Dodecafluoropentane emulsion as an oxygen therapeutic.

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.

Efficacy of a self-made tracheostomy oxygen delivery device for oxygen therapy during postoperative anesthesia recovery.

BACKGROUND: Patients with tracheotomy are often monitored in the anesthesia recovery room after reoperation. During this period, oxygen therapy is necessary, and the existing tracheostomy oxygen supply device has many defects. OBJECTIVE: To evaluate the efficacy of a self-made tracheostomy oxygen delivery device on oxygen therapy during postoperative anesthesia recovery. METHODS: Patients were randomly divided into two groups, E and C, with 30 patients in each group, and admitted to the post-anesthesia care unit (PACU). Patients in group E received oxygen through a self-made tracheostomy oxygen delivery device, while patients in group C were supplied oxygen through a unilateral nasal cannula. Respiration (R), pulse oximetry (SpO2), and the number of patients on ventilators were recorded at the time of admission (T0) and one hour after admission (T1). Rapid dry blood gas analyses were performed on 0.6 ml samples of arterial blood collected at T0 and T1. RESULTS: Compared to group C, patients in group E had significantly higher arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), total carbon dioxide (T-CO2), and actual bicarbonate (AB), while arterial partial pressure of carbon dioxide (PaCO2) was significantly reduced (P< 0.01 or < 0.05). Compared to T0, PaO2 decreased in both groups at T1, PaCO2 decreased in group E, while SaO2, T-CO2, and AB decreased in group C (P< 0.01 or < 0.05). CONCLUSION: We found that using the self-made tracheostomy oxygen delivery device in postoperative anesthesia recovery had advantages such as a secure connection to the tracheostoma, adjustable oxygen concentration, air filtration, and the ability to switch oxygen supply between the ventilator and humidifier.

Hypoxia-Responsive Biomimetic Nanobubbles for Oxygen Delivery Promote Synergistic Ischemic Stroke Protection.

Effective, precise, and controllable oxygen delivery is crucial for regulating the oxygenation balance of brain tissue at the early stages of acute ischemic stroke (AIS) because the absence of oxygen may result in a series of highly interconnected vascular-neural pathological events, including oxidative stress, inflammation, and neuroapoptosis. In this study, platelet membrane-reassembled oxygen nanobubbles (PONBs) were constructed for oxygen delivery to protect AIS. Benefiting from the preserved natural targeting ability of platelet membranes, oxygen can be controlled release into the hypoxia lesion at the preperfusion stage due to vascular injury targeting and oxygen sustained diffusion capability after PONBs administration. Furthermore, synergizing with bioactive components carried by platelet membranes, PONBs can inhibit post-AIS vascular occlusion and maintain blood-brain barrier integrity, thereby facilitating enhanced oxygen delivery of PONBs, establishing a positive feedback loop between oxygen delivery and AIS protection. Additionally, the accumulation of PONBs enhances the ultrasound imaging contrast, enabling precise localization and dynamic monitoring of AIS lesions. Thus, PONBs represent a promising strategy for the diagnosis and treatment of AIS.

Accelerating healing at high altitudes: Oxygen and bFGF delivery through nanoparticle-loaded gel dressings.

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.

Muscle microvascular oxygen delivery limitations during the contraction phase of intermittent maximal effort contractions.

