1. Adverse Drug Events (ADEs)
Holli Temple, PharmD
Chief Pharmacy Advisor for the Partnership for Patients Initiative through CMS
Clinical Assistant Professor
University of Texas at Austin College of Pharmacy

2. Definition of an ADE World Health Organization (WHO) definition
An ADE is “noxious and unintended and occurs at doses used in man for prophylaxis, diagnosis, therapy, or modification of physiologic functions.”
WHO definition includes ADEs from medication errors
Med errors occur at any stage from ordering to administering
Some ADEs are harmless, cause injury, or are “near misses”
Any effort to identify harm needs a clear definition of an adverse event
Near misses – do not cause injury to patient either by chance or because they are intercepted before the medication is administered.

3. Definition of an ADE IHI Global Trigger Tool definition
Harm is defined as “unintended physical injury resulting from or contributed to by medical care that requires additional monitoring, treatment or hospitalization, or that results in death.”
IHI focuses on errors of commission (active delivery of care) and excludes errors of omission
Includes all adverse events – whether preventable or not
IHI tool measures harm over time
-- Errors of omission represent an opportunity for quality improvement, but not the focus of IHI Trigger Tools.
e.g. patient whose hypertension was untreated and had a stroke is a “medical catastrophe” – error of omission, but would not be considered to have suffered and AE using the IHI Trigger Tool. However, if a patient suffered a hemorrhagic stroke as a complication of anti-coagulant therapy – error of commission
-- During reviews, will find errors of omission. Refer these errors to appropriate personnel for improvement opportunities.
-- reviewers should not attempt to determine preventability during a review. By IHI definition, if ADE occurred, a patient was harmed. “Unpreventable events” only an innovation away from being preventable.

4. Measuring Harm from Medications
ADEs – single greatest risk of harm to patients in hospitals
Voluntary reporting and tracking of med errors
Low yield – only 10-20% of errors are reported
Of those reported, 90-95% did not cause harm
Conventional method of sifting through the medical record to uncover errors costly and largely ineffective
Public health researchers established = 10-20%
Historical way of ADE collection (at NAMC): ADE postcard, eMAR (using triggers), abstracted report based on discharge summary coding clues)
Hospitals need a more effective way to identify events that do not cause harm to patients in order to select and test changes to reduce harm

5. Measuring Harm from Medications
National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Error Categorization
Categories below do NOT cause harm
Category A: capacity to cause error
Category B: error did not reach the patient
Category C: error reached the patient, no harm
Category D: error reached patient and required monitoring or intervention to confirm that it resulted in no harm to the patient
IHI tool adapts the NCCMERP error categorization: Examples of categorical errors:
A: in Rx bins, furosemide 20 mg tabs found in famotidine 20 mg bin upon routine expiration date checks
B: nurse found metformin 500 mg in patient’s med bin instead of metronidazole 500 mg tabs
C: Vicodin 5/500 given to patient instead of Norco 5/325
D. Patient received 40 meq of potassium chloride instead of 40 mg of lasix (furosemide)

6. Measuring Harm from Medications
Categories below DO cause harm:
Category E: temporary harm to patient; intervention required
Category F: temporary harm to patient and required initial or prolonged hospitalization
Category G: permanent patient harm
Category H: intervention require to sustain life
Category I: patient death
E: benadryl to treat PCN allergy
F: vancomycin induced renal toxicity, iodinated contrast causing ARF
G: reglan induced EPS (diabetic gastroparesis)
H: excess narcotic administered, rapid response team notified; pt coded => intubated and transferred to ICU; U500 insulin instead of U100??
I: death: high-dose methotrexate without leucovorin rescue (2 patients on MT only enough leucovorin for one); potassium floorstock given instead of lasix

7. ADE Triggers
Before starting chart review, team to agree on list of medication related triggers to review at your hospital.
Example triggers:
M1: C. Diff positive stool
M2: PTT greater than 100 seconds
M3: INR greater than 6
M4: Glucose less than 50 mg/dl
M1: positive C.Diff assay is an ADE if patient has recently been on abx
M2: look for evidence of bleeding, a drop in hgb/hct, bruising to determine if an ADE has occurred. Increased PTT by itself is not an ADE. High PTTs are not rare as heparin rates are being titrated to the patient. High PTTs may be common during cath lab procedures.
M3: look for evidence of bleeding; an increased INR in itself is not an ADE
M4: review nursing notes looking for symptoms such as lethargy and shakiness and also review MAR for administration of glucose, OJ, or other intervention. If patient is not symptomatic, there is no adverse event.
M5: review labs for rising BUN or Scr. If a change of two times greater than baseline is found (e.g. 1.1 => 2.2, review MAR for meds known to cause renal toxicity (e.g. IV dye, NSAIDs, loop diuretics, ACE inhibitors, ARBs, aminoglycoside abx, vancomycin). Review physician progress notes and H&P for other causes of renal failure, e.g. pre-existing renal disease or diabetes than may have put patient at greater risk for renal failure. This is not an ADE, but disease progression.

8. ADE Triggers M5: Rising BUN or serum creatinine 2x over baseline
M6: vitamin K administration (Aqua-mephyton®, Mephyton®, phytonadione)
M7: diphenhydramine (Benadryl®) administration
M8: flumazenil (Romazicon®) administration
M9: naloxone (Narcan®) administration
M10: anti-emetic administration ondansetron (Zofran®), promethazine (Phenergan®)
M5: review labs for rising BUN or Scr. If a change of two times greater than baseline is found (e.g. 1.1 => 2.2, review MAR for meds known to cause renal toxicity (e.g. IV dye, NSAIDs, loop diuretics, ACE inhibitors, ARBs, aminoglycoside abx, vancomycin). Review physician progress notes and H&P for other causes of renal failure, e.g. pre-existing renal disease or diabetes than may have put patient at greater risk for renal failure. This is not an ADE, but disease progression.
M6: if vitamin K given in response to an increased INR, look for evidence of bleeding. Check labs for a drop in hgb/hct or guiac positive stools. Check progress notes for documentation of excessive bruising, GI bleeding, hemorrhagic stroke, or large hematomas.
M7: Benadryl is frequently used to treat allergic reactions to medications but can also be used as a sleep aid, pre-op or pre-procedure medication, seasonal allergies, sleep. If Benadryl (or IV Benadryl) administered, review chart to determine if it was ordered for symptoms of an allergic reaction to a drug or blood transfusion administered either during the hospitalization or prior to admission (used to count only those ADEs that occurred in the hospital, but more info gathered about patient use of meds if reactions that started as an outpatient are also considered)
M8: Romazicon – reverses benzodiazepines. Determine why Romazicon used. Often used after post-procedure to reverse effects of Versed (midazolam). If Romazicon given after benzodiazepine administration (e.g. Xanax -- alprazolam, Ativan – lorazepam, Restoril – temazepam), an ADE may have occurred. With excess benzo admistration, severe hypotension or prolonged sedation may occur .
M9: narcan given to reverse effects of narcotics. Unless given specifically post-procedure, use of narcan on floor probably indicates an ADE
M10: : anti-emetics: N/V commonly the result of drug administration in surgical and non-surgical settings. Anti-emetics are commonly given. N/V that interferes with feeding/eating, post-op recovery, or delayed discharge suggests an ADE. One or two episodes of N/V treated successfully with anti-emetics suggest no ADE. Use clinical judgment to determine whether or not harm occurred.
M11: oversedation/hypotension: review MD progress notes, nursing notes or multi-disciplinary notes for evidence of over-sedation and lethargy. Review VS records or graphics for episodes of hypotension related to the administration of a sedative, analgesic, or muscle relaxant. Intentional OD is not considered and ADE.
M12: abrupt stop: although d/c of meds is a common finding during chart review, abruptly stopping meds is a trigger requiring further investigation for cause. A sudden change in patient condition requiring adjustment of med is often related to an ADE. “Abrupt” is best described as a unexpected stop of deviation from typical ordering practice, e.g. D/C IV abx to change to an oral form is not unexpected
M13: for ADEs detected but not related to one of the medication triggers above

9. ADE Triggers Trigger yield (from Rozich study):
M11: over-sedation/hypotension
M12: abrupt medication stop
M13: Other
Trigger yield (from Rozich study):
anti-emetic use most numerous -- ~ 7% of ADEs
abrupt medication stop accounted for ~ 35% of ADEs
most common: anticoagulants, sedatives, pain medications, antibiotics, insulin
M11: oversedation/hypotension: review MD progress notes, nursing notes or multi-disciplinary notes for evidence of over-sedation and lethargy. Review VS records or graphics for episodes of hypotension related to the administration of a sedative, analgesic, or muscle relaxant. Intentional OD is not considered and ADE.
M12: abrupt stop: although d/c of meds is a common finding during chart review, abruptly stopping meds is a trigger requiring further investigation for cause. A sudden change in patient condition requiring adjustment of med is often related to an ADE. “Abrupt” is best described as a unexpected stop of deviation from typical ordering practice, e.g. D/C IV abx to change to an oral form is not unexpected
M13: for ADEs detected but not related to one of the medication triggers above
Trigger Yield: From 1704 charts, 2187 triggers found and 413 were true ADEs. Anti-emetic trigger found 916 times with 64 ADEs determined = ~ 7% of total ADEs. Abrupt med stop found 248 times with 86 ADEs attributed (35% of ADEs).

10. Identifying and Measuring ADEs
Form multi-disciplinary team – at least 3 people
Decide on list of triggers for your facility
Review trigger tool; each chart review requires its own form whether or not an ADE is identified
Two primary record reviewers who have clinical backgrounds and knowledge about the contents and layout of the hospital’s record as well as about how care is provided in the hospital. IHI trigger tool has traditionally used nurses, pharmacists, and RTs on their team. Experienced nurses have been the best reviewers!
A physician who does not review the records but authenticates the consensus of the two primary record reviewers – findings of adverse events. ratings of severity, and provides answers to questions the reviewers may have

11. Identifying and Measuring ADEs
Random sample of 10 patient charts every 2 weeks
Obtain a few extra in case those selected do not match criteria for evaluation
Records need to be:
Closed and complete
Inpatients with LOS at least 24 hours
Patient age 18 years or older
Exclude inpatient psych and rehab patients
Sample 10 records from 1-15 of each month and 10 records from 16 – end of month => two time points generates two data points
Avoid outpatient records
Instead of reviewing ALL patient records to detect triggers and investigating them to determine if an ADE has occurred, use sampling
Random – each record has an equal change of being selected, e.g. every 10th patient ; small hospitals with fewer than 10 inpatients per 2 weeks, review all charts

12. Identifying and Measuring ADEs Where to look?
Discharge summary – may include adverse events
Medication Administration Record (MAR)
Laboratory results
Prescriber orders
Nursing notes
Physician progress notes

13. Identifying and Measuring ADEs
If time permits, review other areas of record (e.g. H&P, ED report)
Set a 20 minute limit for each chart reviewed (after training completed)
An ADE is defined as unintended harm to a patient (from the patient’s viewpoint)
Would you be happy if event happened to you? If not, likely an ADE
Trigger tool not meant to identify ALL adverse events in a single record

14. Identifying and Measuring ADEs
Systematically/selectively review portions of the chart where the triggers are most likely found
If trigger found, review portion of chart that will reveal whether or not an ADE occurred
If harmful event found, determine level of harm (E – I) and briefly describe ADE
Use professional judgment to make determination
Do not read through entire chart. INR values found in the lab section of the chart
Trigger present? 2) section of chart => trigger 3) if ADE, determine level of harm
Professional judgment: anti-emetic given an hour after a narcotic. If patient continued to receive the narcotic without the anti-emetic, no ADE. If each time the narcotic given, anti-emetic given = ADE.
Reviewers will find many positive triggers, but will identify a few ADEs. Physician input will be critical.

15. Identifying and Measuring ADEs
Complete ADE Patient Record Review Sheet for the sampled charts
Summarize findings in the ADE Monthly Summary Sheet
For each chart reviewed, document
Whether or not an ADE occurred
Number of ADEs
Total number of medication doses received (optional)

16. Outcome Measures/Calculations
Percent of Admissions with an ADE
Total N# with ADE from sample/total N# of records in sample
If a patient experienced more than one ADE, only count that patient once in the numerator.  
ADEs per 1000 doses
 Total N# of ADE from sample/total N# of medication doses administered to the patients in the sample

17. Outcome ADE Measures
We will track your measures (Percent of Admissions with an ADE and ADEs per 1000 doses) over time in a run chart
Are changes to processes making medication use safer in the hospital? Graph results to see if improving

18. Tools available on IHI.org
Trigger Tool for Measuring ADEs –
Improvement Tracker available for use --

19. Tools available on IHI.org
Other trigger tools available
ICU Adverse Event Trigger Tool
Pediatric Trigger Toolkit: Measuring ADEs in the Children’s Hospital
Trigger Tools for Measuring ADEs in the Nursing Home

20. Questions?