Oxygen imaging of hypoxic pockets in the mouse cerebral cortex.

Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension (Po2) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for Po2 imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined "hypoxic pockets" and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.

Rapid and persistent decrease in brain tissue oxygenation in ovine gram-negative sepsis.

The changes in brain perfusion and oxygenation in critical illness, which are thought to contribute to brain dysfunction, are unclear due to the lack of methods to measure these variables. We have developed a technique to chronically measure cerebral tissue perfusion and oxygen tension in unanesthetized sheep. Using this technique, we have determined the changes in cerebral perfusion and Po2 during the development of ovine sepsis. In adult Merino ewes, fiber-optic probes were implanted in the brain, renal cortex, and renal medulla to measure tissue perfusion, oxygen tension (Po2), and temperature, and flow probes were implanted on the pulmonary and renal arteries. Conscious sheep were infused with live Escherichia coli for 24 h, which induced hyperdynamic sepsis; mean arterial pressure decreased (from 85.2 ± 5.6 to 71.5 ± 8.7 mmHg), while cardiac output (from 4.12 ± 0.70 to 6.15 ± 1.26 L/min) and total peripheral conductance (from 48.9 ± 8.5 to 86.8 ± 11.5 mL/min/mmHg) increased (n = 8, all P < 0.001) and arterial Po2 decreased (from 104 ± 8 to 83 ± 10 mmHg; P < 0.01). Cerebral perfusion tended to decrease acutely, although this did not reach significance, but there was a significant and sustained decrease in cerebral tissue Po2 (from 32.2 ± 10.1 to 18.8 ± 11.7 mmHg) after 3 h and to 22.8 ± 5.2 mmHg after 24 h of sepsis (P < 0.02). Sepsis induced large reductions in both renal medullary perfusion and Po2 but had no effect in the renal cortex. In ovine sepsis, there is an early decrease in cerebral Po2 that is maintained for 24 h despite minimal changes in cerebral perfusion. Cerebral hypoxia may be one of the factors causing sepsis-induced malaise and lethargy.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Recovery of Hypoxic Regions in a Rat Model of Microembolism.

OBJECTIVES: Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism. MATERIALS AND METHODS: In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively. CONCLUSIONS: Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk.

Sensitivity of a Next-Generation NIRS Device to Detect Low Mixed Venous Oxyhemoglobin Saturations in the Single Ventricle Population.

Regional cerebral oxygenation index (rSO2) based on near-infrared spectroscopy (NIRS) is frequently used to detect low venous oxyhemoglobin saturation (ScvO2). We compared the performance of 2 generations of NIRS devices. Clinically obtained, time-matched cerebral rSO2 and ScvO2 values were compared in infants monitored with the FORE-SIGHT (n = 73) or FORE-SIGHT ELITE (n = 47) by linear regression and Bland-Altman analyses. In both devices, cerebral rSO2 correlated poorly with measured ScvO2 (FORE-SIGHT partial correlation 0.50 [95% confidence interval {CI}, 0.40-0.58]; FORE-SIGHT ELITE partial correlation 0.47 [0.39-0.55]) and mean bias was +8 (standard deviation [SD] 13.2) for FORE-SIGHT and +14 (SD 12.5) for FORE-SIGHT ELITE. When ScvO2 was <30%, rSO2 was <40 in 8% of FORE-SIGHT ELITE readings. Future NIRS should be validated in more hypoxic cohorts.

Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke.

Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3 ± 3.4%) versus the contralateral hemisphere (25.5 ± 3.1%) of patients with large diffusion-perfusion lesion mismatch (P = 0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI (P = 0.004), suggesting compensation for reduced flow. Patients with perfusion-diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2 ± 0.1 at baseline that normalized (decreased) to 1.0 ± 0.1 at follow-up three days later (P = 0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org :NCT02077582.

Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest.

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1 - quartile 3) tau-A (ng/ml) values were 58 (43-71) versus 51 (43-67), 72 (57-84) versus 71 (59-82) and 76 (61-92) versus 75 (64-89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29-50) versus 36 (29-49), 49 (38-58) versus 48 (33-59) and 48 (39-59) versus 48 (36-62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.

Threshold of metabolic acidosis associated with newborn cerebral palsy: medical legal implications.

