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Aerobic metabolism relies on external oxygen production through photosynthesis and its subsequent transport into each cell of the body via the cardiorespiratory system. This mechanism has successfully evolved over millions of years, enabling animals to inhabit most environments on Earth. However, the insufficient oxygen supply leads to several clinical problems, ranging from non-healing wounds to tumor resistance to therapy. Given that photosynthetic microorganisms are capable of producing oxygen and removing carbon dioxide from the environment, over the last decade, several groups worldwide have proposed their potential use as an alternative tissue oxygenation approach. While most studies have demonstrated safety and efficacy after local tissue administration, recent studies have also suggested that systemic administration could trigger intravascular photosynthesis. If successful, the development of a new generation of circulating cells, known as chlorocytes, may partially replace the role of erythrocytes in gas exchange within the body, without relying on external supply and vascular flow. This work reviews the existing literature on local and systemic administration of photosynthetic microorganisms, highlighting the main challenges in the field and potential solutions to unleash the enormous potential clinical impact of chlorocytes and intravascular photosynthesis. Key points: • Circulating photosynthetic microorganisms could deliver oxygen to tissues • Microalgae and cyanobacteria have shown safety and efficacy for oxygen delivery • Several key challenges need to be addressed for the clinical success of chlorocytes [ABSTRACT FROM AUTHOR]

Key points The present study was designed to test the potential utility of regional cerebral oxygen saturation (rcSO2) in detecting term infants with brain injury. The study also examined whether quantitative rcSO2 features are associated with grade of hypoxic ischaemic encephalopathy (HIE). We analysed 58 term infants with HIE (>36 weeks of gestational age) enrolled in a prospective observational study. All newborn infants had a period of continuous rcSO2 monitoring and magnetic resonance imaging (MRI) assessment during the first week of life. rcSO2 Signals were pre‐processed and quantitative features were extracted. Machine‐learning and deep‐learning models were developed to detect adverse outcome (brain injury on MRI or death in the first week) using the leave‐one‐out cross‐validation approach and to assess the association between rcSO2 and HIE grade (modified Sarnat – at 1 h). The machine‐learning model (rcSO2 excluding prolonged relative desaturations) significantly detected infant MRI outcome or death in the first week of life [area under the curve (AUC) = 0.73, confidence interval (CI) = 0.59−0.86, Matthew's correlation coefficient = 0.35]. In agreement, deep learning models detected adverse outcome with an AUC = 0.64, CI = 0.50−0.79. We also report a significant association between rcSO2 features and HIE grade using a machine learning approach (AUC = 0.81, CI = 0.73−0.90). We conclude that automated analysis of rcSO2 using machine learning methods in term infants with HIE was able to determine, with modest accuracy, infants with adverse outcome. De novo approaches to signal analysis of NIRS holds promise to aid clinical decision making in the future. Hypoxic‐induced neonatal brain injury contributes to both short‐ and long‐term functional deficits. Non‐invasive continuous monitoring of brain oxygenation using near‐infrared‐ spectroscopy offers a potential new insight to the development of serious injury. In this study, characteristics of the NIRS signal were summarised using either predefined features or data‐driven feature extraction, both were combined with a machine learning approach to predict short‐term brain injury. Using data from a cohort of term infants with hypoxic ischaemic encephalopathy, the present study illustrates that automated analysis of regional cerebral oxygen saturation rcSO2, using either machine learning or deep learning methods, was able to determine infants with adverse outcome. [ABSTRACT FROM AUTHOR]

Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO2i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO2i, which yielded a target nadir value (272 mL/min/m2) and an area under the curve (DO2i272AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO2i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO2i measurements above the target nadir DO2i272 ranged from 60.5% to 78.4% with a mean+/−SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO2i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO2i272 (p <.001), with a crude increase of approximately 7.8% for DO2i272AUC, and a 73.8% success rate (p <.001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO2i272 could not be reached. The two most common responses were an 'inability to improve CPB flow rates' and 'restrictive allogeneic red blood cell transfusion policies'. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process. [ABSTRACT FROM AUTHOR]

Shock is a life-threatening clinical condition that arises when there is inadequate oxygen metabolism at a cellular level. It can occur in a wide range of clinical conditions and without prompt identification and management it has a high morbidity and mortality. Treatment focuses on both correcting the cause and managing the abnormal physiology associated with shock. Clinicians use a number of tools including clinical examination, biochemical markers and haemodynamic monitoring to both identify and treat shock. In this article we will review the normal physiology of oxygen delivery, the aetiology and pathophysiology of shock and how haemodynamic monitoring is used to manage patients presenting with shock. [ABSTRACT FROM AUTHOR]

