Brain Shock-Toward Pathophysiologic Phenotyping in Traumatic Brain Injury

Abstract

Severe traumatic brain injury (TBI) is a heterogeneous pathophysiologic entity where multiple interacting mechanisms are operating. This viewpoint offers an emerging, clinically actionable understanding of the pathophysiologic heterogeneity and phenotypic diversity that comprise secondary brain injury based on multimodality neuromonitoring data. This pathophysiologic specification has direct implications for diagnostic, monitoring, and therapeutic planning. Cerebral shock can be helpfully subanalyzed into categories via an examination of the different types of brain tissue hypoxia and substrate failure: a) ischemic or flow dependent; b) flow-independent, which includes oxygen diffusion limitation, mitochondrial failure, and arteriovenous shunt; c) low extraction; and d) hypermetabolic. This approach could lead to an alternative treatment paradigm toward optimizing cerebral oxidative metabolism and energy crisis avoidance. Our bedside approach to TBI should respect the pathophysiologic diversity involved; operationalizing it in types of "brain shock" can be one such approach.

Keywords: brain tissue hypoxia; intracranial pressure; neuromonitoring; shock; traumatic brain injury.

Figure 1.

Mechanisms of secondary injury after brain trauma. Illustration of the various mechanisms discussed in the text. 1. According to the Fick principle, the total amount of oxygen that crosses the blood-brain barrier into the cerebral tissue must be equal to the product of the cerebral blood flow (CBF) and the arteriovenous oxygen content difference (AVDo₂) (see Rosenthal et al [12]); 2. The Lassen CBF pressure autoregulation curve is depicted with right and left shifts, as well as U-shape relationship described between the pressure reactive index (PRx) and cerebral perfusion pressure (CPP) (see Aries et al [13]); 2′. Depiction of normal (pressure-reactive) versus partially collapsed (pressure-passive) microvasculature; 3. Illustration of barrier to oxygen diffusion (see Menon et al [14]); 4. Relationship between CBF and arteriovenous oxygen tension difference (see Rosenthal et al [12]); 5. Mitochondrial dysfunction; 6. Cortical spreading depolarization and depression (see Hartings et al [15]); 7. Shunt physiology due to increased capillary transit time heterogeneity (see Bragin et al [16]). Cao₂ = arterial oxygen content, C_iO₂ = concentration of interstitial oxygen, CMRo₂ = cerebral metabolic rate of oxygen consumption, CSD = cortical spreading depression, C_vO₂ = cerebral venous oxygen content, ISD = isoelectric spreading depression, LDH = lactate dehydrogenase, NAD = nicotinamide adenine dinucleotide, NADH = nicotinamide adenine dinucleotide + hydrogen, ICP = intracranial pressure, Pbto₂ = partial brain tissue oxygen tension, P_vO₂ = partial venous oxygen tension, TCA = tricarboxylic acid.