Interlaboratory variation for NT-proBNP among Swedish laboratories in an external quality program 2011-2021.

OBJECTIVES: NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients. METHODS: Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP. RESULTS: Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median. CONCLUSIONS: The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.

Accuracy of determination of free light chains (Kappa and Lambda) in plasma and serum by Swedish laboratories as monitored by external quality assessment.

BACKGROUND: Free light chain (FLC) measurements are important in diagnosing monoclonal gammopathies. As FLC are heterogeneous, different reagents and instruments for measuring FLC concentrations may give diverging results that affect assessment of patients with monoclonal gammopathies. Here we investigated agreement between different FLC methods using data from the Swedish external quality assurance (EQA) programme. METHODS: The two main FLC assays, N Latex FLC (Siemens) and Serum Freelite (The Binding Site), using four nephelometric or turbidimetric instrument platforms, were compared. Results from 27 EQA rounds distributed to 11-16 Swedish hospital laboratories during 2015-2020 were investigated. RESULTS: The kappa (κ) FLC measurements deviated significantly over time, but when only nephelometry was used, deviation from the mean was lower (median ranges: -5% to 13 %). The CV was significantly higher for the Freelite assay (mean CV = 8.7) than for the N latex assay (mean CV = 5.7) (p < 0.0001). The coefficient of determination between all combinations of reagents and instrument platforms used was generally good (r2 = 0.76-0.87), and the correlation slope acceptable (0.81-1.2). For lambda (λ) FLC measurements, no concordance between combinations of instruments and reagents is apparent, deviating between -40 % to + 48 % from the mean. The CV was significantly higher for the combination with nephelometry and the Freelite assay (CV mean = 13.9 %) than nephelometry and the N latex assay (CV mean = 9.9 %) (p <0.001). The coefficient of determination varied between combinations of reagents and instrument platforms (r2 = 0.59-0.89) and the slope ranged between 0.48 and 1.5. Significant differences between the two reagents used were sometimes noted. CONCLUSIONS: Imprecision in λFLC affects the κFLC/λFLC ratio. This may be important in clinical assessment of patients, especially differentiating between monoclonal and polyclonal gammopathies.

Fraction of inspired oxygen during general anesthesia for non-cardiac surgery: Systematic review and meta-analysis.

BACKGROUND: Controversy exists regarding the effects of a high versus a low intraoperative fraction of inspired oxygen (FiO2 ) in adults undergoing general anesthesia. This systematic review and meta-analysis investigated the effect of a high versus a low FiO2 on postoperative outcomes. METHODS: PubMed and Embase were searched on March 22, 2022 for randomized clinical trials investigating the effect of different FiO2 levels in adults undergoing general anesthesia for non-cardiac surgery. Two investigators independently reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and potential effect measure modification was assessed in subgroup analyses and meta-regression. The evidence certainty was evaluated using GRADE. RESULTS: This review included 25 original trials investigating the effect of a high (mostly 80%) versus a low (mostly 30%) FiO2 . Risk of bias was intermediate for all trials. A high FiO2 did not result in a significant reduction in surgical site infections (OR: 0.91, 95% CI 0.81-1.02 [p = .10]). No effect was found for all other included outcomes, including mortality (OR = 1.27, 95% CI: 0.90-1.79 [p = .18]) and hospital length of stay (mean difference = 0.03 days, 95% CI -0.25 to 0.30 [p = .84). Results from subgroup analyses and meta-regression did not identify any clear effect modifiers across outcomes. The certainty of evidence (GRADE) was rated as low for most outcomes. CONCLUSIONS: In adults undergoing general anesthesia for non-cardiac surgery, a high FiO2 did not improve outcomes including surgical site infections, length of stay, or mortality. However, the certainty of the evidence was assessed as low.