To compare brain injury biomarker release levels between two different cardiopulmonary bypass (CPB) flow rates in elective cardiac surgery and to explore differences in postoperative delirium between groups and associations between age, sex, CPB time, oxygen levels, and near-infrared spectroscopy, and biomarker levels. A randomized controlled substudy trial Sahlgrenska University Hospital, Sweden Forty patients undergoing elective cardiac surgery with CPB Patients were assigned at random to either a standard (2.4 L/min/m2) or a high (2.9 L/min/m2) CPB flow rate. Glial fibrillary acidic protein, neurofilament light chain, total-tau, and phosphorylated-tau217 were sampled in plasma before anesthesia induction, after 60 minutes on CPB, and at 30 minutes, 24 hours, and 72 hours post-CPB. Mixed models for repeated measures were used to analyze differences in biomarker levels between groups and to assess relationships, which showed no differences between the 2 flow rate groups. There also was no difference in the occurrence of delirium between the 2 groups. Associations were found between age and increased neurofilament light chain levels. Female sex, oxygen delivery >330 mL/min/m2, and near-infrared spectroscopy level >60% were associated with lower biomarker levels. An increased flow rate did not have any significant effects on biomarker levels compared to a standard flow rate. Several associations were identified between treatment characteristics and biomarker levels. No difference in delirium was seen. [ABSTRACT FROM AUTHOR]

Introduction Non-compressible torso hemorrhagic (NCTH) shock is the leading cause of potentially survivable trauma on the battlefield. New hypotensive drug therapies are urgently required to resuscitate and protect the heart and brain following NCTH. Our aim was to examine the strengths and limitations of permissive hypotension and discuss the development of small-volume adenosine, lidocaine, and Mg2+ (ALM) fluid resuscitation in rats and pigs. Materials and Methods For review of permissive hypotension, a literature search was performed from inception up to November 2023 using PubMed, Cochrane, and Embase databases, with inclusion of animal studies, clinical trials and reviews with military and clinical relevance. For the preclinical study, adult female pigs underwent laparoscopic liver resection. After 30 minutes of bleeding, animals were resuscitated with 4 mL/kg 3% NaCl ± ALM bolus followed 60 minutes later with 4 h 3 mL/kg/h 0.9% NaCl ± ALM drip (n  = 10 per group), then blood transfusion. Mean arterial pressure (MAP) and cardiac output (CO) were continuously measured via a left ventricular pressure catheter and pulmonary artery catheter, respectively. Systemic vascular resistance (SVR) was calculated using the formula: 80 × (MAP − CVP)/CI. Oxygen delivery was calculated as the product of CO and arterial oxygen content. Results Targeting a MAP of ∼50 mmHg can be harmful or beneficial, depending on how CO and SVR are regulated. A theoretical example shows that for the same MAP of 50 mmHg, a higher CO and lower SVR can lead to a nearly 2-fold increase in O2 supply. We further show that in animal models of NCTH, 3% NaCl ALM bolus and 0.9% NaCl ALM drip induce a hypotensive, high flow, vasodilatory state with maintained tissue O2 supply and neuroprotection. ALM therapy increases survival by resuscitating the heart, reducing internal bleeding by correcting coagulopathy, and decreasing secondary injury. Conclusions In rat and pig models of NCTH, small-volume ALM therapy resuscitates at hypotensive pressures by increasing CO and reducing SVR. This strategy is associated with heart and brain protection and maintained tissue O2 delivery. Translational studies are required to determine reproducibility and optimal component dosing. ALM therapy may find wide utility in prehospital and far-forward military environments. [ABSTRACT FROM AUTHOR]

To estimate whether the association of transfusion and acute kidney injury (AKI) has a threshold of oxygen delivery below which transfusion is beneficial but above which it is harmful. Retrospective study Cardiovascular operating room and intensive care unit Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass None Logistic regression was used to estimate the associations between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis of transfused and nontransfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. Nine hundred ninety-one of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (odds ratio [OR], 0.968; 95% confidence interval [CI], 0.949-0.988; p = 0.002) and transfusions (OR, 1.442; 95% CI, 1.077, 1.932; p = 0.014) were associated with increased odds of AKI by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the OR steeper at <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely than matched nontransfused patients to develop AKI (45% [n = 145] v 31% [n = 101]; p < 0.001). However, after propensity score adjustment, the difference was nonsignificant (OR, 1.181; 95% CI, 0.796-1.752; p = 0.406). We found a nonlinear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a decreased risk of AKI. [ABSTRACT FROM AUTHOR]

Microparticles have demonstrated value for regenerative medicine. Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration. Here, inspired by erythrocytes-associated self-repairing process in damaged tissue, we present novel biomimetic erythrocyte-like microparticles (ELMPs). These ELMPs, which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus, hemoglobin, and growth factors (GFs), are generated by using a microfluidic electrospray. As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen, they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion, stimulating angiogenesis, and adjusting the release profile of cargoes. Based on these features, we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration. Thus, we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.

Dodecafluoropentane emulsion (DDFPe) is a fluorocarbon (FC) under clinical development as an oxygen therapeutic and is regulated as a blood substitute. Compared to all the prior FCs studied, DDFP is the most advantageous for oxygen delivery and it is active at a lower concentration (1/200th to 1/1000th the weight of other FCs). DDFP has a boiling point of 29 °C, is more water soluble than prior FCs, and following IV administration clears via exhalation. Prior FCs had boiling points ≥ 140 °C and were retained long-term in the body causing adverse events. DDFP is a gas at biological temperature while prior FCs were liquids. Gases deliver roughly 1000 times more oxygen than liquids. DDFPe has two mechanisms of action: (1) The size of the molecule is the smallest that is a liquid at room temperature; on a molar volume basis this equates to more dissolution of oxygen. (2) Because of its boiling point close to physiologic temperature, DDFP delivers oxygen more effectively than liquid FCs.Highlight PointsFluorocarbons (FCs) dissolve oxygen and other respirable gases.FC emulsions generally do not have biological effects of and by themselves, but rather they increase the oxygen carrying capacity of the blood.There are a variety of FCs that were developed in the past as blood substitutes but they all caused accumulation in humans leading to toxic responses.Dodecafluoropentane emulsion (DDFPe) is being developed as an oxygen therapeutic to increase the oxygen carrying capacity of the blood and oxygen delivery to tissues.

