Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use.

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting.

Brain Oxygenation Response to Hypercapnia in Patients with Acute Brain Injury.

BACKGROUND: Cerebral hypoxia is a frequent cause of secondary brain damage in patients with acute brain injury. Although hypercapnia can increase intracranial pressure, it may have beneficial effects on tissue oxygenation. We aimed to assess the effects of hypercapnia on brain tissue oxygenation (PbtO2). METHODS: This single-center retrospective study (November 2014 to June 2022) included all patients admitted to the intensive care unit after acute brain injury who required multimodal monitoring, including PbtO2 monitoring, and who underwent induced moderate hypoventilation and hypercapnia according to the decision of the treating physician. Patients with imminent brain death were excluded. Responders to hypercapnia were defined as those with an increase of at least 20% in PbtO2 values when compared to their baseline levels. RESULTS: On a total of 163 eligible patients, we identified 23 (14%) patients who underwent moderate hypoventilation (arterial partial pressure of carbon dioxide [PaCO2] from 44 [42-45] to 50 [49-53] mm Hg; p < 0.001) during the study period at a median of 6 (4-10) days following intensive care unit admission; six patients had traumatic brain injury, and 17 had subarachnoid hemorrhage. A significant overall increase in median PbtO2 values from baseline (21 [19-26] to 24 [22-26] mm Hg; p = 0.02) was observed. Eight (35%) patients were considered as responders, with a median increase of 7 (from 4 to 11) mm Hg of PbtO2, whereas nonresponders showed no changes (from - 1 to 2 mm Hg of PbtO2). Because of the small sample size, no variable independently associated with PbtO2 response was identified. No correlation between changes in PaCO2 and in PbtO2 was observed. CONCLUSIONS: In this study, a heterogeneous response of PbtO2 to induced hypercapnia was observed but without any deleterious elevations of intracranial pressure.

The impact of perfusion computed tomography on the diagnosis and outcome of delayed cerebral ischemia after subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a preventable cause of poor neurological outcome in aneurysmal subarachnoid hemorrhage (aSAH). Advances in radiological methods, such as cerebral perfusion computed tomography (CTP), could help diagnose DCI earlier and potentially improve outcomes in aSAH. The objective of this study was to assess whether the use of CTP to diagnose DCI early could reduce the risk of infarction related to DCI. METHODS: Retrospective cohort study of patients in the intensive care unit of Erasme Hospital (Brussels, Belgium) between 2004 and 2021 with aSAH who developed DCI. Patients were classified as: "group 1" - DCI diagnosed based on clinical deterioration or "group 2" - DCI diagnosed using CTP. The primary outcome was the development of infarction unrelated to the initial bleeding or surgery. RESULTS: 211 aSAH patients were diagnosed with DCI during the study period: 139 (66%) in group 1 and 72 (34%) in group 2. In group 1, 109 (78%) patients developed a cerebral infarction, compared to 45 (63%) in group 2 (p = 0.02). The adjusted cumulative incidence of DCI over time was lower in group 2 than in group 1 [hazard ratio 0.65 (95% CI 0.48-0.94); p = 0.02]. The use of CTP to diagnose DCI was not independently associated with mortality or neurological outcome. CONCLUSIONS: The use of CTP to diagnose DCI might help reduce the risk of developing cerebral infarction after aSAH, although the impact of such an approach on patient outcomes needs to be further demonstrated.

The Effects of Acetazolamide on Cerebral Hemodynamics in Adult Patients with an Acute Brain Injury: A Systematic Review.

BACKGROUND: Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the regulation of cerebral blood flow (CBF). The aim of this review was to understand the effects of acetazolamide on CBF, intracranial pressure (ICP) and brain tissue oxygenation (PbtO2) after an acute brain injury (ABI). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), we performed a comprehensive, computer-based, literature research on the PubMed platform to identify studies that have reported the effects on CBF, ICP, or PbtO2 of acetazolamide administered either for therapeutic or diagnostic purposes in patients with subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, and hypoxic-ischemic encephalopathy. RESULTS: From the initial search, 3430 records were identified and, through data selection, 11 of them were included for the qualitative analysis. No data on the effect of acetazolamide on ICP or PbtO2 were found. Cerebral vasomotor reactivity (VMR-i.e., the changing in vascular tone due to a vasoactive substance) to acetazolamide tends to change during the evolution of ABI, with the nadir occurring during the subacute stage. Moreover, VMR reduction was correlated with clinical outcome. CONCLUSIONS: This systematic review showed that the available studies on the effects of acetazolamide on brain hemodynamics in patients with ABI are scarce. Further research is required to better understand the potential role of this drug in ABI patients.

The effect of increased positive end expiratory pressure on brain tissue oxygenation and intracranial pressure in acute brain injury patients.

Cerebral hypoxia is an important cause of secondary brain injury. Improving systemic oxygenation may increase brain tissue oxygenation (PbtO2). The effects of increased positive end-expiratory pressure (PEEP) on PbtO2 and intracranial pressure (ICP) needs to be further elucidated. This is a single center retrospective cohort study (2016-2021) conducted in a 34-bed Department of Intensive Care unit. All patients with acute brain injury under mechanical ventilation who were monitored with intracranial pressure and brain tissue oxygenation (PbtO2) catheters and underwent at least one PEEP increment were included in the study. Primary outcome was the rate of PbtO2 responders (increase in PbtO2 > 20% of baseline) after PEEP increase. ΔPEEP was defined as the difference between PEEP at 1 h and PEEP at baseline; similarly ΔPbtO2 was defined as the difference between PbtO2 at 1 h after PEEP incrementation and PbtO2 at baseline. We included 112 patients who underwent 295 episodes of PEEP increase. Overall, the median PEEP increased form 6 (IQR 5-8) to 10 (IQR 8-12) cmH2O (p = 0.001), the median PbtO2 increased from 21 (IQR 16-29) mmHg to 23 (IQR 18-30) mmHg (p = 0.001), while ICP remained unchanged [from 12 (7-18) mmHg to 12 (7-17) mmHg; p = 0.42]. Of 163 episode of PEEP increments with concomitant PbtO2 monitoring, 34 (21%) were PbtO2 responders. A lower baseline PbtO2 (OR 0.83 [0.73-0.96)]) was associated with the probability of being responder. ICP increased in 142/295 episodes of PEEP increments (58%); no baseline variable was able to identify this response. In PbtO2 responders there was a moderate positive correlation between ΔPbtO2 and ΔPEEP (r = 0.459 [95% CI 0.133-0.696]. The response in PbtO2 and ICP to PEEP elevations in brain injury patients is highly variable. Lower PbtO2 values at baseline could predict a significant increase in brain oxygenation after PEEP increase.

Cerebrospinal fluid analysis of metabolites is not correlated to microdialysis measurements in acute brain injured patients.

BACKGROUND: Cerebral microdialysis (CMD) has become an established bedside monitoring modality but its implementation remains complex and costly and is therefore performed only in a few well-trained academic centers. This study investigated the relationship between cerebrospinal fluid (CSF) and CMD glucose and lactate concentrations. METHODS: Two centers retrospective study of prospectively collected data. Consecutive adult (>18 years) acutely brain injured patients admitted to the Intensive Care Unit between 2010 and 2021 were eligible if CSF and CMD glucose and lactate concentrations were concomitantly measured at least once. RESULTS: Of 113 patients being monitored with an external ventricular drainage and CMD, 49 patients (25 from Innsbruck and 24 from Brussels) were eligible for the final analysis, including a total of 96 measurements. Median CMD glucose and lactate concentrations were 1.15 (0.51-1.57) mmol/L and 3.44 (2.24-5.37) mmol/L, respectively; median CSF glucose and lactate concentrations were 4.67 (4.03-5.34) mmol/L and 3.40 (2.85-4.10) mmol/L, respectively. For the first measurements, no correlation between CSF and CMD glucose concentrations (R2 <0.01; p = 0.95) and CSF and CMD lactate concentrations (R2 =0.16; p = 0.09) was found. Considering all measurements, the repeated measure correlation analysis also showed no correlation for glucose (rrm = -0.01; 95% Confidence Intervals -0.306 to 0.281; p = 0.93) and lactate (rrm = -0.11; 95% Confidence Intervals -0.424 to 0.236; p = 0.55). CONCLUSIONS: In this study including acute brain injured patients, no correlation between CSF and brain tissue measurements of glucose and lactate was observed. As such, CSF measurements of such metabolites cannot replace CMD findings.

Serum LDH levels may predict poor neurological outcome after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Serum lactate dehydrogenase (LDH) levels are often elevated in cardiovascular diseases. Their prognostic role after subarachnoid hemorrhage (SAH) remains poorly evaluated. METHODS: This is a retrospective single-center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of an University Hospital from 2007 to 2022. Exclusion criteria were pregnancy and incomplete medical records or follow-up data. Baseline information, clinical data, radiologic data, the occurrence of neurological complications as well as serum LDH levels during the first 14 days of ICU stay were collected. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1-3. RESULTS: Five hundred and forty-seven patients were included; median serum LDH values on admission and the highest LDH values during the ICU stay were 192 [160-230] IU/L and 263 [202-351] IU/L, respectively. The highest LDH value was recorded after a median of 4 [2-10] days after ICU admission. LDH levels on admission were significantly higher in patients with UO. When compared with patients with favorable outcome (FO), patients with UO had higher serum LDH values over time. In the multivariate logistic regression model, the highest LDH value over the ICU stay (OR 1.004 [95% CI 1.002 - 1.006]) was independently associated with the occurrence of UO; the area under the receiving operator (AUROC) curve for the highest LDH value over the ICU stay showed a moderate accuracy to predict UO (AUC 0.76 [95% CI 0.72-0.80]; p < 0.001), with an optimal threshold of > 272 IU/L (69% sensitivity and 74% specificity). CONCLUSIONS: The results in this study suggest that high serum LDH levels are associated with the occurrence of UO in SAH patients. As a readily and available biomarker, serum LDH levels should be evaluated to help with the prognostication of SAH patients.

Neurological Pupil Index and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: A Retrospective Multicentric Study.

BACKGROUND: Delayed cerebral ischemia (DCI) occurs in around 30% of patients suffering from nontraumatic subarachnoid hemorrhage (SAH) and is associated with poor neurological outcome. Whether the Neurological Pupil index (NPi) derived from the automated pupillometry could help to diagnose the occurrence of DCI remains unknown. The aim of this study was to investigate the association of NPi with the occurrence of DCI in patients with SAH. METHODS: This was a multicenter, retrospective cohort study of consecutive patients with SAH admitted to the intensive care units of five hospitals between January 2018 and December 2020 who underwent daily NPi recordings (every 8 h) during the first 10 days of admission. DCI was diagnosed according to standard definitions (in awake patients) or based on neuroimaging and neuromonitoring (in sedated or unconscious patients). An NPi < 3 was defined as abnormal. The primary outcome of the study was to assess the time course of daily NPi between patients with DCI and patients without DCI. Secondary outcome included the number of patients who had an NPi < 3 before DCI. RESULTS: A total of 210 patients were eligible for the final analysis; DCI occurred in 85 (41%) patients. Patients who developed DCI had similar values of mean and worst daily NPi over time when compared with patients without DCI. Patients with DCI had a higher proportion of at least one NPi < 3 at any moment before DCI when compared with others (39/85, 46% vs. 35/125, 38%, p = 0.009). Similarly, the worst NPi before DCI diagnosis was lower in the DCI group when compared with others (3.1 [2.5-3.8] vs. 3.7 [2.7-4.1], p = 0.05). In the multivariable logistic regression analysis, the presence of NPi < 3 was not independently associated with the development of DCI (odds ratio 1.52 [95% confidence interval 0.80-2.88]). CONCLUSIONS: In this study, NPi measured three times a day and derived from the automated pupillometry had a limited value for the diagnosis of DCI in patients with SAH.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest.

INTRODUCTION: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. METHODS: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. RESULTS: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. CONCLUSIONS: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study.

INTRODUCTION: Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). METHODS: A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48-72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP ("intervention"). Patients with normal ICP were also sampled at the same time points and served as the "control" group. RESULTS: A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. CONCLUSIONS: In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

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 20 mm 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.

Cervical Ganglion Sympathectomy to Treat Cerebral Vasospasm in Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is still a significant cause of death and disability after aneurysmal subarachnoid hemorrhage. Cerebral vasospasm represents one of the most reported mechanisms associated with DCI. The management of DCI-related vasospasm remains a significant challenge for clinicians; induced hypertension, intraarterial vasodilators, and/or intracranial vessel angioplasty-particularly in refractory or recurrent cases-are the most used therapies. Because an essential role in the pathophysiology of cerebral vasospasm has been attributed to the adrenergic sympathetic nerves, a "sympatholytic" intervention, consisting of a temporary interruption of the sympathetic pathways using local anesthetics, has been advocated to minimize the vascular narrowing and reverse the consequences of cerebral vasospasm on tissue perfusion. In this review, we have analyzed the existing literature on the block of the cervical ganglions, particularly the stellate ganglion, in managing refractory cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. These findings could help clinicians to understand the potential role of such intervention and to develop future interventional trials in this setting.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19-Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis.

Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19-induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a "control" non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19-related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19-associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27; 95% CI, 0.82-1.98; p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS.

The Impact of Invasive Brain Oxygen Pressure Guided Therapy on the Outcome of Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) is a major public health burden, causing death and disability worldwide. Intracranial hypertension and brain hypoxia are the main mechanisms of secondary brain injury. As such, management strategies guided by intracranial pressure (ICP) and brain oxygen (PbtO2) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO2-guided therapy on the outcome of patients with TBI. We performed a systematic search of PubMed, Scopus, and the Cochrane library databases, following the protocol registered in PROSPERO. Only studies comparing PbtO2/ICP-guided therapy with ICP-guided therapy were selected. Primary outcome was neurological outcome at 3 and 6 months assessed by using the Glasgow Outcome Scale; secondary outcomes included hospital and long-term mortality, burden of intracranial hypertension, and brain tissue hypoxia. Out of 6254 retrieved studies, 15 studies (n = 37,245 patients, of who 2184 received PbtO2-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO2/ICP-guided therapy was associated with a higher probability of favorable neurological outcome (odds ratio 2.21 [95% confidence interval 1.72-2.84]) and of hospital survival (odds ratio 1.15 [95% confidence interval 1.04-1.28]). The heterogeneity (I2) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO2-guided therapy was associated with reduced mortality and more favorable neurological outcome in patients with TBI. The low-quality evidence underlines the need for the results from ongoing phase III randomized trials.

Effect of inotropic agents on oxygenation and cerebral perfusion in acute brain injury.

Introduction: Tissue hypoxia and insufficient energy delivery is one of the mechanisms behind the occurrence of several complications in acute brain injured patients. Several interventions can improve cerebral oxygenation; however, the effects of inotropic agents remain poorly characterized. Methods: Retrospective analysis including patients suffering from acute brain injury and monitored with brain oxygen pressure (PbtO2) catheter, in whom inotropic agents were administered according to the decision of the treating physician's decision; PbtO2 values were collected before, 1 and 2 h after the initiation of therapy from the patient data monitoring system. PbtO2 "responders" were patients with a relative increase in PbtO2 from baseline values of at least 20%. Results: A total of 35 patients were included in this study. Most of them (31/35, 89%) suffered from non-traumatic subarachnoid hemorrhage (SAH). Compared with baseline values [20 (14-24) mmHg], PbtO2 did not significantly increase over time [19 (15-25) mmHg at 1 h and 19 (17-25) mmHg at 2 h, respectively; p = 0.052]. A total of 12/35 (34%) patients were PbtO2 "responders," in particular if low PbtO2 was observed at baseline. A PbtO2 of 17 mmHg at baseline had a sensibility of 84% and a specificity of 91% to predict a PbtO2 responder. A significant direct correlation between changes in PbtO2 and cardiac output [r = 0.496 (95% CI 0.122 to 0.746), p = 0.01; n = 25] and a significant negative correlation between changes in PbtO2 and cerebral perfusion pressure [r = -0.389 (95% CI -0.681 to -0.010), p = 0.05] were observed. Conclusions: In this study, inotropic administration significantly increased brain oxygenation in one third of brain injured patients, especially when tissue hypoxia was present at baseline. Future studies should highlight the role of inotropic agents in the management of tissue hypoxia in this setting.

Brain Tissue Oxygenation-Guided Therapy and Outcome in Traumatic Brain Injury: A Single-Center Matched Cohort Study.

Brain tissue oxygenation (PbtO2)-guided therapy can improve the neurological outcome of traumatic brain injury (TBI) patients. With several Phase-III ongoing studies, most of the existing evidence is based on before-after cohort studies and a phase-II randomized trial. The aim of this study was to assess the effectiveness of PbtO2-guided therapy in a single-center cohort. We performed a retrospective analysis of consecutive severe TBI patients admitted to our center who received either intracranial pressure (ICP) guided therapy (from January 2012 to February 2016) or ICP/PbtO2-guided therapy (February 2017 to December 2019). A genetic matching was performed based on covariates including demographics, comorbidities, and severity scores on admission. Intracranial hypertension (IH) was defined as ICP > 20 mmHg for at least 5 min. Brain hypoxia (BH) was defined as PbtO2 < 20 mmHg for at least 10 min. IH and BH were targeted by specific interventions. Mann−Whitney U and Fisher's exact tests were used to assess differences between groups. A total of 35 patients were matched in both groups: significant differences in the occurrence of IH (ICP 85.7% vs. ICP/PbtO2 45.7%, p < 0.01), ICU length of stay [6 (3−13) vs. 16 (9−25) days, p < 0.01] and Glasgow Coma Scale at ICU discharge [10 (5−14) vs. 13 (11−15), p = 0.036] were found. No significant differences in ICU mortality and Glasgow Outcome Scales at 3 months were observed. This study suggests that the role of ICP/PbtO2-guided therapy should await further confirmation in well-conducted large phase III studies.

Automated Pupillometry for Prediction of Electroencephalographic Reactivity in Critically Ill Patients: A Prospective Cohort Study.

Background: Electroencephalography (EEG) is widely used to monitor critically ill patients. However, EEG interpretation requires the presence of an experienced neurophysiologist and is time-consuming. Aim of this study was to evaluate whether parameters derived from an automated pupillometer (AP) might help to assess the degree of cerebral dysfunction in critically ill patients. Methods: Prospective study conducted in the Department of Intensive Care of Erasme University Hospital in Brussels, Belgium. Pupillary assessments were performed using the AP in three subgroups of patients, concomitantly monitored with continuous EEG: "anoxic brain injury", "Non-anoxic brain injury" and "other diseases". An independent neurologist blinded to patient's history and AP results scored the degree of encephalopathy and reactivity on EEG using a standardized scale. The mean value of Neurologic Pupil Index (NPi), pupillary size, constriction rate, constriction and dilation velocity (CV and DV) and latency for both eyes, obtained using the NPi®-200 (Neuroptics, Laguna Hills, CA, USA), were reported. Results: We included 214 patients (mean age 60 years, 55% male). EEG tracings were categorized as: mild (n = 111, 52%), moderate (n = 65, 30%) or severe (n = 16, 8%) encephalopathy; burst-suppression (n = 19, 9%) or suppression background (n = 3, 1%); a total of 38 (18%) EEG were classified as "unreactive". We found a significant difference in all pupillometry variables among different EEG categories. Moreover, an unreactive EEG was associated with lower NPi, pupil size, pupillary reactivity, CV and DV and a higher latency than reactive recordings. Low DV (Odds ratio 0.020 [95% confidence intervals 0.002-0.163]; p < 0.01) was independently associated with an unreactive EEG, together with the use of analgesic/sedative drugs and high lactate concentrations. In particular, DV values had an area under the curve (AUC) of 0.86 [0.79-0.92; p < 0.01] to predict the presence of unreactive EEG. In subgroups analyses, AUC of DV to predict unreactive EEG was lower (0.72 [0.56-0.87]; p < 0.01) in anoxic brain injury than Non-anoxic brain injury (0.92 [0.85-1.00]; p < 0.01) and other diseases (0.96 [0.90-1.00]; p < 0.01). Conclusions: This study suggests that low DV measured by the AP might effectively identify an unreactive EEG background, in particular in critically ill patients without anoxic brain injury.