following email:
Dear Sir , You may be interested to know that
we in Sri Lanka have figured out a way to use magnesium to manage
tetanus patients without using a ventilator. Normally these
patients have to be kept ventilated with a machine even for
weeks. Please add this site to your list. This has been reported
in international journals.
http://www.geocities.com/tetanus_tetanus/
thank you
pras
The page describing the use of magnesium sulphate infusions in
the management of tetanus has been reproduced here. (http://www.geocities.com/tetanus_tetanus/magnesium.html)
Magnesium!
The use of magnesium sulphate infusions in the management of
tetanus enables one to minimise sedation and reduce the need for
mechanical ventilation, and thereby greatly simplifying the care
of the tetanus patient. Magnesium is also able to minimise
sympathetic overactivity associated with tetanus. Furthermore,
magnesium sulphate is already a well-known entity due to its
extensive use in the management of pregnancy induced
hypertension.
The following article introduced this concept for the first
time:
Attygalle D, Rodrigo N, Magnesium sulphate for control
of spasms in severe tetanus. Can we avoid sedation and artificial
ventilation? Anaesthesia 1997
Oct;52(10):956-62
The description below will give you a rough idea of the
concept. However, when reading it, please note the following:
- Try to read the article.
- Since the study was published, many more cases have been
managed and the treatment protocol has been refined.
- The best and easiest way for you to get the latest
information and to get your queries answered is to join the
email
based discussion group . The authors of the paper are also
members of the discussion group and have considerable
experience in managing tetanus patients. Whatever your level of
expertise or interest, you are welcome to join this unique
discussion group.
- Keeping the above points in mind, please read the following
description of the study.
Summary
A prospective pilot study was undertaken to
investigate the ability of magnesium sulphate to control the
spasms of severe tetanus without the need for sedation and
artificial ventilation. All eight patients admitted with severe
tetanus to our intensive care unit within the last year were
given magnesium sulphate 5 g i.v. as a loading dose followed by
an infusion of 2-3 g/h. The infusion rate was increased to
control spasms while retaining the patella tendon reflex, which
proved an effective guide to overdose. Spasms were effectively
controlled and serum magnesium concentrations were maintained
within the therapeutic range. Spontaneous ventilation was
adequate, ventilatory support being provided only for the
management of lung pathology. There was no evidence of
cardiovascular instability due to sympathetic over activity. No
supplementary sedation was required for the control of spasms or
autonomic dysfunction during magnesium therapy.
We conclude that magnesium sulphate can be used as the
sole agent for the control of spasms in tetanus without the need
for sedation and artificial ventilation.
Introduction
Tetanus has been aptly described as a third world disease the
treatment of which requires first world technology1,
as heavy sedation and ventilatory support (with or without muscle
relaxants) are the mainstay of management, and these are not
always available to tetanus patients in those developing
countries in which the disease is prevalent. Even in the
developed world the problems in the management of tetanus have
yet to be solved. Reported mortality for severe tetanus ranges
between 15-40%2, 3, 4, and depends on the availability
and quality of intensive care. Deaths due to cardiovascular
dysfunction have not been convincingly reduced by the various
regimen of sedation, although with management guided by pulmonary
artery catheterisation, mortality has been reduced to 6.5% in one
study5. The complications resulting from long term
heavy sedation and artificial ventilation (pulmonary sepsis,
bronchospasm, atelectasis, pressure sores, deep vein thrombosis,
pulmonary embolism and gastric haemorrhage) also contribute
significantly to morbidity and mortality3, 4, 6, 7.
This is exemplified in Edmondson's6 series in which 6
out of 10 deaths were attributable to respiratory complications.
There is, therefore, a continuing search for drugs which can
control the spasms and the autonomic dysfunction of tetanus
without the need for heavy sedation and artificial
ventilation8, 9, 10.
