Cerebral Oxygen Delivery Research Articles

RBC Transfusion Improves Cerebral Oxygen Delivery in Subarachnoid Hemorrhage.

Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5 mL/100 g/min. PET facility located within the Neurology/Neurosurgery ICU. Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13 g/dL. Transfusion of one unit of RBCs over 1 hour. Baseline hemoglobin was 9.7 g/dL (range, 6.9-12.9), and cerebral blood flow was 43 ± 11 mL/100 g/min. After transfusion, hemoglobin rose from 9.6 ± 1.4 to 10.8 ± 1.4 g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5 mL/100 g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.

Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

Cerebral and lung effects of a new generation synthetic surfactant with SP-B and SP-C analogs in preterm lambs.

Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS. Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed. After delivery, lambs developed severe RDS (FIO2 :1, pH < 7.15, PaCO2 > 70 mmHg, PaO2 < 40 mmHg, Cdyn < 0.1 mL/cmH2 O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, PaCO2 , carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls. Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment.

Abstract TP418: Red Blood Cell Transfusion Increases Cerebral Oxygen Delivery After Subarachnoid Hemorrhage Regardless of Hemoglobin Level

Introduction: Impaired oxygen delivery (DO 2 ), as a result of reduced cerebral blood flow (CBF), is the hallmark of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). Anemia further contributes to reductions in DO 2 and places the brain at risk for infarction. Transfusion, by raising hemoglobin (Hgb) and oxygen content of arterial blood, may be able to reduce the risk of ischemia. However, it is unknown whether an Hgb threshold exists above which CBF will fall sufficient to negate any benefit of transfusion on DO 2 . In this physiologic proof-of-principle study we evaluated whether transfusion improves DO 2 and reduces brain vulnerable to ischemia across a broad range of Hgb values. Methods: 47 SAH patients with/at-risk for DCI with Hgb 7-13 g/dl were transfused 1 unit of red blood cells (RBCs). 15 O-PET imaging was used to measure CBF, DO 2 , and oxygen extraction fraction (OEF) before and after transfusion. Vulnerable brain regions were defined as those with baseline DO 2 &lt; 4.5 ml/100g/min (equivalent to CBF of 25 ml/100g/min at low-normal Hgb). Results: Baseline Hgb was 9.7 g/dl (range 6.9-12.5) and CBF was 43±11 ml/100g/min. After transfusion, Hgb rose by 12% and global DO 2 by 10% (from 5.0 to 5.5 ml/100g/min, p=0.001), with CBF only marginally lower; response to transfusion was not dependent on Hgb level. Transfusion resulted in a greater (16%) rise in DO 2 , associated with a larger reduction in OEF, in vulnerable brain regions (p=0.005 for low vs. normal regions), even after adjusting for Hgb. Number of vulnerable regions was reduced from median 9 to 4 per patient (p=0.005). Conclusions: Transfusion of RBCs to patients at-risk for DCI improves cerebral oxygen delivery, preferentially to vulnerable regions and reduces brain at-risk for ischemia. This physiologic benefit does not appear limited to those with severe anemia but persists to Hgb as high as 13 g/dl. Our findings suggest that restrictive transfusion practices may not be appropriate in this population. Prospective trials are needed to determine if these physiologic benefits outweigh risks of transfusion and translate into clinical prevention of DCI.

Skin-to-skin care in preterm infants receiving respiratory support does not lead to physiological instability

ObjectiveProviding skin-to-skin care (SSC) to preterm infants is standard practice in many neonatal intensive care units. There are conflicting reports on the stability of oxygen saturation (SpO2) during SSC, which...

Cerebral Hemodynamics and Metabolism During Cardiac Arrest and Cardiopulmonary Resuscitation Using Hyperspectral Near Infrared Spectroscopy.

