Intensive care management and outcomes of severe paediatric tetanus in a tertiary care hospital

Introduction

Tetanus is a rare diagnosis, but a few sporadic cases post-vaccination have been documented over the years. Although tetanus is endemic in India, its incidence has substantially decreased (>90% decline) owing to extensive outreach from various vaccination programmes.^1–3 In 2022, 84% of children worldwide received three doses of diphtheria, polio and tetanus vaccine. Additionally, the percentage of vaccine coverage increased from 85% in 2021 to 93% in 2022. ⁴ The decline in the incidence was mainly observed in neonatal tetanus, with India achieving the benchmark of elimination of both maternal and neonatal tetanus in 2015. ⁵ Despite this elimination, non-neonatal tetanus is still a rare but recurring problem in the paediatric intensive care unit. Furthermore, the lack of characteristic paroxysmal muscle spasms in the prodromal phase of generalised tetanus may delay diagnosis and treatment. Despite intensive care management, mortality from tetanus has been quoted as anywhere between 10% and 50%, but with some studies reporting low mortality rates of around 2–7%, based on severity of illness and other socio-economic factors.^6–10 Tetanus can rapidly progress into life-threatening muscle spasms accompanied by respiratory insufficiency and/or autonomic dysfunction. We hereby report six children with tetanus admitted to our hospital from June 2016 to June 2024, comparing the different presentations, modes of therapy and outcomes.

Case series

We present six cases of paediatric tetanus admitted to our paediatric intensive care unit from June 2016 to 2024. Informed consent was obtained from the parents for the use of patient data. Their ages ranged from 3–16 years, with a mean age of 8.7 years, with a male preponderance (66%). Three patients had a definitive history of penetrating injury, but all patients showed a delay in seeking medical care (median: 5 days). Three patients were completely unimmunised, whereas the remaining had only received three primary doses of tetanus vaccine as per the Indian national immunisation programme (Table 1).

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Table 1.

Epidemiology, clinical features, intensive care management and outcomes of paediatric tetanus.

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6
Age	10 years 6 months	3 years	5 years 6 months	11 years	6 years	16 years
Gender	Female	Male	Male	Female	Male	Male
Wounded area	Left foot	Right great toe	None	None	None	Right foot
First symptom	Dysphagia and trismus	Trismus	Fever, aspiration pneumonia. Post extubation-opisthotonus and trismus	Dysphagia, neck stiffness, abdominal pain	Abdominal pain, difficulty in walking, trismus and dysphagia	Trismus, generalised stiffness of the whole body, opisthotonus and recurrent spasms
Time interval between the onset of symptoms and the visit to the doctor	5 days	2 days	25 days from the onset of pneumonia to the first symptom of tetanus	6 days	3 days	5 days
Symptoms and signs	Dysphagia, lock jaw, opisthotonus, clenching of teeth	Fever, lock jaw, spasms, opisthotonus	Disorientation, trismus, opisthotonus	Dysphagia, neck stiffness, abdominal pain	Fever, abdominal pain, trismus, dysphagia, opisthotonus, risus sardonicus	Trismus, opisthotonus, muscle spasms, dysphagia, dyspnea
Immunisation status	Unimmunised	Unimmunised	Three primary doses	Three primary doses	Unimmunised	Three primary doses
Family history of tetanus	Present	Absent	Absent	Absent	Present	Absent
Severity of tetanus3	Grade 3 Severe	Grade 4 Very severe	Grade 4 Very severe	Grade 2 Moderate	Grade 4 Very severe	Grade 4 Very severe
Mechanically ventilated	Yes	Yes	Yes	No	Yes	Yes
Duration of ventilation	6 days	25 days	20 days	Not ventilated	12 days	12 days
IV antibiotics	Metronidazole and ceftriaxone	Metronidazole, ceftriaxone, meropenem and vancomycin	Metronidazole and ceftriaxone	Metronidazole and ceftriaxone	Metronidazole, ceftriaxone and meropenem	Metronidazole, piperacillin - tazobactam, Colistin (for VAP)
Dose of TIG	4000 IU over 5 days	500 IU stat	2000 IU	500 IU stat	2000 IU initially 3000 IU 2 days later	1500 IU
Comorbid factors	Compression fracture of the spine D5–D9	Klebsiella VAP	ARDS, PRES	None	Klebsiella sepsis	Acinetobacter VAP, multiple bed sores
Autonomic dysfunction	Absent	Present	Present	Absent	Present	Present
Cessation of spasms after admission	12 days	No further spasms	28 days	22 days	10 days	23 days
Duration of hospitalisation	43 days	28 days	45 days	24 days	20 days	27 days
Outcome	Recovered	Expired	Recovered with sequelae	Recovered	Recovered	Recovered

IV: intravenous; TIG: tetanus immunoglobulin; VAP: ventilator-associated pneumonia; ARDS: acute respiratory distress syndrome; PRES: posterior reversible encephalopathy syndrome.

