Guideline for the Management of Continuous IV Vancomycin Infusion in A Clinical Guideline recommended for use For Use in: By: For: Division responsible for document: Key words: Name and job title of document author: Name of document author s Line Manager: Job title of author s Line Manager: Supported by: Neonatal Intensive Care Unit Doctors, ANNPs, Nurses, Pharmacists Neonates receiving vancomycin on NICU Women and Children s Services Vancomycin, neonate, continuous infusion, therapeutic drug monitoring Rosalind Howe, Pharmacist NNUH Carol Farrow Clincial Director Pharmacy Services Mark Dyke, Consultant Neonatologist NNUH NICU Guidelines Meeting approved 09/09/2017 Assessed and approved by the: Clinical Guidelines Assessment Panel (CGAP) If approved by committee or Governance Lead Chair s Action; tick here Date of approval: 15/09/2017 Ratified by or reported as approved to (if applicable): To be reviewed before: This document remains current after this date but will be under review To be reviewed by: Clinical Standards Group and Effectiveness Sub-Board 15/09/2020 Rosalind Howe Reference and / or Trust Docs ID No: 11046 Version No: CA6011 v 2 Description of changes: Compliance links: (is there any NICE related to guidance) If Yes - does the strategy/policy deviate from the recommendations of NICE? If so why? Time levels reduced None N/A This guideline has been approved by the Trust's Clinical Guidelines Assessment Panel as an aid to the diagnosis and management of relevant patients and clinical circumstances. Not every patient or situation fits neatly into a standard guideline scenario and the guideline must be interpreted and applied in practice in the light of prevailing clinical circumstances, the diagnostic and treatment options available and the professional judgement, knowledge and expertise of relevant clinicians. It is advised that the rationale for any departure from relevant guidance should be documented in the patient's case notes. The Trust's guidelines are made publicly available as part of the collective endeavour to continuously improve the quality of healthcare through sharing medical experience and knowledge. The Trust accepts no responsibility for any misunderstanding or misapplication of this document. Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 1 of 11
(Title of document needed on every page) Quick reference guideline Give a loading dose of 15 mg/kg over 1 hour. Immediately after this 1 hour infusion is complete start the continuous IV vancomycin infusion as follows:- *Concentration 4.17 mg/ml (125 mg vancomycin in 30 ml glucose 5%) Serum creatinine (µmol/l) Corrected gestational age Total Daily dose Infusion rate* (ml/hr) < 40 40 weeks 50 mg/kg/24hrs 0.5 x weight(kg) < 40 < 40 weeks 40 mg/kg/24hrs 0.4 x weight (kg) 40-60 all 30 mg/kg/24hrs 0.3 x weight (kg) >60 all 20 mg/kg/24hrs 0.2 x weight (kg) Rate adjustments for continuous IV infusion Levels should be taken 12-24 hours after the start of the infusion or a change of infusion rate. The infusion rate should be adjusted according to the results of the level when reported. Vancomycin Level (mg/l) Adjustment of infusion rate <10 mg/l Increase by 50% 10 to <15 mg/l Increase by 25% 15 to 25 mg/l No change, within range >25 to 30 mg/l Decrease by 25% >30 mg/l Stop infusion for at least 6 hours, recheck level. When level <25 mg/l restart at lower rate Frequency of monitoring Levels should be taken 12-24 hours after the start of the infusion or a change of infusion rate (take with routine bloods wherever possible). Once level is within therapeutic range (15 to 25 mg/l) monitor level twice weekly (Monday & Thursday). Recheck the level daily if any of the following conditions are met during vancomycin therapy:- 1. Big changes in dose AND /OR frequency of diuretics (furosemide, spironolactone, potassium canrenoate) e.g doubling dose AND/OR frequency 2. Anti-hypotensive drugs are commenced (dopamine, dobutamine) 3. Deterioration of clinical condition (sepsis, hypoalbuminaemia) 4. Clinically significant hypotension 5. Significant deterioration in renal function Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 2 of 11
