847 the 1980s; this system relied on the arteriovenous pressure gradient to drive circuit flow The advent of continuous venovenous hemofiltration adapted for children in the 1990s, as well as improve[.]
43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents the 1980s; this system relied on the arteriovenous pressure gradient to drive circuit flow The advent of continuous venovenous hemofiltration adapted for children in the 1990s, as well as improvements to filter and circuit design, allowed longer circuit survival and precise ultrafiltration These advancements effectively replaced historical CAVH systems and ushered the way forward for the safe use of CRRT in children [85] Several different commercially available machines may be used to deliver CRRT (not covered here) Ultrafiltration (removal of fluid from the patient) is driven by hydrostatic pressure generated across the semipermeable membrane of the hemofilter Clearance of solutes may be accomplished by convection (continuous venovenous hemofiltration, CVVH), diffusion (continuous venovenous hemodialysis, CVVHD), or both (continuous venovenous hemodiafiltration, CVVHDF) (Fig. 43.3) [72] In CVVHD, as with IHD, solute clearance is achieved by diffusion, with dialysis fluid being run countercurrent to blood flow across the semipermeable membrane of the hemofilter In CVVH, convective solute clearance is achieved by infusing high volumes of sterile replacement fluid solution into the circuit, in order to allow for simultaneous removal of large amounts of fluid across the hemofilter to drive convective clearance With CVVHDF, both dialysis fluid and replacement fluid are used It is theorized that CVVH or CVVHDF, which provides convective (middle molecule) clearance, may provide additional benefit over CVVHD due to clearance of inflammatory molecules (e.g., with sepsis) To date, there is little strong evidence to support this [86], and center practice variation dictates decisions on use of convective clearance in patients with severe inflammatory or infectious conditions Small solute clearance is achievable using either CVVHD or CVVH (or CVVHDF) CVVH and CVVHDF additionally provide middle molecule clearance (via convection) Replacement fluid in CVVH and CVVHDF can be delivered pre-filter (via a port located within the circuit, before the hemofilter) or post-filter The advantage of pre-filter delivery of replacement fluid is a reduced risk of filter clotting (as the replacement 847 fluid “dilutes” the blood entering the hemofilter) compared to post-filter replacement where the blood delivered to the filter is more viscous The risk of circuit clotting with post-filter replacement in CVVH (as well as with CVVHD, where no replacement fluid is used) is increased when the filtration fraction rises above 25% Filtration fraction is the ratio of ultrafiltration rate to plasma flow rate: filtration fraction = QUF/[Qb (1 − Hct) + Qr], where QUF represents ultrafiltrate flow rate, Qb represents blood flow rate, Hct represents hematocrit, and Qr represents pre-dilution replacement flow rate (include where applicable) However, post-filter replacement provides higher solute clearance, as solute concentration in the blood pre-hemofilter is not affected by infused replacement fluid emofilter and Blood Prime H CRRT hemofilters contain hollow fibers that are permeable to non-protein-bound solutes with a molecular weight below approximately 40,000 Daltons Filters are selected according to patient weight Biocompatible filters are the standard for CRRT and include acrylonitrile (AN69)-based and polysulfone-based filters AN69 membranes come with a risk of bradykinin release syndrome, which is worsened by the use of angiotensin- converting enzyme inhibitors and blood prime The risk of this reaction is also pH dependent In order to prevent this complication, the blood prime can be administered post-filter, and bicarbonate (infusion with bolus) is administered to maintain a neutral pH [87] Another method utilized to minimize the bradykinin release syndrome with AN69 membranes and metabolic complications of performing blood prime is to perform a “pre-dialysis” procedure on the blood prime solution, whereby the blood is circulated through the CRRT machine against dialysis solution for 5–10 min (before connecting the patient to the circuit) to normalize pH, calcium, and potassium content of the blood prime solution [88] Bradykinin release syndrome is not a complication of nonAN69 polysulfone membranes and is much less common and severe with newer protein-coated AN69 membranes The size of the hemofilter E H Ulrich