Dialysis Therapies in Acute Kidney Injury for Children

Introduction

AKI affects a significant proportion of critically ill children. Although the reported incidence is variable due its various definitions – a recent study using the KDIGO AKI definition reported that around 25% of all children admitted to a pediatric intensive care unit (PICU) had some form of AKI and of them 6% needed some form of RRT. The mode of RRT available includes the para-corporeal mode i.e. peritoneal dialysis (PD) and the blood based extracorporeal modes which includes HD and HF with or without dialysis (CVVHD/CVVHDF/CVVH). Along with these standard modes is the hybrid mode such as SLED which can be combined with hemofiltration (SLED-F). Pediatric population with AKI presents with challenges quite different from adult population. Among these one of the most important challenge is the wide range of sizes we encounter in pediatric practice- from newborn (term/preterm babies) with weight as low as 1 kg or even below to right up to obese adolescent. As “one size never fits all”; we need to often adapt the RRT prescription on a case by case basis.

We recommend that a unit delivering pediatric RRT should be able to provide full range of RRT, i.e., PD and all modes of blood-based RRT.

We suggest that this should be done in a child-friendly environment through health personnel who have been trained in pediatric RRT. The unit should preferably have access to a multi-disciplinary pediatric team with experience in other pediatric subspecialties.

Indications for initiation of renal replacement therapy in pediatric acute kidney injury

We recommend initiating RRT in AKI when any of the conditions below are present [Table 1].

Table 1.

Indications for initiation of renal replacement therapy in pediatric acute kidney injury

Refractory electrolyte imbalance or anuria (<50 ml/12 h)

Refractory fluid overload (>15% weight gain refractory to diuretics)

Refractory acidosis

Uremic organ involvement (pericarditis, encephalopathy, neuropathy, myopathy)

Progressive severe dysnatremia (Na+ >160 or <115 mEq/L)

Non-obstructive oliguria (<200 ml/12 h)

Malignant Hyperthermia

To create space for nutrition in oliguric/anuric children

Removal of endogenous toxins (e.g., ammonia)/exogenous toxins (i.e., poisons)l

Neonatal hyperammonemia and other inborn errors of metabolism.

Among these indications fluid overload has emerged as a new established indication over the last decade with studies repeatedly showing it to be an independent marker of mortality in paediatric AKI. Most of the PICU will initiate fluid removal once the fluid overload in the child exceeds 15%. If diuretic fails or is not feasible (such as intravascular depletion despite overall fluid overload, as often seen in nephrotic syndrome, liver cirrhosis or congestive cardiac failure) RRT is indicated for fluid removal.

Recommendations for initial choice of type of renal replacement therapy in pediatric acute kidney injury

We suggest that any of the following modes of RRT may be used in the critically ill child with AKI, and that treatment may need to be individualized.

Technically all modes of dialysis as mentioned above can be used in pediatric AKI. Concomitant hypotension/ shock often present in children with AKI in PICU makes IHD difficult as they are not able to tolerate the sudden intravascular volume changes which this mode entails. Table 2 summarizes a detailed account of the pros and cons of the various modalities. Extracorporeal RRT is also challenging in small children particularly in infants because of the difficulty in getting appropriate vascular access as well as size appropriate dialyzers and dialysis tubing.

Table 2.

Modes of renal replacement therapy

	PD	IHD	CVVHD	SLED
Continuous therapy	Yes	No	Yes	Intermediate
Hemodynamic stability	Yes	No	Yes	Yes
Ease of achieving required fluid balance	May not be possible	Difficult if unstable	Yes	Yes
User friendly	Yes	Yes	Yes	Yes
Solute removal	Low	Yes	Yes	Yes
Control over ultrafiltration	Variable	Yes	Yes	Yes
Anticoagulation free	Yes	Possible	Difficult*	Possible
Removal of toxins in poisoning cases	Not very effective	Yes	Variable	Yes
Nursing requirement	Low	Moderate	High	Moderate
Patient mobility	No	Yes	No	Yes
Cost	Low	Moderate	High	Moderate
Need for vascular access	No	Yes	Yes	Yes
Infection risk	Yes	Yes	Yes	Yes
Utility in inborn errors of metabolism	No^	Yes	Yes	Yes

*Regional citrate anticoagulation may be required. PD: Peritoneal dialysis, IHD: Intermittent hemodialysis, SLED: Sustained low-efficiency dialysis, CVVHD: Continuous venovenous hemodialysis

• We suggest that neonates and infants less than 10 kg should be managed with PD except where expertise and infrastructure is available for CVVH/SLED.

