Cerebral fractional tissue oxygen extraction (cFTOE) during immediate fetal-to-neonatal transition: a systematic qualitative review of the literature.

Cerebral monitoring during immediate fetal-to-neonatal transition is of increasing interest. The cerebral fractional tissue oxygen extraction (cFTOE) is a useful parameter to gain insight in the balance between tissue oxygen delivery and consumption during this complex process. The aim of this study was to review the literature on cFTOE during the first 15 min immediately after birth. A systematic qualitative literature research was last performed on 23 November 2023 of PubMed and EMBASE with the following search terms: neonate, infant, newborn, transition, after birth, delivery room, NIRS, near-infrared spectroscopy, spectroscopy, cFTOE, cerebral fractional tissue oxygenation extraction, cerebral oxygenation, and fractional oxygen extraction. Additional published reports were identified through a manual search of references in retrieved articles and in review articles. The methodological quality of the included studies was assessed by predefined quality criteria. Only human studies with data of cFTOE in the first 15 min after birth were included. Accordingly, exclusion criteria were defined as no measurement of cFTOE or no measurement within the first 15 min after birth. Across all studies, a total of 3566 infants (2423 term, 1143 preterm infants) were analysed. Twenty-five studies were identified describing cFTOE within the first 15 min after birth. Four studies established reference ranges for cFTOE and another four studies focused on the effect of pre-/perinatal circumstances on cFTOE in the first 15 min after birth. Six studies investigated the course of cFTOE after transition in infants without complications. Eleven studies analysed different potentially influencing parameters on cFTOE during transition. CONCLUSION: This systematic review provides a comprehensive insight on cFTOE during uncomplicated transition as well as the influence of perinatal circumstances, respiratory, haemodynamic, neurological, and laboratory parameters in preterm and term infants. WHAT IS KNOWN: • The NIRS-measured cerebral fractional tissue oxygen extraction (cFTOE) is a useful parameter to estimate the balance between oxygen delivery and consumption. • During normal transition, the cFTOE decreases in the first minutes after birth and then remains at a stable plateau. WHAT IS NEW: • The cFTOE is a promising parameter that gives additional information on cerebral oxygenation and perfusion in preterm and term infants. • Several hemodynamic, metabolic, respiratory, and perinatal factors are identified, influencing the oxygen extraction of the newborn's brain after birth.

Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.

We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.

Effect of blood flow restriction and electrical muscle stimulation on human glycemic response to a glucose challenge.

PURPOSE: To determine whether reduced tissue oxygen availability through blood flow restriction (BFR) alone, or in combination with electrically induced muscle contractions, can improve glucose clearance after an acute glucose challenge. METHODS: In a randomized crossover design, 21 young participants (females: 12) were allocated to perform 1) electrical muscle stimulation (EMS), 2) BFR, 3) EMS + BFR or 4) no treatment (control). Participants completed each condition immediately preceding a 2 h oral glucose tolerance test (100 g). Primary analyses were performed on the glucose area under the curve (AUC) at time points 0-30, 30-120, and 0-120 min. Secondary analyses were performed on glycemic responses based on biological sex and estimated muscle phenotype. RESULTS: Compared to the control (322±25 mM∙min), the 0-30 min AUC was reduced following EMS (293±22 mM∙min, p = 0.0004), and EMS + BFR (298±36 mM∙min., p = 0.006), whereas BFR in isolation did not differ (306±30 mM∙min, p = 0.1). The 30-120 and 0-120 min glucose AUCs were similar across conditions. Based on effect size from the control conditions, our secondary analysis suggests different 0-30 min glycemic responses after EMS + BFR between females (dz = 0.206) vs. males (dz = 1.461) and/or slow (dz = 0.426) vs. fast (dz = 1.075) muscle phenotype. CONCLUSION: Reducing tissue oxygen availability with BFR did not augment the effects of EMS in the overall group; however, we provide preliminary data to suggest possible sex and/or muscle phenotypic responses in glycemic regulation with these modalities.

Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis.

