Genesis of Antibiotic Resistance (AR) LXXXI: Turbulence Modeling of Simplified Severe Sepsis Protocol‐2 (SSSP‐2), NCT01663701: ERP Induced Fluid Volume Expansion Confer Transition from Laminar to Turbulence by Discontinuity

NCT01663701(PMID:28973227) observed that a primary outcome of in‐hospital mortality (ihm) occurred in 51 of 106 patients (48.1%) in the sepsis protocol group vs 34 of 103 patients (33.0%) in the usual care group while the vital status after hospital discharge at day 28 reported for 97 patients in each study group; 28‐day mortality was 67.0% with the sepsis protocol vs 45.3% with usual care. Hypothesis: Based on the data on risk of ihm by subgroup for patients treated with the sepsis protocol vs usual care (Fig3), compared to elements of sepsis resuscitation (Table 2), and baseline characteristics of the patients (Table 1), we hypothesize that the discontinuity in fluid volume due to ERP is the pivotal determining factor for an exacerbated mortality rate in NCT0166370. Relevance of Central Venous Pressure(CVP) or Jugular Venous Pressure (JVP) for the Determination of Fluid Overload (PMID: 23774337, PMID: 24132054) : NCT01663701, p1237, Table 1: The JVP data indicate that the baseline: by proximity to the sternal angle, ≥ 4cm below : sepsis protocol cohort: 32.1% vs usual care: 40.8%; 1‐3cm below: sepsis protocol cohort: 28.3% vs usual care 21.4%; At the sternal angle, 20.8% vs 27.2%; ≥ 1 cm above: sepsis protocol 20.8% vs usual care 10.7%. Cause(s) of elevated CVP or JVP: A plausible cause would be RV failure (pulmonary edema!) due to fluid volume overload by excessive fluid administration. Geometry, Governing Eq. & Analysis: The mass continuity eq: 2.17, (p14‐ISBN‐13:978‐0521598866); where V 1 = fluid velocity, ρ 1 = fluid density, at terminal arteriole (cross‐sectional area) = A 1 and t is time interval dt, prior to ERP , length dl 1 = V 1 dt mass that enters the A 1 in the time interval is: dm 1 =ρ 1 dV 1 = ρ 1 A 1 dl 1 =ρ 1 A 1 v 1 dt. After the ERP, the expanded fluid volume passing through metarteriole (cross‐sectional area) = A 2 and length dl 2 = V 2 dt in the time interval dt is =dm 2 =ρ 2 dV 2 =ρ 2 A 2 dl 2 =ρ 2 A 2 v 2 dt . As per the mass continuity equation, (flow at any given point in a closed hydraulic system will be equal to flow at any other points) an equal amount of mass that enters the area A 1 in the time interval dt, must pass through area A 2, therefore, dm 1 =dm 2 or ρ 1 A 1 v 1 dt=ρ 2 A 2 v 2 dt. Dividing by dt, will result ρ 1 A 1 v 1 =ρ 2 A 2 v 2 for a steady flow pattern referred to as mass continuity equation for steady flow. Our simulation analysis implicates that for the ERP induced fluid volume overload fluid flow is A 1 v 1 ≠ A 2 v 2 . The rationale is that, the laminar fluid flow is in streamlines with equal space but ERP induced will not be in streamline but widely spaced, ⬆ viscosity, ⬆ rate of LPE aggregation and ⬇ velocity, ⬆ torque & drag with an unknown angular momentum, on endothelial layer in terminal arteriole. Prospects : It is suggested that the total mass of expanded fluid vol. within 6 hrs, entering/exiting the terminal arteriole (Cerebral BBB) elicit CCP rupturing the pre‐capillary vessels due to an adverse pressure gradient (APG). Differential shear stress due to APG, induce temporal regulation of ARGR expression in clinical persisters in vivo w/ or w/o vasoplegia may have been the cause for an exacerbated mortality in NCT01663701.