Background: Fetuses closer to term present predominantly as cephalic, and by the time of delivery 96-97% of them are born headfirst. To date, no coherent hypothesis has been put forth to explain the phenomenon. Observation: As pregnancy advances, there is a progressive increase in cephalic presentation; by 25 weeks, 60% are cephalic, at 35 weeks 90% cephalic and at term only less than 3-4% remain breech. Hypothesis: Oxygen delivery to the fetus comes from the environment through the parturient and it must traverse a very long passage to get to the fetal tissues making oxygen delivery a very precarious process. The fetus develops several compensatory mechanisms to enhance the delivery of oxygen—higher hemoglobin level, hemoglobin with greater affinity for oxygen, the double Bohr phenomenon to improve the diffusion of oxygen from the parturient and lastly redesign of the fetal circulation to increase flow to the brain whilst in the state of near chronic hypoxia whilst in utero. The better flow of blood to the head and therefore more oxygen to the brain makes this organ the densest causing it to progressively present cephalic as pregnancy advances. Implications: The hypothesis aligns well with not only the observed progressive cephalic phenomenon but also the long-term subtle cognitive deficits and neurological sequelae observed in several studies of those born breech. Conclusion: Cephalic presentation at birth is driven by better blood flow to the brain as another compensatory mechanism to cope with hypoxia.

Abstract Background Retinopathy of prematurity (ROP) is a leading cause of avoidable blindness in children, particularly in Latin America, where hyperoxia is a significant risk factor. This study evaluated resource availability and use for administering and monitoring supplemental oxygen in Mexico. Methods In 2011, an observational study in which 32 government neonatal intensive care units (NICUs) across Mexico were visited. Data collected included occupancy, staffing levels, and equipment to deliver and monitor supplemental oxygen. Preterm infants receiving oxygen were observed. In 2023, 13 NICUs were revisited, and similar data collected. Staffing levels were benchmarked against Argentinian and US recommendations. Results In 2011, only 38% of NICUs had adequate medical and staffing levels to meet recommended cot-to-staff ratios for all shifts. Staffing ratios were worse during weekends and at night than during weekdays. Only 25.5% of cots had blenders, and 80.1% had saturation monitors. 153 infants were observed 87% of whom were being monitored. Upper and lower oxygen saturations were ≥ 96% in 53%, and ≤ 89% in 8%, respectively. Alarm settings were inadequate, as 38% and 32% of upper and lower alarms were switched off and 16% and 53% were incorrectly set, respectively. In the 13 NICUs with data from 2011 and 2023, cot-to-staff ratios deteriorated over time, and in 2023 no unit had recommended ratios for all shifts. Equipment provision did not change, with similar proportions of babies in oxygen being monitored (79% 2011; 75% 2023). Rates of hyperoxia decreased slightly from 54% in 2011 to 49% in 2023. More upper alarms were set (46% 2011; 75% 2023), but a higher proportion were incorrectly set (52% 2011; 68% 2023). Conclusions Between 2011 and 2023, cot-to-staff ratios worsened, and equipment for safe oxygen delivery and monitoring remained insufficient. Despite available monitoring equipment, oxygen saturations often exceeded recommended levels, and alarms were frequently not set or incorrectly configured. Urgent improvements are needed in healthcare workforce numbers and practices, along with ensuring adequate equipment for safe oxygen delivery.

Respiratory disorders are a frequent cause of admission in the newborn. Respiratory diseases have unique physiologic, a n a t o m i c a n d c l i n i c a l characteristics during this period necessitating special management. K n o w l e d g e o f t h e pathophysiology of pulmonary diseases and their differential impact on the lungs of differing stages of maturity is essential to the safe and efficacious applications of special techniques of treatment. Principles of respiratory management include establishment of the airway, ensuring oxygenation, assisted ventilation, assessing adequacy of vent i l a t ion, cor r e c t ion of metabolic abnormalities and alleviation of cause of distress. The goal of treatment is safe and effective assistance to oxygen delivery and carbon dioxide removal from the tissues. Inspired oxygen should be administered in a controlled manner to provide adequate but not excessive blood oxygen tension levels. Mechanical ventilation may be required to treat metabolic abnormalities. There is the need for continuous monitoring and re- evaluation. This article is intended to present an overview of the embryology of the respiratory system, pulmonary physiology in the newborn, the principles of oxygen therapy and mechanical ventilation. It also discusses the complications that can follow.

