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Review Article - Tetanus

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 REVIEW ARTICLE

Tetanus

R. Bhatia, S. Prabhakar, V.K. Grover*

Departments of Neurology and Anesthesia*

Postgraduate Institute of Medical Education and Research
Chandigarh - 160 012, India.

Summary

Tetanus is a potentially life threatening disease affecting nearly 50,000 to 1 million people
world wide every year. Four major clinical forms of tetanus are described i.e. generalized,
cephalic, localized and neonatal. Neonatal tetanus is particularly common in developing
countries, due to unhygienic child birth practices, social taboos and improper
immunization of pregnant mothers. Management of this disorder involves a team
approach and aims at eradicating focus of infection, neutralizing the toxin, controlling
spasms and dysautonomia and providing adequate ventilatory and supportive care.
Metronidazole may be the preferred antibiotic although penicillin is still used frequently.
Adequate wound debridement is necessary to prevent spore germination. Spasms are
usually managed by sedatives like diazepam and neuromuscular blocking agents.
Magnesium sulphate is an attractive substitute and may be tried if ventilatory facilities are
unavailable. Use of baclofen is potentially advantageous but cannot be routinely
prescribed. Dysautonomia is difficult to manage and requires therapy with
benzodiazepines, morphine, magnesium sulphate, adrenergic blockers and recently tried
baclofen therapy. Supportive care including ventilatory assistance are highly essential for
successful outcome of the patients. It is imperative that complications are diagnosed early
and managed appropriately. Immunization is extremely effective and is the key to
prevention. Adequate steps and measures should be taken to increase awareness of this
potentially preventable disease.

Key words : Tetanus, Spasms, Lock jaw.

Neurol India, 2002; 50 : 398-407

Tetanus is a potentially fatal disease manifesting itself ‘clostridium tetani’. Despite the availability of a
as painful spasms, autonomic instability and highly effective vaccine, nearly 1 million cases of
respiratory compromise, caused by ‘tetanospasmin’ a tetanus occur worldwide every year.1 Majority of the
potent neurotoxin liberated by the organism tetanus related deaths occur in Africa and South-east
Asia, and the disease remains endemic in many
Correspondence to : Dr. S. Prabhakar, Professor and Head,
Department of Neurology, Postgraduate Institute of Medical countries worldwide.2 The present review deals with a
Education and Research, Chandigarh - 160 012, India. brief overview of the disease, available treatment
E-mail: [email protected] options and methods of prevention.

Neurology India, 50, December 2002 398

Tetanus

Brief History and Epidemiology but are destroyed by autoclaving at 1200C for 15
minutes or boiling for atleast 4 hours. The vegetative
The clinical descriptions of tetanus are available in form produces ‘tetanospasmin’, a potent neurotoxin
records from antiquity (5th Century BC). In the year which is responsible for the clinical manifestations
1884, Nicolaier produced tetanus in animals by and ranks second to the botulinum toxin as the most
injecting them with soil specimens. Kitasato isolated potent microbial toxin known.7
the organism in 1889 from a human tetanus victim and
reported neutralization of toxin by specific antibodies. Pathogenesis
Tetanus toxoid was described by Descombey in 1924
and was effectively used during the world war II. The Under anaerobic conditions, spores present around the
global incidence of tetanus is about 18 cases per wound germinate. This leads to production of two
100,000 population per year, with case fatality known toxins : ‘tetanospasmin’ and ‘tetanolysin’,
ranging between 20 and 50%. In places like USA, the which are disseminated by blood and lymphatics to
incidence of this disease has dramatically reduced several sites within the nervous system. Tetanolysin
over years whereas in developing countries it is still has a uncertain role and major clinical effects of the
observed frequently. At least 40-50% of deaths occur disease are secondary to the action of tetanospasmin.
in neonates, especially due to unhygienic conditions The toxin is produced as a polypeptide but undergoes
during birth and social practices like smearing cow post-translational cleavage into two di-sulfide linked
dung or ghee (clarified butter) on umbilical stump.3 fragments, the light (L) and heavy (H) chains.2 The H
During a tetanus surveillance from USA between chain mediates attachment to gangliosides in
1995-1997, 60% of cases were between 20-59 years peripheral nerves and subsequently the toxin is
of age, whereas in prior reports, population above 60 internalized and moves to the CNS by retrograde
years was more commonly affected.4 Punctures, axonal transport and trans-synaptic spread. Once
lacerations, and abrasions accounted for 64% of inside the CNS, the ‘L’ chain mediated cleavage of
reported cases. The higher risk in elderly is possibly synaptobrevin (an essential component of synaptic
related to a decline in protective levels of antibodies vessels needed for fusion and release of
with ageing and therefore a booster dose of neurotransmitters) prevents presynaptic release of
vaccination is recommended every 10 years to ensure inhibitory neurotransmitter γ-aminobutyric acid
protection.5 Almost all reported cases of tetanus are in (GABA) and glycine, causing sustained excitatory
patients who either have never been vaccinated, or discharge of disinhibited α-motor neurons and muscle
who completed a primary series, but have not had a spasms of tetanus. The toxin exerts its effects on the
booster in the preceding ten years. Although the spinal cord, brain stem, peripheral nerves,
incidence of tetanus is grossly underreported in India, neuromuscular junctions, and directly on muscles.2
it has shown a downward trend due to the national The rapidity of incubation and onset correlates with
immunization programme.6 Considering the severity of the disease. Recovery involves synthesis of
seriousness of this disorder, adequate wound hygiene new presynaptic components and their transport to
and thorough immunization practices are warranted to distal axon,8 accounting for the delay of 2-3 weeks
prevent the occurrence of this potentially fatal disease. before clinical improvement begins.1

