EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy.

OBJECTIVE: To analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE). METHODS: Retrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR). RESULTS: Short-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality. CONCLUSION: The presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients. SIGNIFICANCE: The present findings may help to improve the challenging prognosis estimation in HE patients.

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.

Severe Acute Neurologic Involvement in Children With Hemolytic-Uremic Syndrome.

BACKGROUND AND OBJECTIVES: Acute severe neurologic involvement is the most threatening complication in children with hemolytic-uremic syndrome (HUS). Our primary study objectives were to describe the association between acute neurologic manifestations (ANMs) and in-hospital mortality among children with HUS. METHODS: Using the Pediatric Health Information System database, in this retrospective multicenter cohort study, we identified the first HUS-related inpatient visit among children ≤18 years (years 2004-2018). Frequency of selected ANMs and combinations of ANMs, as well as the rate of mortality, was calculated. Multivariate logistic regression was used to identify the association of ANMs and the risk of in-hospital mortality. RESULTS: Among 3915 patients included in the analysis, an ANM was noted in 10.4% (n = 409) patients. Encephalopathy was the most common ANM (n = 245). Mortality was significantly higher among patients with an ANM compared with patients without an ANM (13.9% vs 1.8%; P < .001). Individuals with any ANM had increased odds of mortality (odds ratio [OR]: 2.25; 95% confidence interval [CI]: 1.29-3.93; P = .004), with greater risk (OR: 2.60; 95% CI: 1.34-5.06; P = .005) among patients with ≥2 manifestations. Brain hemorrhage (OR: 3.09; 95% CI: 1.40-6.82; P = .005), brain infarction (OR: 2.64; 95% CI: 1.10-6.34; P = .03), anoxic brain injury (OR: 3.92; 95% CI: 1.49-10.31; P = .006), and brain edema (OR: 4.81; 95% CI: 1.82-12.71; P = .002) were independently associated with mortality. CONCLUSIONS: In this study, the largest systematic assessment of ANMs among children with HUS to date, we identify differences in in-hospital mortality based on the type of ANM, with increased risk observed for patients with multiple ANMs.

Trends, Predictors and Outcomes After Utilization of Targeted Temperature Management in Cardiac Arrest Patients With Anoxic Brain Injury.

BACKGROUND: Targeted Temperature Management (TTM) is a class I recommendation for the management of sudden cardiac arrest (SCA) patients with presumed brain injury. We aimed to study trends, predictors and outcomes in SCA patients from a nationally represented US population sample. METHODS: We utilized the National Inpatient Sample from years 2005 to 2014 for the purpose of our study. Patients with SCA and anoxic brain injury were selected using relevant ICD-9 codes. Data were analyzed for trends over the years and key outcomes were assessed. Logistic regression analysis was done to determine predictors of TTM utilization in our study population. RESULTS: A total of 78,465 patients with SCA and anoxic brain injury were identified from January 2005 to December 2014. Out of these, approximately 4,481 (5.7%) patients underwent TTM. Patients that underwent TTM were younger compared to patients without TTM utilization (60.67 vs. 63.27 years, P < 0.01). African Americans, Hispanics and women were less likely to undergo TTM. Myocardial infarction, electrolyte disorders and cardiogenic shock were associated with higher odds of TTM utilization. Sepsis, renal failure and diabetes were associated with underutilization of TTM. Inpatient mortality was higher in patients who did not undergo TTM when compared to patients who underwent TTM (67.30% vs. 65.10%, P < 0.01). CONCLUSIONS: Although TTM utilization increased over our study period, the overall application of TTM was still dismal. Factors that circumvent TTM utilization need to be addressed in future studies so more eligible patients could benefit from this life saving therapy.

The Phenomenon of Trombley-Brennan Terminal Tissue Injury in a Neonate: A Case Study.

BACKGROUND: Trombley-Brennan terminal tissue injury (TB-TTI), also known as skin failure, was first identified in 2009 among critically ill adults receiving palliative care. Identification of this skin injury can be misinterpreted as a pressure ulcer. However, this phenomenon is now accepted as an early sign of impending death among critically ill adults. CLINICAL FINDINGS: This case study describes TB-TTI in a terminally ill infant in a neonatal intensive care unit evidenced by intact, 2-cm oval skin discoloration on the lateral side of both knees with rapid progression in size. PRIMARY DIAGNOSIS: TB-TTI was identified on the day of death in an infant with a primary diagnosis of hypoxic-ischemic encephalopathy born at 32 weeks' gestation. INTERVENTIONS: The neonatal intensive care unit (NICU) team mobilized the NICU advanced care team, institution's ethical council, and "Team Lavender" to provide infant comfort measures and emotional support to the family and care givers. OUTCOMES: Infant death occurred 8 hours after TB-TTI was identified. PRACTICE RECOMMENDATIONS: To our knowledge, this case study of TB-TTI in a terminally ill neonate in the NICU has not been previously described in the neonatal or pediatric population. Early recognition of the phenomenon can enable the healthcare team to provide timely emotional, spiritual, and psychosocial support to the family and allow time to "be present" with the infant at "end of life." Future work should explore additional signs of TB-TTI and the occurrence rate.

Monthly variance in UK renal transplantation activity: a national retrospective cohort study.

OBJECTIVE: To identify whether renal transplant activity varies in a reproducible manner across the year. DESIGN: Retrospective cohort study using NHS Blood and Transplant data. SETTING: All renal transplant centres in the UK. PARTICIPANTS: A total of 24 270 patients who underwent renal transplantation between 2005 and 2014. PRIMARY OUTCOME: Monthly transplant activity was analysed to see if transplant activity showed variation during the year. SECONDARY OUTCOME: The number of organs rejected due to healthcare capacity was analysed to see if this affected transplantation rates. RESULTS: Analysis of national transplant data revealed a reproducible yearly variance in transplant activity. This activity increased in late autumn and early winter (p=0.05) and could be attributed to increased rates of living (October and November) and deceased organ donation (November and December). An increase in deceased donation was attributed to a rise in donors following cerebrovascular accidents and hypoxic brain injury. Other causes of death (infections and road traffic accidents) were more seasonal in nature peaking in the winter or summer, respectively. Only 1.4% of transplants to intended recipients were redirected due to a lack of healthcare capacity, suggesting that capacity pressures in the National Health Service did not significantly affect transplant activity. CONCLUSION: UK renal transplant activity peaks in late autumn/winter in contrast to other countries. Currently, healthcare capacity, though under strain, does not affect transplant activity; however, this may change if transplantation activity increases in line with national strategies as the spike in transplant activity coincides with peak activity in the national healthcare system.

Management of moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.

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.

LyTONEPAL: long term outcome of neonatal hypoxic encephalopathy in the era of neuroprotective treatment with hypothermia: a French population-based cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a rare neonatal condition affecting about 1‰ births. Despite a significant improvement in the management of this condition in the last ten years, HIE remains associated with high rates of death and severe neurological disability. From September 2015 to March 2017, a French national cohort of HIE cases was conducted to estimate the extent of long-term moderate and severe neurodevelopmental disability at 3 years and its determinants. METHODS: This prospective population-based cohort includes all moderate or severe cases of HIE, occurring in newborns delivered between 34 and 42 completed weeks of gestation and admitted to a neonatal intensive care unit. Detailed data on the pregnancy, delivery, and newborn until hospital discharge was collected from the medical records in maternity and neonatology units. All clinical examinations including biomarkers, EEG, and imaging were recorded. To ensure the completeness of HIE registration, a registry of non-included eligible neonates was organized, and the exhaustiveness of the cohort is currently checked using the national hospital discharge database. Follow-up is organized by the regional perinatal network, and 3 medical visits are planned at 18, 24 and 36 months. One additional project focused on early predictors, in particular early biomarkers, involves a quarter of the cohort. DISCUSSION: This cohort study aims to improve and update our knowledge about the incidence, the prognosis and the etiology of HIE, and to assess medical care. Its final objective is to improve the definition of this condition and develop prevention and management strategies for high-risk infants. TRIAL REGISTRATION: NCT02676063 . Date of registration (Retrospectively Registered): February 8, 2016.

Monitoring anoxic depolarization at the bedside: A step closer to the 24th century.

