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1 Clinical Safety & Effectiveness Cohort # 10 Improving Weight-Based Vancomycin Dosing and Monitoring DATE Educating for Quality Improvement & Patient Safety

2 Financial Disclosure lizabeth A. Walter, MD, has no relevant financial elationships with commercial interests to disclose. eta Javeri, MD, MPH Fellow, has no relevant inancial relationships with commercial interests to isclose.

3 The Team Infectious Diseases/Clinical Pharm D Dr. Elizabeth Walter, MD Dr. Heta Javeri, MD, MPH James Lewis, Pharm D Bin Xiao, Pharm D Internal Medicine Nursing/Technicians Sponsor Department Internal Medicine

4 What We Are Trying to Accomplish? OUR AIM STATEMENT 1 a. To improve the use of initial weight-based vancomycin dosing in hospitalized patients by implementing and encouraging the use of a vancomycin dosing order set in Sunrise. Currently, 66% of patients with weight > 100 kg are inappropriately dosed with vancomycin and we aim to decrease this to 50%. 1 b. To improve the timing of initial vancomycin trough levels to ensure rapid achievement and maintenance of therapeutic drug levels (TDM).

5 Project Milestones Team Created January 2012 Aim statement created January 2012 Weekly Team Meetings February 2012 Background Data, Brainstorm Sessions, March 2012 Workflow and Fishbone Analyses Interventions March 2012 Data Analysis May 2012 CS&E Presentation June 2012

Background: Dosing in Obesity San Antonio, Texas is one of the most obese cities in the nation. San Antonio obesity rate of 28.2% United States average of 27% 1 A multicenter evaluation of vancomycin dosing found: 86% of overweight patients (BMI= 25-29.9 kg/m 2 ) 91% of obese patients (BMI > 30 kg/m 2 ) with gfr > 60 ml/min Received a fixed dose of 2 g daily divided into two doses 4 A pilot study (n=65) conducted at out institution revealed that only 33% of patients > 100 kg received weight-based vancomycin dosing greater than 30 mg/kg/day.

Background: Guidelines Doses of 15-20 mg/kg actual body weight every 8-12 hr are optimal for most patients with normal renal function to achieve the suggested serum concentration. A loading dose of 25-30 mg/kg (based on ABW) in seriously ill patients to achieve a more rapid target trough concentration 3. Trough serum vancomycin concentrations of 15 20 mg/l are recommended for complicated infections (bacteremia, endocarditis, osteomyelitis, meningitis and hospital acquired pneumonia) caused by MRSA. Maintain trough > 10 mg/l, based on evidence suggesting that strains with VISA like characteristics (hvisa) may develop 3.

Current Status of Therapeutic Drug Monitoring (TDM) Large number of vancomycin trough levels incorrectly ordered. Difficulty in interpreting results of inappropriately drawn levels. Increases unnecessary costs from additional ordering of levels. Potential increase length of stay due to inability to ensure target serum concentration prior to patient discharge.

Background: Review of Literature Effect of the implementation of vancomycin dosing and TDM guidelines in computerized prescriber-order-entry (CPOE) system: Traugott, et al. Demonstrated a significant increase in the number of appropriately obtained serum vancomycin levels (58% to 68%, p = 0.02) 5 McCluggage, et al. Observed a significant increase in the percentage of patients with an initial optimal vancomycin regimen that met nomogram recommendations (36% versus 24%, p = 0.0028) 6 Li, et al. Demonstrated that patients in the post education group on vancomycin dosing protocol had significantly higher, initial median weight-based doses (12.5 mg/kg vs 20.0 mg/kg, p < 0.001), trough concentration (6.8 mg/l to 10.1 mg/l, p= 0.013) and AUC/MICs (262.5 to 365.0, p= 0.001) when compared with the pre-intervention group 7

10 Pre-intervention Process Analysis Tool Pt requiring Vancomycin (Vanc) Weight in chart MD orders Vanc Is weight-based dose ordered Weight-based vancomycin dose given MD reviews dose given and orders level MD requests weight Non- weight based dose given MD reorders level Is level ordered appropriately* Incorrect level obtained Vanc level drawn MD reviews level and orders new dose or continues current dose Is the level drawn appropriately ** RN Blood drawn by RN or tech Pt given next dose Tech hands blood draw to nurse Tech * prior to next or 4 th dose ** 30 mins prior to dose No Yes

