Linking Pharmacy and Data for Better Care

1. Linking Pharmacy and Data for Better Care Part 2: Lab↔Med Candidates, Performance, Tools & Pearls November 11, 2010 1:30pm – 2:30pm CST Voice conferencing: 513-241-1028 Conference ID: 40278 Participant, Please mute your phone by pushing *6 William Galanter MD/PhD Medical Director, Clinical Information SystemsChair Pharmacy & Therapeutics Committee Co-investigator UIC TOP-MED CERTDepartment of Medicine/Department of Pharmacy Practice University of Illinois at Chicago (UIC) This project was supported by grant number U18HS016973 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.

2. Outline -Background of Lab↔Med Linkage decision support -The problem -The issue of timing -The development of high priority Lab↔Med pairs -Selection of pairs -Design of alerts -Results of the first phase of pairs -Summary -Examples -Issues & Tips

3. Drug↔Drug Interaction (DDI) Allergies, vitals, Weight Rx Lab Lab↔Med* Critical Labs Dx Rx↔Dx Targets for Clinical Decision Support (CDS) for medication use Genotypes/Phenotypes Rx↔Everything *Arch Intern Med. 2003 Apr 28;163(8):893-900

4. Communication Issues Registration Clinical Data Alert Clinical Inbox Alert Alert Alert Alert Alert Pharmacy Printer Nurse Physician Orders EMR Rules Engine

5. Synchronous Alerts (synchronous to CPOE) CPOE Clinical Data Alert Registration EMR Rules Engine

6. Asynchronous (to CPOE) Alerts Clinical Data Clinical Inbox Alert Alert Alert Alert Alert Pharmacy Printer Nurse Physician EMR Rules Engine or Reporting tool

7. Timed asynchronous Alerts Clinical Inbox Alert Alert Alert Alert Alert Pharmacy Printer Nurse Physician EMR Rules Engine or Reporting tool

8. Asynchronous Alerts Alert Post-Alert 100% 80% Lab results 60% Proportion of patients Provider Pre-Alert 40% 20% 0 0 1 12 24 Hours Compliance with alert recommendationsLow [Mg++] when on Digoxin EMR Galanter et al. J Am Med Inform Assoc. 2004 Jul-Aug;11(4):270-7.

9. Asynchronous Alerts Alert 100 EMR 80 60 40 Lab results 20 Provider P=0.05 0 5000 10000 15000 20000 25000 0 Exposure to Metformin after a new eGFR <60 % Patients receiving Metformin Post Pre Minutes after new lab

10. The timing of Lab↔Med CDS? Synchronous -Requires CPOE -Compliance is a problem -Immediate feedback Real-time asynchronous -Requires a 24o communication channel -Immediate feedback Non real-time asynchronous reports -Does not require CPOE (~<20% of US Hospitals in 2009*) -Can use a dedicated team for a short period of time, thus adds reliability -delayed feedback *Health Affairs, 28, no. 2 (2009): 404-414 Clin Pediatr (Phila). 2009;48:389-396.

11. Development of an Asynchronous Daily Lab↔Med Report Collaborators University of Illinois at Chicago Bruce L. Lambert, Ph.D., Rob Didomenico, PharmD, Mike Koronkowski, PharmD, Shengsheng Yu, MS, Fang-Ju Lin, BPharm, MS, Jessie Moja, MD Brigham and Women’s Hospital Gordon D. Schiff, MD Stroger Hospital Shane Borkowsky, MD, Mary Wisniewski RN, MSN University of Washington Beth Devine PharmD, MBA, PhD, Tom Payne, MD Cerner Corporation David McCallie MD, Margaret Kolm MD

12. Selecting Inpatient Lab↔Med Pairs Modified Delphi Process Started with 650 Lab↔Med pairs from; -Review of the literature -Experience and CDS of Institutions -Experience of the EMR vendor Panel of experts narrow the list to 24 pairs Yu, Galanter, DiDomenico, Borkowsky, Schiff, Lambert. Consensus list of priority drug-lab linkages for an inpatient asynchronous alert program: Results of a Delphi survey. AJHP. In press.

13. Selecting Inpatient Lab↔Med Pairs Yu, Galanter, DiDomenico, Borkowsky, Schiff, Lambert. Consensus list of priority drug-lab linkages for an inpatient asynchronous alert program: Results of a Delphi survey. AJHP. In press.

