Precise determination of phenobarbital levels may delay patient-centred care in severe poisoning Timothy C Backus 1, Philip C DiSalvo 1, Emma Furlano 1, Kham Ali 2, William K Chiang 1, Josh J Wang 1 1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States Background: Results: Hemodialysis is indicated in severe Roche Cobas 6000 c501 o 27 of 52 hospitals responded (52%) phenobarbital poisoning, as defined by a o 20 could measure serum phenobarbital combination of clinical status and high Roche Cobas 6000 c501 onsite phenobarbital concentrations[1]. Very
11 hospitals reported maximum pre occasionally, dialysis may be indicated based Roche Cobas 6000 c501 dilution concentrations ≤60mg/L on concentration alone. Thus, it is essential
1 reported ≤70mg/L that toxicologists and poison specialists Roche Cobas 8000 c502
1 reported ≤72mg/L understand the laboratory capabilities of their
7 reported ≤80mg/L referral institutions in order to provide optimal Roche Cobas 6000 c501 o 15 of 20 hospitals performed dilutions on treatment recommendations. Our goal was to specimens with phenobarbital assess how phenobarbital was measured and Roche Cobas 6000 c501 concentrations greater than their assay’s reported by hospital laboratories in a large predilution maxima metropolitan area covered by a regional Roche Cobas 8000 c502
8 used the automatic dilution function of poison center. their analyzers Roche Cobas 8000 c502
7 manually diluted specimens to obtain Methods: concentrations We surveyed hospital laboratories within the Roche Cobas 6000 c501
5 hospitals did not dilute despite catchment area of a regional poison center to manufacturer recommendations gather the following data on how they Roche Cobas 8000 c502 • 1 did not dilute because the approach high serum [phenobarbital]: analyzer manufacturer recommendation is to details (brand, model), highest reported pre Roche Cobas 8000 c502 perform manual dilutions which dilution [phenobarbital], dilution protocols, created an unacceptable opportunity highest postdilution [phenobarbital], and Siemens Atellica for human error presence or absence of inpatient dialysis • 1 reported that 60 mg/L was sufficient services. We compared these data to Abbott Architect c8000 for patient care analyzerspecific protocols obtained directly • 3 did not provide an explanation. from the manufacturer. Where there were Beckman Coulter DxC860i deviations from manufacturer protocol, we Conclusion: contacted the laboratory director for an Abbott Architect C8000 Dialysis is not indicated as firstline therapy in explanation. phenobarbital toxicity, and the [phenobarbital] Siemens XPT * only plays a role in the face of failure of supportive care[1]. Obtaining the precise Siemens Dimension Vista 1500 * [phenobarbital] is not necessary to guide poison center recommendations. There are Siemens Dimension Vista 1500 * several limitations of this study. This study is not designed to assess the impact on poison References: Siemens Dimension Vista 1500 * center recommendations based on high 1. Mactier R, Laliberte M, Mardini J, et al. [phenobarbital. Also, compliance with the Extracorporeal treatment for barbiturate poisoning: stated laboratory protocol is not investigated. recommendations from the EXTRIP Workgroup. Am J Beckman Coulter DXC600i * Kidney Dis 2014;64:347-358 Future research should examine how variable lab practices impact patientrelevant outcomes 0 40 80 120 160 in phenobarbital poisoning. Phenobarbital reporting limits from 21 hospitals. Analyzer brand and model are noted on the yaxis. Hospitals without orange bars did not perform dilutions. Units are mg/L. * indicates that the hospital could report a postdilution phenobarbital concentration >160 mg/L. Precise determination of phenobarbital levels may delay patient-centred care in severe poisoning Timothy C Backus1, Philip C DiSalvo1, Emma Furlano1, Kham Ali2, William K Chiang1, Josh J Wang1 1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States Background: Results: Hemodialysis is indicated in severe Roche Cobas 6000 c501 o 27 of 52 hospitals responded (52%) phenobarbital poisoning, as defined by a o 20 could measure serum phenobarbital combination of clinical status and high on-site phenobarbital concentrations[1]. Very Roche Cobas 6000 c501  11 hospitals reported maximum pre- occasionally, dialysis may be indicated based dilution concentrations ≤60mg/L on concentration alone. Thus, it is essential Roche Cobas 6000 c501  1 reported ≤70mg/L that toxicologists and poison specialists Roche Cobas 8000 c502  1 reported ≤72mg/L understand the laboratory capabilities of their  7 reported ≤80mg/L referral institutions in order to provide optimal Roche Cobas 6000 c501 o 15 of 20 hospitals performed dilutions on treatment recommendations. Our goal was to specimens with phenobarbital assess how phenobarbital was measured and Roche Cobas 6000 c501 concentrations greater than their assay’s reported by hospital laboratories in a large pre-dilution maxima metropolitan area covered by a regional Roche Cobas 8000 c502  8 used the automatic dilution function of poison center. their analyzers Roche Cobas 8000 c502  7 manually diluted specimens to obtain Methods: concentrations We surveyed hospital laboratories within the Roche Cobas 6000 c501  5 hospitals did not dilute despite catchment area of a regional poison center to manufacturer recommendations gather the following data on how they Roche Cobas 8000 c502 • 1 did not dilute because the approach high serum [phenobarbital]: analyzer manufacturer recommendation is to details (brand, model), highest reported pre- Roche Cobas 8000 c502 perform manual dilutions which dilution [phenobarbital], dilution protocols, created an unacceptable opportunity highest post-dilution [phenobarbital], and Siemens Atellica for human error presence or absence of inpatient dialysis • 1 reported that 60 mg/L was sufficient services. We compared these data to Abbott Architect c8000 for patient care analyzer-specific protocols obtained directly • 3 did not provide an explanation. from the manufacturer. Where there were Beckman Coulter DxC860i deviations from manufacturer protocol, we Conclusion: contacted the laboratory director for an Abbott Architect C8000 Dialysis is not indicated as first-line therapy in explanation. phenobarbital toxicity, and the [phenobarbital] Siemens XPT * only plays a role in the face of failure of supportive care[1]. Obtaining the precise Siemens Dimension Vista 1500 * [phenobarbital] is not necessary to guide poison center recommendations. There are Siemens Dimension Vista 1500 * several limitations of this study. This study is not designed to assess the impact on poison References: Siemens Dimension Vista 1500 * center recommendations based on high 1. Mactier R, Laliberte M, Mardini J, et al. [phenobarbital. Also, compliance with the Extracorporeal treatment for barbiturate poisoning: stated laboratory protocol is not investigated. recommendations from the EXTRIP Workgroup. Am J Beckman Coulter DXC600i * Kidney Dis 2014;64:347-358 Future research should examine how variable lab practices impact patient-relevant outcomes 0 40 80 120 160 in phenobarbital poisoning. Phenobarbital reporting limits from 21 hospitals. Analyzer brand and model are noted on the y-axis. Hospitals without orange bars did not perform dilutions. Units are mg/L. * indicates that the hospital could report a post-dilution phenobarbital concentration >160 mg/L. Valproic acid reporting cutoffs impact poison control recommendations Emma Furlano1, Philip C DiSalvo1, Timothy C Backus1, Khameinei Ali2, William K Chiang1, Josh J Wang1 1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States

Background:

• Valproic acid (VPA) toxicity causes metabolic Results continued: and neurologic symptoms • 5 hospitals did not perform any dilutions to determine • VPA is typically 90% protein-bound but can [VPA] drop to 15% in massive overdose rendering the • 3 hospitals were unable to determine a [VPA] (not drug amenable to extracorporeal treatment depicted on graph) (ECTR). • Timely and accurate determination of very Conclusion: high VPA concentrations is required to identify • It is helpful to determine the [VPA] in massive overdoses patients who would most benefit from ECTR. for poison centers to provide optimal recommendations. • ECTR is recommended at levels of greater than • Unfortunately, most hospitals were unable to obtain 900mg/L. (1,2) values over 900mg/L. • We sought to identify how many hospitals in • Hospitals should be encouraged to develop protocols to one large metropolitan region can determine a obtain accurate and timely [VPA], including at high [VPA] greater than 900mg/L. concentrations. • Poison centers should also understand the capabilities of