All children were diagnosed based on the presence of trismus. Dysphagia was noted in three, while one presented with features of aspiration pneumonia. Ambulatory difficulties were present in three, with opisthotonus being the most common sign. Five required intubation and mechanical ventilation, whose mean duration was 12.5 days, whereas hospital stay ranged from 28 to 45 days. One child required a surgical tracheostomy. Upon grading these children according to severity, we assessed one to be moderate, one severe and the remaining four very severe. ⁶ Notably, poor prognostic factors were age at presentation, short onset time, short incubation period, the presence of autonomic dysfunction, need for mechanical ventilation and severity. ¹¹

Benzodiazepines, magnesium sulphate infusion, baclofen and other intravenous muscle relaxants were used to control spasms. Baclofen was administered via nasogastric tube, as a last resort for spasm control, considering the risks associated with intrathecal administration. ¹¹ For children classified under very severe, intermittent paralysis with intravenous vecuronium was added. Also, intravenous metronidazole was used in all children with other appropriate antibiotics for nosocomial infections later identified. Human tetanus immunoglobulin (HTIG) and tetanus vaccine were administered simultaneously upon establishing immunisation history. Equine TIG was not used owing to its high risk of anaphylaxis. A minimum dose of 500 IU of HTIG was given in two children, with a maximum of up to 5000 IU. Variations in dosing of HTIG were inevitable owing to financial constraints.

Severe autonomic disturbances, in the form of excessive perspiration, tachycardia and blood pressure instability were observed in 66% (Table 1). One child was found to have a compression fracture of D5–D9 thoracic spinal segments. Three children acquired nosocomial infections, of whom two had ventilator-associated pneumonia and one developed a central line-associated bloodstream infection. Five children survived; one recovered with post-tetanus sequelae in the form of cerebral atrophy and visual tract dysfunction, following a prolonged clinical course complicated by aspiration pneumonia, acute respiratory distress syndrome (ARDS), prolonged mechanical ventilation and late cessation of spasms.

Discussion

Tetanus infection remains a rare but potentially lethal disease in India, caused by Clostridium tetani, which is a spore-forming, obligate anaerobic, Gram-positive bacterium. Four clinical presentations of tetanus have been described in the literature: neonatal, localised, cephalic and generalised. According to the World Health Organisation (WHO), any person above 28 days old, presenting with an acute onset of at least one of the following: trismus, risus sardonicus or generalised muscle spasm, is a suspected case of non-neonatal tetanus. ¹² The most common modes of infection in non-neonatal tetanus have been listed as secondary to otogenic infections, after trauma, as well as idiopathic causes. Only three of our six children presented following trauma. Though the classical symptoms of tetanus may be absent at first presentation, tetanus should always be considered, especially in non-immunised patients with an acute onset of dysphagia and trismus. ¹³ In our centre, five had either dysphagia, trismus or an overlap of both, of whom three were unimmunised, and three were partially immunised (three primary doses and no booster doses).

The diagnosis of tetanus is purely based on historical and clinical findings. Upon arriving at a diagnosis, the modified Patel and Joag grading system was utilised for not only assessing severity but also guiding treatment and predicting the prognosis.^6,14,15 Based on the same scoring system, four children were classified as having very severe tetanus, with the other two falling under severe and moderate, respectively. Cases 2 and 4 both belonged to very severe cases, of which the former succumbed. The case fatality rate of tetanus, without treatment, is nearly 100% but can be reduced to <10% with appropriate immediate intensive care practices.^7,10,15

Management of tetanus needs meticulous medical and supportive care by doctors and nursing staff. The goals of management can be broadly classified into early and aggressive airway management, halting toxin production, muscle spasm control, management of autonomic dysfunction and prevention of nosocomial infections secondary to a prolonged duration of stay. ¹⁷

All our children were isolated and kept in minimally lit environments with as minimal noise as possible to aid recovery. ¹⁶ All six children received anti-toxin, albeit at varying doses and durations. HTIG is available as 250, 500 and 1000 IU. At present, there are no clear recommendations of HTIG based on body weight, but a dosage range of 500–6000 IU has been described in the literature thus far. ¹⁸ It is known that early administration of HTIG can prevent the progression of tetanus of the central nervous system; however, intrathecal administration has not shown any additional benefit and is no longer practised. ¹⁹ Diazepam, both intravenous and oral forms, and baclofen, were used as antispasmodic measures. The mean duration of cessation of spasms was 15.8 days, after which physiotherapy was started for all children. Although there are isolated case reports suggesting better spasm control with continuous benzodiazepine infusion compared to bolus administration in severe to very severe tetanus, either approach may be used. ²⁰ Amongst the five who had been mechanically ventilated, four developed autonomic instability, which was symptomatically managed. At least half of these developed Gram-negative ventilator-associated pneumonia or sepsis, which was managed with appropriate antibiotics according to culture and sensitivity patterns.

Historically, compression fractures, particularly of the mid-thoracic vertebrae, were frequently reported; they are now exceedingly rare, probably reflecting earlier presentation and improved control of spasms. ²¹ Meticulous nursing care to prevent bed sores was given utmost importance. Early enteral feeding was initiated via nasogastric tube (NGT), within the first 24 h of intubation, except for Case 4, in whom it was initiated on admission. Once spasms were controlled, supervised oral feeding was initiated and NGT feeds were gradually tapered off.

Long-term complications of tetanus include neurodevelopmental, behavioural changes as well as severe laryngospasm, amongst many else. One child succumbed, and one, Case 3, recovered with neurological sequelae. These are likely to be multifactorial, reflecting the combined impact of hypoxic injury from aspiration pneumonia, ARDS, extended mechanical ventilation, and delayed resolution of spasms, rather than the effects of tetanus alone.

Conclusion

Tetanus continues to be an important, though sporadic and endemic disease in low-income countries. Although tetanus can never be completely eradicated, vaccination remains a simple, cost-effective solution that significantly reduces the risk of the disease, and its continuation must be propagated. Once a diagnosis of tetanus is established, timely intensive care focusing primarily on airway management and spasm control has been shown to greatly influence morbidity and mortality. This, combined with supportive and rehabilitative measures, while combating autonomic instability and nosocomial infections, has proven to be crucial in the successful outcome of paediatric tetanus.