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OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion

Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion

Inflammatory mediators.

<p><b>Statistics</b>: Values are expressed as median and range.</p><p>WBC  =  White blood cell count (x10⁹/L); IL-1 =  Interleukin 1(pg/ml); TNF-α =  Tumor Necrosis Factor-α (pg/ml); LPS =  Lipopolysaccharide; iNO =  Inhaled nitric oxide.</p>1<p>within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Respiratory variables.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Changes in serum creatinine levels over time, unit = µmol/L. LPS = lipopolysaccharide, IV steroid = intravenous hydrocortisone, iNO = inhaled nitric oxide.

<p>Values are shown as median and range. Data have been collected at 0, 12, 24 and 30(*: p = 0.02). No significances between treatment groups (IV steroid, iNO, IV steroid + iNO) and LPS alone were noted.</p

Circulatory variables.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours.</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences against LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Kidney function.

<p><b>Statistics</b>: Values are shown as median and range.</p>1<p>Within group from baseline to 30 hours (urine output: no baseline value, volume collected over time, from 12 to 30 hours).</p>2<p>Comparison of distribution of differences between LPS-only and control.</p>3<p>Comparison of distribution of differences versus LPS-only (Bonferroni-Holm adjusted p-values within parenthesis).</p

Study protocol.

<p>The scale bar depicts time in hours.</p