Growing burden of sepsis-related mortality in northeastern Italy: a multiple causes of death analysis.

BACKGROUND: Few population-based data are available on mortality due to sepsis. The aim of the study was to estimate sepsis-related mortality rates and to assess the associated comorbidities. METHODS: From multiple causes of death data (MCOD) of the Veneto Region (northeastern Italy), all deaths with sepsis mentioned anywhere in the death certificate were retrieved for the period 2008-2013. Among these deaths the prevalence of common chronic comorbidities was investigated, as well as the distribution of the underlying cause of death (UCOD), the single disease selected from all condition mentioned in the certificate and usually tabulated in mortality statistics. Age-standardized mortality rates were computed for sepsis selected as the UCOD, and for sepsis mentioned anywhere in the certificate. RESULTS: Overall 16,906 sepsis-related deaths were tracked. Sepsis was mentioned in 6.3 % of all regional deaths, increasing from 4.9 in 2008 to 7.7 % in 2013. Sepsis was the UCOD in 0.6 % of total deaths in 2008, and in 1.6 % in 2013. Age-standardized mortality rates increased by 45 % for all sepsis-related deaths, and by 140 % for sepsis as the UCOD. Sepsis was often reported in the presence of chronic comorbidities, especially neoplasms, diabetes, circulatory diseases, and dementia. Respiratory tract and intra-abdominal infections were the most frequently associated sites of infection. CONCLUSIONS: MCOD analyses provide an estimate of the burden of sepsis-related mortality. MCOD data suggest an increasing importance attributed to sepsis by certifying physicians, but also a real increase in mortality rates, thus confirming trends reported in some other countries by analyses of hospital discharge records.

State of the art in the clinical treatment of endotoxic shock.

Sepsis is a major health problem and remains an important cause of death worldwide. The failure to convert advances in our understanding of the biologic features of sepsis into effective new therapies questions the current approach to the development of sepsis drugs, and suggests a need for newer and better clinical trial design. Blood purification for sepsis is a promising therapeutic strategy to improve survival and reduce organ failure in patients with severe sepsis and septic shock.

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury.

INTRODUCTION: In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. METHODS: We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression. RESULTS: Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001). CONCLUSIONS: In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.

Fluid management in the intensive care unit: bioelectrical impedance vector analysis as a tool to assess hydration status and optimal fluid balance in critically ill patients.

BACKGROUND: Fluid balance disorders are a relevant risk factor for morbidity and mortality in critically ill patients. Volume assessment in the intensive care unit (ICU) is thus of great importance, but there are currently few methods to obtain an accurate and timely assessment of hydration status. Our aim was to evaluate the hydration status of ICU patients via bioelectric impedance vector analysis (BIVA) and to investigate the relationship between hydration and mortality. METHODS: We evaluated 280 BIVA measurements of 64 patients performed daily in the 5 days following their ICU admission. The observation period ranged from a minimum of 72 h up to a maximum of 120 h. We observed the evolution of the hydration status during the ICU stay in this population, and analyzed the relationship between mean and maximum hydration reached and mortality--both in the ICU and at 60 days--using logistic regression. RESULTS: A state of overhydration was observed in the majority of patients (70%) on admission, which persisted during the ICU stay. Patients who required continuous renal replacement therapy (CRRT) were more likely to be overhydrated starting from the 2nd day of observation. Logistic regression showed a strong and significant correlation between mean/maximum hydration reached and mortality, both independently and correcting for severity of prognosis. CONCLUSIONS: Fluid overload measured by BIVA is a frequent condition in critically ill patients--whether or not they undergo CRRT--and a significant predictor of mortality. Hence, hydration status should be considered as an additional prognosticator in the clinical management of the critically ill patient. KEY MESSAGES: (i) On the day of ICU admittance, patients showed a marked tendency to overhydration (>70% of total). This tendency was more pronounced in patients on CRRT. (ii) Hyperhydration persisted during the ICU stay. Patients who underwent CRRT showed significantly higher hyperhydration from the 2nd day of hospitalization. (iii) Nonsurvivors showed worse hyperhydration patterns in comparison to survivors in logistic univariate analysis (p < 0.05). This relationship between hydration and mortality is confirmed even when controlling for the effect of a worse prognosis approximated by any of three ICU scoring systems (APACHE II, SAPS II and SOFA). Mean and maximum hydration levels present a stronger correlation with mortality than with mean and maximum cumulative fluid balance reached during the observation period.

