Centers Toxic Exposure Surveillance System Research Articles

Poisoning of Butanol-Containing Products: Clinical Characteristics and Outcomes.

BackgroundButanol (butyl alcohol) is a chemical which occurs naturally in some foods and is used in the manufacture of other chemicals. Current data on butanol poisoning in humans are limited.ObjectiveThis study describes clinical characteristics and outcomes of patients exposed to products containing butanol.MethodsWe performed a 5-year retrospective cross-sectional study by analyzing data from the Ramathibodi Poison Center Toxic Exposure Surveillance System for 2013–2017.ResultsThere were 163 patients included in the study. All products containing butanol reported were agricultural adjuvant products. Most (67.5%) patients were males and had ingested butanol accidentally (75.5%). The median age was 42 years. Almost all patients had oral exposure to butanol. At presentation, most of our patients had normal vital signs and were conscious. Clinical presentations mostly included gastrointestinal symptoms (65%) and local irritation (28.8%). Fifty-four patients (33.1%) had no obvious clinical effects at presentation. Most patients had normal laboratory tests at presentation, although eight developed systemic effects including high anion gap metabolic acidosis (n=8), acute kidney injury (AKI; n=5), depression of consciousness (n=5), and hypotension (n=3). Of these eight patients, two with intentional ingestion developed altered consciousness, hypotension, AKI, severe metabolic acidosis, and eventually died. One of these died within 1 day after ingestion, while the other died later through complications during admission. Therefore, the mortality rate was 1.23%. Sixty-six patients (40.5%) were admitted to hospitals, with a median length of stay of 1 day. Most patients received only supportive treatment and fully recovered.ConclusionAgricultural adjuvant products containing butanol or butanol itself caused only mild effects in most patients, but systemic effects occurred in some. The mortality from this poisoning was very low, and both fatalities were from intentional ingestion. Supportive care and proper management of complications should be the main treatment for this form of poisoning.

Toad Poisoning: Clinical Characteristics and Outcomes.

ObjectiveThis study was performed to describe the clinical characteristics and outcomes of patients with toad poisoning in Thailand.MethodsWe carried out a retrospective study of patients with toad poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012–2016).ResultsWe studied 36 patients poisoned by toad toxin. The median age was 31 years. Most patients were male (66.7%) and had ingested toad meat (50%). The most common presentation was gastrointestinal (GI) symptoms with a median onset of 2 h after ingestion. Twelve patients presented with bradycardia; seven presented with shock and one with cardiac arrest. In the initial EKGs of all patients, the most common abnormality was sinus bradycardia.Two patients developed cardiac arrest early during management in the emergency room (within 15 minutes after ER arrival or within 4.5 h after ingestion). During admission, one patient developed sinus bradycardia, and two developed bradyarrhythmia; however, all three were stable. No tachyarrhythmias such as ventricular tachycardia were detected in any patient. Some patients (11.1%) presented with hyperkalemia. Serum digoxin was detected in five of seven patients tested, ranging from 0.43 to >8 ng/mL. Most patients (75%) were admitted to the hospital; the median duration of hospitalization was 2 d (range 0.5–5 d). The overall mortality rate was 8.3%, and all three patients that died ate toad meat and/or eggs and developed cardiac arrest. All patients received supportive with/without symptomatic care including GI decontamination, inotropic drugs, cardiac pacing, and management of hyperkalemia. One patient received intravenous calcium for hyperkalemia but did not develop dysrhythmia after calcium administration. One patient received digoxin-specific antibody fragments (DsFab), after which he clinically improved and was discharged.ConclusionToad poisoning commonly caused GI symptoms and bradycardia. However, in severe cases, death occurred. Tachyarrhythmia was not observed. Supportive, symptomatic care might be the main therapies for this poisoning, especially if DsFab is not available.

Myotoxic Mushroom Poisoning in Thailand: Clinical Characteristics and Outcomes.

PurposeTo describe the clinical characteristics and outcomes of myotoxic mushroom poisoning in Thailand.Patients and MethodsWe performed a retrospective cohort study of cases of myotoxic mushroom poisoning from the Ramathibodi Poison Center Toxic Exposure Surveillance System during a 5-year period (2012–2016).ResultsForty-one cases were included. Most (53.7%) were male with the average age of 49 years. In three cases, the mushrooms were identified as Russula species by an experienced mycologist. Common presenting symptoms were gastrointestinal (GI) symptoms and myalgia. The median onset of GI symptoms and symptoms suggesting rhabdomyolysis after consuming mushrooms was 2 hours (0.17–24 hours) and 24–48 hours (2–120 hours), respectively. Eight patients who ate the mushrooms together with other patients with rhabdomyolysis had GI symptoms but did not develop rhabdomyolysis. For patients with rhabdomyolysis, acute kidney injury (AKI) and hyperkalaemia occurred in 51.5% and 33.3% of cases, respectively. Median initial and maximum creatine phosphokinase (CPK) levels in patients with rhabdomyolysis were 31,145 and 47,861 U/L, respectively. Fifteen of 17 patients who were investigated for troponin levels had elevated troponin. Three patients had a low ejection fraction. Most patients (95.1%) were admitted to hospital, with a median stay of 5 days. The mortality rate was 26.8%. Treatments included intravenous fluid, urine alkalinization, haemodialysis and peritoneal dialysis. Among patients with rhabdomyolysis, AKI, hyperkalaemia during hospitalisation, maximum CPK level, maximum creatinine level and initial and maximum potassium levels were the factors found to be significantly different between patients who died and those who survived.ConclusionMyotoxic mushroom poisoning had a high mortality rate. Most patients had early or delayed onset of clinical symptoms after mushroom ingestion. Some patients developed severe cardiovascular effects. Early detection, close monitoring (especially serum potassium, creatinine, CPK and cardiac effect) and good supportive care were the main treatment modalities.

Clinical outcome of paraquat poisoning during pregnancy

Objectives: We aimed to describe clinical characteristics and outcomes of paraquat poisoning in pregnant patients, their fetuses, and newborns.Methods: We performed a retrospective study of pregnant patients who were exposed to paraquat, from the Ramathibodi Poison Center Toxic Exposure Surveillance System, during a 5-year period.Results: Thirty-six patients, representing every trimester, were included. All experienced oral exposure with a mean age of 22.7 years and mean gestational age (GA) of 23.1 weeks. Most had gastrointestinal symptoms and signs. Systemic effects, which mainly comprised of acute kidney injury (AKI), were found in 13 patients (36.1%); obstetric complications were noted in five patients (13.9%). Medical treatment included intravenous dexamethasone and cyclophosphamide. Some patients received hemodialysis and endotracheal intubation. Nine patients delivered during hospitalization; four newborns (maternal GAs of 30–36 weeks with systemic effects) died after delivery. One patient with GA 26 weeks delivered and died, but her newborn survived. Mortality rates of pregnant patients and their offspring delivered in-hospital were 25% and 44.4%, respectively; all deaths occurred in patients with systemic toxicity. The median length of hospital stay was 6 days. Notably, AKI, hepatotoxicity, and maximum white blood cell count significantly differed between dead and surviving patients. We followed-up 15 surviving patients who were discharged before delivery to assess delivery outcomes. All 15 patients and newborns survived without reports of congenital anomalies.Conclusions: Paraquat poisoning during pregnancy caused high fatalities in pregnant patients, fetuses, and newborns who were delivered during hospitalization, especially among patients with systemic effects. The GA of the pregnancy affected fetal outcomes, both in utero and at birth. Selective, appropriate management is warranted and might be guided by poisoning severity and the GA of the pregnancy.

Krait envenomation in Thailand.