• We recommend that hemodynamically unstable children with AKI such as those with sepsis should be managed by PD or CVVH or SLED as they are unlikely to tolerate IHD.

• We suggest that if CVVH/SLED are not available, PD may be used as a mode of RRT even among sick in children in PICU.

• CVVH and SLED have some advantages over standard PD such as better clearance and more control over UF but are significantly more expensive than PD and require sophisticated infrastructure and expertise.

• Till date there are no evidence suggesting one mode of RRT to be superior to another in pediatric AKI.

• We suggest that there are very few relative contraindication to PD such as surgical abdomen, gastroschisis and diaphragmatic hernia

• We suggest that hemodynamically stable children with AKI can be managed with IHD provided size appropriate dialyzers and dialysis circuit is available.

• We suggest that the form of CRRT either CVVH, CVVHD, or a CVVHDF, should be chosen according to available clinician expertise.

• We suggest that in presence of appropriate expertise and infrastructure SLED can be tried as a cheaper alternative to CVVH.

• We recommend that all therapies should be veno-venous and pump driven using dedicated machines with safety devices including blood leaks, transmembrane pressure and air detection alarms.

• We do not recommend use of AV techniques as efficacy & safety monitoring may be inadequate.

• We suggest that patients with concomitant AKI and hepatic failure or traumatic brain injury be treated with peritoneal dialysis, CRRT or SLEDD Sustained low efficiency daily dialysis, rather than IHD. Advanced liver disease with AKI and traumatic brain injury are associated with raised intracranial pressure, which is worsened by IHD. By contrast ICP intracranial pressure is unaffected or slightly lowered by CRRT, while a single study suggests that SLEDD is similar to CRRT with respect to ICP.

Vascular Access for Pediatric Blood-based Renal Replacement Therapy

Acute blood-based RRT is usually done though vascular catheters acting as temporary vascular access.

We recommend that:

• Catheters should be of biocompatible material

• Wide range of blood lines should be available as in pediatric one has to deal from small babies to large adolescents [Table 3]

• We suggest that stiff temporary catheters (vascath) use for vascular access be restricted to acute HD for a period of less than 3 weeks

• All temporary lines carries a high risk of catheter acquired infection and should be converted to cuffed permanent line if HD is continued beyond 3–4 weeks.

• Dedicated dual-lumen temporary catheter should be preferred

• Largest possible lumen size should be used. We recommend that the diameter of the vascular access catheter should not exceed 50% of the vein it is being inserted into. Ultrasonographic measurements and real time imaging at the bedside should be used to ensure this.

• We suggest that the vascular access may be inserted in either the femoral or IJVs.

• IJV access is superior to subclavian vein because it preserves the future AVF implantation on the arm of the child if he / she evolve into ESRD.

• Femoral access should be used only in emergency, and should not be in place for longer than 7–10 days because of higher risks of infection as well as thrombosis.

• We suggest that a vein should be dedicated for the dialysis access to prevent interference with antibiotics, nutrition, and inotropes which are being continuously infused. Thus, if an IJV has been chosen by the ICU team for infusions, we suggest siting the dialysis access in the femoral vein at least in the initial stage when a patient is on maximum pressors.

Table 3.

