Tissue Oxygen Monitoring Research Articles

Detecting Hypoxia Through the Non-Invasive and Simultaneous Monitoring of Sweat Lactate and Tissue Oxygenation

Hypoxia, characterized by inadequate tissue oxygenation, may result in tissue damage and organ failure if not addressed. Current detection approaches frequently prove insufficient, depending on symptoms and rudimentary metrics such as tissue oxygenation, which fail to comprehensively identify the onset of hypoxia. The European Pressure Ulcer Advisory Panel (EPUAP) has recognized sweat lactate as a possible marker for the early identification of decubitus ulcers, nevertheless, neither sweat lactate nor oxygenation independently provides an appropriate diagnosis of hypoxia. We have fabricated a wearable device that non-invasively and concurrently monitors sweat lactate and tissue oxygenation to fill this gap. The apparatus comprises three essential components: (i) a hydrogel-based colorimetric lactate biosensor, (ii) a near-infrared (NIR) sensor for assessing tissue oxygenation, and (iii) an integrated form factor for enhanced wearability. The lactate sensor alters its hue upon interaction with lactate in sweat, whereas the NIR sensor monitors tissue oxygenation levels in real-time. The device underwent testing on phantom exhibiting tissue-mimicking characteristics and on human sweat post aerobic and anaerobic activities. Moreover, the device was demonstrated to be capable of real-time “on-body” simultaneous monitoring of sweat lactate spikes and tissue oxygenation (StO2) drops, which showed strong correlation during a hypoxia protocol. This innovative technology has a wide range of potential applications, such as post-operative care, sepsis detection, and athletic performance monitoring, and may provide economical healthcare solutions in resource-limited regions.

Discrepancy Between Pulmonary Artery Catheter and Co-Oximeter Value of Mixed Venous Oxygen Saturation After Graft Reperfusion During Living Donor Liver Transplantation

Monitoring tissue oxygenation is critical in liver recipients. The pulmonary artery catheter (PAC) provides continuous monitoring of mixed venous oxygen saturation (SvO2) using fiberoptic reflectance spectrophotometry. Despite the need for in vivo calibration during liver transplantation, recalibration guidelines are absent, and we frequently observed a significant discrepancy between PAC and reference co-oximeter SvO2 values after graft reperfusion. This study aimed to assess the incidence and risk factors of a significant discrepancy after reperfusion during living donor liver transplantation. This retrospective study included 54 recipients who underwent living donor liver transplantation at our institution between October 2021 and April 2022. A PAC was inserted, and in vivo calibration was conducted using the co-oximeter SvO2 value. We defined a significant discrepancy as a drift was ≥ 3% at 1 hour after reperfusion. Logistic regression analysis was performed to determine the association between perioperative variables and the risk of significant discrepancy. PAC SvO2 was higher than co-oximeter SvO2 in 51 recipients. A significant discrepancy was observed in 37 recipients (68.5%). The risk of significant discrepancy decreased with a high preoperative hemoglobin concentration (odds ratio [OR] = 0.65 [0.47-0.91], P = .011) and a high arterial oxygen partial pressure (PaO2) at 1 hour after reperfusion (OR = 0.96 [0.94-0.99], P = .004) but increased with a high baseline co-oximeter SvO2 value (OR = 1.29 [1.05-1.59], P = .015). PAC SvO2 significantly drifted from the reference co-oximeter value in over two-thirds of recipients after reperfusion. Therefore, in vivo recalibration is required for the reliable measurement of PAC SvO2 during living donor liver transplantation.

Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship. Methods: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator (linac). Oxyphor PdG4 was administered into the subcutaneous tissue of the flank skin one hour before irradiation. Skin oxygen tension (pO2) was manipulated by adjusting oxygen content in the inhaled gas mixture and/or by vasculature compression. A skin surface radiation dose of 19.8±0.3Gy was verified using a calibrated semiconductor diode dosimeter. Dose rate was varied across the UHDR range by changing linac cone length and pulse repetition frequency (PRF). Results: The decrease in pO2 per unit dose during radiation delivery, termed oxygen consumption g-value (gO2, mmHg/Gy), was significantly influenced by tissue oxygen levels in the range 0-65mmHg under UHDR conditions. Within the 0-20mmHg range, gO2 exhibited a sharp increase with rising baseline pO2, plateauing at 0.26mmHg/Gy. Dose rate variations (mean values 25-1170Gy/s, per-pulse doses of 2.5-9.8Gy) were explored by varying both cone length and PRF (10-120Hz) with no significant changes in gO2. Conventional dose rate irradiation resulted in no discernible changes in pO2. Conclusions: The results show significant differences in the radiation-chemical effects of UHDR radiation between hypoxic and well-oxygenated tissues. Similar trends between earlier published in vitro and in vivo experiments presented herein suggest the chemical mechanisms driving the dependencies of gO2 on pO2 are similar, potentially underpinning the FLASH effect. Importantly, significant variations in baseline pO2 were observed in animals kept under identical conditions, underscoring the necessity to control and monitor tissue oxygen levels for preclinical investigations and future clinical applications of FLASH-RT.

Effect of optimizing cerebral oxygen saturation on postoperative delirium in older patients undergoing one-lung ventilation for thoracoscopic surgery.

This randomized controlled trial investigated whether the regional cerebral oxygenation saturation (rScO2)-guided lung-protective ventilation strategy could improve brain oxygen and reduce the incidence of postoperative delirium (POD) in patients older than 65 years. This randomized controlled trial enrolled 120 patients undergoing thoracic surgery who received one-lung ventilation (OLV). Patients were randomly assigned to the lung-protective ventilation group (PV group) or rScO2-oriented lung-protective ventilation group (TPV group). rScO2 was recorded during the surgery, and the occurrence of POD was assessed. The incidence of POD 3 days after surgery-the primary outcome-was significantly lower in the TPV group (23.3% versus 8.5%). Meanwhile, the levels of POD-related biological indicators (S100β, neuron-specific enolase, tumor necrosis factor-α) were lower in the TPV group. Considering the secondary outcomes, both groups exhibited a lower oxygenation index after OLV, whereas partial pressure of carbon dioxide and mean arterial pressure were significantly increased in the TPV group. In addition, minimum rScO2 during surgery and mean rScO2 were higher in the TPV group than in the PV group. Continuous intraoperative monitoring of brain tissue oxygenation and active intervention measures guided by cerebral oxygen saturation are critical for improving brain metabolism and reducing the risk of POD.

Future of neurocritical care: Integrating neurophysics, multimodal monitoring, and machine learning

Multimodal monitoring (MMM) in the intensive care unit (ICU) has become increasingly sophisticated with the integration of neurophysical principles. However, the challenge remains to select and interpret the most appropriate combination of neuromonitoring modalities to optimize patient outcomes. This manuscript reviewed current neuromonitoring tools, focusing on intracranial pressure, cerebral electrical activity, metabolism, and invasive and noninvasive autoregulation monitoring. In addition, the integration of advanced machine learning and data science tools within the ICU were discussed. Invasive monitoring includes analysis of intracranial pressure waveforms, jugular venous oximetry, monitoring of brain tissue oxygenation, thermal diffusion flowmetry, electrocorticography, depth electroencephalography, and cerebral microdialysis. Noninvasive measures include transcranial Doppler, tympanic membrane displacement, near-infrared spectroscopy, optic nerve sheath diameter, positron emission tomography, and systemic hemodynamic monitoring including heart rate variability analysis. The neurophysical basis and clinical relevance of each method within the ICU setting were examined. Machine learning algorithms have shown promise by helping to analyze and interpret data in real time from continuous MMM tools, helping clinicians make more accurate and timely decisions. These algorithms can integrate diverse data streams to generate predictive models for patient outcomes and optimize treatment strategies. MMM, grounded in neurophysics, offers a more nuanced understanding of cerebral physiology and disease in the ICU. Although each modality has its strengths and limitations, its integrated use, especially in combination with machine learning algorithms, can offer invaluable information for individualized patient care.

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.

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. 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 6months, favorable outcome (GOS ≥ 4 or GOSE ≥ 5) at 6months, pulmonary events, cardiovascularevents and sepsis rate. 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 6months (RR 1.17; 95% CI 0.95-1.43; p = 0.134; I2 = 0%), mortality at 6months (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 eventswas significantly higher in the group with combined PbtO2 + ICP monitoring (RR 1.44; 95% CI 1.11-1.87; p = 0.006; I2 = 0%). Our findings suggest that combined PbtO2 + ICP monitoring does not change outcomes such as mortality, functional recovery, cardiovascularevents or sepsis. Furthermore, we found a higher risk of pulmonaryevents in patients undergoing combined monitoring.

Results of using thoraflextm hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital

Background: The aim of this study was to introduce and evaluate the early results after the frozen elephant trunk (FET) procedure with ThoraflexTM Hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital. Methods: This is a retrospective descriptive study of all acceptable patients after the frozen elephant trunk (FET) procedure with ThoraflexTM Hybrid prothesis at Viet Duc University Hospital from January 2021 to May 2023. Results: There were 21 patients with a male rate of 85.7% and an average age 58.2±10 years old (range 40–73). History of patients with hypertension: 19 (90.5%); post-dissection aortic aneurysm: 2 (9.5%) patients. By cause, the number of patients with thoracic aortic aneurysm was 03 (14.3%), acute aortic dissection type A was 16 (76.1%), and aortic dissection type B was 02 (9.5%). In which there were 16 cases of emergency surgery (76.1%). Replacement of the aortic arch was performed under moderate hypothermic (280 °C on average) circulatory arrest and bilateral selective antegrade cerebral perfusion with permanent monitoring of cerebral tissue oxygenation by the MASIMO machine. Average cardio-pulmonary bypass time, aortic cross clamp time, distal hypothermic circulatory arrest time, and operating time were 137,5±22,9 minutes; 86,3±17,6 minutes; 25,2±8,9 minutes; and 7,7±10,3 hours. The average ventilation time, length of intensive care unit stay, and hospital stay were 7,2±9,7 days, 18,8±20,7 days, and 19,9 ± 6,5 days. There was one patient with post-operative cerebrospinal fluid drainage. No patient had bleeding complications, recurrent nerve palsy, reoperation, or in-hospital mortality. Conclusion: The initial results after the frozen elephant trunk procedure with ThoraflexTM Hybrid prothesis for the treatment of complex aortic disease at Viet Duc University Hospital were safe, good, and feasible.

Cerebral oxygenation and perfusion kinetics monitoring of military aircrew at high G using novel fNIRS wearable system.

Real-time physiological episode (PE) detection and management in aircrew operating high-performance aircraft (HPA) is crucial for the US Military. This paper addresses the unique challenges posed by high acceleration (G-force) in HPA aircrew and explores the potential of a novel wearable functional near-infrared spectroscopy (fNIRS) system, named NIRSense Aerie, to continuously monitor cerebral oxygenation during high G-force exposure. The NIRSense Aerie system is a flight-optimized, wearable fNIRS device designed to monitor tissue oxygenation 13-20 mm below the skin's surface. The system includes an optical frontend adhered to the forehead, an electronics module behind the earcup of aircrew helmets, and a custom adhesive for secure attachment. The fNIRS optical layout incorporates near-distance, middle-distance, and far-distance infrared emitters, a photodetector, and an accelerometer for motion measurements. Data processing involves the modified Beer-Lambert law for computing relative chromophore concentration changes. A human evaluation of the NIRSense Aerie was conducted on six subjects exposed to G-forces up to +9 Gz in an Aerospace Environmental Protection Laboratory centrifuge. fNIRS data, pulse oximetry, and electrocardiography (HR) were collected to analyze cerebral and superficial tissue oxygenation kinetics during G-loading and recovery. The NIRSense Aerie successfully captured cerebral deoxygenation responses during high G-force exposure, demonstrating its potential for continuous monitoring in challenging operational environments. Pulse oximetry was compromised during G-loading, emphasizing the system's advantage in uninterrupted cerebrovascular monitoring. Significant changes in oxygenation metrics were observed across G-loading levels, with distinct responses in Deoxy-Hb and Oxy-Hb concentrations. HR increased during G-loading, reflecting physiological stress and the anti-G straining maneuver. The NIRSense Aerie shows promise for real-time monitoring of aircrew physiological responses during high G-force exposure. Despite challenges, the system provides valuable insights into cerebral oxygenation kinetics. Future developments aim for miniaturization and optimization for enhanced aircrew comfort and wearability. This technology has potential for improving anti-G straining maneuver learning and retention through real-time cerebral oxygenation feedback during centrifuge training.

