Systemic Oxygen Research Articles

Effect of Lipid Composition and Stirring Dynamics on Oxygen Microbubble Stability and Oxygen Release.

Lipid-coated oxygen microbubbles (OMBs) are being investigated for biomedical applications to alleviate hypoxia such as systemic oxygenation and image-guided radiosensitization therapy. Additionally, they hold potential for boarder application as oxygen carriers beyond the biomedical filed. Understanding the stability and oxygen release properties of OMBs in dynamic aqueous environments is critical for these applications. In this study, we found that OMBs composed of longer acyl chain phospholipids (DSPC and DBPC) were stable in storage for at least 1 week, unlike the shorter acyl chain phospholipid (DPPC). OMBs were also more stable with a diacyl PEG-PE emulsifier compared with single-chain PEG-40 stearate. Dilution of OMBs did not alter the average diameter. While previous studies have examined the theoretical and experimental aspects of oxygen release from OMBs under static conditions, quantitative evaluations of OMB dispersions under dynamic stirring conditions remain limited. Here, we introduce a novel oxygen measurement method that quantitatively tracks the transition of the dissolved oxygen concentration in an aqueous medium upon mixing with a bolus of OMBs. Our results indicate that a 50 vol % OMB dispersion releases more than 330 mg/L of oxygen, surpassing arterial oxygen levels, and that more than 95% of this oxygen is released within 30 s. The rate of oxygenation of the OMB dispersions was comparable to that of a bolus injection of oxygen-saturated water under sufficient agitation, indicating that convection in the aqueous medium is the limiting transport mechanism. However, the lipid shell had a measurable effect on the oxygen release rate, which correlated with its oxygen permeability. Increasing the stirring speed increased both oxygen release rate and total amount of oxygen released. Overall, this study elucidates the fundamental stability and mass transport properties of the OMB dispersions under practical stirring conditions.

Effect of intermittent infusion hemodiafiltration on cerebral and hepatic oxygenation

BackgroundHepatosplanchnic circulation plays a crucial role in maintaining hemodynamic stability during hemodialysis (HD). In patients undergoing HD, hepatic oxygenation decreases before the onset of intradialytic hypotension. However, clinical studies comparing systemic tissue oxygenation, particularly in the brain and liver, between HD and intermittent infusion hemodiafiltration (I-HDF) are limited. We aimed to compare changes in the cerebral and hepatic oxygenation during I-HDF and HD.MethodsThis single-center prospective observational study included 25 patients undergoing dialysis therapy. I-HDF involved a dialysate infusion volume of 200 mL, administered at a rate of 150 mL/min via back-filtration every 30 min. Cerebral and hepatic regional oxygenation saturation (rSO2) levels were monitored during HD and I-HDF using the INVOS 5100C oxygen saturation monitor. Changes in these parameters were compared between the two modalities.ResultsThe relative blood volume change (%ΔBV) at the end of therapy was significantly smaller with I-HDF compared with HD (−8.0 ± 4.4% versus −10.0 ± 5.0%, p = 0.019). No significant differences in cerebral and hepatic rSO2 were observed at the initiation of HD and I-HDF (cerebral rSO2: 54.5 ± 6.3% versus 54.0 ± 6.0%, p = 0.444; hepatic rSO2: 63.4 ± 11.8% versus 63.4 ± 12.3%, p = 0.977). During I-HDF, cerebral and hepatic rSO2 levels significantly increased in response to dialysate infusion, compared with corresponding time points during HD. The percentage (%) change in hepatic rSO2 after the seventh dialysate infusion was significantly greater than those after the first, third, and fifth infusions. Additionally, percentage changes in hepatic rSO2 were negatively correlated with %ΔBV (ρ = −0.394, p < 0.001) and positively correlated with the ratio of the dialysate infusion volume to circulating BV just before infusion (ρ = 0.387, p < 0.001).ConclusionsThis study demonstrated that BV reduction at the end of I-HDF was significantly smaller than that of HD, and that hepatic oxygenation increased rapidly after dialysate infusion during I-HDF. Further studies are required to elucidate the impact of increased hepatic oxygenation during I-HDF on intradialytic hemodynamic stability.

Ultrasound-Triggered Oxygen Release System for Accelerating Wound Healing of Diabetic Foot Ulcers.