Obstetricians and gynecologists belong to 1 of the medical specialties with the highest rate of litigation claims. Among birth injury cases, those cases with cerebral palsy outcomes account for litigation settlements or judgments often in the millions of dollars. In cases of potential perinatal asphyxia, a threshold level of metabolic acidosis (base deficit ≥12 mmol/L) is necessary to attribute neonatal encephalopathy to an intrapartum hypoxic event. With increasing duration or severity of a hypoxic stress resulting in metabolic acidosis, newborn infant umbilical artery base deficit increases. It may be alleged that, as base deficit levels increase beyond 12 mmol/L, there is an increased likelihood and severity of cerebral palsy. As a corollary, it may be claimed that an earlier delivery (by minutes) would reduce the base deficit and prevent or reduce the severity of cerebral palsy. This issue is of relevance to obstetricians as defendants, because retrospective "expert" analysis of cases may suggest that optimal management decisions would have resulted in an earlier delivery. In addressing the association of metabolic acidosis and cerebral palsy, base deficit should be measured as the extracellular component (base deficitextracellular fluid) rather than the commonly used base deficitblood. Studies suggest that, beyond the base deficit threshold of 12 mmol/L, the incidence and severity of cerebral palsy does not significantly increase (until ≥20 mmol/L), although the risk of neonatal death rises markedly. Thus, among most infants with hypoxia-associated neonatal encephalopathy, the occurrence of cerebral palsy is unlikely to be impacted by delivery time variation of few minutes, and this argument should not serve as the basis for medical legal claims.

Storage after gamma irradiation affects in vivo oxygen delivery capacity of transfused red blood cells in preterm infants.

BACKGROUND: Gamma irradiation of red blood cells (RBCs) is well recognized to exacerbate storage lesion formation, but the effect of storage after irradiation on in vivo oxygen delivery capacity of transfused RBCs is currently not known. STUDY DESIGN AND METHODS: In 24 preterm infants with anemia receiving nonurgent transfusion of irradiated RBCs, we examined cerebral regional tissue oxygenation (crSO2 ) and time spent with peripheral arterial saturation (SpO2 ) less than 88%. Physiologic data were obtained immediately before, immediately after, and 5 days after transfusion. RESULTS: We observed linear negative moderate correlations between time since irradiation and the magnitude of change in crSO2 (r = -0.60; 95% CI, -0.81 to -0.27; p = 0.0018) and time spent with SpO2 of less than 88% (r = -0.42; 95% CI, -0.71 to 0.003; p = 0.04) immediately after transfusion. In infants (n = 9) who received fresher RBCs (irradiated <10 days before transfusion), there was a sustained increase in mean crSO2 up to 5 days after transfusion (3.0%; 95% CI, 0.3% to 5.7%; p = 0.04). Conversely, in infants (n = 15) who received older RBCs (irradiated ≥10 days before transfusion), there were negligible changes in crSO2 after transfusion at any time point. CONCLUSION: Our findings indicate that storage after gamma irradiation may have a detrimental effect on the oxygen delivery capacity of RBCs given to anemic preterm infants.

Determining the venous oxygen reservoir: A novel, hypothetical approach to titration of supplemental oxygen in preterm newborns.

While normal oxygen saturation is commonly thought to be a marker of normal oxygenation, cutaneous saturation does not account for the sufficiency of oxygen within each cell or that of the system overall. Rather, cutaneous oximetry simply defines the saturation of haemoglobin (Hb) with oxygen in a pulsatile vessel. Assessment of sufficiency is best determined by measurement of the amount of oxygen left over following aerobic respiration. This left over oxygen is 'stored' on Hb in the venous compartment and can be calculated as the venous oxygen content. We hypothesize that the development of a venous oxygen content or saturation reference range in a group of well, uninjured very preterm newborns and subsequent application, in a randomised trial, with a structural, functional and molecular outcome will resolve the method for assessment of oxygen sufficiency in preterms by demonstrating both clinical safety and effectiveness. This method could be subsequently used for titration of supplemental oxygen.

24 vs. 72 hours of hypothermia for pediatric cardiac arrest: A pilot, randomized controlled trial.

AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective therapies. The role of biomarkers in assessing response to interventions is unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce more favorable biomarker profiles after pediatric CA. METHODS: This single center pilot randomized trial tested HT (33 ±â€¯1 °C) for 24 vs. 72 h in 34 children with CA. Children comatose after return of circulation aged 1 week to 17 years and treated with HT by their physician were eligible. Serum was collected twice daily on days 1-4 and once on day 7. Mortality was assessed at 6 months. RESULTS: Patient characteristics, baseline biomarker concentrations, and adverse events were similar between groups. Eight (47%) and 4 (24%) children died in the 24 h and 72 h groups, p = .3. Serum neuron specific enolase (NSE) concentration was increased in the 24 vs. 72 h group at 84 h-96 h (median [interquartile range] 47.7 [3.9, 79.9] vs. 1.4 [0.0, 11.1] ng/ml, p = .02) and on day 7 (18.2 [3.2, 74.0] vs. 2.6 [0.0, 12.8] ng/ml, p = .047). Serum S100b was increased in the 24 h vs. 72 h group at 12 h-24 h, 36 h-84 h, and on day 7, all p < 0.05. HT duration was associated with S100b (but not NSE or MBP) concentration on day 7 in multivariate analyses. CONCLUSION: Serum biomarkers show promise as theragnostic tools in pediatric CA. Our biomarker and safety data also suggest that 72 h duration after pediatric CA warrants additional exploration.

Red blood cell antibody-induced anemia causes differential degrees of tissue hypoxia in kidney and brain.

Moderate anemia is associated with increased mortality and morbidity, including acute kidney injury (AKI), in surgical patients. A red blood cell (RBC)-specific antibody model was utilized to determine whether moderate subacute anemia could result in tissue hypoxia as a potential mechanism of injury. Cardiovascular and hypoxic cellular responses were measured in transgenic mice capable of expressing hypoxia-inducible factor-1α (HIF-1α)/luciferase activity in vivo. Antibody-mediated anemia was associated with mild intravascular hemolysis (6 h) and splenic RBC sequestration ( day 4), resulting in a nadir hemoglobin concentration of 89 ± 13 g/l on day 4. At this time point, renal tissue oxygen tension (PtO2) was decreased in anemic mice relative to controls (13.1 ± 4.3 vs. 20.8 ± 3.7 mmHg, P < 0.001). Renal tissue hypoxia was associated with an increase in HIF/luciferase expression in vivo ( P = 0.04) and a 20-fold relative increase in renal erythropoietin mRNA transcription ( P < 0.001) but no increase in renal blood flow ( P = 0.67). By contrast, brain PtO2 was maintained in anemic mice relative to controls (22.7 ± 5.2 vs. 23.4 ± 9.8 mmHg, P = 0.59) in part because of an increase in internal carotid artery blood flow (80%, P < 0.001) and preserved cerebrovascular reactivity. Despite these adaptive changes, an increase in brain HIF-dependent mRNA levels was observed (erythropoietin: P < 0.001; heme oxygenase-1: P = 0.01), providing evidence for subtle cerebral tissue hypoxia in anemic mice. These data demonstrate that moderate subacute anemia causes significant renal tissue hypoxia, whereas adaptive cerebrovascular responses limit the degree of cerebral tissue hypoxia. Further studies are required to assess whether hypoxia is a mechanism for acute kidney injury associated with anemia.

Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential.

The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8-13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30-80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity.

Hippocampal and cerebellar histological changes and their behavioural repercussions caused by brain ischaemic hypoxia experimentally induced by sodium nitrite.

INTRODUCTION: Brain ischaemic hypoxia can produce severe neurological damage that leads to behavioural disorders. This research analysed the hippocampal and cerebellar histological alterations caused by brain ischaemic hypoxia experimentally induced by sodium nitrite (NaNO2) and possible direct repercussions of this hypoxia on behaviour. METHODOLOGY: An experimental study was carried out by administering 60mg/kg NaNO2 to 10 Wistar rats at 3 months of age for 15 consecutive days. Ten control rats did not receive NaNO2. To assess behavioural repercussions, the animals were evaluated in Open Field, Elevated Plus-Maze (EPM), and Forced Swim tests before and after injury to evaluate locomotion, anxiety, and depression, respectively. Markers of stress were evaluated by measuring the blood levels of cortisol, glucose, cholesterol, and lactate. The presence of hippocampal lesions was verified by histologically studying the CA1-CA4 areas. Sections of the cerebellum were also evaluated because Purkinje cells are highly sensitive to ischaemic hypoxia and may serve as markers for this process. RESULTS: The number of neurons with lesions was significantly higher in animals exposed to NaNO2 in the hippocampus areas CA2, CA3, and CA4. The cerebellum was also very vulnerable to hypoxia, presenting extensive lesion áreas. These results are correlated with the parameters of the anxiety and depression tests. CONCLUSION: NaNO2 promoted brain damage due to ischaemic hypoxia in rats. Intoxicated animals showed decreased brain weights; damage in hippocampus and cerebellum; and anxiogenic and depressive behaviour.

A comparison of blood and cerebrospinal fluid cytokines (IL-1ß, IL-6, IL-18, TNF-α) in neonates with perinatal hypoxia.