PurposeThree species in the genus Bungarus inhabit Thailand. Among these, Bungarus candidus (Malayan krait) is the most common and deadliest. Currently, the clinical manifestations of patients envenomed by kraits, especially Bungarus fasciatus (banded krait), have not been thoroughly investigated. This study was performed to elucidate the clinical manifestations and outcomes of patients bitten by kraits in Thailand.Materials and methodsThe data of krait envenomation cases that occurred during a 9-year period were obtained from the Ramathibodi Poison Center Toxic Exposure Surveillance System and retrospectively analyzed.ResultsIn total, 78 cases of krait envenomation were included. Most patients were male (59.0%) and the median age was 28 years. All had minimal local effects. The median duration from the bite to the onset of neurological manifestations was 3 hours (range, 0.5–8 hours). Besides neurological effects, the patients also developed high blood pressure (67.4%), tachycardia (61.7%), hypokalemia (55.3%), and hyponatremia (17.6%). Severe hyponatremia (<120 mEq/L) was noted in four pediatric patients. Other clinical manifestations were bradycardia, abdominal pain, and rhabdomyolysis. The mortality rate was 6.4%, and all deaths occurred from B. candidus bites. Eighty-six percent of patients received antivenom. Most patients (75.6%) were intubated and underwent assisted ventilation for a median of 6 days (range, 1–37 days). The median length of hospital stay was 7 days. Some patients developed complications during hospitalization; the most common was pneumonia. These in-hospital complications were significantly associated with death.ConclusionAlthough krait bites caused only minimal local effects, the mortality rate was still high, particularly from Malayan krait bites. Besides neurological effects, other clinical manifestations were high blood pressure, tachycardia, hypokalemia, and hyponatremia. Thus, vital signs and electrolytes should be frequently and closely monitored in these patients. Apart from antivenom treatment, adequate supportive care including management of complications might help to decrease the mortality rate.

Clinical characteristics and outcome of toxicity from Amanita mushroom poisoning.

ObjectiveTo describe and analyze the clinical characteristics and outcome of amatoxin poisoning cases.MethodsWe performed a retrospective cohort study of amatoxin poisoning cases from Ramathibodi Poison Center Toxic Exposure Surveillance System, from May 2013 to August 2015.ResultsThere were 30 consultations with a total of 55 poisoning cases. Most cases were male and from the north-east region. Hepatitis, acute kidney injury, jaundice, and coagulopathy accounted for 74%, 46.3%, 44.7%, and 52.8% of the cases, respectively. Almost all of the patients were admitted to the hospital, and the median duration of hospital stay was found to be 4 days. Mortality rate was found to be 27.3%. Most patients (73%) received the treatment including multiple-dose activated charcoal (67.5%), intravenous N-acetylcysteine (87.5%), and benzylpenicillin (45%). In 60% of the cases, the treatment was initiated within 24 h after eating mushrooms. Exchange transfusion and liver transplantation were performed in one severe case. However, this patient died eventually. Because intravenous silybinin is not available in Thailand during the study period, 8 patients received oral silymarin instead. All 8 patients had hepatitis and were treated with high dosage of oral silymarin (5 patients with 4.48 g/day, 2 patients with 1.68 g/day, and 1 patient with 1.4 g/day) for a couple of days. One of these patients died as she received treatment very late; she was treated with silymarin at 1.68 g/day dosage. Thus, the fatality in oral silymarin treatment group was 12.5%. We performed the analysis between the dead and survival groups. We found that in hepatitis, initial and maximum serum aspartate transaminase, initial and maximum serum alanine transaminase, and acute kidney injury were significantly different between the two groups.ConclusionAmanita mushroom poisoning caused high fatalities. Serum transaminase and creatinine were the factors associated with death. Treatment with oral high dose silymarin should be investigated further as one of the principal therapies in amatoxin poisoning.