Brain Tissue Oxygenation Guided Therapy in Patients with Traumatic Brain Injury: An Umbrella Review of Systematic Review and Meta-Analysis

AbstractThe present umbrella review aims to summarize the evidence of the efficacy and benefit of combined brain tissue oxygen monitoring and intracranial pressure (ICP) monitoring compared with ICP monitoring based therapy alone. In this study, we systematically searched five databases to retrieve systematic reviews (SRs) regarding the efficacy of ICP monitoring on patient outcomes following traumatic brain injury (TBI). This overview was prepared following the guidelines established by the Joanna Briggs Institute (JBI) for umbrella reviews. No restrictions were placed on the date, language, or country of publication. Three SRs and meta-analyses met the inclusion criteria for the study. The SRs and meta-analyses (SR-MAs) included randomized controlled trials (RCTs) and observational studies. Specifically, two SRs were rated as high quality by A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), while one was rated as moderate quality. Two of the SR-MAs reported on the mortality outcome, with two reporting on the functional outcome and one reporting on the length of hospital stay outcome. One of the SRs indicated that using combined brain tissue oxygen monitoring led to a reduction in mortality. Two of the SRs had mixed results. Two articles found that hospital length tends to be shorter with combined therapy than with ICP monitoring-based therapy alone. Our observations suggested that brain tissue oxygen combined with ICP/cerebral perfusion pressure (CPP) guided therapy provides a favorable outcome in TBI patients than standard ICP-/CPP-guided therapy. The combined therapy has little effect on mortality rate, ICP, CPP, and length of stay.

Short-term cutaneous vasodilatory and thermosensory effects of topical methyl salicylate.

Methyl salicylate, the main compound of wintergreen oil, is widely used in topical applications. However, its vascular and thermosensory effects are not fully understood. The primary aim was to investigate the effects of topical methyl salicylate on skin temperature (Tskin), skin microcirculation (MCskin) and muscle oxygen saturation (SmO2) compared to a placebo gel. The secondary aim was to assess thermosensory responses (thermal sensation, thermal comfort) and to explore to which extent these sensations correspond to the physiological responses over time. 21 healthy women (22.2 ± 2.9years) participated in this single-blind, randomized controlled trial. Custom-made natural wintergreen oil (12.9%), containing methyl salicylate (>99%) and a placebo gel, 1 g each, were applied simultaneously to two paravertebral skin areas (5cm × 10cm, Th4-Th7). Tskin (infrared thermal imaging), MCskin (laser speckle contrast imaging) and SmO2 (deep tissue oxygenation monitoring) and thermosensation (Likert scales) were assessed at baseline (BL) and at 5-min intervals during a 45min post-application period (T0-T45). Both gels caused an initial decrease in Tskin, with Tskin(min) at T5 for both methyl salicylate (BL-T5: Δ-3.36°C) and placebo (BL-T5: Δ-3.90°C), followed by a gradual increase (p < .001). Methyl salicylate gel resulted in significantly higher Tskin than placebo between T5 and T40 (p < .05). For methyl salicylate, MCskin increased, with MCskin(max) at T5 (BL-T5: Δ88.7%). For placebo, MCskin decreased (BL-T5: Δ-17.5%), with significantly lower values compared to methyl salicylate between T0 and T45 (p < .05). Both gels had minimal effects on SmO2, with no significant differences between methyl salicylate and placebo (p > .05). Thermal sensation responses to topical methyl salicylate ranged from "cool" to "hot", with more intense sensations reported at T5. The findings indicate that topical methyl salicylate induces short-term cutaneous vasodilation, but it may not enhance skeletal muscle blood flow. This study highlights the complex sensory responses to its application, which may be based on the short-term modulation of thermosensitive transient receptor potential channels.

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

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. 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. Individualized limits of autoregulation were computed in 55 patients (mean age 38years, mean monitoring time 92h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14mm Hg to 79 ± 17mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6mm Hg to 21.9 ± 5.6mm 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 60min after compared with before an intervention (11% vs. 23%, p = 0.05). 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.

Switchable LED-based laparoscopic multispectral system for rapid high-resolution perfusion imaging.

