Intermittent Convective Therapies in Patients with Acute Kidney Injury: A Systematic Review with Meta-Analysis.

INTRODUCTION: In critically ill patients requiring intermittent renal replacement therapy (RRT), the benefits of convective versus diffusive clearance remain uncertain. We conducted a systematic review and meta-analysis to determine the safety, clinical efficacy, and clearance efficiency of hemofiltration (HF) and hemodiafiltration (HDF) compared to hemodialysis (HD) in patients with acute kidney injury (AKI) receiving intermittent RRT. METHOD: We searched Medline, Embase, Cochrane Library, and PROSPERO. We included clinical trials and observational studies that reported the use of intermittent HF or HDF in adult patients with AKI. The following outcomes were included: mortality, renal recovery, clearance efficacy, intradialytic hemodynamic stability, circuit loss, and inflammation modulation. RESULTS: A total of 3,169 studies were retrieved and screened. Four randomized controlled trials and 4 observational studies were included (n: 615 patients). Compared with conventional HD, intermittent convective therapies had no effect on in-hospital mortality (relative risk, 1.23; 95% confidence interval (CI), 0.76-1.99), renal recovery at 30 days (RR, 0.98; 95% CI, 0.82-1.16), time-to-renal recovery (mean difference [MD], 0.77; 95% CI, -6.56 to 8.10), and number of dialysis sessions until renal recovery (MD, -1.34; 95% CI, -3.39 to 0.72). The overall quality of included studies was low, and dialysis parameters were suboptimal for all included studies. CONCLUSION: This meta-analysis suggests that there is no significant difference in short-term mortality and renal recovery in patients with severe AKI when treated with intermittent HF or HDF compared to conventional HD. This systematic review emphasizes the need for further trials evaluating optimal convective parameters in AKI patients treated with intermittent dialysis.

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis.

OBJECTIVE: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. DATA SOURCES: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. STUDY SELECTION: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. DATA EXTRACTION: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. DATA SYNTHESIS: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40-0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23-0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13-0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07-13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10-2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13-3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29-1.10), endotoxin removal devices (CI 0.05-3.40), nor nonspecific adsorption devices (CI 0.01-14.31) were associated with mortality benefit. CONCLUSION: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

Ultrafiltration for management of fluid overload in patients with heart failure.

Heart failure is the number one cause of death in the United States and a significant burden to the healthcare system. One of the primary complications of heart failure is fluid overload, for which current treatments are limited. Medical therapy is first-line; however, rates of diuretic insensitivity are high, medications are not easily titrated, and they do not address the underlying physiologic derangement that leads to hypervolemia. Removal of isotonic fluid via hemofiltration and peritoneal dialysis is an understudied but promising therapy that enables decongestion without maladaptive stimulation of fluid retention pathways. Published studies report conflicting data on long-term outcomes of ultrafiltration but reach consensus on greater and more durable volume reduction with ultrafiltration than conventional medical therapy. These studies are noteworthy for their neglect to standardize both patient selection and fluid removal protocol, which likely contribute to outcome variation. Novel technology in preclinical testing includes implantable ultrafiltration, which has potential to treat volume overload while minimizing the adverse effects associated with conventional hemofiltration. We performed a literature review of English-language studies on hemo- and peritoneal filtration for management of fluid overload in congestive heart failure. Also included is a discussion of the pathophysiology of congestive heart failure and first-line management as well as emerging technologies for ultrafiltration.

Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. METHODS: Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. RESULTS: Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. CONCLUSIONS: Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.

Patient Demographics and Extracorporeal Membranous Oxygenation (ECMO)-Related Complications Associated With Survival to Discharge or 30-Day Survival in Adult Patients Receiving Venoarterial (VA) and Venovenous (VV) ECMO in a Quaternary Care Urban Center.

