Genesis of Antibiotic Resistance (AR) LIV: “Confounder Effect”: Sepsis with Comorbidity ‐ An Indomitable Turbulence Modeling Consignment

Abstract

To delineate the hemodynamic basis of exacerbated mortality rate in Early Resuscitation Protocol (ERP) for sepsis with comorbidity, here we present the results of a comparative simulation analysis of “Net Filtration Pressure” (NFP) at homeostasis (Laminar) vs Sepsis with comorbidity (Laminar‐transition‐turbulence‐collapse) in the contexture of Fahraeus – Lindqvist Effect (FLE), plasma skimming, swirling & sigma effect and its role in Critical Closing Pressure (CCP) (Transition to Turbulence consequent collapse). At homeostasis, Starling Forces: NFP= (BHP+IFOP) − (BCOP+IFHP)] at the arterial end, net pressure is outward at 10 mmHg (filtration) and at the venous end, net pressure is inward at −9 mmHg (reabsorption). [Starling equation: Jv = Kf ([Pc − Pi] − σ [πc − πi]), where Jv is the net fluid movement between compartments and [Pc − Pi] − σ [πc − πi] is the net driving force, Pc is the capillary hydrostatic pressure, Pi is the interstitial hydrostatic pressure, πc is the capillary oncotic pressure, πi is the interstitial oncotic pressure, Kf is the filtration coefficient – a proportionality constant, and σ is the reflection coefficient (Fig 3a ‐ Ind J Ana. 2019; 63(1):6). The ERP, NCT01663701 (JAMA.2017;318(13):1233) based sepsis cohort data are sepsis‐ suspected infection plus ≥2 (SIRS), MAP < 65mmHg, sepsis‐induced hypotension 89mmHg/55mmHg (~ 2 liters of bolus administered within 1 hr of enrollment, edema, hypoxemia, hypoperfusion, tachypnea, and respiratory failure due to a lack of ventilator support. For simulation of Starling forces, the impact of FLE, plasma skimming effect, sigma effect (blood flow is not continuum), loss and/or dysfunctional glycocalyx (Crit Care. 2019;23(1):259) (substituting πg = 0mmHg (null & void) instead of πi, revised starling equation: Jv = Kf ([Pc − Pi] − σ [πc − πg] (Br J Ana. 2012 Mar;108(3):384) induce sustained leakage & hemoconcentration cellular aggregates (RBC, WBC, thrombocytes) – large eddies, CCP derived based on Law of La Place, and swirling effect (variable Schmidt number) were considered. Based on the simulation analysis, the prediction of NFP at arterial and venous end would be ~ +10mmHg favoring fluid filtration into the interstitial space causing edema, intra vascular hypotension, hypoperfusion and rheological factors predicted to be PI <1.05%, SpO2≦95%, PaO2 of 55 mmHg, SaO2<90%, SvO2<90%, StO2 below normal, DO2I below normal range, FiO2 <0.21(21%), PaCO2< 38 – 42 mmHg and PaO2/FiO2 <200mmHg. If numerous thrombi are forming simultaneously (equivalent to large‐eddy: Laminar to turbulence transition, then coagulation factors and platelets can become depleted (plasma skimming) causing hemorrhage (septic embolism tend to break up but not in this instance since glycocalyx is null and void) analogous to large‐eddy cascading in to smaller eddies (Fully Turbulent flow). Absence of cascading would likely to obstruct the blood flow and induce ischemia‐induced infarcts in the capillary bed. Though the “Counter‐Inflammatory response syndrome” would likely to mitigate thrombosis, plasma skimming/sigma effect on the cellular aggregates, would lead to thrombosis (large eddies) and CCP.Support or Funding InformationSupported by professional development funds provided by SWTJC to Subburaj Kannan