Renal angina index in pediatric septic patients as a predictor of acute kidney injury in remote area


Background: One of the most common sepsis comorbidities is severe acute kidney injury (AKI), which occurs in about 20% of pediatric patients with severe sepsis and is independently associated with poor outcomes. Many studies have shown the ability of renal angina index (RAI) with a cut-off point of 8 to predict the risk of AKI grade 2 and 3, but with varying sensitivity and specificity. Therefore, this study aims to identify a RAI cut-off point to predict the incidence of AKI in pediatric septic patients in the setting of a regional hospital in Indonesia.

Methods: An observational analytic study with a prospective longitudinal design was conducted on 30 pediatric patients in the Resuscitation Room of Dr. Soetomo General Hospital Surabaya. Patients who met the inclusion criteria were given 1-hour standardized resuscitation, then were observed. Every action taken to the patient was recorded, fluid input and output were measured, and mechanical ventilation and vasopressor administration were documented until the third day to determine factors influencing the incidence of AKI.

Results: In this study, 56.7% of pediatric septic patients had AKI. The Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score in this study had a median of 11, in accordance with the pediatric sepsis guideline. RAI, with a cut-off point of 8 as a predictor for AKI grade 2-3, had a sensitivity of 100% and a specificity of 68% (area under the curve [AUC]=0.912). In terms of AKI risk tranche, the majority of patients (93.1%) had mechanical ventilation, while in terms of AKI injury tranche, the majority met the fluid overload criteria (79.3%).

Conclusion: RAI, with a cut-off point of 8, can be used as a predictor for severe AKI in pediatric septic patients.

Authors: Nugroho Setia Budi, Bambang Pujo Semedi, Arie Utariani, Ninik Asmaningsih

Balanced salt solution versus normal saline solution as initial fluid resuscitation in pediatric septic shock: A randomized, double-blind controlled trial


Objective: Initial fluid resuscitation is mandatory in treatment of septic shock. Current sepsis guidelines do not have the recommendation for either balanced salt or normal saline solution for initial fluid resuscitation. The objective of this study was to determine the impact of balanced salt solution (BS) versus normal saline solution (NS) in pediatric septic shock as initial fluid resuscitation.

Design: A double-blind randomized controlled trial study.

Setting: A single tertiary care center in Bangkok, Thailand.

Patients and participants: Children aged 1 month to 18 years who were diagnosed with septic shock. We excluded patients who received fluid resuscitation in the 24 hours prior to septic shock, end-stage disease, and refusal of informed consent.

Interventions: Patients were randomly assigned into 2 groups after being diagnosed with septic shock and required fluid resuscitation (NS or BS).

Measurements and results: Demographic data, vasoactive-inotropic scores, and outcomes were evaluated. The primary outcome was incidence of hyperchloremic metabolic acidosis. Sixty-one septic shock children were enrolled into this study (NS=31 patients, and BS=30 patients). Baseline characteristics between two groups were not different. The incidence of hyperchlor-emic metabolic acidosis was 17 (54.8%) and 10 (33.3%) in NS and BS groups, respectively (p=0.091). The hospital mortality and prevalence of acute kidney injury were not different between groups.

Conclusion: In pediatric septic shock, the initial fluid resuscitation with balanced salt solution and normal saline was associated with similar clinical outcomes. However, normal saline solution had a trend toward more frequent hyperchloremic metabolic acidosis in children with septic shock when compared to balanced salt solution.

Authors: Nattachai Anantasit, Sriwanna Thasanthiah, Rojjanee Lertbunrian

Predicting the circulation’s response to fluid resuscitation


Fluid resucitation plays a crucial role in pediatric resuscitation. Predicting fluid responsiveness is important as excessive fluid may decrease cardiac efficiency, and even induce overload. Various pathophysiology of shock suggest that fluid only benefit in optimizing preload. Various methods to assess fluid responsiveness includes measurement of static preload indices, dynamic indices to estimate volume status, and the use of protocols such as fluid challenge and passive leg raising technique. This paper highlights the mechanisms behind each measurements and summarized their use as predictor of fluid responsiveness in pediatric patients.