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Objective To ensure therapeutic levels of vancomycin are obtained rapidly and maintained throughout the course of antibiotic therapy. Rationale Vancomycin is bactericidal against many gram-positive organisms. The antimicrobial activity of vancomycin is dependent on the time that the serum concentration exceeds the minimum inhibitory concentration of the micro-organism being treated. Prescribing vancomycin according to the dose recommendations in the BNFc frequently leads to subtherapeutic serum levels in neonates. Usual practice is to increase the dose by 10% and repeat serum levels. However using this approach can sometimes mean it takes several days to reach a therapeutic level. Although early preparations of vancomycin caused renal toxicity, it is now thought this was due to impurities in the manufacturing process rather than vancomycin itself and nephrotoxicity does not appear to be a problem with current preparations. (However, vancomycin is excreted virtually unchanged in the urine and should be used with caution in babies that already have poor urine output). Ototoxicity has been seen, but mostly in babies on aminoglycosides or diuretics as well. Evidence is emerging that vancomycin can be infused continuously to obtain therapeutic levels while maintaining patient safety. This guideline has been written to support the prescribing, monitoring, administration and dose adjusting of continuous IV vancomycin infusion on NICU. Definitions of Terms Used / Glossary ANNPs Advanced Neonatal Nurse Practitioners BNFc British National Formulary for Children IV intravenous NICU Neonatal Intensive Care Unit CVC central venous catheter Broad recommendations Indication Vancomycin must be prescribed in accordance with the Trust antibiotic policy Dose Give a loading dose of 15 mg/kg by IV infusion over 1 hour. Immediately after this 1 hour infusion is complete start a continuous IV vancomycin infusion as follows:- Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 4 of 11
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Table 1. Serum creatinine (µmol/l) Corrected gestational age Total Daily dose Infusion rate* (ml/hr) <40 40 weeks 50 mg/kg/24hrs 0.5 x weight (kg) <40 < 40 weeks 40 mg/kg/24hrs 0.4 x weight (kg) 40-60 all 30 mg/kg/24hrs 0.3 x weight (kg) >60 all 20 mg/kg/24hrs 0.2 x weight (kg) * Concentration 4.17 mg/ml (125 mg vancomycin in 30 ml glucose 5%) Prescribing The 15 mg/kg IV loading dose should be prescribed on the once only section of the drug chart. The continuous IV infusion of vancomycin should be prescribed on the drug infusions page of the drug chart as follows. A new prescription should be written for each change of rate. Example 1: baby weight 1.5 kg with a creatinine of 45 µmol/l Drug Infusions 1. Drug (approved name) VANCOMYCI N Dilution Fluid 5% glucose Total Volume 30mL Rate (units (eg mg) per Kg/hour) 30mg/kg/day Rate (ml/hour) 0.5mL/hour Prescriber s Signature A Doctor Prescribe Opiates on Opiate & Epidurals pages Amount or Volume 125mg Route IV Start Date X/XX/X X Pharma cy Bleep No 1234 Name Baby boy Blue Dat e Tim e Rou te Dos e Give n By Hospital No xxxxxx Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 6 of 11
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Attach a Vancomycin Therapeutic Drug Monitoring Sticker (could we have a copy of this as an appendix?)to the antibiotic page of the drug chart and complete the date when the first level is due. Vancomycin Therapeutic Drug Monitoring Date level due Date and time levels taken Result (mg/l) Target 15-25mg/l Action (e.g. increase rate) Levels should be taken 12-24 hours after the start of the infusion or a change of infusion rate (take with routine bloods wherever possible). Adjust infusion rate as per Trust Guideline Once level is within therapeutic range monitor level twice weekly (Monday & Thursday). Recheck the level daily if any of the following conditions are met:- Big changes in dose AND /OR frequency of diuretics (furosemide, spironolactone, potassium canrenoate) e.g. doubling dose AND/OR frequency Starting anti-hypotensive drugs(dopamine, dobutamine) Deterioration of clinical condition (sepsis, hypoalbuminaemia) Clinically significant hypotension Significant deterioration in renal function NB infusion pumps can only be set to one decimal place so round infusion rate to nearest one decimal place. Vancomycin Preparation Add 9.6 ml of water for injection to a 500 mg vial of vancomycin. This gives 500 mg in 10 ml (0.4 ml displacement) Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 8 of 11
