Prevention of iatrogenic fluid overload with naloxone infusions: A patient safety initiative.

A higher number of patients admitted to hospital systems are requiring a naloxone infusion for treatment of opioid toxicity. Although naloxone is a safe antidote for the treatment of opioid toxicity, this is not without the risk of iatrogenic harm. During standard pharmacy medication safety review process, it was identified that our standard naloxone concentration protocol would deliver 4 times the standard maintenance fluid rate to our pediatric patient population. After this risk was identified, a multidisciplinary review process of our naloxone infusion protocol was performed to help mitigate the potential risk of fluid overload. Our updated naloxone infusion protocol will result in close to a 10-fold reduction in fluids required for our naloxone infusion protocol to better align with the American Society of Health-System Pharmacists' Standardize 4 Safety Initiative and reduce the potential for iatrogenic harm.

Influence of Pennsylvania liquor store closures during the COVID-19 pandemic on alcohol withdrawal consultations.

INTRODUCTION: Alcohol withdrawal syndrome (AWS) is a serious consequence of alcohol use disorder (AUD). Due to the current COVID-19 pandemic there was a closure of Pennsylvania (PA) liquor stores on March 17, 2020. METHODS: This is a retrospective, observational study of AWS patients presenting to a tertiary care hospital. We used descriptive statistics for continuous and categorical variables and compared AWS consults placed to the medical toxicology service for six months preceding liquor store closure to those placed between March 17, 2020 and August 31, 2020. We compared this to consults placed to the medical toxicology service placed from October 1, 2019 through March 16, 2020. Charts were identified based on consults placed to the medical toxicology service, and alcohol withdrawal was determined via chart review by a medical toxicologist. This study did not require IRB approval. We evaluated Emergency Department (ED) length of stay (LOS), weekly and monthly consultation rate, rate of admission and ED recidivism, both pre- and post-liquor store closure. RESULTS: A total of 324 AWS consults were placed during the ten month period. 142 (43.8%) and 182 (56.2%) consults were pre- and post-liquor store closure. The number of consults was not statistically significant comparing these two time frames. There was no significant difference by patient age, gender, or race or by weekly or monthly consultation rate when comparing pre- and post-liquor store periods. The median ED LOS was 7 h (95% Confidence Interval (CI) Larson et al. (2012), Pollard et al. (2020) [5, 11]) and did not significantly differ between pre- and post-liquor store periods (p = 0.78). 92.9% of AWS patients required admission without significant difference between the pre- and post-liquor store closure periods (94.4% vs. 91.8%, p = 0.36). There was a significant increase in the number of AWS patients requiring a return ED visit (Odds Ratio 2.49; 95% CI [1.38, 4.49]) post closure. CONCLUSION: There were nearly 2.5 times greater odds of ED recidivism among post-liquor store closure AWS patients compared with pre-closure AWS patients.

Sex differences in patients with suicidal intent that are managed by toxicologists: An analysis of the Toxicology Investigators' Consortium (ToxIC) Registry.

INTRODUCTION: The Toxicology Investigator's Consortium (ToxIC) maintains a prospective case registry of all patients that have been managed at the bedside by medical toxicologists. We set out to characterize the differences in toxicological suicide attempts between men and women among adult patients with poisonings managed by medical toxicologists. METHODS: ToxIC database consults for adults aged 19-65 whose primary reasons for encounter were classified as suicide attempt were used for this study (1/2010-12/2016). Data used for analysis included primary agents of toxic exposure, routes of administration, and complications. The statistical analysis was limited to descriptive methods. RESULTS: Out of 51,440 registry cases, 33,259 cases remained for analysis after applying the ages 19-65 and removing those without complete data. Of these, there were 4827 suicide attempts (14.5% of toxicological exposures) which were sub classified by gender. There were more females (F) than males (M) whose toxicology consults were due to suicidal attempts (57.6% versus 42.4%). We also found that more males used alcohol as their primary agent (2.8%M v 1.5%F) or a nonpharmaceutical (%7.4 M v %2.3 F). CONCLUSIONS: In our study, we found that there were more females than males who attempted suicide by self-poisoning; and more of them used pharmaceuticals than males. In contrast, a greater number of males used nonpharmaceuticals such as alcohol. We did not find large sex-differences in suicide completion rates, routes of administration, or subsequent symptomologies. In summary, sex-based differences were observed between adult patients with suicidal-intent exposures/ingestions managed at the bedside by medical toxicologists.

