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Case Report

Unintentional Infiltration of High Dose Epinephrine in an Infant: A Case Report

Tsai, Phil B. MD, MPH; Bergin, Michael W. MD

Author Information
A & A Practice: April 2020 - Volume 14 - Issue 6 - p e01179
doi: 10.1213/XAA.0000000000001179
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Abstract

Verbal orders in the operating room between the surgeon and circulating nurse are prevalent at many institutions because of practice cultures and perceived delays to the workflow with written or computer orders. However, verbal orders, if inaccurately performed, can lead to treatment delays and even cause patient harm. We present a case in which a communication breakdown involving a verbal order resulted in an infant receiving an excessively high dose of epinephrine via subcuticular infiltration. The patient’s mother provided written Health Insurance Portability and Accountability Act (HIPAA) authorization for publication of this report.

CASE DESCRIPTION

A 7-week-old, 4.8-kg ex-full-term female infant with a history of congenital ptosis of the left eye was scheduled for frontalis suspension of the left upper eyelid under general anesthesia. After consents were verified, an anesthesia time-out was performed with the parents in the preoperative holding area, and the patient was transported to the operating room. The baseline heart rate was 143 beats/min, and the baseline blood pressure was 98/54 mm Hg. Inhalational induction was initiated with nitrous oxide and sevoflurane. A 24-G intravenous catheter was placed in the right foot, the patient was paralyzed with rocuronium 0.6 mg/kg, and the airway was secured with a 3.0 cuffed oral endotracheal tube. Subsequently, the operating room table was rotated 90° to the pediatric ophthalmologist, who announced that she would commence infiltrating local anesthetic with epinephrine at the surgical site.

Within 60 seconds, peaked T-waves were seen on the electrocardiogram (ECG; Figure A), and the heart rate increased suddenly from 116 to 160 beats/min. Blood pressure was immediately cycled, showing a value of 127/85 mm Hg, a significant increase from the prior reading (63/25 mm Hg). For awake infants from birth to 3 months of age, the normal heart rate ranges from 110 to 160 beats/min, while normal blood pressures range from 65 to 85 mm Hg systolic over 45–55 mm Hg diastolic.1 Given the ECG and hemodynamic changes, intravascular injection of epinephrine was suspected. A propofol bolus of 2 mg/kg was given, and the sevoflurane was turned to 8%, increasing the end-tidal concentration of sevoflurane from 2% to 5.5%. Propofol 2 mg/kg was again administered 2 minutes later when the blood pressure remained elevated (116/61 mm Hg).

Figure.
Figure.:
Intraoperative ECG showing T-wave and ST segment changes and subsequent normalization after local anesthetic-epinephrine infiltration. A, 1 min. B, 10 min. C, 15 min. D, 20 min. E, 25 min. F, 120 min. ECG indicates electrocardiogram; HR, heart rate.

The surgeon was queried regarding the possibility of intravascular injection, but she responded that there was negative aspiration before injection of the solution. She reported that a total volume of 0.5 mL had been given. Subsequently, the operating room nurse was asked what medication had been delivered to the surgeon. The nurse replied that she had been given a verbal order by the surgeon to mix “0.25% bupivacaine with epinephrine,” and she had combined 2 mL of 0.25% bupivacaine and 2 mL of epinephrine (1 mg/mL) in a single syringe (total 4 mL), and handed this to the surgeon for infiltration. Given the fact that 0.5 mL of the solution was administered, it was calculated that the patient received 250 µg of epinephrine (52 µg/kg), over 5 times the dose recommended for cardiac arrest.1

Seven minutes after ECG changes were noted, the blood pressure had returned to baseline values (96/32 mm Hg). The sevoflurane concentration was titrated to 3%, and it was felt that the patient was stable for surgery to proceed. However, shortly after surgery began, and 10 minutes after the local anesthetic/epinephrine injection, ST segment depression was observed (Figure B). This worsened over the next 5 minutes (Figure C). Because of concern for cardiovascular injury, a pediatric cardiology consult was initiated. A neurosurgery consult was obtained because of the marked increases in blood pressure at the time of infiltration.

Given that the blood pressure changes were transient, and the patient was hemodynamically stable, both consultants felt that surgery could safely continue, but made recommendations for postoperative care. The pediatric cardiologist recommended a postoperative transthoracic echocardiogram, and the neurosurgeon recommended a computed tomography (CT) of the head. The surgery and anesthesia teams concurred with the treatment plan. The patient’s parents were taken to a consultation room where they were informed of the situation, and they also agreed. The pediatric intensive care unit (PICU) was consulted for postsurgical admission and monitoring.

