Benzodiazepine exposures among women of reproductive age in the US, 2004-2018.

Benzodiazepines, often used to treat anxiety, insomnia, and other conditions, are prescribed more frequently to women than men, and emergency department visits and overdose deaths involving benzodiazepines have increased significantly among women in recent years. This study describes characteristics and trends associated with benzodiazepine exposures among women of reproductive age (15-49 years old) that were reported to United States poison control centers from 2004 through 2018. The National Poison Data System recorded 258,370 first-ranked benzodiazepine exposures among women 15-49 years old during the study period. More than one-half (56.9%) of exposures involved a single-substance and one-third (34.0%) occurred among women 20-29 years old. The majority were categorized as "intentional, suspected suicide" (73.2%) or "intentional" (12.9%). Exposures frequently resulted in admission to a psychiatric facility (20.6%), critical care unit (18.1%), or non-critical care unit (9.3%). Twenty percent of cases resulted in a serious medical outcome, including 205 deaths. The substantial percentage of benzodiazepine exposures among women of reproductive age that were intentional and associated with suicide attempts or suicide deaths indicate that increased prevention efforts are needed to address this issue.

Thirteen years of oxcarbazepine exposures reported to US poison centers: 2000 to 2012.

OBJECTIVES: Oxcarbazepine (OXC) is a 10-keto analogue of carbamazepine used in patients with partial and secondary generalized seizures. We evaluated ingestions of OXC reported to US poison centers for adverse effects from supratherapeutic doses and/or overdose. METHOD: Retrospective analysis of data reported to National Poison Data System from single-substance OXC ingestions between January 2000 and December 2012. RESULTS: There were 18,867cases with a mean of 1451 exposures/year. The patients were predominantly adults with 5464 exposures in children <6 years (29%). The most commonly reported clinical effects were drowsiness (n = 4703, 25%), vomiting (n = 1559, 8%), tachycardia (n = 590, 3%), agitated (n = 342, 1.8%), hypotension (n = 178, 0.9%), electrolyte disturbance (n = 153, 0.8%), coma (n = 156, 0.8%), and seizures (n = 121, 0.6%). There were 176 patients with a major effect of which 31 involved were children and 1728 (9%) patients with moderate effects of which 300 involved were children. Five deaths were reported in adults. Intentional exposure (e.g. suicide) was the reason for exposure in 68% of patients with major effects and in all fatalities. Fifty-three percent of adults and 38% of children were managed in a health-care facility (HCF). HCF utilization levels remained consistent. DISCUSSION: Severe outcomes appear to be infrequent (<1%). Unlike other anticonvulsants OXC does not appear to be proconvulsant in overdose. CONCLUSION: Serious outcomes for OXC overdoses are unlikely in the pediatric patient. With only mild symptoms likely, observation at home may be appropriate for the majority of cases. In the adult population there appears to be few neurologic and cardiovascular complications even in the intentional exposure.

Vitamin D exposures reported to US poison centers 2000-2014: Temporal trends and outcomes.

UNLABELLED: There has been an increased use of vitamin D both by prescription and by the public as a widely available supplement. We evaluated 15 years of single-substance vitamin D exposures to US poison centers. METHODS: Retrospective analysis of data from the National Poison Data System (NPDS) to evaluate clinical effects, trends, and outcomes of exposures to vitamin D over the period January 1, 2000 through June 30, 2014. Cases were limited to exposures involving vitamin D as a single substance. Multiple vitamin products that may have included vitamin D were not included in this study. RESULTS: From 2000 through June 30, 2014, there were 25,397 human exposures to vitamin D reported to NPDS. There was a mean of 196 cases per year from 2000 to 2005, followed by a 1600% increase in exposures between 2005 and 2011 to a new annual mean of 4535 exposures per year. The mean and median ages were 23.4 years and 10 years, respectively. There were no fatalities, but five (0.02%) major effect outcomes. Serious medical outcomes (major or moderate outcome) were infrequent, ranging from 2 patients/year to 22 patients/year. Clinical effects were primarily gastrointestinal (0.7-1.5%) and mild neurological effects (0.2-0.4%). There was a decline in the percentage of patients treated in a health care facility and of patients with serious medical outcome. CONCLUSION: Despite the enormous increase in number of exposures, there was not a significant increase in patients with a serious medical outcome. Rare severe outcomes may occur.