A theoretical framework and nomenclature to characterize the iatrogenic contribution of therapeutic opioid exposure to opioid induced hyperalgesia, physical dependence, and opioid use disorder.

Opioid use, misuse, and risky use contribute to a critically important and complex crisis in current healthcare. Consequences of long-term opioid use, including opioid induced hyperalgesia, physical dependence, and opioid use disorder, can be considered iatrogenic, or partially iatrogenic, in cases where therapeutic opioid exposures were contributory. Research investigation and presumptive clinical action are needed to attenuate the iatrogenic component of the opioid crisis; treatment of individuals already suffering from opioid use disorder will not prevent incident cases. This work will be challenged by a remarkably high degree of complexity involving myriad and highly variable factors along the continuum from initial opioid exposure to long-term opioid use. An organized view of this complex problem should accelerate the pace of innovation and facilitate clinical implementation of research findings. Herein, we propose a theoretical framework and modern nomenclature for characterizing therapeutic opioid exposure and the degree to which it contributes iatrogenically to adverse outcomes. In doing so, we separate the role of exposure from other factors contributing to long-term opioid use, clarify the relationship between opioid exposure and outcomes, emphasize that exposure source is an important consideration for health services research and practice in the areas of pain treatment and opioid prevention, and recommend terminology necessary to quantify therapeutic opioid exposure separately from nonmedical exposure.

Adolescent Intentional Abuse Ingestions: Overall 10-Year Trends and Regional Variation.

OBJECTIVE: Adolescent intentional ingestions remain a significant public health problem in the United States with little research to date on the over-the-counter or prescription medicines that adolescents abuse. These data are important for anticipatory guidance by primary care providers, preventive health, and poison center outreach. METHODS: This was an observational study using the American Association of Poison Control Centers National Poison Data System. The study population consisted of all cases of patients aged 13 to 19 years from 2004 to 2013 with a coding of "intentional abuse." RESULTS: There were 95,695 patient calls that were coded for intentional abuse between 2004 and 2013 for adolescents aged 13 to 19 years. The most common agent reportedly ingested in intentional-abuse cases was antihistamine and/or decongestant with dextromethorphan, and this agent remained the most common throughout the 10-year study period. The next 4 most common agents remained similar across the study period as well and included ethanol, benzodiazepines, dextromethorphan alone, and marijuana. These 5 agents remained the most commonly reported across the study period for all US regions (West, Midwest, South Northeast, and US territories). CONCLUSIONS: Over a recent 10-year period, common cough preparations remain the most commonly reported intentional abuse ingestion among all years and regions for adolescents.

Delayed Salicylate Toxicity in a 17-Year-Old Girl With Initially Undetectable Salicylate Concentration 3.9 Hours After Ingestion.

We report the case of a 17-year-old girl with a 126-mg/kg nonenteric coated aspirin ingestion with nontoxic salicylate concentrations at 1.5 and 3.9 hours postingestion, who developed tinnitus and vomiting an estimated 8 hours postingestion, and who was subsequently found to have a toxic salicylate concentration at 22.7 hours postingestion. This case, as well as previous cases of delayed aspirin therapy, may prompt providers to consider educating patients and their care providers regarding the need to return for further testing if symptoms, such as vomiting or tinnitus, develop after an aspirin ingestion.

Toxicological Emergencies in the Resuscitation Area of a Pediatric Emergency Department: A 12-Month Review.