A role for magnesium in the management of tetanus has been
postulated by many authors. As early as 1906 Blake11
described two cases of severe tetanus treated with intrathecal
magnesium sulphate. James and Lipmann used it intravenously for
the control of autonomic dysfunction12, 13, but its
efficacy in the control of spasms has not been investigated.
Magnesium is a physiological calcium antagonist and there is a
significant correlation between depression of neuromuscular
transmission and serum magnesium concentrations14. The
fact that these effects are dose dependent and controllable is a
great advantage over muscle relaxants. Magnesium is utilized in
the control of spasms in eclampsia and the safety of the
therapeutic range (2-4 mmols/l) has been well established15,
16 as areflexia only occurs at levels above 4 mmol/l and
muscle paralysis above 6 mmol/l. It is therefore possible that
would also control the tetanus without paralysis and the need for
artificial ventilation.
The aim of this study was to investigate the efficacy and
safety of magnesium sulphate i.v. in controlling the spasms of
severe tetanus without the need for sedation and ventilatory
support; efficacy to be assessed by the ability to control spasms
and safety, by monitoring cardiovascular and respiratory function
and serum magnesium concentrations.
Patients and methods
The investigation took the form of a prospective study which
was approved by the institutional ethical committee. Informed
consent was obtained from the patient or relatives.
All eight patients with severe tetanus admitted to the
Anaesthetic Intensive Care Unit (ICU) of the National Hospital of
Sri Lanka between March 1996 and 1997 were included in the study.
The presence of severe trismus and dysphagia, generalized muscle
rigidity, opisthotonus, an frequent spontaneous spasms
embarrassing respiration on admission qualified them for
inclusion to Grade III A of Ablett's classification17.
Exclusion criteria were defined as compromised renal function on
the basis of blood urea > 6 mmol/l or urine output < 50
ml/hour and no patient qualified for exclusion.
Patients had been initially treated in the ward with
antitoxin, toxoid, surgical debridement if the wound could be
identified, and i.v. metronidazole and diazepam. Tracheostomy was
performed in all eight patients as they had spasms sufficiently
frequently and severe enough to interfere with respiration.
On admission to the ICU i.v. diazepam was omitted and
magnesium sulphate therapy commenced within 24 hours, after
ensuring adequate urine output, and obtaining serum magnesium
concentrations and assessing the intensity of the patellar tendon
reflex (knee jerk). A loading dose of i.v. magnesium sulphate 5 g
over 20 minutes, was followed by an infusion of 2 g /hour via an
infusion pump. The rate of infusion was increased by 0.25-0.5 g
every 8 hours till control of spasms was achieved, as long as the
patellar reflex could be elicited. The patellar reflex was
assessed every half-hour in the first 4 hours after commencing
the infusion, whenever the dose was increased, and then less
frequently thereafter. Serum magnesium concentrations were
measured 12 hours after the infusion was commenced, whenever the
dose was increased, and at regular intervals thereafter. Once the
dose was stabilized, regular attempts were made to reduce the
infusion rate to ensure that the minimum required dose was
administered. Evidence of hypocalcaemia was sought using clinical
signs (Chvostek’s and Trousseau’s) and the
measurement of total serum calcium concentrations.
Presence of increased sweating, salivation and bronchial
secretions were noted. Monitoring included continuous
electrocardiography and pulse oximetry, half-hourly measurement
of non-invasive blood pressure measurements, and hourly
measurements of urine volume, tidal volumes and respiratory rate.
End tidal carbon dioxide was monitored at intervals and arterial
blood gases measured when indicated.
The clinical features, circulatory, respiratory and other
parameters were charted and chest radiography, and
bacteriological and haematological investigations were performed
according to our usual intensive care protocol. Incidental
complications (e.g. urinary tract infections) were treated
appropriately. Enteral feeding was given via nasogastric tube on
the basis of 2500 kcals/day with sufficient fluids to maintain a
urinary output of > 50 ml/kg /day. Serum sodium and potassium
were maintained within normal limits.
