Adverse Drug Events (ADEs)

Adverse drug event (ADE)	"injury resulting from medical intervention related to a drug" (Kohn, Corrigan, Donaldson 2000).
Adverse drug reaction (ADR)	"harms directly caused by a drug at normal doses"
Medication error	The "inappropriate use of a drug that may or may not result in harm;" such errors may occur during prescribing, transcribing, dispensing, administration, adherence, or monitoring of a drug (Nebeker, Barach, Samore 2004)

Incidence and prevalence

ADEs Present on Admission

"ADEs account for nearly 700,000 emergency department visits and 100,000 hospitalizations each year.(PSNET 2015).

Inpatient ADE's

ADEs affect nearly 5% of hospitalized patients, making them one of the most common types of inpatient errors; ambulatory patients may experience ADEs at even higher rates."(PSNET 2015). The U.S. Dept. of Health & Human Services, Agency for Healthcare Research and Quality published yearly accounts of reported hospital acquired ADEs associated with five drug treatments for the years 2010 through 2014 as follows:

ADE Source Medication	20101	20112	20123	20134	20145
Digoxin	11,650	9,400	11,000	8,800	10,000
Hypoglycemic Agents	930,863	920,000	760,000	760,000	780,000
IV Heparin	170,973	150,000	140,000	170,00	200,000
Low Molecular Weight Heparin and Factor Xa Inhibitor	335,826	330,000	310,000	240,000	250,000
Warfarin	171,609	180,000	150,000	140,000	120,000
Total ADE (sum)	1,620,921	1,594,000	1,372,000	1,320,000	1,360,000

The current National Action Plan for Adverse Drug Event Prevention is focused on measuring and monitoring the burden of ADEs, identifying key determinants of ADEs, reviewing incentives and strategies to prevent ADEs. High priority prevention targets include anticoagulants, diabetes agents and opioids. Many departments and organizations within the U.S. Government are participating in the National Action Plan for Adverse Drug Event Prevention. The Military Health System's Partnership For Patients Campaign is working to reduce ADEs from high-risk medications by instituting the following Sustainment Guide for Adverse Drug Events January 24, 2014:

Sustainment Guide for Adverse Drug Events January 24, 2014
Improve Management of Heparin	Improve Management of Warfarin
Consistently use standardized weight-based heparin protocol throughout facility Limit to no more than two protocols Use preprinted order forms or ordering protocols Establish guidelines to hold heparin and provide reversal therapy for heparin over-anticoagulation Ensure protocol address how to evaluate and treat patients with heparin-induced thrombocytopenia (HIT) Ensure heparin dosing protocols account for the use of thrombolytics and GIIb/IIIa inhibitors Ensure heparin is not administered within 6-12 hours of a dose of LMWH Ensure appropriate monitoring parameters are implemented and used reliably Implement standardized concentrations of heparin Use pre-mixed infusions and ready-to-administer products when available Remove high-concentration products from floor stock Separate look-alike/sound-alike (LASA) products (names and packaging) when using or storing Implement effective independent double checks Use smart pumps (if available) with accurate drug libraries to infuse heparin Administer boluses from pharmacy prepared syringes or set up smart pump libraries Make heparin-flush available only in syringes Do not accept heparin orders with unapproved abbreviations (i.e. U for units, etc.) Use LMWH when appropriate, instead of heparin Use auxiliary labels for high-alert medications consistently throughout the facility	Consistently use standardized protocols and dosing Use preprinted order forms or ordering protocols that are prominently labeled by indication (i.e. A. Fib, DVT, etc.) Standardized protocols for the initiation and maintenance of warfarin therapy including, Vitamin K dosing guidelines Develop an evidence-based protocol, to discontinue and restart warfarin preoperatively Develop a evidence-based protocol, to bridge warfarin therapy with more rapidly-acting anticoagulants such as heparin or LMWH Use ONLY oral unit-dose products, when these products are available Ensure effective implementation of independent double checks Minimize available strengths of oral formulations to the essential few Ensure efficient access to laboratory results (i.e. available within 2 hrs) and/or use of point-of-care testing at the bedside Include a nutrition consult to avoid drug/food interactions and educate the patient about them Create daily CHCS report of patients on warfarin for nutrition education Use medication reconciliation to improve handoffs of medication information Engage patients by developing educational programs and training at an appropriate literacy level Implement system to properly verify inventory stocking in the Automated Dispensing Cabinets Utilize auxiliary labels for high-alert medications consistently within the organization
Improve Management of Narcotics	Improve Management of Insulin
Consistently use standardized protocols for initiation and maintenance of pain management Use protocols and pre-printed orders (CPOE order sets) where possible for PCA, postoperative, epidural, and intrathecal pain management Include dose calculations, maximum bolus doses, prescribed dose, monitoring guidelines, and options for non-opioid analgesics Establish standard naloxone regime which can be given prior to contacting physician, based on a protocol signed by a physician Standardize monitoring protocols including documentation of vital signs and pain score following each dose Use appropriate monitoring for adverse effects of narcotics and opiates Minimize multiple drug strengths Implement standard concentrations of narcotics/opiates Establish formulas for narcotic dose-equivalences Widely circulate formulas for narcotic dose-equivalences to all staff Prepare narcotic/opiate infusions in the pharmacy ONLY Use smart pumps with accurate drug libraries Label distal end of all access lines to distinguish IV from EPIDURAL Use tubing without injection ports for EPIDURAL Standardize to single drug as opiate of choice for PCA or use dose equivalencies for multiple drug choices Consult a pain specialist if physician are not knowledgeable about pain control Increase use of non-pharmacologic intervention for pain and anxiety Educate patient/family about PCA use before surgical procedure Dose narcotics to a pain score mutually agreed upon by patient & provider prior to procedure Use medication reconciliation to improve handoffs of medication information Educate patients regarding hypotension and dizziness upon rising Anticipate and schedule toileting for high-risk patients	Consistently use standardized pre-printed diabetic and insulin infusion orders When prescribing insulin, include or refer to defined standards for laboratory testing and clinical monitoring of patients Ensure appropriate monitoring through more rapid testing of blood glucose Use a diabetic management flow sheet to track blood glucose values, carbohydrate intake and insulin administration Eliminate or limit the use of sliding insulin dosage scales; if used standardize it through use of a protocol/preprinted order form or computer order set that clearly designates the specific increments of insulin coverage Standardize to a single concentration of IV-infusion insulin Prepare all infusions in the pharmacy Do not accept insulin orders with unapproved abbreviations (i.e. U for units, trailing zero, etc.) Implement different means to separate LASA insulins (i.e. individual bins) and to make them look different or call attention to important information (i.e. auxiliary/colored labels, highlighter, etc.) Utilize Tallman lettering to distinguish LASA insulins Do not dispense insulin in original container only; label the vial with patient’s name and expiration date. Use vial for single patient use ONLY Use smart pumps with accurate drug libraries Implement effective independent double checks Consider patient’s usual time for meals and timeframe for insulin administration Consider unique delivery devices such as insulin pen with proper safeguards (i.e. dispensed by pharmacy ONLY, label each pen with patient’s name, auxiliary label for single patient use, identified authorized staff to administer it, etc.) Allow and encourage patient self-management (or parents for young pediatric patients) when patients and parents are capable and willing Encourage patients to question doses and timing of insulin administration Utilize auxiliary labels for high-alert medications consistently within the organization

