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).
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.
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.
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.
Alkaline phosphatase (ALP) levels are often elevated in cerebrovascular and cardiovascular disease. Their prognostic role after subarachnoid hemorrhage (SAH) remains to be elucidated.
We performed a ...retrospective single center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of Erasme Hospital (Brussels, Belgium) from 2006 to 2019. Exclusion criteria were previous history of liver cirrhosis or malignancies and early death (i.e. within 24 h from ICU admission). Baseline information, clinical data, radiologic data were collected, the occurrence of DCI as well as serum ALP levels during the first 12 days of ICU stay. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1–3.
Six hundred and fifty patients were included; ALP levels increased from baseline after day 6 from admission, in particular among patients with an initial poor clinical status. There was no difference in the ALP levels between patients with or without DCI over time. Patients with UO had higher ALP levels over time than others; however, in the multivariable analysis, nor ALP levels on admission or the highest ALP value during the ICU stay were independently associated with UO.
The results of this study suggested that ALP levels had no prognostic role in SAH patients. Other possible prognostic biomarkers should be evaluated in this setting.
•We have evaluated the role of the alkaline phosphatase in the course of one type of cerebrovascular disease.•Alkaline phosphatase is not associated with poor outcomes in this analysis.•Alkaline phosphatase is increased during the first twelve days in the intensive care unit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients' characteristics, the presence ...of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors.
We performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004-2007; 2008-2011; 2012-2015 and 2016-2018).
A total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008-2011 and 2016-2018 periods (HR 0.55 0.34-0.89 and HR 0.33 0.20-0.53, respectively, when compared to 2004-2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 1.43-3.14) and UO (OR 3.23 1.67-6.25). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 0.43-0.84).
Both hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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 (PbtO
2
) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO
2
-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 PbtO
2
/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 PbtO
2
-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO
2
/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 (
I
2
) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO
2
-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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair ...brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract 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.
Serum lactate dehydrogenase (LDH) levels are often elevated in cardiovascular diseases. Their prognostic role after subarachnoid hemorrhage (SAH) remains poorly evaluated.
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.
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).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain ...unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model.
This is a multicentric retrospective cohort study (2012-2020).
This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria.
All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT.
Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT.
We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL 7.3-8.7 g/dL and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL 0.8-1.8 g/dL (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT.
Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT.
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.
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.
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.
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.
Demographic data (such as age, sex, and presence of comorbidities), as well as clinical scores on admission (such as Charlson Comorbidity Index score, Sequential Organ Failure Assessment score on day ...1, and the Simplified Acute Physiology Score III), were collected. Continuous variables were described either as median and interquartile range or mean and standard deviation. Because of the small number of patients and the asymmetrical distribution of variables, we used the Friedman nonparametric test for comparison between repeated measurements before, during, and after the hyperoxia challenge. Characteristics of the study population N = 29 Age, mean (± SD) 44 (± 14) Male sex, n (%) 20 (69) Comorbidities, n (%) Heart disease 2 (7) Arterial hypertension 13 (45) Diabetes 3 (10) Lung disease 2 (7) Liver cirrhosis 4 (14) Immunosuppression 2 (7) Cancer 2 (7) Previous neurological disease 1 (3) Corticosteroids 1 (3) Alcohol 15 (52) Charlson comorbidity index, median (IQR) 0 (0–2) SAPS, median (IQR) 58 (53–70) GCS score on admission, median (IQR) 8 (5–13) SOFA score day 1, median (IQR) 7 (4–10) Seizure on admission, n (%) 8 (28) Diagnosis and severity on admission Subarachnoid hemorrhage, n (%) 11 (38) WFNS score of 4 or 5, n (%) 7/11 (64) Traumatic brain injury, n (%) 13 (45) Marshall score, median (IQR) 3 (2–4) Intracerebral hemorrhage, n (%) 5 (17) NIHSS score, median (IQR) 22 (18–22) During the ICU stay, n (%) Infection 19 (66) Hyponatremia 7 (24) SIADH 3 (10) Vasopressor agents 26 (90) Inotropic agents 8 (28) Intracranial hypertension 23 (79) Outcomes GOS score at discharge, median (IQR) 3 (2–3) ICU length of stay, mean (± SD) 24 (± 9) Hospital length of stay, median (IQR) 37 (26–50) ICU mortality, n (%) 7 (24) Hospital mortality, n (%) 7 (24) GCS Glasgow coma scale, GOS Glasgow outcome scale, ICU Intensive care unit, IQR Interquartile range, NIHSS National institutes of health stroke scale, SAPS Simplified acute physiological score, SD Standard deviation, SIAHD Syndrome of inappropriate secretion of antidiuretic hormone, SOFA Sequential organ dysfunction assessment, WFNS World federation of neurological surgeons Table 2. Physiological variables assessed at different time points (T0 = baseline, T1 = after 30 min of hyperoxia, T2 = after 30 min of returning FiO2 at baseline values) T0 T1 T2 p value Systolic blood pressure (mm Hg) 154 (139–181) 158 (145–176) 152 (133–168) 0.66 Diastolic blood pressure (mm Hg) 81 (70–87) 79 (72–91) 79 (67–83) 0.11 Median blood pressure (mm Hg) 107 (97–124) 105 (97–114) 101 (92–112) 0.18 Heart rate (bpm) 85 (68–107) 81 (67–106) 76 (68–102) 0.71 Cerebral perfusion pressure (mm Hg) 97 (82–107) 90 (82–103) 85 (79–101) 0.20 Intracranial pressure (mm Hg) 12
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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