OBJECTIVE: Investigate how a multitude of patient demographics and extracorporeal membranous oxygenation (ECMO)-related complications affect 30-day survival or survival to discharge. DESIGN: Retrospective observational study. SETTING: Urban university hospital, quaternary care center. PARTICIPANTS: Patients who underwent ECMO circulatory support from January 2012 to May 2016. INTERVENTIONS: Date-based data extraction, univariate and multivariate regression analysis. MEASUREMENTS AND MAIN RESULTS: The hospital database contained complete data for 235 adult patients who received venoarterial ECMO (74.04 %) and venovenous ECMO (25.96 %); 106 patients (45.11%) survived. The independent predictors significant in the odds of in-hospital mortality in a multiregression model were age (odds ratio [OR] = 1.028, p = 0.008), extracorporeal cardiopulmonary resuscitation (ECPR) after unsuccessful high-quality CPR (OR = 7.93, p =0.002), cardiogenic shock as the primary indication for circulatory support (OR = 2.58, p = 0.02), acute kidney injury (AKI) before ECMO initiation (OR = 7.53, p < 0.001), time spent on ECMO in days (OR = 1.08, p = 0.03), and limb ischemia (OR = 3.18, p = 0.047). CONCLUSION: The most significant findings of advancing age, time spent on ECMO, AKI, ECMO use in the setting of cardiogenic shock, ECPR, and limb ischemia as a complication of ECMO all independently increase the odds of in-hospital and 30-day mortality. To the best of the authors' knowledge, this study is the first to demonstrate a significant relationship between limb ischemia and mortality.

High-volume haemofiltration for sepsis in adults.

BACKGROUND: Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic shock, including early recognition, appropriate treatment with antibiotics and support of organs that may have been affected by the illness. High-volume haemofiltration (HVHF) is a blood purification technique that may improve outcomes in severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used in the ICU to treat critically ill patients with acute kidney injury (AKI). This review was first published in 2013 and was updated in 2016. OBJECTIVES: To investigate whether HVHF improves outcomes in critically ill adults admitted to the intensive care unit with severe sepsis or septic shock. The primary outcome of this systematic review is patient mortality; secondary outcomes include duration of stay, severity of organ dysfunction and adverse events. SEARCH METHODS: For this updated version, we extended searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to 31 December 2015. The original search was performed in 2011. We also searched trials registers. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus standard or usual dialysis therapy, as well as RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus no similar dialysis therapy. These studies involved adults treated in critical care units. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed trial quality. We sought additional information from trialists as required. MAIN RESULTS: We included four randomized trials involving 200 participants. Owing to small numbers of studies and participants, it was not possible to combine data for all outcomes. Two trials reported 28-day mortality, and one trial reported hospital mortality; in the third trial, the number of deaths stated did not match the quoted mortality rates. The pooled risk ratio (95% confidence interval) for 28-day mortality associated with HVHF was 0.89 (0.60 to 1.32, two trials, 146 participants, low-quality evidence). One study (137 participants, low-quality evidence) reported length of stay in the ICU. Two trials (170 participants, low-quality evidence) reported organ dysfunction, but we could not pool results owing to reporting differences. Three studies (189 participants, low-quality evidence) reported on haemodynamic changes, but we could not pool results owing to reporting differences. Investigators reported no adverse events. Overall, the included studies had low risk of bias. AUTHORS' CONCLUSIONS: Investigators reported no adverse effects of HVHF (low-quality evidence). The results of this meta-analysis show that very few studies have been conducted to investigate the use of HVHF in critically ill patients with severe sepsis or septic shock (four studies, 201 participants, low-quality evidence). Researchers should consider additional randomized controlled trials that are large and multi-centred and have clinically relevant outcome measures. The cost-effectiveness of HVHF should also be studied. .

Renal failure requiring dialysis complicating slow continuous ultrafiltration in acute heart failure: importance of systolic perfusion pressure.