Ventilation Strategies During General Anesthesia for Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal ventilation strategy during general anesthesia is unclear. This systematic review investigated the relationship between ventilation targets or strategies (eg, positive end-expiratory pressure [PEEP], tidal volume, and recruitment maneuvers) and postoperative outcomes. METHODS: PubMed and Embase were searched on March 8, 2021, for randomized trials investigating the effect of different respiratory targets or strategies on adults undergoing noncardiac surgery. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and several subgroup analyses were conducted. The certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This review included 63 trials with 65 comparisons. Risk of bias was intermediate for all trials. In the meta-analyses, lung-protective ventilation (ie, low tidal volume with PEEP) reduced the risk of combined pulmonary complications (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.28-0.49; 9 trials; 1106 patients), atelectasis (OR, 0.39; 95% CI, 0.25-0.60; 8 trials; 895 patients), and need for postoperative mechanical ventilation (OR, 0.36; 95% CI, 0.13-1.00; 5 trials; 636 patients). Recruitment maneuvers reduced the risk of atelectasis (OR, 0.44; 95% CI, 0.21-0.92; 5 trials; 328 patients). We found no clear effect of tidal volume, higher versus lower PEEP, or recruitment maneuvers on postoperative pulmonary complications when evaluated individually. For all comparisons across targets, no effect was found on mortality or hospital length of stay. No effect measure modifiers were found in subgroup analyses. The certainty of evidence was rated as very low, low, or moderate depending on the intervention and outcome. CONCLUSIONS: Although lung-protective ventilation results in a decrease in pulmonary complications, randomized clinical trials provide only limited evidence to guide specific ventilation strategies during general anesthesia for adults undergoing noncardiac surgery.

Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia.

BACKGROUND: Binary prediction-models for outcome [death, cognition, presence and severity of cerebral palsy (CP)], using MRI and early clinical data applicable for individual outcome prediction have not been developed. METHODS: From Dec 1st 2006 until Dec 31st 2013, we recruited 178 infants into a population-based cohort with moderate or severe hypoxic-ischaemic encephalopathy (HIE) including postnatal collapse (PNC, n = 12) and additional diagnoses (n = 12) using CoolCap/TOBY-trial entry-criteria including depressed amplitude-integrated EEG (aEEG). Early clinical/biochemical variables and MRI scans (median day 8) were obtained in 168 infants. Injury severity was scored for cortex, basal ganglia/thalami (BGT), white matter (WM) and posterior limb of the internal capsule, summating to a total injury score (TIS, range 0-11). Outcome was categorized as adverse or favourable at 18-24 months from Bayley-III domains (cut-off 85) and neurological examination including CP classification. FINDINGS: HIE and entry-aEEG severity were stable throughout the study. Outcome was favourable in 133/178 infants and adverse in 45/178: 17 died, 28 had low Cognition/Language scores, (including 9 with severe CP and 6 mild); seven had mild CP with favourable cognitive outcome. WMxBGT product scores and TIS were strong outcome predictors, and prediction improved when clinical/biochemical variables were added in binary logistic regression. The Positive Predictive Value for adverse outcome was 88%, increasing to 95% after excluding infants with PNC and additional diagnoses. Using WMxBGT in the regression predicted 8 of the 9 children with severe CP. INTERPRETATION: Binary logistic regression with WMxBGT or TIS and clinical variables gave excellent outcome prediction being 12% better than single variable cross-tabulation. Our MRI scoring and regression models are readily accessible and deserve investigation in other cohorts for group and individual prediction. FUNDING: We thank the National Health Service (NHS) and our Universities and funders in UK and Norway: SPARKS, The Moulton Foundation, The Norwegian Research Council, The Lærdal Foundation for Acute Medicine and charitable donations for their support for cooling therapy.

Features of urine S100B and its ability to rule out intracranial hemorrhage in patients with head trauma: a prospective trial.

PURPOSE: Traumatic brain injury causes morbidity and mortality worldwide. S100B is the most documented emergency brain biomarker and its urine-assay might be advantageous because of easier sampling. The primary aim was to evaluate urine S100B's ability to rule out intracranial hemorrhage. Secondary aims included S100B temporal pattern for 48 h post-trauma and chemical properties of urine that affect urine S100B. METHODS: Patients with head trauma were sampled for serum and urine S100B. Patients who were admitted for intracranial hemorrhage were sampled for 48 h to assess S100B-level, renal function, urine-pH, etc. RESULTS: The negative predictive value of serum S100B was 97.0% [95% confidence interval (CI) 89.5-99.2%] and that of urine S100B was 89.1% (95% CI 85.5-91.9%). The specificity of serum S100B was 34.4% (95% CI 27.7-41.6%) and that of urine was 67.1% (95% CI 59.4-74.1%). Urine-pH correlated strongly with urine S100B during the first 6-h post-trauma. Trend-analysis of receiver operator characteristics of S100B in serum, urine the arithmetic difference between serum and urine S100B showed the largest area under the curve for arithmetic difference, which had a negative predictive value of 93.1% (95% CI 89.1-95.8%) and a specificity of 71.8% (95% CI 64.4-78.4%). CONCLUSION: This study cannot support ruling out intracranial hemorrhage with urine S100B. Urine-pH might affect urine S100B and merits further studies. Serum and urine S100B have poor concordance and interchangeability. The arithmetic difference had a slightly better area under the curve and can be worth exploring in certain subgroups.

