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Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients.
Shao, M, Li, G, Sarvottam, K, Wang, S, Thongprayoon, C, Dong, Y, Gajic, O, Kashani, K
PloS one. 2016;(8):e0160322
Abstract
INTRODUCTION Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. MATERIAL AND METHODS This is a single-center, retrospective cohort study at Mayo Clinic Hospital-Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. RESULTS A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96-104) vs. 102 mmol/L (98-105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ≤94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1-2.6; P = .01). DISCUSSION Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury.
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Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic Study.
Silbert, BI, Ho, KM, Lipman, J, Roberts, JA, Corcoran, TB, Morgan, DJ, Pavey, W, Mas, E, Barden, AE, Mori, TA
Critical care medicine. 2016;(10):e923-9
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OBJECTIVES This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics. DESIGN Prospective cohort. SETTING Tertiary ICU. PATIENTS Thirty critically ill patients with acute kidney injury without preexisting renal impairment or recent diuretic exposure. INTERVENTION A single dose of IV furosemide. MEASUREMENTS AND MAIN RESULTS Baseline markers of intravascular volume status were obtained prior to administering furosemide. Six-hour creatinine clearance, hourly plasma/urinary furosemide concentrations, and hourly urinary output were used to assess furosemide pharmacokinetics/pharmacodynamics parameters. Of 30 patients enrolled, 11 had stage-1 (37%), nine had stage-2 (30%), and 10 had stage-3 (33%) Acute Kidney Injury Network acute kidney injury. Seventy-three percent were septic, 47% required norepinephrine, and 53% were mechanically ventilated. Urinary output doubled in 20 patients (67%) following IV furosemide. Measured creatinine clearance was strongly associated with the amount of urinary furosemide excreted and was the only reliable predictor of the urinary output after furosemide (area under the receiver-operating-characteristic curve, 0.75; 95% CI, 0.57-0.93). In addition to an altered pharmacokinetics (p < 0.01), a reduced pharmacodynamics response to furosemide also became important when creatinine clearance was reduced to less than 40 mL/min/1.73 m (p = 0.01). Acute kidney injury staging and markers of intravascular volume, including central venous pressure, brain-natriuretic-peptide concentration, and fractional urinary sodium excretion were not predictive of urinary output response to furosemide. CONCLUSIONS The severity of acute kidney injury, as reflected by the measured creatinine clearance, alters both pharmacokinetics and pharmacodynamics of furosemide in acute kidney injury, and was the only reliable predictor of the urinary output response to furosemide in acute kidney injury.
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Removal characteristics and total dialysate content of glutamine and other amino acids in critically ill patients with acute kidney injury undergoing extended dialysis.
Schmidt, JJ, Hafer, C, Spielmann, J, Hadem, J, Schönenberger, E, Schmidt, BM, Kielstein, JT
Nephron. Clinical practice. 2014;(1):62-6
Abstract
BACKGROUND Acute kidney injury in critically ill patients is associated with the activation of protein catabolism and a negative nitrogen balance. Renal replacement therapy (RRT) aggravates this problem by eliminating a substantial amount of amino acids. However, there is scarce data on the removal characteristics of modern dialysis membranes in extended dialysis. METHODS This is a prospective study in 10 extended dialysis sessions using a 1.8-m(2) polysulfone membrane (EMiC2 dialyzer or AV 1000S; FMC, Germany). Blood samples for 19 amino acids were drawn before, during, and after 10 h of extended dialysis (blood/dialysate flow 150 ml/min). In addition, samples for the calculation of dialyzer clearance and samples from the total spent dialysate were measured using a Biochrom 30 amino acid analyzer. RESULTS Despite no significant difference in pre- and postdialysis plasma amino acid levels, we found an impressive amount of amino acids in collected spent dialysate, i.e. 10.5 g/10 h of treatment. The dialyzer clearance ranged from 67.6 ml/min for phenylalanine to 140.0 ml/min for valine. The total eliminated masses of the measured amino acids had equal values for both membranes. There was a significant difference between the dialyzer clearance of the investigated membranes for glutamine (AV 1000S: 83.3 ml/min vs. EMiC2: 92.0 ml/min, p = 0.02) and serine (88.8 ml/min vs. 91.8 ml/min, p = 0.005). DISCUSSION Our data indicate that the modern forms of RRT eliminate amino acids to an extent that has not been met by our nutritional support standards. Especially the removal of glutamine, important for immune function and cell regeneration, might have detrimental effects on the recovery of critically ill patients.
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Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.
Yunos, NM, Bellomo, R, Hegarty, C, Story, D, Ho, L, Bailey, M
JAMA. 2012;(15):1566-72
Abstract
CONTEXT Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI). OBJECTIVE To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients. DESIGN, SETTING, AND PATIENTS Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia. INTERVENTIONS During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin. MAIN OUTCOME MEASURES The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival. RESULTS Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P <.001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P <.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge. CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00885404.
