Arch Dis Child: first published as 10.1136/adc.54.8.650-a on 1 August 1979. Downloaded from http://adc.bmj.com/ on 19 August 2018 by guest.

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650 Correspondence
Although there is little doubt that the response of
young infants to bronchodilators is less good than that
Intrathecal ATS and high dosage
of older children, I think that in the acute stage a sub- diazepam in neonatal tetanus
stantial number of them do benefit and it is worth a trial.
Sir,
References We should like to make a few comments about the report
Konig, P. (1978). Treatment of severe attacks of asthma in by Khoo et al. (Archives, 1978, 53, 737). Seven of the 19
children with nebulised B2 adrenergic agents. Annals of neonates studied required total paralysis with IPPV for
Allergy, 40, 185-188. uncontrolled spasms, 2 died, and 5 more might have died
Radford, M. (1975). Effect of salbutamol in infants with but for total paralysis and IPPV. Therefore, it is not
wheezy bronchitis. Archives of Disease in Childhood, 50, justified to say that improved survival was due to admini-
535-538.
Rutter, M., Milner, A. D., and Hiller, E. J. (1975). Effect of stration of high doses of diazepam alone.
bronchodilators on respiratory resistance in infants and Recently we initiated a study on the efficacy of a
young children with bronchiolitis and wheezy bronchitis. regimen consisting of intrathecal administration of anti-
Archives of Disease in Childhood, 50, 719-722. tetanus serum (ATS), and high doses of diazepam (15-30
mg/kg per day) and chlorpromazine (15-30 mg/kg per
PETER K6NIG day) intravenously.
University of Missouri-Columbia, Between July and October 1978, we studied 10 neonates
School of Medicine, (Table). Diagnosis was on clinical grounds, and severity
Department of Child Health, was graded using the criteria of Patel and Joag (1959).
7th Floor North, Immediately after admission an IV line was established
Columbia, and diazepam administered at the rate of 1 mg/kg per
Missouri 65211, minute until the infant was free of spasm and rigidity.
USA This was followed by administration of ATS, 250 IU
intrathecally, and 1500 IU IV. Penicillin and gentamicin
Dr Milner and co-workers comment: (5 mg/kg per day) vere given. Infants were nursed in the
We were interested to hear of Dr Konig's experience paediatric ward. The umbilical cord was cleaned with
with nebulised salbutamol in children under one year. We spirit, and painted with gentian violet routinely. Pharyn-
accept that all our studies were carried out during the geal suction was done at regular intervals.
recovery phase but we have not found that any child Subsequent muscle relaxation was achieved by alter-
under one year has obtained any useful, clinical benefit nate IV administration of 2.5-7.5 mg diazepam and
from nebulised salbutamol when administered in the chlorpromazine, each at 2-4 hourly intervals (total daily
acute phase. Since our paper was published, two children dose of each drug 15-30 mg/kg). Once spasms had been
between the ages of 12 and 18 months have responded controlled, a nasogastric tube was inserted for feeding
well, and we have since heard of another who apparently and giving diazepam and chlorpromazine. Sedation was
obtained benefit by age 11 months. We still recommend gradually tapered off at a rate of 10-15 % of total dose
that salbutamol be given to all wheezing children over administered at intervals of 1-2 days, depending on the
one year but think it unlikely that many children younger degree of hypertonia. None of the infants was given
that this will respond to this form of treatment. IPPV with total paralysis.
Eight neonates recovered completely and 2 died, one
A. D. MILNER of fulminant bronchopneumonia and the other with
University of Nottingham, aspirant pneumonia. The average duration in hospital for
Department of Child Health, the survivors was 20 days, and the average period for IV
Medical School, diazepam and chlorpromazine 3.4 days. We observed
Queen's Medical Centre, that the shorter the interval between the onset of the
Nottingham NG7 2UH tetanus neonatorum and the intrathecal ATS, the quicker
Table The 10 neonates* studied
Case Gestational Age at Instrument Grade Spasm Duration of Hospital Outcome
weight (kg) onset for cord controlled sedation (days)
(days) cutting (hours) (days)
1 2-8 6 Blade V 48 20 30 Recovered
2 2.6 6 Blade V 48 7 13 Recovered
3 2-7 5 Razor V 9 days 25 25 Recovered
4 3.0 9 Scissors IV 24 12 12 Recovered
5 2.0 5 Scissors V Not controlled - - Died 50 hours after being
36 weeks admitted
6 2.4 7 - V 36 9 10 Recovered
7 2.1 6 Kitchen knife V Not controlled - - Died
8 2*8 7 - V 72 19 20 Recovered
9 3-0 7 - V 48 10 it Recovered
10 2.7 6 Blade V 120 30 40 Recovered
*All were term except for Cases 5 and 6.

was the control of spasm and the shorter the duration in
hospital. Besides thrombophlebitis at the site of vene-
punctures (probably secondary to benzoic acid present in
injectable diazepam) a common complication was apnoea,
which responded to partial withdrawal of diazepam. At
3-4 months all 6 neonates who returned for follow-up
were developmentally normal.
