Search

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 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.

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.

Introduction Oxidative stress (OS) is an imbalance between the production of oxidizing chemical species and the antioxidant defense. It is known that OS increases in critically ill patients with acute kidney injury (AKI). Measurement of advanced oxidation protein products (AOPPs) has been found to be a simple tool for monitoring OS. Aims The aims of this study were to evaluate OS in intensive care unit (ICU) patients by AOPP levels and compare its levels between patients with and without AKI; we also wanted to assess the ability of AOPP to predict the development of AKI in this population. Patients, Material, and Methods We performed a prospective cohort study to compare AOPP levels between critically ill AKI (as defined by Risk-Injury-Failure-Loss-End Stage Renal Disease [RIFLE] criteria) and non-AKI patients. Blood samples were collected from all consecutively admitted patients upon arrival to ICU and daily for up to 4 days. We collected 234 blood samples from 86 adult medical and surgical ICU patients. The levels of AOPP were determined in the plasma and measured by spectrophotometry at 340 nm and compared between non-AKI (n = 71) and AKI patients (n = 15). We further subdivided the AKI patients according to severity of AKI (worst RIFLE class attained in ICU). Results Among the 86 patients, 15 (17.44%) developed AKI during their stay in ICU, whereas 71 patients (82.56%) did not. Among the AKI patients, 5 had AKI on ICU admission, whereas 10 developed it later. The levels of AOPP were significantly higher among AKI patients compared with non-AKI patients (153.8 ± 117.8 versus 129.0 ± 114.9 μmol/L, respectively; P = .034). Patients with the most severe AKI (RIFLE class Failure) had markedly elevated AOPP levels compared with RIFLE class Risk and Injury patients (P = .012). Area under the curve of receiver operating characteristic for prediction of AKI within 48 hours after first blood sample collection was 0.5835 (P = not significant). Conclusions This is the first study to explore the relationship between severity of AKI and AOPP. In our adult ICU population, AOPP levels were higher in AKI compared with non-AKI critically ill patients. On the other hand, AOPP levels were not found to be a useful biomarker for AKI, as it was unable to identify patients who developed AKI within 24, 48, 76, and 96 hours.

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 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

The selection of appropriate outcome measures is essential to the design of clinical trials of the prevention or treatment of acute renal failure in critically ill patients. In this paper, we present the consensus opinion from the second Acute Dialysis Quality Initiative Conference held in Vicenza, Italy, in May 2002, regarding the issues that should guide the selection of endpoints in clinical intervention trials of acute renal failure. Important criteria for the selection of these outcome measures include their clinical importance, responsiveness to experimental intervention, precision of definition, accuracy of measurement, and completeness of ascertainment. Although the most appropriate endpoints for individual studies are dependent on specific hypotheses and study designs, the primary endpoint in prevention trials should be based on an assessment of renal function, whereas mortality or renal functional assessment may serve as the primary endpoint in studies of established acute renal failure.

Objective: To test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. Design: Prospective, pilot, crossover clinical trial. Setting: General intensive care unit in a teaching hospital. Subjects: Ten patients with hyperdynamic septic shock. Interventions: Patients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor- (TNF-) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF- production from normal human adherent monocytes incubated with patients’ plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. Results: Mean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p .001). There was an average decrease of norepinephrine requirement of 0.08 g/kg/min with treatment A and 0.0049 g/ kg/min with treatment B (p .003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF- production from patients’ whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p .009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF- by 1 10 6 cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p .019) and after incubation with anti-interleukin-10 monoclonal antibodies (p .028). Conclusions: In patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock. (Crit Care Med 2002; 30:1250 ‐1255)

Acute kidney injury is a frequent condition affecting critical patients. It is the clinician’s responsibility to decide when it is best to initiate diuretic therapy and also which molecule to use and at what dosage. Such decision is based on a previous evaluation of the patient’s volemic state and in consideration of the many difficulties that such an assessment presents when dealing with a critical patient. The clinician must finally be aware of the side effects of ongoing diuretic therapy in order to identify them and solve any related problem.

