Maintain Oxygen Delivery Research Articles

Cerebral Blood flow responses to Hypoxia in Preterm Lambs

BACKGROUND In response to hypoxia, the fetus redistributes blood flow from the periphery to the brain by increasing blood pressure and perhaps decreasing cerebral vascular resistance. This response, which serves to maintain oxygen delivery to the fetal brain, has not been well studied shortly after birth, when a catecholamine surge …

Sex Differences in Response to Acute Sympathetic Activation During Steady State Hypoxia

BackgroundActivation of the sympathetic nervous system causes vasoconstriction and a reduction in peripheral blood flow. This sympathetically‐mediated vasoconstriction may be attenuated during hypoxia to maintain oxygen delivery – termed sympatholysis. However, hypoxic sympatholysis was previously shown to be absent in humans. A limitation of prior work was the failure to directly examine this response in women. Given young women exhibit an increase in blood flow during hypoxia, we hypothesized hypoxic sympatholysis would be present in young women but absent in young men.MethodsBlood pressure (BP, finger photoplethysmography) and forearm blood flow (FBF, venous occlusion plethysmography) were assessed in healthy young men (n=9, 26±1 yrs) and women (n=10, 24±1 yrs). Subjects completed two trials consisting of a 2‐min cold pressor test (CPT) during baseline normoxia (0.21 FiO2, 98±0% SpO2) and following 3 min of steady‐state hypoxia (0.11±0.01 FiO2, 82±1% SpO2). FBF was normalized for BP (forearm vascular conductance, FVC). A change in FVC from steady‐state during the last 1‐min of CPT was calculated (ΔFVC). The difference in ΔFVC between normoxia and hypoxia trials was used as an index of hypoxic sympatholysis.ResultsIn men, ΔFVC did not differ between normoxia and hypoxia (ΔFVC Normoxia: −0.30±0.45, Hypoxia: −0.77±0.41 mL/dL/100mmHg/min; p=0.46). In contrast, in women ΔFVC during normoxia (−0.70±0.27 mL/dL/100mmHg/min) was attenuated during hypoxia (+0.48±0.46 mL/dL/100mmHg/min; p=0.04) – indicating sympatholysis. The magnitude of hypoxic sympatholysis was greater in women than in men (Men: −0.46±0.38, Women: +1.18±0.39 mL/dL/100mmHg/min; p<0.01).ConclusionYoung women attenuate sympathetically‐mediated vasoconstriction during steadystate hypoxia, whereas men do not. In other words, hypoxic sympatholysis is present in young women, but absent in young men. These data advance our understanding of sex‐related differences in hypoxic vascular control.Support or Funding InformationFundingNIH HL130339

Blood Transfusion Requirements for Patients on Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a rescue device used for cardiac and pulmonary dysfunction. Patients on ECMO often require blood transfusions to maintain oxygen delivery and recover from bleeding complications. Goals of the current study are to determine: 1) transfusion requirements while on ECMO, 2) incidence of bleeding complications, 3) transfusion requirements for bleeding complications. Packed Red Blood Cell (PRBC) transfusions and bleeding complications were identified by retrospective chart review of patients on ECMO from 2010 to 2018 at our institution. Patients were categorized into those who did not bleed (group A) and those who bled (group B). Incidence and sites of bleeding were analyzed, and transfusion requirement for each bleeding event was determined. Among a total of 217 patients including veno-arterial (VA) (n=148) and veno-venous (VV) (n=69) ECMO, we identified 62 patients (29%) without bleeding complications (group A) and 155 patients (71%) with bleeding complications (group B). Overall PRBC transfusion requirement was significantly higher in group B (1.6 PRBC/day) than group A (0.5 PRBC/day) [p=<0.0001]. In group A, number of PRBC requirements was 0.6 PRBC/day for VA ECMO (n=42) and 0.2 PRBC/day for VV ECMO (n=20) [p=0.0015]. In group B, number of PRBC requirements was 1.8 PRBC/day for VA ECMO (n=106) and 1.1 PRBC/day for VV ECMO (n=49) [p=0.0006]. In group B, number of PRBC given per major bleeding complication during ECMO was: mediastinal/thoracic bleed (7.3 PRBC), GI bleed (7.1 PRBC), cannulation site bleed (5.2 PRBC), and ENT bleed (4.1 PRBC). Number of PRBC given per event per day for major bleeding complications during ECMO was: mediastinal/thoracic bleed (84events, 4.7 PRBC/event/day), GI bleed (59 events, 4.8 PRBC/event/day), cannula site bleed (88 events, 3.6 PRBC/event/day), and ENT bleed (103 events, 2.8 PRBC/event/day). 30-Day hospital survival rate after ECMO decannulation was higher in group A (71%) than group B (49%) [p=0.003]. Various bleeding complications were observed during ECMO. Transfusion requirements dramatically increased once patients developed bleeding complications. Patient outcomes were exacerbated by bleeding complications. ECMO patients without any clinical bleeding still required transfusion, which was higher in VA than VV ECMO.