The Organism Clinical Manifestations

Clostridium tetani is a gram positive, obligately Four clinical forms of this disease are recognized
anerobe, spore forming bacillus, which give it a depending upon the extent and location of neurons
characteristic drumstick or a tennis racket appearance. involved.1 The incubation period ranges from 7-14
The organism is widely distributed in soil and in days, although periods as short as one day to as long
intestine of horses, sheep, cattle, dogs, cats, rats, as several months have been reported. This may be
chickens and nearly 10% of humans.7 The spores can related to the amount of toxin present at the site of
also be found on skin surfaces and in contaminated wound and immunization status of the patient. The
heroin. In agricultural areas like ours, a significant time of onset is defined as the period between the
number of human adults may harbor the organism. onset of symptoms and start of spasms. This helps in
Although the vegetative forms of this organism are prognostication and correlates with the severity of
sensitive to heat and oxygen, the spores are especially disease,7 with shorter periods associated with a
resistant to heat, usual antiseptics and chemical agents severer disease form.

399 Neurology India, 50, December 2002

 Bhatia et al

Table I Localised tetanus : This is a relatively uncommon and

benign form of the disease process in which patients
Autonomic Disturbances Seen in Tetanus have persistent contraction of muscles in same
anatomic area as the injury preceding the tetanus.
Sustained or labile hypertension
Local tetanus might generalize over time but overall
Progressive and refractory hypotension
Peripheral vasoconstriction mortality is about 1%. However, in a recent
Tachycardia (episodic commonly) retrospective study of localized tetanus in 45 patients,
Bradycardia and asystole 7 (16%) died and 5 (11%) had sequelae.15 The most
Arrythmias important indicator for poor prognosis was the
Fever progression to secondary generalization (27%).
Profuse diaphoresis, salivation
Increased bronchial secretions Cephalic tetanus : This involves cranial nerves and
Gastric stasis and ileus
Urinary retention has an overall incidence of 6%.16,17 It commonly
results from middle ear infections and head injuries.17
Facial muscles are most commonly affected, followed
Generalized tetanus : This represents the commonest by 6th, 3rd, 4th and 12th cranial nerves in the order of
form of the disease and is characterized by increased frequency. Trismus may be present but usually follows
muscle tone and generalized spasms. Usually, the first
other cranial nerve deficits in 42% of patients.16
symptom is difficulty in opening jaw, due to increased
Although, overall mortality described is high
tone of the masseters (trismus or lock jaw).
(15-30%), many cases with a milder disease have been
Subsequently, there is a spread to other body parts.
reported from India.18
Dysphagia, stiffness and pain in neck, shoulder and
back muscles appears. Rigidity of abdomen and facial
Neonatal tetanus : This form of tetanus still has a high
grimacing, popularly known as ‘risus sardonicus’
incidence and mortality in the developing countries
(ironical smile), may appear due to facial muscle
contraction. Eventually, there is appearance of with an estimated 500,000 deaths per year.19 A
generalized muscle spasms, occurring spontaneously hospital based study showed application of `ghee’
or due to minor stimuli such as noise, touch, or (clarified butter) on the umbilical stump as a potential
nursing procedures.2 The spasms are immensely risk factor for tetanus in neonates.3 The common age
painful and may lead to respiratory compromise of onset is between 5 and 15 days following birth.
necessitating respiratory support. Spasms may Common presenting complaints are rigidity, spasms,
complicate the picture by causing compressive failure to suck, trismus, fever and seizures. Due to
fractures of the spine, rupture of muscles, lack of inhibiting influences from higher centers in
rhabdomyolysis and renal failure. These are newborns, the anterior horn cells react more violently,
maximum during the first two weeks of illness and resulting in more spasms.6 Overall mortality is around
decrease thereafter in frequency and intensity. 70% and most patients with severe disease die.
Autonomic instability is of major concern, and usually Improved immunization coverage, clean delivery
develops few days after the onset of the disease practices and cord care , and changes in social taboos
(Table I). There may be labile or sustained are necessary to reduce morbidity and mortality of
hypertension, tachycardia, arrhythmias, hyperpyrexia, neonatal tetanus.19
profuse sweating, peripheral vasoconstriction,
hypotension and bradycardia.9,10 Dysarrhythmia and Many prognostic grading systems (Phillips, Dakar,
myocardial infarction are the most common fatal Udwadia) are reported. Phillips score20 and Ablett
events.11 Possible pathogenesis involves sympathetic (Table II) are outlined. The system reported by Ablett
nervous system disinhibition and elevated is simple, useful and most widely used.21 Overall
catecholamine levels.1,9-12 Severe hypertension and mortality is variable and is dependent upon immune
tachycardia may alternate with profound status, age of the patient and availability of facilities
hypotension, bradycardia or recurrent cardiac arrest.12 for management. In developing countries, mortality
These alterations predominantly result from rapid rates exceed 50% with respiratory failure being the
alterations in systemic vascular resistance rather than major cause of mortality and morbidity.12 Mortality is
cardiac filling or performance.13,14 Other autonomic highest for those older than 60 years and in neonates.
effects include profuse salivation, increased bronchial Complications in tetanus may result from the disease
secretions, gastric stasis, ileus and high output renal itself or are related to management. These have been
outlined in table III.
failure.12