14. Results of the Delphi Exercise Top 24 pairs

15. Results of the Delphi Exercise Top 5 pairs

16. Why did the experts pick these pairs? Linear Regression Model Predicting Global Impression of Usefulness Yu, Galanter, DiDomenico, Borkowsky, Schiff, Lambert. Consensus list of priority drug-lab linkages for an inpatient asynchronous alert program: Results of a Delphi survey. AJHP. In press.

17. First Phase of Lab↔Med pairs implemented at UIMCC -All the potassium and pregnancy were done together -Added another easy one

18. Issues to consider when producing the clinical logic -Choosing cutoffs -sensitivity vs. annoyance -Choosing the time of day for the daily report-Potential to reduce risk -Volume of alerts -Risk of Annoyance -workflow -Basic vs. advanced logic-maturity and depth of EMR

19. How frequently are patients receiving K+ with an ↑K+?

20. Potential report benefit vs. report time * * risk risk risk * * Best Time The best time to run the report depends on the alert, even when all alerts were triggering on K+ ACE/ARB Supplemental K+ Hyperal with K+ Time of Day

21. Logic for ACE/ARB↔K+ Target meds: ACE, ARB, any ACE/ARB combination medication Multum classes:Angiotensin Converting Enzyme Inhibitors (all members of this class) Angiotensin II inhibitors (all members of this class) Antihypertensive combinations (some members of this class) Target labs: venous [K+], arterial [K+] Logic: Presence of an active order for a target med with the most recent target lab is above the threshold at the time of report Age: Any Gender: Either Lab cutoff at University of Illinois Hospital (UIH): ≥90 days of age then >5.4 mEq/L <90 days of age then >5.8 mEq/L Time chosen at UIH: 2:00 PM Exclusion criteria: Hemodialysis order, peritoneal dialysis order Optimal time to run the daily report: 11:00 AM Data to retrieve: Name, MR#, Pair, Weight, CrCl, loc/svc, Med, Dose/Freq, Date/Time, Value

22. Logic for ACE/ARB↔K+ Rationale & Information: The time chosen at UIH was based on pharmacists workflow, not the optimal time based on retrospective data. At UIH, this pair is expected to produce roughly 1-2 alerts per day Optimal time to run the daily report was determined based on the total time in danger for all patients with serum [K+] of greater than 5.4 mEq/L. The specificity of the alert did not decrease much as the threshold rose above 5.4 mEq/L The PPV of the alert is improved by 30% if the report is able to exclude ESRD patients on HD or PD. This distinction is not likely available in most hospitals. In most patients with chronic kidney diseases, the ACE inhibitor or ARB can be continued if serum potassium is ≦5.5 mEq/L.1 For increased serum potassium concentrations of up to 5.5 mEq/L, the dose can be lowered. In patients receiving some combination of an ACE inhibitor, an ARB, and an aldosterone-receptor blocker, discontinuation of one drug may also be effective in lowering the serum potassium concentration. If the potassium concentration increases to a value >5.5 mEq/L despite the precautions noted above, then such drugs may need to be avoided.2,3

23. Logic for ACE/ARB↔K+ Rationale & Information: (continued) For heart failure patients, although potassium elevations up to 5.5 mEq/L during treatment with RAAS antagonists are generally well tolerated and likely can be managed with reductions in dosage or dietary modification alone, levels greater than 5.5 mEq/L are of concern and should prompt discontinuation of one or more offending drugs, with short-term laboratory follow-up to confirm a return to normal.4 If potassium rises >5.5 mEq/L, halve dose of ACEI or ARB and monitor blood chemistry closely. If potassium rises > 6.0 mEq/L, stop ACEI or ARB immediately and monitor blood chemistry closely.5 When a patient starts receiving ACEI/ARB in heart failure or hypertension: Stable K+ increases to ≦6 mEq/L do not usually require change in treatment, although rises to 5.5–5.9 mEq/L should prompt more frequent monitoring. If it rises >6 mEq/L, all drugs that may increase potassium and concomitant nephrotoxic drugs should be stopped and specialist advice sought.6 The "normal" range for serum potassium is higher in neonates than adults7,8, therefore a different cutoff is used for patients under 90 days of age. References: 1 K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43:S1-290. 2 Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med 2004;351:585-92. 3 Palmer BF. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what to do if the serum creatinine and/or serum potassium concentration rises? Nephrol Dial Transplant 2003;18:1973-5. 4 Desai AS. Hyperkalemia in patients with heart failure: incidence, prevalence, and management. Curr Heart Fail Rep 2009;6:272-80. 5 Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388-442. 6 Smellie WS, Forth J, Coleman JJ, et al. Best practice in primary care pathology: review 6. J Clin Pathol 2007;60:225-34. 7 Arch Pediatr. 2007 Mar;14(3):249-53 8 Lexi-comp online; http://online.lexi.com/crlsql/servlet/crlonline