Emerging trends, techniques, and equipment for airway management in pediatric patients.

Pediatric patients present unique anatomic and physiologic considerations in airway management, which impose significant physiologic limits on safe apnea time before the onset of hypoxemia and subsequent bradycardia. These issues are even more pronounced for the pediatric difficult airway. In the last decade, the development of pediatric sized supraglottic airways specifically designed for intubation, as well as advances in imaging technology such that current pediatric airway equipment now finally rival those for the adult population, has significantly expanded the pediatric anesthesiologist's tool kit for pediatric airway management. Equally important, techniques are increasingly implemented that maintain oxygen delivery to the lungs, safely extending the time available for pediatric airway management. This review will focus on emerging trends and techniques using existing tools to safely handle the pediatric airway including videolaryngoscopy, combination techniques for intubation, techniques for maintaining oxygenation during intubation, airway management in patients at risk for aspiration, and considerations in cannot intubate cannot oxygenate scenarios.

A mathematical model of cerebral blood flow control in anaemia and hypoxia.

The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice.

Deer mice, Peromyscusmaniculatus, live at high altitudes where limited O2 represents a challenge to maintaining oxygen delivery to tissues. Previous work has demonstrated that hypoxia acclimation of deer mice and low altitude white-footed mice (P. leucopus) increases the force generating capacity of the diaphragm. The mechanism behind this improved contractile function is not known. Within myocytes, the myofilament plays a critical role in setting the rate and level of force production, and its ability to generate force can change in response to changes in physiological conditions. In the current study, we examined how chronic hypobaric hypoxia exposure of deer mice and white-footed mice influences the Ca2+ activation of force generation by skinned diaphragmatic myofilaments, and the phosphorylation of myofilament proteins. Results demonstrate that myofilament force production, and the Ca2+ sensitivity of force generation, were not impacted by acclimation to hypobaric hypoxia, and did not differ between preparations from the two species. The cooperativity of the force-pCa relationship, and the maximal rate of force generation were also the same in the preparations from both species, and not impacted by acclimation. Finally, the relative phosphorylation of TnT, and MLC was lower in deer mice than white-footed mice, but was not affected by acclimation. These results indicate that species differences in diaphragm function, and the increase in force production with hypoxia acclimation, are not due to differences, or changes, in myofilament function. However, it appears that diaphragmatic myofilament function in these species is not affected by chronic hypobaric hypoxia exposure.

Predictive Capacity of Oxygen Delivery During Cardiopulmonary Bypass on Acute Kidney Injury

The randomized goal-directed perfusion trial confirmed retrospective findings that a goal-directed perfusion strategy to maintain oxygen delivery index (DO2i) during cardiopulmonary bypass greater than 280 mL/min/m2 reduces the incidence of acute kidney injury (AKI). We developed a predictive model for AKI using data from the Australian and New Zealand Collaborative Perfusion Registry to determine whether these findings could be validated in a real-world clinical setting and to identify an optimal DO2i threshold for predictive diagnostic accuracy. Data in 19,410 cardiopulmonary bypass procedures were randomly divided into training (n= 9705) and validation (n= 9705) datasets. Multivariate logistic regression was used to determine the best predictive models for AKI (RIFLE [renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease] classification), incremental predictive value of minimum cardiopulmonary bypass DO2i, and optimal threshold. Minimum DO2i was significantly associated with any AKI, AKI risk, and AKI injury or greater class in both datasets (validation dataset; any AKI odds ratio [OR], 0.993; 95% confidence interval [CI], 0.991-0.995; P < .001; AKI risk OR, 0.994; 95% CI, 0.992-0.996; P < .001, AKI injury or greater 0.993; 95% CI, 0.991-0.996; P < .001), representing on average a 7% increase in the likelihood of AKI for every 10-mL/min/m2 decrease in DO2i. Diagnostic accuracy was similar for both datasets, with an optimal DO2i threshold of 270 mL/min/m2. The odds of any AKI were increased by 52% in those below the threshold (OR, 1.52; 95% CI, 1.29-1.77; P < .001). This study confirms previous findings that minimum DO2i during cardiopulmonary bypass is independently associated with AKI, supporting previous findings in a broader-risk, multicenter cohort.

