Wales Critical Care & Trauma Network (North) CITRATE GUIDELINES (Approved May 2015)

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1 Wales Critical Care & Trauma Network (North) CITRATE GUIDELINES (Approved May 2015) BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 1

2 BCU Critical Care Guideline for Renal Replacement Therapy using Citrate Indication Regional anticoagulation in patients receiving CRRT. Contraindications 1. Severe liver impairment. 2. Paracetamol overdose. 3. Metformin toxicity. 4. Patient already receiving systemic anticoagulation. (All relative, discuss with consultant) Before starting treatment 1. Check the daily blood results before the start of treatment: TOTAL CALCIUM (not the corrected value), magnesium and potassium. 2. Check recent arterial blood gas including calcium (PATIENT IONISED CALCIUM). 3. Ensure patent vascular access (able to withdraw blood at rate of 20mLs/6sec). (NB: APTT levels are not required to operate the treatment.) Equipment needed 1 Prismaflex Filter ST bag of 5L PrismoCitrate 18/0 (citrate used as pre-dilution). 1 bag of 5L Prism0cal B22 (dialysate, calcium-free). 1 bag or 5L Prismasol 4 (post-dilution replacement fluid). 2 bags of 0.9% 1000mLs Sodium Chloride (priming solution - no heparin required). 1 CA250 calcium line. 1 50mL Luer lock syringe. 30mmol calcium (as calcium chloride) made up to 50ml with 0.9% saline. Setting up and priming circuit 1. Select New Patient. 2. Input actual body weight. 3. Input haematocrit. This is found on the full blood count. Unlike in treatment with heparin, haematocrit is important. Update the haematocrit value every morning. 4. Choose CVVHDF. 5. Choose Citrate Anticoagulation via Prismaflex Pump. 6. Follow the installation steps on the screen: Install PrismoCitrate 18/0 on the white scale (PBP = pre blood pump). Install Prism0cal B22 on the green scale. (Dialysate). Install Prismasol 4 on the purple scale (Replacement). 7. Install the calcium chloride in the Prismaflex integral syringe pump. 8. Prime the circuit with 2 X 1L of 0.9% Sodium Chloride (as per on screen instructions) BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 2

3 Starting Parameters (NB: if this is not the first set for this patient, simply set calcium compensation and citrate at their previous rates) MODE: CVVHDF FLUID REMOVAL: as advised by doctor CITRATE DOSE: 3 mmol/l. CALCIUM COMPENSATION: Depends on initial PATIENT IONISED CALCIUM level see table 1 below. Patient Ionised Calcium Starting Calcium Compensation (%) Less than 1mmol/L 110% AND give 10mls calcium chloride 10% over 30 mins before starting mmol/l 110% mmol/l 100% Greater than 1.3mmol/L 90% Table 1: Initial Calcium Compensation INITIAL FLOW SETTINGS: Based on Weight. See table 2 below. Weight (Actual in Kg) (Round up to nearest whole kg) INITIAL SETTINGS WITH CITRATE DOSE of 3 mmols/l blood Blood Flow mls/min Dialysis rate mls/hr Replacement (post filter) rate mls/hr Actual Renal Replacement Dose Up to mls/kg/hr 51 to mls/kg/hr 61 to mls/kg/hr 71 to mls/kg/hr 81 to mls/kg/hr 91 to mls/kg/hr 101 to mls/kg/hr 111 to mls/kg/hr 121 and up mls/kg/hr Table 2: Initial Flow Settings CONNECTION (see Picture 1) 1. Connect access line to patient VasCath (red). 2. Connect yellow line to effluent bag. 3. Connect calcium chloride line to available port on Y connector. 4. Disconnect Y connector from priming bag and attach to Vascath (blue). 5. Connect blue return line to the vacated port on the Y connector. 6. Tape together calcium and return line (near patient). 7. Unclamp lines (as per machine). 8. Press start treatment (note the time). NB: Avoid swapping lines unless absolutely necessary. If lines are swapped ensure the lines are clearly labelled, and the reason for the change is documented. BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 3