24. Logic for Clozapine↔WBC/ANC Target meds: Clozapine Multum classesMiscellaneous antiphsychotic agents (1 member of this class) Target labs: WBC, ABS NEUT Logic:Presence of an active order for the target medication with either of the most recent target labs below the threshold at the time of report. Age: Either Gender: Either Lab cutoff at University of Illinois Hospital (UIH): ABS NEUT <2000 mm3 or WBC <3500 mm3 Time Chosen @ UIH: 2:00 PM Optimal time to run the daily report: 10:00 AM

25. Logic for Clozapine↔WBC/ANC Data to retrieve: Name, MR#, Pair, weight, loc/svc, Med, Dose/Freq, Date/time (WBC), WBC, Date/time (ANC), ANC Rationale: The time chosen at UIH was based on pharmacists workflow, not the optimal time based on retrospective data. At UIH, this pair is expected to produce roughly 0 alerts per day Clozapine is rarely used at UIH. Only 43 patients were prescribed clozapine from January 2007 to December 2009. Among those patients, WBC was never below 3500 mm. Given the rare incidence of clozapine-WBC/ANC alert, FDA monitoring range for WBC and ANC is used as the cutoff for the lab tests. We recommend running the report at 10:00AM when most of the morning labs are posted. Reference: CLOZARIL® (clozapine) Package Insert https://www.clozapineregistry.com/insert.pdf.ashx

26. Logic for Med↔Pregnancy Target meds: Ergotamine, ergotamine/caffeine, dihyroergotamine, warfarin Multum classes:Antimigraine agents (some members of this class) Anticoagulants/coumarins and indandiones (only member of this class) Target labs: -Urine Pregnancy test -Point of Care Testing (POCT) pregnancy test -HCG-Serum Target order at UIH: "patient is pregnant" Logic: Presence of an active order for a target medication with any of the following; -Active order for "patient is pregnant“ -Urine Pregnancy test (+) within 9-months -Point of Care Testing (POCT) pregnancy test (+) within 9-months -HCG-Serum > 25 Age: Any Gender: Either (some errors are made in gender assignment in EMR's) Time Chosen @ UIH: 2:00 PM Best time per analysis: No preference

27. Logic for Med↔Pregnancy Time Chosen @ UIH:2:00 PM Best time per analysis:No preference Data to retrieve: Name, MR#, Pair, loc/svc, Med, Date/time pregnancy order or lab, pregnancy order or lab. Rationale: At UIH, this pair is expected to produce roughly 0 alerts per day The pregnancy test was infrequently ordered at UIH to verify pregnancy status. Therefore, active pregnancy orders, rather than pregnancy lab tests, will perform better as the indicator for pregnancy. A non lab pregnancy trigger is not likely available at most hospitals, but should be used if available. A trigger based on nursing documentation would work well An hCG level above 25mIU/ml is used to be considered positive for pregnancy based on general pregnancy diagnosis guidelines.

28. Logic for K+-Sparing Diuretic↔K+ Target meds: amiloride, eplerenone, spironolactone, triamterene, amiloride/hydrochlorothiazide, spironolactone/hydrochlorothiazide, triamterene/hydrochlorothiazide Multum classes: Potassium sparing diuretics (all members of this class) Target labs: venous [K+], arterial [K+] Logic: Active order for a target med with the most recent target lab above the threshold at the time of report Age: Any Gender: Either Lab cutoff at University of Illinois Hospital (UIH): ≥90 days of age then >5.0 mEq/L, <90 days of age then >6.0 mEq/L Time chosen at UIH: 2:00 PM Exclusion criteria: @UIH: Hemodialysis order, peritoneal dialysis order Potential Additional logic: -If cirrhosis patients can be identified, a [K+] cutoff of >5.4 meq/L would be more appropriate.

