Genesis of Antibiotic Resistance (AR) L: Mechanism of “Hypotension‐Hypoxemia–Hypoxia (H3)” and sepsis, septic shock, and septicemia (S3) engendered mortality
Authors: Escalante Jesus , Garcia Elizabeth , Galindo Rocio , Buentello Lucila , Mendoza Jonathan , Alfaro Maria , Kannan Subburaj 
Published: June 2021

ProCESS, ARISE, ProMISe, PRISM, SSSP‐2, and FEAST are clinical trials exploring the implication of an early resuscitation with intravenous fluids, vasopressors, and blood transfusion (Early Goal Directed Therapy @ EGDT) to reduce mortality as compared with usual care for patients with H3 and S3 showed an overall increase in in‐hospital mortality. In an effort to delineate the underlying mechanism, we have analyzed the hemodynamic factors of NCT01663701. The patient cohort with hypotension had the blood pressure recorded as 95mmHg / 61mmHg (Mean IQR) after 6hr of intravenous fluid administration and SpO2 as 36 (p value<0.03). We have determined the pulse pressure (PP) of 34mmHg indicating the reduced perfusion index (PI) and hypovolemic shock. Our interpretation is that it is hypoxemia (an abnormally low arterial oxygen tension (PAO2) in the blood), escalating hypoxia to dysoxia and/or anoxia? As a result of sustained H3, the SpO2 (peripheral capillary oxygen saturation), as determined an average of 38% which is likely to cause a decrease in PI <50% far below normal PI (95%). Our inference is that such clinical scenario would likely to cause a shift in the hemoglobin ‐ oxygen saturation curve to the left (Ref Figure 41–8 Oxygen‐Hemoglobin Dissociation Curve, p530: Guyton‐Hall Med Phys Elsevier 13ed: 2016) while the Frank – Starling Curve to the left implicit of cardiac output failure with an ensuing endocarditis. It is our interpretation under these conditions; EGDT would unlikely to confer benefit in terms of PI. Our effort to determine the Cardiac Index (CI) was unsuccessful due to the fact that body surface area (BSA) was not available. We have determined the Mean Arterial Pressure (MAP) of 66 mmHg after 2 hr. starting the treatment while 72 mmHg after 6 hr. of intravenous fluid administration indicating an improvement in PI. However, patients with low hemoglobin level (<7g/dl) in sepsis protocol cohort would likely to suffer anemia leading to decrease oxygen delivery to tissues in turn decrease arterial oxygen content. SAPS‐3 (Simplified Acute Physiology Score (SAPS) 52 – 54 indicating the absolute risk of in‐hospital mortality by 15.1% reported in this study probably after the 6hr of intravenous fluid administration (Refer Figure 2 Intensive Care Med. 2005 31(10):1345). 86 patients in the sepsis protocol exhibiting Glasgow Coma Scale (GCS) score 13–15, while eleven patients were in GCS score range of 3–8 indicated that both cohort suffered a trauma possibly with traumatic brain injury (TBI) and meningitis. Based on aforesaid physiological factors, here with we propose that sustained “H3” in patients of sepsis protocol would likely to cause an increase in growth of the anaerobic bacteria leading to Septicemia and/or Bacteremia. With an ensuing septicemia, ARB like P. aeruginosa under hypoxia has been shown to have an increased expression of resistance‐nodulation‐division (RND) family of drug efflux pump genes, conferring AR selection pressure. Taken together, sustained H3 ‐ DIC exacerbate S3 lead ramping up ARG in ARB augmented mortality quotient.Support or Funding InformationSupported by professional development funds from SWTJC and CME activities of Subburaj Kannan MDThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.