Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

A 9-state analysis of designer stimulant, "bath salt," hospital visits reported to poison control centers.

STUDY OBJECTIVE: A new generation of designer stimulants marketed as "bath salts" emerged in late 2010. The goal is to describe the epidemiologic emergence of designer stimulants in 9 states in the Midwest. METHODS: A retrospective review of the National Poison Data System was performed between November 1, 2010, and November 30, 2011. Inclusion criteria were health care-evaluated bath salts or other synthetic stimulants exposures. Cases were excluded if the exposure was unrelated to a designer stimulant. Demographic and clinical characteristics of cases were calculated and differences in outcome and exposure by generation were examined. RESULTS: One thousand six hundred thirty-three patients met the inclusion criteria. Age ranged from 1 day to 61 years (mean=29.2 years), with 67.9% male patients. The most common clinical features were agitation (62.2%), tachycardia (55.2%), and hallucinations (32.7%). In addition to 15.5% of patients having a major medical effect, 0.6% died. Reason for use was primarily intentional abuse (88.5%). However, 0.7% of patients reported withdrawal. Treatment involved primarily benzodiazepines (58.5%), with 8.7% of patients being intubated. Baby Boomers were more likely to have a major medical outcome (24.2%) and to report injection as the method of administration (8.6%-12.9%). CONCLUSION: Synthetic stimulants rapidly swept across the Midwest, resulting in more than 1,600 patients seeking medical care. Serious medical effects or death was observed in 16.1% of cases. Older generations were more likely to inject and to have a major medical outcome.

Does occupational exposure to fentanyl cause illness? A systematic review.

INTRODUCTION: The opioid epidemic in the United States continues to result in an increasing number of deaths and is increasingly dominated by fentanyl and fentanyl analogs. As a result, first responders are likely to come into contact with fentanyl-containing substances daily. Concerns persist regarding occupational exposure resulting in intoxication. We performed a systematic review to describe occupational illnesses from fentanyl and its analogs. METHODS: We conducted a systematic review of the literature following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess the danger of occupational exposure to fentanyl. The PubMed, EMBASE, Google Scholar, SCOPUS, CINAHL, and National Institute for Occupational Safety and Health databases were queried to identify occupational fentanyl exposures. Studies included were single case reports, case series, observational studies, controlled studies, and abstracts from scientific presentations. We reviewed articles meeting the eligibility criteria and abstracted outcome data. Outcomes included study design, number of study subjects and study demographics, description of exposure, personal protective equipment used, duration of symptoms, illness developed, medical evaluation performed, treatment provided, hospitalizations, deaths, drug testing performed, and any situation review performed to prevent illness, analytical confirmation of the identity of culprit agent, and concentrations of drug in serum/blood. RESULTS: Our search yielded 454 citations after deduplication. After abstract and text review, 12 unique reports met the inclusion criteria. All identified studies were observational studies. Ten of the 12 were Health Hazard Evaluation reports from the National Institute for Occupational Safety and Health; two reports describe the same exposure case. There were no reported instances of comprehensive drug testing using liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry in exposed first responders. Among first responders possibly exposed to fentanyl or fentanyl analogs, none were admitted to the hospital, and only three first responders received naloxone. The three officers who received naloxone lacked recommended personal protective equipment and had subjective improvement of symptoms following naloxone. There were no instances of severe respiratory depression requiring assisted ventilation or hospital admission. Among forensic laboratory technicians, only one instance of detectable concentrations of fentanyl in urine was reported, and there were no instances of symptomatic cases. CONCLUSIONS: Among published reports of 27 first responders with symptoms after possible ambient fentanyl exposure, symptoms, recorded physical findings, and vital signs were inconsistent with acute opioid toxicity. Breaches in the recommended use of personal protective equipment appeared common. Only three persons received naloxone, although none had plausible effects of fentanyl. No suspected exposure to fentanyl led to hospitalization or death. Based on these low-quality data, there were no plausible opioid effects from ambient exposure to suspected fentanyl.

A systematic review of second line therapies in toxic seizures.

