Current Treatment of Tetanus

Nur Farhanah

Epidemiology
The symptoms described by Hippocrates
Carle and Rattone in 1884 noticed tetanus in
animals by injecting them with pus from a
fatal human case.
In 1887 Rosenbach detected spores and
bacilli
In 1889,Kitasato found bacilli culture
In 1890 Kitasato and Behring prepared
antitoxin
In world war I antitetanus serum
In the developing world 50% deaths
In the developed world incidence is low

Tetanus is a vaccine
preventable disease
Tetanus is infectious but not contagious
The prevalencereflects a failure of immunization
health care delivery system
Neonatal tetanus eradicated by maternal
immunization
High risk group are in people who have never
been vaccinated, or who completed their
childhood series, but did not have a booster dose
in the preceding 10 years.

Pathogenesis
Tetanus is a toxic infection caused by the obligate
anaerobe Clostridium tetani

C.tetani is a slender,gram
positive,anaerobic rod,
develop a terminal spore
drumstick appearance
The spores are very resistant to heat and the usual
antiseptics
C. tetani cant survive in 121 C for 20 minutes
found in the soil and in animal and human intestines

Mode of transmission
Contaminated wounds
Deep wounds
devitalized (dead) tissue
Puncture, burn, any break in the skin, and
injection-drug sites, mother and newborn
child (uterus umilical cord)

Pathogenesis
C. tetani produces two exotoxins :
tetanolysin and tetanospasmin.
Tetanolysin (hemolysin) causes damage
viable tissue, lowering redox potential
optimizing conditions for bacterial
multiplication
Tetanospasmin (TeTX or TeNT) causes the
clinical manifestations of tetanus.

Effect of tetanospasmin

The presynaptic (yellow) neuron of the CNS

and the postsynaptic neuron (white).
B) Excitatory neurotransmitters potentiating
an action potential.
C) Inhibitory neurons ready to be released
into the synaptic cleft to halt transmission of
the action potential.
D) Tetanospasmin bound at the presynaptic
membrane, preventing the release of the
inhibitory motor neurons.

Inhibits the release of GABA and glycine

(main transmitter inhibitory system)
Symptoms occur
Autonomic dysfunction occur some day
after onset of spasm
Acts at the neuromuscular junction where
it reduces release of acetylcholine

Effect of tetanospasmin

Clinical Features
Incubation period (between exposure to the
bacteria in a contaminated wound and
development of the initial symptoms) of tetanus
1 day-several months (3-21 days:,rate 8 days)
There is a correlation between the distance of
the injury from CNS and the duration of
incubation period
Period of onset : the time between the first
symptom and the first reflex spasm

There are 4 clinical form

1.Localized

Rare, mild, potenstial

generalized

2.Cephalic

Fixed muscle rigidity,painful

spasm in area closer to the site
of the injury
Rare,potential generalized
Wound to the head /face/chronic otitis
media,
Atonic palsy motor cranial nerve

3.Neonatal
Poor sucking, irritability,
trismus

4.Generalized
Most common form
Rigidity and spasm
m.masseter trismus
(lockjaw) grimace
through chenched teeth,
close mouth, wrinkled
forehead,raised eyebrow
(risus sardonicus)
neck,thorak ,back
,extremities rigid and
spasms (opistotonus)
abdominal rigidity

Risus sardonicus

Opistotonus

Characteristic of Tetanic spasm:

- intermitten, irregular, unpredictable
- Triggered by external stimuli or internal
stimuli
- Cognitive function not affected

Diagnosis
Based on clinical and symptoms
Spatula test in early diagnosis
Laboratory test not usually unhelpful
Aspirates from wound (gram + bacilli ,
terminal/subterminal spores)
Anaerobic culture rarely positive

Differential Diagnosis of Tetanus

Symptom

DD

Trismus

Alveolar/dental pathology
Temporo-mandibular disease

Neck stiffness

Muscle spasm
Meningitis

Dysphagia

Acute pharyngeal disease

Spasms

Strychnine poisoning
Intracranial lessions
Drug-induced dystonic reactions
Hypocalcemia

Neonatal Tetanus

Sepsis
Meningitis
Convulsion

Clinical grading /scoring system

- Severity
- Prognosis
- Developed by Dakar, Phillip, Ablett,

Udwadia

Ablett Classification of severity of

tetanus
Grade I (mild) : trismus with little or no
dysphagia
Grade II (moderate) : trismus, dysphagia,
generalized muscle rigidity, fleeting spasms, not
embarrassing respiration
Grade IIIa(severe) : trismus, dysphagia,
generalized muscle rigidity, severe spasms,
embarrassing respiration
Grade IIIb (very severe) Grade IIIa with
autonomic dysfunction

Rating Scale for Severity and

Prognosis of Tetanus
-

Score 1 point for each of the following

Incubation period <7 days
Period of onset <48hours
Acquired from burns, surgical wound, compound
fracture, septic abortion
Narcotic addiction
Generalized tetanus
Pyrexia >40C
Tachycardia >120beats/min (neonates
>150beats/min)

Total score provides indication of

severity and prognosis
Score

Severity

Mortality

0-1

Mild

<10%

2-3
4

Moderate
Severe

10-20%
20-40%

5-6

Very severe

>50%

Cephalic tetanus is always scored as

severe or very severe

Note :
There may not be a history of injury
Long incubation period not as guarantee
of mild course
The virulence of the organism
The immune status of the patient

management

No specific drug can counteract the toxin

which bound nervous tissue
Specific treatment
Neutralization of the circulating toxin
Eradication of the organism
Symptomatic Treatment
Protecting the airway
Supportive treatment

Neutralization of the
circulating toxin
Passive immunization (from human or
eguine)
Early incubation period toxin circulates in
the bloodstream
Clinical symptom mostly toxin is bounded
to nervous system
Administration : i.v or IM or intrathecal ?
Advantage and Disadvantage

Neutralization of the
circulating toxin
Best choice : Human Tetanus Immunoglobulin
(HTIg) 3000-6000 units IM divided dose
( 40-150UI/Kg of HTIG).
-The Optimum dose still in debate
-Recommended 500 units
-Roncentrations reach peak in 24-48 hr
- Long half Life maintained for 10-15 days
Nonavailable HTIg ?

HTIG nonavailable

Antitetanus Serum (ATS)

- 5001000 IU/kg intravenously or
intramuscularly.
- 10,000 or 20, 000 units of ATS (5000 U IM and
5000 U infiltrated around the wound)
- short half life (2days)
- Skin test first
- Anaphylactic reactions

The active immunisation is needed activepassive immunisation

Hystory of TT

Clean, minor
wounds
TT

Unknown oe less than Yes +

3 doses
Basic imm

Three or more doses

No, unless
>10 years
since last
dose

Ig

No

No

All other
wounds
TT

Ig

Yes +
yes (250
basic imm IU HTIG
or ATS
3000 IU
No,unless No
>5y since
last dose

Eradicating the organism

Penicillin doses is 100 000200 000 IU/kg/day IM/IV
for 7 to 10 days
- Johnson and Walker study : iv convulsions, focal
epilepsy
- The structure of penicillin is similar to -aminobutyric acid
(GABA) the principal inhibitory neurotransmitter in the
CNS
- Penicillin acts as a competitive antagonist to GABA.
- side effect of penicillin could synergise with the action of
the toxin in blocking transmitter release at GABA
neurons.

Metronidazole is a safe alternative

rectal intravenous or intramuscular injections
Salim et al compare penicillin and
metronidazole, reduction in mortality in the
metronidazole group (7% compared with 24%).
study Yen et al was no significant difference in
mortality (penicillin : metronidazole )
drug of choice in the treatment of tetanus.
Dose 400 mg rectally every 6 hours, or 500 mg
every 6 hours intravenously for 710 days.

Other Drugs
Erythromycin, tetracycline,
vancomycin, clindamycin,
doxycycline, and chloramphenicol
would be alternatives

Symptomatic Treatment
Keys :
Control of rigidity and spasm
Control of autonomic dysfunction

Control of Rigidity and

spasm
- Sedation control less severe spasm, not rigidity
- Combination drug to control rigidity and spasms
- Benzodiazepines and barbiturates GABA
agonist, inexpensive
Phenobarbital 240mg/8 hours
Diazepam 15-100mg/h i.v
Midazolam
Chlorpromazine 25-50mg/8h is used in
combination with GABA agonist

Propofol in severe tetanus

Loading dose 50 mg Infusion 3.54.5mg/kg/h
- No withdrawl, addiction
- Reduction muscle rigidity, rapid recovery
- Reduces oxygen consumption
- Cardiovascular instability

Control of Autonomic
dysfunction
Sympathetic Over Activity (SOA) :
tachycardia,
depression of bowel motility and bladder
function, hypertension, sweating
Parasympathetic increase : hypersalivation
and bronchial secretion
Combined and blocker
Propanolol, labetilol, esmolol
Should be monitor invasive long-term

Suppression of catecholamine
release
More logical method of controlling SOA
Heavy sedation reduce catecholamine level, but
interfere cardiac compensatory mechanism
Morphine
- Acts centrally to reduce sympathetic tone in
heart and vascular bradycardia, hypotension
- Induce peripheral venous and arterial dilatatio
- Dose 240-2500mg/day
- It causes constipation, paralytic ileus

Clonidine
- Partial agonist for 2 adrenergic receptors
- hypotension by central action as it reduces
sympathetic outflow, cathecolamine release and
peripherally by inhibiting the release of
noradrenaline from the pre-junction nerve
ending

 Magnesium sulfat
is a vasodilator
Reduced the release of catecholamine
After loading dose 5g bolus over 20mnt , the
hourly dose 4-5g/h
The rate of infusion sholud be titrated to control
spasm and rigidity
Monitor serum Mg, depression of ventilation, the
patellar reflex is not valid indicator

Management of Tetanus
Early diagnosis
Neutralization of unbound toxin
Tetanus toxoid vaccine
Eradication of organism
Transfer to HNC/ICU/bedside ventilation support
Wound debridement
Tracheostomy (if dysphagia or generalized rigidity)
NGT for feeding
Control of spasms
Control of Autonomic dysfunction
Nutrition
General nursing, mouth and tracheostomy care
Cornerstones of treatment heavy sedation, muscle paralysis,
artificialventilation

complication
In developed world mortality 20%-40% in severe
tetanus
Death complications of treatment
cardiovascular complication
uncotrolled sympathetic over
activity (SOA)
In developing world higher mortality
method of treatment
ICU limited or nonexistent

Key issues
Prompt diagnosis is very crucial
Prevention of early complications consists
of predicting severity, monitoring the
patient, early tracheostomy
Conventional treatment (heavy sedation,
paralysis, artificial ventilation) in ICU not
reduced the mortality