BACKGROUND: Recent reports have raised concerns regarding renal outcomes in patients with decompensated acute heart failure (HF) treated with slow continuous ultrafiltration (SCUF). The purpose of this study was to identify risk factors for renal failure (RF) requiring dialysis in patients with acute HF initiated on SCUF. METHODS AND RESULTS: We studied 63 consecutive patients with acute HF who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. Median serum creatinine at SCUF initiation was higher in patients who developed RF requiring dialysis [2.5 (interquartile range 1.8-3.3) vs 1.6 (1.2-2.3) mg/dL; P < .001]. Weight loss within 48 hours of SCUF initiation was larger in patients who did not progress to RF [-6 (-10 to -2) vs -4 (-6 to -2) kg; P = .03]. Systolic perfusion pressure had a nonlinear association with RF requiring dialysis, with a threshold effect noted at 90 mm Hg. Twelve-month mortality in patients who were moved to dialysis versus those who were not was 95% versus 35%, respectively (P < .001). CONCLUSIONS: In patients with acute HF initiated on SCUF, onset of RF requiring dialysis is associated with high mortality. Systolic perfusion pressure which incorporates both perfusion and venous congestion parameters may present a modifiable risk factor for worsening RF during SCUF in acute HF patients.

Hemofiltration is not associated with increased mortality in children receiving extracorporeal membrane oxygenation.

OBJECTIVES: To investigate whether the use of continuous renal replacement therapy is independently associated with increased in-hospital mortality in children on extracorporeal membrane oxygenation. DESIGN: Retrospective, 1:1 propensity-matched cohort study. SETTING: Tertiary PICU. PATIENTS: Eighty-six children on extracorporeal membrane oxygenation, 43 of whom also received hemofiltration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, pre-extracorporeal membrane oxygenation hemodynamic data, fluid status, and biochemistry tests were collected, as well as duration of extracorporeal membrane oxygenation, blood product use, complications, and mortality. Forty-three children receiving extracorporeal membrane oxygenation and continuous renal replacement therapy were matched to a cohort of 43 children on extracorporeal membrane oxygenation not receiving continuous renal replacement therapy. The main indication for hemofiltration was fluid overload in 29 patients (67.4%), renal failure in nine patients (20.9%), and electrolyte abnormalities in five patients (11.6%). The median duration of hemofiltration was 108 hours (47-209 hr). Patients receiving hemofiltration had a longer duration of extracorporeal membrane oxygenation (127 hr [94-302 hr] vs 121 hr [67-182 hr]; p = 0.05) and received more platelet transfusions (0.91 mL/kg/hr [0.43-1.58 mL/kg/hr] vs 0.63 mL/kg/hr [0.30-0.79 mL/kg/hr]; p = 0.01). There were otherwise no differences in mechanical or patient-related complications between both groups. There was no difference in the proportion of patients who were successfully decannulated (81.4% vs 74.4%; p = 0.44), survived to ICU discharge (65.1% vs 55.8%; p = 0.38), or survived to hospital discharge (62.8% vs 48.8%; p = 0.19) in the controls versus the hemofiltration group. CONCLUSIONS: In-hospital mortality was similar between children on extracorporeal membrane oxygenation with and without hemofiltration although hemofiltration appeared to be associated with a slight increase in the duration of extracorporeal membrane oxygenation and more liberal platelet transfusions.

Hypothermic, initially oxygen-free, controlled limb reperfusion for acute limb ischemia.