BACKGROUND: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. METHODS: We searched PubMed, Embase, PsychINFO, Cochrane Library, Web of Science, Google Scholar, and International Pharmaceutical Abstracts from inception through August of 2018, following PRISMA Guideline. The MESH terms focused on identifying treatments for seizures induced by drugs or other potentially toxic substances. We excluded the articles if they involved animals, had seizures resulting from alcohol withdrawal, were case reports, or not peer-reviewed. Our primary outcome was seizure termination and/or suppression by the second-line agent as agreed upon by two authors. We used descriptive statistics for analysis. RESULTS: We identified six case series that met inclusion and exclusion criteria. Included case series contained nine to 235 patient cases each. The most common xenobiotic exposures were bupropion, isoniazid, and anti-psychotics. The description of seizure type and duration was diverse. First-line treatments were primarily benzodiazepines. Secondary treatments included propofol, barbiturates, phenytoin, valproic acid, and levetiracetam. Patient outcomes differed, attributable to any of the following: mixed toxic substances, drug-drug interactions, inability to control seizures, or toxicity of the anti-epileptic drugs (AED) themselves. Few cases specifically discussed the success of secondary treatment administration to suppress or terminate seizures. CONCLUSIONS: Available literature discussing second-line treatment for toxic seizures is of poor quality with high heterogeneity. Although the majority of articles used similar second-line agents, it is difficult to compare the efficacy of the regimens. Additional studies are necessary to identify the most efficacious second-line therapies in toxic seizures.

A 29-year analysis of acute peak salicylate concentrations in fatalities reported to United States poison centers.

BACKGROUND/OBJECTIVES: The threshold salicylate concentration commonly recommended to initiate extracorporeal elimination, in the absence of significant end-organ toxicity, is 100 mg/dL. Unfortunately, the grade of evidence to support this decision is low. Our primary aim is to describe highest reported salicylate concentrations in patients who died from acute salicylate ingestions. Our secondary aim is to determine if age or coingestants varied with highest reported salicylate concentration. METHODS: We analyzed acute salicylate fatalities reported to the National Poison Data System (NPDS) between 1 January 1986 and 31 December 2014. Included were patients who died during the index hospitalization and for which acute salicylate toxicity was the primary cause of death. We used descriptive statistics with standard deviations (SD) or 95% confidence intervals (CI) where appropriate. We created a general linear model that evaluated the association of age and coingestions with salicylate concentrations. We divided the patients into age quartiles to assess a possible interaction between age and salicylate concentration. RESULTS: We identified 602 acute salicylate fatalities that fit inclusion criteria. The mean peak reported fatal salicylate concentration across all age groups was 99.19 mg/dL (± 50.2 mg/dL). The median peak fatal salicylate concentration was 97.0 mg/dL. The oldest quartile had a lower mean concentration (age >57 years; 90.4 mg/dL) than the youngest quartile (age <30 years; 111.6 mg/dL, mean difference 21.2 mg/dL, 95%CI 6.1-36.3). Fatalities with a coingestant had a lower mean concentration of 91.5 mg/dL compared to 104.8 mg/dL among those ingesting salicylates alone (mean difference 13.4 mg/dL, 95%CI 21.4-5.3). Increasing age and the presence of any coingestions were negatively associated with fatal concentrations (estimates; 95%CI 0.41; 0.61-0.021 and -14.43; 22.45-6.42, respectively). When opioids were a coingestant, mean concentration was 72.8 (mean difference 32.1 95%CI 23.1-41.1). CONCLUSIONS: Using the current recommended hemodialysis threshold of 100 mg/dL, more than half of the patients would be deprived of this critical life-saving therapy. Additionally, increasing age and ingestion of other substances, especially opioids, are associated with lower peak fatal salicylate concentrations. A prospective, randomized controlled trial considering salicylate concentrations and other clinical factors may provide further guidance for hemodialysis.

Levetiracetam in toxic seizures.

BACKGROUND/OBJECTIVES: The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures. METHODS: We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV. RESULTS: Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy was 1.6 days (0-49). CONCLUSIONS: Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results.

New Psychoactive Substances in Pediatric Patients.

New psychoactive substances (NPS), namely cannabinoids, cathinones, and opioids, have surged in popularity among school-age children, resulting in serious morbidity and mortality globally. In the last decade, there has been a rapid evolution of NPS resulting in hundreds of new compounds. Little to no evidence for humans is available on most compounds. The clinical presentations of patients intoxicated with cannabinoids and cathinones are highly variable but most commonly present with a sympathomimetic toxidrome, for example, agitation, delirium, and tachycardia. Those with opioids present with a classic opioid toxidrome: coma, dilated pupils, and respiratory failure.

