Introduction: There are few reports summarizing the effectiveness of oral and intravenous (IV) acetylcysteine. We determined the proportion of acetaminophen poisoned patients who develop hepatotoxicity (serum transaminase > 1000 IU/L) when treated with oral and IV acetylcysteine.Methods: Studies were double abstracted by trained researchers. We determined the proportions of patients who developed hepatotoxicity for each route using a random effects model. Studies were further stratified by early and late treatment.Results: We screened 4,416 abstracts; 16 articles, including 5,164 patients, were included in the meta-analysis. The overall rate of hepatotoxicity for the oral and IV routes were 12.6% and 13.2%, respectively. Treatment delays are associated with a higher rate of hepatotoxicity.Conclusion: Studies report similar rates of hepatotoxicity for oral and IV acetylcysteine, but direct comparisons are lacking. While it is difficult to disentangle the effects of dose and duration from route, our findings suggest that the rates of hepatotoxicity are similar for oral and IV administration.

BACKGROUND AND OBJECTIVES:The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program.

Hepatoxicity after therapeutic dosing of acetaminophen in children is rarely reported in defined-population studies. Case reports suggest that this phenomenon may occur, but few reports contain sufficient data to support a probable causal relationship.

The introduction of flow restrictors was associated with a decrease in pediatric AUIs of liquid acetaminophen products. Decreases in the dose ingested and risk of hospital admission per exposure may also have resulted. Efforts to optimize flow restrictors and increase their use with medicines associated with high pediatric overdose risk should be encouraged.

BackgroundThe purpose of this report is to evaluate the quality of data sources used to study cough and cold medication (CCM) safety in children via the Pediatric Cough and Cold Safety Surveillance System.MethodsThe System utilized the National Poison Data System (NPDS), FDA Adverse Event Reporting System (FAERS), English-language medical literature, manufacturer postmarket safety databases, and news/media reports to identify cases from January 2008 through September 2016. Each data source was evaluated by the proportion of detected cases determined to be eligible (met case criteria) and the proportion determined to be evaluable (able to determine causal relationship between adverse event and exposure).ResultsA total of 7184 unique cases were identified from 27,597 detected reports. Of these, 6447 (89.7%) were evaluable. The data source with the highest volume of detected cases was news/media; however, only 0.3% of those cases were eligible for panel review and only 0.2% (24 out of 13,450 cases) were evaluable. The data source with the highest proportion of eligible and evaluable cases was NPDS with 7691 detected cases, 6113 (79.5%) eligible cases, and 5587 (72.6%) evaluable cases.ConclusionsThe data sources utilized to evaluate the safety profile of pediatric CCMs yielded variable detection and evaluation rates, but overall provided a comprehensive look at exposures that otherwise cannot be studied in clinical trials. While this study suggests that each source made a valuable contribution and that evaluable cases are generalizable, improvements are needed in case completeness and accuracy to enhance the quality of postmarket safety evaluations.Electronic supplementary materialThe online version of this article (10.1186/s12874-018-0626-3) contains supplementary material, which is available to authorized users.

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 5 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n 5 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n 5 28; 70.0%). In 6 cases (n 5 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n 5 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.

Implementation of a single concentration for pediatric liquid acetaminophen products and packaging changes were associated with a decrease in medication errors reported to poison control centers. Medication errors are particularly problematic for children <2 years of age, for whom there are no specific labeled dosing instructions. Improved efforts to provide caregivers with dosing instructions for these children are encouraged.

Although generally safe, all non-prescription analgesics are associated with some harm, particularly when recommended dosing limits are exceeded. Research to quantify the competing risks of different analgesic strategies is urgently needed.