Diabetic foot ulcer (DFU) is a common complication of chronic diabetes mellitus. Oxygen plays a critical role in the healing process of DFU wounds by promoting cell migration and neovascularization. However, clinical hyperbaric oxygen (HBO) therapy predominantly uses systemic oxygen administration, posing challenges in inadequate DFU local oxygen penetration and potential ectopic organs oxygen toxicity. To address these challenges, a strategy to encapsulate oxygen with lipid microbubbles (OMBs) and incorporate them into a body temperature-sensitive heparin-pluronic copolymer hydrogel (HP/OMBs) have been developed. HP/OMBs showed high biocompatibility both in vitro and in vivo. After in situ administration, oxygen can be released from HP/OMBs to the local deep site of the DFU wounds under ultrasound (US) triggering. Thus, given its biocompatibility and practicality, the combined action of HP/OMBs and the US has important translational value in accelerating diabetic chronic wound healing.

Exercise limitation in chronic kidney disease: An experimental pilot study with leg and arm exercise.

Maximal oxygen uptake (VO2max) in healthy subjects is primarily limited by systemic oxygen delivery. In chronic kidney disease (CKD), VO2max is potentially reduced by both central and peripheral factors. We aimed to investigate the effect on VO2peak of adding arm exercise to leg exercise. Ten individuals with CKD stages 3-5 and 10 healthy controls, matched for age, sex, body size, and physical activity level, were included. Subjects performed two maximal exercise tests, one with legs only (L exercise) and one test where arm exercise was added to leg exercise (LA exercise). The increase in VO2peak, when comparing LA exercise with L exercise, was significantly higher in CKD (0.20 ± 0.18 L/min or 2.31 ± 1.78 mL/(kg·min)) than in controls (0.019 ± 0.12 L/min or 0.26 ± 1.62 mL/(kg·min); p = 0.02 and 0.01, respectively). The decrease in peak leg workload, when comparing L exercise with LA exercise, was larger in controls than in CKD, in absolute terms (p = 0.002) and relative to body weight (p = 0.01). VO2max in individuals with CKD is dependent on the active muscle mass, supporting a peripheral limitation to VO2max in CKD. By contrast, the control group appeared to have a more central limitation to VO2max.

Perinatal iron deficiency alters the cardiac proteome and mitochondrial function in neonatal offspring.

Iron deficiency (ID) is common during gestation and early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. Iron plays a critical role in systemic oxygen transport (via hemoglobin) and aerobic respiration (as a component of mitochondrial complexes). Perinatal ID has been shown to cause cardiac dysfunction in neonates, but the mechanisms underlying these changes have not been characterized. Here, we examined the effects of perinatal ID on cardiac mitochondrial function in rats in the early postnatal period. Female rats were fed an iron-restricted or iron-replete diet before and during pregnancy. Offspring hearts were collected postmortem for quantitative shotgun proteomic analysis [postnatal days (PD) 0 and 28] and mitochondrial function was assessed by high-resolution respirometry (at PD 0, 14, and 28). Markers of oxidative stress were measured by fluorescence microscopy and assessment of antioxidant gene expression profiles. Both male and female ID pups had reduced body weight and increased relative heart weights at all time points assessed, despite recovering from anemia by PD28. Proteomics analysis revealed dysregulation of mitochondrial proteins by ID, and these differences were most pronounced in males. In male hearts, ID increased mitochondrial content and decreased normalized mitochondrial respiration through the NADH-pathway, succinate-pathway, and fatty acid oxidation (FAO)-pathway. In conclusion, ID causes changes in cardiac mitochondrial function in neonates, which may reflect inadequate or maladaptive compensation during the transition from intrauterine to extrauterine life. Furthermore, the results presented herein, which were stratified by offspring sex, underscore the need for follow-up studies to directly assess differences in how male and female offspring cope with ID as a perinatal stressor.NEW & NOTEWORTHY Iron deficiency (ID) is the most common nutritional deficiency worldwide and is highly prevalent among pregnant women and young children. ID causes changes in mitochondrial protein expression and function in neonatal hearts, which may contribute to functional impairments. Improving cardiac energy metabolism may represent a novel approach to improve short- and long-term outcomes in infants affected by ID, but sex of the neonate may be an important determinant of treatment efficacy.

