Dexamethasone in Enteric Fever Encephalitis
Dexamethasone should be administered as adjunctive therapy in enteric fever with encephalopathy, based on evidence showing substantial mortality reduction when high-dose intravenous dexamethasone is used alongside appropriate antimicrobial therapy. 1
Evidence for Use in Enteric Fever Encephalopathy
The most direct evidence comes from a retrospective analysis of diarrheal patients with enteric fever and encephalopathy, which demonstrated that survivors were significantly more likely to have received high-dose dexamethasone compared to those who died (100% vs 0%; p < 0.001). 1 This study specifically examined multi-drug resistant Salmonella Typhi and Salmonella Paratyphi infections. 1
The recommended regimen is high-dose intravenous dexamethasone as an adjunct to appropriate antimicrobial therapy. 1 A case report further supports this approach, describing successful treatment of a child with enteric fever complicated by encephalopathy, myocardial dysfunction, and hemophagocytic lymphohistiocytosis using ceftriaxone combined with dexamethasone. 2
Mechanistic Rationale
The pathophysiology parallels bacterial meningitis, where dexamethasone attenuates the subarachnoid space inflammatory response that contributes to morbidity and mortality. 3, 4 The steroid decreases:
- Cerebral edema 3, 4
- Increased intracranial pressure 3, 4
- Altered cerebral blood flow 3, 4
- Cerebral vasculitis 3, 4
- Neuronal injury mediated by pro-inflammatory cytokines 3, 4
Dosing Considerations
While specific dosing for enteric encephalopathy is not standardized in guidelines, the evidence suggests high-dose dexamethasone is critical. 1 For reference, bacterial meningitis guidelines recommend:
- Adults: 10 mg intravenously every 6 hours for 4 days 4
- Children: 0.15 mg/kg intravenously every 6 hours for 2-4 days 4
The dexamethasone should ideally be administered 10-20 minutes before or concomitant with the first antimicrobial dose, though it can be given up to 4 hours after antibiotics are started. 4
Critical Caveats
Hypoglycemia monitoring is essential, as survivors in the enteric fever encephalopathy study had significantly less hypoglycemia than non-survivors (6% vs 67%; p = 0.045). 1 This suggests hypoglycemia may be both a prognostic marker and a complication requiring vigilant management.
Ensure appropriate antimicrobial coverage for multi-drug resistant Salmonella species, as all isolates in the key study were multi-drug resistant. 1 The combination of effective antibiotics with dexamethasone appears synergistic in reducing mortality. 1
Do not use dexamethasone if enteric fever is ruled out, as the evidence is specific to this condition with encephalopathy. 4 Additionally, early steroid use in certain viral encephalitides (such as enterovirus 71) can worsen outcomes, emphasizing the importance of accurate diagnosis. 5