29. Logic for K+-Sparing Diuretic↔K+ Optimal time to run the daily report: 10:00 AM Data to retrieve: Name, MR#, Pair, Weight, CrCl, loc/svc, Med, Dose/Freq, Date/Time, Value Rationale & Information: -At UIH, this pair is expected to produce roughly 1-2 alerts per day. -Optimal time to run the daily report was determined based on the total time in danger for all patients with serum [K+] of greater than 5.0 mEq/L. -Potassium sparing diuretics are mainly used for 3 indications for adults—heart failure, cirrhosis, and hypokalemia. ---At UIH the proportion of patients with CHF, cirrhosis and hypokalemia on spironolactone was 35%, 50% and 15%. -As UIH is a busy liver transplant center, the cirrhosis proportion might be higher than at some other hospitals. Because the diagnosis cannot be clearly defined, a single [K+] cutoff was used. For hypokalemia, the indication is cleared with high serum potassium concentrations, thus a relatively low [K+] cutoff would be reasonable . For patients with cirrhosis and ascites, the threshold of discontinuing spironolactone in terms of hyperkalemia is not well studied in cirrhosis. For heart failure, potassium sparing diuretics should not be administered to patients with baseline serum potassium > 5.0 mEq/L.1,2 -The development of potassium levels in excess of 5.5 mEq/L should generally trigger discontinuation or dose reduction of the aldosterone antagonist unless patients have been receiving potassium supplementation, which should then be stopped.1,3,4 Therefore as a [K+] cutoff of 5.0 was selected as this is appropriate in patients with an indication of hypokalemia, a good level to consider discontinuation in CHF. This is likely low in cirrhosis patients and if these patients can be identified by the report.

30. Logic for K+-Sparing Diuretic↔K+ Potential Additional logic: (Continued) -Drug information on package inserts: If serum potassium is greater than 5 mEq/L or serum creatinine >4 mg/dl, interrupt or discontinue spironolactone therapy.5 Eplerenone is contraindicated with serum potassium >5.5 mEq/L at initiation for all patients. Patients who develop hyperkalemia (>5.5 mEq/L) may continue eplerenone therapy with proper dose adjustment. Dose reduction decreases potassium levels.6 Amiloride should not be used in the presence of elevated serum potassium level (>5.5 mEq/L).7 -The use of potassium sparing diuretics in neonates for bronchopulmonary dysplasia is controversial8,9, but does occur. In addition, the "normal" range for serum potassium is higher in neonates than adults10,11, therefore a different cutoff is used for patients under 90 days of age. References: 1 Hunt SA. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1-82. 2 Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388-442. 3 Poggio R, Grancelli HO, Miriuka SG. Understanding the risk of hyperkalaemia in heart failure: role of aldosterone antagonism. Postgrad Med J 2010;86:136-42. 3 Brophy DF, Gehr TWB. Pharmacotherapy: a pathophysiologic approach. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Disorders of potassium and magnesium homeostasis. 7 ed: McGraw-Hill Companies, Inc; 2008. 4 Aldactone (spironolactone) [package insert]. New York, NY: G.D. Searle LLC; 2008. 5 http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/012151s062lbl.pdf 6 Inspar (eplerenone) [package insert]. New York, NY: G.D. Searle LLC; 2008. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021437s006lbl.pdf 7 Midamor (amiloride) [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2002. 8 Ann Pharmacother. 2005 May;39(5):823-8. Epub 2005 Apr 5. 9 Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease (Review). 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 10 Arch Pediatr. 2007 Mar;14(3):249-53 11 Lexi-comp online, http://online.lexi.com/crlsql/servlet/crlonline

31. Logic for K+supplement↔K+ Target meds: KCl, K-Phos, K-Phos/Na-Phos, Citric Acid/K-Citrate, K-HCO3, K-HCO3/KCl, KCl/NaCl, K-Gluconate, K-Acetate, Citric Acid/K-Citrate/Na-Citrate Multum classes: Minerals and Electrolytes (some members of this class) Target labs: venous [K+], arterial [K+] Logic: -Active order for a target med with the most recent target lab above the threshold at the time of report. Age: AnyGender: Either Lab cutoff at University of Illinois Hospital (UIH): ≥90 days of age then >5.0 mEq/L <90 days of age then >5.8 mEq/L Time Chosen @ UIH: 2:00 PM Optimal time to run the daily report: -Potassium containing hydration: 10:00 AM -Potassium containing hyperalimentation: 8:00 AM -Potassium Supplementation: 9:00 PM

