Cardiac arrhythmia from epinephrine overdose in epidural test dose.

Medication shortages are a clinical reality that force changes in practice patterns leading to unintended consequences. Potential solutions to any drug shortage require a thoughtful, multidisciplinary and often creative approach. Here, we report a case of unintentional epinephrine overdose leading to an unstable cardiac arrhythmia and our subsequent development of a visual cue system to prevent future errors. A 56-year-old man with a history of rectal adenocarcinoma presented for low anterior resection and creation of diverting loop ileostomy. Epidural placement was requested by the surgical team, and following administration of a second test dose (created by the physician), the patient experienced supraventricular tachycardia with heart rates of 200-210 BPM for approximately 2 minutes. This rhythm then converted to atrial fibrillation with rapid ventricular response with heart rate of 150-170 BPM. The patient was stabilized after cardioversion. Later evaluation of medication administration revealed that the second epidural test dose inadvertently contained 100 mcg epinephrine instead of the intended 10 mcg dose. The test dose had to be created because the original ampule with the kit had been utilized. Since this time, our kits have no test dose, and this shortage is concerning for increased provider error. We suggest a novel visual cue system that may prevent unintentional epinephrine overdoses in the setting of regional anesthesia.

Introduction

Over the recent years, medication shortages have become commonplace in both inpatient and outpatient healthcare settings around the world. Despite legislation in the United States enacted in 2012 requiring manufacturers to notify the Food and Drug Administration “of any change in production that is reasonably likely to lead to reduction in supply”, shortages continue to be a reality.[1] The often-cited reasons for such shortages include manufacturing and quality problems, delays, and discontinuations. However, what is arguably more important than their etiology, is that these medication shortages are driving changes in patient care leading to unintended consequences. Below, we report a case of unintentional epinephrine overdose leading to an unstable cardiac arrhythmia and our subsequent development of a visual cue system to prevent future errors.

Case

A 56-year-old man with a history of rectal adenocarcinoma presented for low anterior resection and creation of diverting loop ileostomy. The surgical service requested epidural analgesia for assistance with post-operative pain management. Following uneventful thoracic epidural placement and negative catheter aspiration, a test dose of 1.5% lidocaine with 5 mcg/ml epinephrine was administered. This resulted in a transient increase in heart rate from approximately 80 beats per minute (BPM) to 115 BPM. There was no change in non-invasive blood pressure measurement and the patient remained asymptomatic. Attempts to aspirate blood through the epidural catheter failed to demonstrate any return of any fluid. Given the transient rise in heart rate, lack of change in blood pressure, negative aspiration, and lack of symptoms reported by the patient, a repeat test dose created by the provider was administered. Following administration of a second test dose, the patient experienced supraventricular tachycardia with heart rates of 200-210 BPM for approximately 2 minutes. This rhythm then converted to atrial fibrillation with rapid ventricular response with heart rate of 150-170 BPM. Initial conservative treatment with esmolol boluses was ineffective and the patient's blood pressure decreased from approximately 140/70 mm Hg to approximately 90/50 mm Hg. He denied chest pressure or other cardiac symptoms, but 12 lead ECG revealed marked ST segment depression in the lateral leads. The patient was sedated with 1 mg midazolam and 30 mg propofol prior to 120 joule synchronized cardioversion at the bedside in the preoperative area. The patient returned to sinus rhythm and ST depression resolved. Later, evaluation of medication administration revealed that the second epidural test dose inadvertently contained 100 mcg epinephrine instead of the intended 10 mcg dose.

The surgeon and patient's family were updated, and surgery was postponed to allow for a formal cardiology evaluation. The patient received a transthoracic echocardiogram which revealed normal heart structure and function. The patient returned 3 days later and underwent an uneventful low anterior resection with diverting loop ileostomy. He declined pre-operative epidural placement but consented to post-operative bilateral quadratus lumborum blockade. The patient's post-operative course was complicated by ileus, but he had no further cardiac complications. He was discharged 8 days post the operation. Written informed consent for treatment and patient's approval for the publication of results were obtained.

Discussion

Medication shortages have unfortunately become a clinical reality. Within the practice of regional anesthesia and pain medicine, rolling shortages of opioids, ketamine and local anesthetics have become commonplace and provisions have been required to ensure that high quality care continues to be provided. Recently, a shortage of epinephrine led to the exclusion of epidural test dose solution (1.5% lidocaine with 5 mcg/ml epinephrine) from epidural kits. While the kit in this case contained one ampule of test dose, subsequent kits from the manufacturer did not. Obviously, the epidural test dose is an important component of ensuring the correct location of an epidural catheter via its ability to rule out inadvertent intravascular or intrathecal catheter placement. Therefore, the shortage of this pre-prepared test dose solution requires the practitioner to fashion a test dose of their own.