General management included chest and limb physiotherapy,
tracheal suction, skin and mouth care. Fentanyl 50 mcg was given
before chest physiotherapy 3-4 times a day. Low dose subcutaneous
heparin was given to the first two patients only.
Indications for supplementary therapy were laid down in the
event of uncontrollable spasms and autonomic dysfunction and
complications of magnesium therapy.
-
i.v. diazepam, and vecuronium (ortubocurarine) were to be
given. If control of spasms could not be achieved without
loss of the patella reflex and within therapeutic serum
magnesium concentrations of 2-4 mmol/l.
-
i.v. morphine was to be given if unacceptable autonomic
dysfunction occurred (systolic hypertension > 160 mm or
tachycardia > 120/minute sustained for over one hour).
-
If signs of magnesium overdose occurred (muscle flaccidity
with loss of the patella reflex, respiratory depression or
prolonged PR interval on the ECG); magnesium therapy was to
be temporarily discontinued, diuresis enforced, and calcium
gluconate given if necessary. Once the signs of overdosage
disappeared the infusion was to be recommenced at a lower
dosage.
-
Ventilatory support was to be given if the tidal volume
was < 5 ml/kg or respiratory rate > 30/minute with
PaCO2 > 6kPa.
-
10 ml of 10% calcium gluconate were to be given i.v. if
clinical signs of hypocalcaemia were evident.
Results
Details of age, sex, approximate weight, incubation period,
onset times, and site of wound are given in Table 1. No patient
gave a history of immunisation to tetanus. All eight patients
were admitted to the ICU within 48 hours of the onset of spasms,
three patients (1, 2 & 6) having suffered pulmonary
aspiration previously in the ward.
Table 1. Patient characteristics
|
Patient No.
|
Sex
|
Age (yrs)
|
Weight (kg)
|
Incubation period (days)
|
Onset time (h)
|
Site of Wound
|
|
1
|
M
|
25
|
45
|
3
|
< 72
|
foot
|
|
2
|
F
|
32
|
50
|
7
|
< 48
|
foot
|
|
3
|
M
|
45
|
55
|
7
|
< 72
|
scalp
|
|
4
|
F
|
28
|
50
|
?
|
< 24
|
no history
|
|
5
|
M
|
58
|
70
|
10
|
< 24
|
foot
|
|
6
|
M
|
69
|
70
|
7
|
18
|
foot + # femur
|
|
7
|
M
|
54
|
70
|
18
|
< 48
|
foot
|
|
8
|
M
|
31
|
60
|
4
|
< 96
|
foot
|
Control of spasms and rigidity
The intensity and frequency of spasms were reduced within 2-3
hours of the commencement of magnesium sulphate therapy and was
suppressed within 24 hours. The rate of infusion had to be
progressively increased with increasing severity of spasms in the
first week but required only minimal adjustments in the second
week and could be reduced in the third week (Table 2).
Table 2. Data on Magnesium (Mg) therapy
|
Patient No.
|
Mg dose g/h
1st week
|
Mg dose g/h
2nd week
|
Mg dose g/h
3rd week
|
Mg dose g/h
4th week
|
Mg Conc. mmol./l
|
Mg therapy (days)
|
|
1
|
1.5 - 2.0
|
1.5 - 2.0
|
1.5 - 1.0
|
-
|
2.0 - 2.2
|
20
|
|
2
|
2.0 - 3.0
|
2.0 - 2.5
|
2.5 - 1.5
|
-
|
2.2 - 2.4
|
20
|
|
3
|
2.0 - 2.5
|
2.25- 2.5
|
2.0 - 0.5
|
-
|
2.4 - 3.2
|
19 + 4**
|
|
4
|
2.0 - 3.0
|
3.0
|
-*
|
-*
|
3.1 - 3.5
|
14*
|
|
5
|
2.0 -
|
2.0 - 1.5
|
1.0
|
-
|
2.0 - 2.6
|
17
|
|
6
|
2.0 - 2.5
|
2.5 - 2.75
|
2.5 - 2.25
|
2.5 -1.0
|
2.5 - 3.0
|
21+ 6**
|
|
7
|
2.0 - 3.0
|
2.5 - 3.0
|
2.5 - 2.0
|
-
|
2.5 - 3.0
|
16
|
|
8
|
2.0 - 3.5
|
3.0 - 3.5
|
3.0 - 1.0
|
-
|
2.6 - 3.3
|
17
|
Mg conc. refers to the range of serum
magnesium concentrations at which spasms were controlled.
* No stocks of magnesium sulphate
** Refers to the days during which magnesium was given for
control of tachycardia after spasms subsided.
Magnesium therapy had to be continued for a few days after the
cessation of spasms as attempts at withdrawal resulted in
unacceptable rigidity in some patients and sustained tachycardia
(> 120/min.) in others. The serum magnesium concentrations
were found to be within the therapeutic range (2-4 mmol/l)
throughout therapy. No patient needed supplementary therapy.
Rigidity was not completely abolished but reduced sufficiently
in all patients to suppress trismus which allowed easy mouth
care. Dysphagia was reduced and all but one patient could swallow
saliva, three of them being able to swallow small quantities of
semisolid diet. Lung and limb physiotherapy could be performed
without difficulty.
Continuous magnesium therapy was interrupted in the following
two patients. Patient 4 had magnesium therapy for the first 14
days but due to inability to obtain further stocks of magnesium
sulphate sedation and paralysis (hourly diazepam 7.5 mg, and
tubocurarine 3 mg to control spasms, and morphine 5 mg to control
autonomic dysfunction) were introduced for the next 12 days.
Patient 6 whose spasms were well controlled on the first two days
was taken off magnesium therapy on the 3rd day, as he needed CMV
for worsening aspiration pneumonia. He was given i.v. midazolam
morphine and vecuronium for 60 hours. On the 6th day all drugs
were discontinued and two hours later when spasms recurred
magnesium therapy was recommenced. Spasms were then controlled
but ventilatory support with SIMV and pressure support had to be
continued for 21 days till the pneumonia resolved.
Spontaneous tidal volumes were adequate to maintain
normocarbia. However patients 1, 2, 3 and 6 required ventilatory
support, for the management of lung pathology (Table 3).
Bronchial secretions were markedly increased but often responded
to nebulisation with ipratropium bromide. Cough was not
sufficiently effective in the presence of increased bronchial
secretions and patients required frequent tracheal suction. Vital
capacity was low in all patients during therapy. (Table 3)
Patients 5, 7, and 8 were sufficiently cooperative and able to
enable us to measure vital capacity without stimulating spasms
prior to magnesium therapy. Patient 5 & 7 had vital
capacities of 2000 ml and 1000 ml respectively which fell further
during the second week of therapy. (Table 3). Patient 7 had a
vital capacity of 1000 ml after the commencement of therapy.
Table 3. Pulmonary function during the course of the
disease
| Patient No. |
Vt (ml/kg) |
f (bpm) |
V. C. (ml) |
Ventilatory support (days) |
| 1 |
6 |
20 - 28 |
700 |
1st - 5th |
| 2 |
7 |
22 - 26 |
800 |
1st - 3rd |
| 3 |
6 |
20 - 22 |
700 |
11th - 12th |
| 4 |
7 |
22 - 26 |
- |
15th - 26th * |
| 5 |
8 |
16 - 20 |
1000 |
None |
| 6 |
6 |
22 - 24 |
600 |
2nd - 21st |
| 7 |
8 |
16 - 20 |
1500 |
None |
| 8 |
6 |
22 - 24 |
700 |
None |
Clinical variables Vt, f & VC measured during spontaneous
ventilation on magnesium therapy without ventilatory support
(CMV, SIMV or pressure support).
| Vt |
= Lowest spontaneous tidal volumes |
| f |
= range of respiratory rates |
| VC |
= Lowest vital capacity |
| * |
on relaxants and IPPV due to shortage off magnesium
sulphate. |
No patient had clinical signs of hypocalcaemia at any time but
total serum calcium concentrations were reduced (range 2.72 to 3
mmol/l). Concentrations were restored to normal within 2-3 days
of stopping magnesium therapy.
