Thrombocytopenia Associated with Elemental Mercury Poisoning in Two Siblings - Connecticut, July 2022.

Two siblings aged 5 and 15 years from Connecticut were hospitalized with petechial rash, oral mucositis, and severe thrombocytopenia approximately 10 days after they played with a jar of elemental mercury they found in their home. Before the mercury exposure was disclosed, the siblings were treated with platelet transfusions, intravenous immune globulin (IVIG) for possible immune thrombocytopenic purpura, and antibiotics for possible infectious causes. When their conditions did not improve after 6 days, poison control facilitated further questioning about toxic exposures including mercury, testing for mercury, and chelation with dimercaptosuccinic acid. The older sibling soon recovered, but the younger child required a prolonged hospitalization for severe thrombocytopenia, ultimately receiving repeated doses of IVIG, steroids, and romiplostim, a thrombopoietin receptor agonist. Close collaboration among multiple agencies was required to identify the extent of mercury contamination, evaluate and treat the other family members, and decontaminate the home. These cases demonstrate the importance of ongoing public health outreach to promote early detection of elemental mercury toxicity, and the need to evaluate for environmental exposures when multiple close contacts experience similar signs and symptoms.

Methadone exposures reported to poison control centers in the United States following the COVID-19-related loosening of federal methadone regulations.

BACKGROUND: Methadone is a highly effective treatment for opioid use disorder. Its use in the United States is highly regulated at both the federal and state level. The regulations related to take-home doses were loosened because of the 2019 Novel Coronavirus public health emergency declaration. The aim was to assess the effect of loosened regulations on methadone-related exposures reported to poison control centers. METHODS: Retrospective analysis of population-based intentional methadone exposures (in persons 18 years of age and older) reported to the American Association of Poison Control Centers' National Poison Data System. A quasi-experimental design looking at one year before and after the March 16, 2020 loosening of methadone take-home regulations. Severity of exposure was assessed by: disposition (discharged from emergency department, admitted to non-critical care versus critical care units), medical treatments received, and medical outcomes (no effect, minor effect, moderate effect, major effect, death). One tail Student t-test and Chi Square were used; p significance was <0.05. RESULTS: The number of adult intentional exposures involving methadone increased by 5.3% in the year following the change in federal regulations (p<0.05). There was no statistically significant difference in distribution of age, gender, whether exposures involved methadone-only or methadone plus other substances, therapies administered or hospitalizations. There was no difference in overall distribution of medical outcomes, including deaths. CONCLUSIONS: Although the number of exposures involving methadone increased post-regulation change, the severity of exposures remained unchanged. Various additional factors (Medicare and Medicaid expansion; increased number of opioid treatment programs) may have also contributed to this increase. As federal officials consider possible permanent changes to the methadone regulations, it is important to evaluate potential related risks and benefits. This study lends support to the consideration that loosening of methadone regulations does not necessarily lead to a substantial increase in severity of exposures.

Using Surveillance With Near-Real-Time Alerts During a Cluster of Overdoses From Fentanyl-Contaminated Crack Cocaine, Connecticut, June 2019.

In 2019, Connecticut launched an opioid overdose-monitoring program to provide rapid intervention and limit opioid overdose-related harms. The Connecticut Statewide Opioid Response Directive (SWORD)-a collaboration among the Connecticut State Department of Public Health, Connecticut Poison Control Center (CPCC), emergency medical services (EMS), New England High Intensity Drug Trafficking Area (HIDTA), and local harm reduction groups-required EMS providers to call in all suspected opioid overdoses to the CPCC. A centralized data collection system and the HIDTA overdose mapping tool were used to identify outbreaks and direct interventions. We describe the successful identification of a cluster of fentanyl-contaminated crack cocaine overdoses leading to a rapid public health response. On June 1, 2019, paramedics called in to the CPCC 2 people with suspected opioid overdose who reported exclusive use of crack cocaine after being resuscitated with naloxone. When CPCC specialists in poison information followed up on the patients' status with the emergency department, they learned of 2 similar cases, raising suspicion that a batch of crack cocaine was mixed with an opioid, possibly fentanyl. The overdose mapping tool pinpointed the overdose nexus to a neighborhood in Hartford, Connecticut; the CPCC supervisor alerted the Connecticut State Department of Public Health, which in turn notified local health departments, public safety officials, and harm reduction groups. Harm reduction groups distributed fentanyl test strips and naloxone to crack cocaine users and warned them of the dangers of using alone. The outbreak lasted 5 days and tallied at least 22 overdoses, including 6 deaths. SWORD's near-real-time EMS reporting combined with the overdose mapping tool enabled rapid recognition of this overdose cluster, and the public health response likely prevented additional overdoses and loss of life.

