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The cerebral oxygen cascade includes three key stages: (a) convective oxygen delivery representing the bulk flow of oxygen to the cerebral vascular bed; (b) diffusion of oxygen from the blood into brain tissue; and (c) cellular utilisation of oxygen for aerobic metabolism. All three stages may become dysfunctional after resuscitation from cardiac arrest and contribute to hypoxic–ischaemic brain injury (HIBI). Improving convective cerebral oxygen delivery by optimising cerebral blood flow has been widely investigated as a strategy to mitigate HIBI. However, clinical trials aimed at optimising convective oxygen delivery have yielded neutral results. Advances in the understanding of HIBI pathophysiology suggest that impairments in the stages of the oxygen cascade pertaining to oxygen diffusion and cellular utilisation of oxygen should also be considered in identifying therapeutic strategies for the clinical management of HIBI patients. Culprit mechanisms for these impairments may include a widening of the diffusion barrier due to peri-vascular oedema and mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal and non-invasive neuromonitoring techniques may aid in detecting pathophysiologic changes in the oxygen cascade and enable patient-specific management aimed at reducing the severity of HIBI. [ABSTRACT FROM AUTHOR]

Abstract Background Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. Methods A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. Results In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p

Abstract Background Multiple clinical conditions are associated with cerebral hypoxia/ischaemia and thereby an increased risk of hypoxic-ischaemic brain injury. Cerebral near-infrared spectroscopy monitoring (NIRS) is a tool to monitor brain oxygenation and perfusion, and the clinical uptake of NIRS has expanded over recent years. Specifically, NIRS is used in the neonatal, paediatric, and adult perioperative and intensive care settings. However, the available literature suggests that clinical benefits and harms of cerebral NIRS monitoring are uncertain. As rates of clinically significant hypoxic-ischaemic brain injuries are typically low, it is difficult for randomised clinical trials to capture a sufficiently large number of events to evaluate the clinical effect of cerebral NIRS monitoring, when focusing on specific clinical settings. The aim of this systematic review will be to evaluate the benefits and harms of clinical care with access to cerebral NIRS monitoring versus clinical care without cerebral NIRS monitoring in children and adults across all clinical settings. Methods We will conduct a systematic review with meta-analysis and trial sequential analysis. We will only include randomised clinical trials. The primary outcomes are all-cause mortality, moderate or severe persistent cognitive or neurological deficit, and proportion of participants with one or more serious adverse events. We will search CENTRAL, EMBASE, MEDLINE, and the Science Citation Index Expanded from their inception and onwards. Two reviewers will independently screen all citations, full-text articles, and extract data. The risk of bias will be appraised using the Cochrane risk of bias tool version 2.0. If feasible, we will conduct both random-effects meta-analysis and fixed-effect meta-analysis of outcome data. Additional analysis will be conducted to explore the potential sources of heterogeneity (e.g. risk of bias, clinical setting). Discussion As we include trials across multiple clinical settings, there is an increased probability of reaching a sufficient information size. However, heterogeneity between the included trials may impair our ability to interpret results to specific clinical settings. In this situation, we may have to depend on subgroup analyses with inherent increased risks of type I and II errors. Systematic review registration PROSPERO CRD42020202986 . This systematic review protocol has been submitted for registration in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/prospero) on the 12th of October 2020 and published on the 12th of November 2020 (registration ID CRD42020202986 ).

Background: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury.Methods: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0-12, 12-24, 24-48 h time-periods and integrated over 0-48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3-5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury.Results: In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0-48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [- 1.17 to 2.94] vs. - 2.71 95% CI [- 4.16 to - 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, p = 0.042).Conclusion: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917 . [ABSTRACT FROM AUTHOR]

Post-cardiac arrest patients are vulnerable to hypoxic-ischaemic brain injury (HIBI), but HIBI may not be identified until computed tomography (CT) scan of the brain is obtained post-resuscitation and stabilization. We aimed to evaluate the association of clinical arrest characteristics with early CT findings of HIBI to identify those at the highest risk for HIBI. This is a retrospective analysis of out-of-hospital cardiac arrest (OHCA) patients who underwent whole-body imaging. Head CT reports were analyzed with an emphasis on findings suggestive of HIBI; HIBI was present if any of the following were noted on the neuroradiologist read: global cerebral oedema, sulcal effacement, blurred grey-white junction, and ventricular compression. The primary exposure was duration of cardiac arrest. Secondary exposures included age, cardiac vs noncardiac etiology, and witnessed vs unwitnessed arrest. The primary outcome was CT findings of HIBI. A total of 180 patients (average age 54 years, 32% female, 71% White, 53% witnessed arrest, 32% cardiac etiology of arrest, mean CPR duration of 15 ± 10 minutes) were included in this analysis. CT findings of HIBI were seen in 47 (48.3%) patients. Multivariate logistic regression demonstrated a significant association between CPR duration and HIBI (adjusted OR = 1.1, 95% CI 1.01–1.11, p < 0.01). Signs of HIBI are commonly seen on CT head within 6 hours of OHCA, occurring in approximately half of patients, and are associated with CPR duration. Determining risk factors for abnormal CT findings can help clinically identify patients at higher risk for HIBI and target interventions appropriately. [ABSTRACT FROM AUTHOR]