Review of toxicity and trends in the use of tiagabine as reported to US poison centers from 2000 to 2012.

BACKGROUND: Tiagabine is a novel antiepileptic that acts by increasing synaptic and extracellular gamma-aminobutyric acid concentrations. Information concerning overdose of tiagabine is limited. After introduction, an increasing number of off-label uses suggested that tiagabine use would increase. However in 2005 and 2008, warnings from the Food and Drug Administration (FDA) were issued on the risk of seizures in non-epileptic and increased suicide ideation. We evaluated the temporal trends associated with these two warnings as well as clinical outcomes from tiagabine overdose. METHOD: A retrospective review of all single substance tiagabine exposures in National Poison Data System (NPDS) from 2000 to 2012. RESULTS: A total of 2147 patients had ingested tiagabine, with a mean of 165 year(-1). This was disproportionally distributed, with a steep rise leading up to 2004 (max 559 year(-1)) and then a significant decline (p < 0.05) between 2005 and 2006. The number of cases reported to NPDS mirrored the sales of tiagabine. Clinical effects were predominantly neurological, with the most commonly reported effects being drowsiness (27%), agitation (19%), confusion (12%), seizures (11%), and tachycardia (10%). In all, 758 patients (35%) showed a major or moderate medical outcome, with no deaths reported. A disproportionate share of the major outcomes was in the suicide attempt group (73%). The majority of patients (75%) were treated in a health-care facility (HCF). CONCLUSIONS: The HCF usage is likely due to high rate of symptomatic patients (59%) and the large proportion of suicide attempt cases. The frequency of tiagabine cases in NPDS mirrored pharmaceutical sales, with steep declines temporally related to the 2005 FDA warning.

Identification of N-Hydroxy-para-aminobenzoic acid in a cyanotic child after benzocaine exposure.

CONTEXT: Methemoglobinemia (MetHb) after exposure to benzocaine (BZC) has been reported for more than 50 years, however the pathophysiologic mechanism has not been previously established. Direct administration of BZC to blood does not produce MetHb. After topical use, due to the lipophilicity and rapid acetylation in the tissue, little BZC reaches the liver for hepatic biotransformation. However, isolated human livers have been shown to produce MetHb forming N-hydroxyl metabolites from BZC. We report a case of BZC-induced MetHb with the first identification and quantification of the reactive metabolite responsible for the oxidative stress: N-Hydroxy-Para-amino benzoic acid (N-OH-PABA). CASE DETAILS: An 8 year old male was admitted to a hospital for an appendectomy. Several applications of BZC spray were used during multiple attempts at nasogastric tube placement. In various attempts to achieve local anesthesia, benzocaine spray was used in both nares and through the mouth aimed at the posterior oropharynx. The patient subsequently became cyanotic with an initial MetHb level of 32.9 %. Methylene blue was administered and the patient promptly responded with resolution of cyanosis. Blood taken within 20 min of the initial symptoms contained benzocaine (5.2ug/mL), bupivacaine (740ng/mL), lidocaine (530ng/mL), acetaminophen (12ug/mL), midazolam (60ng/mL), PABA and N-OH-PABA (35ng/mL). Serum was analyzed using Liquid Chromatography- Quadrupole Time-of-Flight Mass Spectrometry. Mass spectrometry was done using an electrospray ionization source run in negative and positive polarities. A reference standard for N-OH-PABA was synthesized for confirmation and quantification. DISCUSSION: The rare and idiopathic nature of methemoglobinemia after benzocaine use has made study of the pathophysiologic mechanism in humans difficult. Lack of understanding has brought calls for restriction of use of the widely used medication that may not be based on evidence. Our case presents several unique features: 1) benzocaine absorption after topical administration was documented with serum concentrations 2) confirmation of an in vivo formation of MetHb-forming n-hydroxyl-metabolite after benzocaine use and 3) the documentation of N-OH-PABA in humans within 20 min of MetHb post-benzocaine administration.

Incidents of potential public health significance identified using national surveillance of US poison center data (2008-2012).