Neurology India, 50, December 2002 400

Tetanus

Table II Table III

Ablett Classification of the Severity of Tetanus21 Complications of Tetanus

(modified from Cook et al12)
Grade Clinical Features
Body system Complication
I Mild Mild to moderate trismus; general
spasticity; no respiratory embarrass Airway Aspiration, laryngospasm
- ment; no spasms; little or no sedative associated obstruction
dysphagia Respiratory Apnoea, hypoxia, Type I and Type II
II Moderate Moderate trismus; well-marked respiratory failure, ARDS,
rigidity; mild to moderate but short complications of prolonged assisted
spasms; moderate respiratory ventilation (eg. pneumonia)
embarrassment with an increased tracheostomy complications,
respiratory rate greater than 30, Cardiovascular Tachycardia, hypertension, ischemia,
mild dysphagia hypotension, bradycardia,arrythmias,
III Severe Severe trismus; generalized asystolic, cardiac failure
spasticity; reflex prolonged spasms; Renal Renal failure, urinary infection
respiratory rate greater than 40; and stasis
apnoeic spells, severe dysphagia; Gastrointestinal Stasis, ileus, hemorrhage
tachycardia > 120. Miscellaneous Weight loss, thromboembolism
IV Very severe Grade III and violent autonomic sepsis, multiorgan dysfunction
disturbances involving the syndrome, fracture due to spasm
cardiovascular system. Severe
hypertension and tachycardia
poisoning viii) tetany, ix) acute abdomen, x)
alternating with relative hypotension
and bradycardia, either of which stiffman’s syndrome etc. Appropriate history and
may be persistent. physical examination can differentiate most of them.
Apte and Karnad described a bedside `spatula test’ to
aid in diagnosis with a sensitivity of 94% and
Diagnosis and differential diagnosis specificity of 100%.23 A spatula is carefully inserted
into the pharynx. If patient gags and expels the
The diagnosis of tetanus is primarily clinical. History spatula, the test is negative for tetanus. If however, the
of injury, or presence of a wound aids in strengthening patient bites the spatula because of the reflex spasm of
the diagnosis. In patients, where the portal of entry is masseter, the test is considered positive. The test may
not evident, a careful search for signs of parentral drug not hold the same value and sensitivity in areas with
abuse, otitis media, instrumentation, injections or low incidence of tetanus because of the presence of
minor surgical procedures should be inquired.6 No other commoner etiologies.
definite laboratory abnormalities are present and the
CSF is usually normal. Electromyography during
Management
tetanic spasms shows continuous discharges of normal
motor unit potentials similar to normal forceful
Management of tetanus patients involves a team
voluntary muscle contraction. However, the silent
approach. The approach depends upon resources,
period that occurs 50 to 100 ms after reflex
contraction normally is lost. This pause is mediated by personnel, and expertise at one’s command.24
recurrent inhibition of Renshaw cells which is Symptomatic management, early recognition of
inhibited by the tetanus toxin. Peripheral nervous complications, careful monitoring for dysautonomia
system involvement is supported by the observations and respiratory assistance are the anchors for
of muscle fatigue, distal paresis, muscular atrophy, successful outcome of any patient. Presence of
intensive care units have changed the overall outcome
decreased reflexes and electrophysiological studies.6
from a dismal to a more hopeful one. In our country,
Prabhakar et al showed evidence of a predominantly
where intensive unit care cannot be available at all
sensory neuropathy by electrophysiological and
hospitals, general medical and nursing care
histological studies.22 administered conscientiously by those familiar with
the disease can reduce mortality from 30% to 15%.24
Differential diagnosis of tetanus includes: i) painful
The costs of intensive care are tremendous and clearly
conditions of lower jaw, ii) Bell’s palsy, iii)
unrealistic in most parts of the world where tetanus is
meningitis, iv) drug induced dystonia and dyskinesia,
a major problem. The clinical course of tetanus is
v) rabies, vi) globus hystericus, vii) strychnine
often unpredictable and patients need close

401 Neurology India, 50, December 2002

 Bhatia et al

monitoring throughout the illness. Ventilatory immunogenecity and a longer half life of 24-31 days.
assistance, respiratory failure, renal dysfunction, The equine formulation has a high likelihood of
autonomic imbalance and complications of prolonged anaphylactic reactions and has a half life of only 2
critical illness like nosocomial infections, sepsis, days. The usual dose of equine preparation is 500-
thromboembolism and gastrointestinal hemorrhage 1000 IU/kg given intravenously or intramuscularly.
need special attention.2 The defined goals of treatment The dose of HTIG is 5000-8000 IU intramuscularly.
include the following : a) halting production of toxin Local infiltration around the wound is not
within the wound, b) neutralization of unbound toxin, recommended presently. Usual dose for prophylaxis is
c) control of muscle spasms, d) management of 1500-3000 IU of equine and 250-500 IU of human
autonomic instability, e) supportive therapy, preparation.2 The blood concentration of antitoxin for
f) management of complications, g) prevention. protection against tetanus is 0.1 IU/ml. Intrathecal
therapy with antitoxin has been tried in the past, but a
a) Halting the production of toxin meta-analysis of the same showed no obvious benefit
of such a therapy.29
(i) Wound management : Debridement of a wound is
important to eradicate spores and change conditions (c) Control of muscle spasms
for germination, thereby preventing further
elaboration and absorption of the neurotoxin. Wound Spasms in tetanus are potentially life threatening, for
characteristics strongly correlate with the they impair respiratory function, produce exhaustion
development of tetanus. Recent linear wounds with and often lead to aspiration of gastric contents. Many
sharp edges that are well vascularised and not drugs have been used for the effective control of
obviously infected are usually non-tetanus prone. All spasms in tetanus patients. Sedation has been the
other wounds are considered potentially predisposed, mainstay in the past and is still used as the primary
especially those that have resulted from blunt trauma, therapy in most of the centres for its easy availability.
bites and are obviously contaminated.1 However, use of muscle relaxants is frequent in
intensive units and sedation is used as a adjunct to
(ii) Antibiotic therapy : Penicillin and metronidazole management.
are the two major drugs used routinely. Penicillin still
remains a standard therapy in many parts of the world, Sedatives : Benzodiazepines have been traditionally
although metronidazole seems to be replacing it and is used for control of spasms. Diazepam is the most
being considered as a drug of choice by many.1,2,12,25 commonly used drug of this class, and is usually the
Metronidazole has a better safety profile, better tissue first drug to be used in the initial phase of the illness.
penetrability and negligible CNS excitability The doses used have been variable, depending upon
(penicillin can cause seizures at high doses). It can the patients clinical condition and response. The
also be given rectally which minimizes and reduces average dose used as an adjunct to muscle relaxants is
frequency of spasms, which otherwise would be 10-30 mg 6-8 hrly, and is usually the starting dose
precipitated by an I/V or I/M medication. Ahmadsyah even when used solely. Doses upto 120 mg/kg/day
and Salim26 showed improvement in mortality with have also been used.30 Respiratory depression and
use of metronidazole but Yen et al27 and Singhi et al28 prolonged sedation are major problems at high doses
did not report the same benefit. However, where and appropriate ventilatory assistance is imperative.
available, metronidazole should be the preferred Midazolam has been used with beneficial effects but is
antibiotic. The usual dose of penicillin is 100,000 – expensive and needs more respiratory assistance.
200,000 IU/kg/day given intravenously or However, its relative short duration of action and early
intramuscularly. Metronidazole is used at a dose of reversability of sedation are distinct advantages over
500 mg every 6 hours intravenously or per orally and diazepam therapy.31,32 It is imperative to titrate doses
400 mg rectally every 6 hours, for 7-10 days. gradually for the risk of sedation, respiratory
depression and accumulation of metabolites.33 The
(b) Neutralization of the unbound toxin drug should be tapered gradually to avoid withdrawl
reactions. Propofol, a general anesthetic, has been
This is achieved through passive immunization with used with benefit in control of spasms and rigidity,34
either human or equine tetanus immunoglobulin. This and has been corroborated with neurophysiological
should be undertaken as early as possible since the studies.12 Adverse effects include hypotension,
toxin becomes inaccessible once it is bound to the bradycardia, pain at injection site, hypertriglyceri-
nerve terminus. Human tetanus immunoglobulin demia, pancreatic dysfunction and need for
(HTIG) is the preferred form because of lack of mechanical ventilation.33 Prolonged use of propofol

Neurology India, 50, December 2002 402

Tetanus

(>48 hrs) has been associated with lactic acidosis, ease of administration, availability of experience in
bradycardia and lipemia in children and is therefore managing patients with eclampsia, and avoidance of
not recommended for pediatric use.33 It is strongly sedation and mechanical ventilation, the drug seems
recommended that propofol infusion bottles and definitely advantageous in management of tetanus
tubing should be hanging for no more than 12 hours related spasms. However, more trials and experience
and solution transferred from main vial be discarded with the use of this drug is required. It is usually given
after 6 hours for the risk of bacterial overgrowth and as a loading dose of 5 gm over 20 minutes followed by
nosocomial infections. a regular infusion at a rate of 2 gm/hour. Abolition of
patellar reflex is taken as the endpoint and evidence
(ii) Neuromuscular blocking agents : The use of these of hypocalcemia is judged by positive Chvostek’s and
drugs becomes imminent, when sedation produces no Trousseau’s signs. The drug is best avoided in the
benefit. However, intubation with positive pressure presence of severe renal failure.
ventilation is mandatory. Commonly, pancuronium
has been widely used for its lesser cost. However, (iv) Baclofen : Baclofen, a physiological GABA
potential risk of worsening autonomic dysfunction is agonist has been used in few small studies for
present because of its effects on catecholamine effective control of tetanic spasms.40-43 The drug
uptake. Vecuronium is considered the drug of choice inhibits mono and polysynaptic medullary reflexes,
because of negligible cardiovascular effects, but is resulting in a antispastic action.43 It has been shown to
short acting and cost is a limiting factor. It has a stimulate postsynaptic GABA β receptors, thereby
potential risk of accumulation in presence of renal restoring physiological inhibition of α motor neurons.
failure. Recuronium is highly safe but expensive. High dose intrathecal baclofen has been used for the
Monitoring of patients on muscle relaxant therapy is treatment of tetanus induced contractures and spasms,
difficult and it is important that doses of relaxants be thereby limiting the need for general anesthesia and
spaced out after 2 weeks and usually stopped after intubation in afflicted patients.40 The preferred route
three weeks to prevent complications and adverse of administration is intrathecal for the drug is 600
effects on long term use. Prolonged recovery from times more potent at a much lesser dose compared to
paralysis is thought to be related to accumulation of the oral route. The half life of this drug is between 0.9
drugs or their metabolites. Acute quadriplegic to 5 hours. The largest series published is by Engrad
myopathy syndrome or AQMS is common when et al43 who have reported 14 patients treated with this
steroids are taken concomitantly and reports of this regimen, of which it was effective in twelve. However,
dysfunction with use of neuromuscular blocking baclofen has a narrow therapeutic range and a large
drugs alone is uncommon.35 It usually presents as a interindividual pharmacodynamic variability. The cost
acute paresis with myonecrosis, increased CPK and of therapy and need for surgical expertise (in case
abnormal EMG. Other potential hazards with use of infusion pump is required), are major deterrents for its
these drugs is muscle contractures, atrophy and risk of use. The dose is variable and on an average is about
venous thrombosis or embolic events related to 1000 mcg in adults below 55 years, 500 mcg below 16
immobility. Pancuronium may be a safe option to start years of age and 800 mcg for adults above 55 years.
with if no cardiovascular dysfunction is present. In Intermittent boluses may be given initially at an
presence of severe hepatic or renal disease, interval of 10-20 hours depending upon the response
cisatracuronium or atracuronium may be used.36 Eye of the patient or it may be given by a continuous
care is essential and concomitant use of steroids is infusion if frequent doses are necessary. Caution is
discouraged. desired in patients with severe dysautonomia and
when spasticity is used to obtain increased function.
(iii) Magnesium sulfate : Role of magnesium sulfate in
the management of tetanus has been postulated by (v) Dantrolene : It is a directly acting muscle relaxant
many authors.37,38 Blake treated two patients of mediating its action through inhibition of calcium
tetanus with intrathecal magnesium sulfate, as early as release by sarcoplasmic reticulum and thereby
1906.39 Magnesium physiologically antagonizes directly affecting excitation contraction coupling. It
calcium and there is a correlation between depression has been used in isolated cases in the past for
of neuromuscular transmission and serum magnesium managing tetanic spasms and has the major benefit of
concentrations.37 Use of magnesium sulfate has the not requiring artificial ventilation. However, the drug
added advantage of controlling dysautonomia, where is expensive and cannot be recommended for routine
it has been more commonly used. Considering the use.

403 Neurology India, 50, Dectember 2002

 Bhatia et al

(d) Management of dysautonomia Adrenergic blockers : Labetolol has been frequently

used to treat adrenergic overactivity for it produces
Dysautonomia is a significant problem in patients dual adrenergic blockade,47 although the β-blocking
with tetanus and drug therapy is aimed at stabilizing effect is more significant. However, concerns about
the cardiovascular system while preserving myocardial damage and cardiac arrest were raised in
compensatory mechanisms, so as to avoid sudden view of unopossed release of catecholamines, and
collapse and death. Many drugs have been used with impaired peripheral vasodilation.2 Propranolol was
this aim but none is devoid of potential problems. one of the earliest drugs used in its class, but fell out
Drugs have been used with the aim to produce of use because of reports of fatal cardiovascular
adrenergic blockade or to prevent release of failure and irreversible cardiac arrest in the patients
catecholamines and thereby suppress autonomic treated. Esmolol, a short aching β blocker, has been
hyperactivity.44,45 Following drugs have been used useful in suppressing crisis but does not prevent
with the aim to treat dysautonomia. catecholamine release. Clonidine, a centrally acting
sympatholytic agent has been used with beneficial
Sedatives : These drugs were used in the past to
effects and has the added advantage of being an
improve early dysautonomia, and benzodiazepenes
especially diazepam is still used with this aim. Since anxiolytic and sedative.48 Post ganglionic and alpha
this drug has a wide margin of safety, is cheap and adrenergic blocking drugs like guanethidine and
commonly available, can be given through all routes, phentolamine have been used in the past but fell out of
and has muscle relaxant and anticonvulsant use due to disadvantages of hypotension,
properties, its use in the initial part of illness is tachyphylaxis and rebound hypertension.
justified. However, at high doses, it itself is a
respiratory depressant and produces excessive Magnesium sulfate : It is a promising drug and has
sedation which necessitates ventilatory assistance. been used in management of spasms as well as
Phenothiazines, like chlorpromazine were used in autonomic overactivity.37,49,50 Magnesium causes
view of its α-adrenergic blocking action and some presynaptic neuromuscular blockade, blocks release
complex effects which may be due to additional of catecholamines, reduces receptor sensitivity to
blockade of neuronal uptake of amines. Since high released catecholamines, and has anticonvulsant and
doses of this drug may itself increase catecholamine vasodilator properties.2 In view of these properties,
levels, it is preferable to avoid doses above 200 this drug has been extensively used in the
mg/day. It causes a centrally mediated fall in BP, but management of eclampsia worldwide. However, the
despite theoretical advantages, it provides drug has been associated with sedation, impairment of
unsatisfactory control of cardiovascular disturbances.9 tidal volume, cough and need for ventilation at high
Morphine is another drug used for management of doses.2,49 Tacheostomy is mandatory and availability
dysautonomia. It has excellent sedative properties and of ventilatory support is imperative.2 The doses used
minimal effect on cardiovascular performance.2 It have already been outlined in the management of
reduces mean arterial pressure, heart rate and systemic tetanic spasms. Although quite promising, the exact
vascular resistance while having minimal effect on the role of this drug needs more evaluation for
cardiac output.45 However, high doses are required recommendation in routine use.
and a continuous infusion is appropriate. The drug
possibly causes CNS depression of sympathetic Intrathecal baclofen : As outlined in the management
outflow, although multiple sites of action might exist. of spasms, this drug has also been used with success
Intrathecal or epidural morphine might seem in managing dysautonomia. Although it has been
efficacious, but overall results through these routes proposed as a agent of benefit in tropical milieu for
have not been as satisfactory.9 The usual dose is 5-30 the reduction in need for artificial ventilation,40 in all
mg given as a infusion over 30 minutes every 2-8 reports a significant number of patients had developed
hours. Most patients would respond to a dose of 0.1 coma and respiratory depression necessitating
mg/kg every 4-6 hours. Daily doses range between 20- ventilation.2 Probably, interindividual dose variability
180 mg/kg. Epidural anesthesia is another regime is high and therefore dose modifications and
which seems promising. Bhagwanjee et al46 described guidelines for its use are needed. Another potential
their observations on 11 patients treated with epidural problem and concern in tetanic patients is the risk of
bupivacaine and sufentanil using midazolam as an infection through spinal intervention.
adjunct with encouraging results. Further trials are
needed to generalize its use.

