Previous studies demonstrated that a protein-free phospholipid rich emulsion (PRE) improved survival of endotoxin challenged mice (PNAS, 90:12040, '93). Since PRE can absorb endotoxin in vivo, we hypothesized that PRE treatment would attenuate live gram negative infection. Pigs were instrumented to measure cardiac output, LV pressure and diameter, pulmonary and aortic pressures. Seven days after surgery, basal values were obtained (Day 0). Pigs were given a bolus of PRE followed by 48 hrs continuous infusion (CIVI). This protocol will raise serum phospholipid to 200-400mg/dl, depending on dose of PRE.) Thirty min after bolus PRE, a fibrin clot infected with 2-5×105 cfu E.coli O111.B4/kg was implanted intraperitoneally. 0/5 saline treated and 1/5 placebo control (C) pigs survived to 6hrs. 6/6 pigs treated with 100 mg bolus, 50 mg CIVI, 7/8 treated with 100 mg bolus, 25 mg/kg/hr CIVI and 3/5 treated with 50 mg/kg bolus, 25 mg/kg/hr CIVI survived to 40 hrs (p<0.01, chi2). Control treated pigs demonstrated significant time-dependent (0-4 hrs) declines in cardiac output (CO, 5.0±0.2 to 1.1±0.2 L/min), %diameter shortening (%DSh, 18 to 12%) and increases in SVR and PVR (60 to 119; 25 to 134 mmHg/L/min, respectively). PRE-treated pigs demonstrated a similar decline of CO on day 1 (4.3 to 1.9) but recovered on days 2,3 and 4 (3.7-4.9 L/min). %DSh was depressed Day 1 (23 to 12%), but recovered to basal by day 4 (19-26%) following higher doses of PRE; at the low dose, %DSh did not recover. Plasma TNFα levels rose 10xbasal at 6 hrs after infection. PRE treatment reduced this rise in circulating TNFα levels at 6 hrs in all treated groups in a PRE dose dependent manner. These data suggest that pretreatment with phospholipidrich emulsion improved survival and cardiovascular function in a live organism, infection model of severe septic shock. PRE probably produced this beneficial effect by adsorbing endotoxin and reducing endotoxin stimulated inflammatory messages.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine