Performance of plasma measurement of neutrophil gelatinase-associated lipocalin as a biomarker of bacterial infections in the intensive care unit.

PURPOSE: To assess the value of dimeric neutrophil-gelatinase associated lipocalin (NGAL) as an early marker of bacterial infection and its response to antibiotic therapy in intensive care unit (ICU) patients. MATERIALS & METHODS: We measured daily plasma dNGAL in 198 patients admitted to a mixed ICU. Likelihood of infection was determined with International Sepsis Forum criteria. We measured dNGAL in 145 healthy controls to establish normal values. RESULTS: ICU patients had higher dNGAL than healthy controls. A suspected or confirmed infection was independently associated with 90% (95% CI 15-215%) higher dNGAL than absence of infection. We observed no association between acute kidney injury and dNGAL. Diagnostic accuracy at antibiotic treatment initiation, assessed with area under the receiver-operating characteristics curve (AUC-ROC), for dNGAL was 0.70 (95% CI 0.60-0.79). AUC-ROC for dNGAL 24 h before antibiotic treatment initiation was 0.54 (95% CI 0.41-0.66). The mean (95% CI) change of dNGAL in the first 2 days after appropriate antibiotic therapy initiation was -31 (-49,-13)%. CONCLUSIONS: In our cohort of ICU patients, plasma dNGAL was associated with presence of bacterial infections independent of AKI but it performed poor as a predictor of infections. Following antibiotic therapy, dNGAL markedly decreased-supporting further exploration of dNGAL-guided antibiotic de-escalation.

Creatinine- and Cystatin C-Based Incidence of Chronic Kidney Disease and Acute Kidney Disease in AKI Survivors.

BACKGROUND: Renal dysfunction after acute kidney injury (AKI) is common, potentially modifiable, but poorly understood. Acute kidney disease (AKD) describes renal dysfunction 7 to 90 days after AKI and is determined by percentage change in creatinine from baseline. Chronic kidney disease (CKD) is defined as the estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 persisting for more than 90 days. We compared CKD incidence using both creatinine- and cystatin C-based GFR with AKD incidence at 90 days in AKI survivors. METHODS: A prospective cohort study was conducted in a Swedish intensive care unit (ICU) between 2008 and 2010. We included AKI patients alive at 90 days. We excluded patients <18 and >100 years, death before follow-up, CKD prior to admission, and follow-up before 60 days or beyond 270 days. Creatinine and cystatin C were measured at 90 days and converted to eGFR (mL/min/1.73 m2). RESULTS: We included 274 patients. At 90-day follow-up, the median creatinine eGFR (MDRD) was 81.6 (IQR 58.6-106.8) and median cystatin C eGFR was 51.5 (IQR 35.8-70.7). The incidence of CKD (eGFR < 60) was 25.8% based on creatinine but 63.7% using cystatin C estimates. AKD was present in 47 patients (18.9%). Age, discharge cystatin C, creatinine at discharge, and female gender predicted creatinine-defined CKD at follow-up. Age, discharge cystatin C, CRRT on ICU, and diabetes were associated with cystatin C-based CKD. CONCLUSIONS: In AKI survivors followed up at 3 months, CKD criteria were met in a quarter of patients using creatinine and in two-thirds using cystatin C eGFR. Less than one-fifth of patients fulfilled AKD criteria. The application of AKD criteria may underestimate renal dysfunction in AKI survivors.

Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment.

BACKGROUND: Calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, and neutrophil degranulation is a major response to bacterial infections. OBJECTIVES: To assess the value of plasma calprotectin as an early marker of bacterial infections in critically ill patients and compare it with the corresponding values for procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC). METHODS: We measured daily plasma calprotectin levels in 110 intensive care unit patients using a newly developed turbidimetric assay run on clinical chemistry analysers. The likelihood of infection was determined according to the International Sepsis Forum criteria. RESULTS: Overall, 58 patients (52.7%) developed a suspected or confirmed bacterial infection. Plasma calprotectin predicted such infections within 24 hours with an area under the receiver operating characteristics curve (ROC area) of 0.78 (95% CI, 0.68-0.89). The ROC area for calprotectin was significantly greater than the corresponding ROC areas for WBC (P < 0.001) and PCT (P = 0.02) but only marginally better than the ROC area for CRP (0.71; 95% CI, 0.68-0.89). CONCLUSION: Plasma calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than WBC and PCT.

Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU.

OBJECTIVES: Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness. DESIGN: Retrospective observational cohort study. PATIENTS: In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality. CONCLUSIONS: In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Intra-day variability of cystatin C, creatinine and estimated GFR in intensive care patients.

BACKGROUND: Markers of renal function are widely used in intensive care and sudden changes are important indicators of acute kidney injury. The problem is to distinguish between disease progression/improvement from the natural variation in the patient. The aim of the present study was thus to study the normal intraday variation in ICU patients. METHODS: We studied the intra-day variation of creatinine, cystatin C and estimated GFR based on these two markers in 28 clinically stable ICU patients. RESULTS: The median diurnal coefficient of variation sCV) for creatinine was 3.70% (1.92-9.25%) while the median CV for cystatin C was 3.66% (1.36-8.11%). The corresponding CVs for the estimated GFRs were 2.00% (0.89-9.82%) for eGFRcreatinine and 4.60% (1.65-10.24%) for eGFRcystc. CONCLUSIONS: The eGFRcreatinine values in individual patients were clearly higher than the eGFRcystc values. The median CV for creatinine, cystatin C and the eGFR measurements were below 5% which means that 95% of the test results will vary by <10% between sampling times in stable ICU patients. Differences >10% between sampling times are thus likely to be an indication of changes in biomarker levels due to the disease/treatment.

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients.

BACKGROUND: Breakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). METHODS: We studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646-0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752-0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses. CONCLUSIONS: In this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not.

Long-term mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease.

INTRODUCTION: Prevalence of chronic kidney disease (CKD) amongst intensive care unit (ICU) admissions is rising. How mortality and risk of end-stage renal disease (ESRD) differs between those with and without CKD and with acute kidney injury (AKI) is unclear. Determining factors that increase the risk of ESRD is essential to optimise treatment, identify patients requiring nephrological surveillance and for quantification of dialysis provision. METHOD: This cohort study used the Swedish intensive care register 2005-2011 consisting of 130,134 adult patients. Incomplete cases were excluded (26,771). Patients were classified (using diagnostic and intervention codes as well as admission creatinine values) into the following groups: ESRD, CKD, AKI, acute-on-chronic disease (AoC) or no renal dysfunction (control). Primary outcome was all-cause mortality. Secondary outcome was ESRD incidence. RESULTS: Of 103,363 patients 4,192 had pre-existing CKD; 1389 had ESRD; 5273 developed AKI and 998 CKD patients developed AoC. One-year mortality was greatest in AoC patients (54 %) followed by AKI (48.7 %), CKD (47.6 %) and ESRD (40.3 %) (P < 0.001). Five-year mortality was highest for the CKD and AoC groups (71.3 % and 68.2 %, respectively) followed by AKI (61.8 %) and ESRD (62.9 %) (P < 0.001). ESRD incidence was greatest in the AoC and CKD groups (adjusted incidence rate ratio (IRR) 259 (95 % confidence interval (CI) 156.9-429.1) and 96.4, (95 % CI 59.7-155.6) respectively) and elevated in AKI patients compared with controls (adjusted IRR 24 (95 % CI 3.9-42.0); P < 0.001). Risk factors independently associated with ESRD in 1-year survivors were, according to relative risk ratio, AoC (356; 95 % CI 69.9-1811), CKD (267; 95 % CI 55.1-1280), AKI (30; 95 % CI 5.98-154) and presence of elevated admission serum potassium (4.6; 95 % CI 1.30-16.40) (P < 0.001). CONCLUSIONS: Pre-ICU renal disease significantly increases risk of death compared with controls. Subjects with AoC disease had extreme risk of developing ESRD. All patients with CKD who survive critical care should receive a nephrology referral. CLINICAL TRIALS REGISTRATION NUMBER: NCT02424747 April 20th 2015.

Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study.

INTRODUCTION: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI. METHOD: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years. RESULTS: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5). CONCLUSION: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.

Inhaled isoflurane sedation during therapeutic hypothermia after cardiac arrest: a case series.

