841 improvement in CRRT technology and high sol ute clearance, CRRT may also be used to rapidly decrease potassium and endogenous or exoge nous toxins The main reason for the limited use of IHD in AKI[.]
43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents improvement in CRRT technology and high solute clearance, CRRT may also be used to rapidly decrease potassium and endogenous or exogenous toxins The main reason for the limited use of IHD in AKI is the risk of hemodynamic compromise in ICU patients IHD sessions tend to be performed over short periods, relative to CRRT, leading to hemodynamic instability when attempting to achieve fluid removal goals in a short time frame [64–66] In some patients, rapid solute clearance in a short time frame may increase risk for dialysis disequilibrium syndrome There is a need for nursing and nephrology expertise to perform IHD, access to a clean water source, and specialized equipment For non-ICU hemodynamically stable patients with AKI (e.g., acute interstitial nephritis, rhabdomyolysis), IHD is a treatment of choice Continuous Renal Replacement Therapy Continuous renal replacement therapy (CRRT) provides more gradual and controlled ultrafiltration and solute clearance for hemodynamically unstable patients CRRT allows for the precise control of fluid removal in real time while achieving a similar daily solute removal achieved by IHD. This enables liberalized fluid administration (for medications and nutrition) and momentto-moment response to changes in clinical status CRRT technique is also feasible to teach to large numbers of nurses; together with easily portable machines and solutions, CRRT is ideal for ease of use in the ICU setting Data from the USA multicenter Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry showed that CRRT is used safely across a wide range of critically ill children [67], including neonates (weight as low as 1.3 kg) and hemodynamically unstable patients Despite recent technological advancements in many countries, CRRT is performed utilizing machines designed for adults with large extracorporeal circuit volumes This has stimulated development and currently ongoing research on neonatal-specific CRRT machines characterized by low extracorporeal volumes, increased fluid precision, and ability to use small vascular catheters [68–70] CRRT has also been considered to treat specific pediatric 841 populations, including those with sepsis or undergoing cardiac surgery Convective clearance with CRRT may provide a theoretical benefit in sepsis-induced AKI by enabling middle molecule clearance and stabilizing the immune response [71]; however, RCTs and observational studies in adults and children have not demonstrated a clear benefit [72, 73] There has been interest in using CRRT during cardiac surgery, specifically with respect to use of “modified ultrafiltration.” The goal of this practice is to limit FO development and aid in removal of pro-inflammatory mediators The use of intraoperative modified ultrafiltration in children undergoing cardiopulmonary bypass remains an area of extraordinary center-based practice variation and warrants further study [13] CRRT with Extracorporeal Membrane Oxygenation (ECMO) Children treated with ECMO are at very high risk of AKI (see Epidemiology of AKI) [10] Studies have shown that these patients are at risk of FO, which is associated with increased mortality risk and length of ECMO duration About 20 years ago, Swaniker et al reported that the ability to return to “dry weight” was associated with improved survival There is consensus that CRRT aids with fluid removal during ECMO and nutritional status and is generally safe [74, 75] In neonates, CRRT was associated with reduced duration of ECMO by 24 h [76] In an international survey by the KIDMO group, treatment or prevention of FO was the CRRT indication in 59% of patients treated with ECMO [10] The degree of FO at CRRT initiation for children on ECMO is associated with increased mortality [77] Taken together, these data suggest that children on ECMO may benefit from the early initiation of RST on ECMO, and protocols describing this have been published [78] Further studies are needed to understand optimal use of CRRT in this unique patient population The technical aspects of CRRT during ECMO will not be covered in this chapter However, briefly, two methods have been described One is to add a hemofilter in line within the ECMO circuit and run dialysis fluid countercurrent to the blood flow using intravenous pumps Alternatively, and likely the best