Fluid resuscitation and antibiotic administration are critical components of the early treatment of sepsis. We evaluated the impact of three different early resuscitation regimens on cardiac performance in a murine model of sepsis.
3 groups of 8 C57Bl/6 mice were made septic by cecal ligation and double perforation (CLP); 5 controls had sham ligation. After CLP animals received 1 of 3 fluid regimens: 35mL/kg normal saline bolus SQ after surgery only (None), 35mL/kg after surgery and then every 6hr, (Partial) and 100mL/kg after surgery and then every 6hr (Full). All 3 groups received ceftriaxone, 30mg/kg and clindamycin, 25mg/kg at 6 and 12hr. Animals were anesthetized briefly with isoflurane for echocardiography using a high-resolution ultrasound system (30Mhz scan-head). Stroke volume (SV, μL) was assessed by Doppler in the aortic outflow tract and fractional shortening (FS, %) by M-mode in the short axis view. Cardiac output (CO, mL/min) was calculated as SV*HR.
From 3 to 9hr after CLP, CO was reduced from 25±2 to 13±2 (None), 24±4 to 15±5 (Partial) and 26±5 to 17±4mL/min (Full), largely due to a reduction in SV, from 56±6 to 23±2 (None), 51±6 to 28±7 (Partial), and 58±7 to 32±5μL; (Full) (p<0.05 vs baseline and sham operated animals in all groups. Heart rate did not change significantly. Animals that received aggressive resuscitation (Full) reached a normodynamic state at 15hours, CO 23±7; SV 48±9; HR 475±74, p=NS vs baseline and sham operated animals. Unresuscitated and underresuscitated animals remained in a hypodynamic state, CO 14±6; SV 30±10; HR 470±50 (None) and CO 15±3; SV 40±9; 395±35 (Partial), p<0.05 vs baseline, sham operated and aggressively resuscitated animals (Full).
Adequate fluid resuscitation is mandatory to restore a normodynamic state in sepsis. In this murine model, which replicates clinical sepsis, early underresuscitation can lead to a sustained hypodynamic state. Early and aggressive resuscitation is necessary to reestablish normal hemodynamics.
Even seemingly minor degrees of underresuscitation early could potentially impair hemodynamics in later phases of sepsis in patients.
Massimiliano Guglielmi, University grant monies.