Controversial COVID-19 Cures: Hydroxychloroquine and Oleander Pediatric Ingestion Simulation Cases.

INTRODUCTION: The use of hydroxychloroquine has dramatically increased since being touted as a potential therapeutic in combating coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus. This newfound popularity increases the risk of accidental pediatric ingestion, whereby just one or two tablets causes morbidity and mortality from seizures, cardiac dysrhythmias, and cardiogenic shock. The unique management of hydroxychloroquine overdose makes it imperative for emergency medicine physicians to have familiarity with treating this condition. Similarly, ​​during the COVID-19 pandemic, there have been publicized cases touting extracts of oleander as being a potential therapeutic against the illness. Since it is commonly available and potentially lethal ingestion with a possible antidote, we developed a simulation case based on the available literature. The two cases were combined to create a pediatric toxicology curriculum for emergency medicine residents and medical students. Both of these treatments were selected as simulation cases since they were being touted by prominent national figures as potential cures for COVID-19.
METHODS: Two series of simulation cases were conducted in a high-fidelity simulation lab with emergency medicine residents and medical students. The hydroxychloroquine simulation case involved the management of a four-year-old male who presented to the emergency department with nausea, vomiting, and tachycardia after ingesting hydroxychloroquine tablets. As the case unfolded, the child became increasingly unstable, eventually experiencing QT prolongation, torsades de pointes, and ventricular fibrillation arrest requiring appropriate resuscitation to achieve a return of spontaneous circulation. The oleander simulation case involved the management of a three-year-old male who presented to the emergency department with nausea, vomiting, and tachycardia after ingesting parts of an unknown plant. As that case progresses, the child becomes increasingly unstable, eventually experiencing atrial fibrillation, bradycardia, and degenerating into pulseless electrical activity and cardiac arrest requiring appropriate resuscitation to achieve the return of spontaneous circulation. Both series of simulation cases were modifiable based on trainee level and had the ability to include ancillary emergency department staff.
RESULTS: Each simulation case was performed six times at our simulation center, with a total of 22 learners for the hydroxychloroquine case, and 14 for the oleander case. Through pre- and post-simulation confidence assessments, learners demonstrated increases in knowledge of toxidromes, evaluating pediatric overdoses, treating cardiac dysrhythmias, performing pediatric advanced life support, and managing post-arrest care. Learners also demonstrated improvements in recognizing the unique treatment of hydroxychloroquine and oleander toxicity, the toxic dose of both substances in a child, and the most common electrolyte anomaly seen in each toxicity. DISCUSSION: Simulation training enables learners to manage rare and complex disease processes. These cases were designed to educate trainees in recognizing and treating rare overdoses of emerging "therapeutics" that were touted early in the COVID-19 pandemic.

Introduction

The first patients of the coronavirus disease 2019 (COVID-19) pandemic presented in the United States in early 2020. With few effective treatment options immediately available, many unproven substances began to be discussed as potential “cures” for COVID-19. Among the more promulgated theoretical therapies were hydroxychloroquine, an anti-malarial medication, and oleander, a subtropical plant, both of which were being highly touted by prominent national leaders with wide audiences over social and conventional media platforms. Concerns began to arise about potential toxic ingestions in patients taking these medications without instructions from their physicians, or the possibility of children accidentally ingesting their parents’ medications.

Hydroxychloroquine, a medication approved for use in the United States since 1955, is used to treat malaria, rheumatoid arthritis, lupus, and other conditions. While generally considered less toxic than its derivative medication, chloroquine, it has been implicated in cardiac dysrhythmias, cardiomyopathies, retinopathy, and other severe side effects in adults [1]. In a number of case reports, ingestion of hydroxychloroquine by children has caused significant morbidity and mortality from seizures, cardiac dysrhythmias, and cardiogenic shock [2]. Perhaps even more concerning, some children have experienced severe toxic effects after taking a single tablet [1,3]. After a series of toxic ingestions in children, toxicologists have agreed that a combination of diazepam, epinephrine, early intubation, and proactive supportive care can be utilized to prevent fatalities in severe hydroxychloroquine overdoses [4]. Prompt recognition of hydroxychloroquine toxicity is crucial in providing appropriate and timely care.

