Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

INTRODUCTION: Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. METHODS: This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. RESULTS: There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. CONCLUSION: On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 - National Poison Data System, United States, January 1, 2020-March 31, 2020.

On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3). To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019. Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications. Call data from poison centers are uploaded in near real-time to NPDS. During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively. Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.

An assessment of urine THC immunoassay in healthy volunteers receiving an oral proton-pump inhibitor.

Introduction: Limitations of urine drug-screening (UDS) by immunoassay include false-positive results. Pantoprazole, a proton-pump inhibitor (PPI), is reported to cause false-positive results for THC on UDS. The objective of this study was to determine if oral PPIs cause false-positive THC results using the THC One Step Marijuana Test Strip®.Methods: Eligible healthy volunteers completed a 5-day course of a PPI followed by urine testing using the THC One Step Marijuana Test Strip®. Phase one included 3 subjects taking pantoprazole 40 mg once daily for 5 days. On day 5, urine specimens underwent THC screening. Phase two included 9 subjects randomized to 5-day supply of once-daily oral esomeprazole 20 mg, lansoprazole 15 mg, or omeprazole 20 mg. All study methods and testing mirrored those in phase one.Results: All 12 subjects completed the study protocol. All urine samples collected on day 5 were negative for THC in all subjects.Discussion: Our results demonstrate that oral PPIs did not cause a false-positive THC using the THC One Step Marijuana Test Strip®. Limitations include small sample size, use of a single commercial immunoassay, and inability to confirm medication compliance. Further, large-scale research using other commercial urine immunoassays is warranted.

Loperamide toxicity: recommendations for patient monitoring and management.

Who: This position statement is a collaborative effort by the American Academy of Clinical Toxicology (AACT) and the American Association of Poison Control Centers (AAPCC) and has been endorsed by the American College of Medical Toxicology (ACMT). The position statement describes loperamide misuse, proposed mechanisms of toxicity, adverse clinical effects, and recommendations for the acute monitoring and management of patients with loperamide toxicity.Why: Use of high-dose loperamide for its euphoric effects and to self-treat opioid use disorder (in place of evidence-based therapies, like buprenorphine or methadone), is increasing. Despite reports in the medical literature and lay press, many remain unaware of high-dose loperamide use and how to manage patients with loperamide-associated toxicities.Target audience: Providers in Emergency Medicine; Prehospital; Intensive Care; Internal Medicine; Primary Care; Gastroenterology; Addiction Medicine; Pharmacy.

Kratom Use and Toxicities in the United States.

BACKGROUND: Kratom is an herbal supplement containing alkaloids with opioid properties. This review was conducted to determine toxicities associated with kratom use in the United States in order to provide insight into its safety as a dietary supplement. METHODS: We conducted a retrospective review of kratom exposures reported to the National Poison Data System to determine the toxicities associated with kratom use. We also reviewed records from a county medical examiner's office in New York State to identify kratom-associated fatalities. RESULTS: A total of 2312 kratom exposures were reported, with 935 cases involving kratom as the only substance. Kratom most commonly caused agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), and confusion (8.1%). Serious effects of seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%) were also reported. Kratom was listed as a cause or contributing factor in the death of four decedents identified by the county medical examiner's office. CONCLUSIONS: Kratom use is increasing and is associated with significant toxicities. Our findings suggest kratom is not reasonably expected to be safe and poses a public health threat due to its availability as an herbal supplement.

Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuse.

Background: Interest in tianeptine as a potential drug of abuse is increasing in the United States. We performed a retrospective study of calls to the New York State Poison Control Centers (PCCs) designed to characterize one state's experience with tianeptine. Methods: Data were gathered from existing records utilizing the poison center data collection system, Toxicall® entered between 1 January 2000 through 1 April 2017. Information regarding patient demographics, reported dose and formulation of tianeptine, reported coingestants, brief narrative description of the case, disposition, and case outcome was collected. Results: There were nine reported cases of tianeptine exposure. Seven were male with a mean age of 27. Three reported therapeutic use of tianeptine and five reported intentional abuse. One case was an unintentional pediatric exposure. Doses were reported in three cases; 12.5 mg in a pediatric unintentional exposure, and 5 and 10 g daily in the two reports of intentional abuse. Of note, five patients complained of symptoms consistent with opioid withdrawal. In one of two cases in which naloxone was administered, an improvement in mental status and the respiratory drive was noted. Outcomes reported in Toxicall® were minor in two cases, moderate in five cases, major in one case, and not reported in one case. Conclusions: These cases, reported to the New York State PCCs should alert readers to the potential for tianeptine abuse, dependence, and withdrawal.

