Neurological Impact of Slower Rewarming during Bypass Surgery in Infants.

BACKGROUND: Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological sequelae. In this pilot study, we aimed to validate the hypothesis that a slower rewarming rate would lower the risk of cerebral hypoxia and seizures in infants. METHODS: This is a prospective, clinical, single-center study. Infants undergoing cardiac surgery in hypothermia were rewarmed either according to the standard (+1°C in < 5 minutes) or a slow (+1°C in > 5-8 minutes) rewarming strategy. We monitored electrocortical activity via amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation by near-infrared spectroscopy during and after surgery. RESULTS: Fifteen children in the standard rewarming group (age: 13 days [5-251]) were cooled down to 26.6°C (17.2-29.8) and compared with 17 children in the slow-rewarming group (age: 9 days [4-365]) with a minimal temperature of 25.7°C (20.1-31.4). All neonates in both groups (n = 19) exhibited suppressed patterns compared with 28% of the infants > 28 days (p < 0.05). During rewarming, only 26% of the children in the slow-rewarming group revealed suppressed aEEG traces (vs. 41%; p = 0.28). Cerebral oxygenation increased by a median of 3.5% in the slow-rewarming group versus 1.5% in the standard group (p = 0.9). Our slow-rewarming group revealed no aEEG evidence of any postoperative seizures (0 vs. 20%). CONCLUSION: These results might indicate that a slower rewarming rate after hypothermia causes less suppression of electrocortical activity and higher cerebral oxygenation during rewarming, which may imply a reduced risk of postoperative seizures.

Controlled donation after circulatory death in post-cardiac arrest patients: Estimates from a large registry.

BACKGROUND: Controlled donation after circulatory death (cDCD) in post-anoxic brain injury is a valuable source of organs that is still underused in some countries. We assessed the number of potential cDCD donors after out-of-hospital cardiac arrest (OHCA) in Paris and its suburbs and extrapolated the results to the French population. METHODS: Using the large regional registry of the Great Paris area, we prospectively included all consecutive adults with OHCA with a stable return of spontaneous circulation (ROSC) who ultimately died in the intensive care unit (ICU) after withdrawal of life-sustaining treatments (WLST) due to post anoxic brain injury. The primary endpoint was potential for organ donation by cDCD in this population. The number of potential cDCD donors was calculated and extrapolated to the entire French population. RESULTS: Between 2011 and 2018, 4638 patients with stable ROSC were admitted to ICUs after OHCA, and 3170 died in ICU, of which 1034 died after WLST due to post-anoxic brain injury. When considering French criteria, 421/1034 patients (41%) would have been potential cDCD donors (55 patients per year in a 4.67 million population). After standardization for age and sex, the potential for cDCD was 515 (95% CI 471-560) patients per year in France corresponding to an annual incidence of 1.18 per 100 000 inhabitants per year. CONCLUSIONS: Organ donation by cDCD after cardiac arrest could provide a large pool of donors in France.

The Effect of Propofol on the Hippocampus in Chronic Cerebral Hypoxia in a Rat Model Through Klotho Regulation.

BACKGROUND/AIM: Chronic cerebral hypoxia often leads to brain damage and inflammation. Propofol is suggested to have neuroprotective effects under anaesthesia. MATERIALS AND METHODS: This study used rat models with carotid artery coarctation or closure. Four groups of rats were compared: a control group, a propofol-treated group, a group with bilateral common carotid artery blockage (BCAO), and a BCAO group treated with propofol post-surgery. RESULTS: The Morris water maze test indicated cognitive impairment in BCAO rats, which also showed hippocampal structure changes, oxidative stress markers alteration, and reduced Klotho expression. Propofol treatment post-BCAO surgery improved these outcomes, suggesting its potential in mitigating chronic cerebral hypoxia effects. CONCLUSION: Propofol may increase klotho levels and reduce apoptosis and inflammation linked to oxidative stress in cognitively impaired mice.

