Symposium. Principles of Renal Replacement Therapy in Critically ill children- Indian Perspective

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1 Symposium DOI / in Critically ill children- Indian Perspective Sidharth Kumar Sethi *, Aliza Mittal**, Rupesh Raina***, Manindar Dhaliwal**** * Senior Consultant, Pediatric Nephrology & Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon,India** Assistant Professor, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Jodhpur, India,*** Consultant Nephrologist, Adult-Pediatric Kidney Disease/Hypertension, Department of Nephrology, Director of Medical Research in Internal Medicine, Internal Medicine Residency Program, Cleveland Clinic, Akron General and Staff at Akron Children s Hospital, Associate Professor and Council Member for University Council of Internal Medicine, Northeast Ohio, Medical University, Faculty Staff at Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. ****Sr. Consultant Pediatric Intensivist, The Medicity Hospital, Gurgaon, India. Received: 23-Mar-18/Accepted: 05-Apr-18/Published online: 30-Apr-18 ABSTRACT Life threatening complications of dyselectrolytemia, uremia and fluid overload may be prevented by early initiation of Renal Replacement Therapy(RRT).Hemodialysis and Peritoneal dialysis are the modalities available. Hemodialysis is intermittent therapy, even when prolonged beyond the standard 4-hr prescription. Continuous renal replacement therapy (CRRT) is defined as any extracorporeal blood purification therapy intended to substitute for acutely impaired renal function over an extended period of time and prescribed continuously for >24-h.Timely initiation of RRT for AKI in children with fluid overload and sepsis is considered useful in enabling recovery. Key Words: RRT,CRRT, Hemodialysis, SLED Renal replacement therapy in children is challenging and an altogether special scenario as children vary in weight from a few hundered grams to over a 100 kilograms in obese adolescents. Even the etiology of AKI in children is variable and requires a deep understanding of features of multiorgan dysfunction syndrome and management depends on local availability of RRT modalities and expertise. Indications for RRT It has been seen in a number of retrospective studies involving critically ill children, that AKI and multiorgan dysfunction may be associated with an increased duration of ICU stay and increased mortality. In a recent study it was clearly shown that fluid overload affected the outcome of patients with AKI. Early initiation of RRT is the key factor, in preventing life threatening complications of uremia, dyselectrolytemia and fluid overload. These are late manifestations of renal failure, and most physicians Correspondence: Dr.Sidharth Kumar Sethi, Senior Consultant, Pediatric Nephrology & Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, India. Secretary- Indian Society of Pediatric Nephrology. Phone: sidsdoc@gmail.com dealing with sick children having AKI, tend towards relatively early recognition and initiation of RRT. Not only does it help to prevent the complications as stated above but it also provides room for parenteral nutrition and/or blood products while preventing fluid overload. Classification The following physiological mechanisms form the basis of functioning, for the currently available modalities of RRT. (i) Diffusion: Solute exchange across a semipermeable membrane, governed principally by concentration gradient, solute size and charge; (ii) Ultrafiltration: Movement of water across a membrane primarily by hydrostatic pressure (in hemodialysis and hemofiltration) or along an osmotic agent (peritoneal dialysis); and (iii) Convection: Solute transfer along with ultrafiltration across a semipermeable membrane, occurring independent of the concentration gradient. Depending on the duration of therapy one may also classify it as intermittent or continuous. The duration of each intermittent therapy <24-hr, while in continuous therapy is at least 24-hr. Hemodialysis is an intermittent therapy, even when prolonged beyond the standard 4-hr prescription, as during sustained 64