To assess whether monitoring brain tissue oxygen partial pressure (PbtO2) or employing intracranial pressure (ICP)/cerebral perfusion pressure (CCP)-guided management improves patient outcomes, including mortality, hospital length of stay (LOS), mean daily ICP and mean daily CCP during the intensive care unit(ICU)stay. We searched the Web of Science, EMBASE, PubMed, Cochrane Library, and MEDLINE databases until December 12, 2023. Prospective randomized controlled and cohort studies were included. A meta-analysis was performed for the primary outcome measure, mortality, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies with a total of 37,492 patients were included. The mortality in the group with PbtO2 was 29.0% (odds ratio: 0.73;95% confidence interval [CI]:0.56-0.96; P = 0.03; I = 55%), demonstrating a significant benefit. The overall hospital LOS was longer in the PbtO2 group than that in the ICP/CPP group (mean difference:2.03; 95% CI:1.03-3.02; P<0.0001; I = 39%). The mean daily ICP in the PbtO2 monitoring group was lower than that in the ICP/CPP group (mean difference:-1.93; 95% CI: -3.61 to -0.24; P = 0.03; I = 41%). Moreover, PbtO2 monitoring did not improve the mean daily CPP (mean difference:2.43; 95%CI: -1.39 to 6.25;P = 0.21; I = 56%).Compared with ICP/CPP monitoring, PbtO2 monitoring reduced the mortality and the mean daily ICP in patients with severe traumatic brain injury; however, no significant effect was noted on the mean daily CPP. In contrast, ICP/CPP monitoring alone was associated with a short hospital stay.

Letter to editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis of published cases.

This critique evaluates a letter to the editor discussing the role of brain tissue oxygen partial pressure (PbtO2) monitoring in the prognosis of patients with traumatic brain injury (TBI). The meta-analysis aims to synthesize existing evidence, highlighting the potential of PbtO2 monitoring as an early indicator of cerebral hypoxia and its correlation with improved patient outcomes. Despite these promising findings, the analysis is constrained by significant methodological variability among the included studies, potential publication bias, and the practical challenges of implementing PbtO2 monitoring widely. The letter emphasizes the need for standardized protocols and further research to solidify the clinical utility of PbtO2 monitoring and integrate it with other monitoring strategies for comprehensive TBI management.

The Association Between Renal Desaturation Measured Using Near-Infrared Spectroscopy and Postoperative Acute Kidney Injury: A Systematic Review.

OBJECTIVES: The objective of this systematic review was to clarify the status of near-infrared spectroscopy (NIRS) in monitoring perioperative renal regional tissue oxygen saturation (rSO2) and determine whether there is evidence supporting its use in predicting postoperative acute kidney injury (AKI). DESIGN: A systematic search of electronic databases was conducted to identify all clinical studies that utilized NIRS to monitor renal rSO2 during the perioperative period to observe postoperative AKI. SETTING: Studies published online as of May 31, 2024, were included in the review. PARTICIPANTS: Studies involving human participants undergoing surgery with a predefined outcome of AKI were included. INTERVENTIONS: Regional tissue oxygen saturation was measured using NIRS. MEASUREMENTS AND MAIN RESULTS: A total of 144 records were identified in the primary search after removing duplicates. After screening, 18 studies were included in the analysis, consisting of 3 case-control studies and 15 prospective cohort studies. Thirteen reports focused on pediatric surgery, whereas five reports focused on adult surgery. Sixteen studies involved cardiovascular surgery with cardiopulmonary bypass, and two studies focused on liver surgery. All studies received a quality score of 7 or above. Significant heterogeneity and mostly short follow up periods were noted. CONCLUSION: Renal desaturation may indicate AKI in patients; however, further studies are required to substantiate this relationship. Additional clinical trials are necessary to evaluate normal values and establish the exact threshold of renal rSO2 that signifies a meaningful decline in renal function.

The relationship between trajectories of renal oxygen saturation and acute kidney injury: a prospective cohort study with a secondary analysis.

