Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.

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.

A Comparison of Prognostic Factors in a Large Cohort of In-Hospital and Out-of-Hospital Cardiac Arrest Patients.

We investigated independent factors predicting neurological outcome and death, comparing in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) patients. The study was conducted in the mixed 34-bed Intensive Care Department at the Hôpital Universitaire de Bruxelles (HUB), Belgium. All adult consecutive cardiac arrest (CA) survivors were included between 2004 and 2022. For all patients, demographic data, medical comorbidities, CA baseline characteristics, treatments received during Intensive Care Unit stay, in-hospital major complications, and neurological outcome at three months after CA, using the Cerebral Performance Category (CPC) scale, were collected. In the multivariable analysis, in the IHCA group (n = 540), time to return of spontaneous circulation (ROSC), older age, unwitnessed CA, higher lactate on admission, asystole as initial rhythm, a non-cardiac cause of CA, the occurrence of shock, the occurrence of acute kidney injury (AKI), and the presence of previous neurological disease and of liver cirrhosis were independent predictors of an unfavorable neurological outcome. Among patients with OHCA (n = 567), time to ROSC, older age, higher lactate level on admission, unwitnessed CA, asystole or pulseless electrical activity (PEA) as initial rhythm, the occurrence of shock, a non-cardiac cause of CA, and a previous neurological disease were independent predictors of an unfavorable neurological outcome. To conclude, in our large cohort of mixed IHCA and OHCA patients, we observed numerous factors independently associated with a poor neurological outcome, with minimal differences between the two groups, reflecting the greater vulnerability of hospitalized patients.

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.

Delayed Deterioration of Electroencephalogram in Patients with Cardiac Arrest: A Cohort Study.

BACKGROUND: The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings. METHODS: This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24 h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24 h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality. RESULTS: We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU. CONCLUSIONS: Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure.

Cardiac Injury After Traumatic Brain Injury: Clinical Consequences and Management.

Traumatic brain injury (TBI) is a significant public health issue because of its increasing incidence and the substantial short-term and long-term burden it imposes. This burden includes high mortality rates, morbidity, and a significant impact on productivity and quality of life for survivors. During the management of TBI, extracranial complications commonly arise during the patient's stay in the intensive care unit. These complications can have an impact on both mortality and the neurological outcome of patients with TBI. Among these extracranial complications, cardiac injury is a relatively frequent occurrence, affecting approximately 25-35% of patients with TBI. The pathophysiology underlying cardiac injury in TBI involves the intricate interplay between the brain and the heart. Acute brain injury triggers a systemic inflammatory response and a surge of catecholamines, leading to the release of neurotransmitters and cytokines. These substances have detrimental effects on the brain and peripheral organs, creating a vicious cycle that exacerbates brain damage and cellular dysfunction. The most common manifestation of cardiac injury in TBI is corrected QT (QTc) prolongation and supraventricular arrhythmias, with a prevalence up to 5 to 10 times higher than in the general adult population. Other forms of cardiac injury, such as regional wall motion alteration, troponin elevation, myocardial stunning, or Takotsubo cardiomyopathy, have also been described. In this context, the use of ß-blockers has shown potential benefits by intervening in this maladaptive process. ß-blockers can limit the pathological effects on cardiac rhythm, blood circulation, and cerebral metabolism. They may also mitigate metabolic acidosis and potentially contribute to improved cerebral perfusion. However, further clinical studies are needed to elucidate the role of new therapeutic strategies in limiting cardiac dysfunction in patients with severe TBI.

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.

Monitoring of Brain Tissue Oxygen Tension in Cardiac Arrest: a Translational Systematic Review from Experimental to Clinical Evidence.

BACKGROUND: Cardiac arrest (CA) is a sudden event that is often characterized by hypoxic-ischemic brain injury (HIBI), leading to significant mortality and long-term disability. Brain tissue oxygenation (PbtO2) is an invasive tool for monitoring brain oxygen tension, but it is not routinely used in patients with CA because of the invasiveness and the absence of high-quality data on its effect on outcome. We conducted a systematic review of experimental and clinical evidence to understand the role of PbtO2 in monitoring brain oxygenation in HIBI after CA and the effect of targeted PbtO2 therapy on outcomes. METHODS: The search was conducted using four search engines (PubMed, Scopus, Embase, and Cochrane), using the Boolean operator to combine mesh terms such as PbtO2, CA, and HIBI. RESULTS: Among 1,077 records, 22 studies were included (16 experimental studies and six clinical studies). In experimental studies, PbtO2 was mainly adopted to assess the impact of gas exchanges, drugs, or systemic maneuvers on brain oxygenation. In human studies, PbtO2 was rarely used to monitor the brain oxygen tension in patients with CA and HIBI. PbtO2 values had no clear association with patients' outcomes, but in the experimental studies, brain tissue hypoxia was associated with increased inflammation and neuronal damage. CONCLUSIONS: Further studies are needed to validate the effect and the threshold of PbtO2 associated with outcome in patients with CA, as well as to understand the physiological mechanisms influencing PbtO2 induced by gas exchanges, drug administration, and changes in body positioning after CA.

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.

Cardiac power output is associated with cardiovascular related mortality in the ICU in post-cardiac arrest patients.

AIM: Although brain injury is the main determinant of poor outcome following cardiac arrest (CA), cardiovascular failure is the leading cause of death within the first days after CA. However, it remains unclear which hemodynamic parameter is most suitable for its early recognition. We investigated the association of cardiac power output (CPO) with early mortality in intensive care unit (ICU) after CA and with mortality related to post-CA cardiovascular failure. METHODS: Retrospective analysis of adult comatose survivors of CA admitted to the ICU of a University Hospital. Exclusion criteria were treatment with extracorporeal cardiopulmonary resuscitation, ECMO or intra-aortic balloon pump. We retrieved CA characteristics; we recorded mean arterial pressure, cardiac output, CPO (as derived parameter) and the vasoactive-inotropic score for the first 72 hours after ROSC, at intervals of 8 hours. ICU death was defined as related to post-CA cardiovascular failure when death occurred as a direct consequence of shock, secondary CA or fatal arrhythmia, or related to neurological injury if this led to withdrawal of life-sustaining therapy or brain death. RESULTS: Among the 217 patients (median age 66 years, 65% male, 61.8% out-of-hospital CA), 142 (65.4%) died in ICU: 99 (69.7%) patients died from neurological injury and 43 (30.3%) from cardiovascular-related causes. Comparing the evolution over time of CPO between survivors and non-survivors, a statistically significant difference was found only at +8 hours after CA (p = 0.0042). In multivariable analysis, CPO at 8-hour was significantly associated with cardiovascular-related mortality (p = 0.007). CONCLUSIONS: In post-CA patients, the 8-hour CPO is an independent factor associated with ICU cardiovascular-related mortality.

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.

Complications of Intracranial Multimodal Monitoring for Neurocritical Care: A Systematic Review and Meta-Analysis.

Intracranial multimodal monitoring (iMMM) is increasingly used for neurocritical care. However, concerns arise regarding iMMM invasiveness considering limited evidence in its clinical significance and safety profile. We conducted a synthesis of evidence regarding complications associated with iMMM to delineate its safety profile. We performed a systematic review and meta-analysis (PROSPERO Registration Number: CRD42021225951) according to the Preferred Reporting Items for Systematic Review and Meta-Analysis and Peer Review of Electronic Search Strategies guidelines to retrieve evidence from studies reporting iMMM use in humans that mention related complications. We assessed risk of bias using the Newcastle-Ottawa Scale and funnel plots. The primary outcomes were iMMM complications. The secondary outcomes were putative risk factors. Of the 366 screened articles, 60 met the initial criteria and were further assessed by full-text reading. We included 22 studies involving 1206 patients and 1434 iMMM placements. Most investigators used a bolt system (85.9%) and a three-lumen device (68.8%), mainly inserting iMMM into the most injured hemisphere (77.9%). A total of 54 postoperative intracranial hemorrhages (pooled rate of 4%; 95% confidence interval [CI] 0-10%; I2 86%, p < 0.01 [random-effects model]) was reported, along with 46 misplacements (pooled rate of 6%; 95% CI 1-12%; I2 78%, p < 0.01) and 16 central nervous system infections (pooled rate of 0.43%; 95% CI 0-2%; I2 64%, p < 0.01). We found 6 system breakings, 18 intracranial bone fragments, and 5 cases of pneumocephalus. Currently, iMMM systems present a similar safety profile as intracranial devices commonly used in neurocritical care. Long-term outcomes of prospective studies will complete the benefit-risk assessment of iMMM in neurocritical care. Consensus-based reporting guidelines on iMMM use are needed to bolster future collaborative efforts.

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.

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.

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.

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.

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.

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.