LEIGH BRISCOE-DWYER, PHARM.D., BCPS, FASHPCHIEF PHARMACY AND

MEDICATION SAFETY OFFICERNORTH SHORE – LIJ HEALTH SYSTEM

SEPTEMBER 19, 2015

IMPROVING MEDICATION SAFETY IN THE ICU

CONFLICT OF INTEREST DISCLOSURE

I have no conflicts to report

OBJECTIVES1. Discuss national regulations and local (but universally adopted) practices related to medication safety and adverse drug reaction reporting and high reliability organizations.

2.Examine the use of clinical decision support systems (CDSS) in drug-drug interaction (DDIs) identification and prevention.

3.Describe off-label medication use in the ICU setting, implications for patient safety, and strategies to minimize patient harm when medications are being used off-label.

4.Describe the use of trigger tools and the optimization of technology to improve medication use processes.

MEDICATION SAFETY ORGANIZATIONS

• Agency for Health Care Research and Quality

• American Association of Critical-Care Nurses (AACN)

• American College of Physicians (ACP)• American Hospital Association• American Nurses Association (ANA)• American Organization of Nurse

Executives (AONE)• Anesthesia Patient Safety Foundation

(APSF)• Association of periOperative Registered

Nurses (AORN)• American Society for Healthcare Risk

Management• American Society of Health-System

Pharmacists• Annenberg Center• Centers for Disease Control and

Prevention (CDC)

• ECRI• Institute for Healthcare Improvement (IHI)• Institute of Medicine• Institute for Safe Medication Practices

(ISMP)• The Joint Commission• KLAS• Leapfrog• National Coordinating Council for

Medication Error Reporting and Prevention• National Patient Safety Foundation• National Quality Forum (NQF)• Society of Critical Care Medicine (SCCM)• US Food & Drug Administration• VA - National Center for Patient Safety

WHY DO WE STILL HAVE PROBLEMS WITH MEDICATION SAFETY?

• 10,000 prescription medications exist• Nearly 1/3 of adults in the US take 5 or

more medications• ADEs account for 700,00 ED visits and

100,000 hospitalizations annually• 5% of hospitalized patients affected

AHRQ PSNet Patient Safety Primer http://psnet.ahrq.gov

QUESTION

1. Which of the following best describes the relative incidence of adverse drug events (ADE), adverse drug reactions (ADR), and medication errors (ME)?

a. ME > ADR > ADEb. ME > ADE > ADRc. ADE > ADR > MEd. ADR > ME > ADE

QUESTION

1. Which of the following best describes the relative incidence of adverse drug events (ADE), adverse drug reactions (ADR), and medication errors (ME)?

a. ME > ADR > ADEb. ME > ADE > ADRc. ADE > ADR > MEd. ADR > ME > ADE

DETECTION AND CLASSIFICATION OF ADVERSE DRUG EVENTS

Morimoto T et al. Qual Saf Health Care. 2004; 13:306-14

NOMENCLATURE

• Adverse Drug Reaction (ADR) - A response to a medicinal product that is noxious and unintended and that occurs at doses normally used in humans for the prophylaxis, diagnosis, or treatment of disease

• Adverse Event (AE) - An injury, large or small, caused by the use (including non-use) of a drug, test, or medical treatment. This may be as harmless as a drug rash or as serious as death. (modified from IHI definition of an adverse drug event or ADE.)

MEDICATION ERROR CATEGORIZATION

What do you call an organization/industry that is complex

and risky…But very safe?

Highly Reliable Organization

WHAT IS A HIGHLY RELIABLE MEDICATION USE PROCESS?

• The measurable capability of a process to perform its intended function in the required time under commonly occurring conditions

• Ask 5 people how they perform a task or a process, if they all are the same – your process is reliableAction Item:

Choose a timely topic on mediation use Survey people involved in the process Evaluate for reliability

DIFFERENT VIEWS OF RELIABILITY:1 MILLION DOSES DISPENSED/MONTH

Reliability Unreliability “Sigma’s” (approximate)

0.9 10-1 1

0.99 10-2 2

0.999 10-3 3

0.9999 10-4 4

0.99999 10-5 5

0.999999 10-6 6

ERRORS:12,000/year 1000/month 33/day

DESIGN FOR RELIABILITY

Level 1. Intent, vigilance and hard workSTANDARDIZATION

Level 2. Design informed by reliability science and research in human factors

Level 3. Design of high reliability organizations

(Weick)

“TRIGGER” TOOLS

• Institute for Healthcare Improvement• Small percentage of adverse events (AE)

voluntarily reported• Use of "triggers," or clues, to identify AE in

an organization captures larger percentage• Reporting increased by 10 times when a

Global Trigger Tool was utilized

Classen DC et al. Journal of Patient Safety. 2008 Sep; 4(3):169-177.Adler L et al. Journal of Patient Safety. 2008 Dec; 4(4):245-9.

Classen DE et al. Health Aff. 2011 April; 30(4):581-9.

USE OF GLOBAL TRIGGER TOOLS

Type of Adverse EventE F G H I Total

Medication -related 100 46 2 2 0 150Procedure-related 67 26 5 7 4 109Nosocomial Infection 30 37 2 2 1 72Pulmonary/VTE 8 5 2 0 1 16Pressure Ulcers 10 1 0 0 0 11Device Failures 0 6 0 0 0 6Patient Falls 2 1 0 0 0 3Other 10 11 0 3 2 26Total 227 133 11 14 8 393

Severity LevelAdverse Events Detected by All Methods, By Severity Level

Classen DE et al. Health Aff. 2011 April; 30(4):581-9.

50% DEXTROSE AS A TRIGGER TOOL

Site Doses Dispensed

CCMC 9FHH 699FRK 740LIJ 2433NSUH 1849PLV 205SSH 462SYO 40ZHH 1Total 6438

Drug Drug Interactions and Clinical Decision Support

THE PROMISE AND PROBLEM WITH ALERTS

• To err is human. The EMR can be a wise detail-oriented consultant for certain go/no-go decisions -- “Dear Dr., this patient had an anaphylactic reaction to Bactrim. Please consider prescribing an alternative antibiotic.”

• If the EMR commonly alerts in an unwise manner, providers may fail to attend to future alerts.

HOW DO WE TREAT ALERTS?

• Drug-drug interaction alerts• One month study of 39,893 alerts with 45,983

orders (0.87 alerts per med order).• 1,176/45,983 (2.6%) of med orders had a

pharmacist intervention.• 113/45,983 (0.2%) of med orders had a pharmacist

intervention involving the alert.• Only 113/39,893 (0.03%) of drug-drug interaction

alerts on med orders resulted in a pharmacist intervention.

Conclusion: The interventions made by pharmacists were not a result of the alerts that fired.

DUPLICATE ALERTS – WHAT TRIGGERS AN ALERT?

ACE InhibitorsAcetaminophen containing productsAlpha-1 blockersAminoglycosidesAnticoagulants/AntiplateletsBenzodiazepinesBeta-blockersCalcium channel blockersCarbapenemsCephalosporinsCombination analgesics

CorticosteroidsH2 blockersNSAIDsOral anti-diabetic agentsParenteral anticoagulantsParenteral opiatesPenicillinsPhenytoinsPotassium containing productsPPIsQuinolonesSSRIsStatins

Exact match or two drugs in the same class from the following list:

DUPLICATE ALERTS

• 40% of these alerts are for drug class• 98% of the time, the provider finalized the order.• 75% of the time, the provider did not explicate the

reason for overriding the alert. When they acknowledged with text• “provider aware and approved”• “to be addressed by primary provider”• “OK”

• 96% of the duplicate orders that were finalized by providers were verified by pharmacy, 69% of which were verified within 10 minutes of the order being authored, suggesting that no conversation with the provider took place.

THE JOINT COMMISSION LEADERSHIP IN HEALTHCARE INSTITUTIONS (2009)

• Develop a graduated system of safety alerts in

the new technology that helps clinicians determine urgency and relevancy.

• Consider skipped or rejected alerts as important insight into clinical practice.

• Decide which alerts need to be hard stops when using the technology and provide appropriate supporting documentation.

RECOMMENDATIONS

• Establish a governance group responsible for managing changes in alerts.

• Change the mindset regarding alerts from a “10 commandments” view to something we are responsible for managing.

• Recognize that the primary purpose of the governance group is to improve patient safety by driving down low-value alerts.

• Get rid of “duplicate therapy” alerts for PRNs that are not true duplicates.

OFF LABEL DRUG USE IN THE ICU

• FDA is responsible for review and approval of medications for specific indications for which there is safety and efficacy data

• Once a medication is approved, there is usually no limit imposed on FDA for its use

• Off label use is often the standard of care• Oncology, pediatrics, critically ill patients

OFF LABEL USE IN SURGICAL ICU

• 465 orders for 80 medications were reviewed• 26.5% of orders were described as “off-label”

• Indications• Infections, stress ulcer prophylaxis, seizure

prophylaxis and treatment• Reasons for use

• Unapproved indications (66%)• Dosing schedule (27%)• Method of administration (17%)

Albaladejo P, Caillet B, Moine P et al. [In French] Presse Med 2001;30:1484-1488

OFF LABEL MEDICATION USE IN ADULT CRITICAL CARE PATIENTS

• Prospective observational study of 37 ICUs from 24 sites over a 24 hour period

• 414 patients enrolled• 5237 medication orders

• 1897 orders were off-label (36.2%)

Lat I, Micek S, Janzen J et al. Journal of Critical Care 2011; 26:89-94

OFF LABEL MEDICATION USE IN ADULT CRITICAL CARE PATIENTS

• Most frequent drug classes• Bronchorespiratory• Gastrointestinal• Immunology

• 89% of off label orders were written after patients were admitted to ICU

• 928 (48.3%) of off label use had grade C or no evidence to support such use

GOING OFF LABEL WITHOUT GOING OFF COURSE

• Which characteristics of off label use require greater scrutiny?

• Can we differentiate off label use based on available evidence?

Largent E, Miller F, Pearson S. Arch Int Med 2009. 169 (19) 1745-1747.

SIGNALS FOR SCRUTINY

• New drugs• Rule of Thumb: 3 – 5 years of

observational study before making a judgment of risk

• Novel off label use• Combination therapies

• Drugs with known serious adverse effects• High-Cost drugs

LEVELS OF EVIDENCE TO GUIDE OFF-LABEL PRESCRIBING

• Supported• Suppositional• Investigational

SUPPORTED OFF LABEL USE

• Moderate to high level of certainty in net health benefit

• Prescribe in same manner as when indication exists

• Discuss with patient/family benefits and risks of proposed treatment

SUPPOSITIONAL OFF LABEL USE

• Low level of certainty in net health benefit• Is it better than no treatment?• Consultation and Second Opinion

recommended• Risks and benefits should be clearly

communicated to patients and documented in patients chart

• Collect data on outcomes

INVESTIGATIONAL OFF LABEL USE

• Very low level of certainty in net health benefit

• Should be limited to context of research protocols

• Informed Consent

Evidence and Extrapolation: Mechanisms for Regulating off-Label Uses of

Drugs and Devices

EVIDENCE AND EXTRAPOLATION

• Diagnosis Extrapolation• Using an existing drug to treat a new condition

• Using quetiapine to treat anxiety rather than schizophrenia

• Patient Extrapolation • Using an existing drug to treat a new population

with a given condition• Treating children rather than adults

Abbot R and Ayres I. Duke Law Journal 2014. 64;3: 377- 435

EVIDENCE AND EXTRAPOLATION

• Dosage Extrapolation• Using an existing drug for a new duration or

schedule • Using a drug indefinitely for schizophrenia when

studies have looked at 6 weeks

• Treatment Extrapolation• Using an new drug that is related to an

approved counterpart • Using extended release quetiapine based on evidence

that immediate release is safe and effective

Abbot R and Ayres I. Duke Law Journal 2014. 64;3: 377- 435

EVIDENCE AND EXTRAPOLATION: RECOMMENDATIONS

• Improve level of reporting of off label use• Expand post-market testing in the area of

off-label use • Create a tiered labeling system to allow for

distinctions for payers and litigation• “Red Box Warning” to prohibit off label use• “Gray Box Warning” to block reimbursement

OPTIMIZATION OF TECHNOLOGY TO IMPROVE MEDICATION USE PROCESSES

• NSHS has a single enterprise drug library for IV Infusion pumps• AKA “Smart Pumps”

• Technology must be reviewed and maintained continually to get the maximum benefit

PROPOFOL

• ICU sedation in intubated mechanically-ventilated patients• Continuous infusion:

• Initial: 5 mcG/kG/minute • Increase by 5 to 10 mcG/kG/minute every 5 to 10

minutes until desired sedation level is achieved• Usual maintenance: 5 to 50 mcG/kG/minute 

• NS-LIJ Critical Care Library Guardrails® • Soft maximum of 75 mcG/kG/min

PROPOFOL: MEDICATION USE EVALUATION

(MUE)

• LIJMC Medical Intensive Care Unit (MICU)• 23 patients from April through June 2015• Procedure

• Ran a report using SCM® of all patients currently with an active order for propofol infusion

• Obtained the Serial Numbers on the pump• Ran a report using Guardrails® data to look at alerts that

had fired

• Goals• Evaluate whether data documented in SCM® matched the

data we obtained from the pumps • In the case that an alert fired - assess any adverse

events

• Data we evaluated • Accuracy of the patient weight entered in the

pump• Rate of infusion programmed when outside soft

maximum of 75 mcG/kG/min • Pump is being used appropriately for

continuous infusions and not for bolus dosing • Appropriate documentation is found in SCM®

(e.g. order placed, flowsheets, eMAR)• Potential Adverse Effects

• HR, BP, concomitant use of vasopressors

PROPOFOL: MUE

• 4 instances identified when the rate entered exceeded soft maximum of 75 mcG/kG/min

• Alerts were overridden

RESULTS: INFUSION RATE ALERTS OVERRIDDEN

Alaris® Pump Data SCM® Data

ProgrammedDose

patient received

Order in SCM® Documentation in eMAR or flowsheet

Adverse Effects

Identified

999 mL/hr (3330 mcG/kG/min) x 5 mL

50 mG 20 mG IVP x 2 = 40 mG eMAR: 20 mg IVP x 2 = 40 mG None

999 mL/hr (3165 mcG/kG/min)x 5 mL

50 mGNo order for IV bolus or

increase in rate of infusion None None

999 mL/hr (3165 mcG/kG/min) x 2 mL 20 mG

No order for IV bolus or increase in rate of infusion

None None

a. 999 mL/hr (1276 mcG/kG/min)x 76 mL

b. Reprogrammed to 30 mL/hr

767 mG

87 mG excess

No order for IV bolus or increase in rate of infusion None None

• 2 instances identified where the use of Guardrails® prevented potential errors and adverse events

• Alerts fired resulted in reprogramming to ≤ 75 mcG/kG/min

INFUSION RATE ALERTS REPROGRAMMED

Reprogramming Due to Guardrails®

Rate initially entered Rate entered after alert fired 38 mL/hr (100 mcG/kG/min) 20 mL/hr (50 mcG/kG/min)

37 mL/hr (85 mcG/kG/min) 17 mL/hr (40 mcG/kG/min)

• Importance of utilizing weight documented in SCM®

Issues Identified: Entering Patient Weights Patient #1 Patient #2 Patient #3 Patient #4 Patient #5

Weight entered 66.4 kG 50 kG 106 kG 70 kG 70 kG

Alert from Pump

64.4 kG 51.3 kG 106.3 kG 63.8 kG 61.8 kG

Actual weight documented in

SCM®

64.4 kG 51.3 kG 106.3 101.3 kG 68.1 kG

Action taken 64.4 kG 51.3 kG 106.3 63.8 kG 61.8 kG

WEIGHT CHANGE ALERTS

• Presented at System P and T• Bolus dosing vs. continuous infusion

• Area for medication errors = NEVER EVENT• Appropriate documentation in SCM® (order

placed, rates in flowsheets)• Importance of entering the correct weight that

is documented in SCM®

MUE RESULTS

Questions ?