Tetanus


Tetanus is a severe infection due to the bacillus Clostridium tetani, found in soil, and human and animal waste. The infection is noncontagious. C. tetani is introduced into the body through a wound and produces a toxin whose action on the central nervous system is responsible for the symptoms of tetanus.

Tetanus is entirely preventable by immunisation. It occurs in people who have not been fully immunized before exposure or have not received adequate post-exposure prophylaxis. In these individuals, most breaks in the skin or mucous membranes carry a risk of tetanus, but the wounds with the greatest risk are: the stump of the umbilical cord in neonates, puncture wounds, wounds with tissue loss or contamination with foreign material or soil, avulsion and crush injuries, sites of non-sterile injections, chronic wounds (e.g. lower extremity ulcers), burns and bites. Surgical or obstetrical procedures performed under non-sterile conditions also carry a risk of tetanus.

Clinical features

Generalised tetanus is the most frequent and severe form of the infection. It presents as muscular rigidity, which progresses rapidly to involve the entire body, and muscle spasms, which are very painful. Level of consciousness is not altered.

Children and adults

– Average time from exposure to onset of symptoms is 7 days (3 to 21 days).
– Muscular rigidity begins in the jaw muscles (difficulty with then inability to open mouth [trismus] preventing the patient from speaking, eating), spreading to the face (fixed smile), neck (difficulty with swallowing), to the trunk (restriction of respiratory muscles; hyperextension of spine [opisthotonus]), to the abdomen (guarding) and to the limbs (flexion of the upper limbs and extension of the lower limbs).
– Muscle spasms, which are very painful, appear at the onset or when muscular rigidity becomes generalised. They are triggered by stimuli (noise, light, touch) or arise spontaneously. Spasms of the thoracic and laryngeal muscles may cause respiratory distress or aspiration.

Neonates

– In 90% of cases, initial symptoms appear within 3 to 14 days of birth.
– The first signs are significant irritability and difficulty sucking (rigidity of the lips, trismus) then rigidity becomes generalised, as in adults. Any neonate, who initially sucked and cried normally, presenting with irritability and difficulty sucking 3 to 28 days after birth and demonstrating rigidity and muscle spasms should be assumed to have neonatal tetanus.

Treatment

Hospitalisation is needed and usually lasts 3 to 4 weeks. Correct management can reduce mortality even in hospitals with limited resources.

General measures

– Ensure intensive nursing care.
– The patient should be in a dark, quiet room. Blindfold neonates with a cloth bandage.
– Handle the patient carefully, while sedated and as little as possible; change position every 3 to 4 hours to avoid bedsores.
– Teach family the danger signs and instruct them to call the nurse for the slightest respiratory symptom (cough, difficulty breathing, apnoea, excessive secretions, cyanosis, etc.).
– Establish IV access for hydration, IV injections.
– Gentle suction of secretions (mouth, oropharynx).
– Insert a nasogastric tube for hydration, feeding and administration of oral medications.
– Provide hydration and nutrition in feeds divided over 24 hours. In neonates, give expressed breast milk every 3 hours (risk of hypoglycaemia).

Neutralisation of toxin

human tetanus immunoglobulin IM
Neonates, children and adults: 500 IU single dose, injected into 2 separate sites

Inhibition of toxin production

metronidazole1  IV infusion (30 minutes; 60 minutes in neonates) for 7 days
Neonates:
• 0 to 7 days: 15 mg/kg on D1 then, after 24 hours, 7.5 mg/kg every 12 hours
• 8 days to < 1 month (< 2 kg): same doses
• 8 days to < 1 month (≥ 2 kg): 15 mg/kg every 12 hours
Children 1 month and over: 10 mg/kg every 8 hours (max. 1500 mg daily)
Adults: 500 mg every 8 hours

Control of rigidity and spasms, and sedation of the patient

Diazepam should decrease the frequency and intensity of spams without causing respiratory depression. The dose and frequency of administration depend on the patient’s clinical response and tolerance.

– There is a high risk of respiratory depression and hypotension when using diazepam, especially in children and elderly patients. Constant and close monitoring of the patient‘s respiratory rate (RR) and oxygen saturation (SpO2) is essential, with immediate availability of equipment for manual ventilation (Ambu bag, face mask) and intubation, suction (electric if possible) and Ringer lactate.
– A continuous IV infusion of diazepam requires the use of a dedicated vein (no other infusion/injection in this vein); avoid the antecubital fossa if possible.
– Do not stop treatment abruptly; an abrupt stop can cause spasms.