Extracorporeal carbon dioxide removal: the future of lung support lies in the history.

Extracorporeal organ support in patients with dysfunction of vital organs like the kidney, heart, and liver has proven helpful in bridging the patients to recovery or more definitive therapy. Mechanical ventilation in patients with respiratory failure, although indispensable, has been associated with worsening injury to the lungs, termed ventilator-induced lung injury. Application of lung-protective ventilation strategies are limited by inevitable hypercapnia and hypercapnic acidosis. Various alternative extracorporeal strategies, proposed more than 30 years ago, to combat hypercapnia are now more readily available. In particular, the venovenous approach to effective carbon dioxide removal, which involves minimal invasiveness comparable to renal replacement therapy, appears to be very promising. The clinical applications of these extracorporeal carbon dioxide removal therapies may extend beyond just lung protection in ventilated patients. This article summarizes the rationale, technology and clinical application of various extracorporeal lung assist techniques available for clinical use, and some of the future perspectives in the field.

RIFLE-based data collection/management system applied to a prospective cohort multicenter Italian study on the epidemiology of acute kidney injury in the intensive care unit.

The epidemiology of acute kidney injury (AKI) has been difficult to explore in the past, due to different definitions across various studies. Nevertheless, this is a very important topic today in light of the high morbidity and mortality of critically ill patients presenting renal dysfunction during their stay in the intensive care unit (ICU). The case mix has changed over the years, and AKI is a common problem in critically ill patients often requiring renal replacement therapy (RRT). The RIFLE and AKIN initiatives have provided a unifying definition for AKI, making possible large retrospective studies in different countries. The present study aims at validating a unified web-based data collection and data management tool based on the most recent AKI definition/classification system. The interactive database is designed to elucidate the epidemiology of AKI in a critically ill population. As a test, we performed a prospective observational multicenter study designed to prospectively evaluate all incident admissions in ten ICUs in Italy and the relevant epidemiology of AKI. Thus, a simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive incident patients into the study; 25 patients with end-stage renal disease were excluded, leaving 576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 (IQR 3-14) days. Of 576 patients, 246 patients (42.7%) had AKI within 24 h of ICU admission, while 133 developed new AKI later during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75 (19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis during their ICU stay, compared to 33 (16.7%) of non-AKI patients (p < 0.001). 48 patients (8.3%) were treated with RRT in the ICU. Patients were started on RRT a median of 2 (IQR 0-6) days after ICU admission. AKI patients were started on RRT a median of 1 (IQR 0-4) day after fulfilling criteria for AKI. Median duration of RRT was 5 (IQR 2-10) days. AKI patients had a higher crude ICU mortality (28.8 vs. 8.1%, non-AKI; p < 0.001) and longer ICU length of stay (median 7 vs. 3 days, non-AKI; p < 0.001). Crude ICU mortality and ICU length of stay increased with greater severity of AKI. 225 (59.4% of AKI patients) had complete recovery of renal function, with a serum creatinine at time of ICU discharge which was ≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not recovered renal function at the time of death or ICU discharge. The study supports the use of RIFLE as an optimal classification system to stage AKI severity. AKI is indeed a deadly complication for ICU patients, where the level of severity is correlated with mortality and length of stay. The tool developed for data collection was user-friendly and easy to implement. Some of its features, including a RIFLE class alert system, may help the treating physician to systematically collect AKI data in the ICU and possibly may guide specific decisions on the institution of RRT.

Oxidative stress and 'monocyte reprogramming' in septic patients with acute kidney injury requiring CRRT.