Prior to 2020, there was a relatively low baseline prevalence of hydroxychloroquine utilization in American households; therefore, the risk of accidental pediatric ingestion was fairly low. Considered a potential therapy against COVID-19 during the early stages of the pandemic, the magnitude of prescriptions filled nationally for hydroxychloroquine increased substantially [5]. This widespread distribution markedly increased the risk of children's potential accidental ingestion of hydroxychloroquine.

Providing instruction in both the management of hydroxychloroquine toxicity and QT-prolonging medication exposure overall, this case is ideally led by emergency medicine and pediatrics residents and fellows, while also providing useful learning for medical students. There are no known published curricula related to hydroxychloroquine toxicity. In addition, the treatment approach to hydroxychloroquine toxicity is uncommon and is best reinforced via a simulation session in which participants can learn via trial and error.

​​Unlike hydroxychloroquine, Oleander (Nerium oleander) is not a commonly prescribed medicinal, but a common plant that is found worldwide in subtropical and temperate areas. In the United States, it is found in the southern and western regions and is commonly used in residential areas as a small shrub or tree. All parts of the plant contain cardiac glycosides that have significant cardiac effects [6]. This toxicity is magnified in pediatric patients due to their smaller mass. Symptoms of severe toxicity include altered mental status, mydriasis, peripheral neuritis, qt prolongation, hypotension, heart block, atrial fibrillation, and ventricular dysrhythmias [6].

The mechanism for the toxicity stems from the cardiac glycosides that bind and inhibit the sodium/potassium ATPase pump leading to increased myocyte calcium. This leads to increased inotropy and increased extracellular potassium. Increased cardiac irritability with several different dysrhythmias has been noted [6]. Because of the cardiac impacts of oleander, several case reports of fatalities have occurred [6-8]. The use of digoxin immune fab has been shown to be helpful clinically and in the lab [7,9-10].

Oleander extract has been investigated as a remedy for cancer and as a cure for other conditions [11]. During the COVID-19 pandemic in 2020 oleander was touted as a possible treatment or preventative for COVID-19 infection by several high-profile figures in the United States [12,13]. Therefore oleander toxicity may become a concern if people attempt to utilize it as home therapy. Currently, there are no known published curricula related to oleander ingestion. The mechanism of oleander serves to discuss similar pathophysiology in digitalis overdoses. The case allows for discussion of cardiac glycosides and their mechanism and toxicity in clinical situations.

Materials and methods

Curriculum development

Both cases were written by a panel of simulation fellowship-trained faculty, emergency medicine core faculty, and board-certified toxicologists. The facilitators consisted of the emergency medicine core faculty and members of the simulation center professional staff. The simulations occurred on separate days spaced months apart with residents and medical students. It was part of a pilot pediatric toxicology curriculum.

These cases were designed to guide learners through the management of severe, acute toxicity resulting from a hydroxychloroquine overdose and an oleander overdose, respectively. It was designed for resident and fellow physician learners who may encounter such a case in the emergency department, including pediatric emergency medicine fellows, pediatric residents, and emergency medicine residents.

Equipment/environment

The simulation cases were conducted in the simulation lab using a pediatric high-fidelity manikin. The learning management system was preloaded with the requisite vital signs, laboratory values, x-ray imaging, and electrocardiograms (EKG). Medical equipment available in the room included a crash cart, pediatric-size defibrillator pads, defibrillator, stethoscopes, medication vials, Broselow tape, intravenous (IV), interosseous (IO) supplies, endotracheal tubes, laryngoscopes, bag-valve masks, nasal- and oral-pharyngeal airways. A variety of IO and airway equipment sizes, for both pediatrics and adults, were available. Instructors verbalized all physical exam findings and patient responses to the initial history and physical exam.

Personnel

The simulation cases were ideally designed for two to five learners, with the roles somewhat flexible and able to be combined if the case is run with fewer learners. We utilized the roles of team leader, primary/secondary examiner, historian, proceduralist, and crash-cart operator. The role of the team leader is the least flexible and is ideally assumed by a physician trainee, such as a pediatric emergency medicine fellow or an emergency medicine resident. The remaining roles, including primary/secondary examiner, historian, proceduralist, crash-cart operator, etc., can be managed by physician trainees, medical students, or other health professionals. At the onset of each case, the team leader assigns each team member a role. In our simulations, we had the facilitator play the nurse role.

Assessment

Before each case began, learners were given an assessment questionnaire with five confidence-assessment questions and five knowledge-assessment questions via paper exam. These questions were developed by the faculty to emphasize key clinical concepts from the simulation scenario.