Catheter sizes and insertion sites

Patient size	Catheter size	Site of insertion
Neonates/small infants Weight up to 20 kg Weight 20 to 30 kg Weight over 30 kg	Umbilical venous Catheter/umbilical artery Catheter - 3.5/5 F or two single- lumen 5 F or double-lumen 6.5, 7 F Double-lumen 8F Double-lumen 10F Double lumen 11.5F	Umbilicus Femoral/jugular vein Femoral/jugular vein Femoral/jugular veins (NB: rarely, inferior vena cava can be accessed through translumbar or trans hepatic access. Subclavian should be avoided and used only in emergency and where other access attempts have failed)

Selections of Machines for Undertaking Blood- Based Renal Replacement Therapy

Recommendations

Intermittent hemodialysis

We suggest that standard HD machines used for MHD can be used for IHD for AKI.

Sustained low-efficiency dialysis

We suggest that a machine be chosen for SLED, which can deliver the lowest possible dialysate flow, at least as low as 300 mL/min.

In adults most often standard HD machine can be used for SLED. Unfortunately, most of the available HD machines are unable to reduce the dialysate flow below 200 mL/min – 300 ml/min [most machines deliver minimal dialysate flows rate of 300 ml/min, ArrT plus delivers flows of 200 ml/min – Table 4]. Ideally, in SLED, the dialysate flow rate should not exceed twice the BFR lower dialysate flow rate is often required in smaller children. (Currently, Fresinius 5008 is able to provide a dialysate flow rate as low as 100 mL/min). This machine has an optional pediatric module with dedicated software.

Table 4.

Machines for SLEDD

Parameter	Fresenius 5008	Fresenius ArrT plus	DBB-07 Nikissho	Artis (Gambro)	Diamax (Nipro)	Dialog Plus (B Braun)
Water requirement	1.5-6 bar	1.5-6 bar	1-7 bar	1-6 bar	1-4 bar	0.5-6 bar
Electricity requirements	100-240 V AC, 47-63 Hz	100-240 V AC, 47-63 Hz	220-240 V AC, 50/60 Hz	220-240 V AC, 50/60 Hz	220-240 V AC, 50/60 Hz	120-230 V AC, 50/60Hz
Blood Flow	30-600 ml/min	5-500 ml/min	40-600 ml/min	0-580 ml/min	15-600 ml/min	50-600 ml/min
Dialysate flow	0-1000 ml/min in increments of 100	200-800 ml/min	300-700 ml/min in increments of 100	300-800 ml/min in increments of 100	300-700 ml/min in increments of 100	200-1000 ml/min in increments of 1 ml
Heparin pump	Syringe 0.5 to 10 ml/h	Syringe 0.5 to 10 ml/h	Syringe 0-9.9 ml/h	Syringe	Syringe	Syringe 10-30 ml
Ultrafiltration	0-4000 ml/h (in steps of 10 ml)	0-4000 ml/h (in steps of 10 ml)	0.1-4000 ml/h	0-4000 ml/h	100-5000 ml/h	0-5500 ml/h
Maximum treatment time (h)	24	10	12	24	6	10
Compatibility with multiple dialyzer and tubing sets	Dedicated tubing sets	Yes	Yes	Yes	Yes	Yes
Sodium and ultrafiltration profiling	Custom	Custom	Also bicarbonate profiling	Also bicarbonate	Flexible	Flexible
Dialysate sodium/conductivity range	125-151 mmol/L, (12.8-15.7 mS/cm)	125-151 mmol/L, (12.8-15.7 mS/cm)	12.5-15.5 mS/cm	130-160 mmol/L	10-17 mS/cm	12.5-16 mS/cm
Dialysate temperature range	34°C-39°C	34°C-39°C	34°C-40°C	30°C-39°C	30-40°C	33°C-40°C
Dry powder concentrate use*	Bibag (650 or 900 g) Now possible to use with citrate-based acid concentrate	Bibag (650 or 900 g) Now possible to use with citrate-based acid concentrate	No	Yes (Bicart) Acetate-free citrate bicarb sterile concentrate available	No	Yes Solucart or Bicart
Online replacement fluid preparation	Yes 25-600 mL/min	Yes 25-600 mL/min	0.1-30 L/h online Also external scale for fluid bags	Yes (U 9000 disposable filter required) Auto TMP monitored and manual options available	No	yes
Heated citrate	85°C	85°C	85°C	85°C	65°C	85°C
Peracetic acid/sodium hypochlorite	37°C	37°C	37°C	37°C	Not specified	37°C
System self-test	Yes	Yes	Yes	Yes	Yes	Yes
Additional features	OCM, BTM, and BPM	OCM, BTM, and BPM	DDM, BVM and BPM	Diascan and Hemoscan monitors	Not specified	Online Kt/V available