Authors: Antonius Hocky Pudjiadi

Association of fluid balance during first 48 hours and length of mechanical ventilation in pediatric intensive care unit


Background: Prolonged mechanical ventilation can increase mortality and morbidity rate. Study shows that positive fluid balance associated with prolonged mechanical ventilation, longer hospital length of stay, and higher mortality rate in acute lung injury. We conducted this study to show the association of fluid balance and duration of mechanical ventilation in the pediatric intensive care unit.

Methods: This was an analytic observational study in children one month to 18 years old who admitted to Pediatric Intensive Care Unit (PICU) Haji Adam Malik General Hospital Medan during April-November 2019. Fluid balance was recorded during first 48 hours in PICU. Bivariate analysis was done to analyse association of fluid balance and length of mechanical ventilation with logistic regression analysis for the mortality.

Results: One hundred and seventy-one children were included in this study. Positive fluid balance was found in 102 children (59.6%) with length of mechanical ventilation mostly under seven days (64.3%). Chi-square test showed significant association between fluid balance and duration of mechanical ventilation (p<0.001). Univariate logistic regression analysis showed that fluid balance had no significant association with mortality, but Pediatric Logistic Organ Dysfunction-2 (PELOD-2) and Pediatric Index of Mortality 2 (PIM2) had significant association with OR 2.6 (1.6-4.4) and 1.05 (1.02-1.08), respectively. Multivariate model also indicated that PELOD-2>8.5 and PIM2>30% showed significant association with mortality (OR 2.6 [1.6-4.4] and OR 1.05 [1.02-1.08], respectively).

Conclusion: Fluid balance was associated with length of mechanical ventilation, but no effect on mortality. Multivariate model showed independent association of PELOD-2>8.5 and PIM2>30% with mortality.

Authors: Andriamuri P. Lubis, Aridamuriany D. Lubis

Left ventricular end-diastolic volume index as a predictor of fluid responsiveness in children with shock

Objective: To identify role of left ventricular end-diastolic volume index as predictor of fluid responsiveness in children.
Design: This was a diagnostic study in children with shock in the Emergency Room and Pediatric Intensive Care Unit of Cipto Mangunkusumo Hospital from June to November 2018. The left ventricular end-diastolic volume index measurements were performed using ultrasonic cardiac output monitor and compared to the increase in stroke volume of ≥15% after fluid challenge as fluid responsiveness criteria. Sample categorized into fluid responsive and non-responsive.
Results: Of 40 subjects, 60 fluid challenge samples were obtained. There were 31 and 29 samples in the fluid responsive and non-responsive group, respectively. There was no significant mean difference in left ventricular end-diastolic volume index in the two groups (p=0.161). The area under the receiver operating characteristic (AUROC) of left ventricular end-diastolic volume index was 40.9% with cutoff value of 68.95 ml/m2. The sensitivity and specificity were 45.16% and 44.83%, respectively. At the left ventricular end-diastolic volume index value of 81.10 ml/m2, the specificity was 72.41% with 22.6% sensitivity.
Conclusion: This study cannot prove left ventricular end-diastolic volume index can act as a predictor of fluid responsiveness in children.

Authors: Ahmad Bayu Alfarizi, Antonius Hocky Pudjiadi, Rismala Dewi

Lung injury prediction score as a predictor of acute respiratory distress syndrome in intensive care unit


Background: Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxemia and bilateral infiltrates in the lung after a triggered injury. A major obstacle in ARDS prevention is the identification of patients at risk of ARDS. The goal of this study was to assess the validity of lung injury prediction score (LIPS) as a predictor of ARDS in the intensive care unit (ICU).