BACKGROUND: Controlled limb reperfusion has been shown to prevent the deleterious effects of ischemia-reperfusion (IR) syndrome following revascularization of acute limb ischemia (ALI). To reduce the production of cell-toxic oxygen-free radicals, we have established a new initially oxygen-free, hypothermic, heparin-coated perfusion and hemofiltration system and report on our first results. METHODS: In a retrospective single-center study, controlled limb reperfusion was applied in 36 patients (64.7 ± 15 years) with ALI of category IIA to III (33.7 ± 20.7 hr ischemic time). 52.8% had central (aortic and bifurcation) and 47.2% had peripheral (common iliac artery and distal) vascular occlusions. The common femoral artery and vein were cannulated, and a hypothermic (22°C), initially oxygen-free, potassium-free ringer's solution was perfused using a heparin-coated extracorporeal membrane oxygenation (ECMO) and hemofiltration system with low-dose heparinization. Thirty-day mortality, clinical recovery of neurological dysfunction, limb amputation, and fasciotomy rate were analyzed. Laboratory parameters associated with ischemia and IR injury were determined. RESULTS: Average perfusion time was 94 ± 35 min. Thirty-day mortality was 27.8%. 55.5% of patients showed complete recovery of motor and sensory dysfunction. A total of 27.8% of patients developed a compartment syndrome and required fasciotomy. Lower leg amputation was necessary in 11.1% of patients. Lactate levels were reduced in ischemic limbs by 25.3% within 60 min (P < 0.05). Preoperative negative base excess of -1.96 ± 0.96 mmol/L was equalized after 12 hr (P < 0.05), while pH stayed balanced at 7.4. Serum potassium stayed within normal limits throughout 24 hr, and therefore systemic hyperkalemia was prevented and imminent metabolic acidosis was corrected. CONCLUSIONS: An initially oxygen-free, hypothermic, heparin-coated ECMO counteracts local and systemic effects of IR injury. Reduced mortality and morbidity might result from this new treatment, although this could not be conclusively proven in our study. A prospective, randomized controlled trial is needed to prove superiority of this new concept.

The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial.

INTRODUCTION: Acute renal failure (ARF) requiring renal replacement therapy (RRT) occurs frequently in ICU patients and significantly affects mortality rates. Previously, few large clinical trials investigated the impact of RRT modalities on patient outcomes. Here we investigated the effect of two major RRT strategies (intermittent hemodialysis (IHD) and continuous veno-venous hemofiltration (CVVH)) on mortality and renal-related outcome measures. METHODS: This single-center prospective randomized controlled trial ("CONVINT") included 252 critically ill patients (159 male; mean age, 61.5 ± 13.9 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score, 28.6 ± 8.8) with dialysis-dependent ARF treated in the ICUs of a tertiary care academic center. Patients were randomized to receive either daily IHD or CVVH. The primary outcome measure was survival at 14 days after the end of RRT. Secondary outcome measures included 30-day-, intensive care unit-, and intrahospital mortality, as well as course of disease severity/biomarkers and need for organ-support therapy. RESULTS: At baseline, no differences in disease severity, distributions of age and gender, or suspected reasons for acute renal failure were observed. Survival rates at 14 days after RRT were 39.5% (IHD) versus 43.9% (CVVH) (odds ratio (OR), 0.84; 95% confidence interval (CI), 0.49 to 1.41; P = 0.50). 14-day-, 30-day, and all-cause intrahospital mortality rates were not different between the two groups (all P > 0.5). No differences were observed in days on RRT, vasopressor days, days on ventilator, or ICU-/intrahospital length of stay. CONCLUSIONS: In a monocentric RCT, we observed no statistically significant differences between the investigated treatment modalities regarding mortality, renal-related outcome measures, or survival at 14 days after RRT. Our findings add to mounting data demonstrating that intermittent and continuous RRTs may be considered equivalent approaches for critically ill patients with dialysis-dependent acute renal failure. TRIAL REGISTRATION: NCT01228123, clinicaltrials.gov.

Continuous veno-venous hemofiltration to adjust fluid volume excess in septic shock patients reduces intra-abdominal pressure.

OBJECTIVE: To analyze the effect and the time course of continuous veno-venous hemofiltration (CVVH) with net ultrafiltration (UF) on intra-abdominal pressure (IAP) body fluid volumes in septic shock patients with acute kidney injury (AKI). METHODS: Patients were studied at baseline and after 6, 12, 24, 48, 72, and 96 hours of CVVH treatment. IAP was measured via the bladder, and abdominal perfusion pressure (APP) was calculated as mean arterial pressure minus IAP. Fluid volume excess (VE), total body water (TBW), extracellular body water (ECW), and intracellular body water (ICW) were derived from wholebody bioimpedance analysis (BIA). RESULTS: 30 patients entered final analysis, of which 6 died during CVVH (non-survivors). Fluid VE, TBW, ECW, ICW, and IAP significantly decreased in 24 survivors, whereas these variables remained essentially unchangedin non-survivors. APP slowly increased in survivors, while it did not change in nonsurvivors. IAP strongly correlated with VEin survivors: The lower the IAP, the lower the fluid volume excess. CONCLUSION: CVVH with net UF successfully reduced IAP, TBW, ECW, and ICW in critically ill patients who survived 96 h of CVVH. Failure to increase APP was associated with fatal outcome, and, finally, IAP correlated with fluid volume excess. BIA could be helpful to monitor fluid status in patients with AKI.