Background: Retinopathy of prematurity (ROP) is a leading cause of avoidable blindness in children, particularly in Latin America, where hyperoxia is a significant risk factor. This study evaluated resource availability and use for administering and monitoring supplemental oxygen in Mexico. Methods: In 2011, an observational study in which 32 government neonatal intensive care units (NICUs) across Mexico were visited. Data collected included occupancy, staffing levels, and equipment to deliver and monitor supplemental oxygen. Preterm infants receiving oxygen were observed. In 2023, 13 NICUs were revisited, and similar data collected. Staffing levels were benchmarked against Argentinian and US recommendations. Results: In 2011, only 38% of NICUs had adequate medical and staffing levels to meet recommended cot-to-staff ratios for all shifts. Staffing ratios were worse during weekends and at night than during weekdays. Only 25.5% of cots had blenders, and 80.1% had saturation monitors. 153 infants were observed 87% of whom were being monitored. Upper and lower oxygen saturations were ≥ 96% in 53%, and ≤ 89% in 8%, respectively. Alarm settings were inadequate, as 38% and 32% of upper and lower alarms were switched off and 16% and 53% were incorrectly set, respectively. In the 13 NICUs with data from 2011 and 2023, cot-to-staff ratios deteriorated over time, and in 2023 no unit had recommended ratios for all shifts. Equipment provision did not change, with similar proportions of babies in oxygen being monitored (79% 2011; 75% 2023). Rates of hyperoxia decreased slightly from 54% in 2011 to 49% in 2023. More upper alarms were set (46% 2011; 75% 2023), but a higher proportion were incorrectly set (52% 2011; 68% 2023). Conclusions: Between 2011 and 2023, cot-to-staff ratios worsened, and equipment for safe oxygen delivery and monitoring remained insufficient. Despite available monitoring equipment, oxygen saturations often exceeded recommended levels, and alarms were frequently not set or incorrectly configured. Urgent improvements are needed in healthcare workforce numbers and practices, along with ensuring adequate equipment for safe oxygen delivery. [ABSTRACT FROM AUTHOR]

The presence of hypoxics, bacterial infection, and the creation of bacterial biofilms are significant obstacles that hinder the healing of diabetic wounds. Calcium peroxide (CaO2) can be hydrolyzed to produce oxygen (O2) and hydrogen peroxide (H2O2), resulting in the simultaneous creation of oxygen and an antimicrobial effect. However, oxygen delivery is limited by the skin and bacterial biofilm barrier. Herein, we proposed a microneedles patch loading CaO2 nanoparticles (abbreviated as CaO2 NPs@MN). The microneedles can puncture the skin and destroy the biofilm barrier. Meanwhile, upon contact with the biological fluid, the microneedles would be dissolved, and CaO2 NPs would be released into the wound site, further being hydrolyzed to O2 and H2O2 to achieve antibacterial effect and local deep oxygen delivery. Notably, in order to encapsulate CaO2 powders evenly into the microneedle tips and avoid their hydrolysis during the preparation process, we fabricated the nanoscaled CaO2 particles and encapsulated them in microneedles in an ethanol system for the first time. The in vitro experiments demonstrated that CaO2 NPs@MN possessed the desired oxygen delivery and antibacterial effect. Furthermore, the elimination of bacteria, reduction in inflammation, promotion of collagen formation, stimulation of blood vessel growth, and subsequent acceleration of wound healing were observed in in vivo experiments. In conclusion, we provided a simple process for the application of CaO2 in wound healing and also a promising strategy for infected diabetic ulcer treatment. [ABSTRACT FROM AUTHOR]

Background In the management of patients resuscitated from out‐of‐hospital cardiac arrest, a primary goal is to restore sufficient oxygen delivery (DO2) to meet demands in oxygen consumption (VO2). Methods and Results This post hoc analysis of the BOX (Blood Pressure and Oxygen Targets) study included adult patients who were comatose and experienced out‐of‐hospital cardiac arrest from a presumed cardiac cause, who were randomized to a mean arterial blood pressure (MAP) target of 63 mm Hg (MAP63) or 77 mm Hg (MAP77) and a Restrictive PaO2 target of 9 to 10 kPa versus a Liberal target of 13 to 14 kPa in a 2×2 factorial design. A pulmonary artery catheter was inserted following randomization. DO2 and VO2 were calculated as: DO2=cardiac output × arterial oxygen content, and VO2= cardiac output × arteriovenous oxygen difference. Of 789 patients, 730 (92.5%) were included in this substudy. A total of 362 patients were randomized to MAP77, and 368 to MAP63, 368 to a liberal Pao2 target, and 362 to a restrictive target. At all prespecified time points, DO2 in MAP77 was higher compared with MAP63, with a cumulative treatment effect of 203 L (95% CI, 132–274) O2 after 36 hours. VO2 was higher in MAP77 after 36 hours, with a cumulative treatment effect of 21.9 L (95% CI, 5.8–38) O2, compared with the MAP63 group. Conclusions Targeting a MAP of 77 mm Hg resulted in an overall increase in DO2 and a smaller increase in VO2 compared with a MAP target of 63 mm Hg. A higher Pao2 target did not result in any difference in DO2 or VO2.

