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BACKGROUND: Optimal balance between macro- and microcirculation in critically ill patients is crucial for ensuring optimal organ perfusion. Nitric oxide (NO) is a regulator of vascular hemostasis and tone. The availability of NO is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the availability of the NO substrates arginine and homoarginine. We investigated the changes in plasma concentrations of ADMA, SDMA, arginine, and homoarginine days 1-5 of intensive care unit (ICU) admission and the association between the change in concentration days 1-3 and 30-day all-cause mortality. METHODS: Single-center cohort study of adult critically ill patients from the ICU at Copenhagen University Hospital - North Zealand. ADMA, SDMA, arginine, and homoarginine (NO-biomarkers) were measured on days 1-5. Initially, we determined the changes in NO-biomarkers days 1-5 with linear mixed models, and subsequently how the changes in NO-biomarkers days 1-3 were associated with 30-day all-cause mortality. Post-hoc we analyzed the association between plasma concentration at admission and 30-day all-cause mortality. RESULTS: In total 567 out of 577 patients had plasma samples from days 1-5. Plasma concentrations of ADMA and arginine increased from days 1-5. SDMA concentrations increased from days 1-2, followed by a decrease from days 2-5. Concentrations of homoarginine did not change from days 1-3 but slightly increased from days 3-5. In total 512 patients were alive 3 days after ICU admission. Among these patients, a daily twofold increase in ADMA concentration from days 1-3 was associated with decreased mortality in multivariate analysis (HR 0.45; 95% CI 0.21-0.98; p = 0.046). An increase in SDMA, arginine, or homoarginine was not associated with mortality. Post-hoc we found that a twofold increase in ADMA or SDMA concentrations at admission was associated with mortality (HR 1.78; 95% CI 1.24-2.57; p = 0.0025, and HR 1.41; 95% CI 1.05-1.90; p = 0.024, respectively). CONCLUSIONS: Increasing ADMA concentrations on days 1-3 are inversely associated with mortality, however not with the same strength as high ADMA or SDMA concentrations at admission. We suggest that admission concentrations are the focus of future research on ADMA and SDMA as predictors of mortality or potential therapeutical targets in ICU patients.
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BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).
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Pulmão , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Síndrome do Desconforto Respiratório , Ultrassonografia de Intervenção , Humanos , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/mortalidade , Respiração Artificial/métodos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos , Fatores de Tempo , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Medicina de Precisão/métodosRESUMO
Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.
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BACKGROUND: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine in the airways by altering deposition within the lungs, potentially affecting efficacy and side effects. It remains unclear if extrafine particle ICS administration alters the risk of pneumonia compared with standard particle size ICS. METHODS: An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalisation in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox proportional hazards model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis. RESULTS: A total of 35 691 patients were included of whom 1471 received extrafine particle ICS. Among these patients, 4657 were hospitalised due to pneumonia. Patients with COPD receiving extrafine particle ICS had a lower risk of hospitalisation due to pneumonia compared with patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63 to 0.89; p=0.002), subgroup analysis (HR 0.54; 95% CI 0.45 to 0.65; p<0.0001) and the propensity-matched population (HR 0.72; 95% CI 0.60 to 0.87; p=0.0006). INTERPRETATION: The use of extrafine particle ICS administration was associated with a lower risk of pneumonia hospitalisation in patients with COPD compared with those who received standard size treatment.