OBJECTIVE: Therapeutic hypothermia in the ICU requires mechanical ventilation and sedation. Hypothermia reduces the metabolism of commonly used IV sedatives. The use of long-acting sedative agents may confound neurologic assessment. Volatile anesthetics have been reported to provide protection against ischemia-reperfusion injury and have been safely used in the ICU to provide sedation in trials with shorter wake-up times. There are no clinical studies in this setting. We describe a case series and discuss potential benefits. DESIGN: Retrospective study. SETTINGS: Ten-bed ICU, university hospital. PATIENTS: Twelve patients resuscitated from cardiac arrest with Glasgow Coma Scale score less than or equal to 4. INTERVENTION: Isoflurane sedation with the AnaConDa during 24 hours therapeutic hypothermia, until rewarming. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the computerized ICU chart/monitors, hospital and prehospital charts, and the national death index. Patients were 49-76 years old. Median return of spontaneous circulation was 14 minutes. Glasgow Coma Scale scores were assessed within 24 hours from reaching normal body temperature and compared with outcomes at 6 months: six patients had poor Glasgow Coma Scale scores (< 8) that remained low and all died before 6-month follow-up, whereas another six patients had high scores (> 8) and survived to 6 months with good Cerebral Performance Category. In the ICU, four of the survivors were directly extubated after rewarming while two were once more sedated due to pneumonia requiring invasive ventilator therapy. All patients required norepinephrine to maintain adequate mean arterial pressure. Isoflurane sedation was changed to midazolam in two nonsurviving patients because of hemodynamic instability, which persisted despite the change. CONCLUSIONS: Sedation with volatile anesthetics during therapeutic hypothermia may be a feasible short-acting option with potential postconditioning effects protecting vital organs from ischemia-reperfusion injury. Its measurability and insignificant drug accumulation could facilitate early neurologic assessment. Prospective clinical trials are warranted.

Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by injured kidney cells as well as by activated neutrophils in response to bacterial infections. We assessed the influence of acute renal dysfunction on the association between plasma NGAL and sepsis. METHODS: NGAL was measured daily in 138 critically ill patients. Simultaneous recordings of sepsis status and fluctuations in renal function were made. RESULTS: Elevated NGAL was associated with sepsis independent of level of acute renal dysfunction. A cut-off value of 98 ng/mL distinguished sepsis from systemic inflammation with high sensitivity (0.77) and specificity (0.79). CONCLUSIONS: Plasma NGAL can help clinicians to identify bacterial infections in critically ill patients.

ICU admittance by a rapid response team versus conventional admittance, characteristics, and outcome.

OBJECTIVE: To evaluate characteristics and outcome of ICU patients admitted from general wards based on mode of admittance, via a rapid response team or conventional contact. DESIGN: Observational prospective study. SETTING: General ICU of a university hospital. PATIENTS: : A total of 694 admissions to ICU from general wards. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2007 and 2009, two cohorts admitted to ICU from general wards were identified: those admitted by the rapid response team and those admitted in a conventional way. Patients admitted directly from the trauma room, the emergency department, operating room, other hospitals, or other ICUs were excluded. Of 694 admissions, 355 came through a rapid response team call. Rapid response team patients were older (p < 0.01), and they had more severe comorbidities, higher severity score (p < 0.01), and almost three times more often the diagnosis of severe sepsis (p < 0.01) than conventionally admitted patients. Rapid response team patients had higher ICU mortality and 30-day mortality with a crude odds ratio for mortality within 30 days of 1.57 (95% confidence interval 1.08-2.28). Adjusted for age and comorbidities however, the difference was no longer significant with an odds ratio of 1.11 (95% confidence interval 0.70-1.76). CONCLUSIONS: This study suggests that the rapid response team is an important system for identifying complex patients in need of intensive care. More than half of ICU admissions from the wards came through a rapid response team call. Compared with conventional admissions, rapid response team patients had a high proportion of characteristics that could be related to a worse prognosis. Severe sepsis at the wards was mainly detected by the rapid response team and was the most common admitting diagnosis among the rapid response team patients. When adjusted for confounding factors, outcome between the groups did not differ, supporting the use of rapid response systems to identify deteriorating ward patients.

Immunoassays distinguishing between HNL/NGAL released in urine from kidney epithelial cells and neutrophils.

BACKGROUND: The distinction between monomeric human neutrophil lipocalin/neutrophil gelatinase-associated lipocalin (HNL/NGAL), secreted by injured kidney tubular cells, and dimeric HNL/NGAL, released by activated neutrophils, is important to accurately diagnose acute kidney injury (AKI). METHODS: 132 urine samples from 44 intensive care unit (ICU) patients and five urine samples from non-ICU patients with urinary tract infections (UTIs) were analyzed by two monoclonal enzyme-linked immunosorbent assays (ELISA-1 and ELISA-2). The presence of monomeric and/or dimeric HNL/NGAL in each sample was visualized by Western blotting. RESULTS: The ELISA-1 detected both monomeric and dimeric HNL/NGAL whereas the ELISA-2 almost exclusively detected dimeric HNL/NGAL with an area under the receiver-operating characteristics curve (AuROC) of 0.90. The ELISA-1/ELISA-2 ratio detected the monomeric form with an AuROC of 0.92. In 32 AKI patients, dimer-specific ELISA-2 levels decreased pre-AKI whereas the monomer-specific ELISA-1/ELISA-2 ratio gradually increased beyond AKI diagnosis. High ELISA-2 levels and/or low ELISA-1/ELISA-2 ratios detected a predominance of dimeric HNL/NGAL in urine from the patients with UTIs. CONCLUSIONS: In combination, our two ELISAs distinguish monomeric HNL/NGAL, produced by the kidney epithelium, from dimeric HNL/NGAL, released by neutrophils during AKI development, as well as reduce the confounding effect of neutrophil involvement when bacteriuria is present.

