Time to Peak International Normalized Ratio Rise in Acute and Acute-on-Chronic Warfarin Overdoses.

ABSTRACT: Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment.

Impact of a drug safety communication on the severity of benzonatate exposures reported to poison centers.

PURPOSE: Identify if publication of the 2010 drug safety communication (DSC) regarding benzonatate was associated with a decrease in the incidence of severe benzonatate poisonings reported to United States poison centers. METHODS: This retrospective database study utilized the National Poison Data System to compare the incidence of severe benzonatate poisonings before and after the publication of a drug safety communication. We utilized interrupted time series analysis to compare 2000-2010 (pre-DSC) to 2012-2019 (post-DSC). RESULTS: There were 18 619 benzonatate exposures reported to US poison centers during the time period covered and 11 554 exposures were included. There was an increase in exposures throughout the time period. There was no difference in the incidence of severe outcomes in the two time periods. In the pre-DSC era, rates of severe outcomes increased by 0.4% per year followed by an immediate non-significant drop of 2.9% in incidence of severe outcomes (P = .15). Finally, the slope of severe outcomes in the post-DSC era showed an increase of 0.3% per year, which was not significantly different from the pre-DSC era (P = .78). CONCLUSION: Publication of a Drug Safety Communication regarding the risks of benzonatate did not result in a decrease in the proportion of severe benzonatate poisoning reported to US poison centers. Deaths and other severe outcomes continued to occur at a similar rate after the publication.

Characterization of intentional-abuse venlafaxine exposures reported to poison control centers in the United States.

Background: Venlafaxine use to achieve an amphetamine-like high has been described but data regarding the epidemiology and clinical effects are sparse. Objectives: Describe the prevalence and toxicity of venlafaxine abuse reported to US poison control centers. Methods: This was a retrospective review of venlafaxine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016. Inclusion criteria were: age 12 years and older, reason for exposure intentional-abuse, and either single-substance exposure or venlafaxine was the first substance. The primary outcome was prevalence of intentional-abuse of venlafaxine. Secondary outcomes characterized demographics, geographic distribution, toxicity, and outcomes. Results: Intentional-abuse accounted for 752 of 85,621 venlafaxine exposures. Overall prevalence was 87.8 intentional-abuse exposures/10,000 venlafaxine exposures reported to NPDS (range, 59.3-117.6/10,000). Prevalence decreased from 107/10,000 in 2000 to 59.3/10,000 in 2016. Median age was 23 years and 50% were female. Primary route was ingestion (90.8%) with 4.7% using venlafaxine via inhalation/intranasal insufflation, and 3.7% both routes. There were 227 venlafaxine-only exposures; 54.0% were treated/released from the emergency department, 20% were admitted for medical management, 9.0% to a psychiatric facility, and 17.0% managed at home. Known medical outcomes for single-substance exposures were: no effect (24.0%), minor (39.0%), moderate (33.0%), and major (4.0%); no deaths occurred. Most frequent clinical effects were tachycardia (33.9%), drowsiness (20.7%), and agitation (11.5%). Conclusion: The prevalence of venlafaxine abuse reported to poison control centers has decreased. Medical outcomes are usually not serious. Clinicians should be aware that non-medical use is possible but infrequently reported to poison control centers.

Characterizing the Toxicity and Dose-Effect Profile of Tramadol Ingestions in Children.

OBJECTIVES: Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. This study investigates toxicity associated with tramadol ingestions in children. The hypothesis is that children will experience dose-related central nervous system and respiratory depression and seizures. METHODS: A retrospective evaluation of cases from the National Poison Center Data System between January 1, 2000, and December 31, 2013, was performed. Inclusion criteria were age below 6 years and single-substance acute tramadol ingestion. For dose-effect analysis, cases with sufficient dose quantity information were included. RESULTS: There were 7334 cases that met inclusion criteria. Outcomes were 84.8% no effect, 12.6% minor, 2.2% moderate, and 0.4% major effect. There was 1 fatality. Most of the children (36.4%) were treated/released from the emergency department; other management sites were home (36.4%), admission (5.9%), and others (3.2%). In the 1115 children with symptoms, drowsiness (N = 611) and vomiting (N = 178) occurred most frequently. More serious clinical effects included respiratory depression in 36 and seizures in 24 children. Of 2772 children with milligram dose recorded, there were 10 cases of respiratory depression and 6 of seizure. Median doses for respiratory depression and seizure were 225 (range, 50-600 mg) and 525 mg (range, 50-1050 mg), respectively. The minimum weight-based dose for respiratory depression/arrest was 7.9 mg/kg and for seizures, 4.8 mg/kg. CONCLUSIONS: Seizure and respiratory depression are uncommon in pediatric tramadol ingestions. Given the small number of patients with dose data and lack of laboratory confirmation of dose, more studies are needed to determine the minimum dose at which medical management is recommended.