Neonates

diazepam emulsion for injection (10 mg vial, 5 mg/ml, 2 ml)
• 0.1 to 0.3 mg/kg by slow IV injection (3 to 5 minutes) every 1 to 4 hours depending on the severity and the persistence of the spasms as long as the RR is ≥ 30.
• If despite hourly diazepam the spasms persist, start a continuous infusion of diazepam with an electric syringe: 0.1 to 0.5 mg/kg/hour (2.4 to 12 mg/kg every 24 hours). Start with 0.1 mg/kg/hour and if symptoms persist, increase by 0.1 mg/kg/hour as long as RR is ≥ 30.
• If in spite of 0.5 mg/kg/hour symptoms persist, the dose can be increased up to 0.8 mg/kg/hour as long as the RR ≥ 30.
• Diluted diazepam emulsion does not keep for more than 6 hours.

Example:
Neonate weighing 3 kg (administration by electric syringe)
0.1 mg/kg/hour x 3 kg = 0.3 mg/hour
Dilute one 10 mg vial of diazepam emulsion for injection in 50 ml of 10% glucose to obtain a solution containing 0.2 mg of diazepam per ml.
Administer 1.5 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour i.e. 0.3 (mg/hour) ÷ 0.2 (mg/ml) = 1.5 ml/hour].

If an electric syringe is not available, diluting the diazepam emulsion in an infusion bag for continuous infusion may be considered. Weigh the risks associated with this mode of administration (accidental bolus or insufficient dose). The infusion should be monitored closely to avoid any change, however small, of the prescribed rate.

Children
> 1 month and adults

Same doses and protocol as in neonates but:
• Use diazepam solution for injection 5 mg/ml: (10 mg vial, 5 mg/ml, 2 ml)2 .
• These doses can be administered as long as the RR is:
≥ 30 in children under 1 year
≥ 25 in children 1 to 4 years
≥ 20 in children 5 to 12 years
≥ 14 in children over 12 years
≥ 12 in adults

Examples:
• Child weighing 6 kg (continuous IV infusion using a pediatric infusion set; 1 ml = 60 drops)
0.1 mg/kg/hour x 6 kg = 0.6 mg/hour
Dilute one 10 mg vial of diazepam solution for injection in 50 ml of 5% glucose (10% glucose if child < 3 months) to obtain a solution containing 0.2 mg of diazepam per ml. Administer 3 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour i.e. 0.6 (mg/hour) ÷ 0.2 (mg/ml) = 3 ml/hour] or 3 drops/minute (in a paediatric infusion set ml/hour = drops/minute).

• Adult weighing 60 kg (standard adult infusion set, 1 ml = 20 drops)
0.1 mg/kg/hour x 60 kg = 6 mg/hour
Dilute 5 vials of 10 mg of diazepam solution (50 mg) in 250 ml of 0.9% sodium chloride or 5% glucose to obtain a solution containing 0.2 mg of diazepam per ml.
Administer 30 ml/hour [dose (in mg/hour) ÷ dilution (in mg/ml) = dose in ml/hour e.g. 6 (mg/hour) ÷ 0.5 (mg/ml) = 30 ml/hour] or 10 drops/minute.


Count the volume of the infusion of diazepam as part of the patient’s daily fluid intake.

When the frequency and severity of the spasms have decreased, start weaning the diazepam (gradually decrease the rate of infusion):
– Calculate the total daily dose of IV diazepam and administer it orally in 4 divided doses, 6 hours apart, via nasogastric (NG)3 tube.
– Give first NG dose and decrease rate of IV infusion by 50%.
– Give secondNG dose and stop IV diazepam infusion.
– If withdrawal signs4 appear, wean more slowly.
– Once on diazepam PO, wean by 10 to 20% of the original dose daily, until at a dose of 0.05 mg/kg every 6 hours.
– Then increase the interval from every 6 hours to every 8 hours for 24 hours as tolerated (wean more slowly if withdrawal signs appear).
– Continue to increase the interval between the doses from every 8 hours to every 12 hours and then to every 24 hours before stopping the diazepam.
– Each step should be for 24 hours or more if withdrawal signs appear.

Notes:
– It is often at these smaller doses that it is difficult to wean diazepam. If this is the case, slow the wean further: dropping the % wean (e.g. 5% wean every 24 hours instead of 10% wean) or increasing the interval between weans (e.g. going from every 24 hours to every 48 hours).
– If the patient is also receiving morphine, wean diazepam first then, wean morphine.
– Non-pharmacological measures to reduce withdrawal: reduce environmental stimuli; swaddle infants, frequent feedings.
– Infants who have had tetanus remain hypertonic, even when they are no longer having spams.