Decision Making Tool 11

12 Plan: Intervention We implemented the following intervention: A vancomycin dosing order set within the computerized prescriber-order-entry (CPOE) system. Education of physicians and nursing staff on vancomycin dosing, use of CPOE system and accession of appropriate vancomycin level when indicated. Assessment of the effect on vancomycin dosing and therapeutic drug monitoring (TDM).

13 Do: Implementing the Change 1. System Changes within Sunrise Meetings were held with pharmacy staff and sunrise informatics specialists to develop the new order set within Sunrise. The newly developed order set was tested on a sample patient list within Sunrise to identify flaws in functioning. The order set was then reviewed, accepted, implemented by the P &T committee and incorporated into Sunrise on March 1 st, 2012.

14 Do: Implementing the Change The order set provided weight-based dosing. Skin/soft tissue infections Serious infections (bacteremia, endocarditis, osteomyelitis, meningitis and hospital acquired pneumonia) Incorporated patient s renal function Added a loading dose for serious infections. Linked the order for vancomycin trough level to the order set. Default time for vancomycin trough level eliminated Facilitated providers to self-select times for trough levels Odd dosing and continuous infusion order set were retained.

Order Set

Order Set

17 Do: Implementing the Change 2. Staff education Nursing Nursing educators for floor 8, 9 and MICU were contacted and education method and materials were discussed with them. On an average 3 in-service (training sessions) each lasting 10 minutes were scheduled for each of the floors prior to either the morning or evening shift change. The training sessions were conducted by members of the team for the initial 3 sessions and then were followed by nurse educators who were present during the initial training.

18 Do: Implementing the Change Participation of all staff was ensured by an attendance sign in sheet placed prior to all sessions. Entering patient height and weight Appropriate charting of the time of medication administration and level drawn Check out time of vancomycin level lab draw to oncoming nurses at the time of hand off. Schedule lab draw prior to X th dose as ordered by physician (e.g next, 4 th, etc). All levels to be drawn by RN only

19 Do: Implementing the Change Physicians Practitioners were educated on the need for weight-based dosing, especially for patients weighing 95 kg and the need for loading dose in serious infections. A 15 minute presentation was made to the Internal medicine housestaff prior to their daily noon conference. A similar presentation was also made to the family medicine housestaff prior to their weekly didatic session.

Study: Determining Change Types of Measures Percent of patients who have weight entered into Sunrise Percent of physicians/hcws using the order set Comparing pre and post-intervention values of: Patients not receiving weight-based (<30 MG/KG/D) vancomycin dosing Patients weighing less than 95 kg and greater than 95 kg Patients appropriately receiving loading dose Serious infections Patients with appropriate timing of initial vancomycin level Time till first appropriate trough level Time till first appropriately timed level 20

Performance Improvement Design Retrospective chart review Collection of baseline, pre-intervention data Patients initiated on vancomycin from Dec 1, 2011 to Feb 29, 2012 Collection of post-intervention data Patients initiated on vancomycin from April 1, 2012 to April 30, 2012

Subjects Adult inpatients at University Hospital (UHS). 18 years or older Admitted to UHS Medicine, Family Medicine or ICU teams Receiving at least 1 dose of vancomycin Potential subjects were identified through pharmacy records. Information collected: Age, gender, race, height, weight, scr Diagnosis with culture results Initial dosing regimen, loading dose Data on trough level (timing, level, number) Length of vancomycin therapy Length of stay

Subjects Exclusion criteria: Age <18 years Hemodialysis and chronic kidney disease with creatinine clearence (Crcl) <40 ml/min N=195 Pre-intervention N=125 Post intervention N=69 Excluded: Crcl <40 ml/min N=19 Excluded: Crcl <40 ml/min N=12 Final N=106 Final N=57

24 Results No. of patients prescribed vancomycin using the order set Therapeutic Drug Monitoring 53 Time to therapeutic trough level (hrs) 37 11% 89% Order-set Used Order-set Not Used Time to appropriately timed trough level (hrs) 34 47 Pre-intervention Post-Intervention 0 20 40 Hours

25 Results Lower dose vancomycin (1 gm Q12H) Higher dose vancomycin (1 gm Q8H) 90% 80% 80% 70% 60% 50% 40% 30% 20% 10% Pre-intervention 70% 60% 50% 40% 30% 20% 10% Pre-intervention Postintervention Postintervention 0% All pts Weight 95 kg 0% All pts Weight 95 kg

26 Results Inappropriate Weight-based (30 mg/kg/d) Vancomycin dosing 100 90 80 70 60 50 40 30 20 10 0 Pre-intervention Post-intervention Pre-Week 1 2 3 4 5 6 7 8 9 10 Post-Week 1 2 3 4 5 6 7 8 9 % of patients receiving inappropriately dosed vancomycin/week

27 G Chart: Time Between Events 16 Pre-Intervention Days between Weight Based Dosing (> 30mg/kg/d) Days Between Weight- Based Dosing 14 12 10 8 6 4 2 0 13.94 3.1364 Pre-Intervention

Results Days between Weight- Based Dosing 6 5 4 3 2 1 0 Post-Intervention Days between Weight Based Dosing (> 30mg/kg/d) 4.47 0.8163 Post Intervention

Results Length of stay was 2 days shorter in the post-intervention group.

30 Return on Investment Estimated Project Costs Estimated Project Savings Project labor (IT personnel) $514 Implementation costs (RN time) $7,000 ROI Calculation: Internal Rate of Return: 109% Modified Internal Rate of Return: 56% Increased revenue from decreased length of stay Saved costs from decreased levels ordered Soft savings from reduced LVN time $31,200 $2,543 $5,120

31 Act: The Next Step... Continuing education. Plan to expand staff and physician education to other floors and services of the hospital. Post intervention survey.

Limitations Retrospective nature of the study may have led to inaccuracies in data collection. Small sample size. Educational intervention may not have captured all physicians and nursing staff. Ensuring continuing education of all staff. Caution should be exercised in the population with renal impairment as this were not evaluated in this study.

Conclusion The incorporation of a vancomycin dosing order set within the CPOE system in concurrence with provider and nursing staff education led to: Increased the rate of appropriate weight-based dosing. Shortened mean time to achieving appropriate, target serum trough concentrations. Decreased overall length of stay.

References 1. Overweight and obesity [Internet]; Centers for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: http://apps.nccd.cdc.gov/ddtstrs/default.aspx. Retrieved 6/7/2012. 2. Blouin RA, Bauer LA, Miller DD, Record KE, Griffen WO,Jr. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 1982 Apr;21(4):575-80. 3. Rybak M, Lomaestro B, Rotschafer JC, Moellering R,Jr, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the american society of health-system pharmacists, the infectious diseases society of america, and the society of infectious diseases pharmacists. Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. 4. Hall RG,2nd, Payne KD, Bain AM, Rahman AP, Nguyen ST, Eaton SA, et al. Multicenter evaluation of vancomycin dosing: Emphasis on obesity. Am J Med. 2008 Jun;121(6):515-8. 5. Traugott KA, Maxwell PR, Green K, Frei C, Lewis JS,2nd. Effects of therapeutic drug monitoring criteria in a computerized prescriber-order-entry system on the appropriateness of vancomycin level orders. Am J Health Syst Pharm. 2011 Feb 15;68(4):347-52. 6. McCluggage L, Lee K, Potter T, Dugger R, Pakyz A. Implementation and evaluation of vancomycin nomogram guidelines in a computerized prescriber-order-entry system. Am J Health Syst Pharm. 2010 Jan 1;67(1):70-5. 7. Li J, Udy AA, Kirkpatrick CM, Lipman J, Roberts JA. Improving vancomycin prescription in critical illness through a drug use evaluation process: A weight-based dosing intervention study. Int J Antimicrob Agents. 2012 Jan;39(1):69-72.

35 Thank you! Educating for Quality Improvement & Patient Safety