BACKGROUND: Acute kidney injury (AKI) is a major postoperative consequence, affecting prognosis of older patients. Effective prediction or intervention to predict or prevent the incidence of AKI is currently unavailable. AIMS: Dynamic changes of renal tissue oxygen saturation (RSO2) during surgery process are understudied and we intended to explore the distinct trajectories and associations with postoperative AKI. METHODS: This was a secondary analysis including data for older patients who underwent open hepatectomy surgery with informed consent. Latent class mixed models (LCMM) method was conducted to generate trajectories of intraoperative renal tissue RSO2 through different time points. The primary outcome was postoperative 7-day AKI. The univariate and multivariate regression analysis were performed to identify the relationship between distinct trajectories of renal tissue RSO2 and the risk of AKI. Meanwhile, the prediction efficacy of renal tissue RSO2 at different time points was compared to find potential intervention timing. RESULTS: Postoperative AKI occurred in 14 (15.2%) of 92 patients. There are two distinct renal tissue RSO2 trajectories, with 44.6% generating "high-downwards" trajectory and 55.4% generating "consistently-high" trajectory. Patients with "high-downwards" trajectory had significantly higher risk of postoperative AKI than another group (Unadjusted OR [Odds Ratio] = 3.790, 95% CI [Confidence Interval]: 1.091-13.164, p = 0.036; Adjusted OR = 3.973, 95% CI 1.020-15.478, p = 0.047, respectively). Predictive performance was 71.4% sensitivity and 60.3% specificity for "high-downwards" trajectory of renal tissue RSO2 to identify AKI. Furthermore, the renal tissue RSO2 exhibited the lowest level and the best results in terms of the sensitivity during the hepatic occlusion period, may be considered as a "time of concern". CONCLUSIONS: Older patients undergoing hepatectomy may show high-downwards trajectory of renal tissue RSO2, indicating a higher risk of AKI, and the lowest level was identified during the hepatic occlusion period. These findings may help to provide potential candidates for future early recognition of deterioration of kidney function and guide interventions.

Chemical angioplasty vs. balloon plus chemical angioplasty for delayed cerebral ischemia: a pilot study of PbtO2 outcomes.

BACKGROUND: Delayed cerebral ischaemia (DCI) is a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Chemical angioplasty (CA) and transluminal balloon angioplasty (TBA) are used to treat patients with refractory vasospasm causing DCI. Multi-modal monitoring including brain tissue oxygenation (PbtO2) is routinely used at this centre for early detection and management of DCI following aSAH. In this single-centre pilot study, we are comparing these two treatment modalities and their effects on PbtO2. METHODS: Retrospective case series of patients with DCI who had PbtO2 monitoring as part of their multimodality monitoring and underwent either CA or TBA combined with CA. PbtO2 values were recorded from intra-parenchymal Raumedic NEUROVENT-PTO® probes. Data were continuously collected and downloaded as second-by-second data. Comparisons were made between pre-angioplasty PbtO2 and post-angioplasty PbtO2 median values (4 h before angioplasty, 4 h after and 12 h after). RESULTS: There were immediate significant improvements in PbtO2 at the start of intervention in both groups. PbtO2 then increased by 13 mmHg in the CA group and 15 mmHg in the TBA plus CA group in the first 4 h post-intervention. This improvement in PbtO2 was sustained for the TBA plus CA group but not the CA group. CONCLUSION: Combined balloon plus chemical angioplasty results in more sustained improvement in brain tissue oxygenation compared with chemical angioplasty alone. Our findings suggest that PbtO2 is a useful tool for monitoring the response to angioplasty in vasospasm.

Changes in regional tissue oxygen saturation values during the first week of life in stable preterm infants.

OBJECTIVES: Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. METHODS: Prospective observational study of infants born 30-34 weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, and at seven days. Subjects were divided into gestational age (GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. RESULTS: Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to 91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). CONCLUSIONS: The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use when monitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants.