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Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos de Coortes , Tamanho da Partícula , Administração por Inalação , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Corticosteroides , Pneumonia/epidemiologia , Pneumonia/etiologia , Nebulizadores e VaporizadoresRESUMO
Background: Bloodstream infections (BSIs) often lead to critical illness and death. The primary aim of this study was to determine the diagnostic accuracy of the biomarkers C-reactive protein (CRP), procalcitonin (PCT), and leukocyte count for the diagnosis of BSI in critically ill patients. Methods: This was a nested case-control study based on the Procalcitonin And Survival Study (PASS) trial (n = 1200). Patients who were admitted to the intensive care unit (ICU) <24â hours, and not expected to die within <24â hours, were recruited. For the current study, we included patients with a BSI within ±3 days of ICU admission and matched controls without a BSI in a 1:2 ratio. Diagnostic accuracy for BSI for the biomarkers on days 1, 2, and 3 of ICU admission was assessed. Sensitivity, specificity, and negative and positive predictive values were calculated for prespecified thresholds and for a data-driven cutoff. Results: In total, there were 525 patients (n = 175 cases, 350 controls). The fixed low threshold for all 3 biomarkers (CRP = 20â mg/L; leucocytes = 10 × 109/L; PCT = 0.4â ng/mL) resulted in negative predictive values on day 1: CRP = 0.91; 95% CI, 0.75-1.00; leukocyte = 0.75; 95% CI, 0.68-0.81; PCT = 0.91; 95% CI, 0.84-0.96). Combining the 3 biomarkers yielded similar results as PCT alone (P = .5). Conclusions: CRP and PCT could in most cases rule out BSI in critically ill patients. As almost no patients had low CRP and â¼20% had low PCT, a low PCT could be used, along with other information, to guide clinical decisions.
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BACKGROUND: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. METHODS: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799). RESULTS: We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49-1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15-3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66-0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55-1.20). CONCLUSIONS: The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.
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Do we need biomarkers of lung damage and infection: For what purpose and how should they be used properly? Biomarkers of lung damage can be used for diagnosis, risk stratification/prediction, treatment surveillance and adjustment of targeted therapy. Additionally, novel "omics" methods may offer a completely different and effective way of improving the understanding of pathogenesis of lung damage and a way to develop new candidate lung damage biomarkers. In the current review, we give an overview within the field of acute lung damage of (i) disease mechanism biomarkers, (ii) of "ready to use" evidence-based biomarker-guided lung infection management, (iii) of novel strategies of inflammatory phenotyping and how this can be used to tailor corticosteroid treatment, (iv) a future perspective of where "omics" technologies and mindsets may become increasingly important in developing new strategies for treatment and for understanding the development of acute lung damage.
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INTRODUCTION: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide system, may be associated with an adverse outcome in critically ill patients. The aim of the present review was to clarify if plasma ADMA and the arginine-to-ADMA ratio (arginine/ADMA) are associated with mortality in critically ill patients. METHODS: We searched PubMed, EMBASE and Web of Science/BIOSIS Previews on 31 July 2017 for studies published after 2000 including critically ill paediatric or adult patients and evaluating any association between all-cause mortality and admission ADMA and/or arginine/ADMA ratio. We pooled data from studies providing sufficient data in random effects meta-analyses. RESULTS: We identified 15 studies including a total of 1300 patients. These studies have a medium to high risk of bias and substantial clinical heterogeneity. After contacting authors for homogenous data, six studies including 705 patients could be included in a formal meta-analysis. This analysis revealed a strong association between high plasma ADMA upon admission and mortality (pooled odds ratio 3.13; 95% confidence interval (CI) 1.78-5.51). A significant association between ADMA/arginine ratio and mortality was found in two studies only (54 patients) out of a total of six studies (564 patients). CONCLUSIONS: A high plasma ADMA level upon admission is strongly associated with mortality in critically ill patients. However, there is no association between the arginine/ADMA ratio and mortality in this group of patients. The pathophysiological role of ADMA in circulatory collapse and its potential as a target for intervention remains to be explored.
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Arginina/análogos & derivados , Estado Terminal/mortalidade , Área Sob a Curva , Arginina/sangue , Causas de Morte , Humanos , Unidades de Terapia Intensiva , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
BACKGROUND: Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission. RESULTS: This cohort study included 746 critically ill patients with ventilator-demanding respiratory failure from the randomized clinical trial, "Procalcitonin And Survival Study (PASS)." Primary end point was successful weaning from mechanical ventilation within 28 days. We used multivariable Cox regression adjusted for age, sepsis, PaO2/FiO2 ratio and other known and suspected predictors of persistent respiratory failure. Follow-up was complete.For medical patients, baseline-gelsolin below the 25th percentile independently predicted a 40% lower chance of successful weaning within 28 days (HR 0.60, 95% CI 0.46-0.79, Pâ=â0.0002); among surgical patients this end point was not predicted. Low gelsolin levels predicted chance of being "alive and out of intensive care at day 14" for both medical and surgical patients (HR 0.69, 95% CI 0.54-0.89, Pâ=â0.004). Gelsolin levels did not predict 28 day mortality for surgical or medical patients. CONCLUSIONS: Low levels of serum gelsolin independently predict a decreased chance of successful weaning from ventilator within 28 days among medical intensive care patients. This finding has implications for identifying patients who need individualized intervention early in intensive care course to prevent unfavorable lung prognosis in acute respiratory failure. TRIAL REGISTRATION: This is a substudy to the PASS, Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.
