Validation of a Protocol for Continuous Hemodiafiltration with Regional Citrate Anticoagulation with Omni®.

INTRODUCTION: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). METHODS: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and ß2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. RESULTS: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and ß2-microglobulin across the entire duration of circuit lifetime. CONCLUSION: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible.

Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial.

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.

Comparison of the Accuracy of the Novel PrisMax Continuous Renal Replacement Therapy System to the Classic Prismaflex System.

BACKGROUND/AIMS: We assessed how the novel PrisMax continuous renal replacement therapy (CRRT) system performed in an international multicentre setting. The system has multiple novel tools aiming to increase accuracy and dose delivery. METHODS: Data was prospectively collected from 7 intensive care units in 6 countries. The PrisMax device data logs constituted the raw material and last generation Prismaflex data was used as comparison. Clinical parameters like treatment time, filter life span, downtime as well as prescribed and delivered dose were recorded. RESULTS: PrisMax delivered/prescribed effluent ratios (mean ± SD) 0.92 ± 0.15 vs. Prismaflex ratios 0.85 ± 0.21, p < 0.001; delivered effluent dose (mL/kg/h) was 18.16 ± 12.93 vs. 10.95 ± 10.96, p < 0.0001; and (Kt/V) 0.76 ± 0.52 vs. 0.44 ± 0.44, p < 0.0001. Moreover, downtime was 27 minutes less for the newer device. CONCLUSION: The PrisMax CRRT device outperforms its predecessor with regard to dose delivery and accuracy.

Renal Replacement Therapy Modality in the ICU and Renal Recovery at Hospital Discharge.

OBJECTIVES: Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge. DESIGN: Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database. SETTING: Two hundred ninety-one ICUs in France. PATIENTS: A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958. CONCLUSIONS: In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited.

Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter Propensity Analysis.

OBJECTIVE: Recent preclinical and clinical data suggest that thoracic epidural analgesia, a technique primarily aimed at decreasing pain, might exert anti-inflammatory effects, enhance splanchnic and pancreatic blood flow during acute pancreatitis; however, the influence of epidural analgesia on mortality remains under investigated in this setting. This study was therefore designed to assess the impact of epidural analgesia on mortality in ICU patients with acute pancreatitis. DESIGN: Multicenter retrospective, observational, cohort study. SETTING: Seventeen French and Belgian ICUs. PATIENTS: All patients admitted to with acute pancreatitis between June 2009 and March 2014. INTERVENTIONS: The primary exposure was thoracic epidural analgesia versus standard care without epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances. MEASUREMENTS AND MAIN RESULTS: One thousand three ICU patients with acute pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia was used in 46 patients and was associated with reduced mortality in unadjusted analyses (4% vs. 22%; p = 0.003). After adjustment for baseline variables associated with mortality, epidural analgesia was still an independent predictor of 30-day mortality (adjusted odds ratio, 0.10; [95% CI, 0.02-0.49]; p = 0.004). Using propensity score analysis, the risk of all-cause 30-day mortality in patients with acute pancreatitis receiving epidural analgesia was significantly lower than that in matched patients who did not receive epidural analgesia (2% vs. 17%; p = 0.01). CONCLUSIONS: Among critically ill patients with acute pancreatitis, mortality at 30 days was lower in patients who received epidural analgesia than in comparable patients who did not. These findings support ongoing research on the use of epidural analgesia as a therapeutic intervention in acute pancreatitis.

Optimizing continuous renal replacement therapy in the ICU: a team strategy.

PURPOSE OF REVIEW: The consideration of acute kidney injury, its incidence and its impact on the outcome of patients has grown continuously in recent years, leading to an increase in the use of renal replacement therapy (RRT) techniques. However, the successful conduct of RRT depends on the effectiveness of the entire team, doctors and nurses. It is therefore important to know the essential elements to be implemented in the ICU to ensure optimal RRT. RECENT FINDINGS: Recent studies show that the successful conduct of a RRT session requires a good knowledge of the principles of the technique, regular basic training, identification of experts, drafting clear and well followed protocols and good communication between the various stakeholders. In addition, the use of the latest advances, such as regional citrate anticoagulation, allows further optimization of therapy, only if, again, both physicians and nurses are properly trained and highly involved. SUMMARY: We now have a better understanding of the measures to be deployed to optimize RRT. Organization, training, evaluation and protocols are the key points of the team's efficiency for a safe and effective implementation of RRT.

The Novel PrisMax Continuous Renal Replacement Therapy System in a Multinational, Multicentre Pilot Setting.