OBJECTIVE: Few studies of children with toxicological emergencies describe those undergoing acute resuscitation, and most describe exposures to single agents. We describe a 12-month sample of patients evaluated in the resuscitation area of a pediatric emergency department (ED) for a toxicological emergency. METHODS: We conducted a retrospective chart review of patients in a high-volume, academic pediatric ED. We identified patients evaluated in the ED resuscitation area for toxicological exposure and conducted structured chart reviews to collect relevant data. For all variables of interest, we calculated standard descriptive statistics. RESULTS: Of 2999 patients evaluated in the resuscitation area through 12 months (March 2009 to April 2010), we identified 80 (2.7%) whose primary ED diagnosis was toxicological. The mean age was 11.4 years. Eighty-six percent of patients were triaged to the resuscitation area for significantly altered mental status. The most frequent single exposures were ethanol (25%), clonidine (10%), and acetaminophen (5%). At least 1 laboratory test was performed for almost all patients (97%). Interventions performed in the resuscitation area included intravenous access placement (97%), activated charcoal (20%), naloxone (19%), and endotracheal intubation (12%). Eighty-two percent of patients were admitted to the hospital; 37% to the intensive care unit. No patients studied in this sample died and most received only supportive care. CONCLUSIONS: In a high-volume pediatric ED, toxicological emergencies requiring acute resuscitation were rare. Ethanol and clonidine were the most frequent single exposures. Most patients received diagnostic testing and were admitted. Further studies are needed to describe regional differences in pediatric toxicological emergencies.

Emergency Department Prescription Opioids as an Initial Exposure Preceding Addiction.

STUDY OBJECTIVE: Opioid abuse and overdose constitute an ongoing health emergency. Many presume opioids have little potential for iatrogenic addiction when used as directed, particularly in short courses, as is typical of the emergency department (ED) setting. We preliminarily explore the possibility that initial exposure to opioids by EDs could be related to subsequent opioid misuse. METHODS: This cross-sectional study surveyed a convenience sample of patients reporting heroin or nonmedical opioid use at an urban, academic ED. We estimated the proportion whose initial exposure to opioids was a legitimate medical prescription and the proportion of those prescriptions that came from an ED. Secondary measurements included the proportion of patients receiving nonopioid substances before initial opioid exposure, the source of opioids between initial exposure and onset of regular nonmedical use, and time from initial prescription to opioid use disorder. RESULTS: Of 59 subjects, 35 (59%; 95% confidence interval [CI] 47% to 71%) reported they were first exposed to opioids by a legitimate medical prescription, and for 10 of 35 (29%; 95% CI 16% to 45%), the prescription came from an ED. Most medically exposed subjects (28/35; 80%; 95% CI 65% to 91%) reported nonopioid substance use or treatment for nonopioid substance use disorders preceding the initial opioid exposure. Emergency providers were a source of opioids between exposure and onset of regular nonmedical use in 11 of 35 cases (31%; 95% CI 18% to 48%). Thirty-one of the 35 medically exposed subjects reported the time of onset of nonmedical use; median time from exposure to onset of nonmedical use was 6 months for use to get high (N=25; interquartile range [IQR] 2 to 36), 12 months for regular use to get high (N=24; IQR 2 to 36), 18 months for use to avoid withdrawal (N=26; IQR 2 to 38), and 24 months for regular use to avoid withdrawal (N=27; IQR 2 to 48). Eleven subjects (36%; 95% CI 21% to 53%) began nonmedical use within 2 months, and 9 of 11 (82%; 95% CI 53% to 96%) reported nonopioid substance use or treatment for alcohol abuse before initial opioid exposure. CONCLUSION: Although short-term opioid administration by emergency providers is unlikely to cause addiction by itself, ED opioid prescriptions may contribute to the development of addiction in some patients. There is an urgent need for further research to estimate long-term risks of short-course opioid therapy so that the risk of iatrogenic addiction can be appropriately balanced with the benefit of analgesia.

Endotracheal Intubation for Toxicologic Exposures: A Retrospective Review of Toxicology Investigators Consortium (ToxIC) Cases.

