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Brief Reports Indian Pediatrics 2002; 39:654-657 |
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Intrathecal Immunoglobulin in The Treatment of Tetanus |
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Janaki Menon
Tetanus, an acute infectious disease caused by Cl. tetani, continues to be an important cause of mortality and morbidity in India(1). We present a series of cases treated with intrathecal tetanus immunoglobulin (TIG), where the mortality, morbidity and duration of hospital stay were significantly low. Subjects and Methods This study was conducted on patients with tetanus in the age group 0-12 years admitted to the Department of Pediatrics, Medical College, Trichur, Kerala, during the period from May 1995 to June 2001. The objective was to study the safety and efficacy of intrathecal TIG. Tetanus was diagnosed on the basis of a history of trismus, localized or generalized spasms in a partially immunized or unimmunized child along with clinical findings of trismus, risus sardonicus and/or provoked or unprovoked generalized spasms. An incubation period of 7 days or less, period of onset of 3 days or less, fever at onset and generalized disease were considered unfavourable prognostic features at presentation(2). All patients were managed as per the following protocol. On admission, human tetanus immunoglobulin (TIG) 250 U TETGLOB, was administered via the intrathecal route preceded by IV diazepam (1-2 mg/kg) for proper relaxation to ease the procedure. The patients were started on IV Benzyl Penicillin (1 LU/kg/day) which was continued for 10 days. Muscle relaxant therapy was provided with IV Diazepam at a dose of 1mg/kg/dose at 2-3 hourly intervals. Supportive therapy included IV fluids, oral suction and relative isolation in a quiet corner of the general ward. After the first 48-72 hours, Ryle’s tube feeds were initiated with calorie-dense feeds. IV Diazepam was substituted with oral Diazepam in the same dose once good control of spasms was achieved. Those children whose spasms could not be controlled with IV Diazepam alone were also given Chlorpromazine (0.3 - 0.5 mg/kg/dose 6 - 8 hourly). The criteria for discharge were absence of reflex spasms, ability to take oral feeds and ability to walk around unassisted. At discharge, active immunization was initiated. Patients were discharged on oral Diazepam (1 mg/kg/dose 4-6 hourly), were asked to follow up every 2 weeks and the dose was tapered off over 6-8 weeks. Results A total of 41 cases were studied. Three patients were less than 1 yr old, of which 2 were neonates. The median age was 6 year. All cases were unimmunized, except for 3 who were partially immunized. The incubation period was 1 week or less in 17 (41.5%) patients and more than 1 week in 24 (58.5%) patients. The period of onset was 3 days or less in 33 (80.5%) children and more than 3 days in 8 (19.5%). The median period of onset was 1 day. Generalized tetanus was seen in 35 (85.4%) and localized tetanus in 6 (14.6%) patients. Fever at onset was observed in 27 (65.9%) patients. IV Diazepam was needed in 37 (90.2%) patients; in 10 (24.4%) patients for more than 5 days and in one patient for 10 days. The maximum dose of Diazepam needed was 15 mg/kg/day. Sixteen patients (39%) needed doses in excess of 10 mg/kg/day. Chlorpromazine was used additionally only in 8 patients (19.5%). Respiratory complications developing after admission were relatively few. Only one patient had aspiration after starting treatment. Ventilatory support (with resuscitation bag) was needed in 3 cases, one of which was a neonate and required assistance for less than 24 hours. The median duration of hospital stay was 10 days. The longest hospital stay, 30 days, was for a neonate. Thrity eight patients (92.7%) survived. Both neonates in this series survived. Of the 3 patients who expired, 2 deaths were due to spasms and 1 was following aspiration due to a displaced Ryle’s tube. Nine patients returned for long term follow up on call. The longest was a patient admitted 4 years ago. Eight were found to be doing well, with no neurological deficits, scholastic backwardness or behavioral problems. One patient, who had the disease at 11 months of age was found to have mild mental retardation with spastic cerebral palsy. Discussion The toxin produced by CI.tetani binds at the neuromuscular junction and then gets transported to the alpha motor neuron, from where it enters adjacent spinal inhibitory interneurons, here preventing neuro-transmitter release and blocking normal inhibition of antagonistic muscles. Once the toxin has begun its axonal ascent, it cannot be arrested by systemic administration of TIG. Intrathecal TIG probably acts at this level. Though various treatment protocols have been tried in the management of tetanus, no consensus has been reached. Intrathecal serotherapy has been tried by various workers, in India and abroad since 1967(3-7). A recent meta-analysis concluded that intrathecal therapy is of no proven benefit, but urged further studies(3). Our management of tetanus was based on a hitherto unpublished study at Calicut Medical College, Kerala, in which 100 cases of tetanus were randomly allotted to 4 schedules of treatment; (i) IV ATS 10,000U; (ii) IV ATS 10,000U and I/T ATS 500U; (iii)I/T ATS 500U; and (iv) I/T TIG 250U and the mortality was found to be significantly lower in the fourth group(6). In our series of patients, unfavourable prognostic features like incubation period less than 1 week, period of onset less than 3 days, generalized tetanus and fever at onset were present in 41.5%, 80.5%, 85.4% and 65.9% respectively. Yet, when compared to recent reports from well equipped centers in India(8,9), the mortality, morbidity, dose of muscle relaxants, requirement for mechanical ventilation and duration of hospital stay was found to be much lower in our series, the difference in the primary management being the route of administration of TIG. Our hospital is a government general hospital catering to the needs of the poorer strata of society with a catchment area mainly comprising the backward districts of Palakkad, Malappuram and Trissur, including tribal areas and a large coastal belt. Our patients were not treated in an ICU, but in a general ward, with no facility for mechanical ventilation other than a resuscitation bag. This is the kind of hospital setting where the large majority of cases in India will have to be treated. We believe that the use of intrathecal TIG has prevented the progression of disease hence necessitating the use of a smaller dose of muscle-relaxant drugs (mainly diazepam) and a shorter hospital stay. The need for major intervention like intubation. tracheostomy and mechanical ventilation was considerably reduced, as also the incidence of iatrogenic complications. We used 250U TIG per patient (costing Rs. 246/-) as against 2000-8000U (costing Rs. 1568-6262/-) mentioned in other series(8,9). The shorter duration of hospital stay and the lower incidence of iatrogenic complications are added benefits. In resource-poor conditions such as ours, it greatly reduces the financial burden on the health care system. We would like to conclude that intrathecal TIG is a safe and effective mode of treatment of tetanus. Further studies under controlled conditions, need to be done in this direction as this mode of therapy has important implications in developing countries. Acknowledgment We would like to thank Dr. N. Ramachandran MD, Pediatrician, Palakkad, for having kindly permitted us to cite his unpublished work on Tetanus as a major reference. Our thanks is also due to Dr. Usha Mathews, Lecturer, Department of Pediatrics, Medical College, Trissur for the kind help extended to us during data collection. Contributors: JM was responsible for concept and design, data analysis and drafting the article. LM was responsible for concept and design, critical review and final approval, and will act as the guarantor for the study. Funding: None. Competing interests: None stated.
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