A proposed amendment to the current guidelines for mild traumatic brain injury: reducing computerized tomographies while maintaining safety.

PURPOSE: Head trauma is a common complaint in emergency departments. Identifying patients with serious injuries can be difficult and generates many computerized tomographies. Reducing the number of computerized tomographies decreases both cost and radiation exposure. The aim of this study was to evaluate whether the current Scandinavian Neurotrauma Committee guidelines could be revised in such a way that would enable hospitals to perform fewer computerized tomographies while maintaining the ability to identify all patients requiring neurological intervention. METHODS: A retrospective study of the medical records of adult patients suffering a traumatic brain injury was performed. A total of 1671 patients over a period of 365 days were included, and 25 parameters were extracted. Multitrauma patients managed with ATLS™ were excluded. The Scandinavian Neurotrauma Committee guidelines were amended with the previously derived "low-risk proposal" and applied retrospectively to the cohort. RESULTS: Incidence of intracranial hemorrhage was 5.6% (93/1671). Application of the current Scandinavian Neurotrauma Committee guidelines would have resulted in 860 computerized tomographies and would have missed 11 intracranial hemorrhages. The proposed amendment with the low-risk proposal would have resulted in 748 CT scans and would have missed 19 intracranial hemorrhages (a relative reduction of 13%). None of the missed intracranial hemorrhages required neurological intervention. CONCLUSION: For patients with mild and moderate traumatic brain injuries, application of the Scandinavian Neurotrauma Committee guidelines amended with the low-risk proposal may result in a significant reduction of computerized tomographies without missing any patients in need of neurological intervention.

Prospective comparison of capillary and venous brain biomarker S100B: capillary samples have large inter-sample variation and poor correlation with venous samples.

BACKGROUND: Guidelines for the emergency management of mild traumatic brain injury have been used for over a decade and are considered safe. However, they recommend computerized tomography for at least half of these patients. The Scandinavian Neurotrauma Committee guideline uses serum S100B protein level to rule out intracranial hemorrhage. Analysis of capillary serum S100B protein level has not yet been employed for this purpose. The primary aim of this study was to investigate the correlation and agreement of capillary and venous serum S100B protein level over a spectrum of concentrations typical for mild traumatic brain injury. METHODS: Eighteen patients with traumatic intracranial hemorrhage and 39 volunteers without trauma to the head within the past 7 days were recruited. Blood was sampled from patients with intracranial hemorrhage daily up to four consecutive days and healthy volunteers were sampled once during the study. One venous and two capillary samples were drawn at each sampling event. Samples were analyzed using the Cobas e411 S100 electrochemiluminescence assay. RESULTS: Median serum S100B protein level of capillary sampling 1 was 0.12 (IQR 0.075-0.21) µg/l and median serum S100B protein level of capillary sampling 2 was 0.13 (IQR 0.08-0.22) µg/l. Median serum S100B protein level of all venous samples was 0.05 (IQR 0.03-0.07) µg/l. Correlation plots of capillary and venous samples showed poor correlation and Bland-Altman plots showed a large dispersion of samples and wide limits of agreement. CONCLUSION: The results of this study indicate that correlation and agreement between capillary and venous samples are low, and because of this, we cannot recommend studies on capillary serum S100B protein level to rule out intracranial hemorrhage in mild traumatic brain injury. Given the limitations of the current sampling and analysis methods of capillary protein S100B protein level, we conclude that evaluating its predictive ability to rule out intracranial hemorrhage should be withheld until more reliable methods can be incorporated into the study design.

Cardiac Troponin T in Healthy Full-Term Infants.

In this prospective cohort study of healthy full-term infants, we hypothesized that high-sensitivity cardiac troponin T (hs-cTnT) would be elevated in cord blood, compared with adult reference values, and that it would further increase over the first days of age. Cardiac troponin T has been shown to be significantly increased in healthy full-term newborns compared with adult reference values, but there is no established reference range. Most studies of cTnT in newborns have been performed before the introduction of high-sensitivity cTnT (hs-cTnT) assay. We conducted a study including 158 full-term newborns, at Stockholm South General Hospital. High-sensitivity cTnT was analyzed in umbilical cord blood and at 2-5 days of age. Median hs-cTnT (interquartile range) in cord blood was 34(26-44) ng/L; 99th percentile 88 ng/L. Median hs-cTnT at 2-5 days of age was 92(54-158) ng/L; 99th percentile 664 ng/L. We conclude that hs-cTnT is elevated in cord blood in healthy, full-term newborn infants compared with adult reference values, and that it increases significantly during the first days of life. Our findings further underline the need of caution when using hs-cTnT as a measurement of cardiac impact in newborns.

A rapid smartphone-based lactate dehydrogenase test for neonatal diagnostics at the point of care.

There is a growing recognition of the importance of point-of-care tests (POCTs) for detecting critical neonatal illnesses to reduce the mortality rate in newborns, especially in low-income countries, which account for 98 percent of reported neonatal deaths. Lactate dehydrogenase (LDH) is a marker of cellular damage as a result of hypoxia-ischemia in affected organs. Here, we describe and test a POC LDH test direct from whole blood to provide early indication of serious illness in the neonate. The sample-in-result-out POC platform is specifically designed to meet the needs at resource-limited settings. Plasma is separated from whole blood on filter paper with dried-down reagents for colorimetric reaction, combined with software for analysis using a smartphone. The method was clinically tested in newborns in two different settings. In a clinical cohort of newborns of Stockholm (n = 62) and Hanoi (n = 26), the value of R using Pearson's correlation test was 0.91 (p < 0.01) and the R2 = 0.83 between the two methods. The mean LDH (±SD) for the reference method vs. the POC-LDH was 551 (±280) U/L and 552 (±249) U/L respectively, indicating the clinical value of LDH values measured in minutes with the POC was comparable with standardized laboratory analyses.

Point-of-care hemolysis detection in blood gas specimens directly at the emergency department.

Blood gas analysis represents an important and frequently used clinical decision support. Spurious haemolysis is common at the emergency department (ED) and causes clinically relevant bias to many analyses. Blood gas analysers inability to identify hemolysis can therefore lead to clinical misinterpretations. The objective of this study was to assess the proportion of haemolytic blood gas samples performed at the ED and calculate the predictive values of a novel point-of-care solution for haemolysis detection. Approximately 100 µl of blood from anonymized syringes including venous or arterial blood was, directly after performed blood gas analysis, tested with the POC-Method (Helge H10 s-system, Hemcheck, Karlstad, Sweden) at the ED and result recorded. Thereafter the blood was centrifuged (2000 g) for 10 minutes, 100 µl of plasma put into vials and run in batches of 40 daily on an AU680 analyzer (Beckman Coulter, Brea, California, USA) used as reference method. The threshold for clinically relevant hemolysis was defined as ≥50 mg/dL free haemoglobin. Out of 1270 samples, haemolysis was detected in 7.9% (n = 100). The POC-method identified haemolytic samples with a sensitivity of 80%, specificity of 99%, positive and negative predictive values was 89% and 98% respectively. Spurious hemolysis is frequently present in blood gas samples at the ED and should be taken into consideration when assessed in patients. Errors could be detected directly at the point-of-care with a novel technology for hemolysis detection.

Management of mild traumatic brain injury-trauma energy level and medical history as possible predictors for intracranial hemorrhage.

PURPOSE: Head trauma is common in the emergency department. Identifying the few patients with serious injuries is time consuming and leads to many computerized tomographies (CTs). Reducing the number of CTs would reduce cost and radiation. The aim of this study was to evaluate the characteristics of adults with head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage. METHODS: Medical record data have been collected retrospectively in adult patients with traumatic brain injury. A total of 1638 patients over a period of 384 days were reviewed, and 33 parameters were extracted. Patients with high-energy multitrauma managed with ATLS™ were excluded. The analysis was done with emphasis on patient history, clinical findings, and epidemiological traits. Logistic regression and descriptive statistics were applied. RESULTS: Median age was 58 years (18-101, IQR 35-77). High age, minor head injury, new neurological deficits, and low trauma energy level correlated with intracranial hemorrhage. Patients younger than 59 years, without anticoagulation or antiplatelet therapy who suffered low-energy trauma, had no intracranial hemorrhages. The hemorrhage frequency in the entire cohort was 4.3% (70/1638). In subgroup taking anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and in the platelet-inhibitor subgroup, it was 11.8% (20/169). CONCLUSION: This study demonstrates that patients younger than 59 years with low-energy head trauma, who were not on anticoagulants or platelet inhibitors could possibly be discharged based on patient history. Maybe, there is no need for as extensive medical examination as currently recommended. These findings merit further studies.