OCM: Online clearance monitor, BTM: Body temperature monitor, BPM: blood pressure monitor, TMP: transmembrane pressure

Fresenius Medical Care has recently (July 2017) recommended that the 5008 machine not be used in children <17 kg following reports of balancing system errors. This has led to concern that excessive UF can occur in smaller children, a potential hazard.

Sustained low-efficiency dialysis hemodifiltration (sustained low-efficiency dialysis -F)

We suggest that machines capable of generating online fluid may be used for HDF and SLED-f. These should be equipped with at least 2 and preferably a 3^rd ultrafilter in the replacement fluid delivery circuit. All machines should be of a “fail safe” design.

Continuous veno-venous hemofiltration /continuous venovenous hemodiafiltration

We suggest that machines used for CRRT have the following specifications.

All machines used for CRRT should be dedicated, with their own disposables. The machines should have a minimum of 3 and preferably 4 or more pumps to make all forms of treatment possible. The machines should have an error of <2.5% in measurement of UF volumes. Gravimetric balancing scales are preferable to flow measurements. Table 5 summarizes the key features of the available CRRT machines.

Table 5.

Machines for continuous renal replacement therapy

Machine parameter	Prismaflex (Baxter/Gambro)	Multifiltrate (Fresenius)	Multifiltrate (pediatric option)	Diapact (B. Braun)
Electrical requirement	100-240 V, AC, 50/60 Hz	100-240 V, 3.2 A, AC 50/60Hz	100-240 V, 3.2 A, AC 50/60Hz	110-240 V, 3.5 A, AC 50/60Hz
Roller pumps	5	6	6	3
Scales	4	4	4	3
Principle	Gravimetric	Gravimetric	Gravimetric	Gravimetric
Range of load cell	0-11 kg	Up to 24 kg	Up to 24 kg	0-27 kg
Filter sets	Dedicated	Dedicated cartridges, but any filter/dialyzer usable Individual tubing lines can be changed	Dedicated cartridges, but any filter/dialyzer usable Individual tubing lines can be changed	Dedicated but filter change possible with luer lock and Hansen connector system Individual tubing lines can be changed
Blood flow rate	10-450 ml/min	10-500 ml/min	10-100 ml/min	10-500 ml/min
Dialysate flow rates	0-8000 ml/h	100-4800 ml/h	100-1500 ml/h	0-300 ml/min
PBP rate	0-8000 ml/h	-	-	-
Replacement fluid	0-8000 ml/h	100-9600 ml/h	100-3000 ml/h	0-250 ml/min
Effluent	0-8000 ml/h	12 L		0-400 mL/min
UF rate	0-2000 ml/h	0-1800 ml/h	0-500 ml/h	0-2000 ml/h
Heparin	50-ml syringe	50-ml syringe	50-ml syringe	50-ml syringe
Regional citrate anticoagulation	Possible one external pump required	Possible integrated		Not specified

UF: Ultrafiltration, PBP: Pre blood pump

Dialysis Fluid and Replacement Fluid

Recommendations

• For IHD and SLED, we recommend that bicarbonate based dialysate should be used.

• We suggest that Bicarbonate based dialysate be used in CRRT.

• The dialysis fluid sodium is normally kept between 135 and 140 mmol/L with the gap between serum sodium and dialysis sodium not exceeding 10 mmol/L.

• We suggest not using a zero potassium in pediatric HD because of risks of arrhythmia and normally potassium is kept at 2 mmol/L. Higher potassium may be used in cases of hypokalemia.

• We recommend that calcium concentration in the dialysis fluid is normally kept around 1.5 mmol/L.