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

This article discusses the concept of the Laffer curve, which was popularized by economist Arthur Laffer in the 1970s. The Laffer curve illustrates the relationship between tax rates and tax revenue, suggesting that there is an optimal tax rate that maximizes government revenue. The article then applies this concept to the study of lactate kinetics in physiology. Lactate is produced by cells during anaerobic metabolism and is used as a measure of tissue perfusion. The article suggests that there may be two states of perfusion that result in the same blood lactate concentration, which could have implications for the interpretation of lactate levels in clinical practice. [Extracted from the article]

Abstract Purpose Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. Methods Our algorithm was built systematically with 4 components – machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. Results Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. Conclusion We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery.

Abstract Background Recent advances on cardiorespiratory monitoring applied in ARDS patients undergoing invasive mechanical ventilation and noninvasive ventilatory support are available in the literature and may have potential prognostic implication in ARDS treatment. Main body The measurement of oxygen saturation by pulse oximetry is a valid, low-cost, noninvasive alternative for assessing arterial oxygenation. Caution must be taken in patients with darker skin pigmentation, who may experience a greater incidence of occult hypoxemia. Dead space surrogates, which are easy to calculate, have important prognostic implications. The mechanical power, which can be automatically computed by intensive care ventilators, is an important parameter correlated with ventilator-induced lung injury and outcome. In patients undergoing noninvasive ventilatory support, the use of esophageal pressure can measure inspiratory effort, avoiding possible delays in endotracheal intubation. Fluid responsiveness can also be evaluated using dynamic indices in patients ventilated at low tidal volumes (

Introduction. A distinctive feature of cardiopulmonary bypass in minimally invasive coronary artery bypass grafting (CABG) is the significantly longer perfusion time, involving active blood drainage from the vein to the cardiotomy reservoir, which carries the risk of hemolysis development. In this context, mechanical hemolysis disrupts the gas transport function of the blood. The aim of the research. Reducing hemolysis and optimizing oxygen status of patients during minimally invasive coronary artery bypass grafting surgeries. Materials and methods. The study included 60 patients, who underwent minimally invasive coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under moderate hypothermia. The patients were divided into two groups of 30 individuals each. To improve the biocompatibility of the oxygenator, the circuit in Group 1 (Gr1) was treated with an adaptive composition, while in Group 2 (Gr2), the oxygenator circuit remained untreated. The following parameters were examined: hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), oxygen delivery index (DO2I), oxygen consumption index (VO2I), oxygen extraction ratio (O2ER%), oxygen extraction index (O2EI%), venous (SpvO2), and arterial (SpaO2) oxygen saturation, oxygen tension in arterial (PaO2) and venous blood (PvO2), acid-base status of the blood (pH, pCO2,HCO3ˉ, BE), and the degree of hemolysis. Results. Before initiation of cardiopulmonary bypass (CPB), an insignificant increase in O2IE% was observed in Gr1 (26.07±1.57) and Gr2 (27.11±0.81); p=0.875, indicating an increase in tissue oxygen consumption. At the hypothermic stage CPB, both Gr1 and Gr2 demonstrated a statistically significant decrease in Hb, Ht, and RBC levels (p

Purpose: Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. Methods: Our algorithm was built systematically with 4 components – machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. Results: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. Conclusion: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Recent advances on cardiorespiratory monitoring applied in ARDS patients undergoing invasive mechanical ventilation and noninvasive ventilatory support are available in the literature and may have potential prognostic implication in ARDS treatment. Main body: The measurement of oxygen saturation by pulse oximetry is a valid, low-cost, noninvasive alternative for assessing arterial oxygenation. Caution must be taken in patients with darker skin pigmentation, who may experience a greater incidence of occult hypoxemia. Dead space surrogates, which are easy to calculate, have important prognostic implications. The mechanical power, which can be automatically computed by intensive care ventilators, is an important parameter correlated with ventilator-induced lung injury and outcome. In patients undergoing noninvasive ventilatory support, the use of esophageal pressure can measure inspiratory effort, avoiding possible delays in endotracheal intubation. Fluid responsiveness can also be evaluated using dynamic indices in patients ventilated at low tidal volumes (< 8 mL/kg). In patients ventilated at high levels of positive end expiratory pressure (PEEP), the PEEP test represents a valid alternative to passive leg raising. There is growing evidence on alternative parameters for evaluating fluid responsiveness, such as central venous oxygen saturation variations, inferior vena cava diameter variations and capillary refill time. Conclusion: Careful cardiorespiratory monitoring in patients affected by ARDS is crucial to improve prognosis and to tailor treatment via mechanical ventilatory support. Keypoints: The SpO2/FiO2 ratio, corrected minute ventilation and ventilatory ratio are valid surrogates for estimating gas exchange in ARDS patients, and caution should be taken in patients with darker skin pigmentation and moderate–severe ARDS. Changes in esophageal pressure during noninvasive respiratory support and mechanical power must be carefully monitored to estimate PSILI and VILI in ARDS patients undergoing mechanical ventilation. The use of dynamic indexes of fluid responsiveness should be encouraged in ARDS patients. Pulse pressure variation and stroke volume variation have also been validated in mechanically ventilated patients with low tidal volume. A possible alternative to passive leg raising in a mechanically ventilated patient is the PEEP test. Two minimally invasive alternatives to predict fluid responsiveness are changes in central venous oxygen saturation and capillary refill time after a passive leg raising or a fluid challenge. [ABSTRACT FROM AUTHOR]