The ST segment changes improved by 20 minutes after the local anesthetic/epinephrine injection (Figure D), and the ECG returned to baseline by 25 minutes (Figure E). The patient’s vital signs and ECG remained stable when surgery concluded 2 hours later (Figure F). An initial troponin level was mildly elevated at 0.055 ng/mL (normal <0.028 ng/mL, critical high >0.299 ng/mL). The patient was intentionally kept intubated after surgery to facilitate postsurgical interventions and was directly transported from the operating room to the CT scanner, where a noncontrast head CT was performed, showing no acute intracranial pathology. On arrival to the PICU, a 12-lead ECG was obtained, which showed normal sinus rhythm. The consulting pediatric cardiologist performed a transthoracic echocardiogram, which was normal. The patient was extubated 2 hours after arrival to the PICU. A second troponin level drawn 12 hours after the first was normal (0.019 ng/mL). Because the initial troponin was only mildly elevated and had resolved by the second draw, and because the transthoracic echocardiogram was normal, it was felt that the patient had not suffered permanent cardiac injury. Both neurosurgical and cardiac consultants signed off with no further recommendations, and after an uneventful postoperative course, the patient was discharged home with her parents on postoperative day 1. At the 12-month-old well-baby check, the patient was doing well without any apparent ophthalmologic, neurologic, or cardiac sequelae.

A root cause analysis (RCA) meeting with members of the surgery, nursing, pharmacy, and anesthesiology departments was scheduled to discuss potential systems-based issues and propose improvements. Several problems were identified. (1) The surgeon’s preference card listed bupivacaine 0.25% and epinephrine, standardized by the manufacturer at 5 µg/mL, but the pharmacy department did not stock any epinephrine-containing bupivacaine mixtures in the medication-dispensing cabinet in the surgical area. (2) When the nurse informed the surgeon that there were no epinephrine-containing bupivacaine solutions available, the surgeon verbally ordered the circulating nurse to mix plain bupivacaine 0.25% with epinephrine, but she did not provide any specific instructions on how to mix the medications. (3) The circulating nurse did not ask for clarification and drew up a 1:1 mixture of bupivacaine 0.25% and epinephrine (1 mg/mL) in a syringe. (4) The syringe was not labeled before being handed to the surgeon. (5) The surgeon and circulating nurse did not verbally and visually confirm the medications with each other. After the RCA, operating room nursing policy was amended so that nursing staff was not allowed to mix medications, and compounding of medications is solely performed by the pharmacy department. In addition, surgeons are encouraged to limit verbal orders in the perioperative setting and to regularly update medication lists on their preference cards.

DISCUSSION

We describe the report of epinephrine overdose via subcuticular infiltration in an infant. It remains unknown whether or not the medication was intravascularly injected. However, given the high concentration of epinephrine and the high vascularity of the eyelid and forehead, absorption of the medication would have caused the hemodynamic changes. Epinephrine has a variety of uses in the operating room, including the treatment of anaphylaxis, restoration of cardiac rhythm, treatment of septic shock and extreme hypotension, treatment of bronchospasm, to prolong the duration of action of local anesthetics, and provide local vasoconstriction.2 In Kinsella et al’s3 review, administration of doses reaching a maximum of 10 µg/kg at 30-minute intervals for primary palatoplasties was effective in promoting hemostasis and did not result in hemodynamic instability. However, excessive doses of epinephrine can cause acute coronary artery spasm, myocardial ischemia, ventricular dysrhythmias, cardiovascular collapse, pulmonary edema, intracranial hemorrhage, rhabdomyolysis, and hypokalemia.4,5 Another concern with local epinephrine injection is tissue ischemia from vasoconstriction. This has previously been reported to occur in acral areas when excessive doses were administered.6 Fortunately, for our patient, no ophthalmologic complications have been noted.

Freid et al7 was the first to report changes in ST segments and T-waves with unintentional intravascular injection during caudal administration of bupivacaine with epinephrine. Subsequently, Fisher et al8 showed that increases in T-wave amplitude were the most sensitive indicator of intravascular injection of epinephrine. These results were further verified in multiple studies involving pediatric patients receiving inhalational anesthesia.9–12 In our case, an increase in T-wave amplitude was the first sign to alert the anesthesia team of drug overdose and resulted in timely action to lower the blood pressure.