et al 848 should be selected based on patient size, when possible, to avoid the need for a blood prime Children for whom the extracorporeal circuit volume exceeds ~10% of estimated blood volume will generally require a blood prime; most children 300–500 mL/day negative balance) and to aim for ≤1–2 mL/kg/h negative balance (e.g., 10 kg child, ≤20 mL/h negative balance) When achieving negative balance is urgent (e.g., need to stop ECMO as soon as possible), temporary slightly more aggressive negative balance goals may be carefully used Increasing vasopressor support may be required for patients to tolerate fluid removal It is not recommended to keep unstable patients in positive fluid balance by reducing the ultrafiltration; rather, additional fluid or inotropic support should be used to maintain blood pressure Anticoagulation Although there are several options for anticoagulation, CRRT is generally performed using either regional citrate anticoagulation or systemic unfractionated heparin anticoagulation CRRT may be successfully performed with no anticoagulation (with or without flushing of the circuit pre-filter with normal saline); however, circuit life will likely be much lower (high incidence of clotting) As in IHD, systemic heparin anticoagulation is performed by infusing heparin pre-filter and monitoring partial thromboplastin time (PTT) and/or activated clotting time (ACT) for target PTT 1.5 times normal and/or ACT 180–220 s (with higher blood flows or bleeding risk concerns, target ACT may be lower) Patients with severe bleeding risk, active bleeding, or heparin-induced thrombocytopenia should not receive heparin Increasingly, pediatric centers are using regional citrate anticoagulation for CRRT. Studies in adults and children support that though there is no difference in mortality, circuit life is likely to be longer when 43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents using citrate anticoagulation, and bleeding events tend to be higher when using heparin anticoagulation [94, 95] Regional citrate anticoagulation is achieved by infusing a commercially prepared citrate solution pre-filter (Table 43.9) Citrate chelates free ionized calcium, which is required for clotting Citrate may be infused at the access port of the catheter (using an intravenous pump separate from the CRRT machine) or, for some machines, may be administered as a pre-filter replacement solution, incorporated within the machine The goal is to target an ionized calcium concentration of ~0.3–0.4 mmol/L in the blood within the extracorporeal circuit (“circuit ionized calcium”) to prevent clotting Although calcium citrate complexes are cleared at the hemofilter, a substantial amount of citrate in the circuit blood will be returned to the patient, placing them at risk for hypocalcemia Thus, patients must receive a continuous intravenous calcium infusion to prevent systemic hypocalcemia Calcium is ideally infused through a separate central line; however, it may be infused at the end of the circuit, at the return port of the vascular access, or near to the patient’s skin (acknowledging that there is a theoretical risk of access clotting; single-center data has not shown this to be the case) [96] Systemic citrate is metabolized predominantly by the liver (and to a lesser extent by the skeletal muscle and kidney) with one molecule of citrate yielding three molecules of bicarbonate; calcium which is complexed to citrate is released when citrate is metabolized Patient ionized calcium levels must be closely monitored and kept within normal range Several delivery and monitoring protocols for regional citrate anticoagulation exist Table 43.11 shows a sample citrate protocol Typically, citrate is administered at a rate proportional to the blood flow (to ensure adequate anticoagulation) Circuit and serum ionized calcium levels are monitored serially (an hour after any citrate or calcium infusion change and every 4–6 h when stable) with citrate and calcium infusion adjustments accordingly As mentioned, closer circuit and patient calcium monitoring is needed when using high clearance rates (e.g., when treating hyperammonemia, current citrate 851 and calcium administration protocols were based on targeting a clearance rate of ~2 L/1.73 m/h or in patients with severe liver disease since systemic citrate may accumulate due to decreased liver metabolism) Some citrate protocols incorporate a priori modified (lower) citrate rates in patients with severe liver disease Common complications of citrate anticoagulation include hypocalcemia and metabolic alkalosis Hypocalcemia occurs due to inadequate patient calcium delivery or excess systemic citrate binding free ionized calcium Hypercalcemia may occur if the circuit clots and CRRT is stopped suddenly In the setting of elevated systemic citrate, as citrate is metabolized to bicarbonate, previously complexed calcium is released into the bloodstream with limited means of excretion in a patient with severe renal dysfunction Metabolic alkalosis is due to excess bicarbonate generation by citrate metabolism; metabolic alkalosis may also be contributed to by the high bicarbonate load in most commercially prepared solutions Citrate use also contributes to hypomagnesemia, commonly seen in patients receiving CRRT, due to magnesium binding Less commonly, hypernatremia (more commonly with sodium citrate solutions, Table 43.9), hyperglycemia, and metabolic acidosis can occur The occurrence of excess systemic citrate accumulation must be monitored, to avoid the situation commonly referred to in the literature as “citrate lock” or evidence of complications of citrate accumulation described above (i.e., hypocalcemia/increasing calcium infusion needs) To monitor for citrate accumulation, total patient calcium is measured at least every 12–24 h; with significant systemic citrate accumulation, total calcium rises (includes citrate complex and free calcium), and systemic ionized calcium will tend to be low A ratio of total to ionized calcium >2.5–2.8 is a surrogate marker of significant systemic citrate accumulation (or a surrogate marker of high citrate concentration) Risk factors for significant citrate accumulation (or total/ionized calcium >2.5–2.8) include young age (due to the relatively high blood flows required and subsequently high citrate delivery), severe liver failure, and lactic acidosis Citrate accumulation is E H Ulrich et al 852 Table 43.11 Sample CRRT citrate anticoagulation protocol: key items Vascular access Dialysis solution Citrate flow rate Calcium flow rate Serum investigations Target calcium concentration Citrate anticoagulation management Circuit change Hemodialysis central line, ideally second central line for calcium infusion Prism0Calđ Table 43.9 1.5ì blood flow rate For example, if blood flow 50 mL/min, citrate flow (mL/h) rate = 75 mL/h At Hospital for Sick Children, blood flow rate maximum of 100 mL/min to avoid excessive citrate delivery 0.4× citrate flow rate For example, if citrate flow rate is 75 mL/h, calcium flow (mL/h) rate = 30 mL/h Initial iCab, total calcium Electrolytes (sodium, potassium, chloride, bicarbonate, glucose, magnesium, phosphate) Lactate Creatinine, urea, albumin, ALT (assess for liver disease) Complete blood count, PTT, INR Every 2 h iCa Every 4 h Total calcium Electrolytes (sodium, potassium, chloride, bicarbonate, glucose, magnesium, phosphate) Every 12 h Lactate PTT, INR Every 24 h Creatinine, urea, albumin, ALT Complete blood count Circuit iCa 0.25–0.4 mmol/L Call MD if 0.4 mmol/L Patient iCa 1.1–1.3 mmol/L Call MD if 1.5 mmol/L Circuit iCa 20 kg Increase citrate by 10 mL/h Patient iCa 1.3 20 kg Decrease calcium by 10 mL/h Every 72 h Some items taken from CRRT citrate anticoagulation protocol used at the Hospital for Sick Children, Toronto, Canada Ionized calcium ALT alanine aminotransferase, INR international normalized ratio, PTT partial thromboplastin time a b treated by increasing citrate removal or reducing delivery To increase removal, CRRT clearance may be increased (i.e., increasing dialysis fluid rate to increase removal of calcium citrate complexes; being mindful to adjust medication doses and monitor for effects of higher clearance), or blood flow decreased (to reduce citrate needs to maintain anticoagulation) To decrease citrate delivery, the citrate infusion may be decreased or temporarily stopped (e.g., 3–6 h) If the citrate infusion is held, it may be restarted at a lower rate (e.g., ~70%) When there is no evidence of citrate accumulation but there is clinically significant metabolic alkalosis, reducing citrate delivery ... replacement fluid rate to prevent clotting in the circuit; this replacement fluid should be included in the total solute clearance dose This level of solute clearance will be adequate for most... pre-filter replacement solution, incorporated within the machine The goal is to target an ionized calcium concentration of ~0.3–0.4 mmol/L in the blood within the extracorporeal circuit (“circuit ionized... 0.7 m2, then the dialysis solution rate is run at ~2 L/1.73 m2/h or ~800 mL/h If CVVH is used for this patient, the replacement solution is run at ~800 mL/h If CVVHDF is used, the combined rate