Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

A Retrospective Chart Review to Determine Hypophosphatemia Incidence and Phosphorus Supplementation Requirements in Patients With Severe Thermal Cutaneous Injuries Receiving High-Volume Hemofiltration.

Patients with severe thermal injuries have increased metabolic demands necessitating frequent phosphate supplementation. Patients with acute renal failure may have less requirements, due to reduced elimination. However, patients being supported with renal replacement therapy have varying degree of requirements. Little published evidence depicts the incidence of hypophosphatemia and repletion requirements in patients with severe thermal injuries treated with high-volume hemofiltration (HVHF) and a high-flux membrane. The objective of this retrospective chart review was to determine the incidence of hypophosphatemia and characterize repletion requirements and response in this population. Enrolled patients had at least 20% TBSA thermal injuries and required continuous hemofiltration with prefilter replacement fluid doses ≥35 mL/kg IBW/hr. A randomly selected cohort without acute kidney injury (AKI) and matched based on age and extent of TBSA was used to compare phosphorus requirements over an initial 14-day period. Demographics, diet, and variables affecting phosphorus concentrations were collected. Sixteen patients were included in the retrospective HVHF group and 16 patients in a case-control cohort to better depict the impact of HVHF. The average age was 60.2 ± 15.1 years and median TBSA was 30% (23.4, 56.3) in the HVHF group, compared to 53.3 ± 16.4 years (P = .22) and TBSA 29% (26.4, 33.9; P = .73). All patients in the HVHF group were started on HVHF with a 1.6 m2 polyethersulfone membrane for AKI. As expected, the HVHF group exhibited statistically higher than normal baseline potassium and phosphorous laboratory values. The HVHF group experienced more days with hypophosphatemia (49.6 ± 12.4% vs 29.3 ± 16.3%, P = .012), despite 0.75 mmol/kg/day phosphorous supplementation (compared to 0.66 mmol/kg/day for the control group, P = .45). Patients with longer durations of HVHF therapy experienced increasing risk of hypophosphatemia, reaching 100% by the end of the study period. This study demonstrates severe thermally injured patients receiving HVHF for AKI are at increased risk for hypophosphatemia, and require high phosphate supplementation.

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb®).

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons' distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase levels successfully despite ongoing tissue ischaemia. However, CytoSorb® was not enough to maintain microcirculatory perfusion, resulting in the eventual demise of the patient due to severity of the injury. Our report indicates that myoglobin was efficiently removed with CytoSorb® following exchange with the conventional high cut-off filter in continuous venovenous haemodialysis in severe traumatic rhabdomyolysis.

The Effects of High Level Magnesium Dialysis/Substitution Fluid on Magnesium Homeostasis under Regional Citrate Anticoagulation in Critically Ill.

BACKGROUND: The requirements for magnesium (Mg) supplementation increase under regional citrate anticoagulation (RCA) because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT) may not be sufficient to prevent hypomagnesemia. METHODS: Patients (n = 45) on CRRT (2,000 ml/h, blood flow (Qb) 100 ml/min) with RCA modality (4% trisodium citrate) using calcium free fluid with 0.75 mmol/l of Mg with additional magnesium substitution were observed after switch to the calcium-free fluid with magnesium concentration of 1.50 mmol/l (n = 42) and no extra magnesium replenishment. All patients had renal indications for CRRT, were treated with the same devices, filters and the same postfilter ionized calcium endpoint (<0.4 mmol/l) of prefilter citrate dosage. Under the high level Mg fluid the Qb, dosages of citrate and CRRT were consequently escalated in 9h steps to test various settings. RESULTS: Median balance of Mg was -0.91 (-1.18 to -0.53) mmol/h with Mg 0.75 mmol/l and 0.2 (0.06-0.35) mmol/h when fluid with Mg 1.50 mmol/l was used. It was close to zero (0.02 (-0.12-0.18) mmol/h) with higher blood flow and dosage of citrate, increased again to 0.15 (-0.11-0.25) mmol/h with 3,000 ml/h of high magnesium containing fluid (p<0.001). The arterial levels of Mg were mildly increased after the change for high level magnesium containing fluid (p<0.01). CONCLUSIONS: Compared to ordinary dialysis fluid the mildly hypermagnesemic fluid provided even balances and adequate levels within ordinary configurations of CRRT with RCA and without a need for extra magnesium replenishment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01361581.

Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration.