• We suggest that dry powder citrate bicarbonate dialysate be used for SLED in the ICU. The final dialysate contains a citrate concentration of 2–3 mmol/L and this decreases the chance of extracorporeal circuit clotting. Ahmed et al. have shown remarkable success in performing SLED without any anticoagulation using dry citrate bicarbonate concentrates even in AKI patients with acute hepatic failure

• We suggest using high dialysis fluid calcium and sodium and low dialysis fluid temperature to improve tolerance among hemodynamically unstable children in PICU

• Whenever online HDF or SLEDD-f is carried out it is mandatory to ensure that the water used for dialysis is of ultrapure standard

• We recommend that isotonic bicarbonate based fluid be preferred as replacement fluid in CRRT

• We recommend that calcium-free dialysate and replacement fluid (Biphozyl) should be used in patients receiving regional citrate anticoagulation

• The PBP bag should be Regiocit for this treatment.

Table 6 shows the available fluids with their composition for use in CRRT.

Table 6.

Dedicated fluid bags for continuous renal replacement therapy

Composition (mmol/L)	MultiBic (Fresenius)	Multiplus (Fresenius)	Prismasol (Gambro)	Regiocit (Baxter)	Biphozyl (Baxter)
Sodium	140	140	140	140	140
Potassium	0-4	2	0	0	4
Calcium	1.5	1.5	1.75	0	0
Magnesium	0.5	0.75	1	0	0.75
Chloride	110	110	110	86	122
Bicarbonate	35	35	32	0	22
Phosphate	-	1	-	-	1-2
Glucose	5.55	5.55	0	0	0
Citrate	-	-	-	18	-
Osmolality (mOs/L)	290-300	300	287	244	290

Recommendations for dialyzers and hemofilters

Similar to mode of dialysis; strong evidences in favor of any particular type of dialyzer resulting in lower mortality or better long term kidney survival is lacking.

We recommend that

• Synthetic dialyzers (polysulfone [PS], polyacrylonitrile [PAN] and polycarbonate) should be preferred because of their lower immunogenicity and better solute removal.

• Bio-incompatible cuprophane dialyzers should be avoided in ICU since they carry increased risk of mortality compared to bio-compatible membranes.

• High flux dialyzer with bigger pore size does guarantee better solute / fluid clearance but should only be used with ultrapure water as otherwise there is a chance of backfiltration of endotoxins into the blood stream.

• The size of the dialyzer is calculated by its surface area and is available in a wide range (0.2 m² to 1.7 m²). The surface area should be as large as possible to optimize clearances but should not exceed that of the child. However for the first HD session dialyzer surface area should not exceed 75% of body surface area to avoid disequilibrium syndome.

• Standard IHD and SLED may be carried out with low-flux dialyzers.

• SLED-f requires high-flux, ultra-flux or special high-porosity dialyzer

• CRRT requires special hemofilter sets, usually as part of a complete set, each of which is compatible with specific machines only.

Table 7 contains a list of pediatric dialyzers with their specifications while Table 8 contains those of CRRT sets currently available in India.

Table 7.

Dialyzers/hemofilters for sustained low-efficiency dialysis

Parameter	Sureflux 5N (Nipro)	FX40 (Fresenius)	FX ped (Fresenius)	Polyflux 6H (Gambro)
Surface area (m2)	0.5	0.6	0.2	0.6
Priming volume (mL)	34	53	18	52
UF coefficient	2.7	20	7	33
Urea clearance	130*	170#	76!	50¦
Creatinine clearance	109*	144#	64!	50¦
Phosphate clearance	62*	138#	57!	49¦
Material	Cellulose triacetate	Helixone	Helixone	Polyflux^
Fiber inner diameter (micron)	200	185	220	215
Thickness	15	35	35	50
Blood flow (mL/min)		50-200	30-100	50-200
Sterilization	Gamma ray	Inline steam	Inline steam	Inline steam

*At Qb=200 ml/min, ^#At Qb=200 ml/min, ^!At Qb=100 ml/min, ^§At Qb=50 ml/min, ^Polyflux is a blend of polyarylethersulfone, polyvinylpyrrolidone, polyamide, UF: Ultrafiltration

Table 8.

