Neuroprotective effects of lactate and ketone bodies in acute brain injury.

The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage. They are now viewed as integral parts of brain metabolism. In addition to their energetic role, experimental evidence also supports their neuroprotective properties after acute brain injury, regulating in particular intracranial pressure control, decreasing ischemic volume, and leading to an improvement in cognitive functions as well as survival. In this review, we present preclinical and clinical evidence exploring the mechanisms underlying their neuroprotective effects and identify research priorities for promoting lactate and ketone bodies use in brain injury.

Cerebral Lactate Uptake After Half-Molar Sodium Lactate Therapy in Traumatic Brain Injury: A Brief Report.

Exogenous sodium lactate has many advantages after traumatic brain injury, including intracranial pressure control and alternative energetic supply. It remains unclear, however, whether half-molar sodium lactate (HSL) is effectively incorporated in brain metabolism, which we can verify using the arteriovenous difference in lactate (AVDlac). Hence we compared the AVDlac in patients with severe traumatic brain injury receiving an equiosmolar bolus of sodium lactate or mannitol for intracranial hypertension (IH) treatment. We included 23 patients: 14 received HSL for 25 IH episodes, and nine received mannitol for 19 episodes (total of 44 IH episodes). We observed that the median variation in AVDlac was positive in the group that received HSL (Δ +0.1 [IQR -0.08-0.2] mmol/L), which suggests a net lactate uptake by the brain. On the other hand, it was negative in the group that received mannitol (Δ -0.0 [IQR -0.1 to 0.0] mmol/L), indicating a net lactate export. Finally, there were more positive AVDlac values in the group that received HSL and more negative AVDlac values in the group that received mannitol (Fisher exact p = 0.04). Our study reports the first evidence of a positive AVDlac, which corresponds to a net lactate uptake by the brain, in patients who received HSL for severe TBI. Our results constitute a bedside confirmation of the integration of lactate into the brain metabolism and pave the way for a wider dissemination of sodium lactate in the daily clinical care of patients with traumatic brain injury.

Variations in Autoregulation-Based Optimal Cerebral Perfusion Pressure Determination Using Two Integrated Neuromonitoring Platforms in a Trauma Patient.

BACKGROUND: Neuromonitoring devices are often used in traumatic brain injury. The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO). METHODS: We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute. RESULTS: Using the Bland and Altman method, we found a mean variation of - 3.8 (95% confidence internal from - 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from - 26.6 to 19.1 mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10 mm Hg. CONCLUSIONS: These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients.

The primary objective of this study was to compare the plasma levels of copper, selenium, and zinc between critically ill COVID-19 patients and less severe COVID-19 patients. The secondary objective was to investigate the association of these trace element levels with adverse outcomes, including the duration of mechanical ventilation, occurrence of septic shock, and mortality in critically ill COVID-19 patients. All COVID-19 patients admitted to the ICU of the Geneva University Hospitals between 9 March 2020 and 19 May 2020 were included in the study. Plasma levels of copper, selenium and zinc were measured on admission to the ICU and compared with levels measured in COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. To analyze the association of trace elements with clinical outcomes, multivariate linear and logistic regressions were performed. Patients in the ICU had significantly lower levels of selenium and zinc and higher levels of copper compared to COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. In ICU patients, lower zinc levels tended to be associated with more septic shock and increased mortality compared to those with higher zinc levels (p = 0.07 for both). Having lower copper or selenium levels was associated with a longer time under mechanical ventilation (p = 0.01 and 0.04, respectively). These associations remained significant in multivariate analyses (p = 0.03 for copper and p = 0.04 for selenium). These data support the need for interventional studies to assess the potential benefit of zinc, copper and selenium supplementation in severe COVID-19 patients.

Diclofenac Sodium for Fever Control in Neurocritical Care: A Systematic Review.

BACKGROUND: Fever is extremely common in neurocritical care patients and is independently associated with a worse outcome. Non-steroidal anti-inflammatory drugs (NSAIDs) lower the hypothalamic set point temperature through the inhibition of prostaglandin E2 synthesis, and they constitute a second line of pharmacological treatment for temperature control. This systematic review aims to evaluate the effectiveness of DCF in reducing body temperature and its effects on brain parameters. METHODS: A comprehensive search of several databases was run in November 2022 in Ovid EBM (Evidence Based Medicine) Reviews, Cochrane library, Ovid Medline and Scopus (1980 onward). The outcome of interest included DCF control of body temperature and its impact on cerebral parameters. RESULTS: A total of 113 titles were identified as potentially relevant. Six articles met eligible criteria and were reviewed. DCF induce a reduction in body temperature (MD, 1.10 [0.72, 1.49], p < 0.00001), a slight decrease in ICP (MD, 2.22 [-0.25, 4.68] IC 95%; p < 0.08) as well as in CPP and MAP (MD, 5.58 [0.43, 10.74] IC 95%; p < 0.03). The significant heterogeneity and possibility of publication bias reduces the strength of the available evidence. CONCLUSIONS: Diclofenac sodium is effective in reducing body temperature in patients with brain injury, but data in the literature are scarce and further studies are needed to evaluate the benefits of DCF.

Early timing of anesthesia in status epilepticus is associated with complete recovery: A 7-year retrospective two-center study.

OBJECTIVE: This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE). METHODS: Patients with anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended third-line treatment, earlier (as first- or second-line treatment), and delayed (later as third-line treatment). Associations between timing of anesthesia and in-hospital outcomes were estimated by logistic regression. RESULTS: Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio [OR] = .71, 95% confidence interval [CI] = .53-.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score (STESS; STESS = 1-2: OR = .45, 95% CI = .27-.74; STESS > 2: OR = .53, 95% CI = .34-.85), especially in patients without potentially fatal etiology (OR = .5, 95% CI = .35-.73) and in patients experiencing motor symptoms (OR = .67, 95% CI = .48-.93). SIGNIFICANCE: In this SE cohort, anesthetics were administered as recommended third-line therapy in only every fifth patient and earlier in every second. Increasing delay of anesthesia was associated with decreased odds for return to premorbid function, especially in patients with motor symptoms and no potentially fatal etiology.

Anaesthetic and peri-operative management for thrombectomy procedures in stroke patients.

PURPOSE: To provide recommendations for the anaesthetic and peri-operative management for thrombectomy procedure in stroke patients DESIGN: A consensus committee of 15 experts issued from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation, SFAR), the Association of French-language Neuro-Anaesthetists (Association des Neuro-Anesthésistes Réanimateurs de Langue Francaise, ANARLF), the French Neuro-Vascular Society (Société Francaise de Neuro-Vasculaire, SFNV), the French Neuro-Radiology Society (Société Francaise de Neuro-Radiologie, SFNR) and the French Study Group on Haemostasis and Thrombosis (Groupe Français d'Études sur l'Hémostase et la Thrombose, GFHT) was convened, under the supervision of two expert coordinators from the SFAR and the ANARLF. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were required to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. METHODS: Four fields were defined prior to the literature search: (1) Peri-procedural management, (2) Prevention and management of secondary brain injuries, (3) Management of antiplatelet and anticoagulant treatments, (4) Post-procedural management and orientation of the patient. Questions were formulated using the PICO format (Population, Intervention, Comparison, and Outcomes) and updated as needed. Analysis of the literature was then conducted and the recommendations were formulated according to the GRADE methodology. RESULTS: The SFAR/ANARLF/SFNV/SFNR/GFHT guideline panel drew up 18 recommendations regarding anaesthetic management of mechanical thrombectomy procedures. Due to a lack of data in the literature allowing to conclude with high certainty on relevant clinical outcomes, the experts decided to formulate these guidelines as "Professional Practice Recommendations" (PPR) rather than "Formalized Expert Recommendations". After two rounds of rating and several amendments, a strong agreement was reached on 100% of the recommendations. No recommendation could be formulated for two questions. CONCLUSIONS: Strong agreement among experts was reached to provide a sizable number of recommendations aimed at optimising anaesthetic management for thrombectomy in patients suffering from stroke.

Nonconvulsive status epilepticus following cardiac arrest: overlooked, untreated and misjudged.

AIMS: Seizures and status epilepticus (SE) are detected in almost a third of the comatose cardiac arrest survivors. As the literature is quite exhaustive regarding SE with motor symptoms in those patients, little is known about nonconvulsive SE (NCSE). Our aim was to compile the evidence from the literature of the frequency and outcome of NCSE in adult patients remaining in coma after resuscitation. METHODS: The medical search PubMed was screened for most relevant articles reporting the emergence and outcome of NCSE in comatose post-resuscitated adult patients. RESULTS: We identified 11 cohort studies (four prospective observational, seven retrospective) including 1092 patients with SE in 29-96% and NCSE reported in 1-20%. EEG evaluation started at a median of 9.5 h (range 7.5-14.8) after cardiac arrest, during sedation and targeted temperature management (TTM). Favorable outcome after NCSE occurred in 24.5%. We found no study reporting EEG to detect or exclude NCSE in patients remaining in coma prior to the initiation of TTM and without sedation withing the first hours after ROSC. DISCUSSION: Studies on NCSE after ROSC are scarce and unsystematic, reporting favorable outcome in every fourth patient experiencing NCSE after ROSC. This suggests that NCSE is often overlooked and outcome after NCSE is not always poor. The low data quality does not allow firm conclusions regarding the effects of NCSE on outcome calling for further investigation. In the meantime, clinicians should avoid equating NCSE after ROSC with poor prognosis.

Guidelines for the choice of intravenous fluids for vascular filling in critically ill patients, 2021.

PURPOSE: To provide recommendations for the appropriate choice of fluid therapy for resuscitation of critically ill patients. DESIGN: A consensus committee of 24 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Society of Emergency Medicine (Société française de médecine d'urgence, SFMU) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were left ungraded. METHODS: Four fields were defined: patients with sepsis or septic shock, patients with haemorrhagic shock, patients with acute brain failure, and patients during the peripartum period. For each field, the panel focused on two questions: (1) Does the use of colloids, as compared to crystalloids, reduce morbidity and mortality, and (2) Does the use of some specific crystalloids effectively reduce morbidity and mortality. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE methodology. RESULTS: The SFAR/SFMU guideline panel provided nine statements on the appropriate choice of fluid therapy for resuscitation of critically ill patients. After two rounds of rating and various amendments, strong agreement was reached for 100% of the recommendations. Out of these recommendations, two have a high level of evidence (Grade 1 +/-), six have a moderate level of evidence (Grade 2 +/-), and one is based on expert opinion. Finally, no recommendation was formulated for two questions. CONCLUSIONS: Substantial agreement among experts has been obtained to provide a sizable number of recommendations aimed at optimising the choice of fluid therapy for resuscitation of critically ill patients.

Delayed intubation is associated with mortality in patients with severe COVID-19: A single-centre observational study in Switzerland.

INTRODUCTION: Switzerland experienced two waves of COVID-19 in 2020, but with a different ICU admission and treatment management strategy. The timing of ICU admission and intubation remains a matter of debate in severe patients. The aim of our study was to describe the characteristics of ICU patients between two subsequent waves of COVID-19 who underwent a different management strategy and to assess whether the timing of intubation was associated with differences in mortality. PATIENTS AND METHODS: We conducted a prospective observational study of all adult patients with acute respiratory failure due to COVID-19 who required intubation between the 9th of March 2020 and the 9th of January 2021 in the intensive care unit (ICU) at Geneva University Hospitals, Switzerland. RESULTS: Two hundred twenty-three patients were intubated during the study period; 124 during the first wave, and 99 during the second wave. Patients admitted to the ICU during the second wave had a higher SAPS II severity score (52.5 vs. 60; p = 0.01). The time from hospital admission to intubation was significantly longer during the second compared to the first wave (4 days [IQR, 1-7] vs. 2 days [IQR, 0-4]; p < 0.01). All-cause ICU mortality was significantly higher during the second wave (42% vs. 23%; p < 0.01). In a multivariate analysis, the delay between hospital admission and intubation was significantly associated with ICU mortality (OR 3.25 [95% CI, 1.38-7.67]; p < 0.05). CONCLUSIONS: In this observational study, delayed intubation was associated with increased mortality in patients with severe COVID-19. Further randomised controlled trials are needed.

Hypophosphatemia on ICU Admission Is Associated with an Increased Length of Stay in the ICU and Time under Mechanical Ventilation.

Hypophosphatemia is frequently observed in the ICU and is associated with several impairments such as respiratory failure or infections. We hypothesized that hypophosphatemia on ICU admission is associated with a prolonged duration of mechanical ventilation and ICU length of stay (LOS), particularly in COVID-19 patients. This cross-sectional study analyzed data from 1226 patients hospitalized in the ICU of the Geneva University Hospitals from August 2020 to April 2021. Patients were categorized as having hypophosphatemia (phosphatemia ≤ 0.8 mmol/L) or non-hypophosphatemia (phosphatemia > 0.8 mmol/L) on ICU admission. Linear regressions were performed to investigate the association between hypophosphatemia on ICU admission and ICU LOS and duration of mechanical ventilation. Overall, 250 (20%) patients presented hypophosphatemia on ICU admission. In the univariable analysis, hypophosphatemic patients had longer ICU LOS than non-hypophosphatemic patients, 7.4 days (±10.4) versus 5.6 days (±8.3), (p < 0.01). Hypophosphatemia on ICU admission was associated with a prolonged duration of mechanical ventilation, 7.4 days (±11.2) versus 5.6 days (±8.9), (p < 0.01). These associations were confirmed in the multivariable analysis (p < 0.01). In the subgroup of COVID-19 patients, a significant association between hypophosphatemia and ICU LOS and duration of mechanical ventilation was also observed. In conclusion, hypophosphatemia on ICU admission is associated with a longer ICU LOS and time under mechanical ventilation, both in the general ICU population and in COVID-19 patients.

Early Measurement of ROX Index in Intermediary Care Unit Is Associated with Mortality in Intubated COVID-19 Patients: A Retrospective Study.

COVID-19 patients often present with rapidly progressing acute hypoxemic respiratory failure, requiring orotracheal intubation with different prognostic issues. However, ICU specialists lack predictive tools to stratify these patients. We conducted a single-center cross-sectional retrospective study to evaluate if the ROX index, measured under non-invasive oxygenation support, can predict ICU mortality in a COVID-19 intubated patient cohort. This study took place in the division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). We included all consecutive adult patients treated by non-invasive oxygenation support and requiring intubation for acute respiratory failure due to COVID-19 between 9 September 2020 and 30 March 2021, corresponding to the second local surge of COVID-19 cases. Baseline demographic data, comorbidities, median ROX between H0 and H8, and clinical outcomes were collected. Overall, 82 patients were intubated after failing a non-invasive oxygenation procedure. Women represented 25.6% of the whole cohort. Median age and median BMI were 70 (60-75) years and 28 (25-33), respectively. Before intubation, the median ROX between H0 and H8 was 6.3 (5.0-8.2). In a multivariate analysis, the median ROX H0-H8 was associated with ICU mortality as a protective factor with an odds ratio (95% CI) = 0.77 (0.60-0.99); p < 0.05. In intubated COVID-19 patients treated initially by non-invasive oxygenation support for acute respiratory failure, the median ROX H0-H8 could be an interesting predictive factor associated with ICU mortality.