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.

Doxylamine succinate overdose: Slurred speech and visual hallucination.

Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used antihistamine for respiratory allergies including allergic rhinitis as well as for the management of insomnia. As it is available over-the-counter like other nonprescription antihistamines and sleep aids, there is a risk of overdose. It is believed that doxylamine succinate has both peripheral and central activity with its anticholinergic properties. Delirium, seizures, and coma are among the central adverse effects that are rare. This case was presented since it is the first case in the literature who developed slurred speech and visual hallucination after high dose doxylamine succinate use and received antidotal therapy for anticholinergic side effects.

Retrospective review of unintentional pediatric ingestions of doxylamine.

BACKGROUND: Doxylamine is a first-generation antihistamine similar in structure to diphenhydramine. Unlike diphenhydramine, however, there is a paucity of data regarding the risk of toxicity following unintentional exposures in pediatric patients. METHODS: We performed an observational case series with data collected retrospectively from a poison system database for all single-substance pediatric (5 years-old and younger) doxylamine ingestions for the period of 1997-2012. Data collected included age, gender, weight, reason for exposure, exact or estimated maximum dose, clinical effects and medical interventions. RESULTS: A total of 140 cases were identified; 74 (53%) involved males. Ages ranged 6 months to 5 years. In 30 cases (21%), the exact amount ingested was documented and ranged from 6.25-50 mg with a maximum weight-based dose of 6.2 mg/kg. In 76 cases, the estimated maximum dose ranged from 12.5 to 375 mg with a maximum weight-based dose of 37 mg/kg. All symptoms were mild and self-limiting. The only documented intervention was the administration of activated charcoal in 13 cases. CONCLUSION: Unintentional isolated pediatric doxylamine ingestions did not result in significant toxicity in our 140 cases. Reported doses of up to 6.2 mg/kg resulted in only transient drowsiness and tachycardia.

Post-mortem evidence of doxylamine in toxicological analyses.

BACKGROUND: Doxylamine (DA) is widely available in pharmacies without prescription and can be used in suicidal intention because of its sedative and anticholinergic properties. Research of literature shows that only a few publications deal with post-mortem evidence of DA and its interpretation during toxicological examination. MATERIAL AND METHODS: In this study, all cases with a positive detection of DA during toxicological analyses with high-performance liquid chromatography in the time period 2000 to 2010 at the Institute of Legal Medicine and Forensic Sciences in Berlin, Germany were retrospectively analysed and interpreted, taking into account police investigations, autopsy results and toxicological analyses. RESULTS: In total, 22 cases with DA intoxications were discovered (♂=16/♀=6, age-at-death range 17 to 90years). Maximum blood concentration was measured at 77.5µg/mL. Cause of death was due to DA intoxication in eight suicide cases; seven of those were combined intoxications (DA and other substances, particularly diphenhydramine). During the evaluated time period no monointoxications with DA were discovered. CONCLUSION: Benchmarks published in past literature are meant as orientation during evaluation of post-mortem DA evidence. These should not be used as absolute values and need to be interpreted individually in each case. Post-mortem redistribution needs to be considered as a main factor in alteration of DA concentration measurement. Furthermore, proof of DA ingestion found in gastric content should only be interpreted quantitatively due to unreliable calculation of the ingested amount. In conclusion, a variety of factors, such as the time period between time of death and the time of the first toxicological analysis, the condition of the body and the findings at autopsy, must also be critically considered.

Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3 academic hospitals.

Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.

Comparative Analysis of Acute Toxic Poisoning in 2003 and 2011: Analysis of 3 Academic Hospitals

Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 +/- 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.

The associative factors of delayed-onset rhabdomyolysis in patients with doxylamine overdose.