A systematic analysis of methylene blue for drug-induced shock.

CONTEXT: Pharmacologically induced shock can be refractory to standard resuscitation. Methylene blue (MB) acts to prevent nitric oxide-mediated vasodilation and may be a potential treatment for refractory shock. OBJECTIVE: A systematic analysis of the literature to evaluate MB in pharmacologically induced shock. Primary outcome was survival and secondary outcome was hemodynamic improvement. MATERIALS AND METHODS: A search of MedLine/PubMed, EMBASE, Cochrane Library, TOXLINE, Google Scholar and Google was performed 10 August 2015 using a combination of text words and keywords related to MB, shock and specific drugs. We included primary literature articles reporting clinical outcomes in humans. RESULTS: The searches yielded 928 citations, with 255 exact duplicates. Of the 673 entries screened, 16 citations met study criteria and comprised 17 cases. Calcium channel blockers (CCBs) represented ten cases (six amlodipine, two verapamil, and two diltiazem), atenolol three cases as coingestant with amlodipine, five metformin, one ibuprofen, and one multidrug (quetiapine, carbamazepine, valproic acid, oxazepam, and fluoxetine). Twelve patients survived and nine had hemodynamic improvement following MB administration. Four did not respond to MB but survived with other advanced resuscitative measures. None of the seven cases had BP improvement and four died when lipid was given prior to MB, compared to one death and nine cases of BP improvement when lipid was not given. In all cases, MB was used after failing several other treatments. Bolus doses ranging from 1 to 3 mg/kg, with repeat boluses or maintenance infusions. Reported adverse events were temporary self-limited blue discolorations. CONCLUSION: While there are compelling cases describing an improved hemodynamic status following MB, there are also several cases without observed change. Currently, there is not enough evidence available to recommend the routine administration of MB in refractory pharmacologically induced shock.

Non-native (exotic) snake envenomations in the U.S., 2005-2011.

Non-native (exotic) snakes are a problematic source of envenomation worldwide. This manuscript describes the current demographics, outcomes and challenges of non-native snakebites in the United States (U.S.). We performed a retrospective case series of the National Poison Data System (NPDS) database between 2005 and 2011. There were 258 human exposures involving at least 61 unique exotic venomous species (average = 37 per year; range = 33-40). Males comprised 79% and females 21%. The average age was 33 years with 16% less than 20 years old. 70% of bites occurred in a private residence and 86% were treated at a healthcare facility. 35% of cases received antivenom and 10% were given antibiotics. This study is compared to our previous study (1994-2004) in which there was a substantial coding error rate. Software modifications significantly reduced coding errors. Identification and acquisition of appropriate antivenoms pose a number of logistical difficulties in the management of these envenomations. In the U.S., poison centers have valuable systems and clinical roles in the provision of expert consultation and in the management of these cases.

Lethal serotonin syndrome after methylone and butylone ingestion.

INTRODUCTION: A new generation of designer phenethylamines have emerged and aggressively marketed as "legal highs." The drugs are labeled "not for human consumption" to avoid widespread recognition and prosecution under the existing analog drug laws. The newest generation includes methylone and butylone. Methylone and butylone have minor structural changes and similar pharmacodynamics properties to scheduled drugs. CASE REPORT: We report a case of a healthy 24-year-old who ingested a capsule containing methylone and butylone sold as "Ecstasy" at a concert. The patient presented to the emergency department, comatose febrile, tachycardic, tachypnic, and hypertensive. On exam, she was diaphoretic, tremulous, hyperreflexic, and had sustained clonus. The patient was aggressively cooled, and despite maximal supportive care, the patient progressed to multi-system organ failure and ultimately expired. We obtained and analyzed both her urine and a capsule found on her person similar to the capsules ingested. In both samples, laboratory analysis identified only methylone and butylone. CONCLUSION: This is the first reported death for methylone or butylone and the first human or animal ingestion of butylone. Clinicians and public health officials should work together as new designer drugs emerge.