OBJECTIVES: To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH). PATIENTS AND METHODS: Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions. RESULTS: Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ±â€Š15.87 versus 71.31 ±â€Š14.24; P = 0.008) and Day 2 (119.01 ±â€Š27.20 versus 104.54 ±â€Š21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis. CONCLUSIONS: There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.

Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation.

PURPOSE: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. METHODS: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3 -30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. RESULTS: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. CONCLUSIONS: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophosphatemia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs.

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

Hemofiltration with the Cascade system in an experimental porcine model of septic shock.

High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock because of its capacities to remove inflammatory mediators from blood. Nevertheless, HVHF presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload due to the frequent changes of large amounts of expensive sterile substitution fluids. A new hemofiltration system called "Cascade" has been developed, allowing very high ultrafiltration rates (120 mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The objective of this study was to assess the technical feasibility of the Cascade system and to compare its hemodynamic impact to that of the standard HVHF system. Twenty sepsis-induced pigs were randomized in two groups: one group was hemofiltered with the standard HVHF system and the other with the Cascade system during a six-hour session. No technical problems were observed with the Cascade system during the experiment. At the end of the experiment, colloid requirements (989 +/- 355 mL vs. 1913 +/- 538 mL, P = 0.006), epinephrine requirements (0.82 +/- 0.42 mg vs. 3.27 +/- 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 +/- 0.08 vs. 7.10 +/- 0.07, P < 0.001) and mean pulmonary arterial pressure were less pronounced in the Cascade group. These results suggest that Cascade hemofiltration is technically feasible and safe. Moreover, compared with standard HVHF, it can reduce the severity of porcine septic shock.

[Cascade hemofiltration: principle, first experimental data]. / L'hémofiltration en cascade : principe, premières données expérimentales.

High-volume hemofiltration has been suggested as an adjuvant treatment of septic shock (renal support and immunomodulation of the host response via the removal of middle molecular weight molecules such as cytokines). Nevertheless, high-volume hemofiltration presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload. We describe cascade hemofiltration, a new high-volume hemofiltration system, which has been developed to limit these drawbacks by using a special extracorporeal circuit. Results of the first experimental study using this prototype are also reported. They demonstrate the technical feasibility, security and safety of the cascade system although other experimental and clinical studies are needed to continue evaluating this system.

Retransfusion of filtered shed blood in primary total hip and knee arthroplasty: a prospective randomized clinical trial.

BACKGROUND: Allogeneic blood transfusions are associated with a number of well-recognized risks and complications. Postoperative retransfusion of filtered shed blood is an alternative to (reduce) allogeneic blood transfusion. The objectives of this study were to evaluate the clinical efficacy of retransfusion of filtered shed blood and to evaluate the complications, in particular febrile reactions. STUDY DESIGN AND METHODS: In this clinical trial 160 patients undergoing primary total hip or knee replacement were randomly assigned to receive either a retransfusion system (Bellovac, AstraTech AB) or a regular drain (Abdovac, AstraTech AB). Patients with a preoperative hemoglobin (Hb) level of between 13.0 and 14.6 g per dL were included. The shed blood was returned 6 hours after operation. After surgery the anesthesiologist determined the transfusion trigger. When Hb level dropped below this trigger, an allogeneic blood transfusion was given. The following data were obtained: number of allogeneic blood transfusions, total volume of blood collected in the bag used for retransfusion, perioperative Hb levels, febrile reaction, and other complications. RESULTS: In the control group 19 percent of the patients received at least one allogeneic blood transfusion. In the study group this percentage was 6 percent of the patients (p = 0.015). Comparing total knee and total hip arthroplasty (control vs. study) the percentages were, respectively, 16 percent versus 2 percent (p = 0.040) and 21 percent versus 11 percent (NS). On average 308 mL of filtered shed blood was retransfused in the study group. In the study group 18 percent of patients had febrile reactions compared to 20 percent in the control group. CONCLUSION: Postoperative retransfusion of filtered shed blood is effective for decreasing allogeneic blood transfusions after total hip and knee arthroplasty. There was no relationship between retransfusions and postoperative febrile reactions.

In vitro clearance of trace elements via continuous renal replacement therapy.