Anesthesia Management For Brain Abcess And Hidrocephalus In Children During External Ventrikel Drainage With Tetralogy Of Fallot

Background: Congenital heart defects occur due to abnormal changes in the structure of the heart that occur early in pregnancy and are present at birth. This defect is the most common congenital anomaly, occurring in approximately 1 in 125 births. Tetralogy of Fallot (TOF) is a defect in which there is an obstruction of blood flow from the heart to the lungs, resulting in low blood oxygen levels. Brain abscess is a rare, fatal complication, accounting for 5%–18.7% of the population with cyanotic congenital heart disease. This condition is often accompanied by headache, fever, seizures, altered mental status, focal neurologic deficits, nausea, and vomiting. Case: A 10 year old girl with brain abcess and hydrocephalus who will undergo external ventrikel drainage with tetralogy of fallot. Disscussion: The Anaesthetic goals for a case of uncorrected Tetralogy of Fallot posted for a non-cardiac surgery are to avoid hypoxemia, ensure adequate hydration, maintain systemic arterial blood pressure (SVR), minimise additional resistance to pulmonary blood flow (pulmonary vascular resistance) and avoiding sudden increase in systemic oxygen demand (cry, inadequate depth of an aesthesia, seizure, pain, etc). Conclution: Anesthesia management of children with TOF presenting for non-cardiac surgery requires a thorough understanding of the pathophysiology of this condition and the altered haemodynamics.

The Prognostic Value of the Muscle Regional Oxygen Saturation Index in Patients with Acute Respiratory Distress Syndrome.

Background: Impaired systemic tissue oxygenation and microvascular perfusion are associated with adverse outcomes in patients with acute respiratory distress syndrome (ARDS). Tissue oxygenation and microvascular reactivity, assessed by using near-infrared spectroscopy (NIRS), are correlated with disease severity in critically ill populations. This study aimed to detect alterations in these factors and their ability to predict outcomes in patients with ARDS. Methods: We performed NIRS measurements on the first (Day 1) and third (Day 3) days after ARDS diagnosis in 29 patients. We recorded the baseline forearm muscle oxygen saturation (StO2) and calculated the deoxygenation slope (Deoxy) and reoxygenation (Reoxy) slope. We divided the subjects into 28-day survival and non-survival subgroups to compare microcirculatory and oxygenation status differences. Results: The Day 1 StO2 values were significantly higher for the survival subgroup (60.1 ± 13.5%) than the non-survival subgroup (47.2 ± 6.9%) (p = 0.025). The ROC curve showed that Day 1 StO2 was a significant predictor of 28-day mortality (p = 0.025). There was no significant difference between the Deoxy and Reoxy slopes of the two groups (p > 0.05). The ROC of the Day 1 Reoxy slope for survival prediction (AUC0.74) was not statistically significant (p = 0.074). Conclusions: Our study showed poor survival outcomes in patients who had lower skeletal muscle StO2 values in early-stage ARDS. NIRS measurements may provide prognostic value for the survival outcomes in patients with this syndrome.

Genotypic Influences on Actuators of Aerobic Performance in Tactical Athletes

Background: This study examines genetic variations in the systemic oxygen transport cascade during exhaustive exercise in physically trained tactical athletes. Research goal: To update the information on the distribution of influence of eleven polymorphisms in ten genes, namely ACE (rs1799752), AGT (rs699), MCT1 (rs1049434), HIF1A (rs11549465), COMT (rs4680), CKM (rs8111989), TNC (rs2104772), PTK2 (rs7460 and rs7843014), ACTN3 (rs1815739), and MSTN (rs1805086)—on the connected steps of oxygen transport during aerobic muscle work. Methods: 251 young, healthy tactical athletes (including 12 females) with a systematic physical training history underwent exercise tests, including standardized endurance running with a 12.6 kg vest. Key endurance performance metrics were assessed using ergospirometry, blood sampling, and near-infrared spectroscopy of knee and ankle extensor muscles. The influence of gene polymorphisms on the above performance metrics was analyzed using Bayesian analysis of variance. Results: Subjects exhibited good aerobic fitness (maximal oxygen uptake (VO2max): 4.3 ± 0.6 L min−1, peak aerobic power: 3.6 W ± 0.7 W kg−1). Energy supply-related gene polymorphisms rs1799752, rs4680, rs1049434, rs7843014, rs11549465, and rs8111989 did not follow the Hardy–Weinberg equilibrium. Polymorphisms in genes that regulate metabolic and contractile features were strongly associated with variability in oxygen transport and metabolism, such as body mass-related VO2 (rs7843014, rs2104772), cardiac output (rs7460), total muscle hemoglobin content (rs7460, rs4680), oxygen saturation in exercised muscle (rs1049434), and respiration exchange ratio (rs7843014, rs11549465) at first or secondary ventilatory thresholds or VO2max. Moderate influences were found for mass-related power output. Conclusions: The posterior distribution of effects from genetic modulators of aerobic metabolism and muscle contractility mostly confirmed prior opinions in the direction of association. The observed genetic effects of rs4680 and rs1049434 indicate a crucial role of dopamine- and lactate-modulated muscle perfusion and oxygen metabolism during running, suggesting self-selection in Swiss tactical athletes.