BACKGROUND: The Centers for Disease Control and Prevention (CDC) and the American Association of Poison Control Centers conduct national surveillance on data collected by US poison centers to identify incidents of potential public health significance (IPHS). The overarching goals of this collaboration are to improve CDC's national surveillance capacity for public health threats, identify early markers of public health incidents and enhance situational awareness. The National Poison Data System (NPDS) is used as a surveillance system to automatically identify data anomalies. PURPOSE: To characterize data anomalies and IPHS captured by national surveillance of poison center data over 5 years. METHODS: Data anomalies are identified through three surveillance methodologies: call-volume, clinical effect, and case-based. Anomalies are reviewed by a team of epidemiologists and clinical toxicologists to determine IPHS using standardized criteria. The authors reviewed IPHS identified by these surveillance activities from 2008 through 2012. RESULTS: Call-volume surveillance identified 384 IPHS; most were related to gas and fume exposures (n = 229; 59.6%) with the most commonly implicated substance being carbon monoxide (CO) (n = 92; 22.8%). Clinical-effect surveillance identified 138 IPHS; the majority were related to gas and fume exposures (n = 58; 42.0%) and gastrointestinal complaints (n = 84; 16.2%), and the most commonly implicated substance was CO (n = 20; 14.4%). Among the 11 case-based surveillance definitions, the botulism case definition yielded the highest percentage of identified agent-specific illness. CONCLUSIONS: A small proportion of data anomalies were designated as IPHS. Of these, CO releases were the most frequently reported IPHS and gastrointestinal syndromes were the most commonly reported illness manifestations. poison center data surveillance may be used as an approach to identify exposures, illnesses, and incidents of importance at the national and state level.

Medication errors reported to U.S. Poison Control Centers, 2000-2012.

CONTEXT: Previous studies of medication errors have largely focused on healthcare facilities and have not reported generalizable national trends among out-of-hospital medication errors. OBJECTIVE: We sought to understand U.S. trends in medication errors, including the age-related risks, the involved medications, and the medical outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of National Poison Data System (NPDS) data from the American Association of Poison Control Centers for years 2000-2012. Medication error cases were analyzed by age, gender, pharmaceutical involved, substance rank, dosing error type, management site, level of healthcare received, and medical outcome. Trends in medication error rates were analyzed using Poisson regression. RESULTS: From 2000 to 2012, the NPDS recorded 2,913,924 calls reporting unintentional pharmaceutical-related errors that met inclusion criteria. Non-healthcare facility calls comprised 99.2% calls related to unintentional therapeutic errors. Eighty-seven percent of medication errors were managed on site. The annual medication error rate for all callers per 10,000 U.S. population increased significantly (p < 0.0001) by 69.8% from 2000 (4.98 calls per 10,000 population) to 2012 (8.46 calls per 10,000 population). Among adults aged 20 years and older, age was positively correlating (r = 0.96) with the rate of medication error. Analgesics were the most frequent pharmaceutical class involved in medication errors for ages 6-49 (N = 221,061). Among ages 20-49 years, opioid-related medication errors decreased by 7.9% from 2010 to 2012. Cardiovascular drugs were the leading source of injury among all ages (N = 14,440) and also the leading pharmaceutical class involved in medication errors among adults 50 years and older (N = 187,760). CONCLUSION: Medication errors continue to be a source of preventable injury with increasing incidence across the out-of-hospital population.

Characterizing risk factors for pediatric lamp oil product exposures.