Background EEG Suppression Ratio for Early Detection of Cerebral Injury in Pediatric Cardiac Arrest.

BACKGROUND: Our objective was to assess the utility of the 1-h suppression ratio (SR) as a biomarker of cerebral injury and neurologic prognosis after cardiac arrest (CA) in the pediatric hospital setting. METHODS: Prospectively, we reviewed data from children presenting after CA and monitored by continuous electroencephalography (cEEG). Patients aged 1 month to 21 years were included. The SR, a quantitative measure of low-voltage cEEG (≤ 3 µV) content, was dichotomized as present or absent if there was > 0% suppression for one continuous hour. A multivariate logistic regression analysis was performed including age, sex, type of CA (i.e., in-hospital or out-of-hospital), and the presence of SR as a predictor of global anoxic cerebral injury as confirmed by magnetic resonance imaging (MRI). RESULTS: We included 84 patients with a median age of 4 years (interquartile range 0.9-13), 64% were male, and 49% (41/84) had in-hospital CA. Cerebral injury was seen in 50% of patients, of whom 65% had global injury. One-hour SR presence, independent of amount, predicted cerebral injury with 81% sensitivity (95% confidence interval (CI) (66-91%) and 98% specificity (95% CI 88-100%). Multivariate logistic regression analyses indicated that SR was a significant predictor of both cerebral injury (ß = 6.28, p < 0.001) and mortality (ß = 3.56, p < 0.001). CONCLUSIONS: The SR a sensitive and specific marker of anoxic brain injury and post-CA mortality in the pediatric population. Once detected in the post-CA setting, the 1-h SR may be a useful threshold finding for deployment of early neuroprotective strategies prior or for prompting diagnostic neuroimaging.

Quantitative Electroencephalographic Changes Associated With Brain Tissue Hypoxia After Pediatric Traumatic Brain Injury: A Retrospective Exploratory Analysis.

PURPOSE: Brain tissue hypoxia is associated with poor outcomes after pediatric traumatic brain injury. Although invasive brain oxygenation (PbtO 2 ) monitoring is available, noninvasive methods assessing correlates to brain tissue hypoxia are needed. We investigated EEG characteristics associated with brain tissue hypoxia. METHODS: We performed a retrospective analysis of 19 pediatric traumatic brain injury patients undergoing multimodality neuromonitoring that included PbtO 2 and quantitative electroencephalography(QEEG). Quantitative electroencephalography characteristics were analyzed over electrodes adjacent to PbtO 2 monitoring and over the entire scalp, and included power in alpha and beta frequencies and the alpha-delta power ratio. To investigate relationships of PbtO 2 to quantitative electroencephalography features using time series data, we fit linear mixed effects models with a random intercept for each subject and one fixed effect, and an auto-regressive order of 1 to model between-subject variation and correlation for within-subject observations. Least squares (LS) means were used to investigate for fixed effects of quantitative electroencephalography features to changes in PbtO 2 across thresholds of 10, 15, 20, and 25 mm Hg. RESULTS: Within the region of PbtO 2 monitoring, changes in PbtO 2 < 10 mm Hg were associated with reductions of alpha-delta power ratio (LS mean difference -0.01, 95% confidence interval (CI) [-0.02, -0.00], p = 0.0362). Changes in PbtO 2 < 25 mm Hg were associated with increases in alpha power (LS mean difference 0.04, 95% CI [0.01, 0.07], p = 0.0222). CONCLUSIONS: Alpha-delta power ratio changes are observed across a PbtO 2 threshold of 10 mm Hg within regions of PbtO 2 monitoring, which may reflect an EEG signature of brain tissue hypoxia after pediatric traumatic brain injury.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Hyperbaric oxygen treatment in delayed post-hypoxic encephalopathy following inhalation of liquefied petroleum gas: a case report.