BACKGROUND/AIMS: We assessed how the novel PrisMax continuous renal replacement therapy (CRRT) system performed in a prospective international multicentre setting. We compared this device to its predecessor, the Prismaflex, with regards to multiple treatment parameters. Additionally, we performed a survey, aiming to measure user satisfaction. METHODS: Data was prospectively collected from 7 intensive care units (ICU) in 6 countries. The PrisMax device data logs constituted the raw material. Clinical parameters like treatment time, filter life span, downtime, delivered dose and number and type of alarms were recorded. A user questionnaire was sent out to 3 of the participating ICUs. RESULTS: Filter life, downtime, blood pump stops, bag changing time and number of malfunction alarms showed significantly improved values compared to the historic Prismaflex data. The survey showed high scores with regards to user friendliness. CONCLUSION: The PrisMax CRRT device is safe and outperformed its' previous generation counterpart in virtually all aspects. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=489213.

Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis.

OBJECTIVES: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. METHOD: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2-3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. RESULTS: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was 0.84 (0.73-0.92) and 0.85 (0.76-0.94), in low and high nonrenal Sequential Organ Failure Assessment score subgroups. Performance of the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 test was not modified by nonrenal Sequential Organ Failure Assessment (p = 0.70). In multivariate analysis, the addition of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 significantly improved the performance of a clinical model for predicting acute kidney injury (p = 0.015). CONCLUSION: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 accurately predicts acute kidney injury in septic patients with or without other organ failures.

Bioelectrical impedance spectroscopy to estimate fluid balance in critically ill patients.

Fluid management is a crucial issue in intensive-care medicine. This study evaluated the feasibility and reproducibility of bioimpedance spectroscopy to measure body-water composition in critically ill patients, and compared fluid balance and daily changes in total body water (TBW) measured by bioimpedance. This observational study included 25 patients under mechanical ventilation. Fluid balance and bioimpedance measurements were recorded on 3 consecutive days. Whole-body bioimpedance spectroscopy was performed with exact or ideal body weights entered into the device, and with or without ICU monitoring. Reproducibility of bioimpedance spectroscopy was very good in all conditions despite ICU monitoring and mechanical ventilation. Bioimpedance measurements using an ideal body weight varied significantly, making the weighing procedure necessary. Comparison of fluid balance and daily changes in body weight provided the best correlation (ρ = 0.74; P < 0.0001). Daily changes in TBW were correlated with fluid balance (Spearman coefficient ρ = 0.31; P = 0.003) and this correlation was improved after exclusion of patients with a SOFA score >10 (ρ = 0.36; P = 0.05) and with extracorporeal circulation (ρ = 0.50; P = 0.005). Regardless of the technique used to estimate volume status, important limits of agreement were observed. Non-invasive determination of body-water composition using bioimpedance spectroscopy is feasible in critically ill patients but requires knowledge of the patient's weight. The best method to assess volume status after fluid resuscitation and the value gained from information about body composition provided by bioimpedance techniques needs further evaluation.

Renal replacement therapy in acute kidney injury: controversy and consensus.

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future.

High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis.

INTRODUCTION: High-volume hemofiltration (HVHF) is an attractive therapy for the treatment of septic acute kidney injury (AKI). Small experimental and uncontrolled studies have suggested hemodynamic and survival benefits at higher doses of HVHF than those used for the high-intensity arms of the RENAL and ATN studies. Our aim was to evaluate the effects of high-volume hemofiltration (HVHF) compared with standard-volume hemofiltration (SVHF) for septic AKI. METHODS: A systematic review and meta-analysis of publications between 1966 and 2013 was performed. The review was limited to randomized-controlled trials that compared HVHF (effluent rate greater than 50 ml/kg per hour) versus SVHF in the treatment of sepsis and septic shock. The primary outcome assessed was 28-day mortality. Other outcomes assessed were recovery of kidney function, lengths of ICU and hospital stays, vasopressor dose reduction, and adverse events. RESULTS: Four trials, including 470 total participants, were included. Pooled analysis for 28-day mortality did not show any meaningful difference between HVHF compared with SVHF (OR, 0.76; 95% CI, 0.45 to 1.29). No included studies reported statistically significant differences between groups for any of the secondary outcomes. Adverse events, including hypophosphatemia and hypokalemia, were more commonly observed in HVHF-treated patients, although reporting was inconsistent across studies. CONCLUSIONS: Insufficient evidence exists of a therapeutic benefit for routine use of HVHF for septic AKI, other than on an experimental basis. Given the logistic challenges related to patient recruitment along with an incomplete understanding of the biologic mechanisms by which HVHF may modify outcomes, further trials should focus on alternative extracorporeal therapies as an adjuvant therapy for septic AKI rather than HVHF.