Human exposure to insecticide products containing pyrethrins and piperonyl butoxide (2001–2003)

Pyrethrum, used as an insecticide for centuries, is derived from dried and ground flowers of Chrysanthemum cinerariaefolium. Its current major use is in insecticide products to the control insects in the home and food handling establishments. We investigated human incidents reported through the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS ©) associated with regulated insecticides containing pyrethrins and piperonyl butoxide (PY/PBO) from 2001 to 2003. Special attention was paid to dermal and respiratory effects. Although there are limitations associated with TESS data, we observed that ■ Despite extensive use, incidents with reports of moderate or major adverse effects were relatively rare (717 moderate and 23 major outcomes out of 17,873 calls). ■ Following label-directed use of the products, adverse dermal or respiratory reactions were very rare; (dermal – 17 moderate, 1 major; respiratory – 18 moderate, 0 major). ■ The data suggest that asthmatics and people sensitive to ragweed ( Ambrosia artisifolia) are not unusually sensitive to PY/PBO. In view of their widespread use, the data indicates that PY/PBO products can be used with a relatively low risk of adverse effects. Moreover, the data suggest that they are not likely to cause reactions in people with asthma or allergies.

The outcome of North American pediatric unintentional mushroom ingestions with various decontamination treatments: An analysis of 14 years of TESS data

The optimum empiric decontamination therapy for unintentional pediatric mushroom ingestion is not known. We sought to determine case outcomes for unintentional mushroom ingestions in children by decontamination therapies utilized. The 1992–2005 American Association of Poison Control Centers Toxic Exposure Surveillance System was queried for cases of unintentional acute mushroom ingestions in children age <6 years. Cases were excluded if outcome was unknown, if exposure was coded as unrelated to the symptoms, or if there was co-ingestion of a non-mycoid substance. The treatment subgroups analyzed were ipecac, single-dose activated charcoal, and no gastric decontamination. 82,330 cases met the inclusion criteria with 22,454 cases excluded. There were 16 cases with major effects and no deaths. There were 57,531 cases in the three treatment subgroups. There was a significantly smaller percentage of cases with moderate or major outcomes in the ipecac subgroup compared to the no decontamination subgroup. There was a significantly greater percentage of cases with moderate or major outcomes in the activated charcoal compared to the no decontamination subgroup. If decontamination therapy is being performed, and this data suggests it may not be necessary, syrup of ipecac could still be considered an effective option.

Child-Resistant Closures for Mouthwash

The Poison Prevention and Packaging Act of 1970 mandated that certain potentially hazardous drugs and other products be sold in child-resistant containers (CRCs). The Consumer Product Safety Commission estimates that CRCs for aspirin and oral prescription medicine saved the lives of about 700 children since the requirements went into effect in the 1970s. Under this Act, the Consumer Product Safety Commission issued a rule requiring child-resistant packaging for mouthwashes containing 3 g or more of ethanol per package. The effective date was July 24, 1995, and applied to all applicable products packaged on or after that date. To determine the effectiveness of this 1995 ruling, all American Association of Poison Control Center Toxic Exposure Surveillance System data involving children younger than 6 years who ingested ethanol-containing mouthwash 10 years before the implementation of this ruling, the transition year, and 10 years after were reviewed. Only single-substance exposures were included. Data reviewed included the total number of exposures per pre and post years and the outcome. A total of 61,185 cases met the criteria. There were 18,275 exposures from 1985 through 1994 prerequirement (0.12% of all exposures); 39,376 from 1996 to 2005 postrequirement years (AR) (0.17% of all exposures); and 3,534 cases reported in 1995 (0.17% of all exposures). Definitive outcomes were coded in 62.6% of the prerequirement group and 42.2% of the AR group. Numerous factors affect these results. However, in those cases where definitive outcomes were coded, the AR group has better outcomes.