Pathogens in the lower respiratory tract of intensive care unit patients: impact of duration of hospital care and mechanical ventilation.

BACKGROUND: Ventilator-associated pneumonia (VAP), the most common hospital-acquired infection in intensive care unit (ICU) patients, is caused by bacteria in the lower respiratory tract of mechanically ventilated patients. METHODS: The current study was focused on 443 bacterial isolates from the lower respiratory tract of mechanically ventilated ICU patients (n = 346) in a Swedish University Hospital. Data were obtained from a prospective infection control database covering 9 y (2002-2010). We analysed the correlation between duration of hospital care and mechanical ventilation at the time of sampling on the occurrence of different pathogens. RESULTS: Duration of hospital care and mechanical ventilation prior to sampling was similarly short for Streptococcus pneumoniae, beta-streptococci, and Haemophilus influenzae (≤ 2 days). In contrast, duration of hospital care and mechanical ventilation were longest for Stenotrophomonas maltophilia (6 and 11 days). For Staphylococcus aureus, the most common Gram-positive isolate, the duration was longer than for S. pneumoniae but shorter than for most Gram-negative bacteria. With the exception of S. maltophilia and Pseudomonas aeruginosa, the median duration of mechanical ventilation was short and similar for most bacteria. In samples taken on the first day of mechanical ventilation, the rate of pathogens expected to be resistant to cefotaxime was 23%. CONCLUSIONS: The occurrence of pathogens with high antibiotic resistance in the lower respiratory tract increases with increased duration of hospital care and mechanical ventilation. An equally important result is that pathogens resistant to third-generation cephalosporins were more common than expected, even after a very short duration of hospital care and mechanical ventilation.

Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients.

BACKGROUND: Cystatin C is a marker of acute kidney injury (AKI). However, systemic inflammation associated with sepsis, a common AKI-trigger, may affect cystatin C. We studied the impact of sepsis on cystatin C levels in plasma. Furthermore, we investigated whether the presence of sepsis affects the predictive properties of cystatin C. METHODS: Three hundred and twenty-seven intensive care unit (ICU) patients were categorized as having: neither AKI nor sepsis (n = 151), sepsis without AKI (n = 80), AKI without sepsis (n = 24) or AKI and sepsis (n = 72) during their first week in the ICU. Changes in cystatin C and creatinine over time in patients with and without sepsis or AKI were analysed using repeated measures analysis of variance. The performance of cystatin C on admission to predict sustained AKI, worsened AKI or death was assessed from the area under the receiver-operating characteristic curve (AUC-ROC) in septic and non-septic patients separately. RESULTS: In non-AKI patients, cystatin C increased and creatinine decreased significantly over the first week. The change in cystatin C or creatinine did not differ significantly between septic and non-septic patients without AKI. Even in AKI patients, the cystatin C change did not differ significantly between septic and non-septic patients. The AUC-ROCs for prediction of the composite outcome were 0.80 and 0.78 in patients with and without sepsis, respectively, and did not differ significantly (P = 0.76). CONCLUSION: The inflammatory response induced by sepsis has no impact on the levels of cystatin C in plasma during the first week in the ICU.

The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies.

