Sepsis and septic shock: survivorship and the longer-term health and economic implications of hydrocortisone treatment

Sepsis is life threatening organ failure due to a dysregulated host response to infection. It is a leading cause of death and disability worldwide. Priorities of management include early detection and treatment with appropriate antimicrobials, along with organ support therapies administered in the intensive care unit (ICU). Corticosteroids are an adjunctive therapy used to treat patients with septic shock. They modulate the immune and cardiovascular response to infection, reducing the duration of mechanical ventilation and ICU stay. The longer-term health and economic impacts of corticosteroid treatment are unknown. There is also a paucity of data describing the longer-term health and economic burden of sepsis for patients treated in Australian ICUs. This thesis contributes novel data to describe sepsis survivorship in Australia, including the longer-term health and economic burden of sepsis and septic shock, and the longer-term health and economic implications of adjunctive corticosteroid treatment in women and men with septic shock. The main findings are: 1. In a propensity score matched analysis of ICU patients with and without sepsis: 1. Patients with sepsis had increased healthcare resource use and costs, compared to other critically ill patients. 2. In a cost-effectiveness analysis of a clinical trial assessing the impact of hydrocortisone treatment compared to placebo on mortality due to septic shock: 1. Hydrocortisone treatment in the ICU did not significantly impact longer-term mortality, health-related quality-of-life, healthcare resource use or costs. 2. Hydrocortisone treatment was unlikely to be cost-effective overall, but more likely to be cost-effective in women, compared to men. 3. In a follow-up sex-disaggregated analysis of the trial: 1. Women treated with hydrocortisone had a higher risk of shock recurrence, compared to men. 2. Hydrocortisone treatment significantly reduced the time to ICU discharge and cessation of mechanical ventilation in men, but not in women. Sepsis survivors experience ongoing disease sequelae, resulting in increased healthcare resource use and costs. Hydrocortisone treatment, administered in the ICU, does not mitigate the longer-term sequelae of sepsis and is unlikely to be cost-effective. Strategies to reduce the sequelae of sepsis, including understanding sex differences and other health inequalities, is an important direction for future research