Pyrethrin and pyrethroid exposures in the United States: A longitudinal analysis of incidents reported to poison centers

Citing the Food Quality Protection Act, the US Environmental Protection Agency (EPA) decided to phase out and eliminate organophosphate insecticide use in residential environments. The phase out process spanned from 2000 to 2005, and it may have resulted in increased consumer use of insecticides containing other active ingredients. This study utilized data from the national Poison Control Center to assess possible changes in exposure incidents involving pyrethrin and pyrethroid insecticides during the phase out of organophosphates from residential uses. We extracted pyrethrin and pyrethroid insecticide exposure data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) annual reports from 2000 to 2005. We examined pyrethrin and pyrethroid incidents by total exposures for each year, and we stratified exposures by age range, reason, number of cases treated in a health care facility, and medical outcome. Cases were examined as a proportion of all insecticide exposures. We calculated the annual incidence rates for exposures involving pyrethrin and pyrethroid insecticides of the population served. Pyrethrin and pyrethroid exposures increased annually in number and as a percentage of all insecticide exposure incidents. The increase in cases was observed for all age categories and exposure reasons. A statistically significant correlation was observed between advancing years (2000-2005) and the number of pyrethrin and pyrethroid incidents (p<.01). While the number of incidents treated in a health care facility increased annually during the study period, the proportion was constant (0.185 +/- 0.012) over the six year period. During the study period, the incidence rate for pyrethrin and pyrethroid exposures increased each year. 44% of all medical outcomes data was recorded, and the majority of outcomes resulted in no symptoms (37%) or minor symptoms (53%). TESS data showed a clear increase in cases involving pyrethrins and pyrethroids. The increase was temporally associated with the phase out of organophosphates from residential uses. In the future, medical toxicologists and poison control center personnel should be prepared to respond to an increasing number of pyrethrin and pyrethroid insecticide exposures.

Organophosphate Exposures in the United States: A Longitudinal Analysis of Incidents Reported to Poison Centers

The implementation of the Food Quality Protection Act of 1996 resulted in a decision by the U.S. Environmental Protection Agency to phase out and eliminate the use of organophosphate insecticides in residential environments. The phase-out and cancellation process began in the year 2000 and was complete in 2005. The purpose of this investigation was to utilize national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases involving organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) for the years 1995 to 2004. The number of organophosphate exposure incidents peaked at 20,135 in 1997, and declined in each subsequent year. A statistically significant decrease was observed in the average annual number of organophosphate exposure incidents when comparing data from the time periods before (1995–1999) and after (2000–2004) the commencement of the phase-out process. The decrease in organophosphate incident cases was observed for all age categories, as well as for the circumstances surrounding the exposure (unintentional and intentional exposure incidents). TESS data showed a significant decrease in incident cases involving organophosphates in association with the phase-out from residential uses. The results of this investigation are consistent with other studies that have reported that regulatory restriction of access to pesticide formulations may have a significant impact on the number of human exposure incidents.

Incidence and Severity of Neurotoxic Effects due to Acute Pesticide Exposure

P-348 Abstract: Carbamates, organophosphates (OPs), organochlorines, pyrethrins and rotenone insecticides are neurotoxic in mammalian systems. The incidence and severity of neurotoxic effects was compared both among these pesticides and between these and other pesticides. The study was conducted based on acute pesticide exposure data from the American Association of Poison Control Center Toxic Exposure Surveillance System (TESS). Severity was determined based on medical outcome, considering the most severe effects - major effect (symptoms were life-threatening or resulted in significant residual disability or disfigurement) and death. Approximately 900,000 single chemical, human, acute pesticide reported exposures from 1993–2001 were analyzed considering 45 neurological and neurologically-mediated effects. Approximately 200,000 acute pesticide reported exposures were due to the pesticides of interest. Of these selected pesticides, OPs accounted for approximately half of all pesticide reported exposures. Acute exposures with OPs resulted in a higher number of reported 45 neurological effects compared to the other neurotoxic pesticides. Fasciculation was relatively the most common effect among OP poisonings compared to all other pesticides. A relative risk of 12.0 was calculated compared to all other pesticides. The risk was slightly lower when restricted to severe medical outcomes. Carbamate poisonings had a ranking of neurological effects similar to OPs but with lower relative risks. Seizures were a relatively more common neurological effect reported for organochlorines (e.g. incidence of multiple seizures relative risk was 13.6; the severe medical outcome relative risk was 6.1), with one of the highest relative risks reported in this study for any pesticide/neurological effect relationship. Bronchospasm was the most common neurological effect reported for pyrethrin (incidence relative risk of 2.6; severe medical outcome relative risk of 5.1). Few cases of neurological effects were recorded for rotenone. While most poisonings (approximately 60%) occurred by age 5, there was not a consistent age dependent trend of a greater incidence and/or severe medical outcome for all studied pesticides at the 0–5 age interval compared to later age intervals. The merging of multiple, disparate data sets and segmenting specific variables for analysis in addition to critically analyzing clinical effects categories was a novel approach of utilizing AAPCC TESS data. Such methodology provides a new and innovative tool to analyze poisoning data that is applicable to pesticides and other toxic agents. The findings and conclusions in this report (presentation) have not been formally disseminated by United States Environmental Protection Agency and should not be construed to represent any Agency determination or policy.

Fatality from Diphenhydramine Monointoxication

As an antihistamine, diphenhydramine (DPH) is well known for its use in allergy treatment. Since its introduction in 1946, it has been marketed under various trade names, the most popular being Benadryl. Three years after its introduction, the first fatality due to DPH toxicity was reported in 1949. To better understand the incidence of fatalities due to DPH monointoxication, we reviewed deaths that were reported from 2 data sources: (1) the English-language literature using PubMed, from 1946 through 2003; and (2) the Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System (ARAAPCCTESS), from 1983 through 2002. The results were then tabulated using age, gender, clinicopathologic findings, and toxicology results. Combined results from both data sets show the following mean (and range) for age and DPH levels: Adult, 35.6 years (18-84) and 19.53 mg/L (0.087-48.5); pediatric, 8.6 years (1.25-17) and 7.4 mg/L (1.3-13.7); infant, 31 weeks (6 weeks-11 months) and 1.53 mg/L (1.1-2.2), respectively. Most deaths were certified as accident or suicide; however, 6 infant homicides were reported. The most common symptoms for all cases were cardiac dysrhythmias, seizure activity, and/or sympathetic pupil responses. The most common autopsy finding was pulmonary congestion.

Excess Fatality From Desipramine in Children and Adolescents

To compare the case fatality rate (CFR) from desipramine ingestion in children and adolescents with that of other tricyclic antidepressants. All mentions of desipramine, amitriptyline, imipramine, nortriptyline, and doxepin in children and adolescents recorded in the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1983 to 2002 were analyzed. The CFR for each drug was defined as the ratio of the number of deaths/number of mentioned exposures. There were 24 fatalities in children younger than 6 years old (desipramine, n=10; amitriptyline, n=7; doxepin, n=3; imipramine, n=3; nortriptyline, n=1) and 144 fatalities in older children and adolescents (desipramine, n=56; amitriptyline, n=30; doxepin, n=16; imipramine, n=31; nortriptyline, n=11). The CFR from desipramine was significantly higher compared with the other tricyclic antidepressants in children younger than 6 years old (chi=36, p<.001) and in older children and adolescents (chi=155, p<.001). The CFR from desipramine exceeded that of amitriptyline, doxepin, imipramine, and nortriptyline by 7- to 8-, 4-, 6- to 12-, and 7- to 10-fold, respectively. The excess CFR from desipramine in children and adolescents and the reports of sudden death in children treated with therapeutic doses call for caution in prescribing desipramine to children and adolescents.

TESS-based dose–response using pediatric clonidine exposures

The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. 3,458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a "taste or lick" (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) microg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P = 0.0000) and Certainty (P = 0.045). TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.

Evaluation of toxicity of topiramate exposures reported to poison centers

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children < or = 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P <0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P <0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.

2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System

Persistent Choreoathetosis in a Fatal Olanzapine Overdose: Drug Kinetics, Neuroimaging, and Neuropathology

Atypical antipsychotics are a relatively new group of medications for the management of psychosis. Currently approved medications of this category include clozapine, risperidone, quetiapine, and olanzapine. Olanzapine was first marketed in 1996 in the United States as an atypical antipsychotic medication similar to clozapine for schizophrenia. By 2002, olanzapine was widely used and in the top 20 drugs by sales (1). Olanzapine belongs to the thienobenzodiazepine drug class and is known to have a high affinity for dopamine D2, D3, and D4 receptors, all five serotonin HT2 receptor subtypes, the 5-HT6 receptor, acetylcholine muscarinic receptors, and α1-adrenergic and histamine H1 receptors (2). The drug is well absorbed from the gut and reaches maximum plasma concentration about 6 hours after an oral dose (3). In plasma, 93% of the drug is bound to serum proteins, especially albumin (3). The drug is extensively eliminated by first-pass metabolism in the liver and has a mean elimination half-life of 30 hours, with a range of 21–54 hours (3). Olanzapine is considered to have a good overall safety profile at therapeutic doses (4). Adverse effects of olanzapine that affect the nervous system include mental status deterioration and extrapyramidal signs and, rarely, delirium, mutism, confusion, aggression, and lethargy that can progress to coma. Seizures, status epilepticus, and hypersalivation occasionally develop (5, 6). Extrapyramidal signs may include dystonia, parkinsonism, akathisia, choreoathetosis, and neuroleptic malignant syndrome (7– 9). Serious systemic complications include diabetes mellitus, tachycardia and supraventricular tachycardia, arrhythmias, and cardiopulmonary arrest (10, 11). Overdoses can lead to deaths. The American Association of Poison Control Centers Toxic Exposure Surveillance System reported the number of deaths associated with olanzapine to be six in 2000 (12), 10 in 2001 (13), and 10 in 2002 (14). Before some of these deaths, concomitant agents were ingested. The majority of deaths occurred within 12 hours of overdose, and the results of autopsies, when available, were often unremarkable (15–17). We report here a patient who survived the early phase of an overdose. He then developed coma with persistent choreoathetosis and hypersalivation, and neuroimaging and autopsy findings suggested damage to the basal ganglia.

Evaluation of lamotrigine toxicity reported to poison centers.

Lamotrigine is an antiepileptic drug for the treatment of partial and generalized seizures as well as bipolar disorder. Limited published information exists describing the clinical effects of lamotrigine overdose. To examine the toxicity of exposures to lamotrigine utilizing national poison center data. Data on single-substance exposures to lamotrigine reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System in 2000 and 2001 were retrospectively analyzed. There were 493 cases that met the inclusion criteria. The majority of exposures occurred within the age groups 20-59 years old (n = 198, 40.2%), followed by </=4 years old (n = 173, 35.1%). Overall, the majority of patients (52.1%) exposed to lamotrigine in overdose experienced no toxic clinical effects. The most common clinical effects reported in overdose were drowsiness/lethargy (20.9%), vomiting (11%), nausea (5.1%), ataxia (4.9%), dizziness/vertigo (4.5%), and tachycardia (4.3%). Major clinical effects included coma (n = 6), seizures (n = 8), and respiratory depression (n = 3). Medical outcome was reported as minor in 150 (30.4%), moderate in 73 (14.8%), and major in 13 (2.6%) cases. There were no deaths. These data demonstrate that the majority of patients exposed to lamotrigine in overdose experienced minor or no clinical effects. Although rare, serious effects can also occur.

Are 1 or 2 dangerous? Clozapine and olanzapine exposure in toddlers

Clozapine (Clozaril ®) and olanzapine (Zyprexa ®) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.