In response to the tragic situation of many people dying because of end-stage failure of a vital organ, a regulated infl ation of organ waiting lists has developed unevenly in diff erent countries, which has been reported (probably counterproductively) in newspapers. We believe that such list infl ation might be detrimental for the longterm availability of organ transplantation worldwide. We also believe that the defi nition of the threshold level for every waiting list, the length of waiting lists, and the consequent mismatch between needed and available organs are not only biomedical constructs but are also, a social construct. Accordingly, we contend that these waiting lists should be maintained below an agreed threshold level and propose three criteria that could help to establish such a level. In 1968, the Ad Hoc Committee of the Harvard Medical School claimed that a compelling reason for their eff ort to “defi ne irreversible coma as a new criterion for death” was to reduce “controversy in obtaining organs for transplantation”. Organ shortage is also the main reason for the resurgence and diff usion of protocols of donation after circulatory determination of death. Papers on transplantation, donor identifi cation, and organ donation complain that there is a universal shortage of organs and a huge number of people waiting for an organ. These claims recently received wide public attention when Forbes magazine revealed that “over 3400 Californians were waiting for a new liver in 2009. Only 671 got one. 400 died”. Such reports are indicative of the tragic situation of many people dying because of end-stage failure of a vital organ and they also cause societal concern and motivate governments to increase their commitment to organ donation. Despite their widely accepted face validity, we believe that waiting lists deserve deeper consideration. Crucially, not all the patients on waiting lists are actually eligible for transplantation. As reported by The Washington Post, with data from the United Network for Organs Sharing (table 1), “of 97 772 patients on the waiting list...nearly 26 percent of those needing livers... nearly 69 percent of those waiting for a pancreas...[and] nearly 33 percent of those waiting for kidneys...were inactive”. Obviously, some inactivity is inevitable: listed patients might become temporarily ineligible because of infection, intercurrent diseases, or personal or family problems. Yet, The Washington Post claimed that according to reported data “more than 55 percent of the patients on the list for hearts, and nearly 49 percent waiting for livers, had been inactive for more than two years. Nearly half of those waiting for kidneys had been inactive for at least a year—and nearly a third for more than two years...In some cases, evaluations of patients’ suitability for a transplant were never completed...[as in] more than 36 percent of kidney transplant candidates”. How can this happen? The Washington Post suggested that “the size of the list is often used in lobbying eff orts to seek funding or to change organ-procurement policies. Donation advocates are campaigning to revise state laws to make it easier to obtain organs in ways some say may sacrifi ce the needs of dying patients and their families”. If these comments are true, even if only in part and even if they do not change the basic problem (patients in need are many more than available organs), they indicate an undesirable development. Clearly, identifi cation of patients who are fully eligible for transplantation seems essential from many points of view.

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.

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.

Il problema dell’insufficienza renale acuta tocca frequentemente il paziente critico e sta al clinico stabilire il momento adatto per iniziare la terapia diuretica, con quale molecola e con quale dosaggio. Tali considerazioni si basano sul preventivo giudizio sullo stato volemico del paziente con tutte le difficolta che pone tale valutazione in un paziente critico. Per ultimo, ma non meno importante, il clinico deve essere consapevole degli effetti collaterali della terapia diuretica in corso in modo da poterli identificare e porvi rimedio.

Purpose. Strategies for volume assessment of critically ill patients are limited, yet early goal-directed therapy improves outcomes. Central venous pressure (CVP), Bioimpedance Vectorial Analysis (BIVA), and brain natriuretic peptide (BNP) are potentially useful tools. We studied the utility of these measures, alone and in combination, to predict changing oxygenation.Methods. Thirty-four mechanically ventilated patients, 26 of whom had data beyond the first study day, were studied. Relationships were assessed between CVP, BIVA, BNP, and oxygenation index (O2I) in a cross-sectional (baseline) and longitudinal fashion using both univariate and multivariable modeling.Results. At baseline, CVP and O2I were positively correlated (R=0.39;P=.021), while CVP and BIVA were weakly correlated (R=-0.38;P=.025). The association between slopes of variables over time was negligible, with the exception of BNP, whose slope was correlated with O2I (R=0.40;P=.044). Comparing tertiles of CVP, BIVA, and BNP slopes with the slope of O2I revealed only modest agreement between BNP and O2I (kappa=0.25;P=.067). In a regression model, only BNP was significantly associated with O2I; however, this was strengthened by including CVP in the model.Conclusions. BNP seems to be a valuable noninvasive measure of volume status in critical care and should be assessed in a prospective manner.