Methods: their referral sites. • Early transfer to a facility that can appropriately perform • Surveyed hospital laboratory medical directors dialysis and measure [VPA] may be appropriate in within the New York City Poison Control Center patients with suspected massive overdose. catchment area on their institutional approach • We contacted laboratory directors for non-adherence to to very high serum [VPA]. manufacturer guidelines. • Specific data collected included: analyzer brand, ○ Two hospitals were specialized hospitals and do not analyzer model, highest reported pre-dilution routinely encounter overdoses. [VPA], dilution protocol, highest reported post-dilution [VPA]. References: Results: 1. Marc Ghannoum, Martin Laliberté, Thomas D. Nolin, Robert • 27 of 52 hospital laboratory directors (52%) MacTier, Valery Lavergne, Robert S. Hoffman, Sophie Gosselin & On behalf of the EXTRIP Workgroup (2015) Extracorporeal responded to the survey treatment for valproic acid poisoning: Systematic review and • The highest reported pre-dilution concentration recommendations from the EXTRIP workgroup, Clinical was 415.8mg/L and the lowest reported without a Reported initial and post dilution levels for hospitals that provided validated VPA concentration protocols Toxicology, 53:5, 454-465, DOI: protocol for dilution was 150mg/L 10.3109/15563650.2015.1035441 • 25/27 hospitals were not able to determine the 2. 2. Ruben H.K. Thanacoody (2009) Extracorporeal elimination recommended level for hemodialysis of 900mg/L. in acute valproic acid poisoning, Clinical Toxicology, 47:7, • 609-616, DOI: 10.1080/15563650903167772 Laboratory variability in reporting salicylate levels may limit high-quality poison center recommendations Timothy C Backus1, Philip C DiSalvo1, Emma Furlano1, Kham Ali2, William K Chiang1, Josh J Wang1 1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States Background: Results: In the setting of acute salicylate poisoning, Roche Cobas 6000 c501 o 27 of 52 hospitals responded (52%) hemodialysis is indicated under several o 23 could measure serum salicylate on-site conditions: Roche Cobas 6000 c501  8 hospitals reported maximum pre- • Serum salicylate concentration greater dilution concentrations ≤70mg/dL than or equal to 100 mg/dL Roche Cobas 6000 c501  1 reported ≤86mg/dL • Altered mental status  2 reported ≤90mg/dL • New hypoxemia requiring supplemental Roche Cobas 6000 c501  12 reported ≤100mg/dL oxygen Roche Cobas 8000 c502 o 15 of 23 hospitals performed dilutions on • Failure of supportive care and bicarbonate specimens with salicylate concentrations infusion to improve the patient's clinical Roche Cobas 6000 c501 greater than their assay’s pre-dilution status.[1] maxima As dialysis may be indicated based on Roche Cobas 8000 c502  8 used the automatic dilution function of concentration alone, it is essential that their analyzers emergency physicians and consultants Roche Cobas 8000 c502  7 manually diluted specimens to obtain understand the laboratory capabilities of their Roche Cobas 8000 c502 concentrations own hospital in addition to nearby referral  3 hospitals did not dilute despite institutions in order to provide appropriate, Roche Cobas 8000 c502 manufacturer recommendations timely care. We assessed how salicylate was • 1 did not dilute because the measured and reported by hospital Siemens Dimension Vista 1500 * manufacturer recommendation is to laboratories in a large metropolitan area. Siemens Atellica perform manual dilutions which * created an unacceptable opportunity Methods: Siemens ADVIA 1800 * for human error We surveyed hospital laboratories within the • 1 reported that 70 mg/dL was catchment area of a regional poison center to Siemens XPT * sufficient for patient care gather the following data on the measurement • 1 did not provide an explanation. and reporting of high serum [salicylate]: Beckman Coulter DXC860i * analyzer details (brand, model), highest Siemens ADVIA 1800 * Conclusion: reported pre-dilution [salicylate], dilution Although hemodialysis in salicylate toxicity is protocols, highest post-dilution [salicylate], and Siemens Dimension Vista 1500 * recommended for [salicylate] >100mg/dL (or dialysis capabilities. We compared these data >90mg/dL in conjunction with renal to protocols obtained directly from the Siemens Dimension Vista 1500 * impairment);[1] 3 labs did not provide levels analyzer manufacturers. Where there were >70mg/dL. Many labs relied on manual deviations from manufacturer protocol, we Siemens ADVIA 1800 * dilutions for high [salicylate] specimens, contacted the laboratory director for an Abbott Architect C8000 * thereby creating an opportunity for human explanation. error and delayed reporting. There are several Abbott Architect C8000 * limitations to our study. It was not designed to References: assess the impact on poison center 1. Juurlink DN, Gosselin S, Kielstein JT, et al. Abbott Architect C16000 * recommendations based on high [salicylate]. Extracorporeal treatment for salicylate poisoning: Also, compliance with the stated laboratory systematic review and recommendations from the Beckman Coulter DXC600i * EXTRIP workgroup. Ann Emerg Med 2015;66:165-81. protocol is not investigated. Future research is needed to assess how these variations impact 0 50 100 150 200 patient-centered outcomes. Salicylate reporting limits from 23 hospitals. Analyzer brand and model are noted on the y-axis. Hospitals without orange bars did not perform dilutions. Units are mg/dL. * indicates that the hospital could report a post-dilution salicylate concentration >200 mg/dL. Dashed line represents concentration for which hemodialysis is recommended independent of clinical toxicity. Laboratory variability in reporting salicylate levels may limit high-quality poison center recommendations Timothy C Backus 1, Philip C DiSalvo 1, Emma Furlano 1, Kham Ali 2, William K Chiang 1, Josh J Wang 1 1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States Background: Results: In the setting of acute salicylate poisoning, Roche Cobas 6000 c501 o 27 of 52 hospitals responded (52%) hemodialysis is indicated under several o 23 could measure serum salicylate onsite conditions: Roche Cobas 6000 c501
8 hospitals reported maximum pre • Serum salicylate concentration greater dilution concentrations ≤70mg/dL than or equal to 100 mg/dL Roche Cobas 6000 c501
1 reported ≤86mg/dL • Altered mental status
2 reported ≤90mg/dL • New hypoxemia requiring supplemental Roche Cobas 6000 c501
12 reported ≤100mg/dL oxygen Roche Cobas 8000 c502 o 15 of 23 hospitals performed dilutions on • Failure of supportive care and bicarbonate specimens with salicylate concentrations infusion to improve the patient's clinical Roche Cobas 6000 c501 greater than their assay’s predilution status.[1] maxima As dialysis may be indicated based on Roche Cobas 8000 c502
8 used the automatic dilution function of concentration alone, it is essential that Roche Cobas 8000 c502 their analyzers emergency physicians and consultants
7 manually diluted specimens to obtain understand the laboratory capabilities of their Roche Cobas 8000 c502 concentrations own hospital in addition to nearby referral
3 hospitals did not dilute despite institutions in order to provide appropriate, Roche Cobas 8000 c502 manufacturer recommendations timely care. We assessed how salicylate was • 1 did not dilute because the measured and reported by hospital Siemens Dimension Vista 1500 * manufacturer recommendation is to laboratories in a large metropolitan area. Siemens Atellica * perform manual dilutions which created an unacceptable opportunity Methods: Siemens ADVIA 1800 * for human error We surveyed hospital laboratories within the • 1 reported that 70 mg/dL was catchment area of a regional poison center to Siemens XPT * sufficient for patient care gather the following data on the measurement • 1 did not provide an explanation. and reporting of high serum [salicylate]: Beckman Coulter DXC860i * analyzer details (brand, model), highest Siemens ADVIA 1800 * Conclusion: reported predilution [salicylate], dilution Although hemodialysis in salicylate toxicity is protocols, highest postdilution [salicylate], and Siemens Dimension Vista 1500 * recommended for [salicylate] >100mg/dL (or dialysis capabilities. We compared these data >90mg/dL in conjunction with renal to protocols obtained directly from the Siemens Dimension Vista 1500 * impairment);[1] 3 labs did not provide levels analyzer manufacturers. Where there were Siemens ADVIA 1800 >70mg/dL. Many labs relied on manual deviations from manufacturer protocol, we * dilutions for high [salicylate] specimens, contacted the laboratory director for an Abbott Architect C8000 * thereby creating an opportunity for human explanation. error and delayed reporting. There are several Abbott Architect C8000 * limitations to our study. It was not designed to References: assess the impact on poison center 1. Juurlink DN, Gosselin S, Kielstein JT, et al. Abbott Architect C16000 * recommendations based on high [salicylate]. Extracorporeal treatment for salicylate poisoning: Also, compliance with the stated laboratory systematic review and recommendations from the Beckman Coulter DXC600i * EXTRIP workgroup. Ann Emerg Med 2015;66:165-81. protocol is not investigated. Future research is needed to assess how these variations impact 0 50 100 150 200 patientcentered outcomes. Salicylate reporting limits from 23 hospitals. Analyzer brand and model are noted on the yaxis. Hospitals without orange bars did not perform dilutions. Units are mg/dL. * indicates that the hospital could report a postdilution salicylate concentration >200 mg/dL. Dashed line represents concentration for which hemodialysis is recommended independent of clinical toxicity. 40° Congress of European Association of Poisons Centres and Clinical Toxicologists

PEDIATRIC ORAL CAUSTIC INGESTION WITH DRAIN CLEANERS

A. Celentano, F. Sesana, M. Ferruzzi, F. Davanzo

Milan Poison Control Center, ASST Grande Ospedale Metropolitano Niguarda Milan, Italy

Objective Case 1

Oral caustic exposure to drain cleaners is a public health event. Accidental oral exposures A 21-month-old girl ingested a sodium hydroxide-based (25-30%) drain cleaner left on the to drain cleaners reported to an Italian Poison Control Center from 1 November 2017 to floor by her mother. She opened the bottle very easily and drank the pink liquid, mistaking 31 October 2018 were analyzed. There were 35 cases during the study period. Among it for a drink. On arrival to hospital, 15 minutes after ingestion, she presented second them, 42.9% of cases involved children <6 years old. The present contribution is aimed at degree burn of 10% of the body surface. Oral examination showed first and second describing two pediatric cases with severe oral effects and gastroesophageal lesions due degree burns, disepithelization of the lips and necrosis of the oral cavity with blackish to ingestion of drain cleaners. secretions from the mouth. Laryngoscopy revealed epiglottic edema. Gastroscopy found esophageal stenosis and erosions. She was intubated and subjected to multiple Case 2 esophageal dilations. A 21-month-old boy ingested a sulphuric acid-based (75-100%) pink colored, drain cleaner, Conclusion left on a shelf accessible to children at his mother’s friend's house. He was found vomiting with the colored bottle next to him. He was admitted to the emergency room Despite the presence of the safety with dyspnea, dysphonia, edema of the oral cavity, epiglottic edema, disepithelization of closures on the bottle and the hazard the lips, necrosis the oral cavity, hematemesis. Chest x-ray showed an opacity. pictograms on the packaging, the risk Gastroscopy found severe esophageal and gastric erosions and he required endotracheal represented by these products is intubation. underestimated not only in adults but also in children. Message on the bottle. How does

wrong package influence occurrence The Poisoning Information Centre’s objective is to provide adequate advice quickly so as to reduce the incidence of illness, of caustic and corrosive chemical damage to health and death as a result of severe cases of poisoning. Our centres are staffed with internationally trained and highly experienced doctors and nurses working exposures. Estonian experience. in the fields of emergency medicine, anaesthesia and intensive care.

Kastanje R, Kukker A, Oder M www.16662.ee

Estonian Poisoning Information Centre • Phone: +372 79 43 79 4 • E-mail: [email protected] • www.16662.ee Objective

Caustic and corrosive exposures are a worldwide problem. In Estonia primary visits to hospitals due to caustic exposures cost about 25 000 € for national health insurance system every year. There have been 800 primary hospital visits due to caustic/corrosive chemicals exposition over last 10 years per population of 1.3 million people.This retrospective study aims to collect epidemiological data about caustic and corrosive oral exposures in Estonia and establish how big is the role of not original package in causing exposures in different age groups.

Method

Calls to Estonian Poisonings Information Centre (EPIC) from january 2009 to december 2018 were analysed retrospectively in 6 age groups: under 1 year old, 1-3 y, 4-6 y, 7-18 y, 19-69 y and 70 y and older In each group it was evaluated, wheter the substance involved was caustic (pH ≤ 2 or ≥ 11,5) or irritating (pH between 2 - 11,5), was it in original package or not and whether the patient needed to be hospitalized or was referred to home observation.

120

100

80

60

40

20

0 WR-C OR-C WR-C OR-C WR-C OR-C WR-C OR-C WR-C OR-C WR-C OR-C WR-C OR-C WR-C OR-C < 1 year 1-3 y 4-6 y 7-18 y 19-69 y 70-79 y 80-89y >90 y 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Fig. Caustic and corrosive oral exposures in diferent age groups and tipe of package 2009-2018, calls to EPIC (WR-C – wrong container, OR-C – original container) Results Conclusion

Overall 1661 inquiries were registrated. Exposures to Results of the study show, that most affected by caustic and corrosive chemicals were most common wrongly stored chemicals are adults and older in children from 1 to 3 years - 50,5 % of all inquiries, children, while children under 3 years old were more at the same time being mostly asymptomatic or attrackted by colorful original packages and products presenting mild symptoms (80 % referred to home reminding toys (detergent pods, toilet refresheners). observation, overall 79%). Surprising for authors was big part of original PH caustic was 28%, irritating 72% of exposures, package (51%) in under 1 y olds group, who depend caustic pH exposures occurring most often in the mostly on their carers. Probably it could be different group older than 70 (57%) and lowest in the group if under and over 6 month olds were observed in younger than 1 y (16%). separate groups. Having such data helped poisoning The chemicals were in their original package 47% information centre to target our 2020 poisoning (most often in group 1-3 y - 66%, most rarely in group prevention week to wulnerable groups and 19 -69 y - 14%), in wrong package 30%, (67% in problematic products. About reasons and products group 19-69 y, 62% 7-8 y, only 8% in 1-3 y group), behind poisonings among <1 y olds we continue package unknown 23%. research this year. Spanish Toxic Surveillance System (STSS). Comparison between occupational and non- occupational exposures in a two-year period Ferrer-Dufol A 1, Puiguriguer J 2, Nogué S3, Cordoba F4, Merino C5, Supervía A6. 1 Hospital Clínico Universitario, Zaragoza. 2 Hospital Son Espases, Palma de Mallorca. 3 Hospital Clinic, Barcelona. 4 Hospital Moisés Broggi, San Joan d'Espí. 5 Complejo Hospitalario de Navarra, Pamplona. 6 Hospital del Mar, Barcelona.

Objective: Since 1999, a Toxic Surveillance System Methods: We have selected the occupational cases exists in Spain promoted by the Spanish Ministry of gathered by the system between January 2017 and Health and implemented by members of the Spanish December 2018. We have compared some of the variables Foundation on Clinical Toxicology. The system aims to (age, sex, type of chemical, route of entry, symptoms, report the cases of acute poisoning by chemical treatment and evolution) looking for differences between products admitted to the Emergency Department (ED) occupational and non-occupational chemical exposure. of selected Hospitals to evaluate the risks of exposure to Statistics signification of qualitative variables (p < 0.05) was these substances under the current EU regulations. We found by means of ji-square test. compare the characteristics of occupational with non- occupational exposures in the last two-year period. Table 1. Comparison of variables of cases of occupational causes with the rest of the Results: From the total 2290 registered cases, 201 were chemical poisonings in the Spanish Toxic surveillance System occupational. Main origin of the total chemical cases Non-occupational occupational P value N were domestic accidents (78%). 2089 201 NA mean 38 40,6 NA Age The comparative analysis shows the following results median 38 40 NA (Table 1) : DS 24 11,31  Mean age of occupational cases (41±11 years old) was Age range < 1a 97 18 a 77 man 1014 148 0.000 slightly over the non-occupational group (38±24 years Gender old) due to the absence of children. women 1075 53 0.000  Men were overrepresented (70%) in the occupational toxic gases 957 62 0.000 caustic 369 21 0,009 group (p < 0.001) vs a sex even distribution in the non- irritant gases 252 54 0.000 occupational group. Toxic group detergents 158 14 0,075  Main chemicals in the occupational cases were toxic solvents 147 26 0,002 (30%) and irritant (28%) gases while, in the non- pesticides 121 12 0,92 occupational group, caustics were the second involved other 123 12 1,1 substances (18%) following toxic gases. oral 733 11 0,000 respiratory 1274 143 0,004 Contact access  Route of entry respiratory (68%) (p=0.04), ocular (21%) cutaneous 40 17 0,000 (p=0.037) and cutaneous (8%) (p<0.001) predominate ocular 347 45 0,037 in the occupational cases, while, in the non- digestive 670 40 0.000 occupational group, oral (35%) was the second one respiratory 521 72 0.000 after the respiratory one. cardiovascular 116 10 0.731 neurological 566 64 0,15  Respiratory, ocular and cutaneous symptoms were Symptoms cutaneous 44 19 0.000 more prevalent in occupational cases (p<0.001). ocular 146 50 0.000  Antidotes and cutaneous decontamination were more hydroelectrolytic 21 1 0,48 frequently used in the occupational cases (p<0.001), Antidote use 785 50 0,000 while gastric decontamination was more prevalent in Decontamination eyes/ cutaneous 107 58 0.000 non- occupational ones (p=0.022). Decontamination digestive 53 0 0,022  Hospital admission was less frequent in occupational Extra renal elimintaion 7 0 0,411 cases (8%) that non-occupational cases (15%) Hospital admittance 315 16 0,006 (p=0.006). Death 24 0 0,126

Conclusion: There are relevant differences between occupational and non-occupational cases of chemical exposure. Occupational cases present in slightly older population, with a clear male predominance. Toxic and irritant gases and solvents are more prevalent in occupational cases. Occupational cases show a better outcome with less cases of hospital admission and no mortality. Spanish Toxic Surveillance System (STSS). Occupational exposures in a two-year period. Puiguriguer J1, Ferrer-Dufol A2, Nogué S3, Cordoba F4, Merino C5, Supervía A6. 1 Hospital Son Espases, Palma de Mallorca. 2 Hospital Clínico Universitario, Zaragoza. 3 Hospital Clinic, Barcelona. 4 Hospital Moisés Broggi, San Joan d'Espí. 5 Complejo Hospitalario de Navarra, Pamplona. 6 Hospital del Mar, Barcelona.

Objective: Since 1999, a Toxicosurveillance System exists in Methods: The participating hospitals report all cases of Spain promoted by the Spanish Ministry of Health and intoxication due to household, agricultural or industrial chemicals implemented by members of the Spanish Foundation on treated in their ED by means of an on-line 24 hours accessible Clinical Toxicology. The system aims to report the cases of encrypted questionnaire. A yearly report is presented to the acute poisoning by chemical products admitted to the Health Ministry. We have selected the occupational cases Emergency Department (ED) of selected Hospitals to evaluate gathered by the system from the 23 participant hospitals, the risks of exposure to these substances under the current covering a population of about 10 million people, between EU regulations. The register analyses the main circumstances January 2017 and December 2018. The analysed variables were leading to chemical exposure, among them the occupational age, sex, day and month, type of chemical, route of entry, origin. We present the characteristics of these occupational symptoms, treatment and evolution. exposures in the last two-year period.

Results: We collected 201 occupational cases (Fig 1). Median patient age were 40±11 years. 148 (74%) are men and 53 (Fig 2). Higher number of cases in March and September (11,9%). Main routes of entry were respiratory (71%) and ocular (22%). Cutaneous contact (8%) and oral (5%) were much less frequent. Main involved chemicals were carbon monoxide (28%), irritant gases (22%), solvents (11%), and caustics (8%) (Table 1). 91% of the patients were symptomatic at admission presenting with respiratory (36%), neurological (32%), ocular (25%), digestive (20%), and cutaneous (9%) symptoms, most of them mild. Received symptomatic treatment 82% of the cases. Ocular/cutaneous decontamination was used in 29%. Figure 2. Gender distribution In 25% of the cases, oxygen was used as an antidote for CO exposure. Only 16 cases required hospital admission, two of them at the ICU. Sequels presented in 11 cases mainly due to hydrogen sulphide and chlorine exposures. No deaths were recorded.

Table 1. Toxics responsible for poisoning by occupational accidents attended in two years: total cases, admitted and those that generated sequelae. intoxicated admitted sequelae toxic product n % n % n % Carbon Monoxide (includes smoke fire) 57 28,3 6 37,5 Chlorine and irritant vapours 45 22,4 1 6,2 3 27,2 Solvents (include metanol) 23 11,4 2 12,5 1 9,1 Lye (sodium hypochlorite) 16 7,9 Detergents 11 5,5 1 6,2 Unspecified chemical 11 5,5 Sulphydric acid 9 4,5 3 18,7 4 36,3 Degreasers 7 3,5 2 18,2 Salfuman (hydrochloric acid) 7 3,5 Sodium hydroxide 5 2,5 1 6,2 Ammonia 4 2 1 9,1 Glyphosate 3 1,5 Ethylene glycol 2 1 1 6,2 Pyrethroid insecticides 2 1 Other herbicides 2 1 Turpentine 1 0,5 Organophosphate Insecticides 1 0,5 1 6,2

Figure 1. Distribution of cases contributed by each hospital in 2017 and 2018 to the Spanish Toxicovigilance Programme Conclusions: The STSS proves to be a useful tool for keeping an accurate register of the incidents related to chemical exposures attended at the EDs. Occupational toxic exposures in Spain are, right now, rare and with mild consequences. The main hazardous classical chemicals, such as heavy metal or pesticides, do not appear in our series, which proves the success of the regulatory preventive rules implemented these last decades under EU regulations. Case series of chronic occupational lead poisoning in shooting ranges

Gabija Laubner1,2,, Indrė Stražnickaitė1 1Vilnius University, Faculty of Medicine, Lithuania 2Republican Vilnius University Hospital, Centre of Toxicology, Vilnius, Lithuania

Introduction The most common symptoms were fatigue Fig. 2 Even relatively low elevated blood lead level concentrations can have (12 patients out of 20), dizziness (5/20), significant toxic effects over time Despite being widely regarded as an arthralgia (5/20). Other symptoms included occupational health hazard (1, 2, 3), lead is sleep disorders (4/20), impaired memory inevitably used in various professions. It can (3/20), nausea (3/20), metallic or sweet taste enter the human body through skin contact, in the mouth (3/20), coxarthrosis (2/20), inhalation and food consumption making it impaired balance (2/20), paraesthesia (2/20), easy for people working in high-risk abdominal pain (2/20), bloating (1/20), environments, such as shooting ranges, to be impaired eyesight (1/20), heart palpitations exposed to a dangerous amount of lead. (4) (1/20), weight loss (1/20), myalgia (1/20), It is expected that lead removal from soft impaired ability to concentrate (1/20), tissues takes about a month, whereas decreased left arm muscle mass (1/20), removal from bones can take much longer. If transient neuropathy (1/20), decreased the exposure to lead is chronic, the excretion exercise tolerance (1/20), mood lability Conclusion will take even longer. (4) (1/20), tinnitus (1/20), alopecia (1/20), rash Employees, working at shooting ranges, are Even though lead is considered to be an (1/20), (1/20) dryness and peeling of skin highly vulnerable to daily lead exposure. occupational health hazard in Lithuania, around the stomach. 4 patients reported no employees working in shooting ranges still symptoms. The average blood lead level was 25.295 complain of lead poisoning related µg/dL, which falls under the 40 µg/dL mark, stated by the European Commission for symptoms, thus exposing a clear lack of Fig. 1 Chronic occupational lead poisoning proper safety precautions. symptoms presented by the patients diagnosing chronic occupational lead poisoning (3). However, despite not having high enough blood lead levels to classify as Case series an occupational poisoning, many patients presented with at least one symptom. 20 men, whose age ranged from 32 to 57 Therefore, even relatively low constant (mean 41.8 ± 10 years), were consulted at elevated blood lead level concentrations can the Centre of Toxicology at the Republican have significant toxic effects over time. (4) Vilnius university hospital in Vilnius, As our observations suggest, such work Lithuania in the 2016 - 2019 year period. conditions are a health hazard, therefore proper preventative measures in shooting All of the patients were working as shooting ranges must be put in place. instructors in indoor shooting ranges, with their work experience varying from 2 to 30 Each patient was recommended to use References years. Clinical examination showed elevated (1) Order 97/406 of the Ministry of Social Security and Labour of the Republic of Lithuania. "“On protective gear while working, to limit the confirmation of provisions for the protection of workers from chemical agents at work and blood lead levels, ranging from 5.64 µg/dL provisions for the protection of workers from the effects of carcinogens and mutagens at work.” exposure to the environment, in which they Worker protection of chemical factors at work, annex 1. https://e- to 45.8 µg/dL (mean 25.23 ± 2.6) (with the seimas.lrs.lt/portal/legalAct/lt/TAD/TAIS.145860/asr. Accessed 05 May 2020 might be exposed to lead, repeat a blood lead (2) Agency for Toxic Substances and Disease Registry (ATSDR). "Toxicological profile for lead". norm for occupational exposure being <40 https://www.atsdr.cdc.gov/toxprofiles/tp13.pdf. Accessed 06 May 2020 level test after 3 months, as well as a follow- (3) "Information notices on occupational diseases: a guide to diagnosis".Luxembourg: Office for µg/dL). Official Publications of the European Communities, 2009. ISBN 978-92-79-11483-0 doi 10.2767/38249.© European Communities, 2009. https://. Accessed 14 May up consultation with a clinical toxicologist. 2020sam.lrv.lt/uploads/sam/documents/files/Occupational%20diseases_Guide%20to%20diagnosis_2 009.pdf

Air lead levels were not measured at the No medicinal treatment was administered (4) Ab Latif Wani, Anjum Ara, Jawed Ahmad Usmani. Lead toxicity: a review. Interdiscip Toxicol. 2015 Jun; 8(2): 55–64. shooting ranges they worked in. due to possible side effects of chelators. Ingrid Berling1,2,3,4, Jared Brown5

1School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; 2 Department of Emergency Medicine, Calvary Mater Newcastle, NSW, Australia; 3 Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, NSW, Australia 4 NSW Poisons Information Centre, Sydney Children’s Hospitals Network, Australia 5 Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia INTRODUCTION _ METHODS _ 3,4-Methylenedioxymethamphetamine All deaths located in NSW within the (MDMA), often referred to as ecstasy, is a National Coronial Information System commonly used recreational drug in (NCIS) between 2013 and 2017 were Australia, that has recently been associated searched for the term MDMA (and with a number of unintentional, well synonyms). Open cases were excluded publicised deaths. We aimed to identify the (the majority of 2018/2019 cases remain number of deaths in New South Wales open hence these years not included in this (NSW) related to MDMA use over a 5-year audit). Coronial reports, autopsy results, period. We further aimed to classify these police reports and toxicology reports were deaths by mechanism of death (poisoning, then reviewed for each death. risky behaviour causing death or suicide), location of use, and the circumstances of use  Figure 1: Flowchart of results for cases searched. and toxicity from MDMA. .  Figure 2: Number of MDMA related RESULTS _ deaths per year. MECHANISM OF DEATHS _ There were 2,644 coronial deaths in NSW Of the 18 primarily MDMA related deaths, Number of deaths per year where poisoning was ruled as the primary 6 14 died due to the acute effects of MDMA

cause of death over the 5-year period. 57 5 poisoning, three died secondary to risky

(2.2%) closed cases were identified 4 behaviour whilst intoxicated by MDMA

including the term/synonym MDMA. 18 3 (one in a motor vehicle accident, two (0.7%) deaths were due to MDMA as the 2 drowned) and one died secondary to the primary toxin, with the remaining 39 1 chronic effects of repeated MDMA use deaths unlikely to be due to MDMA (delayed acute myocardial infarction). 0 effects. See figure 1. 2013 2014 2015 2016 2017

DEMOGRAPHICS _ LOCATION OF MDMA USE _ CONCLUSION _ The median age of death was 26 years Of the 14 acute poisoning deaths, seven Whilst MDMA is recorded as a contributory (range 19-54 years). Males were highly occurred in the setting of MDMA use at a factor in deaths within NSW, only a small represented at 14:4 male: female deaths. music festival. In all seven cases, MDMA number of deaths, <1% of all poisoning Death by year was 2013:3, 2014:2, 2015:5, was taken in the context of alcohol deaths, are primarily caused by acute 2016:3 and 2017:5. consumption, although in two cases alcohol MDMA poisoning. See figure 2 was not measurable post mortem. The dose of MDMA was often in excess of three Coronial data can be vital for planning tablets or unknown, and at least three cases injury prevention activities by understanding also consumed other substances. Four cases circumstances of death and incidence. collapsed during the festival, with the Increasing use and triangulation with other remaining three found unresponsive the data sources will be critical for future public following morning. health management of drug toxicity. The setting of use of the remaining seven acute poisoning deaths was pub/club (2), house-party (4) and home alone (1). Serotonin Syndrome and/or Opioid Withdrawal After the First Dose of Naltrexone HCl/ Bupropion HCl with Concomitant Use of an Opioid: an Observational Study Susan C. Smolinske, 1 Stefanie Logothetis, 1 Seifert A. Steven, 1 Brandon J. Warrick, 1 Kimberly Trubetskoy, 2 Janetta Iwanicki, 2 Richard C. Dart 2 1University of New Mexico, Albuquerque, United States, 2Rocky Mountain Poison and Drug Center, Denver, United States

Background Methods Results (continued) • Not always possible to attribute outcomes to OWD or SS • Naltrexone/bupropion is a combination drug used for weight loss Hunter’s Criteria for Serotonin Syndrome (SS) o S/S overlap; Outcomes not linked to syndrome • Opioid antagonist and synthetic cathinone (aminoketone) • Use of a serotonergic agent plus at least one of the following: • In September 2014, a sustained release formulation was approved for marketing in the US • 13 of 17 (76.5%) with OWD +/o SS had a Moderate or greater outcome • Spontaneous Clonus o under the brand name Contrave ® • Inducible clonus and agitation or diaphoresis 3 case scored as Major, 10 as Moderate, 4 as Minor outcomes • Approved for • Ocular clonus and agitation or diaphoresis • Of the SS cases, 3 had Moderate and 1 had Minor outcomes • Obese adults (BMI >30) • Tremor and hyperreflexia • Tramadol was the most common opioid involved in patients who experienced an • Overweight adults (BMI >27) with at least one weight-related comorbidity • Hypertonia, temperature above 38 degrees Celsius and ocular clonus or inducible clonus ADR of OWD and/or SS (6/17; 35.3%) • Maximum adult dose: 32 mg naltrexone / 360 mg bupropion • Tramadol was also the most common opioid involved in cases with SS (2/4; 50%) • Package insert Clinical Opiate Withdrawal Scale (COWS) for Opioid Withdrawal (OWD) • States potential for opioid withdrawal (OWD) Aggregate score; 0 to 4 or 5 over specified time periods Limitations • No mention of serotonin syndrome (SS) • Resting pulse rate; Sweating; Restlessness; Pupil size; Bone or joint aches; Runny nose or • Bupropion alone or combined use of opioids and antidepressants have been reported to cause • Retrospective review of RADARS Poison Center Program tearing; GI upset; Tremor; Yawning; Anxiety or irritability; Gooseflesh o serotonin syndrome • Scores ≧ 5 are stratified as mild, moderate, or severe OWD Reporting bias, misclassification, confounders • As of January 2019 at least 12 cases of serotonin syndrome reported involving use of bupropion • Limitations of poison center data • Searched the RADARS Poison Center Program database from January 2014 o Terminology Medications Age/Sex Reference through December 2018 for cases of ADRs involving opioids and a first dose o Voluntary reporting from healthcare facilities o Passive exchange of information over the phone Bupropion 15M Thorpe, 2010 RADARS of naltrexone/bupropion • Study cases defined as having signs and symptoms of SS or OWD • Small sample size Bupropion 43M Szakaly, 2008 • Collected information on medications, treatments, and outcomes Conclusions

Bupropion, sertraline,** trazodone,** linezolid,** lithium** 45M Lavery, 2001 • Reviewed each case to determine if they met Hunter’s Criteria for serotonin • This study provides strong supportive data for the occurrence of an adverse drug syndrome Bupropion, sertraline** 62F Munhoz, 2004 Data Transfer reaction of opioid withdrawal and/or serotonin syndrome with the first dose of to NMPDIC • Reviewed each case to determine if they experienced opioid withdrawal naltrexone/bupropion in patients also taking opioids using the Clinical Opioid Withdrawal Scale (COWS) Bupropion, paroxetine,** atomoxetine** 55M Muzyk, 2010 o This ADR resulted in at least a Moderate or Major outcome in 75.6% of cases o Tramadol was the most common opioid involved in patients who experienced Bupropion, ondansetron,** paroxetine,** duloxetine** 68F Gollapudy, 2012 • Descriptive statistics were used an ADR of OWD +/o SS, and also the most common opioid cases with SS Descriptive Data Bupropion, trazodone,** quetiapine** 70F Cheng, 2015 References Bupropion, fluoxetine,** trazodone,** olanzapine,** risperidone** 24M Little, 2018 Contrave (naltrexone HCl and bupropion HCl) Extended Release Tablets [package insert]. La Jolla, CA. Orexigen Threrapeutics, INC. Results Thorpe EL, Pizon AF, Lynch MJ, Boyer J. Bupropion induced serotonin syndrome: a case report. J Med Toxico l. 2010 Jun;6(2):168-71. doi: 10.1007/s13181-010-0021-x Bupropion, duloxetine,** cyclobenzaprine,** oxycodone! 53M Keegan, 2006 Gollapudy S, Kumar V, Dhamee MS. A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient • 33 cases met inclusion criteria of ADR to first dose naltrexone/bupropion combined with opioid use receiving paroxetine, duloxetine, and bupropion. J Clin Anesth. 2012 May;24(3):251-2 Falls BA, Gurrera RJ. Serotonin syndrome in a patient on tramadol, bupropion, trazodone, and oxycodone. Psychosomatics. • 23 cases had sufficient outcome information for analysis Bupropion, fluoxetine,** olanzapine,** methadone! 53F Dvir, 2007 2014 May-Jun;55(3):305-9. doi: 10.1016/j.psym.2013.05.013 • 17 cases had symptoms and/or signs consistent with SS and/or OWD Cheng YC, Liang CM, Liu HC. Serotonin syndrome after electroconvulsive therapy in a patient on trazodone, bupropion, and o All cases had S/S consistent with OWD; 4 had S/S consistent with SS quetiapine: a case report. Clin Neuropharmacol. 2015 May-Jun;38(3):112-3 Bupropion, citalopram,** tramadol! 62M Shahani, 2012 Munhoz RP. Serotonin syndrome induced by a combination of bupropion and SSRIs. Clin Neuropharmacol. 2004 Sep- Oct;27(5):219-22. Shahani L. Tramadol precipitating serotonin syndrome in a patient on antidepressants. J Neuropsychiatry Clin Neurosci. 2012 Bupropion, trazodone,** tramadol,! oxycodone! 62M Falls, 2014 33 cases 23 cases Fall;24(4):E52 Little K, Lin CM, Reynolds PM. Delayed Serotonin Syndrome in the Setting of a Mixed Fluoxetine and Serotonin Antagonist ______ADR to first dose Followed to outcome Overdose. Am J Case Rep. 2018 May 25;19:604-607 Single substance in 2 cases; With other serotonergics (**) in 9 cases; With opioids (!) in 4 cases Dvir Y, Smallwood P. Serotonin syndrome: a complex but easily avoidable condition. Gen Hosp Psychiatry. 2008 May- Jun;30(3):284-7 • NM Poison Center had four cases where the first dose of naltrexone/bupropion with concomitant 17 cases Szakaly B, Strauss R. Serotonin syndrome in the oral and maxillofacial surgery office: a review of the literature and report of a case. J Oral Maxillofac Surg. 2008 Sep;66(9):1949-52 use of opioids led to a presentation at a healthcare facility With SS and/or OWD • RADARS: Researched Abuse, Diversion and Addiction-Related Surveillance System (RADARS) Lavery S, Ravi H, McDaniel WW, Pushkin YR. Linezolid and serotonin syndrome. Psychosomatics. 2001 Sep-Oct;42(5):432-4 Keegan MT, Brown DR, Rabinstein AA. Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic • Funded by subscriptions from pharmaceutical manufacturers, government and NGAs drugs. Anesth Analg. 2006 Dec;103(6):1466-8. • 53 out of 55 poison centers in the U.S. partner with RADARS to provide weekly detailed 3 major 10 moderate 4 minor Muzyk AJ, Jakel RJ, Preud'homme X. Serotonin syndrome after a massive overdose of controlled-release paroxetine. exposure cases involving prescription opioids Psychosomatics. 2010 Sep-Oct;51(5):437-42. doi: 10.1176/appi.psy.51.5.437 Outcomes Outcomes Outcomes POISINDEX® System: Klasco RK (Ed): POISINDEX® System. Truven Health Analytics, Greenwood Village, Colorado (Edition • Collects data on abuse, misuse, and diversion of prescription drugs for research and reporting expires [2/2017]). • Captures data from diverse sources to ensure early and continuous monitoring of newly Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20. Review. Erratum in: N Engl J approved drugs Opioids Frequency in All Outcomes (17) Frequency in Med. 2007 Jun 7;356(23):2437. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714. Major/Moderate Abadie D, Rousseau V, Logerot S, Cottin J, Montastruc JL, Montastruc F. Serotonin Syndrome: Analysis of Cases Registered in Objectives the French Pharmacovigilance Database. J Clin Psychopharmacol. 2015 Aug;35(4):382-8. Outcomes (13) Dunkley EJC, Isbister GK, Sibbritt D, DawsonAH,Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate • Primary objective diagnostic decision rules for serotonin toxicity. Q J Med . 2003; 96:635–42. Tramadol 6 (35.3%) 3 (23.1%) Jhun P, Bright A, Herbert M. Serotonin syndrome and opioids--what's the deal? Ann Emerg Med. 2015 Apr;65(4):434-5. o Identify cases of serotonin toxicity and/or opioid withdrawal after the first dose of RADARS System https://www.radars.org/terms-of-use.html accessed April 2019 naltrexone/bupropion as an adverse drug reaction (ADR) using the RADARS Poison Center Buprenorphine 3 (17.7%) 3 (23.1%) National Poison Data System. (2016). NPDS Coding Users’ Manual Version 3.2. American Association of Poison Control Centers Program database Morphine 2 (11.8%) 3 (23.1%) • Secondary objective o Assess whether and which specific opioids are more likely to cause an adverse drug reaction (ADR) with a first dose of naltrexone/bupropion Presentations related to novel psychoactive substance use at three urban emergency departments in Switzerland Irene Scholz1, Yasmin Schmid2, Tim Bühler2, Roberta Noseda3, Aristomenis Exadaktylos4, Alessandro Ceschi3,5,6, Matthias Liechti2, Evangelia Liakoni1 1Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; 2Division of Clinical Pharmacology and Toxicology, Basel University Hospital and University of Basel, Switzerland; 3Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland; 4Emergency Department, Inselspital, Bern University Hospital, University of Bern, Switzerland; 5Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Switzerland; 6Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland

Objective Novel psychoactive substances (NPS) have emerged in recent years in response to market trends and legislative control. There are currently limited data on acute medical problems and patient characteristics related to recreational NPS use in Switzerland.

Methods Retrospective analysis within the European Drug Emergencies Network (Euro-DEN) Plus project of cases presenting with acute toxicity related to recreational use of NPS at three emergency departments (ED) in Switzerland: the University Hospital of Bern (May 2012 – July 2019), the University Hospital of Basel (October 2013 – June 2019) and the Ente Ospedaliero Cantonale of Southern Switzerland (October 2016 – June 2019). Results During the study period, there were 16 cases related to acute toxicity of NPS (8 cases in Bern, 8 cases in Basel and no cases in Southern Switzerland). The mean patient age was 29 years (SD 10.8) and 75% (n=12) were male.

Case Age Substance (s) Alcohol co- Main clinical features Severity [1] Analytical results Treatment Outcome Group reported ingestion 1 31-35 MDMC (methylone) Yes Vomiting, palpitations, anxiety, moderate IA: negative Sedation, Discharged home agitation, tremor, muscle spasms, metoclopramide, i.v. within 24h sweating, paresthesias, dizziness fluid administration 2 16-20 2C-B Yes Hallucinations, tachycardia, anxiety, moderate LC-MS/MS: 2C-P Sedation Discharged home agitation, mydriasis, confusion 11h later 3 21-25 2C-B, amphetamine N/A Muscle spasms, anxiety minor IA: amphetamine, benzodiazepines Sedation, i.v. fluid Discharged home (iatrogenic) administration 4 • 16During-20 N/A the study period, N/A190 and 154GCS 3,cases hypotension were, tachycardia, severe IA: negative, LC-MS/MS: carfentanyl Intubation, Discharged home hypopnea, cyanosis, anxiety naloxone, flumazenil the following day

5 16-20 4-AcO-DMT N/A GCS 10, agitation, mydriasis moderate IA: benzodiazepines (iatrogenic) Sedation, i.v. fluid Discharged home administration 6 21-25 2C-B N/A Palpitations, anxiety minor N/A Sedation Discharged home

7 26-30 3-MMC, crystal meth No Panic attack, palpitations, dyspnea moderate N/A N/A Admission to psychiatric clinic 8 26-30 2C-B, cocaine Yes Palpitations, hallucinations, agitation, moderate IA: methamphetamine, cocaine i.v. fluid Discharged home sweating administration 9 26-30 MDMA Yes Hallucinations, chest pain, palpitations, moderate IA: negative, LC-MS/MS: 2C-B N/A Discharged home dyspnea, mydriasis 10 21-25 Amphetamine, MDMA, Yes Psychosis, aggression moderate LC-MS/MS: mephedrone, MDMA, Sedation Discharged home cannabis, cocaine amphetamine 11 36-40 Designer drug from No GCS 5 severe IA: benzodiazepines, cannabis, N/A Admission to internet buprenorphine, LC-MS/MS: morphine, intensive care temazepam unit 12 46-50 Fentanyl-like substance No GCS 3, bradycardia, bradypnoea severe N/A N/A Discharged home from darknet 13 26-30 2C-B N/A Anxiety, fear that he would forget to moderate IA: negative Sedation Discharged home breathe 14 51-55 Tramadol N/A GCS 14, agitation, delusional moderate LC-MS/MS: pentylon, tramadol Sedation Admission to parasitosis, hallucinations, psychosis psychiatric clinic 15 41-45 Superman-XTC (MDMA, N/A GCS 3, hypertension severe IA: cannabis, opiates, Intubation, sedation, Admission to PMMA), methadone, benzodiazepines, LC-MS/MS: naloxone, flumazenil intensive care benzodiazepine negative for NPS unit 16 21-25 2C-P Yes GCS 14, dizziness minor N/A N/A Discharged home

GCS: Glasgow Coma Scale; IA: Immunoassay; LC-MS/MS: liquid chromatography coupled with mass spectrometry; N/A: not available; h: hours; i.v.: intravenous; 2C-B: 2,5-dimethoxy-4-bromophenethylamine; 2C-P: 2,5-dimethoxy-4(n)-propylphenethylamine; 3-MMC: 3-methylmethcathinone; 4-AcO-DMT: O-Acetylpsilocin; MDMC: 3,4-methylenedioxymethylcathinone; PMMA: paramethoxymethamphetamine

Conclusions • ED presentations related to acute NPS toxicity appear to be rare in Switzerland. Most patients were young and male. • The most frequently involved NPS were from the 2C-series with most intoxications of minor or moderate severity • The discrepancy between the reported and analytical results in some cases might be due to analytical limitations (e.g. NPS cannot be detected with the commonly used immunoassays), but might also indicate that some patients are unwilling to report the NPS intake or are unaware of the exact substance used

References: 1.Persson HE, Sjoberg GK, Haines JA, Pronczuk de Garbino J. Poisoning severity score. Grading of acute poisoning. J Toxicol Clin Toxicol. 1998;36(3):205–13 Acknowledgments: The project was financially supported by the Burgergemeinde Bern in Bern, the Swiss Centre for Applied Human Toxicology (SCAHT) in Basel and the Scientific Research Advisory Board of the Ente Ospedaliero Cantonale (ABREOC) and the Department of Health and Social Affairs, Repubblica e Cantone Ticino, in Southern Switzerland Central Pontine Myelinolysis in a Child With Extreme Hypernatremia Dhaliwal N, Jayaweera D. Western Sydney Toxicology Services, Sydney, Australia Objective: • Extreme hypernatraemia (Na > 190 mmol/L) in children is rarely described. • Demyelinating syndromes are a rare complication (1). • Management is challenging with rapid correction and its complications (2). Case report: • A 5 year old girl with severe global developmental delay presented to a tertiary paediatric ED with altered conscious state. • The child had been unwell for one week with reduced oral intake, anuria and vomiting in the preceding 48 hours. • On assessment, the HR was 70 bpm, BP 130/60, respiratory rate 32 / minute with Spo2 of 100% on room air. • She was obtunded, profoundly dehydrated, mottled, with global hyperreflexia and clonus. • Endocrinological causes were excluded. Investigations : Admission 24 hours 48 hours 5 days Na (mmol/L) 198 147 146 142 K (mmol/L) 2.1 3.5 3.6 3.8 Cl (mmol/L) 168 139 124 107 pH 7.32 7.38 7.44 Urea (mmol/L) 8.5 5.3 4.4 3.6 Creatinine 49 48 45 38 (mmol/L) Urine Osmolality 888 447 (mmol/L) Urine sodium 494 487 440 (mmol/L) Serum osmolality 301 (mmol/L) • The child had been consuming salt and cooking products . • The patient developed seizures. • An MRI brain revealed supratentorial extrapontine myelinosis due to severe hypernatremia. • Management was challenging with initial rapid correction of the serum sodium level. • The child made a slow recovery. Conclusion: • Hypernatremia is a life threatening medical emergency warranting expert management to prevent complications of hypernatraemia and its rapid correction (3). • Children with developmental delay are at increased risk of developing hypernatremia. References: 1. Varanda, Sara, et al. “Central Pontine Myelinolysis Caused by Hypernatremia.” Journal of the Neurological Sciences, vol. 370, 2016, pp. 274–276., doi:10.1016/j.jns.2016.10.001. 2. Arambewela, M. H., Somasundaram, N. P., & Garusinghe, C. (2016). Extreme hypernatremia as a probable cause of fatal arrhythmia: a case report. Journal of Medical Case Reports, 10(1). doi: 10.1186/s13256-016- 1062-9 3. Casavant, Marcel J., and Jill A. Fitch. “Fatal Hypernatremia from Saltwater Used as an Emetic.” Journal of Toxicology: Clinical Toxicology, vol. 41, no. 6, 2003, pp. 861–863., doi:10.1081/clt-120025352. 40° Congress of European Association of Poisons Centres and Clinical Toxicologists

LIQUID LAUNDRY DETERGENT PODS: ANALYSIS OF THE RESULTS OBTAINED FROM ADDITIONAL INFORMATION COLLECTED DURING THE FOLLOW UP BY AN ITALIAN POISON CONTROL CENTRE

A. Celentano, F. Sesana, M. Ferruzzi, F. Davanzo Milan Poison Control Center, ASST Grande Ospedale Metropolitano Niguarda Milan, Italy Objective Results The Milan Poison Control Centre observed an increase in the pediatric exposures to liquid During the study period, 109 additional information follow up cases were collected. Of laundry detergent pods but also an increase of number of liquid laundry detergent pods these 45.9% (n=50) were female and 54.1% (n=59) were male. The age group distribution sold during the year 2017 compared to 2016 and we thought it useful to analyze was: less than 1 year (n=1; 0.9%), 1-4 years (n=95; 87.2%), and 5-8 years (n=13; 11.9%). questions to explore behaviors in the home that contribute to incidents. The accident happened in the morning (n=26; 23.8%), afternoon (n=35; 32.11%), evening (n=37; 33.9%), night time (n=11; 10.1%). The incident happened most commonly in the Methods bathroom (n=68; 62.4%), followed by the laundry room (n=23; 21.1%), kitchen (n=7; 6.4%), balcony (n=4; 3.7%), and other (n=4; 3.7%). The incident occurred most commonly Data was collected from 1 January 2018 to 30 September 2019. The questionnaire because the child opened the original box (n=33; 33.0%), the pods were taken from the consists of 21 items, of which 16 are multiple choice and 5 are open, divided into two opened box (n=22; 23%). The pods were occasionally taken from inside the drum of the topics: "General" including age, sex, time of accident, product, relationship to child washing machine (n=14; 12.8%) and the circumstances were unknown in 6 cases (5,5%). involved in the incident, whether the incident happened in or out of home, the room where incident happened, if this is where washing machine is kept, and if other children FIG 1. THE INCIDENT HAPPENED WHERE THE WASHING FIG 2. SEVERITY OF THE EXPOSURES were present in household when incident occurred. “Access description”: access occurred MACHINE IS KEPT? from the place of normal storage, or access happened during the laundry task when the carer was using the product and if the product was out of storage or access happened before new pack was put away following a shopping trip. Conclusion From the data analysis it is clear that the perception of the hazard represented by the liquid laundry detergent pods is underestimated. This study showed that parents usually stored the detergent pods in a place accessible to children. Parents should keep boxes closed and out of reach of children to reduce this kind of incident. Prolonged Neurological Effects After Delayed Antivenin Administration Alfred Aleguas PharmD, D.ABAT, FAACT 1, Benjamin N. Abo, DO, PMD, FAWM 2,3 1Florida Poison Information Center-Tampa, Tampa General Hospital, Tampa FL 2Aesclepius Snakebite Foundation, Seattle, WA 3Florida State University College of Medicine, Sarasota, FL

Background: Bites from Micrurus species produce significant neurologic deficits that may be delayed 12- 18 1 hours and are thought to most likely be due to the effects of the Phospholipase A 2 (PLA 2) component of the venom 2. Once there is an onset of the descending bulbar paralysis, antivenin administration may not fully resolve those effects. We report a case of prolonged ptosis and disconjugate gaze from a M. fulvius bite associated with a delay in antivenin administration despite initial systemic effects.

Case Report: A 10-year-old male presented to a healthcare facility 1.5h after reporting 2 bites to the palm of his hand from a coral snake. A photo of the snake was produced. He reported a syncopal episode and several episodes of N/V during his trip to the ED. It is unclear whether this information was relayed to the consulted poison center. He was initially not treated with antivenin due to the absence of skin changes or a history of the snake latching onto the patient. After developing shooting pain associated with continued retching, he was administered 1 vial of antivenin 9 hours 16h Post-bite post-envenomation. Another 4 vials were given at hour 12. At 15.5 hours, he developed worsening ptosis and diplopia and another 4 vials were administered. He received an additional 4 11.5h Post-bite vials of antivenin at 22h post-bite due to persistent symptoms. A total of 13 vials of antivenin were given. He was discharged on day 4, with persistent (but slightly improved) ptosis and disconjugate gaze. Although his ptosis resolved after a month, his visual disturbances took 7 months to fully normalize, greatly affecting his daily activities.

Case Discussion: Envenomation from coral snakes M. fulvius and M. tener represent a small fraction of snake bites in the United States 3. In contrast to Crotalidae exposures, little local tissue destruction is noted 4. Regional and systemic symptoms may range from mild to life-threatening. Venom discharge may vary from negligible to over 20 mg, although a dose-response correlation of venom discharge to symptom severity has not been established 4. Traditionally, in response to envenomation, Wyeth antivenin has been administered with an average dose of 6.5 vials in one case series 5. Typically, antivenom is given shortly after presentation for medical care or as needed in response to neurological deficits. The timing and specific indications for administration of antivenin after a contact with a Micrurus fulvius snake varies amongst toxicologists. A previous limit of antivenin availability led many toxicologists to wait for the development of symptoms. As our knowledge

has evolved about the composition of M. fulvius venom, and the irreversible binding of PLA 2 to 16h Post-bite Right disconjugate gaze acetylcholine receptors, recommendations have changed. Judicious, appropriate dosing early 40h Post-bite Resolving ptosis after an envenomation is crucial to avoid the development and progression of symptoms that may not fully resolve for months. References: 1) Sasaki J, Khali PA, Madhuradhar C, et al. Coral Snake Bites and Envenomation in Children; A Conclusions: Case Series. Ped Emerg Care 2014; 30:262—65. 2) Vergara I, Pedraza-Escalona M, Padniagua D, et al. Eastern coral snake Micrurus fulvius venom Administration of Micrurus fulvius antivenin should be administered without delay after a toxicity in mice is mainly determined by neurotoxic phospholipase A2. J Proteomics 2014; credible report of a bite, even if just tenderness with tapping on bite/scratch site continues. This 105:295-306. 3) Gummin DD, Mowry JB, Spyker DA, et al., 2018 Annual Report of the American Association of is especially so when systemic effects are present. Previous myths regarding envenomation Poison Control Centers’ National Poison Data System (NPDS): 36 th Annual Report, Clin Tox ; 57: circumstances and need for neurologic findings prior to antivenin administration should be 1220-1413. 4) Fix JD, Venom yield of the North American coral snake and its clinical significance , South Med J, discounted. Delay in antivenin administration may allow neurologic symptoms to develop that 1980; 73:737-738. may be prolonged or permanent. 5) Kitchens CS, Van Mierop LHS, Envenomation by the Eastern coral snake (Micrurus fulvius fulvius): a study of 39 victims. JAMA 1987;258:1615-1618.

Photos courtesy of author and used with permission Cigatoxin Levels in Fish may be Unreliable in Ciguatera Fish Poisoning Toxicovigilance Studies

Dhaliwal N, Jayaweera D. Western Sydney Toxicology Services, Sydney, Australia

Objective: • Ciguatera fish poisoning (CFP) is the most common form of non-bacterial food-poisoning from fish (1). • It is essential that it be detected for public health control of seafood toxin diseases.

Case Report : • Two females, 48 and 60 years, and a male, 53 years, of the same family, presented to a tertiary ED in Western Sydney, with symptoms of CFP. • They bought a large Sweetlip Emperor reef fish (Lethrinus miniatus) from a local store. It was refrigerated overnight, cooked and consumed the following day. • 3 hours later, all patients developed gastrointestinal symptoms and pruritus. They described myalgias, circumoral and extremity paraesthesias. • A diagnosis of CFP was made (3). • Public health traced the supply to the fish markets from which the fish were distributed throughout the state. • Multiple other cases of CFP were detected in New South Wales that week, linked to the same supplier. • A cooked sample of fish was sent for laboratory analysis. Ciguatoxin was not detected. • Ciguatoxin levels in samples may be under-estimated due to matrix suppression from compounds present in fish tissue (2). • Multiple ciguatoxins have been identified (3). The complexity and variability of ciguatoxins poses difficulty in developing reliable methods to diagnose CFP based on ciguatoxin levels with specificity and sensitivity (4). Conclusion: • CFP diagnosis is based on a history of consuming reef fish, time course of symptoms, and exclusion of other causes. • Cigatoxin levels may be unreliable in diagnosing CFP to aid toxicovigilance studies.

References: 1. Gillespie, N. C., Lewis, R. J., Holmes, M. J., Bourke, J. B., Pearn, J. H., Bourke, A. T., & Shields, W. J. (1986). Ciguatera in Australia: Occurrence, clinical features, pathophysiology and management. Medical Journal of Australia, 145(11-12), 584–590. doi: 10.5694/j.1326-5377.1986.tb139504.x 2. Health.gov.au. (2019). Department of Health | Clinical diagnosis and chemical confirmation of ciguatera fish poisoning in New South Wales, Australia. [online] Available at: https:// www.health.gov.au/internet/main/publishing.nsf/ Content/cda-cdi4001a.htm [Accessed 5 Oct. 2019]. 3. Friedman A, Fleming E, Fernandez M, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs 2008;6:456–79 4. Caillaud, A., De la Iglesia, P., Darius, H., Pauillac, S., Aligizaki, K., Fraga, S., Chinain, M. and Diogène, J. (2010). Update on Methodologies Available for Ciguatoxin Determination: Perspectives to Confront the Onset of Ciguatera Fish Poisoning in Europe. Marine Drugs, 8(6),pp.1838-1907. Physostigmine and Cyclobenzaprine Summary of Safety and Efficacy in 30 Patients Timothy J. Wiegand 1, MD; Rachel Gorodetsky, PharmD 1,2 , Rachel Schult, PharmD 1, Nicole Acquisto, PharmD 1, Kim Kaukeinen 1; and Kenneth Conner, MPH, PsyD 1 1.) Department of Emergency Medicine at Strong Memorial Hospital and the University of Rochester Medical Center, Rochester, NY, USA; 2.) D’Youville College School of Pharmacy Physostigmine Effectiveness & Symptom Recurrence Objective: Results Continued: 25 • To describe the incidence of adverse effects, effectiveness and • Physostigmine was effective in reversing coma in 10/15 (66%) to characterize the dosing of physostigmine for reversal of 20 • Physostigmine was effective for agitation/delirium in 14/23 (61%). anticholinergic symptoms for cyclobenzaprine intoxication. • Coma, agitation or delirium returned a mean of 60 minutes in 7/10 15 Methods: (70%), 8/10 (80%) and 11/12 (92%) respectively. • Retrospective review of medical records for a subset of 30 10 Improvement persisted • EKG results were documented in 22 (63%) with mean QRS of 90 patients who ingested cyclobenzaprine out of all patients who Recurrence or persistence of symptom msecs (range 74-116) and QTc 445 msecs (range 360 – 507 msecs). received physostigmine for anticholinergic toxicity at an 5 Ineffective reversal academic 850 bed, tertiary-care hospital from June, 2011 Effective Reversal • Concomitant dosing of benzodiazepines with physostigmine occurred Total* through July, 2016. 0 in 11 with 5 receiving multiple doses of benzodiazepines. *some patients had both coma and • No patients had vomiting, bradycardia or seizures and no cardiac Results: agitation/delirium • 227 patients received physostigmine 30 (13.2%) ingested arrhythmias occurred. cyclobenzaprine. 3 (10% of cyclobenzaprine cases) ingested 5 Discussion: additional anticholinergic agents. Physostigmine Dosing 10 • Most patients had improvement of symptoms yet they recurred within • Reason for ingestion included 28 intentional, 1 unintentional, 1 60 minutes in most (70-92%). related to an adverse effect. Total • Redosing was variable and delayed compared to time of symptom • Mean age was 35.6 (range 4-64 years-old), 6 < 18 years-old, 45 1 dose recurrence in general. and 15 (53%) female. 2 doses • Comprehensive drug testing was not uniformly performed but 30 3 doses • In some patients use was primarily diagnostic; others both diagnostic in 7 (23%) cyclobenzaprine was identified by GC/MS and in 23 & therapeutic. Degree of symptom recurrence was variable. (77%) through history and other corroborating information. • Repeat dosing was more common when the Toxicology Consult • 45 doses of physostigmine were used for these 30 patients. Service was directly bedside and/or administered the antidote. • The 2 mg dose most common given in 22/30 (73%). Mean time to 3rd 20 Conclusion: • 10 patients received a second dose and 8/10 it was 2 mg. Time in hours dose 6.2 • Physostigmine was safe and effective for most patients in our cohort • The mean time to 2 nd dose was 6.2 hours (range 0.1-23 hours) Mean time to 2nd yet symptoms recurred within 1 hour in most. Risk/benefit with more • 5 received a 3 rd dose (3/5 it was 2 mg) a mean of 20 hours dose 0 5 10 15 20 25 frequent dosing; or use beyond diagnostic purposes in some warrants (range 2-54 hours). Mean Time to Redosing of Physostigmine for 2 nd & 3 rd Dose further study.

1

1 Anti-Anginal Asystole: Fatal Ranolazine Overdose Emma Furlano,1 Mark K Su,2 Anne Hoffa,3 Adina Badea,4 Kara Lynch,4 Silas W Smith1 1. Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States. 2. New York City Poison Control Center, New York, NY, USA. 3. New York City Office of Chief Medical Examiner. 4. Department of Laboratory Medicine, University of California–San Francisco. University of California–San Francisco

Background Discussion (continued) • Ranolazine is an antianginal drug, used for chronic angina • Ranolazine inhibits the outward delayed rectifier potassium refractory to first line agents. (1) current (hERG) to cause QT prolongation. • Few reports of ranolazine overdose exist, limiting definitive • Additionally, ranolazine blocks neuronal sodium channels in management recommendations and assessment of toxicity. (2) cellular models. • We present a case report of a fatal ranolazine overdose. • This may underlie seizures occurence in overdose. (2,3) Hospital Course • While on the hospital ward, nine hours after presentation, he Conclusion Initial Presentation experienced three witnessed convulsive episodes, each lasting • Based on limited literature reports and this patient’s • A 67-year-old man with a past medical history of hypertension, several minutes before spontaneous resolution, with return of presentation, ranolazine overdose can cause severe coronary artery disease, chronic angina, and schizophrenia mental status. morbidity and mortality in a delayed fashion, despite initial presented to the emergency department complaining of emesis • Shortly thereafter, the patient experienced pulseless electrical apparent clinical stability. • He reported ingesting approximately 30g of extended-release activity for 20 minutes, followed by ventricular tachycardia, and • Patients with ranolazine overdose should be closely ranolazine (a one-month’s supply) several hours prior in a suicide ultimately, asystole. monitored for rapid cardiac and neurological attempt. Physical examination demonstrated an alert male in no • He received defibrillation, continuous cardiopulmonary decompensation for up to 24 hours based on case data. (3,4) acute distress. resuscitation, and advanced cardiac life support, but was unable to • Previous interventions have included volume resuscitation, • Vitals signs: BP, 160/87 mmHg; HR, 72 beats/min; RR, 18 be resuscitated. inotropes and vasopressors, benzodiazepines (for seizures), breaths/min; pulse oximetry, 99% saturation on room air. • An ante-mortem serum ranolazine concentration was 12 mg/L and ECLS. (3,4) • Electrocardiogram (ECG): normal sinus rhythm (73 beats/min); PR (therapeutic: 0.4-6.1 mg/L). 186 ms; QRS, 96 ms; QTc (Bazett’s) 434 ms. • Laboratory analysis: normal electrolytes, renal and hepatic Discussion References function. Acetaminophen, ethanol, and salicylate concentrations • In normal dosing, peak concentration are obtained in 2-6 hours, and 1. Ranolazine [package insert]. Foster City, CA: Gilead Sciences, Inc; 2019 were undetectable. half-life at steady state is 7 hrs. However, clearance decreases with 2. Cattaneo M, Porretta AP, Gallino A. Ranolazine: Drug overview and • One dose of activated charcoal was provided, but gastrointestinal higher doses, which would be expected in overdose. (2) possible role in primary microvascular angina management. Int J Cardiol. decontamination was not performed. 2015;181:376-381. doi:10.1016/j.ijcard.2014.12.055 • Ranolazine inhibits the late phase of the inward sodium current, the • Seven hours after presentation, he developed acute altered mental 3. Goodnough R, Kim-Katz S, Badea A, Lynch KL, Cotter LE, Smollin CG. A late (sustained/persistent) I , in myocardial cells. status (confusion without agitation or sedation). Na fatal ranolazine overdose after an intentional ingestion. Clin Toxicol • This current exchanges Ca2+ via a Na+/Ca2+ antiporter, which causes (Phila). 2020;58(3):213-214. doi:10.1080/15563650.2019.1618465 • A repeat ECG showed a first-degree atrioventricular block at 66 calcium-induced calcium release from the sarcoplasmic reticulum 4. Akil N, Bottei E, Kamath S. Ranolazine overdose-induced seizures. Am beats/min; PR, 220 ms; QRS, 108 ms; QTc (Bazett’s) 450 ms. • Thus, ranolazine indirectly acts as a calcium channel blocker. J Emerg Med. 2015;33(12):. doi:10.1016/j.ajem.2015.04.062 • He was admitted with a plan for 24-hour telemetry monitoring. A 10-YEAR REVIEW OF ENQUIRIES TO THE UK NATIONAL POISONS INFORMATION SERVICE INVOLVING HIGH-DOSE INSULIN (HDI) Moyns E, 1 Elamin MEMO, 1 Sandilands EA, 2 Thomas SHL, 3 Thompson JP, 4 Bradberry SM. 1 1NPIS (Birmingham Unit), City Hospital, Birmingham, UK; 2NPIS (Edinburgh Unit), Royal Infirmary, Edinburgh, UK; 3NPIS (Newcastle Unit), Regional Drug and Therapeutics Centre, Newcastle, UK; 4NPIS (Cardiff Unit), University Hospital Llandough, Cardiff, UK.

Objective Insulin doses To review enquiries to the UK National Poisons Information Service (NPIS) Maximum administered insulin infusion doses documented were <3 unit/kg/hr involving high-dose insulin (HDI). in 121/340 cases, 4-9 unit/kg/hr in 30 cases, 10 unit/kg/hr in 31 cases and >10 unit/kg/hr in 6 cases as shown in Figure 2. In 152 cases the infusion doses Results were unknown. A retrospective analysis of UK NPIS enquiries between 1 January 2009 and 31 50 December 2018 retrieved 954 relevant enquiries involving 763 patients. Of these 340 received HDI, 125 did not and it was unknown if HDI was given in 298 patients . 45 All cases given HDI

The number of patients given HDI ranged from 10 in 2009 to a peak of 58 in 2017. 40 Ten patients given HDI were aged 16 years or less. The mean age was 48 years (range 12-89 years). 35 Polypharmacy ingestions were involved in 81% of cases (n=274) as shown in Doses prior to Figure 1, most often including calcium channel blockers (CCB) n=196 or beta 30 consulting NPIS blockers (BB) n=129. Single drugs were taken in 65 cases: CCB n=34, beta blocker n=24, tilmicosin n=1, tricyclic antidepressant (TCA) n=1, other drugs n=5. In one 25 case the substance was unknown. 20

200 15 Number Number of enquiries

180 10

160 5

140 0

120

100 Insulin infusion dose unit/kg/hr Figure 2. Maximum insulin infusion dose given 80 The largest insulin infusion dose was 20 unit/kg/hr which was given to 4 patients who had all taken mixed overdoses including amlodipine (n=3),

Number Number of enquiries 60 bisoprolol (n=1) and flecainide (n=1). Further details about these patients is shown in Table 1. Hypoglycaemia and hypokalaemia were not reported in any of 40 the patients given >10 unit/kg/hr. The outcome of these 6 patients was complete recovery (n=2), death (n=2) and the outcome in the remaining 2 20 patients is unknown.

0 CCB BB TCA Other CCB BB TCA Other Outcome Single pharmacy Poly pharmacy Outcome in the 340 cases where HDI was given were complete recovery Figure 1. Agents involved in enquiries where HDI was given (n=124), sequelae (n=12, mainly hypoxic brain injury and renal impairment), (n=340) death (n=86) and ongoing features at the time follow-up was discontinued (n=55). The outcome was unknown in the remaining 63 cases. Conventional inotropes had already been given to 70% (n=239) of patients prior to being treated with HDI and 61% (n=207) had already been given glucagon (60% of these cases involved a beta blocker). Hypoglycaemia was reported in 10% of Conclusion enquiries (n=34) and hypokalaemia in 4.7% (n=16). Advice was sought about the Enquiries regarding the discussion of HDI have increased over the last 10 years. discontinuation of the insulin infusion in 16% of all patients known to have been The majority of enquiries where HDI is given involve polypharmacy overdoses treated with HDI . of CCB and beta blockers. Doses of >10 unit/kg/hr were used in 6 of 340 cases.

PATIENT MAX HDI RATE DRUGS INGESTED OUTCOME AGE Unit/kg/hr

47 Amlodipine , sodium valproate, levetiracetam, clonazepam, citalopram, omeprazole 13 Complete recovery

53 Amlodipine , gliclazide, hyoscine, omeprazole, quetiapine, ramipril, sitagliptin 18 Death

49 Amlodipine , paracetamol, duloxetine 20 Death

57 Amlodipine , citalopram 20 Unknown

Amlodipine, bisoprolol , clopidogrel, aspirin, doxazosin, ramipril, isosorbide 79 20 Complete recovery mononitrate, diazepam, omeprazole

40 Bisoprolol , flecainide, naproxen, cocodamol 20 Unknown

Table 1. Case details for patients given insulin infusion doses>10 unit/kg/hr Poison center recommendations for severe lithium poisoning are limited by laboratory protocol

variations Emma Furlano1, Philip C DiSalvo1, Timothy C Backus1, Khameinei Ali2, William K Chiang1, Josh J Wang1 1 Background: Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York City, NY, United States 2Department of Emergency Medicine, St. John’s Riverside Hospital, Yonkers, NY, United States Results continued: • Severe lithium toxicity may result in seizures, • Twenty hospitals (74.1%) were able to extend the encephalopathy, and permanent neurologic reportable range to 6 mmol/L or higher with sequelae. (1) dilution. • The Extracorporeal Treatments in Poisoning • 6 (22.2%) were unable to measure a level of Workgroup (EXTRIP) recommends greater than 5 mmol/L. extracorporeal toxin removal (ECTR) in cases of • We contacted three laboratory directors for severe lithium poisoning (2) non-adherence to manufacturer guidelines. • Unfortunately, not every hospital laboratory • Two reported a conservative range because the can measure high [lithium]. regional department of health will cite facilities • We studied how lithium was measured and for posting a range they cannot verify. reported in hospital laboratories across a large • The third director explained that lithium levels metropolitan area. at their specialized oncologic hospital are usually therapeutic or sub-therapeutic and they Methods: typically do not encounter specimens requiring dilution. • Electronic survey of hospital laboratory medical

directors within the New York City Poison

Control Center catchment area. Conclusion: • Highest reported pre-dilution [lithium] • Nearly half of surveyed hospitals were unable to • Dilution protocols quantify [lithium] >3mmol/L without further • Compared hospital reported data to dilution. analyzer-specific protocols obtained directly • 2 hospitals that measured up to 4mmol/L did not from manufacturers. perform any dilutions. • If there was a discrepancy between • Toxicologists and laboratorians should be manufacturer and hospital protocols the encouraged to develop protocols to rapidly laboratory medical director was contacted. quantify high [lithium] serum specimens.

Results: References: • Twenty-seven of 52 hospitals responded to the 1.Hoffman RS. Evidence-based recommendations for survey. haemodialysis in lithium-poisoned patients: Getting from • Eighteen hospitals (66%) reported a pre-dilution where we are to where we want to be. British Journal of maximum of 3 mmol/L or less. Clinical Pharmacology. 2020. doi:10.1111/bcp.14149 • 4 (14.8%) reported a maximum pre-dilution 2.Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal lithium concentration of 3.1 to 3.5mmol/L Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J • 2 (7.4%) could report up to 4 mmol/L but did not Reported lithium concentrations from 24 hospitals. perform dilutions. Am Soc Nephrol. 2015;10:875-87 * represents hospitals that could measure post-dilution lithium concentrations >8 mmol/L Variations in the detection, reporting, and interpretation of low acetaminophen concentrations may lead to overtreatment 1 1 1 2 1 1 Philip C DiSalvo, Timothy C Backus, Emma R Furlano, Kham Ali, William K Chiang, Josh J Wang 1. Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU Grossman School of Medicine, 2. St. John’s Riverside Hospital

Background Results When the timing of an acetaminophen (APAP) overdose is Quantified concentrations as low as 1 mg/L are reported to unknown, N-acetylcysteine (NAC) should be administered clinicians by 1 hospital, 1.6 mg/L by 2 hospitals, 2 mg/L by until the serum acetaminophen concentration [APAP] falls 5 hospitals, 3 mg/L by 1 hospital, 5 mg/L by 4 hospitals, 7 to a low or undetectable level. Poison center mg/L by 1 hospital, 8 mg/L by 2 hospitals, 10 mg/L by 5 recommendations rely on precise measurements of serum hospital and 15 mg/L by 1 hospital. Whereas most [APAP] at the treating facility. Variation in laboratory hospitals reported all values within the measurable range measurement and reporting procedures for APAP at low of their analyzer, multiple hospitals used a higher reporting concentrations may therefore affect patient care by cutoff. For example, one hospital employs an analyzer altering the duration of NAC treatment. capable of concentration quantification as low as 5 mg/L, but reports all results less than 15 mg/L only as “<15 mg/L.” Methods The reviewed references recommended stopping NAC when serum [APAP] was <10 mg/L (1 reference), when it was We surveyed hospital laboratory medical directors within undetectable (4 references), or either (2 references). Two the New York City Poison Control Center catchment area. reference did not establish objective cessation criteria. Respondents provided values for the lowest acetaminophen concentration they report and details about their analyzers. Reporting cutoffs were compared to manufacturer-specified minimum-detectable Conclusion concentrations for each laboratory’s analyzer. Our findings demonstrate substantial variations in the For additional context, we examined the criteria for NAC measurement, reporting, and interpretation of low serum cessation recommended by six reference texts (internal [APAP]. We suspect that the reporting of detectable but medicine, emergency medicine, medical toxicology), one physiologically insignificant concentrations increases the toxicology professional society, one acetaminophen cost and duration of NAC therapy but future work is manufacturer, and one online point-of-care needed to determine the impact of different [APAP] decision-support resource. reporting thresholds on patient-centered outcomes. Evaluation of the quality of current procedures in the

Unidad de Toxicología Clínica Hospital Clínico Universitario assistance of ethanol overdose at the ED Zaragoza. Spain

Ferrer-Dufol A1, Menao S 1, Ruiz F1, Founaud B1, Castrillo MA1, Ramos P1 Serrano C.2 1 Hospital Clínico Universitario, Zaragoza. 2 Hospital Príncipe de Asturias, Alcalá de Henares. Spain

Objective: Ethanol overdose is the most frequent Methods: Prospective observational study of the ethanol toxicological emergency in our EDs, in Spain. Ethanol is overdoses cases presenting at the ED of a general Hospital during frequently associated to other drugs overdoses and 2018. contribute to the clinical picture in traumatic lesions. The Analyzed variables are: age, sex, chronology, total involved plasticity and individual variability of the symptoms going agents, diagnostic tools, symptomatology, treatment and from severe agitation to coma, and the overlapping of other evolution. toxic or traumatic pathogens, lead to a high degree of Quality endpoints selected to identify improvement actions are diagnostic inaccuracy and lack of standardized treatment. The analytical confirmation of toxic agents, capture of basic vital aim of this work is to evaluate current deficiencies in order to constants, adequacy of biochemical parameters, treatment of stablish quality criteria for the diagnosis and treatment of agitation and use of antidotes these cases. Results: n 422 cases (50% of total poisoning cases) Mean age = 37,8 y-o (13-85)

Sex distribution Week days’ distribution is uneven with a predominance at weekends

42% Men Women 58%

Symptoms 400 100,00% 364 Agitation/anxiety 150 cases 90,00% 350 86,26% NCS depresion 90 cases 80,00% 300 70,00%

250 60,00%

200 50,00%

40,00% 150 126 29,86% 30,00% 100 60 20,00% 14,22% 50 10,00% average [EtOH]s = 1,65 g/L (sd 0,95) 17 4,03% 0 0,00% Ethanol 266 cases No relevant pathology found Neurologic C-V Digestive Respiratory Ethanol + co-ingestants 65 cases

Etiology

55; 13% 15; 4% Treatment abuse suicide  Gastric decontamination was used in 9 cases due to medicine co-ingestions. unknown

352; 83%

Associated  Symptomatic treatment included fluids (86%), thiamine (14%) and gastric protectors (7%). Trauma 19%  Treatment of agitation:  mechanical restraint (33%)  benzodiazepines 59%, and neuroleptics (21%), alone or associated  Antidotes (flumazenil and or naloxone) were used in 34 cases with no guidelines indication 33% of cases have been discharged with a clinical diagnosis of inebriation without analytical confirmation. Conclusions: We have verified the absence of standardized procedures to diagnosis and treat ethanol overdoses at the ED. Specific improvement points are identified in both areas.