Confidence questions were utilized to track learners’ self-assessed readiness to perform skills required in the simulation, while knowledge questions determined objective knowledge acquisition and learning related to the case content. Confidence questions were rated on a five-point Likert scale, from “very unconfident” (1) to “very confident” (5). Knowledge-based questions were single-best-choice answers with 4 potential answer choices. After both the simulation and debriefing, this same assessment questionnaire was administered to learners again. Results were collected and analyzed using Excel (Microsoft) and analysis was performed by STATA (StataCorp).

A critical actions checklist was enumerated in the case, which facilitators scored as the simulation progressed. Any critical action omitted or performed erroneously by the team was discussed during the debriefing. The critical actions varied in scope, with a mixture of both broad (i.e., “Demonstrate clear communication with team members”) and narrow (“Place the patient on a cardiac monitor”) objectives.

At the end of the scenario, a debriefing session was conducted. The instructor emphasized that simulation is the place for learning, and the environment of the debrief is designed to facilitate discussion of enhancing the skills and knowledge of the entire team. After this announcement, the instructor asked the team leader to self-evaluate how the case went, and what was subjectively good and bad about the progression of the case. Later, each participant was asked to provide their insights regarding the progression of the case and the communication between the leader and the team. Following this, the instructor reviewed the critical actions list and highlighted the team’s strengths and areas for improvement. Lastly, the instructor went over the optimal management of each case, highlighting the unique therapeutics and procedures utilized in hydroxychloroquine and oleander toxicity, respectively. The entire debriefing session lasted 20 to 30 minutes for each case. The PEARLS Healthcare debriefing was the tool used as a model for the debriefing guide [14].

Results

The hydroxychloroquine simulation case was performed at our simulation center six times, in groups of 3 to 4 learners per group with a total of 18 residents and four medical students. Each group comprised emergency medicine residents at various stages of training and medical students. All 22 learners filled out both the pre-simulation and post-simulation assessments, with one learner leaving the final three knowledge-based questions blank on both assessments.

Comparing the pre-test and post-test results using the Wilcoxon signed ranks test, there was a statistically significant increased comfort level for all differences (p<0.01 for each) (Table 1).

Table 1

Hydroxychloroquine confidence question results.

	Mean (SD)		Median (IQR)		P-value
	Pre	Post	Pre	Post
Q1	2.36 (.902)	3.14 (.889)	2 (2-3)	3 (2-4)	<0.01
Q2	2.27 (1.120)	3.05 (.999)	2 (1-3)	3 (2-4)	<0.01
Q3	2.14 (.990)	3.00 (.976)	2 (1-3)	3 (2-4)	<0.01
Q4	2.18 (.958)	3.05 (.921)	2 (1-3)	3 (2.5-4)	<0.01
Q5	2.09 (.868)	2.82 (.795)	2 (1-3)	3 (2-3)	<0.01

In the hydroxychloroquine knowledge-based post-test, 100% of participants correctly identified diazepam as the antidote of choice for hydroxychloroquine toxicity; 95% correctly chose 10mg/kg as the recognized toxic dose of hydroxychloroquine in a child; 90% correctly chose 30 minutes as the time it takes for symptoms to develop after ingestion of a hydroxychloroquine overdose; 100% identified QT prolongation as the most common EKG abnormality of severe hydroxychloroquine overdose; and finally, 100% identified hypokalemia as the most common electrolyte disturbance found on initial lab work of patients experiencing hydroxychloroquine toxicity. Using the McNemar test for comparison of binomials, there was a statistically significant improvement in knowledge of the antidote to hydroxychloroquine, the toxic dose, and the most common electrolyte anomaly (p<0.01 for each), and time from ingestion to symptoms (p=0.016) (Table 2).

Table 2

Hydroxychloroquine knowledge question results, % correct (95% confidence intervals).