BACKGROUND: Endotracheal intubation remains a cornerstone of early resuscitation of the poisoned patient, but little is known about which substances are associated with intubation. OBJECTIVES: Our objective was to describe patient exposures to substances reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) that were managed with intubation between 2010 and 2014. METHODS: We performed a retrospective review of cases managed with endotracheal intubation in the ACMT ToxIC Registry from January 1, 2010 through December 31, 2014. Descriptive statistics were used to describe patient exposures. RESULTS: A total of 2724 exposures to substances were managed with endotracheal intubation. Intubated patients were 52% male and 82% adults. For all ages taken together, the most common known single-substance exposures managed with intubation were sedative hypnotics (9.8%), antidepressants (8.7%), and opioids (8.0%). The most common single ingestions associated with intubation in various age groups were: opioids (<2 years old), alpha-2 agonists (2-6 years old), antidepressants (7-18 years old), sedative-hypnotics (19-65 years old), and cardiac medications (>65 years old). Multiple substances were involved in 29.0% of exposures. Decontamination and elimination processes were used in 12.8% of patients. CONCLUSIONS: The most common substances involved in single- and multiple-substance exposures managed with intubation varied by age group. Most patients were managed with supportive care. Knowledge of substances commonly involved in exposures managed with intubation may inform triage and resource planning in the emergency department resuscitation of critically ill poisoned patients.

Administration of CroFab Antivenom by a Helicopter Emergency Medical Service Team.

The case presented here highlights an unconventional use of a helicopter emergency medical service (HEMS) to provide a specialized medication to a critically ill patient when definitive transport was delayed. A 39-year-old man presented to a rural hospital 1 hour after sustaining a copperhead envenomation. He developed severe symptoms and was intubated. Arrangements were made for transfer to a tertiary referral center by HEMS, but because of incoming weather conditions, the team would not be able to make the return flight safely. The decision was made for the HEMS team to fly antivenom to the patient, administer the medication, and then transport the patient by ground to the tertiary medical center. This plan was executed, and the patient was safely transported to the accepting facility. Antivenom is most effective when administered early because this will halt the progression of edema and may reverse the systemic effects of envenomation. In this case, HEMS transport of antivenom to the patient with severe toxicity prevented a delay to administration and likely improved the patient's outcome. Although the traditional role of HEMS is to provide rapid transport to critically ill patients, HEMS teams can also function to deliver specialized medications to remote settings.

Moving beyond misuse and diversion: the urgent need to consider the role of iatrogenic addiction in the current opioid epidemic.

An epidemic of drug overdose deaths has led to calls for programs and policies to limit misuse and diversion of opioid medications. Any parallel call to consider the risk of iatrogenic addiction when treating pain has been muted in comparison. We have moved beyond questions of nonmedical use, abuse, and diversion to highlight the role of prescription opioids in causing addiction even when prescribed and used appropriately. Unfortunately, current evidence is insufficient, and a rapid expansion of longitudinal research is urgently needed to guide clinicians in balancing the need for opioids with the risk of adverse consequences. Meanwhile, medical education should place greater emphasis on the abuse liability of prescription opioids, and providers should endeavor to attenuate risk when possible.

Variation in suicide occurrence by day and during major American holidays.

BACKGROUND: Due to temporal variations in completed suicides, it has been suggested that impulsivity and environmental factors may influence suicide. STUDY OBJECTIVE: Our intent was to determine if particular days of the week, seasons, or holidays were associated with increased attempted and completed suicides by poisoning. METHODS: All calls recorded in the National Poison Database System coded as "suspected suicide" from 2006 through 2010 were included. Exposures were evaluated by day, season, and holidays, and compared to control dates. RESULTS: There were 1,065,067 exposures (63% female) related to suicide attempts, with completions in 0.4% of cases. Sundays and Mondays for adults, and Mondays and Tuesdays for age < 19 years were the most common. Spring and fall had higher numbers of exposures than summer and winter. New Year's Day had a higher number of exposures, whereas Independence Day, Thanksgiving, and Christmas had fewer exposures. CONCLUSIONS: The beginning of the week, spring and fall, and New Year's Day were associated with higher numbers of ingestions with suicidal intent. This has implications for clinicians advising potential victims and providing emergency care for these patients.