Maintaining cerebral oxygen delivery and metabolism during cardiac arrest (CA) through resuscitation is essential to improve the survival rate while avoiding brain injury. The effect of CA and cardiopulmonary resuscitation (CPR) on cerebral and muscle oxygen delivery and metabolism is not clearly quantified.Methods and Results:A novel hyperspectral near-infrared spectroscopy (hNIRS) technique was developed and evaluated to measure cerebral oxygen delivery and aerobic metabolism during ventricular fibrillation (VF) CA and CPR in 14 pigs. The hNIRS parameters were measured simultaneously on the dura and skull to investigate the validity of non-invasive hNIRS measurements. In addition, we compared the hNIRS data collected simultaneously on the brain and muscle. Following VF induction, oxygenated hemoglobin (HbO2) declined with a 9.9 s delay and then cytochrome-c-oxidase (Cyt-ox) decreased on average 4.4 s later (P<0.05). CPR improved cerebral metabolism, which was reflected by an average 0.4 μmol/L increase in Cyt-ox, but had no significant effect on HbO2, deoxygenated hemoglobin (HHb) and tissue oxygen saturation (tSO2). Cyt-ox had greater correlation with HHb than HbO2. Muscle metabolism during VF and CPR was significantly different from that of the brain. The total hemoglobin concentration (in the brain only) increased after ~200 s of untreated CA, which is most likely driven by cerebral autoregulation through vasodilation. Overall, hNIRS showed consistent measurements of hemodynamics and metabolism during CA and CPR.

Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction

Patients with a single ventricle experience a high rate of brain injury and adverse neurodevelopmental outcome; however, the incidence of brain abnormalities throughout surgical reconstruction and their relationship with cerebral blood flow, oxygen delivery, and carbon dioxide reactivity remain unknown. Patients with a single ventricle were studied with magnetic resonance imaging scans immediately prior to bidirectional Glenn (pre-BDG), before Fontan (BDG), and then 3 to 9 months after Fontan reconstruction. One hundred sixty-eight consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (mean age, 4.8±1.7 months), 118 BDG (2.9±1.4 years), and 54 after Fontan (2.4±1.0 years). Nonacute ischemic white matter changes on T2-weighted imaging, focal tissue loss, and ventriculomegaly were all more commonly detected in BDG and Fontan compared with pre-BDG patients (P<0.05). BDG patients had significantly higher cerebral blood flow than did Fontan patients. The odds of discovering brain injury with adjustment for surgical stage as well as ≥2 coexisting lesions within a patient decreased (63%-75% and 44%, respectively) with increasing amount of cerebral blood flow (P<0.05). In general, there was no association of oxygen delivery (except for ventriculomegaly in the BDG group) or carbon dioxide reactivity with neurological injury. Significant brain abnormalities are commonly present in patients with a single ventricle, and detection of these lesions increases as children progress through staged surgical reconstruction, with multiple coexisting lesions more common earlier than later. In addition, this study demonstrated that BDG patients had greater cerebral blood flow than did Fontan patients and that an inverse association exists of various indexes of cerebral blood flow with these brain lesions. However, CO2 reactivity and oxygen delivery (with 1 exception) were not associated with brain lesion development. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02135081.

Cerebral haemodynamic response to somatosensory stimulation in near-term fetal sheep.

Cerebral haemodynamic response to neural stimulation has been extensively investigated in animal and clinical studies, in both adult and paediatric populations, but little is known about cerebral haemodynamic functional response in the fetal brain. The present study describes the cerebral haemodynamic response measured by near-infrared spectroscopy to somatosensory stimulation in fetal sheep. The cerebral haemodynamic response in the fetal sheep brain changes from a positive (increase in oxyhaemoglobin (oxyHb)) response pattern to a negative or biphasic response pattern when the duration of somatosensory stimulation is increased, probably due to cerebral vasoconstriction with prolonged stimulations. In contrast to adult studies, we have found that changes in fetal cerebral blood flow and oxyHb are positively increased in response to somatosensory stimulation during hypercapnia. We propose this is related to reduced vascular resistance and recruitment of cerebral vasculature in the fetal brain during hypercapnia. Functional hyperaemia induced by a localised increase in neuronal activity has been suggested to occur in the fetal brain owing to a positive blood oxygen level-dependent (BOLD) signal recorded by functional magnetic resonance imaging following acoustic stimulation. To study the effect of somatosensory input on local cerebral perfusion we used near-infrared spectroscopy (NIRS) in anaesthetised, partially exteriorised fetal sheep where the median nerve was stimulated with trains of pulses (2ms, 3.3Hz) for durations of 1.8, 4.8 and 7.8s. Signal averaging of cerebral NIRS responses to 20 stimulus trains repeated every 60s revealed that a short duration of stimulation (1.8s) increased oxyhaemoglobin in the contralateral cortex consistent with a positive functional response, whereas longer durations of stimulation (4.8, 7.8s) produced more variable oxyhaemoglobin responses including positive, negative and biphasic patterns of change. Mean arterial blood pressure and cerebral perfusion as monitored by laser Doppler flowmetry always showed small, but coincident increases following median nerve stimulation regardless of the type of response detected by the NIRS in the contralateral cortex. Hypercapnia significantly increased the baseline total haemoglobin and deoxyhaemoglobin, and in 7 of 8 fetal sheep positively increased the changes in contralateral total haemoglobin and oxyhaemoglobin in response to the 7.8s stimulus train, compared to the response recorded during normocapnia. These results show that activity-driven changes in cerebral perfusion and oxygen delivery are present in the fetal brain, and persist even during periods of hypercapnia-induced cerebral vasodilatation.

Neuroprotection in Critical Care Neurology.

Ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury-all have in common early brain injury due to brain tissue destruction, reduced cerebral blood flow and oxygen delivery, and overall substantial morbidity and mortality. The pathophysiology of brain tissue damage likely includes common cellular mechanisms. Neuroprotection has seldom, if ever, been shown to reduce early brain injury. Secondary brain injury develops after these conditions due to macroscopic events such as increased intracranial pressure and reduced cerebral blood flow, as well as cellular processes including vascular damage, inflammation, and apoptotic/necrotic cell death. Preclinical as well as some human studies show successful neuroprotection with, for example, hypothermia for cardiac arrest. Nevertheless, there remains much room for improvement that will require randomized clinical trials of emerging neuroprotective strategies.

Abstract 13741: Neurologic Injury and Cerebral Blood Flow In Single Ventricles Throughout Staged Surgical Reconstruction

Introduction: Single ventricle pts experience a high rate of brain injury and adverse neurodevelopmental outcome. Hypothesis: The incidence of brain abnormalities is different at various surgical stages and is linked with cerebral blood flow (CBF), oxygen delivery and carbon dioxide reactivity. Methods: Single ventricle pts were studied with MRI scans immediately prior to bidirectional Glenn (pre-BDG), prior to Fontan and then 3-9 months after Fontan reconstruction. Results: 168 consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (4.8±1.7 months), 118 BDG (2.9±1.4 years) and 54 after Fontan (3.4±1.1 years). Non-acute ischemic white matter changes on T2 weighted imaging, focal tissue loss, punctate microbleeds and ventriculomegaly were all more commonly detected in BDG and Fontans compared to pre-BDG (see figure); punctate microbleeds were also more common in Fontan than pre-BDG (P&lt;0.05). CBF was higher in BDG than Fontan and almost reached statistical significance versus pre-BDG (see graph). The odds of discovering brain injury adjusting for surgical stage as well as 2 or more co-existing lesions within a patient all decreased (63-97% and 44% respectively) with increasing amount of CBF (P&lt;0.05). In general, there was no association of oxygen delivery or carbon dioxide reactivity with neurological injury. Conclusion: Significant brain abnormalities are commonly present in single ventricle pts and detection of these lesions increase as children progress through staged surgical reconstruction with multiple co-existing lesions more common earlier than later. Cumulative exposures to surgery may account for increased incidence, though changes in brain maturation may increase detection of white matter injury. In addition, an inverse association of various indices of CBF with these brain lesions is present (CBF highest in BDG stage), however, CO 2 reactivity, oxygen delivery were not associated with brain lesion development.

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia.

Cognitive performance is impaired by hypoxia despite global cerebral oxygen delivery and metabolism being maintained. Using arterial spin labelled (ASL) magnetic resonance imaging, this is the first study to show regional reductions in cerebral blood flow (CBF) in response to decreased oxygen supply (hypoxia) at 2h that increased in area and became more pronounced at 10h. Reductions in CBF were seen in brain regions typically associated with the 'default mode' or 'task negative' network. Regional reductions in CBF, and associated vasoconstriction, within the default mode network in hypoxia is supported by increased vasodilatation in these regions to a subsequent hypercapnic (5% CO2 ) challenge. These results suggest an anatomical mechanism through which hypoxia may cause previously reported deficits in cognitive performance. Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2h) and prolonged (10h) poikilocapnic normobaric hypoxia. We found that 2h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the 'default mode' or 'task negative' network. After 10h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO2 ) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady-state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory.

OC25.01: Cerebral oxygen delivery, brain growth and white matter maturation are reduced in congenital heart disease fetuses

OC25.01: Cerebral oxygen delivery, brain growth and white matter maturation are reduced in congenital heart disease fetuses

Effects of epinephrine on cerebral oxygenation during cardiopulmonary resuscitation: A prospective cohort study

BackgroundEpinephrine has been presumed to improve cerebral oxygen delivery during cardiopulmonary resuscitation (CPR), but animal and registry studies suggest that epinephrine-induced capillary vasoconstriction may decrease cerebral capillary blood flow and worsen neurological outcome. The effect of epinephrine on cerebral oxygenation (rSO2) during CPR has not been documented in the clinical setting. MethodsrSO2 was measured continuously using cerebral oximetry in patients with in-hospital cardiac arrest. During CPR, time event markers recorded the administration of 1mg epinephrine. rSO2 values were analysed for a period beginning 5min before and ending 5min after the first epinephrine administration. ResultsA total of 56 epinephrine doses were analysed in 36 patients during CPR. The average rSO2 value in the 5-min following epinephrine administration was 1.40% higher (95% CI=0.41–2.40%; P=0.0059) than in the 5-min period before epinephrine administration. However, there was no difference in the overall rate of change of rSO2 when comparing the 5-min period before, with the 5-min period immediately after a single bolus dose of epinephrine (0.88%/min vs 1.07%/min respectively; P=0.583), There was also no difference in the changes in rSO2 at individual 1, 2, 3, or 4-min time windows before and after a bolus dose of epinephrine (P=0.5827, 0.2371, 0.2082, and 0.6707 respectively). ConclusionsA bolus of 1mg epinephrine IV during CPR produced a small but clinically insignificant increase in rSO2 in the five minutes after administration. This is the first clinical data to demonstrate the effects of epinephrine on cerebral rSO2 during CPR.

Effects of race and sex on cerebral hemodynamics, oxygen delivery and blood flow distribution in response to high altitude.

To assess racial, sexual, and regional differences in cerebral hemodynamic response to high altitude (HA, 3658 m). We performed cross-sectional comparisons on total cerebral blood flow (TCBF = sum of bilateral internal carotid and vertebral arterial blood flows = QICA + QVA), total cerebrovascular resistance (TCVR), total cerebral oxygen delivery (TCOD) and QVA/TCBF (%), among six groups of young healthy subjects: Tibetans (2-year staying) and Han (Han Chinese) at sea level, Han (2-day, 1-year and 5-year) and Tibetans at HA. Bilateral ICA and VA diameters and flow velocities were derived from duplex ultrasonography; and simultaneous measurements of arterial pressure, oxygen saturation, and hemoglobin concentration were conducted. Neither acute (2-day) nor chronic (>1 year) responses showed sex differences in Han, except that women showed lower TCOD compared with men. Tibetans and Han exhibited different chronic responses (percentage alteration relative to the sea-level counterpart value) in TCBF (−17% vs. 0%), TCVR (22% vs. 12%), TCOD (0% vs. 10%) and QVA/TCBF (0% vs. 2.4%, absolute increase), with lower resting TCOD found in SL- and HA-Tibetans. Our findings indicate racial but not sex differences in cerebral hemodynamic adaptations to HA, with Tibetans (but not Han) demonstrating an altitude-related change of CBF distribution.

Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously.

Neonatal haemodynamic effects following foetal exposure to labetalol in hypertensive disorders of pregnancy

Objective: Hypertensive disorders of pregnancy (HDP) affect foetal outcome. Labetalol is frequently used to lower maternal blood pressure and prolong pregnancy. Conflicting evidence exists for specific neonatal side effects described after maternal labetalol treatment. Our aim was to investigate neonatal effects of foetal exposure to labetalol on cerebral oxygenation and extraction.Methods: In a prospective observational study, clinical characteristics, vital parameters and cerebral oxygen delivery and extraction were collected during the first 24 h of life in labetalol-exposed preterm neonates and compared with two control groups.Results: Twenty-two infants with a mean gestational age of 28.9 weeks, born from labetalol-treated mothers with HDP were included and matched with 22 infants with non-labetalol-treated mothers with HDP and 22 infants without maternal HDP. No significant differences between groups were found neither in heart rate, blood pressure and inotropic support, nor in mean regional cerebral oxygen saturation and fractional tissue oxygen extraction.Conclusion: Foetal labetalol exposure associated effects on preterm heart rate, blood pressure, cerebral oxygenation and extraction are not demonstrated. Maternal disease severity seems to play a more important role in neonatal cerebral haemodynamics. Maternal labetalol treatment has no clinically important short term side effects in the preterm neonate.

E.04 Coma and delirium are associated with low levels of brain tissue oxygen in critically ill patients

Background: The cause of ICU delirium is unknown. We used near infrared spectroscopy (NIRS) to measure brain tissue oxygenation (BtO2) in critically ill patients, to test the hypothesis that poor cerebral oxygen delivery contributes to ICU delirium. Methods: Adult patients were enrolled if they required mechanical ventilation for &gt;24 hours, and/or vasoactive agents. Patients were excluded if they had previous cognitive dysfunction, brain injury on admission, or a life expectancy &lt;24 hours. BtO2 was measured for the first 24 hours of ICU admission. The confusion assessment method-ICU (CAM-ICU) was used to screen for delirium. Participants were designated to one of three groups on the basis of their predominant neurological status (comatose, delirious, or intact). Results: To date, 47 patients have been recruited. Both delirious and comatose patients’ had significantly lower BtO2 levels compared to intact patients (P&lt;0.001). There was a significant correlation between hemoglobin and BtO2 (R2=0.347, P&lt;0.01). However, when correlation analysis was conducted separately amongst the three groups, the delirious patients (R2=0.485, P&lt;0.05) were the strongest contributors to this positive correlation. Conclusions: Delirious patients exhibited the lowest BtO2 recordings and demonstrated a significant association between Hb and BtO2. This study offers potential insight into the pathophysiology of ICU delirium.

Cerebral oxygen delivery is reduced in newborns with congenital heart disease

ObjectiveTo investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. MethodsUsing a “feed-and-sleep” approach to performing neonatal magnetic resonance imaging, we measured cerebral blood flow by using a slice prescription perpendicular to the right and left internal carotid arteries and basilar artery at the level of the clivus. We calculated brain volume by segmenting a 3-dimensional steady-state free procession acquisition of the whole brain, allowing quantification of cerebral blood flow indexed to brain volume. Cerebral oxygen delivery was calculated as the product of cerebral blood flow and preductal systemic arterial oxygen content obtained via a combination of conventional pulse oximetry and laboratory analysis of venous blood samples for hemoglobin concentration. ResultsA complete set of measurements were obtained in 32 newborns with heart disease and 31 controls. There was no difference in gestational age between the heart disease and control groups. There was no difference in cerebral blood flow compared with controls (103.5 ± 34.0 vs 119.7 ± 40.4 mL/min), whereas cerebral oxygen delivery was significantly lower in the congenital heart disease subjects (1881 ± 625.7 vs 2712 ± 915.7 mLO2/min). Ten newborns with congenital heart disease had diffuse excessive high signal intensity in their white matter and 2 had white matter injury whereas another 5 had both. ConclusionsNewborns with unrepaired cyanotic congenital heart disease have decreased cerebral oxygen delivery due to arterial desaturation. If brain growth and development are adversely affected through oxygen conformance, our findings could have clinical implications in terms of timing of surgical repair.

Influence Of Lung Volume On Circulatory Function And Arterial Blood Gases During Prolonged Breath Holding In Elite Apnea Divers

Maximal apnea in elite breath hold divers involves the suppression of involuntary breathing movements (IBMs). During apnea at total lung capacity (TLC), stroke volume (SV) is reduced due to compression of the vena cava; however, IBMs are thought to improve apnea time by elevating cardiac output (Q[Combining Dot Above]) and cerebral oxygen delivery (CDO2) via increased venous return. Although not experimentally investigated, this suggests CDO2 is limited by the reduced Q[Combining Dot Above] secondary to lung inflation. The purpose of this study was to investigate whether a higher Q[Combining Dot Above] during apnea at functional residual capacity (FRC) facilitates CDO2 and determine whether IBM onset and apnea end are linked to PaO2, oxygen content (CaO2) or CDO2. Fifteen elite divers (1F; 185 ± 7 cm, 82 ± 12 kg, 29 ± 7 years) completed two maximal apneas at TLC and FRC. Cardiovascular responses were assessed continuously via photoplethysmography. Global extra-cerebral blood flow (gCBF) and intra-cranial velocities were measured via extracranial and transcranial ultrasound, respectively. Arterial blood gases were assessed at IBM onset and apnea end. Maximal apnea was 38% longer at TLC vs. FRC (304 ± 71 vs. 188 ± 44 sec, P<0.001) and IBM onset occurred later (150 ± 44 vs. 113 ± 36 sec, P <0.001). At FRC, SV and Q[Combining Dot Above] did not change from baseline (P>0.05). In contrast, during the TLC trial SV and Q[Combining Dot Above] were decreased until 80% and 40% of apnea duration, respectively, (P<0.05). Consistent with Q[Combining Dot Above], gCBF was significantly lower at 20% apnea during the TLC trial but recovered for the remainder of the apnea. Mean arterial pressure rose progressively in both trials but to a greater extent at TLC. At apnea end, although PaO2 was lower (30 ± 8 vs. 35 ± 11 mmHg, P=0.004) in the FRC trial, CaO2 was the same due to a higher PaCO2 in the TLC trial. IBM onset occurred at the same PaCO2 (43 ± 5 vs. 43 ± 5 mmHg, P=0.60) but a lower PaO2 (46 ± 14 vs. 71 ± 18 mmHg, p<<0.001) during the FRC trial. Lung volume has a profound effect on SV, Q[Combining Dot Above] and gCBF during the early stages of apnea. However, at apnea end, Q[Combining Dot Above], gCBF and CDO2 are the same irrespective of lung volume. A comparable CaO2 despite a lower PaO2 at FRC apnea end highlights the importance of acidosis on the oxygen dissociation curve. In addition, IBMs appear to be governed by PaCO2 rather than PaO2 suggesting any beneficial effect of IBMs on CDO2 to be indirect and secondary to hypercapnia.

Lessons from altitude: cerebral perfusion insights and their potential translational clinical significance

What is the topic of this review? The long-held assumption that transcranial Doppler middle cerebral artery velocity is a surrogate for cerebral blood flow has been questioned in certain circumstances, particularly where tissue oxygenation changes. What advances does it highlight? Cerebral venous outflow restriction appears to be implicated in the development of high-altitude cerebral oedema. Rapid ascent to high altitude commonly results in acute mountain sickness and, on occasion, potentially fatal high-altitude cerebral oedema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. One of the main theories to explain the development of acute mountain sickness is an increase in intracranial pressure. Vasogenic (extracellular water accumulation attributable to increased permeability of the blood-brain barrier) and cytotoxic (intracellular) oedema have also been postulated as potential mechanisms that underlie high-altitude cerebral oedema. Recently published findings derived from a very challenging field study (obtained at altitudes of up to 7950m), substantiated by sea-level hypoxic magnetic resonance angiography studies, have given new insights into the maintenance of cerebral blood flow at altitude. This report provides new perspectives and potential mechanisms to account for the maintenance of cerebral oxygen delivery at high and extreme altitude. In particular, the long-held assumption that transcranial Doppler middle cerebral artery velocity is a surrogate for cerebral blood flow has been shown to be incorrect in certain circumstances. The emerging evidence for a potential third mechanism, namely the restrictive venous outflow hypothesis, in the development of high-altitude cerebral oedema, over and above the accepted vasogenic and cytotoxic hypotheses, is also appraised.