The Federal Drug Administration and most state agencies refer to the United States Pharmacopeia General Chapter <797> standards for compounding sterile preparations (SP).13 Compounding of SP for direct and immediate use is not subject to ordinary requirements that products be prepared in special facilities. Operating room nurses prepare medications under this provision, which allows the mixing of no more than 3 products. It was subsequently determined at our institution that it would be safer if operating room nurses no longer compounded immediate use medications, but rather this be relegated to the pharmacy department.

This case serves as a reminder to affirm best practice strategies in the operating room, such as (1) limiting verbal orders, (2) performing “read-backs” of verbal orders, (3) verbally and visually confirming the medication name and concentration by reading the label aloud when delivering the medication, and (4) recording orders in the patient’s record as soon as feasible.14 A multidisciplinary approach should be utilized to continue to develop additional risk-reduction strategies, such as identifying high alert medications and creating separate adult and pediatric conversion charts for these medications to calculate maximum dose limits. Communication with the anesthesia team for dose confirmation likely would have prevented this incident, and as stakeholders in the operating room, anesthesiologists should be willing to offer assistance when solicited.

In conclusion, we present a case in which miscommunication with a verbal order resulted in a pediatric patient receiving an overdose of epinephrine. Because of early identification by increase in T-wave amplitude on the ECG, no long-term harm occurred. This report reminds the anesthesia community that our continued vigilance is indeed a safeguard for patients. However, our concern for patient safety involves advocacy for the implementation of best practice strategies for all operating room personnel.

DISCLOSURES

Name: Phil B. Tsai, MD, MPH.

Contribution: This author helped to care for the patient, draft, and revise the manuscript.

Name: Michael W. Bergin, MD.

Contribution: This author helped to care for the patient and revise the manuscript.

This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.

GLOSSARY

CT = = computed tomography;

ECG = = electrocardiogram;

HIPAA = = Health Insurance Portability and Accountability Act;

HR = = heart rate;

PICU = = pediatric intensive care unit;

RCA = = root cause analysis;

SP = = sterile preparations

REFERENCES

1. Hughes HK, Kahl LK. The Harriet Lane Handbook. 2018.21st ed. Philadelphia, PA: Elsevier
2. AHFS Drug Information 2019. 2019.Bethesda, MD: American Society of Health-System Pharmacists, Inc.
3. Kinsella CR Jr, Castillo N, Naran S, et al. Intraoperative high-dose epinephrine infiltration in cleft palate repair. J Craniofac Surg. 2014;25:140–142.
4. Wanamaker HH, Arandia HY, Wanamaker HH. Epinephrine hypersensitivity-induced cardiovascular crisis in otologic surgery. Otolaryngol Head Neck Surg. 1994;111:841–844.
5. Fang W, Chen JY, Fang Y, Huang JL. Epinephrine overdose-associated hypokalemia and rhabdomyolysis in a newborn. Pharmacotherapy. 2005;25:1266–1270.
6. Hartzell TL, Sangji NF, Hertl MC. Ischemia of postmastectomy skin after infiltration of local anesthetic with epinephrine: a case report and review of the literature. Aesthetic Plast Surg. 2010;34:782–784.
7. Freid EB, Bailey AG, Valley RD. Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of bupivacaine with epinephrine in infants. Anesthesiology. 1993;79:394–398.
8. Fisher QA, Shaffner DH, Yaster M. Detection of intravascular injection of regional anaesthetics in children. Can J Anaesth. 1997;44:592–598.
9. Tanaka M, Nishikawa T. Evaluating T-wave amplitude as a guide for detecting intravascular injection of a test dose in anesthetized children. Anesth Analg. 1999;88:754–758.
10. Tanaka M, Nishikawa T. The efficacy of a simulated intravascular test dose in sevoflurane-anesthetized children: a dose-response study. Anesth Analg. 1999;89:632–637.
11. Kozek-Langenecker SA, Marhofer P, Jonas K, Macik T, Urak G, Semsroth M. Cardiovascular criteria for epidural test dosing in sevoflurane- and halothane-anesthetized children. Anesth Analg. 2000;90:579–583.
12. Tanaka M, Kimura T, Goyagi T, Ogasawara K, Nitta R, Nishikawa T. Evaluating hemodynamic and T wave criteria of simulated intravascular test doses using bupivacaine or isoproterenol in anesthetized children. Anesth Analg. 2000;91:567–572.
13. USP General Chapter <797> Pharmaceutical compounding – sterile preparations. In: The United States Pharmacopeia, 42nd rev, and the National Formulary, 2019:37th ed. Rockville, MD: United States Pharmacopeia, 1–36.
14. Association of Perioperative Registered Nurses. AORN guidance statement: safe medication practices in perioperative settings across the life span. AORN J. 2006;84:276–283.
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