Citrate Continuous Renal Replacement Therapy: Which Protocol? Standard Protocol 1 (SP1) Indication: First hours of therapy Effluent dose target: 35ml/kg/hr Blood pump speed: 180ml/min Post dilution rate: 800ml/hr (Adjust up or to achieve target effluent dose Dialysis rate: 500ml/hr Patient ionised calcium target: mmol/l Post filter ionised calcium target: mmol/l ¹⁰ Notes: 1. This protocol is intended to be the initial set up for the majority of patients presenting with acute kidney injury (AKI) requiring renal replacement therapy. 2. This is intended to deliver a high effluent dose for the initial therapy period. 3. It is not intended to run for long periods and should be changed to standard Protocol 2 once metabolic homeostasis is achieved. 4. The intention is to deliver a high citrate load with a high blood pump speed. 5. The intention is to deliver the majority of the effluent dose with the pre-dilution component. 6. The post dilution rate should be adjusted to achieve the required effluent dose. 7. The serum calcium should be checked every morning to allow the iCa2+:Ca2= ratio to be checked daily ¹⁰ Standard Protocol 2 (SP2) Indication: Maintenance Effluent dose Target: 25ml/kg/hr Blood pump speed: 140 ml/min Post dilution rate: ml (Adjust up or down to achieve target effluent dose, minimum 250ml/hr) Dialysis rate: 500 ml/hr Patient ionised calcium target: mmol/l Post filter ionised calcium target: mmol/l ¹⁰ Notes: 1. This Protocol is intended to be used once homeostasis is achieved. 2. It can be used for patients on long term dialysis who require renal support whist unwell, assuming there is no profound metabolic disturbance or fluid disturbance. 3. The intention is that the effluent dose is reduced once the patient is stable. 4. The blood pump speed should be reduced to reduce the effluent dose. 5. The post dilution rate can then be adjusted to achieve the required effluent dose. 6. The serum calcium should be checked every morning to allow the iCa2+:Ca2+ ratio to be checked daily. ¹⁰ Standard Protocol 3 (SP3) Indication: 1. Failure of Standard Protocol 1 to achieve metabolic homeostasis. 2. Severe multi-organ failure with AKI where Standard Protocol 1 is viewed to be insufficient. Effluent dose target: 45 ml/kg/hr (up to 60ml/kg/hr) Blood pump speed: 230 ml/min Post dilution rate: 1000 ml/hr (Titrate to achieve target effluent dose) Dialysis rate: 500 ml/hr Patient ionised calcium: mmol/l Post filter calcium target: mmol/l ¹⁰ Notes: 1. This protocol is intended to be used for patients where there is either a clinical need or desire to deliver a higher effluent dose to the patient. 2. The higher effluent dose should be initially achieved with a higher blood pump speed. 3. This will deliver both an increased effluent dose and a higher citrate load. 4. Once the blood pump speed is increased the post dilution rate can be titrated to achieve the effluent dose required. 5. This protocol is intended to achieve metabolic stability rather that homeostasis. 6. Once stability is achieved then changing back to Standard Protocol 1 should be considered. 7. If metabolic homeostasis has been achieved then standard protocol 2 can be used. 8. The Serum calcium should be checked every morning to allow the iCa2+:Ca2+ ratio to be checked daily. Consider twice daily if the ratio is rising. ¹⁰ Case Report Severe Metabolic acidosis The following case report demonstrates how adjustment from SP1 to SP3 achieved timely metabolic stabilisation. A 37 year old man admitted with AKI secondary to diarrhoea and dehydration. Severely hypothermic and hypotensive The patient was restless and agitated. Initial blood gas: Ph.: un-recordable PCO2: 1.7 PO2: 23 HCO3: un-recordable BE: un-recordable Lactate 14.3 Urea: 36.7 Creatinine: 1255 CVVHDF was commenced using RCA- SP1. Following 2 hours of treatment Ph.: 6.86 and HCO3: 2.3 the patient was changed to SP3. Following a further 3 hours of treatment the patient become lucid and co-operative. 18h post treatment Ph and HCO CVVHDF discontinued at 28h of treatment due to adequate urine output and improving Urea and Creatinine. Case Report Metabolic Alkalosis The following case report demonstrates management strategy for an alkolotic patient on SP2 by increasing dialysate flow and reducing replacement flow rates. A 73 year old gentleman admitted with Acute on Chronic Renal Failure, Secondary to Obstructive nephropathy and recurrence of transitional cell carcinoma of the bladder. Presenting Alkalotic blood gas: Ph.: 7.48 PCO2: 4.4 PO2: 9 HCO3: 24.6 BE: 1.1 Urea: 12.9 Creatinine 214 Commenced on CVVHDF RCA SP1 for 12h due to initial acidosis, then changed to SP2 when Ph.: 7.48 HCO3: The patients Alkalosis increased to Ph.:7.50, 18h into treatment on the maintenance Protocol (SP2). The dialysate was therefor increased from 500ml/h to 750ml/h in which diffused more Citrate-Calcium complexes into the effluent resulting in a Ph.: Background The benefits of Regional Citrate Anticoagulation (RCA) for Continuous Renal Replacement Therapy (CRRT) are prolonged filter life and reduced risk of bleeding in patients without contraindications¹. However, safe implementation of RCA is complicated², there is no standardisation of treatment Protocols³ due to the multi-faceted components to treatment. There are several protocols described in the literature, however, finding similarities amongst them is challenging due to the diversity of haemodialysis fluids, equipment for delivery and mode of treatment used.