An interventional study of Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration in Acute Kidney Injury, sponsored by Hospital Israelita Albert Einstein. Status unknown at 1 site in Brazil. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-10.
Sponsored by Hospital Israelita Albert Einstein · Not applicable, Interventional, and Treatment
Acute Kidney Injure (AKI) is a syndrome with high incidence and prevalence in Intensive Care Units (ICU). It is estimated that 50% of the in the sector present AKI at some point and 10 to 15% require renal replacement therapy (RRT). Although studies do not show the superiority of continuous methods, the most severely ill patients are directed to this type of RRT. A disadvantage of continuous therapies is the need for anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture).
On the one hand, ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter clotting. There is no consensus on what would be the optimal blood flow (Qb) in continuous dialysis, especially when regional citrate anticoagulation (RCA) is used. Theoretically, a higher flow rate would prevent stasis in the system and decrease the risk of filter clotting. Studies show conflicting results. Increasing Qb from 150 to 250 mL/min showed that circuit life and the chance of coagulation were similar. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow. Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter. Therefore, the higher the convection rate, the higher the blood flow should be to keep the FF in the optimal range. Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing the blood flow, the citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could cause its overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when its maximum metabolizing capacity is not reached and there is an excess of citrate infusion relative to the buffering requirement. Thus, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients undergoing continuous venovenous hemodiafiltration (CVVHDF), regional citrate anticoagulation during blood flow augmentation.
Acute kidney injury (AKI) is a clinical syndrome with a high incidence and prevalence in Intensive care units (ICU). It is estimated that 50% of ICU patients have AKI at some point.
About 10-15% of these individuals require renal replacement therapy (RRT). Although studies have not conclusively shown the superiority of continuous methods, the most severe patients are usually referred for this type of therapy.
The main indications for continuous therapies are hemodynamic instability, cardiogenic shock, severe respiratory insufficiency, risk situations for brain edema, hypercatabolism, need for strict volume control, acute liver disease and major sodium disturbances. One of the main disadvantages of continuous therapies is the necessity of anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture). On the one hand, the lack or ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter coagulation. On the other hand, excessive use of anticoagulants, especially heparin, is associated with bleeding and increased transfusions.
In this scenario, regional anticoagulation with citrate (RCA) has become the method of choice in the different modalities of continuous dialysis. When compared to heparin, the use of regional citrate anticoagulation is associated with less bleeding and transfusion need and longer life of the extracorporeal system. It also seems to decrease endothelial activation, neutrophil degranulation and activation of the complement system.
The anticoagulate property of citrate is based on its binding to calcium (Ca). Citrate quenches Ca in the extracorporeal system, an essential cofactor in several steps of coagulation. Optimal anticoagulation is achieved when ionic Ca concentration in the extracorporeal circuit is maintained between 0.25 and 0.35 mmol/L. This is usually achieved with a citrate level in the circuit around 4mmol/L of blood. Depending on the modality chosen and other factors, up to 60% of the citrate-Ca complex is eliminated during passage through the filter (molecular weigh of 298 Daltons and partition coefficient of 1.0). The rest is metabolized in the Krebs cycle mainly in the liver, kidneys and skeletal muscles. Each mol of trisodium citrate causes 3 moles of bicarbonate thus correctly, partially or completely, the metabolic acidosis resulting from renal failure. Ca and sodium (Na) are released into the systemic circulation. Trisodium citrate also increases the strong ion difference due to the high sodium concentration in the solution, thus increasing the buffering capacity. In parallel it is necessary the Ca replacement to maintain normal calcemia. The citrate also quenches magnesium, which can lead to a disturbance of this electrolyte.
There is no consensus on what the optimal blood flow (Qb) would be in continuous dialysis, especially when using regional citrate anticoagulation. Theoretically, a higher blood flow would prevent stasis in the system and thus decrease the risk of filter coagulation. Studies show conflicting results. For example, one study evaluated increasing Qb from 150 to 250 mL/min and showed that circuit useful life and the chance of coagulation of the extracorporeal system were similar between the two groups. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultra-filtrated flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher the convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range.
Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing blood flow, citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could lead to citrate overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when the maximum capacity of citrate metabolization is not reached and there is an excess of citrate infusion relative to the buffering requirement. The total Ca/systemic ionic Ca ration remains normal, below 2.5. The oversupply of citrate can be easily corrected by decreasing the bicarbonate concentration of the dialysate, increasing the dialysate dose or decreasing the citrate infusion.
Therefore, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients with AKI undergoing continuous venovenous hemodiafiltration (CVVHDF), regional anticoagulation with citrate during increased blood flow.
Hypothesis: Increasing blood flow during continuous venovenous hemodiafiltration prevents stasis in the system and thus reduces the risk of filter coagulation. Blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range. Therefore, it is expected that higher blood flow (250 mL/min) will reduce the FF and concomitantly prolong the life of the filter.
1,641 studies on the registry are indexed under Acute Kidney Injury; 380 are open to participants now.
This study's enrollment of 27 is below the median of 100 across 786 interventional studies indexed under Acute Kidney Injury.
Browse Acute Kidney Injury studies →Hospital Israelita Albert Einstein is the lead sponsor of 147 studies on the registry; 32 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The inclusion criteria will be:
Exclusion criteria will be:
This group will be exposed to continuous venovenous therapy with a blood flow of 150ml/min; already standardized by the institution; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency. Both groups will have a "wash out" of 6 hours before crossing the arms of the work.
Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
This group will be exposed to continuous venovenous therapy with a blood flow of 250ml/min; experimental group to evaluate increased blood flow and filter durability; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency. Both groups will have a "wash out" of 6 hours before crossing the arms of the work.
Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
Patients will be exposed to continuous venovenous renal therapy with distinct blood flows in 2 periods, to be defined by draw. The control group will have a flow of 150ml/min and the intervention group 250ml/min. Therapy is intended for a period of 72 hours (maximum defined by the manufacturer); with a 6-hour "washout" and, after that, the arm is changed to be exposed to the other blood flow.
Analyze filter/system useful life
Evaluate the duration of the continuous hemodiafiltration filter according to changes in blood flow
Time frame: 72 hours per filter
Examine the system pressures
Assess changes in system pressures during the 2 blood flows (transmembrane pressure, filter pressure and access pressure)
Time frame: 72 hours per filter
Assess filtration fraction variation
Assess filtration fraction variation during the 2 blood flows
Time frame: 72 hours per filter
Electrolytic control - Potassium
Assess changes in potassium (changes from baseline)
Time frame: 72 hours per filter (dosage every 12 hours according to protocol)
Electrolytic control - Sodium
Assess changes in sodium (changes from baseline)
Time frame: 72 hours per filter (dosage every 12 hours according to protocol)
Acid-base balance - blood pH
Assess changes in blood pH during the 2 blood flows (changes from baseline)
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - sodium bicarbonate
Assess changes in sodium bicarbonate during the 2 blood flows (changes from baseline)
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - base excess
Assess changes in base excess during the 2 blood flows (changes from baseline)
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Mortality of the cohort
Assess the overall mortality of the cohort in 30, 60 and 90 days
Time frame: 30, 60 and 90 days
Plan to share: No
Ran from Jan 2023 to primary completion in Jan 2023, 0 months.
Of 239 non-industry interventional studies with no phase under Acute Kidney Injury, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 44. This study's 0 months is below that.
Counting every sponsor, half of 255 studies reached it within 26 months; a quarter within 12 and three quarters within 44.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Jan 2024. You cannot join it, but the record below documents what was studied.
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