Anoxic depolarization starts the clock for irreversible brain injury. Yet, this critical indicator has been highly elusive and notoriously difficult to capture using currently available clinical monitoring tools. Recent data suggest that it may be possible to detect anoxic depolarization at the bedside. Detection of such terminal events has far-reaching implications for diagnosis, prognostication, and neuroprotection, as well as the ethics of end-of-life decision-making in neurocritical care.

Methods for Defining the Neuroprotective Properties of Xenon.

Xenon has features that make it an ideal general anesthetic agent; cost and scarcity mitigate xenon's widespread use in the operating room. Discovery of xenon's cytoprotective properties resulted in its application to thwart ongoing acute neurologic injury, an unmet clinical need. The discovery that xenon's neuroprotective effect interacts synergistically with targeted temperature management (TTM) led to its investigation in clinical settings, including in the management of the postcardiac arrest syndrome, in which TTM is indicated. Following successful demonstration of xenon's efficacy in combination with TTM in a preclinical model of porcine cardiac arrest, xenon plus TTM was shown to significantly decrease an imaging biomarker of brain injury for out of hospital cardiac arrest victims that had been successfully resuscitated. With the development of an efficient delivery system the stage is now set to investigate whether xenon improves survival, with good clinical outcome, for successfully resuscitated victims of a cardiac arrest.

Cardiopulmonary resuscitation-associated injuries in still-/newborns, infants and toddlers in a German forensic collective.

INTRODUCTION: Cardiopulmonary resuscitation (CPR) may lead to injuries. Forensic experts are sometimes confronted with claims that fatal injuries were caused by chest compressions during CPR rather than by assaults. We want to answer, how often CPR-associated injuries are present in younger children and if they may mimic injuries caused by abuse. MATERIAL AND METHODS: All autopsy records of the Institute of Legal Medicine in Leipzig, Germany in a 6-year study period were used (2011-2016). There were 3664 forensic autopsies in total, comprising 97 autopsies of children ≤4 years. After exclusion criteria we were able to include 51 cases in the study. Following this, all CPR-related variables were collected according to the 'Utstein style'. Standard procedures were used for statistical evaluation of the data. RESULTS: The most common cause of cardiac arrest was SIDS. The mean duration of CPR was 50min. Bystander CPR was performed in 43.1%. In no single case death was declared without at least partly professional CPR. Most of the children were first resuscitated out-of-hospital (41.2%). 27.5% of the children had at least one CPR injury without preference to an age group. None of the recorded CPR-associated injuries were considered significant or life-threatening. The duration of CPR or presence of bystander CPR did not correlate to the presence of any detected injury. CONCLUSION: Skeletal injuries and relevant injuries to the soft tissue and organs seem to occur only very rarely after pediatric CPR. Whenever such injuries are diagnosed, the children should be examined thoroughly for potential abuse.

Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model.

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

Does Traumatic Donor Cause of Death Influence Outcome after Lung Transplantation? A Single-Centre Analysis.

Background Owing to the shortage of donor organs in lung transplantation (LuTX), liberalization of donor selection criteria has been proposed. However, some studies suggested that donor traumatic brain damage might influence posttransplantation allograft function. This article aimed to investigate the association of donor cause of death (DCD) and outcome after LuTX. Methods A retrospective analysis of 186 consecutive double LuTXs at our institution from January 2000 to December 2008 was performed. DCD was categorized into traumatic brain injury (TBI) and nontraumatic brain injury (NTBI). In addition, NTBI was sub classified as spontaneous intracerebral bleeding (B), hypoxic brain damage (H), and intracerebral neoplasia (N). Results DCD was classified as TBI in 50 patients (26.9%) and NTBI in 136 patients (73.1%): B in 112 patients (60.2%), H in 21 patients (11.3%), and N in 3 patients (1.6%). Young male donors predominated in group TBI (mean age 36.0 ± 14.5 vs. 42.8 ± 10.7, p < 0.01; 29 males in the TBI group [58.0%] vs. 48 males in the NTBI group [35.3%], p < 0.01). Groups of DCD did not differ significantly by recipient age or gender, recipient diagnosis, donor ventilation time, or paO2/FiO2 before harvesting. TBI donors received significantly more blood (3.4 ± 3.8 vs. 1.8 ± 1.9, p = 0.03). A chest trauma was evident only in group T (n = 7 [3.7%] vs. 0 [0%], p < 0.001). Mode of donor death did not affect the following indices of graft function: length of postoperative ventilation, paO2/FiO2 ratio up to 48 hours, and lung function up to 36 months. One- and three-year survival was comparable with 84.4 and 70.4% for TBI donors versus 89.4% and 69.2% for NTBI donors. Five-year survival tended to be lower in the TBI group but did not reach statistical significance (43.4 vs. 53.9%). Conclusion This study indicates that traumatic DCD does not affect outcome after LuTX. These results can be achieved with an ideal donor management combined with an individual case-to-case evaluation by an experienced LuTX surgeon.