Hypoxic–ischaemic brain injury (HIBI) has become an increasingly common cause of admission to intensive care units (ICUs) and prolonged or permanent neurological disability. It is essential to provide an accurate prognosis to guide management. Following restoration of spontaneous circulation (ROSC) clinical assessment is often difficult and ancillary investigation is necessary. Outcome depends on the severity of the initial insult, the effectiveness of immediate resuscitation and transfer, and the post-resuscitation management on the ICU. Some patients remain profoundly impaired and others may develop complications including myoclonic epilepsy, cognitive impairment, border-zone infarction and movement disorders. The management of patients with HIBI presents considerable clinical, ethical and legal difficulties. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypoxic-ischaemic brain injury is usually due to cardiac arrest or severe hypotension. The clinical manifestation and outcome will depend on the severity of the initial insult, the promptness and effectiveness of the resuscitation, and the post resuscitation management in the intensive care unit. OBJECTIVE: To highlight the need for vigilance and preparedness in every case of spinal anaesthesia. CASE REPORT: Patient was a 32years old housewife who was booked for emergency lower segment caesarean section on account of transverse lie in labour at term. She had no co-morbidities. A subarachnoid block was established with a 25G Quinke needle through L3 – L4 intervertebral space using 2ml of 0.5% heavy bupivacaine, after preloading, she was then wedged in a left lateral tilt. Five minutes after this procedure, and before the commencement of surgery, the patient had a cardiac arrest. She was resuscitated, intubated, ventilated, and delivered of a live asphyxiated baby. She was then transferred to the intensive care unit, where she eventually made a full recovery. CONCLUSION: While hypoxic-ischaemic brain injury is not commonly associated with spinal anaesthesia, vigilance, and prompt and aggressive management is key to a favourable outcome.

Background: Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules.Objective: To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality.Materials and Methods: Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups.Results: There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths.Conclusion: Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxic–ischaemic brain injury (HIBI) has become an increasingly common cause of admission to intensive care units and prolonged or permanent neurological disability. It is essential to provide an accurate prognosis to guide management. Clinical assessment is often difficult and ancillary investigation is necessary. Outcome depends on the severity of the initial insult, the effectiveness of immediate resuscitation and transfer, and the post-resuscitation management on the intensive care unit. Some patients remain profoundly impaired and others may develop complications including myoclonic epilepsy, cognitive impairment, border-zone infarction and movement disorders. The management of patients with HIBI presents considerable clinical, ethical and legal difficulties. [Copyright &y& Elsevier]

Background A cardiac arrest can lead to hypoxic-ischaemic brain injury which can result in cognitive and emotional impairments and may negatively affect daily functioning, participation in society and quality of life. Furthermore, the impact on the family of the patient can be high. We designed an intervention called 'Stand still..., and move on', which is a concise, individualised, semi-structured intervention for survivors of cardiac arrest and their caregivers, consisting of between one and six face-to-face consultations provided by a trained nurse. The intervention is directed at early detection of cognitive and emotional problems, provision of information, promotion of self-management and referral to specialised care if necessary. The effectiveness of the intervention is being examined in a randomised controlled trial [ISRCTN74835019]. Alongside this trial we performed a process evaluation which aims to investigate the feasibility of the intervention by assessing: 1) the attendance and dose delivered; 2) performance according to protocol; and 3) the opinion of patients, caregivers and nurses on the intervention. Methods Participants of this process evaluation were 97 patients allocated to the intervention group of the RCT, their 91 caregivers, and six nurses who conducted the intervention. Measurement instruments used were evaluation forms for patients and caregivers, registration and evaluation forms for nurses, and semi-structured interviews with nurses. Results Seventy-nine of the patients (81%) allocated to the intervention group and 65 caregivers (71%) participated in the intervention. The mean (SD) number of consultations per patient was 1.8 (1.0), and most consultations were conducted at the patients' home. The intervention was performed largely according to protocol, except that the intervention usually started later than intended, consultations were longer than expected, and the topic of self-management was not regularly addressed. Patients marked the quality of the intervention with a mean score of 7.5 and the performance of the nurse with an 8.0 out of ten. Overall, the intervention was positively evaluated by patients, caregivers and nurses. Conclusions The intervention 'Stand still..., and move on' is a promising intervention which was performed largely according to protocol and seems feasible for implementation after some adaptations, if it is found to be effective. [ABSTRACT FROM AUTHOR]