	Pre	Post	P-value
Q1	18% (5-40)	100% (85-100)	<0.01
Q2	18% (5-40)	95% (77-100)	<0.01
Q3	57% (34-78)	90% (70-99)	0.02
Q4	90% (70-99)	100% (84-100)	0.500
Q5	57% (34-78)	100% (84-100)	<0.01
Mean Score	46% (38-55)	95% (88-101)	<0.01

Of the 12 critical actions on the critical action checklist for the hydroxychloroquine case listed in Table 3, all six groups (100%) obtained IV or IO access, utilized the PALS algorithm in resuscitating the patient, admitted the patient to the intensive care unit (ICU), and demonstrated clear communication with the patient and fellow team members. Five groups (83%) recognized the patient’s decompensation to ventricular fibrillation arrest, defibrillated appropriately, and utilized appropriate weight-based dosing for medications, equipment, and interventions. Four groups (67%) performed an initial primary survey, obtained an accurate history of hydroxychloroquine ingestion, obtained an initial EKG and lab studies, placed the patient on a cardiac monitor, and contacted the poison control center for recommendations. Only three groups (50%) promptly recognized the torsades de pointes dysrhythmias and treated the torsades appropriately with magnesium sulfate.

Table 3

Hydroxychloroquine critical action compliance.

Action #	% (95% CI)
1 Perform initial primary survey	67% (22-96)
2 Obtain intravenous or intraosseous access	100% (54-100)
3  Obtain an accurate history to elicit hydroxychloroquine ingestion information from parents	67% (22-96)
4 Obtain an initial electrocardiogram and appropriate lab studies	67% (22-96)
5 Place patient on a cardiac monitor	67% (22-96)
6 Prompt recognition of Torsades dysrhythmia and appropriate treatment with magnesium sulfate	50% (12-88)
7 Utilize pediatric advanced life support algorithm in the resuscitation of the patient, including stabilizing airway, breathing, and circulation	100% (54-100)
8 Recognize patient’s decompensation to ventricular fibrillation arrest and defibrillate appropriately	83% (36-100)
9 Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions	83% (36-100)
10 Contact the poison control center for hydroxychloroquine-specific recommendations on epinephrine drip and high-dose diazepam	67% (22-96)
11 Admit patient to the intensive care unit	100% (54-100)
12 Demonstrate clear communication with patient’s family and with team members	100% (54-100)
Avg	79% (67-91)

The oleander simulation case was similarly performed at our simulation center six times, in groups of two to three learners per group - a total of 13 residents and 1 medical student. Each group was composed of emergency medicine residents at various stages of training and medical students. All 14 learners filled out both the pre-simulation and post-simulation assessments.

In the pre-oleander simulation assessments, the mean confidence level for evaluating accidental toxic plant ingestion in a pediatric patient and the knowledge and ability to manage a pediatric toxidrome were the lowest assessed. The antidote, timing of the toxicity, and the most common rhythm associated with toxidrome were the lowest areas for knowledge assessment. In the post-oleander toxicity simulation assessment, the mean comfort level for evaluating accidental plant ingestion in a pediatric patient was 3.5± 0.86; the mean level of confidence in managing a pediatric dysrhythmia was 3.79 ± 0.7; the mean level of confidence in managing a pediatric pulseless electrical activity was 3.93 ± 0.73; mean level of confidence stabilizing a pediatric patient after achieving the return of spontaneous circulation (ROSC) was 3.5 ± 0.76; and mean level of confidence and knowledge in their ability to manage pediatric toxidromes was 3.36 ± 0.84. Comparing the pre-test and post-test results using the Wilcoxon signed ranks test, there was a statistically significant increased comfort level for all differences (p<0.01) (Table 4).

Table 4

Oleander confidence questions

	Mean (SD)		Median (IQR)		P-value
	Pre	Post	Pre	Post
Q1	2.07 (.917)	3.50 (.855)	2 (1-3)	4 (3-4)	<0.01
Q2	2.79 (.699)	3.79 (.699)	3 (2-3)	4 (3-4)	<0.01
Q3	2.86 (.949)	3.93 (.730)	3 (2-4)	4 (3-4.25)	<0.01
Q4	2.50 (.650)	3.50 (.760)	3 (2-3)	3.5 (3-4)	<0.01
Q5	1.86 (.770)	3.36 (.842)	2 (1-2.25)	3 (3-4)	<0.01

In the knowledge-based post-test of the oleander case in Table 5, 100% of participants correctly identified digoxin immune fab as the antidote of choice for oleander toxicity; 100% correctly chose digitalis as a similar overdose to oleander; 100% correctly chose 2 hours as the time it takes for symptoms to develop after ingestion of oleander; 100% identified atrial fibrillation with bradycardia as the most common EKG abnormality of severe oleander ingestion; and finally, 100% identified hyperkalemia as the most common electrolyte disturbance found on initial lab work of patients experiencing severe oleander toxicity. Using the McNemar test for comparison of binomials, there were statistically significant improvements in knowledge of all but the second question about digitalis being a similar overdose to oleander.