UNLABELLED: Poisonings from lamp oil ingestion continue to occur worldwide among the pediatric population despite preventive measures such as restricted sale of colored and scented lamp oils. This suggests that optimal prevention practices for unintentional pediatric exposures to lamp oil have yet to be identified and/or properly implemented. OBJECTIVE: To characterize demographic, health data, and potential risk factors associated with reported exposures to lamp oil by callers to poison centers (PCs) in the US and discuss their public health implications. STUDY DESIGN: This was a two part study in which the first part included characterizing all exposures to a lamp oil product reported to the National Poison Data System (NPDS) with regard to demographics, exposure, health, and outcome data from 1/1/2000 to 12/31/2010. Regional penetrance was calculated using NPDS data by grouping states into four regions and dividing the number of exposure calls by pediatric population per region (from the 2000 US census). Temporal analyses were performed on NPDS data by comparing number of exposures by season and around the July 4th holiday. Poisson regression was used to model the count of exposures for these analyses. In the second part of this project, in order to identify risk factors we conducted a telephone-based survey to the parents of children from five PCs in five different states. The 10 most recent lamp oil product exposure calls for each poison center were systematically selected for inclusion. Calls in which a parent or guardian witnessed a pediatric lamp oil product ingestion were eligible for inclusion. Data on demographics, exposure information, behavioral traits, and health were collected. A descriptive analysis was performed and Fisher's exact test was used to evaluate associations between variables. All analyses were conducted using SAS v9.3. RESULTS: Among NPDS data, 2 years was the most common patient age reported and states in the Midwestern region had the highest numbers of exposure calls compared to other regions. Exposure calls differed by season (p < 0.0001) and were higher around the July 4th holiday compared to the rest of the days in July (2.09 vs. 1.89 calls/day, p < 0.002). Most exposures occurred inside a house, were managed on-site and also had a "no effect" medical outcome. Of the 50 PC-administered surveys to parents or guardians, 39 (78%) met inclusion criteria for analysis. The majority of ingestions occurred in children that were 2 years of age, that were not alone, involved tiki torch fuel products located on a table or shelf, and occurred inside the home. The amount of lamp oil ingested did not appear to be associated with either the smell (p = 0.19) or the color of the oil (p = 1.00) in this small sample. Approximately half were asymptomatic (n = 18; 46%), and of those that reported symptoms, cough was the most common (n = 20, 95%) complaint. CONCLUSIONS: Lamp oil product exposures are most common among young children (around 2 years of age) while at home, not alone and likely as a result of the product being in a child-accessible location. Increasing parental awareness about potential health risks to children from these products and teaching safe storage and handling practices may help prevent both exposures and associated illness. These activities may be of greater benefit in Midwestern states and during summer months (including the period around the July 4th holiday).

Demographics and outcome of unintentional insulin overdoses managed by three poison centers.

UNLABELLED: Insulin dosing errors are one of the most dangerous medication issues due to the risk of profound hypoglycemia. The incidence of insulin dosing errors is increasing and there is no standard of care for management location. OBJECTIVE: To determine the types of insulin, follow-up time, number of phone calls, incidence of hypoglycemia, and case outcomes for unintentional insulin overdoses managed by Poison Centers (PCs). METHODS: Observational case series: records of patients with unintentional injected insulin errors from three PCs over a 22-month period were manually reviewed for insulin type, management site, time of exposure, insulin dose, number of calls, presence of hypoglycemia, and case outcome. RESULTS: There were 642 cases: 97.5% occurred in the home and the majority of patients (77.3%) were managed on site with only 17.4% resulting in Emergency Department treatment. Clinical or numerical (blood sugar < 60 mg/dL) hypoglycemia occurred 15.9% (n = 102) of the time in all cases, with 6.9% (n = 41) of cases having numerical hypoglycemia. The median insulin dose when known was 40 Units, with short-acting insulin making up the majority of cases (64.3%) with 13.8% of cases having a dose error of 80 or more units. The average duration of follow-up was 6.9 h. The frequency of hypoglycemia (clinical or numerical) did not differ between short and non-short duration insulin cases (15.7% vs. 16.9%, n = 65 vs. 37, p = 0.91), did not differ with cases receiving more than 50 Units of insulin (14.9% vs. 16.7%, n = 29 vs. 73, p = 0.64), and did not differ between those managed on site and other management locations (14.4% vs. 21.4%, n = 71 vs. 31, p = 0.053). Outcomes were benign in the majority of cases and there were no cases with Major (severe) outcomes or Death. CONCLUSION: Insulin dosing accidents can be routinely managed at home by PCs and have a low rate of hypoglycemia and adverse outcomes. This suggests that these cases can often be managed at home without referral with a potential benefit in no direct cost to the patient, convenience, and immediacy.

Comparison of US population and live birth rates with poison exposures reported to the National Poison Data System (NPDS): children ages 0-5 years from 2000 to 2012.