OXYGEN THERAPY FOR VENTILATION IN CHILDREN

Oxygen therapy is a common practice in the treatment of critically ill children. Increasing the fraction of oxygen in the inhaled mixture (FiO2 ) is one of the mandatory methods of intensive therapy in the presence of hypoxemia in a child. Monitoring of oxygen saturation in children receiving respiratory support is standard worldwide. However, there is no optimal systemic oxygenation target in critically ill children and no ideal PaO2 target in any clinical trial. In pediatric intensive care units, invasive mechanical ventilation with increased FiO2 to maintain peripheral oxygen saturation (SpO2 ) and PaO2 is the most common method of respiratory therapy for severe respiratory disorders in children. At the same time, it is important to determine the optimal level of oxygen saturation for children receiving mechanical ventilation. It is known that the harm of high fractional oxygen delivery and an increase in SpO2 &gt; 97% may exceed their benefit. In this article, we wanted to define and emphasize that the selection of the correct ventilation modes should be based on both the CO2 partial pressure and SpO2 indicators. Striving for SpO2 &gt; 97% can lead to hyperoxia.

Impact of Oxidative Stress on Sperm Quality in Oligozoospermia and Normozoospermia Males Without Obvious Causes of Infertility.

Background: Male factors contribute to approximately 50% of infertile couples. However, obvious causes remain unknown in many cases. This observational study aimed to investigate the associations of clinical and lifestyle parameters with sperm parameters. Methods: This study enrolled 41 men in infertile couples without obvious causes for male infertility from July 2023 to April 2024. Semen samples were evaluated for sperm number, motility, DNA fragmentation, and oxidative stress (OS) marker oxidation-reduction potential (ORP). Blood samples were analyzed for biochemical parameters, including advanced glycation end products (AGEs), and systemic OS marker diacron-reactive oxygen metabolites (d-ROMs). Skin-accumulated AGE levels were identified with an autofluorescence method. Lifestyle factors were assessed with a lifestyle questionnaire. Results: Most of the participants were under 40 years old and non-obese with normal clinical parameters. Multiple regression analyses revealed that body mass index, serum d-ROMs, and semen ORP levels were independently associated with decreased sperm number. Additionally, serum zinc and semen ORP levels were associated with sperm motility. Furthermore, serum zinc and high-density lipoprotein cholesterol levels were associated with sperm progressive motility and DNA fragmentation, respectively. The rest of the clinical and lifestyle factors, including skin-accumulated and serum AGE levels, were not correlated with any sperm parameters. Furthermore, serum d-ROM and semen ORP levels were not correlated with each other or any of the clinical and lifestyle factors. Conclusions: Our present study indicates that both systemic and local OS may be independently involved in sperm abnormality in healthy men without obvious causes for male infertility.

Overcoming Lung Challenges in TA-NRP Assisted Heart Recovery in Donation After the Circulatory Determination of Death.

Thoraco-abdominal normothermic regional perfusion (TA-NRP), utilizing Extra Corporeal Membrane Oxygenation (ECMO) devices, has emerged as an effective strategy for heart recovery in donors declared dead by circulatory criteria (DCDD). After death declaration, TA-NRP restores heart activity by reperfusing the arrested heart with oxygenated blood at normothermia. Mechanical ventilation resumption in the donor enables weaning from ECMO and restores systemic circulation and oxygenation using the donor's heart and lungs. However, if pre-existing conditions prevent the donor's lungs from oxygenating blood post-cardiac activity restoration, weaning from veno-arterial ECMO may lead to systemic hypoxia, jeopardizing the restored cardiac function. Anticipating this scenario may guide planning a split ECMO circuit to facilitate earlier and more effective recovery of donor heart function post-ECMO weaning. This manuscript describes three cases of DCDD donors with hypoxic respiratory failure undergoing TA-NRP for heart recovery. By establishing a bridge in the arterial portion of the circuit, clamped out after weaning from veno-arterial ECMO, donor heart function was assessed exclusively with veno-venous ECMO support, leading to successful heart transplantation.

