References

1. Breitkreutz R, Price S, Steiger HV, Seeger FH, Ilper H, Ackermann H, et al. Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial. Resuscitation 2010;81:1527-33. https://doi.org/10. 1016/j.resuscitation.2010.07.013.
2. Bossone E, LaBounty TM, Eagle KA. acute aortic syndromes: diagnosis and manage- ment, an update. Eur Heart J 2018;39:739-749d. https://doi.org/10.1093/eurheartj/ ehx319.
3. Evangelista A, Isselbacher EM, Bossone E, Gleason TG, Eusanio MD, Sechtem U, et al. Insights from the International Registry of Acute Aortic Dissection: a 20-year expe- rience of collaborative clinical research. Circulation 2018;137:1846-60. https://doi. org/10.1161/CIRCULATIONAHA.117.031264.
4. Kim YW, Jung WJ, Cha KC, Roh YI, Kim YS, Kim OH, et al. Diagnosis of aortic dissec- tion by transesophageal echocardiography during cardiopulmonary resuscitation. Am J Emerg Med 2020. https://doi.org/10.1016/j.ajem.2020.01.026.
5. Via G, Hussain A, Wells M, Reardon R, ElBarbary M, Noble VE, et al. International evidence-based recommendations for focused cardiac ultrasound. J Am Soc Echocardiogr 2014;27:683.e1-683.e33. https://doi.org/10.1016/j.echo.2014.05.001.
6. Breitkreutz R, Walcher F, Seeger FH. Focused echocardiographic evaluation in resus- citation management: concept of an advanced life support-conformed algorithm. Crit Care Med 2007;35:S150-61. https://doi.org/10.1097/01.CCM.0000260626. 23848.FC.
7. Goldstein SA, Evangelista A, Abbara S, Arai A, Asch FM, Badano LP, et al. Multimodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovas- cular Imaging: endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2015; 28:119-82. https://doi.org/10.1016/j.echo.2014.11.015.
8. Hahn RT, Abraham T, Adams MS, Bruce CJ, Glas KE, Lang RM, et al. Guidelines for

performing a comprehensive transesophageal Echocardiographic examination: rec- ommendations from the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists. J Am Soc Echocardiogr 2013;26:921-64. https:// doi.org/10.1016/j.echo.2013.07.009.

1. Nakao S, Eguchi T, Ikeda S, Nagata A, Nishizawa N, Shingu K. Airway obstruction by a transesophageal echocardiography probe in an adult patient with a dissecting aneu- rysm of the Ascending aorta and arch. J Cardiothorac Vasc Anesth 2000;14:186-7. https://doi.org/10.1016/s1053-0770(00)90016-8.
2. Kim CM, Yu SC, Hong SJ. Cardiac tamponade during transesophageal echocardiogra- phy in the patient of circumferential aortic dissection. J Korean Med Sci 1997;12: 266-8. https://doi.org/10.3346/jkms.1997.12.3.266.
3. Dalby Kristensen S, Ramlov Ivarsen H, Egeblad H. Rupture of aortic dissection during attempted transesophageal echocardiography. Echocardiography 1996;13:405-6. https://doi.org/10.1111/j.1540-8175.1996.tb00912.x.

Protocol deviations in intravenous acetylcysteine therapy for acetaminophen toxicity

To the Editor:

Hepatotoxicity secondary to acetaminophen overdose can be prevented with intravenous n-acetylcysteine (IV N-AC). The dosing schedule of IV N-AC is somewhat complex, consisting of a 21-hour reg- imen of three varying doses and infusion rates [1,2]. As a result, dosing and infusion-related errors may occur. We investigated the frequency of infusion-related errors associated with IV N-AC in the treatment of acetaminophen toxicity, and we sought to determine if protocol devia- tions had an impact on clinical outcomes.

Our study entailed a retrospective chart review of patients who were hospitalized at an academic, level I trauma center from June 2006 through May 2012. Patients were included if IV N-AC was administered for suspected, acute, or chronic acetaminophen toxicity. The definition for administration errors was adapted and modified from previously conducted studies [3-5] (Table 1).