Filter sets for continuous renal replacement therapy

Filter specifications	M100	M60	HF20	Ultraflux AV Paed
Membrane	AN-69		Polyarylether sulfone	Polysulfone
Housing and headers	Polycarbonate
Surface area (m2)	1.0	0.6	0.2	0.2
Appropriate patient weight (kg)	30	11-29	<8	<10 kg
Blood flow (mL/min) minimum to maximum	75 and above	50 and above	20-100	No data
Set blood volume (mL)	152	93	60	54 mL
Priming volume (mL)	66	42	24	18
Maximum TMP (mmHg)	450	450	500	500
Clearance in CVVHD mode with UF=0	at Qb=150 mL/min and effluent 2.5 L/h	at Qb=100 mL/min and effluent 1 L/h	at Qb=50 mL/min and effluent 0.5 L/h	No data
Urea (mL/min)	41	17	8.3	No data
Inulin (mL/min)	23	12	6.9	No data

UF: Ultrafiltration, TMP: Transmembrane pressure, CVVHD: Continuous venovenous hemodialysis

Extracorporeal Circuit

Recommendation

We recommend that

• The total extracorporeal blood volume (tubing and dialyzer) should preferably be less than 10% of the child's total blood volume.

  Formula for calculating total blood volume (TBV):

  Infant or < 20 kg: 80 mL/kg

  Children or 20–50 kg: 70 mL/kg

  Adult or > 50 kg: 60 mL/kg

• Blood tubing are available in three sizes that vary in their priming volume:

  (a) Neonatal – 25 mL

  (b) Pediatric – 75 mL

  (c) Adult – 127 mL.

  Dialyzer volume is usually given in the product information package

  N.B. Dialyzer's volume should be added to the tubing volume to estimate the total extra corporeal blood volume

• We suggest that an effort should be made to ensure availability of appropriate size tubing. In its absence and if the blood circuit volume exceeds 10% of blood volume, one can try priming of blood circuit, i.e., filling up the blood circuit with blood or 5% albumin prior to start of dialysis to avoid hypovolemia.

Recommendations for blood and dialysate flow rate

We suggest that even in hemodynamically stable children BFR should not exceed 10 mL/kg/min.

Higher BFR equates to better clearance but as it also entails rapid blood volume shift it is often not tolerated in hemodynamically unstable children. In such scenarios the BFR needs to be reduced and to compensate for this, one needs to increase the duration of dialysis.

High dialysis fluid flow rate (DFR) also improves clearance which plateaus around 500 mL/min. In SLED, reduced DFR ensures lower clearance rates with maintenance of plasma osmolality as well as better hemodynamic stability.

We recommend that

For intermittent hemodialysis

• BFR = Initially at lower limit of 2–3 mL/kg/min and as tolerated increased to an upper limit of 5–7 mL/kg/min, DFR = 500 mL/min

For sustained low-efficiency dialysis

• BFR should be ≤5 mL/kg/min (up to a maximum of 200 mL/min) and DFR should be ≤ twice of BFR

For sustained low-efficiency dialysis-F

• The BFR should be 5–7 mL/kg/min up to a maximum of 200 mL/min.

• The total UF rate (desired hourly UF and replacement fluid rate) should be predetermined by the patient's requirement and the blood flow set thereafter so that the filtration fraction is <25% of the blood flow (specially applicable to HF and HDF). The machine automatically calculates fluid removal from the set UF and replacement fluid volumes, but the filtration fraction has to be calculated by the operator when writing the prescription.

For continuous renal replacement therapy

We recommend a BFR of 2–4 mL/kg/min up to a maximum of 150 mL/min.

We recommend that the total effluent volume should be 2 L/h/1.73 m² or 30 mL/kg/h. This dose has been used in three observational pediatric studies, but unlike in adults no randomized controlled studies on dose comparison have been performed.

The machine calculates and displays the effluent rate and dose in ml/kg/hour from the input values of PBP, dialysate, replacement fluid and patient fluid removal rates. Based on the anthropometric data of weight, hematocrit and choice of pre or post replacement fluid the machine also displays the filtration fraction.

