Genesis of Antibiotic Resistance LIX: Fluid Resuscitation Induced Aberrant Intracranial Pressure (“Monroe‐Kellie” Doctrine (MKD) Contort Tethered Leucocytes / Platelets Crest “Critical Closing Pressure” (CCP)

Abstract

NCT01663701 noted that the median volume of iv fluid administered within 6 hours of presenting to ER in the sepsis intervention group was 3.5 L. The mean volume administered during the similar time interval in prior sepsis resuscitation trials were 5.0 L (EGDT); 5.1 L (ProCESS); and 4.5 L (ARISE). Criticisms of NCT01663701 such as a. the suggested vs administered median volume of fluid administered during the initial phase of resuscitation in the sepsis protocol group (3.5L) may have been higher than the 30 mL/kg recommended by SSC guidelines; b.”Each 1‐hour delay in antibiotic administration was associated with an absolute increase in mortality in the range of 5% to 10%”; and c. the median volume of iv fluid administered between ER presentation and 6 hours for BMI 18.5 kg/m2 ~ 70 mL/kg, here we present a plausible pathophysiological sequel as a contributing factor for mortality rate. Within the six hrs. of fluid resuscitation, a surge of fluid bolus mounted an adverse pressure gradient on the sphincters in metarterioles deregulating the pulsatile blood flow into the capillary bed. Based on the “Whole Brain Fluid and Osmolyte Network Model or” or “The whole brain network” approach a mechanistic model inclusive of major cranial compartments simulated the effect of osmotic therapy predicted that critical intracranial pressure (ICP) increased to >30 mmHg, with insufficient cerebral perfusion, and ventriculomegaly. The ventricular enlargement, in turn, reduces extracellular milieu for fluid exchange lead to a chronic increase in ventricular size shifts attributed to osmolyte administered. It is our hypothesis that after fluid resuscitation blood flows against an adverse pressure gradient in the capillary bed. The fluid particles such as activated and/or aggregating Cellular Aggregates near to the endothelial layer due to their low kinetic energy, “Cellular Aggregates” flows in the opposite direction. Such Cellular Aggregates cannot surmount the adverse pressure, lead to the formation of eddies. Such eddies in the arterial end are likely to cause local flow reversal zone and which retard the velocity concurrently the pressure of the blood flow. Under the low velocity and pressure gradient, the cellular eddies start separating from the endothelium referred to as boundary layer separation causing the blood flow to decelerate against an adverse pressure gradient. Then in the upstream part which is the venous end of the capillary bed, where the cellular eddies achieve boundary layer separation, causing blood pressure to drop from that of the arterial end creating the eddies to drag. At this stage, the pressure distribution in the capillary bed is at the stagnation point, where the velocity becomes zero at which cellular eddies form DIC. Sustained fluid bolus with vasopressor likely to form a non‐pulsatile flow pattern forming turbulent eddies in the venous end and disseminate the coagulated eddies leading to an aberration in the “MKD”. Dysregulated ICP, in turn, alter the ARGR leading to hypoperfusion subsequently coma.Support or Funding InformationSupported by pd funds and in part CME activities of Subburaj Kannan MD PhD for www.aaets.org