Brain Tissue Oxygen Monitoring Research Articles

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.

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.

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.

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.

The impact of brain tissue oxygenation monitoring on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended in patients with moderate to severe traumatic brain injury: A systematic review.

Traumatic brain injuries (TBIs) are one of the leading causes of death or long-term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long-term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP). The aim of this review is to determine the impact of PbtO2 on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended (GOS/GOSE) in patients with moderate to severe TBI. Systematic review with narrative and meta-analysis. All original research in which adult patients undergoing PbtO2 were compared with a control group of traditional ICP/cerebral perfusion pressure (CPP) monitoring. Both randomized controlled trials and observational studies were included in this review. Databases were searched in September 2022. The primary outcome of the review was the impact of PbtO2 monitoring on GOS/GOSE, while secondary outcomes were mortality and length of stay (LOS) in the intensive care unit (ICU). Seven studies with a combined number of 770 patients were included in the review. These patients were adults ≥16 years of age. Only two of the studies included found a statistically significant association between PbtO2 monitoring and improved long-term neurological outcomes in patients with TBI (p = .01, p < .01). A meta-analysis of the secondary outcomes identified an associated reduction of mortality in favour of the group treated with PbtO2 monitoring (p < .0001). Results from studies examining LOS in ICU have demonstrated an associated increase of LOS in ICU in patients treated with PbtO2-guided therapy. From the studies included in this review, only two found a statistically significant association between PbtO2 monitoring and long-term outcomes. It is unclear whether PbtO2 goal-directed therapy has a positive impact on the long-term neurological functions and mortality of patients suffering from TBI. A multicentre randomized controlled trial may provide further evidence, but not necessarily conclusive. Further research is warranted to determine the efficacy of the introduction of this new monitoring system to guide local policy change.

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.

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.

Intracranial Pressure and Brain Tissue Oxygen Multimodality Neuromonitoring in Gunshot Wounds to the Head in Children

Gunshot wounds to the head (GSWH) are a cause of severe penetrating traumatic brain injury (TBI). Although multimodal neuromonitoring has been increasingly used in blunt pediatric TBI, its role in the pediatric population with GSWH is not known. We report on 3 patients who received multimodal neuromonitoring as part of clinical management at our institution and review the existing literature on pediatric GSWH. We identified 3 patients ≤18 years of age who were admitted to a quaternary children's hospital from 2005 to 2021 with GSWH and received invasive intracranial pressure (ICP) and Pbto2 (brain tissue oxygenation) monitoring with or without noninvasive near-infrared spectroscopy (NIRS). We analyzed clinical and demographic characteristics, imaging findings, and ICP, Pbto2, cerebral perfusion pressure, and rSo2 (regional cerebral oxygen saturation) NIRS trends. All patients were male with an average admission Glasgow Coma Scale score of 4. One patient received additional NIRS monitoring. Episodes of intracranial hypertension (ICP ≥20 mm Hg) and brain tissue hypoxia (Pbto2 <15 mm Hg) or hyperemia (Pbto2 >35 mm Hg) frequently occurred independently of each other, requiring unique targeted treatments. rSo2 did not consistently mirror Pbto2. All children survived, with favorable Glasgow Outcome Scale-Extended score at 6 months after injury. Use of ICP and Pbto2 multimodality neuromonitoring enabled specific management for intracranial hypertension or brain tissue hypoxia episodes that occurred independently of one another. Multimodality neuromonitoring has not been studied extensively in pediatric GSWH; however, its use may provide a more complete picture of patient injury and prognosis without significant added procedural risk.

Benchmarking Hospital Practices and Policies on Intrahospital Neurocritical Care Transport: The Safe-Neuro-Transport Study.

An electronic survey was administered to multidisciplinary neurocritical care providers at 365 hospitals in 32 countries to describe intrahospital transport (IHT) practices of neurocritically ill patients at their institutions. The reported IHT practices were stratified by World Bank country income level. Variability between high-income (HIC) and low/middle-income (LMIC) groups, as well as variability between hospitals within countries, were expressed as counts/percentages and intracluster correlation coefficients (ICCs) with a 95% confidence interval (CI). A total of 246 hospitals (67% response rate; n = 103, 42% HIC and n = 143, 58% LMIC) participated. LMIC hospitals were less likely to report a portable CT scanner (RR 0.39, 95% CI [0.23; 0.67]), more likely to report a pre-IHT checklist (RR 2.18, 95% CI [1.53; 3.11]), and more likely to report that intensive care unit (ICU) physicians routinely participated in IHTs (RR 1.33, 95% CI [1.02; 1.72]). Between- and across-country variation were highest for pre-IHT external ventricular drain clamp tolerance (reported by 40% of the hospitals, ICC 0.22, 95% CI 0.00-0.46) and end-tidal carbon dioxide monitoring during IHT (reported by 29% of the hospitals, ICC 0.46, 95% CI 0.07-0.71). Brain tissue oxygenation monitoring during IHT was reported by only 9% of the participating hospitals. An IHT standard operating procedure (SOP)/hospital policy (HP) was reported by 37% (n = 90); HIC: 43% (n= 44) vs. LMIC: 32% (n = 46), p = 0.56. Amongst the IHT SOP/HPs reviewed (n = 13), 90% did not address the continuation of hemodynamic and neurophysiological monitoring during IHT. In conclusion, the development of a neurocritical-care-specific IHT SOP/HP as well as the alignment of practices related to the IHT of neurocritically ill patients are urgent unmet needs. Inconsistent standards related to neurophysiological monitoring during IHT warrant in-depth scrutiny across hospitals and suggest a need for international guidelines for neurocritical care IHT.