32. Logic for K+ supplement↔K+ Data to retrieve: Name, MR#, Pair, weight, loc/svc, Med, Dose/Freq, Date/time, Value Rationale & Information -The time chosen at UIH was based on pharmacists workflow, not the optimal time based on retrospective data. -At UIH, this pair is expected to produce roughly 3 alerts per day -Serum [K+] of greater than 5.0 mEq/L is considered as having hyperkalemia in patients older than 90 days.1 -Optimal time to run the daily report was determined based on the total time in danger for all patients with serum [K+] of greater than 5.0 mEq/L. -The "normal" range for serum potassium is higher in neonates than adults2,3, therefore a different cutoff is used for patients under 90 days of age. References: 1 Strom JA, Harrington JT, Narayan G. Diagnosis of Disorders of Potassium Balance. In: Gennari FJ, ed. Medical Management of Kidney and Electrolyte Disorders. Basel, NY: Marcel Dekker, Inc.; 2001:217-236. 2 Arch Pediatr. 2007 Mar;14(3):249-533 Lexi-comp online; http://online.lexi.com/crlsql/servlet/crlonline

33. The Report Abe Lincoln MR#0123456789 Richard Daley MR#0123456789 Ronald Reagan MR#0123456789 Baby Lude Beethoven MR#123456789 Mary Lincoln MR#123456789 Abe Lincoln MR#123456789

34. Frequency of alerts First 100 days of Phase #1 UIH, ~450 bed hospital

35. A likely useful alert for a rare event WBC & ANC vs. Time in a patient on clozapine

36. A likely useful alert for a non-rare event Creatinine and K+ vs. Time K+ Creatinine

37. Performance of AlertsFirst 100 days of First Phase

38. Med ↔Pregnancy testing performance Are pregnancy tests a good measure of pregnancy? UIH 12/08-12/09, Females 12-52 @admission Testing=POCT or lab, urine preg or HCG during or within 270 days prior to admission Gold Standard is nursing documentation

39. The value of discrete knowledge for lowering false positives [K+]↔ACE/ARB 1/2009 Raw # of instances Knowledge of Dx of ESRD on Dialysis Chart Review for CHF & CRI [K+]

40. How does a computer know that a patient is getting dialysis?

41. Post-Alert Issues at satellite pharmacies by patient location Yes, but only through running the report again in 240 NO Mode of communication -Printing -Placement on-line for on-demand use -Sending to mobile devices Documentation in the patient record -Mandatory? -Not mandatory? -Only when changes made? F/U for compliance? Determining repeat offenders?

42. Pearls and Tips -For the ACE/ARB/K+-sparing diuretic alerts based on serum K+, discrete knowledge of renal and cardiac status can improve the positive predictive value of the alerts. If this is impossible, train those managing the report to look for these issues first before contacting the patients clinical team -Linking medication use to pregnancy testing is not likely to be an accurate intervention, but alerts are rare and errors can have severe consequences so it may still be worthwhile. Look first if patients are pregnant, not if they are women. -Use your own data when possible to set thresholds, but it is easier and likely OK to use other’s or the FDA’s, especially for alerts which will rarely fire. -It would always be best if your EMR knew who was pregnant and who was on dialysis.

43. Pearls and Tips -Both the number of alerts and potential usefulness of the alerts depends on the time of day of the report. Running the report more frequently than once a day may improve performance if it can be managed in terms of workflow and staff needed for multiple runs. -Thresholds can be changed rapidly, so early analysis of alert frequency and usefulness can decrease annoyance or increase value by fine tuning. -Mode of communication and documentation needs to be tailored to each institutions planned workflow, but even if documentation in the patient record is not required, recording the response to the alerts is needed to help determine build errors or needed changes of clinical logic.

44. Conclusions -Automating the use of clinical connections between discrete lab results and medication orders can be a useful way to reduce medication errors. -A daily asynchronous lab↔med report can add a layer of safety, even with CPOE systems including real-time synchronous & asynchronous alerts and clinical pharmacists. -This intervention does not require CPOE nor any advanced communication tools making it an option for almost any inpatient setting which has lab and pharmacy information systems.

45. Resources Clinical logic for the first set of alerts can be found at; http://www.uic.edu/com/dom/gim/TOPMED/Logic-Phase1.pdf A list of all the pairs can be found at; http://www.uic.edu/com/dom/gim/TOPMED/Pairs.pdf An excellent source of references and an explanation of the Delphi process can be found in the reference below when available; Yu et al. Consensus list of priority drug-lab linkages for an inpatient asynchronous alert program: Results of a Delphi survey. AJHP. 2010 In press.

46. Questions? BillG@uic.edu