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Lesão Pulmonar Aguda/sangue , Gelsolina/sangue , Insuficiência Respiratória/sangue , Lesão Pulmonar Induzida por Ventilação Mecânica/sangue , Lesão Pulmonar Aguda/terapia , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Respiratória/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/terapiaRESUMO
Sepsis has over the years proven a considerable challenge to physicians and researchers. Numerous pharmacological and non-pharmacological interventions have been tested in trials, but have unfortunately failed to improve the general prognosis. This has led to the speculation that the sepsis population may be too heterogeneous to be targeted with the traditional one treatment suits all' approach. Recent advances in genetic and biochemical analyses now allow genotyping and biochemical characterisation of large groups of patients via the 'omics' technologies. These new opportunities could lead to a paradigm shift in the approach to sepsis towards personalised treatments with interventions targeted towards specific pathophysiological mechanisms activated in the patient. In this article, we review the potentials and pitfalls of using new advanced technologies to deepen our understanding of the clinical syndrome of sepsis.
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BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.
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Hipotermia Induzida/mortalidade , Insuficiência Respiratória/terapia , Choque Séptico/terapia , APACHE , Idoso , Europa (Continente) , Feminino , Humanos , Hipotermia Induzida/métodos , Unidades de Terapia Intensiva , Masculino , América do Norte , Respiração Artificial/métodos , Respiração Artificial/mortalidade , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Resultado do TratamentoRESUMO
Myocardial injury after non-cardiac surgery (MINS) is associated with significant morbidity and mortality. Routine troponin screening is necessary to identify patients with MINS. Although some evidence indicates benefit with aspirin and statin therapy in these patients, a number of clinical considerations must be done in the practical management of MINS. This article describes current experience with identification and treatment in Denmark of patients with MINS.
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Isquemia Miocárdica/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Troponina T/sangue , Aspirina/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/mortalidade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidadeRESUMO
PURPOSE: Ventilator-associated pneumonia (VAP) is a common and serious complication in patients requiring mechanical ventilation in the intensive care unit. The aims of this study were to identify models used to predict mortality in VAP patients and to assess their prognostic accuracy. METHODS: The PubMed and EMBASE were searched in February 2016. We included studies in English that evaluated models' ability to predict the risk of mortality in patients with VAP. The reported mortality with the longest follow-up was used in the meta-analysis. Prognostic accuracy was measured with the area under the receiver operator characteristic curve (AUC). RESULTS: We identified 19 articles studying 7 different models' ability to predict mortality in VAP patients. The models were Acute Physiology and Chronic Health Evaluation (APACHE) II (9 studies, n = 1398); Clinical Pulmonary Infection Score (4 studies, n = 303); "Immunodeficiency, Blood pressure, Multilobular infiltrates on chest radiograph, Platelets and hospitalization 10 days before onset of VAP" (3 studies, n = 406); "VAP Predisposition, Insult Response and Organ dysfunction" (2 studies, n = 589); Sequential Organ Failure Assessment (7 studies, n = 1019); Simplified Acute Physiology Score II (6 studies, n = 1043); and APACHE III (1 study, n = 198). APACHE II had the highest pooled AUC (95% confidence intervals), 0.72 (0.64-0.80), and CPIS had the lowest pooled AUC, 0.64 (0.55-0.72). CONCLUSION: We identified 7 models that have been evaluated for their ability to predict mortality in patients with VAP. The models had nearly equal predictive accuracies, although some models are more complex and time consuming.