Neurology India, 50, December 2002 404

Tetanus

Supportive Management Table IV

Tetanus Prophylaxis in Acute Injury

General supportive care plays a major role in the
outcome of these patients. In a critically ill patient, the Primary Clean Tetanus prone
complication of prolonged hospital stay and immunization wound wound
instrumentation are sufficient enough to delay the Td* Td* TIG
process of recovery. It is imperative to realize the
necessity of adequate nursing care and regular vigil in Not complete Yes Yes Yes
management. These patients are predisposed to Completed < 5 yrs No No No
nosocomial infection, bed sores, tracheal stenosis and Last > 5 yrs No Yes No
Booster > 10 yrs Yes Yes No
GI hemorrhage.2 Securing the airway is primary and
helps in preventing aspiration and assisting * = adult preparation,
ventilation. Initially, endotracheal intubation is Source : MMWR 1991; 40 : 1-28.
justified, but considering that the recovery is likely to
be slow and need for mechanical ventilation may be schedules are key to prevent this disease. In fact,
long, tracheostomy is a much better option. This also considering the efficacy, availability and cost of this
avoids undue stimulation of upper airway and vaccine, it is sad that still so many deaths occur every
prevents spasms and respiratory complications from year in developing countries. Emphasis on the
aspiration and hypoventilation. Percutaneous preventive aspects of this disease and awareness of the
tracheostomy is preferred to open surgical techniques seriousness of the illness but easy ways of prevention
for it reduces blood loss and long term sequelae.2 need to be stressed upon. Changes in social taboos and
Tracheostomy site should be regularly cleaned using adoption of hygienic practices during child birth are
maximum sterility. Assisted ventilation is often used likely to reduce the high incidence of neonatal tetanus
in tetanus patients, especially where spasms impair present in our country and around the world.
respiration and all attempts should be made to detect Vaccination is highly safe and efficacious. Active
patients with incipient hypoxia and respiratory failure. immunization should be instituted in all partially
We advocate controlled mandatory ventilation in the immunized and unimmunized adults as well as those
initial stage of disease. As stabilization occurs, the recovering from tetanus. In patients with tetanus,
patient is shifted to pressure support and PEEP modes. passive immunization in forms of tetanus
In the later stages, modes allowing spontaneous immunoglobulin is usually combined with active
ventilation (SIMV, CPAP) are preferred. It is vaccination, so called active - passive immunization.2
suggested that weaving be done as early as possible to This adds to a long term hormonal and cellular
minimize the problems associated with prolonged immunity. The prescribed schedule for patients
paralysis and neuromuscular blockade. Chest depending upon the nature of wound is given in
physiotherapy and regular tracheal suction are table IV. It is important that different sites are chosen
essential to prevent atelectasis, lobar collapse and for immunoglobulin and toxoid injection to prevent
pneumonia.2 Secretions and salivations may be interaction. If used together, no more than 1000 IU of
difficult to manage, and can be minimized by using human or 5000 IU of equine antitoxin should be
nebulization with ipratropium. Other supportive administered for the risk of neutralizing the effect of
measures like meticulous mouth care, nursing the toxoid. Tetanus vaccination is instituted in the form of
patient in 150-300 sitting position, regular washing of a toxoid, which consists of a formaldehyle treated
hands and keeping I/V access sites clean are small, but toxin standardized for potency in animal tests. Two
significant steps in patient management. Nutritional types of toxoid are available ; adsorbed (aluminium
requirements of these patients are high and weight salt precipitated) and fluid toxoid. The former is
loss is a common finding, making nutrition preferred because of a better and longer lasting
management a significant factor. This should be response. Tetanus toxoid is available as a single
commenced as early as possible through a nasogastric antigen preparation, combined with diphtheria
tube or where facilities allow, by percutaneous vaccine as pediatric DT or adult Td, and with both
endoscopic gastrostomy, because it prevents undue diphtheria and pertussis vaccine as DTaP. Children
stimulation and reduces spasms. younger than 7 years should receive either DTaP or
pediatric DT and adults and children above 7 years
Prevention and Immunization should receive Td formulation. Single antigen tetanus
toxoid is not recommended. In children, 3 doses of
Hygienic practices during child birth, prompt and DPT vaccine are given at an interval of 4-8 weeks,
adequate wound care and enforced immunization starting at 6 weeks of age, followed by booster at 18

405 Neurology India, 50, December 2002

 Bhatia et al

months. The second booster (DT) is given at 5-6 years Conclusion

and third upto 10 years. The initial series for adults
involves 3 doses. The first and second doses are given Tetanus remains a problem of immense concern
4-8 weeks apart and the third is given 6 months after worldwide, with a high mortality in the elderly and
the second. Booster doses are required every 10 years neonatal population. Management of tetanus with its
to maintain protective antitoxin titers. Tetanus does attendant complications are challenges to the
not confer immunity because of the small toxin physician. Although symptomatic therapy has
amount needed to produce illness. The minimum improved over time no definite consensus on adequate
protective level of antitoxin is 0.01 IU/ml, which is treatment is available. Prevention is the chief priority
usually achieved in all recipients of vaccine who have and it is absolutely essential that people are educated
completed primary series of properly spaced doses of about this potentially serious but extremely
tetanus toxoid. Immunization of all pregnant women preventable disorder, for this is the only step towards
is an important step in preventing neonatal tetanus. global eradication. Probably, a better understanding of
Two or three doses of tetanus toxoid are administered the disease process and its effects on nervous tissue
during pregnancy with last dose administered one will aid in effective management of cases. We look
month before delivery. towards the future with hope of seeing a tetanus free
planet.
Local adverse reactions to the injection include
erythema, induration and pain at injection site which References
are usually self limiting. Fever and other systemic
symptoms are uncommon. Other reactions include 1. Hsu SS, Groleau G : Tetanus in the emergency department
: a current review. J Emerg Med 2000; 20 : 357-365.
exaggerated local (arthrus like) reaction seen
2. Farrar JJ, Yen LM, Cook T et al : Tetanus. J Neurol
commonly in adults who have received frequent Neurosurg Psychiatry 2000; 69 : 292-301.
doses, generalized urticaria, anaphylaxis and 3. Benett J, Azhar N, Rahim F et al : Further observations on
neurological complications like neuropathy, ghee as a risk factor for neonatal tetanus. Int J Epidemiol
Guillaine-Barre syndrome and brachial neuritis have 1995; 24 : 643-647.
also been reported.51 The vaccine is usually 4. Barderheier B, Prevots R, Khetsuriani N et al : CDC.
contraindicated in patients who have had a severe Tetanus Surveillance – United States 1995-1997. MMWR
allergic reaction in the past with the toxoid and 1998; 47 ( SS2 ) : 1-13.
5. Lee HC, Ko WC, Chuang YC : Tetanus of the elderly.
caution is advocated for its use in presence of a
J Microbiol Immunol Infect 2000; 33 : 191-196.
moderate to severe concomitant illness. Research for 6. Prabhakar S, Syal P : Tetanus. In : Tropical neurology.
better and simpler approach for tetanus vaccination is Misra UK, Kalita J, Shakir RA (eds.) Landee Biosciences.
hoped for the future. Single dose vaccination using (In Press).
microencapsulation techniques may be desirable, but 7. Bartlett JG : Tetanus. In : Cecil Textbook of Medicine,
needs more refinement.52 Goldman Lee, Bennett JC (eds). 21st Edition. Philadelphia
: W.B. Saunders 2001; 1675-1677.
8. Bleck TP, Brauner JS : Tetanus. In : Infections of the central
Mortality and Outcome nervous system. Scheld WM, Whitely RJ, Durack DT (eds).
2nd edition. Philadelphia : Lipincott – Raven, 1997; 629-
Overall mortality of this condition is variable and 653.
varies between 25-50% for generalized tetanus and is 9. Wright DK, Lalloo UG, Nayiager S et al : Autonomic nervous
as high as 85-90% for neonatal tetanus, with system dysfunction in severe tetanus : current perspectives.
respiratory failure and cardiac dysautonomia being Crit Care Med 1989; 17 : 371-375.
the chief causes of death. The outcome is poor in 10. Domenighetti GM, Sarary G, Stricker H : Hyperadrenergic
neonates, elderly and in patients with short incubation syndrome in severe tetanus : Extreme rise in
catecholamines responsive to labetolol. BMJ 1984; 288 :
periods and short interval between onset of symptoms
1483-1484.
and the first spasm. In USA, a mortality of 11% was 11. Trujillo MH, Castillo A, Espana J et al : Impact of intensive
recorded between 1995 and 1997.4 In our institute, a care management on the prognosis of tetanus. Chest
mortality of 18% was recorded53 and in a recent study 1987; 92 : 63-65.
from Malaysia, the mortality was again 18%.54 It was 12. Cook TM, Protheoze RT, Handel JM : Tetanus : A review of
observed that mortality is highest in grade III tetanus literature. Br J Anaesth 2001; 87 : 477-87.
13. Toothill C, Dykes JRW, Ablett JJL : Urinary catecholamine
and those with a nosocomial infection.53 The course metabolites concentration in tetanus. Br J Anaesth 1970;
of tetanus extends over 4-6 weeks with long periods of 42 : 524-530.
ventilatory support. Increased tone and minor spasms 14. Kerr JH, Corbert JL, Pryst-Roberts C et al : Involvement of
may persist for months but recovery is generally sympathetic nervous system in tetanus. Lancet 1968; 2 :
complete. 236-241.