OBJECTIVES The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components. METHODS Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates. RESULTS Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2–3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2–3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury. CONCLUSIONS The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury. [ABSTRACT FROM AUTHOR]

Abstract Background Anemia, characterized by low hemoglobin levels, is a global public health concern. Anemia is an independent factor worsening outcomes in various patient groups. Blood transfusion has been the traditional treatment for anemia; its triggers, primarily based on hemoglobin levels; however, hemoglobin level is not always an ideal trigger for blood transfusion. Additionally, blood transfusion worsens clinical outcomes in certain patient groups. This narrative review explores alternative triggers for red blood cell transfusion and their physiological basis. Main Text The review delves into the physiology of oxygen transport and highlights the limitations of using hemoglobin levels alone as transfusion trigger. The main aim of blood transfusion is to optimize oxygen delivery, necessitating an individualized approach based on clinical signs of anemia and the balance between oxygen delivery and consumption, reflected by the oxygen extraction rate. The narrative review covers different alternative triggers. It presents insights into their diagnostic value and clinical applications, emphasizing the need for personalized transfusion strategies. Conclusion Anemia and blood transfusion are significant factors affecting patient outcomes. While restrictive transfusion strategies are widely recommended, they may not account for the nuances of specific patient populations. The search for alternative transfusion triggers is essential to tailor transfusion therapy effectively, especially in patients with comorbidities or unique clinical profiles. Investigating alternative triggers not only enhances patient care by identifying more precise indicators but also minimizes transfusion-related risks, optimizes blood product utilization, and ensures availability when needed. Personalized transfusion strategies based on alternative triggers hold the potential to improve outcomes in various clinical scenarios, addressing anemia’s complex challenges in healthcare. Further research and evidence are needed to refine these alternative triggers and guide their implementation in clinical practice.

Abstract Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No‐Go) and non‐executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2), in a randomized block cross‐over single‐blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No‐Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No‐Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia.

Background: Anemia, characterized by low hemoglobin levels, is a global public health concern. Anemia is an independent factor worsening outcomes in various patient groups. Blood transfusion has been the traditional treatment for anemia; its triggers, primarily based on hemoglobin levels; however, hemoglobin level is not always an ideal trigger for blood transfusion. Additionally, blood transfusion worsens clinical outcomes in certain patient groups. This narrative review explores alternative triggers for red blood cell transfusion and their physiological basis. Main Text: The review delves into the physiology of oxygen transport and highlights the limitations of using hemoglobin levels alone as transfusion trigger. The main aim of blood transfusion is to optimize oxygen delivery, necessitating an individualized approach based on clinical signs of anemia and the balance between oxygen delivery and consumption, reflected by the oxygen extraction rate. The narrative review covers different alternative triggers. It presents insights into their diagnostic value and clinical applications, emphasizing the need for personalized transfusion strategies. Conclusion: Anemia and blood transfusion are significant factors affecting patient outcomes. While restrictive transfusion strategies are widely recommended, they may not account for the nuances of specific patient populations. The search for alternative transfusion triggers is essential to tailor transfusion therapy effectively, especially in patients with comorbidities or unique clinical profiles. Investigating alternative triggers not only enhances patient care by identifying more precise indicators but also minimizes transfusion-related risks, optimizes blood product utilization, and ensures availability when needed. Personalized transfusion strategies based on alternative triggers hold the potential to improve outcomes in various clinical scenarios, addressing anemia's complex challenges in healthcare. Further research and evidence are needed to refine these alternative triggers and guide their implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Background: ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation. Methods and results: Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels. Results: In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions. Conclusions: The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions. [ABSTRACT FROM AUTHOR]

Introduction: cardiac surgery associated acute kidney injury (CSA-AKI) has a number of preoperative and intraoperative risk factors. Cardiopulmonary bypass (CPB) factors have not yet been elucidated in a single multivariate model. The aim of this study is to develop a dynamic predictive model for CSA-AKI. Methods: retrospective study on 910 consecutive adult cardiac surgery patients. Baseline data were used to settle a preoperative CSA-AKI risk model (static risk model, SRM); CPB related data were assessed for association with CSA-AKI. CPB duration, nadir oxygen delivery, time of exposure to a low oxygen delivery, nadir mean arterial pressure, peak lactates and red blood cell transfusion were included in a multivariate dynamic perfusion risk (DPR). SRM and DPR were merged into a final logistic regression model (multifactorial dynamic perfusion index, MDPI). The three risk models were assessed for discrimination and calibration. Results: the SRM model had an AUC of 0.696 (95% CI 0.663–0.727), the DPR model of 0.723 (95% CI 0.691–0.753), and the MDPI model an AUC of 0.769 (95% CI 0.739–0.798). The difference in AUC between SRM and DPR was not significant (p = 0.495) whereas the AUC of MDPI was significantly larger than that of SRM (p = 0.004) and DPR (p = 0.015). Conclusions: inclusion of dynamic indices of the quality of CPB improves the discrimination and calibration of the preoperative risk scores. The MDPI has better predictive ability than the existing static risk models and is a promising tool to integrate different factors into an advanced concept of goal-directed perfusion. [ABSTRACT FROM AUTHOR]

