Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. RESULTS: Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. CONCLUSIONS: Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection.

Postmortem computed tomography and magnetic resonance imaging facilitates forensic autopsy in a fatal case of poisoning with formic acid, diphenhydramine, and ethanol.

A case of fatal poisoning by ingesting formic acid, diphenhydramine, and ethanol by a 25-year-old woman who committed suicide is presented. Prior to autopsy, postmortem computed tomography and postmortem magnetic resonance tomography were performed and revealed severe damage to the stomach, the left thoracic wall, and parts of the liver. Imaging detected acid-induced fluid-fluid level within the thoracic cavity (fat-equivalent fluid and necrotic pleural effusion). This case report illustrates that postmortem cross-sectional imaging may facilitate dissection of severely damaged or complex regions, and may provide additional information compared to autopsy and toxicological examinations alone.

Saving two lives with one dialysis treatment.

Hemodialysis is the extracorporeal treatment of choice for various life-threatening intoxications, with the exception of highly protein-bound substances, which are preferably removed by charcoal hemoperfusion. This technique, however, is limited by its availability and its significant side effects. We present a potentially lifethreatening diphenhydramine (DPH) overdose in a stuporous female patient in which high cut-off hemodialysis was used. Timely detoxification resulted in rapid gain of consciousness, allowing the patient to state the existence and location of another poison victim.

Life-threatening diphenhydramine toxicity presenting with seizures and a wide complex tachycardia improved with intravenous fat emulsion.

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of IFE after a confirmed sole ingestion of diphenhydramine is not previously reported. We present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after IFE administration.

Diphenhydramine's role in death investigations: an examination of diphenhydramine prevalence in 2 US geographical areas.

PURPOSE: Diphenhydramine (DPH), an over-the-counter first-generation H1 receptor antagonist, is not a common drug of abuse; however, it is encountered in cases of overdose both in the clinical setting and in death investigations. The toxicology laboratories in the Tarrant County Medical Examiner's Office and the District of Columbia Office of The Chief Medical Examiner analyze antemortem and postmortem specimens. Presented are the findings of this evaluation and detailed histories of cases involving DPH. METHODS: Toxicology reports, autopsy reports, and death investigator narratives were obtained in cases involving DPH at toxic and lethal levels in which this compound was the primary cause or a contributing factor in the death. RESULTS: Blood concentrations were quantified at a range of 2870 to 21,263 ng/mL. A rare occurrence of DPH abuse via documented intravenous administration leading to death is presented. The cases presented here generally involved much higher concentrations of DPH and an older population than those in previous published data regarding DPH's role in death investigation and abuse. CONCLUSIONS: As people seek legal alternative drugs to abuse and with the ease of obtaining information via online forums, there is a potential to see an increase in the number of cases involving excessive use of DPH.

Fatal diphenhydramine poisoning in a dog.

We report a fatal diphenhydramine poisoning of a 10-year-old, male poodle-cross dog with pre-existing conditions and suspected co-ingestion of ethanol. This case illustrates that diphenhydramine overdose can be fatal in certain circumstances and that analytical toxicology may play an important role in animal death investigations.

Empoisonnement mortel à la diphenhydramine chez un chien. Nous signalons un empoisonnement mortel à la diphenhydramine chez un caniche croisé mâle âgé de 10 ans ayant des conditions préexistantes et une co-ingestion soupçonnée d'éthanol. Ce cas illustre qu'une surdose de diphenhydramine peut être mortelle dans certaines circonstances et qu'une toxicologie analytique peut jouer un rôle important dans les enquêtes sur la mort d'animaux.(Traduit par Isabelle Vallières).

Impact of social media "challenges" on poison center case volume for intentional ingestions among school-aged children: an observational study.

INTRODUCTION: Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. METHODS: We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. RESULTS: There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. DISCUSSION: We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1-2 months later, suggesting a public health opportunity for intervention. LIMITATIONS: This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. CONCLUSIONS: Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges.

CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose.

OBJECTIVES: Fatal drug overdoses often involve multiple co-intoxicants, including opioids. Hydrocodone, the most prescribed opioid for pain management, is metabolized to the active metabolite hydromorphone by hepatic CYP2D6. Inhibition of CYP2D6 by other compounds can disrupt the analgesic properties of hydrocodone and extend its half-life. Diphenhydramine is an over-the-counter cold medication and is known to inhibit CYP2D6 activity. CASE PRESENTATION: A woman in her late 50s was prescribed hydrocodone/acetaminophen (Norco® 10/325). Days before her death, she began taking diphenhydramine for cold symptoms. A post-mortem toxicology report detected the following compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 µg/mL), hydrocodone (410 ng/mL), dihydrocodeine (24 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone was not detected (<2 ng/mL). All compounds were detected in therapeutic concentrations, except for hydrocodone, which was present at lethal concentrations. CONCLUSIONS: This case highlights a fatal drug-drug interaction between hydrocodone and diphenhydramine. The estimated total body burden of hydrocodone was 6- to 12-fold higher than acetaminophen, which is unexpected, as these two drugs were administered as a single formulation and have similar half-lives. Furthermore, hydromorphone was undetectable. Taken together, these findings are highly suggestive of a fatal opioid overdose precipitated by diphenhydramine.

Caution with interpreting laboratory results after lipid rescue therapy.

Intravenous lipid rescue therapy (LRT) may be implemented to attenuate drug toxicity. Little is known about LRT interference with laboratory tests in overdose settings. A 54-year-old man with a history of depression consumed unknown amounts of diphenhydramine, amitriptyline, and acetaminophen (APAP). Initial workup showed aspartate aminotransferase (AST) of 138 U/L, APAP of 177 µg/mL, and a QRS interval of 136 milliseconds. N-acetylcysteine, sodium bicarbonate, and 20% intravenous LRT were initiated. Laboratory test results drawn less than 6 hours later showed an APAP level of 44 µg/mL and an undetectable AST (Siemens Vista 1500 analyzer, lower limit of detection: alanine aminotransferase, 6 U/L; AST, 3 U/L). N-acetylcysteine and LRT infusions were stopped. Eight hours later, serum AST was measured at 488 U/L and increased over the next 2 days to a peak of 1600 U/L before recovery. Given a gradually rising course of AST following APAP ingestion, a single undetectable measurement is highly unlikely and probably erroneous. For this Siemens analyzer, serum lipid concentrations greater than 400 mg/dL cause interference with the AST measurement. Because lipid levels greater than 400 mg/dL with other similar analyzers are known to falsely decrease the AST, it is possible that extreme lipemia caused this laboratory result; a triglyceride level of 3648 mg/dL has been reported after LRT infusion. This conclusion is limited by the lack of repeat measurement of liver enzymes or measurement of serum lipid levels. Lipid rescue therapy may cause lipemia that interferes with the assay for liver enzymes. Suspected abnormal laboratory values should be repeated, or other techniques can be used to remove lipemic interference.

Toxicological identification of diphenhydramine (DPH) in suicide.

Diphenhydramine (DPH), an H1-antihistamine, is identified during postmortem toxicological analyses on a relatively rare but still regular basis. This study examines suicidal intoxications with DPH by analyzing blood and gastric content concentration levels. Twenty cases of DPH intoxications within a 10-year period (2000-2010) were discovered by screening the autopsy records of the Institute of Legal Medicine and Forensic Sciences (ILMFS) in Berlin, Germany. In four cases, DPH levels were lower than 1 µg/mL and hence were not considered likely to be responsible for causing death. In 11 cases, DPH played a role in the fatal episode, and five of these cases were monointoxications. Considering that more than 8,000 autopsies were performed by the ILMFS within the time period under examination, there is only one monointoxication case every 2 years, which makes it a rare occurrence. In two of these intoxications, DPH was only measured in toxic but not "lethal" concentrations in blood, with a concentration of 5 µg/mL being generally used as the cut off between categories according to forensic literature. This raises the question as to whether a strict boundary for a "lethal" blood concentration, as suggested in some literature, can be set and applied in any of these cases. This study shows that an individual interpretation of each case is of utmost importance for correct classification. A thorough toxicological analysis of peripheral venous blood and gastric content, as well as a detailed work-up of the death circumstances, are the basis of an exact interpretation of intoxications with DPH.