Multispectral imaging (MSI) is an approach for real-time, quantitative, and non-invasive tissue perfusion measurements. Current laparoscopic systems based on mosaic sensors or filter wheels lack high spatial resolution or acceptable frame rates. To develop a laparoscopic system for MSI-based color video and tissue perfusion imaging during gastrointestinal surgery without compromising spatial or temporal resolution. The system was built with 14 switchable light-emitting diodes in the visible and near-infrared spectral range, a 4K image sensor, and a 10mm laparoscope. Illumination patterns were created for tissue oxygenation and hemoglobin content monitoring. The system was calibrated to a clinically approved laparoscopic hyperspectral system using linear regression models and evaluated in an occlusion study with 36 volunteers. The root mean squared errors between the MSI and reference system were 0.073 for hemoglobin content, 0.039 for oxygenation in deeper tissue layers, and 0.093 for superficial oxygenation. The spatial resolution at a working distance of 45mm was . The effective frame rate was 20fps. High-resolution perfusion monitoring was successfully achieved. Hardware optimizations will increase the frame rate. Parameter optimizations through alternative illumination patterns, regression, or assumed tissue models are planned. Intraoperative measurements must confirm the suitability during surgery.

Groote Schuur Hospital neurosurgical intensive care unit: A 2-year review of admission characteristics.

At Groote Schuur Hospital (GSH), the neurosurgical intensive care unit (NsICU) is a 6-bed unit headed by a specialist neurosurgeon with extensive experience in neurocritical care, working in close collaboration with intensivists from the Division of Critical Care. There is currently no detailed analysis of the demographics, diagnosis and management of patients admitted to the NsICU at GSH. To provide a detailed descriptive analysis of the demographics, diagnosis and management of patients admitted to the NsICU at GSH from 1 January 2020 to 31 December 2021. A retrospective descriptive analysis was done of patients who received treatment in the NsICU from 1 January 2020 to 31 December 2021. A total of 685 patients were admitted to the unit over a 2-year period, with a male preponderance (68.2%). The average age was 42.5 (standard deviation (SD) 17.2) years. The most common neurosurgical diagnoses were traumatic brain injuries (39.6%), brain tumours (22.6%) and aneurysmal subarachnoid haemorrhages (9.9%). Emergency admissions comprised 76.6% of the total and 86.7% of patients were admitted postoperatively. Three hundred and seventy-two patients (54.3%) required mechanical ventilation, 132 (19.3%) required both an intracranial pressure (ICP) monitor and brain tissue oxygenation monitor, 86 (12.5%) needed placement of an external ventricular drain, 50 (7.3%) needed placement of a tracheostomy tube and 16 (2.3%) needed placement of an ICP monitor only. The average duration of stay was 5.5 (1.3) days and NsICU mortality over 2 years was 11.1%. The NsICU at GSH manages predominantly male trauma patients and a significant number of admitted patients require specialised invasive intracranial monitoring. This is the first in-depth analysis of patients managed in a dedicated neurosurgical intensive care unit in South Africa. The work defines the patient population, neurosurgical pathologies and service level requirements that would likely be encountered by teams building a similar service.

Abstract 135: Identifying Optimal Mean Arterial Pressure in Cardiac Arrest Patients: Are Precision Medicine Approaches Feasible?

