CRRT solutions Benan Bayrakci, 2014

CRRT delivery CVVH is convective, use replasment fluid ( lood side of the filter) CVVHD is diffusive, use dialysate fluid (opposite side of the filter) There are no convincing clinical data to support either CVVH or CVVHD Combination therapy; CVVHDF is also not supported by evidence How fluid is delivered has little impact on the composition of the fluid The replacement and dialysate fluids should have the same composition to reduce staff confusion and the risk for error

Options for fluids in CRRT Custom fluids compounded by the pharmacy - The complications of compounding include increased cost and a shorter shelf life (usually 30 days). Commercially prepared fluids with additives - K, P, Mg and even bicarb can be added as needed but, carries the risque for pharmacy errors and may increase costs. - Whether replacement fluid or dialysate is utilized, the fluid should be ultrapure and sterile. - Each time an additive is injected, this is associated with a chance of human error; contamination; wrong dose; wrong syringe, wrong vial etc. Commercially prepared pre-mixed fluids - The safest approach. Less expensive and have longer shelf life. - Available from multiple manufacturers, generally 3 l and 5 l bags with a discrete number of fluid compositions. - The most common concentrations of these solutes are equal to normal plasma levels

Evaluation of Errors in Preparation of CRRT Solutions Survey of 3 Pediatric Listserves: Pediatric Critical Care, Nephrology, CRRT 16/31 programs reported solution compounding errors Consequences of improper solutions 2 deaths 1 non lethal cardiac arrest 6 seizures (hypo/hypernatremia) 7 without complications Barletta et al, Pediatr Nephrol. 21(6):842-5, 2006 Jun

PD solutions are not recommended PD solutions are not recommended! because of the risque of hyperglycemia and metabolic acidosis

Replacement fluids: Are directly given in to the blood pre- or post filter They are used to increase the amount of convective solute removal Despite their name, replacement fluids do not replace fluid. Fluid removal rates are calculated independently of replacement fluid rates

Predilution: Postdilution: Lower solute clearance, Higher ultrafiltration rate Larger filter surface area Reduced sludging and need for anticoagulation Use of pre-filter replacement fluids invalidate post-filter lab draws Postdilution: Higher filtration fraction

Fluid Composition Sodium Should be in the physiologic range (140 meq⁄l). Customization needed if hypertonic citrate for anticoagulation is used CVVHDF is more likely to achieve serum sodium concentrations within the normal range than CVVH Supraphysiological sodium concentration in the dialysate or replacement solutions would improve the hemodynamic stability or prevent the increase in intracranial pressure, but there are no conclusive data concerning this issue.

Potassium K concentrations between 0 to 4 meq⁄ l are acceptable and commercially available. Most patients have a degree of hyperkalemia at initiation of RRT therapy. If K free fluid is used, careful monitoring is necessary. In cases of severe hyperkalemia associated with arrhythmia and⁄or hemodynamic collapse hemodialysis should be utilized.

Calcium About 60% of total plasma calcium is ultrafilterable, substitution fluid in CVVH must contain about 3 mEq/l of calcium Patients undergoing an exchange of very large volumes of ultrafiltrate carry the risk of hypercalcemia, therefore may require a lower content of calcium in replacement fluids. Calcium is always absent from solutions when phosphate is present During citrate anticoagulation, if calcium is present in the fluid it will neutralize the citrate before it can do its job of keeping the filter free of clots

Magnesium Mg in CRRT fluids ranges between 1 and 1.5 meq ⁄ l. This level is not well studied but has been clinically successful A bolus of 2–4 g should be prescribed when Mg levels fall below normal range.

Phosphorus P plays a key role in cellular metabolism and is essential in several biological processes Phosphorus is not a standard component of replacement or dialysate fluids in CRRT. This is appropriate as CRRT is commonly employed in the setting of hyperphosphatemia Majority of patients on CRRT will require phosphate supplementation shortly after CRRT initiation. Critically ill patients present several conditions predisposing hypophosphatemia such as sepsis, malnutrition, catecholamines, intravenous glucose infusion, hyperventilation, diuretics and rhabdomyolysis. Management of hypophosphatemia: - Ensure proper nutrition. - Add P to the solutions - Use Phosphate-containing ready solutions

The addition of phosphate to the CRRT fluids at concentrations of up to 7.7 mg/dL does not cause problems with precipitation or instability of the mixture.