Increased testicular blood flow maintains oxygen delivery and avoids testicular hypoxia in response to reduced oxygen content in inspired air

Despite a long-standing assertion that mammalian testes operate near hypoxia and increased testicular temperature causes frank hypoxia, we have preliminary evidence that changes are due to hyperthermia per se. The objective was to determine how variations in inspired oxygen concentration affected testicular blood flow, oxygen delivery and extraction, testicular temperature and lactate production. Eight rams were maintained under general anesthesia, with successive decreases in oxygen concentration in inspired air (100, 21 and 13%, respectively). As oxygen concentration decreased from 100 to 13%, there were increases in testicular blood flow (9.6 ± 1.7 vs 12.9 ± 1.9 ml/min/100 g of testis, P < 0.05; mean ± SEM) and conductance (normalized flow; 0.46 ± 0.07 to 1.28 ± 0.19 ml/min/mm Hg/100 g testis (P < 0.05). Increased testicular blood flow maintained oxygen delivery and increased testicular temperature by ~1 °C; this increase was correlated to increased testicular blood flow (r = 0.35, P < 0.0001). Furthermore, oxygen utilization increased concomitantly and there were no significant differences among oxygen concentrations in blood pH, HCO3− or base excess, and no effects of venous-arterial differences in lactate production. In conclusion, under acute hypoxic conditions, testes maintained oxygen delivery and uptake by increasing blood flow and oxygen extraction, with no evidence of anaerobic metabolism. However, additional studies are needed to determine longer-term responses and potential evidence of anaerobic metabolism at the molecular level.

Goal-directed perfusion to reduce acute kidney injury: A randomized trial

ObjectiveTo determine whether a goal-directed perfusion (GDP) strategy aimed at maintaining oxygen delivery (DO2) at ≥280 mL·min−1·m−2 reduces the incidence of acute kidney injury (AKI). MethodsThis multicenter randomized trial enrolled a total of 350 patients undergoing cardiac surgery in 9 institutions. Patients were randomized to receive either GDP or conventional perfusion. A total of 326 patients completed the study and were analyzed. Patients in the treatment arm were treated with a GDP strategy during cardiopulmonary bypass (CPB) aimed to maintain DO2 at ≥280 mL·min−1·m−2. The perfusion strategy for patients in the control arm was factored on body surface area and temperature. The primary endpoint was the rate of AKI. Secondary endpoints were intensive care unit length of stay, major morbidity, red blood cell transfusions, and operative mortality. ResultsAcute Kidney Injury Network (AKIN) stage 1 was reduced in patients treated with GDP (relative risk [RR], 0.45; 95% confidence interval [CI], 0.25-0.83; P = .01). AKIN stage 2-3 did not differ between the 2 study arms (RR, 1.66; 95% CI, 0.46-6.0; P = .528). There were no significant differences in secondary outcomes. In a prespecified analysis of patients with a CPB time between 1 and 3 hours, the differences in favor of the treatment arm were more pronounced, with an RR for AKI of 0.49 (95% CI, 0.27-0.89; P = .017). ConclusionsA GDP strategy is effective in reducing AKIN stage 1 AKI. Further studies are needed to define perfusion interventions that may reduce more severe levels of renal injury (AKIN stage 2 or 3).

Targeting expression of adenosine receptors during hypoxia induced angiogenesis – A study using zebrafish model

Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known. We evaluated the mRNA expression of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH 1a and DLL4 and the phenotypic variations of zebrafish embryos when treated with DAPT, γ-secretase inhibitor of Notch in addition to treating the embryos with SU5416, a VEGF receptor inhibitor. Upregulation of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH1a and DLL4 was observed embryos were when treated with forskolin and NECA could possibly mimic hypoxic condition. Hatching and heart rate also increased with NECA and forskolin. SU5416 showed decreases in blood vessel formation and decreased adenosine receptors, VEGF, VEGFR2, HIF1a and NRP1a expression and DAPT, exhibited decreases in blood vessels and decreased NRP1a, NOTCH1a, DLL4 expression. These embryos developed with poor vasculature, tail bending, abnormal phenotypes and developmental delay. Forskolin treated with inhibitors showed increased blood vessel formation, normal phenotype, development and adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH 1a and DLL4 gene expression suggesting that adenosine mediated Notch and VEGF could play an important role during development and angiogenesis. Targeting VEGF and Notch signaling with adenosine receptors inhibitors which might have a therapeutic significance during hypoxia and abnormal angiogenesis.