PURPOSE: The end-test torque (ETT) during intermittent maximal effort contractions reflects the highest contraction intensity at which a muscle metabolic steady-state can be attained. This study determined if ETT is the highest intensity at which the contraction phase of intermittent exercise does not limit the matching of microvascular oxygen delivery to muscle oxygen demand. METHODS: Microvascular oxygenation characteristics of the biceps brachii muscle were measured in sixteen young, healthy individuals (8M/8F, 22 ± 3 years, 80.9 ± 20.3 kg) by near-infrared spectroscopy during maximal effort elbow flexion under control conditions (CON) and with complete circulatory occlusion (OCC). RESULTS: Increases in total-[heme] were blunted during OCC compared to CON (225 ± 87 vs. 264 ± 88 µM, p < 0.001) but OCC did not elicit a compensatory increase in deoxygenated-[heme] at any timepoint (108 ± 62 vs. 101 ± 61 µM, p > 0.05). Deoxygenated-[heme] was significantly elevated during contraction, relative to relaxation, above ETT (107 ± 60 vs. 98.8 ± 60.5 µM, p < 0.001), but not at ETT (91.7 ± 54.1 vs. 98.4 ± 62.2 µM, p = 0.174). Total-[heme] was significantly reduced during contraction, relative to relaxation, at all contraction intensities during CON (p < 0.05) and OCC (p < 0.05). CONCLUSION: These data suggest that ETT may reflect the highest contraction intensity at which contraction-induced increases in intramuscular pressures do not limit muscle perfusion to a degree that requires further increases in fractional oxygen extraction (i.e., deoxygenated-[heme]) despite limited microvascular diffusive conductance (i.e., total-[heme]).

On the mechanisms of stress-induced human spleen contraction: training for a higher blood oxygen-carrying capacity.

Despite its comparatively limited size in humans, spleen has been shown able to expel red-blood cells in the circulation and thus augment blood oxygen-carrying capacity under certain physiologic conditions. In the present state-of-the-art review, the short- and long-term regulation of spleen volume will be discussed. With regards to the physiological mechanism underlying spleen contraction, sympathetic activation stands as the prime contributor to the response. A dose-dependent relationship between specific interventions of apnea, exercise and hypoxia (imposed separately or in combination) and spleen contraction alleges to the trainability of the spleen organ. The trainability of the spleen is further substantiated by virtue of cross-sectional and longitudinal studies reporting robust increases in both organ volume at rest and subsequent spleen contraction. Alternative ways to assess the relationship between hematologic gains and the magnitude of spleen contraction (i.e., the reduction of spleen volume) will be presented herein. In extension of changes in the conventional measures of hemoglobin concentration and hematocrit, assessment of hemoglobin mass and total blood volume using the (safe, low-cost and time-efficient) CO-rebreathing technique could deepen scientific knowledge on the efficiency of human spleen contraction.

Oxygen delivery and monitoring in neonatal intensive care units in Mexico in 2011 and in 2023: an observational longitudinal study.

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.

Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia.

How to cite this article: Gangireddy S, Jindal A. Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia. Indian J Crit Care Med 2024;28(6):625.

Enzymes in Addressing Hypoxia for Biomaterials Engineering.

Oxygen is essential for normal cellular functions. Hypoxia impacts various cellular processes, such as metabolism, growth, proliferation, angiogenesis, metastasis, tumorigenesis, microbial infection, and immune response, mediated by hypoxia-inducible factors (HIFs). Hypoxia contributes to the progression and development of cancer, cardiovascular diseases, metabolic disorders, kidney diseases, and infections. The potential alleviation of hypoxia has been explored through the enzymatic in situ decomposition of hydrogen peroxide, leading to the generation of oxygen. However, challenges such as limited stability restrict the effectiveness of enzymes such as catalase in biomedical and in vivo applications. To overcome these limitations, targeted delivery of the enzymes has been proposed. This review offers a critical comparison of i) current approaches to enhance the in vivo stability of catalase; and ii) the structure, mechanism of action, and kinetics of catalase and catalase-like nanozymes.

Fabrication and Evaluation of a Soy Protein Isolate/Collagen/Sodium Alginate Multifunctional Bilayered Wound Dressing: Release of Cinnamaldehyde, Artemisia absinthium, and Oxygen.