Hypoxia is known to increase muscle fatigue via both central and peripheral mechanisms. Females are typically less fatigable than males during isometric fatiguing contractions due to greater peripheral blood flow. However, sex differences in fatigue are blunted during dynamic fatiguing tasks. Thus, this study determined the interactions of sex and hypoxia on knee extensor muscle contractile function during a dynamic, ischemic fatiguing contraction. Electrical stimulation was used to determine contractile properties of the knee extensor muscles in eight males and eight females before and after an ischemic, dynamic fatiguing task while inspiring room air or a hypoxic gas mixture (10% O2:90% N2). Fatigue (assessed as time-to-task failure) was ~10% greater during the hypoxic condition (94.3 ± 33.4 s) compared with normoxic condition (107.0 ± 42.8 s, P = 0.041) and ~40% greater for females than males (77.1 ± 18.8 vs. 124.2 ± 38.7, P < 0.001). Immediately after the dynamic fatiguing task, there were reductions in maximal voluntary contraction force (P = 0.034) and electrically evoked twitch force (P < 0.001), and these reductions did not differ based on sex or inspirate. Cerebral tissue oxygenation showed a significant interaction of time and inspirate (P = 0.003) whereby it increased during normoxia and remained unchanged in hypoxia. No sex-related differences in the changes of cerebral tissue oxygenation were observed (P = 0.528). These data suggest that acute hypoxia increases central fatigue during ischemic single-leg exercise resulting in earlier exercise termination, but the effect does not differ based on sex. [ABSTRACT FROM AUTHOR]

The management of severe burns remains a complex challenge. Adenosine, lidocaine, and magnesium (ALM) resuscitation therapy has been shown to protect against hemorrhagic shock and traumatic injury. The aim of the present study was to investigate the early protective effects of small-volume ALM fluid resuscitation in a rat model of 30% total body surface area (TBSA) thermal injury. Male Sprague–Dawley rats (320–340 g; n = 25) were randomly assigned to: 1) Sham (surgical instrumentation and saline infusion, without burn, n = 5), 2) Saline resuscitation group (n = 10), or 3) ALM resuscitation group (n = 10). Treatments were initiated 15-min after burn trauma, including 0.7 mL/kg 3% NaCl ± ALM bolus and 0.25–0.5 mL/kg/h 0.9% NaCl ± ALM drip, with animals monitored to 8.25-hr post-burn. Hemodynamics, cardiac function, blood chemistry, hematology, endothelial injury markers and histopathology were assessed. Survival was 100% for Shams and 90% for both ALM and Saline groups. Shams underwent significant physiological, immune and hematological changes over time as a result of surgical traums. ALM significantly reduced malondialdehyde levels in the lungs compared to Saline (P =.023), and showed minimal alveolar destruction and inflammatory cell infiltration (P <.001). ALM also improved cardiac function and oxygen delivery (21%, P =.418 vs Saline), reduced gut injury (P <.001 vs Saline), and increased plasma adiponectin (P <.001 vs baseline). Circulating levels of the acute phase protein alpha 1-acid glycoprotein (AGP) increased 1.6-times (P <.001), which may have impacted ALM's therapeutic efficacy. We conclude that small-volume ALM therapy significantly reduced lung oxidative stress and preserved alveolar integrity following severe burn trauma. Further studies are required to assess higher ALM doses with longer monitoring periods. [ABSTRACT FROM AUTHOR]

Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O2) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow‐up MRI was performed 6‐months postpartum (n = 16/20). MRI techniques included phase‐contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O2 transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAoabdo), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAothoracic and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O2 delivery in the DAoabdo, UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O2 consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O2 saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental–fetal O2 transport and consumption were similar between left and right lateral maternal positions. In comparison to non‐pregnant findings, DAoabdo and UtA O2 delivery and pelvic O2 consumption increased, while lower‐limb consumption remained constant , despite reduced external iliac artery O2 delivery in late gestation. Key points: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood.Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus.This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O2 delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O2 consumption (gravid uterus, fetus, placenta, lower limbs) was preserved.Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta).Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O2 delivery. [ABSTRACT FROM AUTHOR]

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No‐Go) and non‐executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2), in a randomized block cross‐over single‐blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No‐Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No‐Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. New Findings: What is the central question of this study?We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non‐executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery.What is the main finding and its importance?Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the important complications of the perioperative period, and associated with increased risk of chronic kidney disease, renal replacement therapy requirements, increased cost, and risk of mortality. In this overview, we summarized baseline confounders and surgical procedure related risk factors contributing to the perioperative AKI, which may serve as risk scores, improve early diagnosis, contribute to prevention, and early management of AKI. There are immediate needs for context specific clinical prediction scores and novel biomarkers to very early diagnose AKI. Preventive guidance provided by Kidney Disease: Improving Global Outcomes is a helpful practical tool for clinicians. Potential roles of novel biomarkers and their context specific contributions require further exploration and close attention. Perioperative hemodynamics and oxygenation appear to contribute to AKI. Therefore, while their optimization can be recommended, their detailed and context specific roles need further explored. Overall, decreased exposure to nephrotoxic agents is recommended to further decrease the impact of perioperative AKI.

The article focuses on cerebral physiology, covering topics such as cerebral metabolic rate, cerebral circulation, and factors affecting cerebral blood flow. It discusses how various physiological variables such as cerebral autoregulation, neurovascular coupling, and vasomotor reactivity influence cerebral blood flow and oxygen delivery.