Patients and methods: This is a retrospective observational study conducted in the ICU of Sanglah General Hospital (Bali, Indonesia) in 2019 with 451 subjects were eligible after a systematic random sampling method. Receiver operating characteristics (ROC) analysis was used to assess the ability of LIPS to predict ARDS and determine the best cutoff point for LIPS in predicting ARDS.

Results: The area under ROC curve (AUC) value was 0.86 (95% CI 0.81-0.91). The best cutoff point was at LIPS ≥5 (sensitivity 85.71%, specificity 80.77%). From a cross tabulation calculation, we obtained a relative risk of 18.6 (95% CI 7.4-46.77). A logistic regression analysis obtained an odds ratio of 1.71 (95% CI 1.45-2.03).

Conclusion: LIPS is valid for predicting the incidence of ARDS in ICU patients. It can be used as a screening tool to identify those with a high risk of developing ARDS.

Authors: Tjokorda Gde Agung Senapathi, Made Wiryana, I Made Gede Widnyana, Christopher Ryalino, Budi Hartono

Can emergency medicine residents diagnose neurogenic stunned myocardium in the emergency department by Focused Assessment Diagnostic Echocardiography?


Purpose: To assess the ability of trained emergency medicine (EM) residents to diagnose neurogenic stunned myocardium (NSM) in patients with acute intracranial events in the emergency department (ED) using the Focused Assessment diagnostic Echocardiography (FADE).

Methods: This prospective cross-sectional study was conducted between February 2018 and January 2019. First, four postgraduate year-3 (PGY-3) EM residents were trained through participation in 10 hours of theoretical FADE education and 20 hands-on FADE on ED patients. Then, adult patients (aged over 18 years old) with acute cerebrovascular accidents (CVAs) were enrolled in the study. Patients with a history of prior cardiac disease, concurrent CVA and ST-elevation myocardial infarction (STEMI), and cardiopulmonary arrest in the ED were excluded. The results of echocardiography by the cardiologists were considered as the gold standard.

Results: Eighty-five cases were enrolled in the final analysis. The mean age of participants was 62.7 years, and 47 (55.3%) were male. There was a good agreement between the EM residents and cardiologists in diagnosing left ventricular (LV) dysfunction (Cohen’s Kappa=0.7, 95%CI=0.65-0.8). Troponin I was positive in 3 (3.5%) patients. Based on the diagnosis of cardiologists, all three patients had heart failure and received a definitive diagnosis of NSM. Whereas, according to the FADE exam by EM residents, 2 out of 3 cases with positive enzyme had heart failure (interrater agreement=66.6%).

Conclusion: Our study showed that trained EM residents could use the FADE exam to diagnose the NSM in CVA patients in the ED.

Authors: Ehsan Karimialavijeh, Aaliyeh Zarrabi, Hamideh Akbari, Mehrad Aghili, Elnaz Vahidi, Fatemeh Rasooli

Vasopressor dependency index: a quick prognostic parameter of septic shock patient in emergency and intensive care unit in remote area


Objective: The aim of the this study was to find out the outcome differences in septic shock patients based on the vasopressor dependency index (VDI) value at Dr. Soetomo General Hospital Surabaya.

Design: This was an analytical observational research.

Setting: Resuscitation Room of Dr. Soetomo General Hospital Surabaya from March to May 2019. This study was approved by the Research Ethics Committee of Dr. Soetomo General Hospital Surabaya.

Patients and participants: The inclusion criteria was septic shock patient who met sepsis-3 criteria. There were 44 samples in the inclusion criteria.

Interventions: Samples were taken by consecutive sampling. VDI was measured starting from 10 minutes, 1 hour, 6 hours, 12 hours, 24 hours, and 48 hours after the treatment of vasopressor drug.