Management of Traumatic Brain Injury in the Emergency Department: Guideline Adherence and Patient Safety.

BACKGROUND: Traumatic brain injury is a common reason not only for emergency visits worldwide but also for significant morbidity and mortality. Several clinical guidelines exist but adherence is generally low. AIM: To study attitudes toward computed tomography of the head among emergency department Change to physicians throughout the article who manage patients with trauma to the head and doctors' adherence to guidelines. METHODS: Quantitative questionnaire study with questionnaires collected over 3 months before introduction of new guidelines. After introduction, intermission of 8 months passed when information and education were given. Thereafter, questionnaires were collected for another 3 months. RESULTS: A total of 694 patients were registered at the emergency department. A total of 161 questionnaires were analyzed; 50.9% did not use guidelines, 39% before intermission, and 60.5% after. When Canadian CT Head Rule was applied, 30.4% of patients with no loss of consciousness were referred to computed tomography, violating guideline recommendation. CONCLUSION: Guidelines are designed to improve performance but are not always applied correctly or as frequently as intended. Information and education did not increase guideline adherence. To improve guideline adherence, more innovative measures than formal guidelines must be undertaken. To find out what these measures are, we suggest qualitative studies to elucidate interventions that will have bigger impact on performance.

Predicting in-hospital mortality for initial survivors of acute respiratory compromise (ARC) events: Development and validation of the ARC Score.

AIM: Acute respiratory compromise (ARC) is a common and highly morbid event in hospitalized patients. To date, however, few investigators have explored predictors of outcome in initial survivors of ARC events. In the present study, we leveraged the American Heart Association's Get With The Guidelines®-Resuscitation (GWTG-R) ARC data registry to develop a prognostic score for initial survivors of ARC events. METHODS: Using GWTG-R ARC data, we identified 13,193 index ARC events. These events were divided into a derivation cohort (9807 patients) and a validation cohort (3386 patients). A score for predicting in-hospital mortality was developed using multivariable modeling with generalized estimating equations. RESULTS: The two cohorts were well balanced in terms of baseline demographics, illness-types, pre-event conditions, event characteristics, and overall mortality. After model optimization, nine variables associated with the outcome of interest were included. Age, hypotension preceding the event, and intubation during the event were the greatest predictors of in-hospital mortality. The final score demonstrated good discrimination in both the derivation and validation cohorts. The score was also very well calibrated in both cohorts. Observed average mortality was <10% in the lowest score category of both cohorts and >70% in the highest category, illustrating a wide range of mortality separated effectively by the scoring system. CONCLUSIONS: In the present study, we developed and internally validated a prognostic score for initial survivors of in-hospital ARC events. This tool will be useful for clinical prognostication, selecting cohorts for interventional studies, and for quality improvement initiatives seeking to risk-adjust for hospital-to-hospital comparisons.

Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial.

RATIONALE: Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to patients with sepsis may reduce the incidence and severity of sepsis-related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT). OBJECTIVES: To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. METHODS: This was a secondary analysis of a single-center, randomized, double-blind trial comparing thiamine to placebo in patients with septic shock. Renal function, need for RRT, timing of hemodialysis catheter placement, and timing of RRT initiation were abstracted. The baseline creatinine and worst creatinine values between 3 and 24 hours, 24 and 48 hours, and 48 and 72 hours were likewise abstracted. RESULTS: There were 70 patients eligible for analysis after excluding 10 patients in whom hemodialysis was initiated before study drug administration. Baseline serum creatinine in the thiamine group was 1.2 mg/dl (interquartile range, 0.8-2.5) as compared with 1.8 mg/dl (interquartile range, 1.3-2.7) in the placebo group (P = 0.3). After initiation of the study drug, more patients in the placebo group than in the thiamine group were started on RRT (eight [21%] vs. one [3%]; P = 0.04). In the repeated measures analysis adjusting for the baseline creatinine level, the worst creatinine levels were higher in the placebo group than in the thiamine group (P = 0.05). CONCLUSIONS: In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area.