[Analysis of mortality of patients undergoing veno-venous hemofiltration after cardiac surgery]. / Análise dos resultados de doentes submetidos a hemodiafiltração venosa no pós-operatório de cirurgia cardíaca.

OBJECTIVE: In this study we aim to assess the mortality of patients undergoing cardiac surgery and that in the post operative period required veno-venous hemofiltration. METHODS: The population studied includes 77 patients (44 men and 33 women, with mean age 67,04±12.99 years), that underwent cardiac surgery between January 2008 and March 2013, requiring veno-venous hemofiltration after surgery. 3 surgeries were urgent, 3 emergent and the other elective, 18 of which were re operations. 31 patients underwent valvular surgery, 14 myocardial revascularization surgery, 8 patients combined valvular and myocardial revascularization surgery and 22 patients other surgery. The mean EuroScore I of the study group was 15,8% (maximum of 57 and minimum of 2.2%). The mean length of stay in the intensive care unit was 18 days (maximum of 185 days and minimum of 1 day). The mean length of hospital stay was 26 days (maximum of 190 days and minimum of 1 day). RESULTS: The overall mortality of the study group was 40,3% (31 patients), the hospital mortality was 31,2%(24 patients) and mortality after discharge was 9,1% (7 patients). The mean EuroScore of patients undergoing cardiac surgery alone was 5,8% and the hospital mortality was 2,8%. Mortality after 1 year follow up was 6.1%. CONCLUSIONS: Patients undergoing veno-venous hemofiltration have a much higher EuroScore and mortality rate when compared to the population undergoing cardiac surgery alone. We conclude that the mortality of patients undergoing cardiac surgery and that require hemofiltration after surgery is similar to the other published studies regarding this type of patient.

Validity of low-intensity continuous renal replacement therapy*.

OBJECTIVE: To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. DESIGN: Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). SETTING: Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). PATIENTS: Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10-15, 15-20, 20-25, 25-30, 30-35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20-25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. CONCLUSIONS: Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20-25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

BACKGROUND: Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF. METHODS AND RESULTS: Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E' ≥15 (OR 3.78, 95% CI 1.26-17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate. CONCLUSIONS: WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.

Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury.

INTRODUCTION: The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI). METHODS: 760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia. RESULTS: The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103-1.910, p = 0.008). CONCLUSIONS: Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.

High-volume haemofiltration for sepsis.

BACKGROUND: Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU). This is despite advances in the management of patients with severe sepsis and septic shock including early recognition, source control, timely and appropriate administration of antimicrobial agents, and goal directed haemodynamic, ventilatory and metabolic therapies. High-volume haemofiltration (HVHF) is a blood purification technique which may improve outcomes in critically ill patients with severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used to treat acute kidney injury (AKI) in critically ill patients in the ICU. OBJECTIVES: This review assessed whether HVHF improves clinical outcome in adult critically ill patients with sepsis in an ICU setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, Issue 7); MEDLINE (1990 to August 2011), EMBASE (1990 to August 2011); LILACS (1982 to August 2011), Web of Science (1990 to August 2011), CINAHL (1982 to August 2011) and specific websites. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to standard or usual dialysis therapy; and RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration to no similar dialysis therapy. The studies involved adults in critical care units. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed trial quality. We sought additional information as required from trialists. MAIN RESULTS: We included three randomized trials involving 64 participants. Due to the small number of studies and participants, it was not possible to combine data or perform sub-group analyses. One trial reported ICU and 28-day mortality, one trial reported hospital mortality and in the third, the number of deaths stated did not match the quoted mortality rates. No trials reported length of stay in ICU or hospital and one reported organ dysfunction. No adverse events were reported. Overall, the included studies had a low risk of bias. AUTHORS' CONCLUSIONS: There were no adverse effects of HVHF reported.There is insufficient evidence to recommend the use of HVHF in critically ill patients with severe sepsis and or septic shock except as interventions being investigated in the setting of a randomized clinical trial. These trials should be large, multi-centred and have clinically relevant outcome measures. Financial implications should also be assessed.