Persistent generalized periodic discharges: A specific marker of fatal outcome in cerebral hypoxia.

OBJECTIVES: Electroencephalography (EEG) is one of the methods used in predicting the outcome after cerebral hypoxia. In this study we aim to evaluate the significance of generalized periodic discharges (GPD) as a prognostic marker. METHODS: We retrospectively analyzed the medical histories of patients, who underwent an EEG after cardiac arrest during the time period from 2005 to 2013 at the University Hospital Zurich. All EEGs were re-interpreted using the 2012 American Clinical Neurophysiology Society (ACNS) classification for intensive care unit (ICU) EEGs. RESULTS: Out of 131 patients, in which an EEG was recorded after cardiopulmonary resuscitation, 119 were included in our study. The average interval between cardiac arrest and EEG-recording was 3.8±3.0days (range: 0-14days). Persistent GPDs (i.e. GPDs more than 24h after the event) were found in thirty-two (26.9%) of the patients initial EEGs. The appearance of persistent GPDs preceded fatal outcome in 100% of all cases (vs. 69.0% in the non-GPD-group, p<0.0001). CONCLUSION: Among other encephalopathic markers in EEG persistent GPDs are a highly specific prognostic marker of fatal outcome in patients with hypoxic encephalopathy. SIGNIFICANCE: Using standardized EEG interpretation, this study identified persistent GPDs as a specific prognostic marker in post cardiac arrest syndrome.

Is venous congestion associated with reduced cerebral oxygenation and worse neurological outcome after cardiac arrest?

BACKGROUND: Post-cardiac arrest (CA) patients are at risk of secondary ischemic damage in the case of suboptimal brain oxygenation during an ICU stay. We hypothesized that elevated central venous pressures (CVP) would impair cerebral perfusion and oxygenation (venous cerebral congestion). The aim of the present study was to investigate the relationship between CVP, cerebral tissue oxygen saturation (SctO2) as assessed with near-infrared spectroscopy (NIRS) and outcome in post-CA patients. METHODS: This was an observational study in 48 post-CA patients with continuous CVP and SctO2 monitoring during therapeutic hypothermia. RESULTS: The relationship between CVP and mean SctO2 was best described by an S-shaped, third-degree polynomial regression curve (SctO2 = -0.002 × CVP(3) + 0.08 × CVP(2) - 1.07 × CVP + 69.78 %, R (2) 0.89, n = 1,949,108 data points) with high CVP (>20 mmHg) being associated with cerebral desaturation. Multivariate linear regression revealed CVP to be a more important determinant of SctO2 than mean arterial pressure (MAP) without important interaction between both (SctO2 = 0.01 × MAP - 0.20 × CVP + 0.001 × MAP × CVP + 65.55 %). CVP and cardiac output were independent determinants of SctO2 with some interaction between both (SctO2 = 1.86 × CO - 0.09 × CVP - 0.05 × CO × CVP + 60.04 %). Logistic regression revealed that a higher percentage of time with CVP above 5 mmHg was associated with lower chance of survival with a good neurological outcome (cerebral performance category (CPC) 1-2) at 180 days (OR 0.96, 95 % CI 0.92-1.00, p = 0.04). In a multivariate model, the negative association between CVP and outcome persisted after correction for hemodynamic variables, including ejection fraction and MAP. CONCLUSIONS: Elevated CVP results in lower brain saturation and is associated with worse outcome in post-CA patients. This pilot study provides support that venous cerebral congestion as indicated by high CVP may be detrimental for post-CA patients.