Measurements and results: The most common causes of sepsis was pneumonia (47.7%). Septic shock patients were given norepinephrine (80.0%) as the first line vasopressor drug. There were patient outcome differences within 7 days of treatment based on the VDI value. The VDI value at the 24th hour and the 48th hour were the most influential variable to the patient outcome (p=0.034). The VDI value threshold of the 24th hour was 0.176/mmHg (81.8% sensitivity; 85.2% specificity; 95% CI 0.818-1.000; p=0.000) and of the 48th hour was 0.150/mmHg (88.9% sensitivity; 92.6% specificity; 95% CI 0.859-1.000; p=0.000).

Conclusion: There were significant differences in septic shock patient's outcome in the first 7 days of treatment based on VDI value. The VDI value at the 24th hour and the 48th hour were the most influential variables to the patient outcome (p=0.034). The threshold of VDI at the 24th hour was 0.176/mmHg. The threshold value of VDI at 48th hour was 0.150/mmHg.

Authors: Imamuddin Arif Wicaksono, Arie Utariani, Kuntaman

Venous-arterial CO2 difference to arterial-venous O2 content difference ratio as marker of resuscitation in pediatric septic shock


Objective: Sepsis is still a major cause of mortality in pediatric intensive care units. During initial resuscitation, central venous oxygen saturation (ScvO2) and/or lactate level have become a standard monitoring target nowadays. Carbon dioxide (CO2) partial pressure difference between central vein and artery (Pv-aCO2) has also been recommended as an additional marker to identify persistent global hypoperfusion. Recently, the Pv-aCO2/Ca-vO2 ratio, which represents respiratory quotient, is presumed to be superior in detecting anaerobic metabolism.

Design: Single center observational analytic research with cross-sectional study.

Setting: Resuscitation Room at academic hospital.

Patients and participants: Twenty-four pediatric patients with septic shock, aged 2 months to 12 years old.

Interventions: Patients were resuscitated at the Emergency Department of Dr. Soetomo General Academic Hospital, Surabaya. Initial first hour therapy included oxygenation, antibiotic administration, fluid bolus, and catecholamine titration. Central venous catheter was inserted in all patients through subclavian or jugular veins.

Measurements and results: Lactate was measured in the first and third hour after patient arrival. Arterial and central vein blood gas analysis was performed concurrently at the third hour. Patients were followed up after 48 hours to assess outcome. Pv-aCO2/Ca-vO2 ratio was more effective compared to ScvO2 and lactate clearance in predicting the 48-hour mortality rate (p 0.047). The cutoff value of the Pv-aCO2/Ca-vO2 ratio of 1.54 had the highest sensitivity and specificity to represent global hypoxia in pediatric patients with sepsis.

Conclusion: Pv-aCO2/Ca-vO2 ratio is a useful marker in predicting mortality in pediatric patients with septic shock.

Authors: Yos Kowara, Arie Utariani, Bambang Pujo Semedi, Purwo Sri Rejeki

Prediction of respiratory complications guided by Clara cell protein CC16 in plasma in polytrauma patients


Objective: To evaluate the value of serum levels of Clara cell protein (CC16) as a diagnostic and prognostic utility in patients with polytrauma and relate these levels to respiratory complications compared to plasma levels of healthy control group.

Subjects and methods: A prospective cohort study was carried out on one hundred and fifty patients with polytrauma (blast, blunt, and penetrating) who admitted to Intensive Care Units of Maadi and Kobry El Kobba Hospitals, Cairo, Egypt, from June 2016 and June 2019. Full history taking, clinical examination, radiology investigations, laboratory investigations, CC16 protein and other inflammatory biomarkers were investigated.

Results: There was no statistically significant difference between both groups as regarding age (p=0.09), comorbid conditions (p>0.05), Glasgow coma scale (p=0.09), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p=0.07) and abbreviated injury scale (p=0.08). Along 5 days there was a significantly higher C-reactive protein (CRP) level, neutrophil-lymphocyte ratio in Group I. PO2 level was significantly higher in the first 2 days in Group II than Group I. Chest computed tomography (CT) scan revealed the presence of lung contusion in 30 patients, hemothorax in 20 patients, and pneumothorax in 25 patients, all in Group I. Also, there was a statistically significant difference on day 0 between both groups with much higher serum CC16 in Group I than Group II, while on day 3 the difference was insignificant. Whereas, respiratory complications were significantly higher serum and broncho alveolar lavage (BAL) level of CC16 on day 3, while this difference was insignificant on day 0.