Table 5

Oleander Knowledge question results, % correct (95% Confidence Intervals)

	Pre	Post	p-value
Q1	43% (18-71)	100% (77-100)	<0.01
Q2	79% (49-95)	100% (77-100)	0.25
Q3	14% (2-43)	100% (77-100)	<0.01
Q4	14% (2-43)	100% (77-100)	<0.01
Q5	50% (23-77)	100% (77-100)	0.02
Mean score (95% CI)	40% (24-56)	100%

Of the 12 critical actions on the critical action checklist for the oleander case in Table 6, six groups (100%) performed the initial primary assessment, obtained IV or IO access, obtained an accurate history of oleander ingestion, placed the patient on a cardiac monitor, recognized the patient’s decompensation to pulseless electrical activity, utilized appropriate weight-based dosing for medications, and admitted the patient to the ICU. Five groups (83%) contacted the poison control center for recommendations and demonstrated closed-loop communication with team members. Four groups (67%) obtained an initial EKG and lab studies.

Table 6

Oleander critical action compliance

Action #	% (95% CI)
1  Perform initial primary survey (including assessment of airway, breathing, circulation)	100% (54-100)
2 Obtain intravenous or intraosseous access	100% (54-100)
3 Obtain an accurate history to elicit unknown plant ingestion information from the mother	100% (54-100)
4 Obtain an initial electrocardiogram, radiological and lab studies	67% (22-96)
5 Place patient on a cardiac monitor	100% (54-100)
6 Recognition of atrial fibrillation with bigeminy and appropriate treatment with digibind	33% (4-78)
7 Utilize pediatric advanced life support bradycardia algorithm in the resuscitation of the patient, including stabilizing the airway, breathing, and circulation	33% (4-78)
8 Recognize patient’s decompensation to pulseless electrical activity if no digibind given and begin pediatric advanced life support algorithm	100% (54-100)
9 Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions	100% (54-100)
10 Contact the poison control center for unknown plant ingestion or oleander specific recommendations for digibind	83% (36-100)
11 Admit patient to the intensive care unit	100% (54-100)
12 Demonstrates closed-loop communication with team members	83% (36-100)
Avg	83% (78-89)

Discussion

These cases were designed to teach emergency medicine residents and medical students how to resuscitate a pediatric patient after accidental ingestion of near-fatal doses of hydroxychloroquine or oleander. During the COVID-19 pandemic, hydroxychloroquine experienced a dramatic increase in availability in American households. Unfortunately, many parents and physicians were unaware of the medication’s potentially deadly risk to children who accidentally ingest even a few tablets [1]. Few physicians in the United States have previously cared for patients experiencing hydroxychloroquine toxicity, however, case reports and therapeutic guidelines are fairly well-established in the toxicology literature [4]. Early intubation, cardiovascular support, diazepam administration, epinephrine drips, and careful electrolyte monitoring, have all been described as pivotal measures for physicians to employ early in the process of resuscitating a patient with severe hydroxychloroquine toxicity [2]. While some of these measures are already part of typical resuscitation protocols, others are less commonly considered - especially the administration of diazepam, even in patients who are not actively seizing. This unique therapeutic approach made the creation and execution of this simulation case both timely and important for the learners involved.

To ensure a seamless case flow without overly cumbersome complexity, certain features of hydroxychloroquine toxicity were left out or de-emphasized but discussed during the post-simulation debriefing. For example, the case takes place more than an hour after the child ingested hydroxychloroquine. This timing was chosen to avoid the debate among toxicologists regarding the utility of gastric lavage for patients who present to the emergency department less than one hour after ingestion. Case reports on the subject demonstrate equivocal advice regarding this decision [4]. The child did not experience a seizure even though nearly half of the case reports of severe hydroxychloroquine toxicity involve seizures as a presenting symptom [2]. This decision was made primarily out of time constraints and case-flow concerns, but also to highlight the use of diazepam, even for patients who are not actively seizing. Thirdly, hydroxychloroquine commonly presents with hypokalemia [4]. However, hydroxychloroquine-induced hypokalemia is a temporary condition, transpiring while potassium is driven intracellularly [15]. Theoretically, there is a risk that once the patient stabilizes, the potassium will shift back into the serum, and severe hyperkalemia may result if the potassium has been replaced too aggressively. Case reports are mixed on the subject, as are toxicologists’ recommendations on repletion, so this aspect of the toxicity was avoided. Lastly, the case was intentionally designed to result in cardiac arrest. Even if teams performed optimal resuscitation during the early phase of the simulation, barriers were intentionally placed (such as delayed availability of medications) to ensure that the primary learning objective for the learners - assisting during a pediatric code - was a key component of the simulation.