Poisoning in Israel: Annual Report of the Israel Poison Information Center, 2017.

BACKGROUND: The Israel Poison Information Center (IPIC), Rambam Health Care Campus, provides 24-hour telephone consultations on clinical toxicology and drug and reproductive toxicology. It participates in research, teaching and regulatory activities, and provides laboratory services. In 2014, nurse specialists in poison information joined the IPIC. OBJECTIVES: To report the epidemiology of poison exposures in Israel. METHODS: We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017. RESULTS: A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children < 6 years of age were involved in 47.0% of cases; 80.4% of calls were made by the public and 17.8% by physicians; 74.2% of exposures were unintentional and 7.3% intentional. Pharmaceuticals were involved in 51.4% of cases, chemicals in 36.9%, bites and stings in 2.2%, and plants and mushrooms in 1.5%. Substances most frequently involved were analgesics, cleaning products, and antimicrobials. Clinical severity was moderate/major in 3.3%, mainly due to insecticides, drugs of abuse, and corrosives. Three fatalities were recorded (due to colchicine, organophosphates, and volatile substance inhalant abuse). CONCLUSIONS: Poison exposures and poisonings have markedly increased in Israel, contributing substantially to morbidity. The IPIC prevented unnecessary referrals to emergency departments. Its database is a valuable national resource for collecting and monitoring poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory, and its activities adequately supported by national resources.

Treatment of sulfonylurea and insulin overdose.

The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l(-1) . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide.

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

Poisoning in Israel: annual report of the Israel Poison Information Center, 2012.

BACKGROUND: The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services. OBJECTIVES: To report data on the epidemiology of poisonings and poison exposures in Israel. METHODS: We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012. RESULTS: A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children < 6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink). CONCLUSIONS: Poison exposures and poisonings have increased significantly and have contributed substantially to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.

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.

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.

Evaluation of the use and safety of octreotide as antidotal therapy for sulfonylurea overdose in children.

OBJECTIVES: The objectives of this study were to evaluate the effect of octreotide on number of hypoglycemic episodes and blood glucose concentrations (BGCs) in a case series of young children who received octreotide for treatment of sulfonylurea-induced hypoglycemia and to identify the frequency of adverse effects associated with octreotide's use for this indication. METHODS: A retrospective review of 9 years of National Poison Data System pediatric sulfonylurea overdoses treated with octreotide was conducted. Inclusion criteria were age younger than 6 years with acute sulfonylurea overdose managed in a health care facility. Redacted poison center charts were obtained, and data on pretreatment and posttreatment number of hypoglycemic episodes and BGCs as well as medical outcomes and adverse reactions were extracted and analyzed. RESULTS: There were 121 octreotide cases. Patients experienced a median of 2.0 and 0.0 hypoglycemic episodes before and after treatment, respectively (P < 0.0001). The median lowest BGC was significantly higher after octreotide administration (P < 0.001). In 73% of children, only 1 dose of octreotide was given. Hyperglycemia was noted in 3 children who also received dextrose in whom adverse effects to therapy were coded. CONCLUSIONS: Octreotide administration decreases number of hypoglycemic events and increases BGCs. The majority of children who receive octreotide require only 1 dose. There were no adverse effects documented in these children who received octreotide as an antidote for sulfonylurea-induced hypoglycemia.

Unexpected late rise in plasma acetaminophen concentrations with change in risk stratification in acute acetaminophen overdoses.