Neurology India, 50, December 2002 406

Tetanus

15. Kakou AR, Eholic S, Ehui E et al : Localised tetanus in 36 Murray MJ, Cowen J, DeBlock H et al : Clinical practice
Abidjan : Clinical and prognostic features (1976-1997). Bull guidelines for sustained neuromuscular blockade in adult
Soc Pathol Exot 2001; 94 : 308-311. critically ill patients. Crit Care Med 2002; 30 : 142-156.
16. Jagoda A, Riggio S, Burgieres T : Cephalic tetanus : A case 37. Attygalle D, Rodrigo N : Magnesium sulfate for control of
report and review of literature. Am J Emerg Med 1988; 6 : spasms in severe tetanus. Can we avoid sedation and
128-130. artificial ventilation? Anaesthesia 1997; 52 : 952-962.
17. Vakil BJ, Singhal BS, Pandya SS et al : Cephalic tetanus. 38. Attagylle D, Rodrigo N : Magnesium sulfate for the control
Neurology 1973; 23 : 190-196. of spasms in severe tetanus. Anaesthesia 1999; 54 : 302-
18. Patel JC, Kale PA, Mehta BC : Otogenic tetanus - Study of 303.
922 cases. In : Proceedings of an international conference 39. Blake JA : The use of magnesium sulfate in the production
on Tetanus. Patel JC (ed). Bombay. 1965; 640-644 of anaesthesia and in the treatment of tetanus. Surgical
19. Nida H : Neonatal tetanus in Awassa. Retrospective Gynaecology and Obstetrics 1906; 2 : 541-550.
analysis of patients admitted over 5 years. Ethiop Med J 40. Engrand N, Vilain G, Rouamba A et al : Value of intrathecal
2001; 39 : 241-246. baclofen in the treatment of severe tetanus in the tropical
20. Phillips LA : A classification of tetanus. Lancet 1967; 1 : milieu. Med Trop 2000; 60 : 385-388.
1216-1217. 41. Boots RJ, Lipman J, O’Lallagan J et al : The treatment of
21. Ablett JJL : Analysis and main experiences in 82 patients tetanus with intrathecal baclofen. Anaesth Intensive Care
treated in the Tetanus unit. In : Symposium on tetanus in 2000; 28 : 438-442.
great Britain. Ellis M (ed). Boston Spa, National Lending 42. Engrand N, Van De Perre P et al : Intrathecal baclofen for
Library, U.K. 1967; 1-10. severe tetanus in a pregnant woman. Eur J Anaesthesiol
22. Prabhakar S, Singh G, Chopra JS et al : Peripheral 2001; 18 : 261-263.
neuropathy in tetanus : A clinical, neuroelectrophysiological 43. Engrand N, Guerot E, Rouamba A et al : The efficacy of
and histological evaluation. Neurol Ind 1997; 45 : 81-86. intrathecal baclofen in severe tetanus. Anesthesiology
23. Apte NM, Karnad DR : Short report - the spatula test : a 1999; 90 : 1773-1776.
single bedside test to diagnose tetanus. Am J Trop Med 44. Prys-Roberts C, Corbett JL, Kerr JH et al : Treatment of
Hyg 1995; 53 : 386-387. sympathetic overactivity in tetanus. Lancet 1969; 1 : 542.
24. Dastur FD : Emergency treatment of tetanus. JAPI 1997; 45. Rocke DA, Pather M, Calver AD et al : Morphine in tetanus
(suppl 2) : 44-46. – the management of sympathetic nervous system
25. Garlicki A, Caban J, Bociaga JM et al : Modifications in overactivity. S Afr Med J 1986; 70 : 666-668
treatment of tetanus and prognosis : Observations from the 46. Bhagwanjee S, Bosenberg AT, Muckart DJT : Management
Gacon Department of Infectious Diseases. Przegl Lek of sympathetic overactivity in tetanus with epidural
1999; 56 : 566-567. bupivacaine and sufentanil. Experience with 11 patients.
26. Ahmadsyah I, Salim A : Treatment of tetanus : An open Crit Care Med 1999; 27 : 1721-1725.
study to compare the efficacy of procaine penicillin and 47. Wesley AG, Hariprasad D, Pather M et al : Labetalol in
metronidazole. BMJ 1985; 291 : 648-650. tetanus. The treatment of sympathetic nervous system
27. Yen LM, Dao LM, Day NPJ et al : Management of tetanus : overactivity. Anaesthesia 1983; 38 : 243-249.
A comparison of penicillin and metronidazole. Symposium 48. Gregorakos L, Kerezoudi E, Dimopoulos G et al :
of antimicrobial resistance in Southern Vietnam . 1997. Management of blood pressure instability in severe tetanus
28. Singhi S, Jain V, Subramanian C : Post-neonatal tetanus : : the use of clonidine. Intensive Care Med 1997; 23 : 893-
Issues in intensive care management. Indian J Pediatr 894.
2001; 68 : 267-272. 49. James MFM, Manson EDM : The use magnesium infusions
29. Abrutyn E, Berlin JA : Intrathecal therapy in tetanus : a in management of very severe tetanus. Intensive Care
meta-analysis. JAMA 1991; 226 : 2262-67. Medicine 1985; 11 : 5-12.
30. Al-Kaabi JM, Scrimgeour EM, Louon A et al : Tetanus : A 50. Lipman J, James MFM, Esskire J et al : Autonomic
clinical review. Saudi Med J 2001; 22 : 606-609. dysfunction in severe tetanus : magnesium sulfate as an
31. Gyasi HK, Fahr J, Kurian et al : Midazolam for prolonged adjunct to deep sedation. Crit Care Med 1987; 15 : 987-988.
intravenous sedation in patients with tetanus. Middle East J 51. Halliday PL, Bauer RB : Polyradiculitis secondary to
Anesth 1993; 12 : 135-141. immunization with tetanus and diphtheria toxoids. Arch
32. Tobias JD : Anesthetic implications of tetanus. South Med J Neurol 1983; 40 : 56-57.
1998; 91 : 384-87. 52. Schwendeman SP, Tobio M, Joworonicz M et al : New
33. Jacobi J, Fraser GL, Coursin DB et al : Clinical practice strategies for the microencapsulation of tetanus vaccine.
guidelines for the sustained use of sedatives and J Microencapsul 1998; 15 : 299-318.
analgesics in the critically ill adult. Crit Care Med 2002; 30 53. Grover VK, Gupta S, Sharma S et al : Management of
: 117-141. tetanus : a review of 100 consecutive cases. J Anaesth Clin
34 Borgeat A, Popovic V, Schwander D : Efficacy of a Pharmcol 1992; 10 : 23-27.
continuous infusion of propofol in a patient with tetanus. Crit 54. Lau LG, Kong KO, Chew PH : A ten year retrospective
Care Med 1991; 19 : 295-297. study of tetanus at a general hospital in Malaysia.
35. Doxacurium – corticosteroid acute myopathy : another Singapore Med J 2001; 42 : 346-350.
piece to the puzzle. Crit Care Med 1996; 24 : 1266-1267.
Accepted for publication : 20th August, 2002.

407 Neurology India, 50, December 2002

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