Opioid exposure associated with poppy consumption reported to poison control centers and the U.S. Food and Drug Administration.

OBJECTIVE: To assess characteristics of exposures to contaminated poppy and identify trends in exposure and poppy-related deaths. METHODS: Cross-sectional analysis of adverse events associated with exposure to poppy products (primarily poppy seeds) from the American Association of Poison Control Centers' National Poison Data System (NPDS), 2000-2018, supplemented with analysis of overdoses and deaths related to poppy from the U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition's Adverse Event Reporting System (CAERS) (2004-2018), and the FDA Adverse Event Reporting System (FAERS) (1968-2018). RESULTS: There were 591 NPDS exposure cases involving poppy between 2000 and 2018 including 392 in persons aged 13+. Rates of intentional exposures in NPDS increased among the age 13+ group over the study period. Most intentional exposures occurred in males in their teens and twenties. NPDS included 18 overdoses and three deaths likely attributable to poppy, most involving poppy seed tea. CAERS and FAERS included five additional deaths likely attributable to opioids in poppy. CONCLUSIONS: Including previously reported cases, there are now at least 19 U.S. deaths associated with poppy seeds in the literature. We recommend that practitioners working in opioid treatment and recovery be alert to use of poppy to treat pain and symptoms of withdrawal.

Incorporation of poison center services in a state-wide overdose education and naloxone distribution program.

BACKGROUND: To help curb the opioid overdose epidemic, many states are implementing overdose education and naloxone distribution (OEND) programs. Few evaluations of these programs exist. Maryland's OEND program incorporated the services of the poison center. It asked bystanders to call the poison center within 2 hours of administration of naloxone. Bystanders included law enforcement (LE). OBJECTIVE: Description of the initial experience with this unique OEND program component. METHODS: Retrospective case series of all cases of bystander-administered naloxone reported to the Maryland Poison Center over 16 months. Cases were followed to final outcome, for example, hospital discharge or death. Indications for naloxone included suspected opioid exposure and unresponsiveness, respiratory depression, or cyanosis. Naloxone response was defined as person's ability to breathe, talk, or walk within minutes of administration. RESULTS: Seventy-eight cases of bystander-administered naloxone were reported. Positive response to naloxone was observed in 75.6% of overall cases. Response rates were 86.1% and 70.9% for suspected exposures to heroin and prescription opioids, respectively. Two individuals failed to respond to naloxone and died. DISCUSSION: Naloxone response rates were higher and admission to the intensive care unit rates were lower in heroin overdoses than prescription opioid overdoses. CONCLUSIONS: This retrospective case series of 78 cases of bystander-administered naloxone reports a 75.6% overall rate of reversal. SCIENTIFIC SIGNIFICANCE: The findings of this study may be more generalizable. Incorporation of poison center services facilitated the capture of more timely data not usually available to OEND programs. (Am J Addict 2016;25:301-306).

Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone.

BACKGROUND: Polysubstance use is prevalent in individuals using buprenorphine or methadone nonmedically, with benzodiazepines being a common co-ingestant. The objective of this study was to compare the severity of buprenorphine and methadone toxicity with concomitant use of benzodiazepines. METHODS: A retrospective analysis of buprenorphine and methadone cases from November 1, 2002 to December 31, 2010 reported to the American Association of Poison Control Centers' National Poison Data System (NPDS) was conducted. INCLUSION CRITERIA: age ≥ 18 years, nonmedical use of methadone with benzodiazepines (methadone-BZD) or buprenorphine with benzodiazepines (BUP-BZD), and case followed to a documented outcome. Cases with co-ingestants other than benzodiazepines were excluded. Clinical effects, treatments, disposition and final medical outcomes were evaluated. RESULTS: There were 692 methadone-BZD cases and 72 BUP-BZD cases. Clinical effects in methadone-BZD and BUP-BZD groups were lethargy (71.1%, 59.7%), respiratory depression (29.0%, 15.3%), coma (22.4%, 5.6%), respiratory arrest (4.5%, 0), hypotension (11.8%, 2.8%) and cardiac arrest (1.9%, 0), respectively. Patients in the methadone-BZD group were four-times more likely to receive naloxone (60.4% vs 15.3%) or be intubated (16.3% vs 4.2%) than in the BUP-BZD group. Hospitalization rates were highest for methadone-BZD patients with 67.3% receiving medical admissions compared to 43.3% of BUP-BZD patients. Outcomes were more serious for methadone-BZD cases (p<0.0001); while there were no BUP-BZD deaths, exposure to methadone-BZD yielded 16 deaths. CONCLUSIONS: Nonmedical use of benzodiazepines with methadone is associated with higher hospitalization rates, greater ICU utilization rates and considerably worse medical outcomes when compared to nonmedical use of benzodiazepines with buprenorphine.

Fatalities involving acetaminophen combination products reported to United States poison centers.

CONTEXT: Deaths from overdose of acetaminophen (APAP) combination medications are reported, yet the individual ingredients are not well examined as individual putative causes of death. OBJECTIVE: To examine the individual contribution of APAP or other ingredient(s) to fatalities resulting from ingestion of APAP combination products reported to poison centers. MATERIALS AND METHODS: A search in the United States (US) National Poison Data System between 1 January 2000 and 31 December 2009 (10 years) was conducted. Only fatal cases determined by American Association of Poison Control Centers Fatality Review team to be caused by ingestion of one or more APAP combination products were included. The fatality abstract narrative for each case was obtained. Each narrative abstract was rated independently by four reviewers and putative cause of death was determined to be APAP, 'other ingredient' or 'unable to determine'. Fleiss' Kappa test was utilized to assess interrater agreement. RESULTS: Three hundred and thirty-seven deaths met inclusion criteria: 204 were due to suicides, 96 were the result of nonmedical use, 3 were from a therapeutic error, 1 resulted from an unsupervised pediatric ingestion, and 33 were due to unknown reason for exposure. The overall putative cause of death was APAP in 60.8%, other ingredients in 29.7%, and unable to determine in 9.5% of fatalities. APAP was responsible for the fatality in 79.2% of deaths resulting from nonmedical use of APAP combination products. Fleiss Kappa was 0.74, indicating substantial interrater agreement. DISCUSSION AND CONCLUSION: The most common putative cause of death in fatal overdoses involving APAP combination products reported to US poison centers is the APAP component.

Methylenedioxypyrovalerone ("bath salts"), related death: case report and review of the literature.

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4-methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self-reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life-threatening hyperthermia was consistent with an MDPV-induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.

Medical outcomes associated with nonmedical use of methadone and buprenorphine.

BACKGROUND: There exists a significant amount of misinformation regarding methadone and buprenorphine, and a belief that toxicity associated with nonmedical use of methadone and nonmedical use of buprenorphine is similar in severity and outcomes. OBJECTIVE: The objective of this study is to compare outcomes associated with nonmedical use of methadone vs. nonmedical use of buprenorphine in patients presenting to the Emergency Department (ED) and reported to poison centers. METHODS: This was a retrospective cohort study using data from the American Association of Poison Control Centers from January 1, 2003 to December 31, 2009 (7 years). Inclusion criteria were nonmedical use of methadone or buprenorphine (or buprenorphine/naloxone) as a single substance by history, age 18 years or older, ingestions only, evaluated in an ED. Outcome measures were clinical effects, treatments, disposition, and final medical outcomes. RESULTS: Of 1,920 cases, 1,594 were in the methadone group and 326 were in the buprenorphine group. Frequently reported clinical effects were lethargy, 59.2% vs. 29.4%, and respiratory depression, 28.7% vs. 2.5%, for methadone and buprenorphine groups, respectively. Hospitalization rates were 67.4% in the methadone group and 32.2% in the buprenorphine group. Half of all patients in the methadone group were admitted to the intensive care unit (ICU) vs. only 15% of all the patients in the buprenorphine group. Twenty-six patients in the methadone group died vs. no deaths in the buprenorphine group. There were significant differences in the distribution of clinical effects, disposition, and medical outcomes (p < 0.001). CONCLUSIONS: Patients who use methadone nonmedically have higher hospitalization rates, greater ICU utilization rates, and considerably worse medical outcomes when compared with patients who use buprenorphine nonmedically.

Anaphylaxis after the injection of buprenorphine.

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward "drug deaths." However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously.

A novel approach to informing the public about the risks of overdose and nonmedical use of prescription medications.