Of the 93 patients who met inclusion criteria, 86 (93%) patients pre- sented with suspected, acute, or chronic toxicity (Table 2). 79 administra- tion errors were observed in 49 (53%) cases. The most commonly observed protocol deviations were interruption of the infusion for N30 min and deviation in the rate of the third dose by at least 10% (Fig. 1). In 19 patients, N60 min elapsed between Order entry and infusion initia- tion. Administration errors were not found to correlate with the incidence of hepatotoxicity or coagulopathy. However, administration errors were

more likely to occur in those patients who received the infusion beyond 21 h (p = 0.0147) (Table 3). In addition, protocol deviations were found to be associated with prolonged length of stay, independent of the initial acetaminophen concentration, presence of co-ingestants, and discharge status (p = 0.0227). In a subgroup of patients whose hospital length of stay exceeded one week, 72% had administration errors with the antidote. These results are replicable to other investigations of errors associated with IV N-AC in the treatment of acetaminophen toxicity [3-6]. However, in our investigation, errors associated with the antidote were found to in- fluence length of hospital stay. Although it may not be clearly defined as to whether delays in administration of the antidote may lead to hepato- toxicity, it has been suggested that delays of 1 h or more may be signifi-

cant, as the elimination half-life of IV N-AC is 5.7 h [3].

Deviations in the rate of infusion of the antidote accounted for over 40% of the total errors observed in this study. Investigators of other studies have advocated for a modified and simplified method of preparation and administration of IV N-AC through the use of one- or two-bag infusions as opposed to the three-bag method currently approved by the FDA [4,7-9]. These alternative strategies may not only theoretically minimize the risk of errors re- lated to administration of IV N-AC, but may also mitigate the inci- dence of some of the adverse effects associated with the antidote.

The dosing weight used as a means to calculate the doses re- quired for administration of the three-part regimen of IV N-AC was erroneous by at least 10% of the actual patient weight in nearly 15% of patients. An order sentence is available within our institu- tional electronic health record for prescribing the antidote. In other investigations, the use of weight-based dosing charts for the antidote reduced the rate of prescribing errors associated with IV N-AC for acetaminophen toxicity [10,11]. Another evalua- tion by demonstrated that computerized prescriber order entry can reduce prescribing errors of IV N-AC [12]. However, estimation of weight and incorrect unit conversion related to units of measure (pounds versus kilograms) may serve as contributors to errors in dosing weight used for many medications in general, even in the presence of institution-wide computerized prescriber order entry [13].

Several publications have highlighted the valuable roles of pharmacists in the emergency department [14,15]. In the case of IV N-AC administration for the management of acetaminophen toxicity, emergency medicine pharmacists can have various func- tions in optimizing treatment and minimizing the incidence of pro- tocol deviations associated with administration of the antidote, including verification of patient weight prior to prescribing and entry of the order within the electronic health record; facilitation of the preparation and administration of the antidote, including bedside confirmation of the dosing program within the electronic infusion pump; monitoring of the efficacy and safety of administra- tion of the antidote; and determination of whether continuation of the infusion of the antidote is warranted based on patient-specific parameters.

This is the first study to provide a comprehensive overview of the frequency of protocol deviations associated with administration of IV N-AC and its influence on patient-oriented outcomes. Protocol devia- tions associated with IV N-AC for the management of acetaminophen toxicity occurred in nearly one-half of all cases, which was associated with prolonged length of hospital stay. The presence of emergency medicine pharmacists and alternative and simplified methods for ex- temporaneous preparation and administration of the antidote may be beneficial to minimize the incidence of errors.

Declaration of competing interest

The investigators have no financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this manuscript.

Appendix A

Table 1

Definition of administration error. (Adapted from previous studies [3-5]).