What do we know about steroids metabolism and 'PK/PD approach' in AKI and CKD especially while on RRT--current status in 2014.

The knowledge on PK behavior of steroid drugs such as prednisolone or prednisone has indeed been expanding but at a rather slow pace. First, convenient, rapid, and specific determination of plasma levels of these steroids was largely indebted to the breakthrough of high performance liquid chromatography (HPLC). Second, prednisolone is non-linearly protein-bound. Since unbound prednisolone is the biologically active compound, only the measurement of this free fraction in plasma is relevant. Third, the short half-life of prednisolone precludes to reach steady-state levels and requires determination of the area under the concentration-time curve. Fourth, prednisolone and prednisone are mutually convertible. Intravenous prednisolone, however, is administered as a pro-drug ester, which renders comparison and interpretation of reported PK data of both agents unreliable. A poignant lack of awareness and knowledge regarding catabolism, clearance mechanisms, and elimination route of steroids fuels the ongoing controversy that surrounds adjunctive corticosteroid therapy in patients with chronic or acute inflammatory disease. This particular patient population is also more prone to develop early and significant kidney dysfunction, necessitating extra-renal support. A better understanding of steroid PK/PD, preferentially guided by HPLC measurement of plasma steroid concentrations, likely will have direct clinical implications, for instance by adapting steroid doses in IHD or implementing higher dose regimens during CRRT.

Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review.

Polymyxins are 'old' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise in multiresistant Gram-negative bacterial infections worldwide has revived interest in these 'forgotten' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the prodrug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used to treat pneumonia and bacteremia in critically ill patients. During their intensive care unit stay, many of these patients will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and our own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e. a high loading dose, followed by a maintenance dose of up to 4.5 million IU t.i.d.). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such a 'CRRT rescue' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

Accuracy of determining hemoglobin level using occlusion spectroscopy in patients with severe gastrointestinal bleeding.

BACKGROUND: In patients presenting with severe hemorrhage, the authors conducted an equivalence trial that compared noninvasive occlusion spectroscopy and the capillary blood method to determine hemoglobin level. METHODS: This prospective observational study included patients admitted to their intensive care unit for gastrointestinal bleeding. A ring-shaped sensor, connected to a NBM-200MP (OrSense, Nes Ziona, Israel), was fitted onto the patient's thumb to intermittently measure hemoglobin (SotHb). During the first 24 h after admission, venous hemoglobin level, considered as the reference method, was determined at the laboratory every 8 h and was compared to SotHb and the capillary blood method. The primary endpoint was the proportion of inaccurate measurements, defined as greater than 15% difference compared with reference values or their unavailability for any technical reason. RESULTS: The study was scheduled to include 68 patients but was stopped prematurely after an interim analysis of 34 patients. The proportion of inaccuracies revealed that SotHb could not be considered equivalent to the capillary blood method (47% [95% CI, 43-51] and 24% [95% CI, 20-28]). Considering venous hemoglobin level as a reference method, the mean biases for SotHb (n = 133) and the capillary blood method (n = 135) were, respectively, -0.4 ± 2.0 and 0.8 ± 1.2 g/dl (P < 0.05). SotHb was associated with an increased incidence of failed transfusion. The inaccuracy of SotHb tended to be increased in patients receiving vasopressor agents. CONCLUSIONS: Noninvasive determination of hemoglobin level based on occlusion spectroscopy lacks accuracy in patients presenting with severe gastrointestinal bleeding and cannot be considered equivalent to the capillary-based method. This inaccuracy seems to be moderately influenced by the infusion of vasopressor agents.

Con: Dialy- and continuous renal replacement (CRRT) trauma during renal replacement therapy: still under-recognized but on the way to better diagnostic understanding and prevention.

Dialy- and continuous renal replacement (CRRT) trauma are still un(der)recognized conditions that may be encountered during blood purification therapy. This particular form of trauma requires timely identification, a better understanding of pathophysiology and a definition of at-risk groups to prevent or correct any associated unwarranted effects. Among others, progress in the knowledge of antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) behaviour during CRRT to obtain more efficient antimicrobial therapy with less side-effects is one key example of limiting CRRT trauma. Optimal anticipation and prevention of CRRT trauma will preserve the safe use of CRRT in haemodynamically unstable critically ill patients with acute kidney injury (AKI), especially in septic patients who are at the greatest risk.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

Nutritional and metabolic alterations during continuous renal replacement therapy.

Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.

The Use of Adsorption in Extracorporeal Liver Support: The Double Plasma Molecular Adsorption System (DPMAS).

Liver failure in the intensive care unit (ICU), whether acute or acute-on-chronic, remains a serious condition with reduced functions, various metabolite and toxin accumulation in the systemic circulation, and a high mortality rate. While transplantation remains the treatment of choice, the lack of organ transplants necessitates finding alternative solutions. Within the last years, several therapies aiming to support liver function have been developed in order to serve as a bridge to liver transplantation or as replacement therapy, allowing regeneration of the injured liver. In those therapies, nonbiological extracorporeal liver support devices are the most widely used, mainly based on detoxification by eliminating accumulated toxins notably by adsorption on specific membranes and/or with plasmapheresis. One of the most recent techniques is the double plasma molecular adsorption system combining plasma filtration and two specific adsorption membranes, which is largely described and studied in this chapter. This technique seems promising to remove deleterious toxins, cytokines and bilirubin in particular, is fairly simple to use, does not require a specific machine (it works on continuous renal replacement therapy machines), and has given encouraging results in the pilot studies published recently, in association with plasmapheresis or alone. However, further studies and evaluations are needed before this technique can be used routinely in ICU.

Moving from a cytotoxic to a cytokinic approach in the blood purification labyrinth: have we finally found Ariadne's thread?

For almost three decades, researchers have invested in strategies that involved removal of excess inflammatory mediators from the circulation (that is, the "cytotoxic" approach). Blood purification techniques using an extracorporeal device can indeed non-specifically remove a wide array of inflammatory mediators from the circulation. In animal models, this multimediator targeting or pleiotropic approach was shown to downregulate systemic inflammation and to restore immune homeostasis. In this issue, Namas et al. seriously challenge this cytotoxic hypothesis and propose to replace it by a cytokinic approach. In a rodent model of sepsis, these authors elegantly demonstrate that hemoadsorption using a large surface-area polymer could reduce and, more importantly, relocalize and reprogram sepsis-induced acute inflammation, while simultaneously lowering infectious burden and liver damage. Although challenging, this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling reduced endothelial damage at the interstitial level (cytotoxic approach) with the concept of reprogramming leucocytes and mediators toward infected tissue, thus emptying the bloodstream of important promoters of remote organ damages (cytokinic approach).

Precision of noninvasive hemoglobin-level measurement by pulse co-oximetry in patients admitted to intensive care units for severe gastrointestinal bleeds.

OBJECTIVES: Measurement of total hemoglobin, based on pulse co-oximetry, is a continuous and noninvasive method that has been principally evaluated in healthy volunteers subjected to hemodilution. We tested the hypothesis that its accuracy could adversely affect patients presenting with severe hemorrhage, which is traditionally associated with increased microvascular tone. DESIGN: Observational study. SETTING: Twelve-bed mixed medico-surgical intensive care unit. PATIENTS: Thirty-three patients admitted to our critical care unit for gastrointestinal bleeds were included. INTERVENTIONS: A spectrophotometric sensor was positioned on the patient's fingertip and connected to a pulse co-oximeter. During the first 24 hrs following admission, venous hemoglobin level was determined at the laboratory every 8 hrs and was compared with hemoglobin levels displayed on the pulse co-oximeter measurements screen and/or measured from capillary blood using a portable photometer. MEASUREMENTS AND MAIN RESULTS: The primary end point was the percentage of inaccurate measurements, which were defined as >15% difference compared with reference values or their unavailability for any technical reason. Twenty-five (19%) measurements of pulse co-oximeter measurements were unavailable from the screen. Pulse co-oximeter measurements and capillary hemoglobin levels were significantly correlated to venous hemoglobin level. For venous hemoglobin level compared with pulse co-oximeter measurements (n = 105), and for venous hemoglobin level compared with capillary hemoglobin levels (n = 111), the biases were, respectively, 1.0 ± 1.9 g dL and 0.4 ± 1.0 g dL (p < .05). The proportion of inaccurate measurements was significantly higher for pulse co-oximeter measurements (56% vs. 15%, p < .05). Although the use of norepinephrine did not affect concordance parameters, unavailability of measurements was frequently observed (42% vs. 15%, p < .05). CONCLUSIONS: Determination of pulse co-oximetry-based hemoglobin in patients presenting with severe gastrointestinal bleeds can be inaccurate, which renders its use to guide transfusion decisions potentially hazardous. The unavailability of measurements, especially during vasopressor infusion, represents another serious limitation for hemorrhagic patients.