Unfortunately, epinephrine is a medication with a long history of inadvertent overdoses and other administration errors. In fact, previous studies have demonstrated that when utilized for anaphylaxis, recognized potentially life-threatening dosing errors occur with epinephrine in approximately 2.4% of cases. It is possible that dosing errors occur with an even greater frequency but are missed because the effect of epinephrine is transient or because dosing errors are not considered in unstable patients.[2] Likely, part of this risk is related to the narrow therapeutic window for epinephrine and the potential for serious adverse events to occur with dosing miscalculations. In addition, the nomenclature for reporting epinephrine concentration can be incredibly confusing to even experienced providers. For example, epinephrine concentration can variably be reported in mcg/ml, percentage and/or as a dilution ratio. This variety in concentration nomenclature and the small volume/mass of normally administered doses presents a legitimate opportunity for error. In fact, a previous study demonstrated that 40% of physicians may make incorrect calculations when converting drug doses from percentage to mass calculations.[3] Further studies have demonstrated the danger of presenting epinephrine dosing in ratios where it was found that medication errors with that form of concentration occurred much more frequently than when dosing was reported with mass labels.[4] In addition to dosing errors, epinephrine may be administered via the incorrect route or may be confused with other agents (i.e., ephedrine).[5]

Complications of epinephrine overdoses have been reported a number of times in the published literature and can include arrhythmia, hypertension, chest pain, tremor, anxiety, paleness, headache, peripheral vasoconstriction and nausea/vomiting.[67] Reported severe complications associated with iatrogenic epinephrine overdosages have included ventricular dysfunction, myocardial infarction, cardiac arrest, pulmonary edema and renal failure.[891011] Adverse events tend to be more severe in older patients that receive high doses of epinephrine via the intravenous routes.[712] Laboratory findings of excessive epinephrine dosing may include hyperglycemia, leukocytosis and hypokalemia. Treatment of epinephrine overdose is generally supportive in nature and targeted at specific symptom management.[6]

In the event of medication shortages of this nature, it is incumbent upon the faculty at any given institution to develop practices and guidelines to minimize the occurrence of adverse events related to medication administration errors. In the case of epinephrine shortages for epidural test dose, there are other considerations that may include the potential infectious complications that could arise from obtaining epinephrine from multi-dose vials or preparing the test dose under non-sterile conditions. There are also potential concerns related to selecting the correct local anesthetic for the epidural test dose and ensuring that it is preservative-free.

Potential solutions to any drug shortage require a thoughtful, multidisciplinary and often creative approach. In the case of epidural test dose shortages, pharmacy preparation of test dose supplies could occur in a sterile hood and may reduce the opportunity for physician error. Education is clearly needed, but should be performed frequently enough to reinforce vital concepts and may require competency assessments to identify areas of weakness. Visual point of care labeling clues have been successfully implemented in an emergency department setting where they have been utilized to guide decision making for anaphylaxis versus cardiac arrest dosing.[2] In response to this adverse cardiac event following and overdose of local anesthetic our institution decided upon a multi-faceted approach to ensuring that this does not occur again. First, all faculty and nurses were educated regarding the nature of the dosing error and how to subsequently avoid similar errors in the future. Visual cues were then plastered about our work area and epidural test dose dilution instructions were affixed to the “block cart.” Finally, epidural test dose solution instructions were affixed to all epidural kits that were found to be missing a pre-packaged test dose [Figure 1]. An effort was made to both convey the intent of this project to all providers and create visual cues that were informative and highly visible [Figure 2].

Figure 1

Epidural kit used with sticker (novel cue) reminder that the epidural kit does not include a premade by the manufacturer test dose

Figure 2

Bright sticker created by the author's acute pain team that clearly emphasizes the lack of test dose by the manufacturer. (Publish in color requested)

We therefore present a case of epinephrine overdose related to an inadvertently high dose of epinephrine being administered as part of an epidural test dose that was prepared by a member of the regional anesthesia team because of an ongoing medication shortage. Further work is required to validate a novel visual cue system to prevent epinephrine dosing errors in the context of regional anesthesia and pain management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.