Recommendation for duration of renal replacement therapy

Duration of the RRT session depends on multiple factors including:

• (a)Degree of uremia and whether it is the first session or whether the child already has had previous sessions of RRT.
• (b)Extent of fluid overload and the fluid removal target for the specific session.
• (c)Type of RRT, i.e., whether IHD or SLED or CVVH
• (d)Manpower and machine availability.

• Classical IHD is for 3–4 h and SLED is defined as session of 6 h or longer

• We recommend that the duration for first HD is kept to a minimum particularly in cases with severe azotemia, to avoid dialysis disequilibrium. Initial target is to reduce urea by 30% and hence first IHD session is usually for less than an hour

• We suggest that formal urea kinetic modeling can be used to calculate the first session length from the dialyzer specifications, blood flow and initial blood urea level

• Mannitol at 1 g/kg can be given at the starting of the initial RRT session in order to maintain vascular volume / prevent fluid shift into cells, even in the face of sudden drop in osmoles which can happen as the urea is reduced by dialysis. Addition of mannitol does increase the risk of intravascular fluid overload/ pulmonary edema and potential spike in BP but with mannitol one can aim a higher initial urea reduction up to 50%

• We recommend that the frequency of acute HD is decided as per the clinical requirement of the child depending on biochemical parameters and fluid overload. Usually in AKI daily RRT is needed at least initially

• We recommend that CRRT be performed as a continuous therapy and out of unit procedures be kept to a minimum during this time

• We recommend that effluent volumes be temporarily increased to compensate for down time during out of unit procedures.

Recommendation for ultrafiltration goal

We recommend that the UF goal be chosen based on degree of fluid overload and the hemodynamic status of the child.

• The initial rate of UF during conventional HD should be about 10 mL/kg/h and should not exceed 0.2 mL/kg/min or 5% of body weight in one session.

• In critically ill children with hemodynamic instability, rate of UF has to be much lower and these children benefit from CVVH or SLED where in significant UF is possible without hemodynamic compromise as small volumes are removed hourly but over a prolonged period resulting in significant cumulative fluid removal.

• We suggest that patient net fluid removal in CRRT be set at 2–4 mL/kg/h

• We recommend that UF in CRRT or SLEDD-f is the total of desired UF, and replacement fluid and should not exceed 25% of the blood flow.

Recommendation for anticoagulation

As blood comes in contact with blood circuit it tends to clot and hence anticoagulation is required. Anticoagulation becomes a concern if clotting is altered such as in children with sepsis and disseminated intravascular coagulation (DIC) or liver failure. Standard anticoagulation protocol is usually heparin at specified dose.

We recommend that

• If not contraindicated unfractionated, heparin should be the anticoagulant of choice during IHD/SLED and CRRT. Doses according to body weight are shown in Table 10.

• After an initial loading dose of heparin, infusion may be initiated and adjusted according to the aPTT reports [Table 7]. In patients receiving LMWH, the same can be continued with the doses given just before a session of IHD or SLED. Bedside monitoring is not possible and the risk of bleeding is increased with the use of LMWH in AKI

• IHD can be conducted without heparin by using regular saline flushes. As usually children with altered coagulation in PICU are septic, hypotensive and on multiple inotrope standard IHD is difficult

• SLED is often more feasible in such critically ill children and recent publications have proven that heparin-free dialysis is possible in them

• For conducting heparin-free session the most commonly used process is regular flushes with saline equal to the circuit volume. One has to incorporate these volumes when estimating the net UF

• CRRT almost always requires anticoagulation and in patients with DIC, regional anticoagulation with citrate and calcium may be used

• We recommend that regional citrate anticoagulation be used for patients undergoing CRRT in whom systemic anticoagulation is contraindicated

• We recommend monitoring the blood and circuit levels of ionic calcium 2 hourly and the infusion rates adjusted in regional citrate anticoagulation.