Autonomic dysfunction
Continuous ECG monitoring and 12 lead ECG records showed no
dysrhythmias or heart block in any of the patients. During
magnesium therapy there was no hypertension or tachycardia and
the variability in heart rates and blood pressures were minimal
(Table 4) even during tracheal suction. Occasional episodes of
bradycardia (45 bpm) which occurred in patient 6 were by
stimulation of the patient and i.v. atropine. During the periods
off magnesium, patients 4 and 6 showed some cardiac instability.
In patient 4 during the 12 days of sedation there were periods of
sustained tachycardia (> 120 /min) with a greater variability
when compared with the two weeks on magnesium therapy. In patient
6 during the three days off magnesium the variability in blood
pressures and more so in heart rates (SD in Table 4) was greater
and episodes of bradycardia more frequent when compared with that
of the period on magnesium therapy.
Table 4. Blood pressures and heart rates during the
first 3 weeks tetanus.
Patient No.
|
Mean BP (mm Hg)
Mean Heart rate
(beat min-1) |
1st week
|
2nd week
|
3rd week
|
1
|
Mean BP
Mean HR |
81 (10.2)
96 (13.3) |
91 (5.5)
85 (10.8) |
89 (7.3)
87 (14.1) |
2
|
Mean BP
Mean HR |
87 (12.1)
99 (10.5) |
86 (11.2)
87 (6.3) |
87 (11.2)
86 (8.5) |
3
|
Mean BP
Mean HR |
94 (8.1)
92 (9.01) |
85 (6.1)
97 (8.7) |
86 (7.5)
100 (10.8) |
4
|
Mean BP
Mean HR |
80 (6.4)
86 (7.2) |
79 (4.5)
88 (7.3) |
*83 (6.1)
*109 (10.7) |
5
|
Mean BP
Mean HR |
95 (6.8)
64 (7.09) |
96.95 (8.0)
67.46 (6.1) |
|
6
|
Mean BP
Mean HR |
*95 (16.6), **83 (11.6)
*94 (29.0), **77 (9.1) |
80 (12.8)
70 (9.4) |
74 (12.8)
71 (9.1) |
7
|
Mean BP
Mean HR |
101 (7.3)
71 (9.4) |
91 (6.6)
74 (7.5) |
|
8
|
Mean BP
Mean HR |
84 (8.2)
75 (14.2) |
63 (8.3)
79 (6.0) |
87 (5.6)
67 (12.0) |
Mean (SD) of hourly of blood pressures and heart rates are
given for each of the 3 weeks.
* Refers to periods off magnesium therapy
The mean (SD) for patient 6 in the first week is given
separately for the * 3 days off magnesium and ** 3 days on
magnesium
Excessive sweating unrelated topyrexia was noted in all except
patient 7 after about the fifth day and was more profuse in
patients 4 and 6 when off magnesium. Increased salivation was not
a problem because patients were able to swallow saliva. In all
parenteral feeding was well tolerated but constipation was a
problem till they were mobilized out of bed. There were no
indications for supplementary therapy during the period on
magnesium therapy.
Patients were conscious, rational and cooperative and were
able to communicate with staff and relatives which simplified
nursing care. They were comfortable during the day but were given
5-10 mg. oral diazepam to promote sleep at night.
Mobilization and discharge from ICU were delayed in patient 4
who was on sedation and paralysis and in patient 6 who had a
fracture neck of femur and remained in the ICU till surgery was
performed. In the others the mean (range) period to mobilization
out of bed was 15.8 day (8-21) and mean (range) duration of ICU
stay was 21 days (18-31).
