Introduction Acute renal failure (ARF) is uncommon in childhood, but its incidence may be increasing and modalities of treatment changing with an increasing number of children being treated in the intensive care unit (ICU) with multi-organ failure. Traditionally children with ARF with renal involvement were only treated with peritoneal dialysis, but extracorporeal techniques are being increasingly used in ICUs. Members of the European Pediatric Dialysis Working Group reviewed all modalities of renal replacement therapy for ARF in children and developed the following guidelines in collaboration with nursing staff during three meetings and extensive e-mail discussion. There are no randomized trials of renal replacement treatment in children with ARF. The guidelines are based upon published reports and consensus opinion to emphasize good practice. 1 2 3 4 4 5 6 7 8 6 Recommendations 9 All children with ARF as part of multi-organ failure require transfer to a designated regional pediatric ICU where there should be access to pediatric nephrology advice and support (good practice). Rationale Since there are few comprehensive regional pediatric nephrology centers the distances that families may have to travel can be considerable. Children with acute renal impairment may be managed in local hospitals, but it is essential that early referral is made, especially if children have evidence of rapidly deteriorating renal function and require an urgent histological diagnosis to determine if immunosuppressive therapy or other treatment is required. Indications for referral include oligoanuria, especially if associated with fluid overload, hypertension, hyperkalemia, hyponatremia, acidosis, or the need for blood transfusion. Dialysis is often accompanied by early nutritional support and pediatric nephrology units should be equipped to provide the necessary medical and nursing expertise, combined with dietetic and psychosocial support. The latter support is also important if the child is managed conservatively. Neonates and premature infants with ARF require transfer to a tertiary neonatal unit with pediatric nephrology team expertise. Patients with ARF and multi-organ failure require prompt transfer to a designated regional PICU. The choice of dialysis therapy for ARF depends upon the clinical circumstances, patient location, and expertise available. Peritoneal dialysis (PD) has generally been considered the preferred therapy if there is isolated failure of the kidneys, such as HUS. It is regarded as a simpler technique that is universally available. However, hemofiltration (HF) and hemodiafiltration (HDF) are increasing in popularity in PICUs where the facilities to perform hemodialysis (HD) may not be available. HD may be the preferred mode of treatment in more-stable patients with adequate vascular access treated on renal units where specialist nurses are available. 10 11 12 Recommendation 1 6 13 Table 1 CVVH  CVVHDF Type Complexity Use in hypotension Efficiency Volume control Anticoagulation Peritoneal dialysis Low Yes Moderate Moderate No Intermittent hemodialysis Moderate No High Moderate Yes CVVH Moderate Yes Moderate Good Yes CVVHDF High Yes High Good Yes Choice of therapy Acute PD 14 15 16 17 18 19 20 21 22 Limitations in the use of PD 23 24 25 26 Preparation for PD Dialysis is only possible if the access provides free flow in and out of the abdomen. The choice is between catheters inserted at the bedside under sedation or the placement of a chronic PD catheter by a pediatric surgeon in the operating theater, or exceptionally at the bedside in the ICU. 27 28 29 13 30 31 32 For catheters that are inserted percutaneously, prophylactic antibiotics, e.g., cefuroxime 125 mg/l, should be added to the dialysis fluid unless the patient is on systemic treatment. 33 34 PD prescription 30 35 36 Choice of dialysis solution 37 The general principle is to commence with the lowest concentration of glucose solution possible (1.36%), with stepwise increments. Care is needed if 3.86% glucose solution is required as (1) rapid ultrafiltration can occur (especially in infants) and (2) hyperglycemia may develop (especially in septic and multi-organ failure patients) leading to hyperosmolarity and loss of effective ultrafiltration. 38 39 Practical points 33 34 2 A PD program with 1-h dwells should be used during the first 24 h. Shorter cycles can be considered initially if hyperkalemia needs urgent treatment. 2 40 41 42 43 The amount of ultrafiltration that is prescribed will partly depend upon the volume of oral, nasogastric, or total parenteral nutrition that is required, combined with fluid for drugs. Ultrafiltration may not be enough without the use of 2.27% or 3.86% glucose solutions. 44 Rationale 40 45 Complications of acute PD 46 47 48 49 Hernias can be a problem in neonates and infants, particularly males. They do not usually require interruption of PD and can be repaired electively by laparoscopic or direct measures when the child’s clinical condition has improved or stabilized. 50 Continuous extracorporeal techniques 51 52 53 54 Practical guidelines for prescription Since the concentration of solutes in the filtrate is the same as in the plasma, biochemistry is controlled by removing large volumes of filtrate and replacing it with electrolyte-containing fluid (HF replacement fluid). As most solutes are distributed within the extracellular and intracellular fluid compartments (total body water), the exchange volume of filtration necessary to control biochemistry relates to total body water. Clinical experience has shown that a turnover of approximately 50% of body weight in 24 h is usually adequate for CVVH. Patient size (kg) Vascular access 2.5–10 6.5-FG dual-lumen (10 cm) 10–20 8-FG dual-lumen (15 cm) >20 10.8-FG or larger dual-lumen (20 cm) 55 56 57 58 59 60 Patient size (kg) Maximum filtration rate (ml/h) <8.5 250 8.5–20 500 >20 2,000 61 A variety of replacement fluids are available such as lactate, bicarbonate, and buffer-free solutions. Bicarbonate or buffer-free solutions should be used in young infants and those intolerant of lactate. If a commercially available bicarbonate solution were freely available, then this would be the solution of choice. Careful monitoring of electrolytes, glucose, and phosphate is essential, as the constituents