Chronic wounds, such as diabetic ulcers and pressure sores, pose significant challenges in modern healthcare due to their prolonged healing times and susceptibility to infections. This study aims to engineer a bilayered wound dressing (BLWD) composed of soy protein isolate/collagen with the ability to release Cinnamaldehyde, Artemisia absinthium (AA), and oxygen. Cinnamaldehyde, magnesium peroxide (MgO2), and AA extract were encapsulated. Nanoparticles were evaluated using scanning electron microscopy (SEM), dynamic light scattering, and ZETA potential tests. Swelling, degradation, water vapor penetration, tensile, MTT, SEM, oxygen release, AA extract release, and antibacterial properties were performed. An in vivo study was carried out to assess the final wound dressing under Hematoxiline&Eosin and Masson trichrome staining analysis and compared to a commercial product. According to the results, the synthesized nanoparticles had an average diameter of about 20 nm with a zeta potential in the range of -20 to -30 mV. The layers had uniform and dense surfaces. The maximum swelling and degradation of the dressing was about 130 and 13% respectively. Generally, better mechanical properties were observed in BLWD than in the single-layer case. More than 90% biocompatibility for the wound dressing was reported. The BLWD could inhibit the growth of Gram-positive and Gram-negative microorganisms. Histopathological analysis showed an acceptable wound-healing property. To sum up, the engineered wound dressing can be a good candidate for more clinical trials.

Standard versus High Cardiopulmonary Bypass Flow Rate: A Randomized Controlled Subtrial Comparing Brain Injury Biomarker Release.

OBJECTIVES: 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. DESIGN: A randomized controlled substudy trial SETTING: Sahlgrenska University Hospital, Sweden PARTICIPANTS: Forty patients undergoing elective cardiac surgery with CPB INTERVENTION: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Effect of automated titration of oxygen on time spent in a prescribed oxygen saturation range in adults in the ICU after cardiac surgery.

Objective: The objective of this study was to determine whether automated titration of the fraction of inspired oxygen (FiO2) increases the time spent with oxygen saturation (SpO2) within a predetermined target SpO2 range compared with manually adjusted high-flow oxygen therapy in postoperative cardiac surgical patients managed in the intensive care unit (ICU). Design: Single-centre, open-label, randomised clinical trial. Setting: Tertiary centre ICU. Participants: Recently extubated adults following elective cardiac surgery who required supplemental oxygen. Interventions: Automatically adjusted FiO2 (using an automated oxygen control system) compared with manual FiO2 titration, until cessation of oxygen therapy, ICU discharge, or 24 h (whichever was sooner). Main outcome measures: The primary outcome was the proportion of time receiving oxygen therapy with the SpO2 in a SpO2 target range of 92-96 %. Results: Among 65 participants, the percentage of time per patient spent in the target SpO2 range was a median of 97.7 % (interquartile range: 87.9-99.2 %) and 91.3 % (interquartile range: 77.1-96.1 %) in the automated (n = 28) and manual (n = 28) titration groups, respectively. The estimated effect of automated FiO2, compared to manual FiO2 titration, was to increase the percentage of time spent in the target range by a median of 4.8 percentage points (95 % confidence interval: 1.6 to 10.3 percentage points, p = 0.01). Conclusion: In patients recently extubated after cardiac surgery, automated FiO2 titration significantly increased time spent in a target SpO2 range of 92-96 % compared to manual FiO2 titration.

The Effect of Co-Delivery of Oxygen and Anticancer Drugs on the Viability of Healthy and Cancer Cells under Normoxic and Hypoxic Conditions.

Hypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O2 supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O2 and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O2 release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O2 and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions.

Novel gas mixture combined with an auto-transfusion tourniquet enhances cerebral O2 transport and hemodynamic indices in CPR swine. Part B - A pilot experimental study.