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Pneumonia Associada à Ventilação Mecânica/mortalidade , Medição de Risco , APACHE , Área Sob a Curva , Humanos , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Respiração Artificial , RiscoRESUMO
INTRODUCTION: Nitric oxide (NO) likely plays a pivotal role in the pathogenesis of sepsis. Arginine is a substrate for NO, whereas the methylated arginines-asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)-are endogenous by-products of proteolysis that inhibit NO production.We investigated if high-plasma levels of ADMA, SDMA, and arginine/ADMA ratio were associated with 90-day mortality in patients with severe sepsis or septic shock. METHODS: We included 267 adult patients admitted to intensive care unit with severe sepsis or septic shock. The patients had previously been included in the randomized controlled trial "Scandinavian Starch for Severe Sepsis and Septic Shock (6S)." ADMA, SDMA, and arginine/ADMA ratio were measured in plasma. The risk of death within 90 days was estimated in multivariate Cox regression analyses adjusted for gender, age ≥65 years, major cardiovascular disease, diabetes, hypertension, respiratory failure, vasopressor treatment, highest quartile of creatinine and bilirubin, and lowest quartile of platelet count. In the regression analyses missing values were estimated using multiple imputation. RESULTS: Twenty-five patients had missing data in one or more of the baseline variables and 44 patients had missing methylarginine values. Both ADMA and SDMA were independently associated with 90-day mortality (ADMA: hazard ratio 1.54; 95% CI, 1.00-2.38; Pâ=â0.046, and SDMA: hazard ratio 1.78; 95% CI, 1.14-2.72; Pâ=â0.011). Arginine/ADMA ratio was not associated with 90-day mortality neither in univariate nor in multivariate analyses. The difference in mortality between patients with high and low ADMA was most pronounced in the first week after inclusion. CONCLUSIONS: High levels of ADMA and SDMA in plasma were associated with increased 90-day mortality in patients with severe sepsis or septic shock. Interfering with the methylarginine-NO systems may be a novel target in these patients.
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Arginina/análogos & derivados , Sepse/sangue , Sepse/mortalidade , Idoso , Arginina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Modelos de Riscos Proporcionais , Choque Séptico/sangue , Choque Séptico/mortalidadeRESUMO
BACKGROUND: Neutrophil gelatinase associated lipocalin (NGAL) is proposed as a biomarker of acute kidney injury (AKI). NGAL has been studied in a range of body fluids including serum and EDTA plasma. The aim of the present study was to establish relationship between serum NGAL concentrations and EDTA plasma NGAL concentrations in patients admitted to intensive care units (ICUs) and whether these determinations are directly comparable in this setting. METHODS: NGAL was measured in 40 paired samples of serum and EDTA plasma from 25 patients admitted to intensive care with a commercial particle-enhanced turbidimetric immunoassay (The NGAL Test™, BioPorto Diagnostics A/S, Gentofte, Denmark) on a Roche Hitachi 917 (Roche-Hitachi, Inc., Tokyo, Japan) analyzer. RESULTS: Serum NGAL concentrations ranged from 26.8 to 1,808 ng/ml (median 281 ng/ml, interquartile range (IQR) 453 ng/ml). EDTA plasma NGAL concentrations ranged from 25.7 to 1,752 ng/ml (median 225 ng/ml, IQR 352 ng/ml). The difference in NGAL concentrations in paired serum and EDTA plasma samples (serum- plasma) ranged from -13.8 to 321 ng/ml (median 79 ng/ml, IQR 116 ng/ml; difference from zero, P < 0.0001, Wilcoxon's signed rank test). Although serum and EDTA plasma values were correlated (Spearman's r = 0.95, P < 0.0001), Deming regression analysis showed a slope of 1.1 that was not significantly different from unity (95% confidence interval (CI) 1.0-1.1) and a highly significant intercept of 67.9 ng/ml with a wide confidence interval (95% CI 29.8-106). CONCLUSION: NGAL concentration values measured in serum and EDTA plasma cannot be directly compared and should not be used as equivalents in studies of patients admitted to intensive care.