Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury.

Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho -0.33, P < 0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.

Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19.

The prolonged mechanical ventilation that is often required by patients with severe COVID-19 is expected to result in significant intensive care unit-acquired weakness (ICUAW) in many of the survivors. However, in our post-COVID-19 follow-up clinic we have found that, as well as the anticipated global weakness related to loss of muscle mass, a significant proportion of these patients also have disabling focal neurological deficits relating to multiple axonal mononeuropathies. Amongst the 69 patients with severe COVID-19 that have been discharged from the intensive care units in our hospital, we have seen 11 individuals (16%) with such a mononeuritis multiplex. In many instances, the multi-focal nature of the weakness in these patients was initially unrecognised as symptoms were wrongly assumed to relate simply to "critical illness neuromyopathy". While mononeuropathy is well recognised as an occasional complication of intensive care, our experience suggests that such deficits are surprisingly frequent and often disabling in patients recovering from severe COVID-19.

Prediction of early unplanned intensive care unit readmission in a UK tertiary care hospital: a cross-sectional machine learning approach.

OBJECTIVES: Unplanned readmissions to the intensive care unit (ICU) are highly undesirable, increasing variance in care, making resource planning difficult and potentially increasing length of stay and mortality in some settings. Identifying patients who are likely to suffer unplanned ICU readmission could reduce the frequency of this adverse event. SETTING: A single academic, tertiary care hospital in the UK. PARTICIPANTS: A set of 3326 ICU episodes collected between October 2014 and August 2016. All records were of patients who visited an ICU at some point during their stay. We excluded patients who were ≤16 years of age; visited ICUs other than the general and neurosciences ICU; were missing crucial electronic patient record measurements; or had indeterminate ICU discharge outcomes or very early or extremely late discharge times. After exclusion, 2018 outcome-labelled episodes remained. PRIMARY AND SECONDARY OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) for prediction of unplanned ICU readmission or in-hospital death within 48 hours of first ICU discharge. RESULTS: In 10-fold cross-validation, an ensemble predictor was trained on data from both the target hospital and the Medical Information Mart for Intensive Care (MIMIC-III) database and tested on the target hospital's data. This predictor discriminated between patients with the unplanned ICU readmission or death outcome and those without this outcome, attaining mean AUROC of 0.7095 (SE 0.0260), superior to the purpose-built Stability and Workload Index for Transfer (SWIFT) score (AUROC=0.6082, SE 0.0249; p=0.014, pairwise t-test). CONCLUSIONS: Despite the inherent difficulties, we demonstrate that a novel machine learning algorithm based on transfer learning could achieve good discrimination, over and above that of the treating clinicians or the value added by the SWIFT score. Accurate prediction of unplanned readmission could be used to target resources more efficiently.

Blood pressure management in acute head injury.

Head injury remains a major cause of preventable death and serious morbidity in young adults. Based on the available evidence, it appears that a cerebral perfusion pressure of 50 to 70 mm Hg is generally adequate to ensure cerebral oxygen delivery and prevent ischemia. However, evidence suggests that perfusion requirements may not only vary across the injured brain but also differ depending on the time since injury. Such heterogeneity, both within and between subjects, suggests that individualized therapy may be an appropriate treatment strategy. Future studies should aim to assess which groups of patients, and what regional pathophysiological derangements, may benefit with improvements in functional outcome from therapeutic increases or decreases in cerebral perfusion pressure beyond these proposed limits. Such functional improvements may be of immense importance to patients and require formal neurocognitive assessments to discriminate improvements.

Early derangements in oxygen and glucose metabolism following head injury: the ischemic penumbra and pathophysiological heterogeneity.

INTRODUCTION: Conclusive evidence of cerebral ischemia following head injury has been elusive. We aimed to use (15)O and (18)Fluorodeoxyglucose positron emission tomography (PET) to investigate pathophysiological derangements following head injury. RESULTS: Eight patients underwent PET within 24 h of injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), oxygen extraction fraction (OEF), and cerebral glucose metabolism (CMRglc). Physiological regions of interest (ROI) were generated for each subject using a range of OEF values from very low (<10), low (10-30), normal range (30-50), high (50-70), and critically high (> or =70%). We applied these ROIs to each subject to generate data that would examine the balance between blood flow and metabolism across the injured brain independent of structural injury. DISCUSSION: Compared to the normal range, brain regions with higher OEF demonstrate a progressive CBF reduction (P < 0.01), CMRO2 increase (P < 0.05), and no change in CMRglc, while regions with lower OEF are associated with reductions in CBF, CMRO2, and CMRglc (P < 0.01). Although all subjects demonstrate a decrease in CBF with increases in OEF > 70%, CMRO2 and CMRglc were generally unchanged. One subject demonstrated a reduction in CBF and small fall in CMRO2 within the high OEF region (>70%), combined with a progressive increase in CMRglc. CONCLUSIONS: The low CBF and maintained CMRO2 in the high OEF ROIs is consistent with classical cerebral ischemia and the presence of an 'ischemic penumbra' following early head injury, while the metabolic heterogeneity that we observed suggests significant pathophysiological complexity. Other mechanisms of energy failure are clearly important and further study is required to delineate the processes involved.