Adverse drug reactions in the emergency department (Hohl 2018)

Adverse drug events might be responsible for as many as 1 in 9 emergency department visits.^1,2,3 Physicians frequently miss the diagnosis of medication related adverse events.^4,5,6 Pharmacists can be very helpful in assessing patients for adverse drug events, but are a scarce or non-existent resource in most emergency departments. This paper asks whether clinical decision tools can help us identify adverse drug reactions among emergency department patients.

The paper

Hohl CM, Badke K, Zhao A, et al. Prospective validation of clinical criteria to identify emergency department patients at high risk for adverse drug events. Academic emergency medicine. 2018; PMID: 29517818 [full text article]

The Methods

This is a prospective cohort study looking to validate 2 previously derived clinical decision tools.

Patients: A quasi-randomly selected convenience sample of English speaking adult emergency department patients using at least one prescription or over the counter medication in the 2 weeks prior to emergency department presentation.

• Exclusions: Violent patients, self-poisoning, needlestick injury, sexual assault, patients who were previously enrolled, patients returning for scheduled visits or transferred directly to an admitting team, and patients triaged to the fast track area.

Intervention: Two different decision tools were studied.

Outcome: The primary outcome was severe or moderate adverse drug events. Adverse drug events were defined by clinical assessment by the treating physician and study pharmacist. If there wasn’t agreement, the outcome was adjudicated by an independent physician and pharmacist team.

• The definition of ADE was relatively broad, including “adverse drug reactions, a response to a prescription or over-the-counter drug that is noxious and unintended, and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, and events due to non-adherence or drug withdrawal, errors in prescribing, dispensing or medication administration, drug interactions, supra or subtherapeutic dosing, untreated indications and inappropriate drug use”.
• “Severe” ADEs were defined as resulting in death or hospital admission. “Moderate” ADEs resulted in a change in medical management.

The Results

1529 patients were enrolled over a 1 year period at 3 hospitals.

182 patients (12%) were diagnosed with a total of 202 moderate or severe adverse drug reactions.

96 (6.3%) of these events were adverse drug reactions, with the remainder being things like withdrawal, ineffective drugs being used, or patient non-adherence to medications.

Rule #1 had a sensitivity of 91.3% (95% CI 86.3-95.0%) and a specificity of 37.9% (95% CI 35.3-40.6%).

Rule #2 had a sensitivity of 95.7% (95% CI 91.6-98.1%) and a specificity of 22.8% (95% CI 20.6-25.2%).

My thoughts

This is an important issue to study, and I give a lot of credit to the researchers for getting this validation done. I also like that the rules are simple and easy to understand.

One potential issue with this study is selection bias. This was a convenience sample based on the presence of research assistants being in the emergency department. Patients arriving at night were not included, and I imagine that performing medication reconciliation is much more difficult in the middle of the night. Furthermore, although the first patient of every day was selected randomly, subsequent patients were selected based on time, but the rules are unclear, which could allow for subjective selection of patients by the research assistants. That being said, the demographic data of the selected patients did match well with the larger population.

The biggest issue with this study is the subjective definition of adverse drug events. Because there is no objective definition available, the criterion standard had to be the clinical impression of the treating physician and study pharmacist, with adjudication by an independent committee in cases of disagreement. It is possible, if not probable, that this definition will both miss some adverse drug reactions and overcall others.

A strong point of this manuscript is that the authors provide us with details of every single ADE, so we can judge for ourselves. Based on their list, there are a number of ADEs that I would disagree with (based on the limited information I have). For example, there was one case of a patient diagnosed with discitis where intravenous vitamins are defined as a culprit ADE. It is possible these vitamins were contaminated, but it is hard to be sure this is an adverse drug event.

These clinical details also provide insight into the difficulties with composite outcomes. A potassium of 8.2 and acute kidney injury in a patient on ramipril is an adverse drug event I want to identify. On the other hand, an INR of 3.4 in a patient known to be on warfarin who presents just for palpitations is not nearly as important to know about. Similarly, a patient on oxycodone and methadone admitted for septic arthritis, but who happens to have colace added for constipation gets classified as a “moderate ADE” because it required a medication change. These outcomes are not equally important.

It is interesting that when they asked nurses to assess patients using these 2 rules, they were incredibly inaccurate. For example, they were wrong 45% of the time when considering whether the patient was taking 4 or more regular medications, and 40% of the time when considering whether the patient had recent changes to their medications. That makes me wonder whether these rules could actually be used clinically.

I don’t doubt that physicians, especially busy emergency physicians, miss adverse drug events frequently. Ensuring that we have ADEs on our differential diagnoses for all patient makes a lot of sense, but I don’t think I see a lot of value in these rules in most clinical practice enviroments.

Bottom line

Adverse drug events are common and easy to overlook. Keep them on your radar for all patients. For now, I don’t think these tools have a role in my department (where we don’t have clinical pharmacists), but they are worth reviewing as a reminder of risk factors for ADEs.

Other FOAMed

This paper was the topic of this week’s SGEM Hot Off The Press episode. You can hear a more in-depth clinical appraisal, including a discussion with the lead author, on the SGEM. If you have questions or comments for the author, head over to the SGEM site to get involved in the conversation.

References

1. Forster A, Asmis T, Clark H, et al. Ottawa Hospital Patient Safety Study: incidence and timing of adverse events in patients admitted to a Canadian teaching hospital. Canadian Medical Association Journal. 2004;170:1235-40. 4.
2. Leape LL, Brennan TA, Laird N, et al. The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med. 1991;324:377-84. 5.
3. Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication- related visits to the emergency department: a prospective study. Canadian Medical Association Journal. 2008;178:1563-9. 6
4. Hohl CM, Robitaille C, Lord V, et al. Emergency physician recognition of adverse drug-related events in elder patients presenting to an emergency department. Acad Emerg Med. 2005;12:197-205. 8.
5. Hohl CM, Zed PJ, Brubacher JR, Abu-Laban RB, Loewen PS, Purssell R. Do Emergency Physicians Attribute Drug-Related Emergency Department Visits to Medication-Related Problems? Annals of Emergency Medicine. 2010;55:493-502. 9.
6. Classen D, Pestotnik S, Evans S, Lloyd J, Burke J. Adverse Drug Events in Hospitalized Patients. Journal of the American Medical Association. 1997;277:301-6. 10.