Delayed post-hypoxic encephalopathy can occur after an episode of anoxia or hypoxia. Symptoms include apathy, confusion, and neurological deficits. We describe a 47-year-old male patient who inhaled gas from a kitchen stove liquid petroleum gas cylinder. He was diagnosed with hypoxic ischaemic encephalopathy 12 hours after his emergency department admission. He received six sessions of hyperbaric oxygen treatment (HBOT) and was discharged in a healthy state after six days. Fifteen days later, he experienced weakness, loss of appetite, forgetfulness, depression, balance problems, and inability to perform self-care. One week later, he developed urinary and fecal incontinence and was diagnosed with post-hypoxic encephalopathy. After 45 days from the onset of symptoms, he was referred to the Underwater and Hyperbaric Medicine Department for HBOT. The patient exhibited poor self-care and slow speech rate, as well as ataxic gait and dysdiadochokinesia. Hyperbaric oxygen was administered for twenty-four sessions, which significantly improved the patient's neurological status with only hypoesthesia in the left hand remaining at the end of treatment. Hyperbaric oxygen has been reported as successful in treating some cases of delayed neurological sequelae following CO intoxication. It is possible that HBO therapy may also be effective in delayed post-hypoxic encephalopathy from other causes. This may be achieved through mechanisms such as transfer of functional mitochondria to the injury site, remyelination of damaged neurons, angiogenesis and neurogenesis, production of anti-inflammatory cytokines, and balancing of inflammatory and anti-inflammatory cytokines.

Preterm Infants off Positive Pressure Respiratory Support Have a Higher Incidence of Occult Cerebral Hypoxia.

OBJECTIVE: To use cerebral near-infrared spectroscopy (NIRS) to quantify occult cerebral hypoxia across respiratory support modes in preterm infants. STUDY DESIGN: In this prospective, longitudinal, observational study, infants ≤32 weeks gestation underwent serial pulse oximetry (oxygen saturation [SpO2]) and cerebral NIRS monitoring (4-6 hours per session) following a standardized recording schedule (daily for 2 weeks, every other day for 2 weeks, then weekly until 35 weeks corrected gestational age). Four calculations were made: median cerebral saturation, median cerebral hypoxia burden (proportion of NIRS samples below the hypoxia threshold [<67%]), median systemic saturation, and median systemic hypoxia burden (proportion of SpO2 samples below the desaturation threshold [<85%]). During each recording session, respiratory support mode was noted (room air, low-flow nasal cannula, high-flow nasal cannula, noninvasive positive pressure ventilation, continuous positive airway pressure, and invasive ventilation). RESULTS: There were 1013 recording sessions made from 174 infants with a median length of 6.9 hours. Although the systemic (SpO2) hypoxia burden was significantly greater for infants on the highest respiratory support (invasive and noninvasive positive pressure ventilation), the cerebral hypoxia burden was significantly greater during recording sessions made on the lowest respiratory support (8% for room air; 29% for low-flow nasal cannula). CONCLUSIONS: Premature infants on the highest levels of respiratory support have less cerebral hypoxia than those on lower respiratory support. These results raise concern about unrecognized cerebral hypoxia during lower acuity periods of neonatal intensive care unit hospitalization and adverse outcomes.

Discrepancies in the late auditory potentials of post-anoxic patients: Watch out for focal brain lesions, a pilot retrospective study.