OBJECTIVES: The aim of this study was to investigate the associative factors of rhabdomyolysis in patients with doxylamine overdose who had normal creatine phosphokinase levels at admission. METHODS: This study included 169 patients who visited the emergency department of a tertiary teaching hospital after doxylamine overdose between January 1, 1998, and March 31, 2009. Demographic information, clinical variables, and laboratory data were investigated for the associative factors of rhabdomyolysis. RESULTS: Thirty-five (21%) of the 169 patients developed rhabdomyolysis. Patients who developed rhabdomyolysis differed from those who did not in the amount of doxylamine ingested, sex, heart rate, initial value of serum creatinine, and alanine aminotransferase. In the multivariate regression analysis, the only reliable predictors of rhabdomyolysis were the amount of doxylamine ingested (P = .004) and heart rate (P < .001). CONCLUSION: Observation and laboratory follow-up are required for patients with large reported ingestions or tachycardia on admission, even if their creatine phosphokinase levels were normal.

The identification of ingested dandelion juice in gastric contents of a deceased person by direct sequencing and GC-MS methods.

DNA and chemical analysis of gastric contents of a deceased person were handled in this work. The body of the victim was discovered in his car, submerged in a lake. We were asked to determine whether or not the gastric contents of the victim harbored drugs and dandelion material. It was suspected that the victim had been murdered by poisoning with an excess amount of sleeping medication (doxylamine), which had been homogenized with dandelion. The concentrations of 11.4 and 27.5 mg/kg of doxylamine detected from spleen and liver of the victim were far higher than the assumed therapeutic concentration. Via gas chromatography-mass spectrometry (GC-MS) analysis and direct sequencing analysis of plant genetic markers such as intergenic transcribed spacer, 18S ribosomal RNA (rRNA), rbcL and trnLF, it was confirmed that the gastric contents of the victim contained taraxasterol, which is one of the marker compounds for dandelion and contained dandelion species-specific rbcL and trnL-trnF IGS (trnLF) sequences. The initial PCR of the genomic DNA isolated from the gastric contents showed insufficient quantity, and the second PCR, of which the template was a portion of the initial PCR products, exhibited a sufficient quantity for direct sequencing. rbcL and trnLF located in the cpDNA resulted in the successful determination of dandelion DNA in a decedent's stomach contents. GC-MS identifies the actual presence of a taraxasterol at 28.4 min. Raw dandelion was assumed to be used as a masking vehicle for excess sleeping drug (doxylamine).

Risk factors for rhabdomyolysis following doxylamine overdose.

The objective of this prospective study was to identify risk factors for developing rhabdomyolysis in patients with doxylamine overdose. Patients who were admitted to a university teaching hospital between July 2000 and September 2005 due to doxylamine overdose were recruited. Demographic information, clinical variables, and laboratory data were investigated. Twenty-seven (M/F 12/15, age 33.2 +/-13.1 years) patients were enrolled. Sixteen (59%) of 27 patients developed rhabdomyolysis and three (19%) of 16 patients with rhabdomyolysis also developed acute renal failure. Patients who developed rhabdomyolysis differed from those who did not in the amount of doxylamine ingested, initial serum creatitnine and arterial pH. In multivariate regression analysis, the only reliable predictor of rhabdomyolysis was the amount of doxylamine ingested (P = 0.039). The amount of doxylamine ingested (>/= 20 mg/kg) predicted the development of rhabdomyolysis with a sensitivity of 81%, a specificity of 82%, a positive predictive value of 87%, and a negative predictive value of 75%.In conclusion, rhabdomyolysis following doxylamine overdose was common, occurring in 87% of patients who ingested more than 20 mg/kg. The amount of doxylamine ingested was the only reliable predictor for developing rhabdomyolysis following doxylamine overdose.

Comparison of lactated Ringer's solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxication.

OBJECTIVE: To compare the effectiveness and side effects of lactated Ringer's solution (LR) and 0.9% saline (NS) in the treatment of rhabdomyolysis induced by doxylamine intoxication. METHODS: In this 15-month-long prospective randomised single-blind study, after excluding 8 patients among 97 doxylamine-intoxicated patients, 28 (31%) patients were found to have developed rhabdomyolysis and were randomly allocated to NS group (n = 15) or LR group (n = 13). RESULTS: After 12 h of aggressive hydration (400 ml/h), urine/serum pH was found to be significantly higher in the LR group, and serum Na+/Cl- levels to be significantly higher in the NS group. There were no significant differences in serum K+ level and in the time taken for creatine kinase normalisation. The amount of sodium bicarbonate administered and the frequency administration of diuretics was significantly higher in the NS group. Unlike the NS group, the LR group needed little supplemental sodium bicarbonate and did not develop metabolic acidosis. CONCLUSION: LR is more useful than NS in the treatment of rhabdomyolysis induced by doxylamine intoxication.

Antihistamine-induced rhabdomyolysis.

Antihistamines, which are readily available over the counter in sleeping aids, are commonly found in intentional overdoses. We report three new cases of severe rhabdomyolysis related to ingestion of these agents. This is a rarely reported but potentially overlooked complication among patients who present to the emergency center after intentional overdoses. We also describe the potential mechanism of muscle injury in antihistamine overdoses and comment on the potential for cross-reactivity of antihistamines with the urine screen for phencyclidine.

Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.

Suicide through doxylamine poisoning.

Doxylamine is an antihistamine of the ethanolamine class. It is used primarily as a sleep-inducing agent. Only a few reports can be found in the literature about lethal intoxications with doxylamine, but many with combined intoxications. Doxylamine is, aside from diphenhydramine, the only chemically defined active ingredient in some sleeping medications which is available without a prescription in the Federal Republic of Germany. Two cases of doxylamine poisoning are presented, in which high doxylamine concentrations were found in the blood and organs.

Severe rhabdomyolysis after doxylamine overdose.

Clinicians should be aware of the complications of rhabdomyolysis in patients who ingest doxylamine succinate and other over-the-counter antihistamines. The easy availability of these substances increases the potential not only for intentional overdose by adults but also for inadvertent ingestion by children. Prompt intervention and careful assessment of renal function, urinary output, and serum creatine kinase levels may represent the difference between an uncomplicated course and acute renal failure.

Documentation of a doxylamine overdose death: quantitation by standard addition and use of three instrumental techniques.

To answer the question, "Is this death due to a drug overdose?" requires at least that the drug be unequivocally identified and a blood concentration reliably determined. The approach taken in this case as standard addition technique and use of three different chromatographic techniques-high performance liquid chromatography (HPLC), high performance thin-layer chromatography (HP-TLC) and gas chromatography/mass spectrometry (GC/MS). Each of the chromatographies was carried out on the same extract by splitting the residue three ways. HPLC provided a quantitative result which was 1.2 mg/L in blood and HP-TLC and GC/MS confirmed this result with additional quantitative data, information about two metabolites (nordoxylamine and dinordoxylamine) and conclusive identification. Blood nordoxylamine was 0.52 mg/L and doxylamine plus metabolites in urine was 25 mg/L.

Non-traumatic rhabdomyolysis complicating antihistamine overdose.

Antihistamines are common over the counter medications which are frequently involved in overdoses. The usual clinical course is dominated by the anticholinergic affects of these agents; it includes significant autonomic and central nervous system effects and direct cardiac toxicity (1). We report a case of a suicide attempt in a young adult male where ingestion of the antihistamines diphenhydramine and doxylamine was complicated by non-traumatic rhabdomyolysis and acute renal failure.

Nyquil-associated liver injury.

Acetaminophen, a commonly used medication, is present in many over-the-counter remedies. In recent years, its potential to cause severe liver injury has been increasingly appreciated. Chronic abusers of alcohol may be particularly susceptible to hepatotoxicity from acetaminophen. We report two cases of unintentional liver injury associated with ingestion of Nyquil, a liquid cold remedy containing acetaminophen and 25% alcohol.