Hypoxia during VV ECMO

Venovenous extracorporeal membrane oxygenation (VV ECMO) is the preferred mode for any kind of acute respiratory failure. The desired PO2 is > 50 and SPO2 > 88% but the acceptable values can be PO2 > 45 and SPO2 > 80%. In case if we are accepting lower PO2, we have to keep a higher hematocrit and meticulously monitor neurological status, lactates, and urine output to maintain oxygen delivery. Saturation during ECMO run depends on ECMO circulation, native circulation, and ratio of ECMO flow to cardiac output ([Table 1]). Whenever the effective ECMO circulation decreases, saturation decreases. So, decrease in ECMO flow, ECMO FiO2, failing membrane oxygenator, and increase in recirculation will lead to hypoxia. Similarly, anything that decreases the contribution from native circulation will also lead to hypoxia. So, decrease in ventilator settings and worsening lung status lead to hypoxia. Anything that increases metabolism, such as fever and restlessness, will also cause hypoxia due to increased consumption.

Research status and future of goal-directed fluid therapy

Fluid therapy plays an important role in maintaining the stability of vital signs and the good perfusion of tissues.Therefore, it is the basis for treatment of diseases.The purpose of fluid therapy is to keep the patient′s effective circulating volume, increase cardiac output, and ensure adequate tissue perfusion, which may facilitate the transport of oxygen and nutrients.Perioperative fluid therapy has gone through the progress from choosing the type of liquid to reforming the mode of fluid treatment.Since the concepts of fast track surgery and precision medicine appeared, the anesthesiologists and surgeons have pay more attention to the goal-directed fluid therapy(GDFT). GDFT aims to maintain organ perfusion and oxygen transport of tissues by regulating the amount of fluid on basis of a physiological index.As a new fluid therapy, GDFT contributes to maintaining oxygen delivery and reducing both morbidity and mortality.This article reviews the progress and challenges for GDFT. Key words: Fluid therapy; Goal-directed fluid therapy; Hemodynamics

Towards individualized perioperative, goal-directed haemodynamic algorithms for patients of advanced age: observations during a randomized controlled trial (NCT01141894)

BackgroundDuring a previous study on intraoperative goal-directed haemodynamic treatment (GDHT) in elderly patients, cardiac performance did not improve as anticipated (ClinicalTrials.gov NCT01141894). We hypothesized that in this group, responsiveness to interventions could be predicted by individual patient characteristics. MethodsData for the present study were collected during a previously performed, single-centre, open, randomized, and controlled parallel-group superiority trial in patients aged ≥70 yr undergoing hip-fracture surgery. Haemodynamic parameters were collected by the LiDCOplus™ monitor. The GDHT group received oxygen delivery-guided fluid challenges and dobutamine infusion. Management in the routine fluid treatment group was clinician guided without access to LiDCOplus™ readings. In the GDHT group, independent predictors were assessed by multiple logistic regression analyses of two outcomes: first fluid challenge response (defined as increase of stroke volume by ≥10%); and overall intervention response (maintenance of oxygen delivery at the end of surgery). ResultsData from 72 routine fluid treatment and 70 GDHT patients were analysed. Clinician-guided pre-anaesthesia fluid loading increased the stroke volume in 14% of patients, and 17% of patients increased or maintained oxygen delivery at the end of surgery. The GDHT-guided first and subsequent fluid challenges were associated with increased stroke volume in 39 and 9% of patients, respectively, and increased or maintained oxygen delivery was present in 47% of patients at the end of surgery. In the GDHT group, a baseline stroke volume index (<28 ml m−2) was an independent predictor of first fluid challenge response, and a baseline oxygen delivery index (<330 ml min−1 m−2) was a predictor of maintained or increased oxygen delivery. ConclusionsFewer patients responded to GDHT than anticipated. Our data suggest that individual characteristics could predict the haemodynamic responses. Clinical trial registrationNCT01141894.

Some like it hot: Thermal tolerance and oxygen supply capacity in two eurythermal crustaceans.