Introduction: Loss of cerebral autoregulation after cardiac arrest (CA) is associated with worse outcomes. A population-based mean arterial pressure (MAP) threshold, such as a post-resuscitation goal of ≥ 65 mmHg, may be insufficient to account for patient-specific factors, like autoregulatory failure. We investigated the feasibility of determining optimal MAP (MAP OPT ) using regional cerebral tissue oxygen monitoring with near-infrared spectroscopy (NIRS). Hypothesis: Autoregulatory failure and MAP OPT can be identified in individual patients after CA. Methods: We prospectively enrolled adult comatose CA survivors undergoing invasive MAP and regional cerebral oxygen monitoring with NIRS in an ICU between April 2022 and May 2023. Tissue oxygenation autoregulatory index (TOx) was derived using a moving Pearson correlation coefficient of 30 consecutive, 10-second averaged values of MAP and tissue oxygen index signals. TOx ≥ 0.3 defined impaired autoregulation. MAP values were divided into bins of 5 mmHg for which each corresponding TOx was averaged. Parabolic curve fitting determined the MAP value with the lowest associated TOx value (MAP OPT ). Results: Of 35 patients enrolled, 74.3% experienced out-of-hospital cardiac arrest with a mean (SD) age of 55.0 (13.9) years. Six (17.1%) patients survived to hospital discharge and 4 (11.4%) progressed to brain death. Monitoring was initiated at a median [IQR] of 14.9 [10.9 - 20.6] hours from CA for a duration of 47.5 [27.1 - 75.1] hours. The time spent with impaired autoregulation was 22.6 [18.4 - 31.6] % of the recording duration, corresponding to 10.1 [6.9 - 15.9] hours. MAP OPT could be identified in 33 (94.3%) patients and 47.7 [32.1 - 59.6] % of the recording duration. The average MAP OPT was &lt;75 mmHg in 2 (6.1%), 75 - 85 mmHg in 14 (42.4%), and &gt;85 mmHg in 17 (51.5%) patients. MAP OPT did not differ between survivors and non-survivors (mean (SD) 87.2 (9.6) vs. 88.2 (12.1) mmHg respectively, p=0.86). Conclusion: MAP OPT could be identified in all but two patients and calculated for half of the recording duration. Average MAP OPT was ≥ 75 mmHg in 94% of our cohort. Future studies are needed to evaluate whether targeting personalized physiologic thresholds influences outcomes.

Analysis of tumour oxygenation in model animals on a phosphorescence lifetime based macro-imager

Monitoring of tissue O2 is essential for cancer development and treatment, as hypoxic tumour regions develop resistance to radio- and chemotherapy. We describe a minimally invasive technique for the monitoring of tissue oxygenation in developing grafted tumours, which uses the new phosphorescence lifetime based Tpx3Cam imager. CT26 cells stained with a near-infrared emitting nanoparticulate O2 probe NanO2-IR were injected into mice to produce grafted tumours with characteristic phosphorescence. The tumours were allowed to develop for 3, 7, 10 and 17 days, with O2 imaging experiments performed on live and euthanised animals at different time points. Despite a marked trend towards decreased O2 in dead animals, their tumour areas produced phosphorescence lifetime values between 44 and 47 µs, which corresponded to hypoxic tissue with 5–20 μM O2. After the O2 imaging in animals, confocal Phosphorescence Lifetime Imaging Microscopy was conducted to examine the distribution of NanO2-IR probe in the tumours, which were excised, fixed and sliced for the purpose. The probe remained visible as bright and discrete ‘islands’ embedded in the tumour tissue until day 17 of tumour growth. Overall, this O2 macro-imaging method using NanO2-IR holds promise for long-term studies with grafted tumours in live animal models, providing quantitative 2D mapping of tissue O2.

Brain tissue oxygen monitoring in traumatic brain injury—part II: isolated and combined insults in relation to outcome

BackgroundThe primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO2) in relation to outcome in traumatic brain injury (TBI).MethodsA total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO2 monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke’s Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4–5/1–3) and survival/mortality (GOS 2–5/1). PbtO2 was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration.ResultsMedian pbtO2 was slightly, but not significantly, associated with outcome. A pbtO2 threshold at 25 and 20 mmHg, respectively, yielded the highest x2 when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO2 below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO2 went below 25–30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO2 under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO2 < 15 mmHg was associated with a higher rate of unfavourable outcome.ConclusionsLow pbtO2, under 25 mmHg and particularly below 15 mmHg, for longer durations and in combination with disturbances in global cerebral physiological variables were associated with poor outcome and may indicate detrimental ischaemic hypoxia. Prospective trials are needed to determine if pbtO2-directed therapy is beneficial, at what individualised pbtO2 threshold therapies are warranted, and how this may depend on the presence/absence of concurrent cerebral physiological disturbances.

An Exploratory Review on the Potential of Artificial Intelligence for Early Detection of Acute Kidney Injury in Preterm Neonates.