AIMS: Late auditory evoked potentials, and notably mismatch negativity (MMN) and P3 responses, can be used as part of the multimodal prognostic evaluation in post-anoxic disorders of consciousness (DOC). MMN response preferentially stems from the temporal cortex and the arcuate fasciculus. Situations with discrepant evaluations, for example MMN absent but P3 present, are frequent and difficult to interpret. We hypothesize that discrepant MMN-/P3+ results could reflect a higher prevalence of lesions in MMN generating regions. This study presents correlations between neurophysiological and neuroradiological results. METHODS: This retrospective study was conducted on 38 post-anoxic DOC patients. Brain lesions were analyzed on 3T MRI both anatomically and through computation of the local arcuate fasciculus fractional anisotropy values on Diffusion Tensor Imaging sequences. Neurophysiological data and outcome were also analyzed. RESULTS: Our cohort included 8 MMN-/P3+, 7 MMN+/P3+, 21 MMN-/P3- and 2 MMN-/P3+ patients, assessed at a median delay of 20.5 days since cardiac arrest. Our results show that MMN-/P3+ patients tended to have fewer temporal and basal ganglia lesions than MMN-/P3- patients, and more than MMN+/P3+ patients (p-values for trend: p = 0.02 for temporal and p = 0.02 for basal ganglia lesions). There was a statistical difference across groups for mean fractional anisotropy values in the arcuate fasciculus (p = 0.008). The percentage of patients regaining consciousness at three months in MMN-/P3+ patients was higher than in MMN-/P3- patients and lower than in MMN+/P3+ patients. CONCLUSION: This study suggests that discrepancies in late auditory evoked potentials may be linked to focal post-anoxic brain lesions, visible on brain MRI.

"THE MANTLE" bundle for minimizing cerebral hypoxia in severe traumatic brain injury.

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.

Transient central hypoxemia due to intermittent high-degree atrioventricular block in a heart-transplanted patient diagnosed during routine electroencephalography: a case report.

BACKGROUND: Bradycardia frequently occurs in heart-transplanted patients, mainly as a temporally restricted manifestation early after transplantation and often without symptoms. A high-degree atrioventricular block is mostly symptomatic through cerebral hypoxia induced through cerebral hypoperfusion. Only a few published cases show this specific electroencephalography result in this context. The purpose of this case is to bring attention to atypical manifestations of typical cardiac complications after heart transplantation and the importance of perseverance in the diagnostic. CASE PRESENTATION: A Central European man in his 50s with history of heart transplantation 31 years previously was admitted to the internal medicine ward for short-lived recurrent episodes of generalized weakness with multiple falls but without loss of consciousness. During routine electroencephalography, the patient perceived this recurrent sensation. This episode coincided with a transient third-degree atrioventricular block followed 8-10 seconds later by a generalized slowing of the electroencephalography, reflecting cerebral hypoxia due to cerebral hypoperfusion. Holter monitoring confirmed the diagnosis. A pacemaker was implanted, consequently resolving the episodes. CONCLUSION: This case report illustrates the pathophysiological central hypoxemic origin of episodes of generalized weakness caused by a high-degree atrioventricular block in a patient surviving 29 years after heart transplant. It highlights the benefit of electroencephalography as a diagnostic tool in well-selected patients.

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear. METHODS: We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1ß. RESULTS: The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1ß) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1ß pathway-related proteins decreased. CONCLUSION: The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH.

Mechanisms of hypoxia in the hippocampal CA3 region in postoperative cognitive dysfunction after cardiopulmonary bypass.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication with high morbidity and mortality, commonly observed in the elderly who underwent anesthesia and surgery. The incidence is much higher in cardiac surgery. However, the reason and the mechanism of POCD remains unclear, but cerebral hypoxia is a common neurological complication after cardiac surgery. This study aims to investigate what role cerebral hypoxia plays in the pathogenesis of POCD. METHODS: The POCD model was established using cardiopulmonary bypass (CPB) surgery. Cognitive function was detected using Y maze and Morris water maze. The hypoxia in central nervous system was assessed using HE staining, western blot, and immunofluorescence. Inflammatory factors in hippocampus and plasma were detected by enzyme-linked immunosorbent assay. Evans blue was used to detect destruction of the blood brain barrier (BBB). RESULTS: Cognitive impairment markedly occurred to rats underwent 2-h CPB operation. Cerebral thrombosis and hypoxia occurred in the hippocampal CA3 region of rats after surgery. In addition, microglia in hippocampal was activated and the expression of inflammatory factors such as IL-1ß, IL-6 and TNF-α was upregulated. Moreover, the permeability of BBB increased in rats after CPB. CONCLUSION: Hypoxia in hippocampal CA3 region was involved in the occurrence and the mechanism may be associated with neuroinflammation and the damage of BBB.