Reports of adverse health effects related to synthetic cannabinoid use in New York State.

BACKGROUND/OBJECTIVES: We assessed synthetic cannabinoid (SC) outbreaks from 2011-2012 and 2015. METHODS: The National Poison Data System was utilized to collect reports of SC adverse effects in New York State from 2011-2012 and 2015 (N = 713). RESULTS: Cases from 2015 were more likely to be admitted to intensive care units and had different symptoms than those in 2011-2012. We identified two new SC structural classes from 2015 samples. DISCUSSION/CONCLUSIONS: The 2015 outbreak was associated with more severe SC-related illnesses than in 2011-2012. SCIENTIFIC SIGNIFICANCE: New SC compounds may pose a different or more severe risk than those previously identified. (Am J Addict 2017;26:772-775).

Serum Calcium Concentration in Ethylene Glycol Poisoning.

INTRODUCTION: The diagnosis of ethylene glycol intoxication can be challenging. Definitive testing for ethylene glycol is not readily available and clinical decisions are often based on clinical suspicion and the results of more readily available tests. One of these findings is hypocalcemia, presumable through complexation with the ethylene glycol metabolite oxalate. METHODS: We performed a retrospective review of all patients admitted to a tertiary care hospital between 2005 and 2013 with laboratory confirmed ethylene glycol intoxication. Serum calcium on presentation was compared to blood gas pH on presentation as well as presentation serum bicarbonate. RESULTS: We did not find any relationship between calcium and serum pH either by linear regression or when dichotomized by pH ≥ or <7.3. We did observe an inverse relationship between serum calcium and bicarbonate. CONCLUSIONS: Hypocalcemia is not commonly observed following ethylene glycol poisoning, even in acidotic patients.

Loperamide Abuse Associated With Cardiac Dysrhythmia and Death.

Loperamide is an over-the-counter antidiarrheal with µ-opioid agonist activity. Central nervous system opioid effects are not observed after therapeutic oral dosing because of poor bioavailability and minimal central nervous system penetration. However, central nervous system opioid effects do occur after supratherapeutic oral doses. Recently, oral loperamide abuse as an opioid substitute has been increasing among patients attempting to self-treat their opioid addiction. Ventricular dysrhythmias and prolongation of the QRS duration and QTc interval have been reported after oral loperamide abuse. We describe 2 fatalities in the setting of significantly elevated loperamide concentrations.

Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse - New York, 2008-2016.

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Incidence and characteristics of snakebite envenomations in the New York state between 2000 and 2010.

OBJECTIVE: We sought to evaluate the incidence of reported venomous snakebites in the state of New York between 2000 and 2010. METHODS: Data were collected retrospectively from the National Poison Data System (NPDS) and then reviewed for species identification and clinical outcome while using proxy measures to determine incidence of envenomation. RESULTS: From 2000 to 2010 there were 473 snakebites reported to the 5 Poison Control Centers in the state of New York. Venomous snakes accounted for 14.2% (67 of 473) of these bites. Only 35 bites (7%) required antivenom. The median age of those bitten by a venomous snake was 33. Most victims were male. CONCLUSIONS: Although not rare, venomous snakebites do not occur commonly in New York State, with a mean of just 7 bites per year; fortunately most snakebites reported are from nonvenomous snakes. Yet even nonvenomous bites have the potential to cause moderately severe outcomes. Medical providers in the state should be aware of their management.

Quantitative measurement of acetyl fentanyl and acetyl norfentanyl in human urine by LC-MS/MS.

Opioid abuse involving emerging opioid compounds is a growing public health problem, which was highlighted recently by cases of human morbidity and mortality linked to acetyl fentanyl abuse. Unfortunately, the lack of information available on the toxicology and metabolism of acetyl fentanyl precludes its detection in human samples. The following study was conducted to test a new analytical procedure for the simultaneous quantification of acetyl fentanyl and its predicted metabolite, acetyl norfentanyl, in human urine. Metabolic reference standards and deuterium-labeled internal standards were synthesized for use in an assay that coupled solid-phase extraction (SPE) with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The accuracy (% Relative Error <5%) and inter- and intrarun precision (%CV <20%) of this new method resulted in low levels of quantification (∼1 ng/mL). Similar results were obtained using liquid chromatography columns manufactured with phenyl-hexyl and biphenyl stationary phases (r(2) > 0.98). Preliminary human liver microsomal and in vivo rodent studies demonstrated that acetyl fentanyl is metabolized by cytochrome P450s to acetyl norfentanyl. Urine samples from rats treated with a toxic dose of acetyl fentanyl contained high concentrations of acetyl fentanyl and acetyl norfentanyl. Further toxicokinetic studies are required to fully elucidate the metabolic pathways responsible for acetyl fentanyl detoxification and excretion.

Compounded ointment results in severe toxicity in a pediatric patient.

BACKGROUND: Dermal drug delivery is becoming more common, as evidenced by the increased numbers of compounding pharmacies preparing topical products for chronic pain management. Consumers may not appreciate the potency or dangers associated with some of the drugs in these preparations. Pediatric patients are especially at risk for significant toxicity with accidental exposures. We report a case of severe toxicity in an 18-month-old boy from exposure to his father's compounded pain ointment. CASE: An 18-month-old previously healthy child had an ointment applied topically to a diaper rash by his mother, consisting of a single pump of a prescription ointment that her husband received from a compounding pharmacy for neck pain. Approximately 20 minutes later, when the child had been put down for a nap, he had gasping respiration but was otherwise unresponsive. Emergency medical services was called, and the child was unresponsive. In the ED, vital signs were pulse of 57 beats/min, blood pressure 74/35 mm Hg, respiratory rate 21 breaths/min, and O2 saturation 98% on a nonrebreather. Fingerstick glucose was 105 mg/dL. In the ED, physical examination was significant for unresponsiveness, pinpoint pupils, and hyporeflexia. The patient's mental status continued to deteriorate with depressed respirations, and he was intubated. Laboratory results were noncontributory. Electrocardiogram revealed only sinus bradycardia. The patient was transported to a pediatric intensive care unit. He did well over the next several hours with supportive care and had return to normal vital signs over the following 12 hours. He was extubated the following morning without problems. Blood taken at the time of ED presentation had a serum clonidine level of 9.2 ng/mL (reference range, 0.5-4.5 ng/mL) and a norketamine level of 41 ng/mL (reporting limit, >20 ng/mL). CONCLUSIONS: Dermal absorption of drugs leading to significant toxicity in children is well known. Our patient had toxicity from a topical pain medication compounded with several potent drugs known to cause central nervous system depression. There has been an increase in the use of this drug delivery system for management of chronic painful conditions. The popularity and attractiveness of such preparations may be the perception that they are somehow safer and more natural than taking pills. This perception and the fact that these are not dispensed in child-proof containers and are often mailed to the patients without pharmacist counseling can lead to increased inadvertent exposures in the pediatric population.

Sodium channel blockade with QRS widening after an escitalopram overdose.

INTRODUCTION: Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. CASE: A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 µg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. DISCUSSION: Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. CONCLUSIONS: Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

Death following injection sclerotherapy due to phenol toxicity.

Prolapse rectum (PR) or protrusion of the rectum beyond the anus occurs frequently in populations at both extremes of age. In the pediatric population, in developed countries, the commonest cause for PR is thought to be cystic fibrosis (CF). Treatment options for CF include conservative management, surgical resection and fixation, suturing, and injection sclerotherapy (IS). The last is considered an attractive treatment option because it is minimally invasive. In this case report, the authors present the details about a 2-year-old female child, with PR and CF, who died after IS, using phenol as the sclerotherapeutic agent. Autopsy findings and toxicology tests performed to establish phenol toxicity are documented. The available literature is reviewed. This case report underscores the risks of using phenol for IS and emphasizes the point that the procedure is not innocuous and an adverse outcome including fatality is a possibility.