Thermal sensitivity of the cardiorespiratory oxygen supply capacity has been proposed as the cardinal link underlying the upper boundary of the temperature niche in aquatic ectotherms. Here we examined the evidence for this link in two eurythermal decapods, the Giant tiger shrimp (Penaeus monodon) and the European crayfish (Astacus astacus). We found that both species have a temperature resistant cardiorespiratory system, capable of maintaining oxygen delivery up to their upper critical temperature (Tcrit). In neither species was Tcrit reduced in hypoxia (60% air saturation) and both species showed an exponential increase in heart and gill ventilation rates up to their Tcrit. Further, failure of action potential conduction in preparations of A. astacus motor neurons coincided with Tcrit, indicating that compromised nervous function may provide the underlying determinant for Tcrit rather than oxygen delivery. At high temperatures, absolute aerobic scope was maintained in P. monodon, but reduced in A. astacus. However, A. astacus also displayed reduced exercise intensity indicating that impaired muscle performance with resulting reduced tissue oxygen demand may explain the reduced scope rather than insufficient oxygen supply capacity. This interpretation agrees with early literature on aquatic ectotherms, correlating loss of nervous function with impaired locomotion as temperatures approach Tcrit.

Skeletal muscle vasodilation during systemic hypoxia in humans.

In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response.

Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is mechanistically and therapeutically challenging, not only because of the molecular and cellular perturbations that generate vascular abnormalities, but also the modifications to circulatory physiology that result, and are likely to exacerbate vascular injury. First, most HHT patients have visceral arteriovenous malformations (AVMs). Significant visceral AVMs reduce the systemic vascular resistance: supra-normal cardiac outputs are required to maintain arterial blood pressure, and may result in significant pulmonary venous hypertension. Secondly, bleeding from nasal and gastrointestinal telangiectasia leads to iron losses of such magnitude that in most cases, diet is insufficient to meet the ‘hemorrhage adjusted iron requirement.’ Resultant iron deficiency restricts erythropoiesis, leading to anemia and further increases in cardiac output. Low iron levels are also associated with venous and arterial thromboses, elevated Factor VIII, and increased platelet aggregation to circulating 5HT (serotonin). Third, recent data highlight that reduced oxygenation of blood due to pulmonary AVMs results in a graded erythrocytotic response to maintain arterial oxygen content, and higher stroke volumes and/or heart rates to maintain oxygen delivery. Finally, HHT-independent factors such as diet, pregnancy, sepsis, and other intercurrent illnesses also influence vascular structures, hemorrhage, and iron handling in HHT patients. These considerations emphasize the complexity of mechanisms that impact on vascular structures in HHT, and also offer opportunities for targeted therapeutic approaches.

Abstract T P370: Blood Transfusions in Pediatric Sickle Cell Disease Normalize Cerebral Blood Flow While Maintaining Constant Cerebral Oxygen Metabolism

Background: Chronic blood transfusions (Tx) reduces stroke risk in pediatric sickle cell disease (SCD). Cerebral blood flow (CBF) is elevated in SCD, likely representing a compensatory mechanism to maintain cerebral oxygen metabolism (CMRO2) in the setting of reduced arterial oxygen content (CaO2) from chronic anemia. When exhausted compensatory mechanisms are unable to meet oxygen demands, stroke ensues. We measured MR-derived CBF and oxygen extraction fraction (OEF) pre- and post-Tx, hypothesizing that Tx ‘resets’ the CBF baseline by increasing CaO2 via increased hemoglobin (Hb), while maintaining cerebral oxygen delivery and metabolism. Methods: SCD children on chronic Tx were enrolled in a prospective, observational MRI study. MR-CBF and MR-OEF were acquired before and 2 hours after exchange Tx. MR-CBF and MR-OEF were measured using pseudocontinuous arterial spin labelling and a novel asymmetric spin echo sequence, respectively. CaO2 =1.35 x [Hb] x SaO2. CMRO2 = CaO2 x CBF x OEF. Results: Two SCD children underwent MRI pre- and post-Tx (six more are anticipated prior to ISC). For subject #1 (18 yo F with overt stroke), mean global CBF was 128 and 98 ml/min/100g pre- and post-Tx, respectively, indicating a 24% CBF reduction. For subject #2 (6 yo F with elevated transcranial Doppler velocities), mean global CBF was 189 and 129 ml/min/100g pre- and post-Tx, respectively, a 32% CBF reduction (Fig). Both Hb and CaO2 were increased after Tx, resulting in unchanged oxygen delivery (CaO2 x CBF) post-Tx. Moreover, OEF and CMRO2 were not significantly different pre- and post-Tx, consistent with our hypothesis that CBF increases to maintain oxygen delivery. Conclusions: Elevated CBF is likely a compensatory mechanism to maintain constant oxygen delivery in SCD children who have chronically low CaO2. In our subjects, Tx improved CaO2, allowing CBF to normalize. This reduced hemodynamic stress likely contributes to the lower stroke risk in chronically transfused SCD children.