OBJECTIVES: The aim of this study was to test the hypothesis that, without diagnostic changes in serum creatinine, increased neutrophil gelatinase-associated lipocalin (NGAL) levels identify patients with subclinical acute kidney injury (AKI) and therefore worse prognosis. BACKGROUND: Neutrophil gelatinase-associated lipocalin detects subclinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function. METHODS: We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospective observational studies of NGAL. We used the terms NGAL(-) or NGAL(+) according to study-specific NGAL cutoff for optimal AKI prediction and the terms sCREA(-) or sCREA(+) according to consensus diagnostic increases in serum creatinine defining AKI. A priori-defined outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination, and duration of stay in intensive care and in-hospital. RESULTS: Of study patients, 1,296 (55.8%) were NGAL(-)/sCREA(-), 445 (19.2%) were NGAL(+)/sCREA(-), 107 (4.6%) were NGAL(-)/sCREA(+), and 474 (20.4%) were NGAL(+)/sCREA(+). According to the 4 study groups, there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(-): 0.0015% versus NGAL(+)/sCREA(-): 2.5% (odds ratio: 16.4, 95% confidence interval: 3.6 to 76.9, p < 0.001), NGAL(-)/sCREA(+): 7.5%, and NGAL(+)/sCREA(+): 8.0%, respectively, hospital mortality (4.8%, 12.4%, 8.4%, 14.7%, respectively) and their combination (4-group comparisons: all p < 0.001). There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity: NGAL(-)/sCREA(-): 4.2 and 8.8 days; NGAL(+)/sCREA(-): 7.1 and 17.0 days; NGAL(-)/sCREA(+): 6.5 and 17.8 days; NGAL(+)/sCREA(+): 9.0 and 21.9 days; 4-group comparisons: p = 0.003 and p = 0.040, respectively. Urine and plasma NGAL indicated a similar outcome pattern. CONCLUSIONS: In the absence of diagnostic increases in serum creatinine, NGAL detects patients with likely subclinical AKI who have an increased risk of adverse outcomes. The concept and definition of AKI might need re-assessment.

The deteriorating ward patient: a Swedish-Australian comparison.

OBJECTIVE: Most centres in Europe have not introduced a rapid response team (RRT), partly because of concerns that data from other health-care systems may not be relevant. We tested whether patient characteristics and outcomes for deteriorating patients differ between two health-care systems separated by distance and culture. METHODS: We obtained data from 3,063 RRT calls: 815 calls at Karolinska University Hospital (Sweden) and 2,248 calls at Austin Hospital (Australia) and compared demographic and clinical data, as well as outcomes for patients reviewed by a RRT. RESULTS: At Karolinska, 46.9% of patients were female compared with 45.1% at Austin. Mean age was 66.5 years versus 69.4 years. The unit of admission was surgical/medical in 49.1%/50.9% versus 48.8%/51.1% of patients, respectively. Overall, 56.7% versus 55.8% of the calls were out-of-hours (1700-0800 hours). There was a predominance of respiratory triggers at both centres and the "worried" criterion was frequently used in both hospitals (17.2% versus 14.4%) as a trigger for RRT activation. Overall, 30-day mortality was 27.7% versus 29.4% and allocation of Limitations of Medical Treatment (LOMT) orders was 34.2% versus 30.8%. The allocation of LOMT orders was influenced by the RRT in 14.4% versus 12.6% of cases. CONCLUSION: In two different health-care systems separated by geography, language, culture and organizational features, the characteristics of deteriorating ward patients, their disposal and outcomes were similar, suggesting that the care of the deteriorating ward patient is a global problem in modern hospitals and confirming that their hospital mortality is high.

Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury.

PURPOSE: To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock. METHODS: Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine alpha1-microglobulin. RESULTS: Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock. CONCLUSIONS: pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.

Reducing in-hospital cardiac arrests and hospital mortality by introducing a medical emergency team.

PURPOSE: To prospectively evaluate the implementation of a rapid response team in the form of a medical emergency team (MET) with regard to cardiac arrests and hospital mortality. METHODS: Prospective before-and-after trial of implementation of a MET at the Karolinska University Hospital, Stockholm, Sweden. All adult patients, apart from cardiothoracic, admitted to the hospital were regarded as participants in the study. A control period of 5 years and 203,892 patients preceded the 2-year intervention period of 73,825 patients. MAIN RESULTS: Number of MET calls was 9.3 per 1,000 hospital admissions. Cardiac arrests per 1,000 admissions decreased from 1.12 to 0.83, OR 0.74 (95% CI 0.55-0.98, p = 0.035). Adjusted for age, sex, hospital length of stay, acute/elective admission as well as co-morbidities, MET implementation was associated with a reduction in total hospital mortality by 10%, OR 0.90 (95% CI 0.84-0.97), p = 0.003. Hospital mortality was also reduced for medical patients by 12%, OR 0.88 (95% CI 0.81-0.96, p = 0.002) and for surgical patients not operated upon by 28%, OR 0.72 (95% CI 0.56-0.92, p = 0.008). FOR PATIENTS FULFILLING THE MET CRITERIA: Thirty-day mortality pre-MET was 25% versus 7.9% following MET compared with historical controls. Similarly, 180-day mortality was 37.5% versus 15.8%, respectively. CONCLUSIONS: Implementing the MET team was associated with significant improvement in both cardiac arrest rate and overall adjusted hospital mortality. Significant reductions in hospital mortality for un-operated surgical patients as well as for medical patients were also seen. Thus, introduction of the MET seemed to improve outcome for hospitalized patients.