Tetanus
Andrew Michael Taylor FRCA
Tetanus is caused by a neurotoxin released by
Clostridium tetani, a spore-forming anaerobic
bacterium. It occurs throughout the world
and remains an important cause of death with
an estimated annual mortality of 800 000
1 000 000. Over half of these deaths are in
neonates. Tetanus is relatively rare in the
developed world. For example, there are
510 cases per year in the UK; 75% of
these occur in individuals over the age of
45 yr. There have been no cases in the UK
of tetanus in the newborn for over 30 yr.
Tetanus is a clinical diagnosis. Individuals
with symptoms and signs of tetanus should be
closely monitoredideally within an intensive
care unit with immediate access to ventilatory
support. Modern management encompasses
wound debridement, antimicrobial therapy,
active and passive immunization, sedation
and vigilant monitoring.
Epidemiology
Tetanus is an entirely preventable disease; the
first vaccine was produced in 1924. Routine
vaccination began in the UK in 1961. It is
given as a combined vaccine along with diph-
theria and pertussis (DPT). Unfortunately,
immunity to tetanus may not be life-long
and booster injections may be required after
individuals sustain tetanus-prone wounds.
Tetanus immunization guidelines are avail-
able in the British National Formulary.1
Poor access to a programme of immunization
accounts for the high prevalence of the disease
in the developing world. Implementation
of global tetanus immunization has been a
target of the World Health Organization
since 1974.
Recently there has been a cluster of tetanus
cases amongst injecting drug-users in the UK.
Twenty-four cases were reported between 2003
and 2004. The majority of these had no record
of (or, at best, incomplete) immunization.
This outbreak is thought to be a result of
a batch of contaminated heroin.2 I.M or s.c.
drug-use is a particularly high risk activity for
developing tetanus.
doi:10.1093/bjaceaccp/mkl014
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Pathophysiology
Key points
C. tetani spores are widespread in the environ-
Tetanus is a preventable
ment residing in soil, faeces and dust.3 Tetanus
disease; it is a significant cause
spores are extremely hardy and can survive of mortality worldwide
extreme conditions for prolonged periods. causing one million deaths
They usually enter the body after contamina- annually.
tion of an abrasion or minor puncture wound,
At least 20 cases of tetanus
although, in 20% of cases, no entry site can occur in the UK each year.
be found. Spores also gain entry through skin
Management of tetanus is
ulcers, abscesses, gangrene, burns or after
essentially supportive using
abdominal/pelvic surgery, childbirth and
antibiotics, surgery,
abortion.4 The incubation period of the dis- immunization, sedation and,
ease is between 3 and 21 days (average 7 days). when necessary, ventilation.
The manifestations of tetanus are caused by
The mortality from tetanus
tetanospasmin, which is released by the teta-
remains high despite modern
nus bacillus on entry into the body. Symptoms intensive care.
arise 12 weeks after infection. Tetanospasmin
is an extremely potent neurotoxin; it is estim-
ated that as little as 240 g is enough to kill the
entire world population. The toxin spreads
into the nervous system by binding to the
neuromuscular junction. Once bound, it is
transported retrogradely to the cell body.
Further spread occurs trans-synaptically to
adjacent motor and autonomic nerves.4
Tetanospasmin exerts its effect by cleaving
synaptobrevin, a vesicle-associated membrane
protein which is essential for the release of
neurotransmitter. The toxin primarily affects
inhibitory pathways, preventing the release of
glycine and g-amino butyric acid (GABA).
When interneurones inhibiting alpha motor
neurones are affected, there is failure to inhibit
motor reflexes. This causes increased muscle
tone and rigidity, interposed by sudden
and potentially devastating muscle spasms.
Muscles of the face are affected early because
of their short axonal pathways. Sympathetic
neurones become affected later in the disease.