​​Similarly, oleander ingestion was chosen as the second toxic substance because, at the time of the inception of this case during the COVID-19 pandemic, oleander and oleander extract had also been proposed as having possible curative or preventative properties to COVID-19 [12-13]. Unfortunately, many were unaware of the medication’s potentially deadly risk to children who accidentally ingest the plant, extracts, or teas [6,8]. Few physicians in the United States have previously cared for patients experiencing oleander toxicity, however, case reports and therapeutic guidelines are in the toxicology literature [6-8]. Cardiovascular support, digoxin immune fab administration, and careful electrolyte monitoring have all been described as pivotal measures for physicians to employ early in the process of resuscitating a patient with severe oleander toxicity [6,8].

In each of these two disparate simulation cases, learners demonstrated improvements in their knowledge base regarding the specific details of the respective pediatric toxidrome management. Learners also demonstrated improved confidence scores in all categories - confidence in evaluating a pediatric drug overdose, managing a pediatric cardiac dysrhythmia, managing a pediatric code, stabilizing a pediatric patient after ROSC, and managing pediatric toxidromes overall. Some learners with the lowest initial pre-simulation confidence scores reported some of the largest increases in post-simulation confidence. This may be a result of more inexperienced learners, with a lack of initial exposure to pediatric resuscitations overall, or certainly lack of exposure to these rare toxidromes, suddenly receiving a surge of information and confidence on these relevant topics. On knowledge and confidence assessments some statistically significant increases were seen, most learners ended up with an average of “3,” which equates to neutral on the scale. Since we attempted to balance teams by training level it is unclear why some performed more critical actions than others. We were unable to discern a pattern in why some groups performed better than others in the simulation.

Limitations

Perhaps ironically, the inspiration for these cases, the COVID-19 pandemic, was the biggest barrier to the implementation of the simulation. The pediatric emergency department made the decision to postpone in-situ simulations because of concern for an excess number of people congregating at the same time in a confined area. As a result, the cases were executed in a simulation lab with emergency medicine residents and medical students.

In addition, as described in the discussion section, we did not study long-term knowledge retention as part of our study. It is possible that, while short-term knowledge gains were identified, over time, that knowledge base will wane. Ideally, even if learners do not recall specifics of the case management, they will retain basic tenets, such as obtaining as much collateral information from patients and their families as possible, calling poison control for help in managing potential intoxications, and being careful when determining age-appropriate dosages and equipment sizes during pediatric resuscitations.

Lastly, both cases were intentionally designed to result in pulseless arrest. Even if teams performed optimal resuscitation during the early phases of the simulations, barriers may be intentionally placed (such as delayed availability of medications) to ensure that one of the primary learning objectives, managing a pediatric code, was a key component of the simulations.

Conclusions

This simulation case series was developed to educate emergency physicians about the management of overdoses from popularized COVID-19 therapies. The oleander and hydroxychloroquine pediatric toxicity cases are easily performed using commonly available simulation materials. Simulation is the ideal methodology for increasing learner knowledge, skills, and attitudes about low-frequency high-risk cases such as pediatric overdoses.