Glucose Physiologic concentrations of glucose in the dialysate and replacement fluids is advised to compensate extracorporeal losses Glucose-free solutions might be used when an adequate nutritional regimen has been established

Lactate The simplest, most economical solution; no mixing required. Effectiveness is well-supported in clinical literature. Many adults are successfully treated with CVVH using Lactated Ringer's solution as it is: - convenient - cheap - eliminates risk of pharmacy error Patients with severe liver failure, and particularly those with reduced muscle blood flow, may fail to metabolise lactate and develop a metabolic acidosis. In ICU patients suffering from multiple organ dysfunction, the conversion of lactate to bicarbonate is frequently impaired Lactic acidosis causes cardiac dysfunction and hypotension Many fluids contain a small, clinically insignificant amount of lactate to improve stability

Sodium bicarbonate The sodium bicarbonate concentration in CRRT fluids can be variable. With customized solutions bicarbonate theoretically can vary from 0 to 150 meq ⁄ l. With prescribed CRRT clearances of 20 ml⁄kg⁄hour, most acid base disturbances can be managed with commercially available bicarbonate compositions of 25 meq⁄ l to 35 meq⁄ l. If there is difficulty improving pH with a commercially available solution, therapy can be changed to accommodate the patient’s needs. Options: Pharmacy customized solutions with higher bicarb Supplemental bicarbonate drip Increase the clearance rate of the CRRT system. By increasing the clearance rate, acid removal is increased as is bicarbonate administration. The first two options have a risk of human error, whereas it is simple to increase clearances to significantly greater than 35 ml ⁄kg ⁄hour.

Bicarb-buffered replacement fluids can improve acid-base status and reduce cardiovascular events better than lactate fluids The buffer concentration should exert a buffer load that may compensate for deficits, for losses in the buffer process, and for extracorporeal losses and should therefore usually be supraphysiological. Be avare of hypercapnia! Citrate is metabolized to bicarbonate, each citrate ion producing three bicarbonate ions, no additional anionic base is required during citrate anticoagulation Bicarbonate-based dialysate/replacement fluids are considered standard of care today

Dialysate solutions containing bicarbonate have low compatibility with calcium. If calcium is added to a bag containing bicarbonate, calcium carbonate produces , which could precipitate out of solution and clog the filter. Calcium can be added to bicarbonate-containing solutions in limited amounts; calcium concentrations of less than 2.5 mEq/L usually do not result in precipitation. The two-compartment bag with unique peel-seam interface simplifies preparation and mixing prior to use.

A total of 62 patients Bicarbonate-based CRRT fluids cost some 28% more than standard lactate fluids Bicarbonate fluids led to a more rapid fall in lactate and greater improvement in base excess during CRRT, but not overall control of acidosis The choice of fluid for CRRT did not affect blood pressure or vasopressor requirements.

Albumin Can be added in dialysate to remove protein bound medications in the setting of intoxication as well as substances such bilirubin

Fluid temperature The use of replacement fluids or dialysate solutions at room temperature as well as continuous blood flow through the extracorporeal system cause an average 2C reduction in body temperature, and an energy loss of about 1,000 kcal/day The energy loss during CVVHD is important in hemodynamic stability and prognosis Heat loss and consequent hypothermia may also affect immune functions and increase the risk of clotting of circuit Lower body temperature may be desirable in patients with excessive oxygen consumption and low systemic vascular resistance It is not clearly known in which patients the net effect of CRRT-induced hypothermia is useful or harmful

Formula of an Ideal CRRT Solution Physiological Reliable Inexpensive Easy to prepare Simple to store Quick to the bedside Widely available Fully compatible

We dont really know the solution of this formula but what we know is…

A successful CRRT program can only run on safe fluids !