method, is to add a CRRT machine in line to the ECMO E H Ulrich et al 842 circuit, typically pre-ECMO pump at the venous end of the circuit Additional anticoagulation is not needed because ECMO requires systemic heparinization [79] Table 43.6 Sample acute PD prescription Fill volume Solution erforming Acute Peritoneal Dialysis P for AKI The International Society for Peritoneal Dialysis (ISPD) released guidelines for the use of peritoneal dialysis in AKI in 2014 for adults and children [80] ccess A A peritoneal dialysis catheter can be relatively easy and safe to insert in the acute setting PD catheters are most commonly inserted surgically using a Tenckhoff catheter; this method has the lowest risk for catheter-related complications and promotes higher-efficiency dialysis (ability to deliver higher dialysis flow rates, maximizing dwell times) Temporary catheters can also be inserted percutaneously at the bedside The drawback of this approach is the increased risk of PD catheter site leakage, infection, and reduced efficacy given the requirement for low fill volumes Expertise is highly recommended for successful temporary catheter insertion Complications related to PD catheter insertion include bleeding and infection; rarely, perforation of the bowel or bladder can occur with insertion of rigid catheters Perioperative antibiotics should be given for surgical prophylaxis; a single dose of cefazolin is the typical choice cute Peritoneal Dialysis Prescription A (Table 43.6) For acute PD, patients typically require starting RST shortly after catheter insertion and catheter flushing with dialysis solution containing heparin (500 units/L) until fluid is clear Commercial solutions are typically used containing sodium, chloride, calcium, magnesium, buffer, and variable amounts of dextrose At our centers, “physiologic” (neutral pH with bicarbonate buffer) dextrose solutions are used These solutions promote preservation of the peritoneal membrane in Cycle length Total dialysis duration 10 mL/kg when catheter is inserted acutely Commercially available solution (e.g., Physioneal® 1.36% or Dianeal® 1.5%) + heparin 500 units/L Hourly cycles: 5-min fill time, 45-min dwell time, and 10-min drain time Typically, 24 h in infants and smaller children Depends on fluid requirements and other components of dialysis prescription (i.e., cycle length) Cycle duration can be reduced to 30 min for several cycles to allow rapid fluid removal Depends on metabolic and fluid requirements the long term and reduce abdominal pain with filling Heparin is added to the dialysis solution for a minimum of 48–72 h in order to prevent catheter obstruction with fibrin clot; heparin may be kept in the dialysis solution bags for longer if there are concerns or there is evidence of fibrin (the goal being to reduce risk of catheter blockage) With reduced time for wound healing, the risk of catheter leakage is high; therefore, low dextrose solutions (Table 43.6) are used with low fill volumes (10 mL/kg) Dextrose concentration is increased to achieve required ultrafiltration acutely; higher dextrose concentrations may be needed to achieve ultrafiltration needs when low fill volumes are used Fill volumes are increased gradually; if tunneled catheter insertion was uncomplicated, fill volumes may be increased over several days to 20–35 mL/kg with close attention for catheter site leak If there is leak, dialysis may be held, and fluid cell counts and cultures sent to rule out peritonitis (particularly with evidence of leak) with or without empiric antibiotic therapy With low fill volumes, manual intermittent PD (IPD) can be performed 24 h/day; automated PD (APD) with a cycler may be used with higher fill volumes, often in non-ICU settings In general, with low fill volumes, dwell durations are short with approximately hourly cycles If higher ultrafiltration or solute clearance is needed, 43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents dialysis solution dextrose concentration may be increased, or cycle duration decreased (minimize fluid absorption via the peritoneal membrane; promote water and solute removal) Cycle durations as short as 30–45 (dwell times ~15– 20 min) may help achieve rapid fluid removal and solute clearance Despite ISPD guideline recommendations, there is little data on ideal “dose” for acute PD [57] Complications There is increased risk for poor efficiency dialysis and ultrafiltration with acute PD due to use of low fill volumes Severely ill children may have poor perfusion of the peritoneal membrane, which further