Evaluation of an Intravenous Acetaminophen Protocol in the Emergency Department.

BACKGROUND: Acute pain is a leading reason for Emergency Department (ED) evaluation, accounting for nearly half of all ED visits. Therefore, providing effective non-opioid analgesics in the ED is critical. Oral acetaminophen (APAP) is commonly administered in the ED but is limited to patients tolerating oral intake. Intravenous (IV) APAP provides significant pain reduction parenterally. The purpose of this quality assessment project was to evaluate the frequency of opioid use in patients receiving IV APAP, the safety of IV APAP, and compliance with an ED IV APAP protocol. METHODS: This study included all patients who received IV APAP in the ED of a tertiary care, level I trauma center, during a three-month period. The protocol required ED patients to be NPO (nil per os), 18 years or older, and administered with a single 1000 mg dose. The adverse reactions within 24 hours post-IV APAP, ED length of stay (LOS), and opioid administration within four hours post-IV APAP were assessed. RESULTS: Ninety-four patients received IV APAP. All patients received a 1000 mg dose. One patient received more than one dose, but this patient had a 22-hour ED LOS. Two patients received oral medications within one hour of IV APAP (one received an antacid, and the other received carbamazepine and lamotrigine). An opioid was administered to 22 of the 94 (23.4%) patients during the four-hour protocol period. There were no reports of adverse reactions. CONCLUSIONS: The results show excellent compliance with the protocol. IV APAP was safe and well-tolerated. Notably, most patients did not receive an opioid within four hours of IV APAP. IV APAP can be safely and effectively utilized as an analgesic and lessen ED opioid use.

Novel Use of Clonidine Patch to Treat Tizanidine Withdrawal.

Tizanidine is commonly prescribed for muscle spasticity and pain. Yet, withdrawal is rarely reported. Tizanidine stimulates presynaptic α-2 adrenergic and imidazoline receptors decreasing norepinephrine release. Abrupt cessation can cause withdrawal. Current treatment strategies include tapering oral tizanidine or substituting oral clonidine. A 52-year-old male with a history of hypertension, diabetes, coronary artery disease, and chronic back pain presented with altered mental status, agitation, hypertensive emergency (blood pressure: 250/145 mmHg), and tachycardia. The patient had been prescribed tizanidine for chronic back pain for two years and had recently run out with suspicion of misuse. Tizanidine withdrawal was diagnosed, and he improved with 0.1 mg oral clonidine three times daily weaned over five days while hospitalized. One month later the patient was admitted for persistent hypertension, tachycardia, diaphoresis, and anxiety. Alpha-2 agonist withdrawal was again diagnosed. Utilizing a clonidine patch taper may offer a reasonable approach in patients with tizanidine withdrawal.

Mass Carbon Monoxide Poisoning at a Daycare: A Public Health Lesson.

INTRODUCTION: Carbon monoxide (CO) poisoning is a leading cause of preventable toxicity-related deaths in the United States. We describe a case series of 16 individuals who were exposed to CO due to a malfunctioning furnace at a Pennsylvania daycare, a state which did not mandate CO detectors in daycares. METHODS: An institutional review board-approved retrospective analysis was performed, and de-identified patient records were examined. Collected data included age, sex, race, ethnicity, CO concentrations, arrival time, time to hyperbaric oxygen center contact, and time to transfer and discharge. RESULTS: Emergency medical services transported 16 patients to a tertiary care emergency department (ED) with both adult and pediatric departments. Fourteen patients were 10 years of age or younger. Fifteen patients arrived within one hour. Sixty-two percent (N=10) were male, and 94% (N=15) identified as Hispanic. Emergency physicians, medical toxicologists, clinicians, interpreters, and volunteers from across the hospital system were mobilized to the ED to assist with management. CONCLUSION: This large-scale daycare CO poisoning represents a potentially avoidable mass casualty incident among children and daycare staff and necessitated significant coordination of care. CO detectors in Pennsylvania daycares would provide early warning for staff, prevent or minimize toxicity, inform first responders, and better prepare EDs to handle similar situations.