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Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial.
Hetzel, GR, Schmitz, M, Wissing, H, Ries, W, Schott, G, Heering, PJ, Isgro, F, Kribben, A, Himmele, R, Grabensee, B, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011;(1):232-9
Abstract
BACKGROUND Continuous venovenous haemofiltration (CVVH) in the intensive care setting requires anticoagulation to prevent clotting of the extracorporeal circuit. Several protocols avoiding heparin and using regional citrate anticoagulation have been developed to diminish bleeding risks. However, data from randomized trials comparing citrate anticoagulation with systemic heparinization are very limited. METHODS One hundred and seventy-four patients on mechanical ventilation, requiring renal replacement therapy for acute renal failure, were included in this prospective randomized multicentre trial comparing regional citrate with systemic heparin. The study was performed at nine different intensive care units at university or academic teaching hospitals. The participants were randomized to either CVVH using regional citrate anticoagulation or CVVH using systemic anticoagulation with unfractionated heparin. The primary outcome was to compare treatment efficacy represented by the patients' acid base status on Day 3 and on each consecutive day. Several parameters of safety and efficacy were analysed as secondary outcomes. RESULTS Comparison of standard bicarbonate from Day 3 to Day 11 revealed no difference between both treatment modalities. Use of citrate resulted in less systemic anticoagulation, a lower risk of bleeding and a longer haemofilter patency. Episodes of hypercalcaemia, hypocalcaemia and the need for additional bicarbonate infusions occurred more often under citrate. The patients' high mortality was not influenced by the mode of anticoagulation. CONCLUSIONS Citrate may be used as a regional anticoagulant and the only buffering agent in CVVH with adequate treatment efficacy and safety. However, neither citrate nor heparin anticoagulation should be regarded as a therapeutic standard, since there is no advantage of one of these substances with regard to patient mortality.
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Citrate anticoagulation protocol for slow extended hemodialysis with the Genius dialysis system in acute renal failure.
Schneider, M, Liefeldt, L, Slowinski, T, Peters, H, Neumayer, HH, Morgera, S
The International journal of artificial organs. 2008;(1):43-8
Abstract
BACKGROUND The Genius dialysis system is increasingly used as an intermittent hemodialysis device in the setting of acute renal failure. Slow extended hemodialysis is preferred in the case of critical ill patients. In this study we established a safe and feasible citrate anticoagulation protocol for slow extended hemodialysis (SLED) with the Genius system. METHODS We compared six anticoagulation protocols using SLED in 34 critically ill patients with acute renal failure. One group (A) received only citrate anticoagulation. Four groups (B - D) were treated with citrate and different additional systemic anticoagulation. Patients in the last group (F) were anticoagulated with heparin and were free of citrate anticoagulation. The total number of treatments was 103. A 4% sodium citrate solution was infused into the arterial line of the dialysis device for citrate anticoagulation. The dialysis solution contained one mmol/L of calcium. No additional calcium supplementation was done. We monitored electrolyte, acid-base and cardiovascular status prospectively. RESULTS Hemodialysis was well tolerated hemodynamically. Electrolytes remained stable throughout hemodialysis in all groups. The decrease in ionized and total calcium was within the expected, clinically acceptable range. Bicarbonate and pH levels increased during dialysis, especially if citrate was used. CONCLUSIONS Slow extended Genius hemodialysis with citrate is well tolerated and offers a safe and effective alternative to systemic anticoagulation.
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Commercial low-citrate anticoagulation haemofiltration in high risk patients with frequent filter clotting.
Naka, T, Egi, M, Bellomo, R, Cole, L, French, C, Botha, J, Wan, L, Fealy, N, Baldwin, I
Anaesthesia and intensive care. 2005;(5):601-8
Abstract
This study assessed the safety and efficacy of a commercial low-citrate concentration-based pre-filter replacement fluid during continuous veno-venous haemofiltration (CVVH) in patients with frequent filter clotting and high risk of bleeding. We used a commercial low-citrate fluid as pre-dilution replacement fluid during CVVH (citrate: 11 mmol/l (33 meq/l), sodium: 140 mmol/l, chloride: 108 mmol/l and potassium: 1 mmol/l). A calcium and magnesium infusion was delivered separately by central line for the maintenance of serum ionized calcium (Cai) and total magnesium (Mg). In this prospective observational study, 30 patients, 124 filters and 1,515 treatment-hours were observed. Median filter life of citrate CVVH was 9.5 hours. Filter life in the 48 hours prior to citrate CVVH was also observed. In the patients on prior non-anticoagulant CVVH (n=14) filter life increased significantly with citrate (9.5 hours vs 5 hours; P<0.0001). In patients on prior heparin CVVH (n = 15), filter life was similar with citrate (10 hours vs 8 hours; P = 0.68). However, in patients with prior early/frequent filter clotting despite heparin (n = 11) filter life increased significantly (10 hours vs 7 hours; P=0.038). Of 411 serum Cai measurements, none showed a Cai < 0.85 mmol/l and, of 84 observations, none showed a serum Mg<0. 6 mmol/l. One patient with sepsis and shock needed to cease citrate CVVH because of progressive ionized hypocalcaemia and increasing anion gap. No other adverse effects were observed. In selected patients, CVVH with a commercial low-citrate concentration solution as pre-filter replacement fluid and a simultaneous calcium and magnesium infusion protocol appears generally safe. Filter life was acceptable and superior to that achieved with previous treatment.