reduces dialysis efficacy As a result, patients with severe metabolic disturbances (e.g., hyperammonemia) or FO may need to be considered for alternative RST modalities (IHD or CRRT) Early PD catheter insertion in high-risk patients to reduce catheter-related complications is ideal, where possible Of note, ultrafiltration may be unpredictable, resulting in less precise fluid removal that can result in dehydration and further renal injury [57], mandating frequent assessment of ultrafiltration and fluid balance after PD initiation Mechanical complications are similar to those of chronic PD (leaks around the catheter, in the subcutaneous tissue, or into pleural space; catheter kinking/malposition; catheter dysfunction due to constipation or obstruction by clot or omentum; hernias) These complications are lower with Tenckhoff catheters compared to rigid catheters Tidal PD prescriptions are sometimes used in patients with significant fill and drain pain As in chronic PD, vigilance for infection and use of aseptic technique when handling the catheter and performing dressing changes are crucial; this is important to impress upon ICU healthcare teams who may have limited experience with performing PD. Topical mupirocin ointment is applied to the PD catheter exit site at our center to reduce infection risk Consideration for use of antifungal therapy (such as nystatin) should be made for patients receiving antimicrobials Other complications include the risk of hyperglycemia with high glucose concentration solutions There is also risk for malnutrition due 843 to PD-related protein loss and sodium disturbances associated with water and sodium losses Hypothermia may occur if the dialysis fluid is not adequately warmed PD is fairly well tolerated from a hemodynamic perspective Tidal PD prescriptions should be considered in pre-load-dependent patients that may not tolerate fill and drains Patients with respiratory distress or infants with severe gastroesophageal reflux may not tolerate large fill volumes Patients with prune belly syndrome and ventriculo-peritoneal shunts can receive peritoneal dialysis; however, a history of other abdominal surgeries may make PD quite challenging Acute Hemodialysis for AKI Although there has been significant shift away from PD toward CRRT, the use of intermittent hemodialysis (IHD) in AKI has remained relatively constant for the treatment of life- threatening emergencies (e.g., severe hyperkalemia; ingestions; hyperammonemia) or non-critically ill patients with AKI. A limited discussion below will highlight unique aspects of IHD in AKI; more detail is provided in chronic hemodialysis chapters, and vascular access is discussed below in the CRRT section of this chapter cute Hemodialysis Prescription A Acute IHD prescription is similar to initial prescription of chronic hemodialysis [81] When IHD is performed outside the HD unit, access to water and use of a portable reverse osmosis device are needed Dialysis fluid prescription is similar to that of chronic hemodialysis; prescribed potassium and phosphate concentration should be based on patient labs Biocompatible dialyzers are used with a surface area close to the body surface area of the child Blood priming of the circuit should be done if the extracorporeal volume is >10% of the total blood volume Dialysis flow rate is typically set at a standard rate of 500 mL/min IHD for AKI is performed over a short period, and rapid urea reduction can cause disequilibrium syndrome (i.e., headache, cerebral edema, sei- E H Ulrich et al 844 zures, and potentially death) Although patients with underlying CKD are at highest risk for disequilibrium syndrome, patients with AKI (especially if progression to RST need is over days to weeks), very high blood urea nitrogen levels (e.g., >30 mmol/L), and concomitant risks for cerebral edema (as often seen in ICU patients) may be at risk Rapid urea reduction should be avoided in the first two to three IHD sessions Some centers use slightly higher than usual dialysis fluid sodium concentration (i.e., 145 mmol/L), and most centers will administer intravenous mannitol (0.5–1 g/kg over the first 1–2 h of IHD) if there is concern for dialysis disequilibrium or blood urea nitrogen levels are very high At our centers, two approaches are used to avoid rapid urea reduction and disequilibrium syndrome in AKI. The first is based on the fact that the primary determinant of solute clearance with IHD is blood flow Thus, in the first IHD session for AKI, low blood flow rates (e.g., ~2 mL/kg/min) are used, and duration