BACKGROUND: The acetaminophen risk analysis nomogram is used to predict hepatotoxicity risk in acute acetaminophen overdose based on a single plasma acetaminophen concentration (PAC) measured between 4 and 24 h after ingestion. There are case reports of patients with acute overdoses of acetaminophen combination products in whom a toxic PAC occurred later after an initial non-toxic PAC at approximately 4 h. OBJECTIVES: The objective was to describe patients who had an initial non-toxic PAC and a subsequent toxic PAC. METHODS: A poison center's database was searched for records in which patients were administered N-acetylcysteine. Cases were included if they involved an acute overdose of an acetaminophen-containing product with at least 2 plottable PACs, the first of which was obtained at least 4 h after ingestion and was below the treatment line on the nomogram with a subsequent toxic PAC. Data were analyzed for doses, timed PACs, specific acetaminophen preparation, coingestants, activated charcoal administration, and clinical effects. RESULTS: Twenty patients were included. Thirteen patients ingested combination products. All patients experienced vomiting, neurologic, or cardiovascular effects at presentation or before obtaining the second PAC. Two patients developed hepatotoxicity, one of which died from the complications of acetaminophen-induced hepatotoxicity. CONCLUSION: The nomogram fails to predict toxicity based on a single PAC in a small subset of patients.

Adolescent Occupational Exposures Reported to United States Poison Centers, 2011-2020.

OBJECTIVE: The aim of this study was to perform an updated description of adolescent occupational exposures reported to the US poison centers. METHODS: We performed a descriptive analysis of adolescents aged 13 to 19 years with unintentional occupational exposures from 2011 to 2020 using the National Poison Data System. A clinically significant occupational poisoning (CSOP) case is defined as exposures with moderate effect, major effect, or death. Differences in substance categories between younger (13 to 17 years) and older (18 to 19 years) adolescents with CSOP were compared. RESULTS: There were 14,374 adolescent occupational exposures. There were 2151 CSOPs. The most common substance categories associated with CSOP were household cleaners (22.3%), chemicals (20.8%), industrial cleaners (14.2%), fumes/gases/vapors (10.8%), and hydrocarbons (5.9%). Categories of exposures were similar across age groups. CONCLUSIONS: This study found that, despite a reduction in the number of adolescent occupational exposures, CSOPs persist.

Clinical effects and outcomes of perampanel overdoses reported to U.S. poison centers.

INTRODUCTION: Perampanel is indicated for partial onset seizures in children and adults. The mechanism is unique among antiepileptic agents as it inhibits glutamate activity on AMPA receptors. Currently, there are few published case reports describing overdose. METHODS: This is a retrospective observational study of all single substance perampanel ingestions from January 2014 to December 2019 reported to the national poison data system (NPDS). The primary outcome is to describe the clinical effects of perampanel exposures. Secondary outcomes include evaluation of management and investigation of a dose-effect relationship for the purpose of triaging acute unintentional exposures. RESULTS: A total of 138 exposures were reported to NPDS since the release of the agent. Median age was 20 years (IQR 10-38) with 68 (49.3%) males. The reason for exposure was most commonly therapeutic error (80, 58.0%), followed by exploratory ingestion (24, 17.4%), and suicidal ingestion (14, 10.1%). A total of six (4.3%) patients developed major effects, 20 (14.5%) moderate, 32 (23.2%) minor effects and 22 (15.9%) no effect. An additional 54 (39.1%) cases were not followed. Almost half of cases were managed at home. Of those that were in a healthcare facility (HCF) (n = 72), most were treated/evaluated and released (31, 43.1%), followed by admission to a non-critical care unit (20, 27.8%), and critical care unit (13, 18.1%). Most frequently reported symptoms were drowsiness (27, 19.6%), agitation (20, 14.5%), ataxia (13, 9.4%), and confusion (12, 8.7%). The most common therapies provided in a HCF were intravenous fluids (22,30.6%), followed by benzodiazepines (14, 19.4%), then other types of sedation (9, 12.5%). There were too few cases to determine a dose cut off for triaging. CONCLUSIONS: While drowsiness, agitation, ataxia, and confusion were the most often reported symptoms, close to 19% developed moderate/major effects and almost 4% of patients received potentially life-saving interventions.

Critical care interventions in children aged 6 months to 12 years admitted to the pediatric intensive care unit after unintentional cannabis exposures.

BACKGROUND: Cannabis exposures in children have risen sharply in recent years, resulting in increased hospital visits and admission to pediatric intensive care units (PICUs). The intent of this study was to describe the proportion of pediatric patients admitted to the PICU after unintentional cannabis ingestion that received critical care interventions (CCIs) along with describing trends over time in hospitalization, admission to the PICU, and clinical effects and treatments outside of the PICU. METHODS: This was a retrospective database study utilizing the National Poison Data System (NPDS) from 1/1/2000 to 12/31/2020. Children 6 months to 12 years of age with single substance cannabis exposures were included. RESULTS: A total of 12,882 cases were included. There was an increase in the proportion of cases seen in a hospital over time from 43.8% in 2000 to 54.6% in 2020 (range 29.1-62.6%). In patients seen in a HCF, the proportion admitted to the PICU was 9.5% in 2000 and 14% in 2020 (range: 5.6-29.0%). The 875 (6.8%) children admitted to the PICU were analyzed for the primary outcome. CCIs were performed in 69/875 (7.9%) cases that were admitted to the PICU. The most common CCIs in the PICU were intubation and sedation, 4.9 and 3.7%, respectively. CONCLUSIONS: Unintentional pediatric cannabis exposures are associated with clinically significant effects, including respiratory depression, hypotension, and bradycardia, but fewer than 5% of exposures were treated with CCIs, like intubation or vasopressors, in patients admitted to the PICU. Further work should assess specific reasons for admission to the PICU.

Single-substance trazodone exposures reported to US poison centers from 2000 to 2019.

BACKGROUND: Individual case reports describe trazodone overdose resulting in QTc prolongation and cardiac arrhythmias. The clinical effects and outcomes associated with trazodone exposures on a large-scale basis are less well known. OBJECTIVE: The primary objective was to characterize the severity of single substance trazodone exposures and identify any relationships that may exist between dose of trazodone and severity of exposure. The secondary objective was to describe these exposures from a demographic and clinical symptom standpoint. METHODS: A retrospective review of single-substance trazodone exposures reported to the National Poison Data System (NPDS) from 1 January 2000 to 31 December 2019 was performed. The primary objective was to characterize the severity of trazodone exposures and relationships between ingested dose and level of care required or medical outcome. RESULTS: A total of 118,773 cases were included in the analysis of demographics and level of care required. A majority (59.5%) of cases did not require medical admission. Of the 81,698 cases with known medical outcomes, the most common clinical effects included mild-moderate CNS depression (49.7%), QTc prolongation (12.2% of cases in 2019), vomiting (9.0%), hypotension (7.0%), and tachycardia (7.0%). The median ingested dose associated with treatment, and release from the emergency department was 600 mg compared to 1500 mg in those admitted to the intensive care unit (ICU). Regarding medical outcome, median ingested dose ranged from 600 mg in those experiencing no effect to 1500 mg in those experiencing major effects. Cardiac-related clinical effects and the need for cardiac-specific interventions were overall infrequent. A dose-response relationship was identified for level of care and medical outcome. CONCLUSIONS: Many trazodone exposures can be characterized as low severity due to the infrequent need for healthcare facility admission and large proportion of cases that experienced no effects or only minor effects.

Exposures in pregnant patients reported to United States Poison Centers.

BACKGROUND: Limited data describe poisoning exposures in pregnant women. Previous studies are limited to inpatient populations, those seen only by toxicologists, or single poison centers. This study aimed to describe poison exposures reported to U.S. poison control centers in pregnant patients compared to non-pregnant controls. METHODS: This was a retrospective observational study of exposures reported to the American Association of Poison Control Centers National Poison Data System from 2000 through 2019. Pregnant patients were included from 15-44 years along with a random sampling of 5:1 age and year matched control group of non-pregnant exposures. Demographics, primary substance, and known medical outcomes were described. Chi square analysis was performed for comparisons. RESULTS: From 2000 to 2019, a total of 131,619 pregnant cases and 658,095 non-pregnant controls were identified. The median age was 27 years (IQR: 22, 31) for the matched groups. For known trimester of pregnancy: 29.8, 37.0, and 28.2% were in the first, second, and third trimester, respectively. Most common exposures were analgesics and cleaning products. Intentional exposures were more common in non-pregnant compared to pregnant cases (41.2 vs 21.9%; OR 2.71, 95% CI 2.67-2.75), mostly self-harm attempts (31.5 vs. 15.8%). Notably, there was a large discrepancy in the proportion of environmental exposures, with fewer in non-pregnant controls compared with pregnant cases (3.8 vs. 12.1%; OR 0.29, 95% CI 0.28-0.29). More non-pregnant cases had multiple substance exposures compared with pregnant cases (22.2 vs. 10.9%; OR 2.34, 95% CI 2.29-2.38). There were more moderate effect outcomes in non-pregnant compared with pregnant cases (13.2 vs. 6.3%; OR 2.25, 95% CI 2.20-2.30). CONCLUSIONS: Outcomes of poisoning exposures in pregnant patients reported to U.S. poison centers are less serious compared to non-pregnant controls, likely due to the lower rates of intentional abuse and self-harm exposures and greater number of minimally toxic environmental exposures.