Loading dose: Withdraw required dose and dilute to 10 times the volume with sodium chloride 0.9% or glucose 5% and infuse over one hour. Continuous infusion: Withdraw 125 mg (2.5mL) and make up to 30 ml with sodium chloride 0.9% or glucose 5%. This provides a concentration of 4.17 mg in 1 ml. Administration Administer either via a central venous catheter (CVC) (preferred due to ph about 3.0-4.0) or a peripheral line. The infusion solution should be replaced every 24 hours. Table 3. Infusion compatibility Y-site compatible TPN, lipid, aciclovir, atracurium, caffeine citrate, calcium gluconate, dobutamine, dopamine, fluconazole, gentamicin, hydrocortisone, insulin, magnesium sulphate, meropenem, midazolam, morphine, pancuronium, potassium chloride, ranitidine Not compatible Albumin, amphotericin, cefotaxime, ceftazidime, cefuroxime, dexamethasone, furosemide, heparin, phenytoin, sodium bicarbonate This list is not exhaustive. Please check concentrations with pharmacy (Monday Friday 9.00 17.00 bleep 0500; out of hours via on-call pharmacist). Frequency of monitoring Levels should be taken 12-24 hours after the start of the infusion or a change of infusion rate (take with routine bloods wherever possible) The infusion rate should be adjusted according to the results of the level when reported. Adjust infusion rate as per Table 2 below Once level is within therapeutic range (15 to 25 mg/l) monitor level twice weekly (Monday & Thursday) Recheck the level daily if any of the following conditions are met during vancomycin therapy:- 1. Big changes in dose AND /OR frequency of diuretics (furosemide, spironolactone, potassium canrenoate) e.g. doubling dose AND/OR frequency Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 9 of 11
2. Starting anti-hypotensive drugs(dopamine, dobutamine) 3. Deterioration of clinical condition (sepsis, hypoalbuminaemia) 4. Clinically significant hypotension 5. Significant deterioration in renal function Rate adjustments The infusion rate should be adjusted according to the results of the level when reported. Table 2 Vancomycin Level (mg/l) Adjustment of infusion rate < 10 mg/l Increase by 50% 10 to <15 mg/l Increase by 25% 15 to 25 mg/l No change, within range >25 to 30 mg/l Decrease by 25% >30 mg/l Stop infusion for at least 6 hours, recheck level, when level <25 mg/l restart at lower dose Example 2 Baby on 30 mg/kg/day (0.5 ml/hour) Serum level reported as 12 mg/l, 14 hours after vancomycin started, therefore from table 2, increase infusion rate by 25% (0.5 ml/hour 100) 125 = 0.625 ml/hour (round to 0.6 ml/hour) (30 mg/kg/day 100) 125 = 37.5 mg/kg/day Clinical audit standards 100% of NICU babies who need vancomycin therapy are given a loading dose of 15mg/kg 100% of NICU babies on continuous IV vancomycin infusions have an initial level checked 12-24 hours after the infusion started 100% of NICU babies on continuous vancomycin infusion with subtherapeutic vancomycin levels (serum level <15 mg/l) have their infusion rates increased in accordance with this guideline The audit results will be sent to NICU Clinical Director who will ensure that these are discussed at relevant governance meetings to review the results and make recommendations for further action. Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 10 of 11
Summary of development and consultation process undertaken before registration and dissemination This guideline was drafted by Rosalind Howe (pharmacist) on behalf of the Neonatal Intensive Care Unit. It was circulated for comments to Neonatal Consultants, registrars, ANNPs, senior nurses and Catherine Tremlett (Consultant microbiologist). Comments and suggested amendments have been incorporated in the revised draft presented and agreed at a Departmental Guideline meeting 27/08/2014. Distribution list/ dissemination method Trust Intranet. References 1. Neonatal Formulary 6 Drug Use in Pregnancy and the First Year of Life(NNF6), 6 th edition 2011. Wiley-Blackwell, BMJ-Books 2. Patel A et al. Continuous infusion of vancomycin in neonates. Arch Dis Child June 2013 Vol 98 No 6 3. Trissel LA Hanbook of Injectable Drug http://www.medicinescomplete.com/mc/hid/current/a582208.htm 4. Vancomycin Intravenous Infusion administration in Neonates and Infants. Oxford University Hospitals NHS Trust. April 2012 5. Zhao W, et al. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring. Arch Dis Child 2013;98:449-453. Available via Trust Docs Version: CA6011 v2 Trust Docs ID: 11046 Page 11 of 11