BACKGROUND: Poison centers answer telephone calls from persons requesting identification of tablets. Many of these calls are from people for whom the tablets were not prescribed and potentially represent nonmedical use. Implementation of a telephone-based program of overdose prevention and screening for nonmedical use of prescription medications is examined. METHODS: Social workers with experience in substance abuse disorders were hired by a poison center to answer telephone calls from persons asking for tablet identification. The social workers asked questions regarding demographics, provided the ingredients, provided overdose prevention/safety information, and offered referral to treatment to callers who desired it. RESULTS: A total of 17,616 tablet identification calls from the public were answered by the social workers during the 20-month study period. Most callers were Caucasian with median age 33 years (range 18-93 years). Overdose prevention/safety information, aimed mostly at reducing polydrug use, was delivered to 6,635 (37.7%) callers. CONCLUSIONS: Treatment resource information was provided to 3,775 (21.4%) callers. A telephone-based service made up of social workers interacted with several thousand individuals potentially at risk for adverse outcomes from nonmedical use of prescription medications and delivered overdose/safety information. Although further study is needed, this type of service can complement existing state/community efforts aimed at education regarding the nonmedical use of prescription medications.

Decrease in therapeutic errors involving prescription cough and cold medications in young children.

OBJECTIVES: This study sought to determine whether an increase in therapeutic errors involving prescription cough and cold medications (CCM) reported to poison centers was observed following the October 2007 voluntary withdrawal of over-the-counter CCM. METHODS: Analysis of therapeutic errors involving prescription CCM in children under 2 years of age for the 33 months before and the 27 months after the October 2007 withdrawal. RESULTS: Total counts of therapeutic errors involving prescription CCM in children under 2 years of age decreased from 452 to 337 per year. Rates of therapeutic errors decreased from 0.43 cases/100,000 person-month prewithdrawal to 0.32 postwithdrawal, a 25.6% decrease (p<0.0001). CONCLUSIONS: An increase in harm as measured by the number of poison center calls for therapeutic errors involving prescription CCM was not observed in the 27-month time period after the withdrawal. A significant decrease in therapeutic errors involving these products is reported.

Intravenous acetylcysteine for the treatment of acetaminophen overdose.

IMPORTANCE OF THE FIELD: Acetaminophen is a leading cause of overdose-related hepatotoxicity. Although acetylcysteine prevents or minimizes acetaminophen-induced hepatotoxicity and reduces mortality, some patients presenting with complicated overdose scenarios (massive ingestions or combination or modified-release formulations) may develop toxicity despite administration of recommended dosage regimen. AREAS COVERED IN THIS REVIEW: The article evaluates evidence regarding intravenous acetylcysteine's effectiveness in patients with acute overdoses who receive treatment within 10 h or > 10 h, patients with chronic supratherapeutic ingestions, and those with acetaminophen-induced fulminant hepatic failure. Intravenous and oral acetylcysteine are compared. WHAT THE READER WILL GAIN: A one-size-fits-all approach towards acetylcysteine therapy provides suboptimal care in some patients. High-risk patients are identified. Specific discontinuation criteria are presented. TAKE HOME MESSAGE: The standard intravenous regimen will effectively treat most early-presenting uncomplicated overdoses. Acetylcysteine dosing should be individualized in patients with complicated presentations and in particular situations in which plasma acetaminophen concentrations may be persistently elevated at the end of the infusion or in late presenters. More studies are needed to evaluate the optimal intravenous dosage regimen and the role of oral acetylcysteine in these high-risk patients. Treatment decisions may be aided by consultation with a poison center and/or clinical toxicologist.

Drug adsorption efficacy and palatability of a novel charcoal cookie formulation.