2 low efficiency dialysis (SLED) and extended daily dialysis. Choice of Modality The choice of the dialysis modality is influenced by a number of characteristics pertaining to the patient and the organisation. Patient Characteristics Goal of dialysis; In cases where fluid removal is the only target, any of the modalities such as Peritoneal Dialysis, hemodialysis or slow continuous ultrafiltration may be used. These may be further chosen depending on the institutional preferences and hemodynamics. Size: In tiny children such as in neonates, it may be technically difficult to insert a double lumen catheter and one may be unable to achieve adequate flows. Peritoneal dialysis may be a better option in such scenario. Urgency of solute clearance; In certain cases, there is rapid solute generation, which needs to be cleared urgently and associated need for rapid fluid removal such as tumor lysis syndrome, hyperammonemia symptomatic hyperkalemia and ingestion of a dialyzable toxin. In these cases relatively efficient modalities hemodialysis or continuous RRT are preferred over Peritoneal Dialysis. Hemodynamic Status; There are at times conditions such as children with sepsis with Multi-organ dysfunction with shock requiring inotropes. In these cases CRRT may be the only viable option, however in post-operative infants eg following cardiopulmonary bypass, peritoneal dialysis may be used. Co-existent Coagulopathy: In patients with coexistent coagulopathy and prolonged bleeding and clotting time, it may be risky to secure a vascular access and at the same time to anti-coagulate for CRRT/HD. PERITONEAL DIALYSIS The most commonly used modality worldwide specially in resource constrained settings is Peritoneal dialysis by virtue of simplicity with which it can be instituted.it is usually the procedure of choice in small infants owing to the relative ease, safety, minimal hemodynamic consequences and that it eliminates need for a vascular access. Catheters: There are two types of catheters that may be used for acute dialysis in children i.e. non-cuffed rigid acute catheter and the surgically placed cuffed silicone Tenckhoff catheter. Among the two, it is the Tenckhoff catheter that is preferred for use while anticipating prolonged dialysis, as there is an increasing risk of Peritonitis when stiff catheters are used beyond 72 hours Prescription: The dialysis prescription may be individualized as per clinical scenario. The dialysate volume is decided based on the body surface area(bsa), because in children the surface area of peritoneal membrane closely relates to BSA. The volume infused is typically ml/m 2 and one should start with a lower volume initially. The exchange time is 1 hour with inflow for 10 minutes, dwell for 30 min and an outflow time of 20 minutes. Hypertonic fluid along with shorter cycles may be used in cases of fluid overload and hyperkalemia and may be tailored to patient need. Complications; The most important complication encountered with Peritoneal Dialysis is the occurrence of Peritonitis, specially if the catheter has been manipulated. It may have to be managed by Intraperitoneal or Intravenous antibiotics. It is for this reason that the catheter needs to be removed if a stiff catheter was used initially or the response to therapy was inadequate. The other important complications are leakage, poor drainage and ultrafiltration that are commonly encountered. Contraindications: A recent abdominal surgery, necrotizing enterociolitis and presence of VP shunt pose a high risk for peritonitis and are hence contraindications to Peritoneal dialysis HEMODIALYSIS Hemodialysis achieves good solute transfer and high rates of ultrafiltration, and hence is considered the most efficient method of RRT. It is effective in acute settings in management of volume overload, intoxication, tumor lysis syndrome or hyperammonemia. It however becomes unsuitable for children with hemodynamic instability or bleeding tendency and in small babies where vascular access is 65

3 difficult to establish Vascular Access: A double lumen catheter placed in a femoral or the Internal Juglar vein achieves an access for hemodialysis. Adequate blood flow is achieved at these sites and they may be acceptable for use in short term in patients who are hospitalized. Due to the risk of soiling, it is better to use femoral access only in emergency situations. Dialyser: The choice of dialyser to be used again depends on the size of the patient for whom it is to be used as the size approximates the body surface area of the patient. Newer generation dialysis membranes are made of materials such as polysulfone and polymethyl-methacrylate as these cause less proinflammatory cytokine activation. Prescription: While prescribing hemodialysis, one must account for the extracorporeal blood volume in dialyser and tubings, rate of blood and the counter current dialysate flow, the duration and ultrafiltration desired during the procedure.the most commonly used anticoagulant is heparin and one can use saline flushes to keep the circuit free of any clots in case there is bleeding diatheses or there is contraindication to its use. A priming of the dialysis circuit(tubings and dialyser) may be required using, saline, blood or 5% albumin depending on the ratio of body size and volume of the circuit. Complications: Hypotension, leg cramps, abdominal pain and vomiting may result from excessive ultrafiltration or dyselectrolytemia. Problems related to vascular access, such as thrombosis, stenosis, and infection, may require catheter removal. CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT) CRRT is defined as any extracorporeal blood purification therapy intended to substitute for acutely impaired renal function over an extended period of time and prescribed continuously for >24-hr. CRRT classically refers to continuous solute clearance via convection also known as Continous Veno-venous hemofiltration(cvvh), or via diffusive clearance i.e. continuous venovenous hemofiltration with dialysis (CVVHD), or a combination of convective and diffusive clearance as in continuous venovenous hemodiafiltration. It is a modality most preferred for use in sick patients in intensive care units as it closely mimics the functioning of a normal kidney with slow solute removal. Since there is a precise control on the removal of solute and fluid, it is better tolerated as compared to peritoneal dialysis or hemodialysis by children who are on multiple inotropes. Issues pertaining to vascular access are similar to those in hemodialysis. Blood flow rate that chiefly depends on the access is approx 5-10 ml/kg/min, while the Dialysate/replacement flow rate: ml/kg/h or L/ 1.73 m 2 /h. Ultrafiltration: Dependent on patient s hemodynamic status; begin at zero and slowly increase to ml/kg/h net until fluid balance goal is achieved Thermic control: Maintained by the machine with addition of external warming devices if needed. Anticoagulation is achieved using heparin, but regional anticoagulation using citrate or no anticoagulation (Saline Flushes) may also be done. A replacement S No Modality Used Advantage Disadvantage 1 Peritoneal Dialysis Low Cost Easy to administer, even in small babies 2 Haemodialysis Faster solute clearance Ultrafiltration can be controlled as per patient hemodynamics 3 CRRT Slower clearance of solute and precise control of fluid removal, well suited for sick children on inotropes 4 SLED Slower clearance of solute and fluid and well suited for sick children on inotropes, Cheaper to use than CRRT Risk of infections Poorer control of solute clearance, leakage, poor flow. May be difficult technically in young infants and sick children on inotropes may not tolerate it. Expensive Need for anticoagulation Intermittent therapy hence dosing medications may be difficult. 66

