Genesis of Antibiotic Resistance LXXII: Turbulence Modeling (TM) of Simplified Severe Sepsis Protocol‐2 (SSSP‐2), NCT01663701: Mechanism(s) of Fluid Volume Overload/endotoxemia Induced Thrombocytopenia / Thrombotic Cascade Augment vasoplegia to elicit Leucocyte(s)‐Platelet(s)‐Erythrocyte(s) aggregates (LPE) rescind starling forces

Abstract

Here we present a plausible schema for fluid resuscitation induced fluid volume overload altering net filtration pressure (NFP) and the onset of comatose. NCT01663701 (PMID: 28973227) noted that the median volume of iv fluid administered between presentation at ED (Emergency department) (Zero hours) (PMID: 20035633) and 6 hours in the sepsis cohort was 3.5 L. The mean volume administered during a similar time interval in prior sepsis ERP trials were 5.0 L (PMID: 11794169, Rivers et.al.,); 20mls/kg iv 0.9% saline with 5% HAS, FEAST, ISRCTN69856593- PMID: 21615299, Maitland et.al.,); Refer Table 1, list of randomized control EGDT, (PMID: 28460438); 5.059L, PMID: 11794169; ProCESS, NCT00510835. (PMID: 24635773); 4.479L; EGDT, ARISE NCT00975793; (PMID: 25272316); 4.2216 L; ProMISe ISRCTN36307479, (PMID: 25776532) (Table 4, Crit Care. 2016; 20: 160. (PMID: 27364620; PMID: 27756870). In essence, fluid overload induced volume expansion is implicit of a pattern of decline in blood flow velocity leading to hypoxia plausibly dysoxia ultimately to anoxia and/or oxygen debt augment platelet activation - aggregation forming LPE occluding thoroughfare capillary bed at the arterial end educe NFP < 10 mmHg impairing filtration, in turn, CCP⇨ vascular shunt. Experimental evidence suggests that the thrombocytopenia in sepsis is initiated by acute and/or chronic viral infection, Rx-immunosuppression, antibiotic therapy, vascular infusion of fluids, which in turn cause an increase in platelet activation, DIC, hemophagocytic lymphohistiocytosis, IgG associated platelets (PAIgG), in a pathogen-associated molecular pattern (PAMPs), subsequent sequestration with leucocytes in neutrophils extracellular traps (NETs) dependent of damage-associated molecular patterns (DAMPs) form a patient-specific LPE occluding the blood flow into the capillary bed (PMID: 31315248; PMID: 29053592). Based on the aforesaid, pathogenesis, we suggest that prior to the admission to the ER, bacteremia with parasitic infection may have caused an increased in LPE formation and sequestration on the damaged glycocalyx impeding the blood flow in turn perfusion (hypovolemia). Our interpretation is that the volume overload exacerbates reperfusion injury of hypoperfused tissues leading to a remote organ injury consequent multiple organ failure due to hypoxia-dysoxia-anoxia cascade fostering an anaerobic/microaerophilic G- pathogens to colonize at an increased rate in vivo. Thus, the impairment of vasomotion by endotoxemia-vasoplegia in the thoroughfare capillary bed is outflanking our TM efforts of defining the mechanisms leading to the increased mortality rate in NCT01663701 (PMID:29332515; PMID:32019600). Taken together we suggest that the mechanism for induction of comatose requires a minimal time constraint (max 30min) in the following sequence: endotoxemia ⇨ vasoplegia ≠⇨ hemostasis≠⇨ homeostasis ≠⇨ NFP <10mmHg ⇔ CCP⇔ GCS scale 3⇔Hypnotic Trans⬅ exception of Lazarus phenomenon ➡ Clinical End Point (mortality).