Disinhibited autonomic discharge leads to loss
Andrew Michael Taylor FRCA
of autonomic control, resulting in sympathetic
Consultant Anaesthetist
overactivity and increased catecholamine Department of Anaesthesia
levels. Nottingham University Hospitals
NHS Trust
Neuronal binding of the toxin is irrevers-
Nottingham NG7 2UH
ible. Recovery requires the growth of new UK
nerve terminals, which explains the prolonged Tel: 0115 9249924
Fax: 0115 970 0739
duration of the disease.
E-mail: andytanaes@hotmail.com
101
Tetanus
Mortality
In developing countries, the mortality from tetanus exceeds
50%. Death occurs mainly from acute respiratory failure. In
the developed world, with intensive care support, mortality is
around 10%, rising to 20% in severe cases. Mortality increases
with increasing age (exceeding 50% if more than 60 yr old) and
previously unvaccinated individuals (22%). A short incubation
period (<5 days) signifies more severe disease. The severity of
illness may be decreased by partial immunity.
Clinical features
Tetanus is a clinical diagnosis characterized by a triad of
muscle rigidity, muscle spasms and autonomic instability.
Early symptoms of tetanus include neck stiffness, sore throat,
dysphagia and trismus. Muscle spasms are extremely painful.
They occur spontaneously but are also provoked by touch, visual,
auditory or emotional stimuli. Muscle spasms can be so intense
that they cause tendon rupture, joint dislocation and bone
fractures. Spasm extending to the facial muscles causes the
typical facial expression, risus sardonicus. Truncal spasm causes
opisthotonus. During prolonged spasms, severe hypoventilation
and life-threatening apnoea may occur. Laryngeal spasms also
occur resulting in sudden airway obstruction and respiratory
arrest.
Severe tetanus is associated with profound autonomic
instability. This usually starts a few days after the spasms and
lasts 12 weeks. Increased sympathetic tone causes vasoconstric-
tion, tachycardia and hypertension. Autonomic storms are
associated with raised catecholamine levels. These alternate
with episodes of sudden hypotension, bradycardia and asystole.
Other features of autonomic disturbance include salivation,
sweating, increased bronchial secretions, hyperpyrexia, gastric
stasis and ileus.
Classification of tetanus
Four different forms of tetanus are described; local, cephalic,
generalized and neonatal. In local tetanus, spasm and rigidity
are confined to the site of injury. It is an uncommon and relatively
mild form of tetanus with a low mortality (1%). Cephalic tetanus
occurs after a wound to the head and neck or otitis media. It is
characterized by cranial nerve palsies (especially the seventh)
and leads to paralysis; it is associated with a high mortality.
The most common type is generalized tetanus which is
responsible for 80% of cases. It results from the haematogenous
spread of the toxin. The muscles of the head and neck are affected
first with progressive distal spread of spasm and rigidity through-
out the body. Neonatal tetanus is responsible for over 50% of
deaths associated with tetanus. It is caused by poor umbilical
hygiene and is entirely preventable by maternal vaccination. It
carries a poor prognosis. Neonatal tetanus has been completely
eliminated from the UK.
102 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 3 2006
Table 1 Ablett classification of tetanus severity
Grade 1 (mild)
Mild trismus, general spasticity, no respiratory compromise, no spasms,
no dysphagia
Grade 2 (moderate)
Moderate trismus, rigidity, short spasms, mild dysphagia, moderate respiratory
involvement, ventilatory frequency >30
Grade 3 (severe)
Severe trismus, generalized rigidity, prolonged spasms, severe dysphagia,
apnoeic spells, pulse >120, ventilatory frequency >40
Grade 4 (very severe)
Grade 3 with severe autonomic instability
Table 2 Differential diagnosis of tetanus
Hypocalcaemic tetany
Epilepsy
Chorea
Meningitis
Encephalitis
Subarachnoid haemorrhage
Strychnine poisoning
Rabies
Sepsis
Drug withdrawal
Grading severity
There are several grading systems; the scale proposed by Ablett5
is the most widely used (Table 1). This categorizes patients
into four grades depending upon the intensity of spasms, and
respiratory and autonomic involvement.