A preterm birth is a live birth that occurs before 37 completed weeks of pregnancy. Approximately 15 million babies are born preterm annually worldwide, indicating a global preterm birth rate of about 11%. Up to 50% of premature neonates in the gestational age (GA) group of <29 weeks' gestation will develop acute kidney injury (AKI) in the neonatal period; this is associated with high mortality and morbidity. There are currently no proven treatments for established AKI, and no effective predictive tool exists. We propose that the development of advanced artificial intelligence algorithms with neural networks can assist clinicians in accurately predicting AKI. Clinicians can use pathology investigations in combination with the non-invasive monitoring of renal tissue oxygenation (rSO2) and renal fractional tissue oxygenation extraction (rFTOE) using near-infrared spectroscopy (NIRS) and the renal resistive index (RRI) to develop an effective prediction algorithm. This algorithm would potentially create a therapeutic window during which the treating clinicians can identify modifiable risk factors and implement the necessary steps to prevent the onset and reduce the duration of AKI.

Brain tissue oxygen monitoring in traumatic brain injury: part I—To what extent does PbtO2 reflect global cerebral physiology?

BackgroundThe primary aim was to explore the association of global cerebral physiological variables including intracranial pressure (ICP), cerebrovascular reactivity (PRx), cerebral perfusion pressure (CPP), and deviation from the PRx-based optimal CPP value (∆CPPopt; actual CPP-CPPopt) in relation to brain tissue oxygenation (pbtO2) in traumatic brain injury (TBI).MethodsA total of 425 TBI patients with ICP- and pbtO2 monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke’s Hospital, Cambridge, UK, between 2002 and 2022 were included. Generalized additive models (GAMs) and linear mixed effect models were used to explore the association of ICP, PRx, CPP, and CPPopt in relation to pbtO2. PbtO2 < 20 mmHg, ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, and ∆CPPopt < − 5 mmHg were considered as cerebral insults.ResultsPbtO2 < 20 mmHg occurred in median during 17% of the monitoring time and in less than 5% in combination with ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, or ∆CPPopt < − 5 mmHg. In GAM analyses, pbtO2 remained around 25 mmHg over a large range of ICP ([0;50] mmHg) and PRx [− 1;1], but deteriorated below 20 mmHg for extremely low CPP below 30 mmHg and ∆CPPopt below − 30 mmHg. In linear mixed effect models, ICP, CPP, PRx, and ∆CPPopt were significantly associated with pbtO2, but the fixed effects could only explain a very small extent of the pbtO2 variation.ConclusionsPbtO2 below 20 mmHg was relatively frequent and often occurred in the absence of disturbances in ICP, PRx, CPP, and ∆CPPopt. There were significant, but weak associations between the global cerebral physiological variables and pbtO2, suggesting that hypoxic pbtO2 is often a complex and independent pathophysiological event. Thus, other variables may be more crucial to explain pbtO2 and, likewise, pbtO2 may not be a suitable outcome measure to determine whether global cerebral blood flow optimization such as CPPopt therapy is successful.

Engineered porosity for tissue-integrating, bioresorbable lifetime-based phosphorescent oxygen sensors

Versatile silk protein-based material formats were studied to demonstrate bioresorbable, implantable optical oxygen sensors that can integrate with the surrounding tissues. The ability to continuously monitor tissue oxygenation in vivo is desired for a range of medical applications. Silk was chosen as the matrix material due to its excellent biocompatibility, its unique chemistry that facilitates interactions with chromophores, and the potential to tune degradation time without altering chemical composition. A phosphorescent Pd (II) benzoporphyrin chromophore was incorporated to impart oxygen sensitivity. Organic solvent-based processing methods using 1,1,1,3,3,3-hexafluoro-2-propanol were used to fabricate: 1) silk-chromophore films with varied thickness and 2) silk-chromophore sponges with interconnected porosity. All compositions were biocompatible and exhibited photophysical properties with oxygen sensitivities (i.e., Stern-Volmer quenching rate constants of 2.7–3.2 × 104 M−1) useful for monitoring physiological tissue oxygen levels and for detecting deviations from normal behavior (e.g., hyperoxia). The potential to tune degradation time without significantly impacting photophysical properties was successfully demonstrated. Furthermore, the ability to consistently monitor tissue oxygenation in vivo was established via a multi-week rodent study. Histological assessments indicated successful tissue integration for the sponges, and this material format responded more quickly to various oxygen challenges than the film samples.

Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury.

To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI). Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results. Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001). Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.