Differences in Drug Poisonings Among Those Who Identify as Transgender Compared to Cisgender: An Analysis of the Toxicology Investigators Consortium (ToxIC) Core Registry, United States 2017-2021.

PURPOSE: In this manuscript, the abbreviation TG is defined as persons who identify as transgender, GNC is defined as persons who identify as gender nonconforming, and CG is defined as persons who identify as cisgender. TG and GNC (e.g., nonbinary), are those whose gender identity and sex assigned at birth do not align, as opposed to CG. This study describes drug poisonings among TG, GNC, and CG captured in the Toxicology Investigators Consortium (ToxIC) Core Registry during 2017-2021. METHODS: Authors conducted a secondary data analysis of medical toxicology physician consultations involving intentional exposures (i.e., use with the knowledge of the exposed person) within the ToxIC Core Registry from 2017 through 2021. Demographic characteristics, exposure intent, and reported drug classes are reported by gender identity and sex assigned at birth. FINDINGS: From a total of 15,800 medical toxicology consultations, 213 (1.3%) involved both TG (n = 187, 1.2%) and GNC (n = 26, 0.2%), and 15,587 (98.7%) involved CG. Among TG, 128 (68.8%) were transgender men, 58 (31.2%) transgender women. Sixty-two percent of TG/GNC (n = 132) and 34.8% of CG (n = 5,428) were aged ≤18 years. Reported intent for exposure (i.e., self-harm and misuse/harmful use) differed proportionally across both sexes assigned at birth and gender identity among transgender men and cisgender men. IMPLICATIONS: In the ToxIC Core Registry, the consultations varied proportionally by age group across TG/GNC and CG, with more than half of TG/GNC aged ≤18 years. The proportion of consultations also varied by intent across TG/GNC and CG. Further research to delineate differences between TG/GNC and CG could increase knowledge in prevention, assessment, and treatment of drug poisonings in this population.

Weight Loss or Liver Loss: A Case Report on Fulminant Hepatic Failure Secondary to Garcinia cambogia Supplementation.

This case describes a 56-year-old man with a past medical history including sickle cell trait requiring blood transfusions, who presented to the emergency department (ED) with generalized weakness and fatigue following Garcinia cambogia supplementation. Initial laboratory abnormalities included: aspartate aminotransferase (AST) and alanine transaminase (ALT) 4,222 U/L and 4,664 U/L respectively, alkaline phosphatase 215 U/L, international normalized ratio (INR) 3.2, and his model for end-stage liver disease was 37. Creatinine, hemoglobin and hematocrit, and ferritin levels were all elevated. The differential diagnosis for his acute illness was broad ranging from hemochromatosis, anabolic steroid use, and portal venous thrombosis. The patient was started on N-acetylcysteine (NAC) and his liver function improved. He was discharged on hospital day 10 and instructed to discontinue his supplements and follow up for repeat blood work. This case explores the critical management of G. cambogia toxicity. The patient explored G. cambogia as an herbal supplementation resulting in weight loss, worsening generalized fatigue, and fulminant hepatic failure.

From Crashing Waves to Crashing Sodium: A Rare Case of Nearly Asymptomatic Severe Hyponatremia.

Hyponatremia refers to an abnormally low serum sodium level, and it is the most common electrolyte disorder encountered in the clinical setting. Despite its prevalence, hyponatremia can be challenging to clinically identify in some cases due to non-specific symptom presentation. In this case report, we illustrate the rare clinical course of a nearly asymptomatic patient with severe hyponatremia and discuss potential explanations for this uncommon presentation.