Conclusions: These findings showed that we may benefit from detecting serum CC16 levels in polytrauma victims in prediction of respiratory complications.

Authors: Kamel Abd El Aziz Mohammed Abd Allah, Moataz Mohamed Ibrahim Aly, Ibrahim Mohamed Atia, Samir El Hadedy Tawfik, Khaled Farid Mohamed Hassan

Early hydrocortisone, ascorbate and thiamine therapy for severe septic shock


Objective: Septic shock is a devastating physiological state with significant mortality risk. Recently, trials have suggested clinical benefits of adjunctive treatment with iHAT. These agents may reduce oxidative stress, inflammation, mitochondrial dysfunction and endothelial injury in patients with septic shock. The primary objective of this study was to evaluate intensive care unit (ICU) and hospital mortality for patients with septic shock treated with and without intravenous hydrocortisone, ascorbic acid and thiamine (iHAT).

Design: A retrospective cohort study was performed evaluating patients admitted with septic shock requiring vasopressors to the ICU treated with and without iHAT.

Setting: The intensive care unit of a tertiary care academic center in Madison, WI

Patients: Of 3,463 patients admitted to the ICU, 206 met inclusion criteria with 127 treated according to standard care (SC) and 79 receiving additional adjunctive iHAT.

Intervention: Hydrocortisone 50 mg IV q6h, Ascorbic Acid 1500 mg IV q6h and Thiamine 200 mg IV q12h.

Measurements and results: Acute Physiology And Chronic Health Evaluation (APACHE) scores were higher in the SC cohort. Observed ICU mortality was lower in the iHAT cohort compared to SC as was APACHE-adjusted ICU mortality (OR 0.44, p=0.043). APACHE-adjusted ICU mortality was lowest when iHAT was initiated within 6 hours (OR 0.08, p<0.01). Hospital mortality, vasopressor duration, initiation of renal replacement therapy and lengths of stay were not significantly different between cohorts.

Conclusion: There was a time-sensitive improvement in APACHE-adjusted ICU mortality in septic shock patients treated with adjunctive iHAT. The strong temporal benefit of iHAT therapy has important implications towards future studies.

Authors: Micah T. Long, Mark A. Frommelt, Michael P. Ries, Melissa Murray, Fauzia Osman, Bryan M. Krause, Pierre Kory

Correlation between middle cerebral artery pulsatility index and optic nerve sheath diameter with intracranial pressure in traumatic and non-traumatic brain injury patients of Dr. Soetomo General Hospital Surabaya


Background: Patients with brain injury experience pathology of increased intracranial pressure (ICP), which is the cause of secondary brain injury, brain herniation at the risk of brain damage. Intracranial pressure control and monitoring is one of the most important strategies in managing patients in the neurosurgery and neurointensive care fields. Intracranial pressure monitoring in Dr. Soetomo General Hospital Surabaya is still limited by intraventricular catheter installation, which is invasive. The middle cerebral artery pulsatility index (PI) and sonographic optic nerve sheath diameter enable non-invasive monitoring of intracranial pressure. This study aimed to find out the correlation between middle cerebral artery pulsatility index and optic nerve sheath diameter with intracranial pressure.

Methods: Transcranial doppler measurement was made transtemporally to measure middle cerebral artery pulsatility index. Optic nerve sheath diameter was measured 3 mm behind the globe using 12 MHz US probe. Intracranial pressure was measured using intraventricular catheter. The correlation and regression between intracranial pressure, pulsatility index, and optic nerve sheath diameter were investigated.