1. Failure to order loading, second, or third doses
2. Deviation in loading dose by at 10% (+- 15 mg/kg)
3. Deviation in second dose by 10% (+- 5 mg/kg)
4. Deviation in third dose by 10% (+- 10 mg/kg)
5. Deviation in rate of infusion of loading dose by 10% (+-6 min)
6. Deviation in rate of infusion of second dose by 10% (+-24 min)
7. Deviation in rate of infusion of third dose by 10% (+-96 min)
8. Interruption in the infusion for greater than 30 min
9. Continuation of the infusion beyond the recommended 21 h with no evidence of elevated Liver enzymes or detectable acetaminophen levels

Table 2

Patient demographics.

Baseline characteristics (N = 93) Age (years)

Median (range) 35 (21-69)

Gender, n (%)

Female 59 (63.4)

Male 34 (36.6)

Race, n (%)

Caucasian 69 (74.2)

Non-Caucasian 24 (25.8)

Weight (kg)

Median (range) 75 (45-150)

Length of stay (days)

Median (range) 4 (1-65)

Type of ingestion, n (%)

Suspected, acute, or chronic toxicity 86 (92.5)

Elevated liver enzymes of unknown etiology 7 (7.5)

Co-ingestants, n (%)

Acetaminophen only 27 (29.0)

Other co-ingestants present 66 (71.0)

Time elapsed from ingestion to presentation, n (%)

Unknown	49 (52.7)
Under 4 h	21 (22.6)
Under 8 h	29 (31.2)
>=8h	15 (16.1)
Presence of expert consultation, n (%) toxicology service	51 (54.8)
Poison control center	25 (26.9)
None	17 (18.3)
patient location during infusion of IV N-AC, n (%)
Emergency department and Inpatient unit	45 (48.4)
Emergency department	38 (40.9)
Inpatient unit	10 (10.8)
Discharge status, n (%) Discharged	42 (45.2)
Transferred to psychiatric facility	41 (44.1)
Left against medical advice	4 (4.3)
Transferred for evaluation of liver transplantation	4 (4.3)
Other	2 (2.2)

Table 3

Administration errors and clinical outcomes.

Parameters	No errors	Errors	p-Value
Initial acetaminophen level
Mean +- SD (mcg/mL)	73.64 +- 123.72	103.49 +- 127.29	0.4266
Presence of co-ingestants
Acetaminophen only	9	18	0.0733
Co-ingestants	32	27
Discharge status
Discharged	23	19	0.4248
Psychiatric facility	17	24
Other	4	6
Hepatotoxicity Aminotransferase b1000 IU/L	41	39	0.0606
Aminotransferase >=1000 IU/L	3	10
Coagulopathy
INR b 2	35	35	0.0753
INR >= 2	3	10
Duration of infusion 21 h	37	30	0.0147
N21 h	7	19
Length of stay
0 to 2 days	12	7	0.0227
3 to 6 days	23	19
N7 days	9	23

Fig. 1. Administration errors associated with IV N-AC infusion (n = 79).

Nadia I. Awad PharmD, MS, BCPS

Department of Pharmacy, Robert Wood Johnson University Hospital, New

Brunswick, NJ, United States of America Corresponding author at: Department of Pharmacy, 1 RobertWood Johnson Place, New Brunswick, NJ 08901, United States of America.

E-mail address: [email protected]

Patrick J. Bridgeman PharmD, BCPS

Department of Pharmacy, Robert Wood Johnson University Hospital, New

Brunswick, NJ, United States of America Department of Pharmacy Practice and Administration, ErnestMario School of Pharmacy at Rutgers, The State University of New Jersey, Piscataway, NJ,

United States of America

Ann-Jeannette Geib MD, FACEP, FACMT

Department of Emergency Medicine, Carolinas Medical Center, Charlotte,

NC, United States of America

https://doi.org/10.1016/j.ajem.2019.158405

25 July 2019

Akshay Roy DO

Department of Anesthesiology, Jefferson Health, Philadelphia, PA, United

States of America

Craig Cocchio PharmD, BCPS

Department of Pharmacy, CHRISTUS TrinityMother Frances Hospital, Tyler,

TX, United States of America

References

1. Acetadote (N-acetylcysteine) [package insert]. Nashville, TN: Cumberland Pharma- ceuticals, Inc.; 2016.
2. Klein-Schwartz W, Doyon S. Intravenous acetylcysteine for the treatment of acet- aminophen overdose. Expert Opin Pharmacother 2011;12:119-30.
3. Hayes BD, Klein-Schwartz W, Doyon S. Frequency of Medication errors with intrave- nous acetylcysteine for acetaminophen overdose. Ann Pharmacother 2008;42: 766-70.
4. Johnson MT, McCammon CA, Mullins ME, et al. Evaluation of a simplified n- acetylcysteine dosing regimen for the treatment of acetaminophen toxicity. Ann Pharmacother 2011;45:713-20.
5. Zyoud DH, Awang R, Sulaiman SA, et al. Effects of delay in infusion of n- acetylcysteine on appearance of Adverse drug reactions after acetaminophen over- dose: a retrospective study. Pharmacoepidemiol Drug Saf 2010;19:1064-70.
6. Bailey GP, Najafi J, Elamin ME, et al. Delays in the administration of acetylcysteine for the treatment of paracetamol overdose. Br J Clin Pharmacol 2016;82:1358-63.
7. Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of ad- verse Drug reactions. Clin Toxicol 2016;54:115-9.
8. McNulty R, Lim JME, Chandru P, et al. Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose. Clin Toxicol 2018;56:618-21.
9. Schmidt LE, Rasmussen DN, Petersen TS, et al. Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared to traditional three-bag regimen in paracetamol overdose. Clin Toxicol (Phila) 2018 Nov;56(11): 1128-34 [Epub ahead of print].
10. Selvan V, Calvert SH, Gavell G, et al. Weight-based n-acetylcysteine dosing chart to minimize the risk of calculation errors in prescribing and preparing n-acetylcysteine infusions for adults presenting with paracetamol overdose in the emergency depart- ment. Emerg Med J 2007;24:482-4.
11. McIntyre S, McD Taylor D, Greene S. Introduction of an N-acetylcysteine weight-

based dosing chart reduced prescription errors in the treatment of paracetamol poi- soning. Emerg Med Australas 2013;25:28-35.

1. Thompson TM, Lu JJ, Blackwood L, et al. Computerized N-acetylcysteine physician order entry by template protocol for acetaminophen toxicity. Am J Ther 2011;18: 107-9.
2. Flentje KM, Knight CL, Stromfeldt I, et al. Recording patient body weight in hospitals: are we doing well enough? Intern Med J 2018;48:124-8.
3. Morgan SR, Acquisto NM, Coralic Z, et al. clinical pharmacy services in the emer- gency department. Am J Emerg Med 2018;36:1727-32.
4. Farmer BM, Hayes BD, Rao R, et al. The role of clinical pharmacists in the emergency

department. J Med Toxicol 2018;14:114-6.

In-Situ simulation for enhancing teamwork in the emergency department

medical professionals working in the emergency department (ED), a high-stress/high-acuity environment, often deviate from clinical guide- lines and policies despite knowing of their existence [1]. Therefore, sim- ulation-based learning activities are often used in the ED to improve communication and teamwork and familiarize ED personnel with existing protocols [2]. Prior to implementing this project, a needs as- sessment for ED simulation was conducted by the authors which showed a significant Perceived knowledge gap among personnel in

(1) adherence to ED guidelines, (2) inter-team communication and

(3) dealing with difficult families. Respondents agreed unanimously to shift from traditional didactic teaching to integrated simulation-based learning [3]. SimZones is an innovative approach to simulation-based learning encompassing 0-4 zones targeted to different learner groups and goals [4]. SimZone 3 describes a simulation for double loop learning for team and system development followed by expert facilitator-led debriefing; the latter is meant to discover the assumptions and values guiding team behavior [5-7]. To address the identified gaps in our ED, the authors developed standardized in-situ simulations within the pa- rameters of SimZone 3.

The initiative was reviewed and approved by the Institutional Re- view Board (IRB) of the hospital as a quality improvement educational intervention. Seven scenarios were developed by the authors based on

Abbreviations: ACLS, Advanced Cardiac Life Support; CRM, Crisis Resource management; Ddx, Differential diagnosis; ED, Emergency Department; HFS, High Fidelity Simulation; IO, Intraosseous; IVF, Intrave- nous fluids; MVA, Motor vehicle accident; PALS, pediatric advanced life support; SAMPLE, Sign/symptoms, allergies, medications, past illness, last meal and events preceding; SBT/SBL, Simulationbased Training/

existing ED guidelines and protocols (Table 1). They were piloted and refined in the simulation laboratory prior to the in-situ intervention. Each team composed of 3-5 participants (N = 46 ED personnel) was in- volved in 2 simulation interventions 2 weeks apart between March 2017-February 2018; each simulation followed by a debriefing with good judgement [8]. To counteract the inherent bias of the pre-post study design, simulation I participants were considered their own con- trol when compared to Simulation II. All simulations and debriefings were video recorded for analysis and review.

The primary measure for team performance was the Simulation Team Assessment Tool (STAT) Score [9]. The STAT includes assessment of basic, airway, circulation, and teamwork skills. Each item is measured on a scale of 2-0 based on the timely completion of 94 tasks. For the pur- poses of this study, 17 tasks concerning cardiopulmonary resuscitation (CPR) and arrhythmias were removed, for a total adapted STAT¹ score of 171. Two of the investigators assessed the team immediately follow- ing the simulation (preliminary Cronbach ? 0.74); interrater disagree- ments were resolved by a review of the simulation videos and a second evaluation (Cronbach ? 0.90). The secondary measure was a post-intervention survey on participants’ experience and their willing- ness to partake in future simulations.

Quantitative data was analyzed using the Statistical Package for So- cial Sciences (SPSS) (IBM Corp). Reliability analyses were performed for overall and domain scores. Paired T-tests were used to analyze dif- ferences of team performance scores; Independent T-tests were used to analyze for differences between pediatric and adult scenarios. Forty-six ED personnel participated in the simulations (28 residents, 12 nurses, 6 attendings). Overall STAT scores improved significantly be- tween simulation I (60.5 (28.3)) and II (81.1 (24.6)) (p. 029) (Table 2);

notably in basic skills from a score of 11.8 (5.15) to 16.5 (3.9) (p. 022)

and teamwork from 20.3 (11.9) to 30.9 (13.7) (p 023). In the airway and circulation domains, scores improved between simulation I and II, albeit not significantly. A sub-analysis showed that participants per- formed significantly better overall when treating adult versus pediatric simulated patients (p. 003), particularly in teamwork (p. 01).

Personnel performance scores in basic skills, airway management and teamwork were successfully increased. Participants noted the inter- vention’s relevance/realism and asked for more future in-situ simula- tions. In-situ simulation succeeded in translating participant knowledge into practice. Future scheduled scenarios and deliberate and just-in-time practice [10] will help mitigate knowledge and avoid skills decay. The discrepancy of care for adult vs. pediatric simulated cases and participants’ lack of knowledge of established ED protocols highlight areas requiring future interventional initiatives.

Juggling high-quality learning and patient care in the ED can be challenging. Implementing new teachings and methodologies should be valued, yet it is met with skepticism. Allocating human and space resources to educational/quality improvement initiatives raises an ethical dilemma by diverting the focus away from treating actual patients.

The project yielded significant improvement between simulation I and II in clinical management, teamwork and resource management skills among ED personnel; participants are willing and eager to partake in similar in-situ simulation exercises. A recurrent program will be help- ful in reviewing and reaffirming ED protocols and guidelines, as well as improving participants’ teamwork and communication skills.

Acknowledgement

We would like to thank the administration of the emergency depart- ment for their constant support, especially Ms. Rima Jabbour and Mr. Samer Al-Halabi. We also wish to thank Ms. Aurelie Mailhac, MS from the Clinical Research Institute who provided valuable statistical input.

Simulation-based Learning; STAT, Simulation Team Assessment

Tool; STEMI, ST-elevation myocardial infarction 1 see Supplementary File for the STAT Adapted.