4 solution, typically bicarbonate based, is required. Blood and dialysate flow rates are considerably lower as compared to hemodialysis. The targets of ultrafiltration are titrated as per fluid balance and hemodynamic status and the choice between the use of convective or diffusive modality is based on physician preference. While any modality may be theoretically used for clearance of small molecules, it is the convective clearance that achieves removal of toxins and cytokines. CRRT requires to be carried out in an intensive care unit for close supervision. The chief disadvantages are its cost, the need for technical expertise and equipment, and risk of hemorrhage in critically sick children. SUSTAINED LOW EFFICIENCY DAILY DIALYSIS (SLEDD) The concept of Sustained low-efficiency daily diafiltration (SLEDD-f) combines the benefit of CRRT with intermittent Hemodialysis. Various studies have demonstrated benefit of use of SLEDD in critically ill children. The difference between the two is primarily the number of hours each therapy is delivered. While one typically administers CRRT 24 hours a day, while SLEDD is done for just about 5-6 hours every day. For the same reason that it is done only for a short while, one can perform it at night, leaving the day time for other procedures without interruption. The disadvantage of SLED, as mentioned, is the limitation of the number of hours, making volume management and kinetics of drugs and nutrition delivery a bit more challenging. One can achieve a very low dialysate flow of about 100 ml/min, or 6 L/h, blod flow would be dependent on access and size of the child (5-10 ml/kg/min), however it may be used in only a diffusive mode. Vascular access and anticoagulation are same as IHD and CRRT. The dialysate solution is produced either by online prescription or by RO / Ultrapure water mixed with acid base solutions used in HD commonly. One can thus adjust the amount of, bicarbonate, sodium, or calcium and potassium concentrations based on the needs of the patient and within the constraints of the conductivity of the HD machine. Net ultrafiltration: Hemodynamic dependent, similar to CRRT. Thermic control: maintained by the machine with addition of external warming devices if needed. Choice between CRRT and SLEDD The advantage of a SLEDD machine is that if it is used for nocturnal SLEDD, that same machine could be used during the day for HD. The procedure is overall much less expensive. The disadvantage of SLEDD is its lack of continuous dialyzing. Most of centers throughout the world use CRRT in hemodynamically compromised children. The advantage of convective over diffusive clearance cannot be undermined in highly catabolic states where CRRT is better. There always is a risk of underdosing medications, as well as sieving nutrition from patients. Outcomes There are ta present no RCTs comparing the outcomes of various dialysis modalities in children and the results of an adult study has shown no benefit of early versus late initiation of RRT. However it is important to initiate RRT timely in AKI in children who are suffering from sepsis or fluid overload, which is useful in enabling recovery. Retrospective studies suggest that patient survival is predicted by underlying diagnosis and hemodynamic stability, and the severity of illness is more closely associated with risk of mortality than the choice of RRT. Key Messages Life threatening complications of dyselectrolytemia, uremia and fluid overload may be prevented by early initiation of RRT. Hemodialysis and Peritoneal dialysis are the modalities available. Hemodialysis is intermittent therapy, even when prolonged beyond the standard 4-hr prescription. Continuous renal replacement therapy is defined as any extracorporeal blood purification therapy intended to substitute for acutely impaired renal function over an extended period of time and prescribed continuously for >24-h. Timely initiation of RRT for AKI in children with fluid overload and sepsis is considered useful in enabling recovery. 67

5 Source of Funding - Nil Conflict of Interest - Nil References 1. Bridges BC, Askenazi DJ, Smith J, Goldstein SL. Pediatric renal replacement therapy in the intensive care unit. Blood Purif 2012; 34: Fortenberry JD, Paden ML, Goldstein SL. Acute kidney injury in children: an update on diagnosis and treatment. Pediatr Clin North Am 2013; 60: Goldstein SL. Advances in pediatric renal replacement therapy for acute kidney injury. Semin Dial 2011; 24: Sethi SK, Bunchman T, Raina R, Kher V. Unique considerations in renal replacement therapy in children: Core curriculum Am J Kidney Dis 2014; 63: Sutherland SM, Alexander SR. Continuous renal replacement therapy in children. Pediatr Nephrol 2012; 27: How to cite this article: Sethi S, Mittal A, Raina R, Dhaliwal M. in critically ill children- Indian Perspective. J Pediatr Crit Care 2018;5(2): How to cite this URL: Sethi S, Mittal A, Raina R, Dhaliwal M. in critically ill children- Indian Perspective. J Pediatr Crit Care 2018;5(2): Available from: 68