Changes in unintentional cannabis exposures in children 6 months to 5 years reported to United States poison centers during the first nine months of the coronavirus-19 pandemic.

INTRODUCTION: Almost half of exposures reported to United States (US) poison centers are exploratory ingestions in children under the age of 5 years. Pediatric cannabis exposures reported to US poison centers have risen over the last twenty years, with greater increases in the last 5 years. In 2020, the Coronavirus disease 2019 (COVID-19) pandemic resulted in widespread stay-at-home orders and subsequent changes in work, education, and daycare. This study describes the changes in pediatric cannabis exposures during the first nine months of the COVID-19 pandemic relative to the three years before the pandemic. METHODS: Cases were identified from the National Poison Data System. Inclusion criteria was unintentional cannabis exposure in children aged 6 months to 5 years between January 1, 2017 and December 31, 2020. Analysis was performed with segmented regression of interrupted time series analysis comparing January 2017-March 2020 (pre-COVID-19) to April 2020-December 2020 (COVID-19 period). Autocorrelation was assessed using Dubin-Watson test. RESULTS: There were 7,679 unintentional pediatric exposures from January 1, 2017 through December 31, 2020. There was a significant increase of 3.1% per month during the pre-COVID-19 period (p < .0001). A statistically significant immediate increase in number of exposures per month occurred in April 2020 (58.4%; p < .0001). The slope in the COVID-19 period was -0.01% (p = .99). No autocorrelation was detected. DISCUSSION AND CONCLUSIONS: Unintentional cannabis exposures in children aged 6 months to 5 years reported to United States poison centers increased significantly after the initial COVID-19 stay-at-home orders. This trend may be associated with COVID-19 quarantines, increased time children are spending at home, increased availability of cannabis products in homes, or other reasons. Future efforts should evaluate specific factors that resulted in the observed increases in pediatric exposures.

In vitro analysis of n-acetylcysteine (NAC) interference with the international normalized ratio (INR).

BACKGROUND: Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro. METHODS: Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p = .0008, Stago p < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p = .02 and p = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p < .0001, Stago p < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p < .05). CONCLUSION: Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

An analysis of fatal iatrogenic therapeutic errors reported to United States poison centers.

OBJECTIVE: This is a descriptive study evaluating fatal iatrogenic and in-hospital medication errors reported to United States poison centers. METHODS: A retrospective evaluation of the National Poison Data System from 2000-2017 of all therapeutic errors with a scenario coded as iatrogenic/healthcare professional or occurring in a healthcare facility. Death abstracts were reviewed for details of the exposure and therapeutic error scenarios were recoded or added to the case as appropriate. Cases, where death was considered not related to the exposure, were excluded. Additionally, we created one additional scenario (rate-related) and one additional route of administration (intrathecal) to better describe the cases. RESULTS: A total of 172 cases were evaluated. The majority of the patients were female (52.3%) with a median age of 58.5 years (range: 2 days to 96 years). The most commonly reported medication error was "other incorrect dose" (22.7%) followed by other/unknown error (15.1%). The route of exposure was primarily parenteral (54.9%), followed by ingestion (30.2%), then intrathecal (7.0%). The most common medications were cardiac drugs, chemotherapeutics, opioids, anticoagulants, and sedative-hypnotic/antipsychotics. CONCLUSIONS: Iatrogenic and in-hospital medication errors have been studied extensively with goals to reduce their occurrence. Specific controls to prevent incorrect dosing routes, 10-fold overdoses, and incorrect intrathecal administration have been instituted. Despite interventions, all three of these therapeutic errors continued to occur in 2017, suggesting that more preventive controls should be instituted.