Aim: To examine brainstem auditory function in preterm infants after perinatal hypoxia-ischaemia (HI). Methods: Brainstem auditory evoked response (BAER) was studied at 37–42 wk postconceptional age in preterm infants who suffered perinatal HI, and were compared with those in preterm and term infants without any major perinatal problems. Results: None of the latencies of waves I, III and V in the BAER in preterm infants after perinatal HI differed significantly from those in preterm and term controls. There were also no significant differences in the I–V and I–III interpeak intervals between preterm infants after HI and the controls. However, III–V interval in infants after HI tended to increase, and was significantly longer than in term controls (p<0.01), although it did not differ significantly from that in preterm controls. Similarly, the III–V/I–III interval ratio was greater than in term controls (p<0.05), but was similar to that in preterm controls. All amplitude variables did not differ significantly from the controls.Conclusion: BAER in preterm infants after perinatal HI did not differ significantly from that in preterm infants without perinatal problems, but differed slightly from that in normal term infants. The prolonged III–V interval as compared with the term controls suggests a minor impairment in central auditory function. [ABSTRACT FROM AUTHOR]

Aim: to identify patterns of hypoxic-ischemic brain injury by magnetic resonance imaging (MRI) in the first 10 days of life in affected neonates. Material and methods: standard T1- and T2-weighted MRI sequences performed in the first 10 days of life in 25 asphyxiated term neonates were reviewed retrospectively. All neonates were subjected to therapeutic hypothermia. Results: out of the 25 asphyxiated neonates who underwent MRI, 18 (72%) had brain injury detected on MRI. In moderate hypoxicischemic encephalopathy (HIE) group 3 out of 9 (33.3%) and in severe HIE group 15 out of 16 (93.75%) showed abnormalities in their scans. The most frequent pattern of hypoxic-ischemic injury in newborns with moderate HIE was the primarly deep gray matter involvment found in 2 (66.67%) newborns, whereas in severe HIE group, it was the mixed injury pattern found in 9 (60%) neonates. Primarily cortical involvment was only present in two neonates (13.3%), both with severe HIE. One (6.67%) neonate with severe encephalopathy showed multiple punctate lesions in periventricular white matter. Conclusion: MRI can show brain damage in asphyxiated neonates during the first 10 days of life. [ABSTRACT FROM AUTHOR]

Birth asphyxia in term neonates affects 1-2/1000 live births and results in the development of hypoxic-ischaemic encephalopathy with devastating life-long consequences. The majority of neuronal cell death occurs with a delay, providing the potential of a treatment window within which to act. Currently, treatment options are limited to therapeutic hypothermia which is not universally successful. To identify new interventions, we need to understand the molecular mechanisms underlying the injury. Here, we provide an overview of the contribution of both oxidative stress and endoplasmic reticulum stress in the development of neonatal brain injury and identify current preclinical therapeutic strategies., (© 2017 The Author(s).)

There is growing interest in the long-term outcomes of patients surviving out-of-hospital cardiac arrest (OHCA). This paper aims to summarise the available literature on the long-term cognitive, health-related quality of life (QoL) and mental health outcomes of survivors of OHCA. Between 30% and 50% of survivors of OHCA experience cognitive deficits for up to several years post-discharge. Deficits of attention, declarative memory, executive function, visuospatial abilities and verbal fluency are commonly reported. Survivors of OHCA appear to report high rates of mental illness, with up to 61% experiencing anxiety, 45% experiencing depression and 27% experiencing post-traumatic stress. Fatigue appears to be a commonly reported long-term outcome for survivors of OHCA. Investigations of long-term QoL for these patients have produced mixed findings. Carers of survivors of OHCA report high rates of depression, anxiety and post-traumatic stress, with insufficient social and financial support. The heterogeneous range of instruments used to assess cognitive function and QoL prevent any clear conclusions being drawn from the available literature. The potential biases inherent in this patient population and the interaction between QoL, cognitive performance and mental health warrant further investigation, as does the role of post-discharge support services in improving long-term patient outcomes.