Perinatal hypoxia-ischemia is a specific and important pathological event in neonatal care practice. The data on relationship between the concentrations of cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are scarce. The aim of this study is to evaluate changes in interleukin (IL-1ß, IL-6, and IL-18) and tumor necrosis factor alpha (TNF-α) levels in newborns with perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40 weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme-linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non-hypoxic infants of the same age sampled for clinically suspected perinatal meningitis, but proven negative and healthy otherwise. The cytokine values in CSF and serum samples were determined in relation to initial hypoxic-ischemic encephalopathy (HIE) staged according the Sarnat/Sarnat method, and compared with neurological outcome at 12 months of age estimated using Amiel-Tison procedure. The concentrations of IL-6 and TNF-α in serum of PNH patients were significantly higher compared to control group (p = 0.0407 and p = 0.023, respectively). No significant difference between average values of cytokines in relation to the stage of HIE was observed. Significantly higher levels of IL-6 and IL-18 corresponded to a mildly abnormal neurological outcome, while higher levels of IL-6 and TNF-α corresponded to a severely abnormal neurological outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-α better corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of birth. Also, higher serum levels of IL-6, TNF-α, and IL-18 corresponded better with abnormal neurological outcome at 12 months of age, compared to CSF values.

Blood Biomarkers of Hypoxic-Ischemic Brain Injury after Cardiac Arrest.

Biomarkers are part of the recommended outcome predictors after cardiac arrest. In general, blood biomarkers can easily be performed as routine laboratory tests, and they are unaffected by sedation, but bear the potential risk of laboratory errors. Nonetheless, if used properly, with the potential limitations in mind, they certainly help predict outcome after cardiac arrest. Among the routinely used and available blood biomarkers, neuron-specific enolase (NSE) has the best predictive value for poor outcome if measured serially from 24 to 72 hours. Cutoff values per se should be taken with caution because there is no 100% specificity (0% false-positive rate) in clinical practice. Rather, the increase over time of high NSE values is predictive of poor outcome. Other biomarkers like protein S100 and inflammatory markers also bear a potential to predict outcome, but they are outperformed by NSE. New blood biomarkers are currently under investigation and might improve the accuracy of outcome prediction. The family of noncoding RNAs, including microRNAs, is probably the most promising as microRNAs are not only associated with outcome, but also have the potential for therapeutic implications through their mechanism of action.

The value of serum pro-oxidant/antioxidant balance in the assessment of asphyxia in term neonates.

OBJECTIVE: Asphyxia is a major cause of disabilities in term-born infants. Here we have explored the value in HIE (hypoxic-ischemic-encephalopathy) of using a combination of serum pro-oxidant/antioxidant balance (PAB) assay for predicting the prognosis of asphyxia. METHOD: Ninety term neonates with asphyxia were enrolled and followed up for two years. Serum PAB, demographic/biochemical characteristics of mothers, and their neonates were determined. The Denver II test was used to assess outcomes. RESULTS: Of the 90 asphyxiated neonates, 47 (52.2%) had a normal outcome and 43 babies (47.8%) had abnormal outcome. Serum PAB levels in neonates with normal and abnormal outcomes were 17.1 ± 9.23 and 48.27 ± 41.30 HK, respectively. A combination of HIE intensity and PAB, compared to other indicators, had a higher predictive-value (95.2%) for outcomes in asphyxiated babies. CONCLUSION: We demonstrate that PAB in combination with HIE grade may have a better predictive value for the prognosis of asphyxiated babies and predicting future neurologic problems in asphyxiated term infants.

Serum potassium concentration predicts brain hypoxia on CT after avalanche-induced cardiac arrest.

BACKGROUND: Brain anoxia after complete avalanche burial and cardiac arrest (CA) may occur despite adequate on-site triage. PURPOSE: To investigate clinical and biological parameters associated with brain hypoxia in a cohort of avalanche victims with whole body computed tomographic (CT) scan. METHODS: Retrospective study of patients with CA and whole body CT scan following complete avalanche burial admitted in a level-I trauma center. MAIN FINDINGS: Out of 19 buried patients with whole body CT scan, eight patients had refractory CA and 11 patients had pre-hospital return of spontaneous circulation. Six patients survived at hospital discharge and only two had good neurologic outcome. Twelve patients had signs of brain hypoxia on initial CT scan, defined as brain edema, loss of gray/white matter differentiation and/or hypodensity of basal ganglia. No clinical pre-hospital parameter was associated with brain anoxia. Serum potassium concentration at admission was higher in patients with brain anoxia as compared to patients with normal CT scan: 5.5 (4.1-7.2) mmol/L versus 3.3 (3.0-4.2) mmol/L, respectively (P<.01). A threshold of 4.35 mmol/L serum potassium had 100% specificity to predict brain anoxia on brain CT scan. CONCLUSIONS: Serum potassium concentration had good predictive value for brain anoxia after complete avalanche burial. This finding further supports the use of serum potassium concentration for extracorporeal life support insertion at hospital admission in this context.