An exploratory study investigating the effect of targeted hyperoxemia in a randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma and hemorrhagic shock in cardiovascular healthy pigs

Abstract

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg−1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (PaO2 = 200 – 250 mmHg) or normoxemia (PaO2 = 80 – 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data.

13C-Metabolic flux analysis detected a hyperoxemia-induced reduction of tricarboxylic acid cycle metabolism in granulocytes during two models of porcine acute subdural hematoma and hemorrhagic shock

“…1316). This study is an exploratory post hoc analysis of blood samples obtained during two long-term studies of combined ASDH and HS investigating swine with or without coronary artery disease over a period of three days ( 7 , 8 ). The experimental procedures were identical for both studies except for the utilization of the two different swine strains ( 7 , 8 ).…”

“…This study is an exploratory post hoc analysis of blood samples obtained during two long-term studies of combined ASDH and HS investigating swine with or without coronary artery disease over a period of three days ( 7 , 8 ). The experimental procedures were identical for both studies except for the utilization of the two different swine strains ( 7 , 8 ). Data of studies pertaining to survival, hemodynamics, gas exchange, acid-base state, brain perfusion, oxygenation, and neurologic outcome are reported in the respective publication.…”

“…Similar positive effects could manifest for TBI patients by counteracting TBI-induced vasodilation and brain edema due to allowing the reduction of intracranial pressure (ICP) while maintaining tissue oxygen supply ( 6 ). In this regard, we had recently demonstrated that targeted hyperoxemia improved neurological function in a porcine model of combined acute subdural hematoma (ASDH) and HS ( 7 , 8 ).…”

Porcine blood cell and brain tissue energy metabolism: Effects of “early life stress”

“…Mitochondrial respiration in the isolated immune cells as well as the brain tissue specimens (pre-frontal cortex) was measured by high-resolution respirometry using the Oxygraph-2K ® (Oroboros Instruments, Innsbruck) as described previously ( Datzmann et al, 2023 ; Datzmann et al, 2021 ; Zink et al, 2021 ; Wolfschmitt et al, 2023 ) This device allows for simultaneous recording of the O 2 concentration in two parallel chambers calibrated for 2 mL of respiration medium MiR05 ( Doerrier et al, 2018 ; Zink et al, 2021 ). This medium is composed of 110 mM D-Sucrose (Sigma Aldrich, St. Louis, MO, United States), 60 mM K-Lactobionate (Sigma Aldrich, St. Louis, MO), 0.5 mM ethylene glycol tetra acetic acid (Sigma Aldrich, St. Louis, MO), 1 g/L bovine serum albumin free from essentially fatty acids (Sigma Aldrich, St. Louis, MO), 3 mM MgCl 2 (Scharlau, Hamburg), 20 mM taurine (Sigma Aldrich, St. Louis, MO), 10 mM KH 2 PO 4 (Merck, Darmstadt), 20 mM HEPES (Sigma Aldrich, St. Louis, MO), adjusted to pH = 7.1 with KOH and equilibrated with 21% O 2 at 37°C.…”

“…Whole blood superoxide anion (O 2 •− ) concentrations were determined immediately after sampling as described previously ( Zink et al, 2021 ; Datzmann et al, 2022 ; Datzmann et al, 2023 ). For this purpose, 25 µL of whole blood were mixed with an aliquot of 25 µL freshly thawed CMH spin probe solution.…”