is short (2–2.5 h) In future sessions, blood flow and IHD duration are gradually increased as tolerated Another approach is based on (a) initially aiming for urea reduction of 30%, which is relatively safe to avoid disequilibrium syndrome, (b) using the known logarithmic relationship between urea reduction and Kt/V (shown in Table 43.7) to determine duration of the first IHD session, and (c) slowly increasing urea reduction goals for future IHD sessions using data from previous IHD sessions (detailed in Table 43.7) Fluid management when using IHD for AKI is challenging for oligoanuric patients as daily fluid Table 43.7 Example approach to prescribing urea reduction for acute hemodialysis Step Determine urea reduction (UR) goal for first IHD session and Calculate first IHD session duration (minutes) Logarithmic relationship between UR and Kt/V is: − ln (post IHD urea concentration/pre ‐ urea concentration) = Kt/V t = time (min) V = volume = total body water in mL (consider patient age when calculating − this parameter is estimated) K = urea reduction coefficient in mL/min (based on dialyzer, QB, QD) Often similar to blood flow, so if blood flow is 50 mL/min, K will often be 50 mL/min First IHD treatment example: UR goal is 30%: −ln(post IHD urea concentration/pre-urea concentration) = −ln(0.7) = 0.36 Using formula above, solve for t (minutes) or duration of first IHD treatment: t minutes of IHD Step Recalculate V (total body water in mL) based on previous IHD session data Step Calculate t (minutes) to achieve desired UR for future IHD sessions (e.g., second, third) ln post urea / pre - urea V mL K mL / Ensure to order pre- and post-urea concentration testing for first 3–4 IHD treatments Solve for V using equation above and data from previous session: t minutes of IHD of previous session K mL / of previous IHDsession NewV mL ln post urea / pre - urea from the previous IHDsession recalculated V mL to use for the current IHDsession Solve for t (minutes) of subsequent IHD treatments, using New (recalculated) V: t minutes of IHD ln post urea / pre - urea NewV mL K mL / New V = V calculated in step 2, from data of previous IHD treatment Proposed UR goals for second and third IHD treatment: Second IHD treatment UR goal 50%: −ln(post urea/pre-urea) = −ln(0.5) = 0.69 Third IHD treatment UR goal 70%: −ln(post urea/pre-urea) = −ln(0.3) = 1.2 ln natural logarithm function, IHD intermittent hemodialysis, QB blood flow rate (mL/min), QD dialysis flow rate, (mL/min) 43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents removal must be performed within a short session Fluid restriction is often required If IHD is tolerated and safe with regard to urea reduction, longer IHD sessions may help achieve fluid removal goals In very hemodynamically stable patients, ultrafiltration rate as high as ~0.2 mL/ kg/min (or 12 mL/kg/h) may be tolerated; however, in acutely ill patients, hypotension is common, limiting ability to achieve ultrafiltration >1–3 mL/kg/h Some centers use blood volume monitoring software available with some dialysis machines to help guide fluid removal As in chronic IHD, heparin anticoagulation is used (10–20 units/kg bolus, followed by continuous infusion), and activated clotting time is monitored However, in many acute illnesses, bleeding risk may be high, in which case IHD may be performed without anticoagulation This often requires frequent flushing with normal saline to the circuit pre-filter to prevent clotting Administering frequent fluid boluses to prevent clotting complicates fluid removal in infants, because this fluid must be removed, which may not be tolerated in small, sick children For hemodynamically unstable patients, CRRT is thus a better option ontinuous Renal Replacement C Therapy for AKI CRRT offers several advantages, most importantly the delivery of highly precise therapy [82] Gradual fluid removal offers improved hemodynamic stability and enables nutrition CRRT provides more efficient clearance than PD, allowing rapid correction of electrolyte and metabolic disturbances The major limitation of CRRT has historically been requirement for technical expertise; however, this barrier has decreased, with simpler and safer machines adapted for use in children [83] Vascular Access (Table 43.8) Vascular access is challenging in children, especially infants However, it is key to administering efficient CRRT, as access issues may lead to cessation of CRRT, circuit clotting, and, ultimately, time off therapy 845 Table 43.8 Vascular access for CRRT Neck lines Femoral lines Weight