Brain tissue oxygen plus intracranial pressure monitoring versus isolated intracranial pressure monitoring in patients with traumatic brain injury: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Intracranial pressure (ICP) monitoring plays a key role in patients with traumatic brain injury (TBI), however, cerebral hypoxia can occur without intracranial hypertension. Aiming to improve neuroprotection in these patients, a possible alternative is the association of Brain Tissue Oxygen Pressure (PbtO2) monitoring, used to detect PbtO2 tension. METHOD: We systematically searched PubMed, Embase and Cochrane Central for RCTs comparing combined PbtO2 + ICP monitoring with ICP monitoring alone in patients with severe or moderate TBI. The outcomes analyzed were mortality at 6 months, favorable outcome (GOS ≥ 4 or GOSE ≥ 5) at 6 months, pulmonary events, cardiovascular events and sepsis rate. RESULTS: We included 4 RCTs in the analysis, totaling 505 patients. Combined PbtO2 + ICP monitoring was used in 241 (47.72%) patients. There was no significant difference between the groups in relation to favorable outcome at 6 months (RR 1.17; 95% CI 0.95-1.43; p = 0.134; I2 = 0%), mortality at 6 months (RR 0.82; 95% CI 0.57-1.18; p = 0.281; I2 = 34%), cardiovascular events (RR 1.75; 95% CI 0.86-3.52; p = 0.120; I2 = 0%) or sepsis (RR 0.75; 95% CI 0.25-2.22; p = 0.604; I2 = 0%). The risk of pulmonary events was significantly higher in the group with combined PbtO2 + ICP monitoring (RR 1.44; 95% CI 1.11-1.87; p = 0.006; I2 = 0%). CONCLUSIONS: Our findings suggest that combined PbtO2 + ICP monitoring does not change outcomes such as mortality, functional recovery, cardiovascular events or sepsis. Furthermore, we found a higher risk of pulmonary events in patients undergoing combined monitoring.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Evaluation of cerebral autoregulation of oxygen by NIRS method during postnatal transition period in term and late preterm newborns without resuscitation requirement.

BACKGROUND: Pulse oximetry is commonly used to monitor arterial oxygen saturation and heart rate during the transition period and reference intervals have been determined. However, the effect of the change in arterial oxygen saturation on tissue oxygenation does not seem to be the same. So, a non-invasive method for monitoring cerebral or regional tissue oxygenation will be potentially useful for vulnerable infants. This study aims to evaluate the effectiveness of cerebral autoregulation in the first 10 min after delivery in term and late preterm newborns without resuscitation requirement. METHODS: Cerebral tissue oxygen saturation was measured in the first 10 min after birth with near-infrared spectroscopy (NIRS) from the left forehead. Peripheral oxygen saturation was measured with pulse oximetry from the right hand and cerebral fractional tissue oxygen extraction was calculated. RESULTS: Nineteen late preterms and 20 term infants were included in the study. There was no statistically significant difference between median cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction values of late preterm and term infants (p < 0.001). There was a strong inverse relationship between cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction (p < 0.001). CONCLUSIONS: In late preterm infants similar to term infants, arterial oxygen saturation and cerebral tissue oxygen saturation increased with time, but inverse reduction of cerebral fractional tissue oxygen extraction showed the presence of an active autoregulation in the brain. This can be interpreted as the ability of the brain to protect itself from hypoxia by regulating oxygen uptake during normal fetal-neonatal transition process. A larger scale multi-center randomized control trial is now needed to further inform practice.

Treatment of hard-to-heal wounds in ischaemic lower extremities with a novel fish skin-derived matrix.

OBJECTIVE: To evaluate the efficacy of treatment of hard-to-heal wounds of patients with ischaemia of the lower extremities, and compare an omega-3 wound matrix product (Kerecis, Iceland) with a standard dressing. METHOD: A single-centre, prospective, randomised, controlled clinical trial of patients with hard-to-heal wounds following three weeks of standard care was undertaken. The ischaemic condition of the wound was confirmed as a decreased transcutaneous oxygen pressure (TcPO2) of <40mmHg. After randomising patients into either a case (omega-3 dressing) or a control group (standard dressing), the weekly decrease in wound area over 12 weeks and the number of patients that achieved complete wound closure were compared between the two groups. Patients with a TcPO2 of ≤32mmHg were taken for further analysis of their wound in a severe ischaemic context. RESULTS: A total of 28 patients were assigned to the case group and 22 patients to the control group. Over the course of 12 weeks, the wound area decreased more rapidly in the case group than the control group. Complete wound healing occurred in 82% of patients in the case group and 45% in the control group. Even in patients with a severe ischaemic wound with a TcPO2 value of <32 mmHg, wound area decreased more rapidly in the case group than the control group. The proportions of re-epithelialised area in the case and control groups were 80.24% and 57.44%, respectively. CONCLUSION: Considering the more rapid decrease in wound area and complete healing ratio in the case group, application of a fish skin-derived matrix for treating lower-extremity hard-to-heal wounds, especially with impaired vascularity, would appear to be a good treatment option.

Measurements of Electrodermal Activity, Tissue Oxygen Saturation, and Visual Analog Scale for Different Cuff Pressures.

The quantification of comfort in binding parts, essential human-machine interfaces (HMI) for the functioning of rehabilitation robots, is necessary to reduce physical strain on the user despite great achievements in their structure and control. This study aims to investigate the physiological impacts of binding parts by measuring electrodermal activity (EDA) and tissue oxygen saturation (StO2). In Experiment 1, EDA was measured from 13 healthy subjects under three different pressure conditions (10, 20, and 30 kPa) for 1 min using a pneumatic cuff on the right thigh. In Experiment 2, EDA and StO2 were measured from 10 healthy subjects for 5 min. To analyze the correlation between EDA parameters and the decrease in StO2, a survey using the visual analog scale (VAS) was conducted to assess the level of discomfort at each pressure. The EDA signal was decomposed into phasic and tonic components, and the EDA parameters were extracted from these two components. RM ANOVA and a post hoc paired t-test were used to determine significant differences in parameters as the pressure increased. The results showed that EDA parameters and the decrease in StO2 significantly increased with the pressure increase. Among the extracted parameters, the decrease in StO2 and the mean SCL proved to be effective indicators. Such analysis outcomes would be highly beneficial for studies focusing on the comfort assessment of the binding parts of rehabilitation robots.

Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Microvascular effects of oxygen and carbon dioxide measured by vascular occlusion test in healthy volunteers.

BACKGROUND: Changes in near-infrared spectroscopy-derived regional tissue oxygen saturation (StO2) during a vascular occlusion test (VOT; ischemic provocation of microcirculation by rapid inflation and deflation of a tourniquet) allow estimating peripheral tissue O2 consumption (desaturation slope; DS), vascular reactivity (recovery slope; RS) and post-ischemic hyperperfusion (AUC-H). The effects of isolated alterations in the inspiratory fraction of O2 (FiO2) and changes in expiratory CO2 remain to be elucidated. Therefore, in this secondary analysis we determined the effects of standardized isolated instances of hypoxia, hyperoxia, hypocapnia and hypercapnia on the VOT-induced StO2 changes in healthy volunteers (n = 20) to establish reference values for future physiological studies. METHODS: StO2 was measured on the thenar muscle. Multiple VOTs were performed in a standardized manner: i.e. at room air (baseline), during hyperoxia (FiO2 1.0), mild hypoxia (FiO2 ≈ 0.11), and after a second baseline, during hypocapnia (end-tidal CO2 (etCO2) 2.5-3.0 vol%) and hypercapnia (etCO2 7.0-7.5 vol%) at room air. Differences in DS, RS, and AUC-H were tested using repeated-measures ANOVA. RESULTS: DS and RS remained constant during all applied conditions. AUC-H after hypoxia was smaller compared to hyperoxia (963 %*sec vs hyperoxia 1702 %*sec, P = 0.005), while there was no difference in AUC-H duration between hypoxia and baseline. The StO2 peak (after tourniquet deflation) during hypoxia was lower compared to baseline and hyperoxia (92 % vs 94 % and 98 %, P < 0.001). CONCLUSION: We conclude that in healthy volunteers at rest, common situations observed during anesthesia and intensive care such as exposure to hypoxia, hyperoxia, hypocapnia, or hypercapnia, did not affect peripheral tissue O2 consumption and vascular reactivity as assessed by VOT-induced changes in StO2. These observations may serve as reference values for future physiological studies. TRIAL REGISTRATION: This study represents a secondary analysis of an original study which has been registered at ClinicalTrials.gov nr: NCT02561052.