Abstract Su1207: Influence of Duration of Device-based Fever Prevention on Inflammation, Vasopressor Usage, and Oxygen Consumption after Cardiac Arrest - a Substudy of a Randomized Controlled Trial

Background: In the post-resuscitation phase, cardiac arrest patients develop a systemic inflammatory response and fever is likely if not actively treated. The Blood Pressure and Oxygenation Targets after Out-of-hospital Cardiac Arrest (BOX) trial, randomized patients to a total duration of device-based fever prevention for 36 or 72 hours. The trial found no differences in mortality or neurologic outcome. Use of device-based fever prevention for a shorter or longer duration could however result in clinically relevant differences in the magnitude of inflammation, vasopressor usage, and oxygen consumption. Aim: To assess the effect of a shorter or longer duration of device-based fever prevention on inflammation, vasopressor usage, and oxygen consumption in the intervention period from 36 to 72 hours. Methods: The BOX trail [NCT03141099] randomized comatose resuscitated out-of-hospital cardiac arrest (OHCA) patients to three different treatment targets in the post-resuscitation phase: mean arterial blood pressure target of 63 or 77mmHg; oxygenation targets of 68-75 or 98-105 mmHg; and duration of device-based fever prevention in comatose patients for a total of 36 or 72 hours. Endpoints at 48 and 72 hours: leukocytes; CRP; vasoactive-inotropic score (VIS); systemic oxygen consumption determined by use of Fick’s principle. Analyses were performed both on the total BOX population, and for a sensitivity analysis, selectively on patients still comatose at 72 hours (i.e., not awake or dead) as these had the most exposure to the intervention. Results: The total population consists of 789 patients, with 393 and 396 randomized to a total duration of device-based fever prevention for 36 and 72 hours respectively. For the analysis of patients still comatose at 72 hours, 122 and 148 were available for analysis in the 36-hour and 72-hour group respectively. There were no differences between the 36- and 72-hour group for leukocytes, CRP, VIS, or oxygen consumption during the intervention period from 36 until 72 hours, neither for the total population (Figure 1, all p&gt;0.05) or the cohort of patients still comatose at 72 hours (Figure 2, all p&gt;0.05). Conclusions: There were no group differences for patients randomized to device-based fever prevention for 36 or 72 hours with respect to the magnitude of inflammation, vasopressor usage, or oxygen consumption. These findings were consistent for the cohort as a whole, and when examining those with most exposure to the intervention.

Impact of persistent pulmonary hypertension on cerebral oxygenation in infants with neonatal encephalopathy.

Persistent pulmonary hypertension of the newborn (PPHN) affects systemic oxygenation and may worsen brain injury in infants with neonatal encephalopathy (NE). Evidence suggests that higher cerebral regional oxygenation (crSO2) indicates derangement in cerebral autoregulation, energy metabolism, and blood flow following NE. Our aim was to evaluate the impact of PPHN on crSO2, in infants with NE treated with therapeutic hypothermia (TH). We retrospectively evaluated infants with NE and PPHN vs without PPHN, between 2018-2022. Linear regression analysis was performed to evaluate the impact of PPHN on crSO2 and total MRI score, adjusted for perinatal factors. 164 infants were analyzed, including 19(12%) with PPHN and 145(88%) without. PPHN-infants had significantly higher crSO2 during rewarming and post-rewarming compared to non-PPHN infants (87 ± 6 vs 80 ± 6, p = 0.001; 87 ± 5 vs 80 ± 7, p = 0.008, respectively), and a significantly higher total MRI score [7(2-19) vs 1(0-3), p < 0.001]. PPHN was significantly associated with higher crSO2 during rewarming (b = 6.21, 95% CI 2.37-10.04, p = 0.002) and post-rewarming (b = 8.60, 95% CI 2.28-14.91, p = 0.009), and total MRI score (b = 7.42, 95% CI 4.88-9.95, p < 0.001). PPHN was associated with higher crSO2 during and after rewarming, and worse brain MRI score, indicating a significant impact of PPHN on brain injury in infants with NE undergoing TH. Cerebral oxygenation was significantly higher in infants with neonatal encephalopathy (NE) and persistent pulmonary hypertension (PPHN) compared to infants without PPHN, during the rewarming and post-rewarming periods of therapeutic hypothermia (TH). PPHN is associated with brain injury in infants with NE undergoing TH. In infants with NE and PPHN, monitoring of cerebral oxygenation would help detect infants at higher risk of adverse outcomes.