Oxidative stress (OS) and monocyte HLA-DR expression are known to be predictive of mortality in sepsis; nevertheless, limited information exists regarding sepsis with acute kidney injury (AKI). The aim of the study was to correlate these markers with outcome in septic patients with AKI requiring continuous renal replacement therapy (CRRT). Advanced oxidation protein products (AOPP) were measured in 32 patients on days 1, 3, 7, 14, 21, and 28. In 14 we assessed the percentage of monocytes expressing HLA-DR (%DR+) and the HLA-DR mean fluorescence intensity (MFI). 20 healthy volunteers, 17 septic patients without AKI and 20 septic AKI patients not treated by CRRT were used for comparison. The mortality rate was 59%. Septic CRRT patients had higher AOPP and lower %DR+ (p < 0.001, both) than healthy controls. They also had higher AOPP than septic patients who did not develop AKI (p < 0.001). No difference was found in AOPP, %DR+ and MFI between survivors and non-survivors (day 1 and subsequent measurements). No correlation was seen between severity scores and OS/HLA-DR. OS and HLA-DR expression are altered in septic patients with AKI undergoing CRRT. However, this study was not able to confirm the usefulness of these markers in predicting survival in this subset of patients.

Early isovolaemic haemofiltration in oliguric patients with septic shock.

OBJECTIVE: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock. DESIGN: Retrospective study before and after a change of unit protocol (study period 8 years). SETTING: Intensive care unit of metropolitan hospital. PATIENTS: Eighty patients with septic shock. INTERVENTIONS: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged. MEASUREMENTS AND MAIN RESULTS: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002). CONCLUSIONS: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy.

Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival.

INTRODUCTION: Severe sepsis is the leading cause of mortality in critically ill patients. Abnormal concentrations of inflammatory mediators appear to be involved in the pathogenesis of sepsis. Based on the humoral theory of sepsis, a potential therapeutic approach involves high-volume haemofiltration (HVHF), which has exhibited beneficial effects in severe sepsis, improving haemodynamics and unselectively removing proinflammatory and anti-inflammatory mediators. However, concerns have been expressed about the feasibility and costs of continuous HVHF. Here we evaluate a new modality, namely pulse HVHF (PHVHF; 24-hour schedule: HVHF 85 ml/kg per hour for 6-8 hours followed by continuous venovenous haemofiltration 35 ml/kg per hour for 16-18 hours). METHOD: Fifteen critically ill patients (seven male; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score 31.2, mean Simplified Acute Physiology Score [SAPS] II 62, and mean Sequential Organ Failure Assessment 14.2) with severe sepsis underwent daily PHVHF. We measured changes in haemodynamic variables and evaluated the dose of noradrenaline required to maintain mean arterial pressure above 70 mmHg during and after pulse therapy at 6 and 12 hours. PHVHF was performed with 250 ml/min blood flow rate. The bicarbonate-based replacement fluid was used at a 1:1 ratio in simultaneous pre-dilution and post-dilution. RESULTS: No treatment was prematurely discontinued. Haemodynamics were improved by PHVHF, allowing a significant reduction in noradrenaline dose during and at the end of the PHVHF session; this reduction was maintained at 6 and 12 hours after pulse treatment (P = 0.001). There was also an improvement in systolic blood pressure (P = 0.04). There were no changes in temperature, cardiac index, oxygenation, arterial pH or urine output during the period of observation. The mean daily Kt/V was 1.92. Predicted mortality rates were 72% (based on APACHE II score) and 68% (based on SAPS II score), and the observed 28-day mortality was 47%. CONCLUSION: PHVHF is a feasible modality and improves haemodynamics both during and after therapy. It may be a beneficial adjuvant treatment for severe sepsis/septic shock in terms of patient survival, and it represents a compromise between continuous renal replacement therapy and HVHF.

In vivo validation of the adequacy calculator for continuous renal replacement therapies.

INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (KCALC). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (KDEL) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT.

A new machine for continuous renal replacement therapy: from development to clinical testing.

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

Utilization of small changes in serum creatinine with clinical risk factors to assess the risk of AKI in critically lll adults.

BACKGROUND AND OBJECTIVES: Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient's clinical course. We set out to assess the performance of this combination approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1-0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit. RESULTS: Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001). CONCLUSION: Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.

Continuous real-time urine output monitoring for early detection of acute kidney injury.