Optimizing Tissue Oxygenation in Reduction Mammoplasty: The Role of Continuous Diffusion of Oxygen: A Feasibility Pilot Randomized Controlled Trial.

INTRODUCTION: Bilateral reduction mammoplasty (BRM) aims to alleviate macromastia-related symptoms in women. This procedure involves a T-Junction suture at the medial inframammary fold that encompasses 12%-39% of wound breakdowns mainly due to reduced perfusion. Continuous diffusion of oxygen (CDO) may enhance breast tissue oxygenation to prevent such complication. We explored the feasibility of this therapy. METHODS: A 4-wk feasibility-pilot randomized controlled trial of women undergoing BRM was conducted. By internal randomization (left/right side), participants received standard of care (SOC) in one breast using topical skin adhesive, while their other breast received SOC + CDO at the T-junction covered by a silicon sheet (sCDO), or CDO directly to the T-Junction skin (dCDO). Feasibility outcomes included protocol delivery, outcome measurement, device-related adverse events, and device acceptability. Exploratory outcomes were T-Junction SatO2 and deoxyhemoglobin assessed with near-infrared spectroscopy and wound dehiscence. RESULTS: Sixteen participants (age = 33 ± 8 y; body mass index = 34.34 ± 5.85 kg/m2) were recruited, conforming n = 32 breasts (SOC, n = 16; dCDO, n = 10, sCDO, n = 6). At 4 wk, protocol delivery was 93.7%, outcome measuring 100%, and device-related adverse events 0%. Device acceptability showed an 85.4% strong agreement for attitude toward use, 78.2% perceived ease of use, and 77.7% perceived usefulness. Breasts undergoing sCDO showed higher SatO2 (P < 0.001), whereas lower deoxyhemoglobin (P < 0.001) compared to all other breast groups. However, wound dehiscence was not different between groups (P = 0.66). CONCLUSIONS: Self-applied CDO to the T-Junction is feasible, safe, and acceptable, in patients undergoing BRM. In a proper wound environment, CDO may enhance breast tissue oxygenation. However, it is unclear whether CDO leads to decreased wound dehiscence. This study showed reproducibility for larger randomized trials.

The oxygen reactivity index indicates disturbed local perfusion regulation after aneurysmal subarachnoid hemorrhage: an observational cohort study.

BACKGROUND: Cerebral autoregulation (CA) can be impaired in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). The Pressure Reactivity Index (PRx, correlation of blood pressure and intracranial pressure) and Oxygen Reactivity Index (ORx, correlation of cerebral perfusion pressure and brain tissue oxygenation, PbtO2) are both believed to estimate CA. We hypothesized that CA could be poorer in hypoperfused territories during DCI and that ORx and PRx may not be equally effective in detecting such local variances. METHODS: ORx and PRx were compared daily in 76 patients with aSAH with or without DCI until the time of DCI diagnosis. The ICP/PbtO2-probes of DCI patients were retrospectively stratified by being in or outside areas of hypoperfusion via CT perfusion image, resulting in three groups: DCI + /probe + (DCI patients, probe located inside the hypoperfused area), DCI + /probe- (probe outside the hypoperfused area), DCI- (no DCI). RESULTS: PRx and ORx were not correlated (r = - 0.01, p = 0.56). Mean ORx but not PRx was highest when the probe was located in a hypoperfused area (ORx DCI + /probe + 0.28 ± 0.13 vs. DCI + /probe- 0.18 ± 0.15, p < 0.05; PRx DCI + /probe + 0.12 ± 0.17 vs. DCI + /probe- 0.06 ± 0.20, p = 0.35). PRx detected poorer autoregulation during the early phase with relatively higher ICP (days 1-3 after hemorrhage) but did not differentiate the three groups on the following days when ICP was lower on average. ORx was higher in the DCI + /probe + group than in the other two groups from day 3 onward. ORx and PRx did not differ between patients with DCI, whose probe was located elsewhere, and patients without DCI (ORx DCI + /probe- 0.18 ± 0.15 vs. DCI- 0.20 ± 0.14; p = 0.50; PRx DCI + /probe- 0.06 ± 0.20 vs. DCI- 0.08 ± 0.17, p = 0.35). CONCLUSIONS: PRx and ORx are not interchangeable measures of autoregulation, as they likely measure different homeostatic mechanisms. PRx represents the classical cerebrovascular reactivity and might be better suited to detect disturbed autoregulation during phases with moderately elevated ICP. Autoregulation may be poorer in territories affected by DCI. These local perfusion disturbances leading up to DCI may be more readily detected by ORx than PRx. Further research should investigate their robustness to detect DCI and to serve as a basis for autoregulation-targeted treatment after aSAH.

Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 - Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cerebral and intestinal oxygen saturation of different volumes of red blood cell transfusion in preterm infants.

OBJECTIVES: The purpose of this study was to investigate and compare the effects of 20 ml/kg and 15 ml/kg red blood cell transfusion (RBCT) on cerebral and intestinal tissue oxygenation, the number of administered transfusions, and neonatal complications in premature infants with anemia. METHODS: This prospective, randomized, partially blinded observational study investigated anemic neonates of gestational age < 32 weeks (Registration ID: ChiCTR 1,900,026,672). The infants were randomly assigned to receive 15 or 20 ml/kg red blood cell transfusion. Cerebral and intestinal tissue oxygen saturation (cer rSO2 and int rSO2) were collected 2 h before transfusion, 2, 4, 6, 12, 24, and 48 h after the beginning of transfusion by Near-infrared spectroscopy (NIRS). We also collected vital signs including heart rate (HR), peripheral oxygen saturation (SpO2), and mean arterial blood pressure (MABP) 2 h before infusion, 2 h, and 6 h after the beginning of transfusion. Then we analyzed and compared regional oxygen saturation(rSO2), fractional tissue oxygen extraction (FTOE), and other outcome readouts (blood transfusion numbers, changes in hematocrit and hemoglobin, hospitalization days, HR, SpO2, MABP, and complications) between the two groups. The intraindividual comparisons of the above readouts before transfusion and those after transfusion were also evaluated within each group. RESULT: 73 newborns received 20 ml/kg (large volume group) and 78 newborns received 15 ml/kg transfusion (small volume group). There was no significant difference in cer rSO2, int rSO2, Cerebral fractional tissue oxygen extraction (cFTOE), and intestinal fractional tissue oxygen extraction (iFTOE) between the two groups. rSO2, MABP, and SpO2 increased; HR, cFTOE, and iFTOE decreased following transfusion in both groups. The transfusion number of the large volume group is significantly less than that of the small volume group (1.9 ± 0.3 vs. 2.6 ± 0.9, p < 0.01) and hospitalization days were also less than those in the low volume group (44.3 ± 8.2 vs. 47.6 ± 9.8, p < 0.05). The increases in hematocrit and hemoglobin were higher in the large volume group than those in small volume (hematocrit increment (%),10.7 ± 4.2 vs. 10.1 ± 5.9, p = 0.015; Hb concentration after blood transfusion (g/L) 132.3 ± 11.1 vs. 127.4 ± 15.4, p = 0.028). CONCLUSION: After the transfusion, cer rSO2 and int rSO2 increased significantly, FTOE decreased and vital signs improved in both the 15 ml/kg and 20 ml/kg groups, and these changes were not significantly different between the two groups. However, the larger group showed a more pronounced increase in hematocrit and hemoglobin, a reduction in the total number of transfusions, and a shorter duration of hospitalization after transfusion in preterm infants without increasing complications.