Table 7

Pediatric hydroxychloroquine ingestion simulation case

PATIENT NAME: Alex   PATIENT AGE: 4 years old   PATIENT WEIGHT: 15 kg   CHIEF COMPLAINT: “Nausea & Vomiting”
Brief narrative description of the case	Alex is a 4-year-old male with no past medical history who complained to his parents that he was feeling “yucky” before vomiting. When his mother went to the bathroom to grab a thermometer, she noticed her hydroxychloroquine tablets were spilled out on the counter, prompting her to bring Alex straight to the Emergency Department. (ED) Upon initial evaluation in the ED, Alex is mildly tachycardic, but their vitals are otherwise stable. Initial lab values are normal, while the EKG demonstrates QT prolongation. Shortly thereafter, Alex becomes unresponsive and goes into a Torsades dysrhythmia. Anticipated interventions include primary and secondary surveys, establishing IV access, placing the patient on a cardiac monitor, recognizing the changes in the patient condition, including the dysrhythmia and eventual ventricular fibrillation arrest, and treating per Pediatric advanced life support (PALS) algorithms, including securing his airway and evaluating his breathing and circulation, defibrillation, administering appropriate medications, stabilizing the patient hemodynamically, obtaining appropriate laboratory values and electrocardiogram (EKG), and calling various consultants.
Primary Learning Objectives	By the end of this module, the learner will be able to: Demonstrate a systematic approach to the evaluation and management of a pediatric toxic ingestion Describe the signs and symptoms of hydroxychloroquine intoxication in a pediatric patient Demonstrate competence in pediatric resuscitation protocols
Critical Actions	Perform initial primary survey  Obtain intravenous or intraosseous (IV/IO) access Obtain an accurate history to elicit hydroxychloroquine ingestion information from parents Obtain an initial EKG and appropriate lab studies Place patient on a cardiac monitor Prompt recognition of Torsades dysrhythmia and appropriate treatment with magnesium sulfate Utilize PALS algorithm in the resuscitation of the patient, including stabilizing airway, breathing, and circulation Recognize patient’s decompensation to ventricular fibrillation arrest and defibrillate appropriately Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions Contact the poison control center for hydroxychloroquine-specific recommendations on epinephrine drip and high-dose diazepam Admit patient to ICU Demonstrate clear communication with the patient’s family and with team members
Learner Preparation	General knowledge of toxidromes and pediatric emergency medicine PALS course competency

Table 8

Pediatric toxicology hydroxychloroquine overdose simulation

ROSC: Return of spontaneous circulation 

Pre-Simulation

Post-Simulation

Table 9

Pediatric oleander ingestion simulation case

PATIENT NAME: Caleb   PATIENT AGE: 3 years old   PATIENT WEIGHT: 13 kg   CHIEF COMPLAINT: “Nausea, Vomiting and Diarrhea”
Brief narrative description of case	Caleb is a 3-year-old male with history of autism spectrum disorder who reports nausea, vomiting, and diarrhea. He also reports a funny feeling in his chest and a change in his vision. He was unsupervised in the backyard and may have ingested some seeds from their bushes. His mother reported he did not have any symptoms until about an hour ago. Upon initial evaluation Caleb is tachycardic and normotensive. Initial labs show hyperkalemia and the initial EKG shows atrial fibrillation with ventricular bigeminy. The case progresses to atrial fibrillation with a slowed ventricular response with bradycardia. The case will require primary and secondary surveys, establishing intravenous (IV) access, continuous cardiopulmonary monitoring, and recognition and management of the toxidrome of oleander. Critical actions will include securing an airway. Treatment PALS algorithm for pediatric bradycardia and then pediatric asystole.   Anticipated interventions include primary and secondary surveys, establishing IV access, placing patient on a cardiac monitor, recognizing the changes in patient condition, including the dysrhythmia and eventual pulseless electrical activity arrest if treatment with digoxin immune fab is delayed.     Treatment will include securing his airway and evaluating his breathing and circulation, administering appropriate medications including digoxin immune fab. There will be an expectation to obtain appropriate laboratory values and EKG, and calling various consultants including poison center and intensive care unit.
Primary learning objectives	By the end of this module, the learner will be able to: Describe the signs, symptoms, and treatment of oleander intoxication in a pediatric patient Demonstrate a systematic approach to the evaluation and management of pediatric toxic ingestion Demonstrate competence in pediatric bradycardia pulseless electrical activity and/or asystole management
Critical actions	Perform initial primary survey (including ABCDE, GCS) Obtain IV or intraosseous (IO) access Obtain an accurate history to elicit unknown plant ingestion information from mother, then obtain plant type from father Obtain an initial EKG and appropriate lab studies Place patient on a cardiac monitor Prompt recognition of digitalis-like effect and dysrhythmia of atrial fibrillation with bigeminy and appropriate treatment with digoxin immune fab if recognized Utilize pediatric advanced life support (PALS) algorithm in resuscitation of patient, including stabilizing airway, breathing and circulation Recognize patient’s decompensation to pulseless electrical activity/ asystole arrest and treat appropriately while searching for reversible cause Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions Contact the poison control center for oleander-specific recommendations including digoxin immune fab dosing Admit patient to ICU Demonstrate closed loop communication with patient’s family and with team members
Learner preparation	General knowledge of toxidromes and pediatric emergency medicine PALS course competency