Discussion
The efficacy of magnesium sulphate was clearly demonstrated in
all eight patients as spasms were controlled without the need for
benzodiazepines, opiates, muscle relaxants or ventilatory
support. The safety of our regime was shown by the fact that
control of spasms was achieved with serum magnesium
concentrations within the therapeutic range. Since areflexia
occurs only at serum magnesium concentrations above 4 mmols, the
presence of the patellar reflex proved a valid end point to
ensure that the therapeutic range was not exceeded. We were
successful in using this simple clinical guide as our patients
were not paralysed and the patellar reflex was retained at
concentrations which controlled spasms. James12 who
titrated the dose to serum magnesium concentrations (for the
control of autonomic dysfunction in paralysed patients) was not
always successful in keeping within the therapeutic range. The
patellar reflex should in fact prove a more valid index of muscle
tone in the presence of hypocalcaemia (which occurs during
magnesium therapy), since the depression of neuromuscular
transmission has a better correlation with the serum Mg/Ca ratio
than with serum magnesium concentrations14. The
development of hypocalcaemia seen in our patients in response to
hypermagnesaemia has been well documented18, 19. and
the absence of clinical signs in spite of low serum calcium
concentrations is similar to the findings of Cholst20.
Its return to normal within 2-3 days of stopping magnesium
therapy indicates that hypocalcaemia was only temporary. The main
advantage of magnesium therapy namely the avoidance of
ventilatory support is lost if aspiration occurs, as was the case
in three of our patients. Aspiration however could have been
prevented by timely tracheostomy at the stage of severe dysphagia
before the onset of severe spasms.
Though ventilation was adequate, vital capacity was reduced in
all patients. Magnesium in the therapeutic range has been
reported to produce a small but significant reduction of vital
capacity in obstetric patients receiving similar regimes21,
22. Such a reduction would assume a greater clinical
significance in tetanus in view of the reduction in vital
capacity that is already present due to rigidity as was seen in
patients 5, 7 and 8. Whatever the cause, reduced vital capacity
and ineffective cough in the presence of profuse secretions
required frequent tracheal suction. The tracheostomy which was
originally performed to prevent aspiration during spasms was
essential to clear the lungs of secretions and could only be
closed when the secretions subsided. The reduction in vital
capacity also probably compromises the ability of patients to
cope with severe infections without respiratory support as seen
in patient 6.
If respiratory complications are avoided or managed
successfully deaths occur due to sympathetic over activity. The
physiological basis of the effects of magnesium on SOA is its
ability to reduce catecholamine concentrations to normal13,
23 by inhibiting their release and also reducing the
sensitivity of receptors to these neurotransmitters24,
25. Magnesium sulphate has been previously used in the
control of sympathetic over activity of tetanus12, 13
and phaeochromocytoma23. In these reports12,
13, magnesium therapy was given after SOA occurred. In our
study magnesium therapy was commenced before autonomic
dysfunction could set in but evidence for the prevention of SOA
was seen in patients 4 and 6, who during the periods of sedation
and paralysis acted as their own controls.
In all our patients cardiovascular stability was maintained
during magnesium therapy without the need for sedatives. This is
contrary to the findings in the case report by
Lipman13 who questioned the ability of magnesium
sulphate to control autonomic dysfunction in the absence of
sedation.
Parasympathetic over activity also plays an important role in
the autonomic dysfunction of tetanus. Although magnesium is said
to suppress acetylcholine at the ganglia26 and vagal
nerve terminals27, all our patients except patient 7
had increased salivation and bronchial secretions which were not
suppressed by magnesium therapy.