Treatment of pain

morphine PO (via nasogastric tube) if necessary (see Pain, Chapter 1).
When morphine is administered with diazepam the risk of respiratory depression is increased, thus closer monitoring is required. When morphine is no longer required, wean the same way as diazepam.

Treatment of the point of entry

– Search systematically the entry wound. Provide local treatment under sedation: cleansing and for deep wounds, irrigation and debridement.
– Cord infection: do not excise or debride; treat bacterial omphalitis and sepsis, add to metronidazole IV: cloxacillin IV + cefotaxime IV or cloxacillin IV + gentamicin IV (for doses, see Bacterial meningitis).

Tetanus vaccination

As tetanus does not confer immunity, immunisation against tetanus must be administered once the patient has recovered.
In case of neonatal tetanus, initiate the immunisation of the mother.

Prevention

Of critical importance, given the difficulty of treating tetanus once established.

1) Post-exposure prophylaxis

– In all cases:
• Cleansing and disinfection of the wound, and removal of any foreign body.
• Antibiotics are not prescribed routinely for prophylaxis. The decision to administer an antibiotic (metronidazole or penicillin) is made on a case-by-case basis, according to the patient’s clinical status.

– Depending on pre-exposure vaccination status:
Tetanus vaccine (TV)5  and immunoglobulin: see indications below.

Risk

Complete immunisation (3 or more doses)

Time since administration of latest dose:

Incomplete immunisation (less than 3 doses)
or no immunisation
or unknown status

< 5 years 5-10 years > 10 years

Minor clean wound

None

None

TV
one booster dose

Initiate or complete TV

All other wounds

None

TV
one booster dose

TV
one booster dose

Initiate or complete TV
and administer tetanus immunoglobulin

tetanus vaccine IM
Children and adults: 0.5 ml per dose
If no immunisation or unknown immunisation status: administer at least 2 doses at an interval of 4 weeks.
If incomplete immunisation: administer one dose.
Then, to ensure long-lasting protection, administer additional doses to complete a total of 5 doses, as indicated in the table below.

human anti-tetanus immunoglobulin IM
Children and adults: 250 IU single dose; 500 IU for wounds more than 24 hours old.
Inject the vaccine and the immunoglobulin in 2 different sites, using a separate syringe for each.

2) Routine immunisation (pre-exposure prophylaxis)

– Children: 5 doses in total: a first series of 3 doses of DTP or DTP + HepB or DTP + Hib + HepB before the age of 1 year, administered at an interval of 1 month (e.g. at the age of 6, 10 and 14 weeks), then a 4th dose of a vaccine containing tetanus toxoid between the ages of 4 to 7 years, then a 5th dose between 12 and 15 years.

– Women of childbearing age: 5 doses during the reproductive years: a series of 3 doses (dT or TT) with an interval of at least one month between the 1st and 2nd dose and an interval of at least 6 months between the 2nd and 3rd dose, then two other doses, each at minimum interval of one year, e.g. during pregnancies (see table below).

– Pregnant women: if a woman has never been immunized or if her immunisation status is unknown: 2 doses of dT or TT during the pregnancy to reduce the risk of tetanus in mother and newborn: the first as soon as possible during the pregnancy and the second at least 4 weeks later and at least 2 weeks before delivery. This immunisation schedule protects more than 80% of neonates from tetanus. A single dose offers no protection


Dose

Vaccination schedule in adults

Degree and duration of protection

TV1

On first contact with the health care system
or as soon as possible during pregnancy

No protection

TV2

At least 4 weeks after TV1

80%
1 to 3 years

TV3

6 months to 1 year after TV2
or during the following pregnancy

95%
5 years

TV4

1 to 5 years after TV3
or during the following pregnancy

99%
10 years

TV5

1 to 10 years after TV4
or during the following pregnancy

99%
Throughout the reproductive years



Footnotes
Ref Notes
1 Clindamycin IV for 7 days is an alternative (for doses, see Periorbital and orbital cellulitis, Chapter 5).
2 Administer the first dose rectally if an IV cannot be placed immediately.
3 Administration of oral diazepam tablets to infants: calculate the exact dose of diazepam, e.g. to obtain 0.5 mg of diazepam, cut a scored diazepam 2 mg tablet in half along scoring then split in half again. Crush quarter tablet and dissolve in expressed breast milk or infant formula.
4 Withdrawal signs: excessive irritability, tremors, increased muscle tone, frequent yawning, poor feeding, watery stools and sweating.
5 Tetanus-containing vaccine, such as TT or DT or dT or DTP or DTP + HepB or DTP + Hib + HepB according to availability and patient’s age