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.

Time course of outcome in poor grade subarachnoid hemorrhage patients: a longitudinal retrospective study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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]). CONCLUSIONS: 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.

Phosphatase alkaline levels are not associated with poor outcomes in subarachnoid hemorrhage patients.

INTRODUCTION: Alkaline phosphatase (ALP) levels are often elevated in cerebrovascular and cardiovascular disease. Their prognostic role after subarachnoid hemorrhage (SAH) remains to be elucidated. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

The use of automated pupillometry in critically ill cirrhotic patients with hepatic encephalopathy.

PURPOSE: To evaluate whether pupillary abnormalities would correlate with the severity of encephalopathy in critically ill cirrhotic patients. METHODS: In this retrospective study, we enrolled adult cirrhotic patients admitted to the Intensive Care Unit undergoing automated pupillometry assessment within the first 72 h since ICU admission. Encephalopathy was assessed with West-Haven classification and Glasgow Coma Scale. Pupillometry-derived variables were also correlated with biological variables, including ammonium, renal function or inflammatory parameters, measured on the day of pupillary assessment. RESULTS: A total of 62 critically ill cirrhotic patients (Age 61 [52-68] years; 69% male) were included. Median GCS and West-Haven classification were 14 [11-15] and 1 [0-3], respectively. There was a significant although weak correlation between GCS and constriction velocity (CV; R2 = 0.1; p = 0.017). We observed significant differences in CV and DV values among different levels of West-Haven classification. When only patients with encephalopathy (n = 42) or severe HE (n = 18) were considered, a weak correlation between GCS and worst CV was observed. When patients receiving sedatives or opioids were excluded, no significant correlation between pupillometry and clinical variables was observed. CONCLUSIONS: Pupillary function assessed by the automated pupillometry was poorly associated with encephalopathy scales in cirrhotic patients.

Brain tissue oxygenation guided therapy and outcome in non-traumatic subarachnoid hemorrhage.

Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO2) can be measured as a part of a neurological multimodal neuromonitoring. Low PbtO2 has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO2 guided-therapy on patients' outcome. This single-center cohort study (June 2014-March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO2-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO2 and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO2-guided therapy (OR 0.33 [CI 95% 0.12-0.89]) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO2-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.

Evaluation of Nociception Using Quantitative Pupillometry and Skin Conductance in Critically Ill Unconscious Patients: A Pilot Study.

BACKGROUND: Pain assessment is a challenge in critically ill patients, in particular those who are unable to express movements in reaction to noxious stimuli. The purpose of the study was to compare the pupillary response and skin conductance to pain stimulation in critically ill unconscious patients. METHODS: This observational study included adult patients admitted to the intensive care unit (ICU) with acute brain injury (Glasgow Coma Scale < 9 with a motor response < 5) and/or requirements for deep level of sedation. Automated pupillometry (Algiscan, ID-MED, Marseille, France) was used to determine pupillary reflex dilation during tetanic stimulation. The maximum intensity of the stimulation value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception): a pupillary pain index (PPI) score of ≤4 was used to reflect adequate pain control. For skin conductance (SC), the number of SC peaks per second (NSCF) was collected concomitantly to tetanic stimulation. An NSCF of ≤0.07 peak/second was used to reflect adequate pain control. RESULTS: Of the 51 included patients, there were 32 with brain injury and 19 receiving deep sedation. Mean PPI score was 5 (Interquartile Range= 2-7); a total of 28 (55%) patients showed inadequate control of the nociceptive stimulation according to the PPI assessment. Only 15 (29%) patients showed a detectable skin conductance, with NSCF values from 0.07 to 0.47/s. No correlation was found between skin conductance algesimeter (SCA)-derived variables and PPI score or pupillary dilation to pain. CONCLUSIONS: Detection of inadequate pain control might vary according to the method used to assess nociception in ICU patients. A poor agreement between quantitative pupillometry and skin conductance was observed.

The Future of Biomarkers.

Numerous compounds have been tested as potential biomarkers for multiple possible applications within intensive care medicine but none is or will ever be sufficiently specific or sensitive for the heterogeneous syndromes of critical illness. New technology and access to huge patient databases are providing new biomarker options and the focus is shifting to combinations of several or multiple biomarkers rather than the single markers that research has concentrated on in the past. Biomarkers will increasingly be used as part of routine clinical practice in the future, complementing clinical examination and physician expertise to provide accurate disease diagnosis, prediction of complications, personalized treatment guidance, and prognosis.

The Prognostic Role of Lactate Concentrations after Aneurysmal Subarachnoid Hemorrhage.

Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8-3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38-7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52-6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies.