• Cases & Commentaries
  • Published April 2009

Eptifibatide Epilogue

The Case

A 62-year-old man was admitted at 11:00 PM on a Saturday night with the provisional diagnosis of acute coronary syndrome. Serial testing for markers of cardiac injury was begun, and he was treated with a beta-blocker, enoxaparin, and a statin. At 6:00 AM Sunday, the patient's troponin was elevated and the diagnosis was upgraded to NSTEMI (non-ST segment elevation myocardial infarction). The intern entered an order for intravenous eptifibatide (a powerful anticlotting agent given by intravenous drip) into the computerized order entry system in anticipation of expedited coronary intervention on Monday morning. The intern entered the correct weight-based dosage of eptifibatide (a loading dose, followed by a maintenance infusion of 2 µg/kg/min) into the order template. Because of a forcing function in the template, he also had to enter a maintenance infusion rate in milliliters per hour (mL/hr). He was unsure of the proper infusion rate, so he arbitrarily chose 0.5 mL/hr. He expected the pharmacist on duty to make adjustments to the order as needed. [Note: The correct infusion rate for this patient should have been 20 mL/hr.]

The eptifibatide order was electronically transferred to the pharmacy for processing. The pharmacist processed the order as entered, and eptifibatide was sent to the floor for administration. The nurse on duty was harried because he was caring for six patients instead of the usual four. He correctly administered the loading dose and ran the maintenance infusion at 0.5 mL/hr, under-dosing the patient by a factor of 40. The night shift nurse continued the infusion at this rate, as did the nurse on the following day shift. The day shift nurse was curious about the low dose and queried the intern, but the nurse was distracted by her additional charge nurse duties. The patient was taken to the percutaneous cardiac intervention (PCI) lab at 2:00 PM on Monday, by which time his troponin values had peaked and were trending down. In the PCI lab, the eptifibatide infusion error was immediately noted. The patient subsequently underwent coronary angioplasty with stenting. It is impossible to say whether the underdose of the blood thinner led to more cardiac damage.

The Commentary

The Institute of Medicine report "To Err Is Human" estimated that more than a million injuries and nearly 100,000 deaths are caused by medical errors every year.(1) Mistakes involving medications are often preventable and are associated with significant clinical and financial consequences.(2) An analysis of serious medication errors determined that 39% of these errors occurred during medication ordering.(3) Fortunately, computerized prescriber order entry (CPOE) systems have been found to decrease medication order entry errors by 55%–80%, thereby significantly improving patient safety and health care performance.(4-6) However, this case highlights the shortcomings and unintended consequences inherent to many CPOE systems.

Clinical Decision Support

CPOE systems are most effective when they are integrated into a comprehensive medication use process designed to decrease medication errors and improve prescribing practices. Unfortunately, many institutions have implemented CPOE as a stand-alone, nonintegrated function where it serves as a very expensive typewriter. These CPOE systems require prescribers to enter medication orders into the computer, often without providing critical feedback on therapy appropriateness or other pertinent clinical decision support. These types of CPOE systems may be effective at preventing some medication errors, such as those resulting from illegible handwriting, but they are not as effective at reducing prescribing errors associated with drug–drug interactions, drug allergy alerts, or dosing errors. The efficient and effective integration of evidence-based decision support systems within CPOE is a necessary component to improve prescribing practices. Every effort needs to be made to ensure that critical alerts are shown to prescribers to alert them to potential safety issues, while at the same time preventing an excessive frequency of alerts and resultant alert fatigue. When this happens, clinical decision support systems are rendered ineffective.(7)

Similarly, some CPOE systems may actually facilitate medication errors. One recent study identified 22 situations in which CPOE increased the probability of prescribing errors.(8) The error in the case above is a classic example of how a forcing function of a CPOE system can introduce error. During the ordering of complex medications such as eptifibatide, which require calculation of a weight-based loading dose, maintenance dose, and calculation of infusion rate, the potential for order entry error is high. Ideal CPOE systems should be designed with clinical decision support to calculate infusion rates based on a maintenance dose and standardized drug concentration. The system software should alert the prescriber to any calculation discrepancies or orders that are outside of the normal range.

Team Care—Importance of Communication at Handoff

Medication errors can also be prevented using nontechnological solutions. Recent data suggest that adding clinical pharmacists to the medical team can reduce medication-related problems and prescribing errors by 66%.(9) In a study evaluating the effects of pharmacists in the emergency department (ED) setting, researchers determined that pharmacist participation on rounds improved processes for managing high-risk/high-alert medications, enhanced continuity of care, and increased monitoring for adverse effects of medication administration.(10) Many patients admitted to the hospital for evolving acute coronary syndromes are admitted through the ED. The acuity of care and the fast-paced nature of most ED settings often result in high error rates. In the case above, if the patient was admitted via the ED and there was a clinical pharmacist in the unit with experience in dosing of emergency medications and reconciling dosages with appropriate infusion rates, the dosing error may have been noted and communicated to the ordering clinician.

Failures in communication and ineffective teamwork are leading causes of patient harm. A Joint Commission analysis of more than 2400 sentinel events indicated that the root cause of error was communication failure in 70% of the events.(11) Often, clinicians who provide care have different perceptions of a patient's clinical course. Also, the hierarchal nature of medical practice frequently inhibits team members from speaking up. In recent years, much effort and research have been dedicated to improving communication between clinicians (e.g., nurse to physician) and to improving communication during handoffs. The use of standardized checklists and simple communication tools such as SBAR (situation, background, assessment, and recommendation) during interdisciplinary communication can reduce the potential for medical errors.(12)

In 2005, the Joint Commission issued a National Patient Safety Goal requiring hospitals to standardize communication processes to reduce the potential for errors during handoffs. Many hospitals have implemented systems designed to comply with the Joint Commission requirement, such as standardizing the handoff process, ensuring that handoff information is communicated in both verbal and written formats, and implementing a team approach to patient care that allows and encourages all members of the clinical team to exchange ideas and concerns. The error described in the present case may have been prevented with the use of a standardized checklist requiring that infusion rates be checked during the handoff process. The National Quality Forum also recommends that hospitals establish organization-wide approaches to team care as a safe practice for better health care.(13)


High-Alert/High-Risk Medications

Medications that have a high risk of causing significant patient harm when misused are known as high-alert medications. Errors aren't necessarily more common with high-alert medications, but the consequences of error are potentially more severe. The Institute for Safe Medicine Practices (ISMP) has classified 19 medications or medication classes (including eptifibatide) as high risk.(14) Many institutions have implemented universal protocols for managing high-alert or high-risk medications.(15) Some recommended precautions include: implementation of double-check processes for calculations and pump programming; barcode verification of all medications during preparation, dispensing, and administration; use of intelligent infusion technology; standardization of dilution guidelines and drug administration guidelines; and use of tall man lettering for look-alike, sound-alike medications (e.g., HYDROmorphone). Implementation of some of these precautions, including an independent double-check process during pharmacy order review and medication administration, may help to prevent the type of error described in this case.

Smart Pump Technology

Including smart infusion pump technology as part of a comprehensive medication safety system can further help to improve medication safety. Smart pumps are intravenous infusion devices equipped with dose-error–reduction software (DERS). The software contains a customizable list of parenteral medications, standardized admixture concentrations, and approved dose ranges. If users program an infusion rate that falls outside of approved ranges (i.e., over-doses or under-doses the patient), an alert sounds and must be acknowledged prior to the start of the infusion. In the case above, the nurse programming the pump was caring for a larger number of patients than usual. In situations of stress, the use of alerting systems may function as a double check. In one study, Fanikos and colleagues demonstrated a 73% reduction in the frequency of reported infusion rate programming errors 16 months following implementation of smart pump technology.(16) The use of smart infusion technology could have alerted the pump programmer to a potential error.

System Connectivity

It is also important to ensure that CPOE, pharmacy, electronic medication administration record (eMAR), and smart pump systems all share key information with each other in real time. System connectivity via wireless networks will help to maximize the value of electronic system double checks in the pharmacy and at the bedside, improve the synergy between CPOE clinical decision support and pharmacy systems, and provide real-time information about medication administration for all care providers including drug, dose, route, rate, and time of administration.