4 Picture 1: Connecting Tubing to VasCath. BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 4

5 Treatment Monitoring Low PATIENT IONISED CALCIUM values should ALWAYS be attended to as a priority as it will have the biggest impact on patient physiology and stability. If at any time during treatment the patient s ionised calcium is less than 0.7 mmol/l, administer 10mL calcium chloride 10% through peripheral or central line. The PATIENT IONISED CALCIUM from the patient s arterial line* is used to ensure that enough calcium chloride is being given to the patient to replace the calcium used up in the reaction with the citrate. A PATIENT IONISED CALCIUM of >1 is required TO KEEP THE PATIENT SAFE from the effects of hypocalcaemia. The calcium replacement, initially estimated by the Prismaflex machine, may need to be changed based on these results. The FILTER IONISED CALCIUM (from the blue port on the Prismaflex [i.e. post filter]) is checked on the blood gas machine to ensure that enough calcium is being removed by the citrate infusion via the pre-blood pump. A FILTER IONISED CALCIUM concentration of mmol/l is required TO PREVENT FILTER CLOTTING. The citrate dose, initially based on patient weight, may need to be changed based on these results. So, once treatment is initiated and blood flow established, wait 60 minutes then check the: PATIENT IONISED CALCIUM from the patient s arterial line*. FILTER IONISED CALCIUM (from blue port on Prismaflex). The table below gives the timings of the FILTER IONISED CALCIUM and PATIENT IONISED CALCIUM checks (as well as other blood tests which will be needed). Parameter Initial check And then FILTER IONISED CALCIUM ABG from blue port on circuit Target 0.25 to 0.50 mmol/l PATIENT IONISED CALCIUM ABG from arterial line* Target 1.00 to 1.30 mmol/l Hourly until stable** Hourly until stable** 6 Hourly 6 Hourly TOTAL CALCIUM yellow tube sent to lab Target 2.20 to 2.50 mmol/l After 6 hours Daily TOTAL CALCIUM to PATIENT IONISED CALCIUM ratio Target ratio <2.5 After 6 hours U&E 6 hourly 12 hourly when stable FBC/haematocrit Daily Daily Magnesium/phosphate Daily Daily Glucose As per protocol As per protocol Table 3: Frequency of blood tests. *Or central line, or peripheral venesection: the point is that it comes from the patient, not the machine. ** Stable = No changes required for 2 consecutive hours Daily BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 5

6 Treatment Monitoring continued Adjust the Calcium Compensation and Citrate Dose based on the table below. Adjustments are made through the Anticoag screen. Filter Ionised Calcium >0.50 Filter Ionised Calcium Filter Ionised Calcium <0.25 Patient Ionised Calcium < 1.0 Citrate dose increased by 0.5mmols/L blood AND Calcium compensation increased by 10% Calcium compensation increased by 10% Citrate dose decreased by 0.5mmols/L blood Patient Ionised Calcium Citrate dose increased by 0.5mmols/L blood Normal Ideal Values Citrate dose decreased by 0.5mmols/L blood Patient Ionised Calcium > 1.3 Calcium compensation decreased by 10% Calcium compensation decreased by 10% Calcium compensation decreased by 10% AND Citrate dose decreased by 0.5mmols/L blood RECHECK ONE HOUR AFTER ANY CHANGE Table 4: Adjusting Calcium and Citrate Dose With the exceptions given in the table above, aim to make only one adjustment at a time. Then recheck for desired effect in one hour. Making multiple changes to citrate dose, calcium compensation, blood flow or dialysis flow simultaneously will make the interpretation of actions and subsequent troubleshooting difficult. Total calcium to ionized calcium ratio monitoring A high total calcium to ionized calcium ratio is a surrogate marker of citrate toxicity. To obtain the value, perform the following calculation manually TOTAL CALCIUM PATIENT IONISED CALCIUM. Note that it is the total calcium and not the corrected calcium that is used in the equation. After 6 hours of treatment commencing, request a total calcium from the lab (yellow tube, best sent with U&Es). However, increasing calcium compensation in the preceding hours could indicate citrate accumulation. In these circumstances, a total calcium level may be checked before the 6 hour mark. Ratio Action <2.5 Check ratio daily >2.5 Consult medical staff. Stop the PrismoCitrate for 20 minutes and restart afterwards with 70% of prior citrate dose. Leave the calcium unchanged. This should result in a slightly higher filter ionised calcium. (0.4 to 0.5 acceptable) If ratio remains above 2.5 despite filter Ionised calcium of mmol/L then consider: 1. Doubling baseline dialysate flow (will increase citrate clearance) 2. Reducing blood pump speed (will reduce total administered citrate dose). 3. Stopping citrate and using an alternative anticoagulant (or no anticoagulant) Table 5: Citrate Accumulation. BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 6

7 Troubleshooting Acid/Base Disturbances BLOOD GASES POSSIBLE REASON POTENTIAL SOLUTIONS TO CONSIDER ph > 7.45 and BE > +5 Too much citrate (metabolised by the liver to bicarbonate). Boost citrate removal in dialysis by increasing dialysis flow by 500mLs/hr. Maximum dialysis dose of 3000mLs/hr. Or: Consider reducing citrate dose to patient by reducing blood flow rate in 20mLs/min increments. Or: Consider accepting higher post filter ionised calcium by reducing citrate dose by 0.5mmol/L ph < 7.35 and BE < -5 Total calcium and patient ionised calcium normal NB: NORMAL LIVER FUNCTION Metabolic acidaemia more citrate may help Reduce dialysis dose to reduce clearance of citrate, thus increasing citrate buffer load to patient. Or: Consider increasing blood flow rate, which will increase citrate dose. Or: Consider systemic sodium bicarbonate infusion. ph < 7.35 and BE < -5 Total calcium increased; patient ionised calcium normal or decreased Ratio of total Ca/ionised Ca > 2.5 Patient Acidaemic - too much citrate (and the liver can t handle it) Only generally seen in liver dysfunction CONSULTANT DISCUSSION REQUIRED See Section on total calcium to ionised calcium ratio Table 6: Acid/Base RECHECK BLOODS ONE HOUR AFTER ANY CHANGE ALWAYS REVIEW UNDERLYING PATHOLOGY BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 7