Culture of safety

Medication error is a term that assigns blame and presumes wrongdoing. In a culture of safety, shame and blame are no longer the preferred institutional response to patient harm. The preferred response is systemic change that reduces the possibility of similar events.

The term "adverse drug event" (ADE) is preferred over "medication error" because it is patient centered. Rather than blaming one healthcare provider, it focuses attention upon actual harm experienced by a patient within a healthcare setting.

Nursing deserves tremendous credit for its success in limiting ADEs. In spite of chronic understaffing and minimal technological support, nursing has protected the patient. A study by Bates, Boyle, Vander (1995) determined that nurses intercepted about half of all preventable ADEs prior to drug administration.

Prevention of ADEs by the healthcare facility

• Implementation of computerized provider order entry (CPOE) with a Decision-Support System can reduce pADEs by greater than 50%. (Nuckols, Smith-Spangler, et al. 2014)
• Including a pharmacist during rounds of medical ICU can reduce pADEs. (Kucukarslan, Corpus, et al. 2013)
• Have a pharmacist available on call for consultation after normal pharmacy hours.
• Employ special procedures and written protocols for the use of high-risk IV and oral medications.

Reduce your risk of pADE involvement:

Knowledge:

• Take all the time necessary to thoroughly understand your patient's diagnoses and the side-effects common to the drug treatments for those ailments.
• Use your resources; the pharmacy is your ally; consult with them.
• Identify an "on-site consultant" to lead intervention when an ADE occurs.
• Demand real-time access to current nursing, medical and pharmaceutical references and use them to improve care.
• Consider carrying a handheld medication reference with drug indications, doses, routes, interactions, and other considerations.
• Demand the time and support necessary to master drug administration devices common to your work setting.
• Promote practice drills to identify and reinforce appropriate staff response to ADEs.
• Share what you learn.

Communications:

• Document and clarify any confusing orders with the prescriber.
• Confirm any order, or dispensing circumstance, that is unusual with pharmacy.
• Encourage adoption of Point of Care electronic charting and computerized physician order entry with decision support.
• Transcribe orders in printed block letters.
• Avoid abbreviations when transcribing.
• Verify every order which contains an abbreviation on the the Joint Commission "Do Not Use" list.
• Reduce decimal point confusion: 'Always lead; never follow'
  • DO precede a decimal point with a numeral; e.g., 0.5 mg "Do Not Use" list.
  • Do Not place a decimal point & zero after a numeral; e.g., 20.0 mg
  • Document, clarify and "incident report" any order which does not conform to policy
• Notify pharmacy and "Incident report" any circumstance that could lead to "Look-alike, Sound-alike" confusion.
• Don't rely on memory; document each drug administration as soon as possible.
• Verify the completeness and accuracy of patient information as the patient enters and transitions through the medical system. Incomplete information is responsible for about 50% of errors and 20% of pADEs.
• "Incident report" every near-miss as well as ADEs that cause harm. Organizations can't improve without information.

Preparation and Administration of Medications

• Identify your patient using multiple identifiers.
• Assess your patient for contraindications to each medication.
• Patient centered education so that your patient expects announcement of the drug name, dose, purpose and the next scheduled dose before each administration of a medication.

• Some hospitals employ a No Interruption Zone (NIZ) around nurses while preparing and administrating medications. These zones are made visible by cordoning off a quiet area and donning colored vests or other specially designated clothing. Do Not Disturb signage can useful.

  No interruption also applies to mobile devises which should have calls transferred to staff that not are not actively dispensing medications.

  Staff should be educated to avoid interrupting nurses that are preparing or administering medications and physicians writing orders.

  Only during significant changes in a patient’s condition, when no one else is available, should someone involved in the ordering, preparing or administrating of medications be interrupted (Wiencek, Bauer, Daly, Anthony, 2010).

High Risk Populations:

• Neonate/Infant body mass, smaller plasma volume, and inefficient liver and kidney clearance, compared to older children and adults, tend to make drug and dose errors significantly more serious. Reiter (2002) succinctly expresses the issue with: "The neonate is in a rapid and continuous state of maturation, which can influence significantly the therapeutic and toxic effects of drug therapy."
• Geriatric patients often require daily medications, both OTC and prescribed, to manage multiple diagnoses. Ensuring continuation of necessary medications after an intervention is an important aspect of safe care. The more complex the medication regimen, the greater the chance of interactions and side-effects. Alterations in drug absorption and clearance must be anticipated in even the healthy elderly.
• Critical Care (High-Risk OB, ER, OR, ICU) environments are known to have the greatest risk of serious adverse drug events and outcomes. These practice areas require the highest level of vigilance and the lowest tolerance for deviations from policy.

References

• Kohn LT, Corrigan JM, Donaldson MS (Institute of Medicine) To err is human: Building a safer health system. Washingto DC: National Academy, 2000
• VA Center for Medication Safety and VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. Adverse drug events, adverse drug reactions and medication errors: Frequently asked questions. 2006. Available from: http://www.va.gov/MS/Professionals/medications/Adverse_Drug_Reaction_FAQ.pdf
  
• Nebeker JR, Barach P, Samore MH. Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting. Ann Intern Med. 2004;140:795-801.
• PSNET. Medication Errors. Patient Safety Network. Agency for Healthcare Research and Quality 3/2015. Accessed 2/29/2016. https://psnet.ahrq.gov/primers/primer/23/medication-errors
• Weiss A, Elixhauser A, Bae J, Encinosa W. Statistical Brief #158. Healthcare Cost and Utilization Project (HCUP). September 2013. Agency for Healthcare Research and Quality, Rockville, MD. www.hcup-us.ahrq.gov/reports/statbriefs/sb158.jsp.
• Nuckols, T. K., Smith-Spangler, C., Morton, S. C., Asch, S. M., Patel, V. M., Anderson, L. J., … Shekelle, P. G. (2014). The effectiveness of computerized order entry at reducing preventable adverse drug events and medication errors in hospital settings: a systematic review and meta-analysis. Systematic Reviews, 3, 56. http://doi.org/10.1186/2046-4053-3-56
• Kucukarslan S, Corpus K, Mehta N, Mlynarek M, Peters M, Stagner L, Zimmerman C. (2013) Evaluation of a Dedicated Pharmacist Staffing Model in the Medical Intensive Care Unit. Hospital Pharmacy: December 2013, Vol. 48, No. 11, pp. 922-930
• Bates D, Boyle D, Vander Vilet M, Schneider J, Leape L. Relationship between medication errors and adverse drug events. Journal General Internal Medicine. 1995 Apr;10(4):199-205.
• The Military Health System's Partnership For Patients Campaign. Sustainment Guide for Adverse Drug Events. Accessed 4/1/16. http://www.health.mil/Reference-Center/Technical-Documents/2014/01/24/Sustainment-Guide-for-Adverse-Drug-Events
• Anthony, K., Wiencek, C., Bauer, C., Daly, B., Anthony, M.K. (2010). No interruptions please: impact of a no interruption zone on medication safety in intensive care units. Crit Care Nurse. 30, 21-29. http://ccn.aacnjournals.org/content/30/3/21.long
• Reiter, P. (2002) Neonatal Pharmacology and Pharmacokinetics. NeoReviews Vol.3 No.11 p. 229.
• Lucado, J. (Social & Scientific Systems, Inc.), Paez, K. (Social & Scientific Systems, Inc.), and Elixhauser A. (AHRQ). Medication-Related Adverse Outcomes in U.S. Hospitals and Emergency Departments, 2008. HCUP Statistical Brief #109. April 2011. Agency for Healthcare Research and Quality, Rockville, MD. Available from: http://www.hcup- us.ahrq.gov/reports/statbriefs/sb109.pdf.