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.

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.

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 (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.

Acute kidney injury (AKI) and fluid overload are conditions that require an early diagnosis and a prompt intervention. The recognition of these pathologic conditions is possible in the early stages if specific signs and symptoms are taken into account. Among them, oliguria represents an important sign. Reduced urine output for a certain number of hours may be an important sign of kidney dysfunction. This must be evaluated in conjunction with other factors such as hydration status and use of drugs. At the same time, traditional markers of kidney function such as urea nitrogen and creatinine must be evaluated in light of a possible altered balance. Increased levels may be due to reduced kidney function but also increased generation or altered solute distribution space due to non-optimal hydration status. Finally, novel biomarkers for renal tissue damage are becoming popular. Molecules such as NGAL or cystatin C may become altered well before creatinine or oliguria signal a condition of reduced kidney function. Here, the difference between insult and dysfunction becomes evident. Novel biomarkers seem to enable the clinician to make early diagnosis of kidney damage, distinguishing between AKI and acute kidney failure. Reduced glomerular filtration rate is, in fact, a late event in the continuum of the AKI syndrome.

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/hemofiltrati

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.

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 PaO2/FiO2 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.

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.

Acute kidney injury (AKI) and fluid overload are conditions that require an early diagnosis and a prompt intervention. The recognition of these pathologic conditions is possible in the early stages if specific signs and symptoms are taken into account. Among them, oliguria represents an important sign. Reduced urine output for a certain number of hours may be an important sign of kidney dysfunction. This must be evaluated in conjunction with other factors such as hydration status and use of drugs. At the same time, traditional markers of kidney function such as urea nitrogen and creatinine must be evaluated in light of a possible altered balance. Increased levels may be due to reduced kidney function but also increased generation or altered solute distribution space due to non-optimal hydration status. Finally, novel biomarkers for renal tissue damage are becoming popular. Molecules such as NGAL or cystatin C may become altered well before creatinine or oliguria signal a condition of reduced kidney function. Here, the difference between insult and dysfunction becomes evident. Novel biomarkers seem to enable the clinician to make early diagnosis of kidney damage, distinguishing between AKI and acute kidney failure. Reduced glomerular filtration rate is, in fact, a late event in the continuum of the AKI syndrome.

This chapter's objectives are to present the main bioethical problems associated with the management of renal replacement therapy (RRT) in critically ill patients; to discuss a strategy, based on moral principles, for guiding the decision-making process; to present a protocol to guide a practical possible approach to difficult decisions in critically ill patients; to present and discuss some of the problems associated with clinical research in RRT in critically ill patients and finally to present some biosocial issues related to RRT.