OBJECTIVE: Trace element loss during continuous renal replacement therapy in patients with acute renal failure has not been quantified sufficiently. DESIGN: Trace element loss was quantified using an in vitro model of continuous venovenous hemofiltration. Bovine blood was used for the experiment, and the plasma was analyzed for its chromium, copper, selenium, manganese, and zinc content. Two different polysulfone hemodiafilters, a low-flux F8 and high-flux F70 were used, and tested at two different ultrafiltrate flow rates of 1 L/hr and 2 L/hr, respectively. Trace element concentrations in the plasma and ultrafiltrate were analyzed using inductively coupled plasma mass spectrometry. The sieving coefficient and clearance of each trace element were calculated and compared between the two hemodiafilters. SETTING: In vitro bovine model of continuous venovenous hemofiltration. PATIENTS OR OTHER PARTICIPANTS: Not applicable. RESULTS: Mean sieving coefficients of both F8 and F70 hemodiafilters were similar for each trace element. Copper, chromium, manganese, selenium, and zinc all were detected in the ultrafiltrate. Estimated trace element loss using typical trace element blood concentrations and study-derived sieving coefficients suggest that daily losses of selenium are greater than what is replenished with a standard daily trace element supplement in total parenteral nutrition. CONCLUSION: These data suggest that the degree of continuous venovenous hemofiltration clearance chromium, copper, selenium, manganese, and zinc differ between elements and that selenium and copper might need to be replaced with doses that exceed typical supplementation guidelines.

Electrolyte disorders and substitution fluid in continuous renal replacement therapy.

Electrolyte balances during acute renal failure treated with continuous convective techniques, such as continuous arteriovenous hemofiltration (CAVH) and its pumped variants, are largely dependent on the eloctrolyte plasma concentration available for ultrafiltration, the ultrafiltration rate and the composition of the replacement solution. As blood sodium concentrations measured by potentiometry (Na +P) and the total ultrafiltrate sodium concentration are very similar, Na +P can be taken as the value of ultrafilterable sodium when choosing the correct sodium concentration in the substitution fluid. In CAVH, the ultrafiltrate contains about 3 m Eq/liter of calcium and 1 m Eq/liter of magnesium that must be replaced by the substitution fluid in order to prevent hypocalcemia and hypomagnesemia. In addition, if plasma potassium levels are normal, 3 to 4 mEq/liter of potassium should be added to the replacement fluid to avoid hypokalemia. Although convection and diffusion are combined in continuous hemodialysis, solute transport is largely mediated by convection; however, the net removal of sodium and calcium is significantly influenced by their concentrations in the dialysate, and the risk of hypomagnesemia and hypokalemia can be attenuated by adjusting magnesium and potassium concentrations in the dialysis solution to levels near to the plasma water values. Since critically ill patients are prone to developing dialysis-induced hypophosphatemia, phosphorous must be monitored and supplemented if necessary, Since CRRT works continuously, serious derangement in fluid and electrolyte homeostasis may occur in the absence of careful prescription and extremely vigilant monitoring.

Continuous arteriovenous hemofiltration: an alternative dialysis therapy in neonates.

Modifications have made it possible to perform CAVH in the neonate. One of these is decreasing the extravascular volume in the tubing and filter to a minimal amount to allow for adequate intravascular blood volume in the infant. Another is utilizing predilutional fluid to decrease the need for heparinization. A third modification is utilizing the suction-assist pumps to help control the amount of fluid removed from the infant. With modifications of this system to fit the special needs of neonates and intensive nursing and medical management, CAVH can be a successful alternative to traditional dialysis therapies in neonates.

Continuous arteriovenous hemofiltration in the treatment of 100 critically ill patients with acute renal failure: report on clinical outcome and nutritional aspects.

The clinical outcome for 100 consecutive patients with multiorgan failure including acute renal failure (ARF) was studied. Fifty-eight of the patients had acute renal failure due to complications during and after major surgery. Seventy-three of the patients had a urine output of less than 400 ml/24 hours. The majority of the patients also had complications such as septicemia or respiratory insufficiency and required vasopressor infusions. All patients were treated with continuous arteriovenous hemofiltration (CAVH). The duration of the CAVH treatment varied between a few hours and 90 days, with a mean of 8 days. The mean ultrafiltration volume per 24 hours was, on the average, 12 liters. CAVH resulted in adequate uremic control in 89 cases, but additional treatment with intermittent hemofiltration was necessary in 11 patients. The total survival rate was 45% including survival rates as high as 54% in patients with ARF complicating abdominal aortic surgery. Only three patients were referred for chronic dialysis therapy. In a subgroup of 17 patients with ARF complicating abdominal aortic surgery the nutritional aspects during CAVH were studied. It is concluded that during CAVH therapy it is possible to give adequate nutritional support even to hypercatabolic and anuric patients.