The combined use of three widely available biochemical markers as predictor of organ failure in critically ill patients.

BACKGROUND: We hypothesized that lactate dehydrogenase, LDH/albumin ratio in combination with or without magnesium (Mg(2+)) could predict organ failure in critically ill adult patients. The aim of this study was to describe a new risk index for organ failure or mortality in critically ill patients based on a combination of these routinely available biochemical plasma biomarkers. METHODS: Patients ≥ 18 years admitted to the intensive care unit (ICU) were screened. Albumin and LDH were analyzed at the time of admission to ICU (n = 347). Organ failure assessed with 'Sequential Organ Failure Assessment' (SOFA) score was used, and 30-day mortality was recorded. The predictive value of the test was calculated using the areas under the receiving operating characteristic (ROC) curve. RESULTS: The LDH/albumin ratio was higher in patients who developed organ failure as compared to those who did not (p < 0.001). The areas under the ROC curve were 0.77 both for prediction of multiple organ failure and for 30-day mortality. In a subgroup of patients (n = 183) admitted to ICU from the emergency department, the predictive values were 0.86 and 0.80, respectively. CONCLUSION: The LDH/albumin ratio at ICU admission was associated with the development of multiple organ failure and 30-day mortality in this prospective study. The clinical value of this biomarker as a predictor of organ failure in critically ill patients is yet to be defined.

Lactate dehydrogenase as an indicator of severe illness in neonatal intensive care patients: a longitudinal cohort study.

AIM: Lactate dehydrogenase (LDH) increases in several critical conditions that cause cell damage and could potentially be used for early detection of serious illness in the newborn. Our aim was to investigate the relationship between the early clinical course of NICU infants and LDH in plasma at admission. METHODS: LDH was measured in a cohort of patients consecutively admitted to a major NICU in Hanoi. The infants were classified as 'obviously needing intensive care during the first week' (n = 83) or 'not receiving intensive care measures during the first week' (n = 260) by a senior neonatologist blinded to the LDH and lactate activity. RESULTS: LDH differed significantly between the groups in infants born after 32 gestational weeks. LDH differed with the vitality of the patient (F = 26.25, p < 0.0001) at admittance and correlated with lactate (R = 0.496, p < 0.0001). Also, the predictive value for obvious need of intensive care was higher for LDH than for lactate assessed by area under the curve calculated with ROC-curves [0.82 (0.77-0.88) vs. 0.67 (0.60-0.75)]. CONCLUSION: There is a strong relationship between bad clinical condition of infants during first week of life and elevated plasma LDH. The results suggest that LDH might be a valuable support in decision making in the neonatal period.

Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxic-ischaemic encephalopathy.

AIMS: We investigated whether plasma lactate dehydrogenase (LDH) predicts outcome in hypothermia (HT)-treated term infants with moderate/severe hypoxic-ischaemic encephalopathy (HIE) and additionally whether LDH differs between infants with evidence for acute and nonacute perinatal insults and postnatal collapse (PNC). METHODS: Data from HT-treated infants with HIE (n = 39) were analysed retrospectively. Adverse outcome was defined as a Mental and/or Psychomotor Developmental Index (Bayley Scales of Infant Development II), at 18 months <70. The likely timing of insult onset was assessed in infants with an LDH sample obtained within 6 h of birth or PNC (n = 20). RESULTS: LDH differed between the favourable/adverse outcome groups at the end of HT treatment (median (IQR) 1540 (1400-1950)U/L vs. 3555 (3003-8705)U/L, (p < 0.01)). All infants (n = 22) with LDH <2085U/L had a favourable outcome while 6 of 11 infants with LDH ≥ 2085U/L had an adverse outcome. LDH in those who died (n = 4) was higher than the favourable outcome group (5090 (2915-12222)U/L, (p < 0.01)) but sampled earlier. Early LDH differed significantly (p < 0.01) between infants with evidence for acute or nonacute insults or PNC. CONCLUSION: THESE results offer a biomarker, with high negative predictive value in the assessment of outcome in HT-treated term infants, needing prospective validation.