New viewpoint in exaggerated increase of PtiO2 with normobaric hyperoxygenation and reasons to limit oxygen use in neurotrauma patients

Abstract

Multiple studies have shown that some of cerebral metabolic abnormalities occurring after traumatic brain injuries (TBI) are not of ischemic origin (1-4). The described pattern is called "metabolic crisis without brain ischemia" (5), and is associated with poor outcome within 6 months after trauma (6-8). Nevertheless, targeting adequate cerebral blood flow (CBF) and oxygen delivery (DO2) remains the cornerstone in the clinical management of TBI, especially in the early phase. Surprisingly, DO2 targeted therapy based on an escalation of dissolved O2, has been shown positive outcome in a few cases only, although it causes a significant increase in O2 pressure in cerebral tissue (PtiO2). High inspired O2 fraction or normobaric hyperoxia (NH) leads to a dramatic elevation of PtiO2 to "arterial" levels of 147 ± 36 mmHg (9). This daily and well-known phenomenon so far does not have definitive explanation and differs from the classical notions: oxyhemoglobin saturation (SO2) must remain nearly 100% over a wide range of O2 partial pressures (PO2) greater than 80 mmHg (10). NH induces a negligible increase in the amount of arterial O2 content and DO2, whereas it is associated with an important augmentation of PtiO2, without significant change in cerebral metabolic rate of O2 consumption (CMRO2) (11-14). Furthermore, studies using positron emission tomography, magnetic resonance imaging (MRI), and near-infrared spectroscopy showed an active O2 extraction fraction (OEF) in the non-necrotic tissue during NH (9, 15-18) with negligible increase of regional SO2 (rSO2) at 2.8 ± 1.82% (9) or without changes in rSO2 in tissue with intact autoregulation (16). The data of OEF at 0.56 ± 0.06 in reversible tissue, which although reduced from viable tissue to infarction (19), discards the possibility of a luxury perfusión in these cases. In general, NH causes an insignificant increase or no in rSO2 with an exaggerated elevation of PtiO2, which is equal to or less than end capillary PO2 (20). Thus, with NH the PO2 of end capillary venous blood reaches to "arterial" levels. Therefore, the exaggerated increase of PtiO2 with a negligible increase of rSO2 is incompatible with the classical sigmoidal form of the oxyhemoglobin dissociation curve (ODC). Hereby, the circulated hypotheses of mitochondrial dysfunction as a contributor (21) to high PtiO2 and the loss of O2 homeostatic mechanisms in the injured tissue during NH (22) requires an alternative explanation based on the conformational change of hemoglobin (Hb) quaternary structure (Max Perutz-the Nobel prize in chemistry 1962). This change produces a significant decrease in Hb-O2 affinity, considerable Hb buffering capacity augmentation, and convert the sigmoidal form of ODC to hyperbola. In this commentary, we explain the mechanisms underlying the exaggerated rise in PtiO2 with NH and consider the factors that limiting oxygen use in the damaged cerebral tissue.