We feel a combination of high doses of diazepam and
chlorpromazine with intrathecal ATS (given early after
onset of tetanus) is effective in reducing mortality.
Reference
Patel, J. C., and Joag, C. G. (1959). Grading of tetanus to
evaluate prognosis. Indian Journal of Medical Sciences, 13,
834-840.
SUNIT SINGHI AND PRATIBHA SINGHI
Department of Paediatrics,
JLN Medical College,
Ajmer (Rajasthan) 305001,
India
Dr Khoo and co-workers comment:
We did not claim that the low mortality rate in our
patients with neonatal tetanus was due to high dose
diazepam alone. Other equally important therapeutic
measures that contributed to the improved survival rate
in our patients included good nursing care, tetanus
antitoxins, antibiotics, nutritional support, and the
judicious use of sedatives. In our study, the use of
continuous high dose IV diazepam (20-40 mg/kg per day)
certainly decreased the mortality rate and also the need
for artificial ventilation from 77 to 37% (Khoo et al.,
1978).
The treatment regimen advocated by Singhi and
Singhi is very similar to ours except for the use of intra-
thecal ATS and the very high dose of chlorpromazine.
The role of intrathecal ATS in the management of
neonatal tetanus is still controversial (Laurence, 1975).
The reason for injecting ATS into the CSF is to neutralise
the tetanus toxin that has penetrated the CNS but has
not yet begun to act. Besides, ATS given via the IV route
penetrates the blood/CNS barrier poorly, and the levels
of antitoxin in the CSF are approximately 400 times less
than in the blood (Patel et al., 1963; Ildirim et al., 1969).
In 1917, Sherrington obtained good results from the use
of intrathecal ATS in monkeys with tetanus. It was
subsequently tried in man but eventually abandoned
because of adverse reactions to the CNS and doubts
about its efficacy (Dietrich, 1940; Pratt, 1945). However,
Arch Dis Child: first published as 10.1136/adc.54.8.650-a on 1 August 1979. Downloaded from http://adc.bmj.com/ on 19 August 2018 by guest. Protected by copyright.
Correspondence 651
recent reports of the use of intrathecal ATS in tetanus are
encouraging (Ildirim, 1970; Sanders et al., 1977;
Salimpour, 1978). Ildirim (1970) treated 28 cases of
neonatal tetanus with intrathecal ATS and prednisolone
mixture and had a low mortality rate of 10 7 %. In another
-
clinical trial on 322 cases of adult-type tetanus, 200 units
intrathecal ATS (horse) was found to be an effective
adjuvant in reducing the mortality rate from 14.5 to
4.5 % (Sanders et al., 1977). No complication was
encountered apart from occasional difficulty in giving
ATS intrathecally, while remarkable relaxation was
observed in the patients.
With the availability of human antitetanus serum,
which is relatively free of allergic side effects and less
irritating to the CNS, the prospects for intrathecal ATS
(human) is promising, but needs further tests before it
can be recommended.
References
Dietrich, H. F. (1940). Tetanus in childhood with special
reference to treatment. American Journal of Diseases of
Children, 59, 693-710.
Ildirim, I. (1970). Intrathecal treatment of tetanus with
antitetanus serum and prednisolone mixture. Third Inter-
national Conference on Tetanus. Pan American Health
Organisation, 253, 119-127.
Ildirim, I., Meira, A. R., and Furcolow, M. L. (1969).
Letter: Tetanus. New England Journal of Medicine, 280,
1243.
Khoo, B. H., Lee, E. L., and Lam, K. L. (1978). Neonatal
tetanus treated with high dose diazepam. Archives of
Disease in Childhood, 53, 737-739.
Laurence, D. R. (1975). Therapeutic measures in tetanus.
Progress in Drug Research, 19, 323-328.
Patel, J. C., Metha, B. C., Nanavati, B. H., Hazra, A. K.,
Rao, S. S., and Swaminathan, C. S. (1963). Role of serum
therapy in tetanus. Lancet, 1, 740-743.
Pratt, E. L. (1945). Clinical tetanus: study of fifty-six cases,
with special reference to methods of prevention and a plan
for evaluating treatment. Journal of the American Medical
Association, 129, 1243-1247.
Salimpour, R. (1978). Tetanus of the newborn in Tehran. A
ten year study of 880 cases. Journal of Tropical Pediatrics
and Environmental Child Health, 24, 140-142.
Sanders, R. K. M., Martyn, B., Joseph, R., and Peacock,
M. L. (1977). Intrathecal antitetanus serum (horse) in the
treatment of tetanus. Lancet, 1, 974-977.
Sherrington, C. S. (1917). Observations with antitetanus
serum in monkeys. Lancet, 2, 964-996.
B. H. KHoo, E. L. LEE, AND K. L. LAM
Department of Paediatrics,
University Hospital,
Kuala Lumpur,
Malaysia