Neurovascular dysregulation in systemic sclerosis: novel insights into pathophysiology, diagnosis, and treatment utilizing invasive cardiopulmonary exercise testing.

Pathologic abnormalities in skeletal muscle and the systemic vasculature are common in patients with systemic sclerosis (SSc). These abnormalities may lead to impaired systemic peripheral oxygen extraction (EO 2 ), known as neurovascular dysregulation, which may be because of abnormal blood flow distribution in the vasculature, microvascular shunting, and/or skeletal muscle mitochondrial dysfunction. Findings from invasive cardiopulmonary exercising testing (iCPET) provide important insights and enable diagnosis and treatment of this SSc disease manifestation. Recent findings from noninvasive cardiopulmonary exercise testing (niCPET) support the existence of neurovascular dysregulation in patients with SSc. Invasive cardiopulmonary exercise testing (iCPET) has pointed to reduced systemic vascular distensibility as a possible mechanism for neurovascular dysregulation in patients with connective tissue diseases, including SSc. Neurovascular dysregulation is likely an underappreciated cause of exercise impairment and dyspnea in patients with SSc in the presence or absence of underlying cardiopulmonary disease. It is posited to be related to microcirculatory and muscle dysfunction. Further studies are needed to clarify the pathophysiology of neurovascular dysregulation in SSc and to identify novel treatment targets and additional therapies.

Association of agonal phase duration with heart utilization and post-transplant outcomes in donation after circulatory death heart transplantation

BackgroundThis study evaluates the impact of the agonal phase and related hemodynamic measures on post-transplant outcomes and heart utilization in donation after circulatory death (DCD) heart transplantation. MethodsUNOS registry was queried to analyze adult recipients who underwent isolated DCD heart transplantation between 1/1/2019-9/30/2023. The recipients were stratified into two groups based on donor agonal period: <30 and ≥30 minutes. Outcome was 90-day post-transplant survival. Propensity score-matching was performed. Sub-analysis was performed to evaluate the association of agonal period with donor heart utilization. Additionally, the associations between different hemodynamic thresholds used to indicate onset of warm ischemia during the agonal phase with 90-day mortality were compared. Results889 recipients were included, with 179 (20.1%) receiving hearts from donors with an agonal period of ≥30 minutes. 90-day survival (88.1% vs. 95.6%, p<0.001) was lower among the recipients of donors with an agonal period of ≥30 minutes. The lower 90-day survival persisted in a propensity score-matched comparison. Furthermore, longer agonal periods were associated with reduced donor heart utilization. Lastly, a time interval from a systolic blood pressure of 80±5mmHg to death exhibited significantly higher association with 90-day mortality than a time interval from a systemic oxygen saturation 80±5% to death. ConclusionsUtilizing DCD donor hearts with agonal periods ≥30 minutes is associated with reduced post-transplant survival and decreased donor heart utilization. When assessing the onset of warm ischemia during the agonal phase, hypotension may serve as a more accurate indicator of myocardial ischemia and provide improved post-transplant prognostic insight than hypoxia.

Effect of increased systemic oxygen delivery on postoperative outcomes and quality of life in elderly undergoing major abdominal surgery: A randomised controlled trial.

Studies comparing the intentional increase in oxygen delivery and normal oxygen delivery during general anaesthesia in elderly patients undergoing major abdominal surgery are limited and have reported contradictory findings. Therefore, the study aimed to evaluate the effect of intraoperative increase in systemic oxygen delivery on postoperative outcomes and quality of life in elderly patients undergoing major abdominal surgery. This randomised, blinded, parallel-arm, pragmatic clinical trial included elderly patients of >60 years of age undergoing major abdominal surgery. The patients in the intervention arm received noradrenaline or increased fractional inspiration of oxygen to augment central venous oxygen saturation ⩾75%. The primary outcome measure was composite of in-hospital mortality and major organ complications. The secondary outcome measure included comparison of quality of life. A total of 160 patients were assessed for eligibility, and 146 were randomised in the study groups. The mean arterial and central venous oxygen saturation increased and were significantly higher in the intervention arm. The composite primary outcome occurred in 49.31% in the intervention arm and 57.53% in the usual care arm (relative risk; 95% confidence interval: 0.85; 0.63-1.16; absolute risk reduction; 8.22%; p = 0.32). Furthermore, quality of life at the end of three months was similar (0.658 ± 0.19 versus 0.647 ± 0.19; p = 0.771). In conclusion, central venous oxygen saturation-guided increase in systemic oxygen delivery during the intraoperative period of major abdominal surgery in elderly patients did not reduce predefined composite outcome of in-hospital mortality or organ-specific complications.

Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH) study

Abstract Introduction Pulmonary arterial hypertension (PAH) is characterised by pre-capillary pulmonary vascular remodelling. Imatinib, a tyrosine kinase inhibitor, was the first treatment investigated in PAH patients with the primary aim of targeting vascular remodelling. A Phase 3 study showed that imatinib 400mg daily reduces pulmonary vascular resistance and increases exercise capacity but only 43% of patients continued the drug for 6 months. Concerns about safety prevented regulatory approval. Purpose To identify a safe and tolerated dose of oral Imatinib and evaluate efficacy in the dose range 100-400mg daily. Methods Oral Imatinib was added to the background therapy of 17 patients with PAH; prior intracranial haemorrhage was excluded by cross sectional imaging and none were receiving an anticoagulant. The first patient started on 100mg daily. The next 12 patients were recruited serially at a minimum of 4 week intervals and started on 200mg, 300mg or 400mg, according to a Bayesian adaptive design (Continuous Reassessment Method, CRM). Patients 14-17 were recruited as an extension cohort to better understand the safety and tolerability of the 100mg and 200mg doses. The primary endpoint was safety and tolerability at 4 weeks. Imatinib was continued for up to 24 weeks. Thirteen patients had implanted devices that provided remote daily measurements of cardiopulmonary haemodynamics and heart rate and rhythm and physical activity. Non-invasive measures of systemic blood pressure, weight and oxygen saturations were made remotely. We compared the time-haemodynamic response relationship with that produced by licensed treatments in a similar patient cohort. Results The recommended starting dose from the CRM was 200mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (P&amp;lt;0.01), increased cardiac output (P=0.08) and reduced total pulmonary resistance (TPR, P&amp;lt;0.001, Figure). There was a clear dose-TPR response relationship (r2=0.52, p&amp;lt;0.01). A reduction in TPR was evident within the first week and plateaued at 4-5 weeks. Withdrawal of Imatinib led to an increase to baseline in TPR over 4-5 weeks. This contrasts with a sharp fall in TPR with licensed therapy and rapid increase on treatment withdrawal. There was a small reduction in systemic vascular resistance (P&amp;lt;0.05) with Imatinib that reached plateau before TPR. Conclusions Oral Imatinib 200mg daily is well tolerated and effective as an add-on treatment in PAH. The time course of the initial haemodynamic response and the gradual return to baseline on withdrawal distinguishes Imatinib from licensed treatments and is supportive of a mechanism of action beyond reliance on vasodilation. Remote monitoring enables the safe evaluation of the withdrawal of an investigational drug in patients established on best medical therapy.Figure 1.

Poor correlation of venous lactate with systemic oxygen saturation in the paediatric cardiac ICU: a pilot study.

Cardiac intensive care providers require a comprehensive understanding of cardiac output and oxygen delivery. The estimation of cardiac output in clinical practice often relies on thermodilution and the Fick principle. Central venous saturation and lactate levels are commonly used indicators for cardiac output assessment. However, the relationship between venous lactate levels and venous oxygen saturation in paediatric cardiac intensive care patients remains unclear. This is a single-centre retrospective pilot study aimed to investigate the correlation between venous lactate and venous oxygen saturation in paediatric patients. Data collected included venous saturation, heart rate, mean arterial blood pressure, arterial saturation by pulse oximetry, cerebral and renal near-infra-red spectroscopy values, and the presence of a functionally univentricular heart. Statistical analyses included Bayesian Pearson correlation and regression analyses. A total of 203 data points from 37 unique patients were included in the analysis. There was no significant correlation between serum lactate and venous saturation (correlation coefficient = -0.01; Bayes factor 10 = 0.06). Serum lactate also did not correlate with other haemodynamic metrics. Venous saturation showed correlations with arterial saturation and cerebral and renal near-infra-red spectroscopy. Regression analysis revealed that parallel circulation, arterial saturation, and cerebral near-infra-red spectroscopy were predictive of venous saturation. The following equation resulted from the regression analysis: 68.0 - (12.7 x parallel circulation) - (0.8 x arterial saturation) + (0.3 x cerebral near-infra-red spectroscopy). This model had a Bayes factor 10 of 0.03 and adjusted R-squared was 0.29. In paediatric cardiac intensive care patients, there is no significant correlation between venous lactate and venous saturation, suggesting that lactate may not be a reliable marker for assessing the adequacy of oxygen delivery in this population. Only a weak correlation could be identified once the venous saturation was 70% or lower. Additional research is needed to explore alternative markers for monitoring oxygen delivery in critically ill paediatric patients.