BACKGROUND: Monitoring of poison control center data has provided an important public health surveillance tool. Previous work has identified the population with the greatest risk of poisoning as children of < 6 years. It follows that the size of the population at highest risk should be an important driver/factor of poison center volume. Therefore, one would expect population changes to be reflected in corresponding National Poison Data system (NPDS) call volume changes. We examined this relationship. METHOD: This was a retrospective comparison of young children's poison exposures reported to NPDS with changes in US population as reported by the US Census Bureau and by live birth counts in the United States. We examined the relation of population and live birth counts to NPDS exposures in children of 0-5 years and for the total (children of 0-5 years). RESULTS: There was a statistically significant relation between exposures and population for the three of the seven age groups (1-3 years old) and between exposures and live birth counts for the five of the seven age groups (1-4 years old and total (0-5)). The highest correlation was seen with the age groups of 2-year olds (r = 0.815; slope, 4.7373; 95% CI, 2.36-7.11) and 1-year olds (r = 0.785; slope, 4.878; 95% CI, 2.163-7.592). Live birth count was more closely related than population for all but the 1-year-old age groups. DISCUSSION: Our study reports a number of interesting findings including 1) live birth counts and population are closely associated with each other, 2) poison exposures in NPDS were more strongly associated with live birth counts than with population, 3) the population at greatest risk is the 1- and 2-year-old age groups and the strongest associations between exposures and population and exposures and live birth counts occurred in these two age groups, and 4) changes occurring in the live birth counts, both positive and negative, were reflected in annual changes reported in NPDS human exposures in children < 6 years. These results mean that population changes underlie 37%-66% of the changes in poison exposures and suggests that the population at risk should be considered in monitoring poisoning injuries in the future. CONCLUSION: These results provide a quantitative assessment of the age-based risk rates and changes over time for NPDS exposure in children who are 0-5 years old. With the decrease in live births noted over the last 4 years (2008, 2009, 2010, and estimated 2011), US poison centers may expect a similar decline in human exposures in children of 0-5 years. Our analysis adds additional support to the validity of this data set as a public health surveillance tool.

Evaluation of administration of activated charcoal in the home.

OBJECTIVE: Activated charcoal (AC) is recognized as the treatment of choice for gastrointestinal decontamination after many ingestions. AC use in the home has been limited by concerns that parents would not administer it properly and that children would refuse to take AC. Previous descriptions of home administration have reported mixed results. METHODS: This was an 18-month consecutive case series of all patients for whom AC administration was recommended in the home. Data collected included AC availability in the home and/or a local pharmacy, success in administration, amount administered, time after ingestion to AC administration, difficulties in administration, adverse effects, age and gender of patient, substance involved in poisoning, and medical outcome. All cases were followed for at least 3 days after the ingestion. Patients who initially had home AC recommendation but who ultimately were treated in the emergency department (ED) served as a comparison group. RESULTS: Home administration of AC was recommended in 138 cases. A total of 115 individuals (83%) were treated with AC in the home, with no failures to administer AC. Reasons for failure to manage at home were 1) mother preferred ED (8 cases), 2) could not locate AC (7 cases), 3) pharmacy closed for the night (6 cases) and 4) no home telephone for follow-up (2 cases). Time to AC administration after ingestion was a mean of 38 minutes (+/-18.3) for home treatment and 73 minutes (+/-18.1) for ED treatment. Ninety-five percent of home cases received AC in < or =60 minutes versus 33% for ED management. AC was in the home in 11 cases at the time of recommendation. The amount of AC administered was a mean of 12.1 g (standard deviation: 6.9) and a median of 12 g. Eight children (6.9%) who were treated at home vomited after AC versus 3 (13%) who received ED treatment. No aspirations or complications occurred. CONCLUSIONS: AC can be administered successfully by the lay public in the home. Home use of AC significantly reduces the time to AC administration.

Timely antemortem and postmortem concentrations in a fatal carbamazepine overdose.

There are no published reports that include both timely antemortem and postmortem carbamazepine concentrations after massive overdose. We report a fatal overdose of carbamazepine with both timely antemortem and postmortem carbamazepine concentrations. Carbamazepine concentrations were 47.7 mcg/mL 2 h antemortem and 53 mcg/mL at 9 h postmortem. The slight rise in drug concentration may reflect continued absorption of the drug in the last 2 h before death. Postmortem carbamazepine concentrations drawn from a peripheral vessel in this patient appeared to reflect drug concentrations at the time of death.

Persistently elevated acetaminophen concentrations for two days after an initial four-hour non-toxic concentration.

The decision to treat patients who overdose with n-acetylcysteine is routinely made with a single APAP concentration drawn 4 or more hours post-ingestion. However, in cases where there are co-ingestants that may delay gastric emptying, there have been recommendations for additional concentrations to determine peak APAP concentrations. This report is of a case of acetaminophen overdose involving narcotic co-ingestants with persistenty elevated acetaminophen concentrations for 2 d, suggesting delayed gastric emptying and/or bezoar formation. A second striking feature of this case was the persistently elevated acetaminophen concentrations without evidence of liver injury despite antidotal therapy not being employed.

Multi-center retrospective evaluation of oral benzocaine exposure in children.

On rare occasions benzocaine has produced methemoglobinemia from oral, rectal and dermal exposures. There is disagreement whether this is an idiosyncratic event or a dose-related event. To gain a better perspective on this problem we retrospectively reviewed cases at 4 large regional poison centers of children <18-y of age from 1993-1996. One hundred and eighty-eight benzocaine exposures were reported. Mean and median ingested dosage were 86.8 (+/- 89.5) mg/kg and 50 mg/kg, respectively. Fifty-eight patients (30%) were managed in the emergency department; 8 patients had methemoglobin levels determined. One child had a methemoglobin level of 19%; all others were <1%. One hundred and seventy-three patients (92%) remained asymptomatic. Other symptoms were minor: oral numbness (8), vomiting (3), and 1 each of oral irritation, dizziness and nausea. In this series of accidental ingestions of benzocaine-containing products cyanosis was rare and apparently not dose related. These cases may be safely managed at home with telephone follow up for at least 2 h. If there is evidence of cyanosis, dusky pallor, shortness of breath, or change in mental status direct medical evaluation should be recommended.

A fatal case of gun blue ingestion in a toddler.

Acute selenium poisoning occurs infrequently. The form of selenium encountered plays a great role in toxicity. Several fatalities have been reported and all but I involved ingestion of selenious acid or selenium dioxide. A healthy 22-mo-old male ingested up to 15 ml of Gun Blue solution (selenious acid). Initially he was pink, alert, and combative in the ambulance but his condition rapidly deteriorated. There was no measurable blood pressure, his oxygen saturation was 84% by pulse oximetry, and his mental status deteriorated to require hand ventilation. The child was cyanotic, unresponsive, and without palpable pulses upon presentation. Cardiopulmonary resuscitation was initiated unsuccessfully and was terminated after 35 minutes.

Multicenter case series of pediatric metformin ingestion.

OBJECTIVE: There are no large studies, case series, or case reports of metformin ingestion in children. This study summarizes the clinical course and outcomes of metformin ingestion in children reported to the American Association of Poison Control Centers-certified regional poison centers. METHODS: This was a case series of all metformin ingestions in patients <18 years of age reported to eight regional poison centers. Data collection included age, gender, dose ingested, co-ingestants, symptoms, vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required at least 24 hours of follow-up. RESULTS: Fifty-five cases were collected. Ages ranged from 15 months to 17 years, with a mean (+/- SD) of 42+/-4.4 years. The dose ingested, by history, ranged from 250 mg to 16.5 g, with a mean and median of 1710+/-3391 and 500 mg, respectively. Forty-one children (76%) ingested a maximum of two tablets (< or =1700 mg). In the children younger than six years, dosage ranged from 9 to 196 mg/kg, with a mean and median of 60+/-41.1 and 40 mg/kg, respectively. Thirty-seven children were evaluated in a healthcare facility. Clinical effects were limited to nausea (2), diarrhea (2), and dizziness (1). None of the 38 children who had serial glucose measurements experienced hypoglycemia. Arterial blood gas and electrolyte measurements were performed in three and 19 children, respectively. No evidence of acidosis was demonstrated. Two children had lactate concentrations measured and were determined to be in the normal range. Twenty-nine patients received activated charcoal. Five patients received parenteral glucose and one adolescent with a history of diabetes received insulin for hyperglycemia. CONCLUSIONS: Unintentional ingestion of < or =1700 mg of metformin in the healthy pediatric population does not appear to pose a significant health risk of hypoglycemia or detrimental outcome. In the 21 children who were tested for either blood glucose, electrolyte, or lactate concentrations, no evidence of lactic acidosis was seen.

Multicenter case series of valproic acid ingestion: serum concentrations and toxicity.