Two other drugs, baclofen and dantrolene, have been used for
the control of spasms without the need for sedation and
artificial ventilation but have their own limitations. Baclofen a
gaba B agonist has been used intrathecally in tetanus both as an
adjunct to sedation and paralysis 28, 29 and also as
the sole therapy8, 9. Muller8 using
continuous infusions was able to control spasms without causing
sedation or ventilatory compromise in two patients. The practical
considerations are however the technical difficulties and the
risk of infection with an external infusion device, and the high
cost of the implantable variety. Due to these constraints in
developing countries Saissy9 administered baclofen as
intermittent intrathecal injections to ten patients but he failed
to control spasms in two of them and five patients developed coma
and ventilatory depression. The ability of baclofen to control
cardiovascular dysfunction demonstrated by Muller was not
confirmed by Saissy. Dantrolene has been used in two
patients9 but sedation is required to control
autonomic dysfunction. Disadvantages of dantrolene are its
potential hepatotoxicity and prohibitive cost.
In comparison magnesium sulphate effectively controlled the
spasms of severe tetanus with no failures, no need for additional
sedation and no need for ventilatory support except when
indicated for lung pathology. The fact that magnesium does not
cause sedation at serum concentrations less than 8 mmol/l as long
as ventilation is adequate (as it does not easily cross the blood
brain barrier)30 was confirmed in all eight patients.
Their ability to communicate, open the mouth, swallow saliva and
move about in bed helped considerably in nursing. The ease of
nursing care in conscious cooperative patients was in marked
contrast to the authors’ personal experience of 60 patients
previously managed with sedation and paralysis.
We conclude that magnesium sulphate in a dosage titrated to
the preservation of the patellar reflex and maintaining serum
concentrations within the therapeutic range could be used as the
sole drug to control the spasms of severe tetanus. Spontaneous
ventilation in this dose range is adequate and ventilatory
support will be needed only for those patients who develop
pulmonary complications. Tracheostomy is required both to protect
the airway till spasms are brought under control and for the
clearance of profuse secretions when cough is not effective.
Magnesium therapy could possibly prevent SOA in the majority of
patients, but is not effective in preventing parasympathetic
effects.
The avoidance of ventilatory support and sedation would be
cost effective, simplify nursing care and reduce the
complications of deep vein thrombosis, barotrauma and respiratory
infections. In addition its low cost and ease of administration
are major advantages in developing countries.
References
1. Delport SD. Neonatal tetanus--an opportunity for
prevention. South African Medical Journal 1990;
77: 78-9.
2. Trujillo MH, Castillo A, Espana J, Manzo A, Zerpa R. Impact
of intensive care management on the prognosis of tetanus.
Analysis of 641 cases. Chest 1987;
92:(1)63-5.
3. Sun KO, Chan YW, Cheung RTF, So PC, Yu YL, Li PCK.
Management of tetanus: A review of 18 cases. Journal of the
Royal Society of Medicine. 1994; 87:
135-37.
4. Reis E, Freire E, Alexandrino S. Tetanus in an ICU in
Portugal. International Journal of Intensive Care
1994/95; 1 (4): 120-21.
5. Udwadia FE, Sunavala JD, Jain MC, D’Costa R, Jain PK,
Lall A, Sekhar M, Udwadia ZF, Kapadia F, Kapur KC, Mehta SK,
Kharas RJ. Haemodynamic studies during the management of severe
tetanus. Quarterly Journal of Medicine, New Series.
1992; 83: No. 302: 449-60.
6. Edmondson RS, Flowers MW. Intensive care in tetanus:
management, complications, and mortality in 100 cases.
British Medical Journal. 1979;
1:1401-4.
7. Kerr JH, Corbett JL, Prys-Roberts C, Crampton Smith A,
Spalding JMK. Involvement of the sympathetic nervous system in
tetanus. Studies on 82 cases. The Lancet 1968; 2: 236-41.
8. Muller H, Borner U, Zierski J, Hempelmann G. Intrathecal
baclofen for treatment of tetanus induced spasticity.
Anaesthesiology 1987; 66,No 1:
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