Topical Bicarbonate Therapy to the Spleen Improves Survival in Rats with Severe Intra-Abdominal Sepsis

Sepsis remains a leading cause of mortality in critically ill patients, particularly those with intra-abdominal infections, which account for up to two-thirds of surgical sepsis cases. Despite extensive research, treatment has been limited to infectious source control, antibiotics, and supportive care. Excessive immune activation, particularly from splenic cytokine production, drives systemic inflammation and organ failure in sepsis. Emerging evidence suggests oral sodium bicarbonate (NaHCO₃) may induce a splenic anti-inflammatory phenotype. The present study postulated that direct topical splenic application of NaHCO₃ during source control laparotomy may attenuate splenic proinflammatory signaling and improve survival in rats with feculent peritonitis.

Male Sprague-Dawley rats underwent cecal ligation and incision (CLI) to induce sepsis. Two hours post-CLI, animals underwent peritoneal washout with either physiologic saline (0.5 mL/g, PS, control), 0.1 mEq/mL NaHCO₃ (bicarbonate peritoneal washout group), PS washout plus topical splenic NaHCO₃ application (1 mEq/mL, 1 µL/g), or PS washout with osmolality-matched 5.8% hypertonic saline (HTS) topical splenic application (osmolality control, 1 µL/g). Survival was monitored for 10 days.

Peritoneal NaHCO₃ washout prolonged survival (median 13.5 vs. 9.0 h, p = 0.01); however, all animals died within 36 h. In contrast, topical splenic NaHCO₃ resulted in 60% survival at 10 days, an effect not replicated with HTS. Splenic NaHCO₃ application inhibited the Caspase-1/NLRP3/IL-1β axis, neutrophil extracellular traps and promoted an anti-inflammatory M2 phenotype.

Topical splenic NaHCO₃ application was associated with improved survival in severe intra-abdominal sepsis by modulating splenic immune function. This novel tactic holds translational potential as a targeted immunomodulatory adjunct during surgical source control.