Is Impaired Autoregulation Associated with Mortality in Patients with Severe Cerebral Diseases?

BACKGROUND: Cerebral autoregulation (CA) is a mechanism that compensates for variations in cerebral perfusion pressure (CPP) by changes in cerebral blood flow resistance to keep the cerebral blood flow constant. In this study, the relationship between lethal outcome during hospitalisation and the autoregulation-related indices PRx and Mx was investigated. MATERIALS AND METHODS: Thirty patients (aged 18-77 years, mean 53 ± 16 years) with severe cerebral diseases were studied. Cerebral blood flow velocity (CBFV), arterial blood pressure (ABP) and intracranial pressure (ICP) were repeatedly recorded. CA indices were calculated as the averaged correlation between CBFV and CPP (Mx) and between ABP and ICP (PRx). Positive index values indicated impairment of CA. RESULTS: Six patients died in hospital. In this group both PRx and Mx were significantly higher than in the group of survivors (PRx: 0.41 ± 0.33 vs 0.09 ± 0.25; Mx: 0.28 ± 0.40 vs 0.03 ± 0.21; p = 0.01 and 0.04, respectively). PRx and Mx correlated significantly with Glasgow Outcome Scale (GOS) score (PRx: R = -0.40, p < 0.05; Mx: R = -0.54, p < 0.005). PRx was the only significant risk factor for mortality (p < 0.05, logistic regression). CONCLUSION: Increased PRx and Mx were associated with risk of death in patients with severe cerebral diseases. The relationship with mortality was more pronounced in PRx, whereas Mx showed a better correlation with GOS score.

Consciousness, unconsciousness and death in the context of slaughter. Part I. Neurobiological mechanisms underlying stunning and killing.

This review describes the neurobiological mechanisms that are relevant for the stunning and killing process of animals in the abattoir. The mechanisms underlying the loss of consciousness depend on the technique used: mechanical, electrical or gas stunning. Direct exsanguination (without prior stun) causes also a loss of consciousness before inducing death. The underlying mechanisms may involve cerebral anoxia or ischemia, or the depolarisation, acidification and/or the destruction of brain neurons. These effects may be caused by shock waves, electrical fields, the reduction or arrest of the cerebral blood circulation, increased levels of CO2 or low levels of O2 in the inhaled air, or the mechanical destruction of neurons. The targeted brain structures are the reticular formation, the ascending reticular activating system or thalamus, or the cerebral hemispheres in a general manner. Some of the techniques, when properly used, induce an immediate loss of consciousness; other techniques a progressive loss of consciousness.

Brain hypoxia is exacerbated in hypobaria during aeromedical evacuation in swine with traumatic brain injury.

BACKGROUND: There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury. We tested the hypothesis that the effects of prolonged aeromedical evacuation on critical neurophysiologic parameters (i.e., brain oxygenation [PbtO2]) of swine with a fluid percussion injury/TBI would be detrimental compared with ground (normobaric) transport. METHODS: Yorkshire swine underwent fluid percussion injury/TBI with pretransport stabilization before being randomized to a 4-hour aeromedical transport at simulated flight altitude of 8,000 ft (HYPO, n = 8) or normobaric ground transport (NORMO, n = 8). Physiologic measurements (i.e., PbtO2, cerebral perfusion pressure, intracranial pressure, regional cerebral blood flow, mean arterial blood pressure, and oxygen transport variables) were analyzed. RESULTS: Survival was equivalent between groups. Measurements were similar in both groups at all phases up to and including onset of flight. During the flight, PbtO2, cerebral perfusion pressure, and mean arterial blood pressure were significantly lower in the HYPO than in the NORMO group. At the end of flight, regional cerebral blood flow was lower in the HYPO than in the NORMO group. Other parameters such as intracranial pressure, cardiac output, and mean pulmonary artery pressure were not significantly different between the two groups. CONCLUSION: A 4-hour aeromedical evacuation at a simulated flight altitude of 8,000 ft caused a notable reduction in neurophysiologic parameters compared with normobaric conditions in this TBI swine model. Results suggest that hypobaric conditions exacerbate cerebral hypoxia and may worsen TBI in casualties already in critical condition.