In critically ill patients, acute kidney injury (AKI) is a common complication. In some cases, oliguria may be the only sign verifying this condition. The consensus definitions of RIFLE and AKIN are based on changes in creatinine and urine output and define classes of severity within AKI. While meaningful change in serum creatinine is often not detectable until 48 h after deterioration in kidney function, urine output is a more rapid physiological parameter and detectable at the patient's bedside. Although urine output is a critical parameter in the intensive care unit, routine urine output measurements are performed manually. As a result, they may not be done timely and may be subject to inaccuracies due to human factors. The URINFO(®) system is an innovative digital urine meter that provides continuous minute-to-minute monitoring of urine output, thereby enhancing kidney monitoring and the acquisition of more reliable urine output information in realtime. Consequently, monitoring of urine output with URINFO may enable rapid therapeutic interventions and can be incorporated into patient data systems, thereby improving therapy management.

B-type natriuretic Peptide in the critically ill with acute kidney injury.

Introduction. Acute kidney injury (AKI) is common in the intensive care unit (ICU) and associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to myocardial overload, and is elevated in some ICU patients. There is a high prevalence of both cardiac and renal dysfunction in ICU patients. Aims. To investigate whether plasma BNP levels in the first 48 hours were associated with AKI in ICU patients. Methods. We studied a cohort of 34 consecutive ICU patients. Primary outcome was presence of AKI on presentation, or during ICU stay. Results. For patients with AKI on presentation, BNP was statistically higher at 24 and 48 hours than No-AKI patients (865 versus 148 pg/mL; 1380 versus 131 pg/mL). For patients developing AKI during 48 hours, BNP was statistically higher at 0, 24 and 48 hours than No-AKI patients (510 versus 197 pg/mL; 552 versus 124 pg/mL; 949 versus 104 pg/mL). Conclusion. Critically ill patients with AKI on presentation or during ICU stay have higher levels of the cardiac biomarker BNP relative to No-AKI patients. Elevated levels of plasma BNP may help identify patients with elevated risk of AKI in the ICU setting. The mechanism for this cardiorenal connection requires further investigation.

Rationale of extracorporeal removal of endotoxin in sepsis: theory, timing and technique.

Several signs and symptoms in sepsis are due to the presence of endotoxin in the circulation. Both in animal and human models, there is an evident immunological response to the endotoxin insult. Furthermore, altered cardiovascular function, lung dysfunction and acute kidney injury are common in sepsis and endotoxemia. In these circumstances it would be extremely important to identify patients with sepsis in the early phases and to characterize the humoral alterations involved with it, including the identification and quantification of circulating endotoxin. Once this is obtained, it seems logical to try to remove as much of the circulating endotoxin as possible in order to mitigate the clinical effects of this condition. This can be achieved today with a very specific hemoperfusion process utilizing cartridges with immobilized polymixin B in an extracorporeal circuit. This approach seems to provide a significant removal of endotoxin with a significant reduction of its circulating levels. The clinical consequences of this approach can be summarized in a mitigation of the septic cascade in the early phases, with improvement of outcome. Recent clinical results seem to confirm these expectations showing a reduction of mortality in patients with early signs of abdominal sepsis due to recent surgery. This opens a new avenue for intervention in sepsis.

Polymyxin-B hemoperfusion and endotoxin removal: lessons from a review of the literature.

Sepsis involves a complex interaction between bacterial toxins and the host immune system. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis producing proinflammatory cytokines and activating the complement system, and is thus an ideal potential therapeutic target. Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-F) has been shown to bind and neutralize endotoxin in both in vitro and in vivo studies. Therefore, this extracorporeal therapy with PMX-F can potentially interrupt the biological cascade of sepsis. A systematic review of the published literature found positive effects of PMX-F on blood pressure and dopamine/dobutamine use, the PaO(2)/FiO(2) ratio, endotoxin removal, and mortality. It should be noted, however, that many of the analyzed studies were of suboptimal quality, which may then exaggerate the magnitude of these effects. Since this meta-analysis, other studies have been published including a multicenter randomized controlled trial on abdominal septic shock. In this study, PMX-F, when added to conventional therapy, significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in this targeted population. There is clear biological rationale for endotoxin removal in the clinical management of severe sepsis and septic shock. The current literature seems to provide some support for this premise, and provides the basis for further rigorous study.

Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population.

PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) is a useful marker for acute kidney injury (AKI), particularly when the timing of renal insult is known. However, its performance in an adult critical care setting has not been well described. We performed this study to estimate the diagnostic accuracy of plasma NGAL for early detection of AKI and need for renal replacement therapy (RRT) in an adult intensive care unit (ICU). METHODS: We enrolled 307 consecutive adult patients admitted to a general medical-surgical ICU; 301 were included in the final analysis. Serial blood samples were analyzed for plasma NGAL using a standardized clinical platform. The primary outcome was AKI, defined as an increase in creatinine of at least 50% from baseline or a reduction in urine output to <0.5 ml/kg/h for >6 h. RESULTS: Of 301 patients, 133 (44%) had AKI during their ICU stay. Plasma NGAL was a good diagnostic marker for AKI development within the next 48 h (area under ROC 0.78, 95% CI 0.65-0.90), and for RRT use (area under ROC 0.82, 95% CI 0.70-0.95). Peak plasma NGAL concentrations increased with worsening AKI severity (R = 0.554, P < 0.001). CONCLUSIONS: Plasma NGAL is a useful early marker for AKI in a heterogeneous adult ICU population, in which the timing of renal insult is largely unknown. It allows the diagnosis of AKI up to 48 h prior to a clinical diagnosis based on AKI consensus definitions. Additionally, it predicts need for RRT and correlates with AKI severity. Early identification of high risk patients may allow potentially beneficial therapies to be initiated early in the disease process before irreversible injury occurs.

Extracorporeal CO2 removal--a way to achieve ultraprotective mechanical ventilation and lung support: the missing piece of multiple organ support therapy.

Extracorporeal therapies are able to sustain life through different mechanisms. This approach, called multiple organ support therapy, can in fact obtain blood purification by hemodialysis/hemofiltration to replace kidney function, temperature control, electrolyte and acid-base control to mimic homeostatic regulation of the kidney and circulation, fluid balance control to support the right hydration and cardiac performance, cardiac support removing cardiodepressant substances and equilibrating potassium levels, blood detoxification and liver support by coupled plasma filtration and adsorption or direct adsorption on blood (hemoperfusion), immunomodulation and endothelial support in the presence of sepsis by cutting the peaks of pro- and anti-inflammatory mediators, and immunoadsorption or adsorption of specific substances such as endotoxin. A missing piece of this group of therapies was the protective lung support. Today this is made possible by removal of CO(2) either by complete extracorporeal membrane oxygenation or by using decapneization in conjunction with hemofiltration in a system called DECAP/DECAPSMART. In conclusion, circulating blood outside the body and treating it with different filters or cartridges in a multiple organ support therapy may represent an important support for multiple organ dysfunction conditions induced by sepsis, acute respiratory distress syndrome and in recent times by complicated H1N1-related infections.

Renal replacement therapy in adult critically ill patients: when to begin and when to stop.

Renal replacement therapy (RRT) is an important therapeutic and supportive measure for acute kidney injury (AKI) in the critical care setting. While RRT is extensively used in clinical practice, there remains uncertainty about the ideal circumstances of when to initiate RRT and for what indications. Many factors, including logistics, resource availability, physician experience and patient-related factors are involved in the decision of when to start and stop RRT for those with AKI. Among the patient-related factors, examples include 'dynamic' trends in AKI and/or non-kidney organ dysfunction, additional measures of acute physiology, such as fluid accumulation and relative oliguria. There currently exists a large variation in clinical practice regarding starting and stopping RRT, due in part to the lack of consensus on this issue. In this article, we briefly review a new opinion-based algorithm to aid in the decision on when to initiate RRT in adult critically ill patients. This algorithm was developed using available clinical evidence, recognizing the inherent limitations of observational studies. It aims to provide a starting point for clinicians and future prospective studies. We also review the available literature on discontinuation of RRT and propose a few simple recommendations on how to 'wean' patients from RRT.