Background: Abdominal normothermic regional perfusion (A‐NRP) allows in‐situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A‐NRP. Methods: To refine liver viability assessment during A‐NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A‐NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. Results: Twenty‐seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A‐NRP was comparable, whereas oxygen consumption (VO2) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2) and VO2. Lactate clearance was correlated to transaminase levels and DO2‐normalized lactate clearance was the parameter best discriminating between study groups. Conclusions: DO2‐normalized lactate clearance may represent an element of liver viability assessment during A‐NRP. [ABSTRACT FROM AUTHOR]

Tumor hypoxia, which is mainly caused by the inefficient microvascular systems induced by rapid tumor growth, is a common characteristic of most solid tumors and has been found to hinder treatment outcomes for many types of cancer therapeutics. In this study, an amphiphilic block copolymer, poly (ethylene glycol) methyl ether acrylate-block-n-butyl acrylate (PEGA-BA), was prepared via the ATRP method and self-assembled into core-shell micelles as nano radiosensitizers. These micelles encapsulated a photosensitizer, Chlorin e6 (Ce6), and demonstrated well-defined morphology, a uniform size distribution, and high oxygen loading capacity. Cell experiments showed that PEGA-BA@Ce6@PFCE micelles could effectively enter cells. Further in vitro anticancer studies demonstrated that the PEGA-BA@Ce6@PFCE micelles significantly suppressed the tumor cell survival rate when exposed to a laser. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the important complications of the perioperative period, and associated with increased risk of chronic kidney disease, renal replacement therapy requirements, increased cost, and risk of mortality. In this overview, we summarized baseline confounders and surgical procedure related risk factors contributing to the perioperative AKI, which may serve as risk scores, improve early diagnosis, contribute to prevention, and early management of AKI. There are immediate needs for context specific clinical prediction scores and novel biomarkers to very early diagnose AKI. Preventive guidance provided by Kidney Disease: Improving Global Outcomes is a helpful practical tool for clinicians. Potential roles of novel biomarkers and their context specific contributions require further exploration and close attention. Perioperative hemodynamics and oxygenation appear to contribute to AKI. Therefore, while their optimization can be recommended, their detailed and context specific roles need further explored. Overall, decreased exposure to nephrotoxic agents is recommended to further decrease the impact of perioperative AKI. [ABSTRACT FROM AUTHOR]

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S -nitrosothiol (RSNO) and nitrite ( NO 2 − ) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and NO 2 − . Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO 2 − , while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans. [ABSTRACT FROM AUTHOR]

The benefits of exercise involve skeletal muscle redox state alterations of nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). We determined the fiber-specific effects of acute exercise on the skeletal muscle redox state in healthy adults. Muscle biopsies were obtained from 19 participants (11 M, 8 F; 26 ± 4 yr) at baseline (fasted) and 30 min and 3 h after treadmill exercise at 80% maximal oxygen consumption (VO2max). Muscle samples were probed for autofluorescence of NADH (excitation at 340-360 nm) and oxidized flavoproteins (Fp; excitation at 440-470 nm) and subsequently, fiber typed to quantify the redox signatures of individual muscle fibers. Redox state was calculated as the oxidation-to-reduction redox ratio: Fp/(Fp + NADH). At baseline, pair-wise comparisons revealed that the redox ratio of myosin heavy chain (MHC) I fibers was 7.2% higher than MHC IIa (P = 0.023, 95% CI: 5.2, 9.2%) and the redox ratio of MHC IIa was 8.0% higher than MHC IIx (P = 0.035, 95% CI: 6.8, 9.2%). MHC I fibers also displayed greater NADH intensity than MHC IIx (P = 0.007) and greater Fp intensity than both MHC IIa (P = 0.019) and MHC IIx (P < 0.0001). Fp intensities increased in all fiber types (main effect, P = 0.039) but redox ratios did not change (main effect, P ¼ 0.483) 30 min after exercise. The change in redox ratio was positively correlated with capillary density in MHC I (rho = 0.762, P = 0.037), MHC IIa fibers (rho = 0.881, P = 0.007), and modestly in MHC IIx fibers (rho = 0. 771, P ¼ 0.103). These findings support the use of redox autofluorescence to interrogate skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Background: Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS). Methods: Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min. Results: For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397–0.701). When comparing SveO2 and NIRS using a Bland–Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was − 17.28–33.09, with an error of 32.5%. Conclusion: DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304. [ABSTRACT FROM AUTHOR]

The authors present a review paper that addresses the cardiac component of shock and its definition. We reviewed the concepts of oxygen delivery and consumption and approached the evaluation of these complex patients through measures that obviated the need for pulmonary artery catheters or PICCO monitoring. Hence, this review will briefly explain the concepts of oxygen delivery, oxygen consumption, oxygen extraction ratio, mixed venous saturation, lactate, mixed venous-to-arterial carbon dioxide (CO2) tension difference, and echocardiographic evaluation of cardiac output. We aimed to clarify such concepts and provide a systematic approach to evaluate this population and surrogates for cardiac output. [ABSTRACT FROM AUTHOR]

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure. [ABSTRACT FROM AUTHOR]