BACKGROUND: Valproic acid exposures reported to poison centers have increased more than 4-fold over the last 5 years. There are no large case series published on valproic acid ingestion. METHODS: A prospective multicenter case series of all patients reporting an ingestion of valproic acid. Data collected included: age, gender, dose ingested, concomitant medications, symptoms and vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required a serum valproic acid concentration above the therapeutic threshold of 100 microg/mL. Statistical analysis was by Fisher's exact test. RESULTS: A total of 335 patients were reported to participating centers of which 186 (55%) had serum valproic acid concentrations greater than 100 microg/mL. Of the 186 cases, 53 were multiple drug exposures leaving 133 cases of sole valproic acid ingestion for evaluation. Age ranged from 2 to 66 years with a mean of 30.1 years +/- 12. Peak serum valproic acid concentrations ranged from 110 microg/mL to 1840 microg/mL with a mean of 378.3 microg/mL +/- 310.2 microg/mL. Time from postingestion to the peak measured valproic acid concentration ranged from 1 to 18 hours, with a mean of 7.4 hours +/- 3.9. Symptoms included lethargy (n = 94), coma (n = 19), tachycardia (n = 24), aspiration (n = 8), metabolic acidosis (n = 8), and hypotension (n = 4). A peak concentration of > 450 microg/mL was more likely to be associated with a moderate or major adverse outcome (p < 0.005). A peak concentration > 850 microg/mL was more likely to be associated with coma (p < 0.005) and acidosis (p < 0.005). Eleven patients experienced transient thrombocytopenia (platelets < 150,000) and all had peak valproic acid concentrations >450 microg/mL. Four patients experienced transient leukopenia (WBC < 3,500). The mean hospital stay for all patients was 42 +/- 33.1 hours. A hospital stay > 48 hours was more likely to be associated with a peak valproic acid concentration > 450 microg/mL (p < 0.05). There were 2 fatalities. CONCLUSIONS: In this case series, patients with peak valproic acid concentrations above 450 microg/mL were more likely to develop significant clinical effects and have longer hospital stays. A peak valproic acid concentration above 850 microg/mL was more likely to be associated with coma, respiratory depression, aspiration, or metabolic acidosis.

Management of sulfonylurea ingestions.

In the majority of pediatric patients with an unintentional ingestion of a sulfonylurea, observation and, if necessary, intravenous glucose supplementation, are sufficient. However, with cases of persistent hypoglycemia or cases refractory to IV glucose supplementation, attempts to inhibit insulin secretion should be considered. Octreotide appears effective and safe. It may eliminate the need for prolonged infusions of hypertonic dextrose solutions and secondarily the risks associated with central line access. It has been successful in restoring euglycemia in cases refractory to glucose infusions. In the absence of octreotide, diazoxide remains a viable alternative to decrease insulin secretion.

Fatal ingestion of sodium hypochlorite bleach with associated hypernatremia and hyperchloremic metabolic acidosis.

Ingestion of sodium hypochlorite bleach is usually benign, leading most poison centers to advocate conservative, home management. We report a rare, fatal case of household bleach ingestion. A 66-y-old female ingested an unknown quantity of regular CLOROX bleach (5.25% sodium hypochlorite, pH = 11.4). Upon discovery, she was vomiting spontaneously, and had slurred speech and oral mucosal discoloration. On hospital arrival the patient became unresponsive with shallow respirations. Laboratory studies revealed hypernatremia (169 mEq Na/L), hyperchloremia (143 mEq Cl/L), and metabolic acidosis (5 mmol total CO2/L). Radiographic evaluation showed bilateral pneumothoraces and pneumoperitoneum. The patient was intubated and ventilated, hypotension was treated with fluid resuscitation, and metabolic acidosis corrected with sodium bicarbonate. Naloxone and flumazenil were given without effect, and thoracostomy tubes were placed. Rapid deterioration of vital signs and mental status ensued, with cardiorespiratory arrest from which she was resuscitated. A second cardiac arrest resulted in death. Autopsy revealed esophageal and gastric mucosal erosions, perforation at the gastroesophageal junction, and extensive necrosis of adjacent soft tissue. Stomach contents contained sodium hypochlorite, and pleural and peritoneal fluid had the aroma of bleach. Postmortem vitreous humor Na was 187 mEq/L and Cl was 169 mEq/L. Toxicologic analysis revealed meprobamate metabolites in the urine, and lidocaine in the blood. The literature regarding fatal bleach ingestion is reviewed.