Take-Home Points

  • CPOE systems (with clinical decision support) are one type of technology solution designed to reduce medication errors. Additional medication error reduction strategies include robust clinical pharmacy information systems, barcode verification of medication dispensing and administration, and smart pump technology—with all systems connected to each other in real time.
  • Clinical decision support tools need to be carefully evaluated and designed to ensure that key alerts are received and acted upon and do not result in clinician alert fatigue.
  • Specific processes for high-alert, high-risk medications, such as process double-check protocols, can help to draw attention to medications associated with significant clinical sequelae when used in error.
  • Smart pump technology should be used to alert pump programmers of potential overdoses and under-doses.
  • Team training should be a key step in educating care providers about the roles and responsibilities for each discipline in caring for acutely ill patients.

William W. Churchill, MS, RPh

Executive Director of Pharmacy

Brigham and Women's Hospital

Boston, Massachusetts

Karen Fiumara, PharmD

Medication Safety Officer

Brigham and Women's Hospital

Boston, Massachusetts

References

1. Kohn LT, Corrigan JM, Donaldson MS, eds. To Err is Human. Building a Safer Health System. Washington, DC: Committee on Quality of Health Care in America, Institute of Medicine. National Academies Press; 2000. ISBN: 9780309068376.

2. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA. 1995;274:29-34. [go to PubMed]

3. Leape LL, Bates DW, Cullen DJ, et al. System analysis of adverse drug events. ADE Prevention Study Group. JAMA. 1995;274:35-43. [go to PubMed]

4. Bates DW, Leape LL, Cullen DJ, et al. Effect of computerized physician order entry and a team intervention on prevention of serious medication errors. JAMA. 1998;280:1311-1316. [go to PubMed]

5. Bates DW, Teich JM, Lee J, et al. The impact of computerized physician order entry on medication error prevention. J Am Med Inform Assoc. 1999;6:313-321. [go to PubMed]

6. Kuperman GJ, Teich JM, Gandhi TK, Bates DW. Patient safety and computerized medication ordering at Brigham and Women's Hospital. Jt Comm J Qual Improv. 2001;27:509-521. [go to PubMed]

7. Isaac T, Weissman JS, Davis RB, et al. Overrides of medication alerts in ambulatory care. Arch Intern Med. 2009;169:305-311. [go to PubMed]

8. Bobb A, Gleason K, Husch M, Feinglass J, Yarnold PR, Noskin GA. The epidemiology of prescribing errors: the potential impact of computerized prescriber order entry. Arch Intern Med. 2004;164:785-792. [go to PubMed]

9. Leape LL, Cullen DJ, Clapp MD, et al. Pharmacist participation on physician rounds and adverse drug events in the intensive care unit. JAMA. 1999;282:267-270. [go to PubMed]

10. Fairbanks RJ, Hayes DP, Webster DF, Spillane LL. Clinical pharmacy services in an emergency department. Am J Health Syst Pharm. 2004;61:934-937. [go to PubMed]

11. The Joint Commission. Sentinel Event Statistics. [Available at]

12. Leonard M, Graham S, Bonacum D. The human factor: the critical importance of effective teamwork and communication in providing safe care. Qual Saf Health Care. 2004;13 Suppl 1:i85-i90. [go to PubMed]

13. National Quality Forum. Safe Practices for Better Healthcare: 2009 Update: A Consensus Report. [Available at]

14. Institute for Safe Medication Practices. ISMP's List of High-Alert Medications. [Available at]

15. Mansur JM, ed. A Guide to The Joint Commission's Medication Management Standards, Second Edition. Oak Brook, IL: Joint Commission Resources; 2008. ISBN: 9781599402727.

16. Fanikos J, Fiumara K, Baroletti S, et al. Impact of smart infusion technology on administration of anticoagulants (unfractionated Heparin, Argatroban, Lepirudin, and Bivalirudin). Am J Cardiol 2007;99:1002-1005. [go to PubMed]

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