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Incidence of contrast nephropathy in patients receiving comprehensive intravenous and oral hydration.
Mueller, C, Seidensticker, P, Buettner, HJ, Perruchoud, AP, Staub, D, Christ, A, Buerkle, G
Swiss medical weekly. 2005;(19-20):286-90
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) remains a major complication of percutaneous coronary interventions (PCI) and a common cause of acute renal failure. The most effective preventive strategy is unknown. OBJECTIVES This study sought to estimate the incidence of CIN in patients receiving comprehensive intravenous and oral volume supplementation for PCI during which iopromide (Ultravist 370, Schering, Berlin, Germany) was used. METHODS We prospectively studied the development of CIN in 425 consecutive patients undergoing PCI, applying comprehensive intravenous and oral hydration in all patients. Baseline renal function was assessed by calculating the glomerular filtration rate (GFR) with the use of the abbreviated Modification of Diet in Renal Disease Study equation. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dl (44 mmol/l) within 48 hours. RESULTS Mean patients' age (mean +/- SD) was 64 +/- 10 years. A total of 133/425 patients (31%) were 70 years or older, 107 (25%) were women, 70 (16%) were diabetics, 218 (51%) had prior myocardial infarction, and 43 (10%) underwent PCI for an acute ST-segment elevation myocardial infarction. Mean GFR was 89 ml/min/1.73 m2. Glomerular filtration rate was below 60 ml/min/ 1.73 m2 in 43 patients (10%). During PCI 226 +/- 80 ml of iopromide were used. With the comprehensive hydration strategy used, CIN developed in only 6 of 425 (1.4%; 95% confidence interval 0.5-3.1%) patients. No patient required dialysis. CONCLUSIONS Applying the combination of intravenous and oral volume supplementation results in a very low incidence of CIN following PCI. Hydration remains the cornerstone for the prevention of CIN.
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Regional citrate anticoagulation in continuous hemodialysis--acid-base and electrolyte balance at an increased dose of dialysis.
Morgera, S, Haase, M, Ruckert, M, Krieg, H, Kastrup, M, Krausch, D, Vargas-Hein, O, Zuckermann-Becker, H, Peters, H, Pohlmeier, R, et al
Nephron. Clinical practice. 2005;(4):c211-9
Abstract
BACKGROUND Citrate anticoagulation is an excellent alternative to heparin anticoagulation for patients at high risk of bleeding requiring continuous renal replacement therapy. However, citrate anticoagulation has some potential adverse effects such as metabolic alkalosis and acidosis, hypernatremia, hypo- and hypercalcemia. Thus, most citrate anticoagulation protocols use specially designed dialysis fluids to compensate for most of these disarrangements. This study aimed at establishing a citrate anticoagulation protocol designed for a dialysate flow rate of about 2 l/h. METHODS Based on theoretical considerations we composed a dialysis fluid suitable for a 2 l/h dialysis flow rate. The dialysate contained 133 mmol/l sodium, 2 mmol/l potassium, 1.1 mmol/l magnesium, 25 mmol/l lactate, and 112.2 mmol/l chloride. RESULTS Twenty-three patients were included in the study. During the treatments minor flow rate adaptations were needed and the treatments were well tolerated. Filter life was appropriate (51.3 +/- 24.6 h). Thirteen patients developed a mild metabolic alkalosis (pH > 7.45 plus BE > +3) which was easily counteracted by increasing the dialysis fluid flow (by increments of 500 ml). Acid-base values returned to normal within 24 h after increasing the dialysate flow. The maximum dialysate flow was 3,000 ml/h. Hypernatremia and hypocalcemia were not observed. The systemic ionized calcium concentration was successfully controlled by adjustments of a continuous calcium infusion made with respect to the results of 6-hourly measurements. CONCLUSION The analyzed citrate anticoagulation protocol was well tolerated and filter lifetime was appropriate. Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.
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Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.
Kutsogiannis, DJ, Gibney, RT, Stollery, D, Gao, J
Kidney international. 2005;(6):2361-7
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BACKGROUND We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. METHODS Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. RESULTS The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). CONCLUSION Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.