Double peak and prolonged absorption after large acetaminophen extended release and diphenhydramine ingestion.

Acetaminophen and acetaminophen combination products are the most frequent medications involved in intentional and unintentional poisonings. The 2008 National Poison Data System compiled by the American Association of Poison Control Centers documented 98,578 acetaminophen-related poisonings, which includes 91 fatalities. Very few case reports of ingestions of acetaminophen extended release with anticholinergics are reported in the literature.

Effects of the antitussive drug cloperastine on ventricular repolarization in halothane-anesthetized guinea pigs.

Cloperastine is an antitussive drug, which can be received as an over-the-counter cold medicine. The chemical structure of cloperastine is quite similar to that of the antihistamine drug diphenhydramine, which is reported to inhibit hERG K⁺ channels and clinically induce long QT syndrome after overdose. To analyze its proarrhythmic potential, we compared effects of cloperastine and diphenhydramine on the hERG K⁺ channels expressed in HEK293 cells. We further assessed their effects on the halothane-anesthetized guinea-pig heart under the monitoring of monophasic action potential (MAP) of the ventricle. Cloperastine inhibited the hERG K⁺ currents in a concentration-dependent manner with an IC50 value of 0.027 µM, whose potency was 100 times greater than that of diphenhydramine (IC50; 2.7 µM). In the anesthetized guinea pigs, cloperastine at a therapeutic dose of 1 mg/kg prolonged the QT interval and MAP duration without affecting PR interval or QRS width. Diphenhydramine at a therapeutic dose of 10 mg/kg prolonged the QT interval and MAP duration together with increase in PR interval and QRS width. The present results suggest that cloperastine may be categorized as a QT-prolonging drug that possibly induces arrhythmia at overdoses like diphenhydramine does.

Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate.

INTRODUCTION: Diphenhydramine is an antihistamine commonly implicated in overdose. It has many pharmacologic effects, including sodium channel blockade. Overdoses in toddlers causing QRS prolongation are only rarely reported and never with effective use of sodium bicarbonate. We report a diphenhydramine overdose in a toddler with multiple markers of sodium channel blockade effectively treated with sodium bicarbonate. METHODS: A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae. RESULTS AND DISCUSSION: Diphenhydramine toxicity is a common poisoning in children. Toxicity typically presents with signs and symptoms of the anticholinergic toxidrome. Diphenhydramine also has sodium channel-blocking properties, and this can be shown in the form of prolonged QRS and a terminal R wave in aVR. QRS prolongation and aVR abnormalities from diphenhydramine ingestion in a toddler have been reported, but effective use of sodium bicarbonate has not. CONCLUSIONS: Electrocardiographic finding consistent with sodium channel blockade should be recognized as a complication of pediatric diphenhydramine overdose, and they seem responsive to hypertonic sodium bicarbonate.

[Suicide by hypothermia with intentional partial undressing]. / Suizid durch allgemeine Unterkühlung mit absichtlicher Teilentkleidung.

Most cases of fatal hypothermia are accidental, often in connection with alcoholisation, homelessness, age-related confusedness and others. The phenomenon of paradoxical undressing may be observed. A paradoxical feeling of warmth in the advanced condition of hypothermia leads to the behaviour of undressing, partly or completely. Suicides with intentional hypothermia are rare. Fatal hypothermia often appears as a concomitant mechanism, e. g. in drug poisoning. The case report describes the fatality of a young woman dying from suicidal hypothermia. She was found partly undressed. This was part of her scheduled plan and not a consequence of paradoxical undressing.

Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

BACKGROUND AND OBJECTIVES: In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children <12 years old that were detected by a safety surveillance system from 2008 to 2016. METHODS: Fatalities in children <12 years old that occurred between 2008 and 2016 associated with oral exposure to one or more CCMs were identified by the Pediatric Cough and Cold Safety Surveillance System. An expert panel reviewed all cases to determine the causal relationship between the exposure and death, if the intent of exposure was therapeutic, and if the dose was supratherapeutic. Other contributing factors related to the child's death were also identified as part of a root cause analysis. RESULTS: Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n = 28; 70.0%). In 6 cases (n = 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n = 7; 17.5%), death followed the intentional use of the CCM to sedate the child. CONCLUSIONS: Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.

Increased rates of diphenhydramine overdose, abuse, and misuse in the United States, 2005-2016.

OBJECTIVES: To describe trends in abuse, misuse, and suicide attempts involving diphenhydramine (DPH). METHODS: We analyzed intentional DPH exposures of individuals ≥10 years old reported to U.S. Poison Control Centers using data from the National Poison Data System, 2005-2016. RESULTS: There were 158,774 intentional DPH exposures in our dataset. The rate of intentional exposures increased 63% over the 12-year study period for all ages combined. Suicide attempts involving DPH showed a bimodal distribution-increasing 263% among children 10-14 years of age, and 126 and 143% among those 55-64 and ≥65 years of age, respectively. Older adults in both the 55-64 and ≥65-year-old age groups had about a 230% increase in rates of misuse. Major adverse clinical effects increased by 91%. There were 745 total reported deaths with a 3.6% increase across all age groups. CONCLUSIONS: Intentional DPH exposures among individuals ≥10 years old have been increasing since 2005. Increasing rates of suicide attempts among children ages 10-14 and increasing misuse among individuals ≥65, coupled with a trend toward greater severity of overdoses, highlight the significant public health impact of this commonly available over-the-counter drug.

Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity.

BACKGROUND: Diphenhydramine is frequently misused and ingested recreationally for its antihistaminergic and antimuscarinic effects and is often involved in both serious and fatal poisonings, either in isolation or in combination with other xenobiotics. OBJECTIVE: This analysis sought to determine which patient and encounter characteristics were associated with severe outcome after diphenhydramine overdose. METHODS: This is an analysis of the multi-center ToxIC registry (2010-2016). Descriptive analysis of all cases with diphenhydramine listed as the "primary agent" contributing to toxicity were included. Analysis sought to determine which patient and encounter characteristics were associated with severe outcome, defined as occurrence of seizure, ventricular dysrhythmia, or intubation. To determine which patient and encounter characteristics were individually associated with severe outcome, we performed chi-square tests. Fisher's exact tests were used in the case of sparse data. We also performed multivariable logistic regression to further determine independent risk factors for severe outcome in diphenhydramine overdose. RESULTS: Eight hundred and sixty-three cases remained after exclusion with 15.6% (n = 135) of all patients having one or more severe outcome. The most common severe outcome was seizures which occurred in 98 (11.6%) of all ingestions. Females comprised 59.1% (n = 510) of all ingestions. Most ingestions were intentional (86.0%, n = 742) with the most common known reason for an intentional ingestion being self-harm, accounting for 37.5% (n = 324) of all ingestions. Self-harm ingestions and ingestions in males were more commonly associated with intubation. When examining outcomes by age, there were no significant differences overall or in any individual outcome except intubation in which children 0-12 were less likely to be intubated as compared to teens and adults. Signs and symptoms most strongly associated with a severe outcome included acidemia (pH < 7.2), QRS prolongation (QRS > 120 ms), and elevated anion gap (AG > 20). DISCUSSION: Acidemia, QRS prolongation, and elevated anion gap are associated with severe outcomes in diphenhydramine toxicity. Further research is warranted to determine their predictive characteristics.