Results: Thirty patients with various intracranial pathology, who underwent intraventricular catheter placement, were included in the study. A total of 86 intracranial pressure examinations, middle cerebral artery pulsatility index, and optic nerve sheath diameter were conducted. A significant correlation was found between pulsatility index and intracranial pressure with a correlation coefficient of 0.639; intracranial pressure = 9.23 x PI + 4 mmHg. Pulsatility index sensitivity was 93.2% with specificity 75.0%. Cut-off point was >1.11 for pulsatility index to detect increased intracranial pressure. The optic nerve sheath diameter and intracranial pressure correlation coefficient is 0.746; intracranial pressure = 7.88 x optic nerve sheath diameter - 26.84 mmHg with sensitivity 92.3% and specificity 95.83%. Optic nerve sheath diameter cut-off value was 5.4 mm.

Conclusion: There was a correlation between middle cerebral artery pulsatility index and optic nerve sheath diameter with intracranial pressure. Pulsatility index and optic nerve sheath diameter can be used as alternative for ICP monitoring.

Authors: Hamzah, Arie Utariani, Bambang Pudjo Semedi, Yoppie Prim Avidar, Nanang Nurofik

Role of S100B, sTNFR-1, lactate, ScvO2, and SctO2 measured by NIRS as predictor of neurological deficit in pediatric congenital heart surgery


Background: Process related to systemic inflammatory response syndrome (SIRS) in congenital heart disease (CHD) surgery using cardiopulmonary bypass (CPB) machine often causes post-operative complications. This process begins with mitochondrial dysfunction in SIRS, initiated by the release of inflammatory mediators such as tumor necrosis factor receptor-α (TNF-α) and soluble tumor necrosis factor receptor-1 (sTNFR-1). Neurological injury following pediatric congenital heart surgery remains common. Studies related to brain-derived protein (S100B) biomarker for cerebral hypoxia caused by microcirculation and mitochondrial dysfunction as a consequence of SIRS in CPB or pediatric CHD surgery have yet to be conducted. Observation to identify cerebral hypoxia is necessary due to the fact that early stages of cerebral hypoxia are often asymptomatic. Near-infrared spectroscopy (NIRS) is a tool used for observing oxygen delivery to the brain by measuring cerebral oxygen saturation (SctO2). In Indonesia, NIRS remains uncommon and no study has been conducted to date.

Objectives: To evaluate the role of S100B, sTNFR-1, lactate, and superior vena cava and cerebral saturations as predictors of neurological injury in CHD patients undergoing corrective surgeries, as measured using NIRS during and after surgical procedure.

Methods: This was a prospective cohort study. Inclusion criteria were pediatric patients with CHD aged 1 month to 6 years old undergoing corrective surgery. Exclusion criteria were patients with Down syndrome, single coronary artery, and not consented to participate in the study. For analysis, subjects were divided into 2 groups: (1) those with neurological deficits and (2) those without neurological deficits. All subjects were observed closely in intensive care unit (ICU) until they were discharged. Blood examinations were performed 3 times: before surgery, after CPB, and 4 hours after CPB.

Results: Fifty-one patients were observed from March to October 2015. Significant differences were observed in the value of S100B, STNFR-1, lactate, and area under the curve (20% AUC) baseline for cerebral saturation between both groups, as measured using NIRS. Those parameters could be used as predictors of post-CPB neurological deficit incidence in children with CHD.

Summary: In CHD patients undergoing corrective surgery, S100B value, sTNFR-1, lactate, and 20% AUC baseline for cerebral saturation could be used as predictors of neurological deficit following corrective surgery.

Authors: M. Tatang Puspanjono, Sri Rezeki SH Hadinegoro, Bambang Sutrisna, Suhendro, Tjipta Bahtera, Amir S. Madjid, Siti Boedina Kresno, Dwi Putro Widodo, Rubiana Sukardi

Blood lactate levels during cardiopulmonary bypass as indicator of outcome in pediatric cardiac surgery


Objectives: In pediatric cardiac surgery, high blood lactate levels during cardiopulmonary bypass (CPB) are associated with tissue hypoperfusion and contribute to postoperative complications. Studies indicate that blood lactate level is proportional to tissue oxygen debt. The objective of this study was to evaluate the change in blood lactate levels and perioperative morbidity and mortality.