Background. Several controversies have developed over acute renal failure (ARF) definition and treatment: which approach to patient care is most desirable and which form of renal replacement therapy (RRT) should be applied is an everyday matter of debate. There is also disagreement on clinical practice for RRT including the best timing to start, vascular access, anti-coagulation, membranes, equipment and finally, if continuous or intermittent techniques should be preferred. In this lack of harmony, the epidemiology of ARF has recently displayed an outbreak of cases in the intensive care units and nephrologists and intensivists are now called to work together in the case of such a syndrome. Subjects and methods. We report on the responses of 560 contributors, mostly coming from Europe, to a questionnaire submitted during the third International Course on Critical Care Nephrology held in Vicenza, Italy in June 2004. The questionnaire was divided into several sections concerning demographic and medical information, definition of ARF, practice of RRT, current opinions about clinical advantages and problems related to different RRTs and modalities, and beliefs on alternative indications to extracorporeal treatments. Results. More then 200 different definitions of ARF and about 90 RRT start criteria were reported. Oliguria and RIFLE (an acronym classifying ARF in different levels of severity: Risk of renal dysfunction; Injury to the kidney; Failure of kidney function; Loss of kidney function; End-stage kidney disease.) were the most frequent criteria used to define ARF. In 10% of centres all forms of renal replacement techniques are available, and in 70% of cases two or more different techniques are available: absolute analysis of different techniques showed that continuous renal replacement therapies are utilized by 511 specialists (91%), intermittent haemodialysis by 387 (69%) and sustained low efficiency dialysis by 136 (24%). Treatment prescription showed significant differences among specialists, 60% of intensivists being uncertain on RRT dose prescription compared to 40% of nephrologists (P ¼ 0.002). The most frequently selected dosage was ‘35 ml/kg/h’ for urea (25%) and creatinine targets (26%), and ‘2–3 l/h’ for the septic dose (25%). Of the participants, 90% said that they used RRT for non-renal indications, 60% although responders admitted the lack of scientific evidence as a limiting factor to its use. Conclusions. New classifications such as RIFLE criteria might improve well-known uncertainty about ARF definition. Different RRT techniques are available in most centres, but a general lack of treatment dose standardization is noted by our survey. Non-renal indications to RRT still need to find a definitive role in routine practice.

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).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.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%.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.

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.

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.

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

Evolution in the field of hemodialysis has led to a parallel development of new systems for acute renal replacement therapy in the intensive-care patients (1). The use of new devices and machines, together with a better understanding of the underlying mechanisms of solute and water removal in continuous renal replacement therapies (CRRT), have made it possible to achieve higher levels of efficiency and clinical tolerance. The first objective has been reached by increasing the automation of the extracorporeal circuits and the setting of operational levels at higher levels; the second has been reached by means of a new generation of monitoring techniques and new machines equipped with specific interfaces and alarms (2–4). A brief review of the evolution and the most recent technology available in the field of CRRT is presented in this chapter.

Objective: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT).¶Design: A questionnaire.¶Setting: The First International Course on Critical Care Nephrology.¶Participants: The participants in the course (around 500).¶Results: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55 % believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a “first-come, first-served” basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU.¶Conclusions: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.

Adsorption in sepsis. The pathophysiology of sepsis offers a highly complicated scenario. In sepsis, endotoxin or other gram-positive–derived products induce a complex and dynamic cellular response, giving rise to several mediators known to be relevant in the pathogenesis of septic shock such as specific mediators, substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of translational or transductional pathways, and precursor molecules. In this review, we delve into some new concepts stemming up from the use of sorbents in continuous plasma filtration. Nonspecific simultaneous removal of several mediators of the inflammatory cascade have led to improved outcomes in animal models of septic shock and to improved hemodynamics in a pilot clinical study. It seems of great importance to explore all possible treatment techniques that may have a direct impact on circulating mediators of sepsis and that also may interfere with the imbalance between proinflammatory and anti-inflammatory substances in the critically ill patient with multiple organ failure. In this view, the application of sorbents appears to open new and interesting therapeutic options. The search for innovative treatments specifically targeted to the special needs of the critically ill patients seems therefore more important than the attempt to adjust concepts and technologies that are normally applied to patients with chronic renal failure.

Use of adsorptive mechanisms in continuous renal replacement therapies in the critically ill. The pathophysiology of sepsis is becoming a more complicated scenario. In sepsis, endotoxin or other gram-positive derived products induce a complex and dynamic cellular response giving rise to several mediators known to be relevant in the pathogenesis of septic shock, such as specific mediators, substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of nuclear factor B or signal transduction pathways, and precursor molecules. In this article, we delve into some new concepts stemming from the use of sorbents in continuous plasma filtration. The rationale is based on the assumption that the nonspecific removal of several mediators of the inflammatory cascade and cytokine network may improve outcome in a rabbit model of septic shock and hemodynamics in a pilot clinical study. The importance of looking for innovative treatments specifically targeted for the special needs of the critically ill patients rather than using concepts and technology applied to the treatment of chronic renal failure is underlined.

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P