vary between the solutions. Anticoagulation 6 62 63 64 65 Adjustment of the prescription Any formula for the prescription of HF is at best an approximation or starting point, as the needs will be determined by many unmeasured variables, such as the rate of solute production, nutritional intake, and the actual volumes of the extracellular fluid and intracellular fluid compartments. If only fluid removal is required, then relatively low rates of filtration are needed, often referred to as slow continuous ultrafiltration (SCUF). There will be negligible solute removal under these circumstances. Correction of “uremia” and electrolyte disturbance requires the turnover of large volumes per kilogram of fluid, typically of the order of 50% of body weight per day for post-dilution and 75% for pre-dilution (approximately 20–30 ml/kg per hour). In catabolic patients, the clearances achieved with standard CVVH may not be sufficient. Solute removal may be increased by attempting “high-volume exchange,” but this may be limited by the practical problems of pediatric patients with limitations of vascular access and hemoconcentration in the filter. In these cases, small solute clearances can be maximized by establishing diffusive mass transport via a dialysis circuit. This can be performed with CVVHDF or without an additional major ultrafiltration component (CVVHD). CVVHDF latter technique requires an additional pump to achieve separate control of the dialysate in- and outflow and of the replacement fluid flow. CVVH substitution fluid bags can be used as dialysis fluid. Dialysis fluid flow should be 2–3 times the blood flow if maximal efficacy is desired. This setting requires frequent manual bag exchanges and continuous supervision of the system. For practical purposes, the HD component can be added for several hours per day to a CVVH regimen. 66 When high turnover and blood flow rates are in use, patients should be carefully monitored for hypothermia, hypokalemia, and circulatory failure. Hypothermia may need to be treated with an external warming blanket and hypokalemia will require replacement. Blood flow should not be increased if the patient develops cardiovascular instability. CVVH and extracorporeal membrane oxygenation In the authors′ experience, the best results are achieved when pre-diluted fully automated CVVH is used, attached to the venous (outflow from patient) side of the extracorporeal membrane oxygenation (ECMO) circuit. This appears to reduce problems of shunting blood around the oxygenator and overcomes the problems of the increased hematocrit that may be associated with ECMO. It also reduces the complications of excessive fluid and solute clearances, with a free flow when systemic hemofilters are used in line with the ECMO circuit. When using CVVH in the suggested configuration, the “pigtails” provide access with very little resistance, causing the arterial and venous pressure alarms to activate and shut down the circuit. Therefore, three-way taps are used to create more resistance to flow into and out of the CVVH circuit. When treating neonatal patients, the ECMO circuit increases the extracorporeal blood volume very significantly. Therefore, the blood pump speed should be calculated taking into account the patient’s blood volume and the priming volume of the ECMO circuit. Complications of continuous extracorporeal techniques 67 Hypotension 6 Clotting of the filter and lines This is one of the commonest complications and again is related to the patient’s changing clinical status and problems with anticoagulation. This complication occurred in 24% of 89 patients treated with CVVH in a 2-year local audit (B. Harvey, unpublished observations). Other potential complications of bleeding, anticoagulation toxicity, and infections appear to be minimal. Air embolism is a rare but preventable complication of extracorporeal circuits, and is greatly reduced with the proper use of automated machinery. Intermittent HD 68 Advantages The main advantage of HD is the relatively rapid removal of uremic toxins and ultrafiltration of fluid. This makes the technique well suited for acute situations. Limitations 69 70 Practical guidelines for prescription HD is only possible with good vascular access provided either by a double-lumen HD catheter or a single-lumen catheter of sufficient diameter to achieve flows for single-needle dialysis. Catheter lengths vary from 5 cm for neonates to 20 cm for large adolescents. Bloodline choice depends on the priming (extracorporeal) volume, which traditionally has not exceeded 10% of the blood volume (approximately 80 ml/kg). 71 Bloodline priming is usually performed with isotonic saline. Small babies, anemic patients, and those in an unstable cardiocirculatory condition, require priming with albumin or blood. HD catheter care After the session the catheter should be flushed with isotonic saline and filled with undiluted heparin (1,000 IU/ml), with volumes according to manufacturer’s recommendations (usually marked on the catheter itself). HD prescription The first session should not exceed 2–3 h, but the standard time is usually 4 h. Longer sessions are advisable to avoid too-rapid ultrafiltration and disequilibrium syndrome. All children should be dialyzed using volume-controlled machines and with bicarbonate dialysate. 69 The ultrafiltration target should not exceed 0.2 ml/kg per min for acute patients who should be carefully monitored for hypovolemia and hypotension. Sodium profiling is rarely used in pediatric HD practice. Anticoagulation is usually with heparin (50–100 IU/kg per session including initial bolus). Reinfusion is usually performed with isotonic saline. Complications occurring during acute HD For hypotension, the ultrafiltration should be switched off and isotonic saline infused into the venous line until the blood pressure normalizes; additional 20% albumin 5 ml/kg might be helpful. 72 Disequilibrium syndrome is now a rare event with adequate control of ultrafiltration and stepwise reduction of uremic toxins. Hypoglycemia should not occur with the use of glucose-containing dialysis fluid. In cases of anemia transfusions are avoided unless patient symptomatic. Erythropoietin may be given intravenously at the end of dialysis (50–200 IU/kg) to maintain hemoglobin levels. Medications 73 74