A Severe Baclofen Intoxication Mimicking Post-Hypoxic Encephalopathy: Wait and See!

BACKGROUND: A severe baclofen intoxication is a potentially life-threatening condition. It is associated with coma and can cause brainstem reflexes to disappear, simulating a brain death-like condition. When given intensive supportive care and time, patients can recover without residual neurological damage. CASE REPORT: We present a case of a patient with known spastic cerebral palsy who was found unresponsive with no signs of breathing. He was brought to the Emergency Department, intubated, put on the ventilator, and hemodynamically stabilized. Brainstem reflexes were absent and he appeared brain dead. During the secondary survey, an intrathecal baclofen pump was found at his left lower abdomen, with a swelling next to it. A baclofen intoxication was suspected. He was admitted to the Intensive Care Unit, and after 72 h of supportive care complete neurological recovery was achieved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Systemic baclofen intoxication can simulate a brain death-like condition. There is no reliable correlation between baclofen serum levels and central nervous system depression in case of an intoxication. It is important for emergency physicians to recognize a baclofen intoxication as a possible cause of coma and absent brainstem reflexes. Recuperation is spontaneous and can follow within days without residual damage. Because these patients may be brought in after a period of apnea or cardiopulmonary resuscitation, focus may be on post-hypoxic encephalopathy considerations instead of a possible baclofen intoxication.

Early cerebral hypoxia in extremely preterm infants and neurodevelopmental impairment at 2 year of age: A post hoc analysis of the SafeBoosC II trial.

BACKGROUND: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. METHODS: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. RESULTS: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49). CONCLUSIONS: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial.

Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model.

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.

Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis.

BACKGROUND: Cerebral and myocardial hypoperfusion occur during hemodialysis in adults. Pediatric patients receiving chronic hemodialysis have fewer cardiovascular risk factors, yet cardiovascular morbidity remains prominent. METHODS: We conducted a prospective observational study of pediatric patients receiving chronic hemodialysis to investigate whether intermittent hemodialysis is associated with adverse end organ effects in the heart or with cerebral oxygenation (regional tissue oxyhemoglobin saturation [rSO2]). We assessed intradialytic cardiovascular function and rSO2 using noninvasive echocardiography to determine myocardial strain and continuous noninvasive near-infrared spectroscopy for rSO2. We measured changes in blood volume and measured central venous oxygen saturation (mCVO2) pre-, mid-, and post-hemodialysis. RESULTS: The study included 15 patients (median age, 12 years; median hemodialysis vintage, 13.2 [9-24] months). Patients were asymptomatic. The rSO2 did not change during hemodialysis, whereas mCVO2 decreased significantly, from 73% to 64.8%. Global longitudinal strain of the myocardium worsened significantly by mid-hemodialysis and persisted post-hemodialysis. The ejection fraction remained normal. Lower systolic BP and faster blood volume change were associated with worsening myocardial strain; only blood volume change was significant in multivariate analysis (ß-coefficient, -0.3; 95% confidence interval [CI], -0.38 to -0.21; P<0.001). Blood volume change was also associated with a significant decrease in mCVO2 (ß-coefficient, 0.42; 95% CI, 0.07 to 0.76; P=0.001). Access, age, hemodialysis vintage, and ultrafiltration volume were not associated with worsening strain. CONCLUSIONS: Unchanged rSO2 suggested that cerebral oxygenation was maintained during hemodialysis. However, despite maintained ejection fraction, intradialytic myocardial strain worsened in pediatric hemodialysis and was associated with blood volume change. The effect of hemodialysis on individual organ perfusion in pediatric versus adult patients receiving hemodialysis might differ.

Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .