Hrev_master [page 18] [Emergency Care Journal 2025; 21:12945] Emergency Care Journal 2025 volume 21:12945 Abstract Data on patients with poisoning requiring ICU (Intensive Care Unit) & HD (High Dependency) care in Singapore is inadequate. In this study, we describe the epidemiological, clinical characteristics, implicated agents, interventions, and outcomes of patients with toxic exposures admitted to HD & ICU. We conducted a retrospective and observational study. Hospital records of all cases referred to CGH Toxicology Service from 1 January 2015 to 31 December 2022 were reviewed. A total of 245 (9.6%) out of 2547 patients reviewed required HD or ICU care. 131 patients were admitted to ICU, while 114 patients were admitted to HD beds. Amongst those admitted to ICU, male to female ratio was approximately 60:40, and the commonest age group was 31-40 years old (19.9%), while deliberate self-harm poi- soning accounted for 52.7 % of these cases. Benzodiazepines, anti- psychotics, anti-depres-sants, and opioids class of drugs and medica- tions were the most associated with ICU admissions. The fatality rate was 3.2 %. Car-diotoxic drugs, anti-psychotics, and anti-depressants class of med-ications were associated with most fatalities. Introduction Poisoning poses a significant health problem worldwide. Locally a significant proportion (36%)1 of patients presenting to the Emergency Department (ED) for acute poisoning require inpa- tient care. Previous local studies found between 1.7 – 9 %1-3 of hos- pitalizations for poisoning required admission to a High Dependency (HD) ward or Intensive Care Unit (ICU). There is still very limited information about the poisoning characteristics of patients with toxic exposures requiring HD or ICU care, and there is a paucity of local studies1,2,4 illustrating patients presenting with poisoning admitted to these units in Singapore. The aim of this study is to describe the types and patterns of toxic exposures associated with HD and ICU stay, their epidemio- logical, demographic, and clinical characteristics, severity and cer- tainty, interventions and outcomes including length of stay and mortality. Materials and Methods The study was conducted at the Changi General Hospital (CGH) Accident and Emergency Department (A&E). This is a ter- tiary care center and an academic hospital of over 1000 beds capacity. The A&E has an annual attendance of over 143,000 patients.5 The Toxicology Service at CGH (now integrated with the SingHealth Cluster Toxicology Service) provides round-the-clock consultation for patients with poisoning, and is run by clinical tox- icologists, who have a primary training background in emergency medicine. This is a retrospective review of all poisoning cases referred to the toxicology service from 1/1/2015 to 31/12/2022, which required either HD or ICU admission. The toxicology service con- sultation records and database during the study period were reviewed to identify the cases. The A&E and in-patient case note records were reviewed as well. The data analysis was done by the various authors and in case of doubts and uncertainties, there was intra-group consultation to arrive at a consensus between the study authors. Analysis was done by descriptive statistics and MicrosoftÓ Excel was mostly used for the statistical calculations. The poisoning severity score (PSS)6 was used to grade poison- ing severity for all patients. The score ranges from 0 to 4 in clinical severity and the highest score for the patient in the A&E was counted. The organ system effect that resulted in the score was also determined. The likelihood of poisoning exposure was adapted from the WHO Uppsala Monitoring Centre system on causality assessment7 and we classified the certainty of poisoning as a score of either 4) definite, 3) probable, 2) possible, and 1) unlikely. For mortality cases, a Relative Contribution to Fatality (RCF)8 scale was assigned. A RCF score of 1 to 3 is considered to be asso- ciated with the poisoning exposure, whereas a RCF score of 4 to 6 was deemed not to be associated with the poisoning exposure. Correspondence: Abhay Kant, Accident and Emergency Department, Changi General Hospital, Singapore. E-mail: dr.abhaykant2007@gmail.com Key words: poisoning and toxicology patients; patients with toxic exposures; emergency department. Conflict of interest: the authors declare no conflict of interest. Ethics approval and consent to participate: a central institutional review board (CIRB) approval was applied for, which deemed that a CIRB review was not required for this study. Availability of data and materials: the data supporting the findings of this study are available within the article and its supplementary materials. Received: 19 August 2024. Accepted: 7 November 2024. Early view: 23 December 2024. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2024 Licensee PAGEPress, Italy Emergency Care Journal 20245; 21:12945 doi:10.4081/ecj.2024.12945 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Emergency department poisoning and toxicology patients admitted to the high dependency and intensive care units: an eight-year analysis Abhay Kant, Rupeng Mong, Gabriel Joseph Arciaga, Kelvin Kaibin Kuan, Hock Heng Tan Accident and Emergency Department, Changi General Hospital, Singapore For the purpose of this study, we included multiple drug class- es under the group cardiotoxic drugs like Beta-Blockers (BBs), Calcium Channel Blockers (CCBs), aconite like Traditional Chinese Medications (TCM), and anti-arrhythmic medications like amiodarone, due to their predominantly potentially lethal car- diotoxic effects in poisoning. Multi-substance ingestions were classified based on the presentation history as well as the biochem- ical drug analysis results. Results During the 8-year period 2015 to 2022, 2547 patients were referred to the toxicology service; of the 250 patients who were admitted to HD or ICU, 5 were excluded as poisoning was deemed unlikely in them, leaving 245 (9.6%) for analysis (Figure 1). Amongst the 245 patients, 131 were admitted to ICU, while 114 patients were admitted to HD. Patients who were admitted to both HD and ICU were categorized under the ICU group. The trend showed an unexplainable dip in the ICU and overall admissions in 2018 which improved slightly in 2019 and showed a downwards trend again during the pandemic years of 2020-2021 (Figure 2). Characteristics of patients admitted to ICU There were 79 males and 52 females. The age groups 31-40, 41-50 and 21-30 had the highest numbers at 26, 24 and 24 respec- tively (Figure 3). Deliberate self-harm exposures accounted for 69 (52.7 %) while drug abuse was noted in 31 (23.7 %) patients. Certainty of poisoning7 score of 4 was determined in 81 (61.8 %), 36 patients had score of 3 while 14 patients were thought to have score of 2. Highest PSS6 in the A&E were 3 for 99 (75.6 %), 2 for 25 and 1 for 7 patients. Highest PSS involving Central Nervous system was found in 87 (66.4 %), Cardiovascular System in 36, Renal System in 14, Gastrointestinal and Hepatic System in 11, Respiratory System in 9 while musculoskeletal system involvement was found in 1 patient. Twenty-six (19.8 %) patients had multiple systems’ involvement wherein the PSS was equal for each organ system. The routes of exposures were determined to be via oral route in 119 (90.8 %), via inhalational route in 6, via intravenous route in Article [Emergency Care Journal 2025; 21:12945] [page 19] Figure 1. Study recruitment and eventual outcomes. 2, and both oral and inhalational in 1 patient while route of expo- sure could not be determined for the remaining 3 patients. Benzodiazepines were implicated in 51, anti-psychotic medi- cations in 36, anti-depressants in 32, opioids in 32, while car- diotoxic agents were implicated in 18 patients. Ethanol was ingest- ed by 5 patients while Paracetamol was detected in 13 patients. Drug withdrawal syndrome accounted for 11, stimulants and sym- pathomimetics in 18, 5 were exposed to anti-diabetic and hypo- glycemic agents while 4 others were exposed to household bleach. Benzodiazepines had nitrazepam (n=14), diazepam (n=13), alpra- zolam (n=8), anti-psychotic medications had quetiapine (n=19), olanzapine (n=9), while the anti-depressants had fluoxetine (n=6), and amitriptyline (n=4) as the commonest individual agents. Opioids had codeine (n=14) and tramadol (n=10) while cardiotoxic drugs had amlodipine (n=6), digoxin (n=2) and nifedipine (n=2) as the commonest agents. Serum lactate levels done in the ED were available only for 37 patients, wherein the median lactate level was 4.96 (2.93-11.56). Similarly, lactate levels in the ICU were available only for 39 patients and the median lactate level was 2.72 (1.78-4.91). The pH levels done in ED were available for 44 patients, and the median pH level was 7.278 (7.18 - 7.38) while the pH levels done in the ICU were available for 43 patients wherein the median pH level was 7.319 (7.25 – 7.36). The APACHE II scores were available only for 23 patients in the ICU and the median score was 17 (12- 26.5). Article [page 20] [Emergency Care Journal 2025; 21:12945] Figure 2. ICU, HD and overall admissions by year. Figure 3. Age distribution of ICU, HD patients and overall numbers. A trial of an anti-dote either in the A&E or in ICU was given for 54 (41.2%) patients. Intravenous Naloxone (n=17), IV N- Acetylcysteine (n=13), IV Sodium Bicarbonate (n=11) and IV Flumazenil (n=7) were used most. Decontamination measures were administered in 29 patients. Activated Charcoal was used in 27, gastric lavage in 4 and whole bowel irrigation (WBI) in 1 patient. Three patients underwent a gastric lavage and were given activated charcoal as well. Intubation was performed for 98 (74.8 %) patients, of which majority (n=74) were intubated in the A&E. Most common expo- sures requiring intubations were benzodiazepines (n=43), anti-psy- chotic medications (n=29), anti-depressants (n=26), antihistamines (n=16), opioids (n=15), stimulants & sympathomimetics (n=14) and cardiotoxic drugs (n=12). some common agents associated with the intubations were quetiapine (n=16), diazepam (n=12), promethazine (n=9), nitrazepam (n=9), olanzapine (n=7), and lorazepam (n=4). Vasopressor or inotropic support was required in 46 patients. Cardiotoxic agents (n=16) were most associated with their usage followed by benzodiazepines (n=12), anti-depressants medications (n=7) and anti-psychotic medications (n=7) while calcium channel blockers (n=7; amlodipine=5, nifedipine=2), diazepam (n=4), amphetamine (n=4) and aconite (n=3) were the most associated individual agents. Single agent was used in 16 patient, dual agents in 14, while more than two agents were required in 16 patients. Five patients were administered HIET (High Insulin Euglycemic therapy)9 and were exclusive to the cardiotoxic drugs. Amlodipine (n=4) and nifedipine (n=1) exposure was found in these and the nifedipine patient had also ingested atenolol concurrently. ECMO (Extra Corporeal Membrane Oxygenation) therapy was instituted for two patients. First ECMO patient had ingested massive amounts of amlodipine (550 mg) together with paracetamol (13 grams). The patient successfully underwent a VA (Veno- Arterial)10,11 ECMO therapy for 3 days concurrently with Therapeutic Plasma Exchange (TPE) using 2/3 albumin and 1/3 Fresh Frozen Plasma (FFP). The second ECMO patient had ingest- ed massive amounts of Quetiapine and unfortunately died from the poisoning effects. The Quetiapine blood levels were 5.3 mcg/ml. Our study noted the usage of Extracorporeal Treatments (ECTRs)12,13 for 21 patients (17 in the ICU patients’ group and 4 in the HD patients’ group). Out of these 22 patients, 20 patients did not have any regular dialysis requirement prior to their toxicologic exposure. Cardiotoxic drugs (n=8) followed by stimulants & sym- pathomimetics (n=3), alcohols including ethanol (n=3), drug with- drawals (n=2) and metformin (n=2) required Renal Replacement Therapy (RRT). Most common indications were acidosis, and olig- uric acute kidney injury. Two of these 22 patients in the ICU group had pre-existing end stage renal failure requiring regular dialysis prior to their toxicologic exposure. Drug removal was the primary requirement in 6 patients and the most common drugs were ethylene glycol, methanol, salicy- late, metformin induced lactic acidosis (n=2) and Theophylline. We also noted that there was progression of the initial ED Poisoning severity Scores in the inpatient ward for 30 patients, including the 14 patients who demised eventually. This progres- sion was associated with anti-depressants medications, benzodi- azepines, drug withdrawal syndromes, anti-psychotic medications, caustic agents, cardiotoxic drugs, unknown medications and poi- sons, non-opioid analgesics and salicylates, anti-epileptics, alco- hols including ethanol, opioids, cellular asphyxiants, antihis- tamines, stimulants and sympathomimetics and non-benzodi- azepine sedatives in decreasing order of frequency. Benzodiazepine withdrawal, lorazepam, household bleach inges- tion, ethanol, fluoxetine, olanzapine, pregabalin and quetiapine were the most common individual agents associated with worsen- ing of PSS after transfer to inpatient ward, in the order of their fre- quency. Outcomes Eighty-one patients (61.8 %) were eventually discharged home, 33 patients required transfer to a long-term psychiatric hos- pital, 1 patient requested transfer to a private hospital, 1 was trans- ferred to a rehabilitation hospital, 1 to a specialized neurology intensive care unit under a different hospital, while 14 patients died. Amongst the 14 deaths, only 12 were deemed to be poisoning related wherein 6 with RCF score of 1, the respective implicated agents were nifedipine and atenolol; amlodipine; amphetamine; salicylate; hydrogen peroxide; and quetiapine. One patient with RCF score of 2 had amitriptyline while another one had exposure to fluoxetine, olanzapine and fentanyl. Two patients with RCF score of 3 had ethanol, sotalol and unknown exposures respective- ly. 1 patient who died from spontaneous intracranial hemorrhage had RCF score of 4 and the nature of the poisoning involved was not clear in this case. Another patient with RCF score of 4, blood toxicology analysis revealed nitrazepam. He had presented with cardiogenic shock, acute pulmonary oedema, and severe metabolic acidosis. Emergency coronary angiography showed clean and unobstructed coronary vessels with TIMI 3 flow.14 Even though blood toxicology revealed nitrazepam, it was unlikely to account for the presentation and mortality. The median ICU length of stay (LOS) was 1.72 days or 41.30 hours (IQR=25.73 Hours – 75.21 Hours). During the same admission, 42 patients were admitted to both the HD as well as the ICU. Agents associated with longest ICU LOS were sotalol (17.8 days), malathion (15.3 days), amio- darone (14.8 days), ethanol (14.4 days) and household bleach (12.6 days). Characteristics of patients admitted to HD only There were 74 (64.9 %) males and 40 (35.1 %) females. Deliberate self-harm exposures accounted for 51 (44.7 %) while drug abuse was noted in 38 (33.3 %) and unintentional overdose in 16 (14 %) patients. Highest PSS in the A&E were 3 for 54, 2 for 43 and 1 for 17 patients. Highest PSS involving central nervous sys- tem was found in 80, and cardiovascular system in 29. The routes of exposures were determined to be via oral route in 108 patients. Benzodiazepines were implicated in 90 patients, opioids in 57, anti-depressants in 48, antihistamines in 43, anti-psychotic medi- cations in 28, stimulants and sympathomimetics in 24, anti-epilep- tics in 17 and cardiotoxic agents in 16 patients. A trial of anti-dotes was given in 53 (46.5%) patients. IV naloxone (n=25), IV n-acetyl- cysteine (n=8), and IV flumazenil (n=8) were the commonest used anti-dotes. Decontamination measures were administered in 12 patients. Activated charcoal was used in 10, Whole Bowel Irrigation (WBI) in 1 patient while one patient with organophos- phate poisoning was scrub washed and showered. Ten patients required vasopressors and inotropes while five patients required RRT and dialysis. Eighty-five patients were eventually discharged home, 26 patients required transfer to a long-term psychiatric hos- pital, and 1 patient to a specialized women’s hospital while two were transferred to a long-term rehabilitation hospital. The median HD length of stay (LOS) was 1.39 days or 33.3 hours (IQR=21 Hours -48.1 Hours). Paracetamol Poisoning with concomitant hep- ato-biliary sepsis (12.4 days), Methamphetamine (7.5 days) and Lithium (5.9 days) were associated with the longest HD LOS. Article [Emergency Care Journal 2025; 21:12945] [page 21] The results of the patients admitted to both HD and ICU wards are illustrated in the Figure 2 and 3 and Supplementary Materials Table 1a, 1b and 1c. Discussion Benzodiazepines,15 anti-psychotic medications, anti-depres- sant medications, opioids, antihistamines, cardiotoxic drugs and stimulants and sympathomimetics for the ICU group while benzo- diazepines,15 opioids, anti-depressants, antihistamines, anti-psy- chotic medications, and stimulants and sympathomimetics were the commonest class of agents associated with the HD admissions. This contrasts with the local study by Tay et al.4 in 1998, where the predominant agents were organophosphates and carbamates, ben- zodiazepines, tri-cyclic antidepressants and phenothiazines. Forty- one patients in the ICU group and 48 patients in the HD only group had three or more implicated agents, which makes it somewhat dif- ficult in these patients to link the associations with any individual class of agent. Ethanol and Toxic alcohols did not rank amongst the top 10 class of agents in our study unlike an Italian based demo- graphic study by Botti et al.16 where in alcohol accounted for more than one-third of the exposures. Some of the indications for ICU admissions17 were initial depressed GCS with anticipated further deterioration, severe cardiovascular instability, arrhythmias, recur- rent seizures at presentations, severe end organ dysfunctions and requiring intubation with mechanical ventilation in ED. For HD admissions, the indications were usually low GCS but not comatose and not requiring intubation or mechanical ventilation, moderate cardiovascular instability requiring low doses of inotropes and vasopressors. Deliberate Self Harm (DSH) or attempted suicide as a reason for exposure accounted for about 52.3 % of ICU and about 44.7 % of the HD patients. This is similar to another study by Banderas- Bravo et al.18 More patients were above 40 years age in the ICU group (<40:>40=60:71) while the ratio was inverse in the HD group (<40:>40=68:46). There was a male preponderance in this study contrary to a local study by Chiu et al.1 in 2011. From 2015 to 2017, the blood and urine toxicology screening tests were not available readily, whereas from 2018 onwards their availability became more common. Hence 2018 onwards, more patients had certainty of poisoning score at 4. Our study also shows a male pre- ponderance with over 60% of patients as males in both the ICU and HD groups. This contrasts with other studies which show a pre- dominance of the female sex using pharmacological method for deliberate self-harm.19,20 Lactate levels and pH have shown to be good prognostic fac- tors for poisoned patient in studies by Manini et al.,21 Golaghaei et al.,22 and Uzucek et al.23 The results for serum pH, lactate levels, and APACHE II scores were not available for all the patients in this study. In our study the lactate levels were available for less than 30% while pH levels were available for about 33% of the total number of ICU patients. The median lactate levels done in the ED were higher than that in the ICU while the median pH levels in done in ED were lower than that in the ICU, indicating a relatively favorable prognosis over time for these patients. The main indication for intubations24 was low GCS15,25 with decreased level of consciousness and inability to protect airways requiring a definitive airway. Other reasons were airways’ oedema and an impending loss of airway, respiratory failure, severe cardio- vascular instability leading to cerebral hypoperfusion and decreased GCS, and to reduce the cardiac workload from likely increased ventilatory requirements. The requirement for a vaso- pressor and inotropic support was indicated due severe hemody- namic instability. A total of five (5) patients in our study from the ICU patients’ group required HIET (Hyperinsulinemic-Euglycemic Therapy) which were exposed to significant amounts of Calcium Channel Blocking Agents (CCB) and Beta Blocking Agents (BB). Two patients underwent an ECMO therapy wherein one had presented after massive Amlodipine overdose26 concurrently with Paracetamol while the other had taken massive amounts of Quetiapine. ECMO therapy for poisoning patients has gained pop- ularity rapidly over the last few years due to improved outcomes. Wang et al.27 showed that only 10 patients (0.0004 %) out of 26,271 toxicologic exposures received ECMO therapy over a peri- od of 4 years from 2010 to 2013 which included 4 paediatric patients. Another retrospective study by Ramanathan et al.28 analysing data from the Extracorporeal Life Support Organization registry from 1999 to 2014 showed increasing use of ECMO for poisoning cases, with survival in majority (59%) of adults receiv- ing ECMO. ECMO can be a very effective treatment modality for patients with toxicological exposures as it provides haemodynamic and oxygenation support while the toxic agent is either metabo- lized by the body over time or is eliminated using a simultaneous ECTR therapy. Some patients in this cohort required ECTR and Dialysis ther- apy for metabolic acidosis, acute kidney injury and anuria, which is associated with many classes of poisonings, as illustrated by Rogliano et al.29 The Median ICU and HD Length of Stay (LOS) were 1.72 days and 1.39 days respectively and is is comparable to other stud- ies.15 More than one substance was identified in 149 patients (60.8 %) based on available history, laboratory biochemical testing, and blood & urine drug analysis. Overall, acute poisoning accounted for about 367.53 ICU bed days and about 308.38 HD bed days dur- ing the 8-year study period. The hospitalisation costs for these patients are substantial as they may require many additional inva- sive interventions. The fatality rate for this selected cohort of patients was deter- mined as 3.2%, which is higher than other local studies1,3,4 and other international studies15,30,31,32 done in Iran, the UK, and USA. Rezar et al.32 described lower mortality rates in patients with poi- soning compared to other critically ill patients in the ICU. The authors feel the mortality rate in our study is higher as only ICU & HD patients were considered while the other studies compared it with a larger cohort. A local ICU study by Tay et al.4 showed a higher mortality rate at 8%. Limitations of the study This study did neither ascertain the poisoning patients as a per- centage of all the HD & ICU admissions nor did it perform any health care costs comparison with those patients. Laboratory ana- lytical confirmation for the implicated agents, serum lactate levels, pH and ICU disease severity score of APACHE II was not avail- able for all the patients. The study did not factor in the quantifica- tion of the drugs and toxins involved leading to the HD & ICU admissions. Even though this study attempts to establish the asso- ciations with various drug classes, it is difficult to interpret in many cases if the association is due to the individual class of drug alone or due to the combined effects of more than one class of drug. Statistical and regression analysis have not been performed in this study. There might have been patients with poisoning who were admitted to the HD & ICU wards and not consulted by the Article [page 22] [Emergency Care Journal 2025; 21:12945] Toxicology service during their hospital stay, implying that the actual numbers may be marginally higher. The patients’ occupa- tional, medical, and social history was not ascertained and factored in for this study, which may have shed some light on the reasons for the poisoning. Conclusions Benzodiazepines, anti-depressants, anti-psychotic medica- tions, opioids, antihistamines medications and cardiotoxic drugs were the most common class of agents associated with ICU & HD admissions. The most common reasons were high PSS scores involving either the CNS or the CVS systems. More than 60% of the cases had exposure to more than 1 agent. Cardiotoxic effect drugs, anti-psychotic medications, and anti-depressant medications were found to be the most lethal. This study is one of the biggest studies in toxicology regionally involving the critical care patients and the conclusions can potentially form basis of better prediction models2,17 as well health care planning in future. References 1. Ponampalam R, Tan HH, Ng KC, et al. Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003. Int J Emerg Med 2009;2:25-31. 2. Chiu LQ, Lim BL, Vasu A, et al. Poison exposure in the emer- gency department: a Singaporean experience. Hong Kong J Emerg Med 2011;18:197-203. 3. Arciaga GJ, Tan HH, Kuan KK, et al. A 24/7 hospital toxicol- ogy service: Experience of a new start-up. Proceedings of Singapore Healthcare. 2018 4. 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Extracorporeal therapy for amlodipine poisoning. J Artif Organs 2020;23:183-6. 27. Wang GS, Levitan R, Wiegand TJ, et al. Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC). J Med Toxicol 2016;12:95-9. 28. Ramanathan K, Tan CS, Rycus P, MacLaren G. Extracorporeal membrane oxygenation for poisoning in adult patients: out- comes and predictors of mortality. Intensive Care Med 2017;43:1538–9. 29. Rogliano PF, Voicu S, Labat L, et al. Acute poisoning with rhabdomyolysis in the intensive care unit: risk factors for acute kidney injury and renal replacement therapy requirement. Toxics 2020;8:79. 30. Taghaddosinejad F, Sheikhazadi A, Yaghmaei A, et al. Article [Emergency Care Journal 2025; 21:12945] [page 23] Epidemiology and treatment of severe poisoning in the inten- sive care unit: lessons from a one-year prospective observa- tional study. J Clinic Toxicol 2012;S1:007. 31. D Clark, DB Murray, D Ray. Epidemiology and outcomes of patients admitted to critical care after self-poisoning. J Intensive Care Soc 2011;12:4. 32. Rezar R, Jung C, Mamandipoor B, et al. Management of intox- icated patients - a descriptive outcome analysis of 4,267 ICU Article [page 24] [Emergency Care Journal 2025; 21:12945] Online Supplementary Materials Table 1a. Patient demographics and poisoning characteristics. Table 1b. Therapeutic interventions. Table 1c. Length of stay and outcomes.