Genesis of Antibiotic Resistance (AR) LX: Sepsis: Mechanism(s) of differential activation of Extracellular Nucleotide Metabolizing Protein Complex (Ecpx) Augment Cellular Aggregates tethering consequently “Inviscid Instability” for laminar to turbulent transition

The timing, dosage, volume of fluid, antibiotic therapy of the fluid resuscitation strategy for treating sepsis cohort is considered as a pivotal for determining the mortality rate of treating sepsis cohort. NCT01663701 SSSP‐2 noted that the median volume of iv fluid administered between presentation at ER and 6 hours in the sepsis cohort was 3.5 L. The mean volume administered during a similar time interval in prior sepsis resuscitation trials were 5.0 L (N Engl J Med. 2001; 345(19):1368); 5.1 L; and 4.5 L. Given the significance of such as the suggested vs administered median volume of fluid administered during the initial phase of resuscitation, 3.5L may have been higher than the 30 mL/kg recommended by the Surviving Sepsis Campaign guidelines. As presented, the median volume of intravenous fluid administered between presentation in ER and 6 hours for BMI 18.5 kg/m2 ~ 70 mL/kg (NCT01663701). Based on the aforesaid clinical estimates, here we present a plausible physiological the sequel as a contributing contraption for increased mortality rate not withstanding another unknown clinical variable (s) in EGDT. The 6 hrs period between the time of presentation to ER and iv fluid resuscitation is considered physiologically pivotal for the hemodynamic aberration for the transition of laminar to turbulent blood flow pattern in the capillary bed of microcirculation. The plausible role of EC 3.6.1.15–CD36 ∞ Myoglein complex and EC 3.6.1.5 (Thr Hae. 1999;82(5):1538) induced leucocyte tethering causing the formation of eddies with an eventful of “DIC” amalgamated to “CCP” remains to be elucidated. Metabolic studies of CD39/CD73 function in intact intestinal epithelia revealed that hypoxia enhances CD39/CD73 function as much as 6 +/− 0.5‐fold over normoxia (Modified in part & verbatim J Clin Invest. 2002; 110(7):993). “Linear hydrodynamic stability theory” attribute the sheared flow as a fundamental cause for amplification of disturbances and predicted values of the Reynolds numbers (Re) Rex,crit (= Uxcrit/V) amplification and Rex,tr (= Uxtr/V) for fully turbulent flow to occur. Flows with a velocity distortion due to unpredictable size of cellular aggregates represents the point of inflexion (Ref. Compare Figure 3.4 a & b: An Intro to CFD, p 45: ISBN 978‐8131720486) and infinitesimal disturbances in part because of high Re in turn, referred as “inviscid instability”. Such fluctuating velocity profiles are known to form “Jet Flow”, mixing of aggregates inclusive of boundary layer separation, and wakes. Blood flow in sepsis cohort where the cellular aggregates flowing with laminar velocity distributions prior to the fluid resuscitation without a point of inflexion Ref Fig: 3.4b are subjected to viscous instability within the 6hrs period. It is our hypothesis that such flow pattern at high Re likely to cause turbulence in venous end of the capillary bed. Such anomaly would likely to be the contributing factor for higher mortality rate in NCT01663701 sepsis cohort. Support or Funding Information Supported by professional development funds and in part CME activities of Subburaj Kannan MD PhD for www.aaets.org