Differential diagnosis
Tetanus is a purely clinical diagnosis. The differential diagnosis
is listed in Table 2.
Management
All patients suspected of tetanus should be managed on an
intensive care unit. To minimize the risk of precipitating spasms,
the patient should be nursed in a dark, quiet room. A low thresh-
old to secure the airway must be maintained at all times and
constant vigilance is required. Patients with respiratory distress
should be intubated immediately. Death caused by sudden laryn-
gospasm, diaphragmatic paralysis, and inadequate respiratory
muscle contraction is a frequent occurrence in parts of the devel-
oping world where there is no immediate access to ventilatory
support.
Neutralization of unbound toxin
Free circulating toxin should be neutralized with human tetanus
immunoglobulin (HTIG); HTIG does not affect toxin which is
already fixed to nerve terminals. It has a long half-life (23 days)
and does not need to be repeated. There is no consensus on
the correct dose of HTIG; 500010 000 units by infusion is

recommended in the British National Formulary.1 HTIG is given
on a named-patient basis. Recovery from tetanus does not result
in immunity and vaccination with tetanus toxoid is indicated
during the convalescent stage of the disease.
Surgical debridement
If present, the infected site should be cleaned thoroughly and
necrotic tissue extensively debrided to reduce the bacterial and
toxin load. A number of antibiotics are effective in eradicating
the tetanus bacterium. Metronidazole is the antibiotic of choice.
The recommended regimen is 500 mg 8-hourly for 710 days.
Erythromycin, tetracycline, chloramphenicol and clindamycin
are each acceptable alternatives. The use of penicillin in proven
cases of tetanus remains controversial; one randomized,
controlled trial showed that patients treated with penicillin
had a higher mortality when compared with metronidazole
(24% vs 7%; P < 0.01).6
Control of muscle rigidity and spasms
Muscle spasms and rigidity are treated effectively by sedation.
Many different drugs alone and in combination have been used
to achieve this. Benzodiazepines are considered first line treat-
ment; both diazepam and midazolam have been extensively used.
Large doses (up to 100 mg h 1) may be required. Morphine can be
equally efficacious and is usually used as an adjunct to benzo-
diazepine sedation. Morphine has a central action which can
minimize the effects of tetanospasmin. More recently, experience
has been gained using remifentanil in tetanus. Although it is a
pharmacologically attractive choice as a short-acting sedative
and analgesic, its use is prohibitively expensive and associated
with a number of undesirable side-effects. Propofol has also
been used successfully; however, in order to achieve adequate
plasma concentrations to relieve muscle rigidity, mechanical
ventilation is necessary.
Additional, useful sedation may be provided using anti-
convulsants, in particular phenobarbital (which enhances
GABA activity) and phenothiazines such as chlorpromazine.
Other agents that have been used with success include dantrolene
and intrathecal baclofen. Baclofen is a structural analogue of
GABA. When given intrathecally, it diffuses into the spinal
cord inhibiting neuronal transmission. Complete abolition of
rigidity and spasms has been achieved in a limited number
of cases using the intrathecal route. There is a significant risk
of respiratory depression associated with its use. There have been
only a few case reports which support the use of dantrolene.
Disadvantages include potential hepatotoxity and cost.
Muscle spasms refractory to benzodiazepines should be
managed with neuromuscular blocking agents. There have
been no comparative trials of neuromuscular blocking agents
with tetanus and recommendations are again based on case
reports. Atracurium is probably the neuromuscular blocking
agent of choice. Vecuronium has also been used because of
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 3 2006
Tetanus
its cardiostability. The use of aminosteroid neuromuscular
blocking agents is not recommended because of their association
with critical care neuropathy.
