Phospholipid Nanoparticles Increase P/F Ratio in Septic Shock

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Critical Care Medicine


Introduction: Acute respiratory and cardiac failure commonly occur in septic shock patients and may contribute to higher in-hospital mortality. The current protocol for treating septic shock has continued controversy with the use of vasopressors to elevate the mean arterial pressure (MAP) between 60 to 65 mmHg. Hypotension that is minimally responsive to vasopressors occurs in septic shock primarily because of the overproduction of nitric oxide (NO). VBI-S is a phospholipid nanoparticle emulsion that exhibits concentration-dependent absorption and release of NO. We hypothesized that because of this property, infusion of VBI-S would result in the reversal of the patient’s hypotensive state. In our phase IIa clinical trial, VBI-S was administered to severely ill septic patients in whom fluids had failed to increase their MAP greater than or equal to 65 mm Hg. In addition to measuring the changes in MAP, we measured the ratio of arterial pO2 over the fraction of inspired oxygen (P/F).

Methods: This was an open-label phase IIa study of 20 patients aged 18 years and above. Hypotensive septic shock patients in whom fluids had failed to elevate MAP above 65 mmHg received VBI-S infusion. VBI-S was infused as a volume sufficient to increase MAP by 10 mmHg or more. A mean of 560.96 ± 83.24 cc was given within 24 hours. The P/F ratio was measured in 17 patients and were analyzed at 24 hours and 48 hours post VBI-S infusion. Data are mean ± SE.

Results: The enrolled patients (N = 20) had a sequential organ failure assessment (SOFA) score of 14.0 indicating severe sepsis. All patients were on 1-4 vasopressors. Within a mean of 90 minutes after VBI-S infusion, the MAP increased from 64.50 ± 0.96 to 77.50 ± 1.06 mmHg (p < 0.0001). Patients (N=17) also had an increased P/F from 2.0 ± 0.20 to 2.6 ± 0.20 (p = 0.0024) within 24 hours post-VBI-S infusion and to 2.5 ± 0.22 (p = 0.0210) within 48 hours post-VBI-S infusion.

Conclusions: Intravenous infusion of VBI-S increased both the MAP and P/F ratio in septic shock patients. No adverse effects of VBI-S were observed. Future research should establish the biochemical effects of VBI-S in other medical conditions mediated by NO overproduction resulting in decreased MAP and P/F.



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