Critical values for carbon monoxide in cases admitted to the emergency department in a local hospital

Abstract Carbon monoxide (CO) poisoning has been an important concern in winter particularly due to malfunctioning coal stoves, in many developing countries, including Turkey. Winter months, especially February, were the most dangerous periods for CO exposure. Carbon monoxide has no color or smell so has known as the silent killer. Brain, heart, and other organs are under risk in CO poisoning. Because patients usually present with non-specific symptoms, CO poisoning should be considered in the differential diagnosis of unexplained nausea and vomiting, neurological or cardiac signs and symptoms. Carboxyhemoglobin (COHb) is a reliable marker to monitor the patient. Lactate is also important as a measure of impaired systemic oxygen delivery. Fifteen patients with a diagnosis of CO poisoning were included in the study. This is the number of all cases admitted to the emergency in the last one and a half months in our local hospital located in a town with almost 48.918 residents. Blood gas analysis was performed by ABL90 FLEX, Radiometer. Reference for COHb was 0.6-1.5 % and for lactate was 0.5-1.6 mmol/L. Troponin I levels were also analyzed in some patients to assess possible myocardial ischemia. Troponin levels were analyzed by ARCHITECT i2000, Abbott and reference range was &amp;lt;16 ng/mL in woman, &amp;lt;34 ng/mL in men. Graph Pad Prism program was used for statistical analysis of the data. We had 15 cases aged between 4-56 years with COHb values with panic values (&amp;gt; 20%) except two of the cases with values 16.5% and 19%. The female-male ratio was 6/9. On admission to the Emergency Department, 46.6% of patients (n=7) had headache and vomiting, 40% of patients (n=6) had headache, 6.6% (n=1) fatigue and 6.6% of patients (n=1) had syncope. Median value of COHb % was 23.7(16.5-40.8), lactate was 1.9 (0.8-4.8), pH was 7.39 (7.30-7.47). Excluding three patients as outliers, lactate levels had a good correlation with carboxyhemoglobin values (R2=0.9413). It was notable that 1 patient had a higher-than-normal Troponin I level (24.9 ng/mL) who has highest lactate level (4.8 mmol/L). Four of the patients, from the same family was admitted for suspected food poisoning for the symptoms of nausea, vomiting, diarrhea. A diagnosis of CO poisoning was made after a COHb value between 16.5-25.7% for these patients. This was very critical for the accurate treatment given to those patients being hyperbaric oxygen treatment in CO poisoning cases. CO poisoning should be considered in patients admitting to the emergency department with complaints of headache, dizziness, weakness, nausea, and vomiting. Reporting panic values is a means of alerting the clinician for the right diagnosis.

Efficacy of combined hyperbaric oxygen therapy and topical haemoglobin spray in treating hard-to-heal sloughy wounds.

This study examined the effectiveness of a combination of hyperbaric oxygen therapy (HBOT) and topical haemoglobin spray in treating hard-to-heal, sloughy diabetic foot ulcers (DFUs). Patients with hard-to-heal DFUs at least 25% sloughy or necrotic were included in the study. We compared the results of patients who received standard of care and HBOT with topical haemoglobin spray (oxygen group) to an equal number of patients who only received standard personalised wound care (control group). The initial values of haemoglobin A1C and C-reactive protein, wound culture results and SINBAD (site, ischaemia, neuropathy, bacterial infection, area, depth) scores were documented. Wounds were considered healed when completely closed within 16 weeks. The oxygen group (n=21) had a mean SINBAD score of 5.00±0.89, while the control group (n=21) had a mean score of 4.62±0.80 (p=0.155). After 16 weeks, 85.7% of wounds in the oxygen group showed complete recovery, compared with 52.4% in the control group (p=0.02). In this study, a greater number of wounds in the oxygen group healed. Combining HBOT with topical haemoglobin spray provides oxygenation to the wound for longer, primarily because patients can receive 90 minutes of HBOT daily. This ensures that patients benefit from both systemic and local oxygen. This combination therapy may effectively address the problem of hypoxia and promote healing in hard-to-heal wounds.