Is continuous venovenous hemofiltration effective against severe acute pancreatitis?

Our aim was to investigate the efficacy of continuous venovenous hemofiltration (CVVH) in treating severe acute pancreatitis (SAP). A literature search was performed using PubMed (1992-present), and all studies investigating the efficacy of CVVH in treating SAP were included. Four comparative studies and seven case series comprising a total of 354 patients were included. The overall mortality rate of patients receiving CVVH was 20% (55/275). A decreased mortality rate and decreased serum cytokine levels were reported in the CVVH groups in only two studies. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of CVVH varied among the studies, and the impact of these parameters on the efficacy of CVVH was poorly reported. High-volume CVVH, when started early, was demonstrated to be more effective in eliminating cytokines in only one study. After the application of CVVH, the patient conditions started to improve between the 6th and 72nd hours. In conclusion, no solid clinical evidence has proven the efficacy of CVVH in treating SAP. High-volume CVVH that is started early and sustained for at least 72 h may be adopted to investigate the efficacy of CVVH for treating SAP.

Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality.

BACKGROUND: Existing systems for grading severity of acute kidney injury (AKI) rely on a change of serum creatinine concentration over a defined time interval. The rate of change in serum creatinine increases by degree of reduction in glomerular filtration rate, but is mitigated by low creatinine generation rate (CGR). Failure to appreciate variation in CGR may lead to erroneous conclusions regarding severity of AKI and distorted predictions regarding patient outcomes based on AKI severity. METHODS: Cohort study of 103 patients who received continuous venovenous hemodialysis (CVVHD) over a 2-year period in a tertiary care hospital setting. Study participants entered the cohort when they were anuric, receiving a stable and uninterrupted dose of CVVHD with serum creatinine in steady state. They were followed until hospital discharge. CGR was measured based on dialyzate effluent volume and effluent creatinine concentration (prospective cohort) and via effluent volume and serum creatinine concentration (retrospective cohort). RESULTS: CGR (mean 10.5, range 1.7-22.4 mg/kg/day) was substantially lower in this patient population than what would be predicted from existing equations. Correlates of CGR in multivariable analysis included the length of hospitalization prior to measurement and presence of an oncologic diagnosis. Lower CGR was independently associated with in-hospital mortality in unadjusted analysis and after multivariable adjustment for measures of severity of illness. CONCLUSIONS: Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population.

Continuous renal replacement therapy in children.

Over the past several decades, the epidemiology of acute kidney injury (AKI) in children has changed significantly. Pediatric patients with AKI frequently have co-morbid conditions, substantial fluid overload, and marked disease severity. At the same time, continuous renal replacement therapy (CRRT) has become the preferred modality for the management of these patients. This manuscript provides a state-of-the-art review of the technical aspects of pediatric CRRT and examines the most recent data regarding CRRT indications, timing of initiation, dosing, and outcomes in critically ill children.

Evidence-based used, yet still controversial: the arterial filter.

Arterial line filters are considered by many as an essential safety measure inside a cardiopulmonary bypass circuit. There is no doubt that this was true during the bubble oxygenator era, but we can question whether the existing arterial line filter design and positioning of the filter are still optimal seeing the tremendous progress in cardiopulmonary bypass circuit components. This overview gives a critical overview of existing arterial line filter design.