The Role of Brain Tissue Oxygenation Monitoring in the Management of Subarachnoid Hemorrhage: A Scoping Review.

Monitoring of brain tissue oxygenation (PbtO2) is an important component of multimodal monitoring in traumatic brain injury. Over recent years, use of PbtO2 monitoring has also increased in patients with poor-grade subarachnoid hemorrhage (SAH), particularly in those with delayed cerebral ischemia. The aim of this scoping review was to summarize the current state of the art regarding the use of this invasive neuromonitoring tool in patients with SAH. Our results showed that PbtO2 monitoring is a safe and reliable method to assess regional cerebral tissue oxygenation and that PbtO2 represents the oxygen available in the brain interstitial space for aerobic energy production (i.e., the product of cerebral blood flow and the arterio-venous oxygen tension difference). The PbtO2 probe should be placed in the area at risk of ischemia (i.e., in the vascular territory in which cerebral vasospasm is expected to occur). The most widely used PbtO2 threshold to define brain tissue hypoxia and initiate specific treatment is between 15 and 20mm Hg. PbtO2 values can help identify the need for or the effects of various therapies, such as hyperventilation, hyperoxia, induced hypothermia, induced hypertension, red blood cell transfusion, osmotic therapy, and decompressive craniectomy. Finally, a low PbtO2 value is associated with a worse prognosis, and an increase of the PbtO2 value in response to treatment is a marker of good outcome.

Brain Tissue Oxygen Levels as a Perspective Therapeutic Target in Traumatic Brain Injury. Retrospective Cohort Study.

Management of traumatic brain injury (TBI) requires a multidisciplinary approach and represents a significant challenge for both neurosurgeons and intensivists. The role of brain tissue oxygenation (PbtO2) monitoring and its impact on posttraumatic outcomes remains a controversial topic. Our study aimed to evaluate the impact of PbtO2 monitoring on mortality, 30 days and 6 months neurological outcomes in patients with severe TBI compared with those resulting from standard intracranial pressure (ICP) monitoring. In this retrospective cohort study, we analysed the outcomes of 77 patients with severe TBI who met the inclusion criteria. These patients were divided into two groups, including 37 patients who were managed with ICP and PbtO2 monitoring protocols and 40 patients who were managed using ICP protocols alone. There were no significant differences in demographic data between the two groups. We found no statistically significant differences in mortality or Glasgow Outcome Scale (GOS) scores one month after TBI. However, our results revealed that GOS scores at 6 months had improved significantly among patients managed with PbtO2; this finding was particularly notable for Glasgow Outcome Scale (GOS) scores of 4-5. Close monitoring and management of reductions in PbtO2, particularly by increasing the fraction of inspired oxygen, was associated with higher partial pressures of oxygen in this group. Monitoring of PbtO2 may facilitate the appropriate evaluation and treatment of low PbtO2 and represents a promising tool for the management of patients with severe TBI. Additional studies will be needed to confirm these findings.

The impact of brain tissue oxygenation monitoring on mortality in adult patients with severe traumatic brain injuries: a systematic review