⁴⁻⁹ This Unit started using RCA in 2009 and is one of the first centres in the United Kingdom to implement it. The goal is to achieve metabolic control by increasing the citrate load to the patient and by accelerating treatment through high effluent doses, with the option to change to a maintenance protocol once metabolic stability achieved. Kidney disease Improving Global outcomes (KDIGO) state the requirement for a strict protocol due to the increased procedural complexity and risk of metabolic complications². 1 Citrate = 3 Bicarbonate Flow rateAffect on Citrate load Affect on ml/kg/min** ↑ Blood ml/min ↓ Blood ml/min ↑ ↓ ⁶ ↑ † ↓ † ↑ Dialysate ↓ Dialysate ↓ ↑ ³ ↑ ↓ ↑ PBP † ↓ PBP † ↑ ↓ ↑ ↓ ↑ Replacement* ↓ Replacement* ↑ Buffer* ↓ Buffer* ↑ ↓ ** Effluent dose ↑ Increase ↓ Decrease PBP=Pre blood pump † Citrate in mmol/l of blood filtered therefor the machine will adjust according to blood flow rate indirectly ↑ ml/kg/hr with an ↑blood flow rate. * Replacement fluid contains 30mml/l of sodium bicarbonate. References 1.Mariano, F et al Citrate Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients: Success and Limits. International Journal of Nephrology 28 (4): Kidney Disease Improving Global Outcomes Chapter 5.3: Anticoagulation In: KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Kidney International Supplements 2 (1): Tolwani, A.J. et al A Practical Citrate Anticoagulation Continuous Venovenous Hemodiafiltration Protocol for Metabolic Control and High Solute Clearance. Clinical Journal American Society of Nephrology 1: Morabito, S et al Regional citrate anticoagulation in CVVH: A new protocol combining citrate solution with a phosphate-containing replacement fluid. Hemodialysis International. 17: Tobe, S et al A Novel Regional Citrate Anticoagulation Protocol for CRRT Using Only Commercially Available Solutions. Journal of Critical Care 18 (2): Morgora, S et al A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of acid-base status. Critical Care Medicine 37 (6): Morgera, S et al Metabolic Complications during regional Citrate Anticoagulation in Continuous Venovenous Hemodialysis: Single-Centre Experience. Nephron 97 (4): Davies, H., Morgan, D. and Leslie, G A regional citrate anticoagulation protocol for pre-dilutional CVVHDF: The ‘Modified Alabama Protocol’. Australian Critical Care 21: Morabito, S. et al 2012 Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution. Critical Care. 16:R Lowe, A. McNeillis, N and Stedman, F 2013 Citrate RRT Management Protocols. East Sussex Healthcare NHS Trust. Unpublished. 11.Mariano, F. et al Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients. Nephrology Dialysis Transplantation 26: Link, A et al 2012 Total-to-ionised calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients. Critical Care 16:R97 13.Shingarev, R., Wille, K, and Tolwani, A Management of Complications in Renal Replacement Therapy. Seminars in Dialysis. 24(2): Ph. Scale. Google Images Flow rates The table below is designed to assist the user, at a glance, to determine the affect of filter flow rates on citrate load to the patient and the affect on the effluent dose. Depletion of the patients ionised calcium requires supplemental infusion of calcium to replace loses¹² and normalise the patients coagulation = regional anticoagulation. Nursing Considerations Problem Indication Action Citrate accumulationRising total calcium/ionised calcium ratio¹² New or worsening acidosis ¹² Monitor ratio twice daily ¹⁰ ↑Dialysate ↓Blood flow¹¹ rate to no less than 140ml/min Change method of anticoagulation if ratio >2.5 ¹⁰ Liver FailureBilirubin >60 ¹⁰ Bilirubin <60mmol/L ¹⁰ Alternative anticoagulant required ¹⁰ Proceed with caution and follow actions for Citrate accumulation as above ¹⁰ AcidosisPh. <7.2 ³ or persistently low Commence SP3. Change to SP2 when Ph. Normal ¹⁰. Metabolic AlkalosisPh. >7.45 ³Commence SP2 ↑Dialysate ³ ↓Replacement Poor Urea and Creatinine clearance with Ph. >7.35 Failure to correct or reduce daily serum blood levels Commence SP1 when Ph Commence SP2 when Ph. >7.45 ↑Dialysate Hypomagnesaemia ⁶Serum blood Magnesium level <1mmol/L Daily serum level. Supplement with Intravenous Magnesium. Hypophosphatemia⁴Serum blood Phosphate level <1mmol/L Daily serum level. Supplement with Intravenous Phosphate. This is the third revision of previously used Protocols due to:  The addition of extra bicarbonate to dialysis bags, increases the risk of drug error, sharps injury and cost.¹⁰  The variable nature of the effluent dose leads to unnecessary electrolyte replacement and increased cost due to the extra RRT fluids used. ¹⁰  Ongoing concern that in certain patients (predominantly sick multi-organ failure) we are failing to correct the academia in an appropriate time.¹⁰ How Citrate works? Citrate binds to Calcium in the blood¹³as it is infused into the venous access limb of the haemodialysis circuit. Calcium, an essential component of the clotting cascade⁸, bound to Citrate, is largely removed through extracorporeal convection and diffusion⁴ (dialysate fluid containing 0 Calcium). The remaining Citrate-Calcium complexes are metabolised by the patients liver, skeletal muscle and kidney¹¹ to form one calcium and 3 bicarbonate molecules thus contributing to control of acid base. Kelly Trebell NH6144 September 2013