Control of autonomic instability
A major cause of mortality in tetanus is circulatory collapse
caused by autonomic instability. Sudden cardiac arrest is com-
mon and is thought to be precipitated by a combination of high
catecholamine levels and the direct action of the tetanus toxin
on the myocardium. Prolonged sympathetic activity may end
with profound hypotension and bradycardia. Parasympathetic
over activity may lead to sinus arrest. Direct damage to the
vagal nucleus by the tetanus toxin has been implicated. High
dose atropine (up to 100 mg h 1) has been advocated where
bradycardia is a prominent feature.
Sedation is also the first line manoeuvre to control autonomic
instability. Morphine is particularly useful and is effective in
decreasing catecholamine output. b-Blockade, although theoret-
ically useful to control episodes of hypertension and tachycardia,
is associated with sudden cardiovascular collapse, pulmonary
oedema and death. Other agents that have been used include
clonidine and magnesium. Clonidine is an a2-adrenergic agonist
which reduces sympathetic outflow, arterial pressure, heart rate
and catecholamine release. It can be administered orally or
parenterally and is, in addition, a sedative.
Magnesium is increasingly being utilized as part of mul-
timodal therapy for tetanus.7 It has a number of actions which
are effective in countering the state of autonomic hyperactivity;
in particular, blocking catecholamine release from nerves and
the adrenal medulla, and reducing receptor responsiveness to
released catecholamines. It is also a pre-synaptic neuromuscular
blocker, becoming a useful adjunct in the control of rigidity and
spasms. The recommended dose is 20 mmol h 1, adjusted to
achieve a plasma concentration of 2.54.0 mmol litre 1. It is
important to monitor plasma calcium concentrations during
the administration of magnesium as it inhibits the release of
parathyroid hormone.
Supportive treatment
Successful management of tetanus requires the entire arma-
mentarium of the modern intensive care unit. A multidisciplinary
approach is essential. Most cases require 46 weeks of supportive
treatment. Poor nutrition and weight loss occur rapidly because
of dysphagia, altered gastrointestinal function and increased
metabolic rate. Enteral nutrition should be established as early
as possible. Nosocomial infections are common because of the
prolonged course of tetanus and remain an important cause of
mortality. Prevention of respiratory complications involves
meticulous mouth care, chest physiotherapy and tracheal suction.
Adequate sedation during invasive procedures is mandatory to
prevent provoking spasm or autonomic instability. Pulmonary
embolism is a particular problem and thromboprophylaxis is
103
Tetanus
essential. Rhabdomyolysis is a common finding after a prolonged
tetanic spasm. This may lead to acute renal failure.
Recovery from tetanus is slow but often complete. The
psychological support needed following prolonged illness should
not be forgotten.
References
1. British National Formulary Number 49. British Medical Association and
Royal Pharmaceutical Society of Great Britain: Pharmaceutical Press, 2005
2. Health Protection Agency. Ongoing national outbreak of tetanus in
injecting drug users. Commun Dis Rep CDR Wkly [serial online] 2004;
14(a): news. Available at http://www.hpa.org.uk/cdr/ PDFfiles/2004/
cdr0904.pdf
104 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 3 2006
3. Thwaites CL. Tetanus. Curr Anaesth Crit Care 2005; 16: 5057
4. Cook TM, Protheroe RT, Handel JM. Tetanus: a review of the literature.
Br J Anaesth 2001; 87: 47787
5. Ablett JJL. Analysis and main experiences in 82 patients treated
in the Leeds Tetanus Unit. In: Ellis M. ed. Symposium on tetanus
in Great Britain. Boston Spa, UK: Leeds General Infirmary, 1967;
110
6. Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare
the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res Ed)
1985; 291: 64850
7. Attygalle D, Rodrigo N. Magnesium as first line therapy in the
management of tetanus: a prospective study of 40 patients. Anaesthesia
2002; 57: 81117
Please see multiple choice questions 610.