Methods: We conducted a retrospective analysis of 81 pediatric patients who have undergone cardiac surgery with continuous monitoring of serial measurement of blood lactate in Integrated Cardiac Service Unit, Dr. Cipto Mangunkusumo Hospital, Jakarta. Arterial blood samples were taken before, during CPB, and on admission to the Intensive Care Unit (ICU) and every 6 hours afterward. Duration of CPB, hemodynamic parameters, inotrope dosage and perioperative outcome were documented.

Results: The largest increment in lactate level occurred during CPB and decreased on admission to the ICU. Patients who had complications exhibited higher lactate levels at all time points. Lactate levels were higher in the group with complications at the end of surgery (4.4 vs 2.7 mmol/l; p=0.000), immediately after ICU admission (2.9 vs 1.9 mmol/l; p=0.000), 6 hours (1.9 vs 1.4 mmol/l; p<0.003), and 12 hours after admission (4.6 vs 2.8 mmol/l; p=0.000). Increased lactate concentration was reliably associated with patient length of ICU stay, liver function parameter and anion gap. Logistic regression analysis revealed that peak blood lactate levels of 3.5 mmol/l or higher during CPB were strongly associated with postoperative mortality and morbidity.

Conclusions: Hyperlactatemia occurs during CPB may become an early indicator/predictive index for postoperative morbidity and mortality in pediatric patients. This study generates the hypothesis that strategies aimed to preserve oxygen delivery during CPB may reduce the occurrence of elevated lactate levels.

Authors: M. Tatang Puspanjono, Antonius H. Pudjiadi, Jusuf Rachmat, S. Harry Purwanto

Serum glial fibrillary acidic protein is a more specific biomarker than phosphorylated neurofilament heavy subunit, heart-fatty acidic protein, neuron specific enolase, and S100B protein for CT-positive mild-to-moderate traumatic brain injury


Background: Several biomarkers show diagnostic value for traumatic brain injury (TBI), especially in patients with severe TBI. In the present study, we examined whether glial fibrillary acidic protein (GFAP), phosphorylated neurofilament heavy subunit (pNF-H), heart-type fatty acid binding protein (H-FABP), neuron-specific enolase (NSE), and S100B protein (S100B) measured on admission to an emergency department showed diagnostic value in patients with mild-to-moderate TBI.

Methods: A prospective study performed in our emergency department. After collecting informed consent, blood samples were obtained to measure GFAP, pNF-H, H-FABP, NSE, and S100B concentrations. All of the patients underwent head computed tomography (CT). The CT findings were considered positive if hemorrhagic brain injury was present. Receiver-operating characteristic (ROC) curve analysis was performed for each biomarker with positive head CT findings as the outcome variable.

Results: Fifty-seven patients were included (39% male). Their median age was 70 years and the median Glasgow coma scale score was 15. Twelve patients (21%) had positive head CT findings (CT-positive group). The area under the ROC curves for GFAP, pNF-H, H-FABP, NSE, and S100B were 0.845, 0.569, 0.518, 0.744, and 0.753, respectively, and were statistically significant for GFAP, NSE, and S100B (p<0.001, p=0.013, and p=0.010, respectively). The area under the ROC curve was greater for GFAP than those for the other biomarkers.

Conclusions: Our results suggest that serum GFAP measured shortly after emergency department admission shows greater diagnostic potential for head CT-positive TBI as compared with pNF-H, H-FABP, NSE, and S100B.

Authors: Tadashi Kaneko, Tadashi Era, Kohei Karino, Shu Yamada, Maki Kitada, Toshihiro Sakurai, Masahiro Harada, Fumihiko Kimura, Takeshi Takahashi, Shunji Kasaoka