Profile of Immunomodulation in Children with Severe Dengue Admitted in PICU

INTRODUCTION: Children with severe dengue have high mortality with limited therapeutic options. Many factors are thought to contribute to organ dysfunction in dengue, including hypoxic injury due to decreased perfusion, direct damage by the virus and immune mediated injury. Although there has been progress in understanding the mechanistic basis for the initiation and propagation of cytokine storm syndromes, there remains a considerable unmet need for effective therapies. Hypoxic damage (prolonged hypotension) carries poor prognosis and has high mortality inspite of using immunomodulatory therapy. OBJECTIVE: PRIMARY OBJECTIVE: To evaluate difference in mortality among severe dengue patients receiving immunomodulation therapy, with a focus on hemodynamic status at the time of intervention. SECONDARY OBJECTIVE: Profile of patients on immunomodulation. Factors affecting outcomes. MATERIALS AND METHODS: The study was carried out in 24 bedded PICU at RCH, Bengaluru. It was a single Centre descriptive Observational study over a period of 25 months. INCLUSION CRITERIA: 1 month-18 years. Children with severe dengue in PICU who have received immunomodulation of any form. EXCLUSION CRITERIA: Children having an alternative diagnosis like sepsis at admission. Patients on immunosuppressive therapy or have taken other biologics in the past 1 month, underlying malignancy, immunosuppression or chronic illness. Methodology. Immunomodulation will be administered if >30 mL/kg colloid/crystalloid resuscitation, severe plasma leakage leading to shock/fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as hepatitis (elevated transaminases ≥1,000 IU/L), impaired consciousness, cardiac dysfunction. The choice and dose of immunomodulation will be administered at discretion of the treating consultant (Rheumatology Team and Intensive care). The choice of immunomodulation will include Anakinra, Corticosteroids, IVIG, Plasmapheresis. RESULTS: A total of 52 pediatric patients received immunomodulation therapy, consisting of Anakinra combined with IVIG, steroids, or plasmapheresis and mortality rate was 32.6%(17/52). Among children with Decompensated Shock all received Anakinra(21/21),42% (9/21) received IVIG, 28% (6/21) underwent TPE, 71% (15/21) received steroids. Decompensated shock was associated with significantly higher mortality compared to compensated shock (57% vs. 16%) and was statistically significant (p < 0.001). Patients presenting with decompensated shock had higher peak median values of ferritin (64393.6 ± 50259.9), CRP (52.7 ± 69.3), SGOT (2488.3 ± 2934.2), INR (2.5 ± 1.2), lactate (8.4 ± 5.0). In children presenting with compensated shock and multiorgan failure, immunomodulation resulted in improvement in pSOFA which was statistically significant (p0.001). Cause of death in children presenting with compensated shock were CNS infarcts/bleed(3/5), culture positive sepsis(1/5), SMOF(1/5) Among those presenting with decompensated shock, Mean VIS score was 85(100-253) vs 13(0-100) among compensated shock group, duration of shock reversal was >36 hrs and cause of death was progressive hemodynamic instability. DISCUSSIONS: While immunomodulation therapies, such as IVIG, steroids, or Anakinra, show promise in severe dengue cases, it is critical to identify patients who will truly benefit from such therapies. Patients with end-organ damage from prolonged hypoxia may not exhibit the same inflammatory pathways that are targeted by immunomodulatory therapies. In these cases, the immune system may be in a state of exhaustion or dysregulation, rather than a hyper-inflammatory state that would respond to immunomodulation.