The Antiedematous Effect of Exogenous Lactate Therapy in Traumatic Brain Injury: A Physiological and Mechanistic Approach

Background Sodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K–Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL. Methods In a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI. Results An equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K–Cl cotransporter 2. Conclusions SL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL.

Incidence and characteristics of cerebral hypoxia after craniectomy in brain-injured patients: a cohort study

OBJECTIVEAfter craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’ objective was to describe the incidence and characteristics of brain hypoxia after craniectomy.METHODSThe authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor.RESULTSThe frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%).CONCLUSIONSCerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors’ findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

Mild Hyperoxia Stimulation Increases Regional Tissue Oxygen Pressure in Rat Hippocampus via Oxygen Radical

Aims: The purpose of this study is to examine a rise of the local tissue oxygen pressure in hippocampus (Hip-pO2) which means neuronal activation by mild hyperoxia through oxygen radical. Study Design: Study was an animal experiment with rat. Place and Duration of Study: Department of Department of Life Science and Applied Chemistry, Nagaya Institute of Technology, between January 2014 and January 2018. Methodology: Rats were exposed to air or mild oxygen gas. At the same time, Local tissue oxygen pressure in hippocampus (Hip-pO2) were measured for 20 min with or without treatment of two type of radical scavengers. Results: The Hip-pO2 levels were significantly increased by mild hyperoxia exposure (50-60% above resting level). The mild hyperoxia-induced enhancement of the Hip-pO2 levels were inhibited by MnTMPyP (radical scavenger), but not by NADPH oxidase (NOX) inhibitor Apocynin. Conclusion: These findings suggested that mild hyperoxia could activate hippocampus through generation of oxygen radicals.

Prognostic value of changes in brain tissue oxygen pressure before and after decompressive craniectomy following severe traumatic brain injury

OBJECTIVEIn severe traumatic brain injury (TBI), the effects of decompressive craniectomy (DC) on brain tissue oxygen pressure (PbtO2) and outcome are unclear. The authors aimed to investigate whether changes in PbtO2 after DC could be used as an independent prognostic factor.METHODSThe authors conducted a retrospective, observational study at 2 university hospital ICUs. The study included 42 patients who were admitted with isolated moderate or severe TBI and underwent intracranial pressure (ICP) and PbtO2 monitoring before and after DC. The indication for DC was an ICP higher than 25 mm Hg refractory to first-tier medical treatment. Patients who underwent primary DC for mass lesion evacuation were excluded. However, patients were included who had undergone previous surgery as long as it was not a craniectomy. ICP/PbtO2 monitoring probes were located in an apparently normal area of the most damaged hemisphere based on cranial CT scanning findings. PbtO2 values were routinely recorded hourly before and after DC, but for comparisons the authors used the first PbtO2 value on ICU admission and the number of hours with PbtO2 < 15 mm Hg before DC, as well as the mean PbtO2 every 6 hours during 24 hours pre- and post-DC. The end point of the study was the 6-month Glasgow Outcome Scale; a score of 4 or 5 was considered a favorable outcome, whereas a score of 1–3 was considered an unfavorable outcome.RESULTSOf the 42 patients included, 26 underwent unilateral DC and 16 bilateral DC. The median Glasgow Coma Scale score at the scene of the accident or at the initial hospital before the patient was transferred to one of the 2 ICUs was 7 (interquartile range [IQR] 4–14). The median time from admission to DC was 49 hours (IQR 7–301 hours). Before DC, the median ICP and PbtO2 at 6 hours were 35 mm Hg (IQR 28–51 mm Hg) and 11.4 mm Hg (IQR 3–26 mm Hg), respectively. In patients with favorable outcome, PbtO2 at ICU admission was higher and the percentage of time that pre-DC PbtO2 was < 15 mm Hg was lower (19 ± 4.5 mm Hg and 18.25% ± 21.9%, respectively; n = 28) than in those with unfavorable outcome (12.8 ± 5.2 mm Hg [p < 0.001] and 59.58% ± 38.8% [p < 0.001], respectively; n = 14). There were no significant differences in outcomes according to the mean PbtO2 values only during the last 12 hours before DC, the hours of refractory intracranial hypertension, the timing of DC from admission, or the presence/absence of previous surgery. In contrast, there were significant differences in PbtO2 values during the 12- to 24-hour period before DC. In most patients, PbtO2 increased during the 24 hours after DC but these changes were more pronounced in patients with favorable outcome than in those with unfavorable outcome (28.6 ± 8.5 mm Hg vs 17.2 ± 5.9 mm Hg, p < 0.0001; respectively). The areas under the curve for the mean PbtO2 values at 12 and 24 hours after DC were 0.878 (95% CI 0.75–1, p < 0.0001) and 0.865 (95% CI 0.73–1, p < 0.0001), respectively.CONCLUSIONSThe authors’ findings suggest that changes in PbtO2 before and after DC, measured with probes in healthy-appearing areas of the most damaged hemisphere, have independent prognostic value for the 6-month outcome in TBI patients.