STUDY OBJECTIVES: To determine the effect of a novel charcoal cookie formulation compared with a standard aqueous charcoal product on the absorption of orally administered cimetidine, and to compare the palatability of the two charcoal products. DESIGN: Prospective, open-label, three-way, crossover trial. SETTING: General clinical research center. SUBJECTS: Eight healthy volunteers (five men, three women; mean age 23.4 yrs). INTERVENTION: After an overnight fast, each subject ingested a single cimetidine 800-mg tablet. Fifteen minutes later, subjects were randomly assigned to receive either water (control), three charcoal cookies (equivalent to 7.2 g of charcoal), or 7.2 g of aqueous activated charcoal suspension. Subjects then received each of the other study treatments-cimetidine with water, cimetidine with charcoal cookies, and cimetidine with charcoal suspension-separated by a 1-week washout period between each treatment. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were obtained before and 8 hours after administration of the cimetidine dose. Noncompartmental pharmacokinetic analysis was performed, and area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) were compared for each study drug combination. In addition, subjects evaluated the palatability of each charcoal product by using a visual analog scale. Both charcoal products effectively adsorbed cimetidine, resulting in decreased absorption of most of the cimetidine dose. No significant difference was noted in the median percent decrease in cimetidine AUC between the charcoal suspension and charcoal cookie (91.8% vs 82.1%, p=0.505). Similarly, no significant difference was noted in the median percent decrease in C(max) between the two charcoal formulations (82.6% vs 64.0%, p=0.574). The palatability scores, however, were significantly higher for the charcoal cookie than for the charcoal suspension. All study drugs were well tolerated, and no adverse events were reported. CONCLUSION: The new charcoal cookie formulation appears to be as effective as the aqueous charcoal suspension at reducing absorption of cimetidine. In addition, the charcoal cookie was rated as more palatable than the aqueous charcoal suspension, suggesting that the charcoal cookie could be an attractive alternative to the charcoal slurry for managing drug overdoses.

Impact of the voluntary withdrawal of over-the-counter cough and cold medications on pediatric ingestions reported to poison centers.

PURPOSE: To assess the impact of a voluntary withdrawal of over-the-counter cough and cold medications (OTC CCMs) labeled for children under age 2 years on pediatric ingestions reported to the American Association of Poison Control Centers. METHODS: Trend analysis of OTC CCMs ingestions in children under the age 6 years resulting from therapeutic errors or unintentional poisonings for 27 months before (pre-) and 15 months after (post-) the October 2007 voluntary withdrawal was conducted. The rates and outcome severity were examined. RESULTS: The mean annual rate of therapeutic errors involving OTC CCMs post-withdrawal, in children less than 2-years of age, 45.2/100,000 (95%CI 30.7-66.6) was 54% of the rate pre-withdrawal, 83.8/100,000 (95%CI 67.6-104.0). The decrease was statistically significant p < 0.02. In this age group, there was no difference in the frequency of severe outcomes resulting from therapeutic errors post-withdrawal. There was no significant difference in unintentional poisoning rates post-withdrawal 82.1/100,000 (66.0-102.2) vs. pre-withdrawal 98.3/100,000 (84.4-114.3) (p < 0.21) in children less than 2-years of age. There were no significant reductions in rates of therapeutic errors and unintentional poisonings in children ages 2-5 years, who were not targeted by the withdrawal. CONCLUSIONS: A significant decrease in annual rates of therapeutic errors in children under 2-years reported to Poison Centers followed the voluntary withdrawal of OTC CCMs for children under age 2-years. Concerns that withdrawal of pediatric medications would paradoxically increase poisonings from parents giving products intended for older age groups to young children are not supported.

Hepatotoxicity despite early administration of intravenous N-acetylcysteine for acute acetaminophen overdose.

OBJECTIVES: The objective was to evaluate the effectiveness of intravenous N-acetylcysteine (IV NAC; 300 mg/kg over 21 hours) in early acute acetaminophen (APAP) overdose patients. METHODS: This observational case series included patients hospitalized between 2004 and 2007 for acute APAP overdoses and who were reported to a regional poison center. Inclusion criteria were plasma APAP concentrations on or above the treatment line on the Rumack-Matthew nomogram, administration of IV NAC within 8 hours of ingestion, and follow-up to known outcome. The hospital chart of each patient who received IV NAC for longer than the standard 21 hours was reviewed. Hepatotoxicity was defined as hepatic aminotransferase levels greater than 1,000 IU/L. RESULTS: Seventy-seven patients met inclusion criteria and received at least 21 hours of IV NAC for an acute APAP overdose. Seven patients received antidotal therapy for greater than 21 hours. These patients tended to have ingested combination preparations, have very high initial plasma APAP concentrations, and had persistently elevated plasma concentrations during their hospital stay. Hepatotoxicity occurred in 4 patients (5.2%, 95% confidence interval [CI] = 0.2% to 10.1%), including 1 death and 1 liver transplantation. CONCLUSIONS: Hepatotoxicity developed in 5.2% of cases, suggesting that the 21-hour IV NAC regimen is suboptimal in some patients. In addition to high initial plasma APAP concentrations, APAP product formulation and persistently elevated plasma APAP concentrations were identified as factors possibly associated with developing hepatotoxicity. The authors propose a tailored approach to the discontinuation of IV NAC and point out the need for reevaluation of optimal doses and duration of therapy.