8 Frequently Asked Questions Q. Is heparin used to prime the circuit? No. However patient s lines should be hep-locked at the end of treatment. Q. My patient is septic, and I want to increase my dose of RRT. How can I do this? Increase the replacement by 10ml/kg/hr. For example, if you have a 70kg patient receiving a total RRT dose of 35ml/kg/hr, and you want to up it to 45, then increase their replacement by 700ml/hr. Q. What do I do if I want to increase clearance? Depending on solute to be removed, either increase replacement flow or dialysate flow or alternatively move patient up to the next weight bracket. Changes to blood flow and dialysate flow rates will affect the citrate and calcium doses delivered. So change flow rates with caution. Increases to post filter replacement flow should not have a demonstrable effect on patient ionised calcium or citrate requirements. Increasing replacement rates to increase effluent dose does NOT require a change in dialysis flow UNLESS the blood flow rate is changed also. Q. How quickly does a change in citrate dose have its effect? Changes to citrate dose will have a rapid effect on post filter calcium concentration, usually within 5 to 10 mins. Q. The protocol says to reduce the citrate dose, and now the overall effluent dose has dropped. What should I do? Should the protocol stipulate that the citrate dose be reduced, pre-blood pump flow and hence total effluent dose will also fall. If the total effluent dose falls below 30mls/kg/hr as a result, increase the replacement flow until a dose of 30mls/kg/hr is achieved. Q. My calcium compensation is very high. Is that normal? There are lots of reasons why a patient s calcium needs can increase, but if calcium compensation is above 150% this could indicate citrate accumulation (citrate is not being metabolised and calcium is not being released). Check patient total calcium/patient ionised calcium ratio if >2.5 follow protocol guideline above. Q. What do I do if my bicarbonate is consistently low? This could be a sign of citrate accumulation. Check calcium ratio. If within normal levels, consider giving bicarbonate. Q. My calcium levels remain high, or are suddenly very low. What s going on? If post filter ionised calcium remains high with increasing citrate doses then check that the correct arrangment and type of fluid has been installed on the replacement and dialysis lines. A sudden and unexplained drop in the patient ionised calcium value and high post filter calcium should signal to check the PrismoCitrate bag has been installed correctly on the pre blood pump and not the replacement line! Q. Should I recheck bloods if the calcium chloride (CaCl) infusion adjusts by a very small amount? Sometimes the calcium chloride infusion will adjust by mls when the Prismaflex attempts to compensate for downtime when pumps have been stopped. No checks are required at very small levels if you are happy that there have been recent reasons for pumps being stopped (e.g. for bag changes). Q. How should citrate be re-started following a circuit change? If a new circuit is started in less than an hour after stopping, then start at the previous levels of citrate and calcium compensation. If more than an hour, then start all over again as if with a new patient. BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 8

9 Q. Why do I keep getting calcium line clamped alarm?? Before filling syringe, pump the plunger up and down in the barrel of the syringe to improve movement. After making up your syringe, discard some of the volume so that syringe volume is below 50mls. If alarm still persists consider moving calcium line to patient s central line. Q. How can I avoid machine interruptions? Ensuring machine interruptions are kept to a minimum will maintain continuous blood circulation and therefore seamless therapy. The following will help: Do not persist with therapy if ve access pressure (>200mmHg) unresolved within 5-10 minutes (contact Superuser/Consultant for advice immediately) Recirculate blood in set ASAP in order to give time (60 mins) for VasCath manipulation (as required) or other lengthy procedures that reduce VasCath patency. Ensure movement of fluid bags is kept to a minimum. Q. The filter has clotted early despite following the protocol. What should I do? If the patient demonstrates early filter clotting (less than 72 hours) then consider a lower target of FILTER IONISED CALCIUM of mmol/L by increasing the citrate dose by 0.2mmols/L from the previous dose. Be aware of risks of citrate accumulation and metabolic alkalosis. Q. Does citrate affect drug pharmacokinetics or clearance? Not appreciably. BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 9

10 APPENDIX: FLUID INFORMATION PrismoCitrate 18/0 Predilution anticoagulant (mmol/l) (white scale) Citrate 18 Na 140 Cl 86 K 0 PrismOcal B22 Dialysate (mmol/l) (green scale) Na 140 Cl 120 Lactate 3 HCO3 22 K 4 Glucose 6.1 Mg 0.75 Calcium None Prismasol 4 Replacement (mmol/l)(purple scale) Na 140 Cl Lactate 3 HCO3 32 K 4 Glucose 6.1 Mg 0.5 Calcium 1.75 BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 10

11 Who contact with questions/ queries regarding citrate therapy CSIG superusers: Dr John Glen For all Prismaflex machine questions/ queries: Prismaflex Helpline BCU Citrate Guideline v6 Nov 2015 (Approved by CCSC May 15) 11