PO-0422 Evaluation Of Cerebral Perfusion In Small For Gestational Age Neonates In The First Postnatal Week Using Colour Doppler Sonography

Background and aims Small for gestational age neonates (SGA) living in conditions of chronic hypoxia during fetal life may develop different autoregulation mechanisms in cerebral perfusion in order to maintain oxygen delivery to the brain in comparison to appropriate for gestational age (AGA) neonates. The aim of the current study was to estimate brain perfusion in SGA neonates during first postnatal week with the use of colour Doppler sonography. Patients/methods Transcranial Doppler sonography from the temporal acoustic window was performed bilaterally with CX50 PHILIPS device using S8–3 transducer in the first, third and seventh day of life of SGA neonates with mean gestational age 31.6 ± 2.2w and to comparable AGA ones. Recorded parameters were Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV), Pulsatility Index (PI) and Resistance Index (RI) in middle cerebral artery MCA. Results 26 SGA and 26 matched for GA control AGA neonates were prospectively enrolled with statistically significant difference in birth weight (1.201, 9 ± 369.1 vs 1.805, 3 ± 431.7, p Conclusion Increased brain metabolism in the first postnatal days is responsible for the observed augmentation of cerebral perfusion in order to maintain the balance between oxygen delivery and consumption. It seems that SGA neonates manage to develop compensatory mechanisms probably with an increase of their brain perfusion.

Traumatic hypovolemic shock revisited: the spectrum of contrast-enhanced abdominal computed tomography findings and clinical implications for its management.

Hypovolemic shock is often seen in patients with severe blunt trauma who have suffered from blood circulation inadequate to maintain oxygen delivery to multiple organs. The early recognition and prompt management of hypovolemic shock in patients with multiple injuries are mandatory to improving prognosis and patient conditions. The diagnostic accuracy of computed tomography (CT) as a primary diagnostic tool is well established. The abdominal organs show several common and classic appearances on contrast-enhanced CT in patients with trauma. The hypovolemic shock complex is reported in the previous literature as decreased enhancement of the viscera, increased mucosal enhancement and luminal dilation of the small bowel, mural thickening and fluid-filled loops of the small bowel, the halo sign and flattening of the inferior vena cava, reduced aortic diameter, and peripancreatic edema. However, there have been controversial CT reports with contradictory appearances. Physicians understanding these findings could prompt alternative approaches to the early assessment and management of hypovolemic shock. The aim of this article is to illustrate common and well-known abdominal CT features in patients with traumatic hypovolemic shock, to discuss controversial CT signs in the pancreas and adrenal gland, and to describe CT findings' clinical implications when managing hypovolemic shock.

Curable hypoxia in an octogenarian with an undiagnosed inherited condition: a case commentary

The accompanying case is an excellent illustration of why pulmonary arteriovenous malformations (PAVMs) have been considered very rare. Patients with PAVMs are generally asymptomatic and may be highly athletic, even in the presence of profound hypoxaemia due to right-to-left shunting through PAVMs. Data in papers published this year help explain why patients are so rarely symptomatic [1–3]; why some become symptomatic [1, 2]; and why, irrespective of respiratory symptoms, all PAVMs should be considered for treatment [4, 5]. PAVM development is usually complete by the end of puberty, and the octogenarian in this case would have spent decades undiagnosed with “silent” PAVMs and hypoxaemia. To understand how this could be the case, it is important to realise that, although this patient had low blood oxygen levels, his tissues were not more “hypoxic” than normal. Instead, as recently emphasised [1–3], PAVM patients use multiple mechanisms to maintain oxygen delivery. First, the relevant term for oxygen transport is not the arterial oxygen tension ( P aO2) or arterial oxygen saturation ( S aO2), but the arterial oxygen content ( C aO2) which also depends upon the concentration of haemoglobin [6]. Hypoxaemic PAVM patients generally utilise polycythaemic responses so that, irrespective of the S aO2, C aO2 on standing is preserved at just under 18 mL·dL−1 [1]. Secondly, the overall transport of oxygen to the tissues also depends on the volume of blood reaching the tissues in any given period (cardiac output) [6]. Cardiac output is the product of the heart rate and stroke volume, and both are increased in PAVM patients to compensate for hypoxaemia [2, 3]. For example, in the 165 PAVM patients reported …