Table 10

Knowledge assessment (select one answer for each question)

Question	Possible Answers
1. Which medication is administered as an antidote in patients experiencing serious adverse effects of hydroxychloroquine toxicity?	a. Haloperidol b. Diazepam c. Lorazepam  d. Midazolam
2. Without medical intervention, what is the commonly accepted toxic dose of hydroxychloroquine in a child?	a. 1mg/kg b. 5mg/kg c. 10mg/kg d. 50mg/kg
3. From time of ingestion, how long does it take for symptoms to appear in a severe hydroxychloroquine overdose?	a. 15 minutes b. 30 minutes c. 2 hours d. 6 hours
4. What is the most common abnormality seen on EKG with severe hydroxychloroquine overdose?	a. QT prolongation b. Supraventricular Tachycardia c. Ventricular Fibrillation d. Sinus Bradycardia
5. What is the most common electrolyte disturbance found on initial lab work in patients with hydroxychloroquine toxicity?	a. Hypocalcemia b. Hyponatremia c. Hypomagnesemia d. Hypokalemia
Answers:	1. b           2. c        3.b            4.a           5.d

Table 11

Knowledge assessment for oleander case (select one answer for each question)

Question	Answers
Which medication is administered as an antidote in patients experiencing serious adverse effects of oleander toxicity?	Midazolam Haloperidol Carnitine Digoxin Immune Fab (Digibind)
What unintentional overdose is oleander most likely to resemble?	topiramate valproic acid digitalis metoprolol
From time of ingestion, how long does it take for symptoms to appear in an oleander ingestion?	5 minutes 30 minutes 2 hours 72 hours
What is the most common abnormality seen on EKG with severe oleander overdose?	QT prolongation Atrial fibrillation with bradycardia Ventricular Fibrillation Sinus Bradycardia
5.What is the most common electrolyte disturbance found on initial lab work in patients with oleander toxicity?	a. Hypokalemia b. Hyponatremia c.Hypocalcemia d. Hyperkalemia
Answers:	d c c b 5. d

Table 12

Hydroxychloroquine critical actions checklist

ABCDE: Airway, Breathing, Circulation, Disability, Exposure; GCS: Glasgow Coma Scale; IV: Intravenous; IO: interosseous; PALS: Pediatric Advanced Life Support; 

Critical Actions	Performed Completely	Not Performed/Incomplete
Perform initial primary survey (including ABCDE, GCS)
Obtain IV/IO access
Obtain an accurate history to elicit hydroxychloroquine ingestion information from parents
Obtain an initial EKG and appropriate lab studies
Place patient on a cardiac monitor
Prompt recognition of Torsades dysrhythmia and appropriate treatment with magnesium sulfate
Utilize PALS algorithm in resuscitation of patient, including stabilizing airway, breathing and circulation
Recognize patient’s decompensation to ventricular fibrillation arrest and defibrillate appropriately
Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions
Contact the poison control center for hydroxychloroquine-specific recommendations on epinephrine drip and high-dose diazepam
Admit patient to intensive care unit
Demonstrate clear communication with patient’s family and with team members

Table 13

Pediatric toxicology oleander overdose assessment

Pre-Simulation

Post-Simulation

Table 14

Oleander simulation critical actions checklist

IV: Intravenous; IO: Interossessous 

Critical Actions	Performed Completely	Not Performed/Incomplete
Perform initial primary survey (including assessment of airway, breathing, circulation, disability, and exposure of the patient, glucose)
Obtain IV/IO access
Obtain an accurate history to elicit unknown plant ingestion information from mother
Obtain an initial EKG, radiological and lab studies
Place patient on a cardiac monitor
Recognition of atrial fibrillation with bigeminy and appropriate treatment with digibind
Utilize PALS bradycardia algorithm in resuscitation of patient, including stabilizing airway, breathing and circulation
Recognize patient’s decompensation to pulseless electrical activity if no digibind given and begin PALS algorithm
Utilize appropriate pediatric weight-based dosing for medications, equipment, and interventions
Contact the poison control center for unknown plant ingestion or oleander specific recommendations for digibind
Admit patient to intensive care unit
Demonstrates closed loop communication with team members