  We suggest that the rates of citrate and calcium infusions be adjusted according to Table 9 We suggest not using the option “Citrate anticoagulation with External Pump” in children or if used decreasing the blood flow to 2 to 2.5 mL/kg/h

  Rationale – When the regional citrate anticoagulation with an external pump is used the PBP rate is automatically set at ten times the BFR by an inbuilt program to obtain a citrate concentration of 3 mmol/L. If the blood pump is set at 4 mL/kg/min, the PBP will automatically run at 40 ml/kg/h, which exceeds the prescribed effluent rate. Thus very little Biphozyl is delivered and the patient receives an overdose of citrate often leading to metabolic acidosis and excessive anticoagulation We suggest that regional anticoagulation with Regiocit and Biphozyl may be performed as follows:

  Set desired BFR. Start Regiocit (mL/hour) on the PBP line at 6 to 7.5 times the BFR (e.g., 600–750 mL/h for a blood flow of 100 mL/min). Prepare calcium gluconate solution of 250 mL of 10% calcium gluconate with 750 mL 0.9% normal saline. Start calcium gluconate infusion (mL/hour) through a separate central line and infusion pump at 0.5 times the blood flow (e.g., 50 mL/h for a blood flow of 100 mL/h) Adjust the rate of dialysate and replacement fluid with Biphozyl, desired UF and calcium gluconate infusion to obtain a total effluent volume of 2 L/h/1.73 m² or 30 mL/kg/h

• Monitor ionic calcium, potassium, and pH from the blood and ionic calcium from the circuit every 2–4 h and adjust infusion rates as per Table 9

• In heparin protamine regional anticoagulation, the aPTT of both the patient and the extracorporeal circuit between the sampling ports should be monitored. For an infusion of 500 units/h of heparin a neutralizing infusion of 5 mg/h of protamine will be required.

Table 10.

Heparin dose

Initial heparin bolus
Weight (kg)	Heparin dose (IU/kg)	Total initial dose (IU)
5-15	10-16	50-250
>15-25	16-20	250-500
>25	20	500-1000

Heparin rates per hour: 10-20 unit/kg/h aiming for ACT 150% or aPTT in 120-160 s, ACT: Activated clotting time, aPTT: Activated partial thromboplastin time

Table 9.

Dosing in regional citrate anticoagulation

Circuit ionic calcium	Citrate dose adjustment
Patient weight	>20 kg	<20 kg
<0.35	Decrease by 40 mL/h	Decrease by 20 mL/h
0.35-0.5	No change	No change
0.5-0.6	Increase by 40 (mL/h)	Increase by 20 mL/h
>0.6	Increase by 80 (mL/h)	Increase by 40 mL/h
Patient ionic calcium	Calcium dose adjustment
>1.3	Decrease by 10 mL/h	Decrease by 5 mL/h
1.1-1.3	No change	No change
0.9-1.1	Increase by 10 mL/h	Increase by 5 mL/h
<0.9	Increase by 20 mL/h	Increase by 10 mL/h

Monitoring

As during extra corporeal RRT a significant percentage of TBV is outside the body it always has the potentiality of causing medical catastrophes. This is particularly so for hemodynamically unstable children. Monitoring of patient's clinical condition is hence essential.

We recommend that the following clinical and laboratory parameters be monitored

• Vitals such as respiratory rate, pulse rate/pulse volume, BP, and oxygen saturation in critically ill children

• Input (IV fluids + oral fluids + IV medications and other infusions) and output (ultrafiltrate + urine output + extra renal loss) charting

• Hemoglobin, platelets, and bleeding parameters (prothrombin time and aPTT)

• Renal parameters including electrolytes

• Blood born virus screen (HBsAg, HCV, and HIV) should be done prior to HD.

N.B. SLED as it is done over a prolonged period has the potential of causing low electrolytes/phosphate and hence in children undergoing SLED they need to be monitored and sometime even may need to be supplemented.

Recommendations for goals of renal replacement therapy

• Steady level in CRRT and predialysis level in IHD or SLED of BUN of ≤ 60 mg/dL should be achieved within 48 h after initiating dialysis

• Volume status as close to euvolemia as possible

• Correction of acidosis to maintain pH ≥7.2

• Maintain serum electrolyte levels within reasonably normal limits (sodium: 130–148 mmol/L, potassium: 3.5–5.5).