Background: Intracranial pressure (ICP) monitoring and cerebral perfusion pressure (CPP) monitoring are long established adjuncts in the management of traumatic brain injuries (TBIs). However, brain tissue oxygenation (PbtO2) monitoring, used in conjunction with ICP or CPP monitoring, is an additional element that could be used in directing the management of TBIs. Aims: To determine the impact of PbtO2 monitoring on mortality in adult patients with severe TBIs. Methods: A systematic review of electronic databases was performed in October 2021. A total of six articles were identified for inclusion. Data were extracted using a pre-designed extraction tool. Analysis was undertaken using RevMan for the mortality rates and a narrative analysis for the secondary outcomes. Findings: A total of 926 participants were evaluated. Of these, 269 received PbtO2 monitoring. There was no significant difference in mortality rates between the groups, with the PbtO2 and ICP/CPP groups having a mortality rate of 25% (72/284) and 26% (171/662), respectively. The odds ratio was calculated as 0.88 (0.63–1.23, P=0.45) suggesting a 37% reduction in the odds of mortality when PbtO2 is used. However, the 95% confidence intervals do indicate a non-statistical finding. Morbidity rates between the two groups were also similar, with some limited evidence (one study) demonstrating a higher fiscal cost associated with PbtO2 monitoring. Conclusions: There was no significant difference in mortality or morbidity rates between the two groups. Based on these results, this systematic review cannot support the addition of PbtO2 monitoring to guide the treatment of adult patients with severe TBIs.

Brain tissue oxygenation monitoring in subarachnoid hemorrhage for the detection of delayed ischemia: a systematic review and meta-analysis.

Subarachnoid hemorrhage (SAH) is a severe subtype of stroke which can be caused by the rupture of an intracranial aneurysm. Following SAH, about 30% of patients develop a late neurologic deterioration due to a delayed cerebral ischemia (DCI). This is a metanalysis and systematic review on the association between values of brain tissue oxygenation (PbtO<inf>2</inf>) and DCI in patients with SAH. The protocol was written according to the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and approved by the International Prospective Register of Systematic Reviews (PROSPERO registration number CRD42021229338). Relevant literature published up to August 1, 2022 was systematically searched throughout the databases MEDLINE, WEB OF SCIENCE, SCOPUS. A systematic review and metanalysis was carried out. The studies considered eligible were those published in English; that enrolled adult patients (≥18years) admitted to neurointensive care units with aneurysmal SAH (aSAH); that reported presence of multimodality monitoring including PbtO<inf>2</inf> and detection of DCI during the period of monitoring. We founded 286 studies, of which six considered eligible. The cumulative mean of PbtO<inf>2</inf>was 19.5 mmHg in the ischemic group and 24.1mmHg in the non ischemic group. The overall mean difference of the values of PbtO<inf>2</inf> between the patients with or without DCI resulted significantly different (-4.32 mmHg [IC 95%: -5.70, -2.94], without heterogeneity, I2 = 0%, and a test for overall effect with P<0.00001). PbtO<inf>2</inf> values were significantly lower in patients with DCI. Waiting for definitive results, monitoring of PbtO<inf>2</inf> should be considered as a complementary parameter for multimodal monitoring of the risk of DCI in patients with SAH.

Experience with clinical cerebral autoregulation testing in children hospitalized with traumatic brain injury: Translating research to bedside.

To report our institutional experience with implementing a clinical cerebral autoregulation testing order set with protocol in children hospitalized with traumatic brain injury (TBI). After IRB approval, we examined clinical use, patient characteristics, feasibility, and safety of cerebral autoregulation testing in children aged <18 years between 2014 and 2021. A clinical order set with a protocol for cerebral autoregulation testing was introduced in 2018. 25 (24 severe TBI and 1 mild TBI) children, median age 13 years [IQR 4.5; 15] and median admission GCS 3[IQR 3; 3.5]) underwent 61 cerebral autoregulation tests during the first 16 days after admission [IQR1.5; 7; range 0-16]. Testing was more common after implementation of the order set (n = 16, 64% after the order set vs. n = 9, 36% before the order set) and initiated during the first 2 days. During testing, patients were mechanically ventilated (n = 60, 98.4%), had invasive arterial blood pressure monitoring (n = 60, 98.4%), had intracranial pressure monitoring (n = 56, 90.3%), brain-tissue oxygenation monitoring (n = 56, 90.3%), and external ventricular drain (n = 13, 25.5%). Most patients received sedation and analgesia for intracranial pressure control (n = 52; 83.8%) and vasoactive support (n = 55, 90.2%) during testing. Cerebral autoregulation testing was completed in 82% (n = 50 tests); 11 tests were not completed [high intracranial pressure (n = 5), high blood pressure (n = 2), bradycardia (n = 2), low cerebral perfusion pressure (n = 1), or intolerance to blood pressure cuff inflation (n = 1)]. Impaired cerebral autoregulation on first assessment resulted in repeat testing (80% impaired vs. 23% intact, RR 2.93, 95% CI 1.06:8.08, p = 0.03). Seven out of 50 tests (14%) resulted in a change in cerebral hemodynamic targets. Findings from this series of children with TBI indicate that: (1) Availability of clinical order set with protocol facilitated clinical cerebral autoregulation testing, (2) Clinicians ordered cerebral autoregulation tests in children with severe TBI receiving high therapeutic intensity and repeatedly with impaired status on the first test, (3) Clinical cerebral autoregulation testing is feasible and safe, and (4) Testing results led to change in hemodynamic targets in some patients.

Cerebrovascular pressure reactivity and brain tissue oxygen monitoring provide complementary information regarding the lower and upper limits of cerebral blood flow control in traumatic brain injury: a CAnadian High Resolution-TBI (CAHR-TBI) cohort study

BackgroundBrain tissue oxygen tension (PbtO2) and cerebrovascular pressure reactivity monitoring have emerged as potential modalities to individualize care in moderate and severe traumatic brain injury (TBI). The relationship between these modalities has had limited exploration. The aim of this study was to examine the relationship between PbtO2 and cerebral perfusion pressure (CPP) and how this relationship is modified by the state of cerebrovascular pressure reactivity.MethodsA retrospective multi-institution cohort study utilizing prospectively collected high-resolution physiologic data from the CAnadian High Resolution-TBI (CAHR-TBI) Research Collaborative database collected between 2011 and 2021 was performed. Included in the study were critically ill TBI patients with intracranial pressure (ICP), arterial blood pressure (ABP), and PbtO2 monitoring treated in any one of three CAHR-TBI affiliated adult intensive care units (ICU). The outcome of interest was how PbtO2 and CPP are related over a cohort of TBI patients and how this relationship is modified by the state of cerebrovascular reactivity, as determined using the pressure reactivity index (PRx).ResultsA total of 77 patients met the study inclusion criteria with a total of 377,744 min of physiologic data available for the analysis. PbtO2 produced a triphasic curve when plotted against CPP like previous population-based plots of cerebral blood flow (CBF) versus CPP. The triphasic curve included a plateau region flanked by regions of relative ischemia (hypoxia) and hyperemia (hyperoxia). The plateau region shortened when cerebrovascular pressure reactivity was disrupted compared to when it was intact.ConclusionsIn this exploratory analysis of a multi-institution high-resolution physiology TBI database, PbtO2 seems to have a triphasic relationship with CPP, over the entire cohort. The CPP range over which the plateau exists is modified by the state of cerebrovascular reactivity. This indicates that in critically ill TBI patients admitted to ICU, PbtO2 may be reflective of CBF.

High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

PurposeThe effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation.MethodsThis is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO2) and the oxygen inspired fraction (FiO2). We explored the association between high PaO2 and FiO2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO2 and FiO2 levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).ResultsThe analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO2 ranged from 93 to 166 mmHg. Exposure to higher PaO2 and FiO2 in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO2 and FiO2 levels, which remained independently associated with 6-month mortality.ConclusionsIn two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO2 and FiO2 varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO2 were due to use of higher FiO2 in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO2 and PaO2 are titrated to brain tissue oxygen monitoring (PbtO2) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.

Invasive brain tissue oxygen and intracranial pressure (ICP) monitoring versus ICP-only monitoring in pediatric severe traumatic brain injury.

Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population. While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes. The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have better outcomes than those who underwent ICP-only monitoring and treatment. Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children's hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay (LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow Outcome Score-Extended (GOS-E) scale at 6 months postinjury. Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak negative association between ICP and PbtO2 (β = -0.04). Conversely, there was a strong positive correlation between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (β = 0.30 and β = 0.29, p < 0.001, respectively). An increased number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p = 0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation (p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively). An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p = 0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E score difference between groups (p = 0.733). An increased number of cerebral hypoxic episodes and an increased number of intracranial hypertension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance of multimodal invasive neuromonitoring in pediatric severe TBI.

Adjustable and Magnetic Resonance Imaging Conditional Implantation of a Licox Brain Tissue Oxygenation Probe in Neurosurgery: Technical Note

Continuous bedside brain tissue oxygen monitoring is an essential part of managing comatose patients with acute brain injury. Maintenance of adequate brain oxygenation has been established as an important goal in neurocritical care to prevent patients from secondary ischemia. As patients with subarachnoid hemorrhage and traumatic brain injury often require early magnetic resonance imaging, conventionally implanted metal bolts are disadvantageous due to massive artifacts. We hereby report a novel technique of magnetic resonance imaging conditional bedside implantation of a brain tissue oxygenation probe. We performed bedside implantation of a Licox brain tissue oxygenation probe with a peripheral venous cannula that is placed through a plastic bolt placed on a burr hole. Bedside implantation of a Licox brain tissue oxygenation probe was successfully performed in a novel fashion. This article describes the feasibility of a novel technique of bedside implantation of a Licox brain tissue oxygenation probe, resulting in a length-adjustable insertion and rigid fixation without metal artifacts in early magnetic resonance imaging.