Objectives: The cognitive outcome of CPR is poor. This study aims to evaluate if enhancing blood flow to the brain and oxygen dissociation from the hemoglobin improve cerebral O2 transport during CPR in cardiac arrest swine. Methods: Standard swine-CPR model of induced VF and recovery was treated with an auto-transfusion tourniquet (A-TT®; HemaShock® (HS) Oneg HaKarmel Ltd. Israel) and ventilation with a novel mixture of 30% Oxygen, 5% CO2, and 65% Argon (COXAR™). Five swine received the study treatment and 5 controls standard therapy. Animals were anesthetized, ventilated, and instrumented for blood draws and pressure measurements. Five minutes of no-CPR arrest were followed by 10 min of mechanical CPR with and without COXAR-HS™ enhancement followed by defibrillation and 45 min post ROSC follow-up. Results: All 5 COXAR-HS™ animals were resuscitated successfully as opposed to 3 of the control animals. Systolic (p < 0.05), and diastolic (p < 0.01) blood pressures, and coronary (p < 0.001) and cerebral (p < 0.05) perfusion pressures were higher in the COXAR-HS™ group after ROSC, as well as cerebral flow and O2 provided to the brain (p < 0.05). Blood pressure maintenance after ROSC required much higher doses of norepinephrine in the 3 resuscitated control animals vs. the 5 COXAR-HS™ animals (p < 0.05). jugular vein PO2 and SO2 exceeded 50 mmHg and 50%, respectively with COXAR-HS™. Conclusions: In this pilot experimental study, COXAR-HS™ was associated with higher diastolic blood pressure and coronary perfusion pressure with lower need of vasopressors after ROSC without significant differences prior to ROSC. The higher PjvO2 and SjvO2 suggest enhanced O2 provision to the brain mitochondria, while limb compression by the HS counteracts the vasodilatory effect of the CO2. Further studies are needed to explore and validate the COXAR-HS™ effects on actual post-ROSC brain functionality.

The Association of Oxygen Delivery and Transfusion on Cardiopulmonary Bypass with Acute Kidney Injury.

OBJECTIVES: 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. DESIGN: Retrospective study SETTING: Cardiovascular operating room and intensive care unit PARTICIPANTS: Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Focus on oliguria during renal replacement therapy.

Oliguria is a clinical symptom characterized by decreased urine output, which can occur at any stage of acute kidney injury and also during renal replacement therapy. In some cases, oliguria may resolve with adjustment of blood purification dose or fluid management, while in others, it may suggest a need for further evaluation and intervention. It is important to determine the underlying cause of oliguria during renal replacement therapy and to develop an appropriate treatment plan. This review looks into the mechanisms of urine production to investigate the mechanism of oliguria during renal replacement therapy from two aspects: diminished glomerular filtration rate and tubular abnormalities. The above conditions all implying a renal oxygen supply-demand imbalance, which is the signal of worsening kidney injury. It also proposes a viable clinical pathway for the treatment and management of patients with acute kidney injury receiving renal replacement therapy.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and critical impulse during maximal effort forearm exercise in males: a randomized crossover trial.

Beetroot juice supplementation (BRJ) should increase nitric oxide bioavailability under conditions of muscle deoxygenation and acidosis that are a normal consequence of the maximal effort exercise test used to identify forearm critical impulse. We hypothesized BRJ would improve oxygen delivery:demand matching and forearm critical impulse performance. Healthy males (20.8 ± 2.4 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON). Participants completed 10 min of rhythmic maximal effort forearm handgrip exercise 2.5 h post placebo (PL) vs. BRJ (9 completed PL/BRJ vs. 4 completed BRJ/PL) within a 2 week period. Data are presented as mean ± SD. There was a main effect of drink (PL > BRJ) for oxygen extraction (P = 0.033, ηp2 = 0.351) and oxygen consumption/force (P = 0.017, ηp2 = 0.417). There was a drink × time interaction (PL > BRJ) for oxygen consumption/force (P = 0.035, ηp2 = 0.216) between 75 and 360 s (1.25-6 min) from exercise onset. BRJ did not influence oxygen delivery (P = 0.953, ηp2 = 0.000), oxygen consumption (P = 0.064, ηp2 = 0.278), metabolites ((lactate) (P = 0.196, ηp2 = 0.135), pH (P = 0.759, ηp2 = 0.008)) or power-duration performance parameters (critical impulse (P = 0.379, d = 0.253), W' (P = 0.733, d = 0.097)). BRJ during all-out handgrip exercise does not influence oxygen delivery or exercise performance. Oxygen cost of contraction with BRJ is reduced as contraction impulse is declining during maximal effort exercise resulting in less oxygen extraction.