webPOISONCONTROL: can poison control be automated?

BACKGROUND: A free webPOISONCONTROL app allows the public to determine the appropriate triage of poison ingestions without calling poison control. If accepted and safe, this alternative expands access to reliable poison control services to those who prefer the Internet over the telephone. This study assesses feasibility, safety, and user-acceptance of automated online triage of asymptomatic, nonsuicidal poison ingestion cases. METHODS: The user provides substance name, amount, age, and weight in an automated online tool or downloadable app, and is given a specific triage recommendation to stay home, go to the emergency department, or call poison control for further guidance. Safety was determined by assessing outcomes of consecutive home-triaged cases with follow-up and by confirming the correct application of algorithms. Case completion times and user perceptions of speed and ease of use were measures of user-acceptance. RESULTS: Of 9256 cases, 73.3% were triaged to home, 2.1% to an emergency department, and 24.5% directed to call poison control. Children younger than 6 years were involved in 75.2% of cases. Automated follow-up was done in 31.2% of home-triaged cases; 82.3% of these had no effect. No major or fatal outcomes were reported. More than 91% of survey respondents found the tool quick and easy to use. Median case completion time was 4.1 minutes. CONCLUSION: webPOISONCONTROL augments traditional poison control services by providing automated, accurate online access to case-specific triage and first aid guidance for poison ingestions. It is safe, quick, and easy to use.

Risk-based strategy for outpatient pharmacy practice: Focus on opioids.

OBJECTIVES: To highlight the limitations of community pharmacy practice and to propose a system change by implementing a risk-assessment method and management strategy for opioids in this arena. DATA SOURCES: Selected by the author. SUMMARY: Numerous studies show that the U.S. health care system is subject to a high rate of drug misadventures involving primarily low therapeutic index drugs, especially opioids. Currently proposed approaches to managing opioids focus on access control, but without a broader consideration of patient-use problems that lead to morbidity and mortality. While pharmacists are well-trained health professionals, their primary focus has been on drug distribution rather than proper use. This article highlights the limitations in contemporary community pharmacy practice that likely contribute to the problem of opioid misuse and resultant morbidity. CONCLUSION: A new model of practice is proposed whereby the most dangerous agents such as opioids are preidentified for a more formalized risk-based strategy focused upon optimal patient education and required follow-up.

Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients.

CONTEXT: A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations. METHODS: A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT. RESULTS: The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in "body packers." However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. CONCLUSION: WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.

An analysis of energy-drink toxicity in the National Poison Data System.

CONTEXT: Small studies have associated energy drinks-beverages that typically contain high concentrations of caffeine and other stimulants-with serious adverse health events. OBJECTIVE: To assess the incidence and outcomes of toxic exposures to caffeine-containing energy drinks, including caffeinated alcoholic energy drinks, and to evaluate the effect of regulatory actions and educational initiatives on the rates of energy drink exposures. METHODS: We analyzed all unique cases of energy drink exposures reported to the US National Poison Data System (NPDS) between October 1, 2010 and September 30, 2011. We analyzed only exposures to caffeine-containing energy drinks consumed as a single product ingestion and categorized them as caffeine-containing non-alcoholic, alcoholic, or "unknown" for those with unknown formulations. Non-alcoholic energy drinks were further classified as those containing caffeine from a single source and those containing multiple stimulant additives, such as guarana or yerba mate. The data were analyzed for the demographics and outcomes of exposures (unknown data were not included in the denominator for percentages). The rates of change of energy drink-related calls to poison centers were analyzed before and after major regulatory events. RESULTS: Of 2.3 million calls to the NPDS, 4854 (0.2%) were energy drink-related. The 3192 (65.8%) cases involving energy drinks with unknown additives were excluded. Of 1480 non-alcoholic energy drink cases, 50.7% were children < 6 years old; 76.7% were unintentional; and 60.8% were males. The incidence of moderate to major adverse effects of energy drink-related toxicity was 15.2% and 39.3% for non-alcoholic and alcoholic energy drinks, respectively. Major adverse effects consisted of three cases of seizure, two of non-ventricular dysrhythmia, one ventricular dysrhythmia, and one tachypnea. Of the 182 caffeinated alcoholic energy drink cases, 68.2% were < 20 years old; 76.7% were referred to a health care facility. Educational and legislative initiatives to enhance understanding of the health consequences of energy drink consumption were significantly associated with a decreased rate of energy drink-related cases (p = 0.036). CONCLUSIONS: About half the cases of energy drink-related toxicity involved unintentional exposures by children < 6 years old. Educational campaigns and legal restrictions on the sale of energy drinks were associated with decreasing calls to poison centers for energy drink toxicity and are encouraged.

Comparison of citalopram and other selective serotonin reuptake inhibitor ingestions in children.

CONTEXT: In adults, citalopram is more likely to cause seizures and ECG changes than other selective serotonin reuptake inhibitors (SSRIs). Data in children are lacking, yet the 2007 American Association of Poison Control Centers out-of-hospital citalopram consensus guideline mirrors the guideline for other SSRIs. OBJECTIVE: To compare the clinical effects and hazard index of citalopram with other SSRIs in pediatric ingestions. METHODS: An 11-year retrospective analysis of national poison center data was conducted. Acute, known-type SSRI ingestions in children younger than 6 years with known outcome were included. Clinical effects and hazard index (number of major or fatal outcomes/1000 SSRI ingestions) were compared. Citalopram dose-response was evaluated. RESULTS: The 35 296 included cases by SSRI type were citalopram (3747), escitalopram (4815), fluoxetine (5946), fluvoxamine (273), paroxetine (7157), and sertraline (13 358). The overall hazard index was 0.340. The hazard index for citalopram (0.801) was 2.8-fold higher than for non-citalopram SSRIs (0.285). Comparing seizures (single or multiple discrete) and cardiac effects (conduction disturbances, other ECG changes or other dysrhythmia) of citalopram with the other SSRIs, pediatric citalopram ingestions were more likely to develop seizures (5 of 3747 [0.13%] vs. 10 of 31 549 [0.03%], OR = 4.2; 1.4-12.3) and cardiac toxicity (9 of 3747 [0.24%] vs. 25 of 31 549 [0.08%], OR = 3.0; 1.4-6.5). Clinical effects occurring more frequently with other SSRIs included tachycardia (p = 0.0236), oral irritation (p = 0.0412), vomiting (p = 0.0036), agitation/irritability (p = 0.0104), and hyperthermia (p = 0.0314). There was a dose response only for single or multiple discrete seizures, mydriasis and clinically significant responses (a predetermined subset of CNS and cardiopulmonary clinical effects). Meaningful triage thresholds for citalopram could not be determined due to the low frequency of significant clinical effects. CONCLUSION: Children develop minimal toxicity with SSRI ingestions. Seizures and ECG changes, while uncommon, occur more frequently with citalopram. Doses associated with significant outcomes suggest that the triage guideline for citalopram does not need to be modified.

Interactive voice response systems for medication identification requests: poison or cure?

Interactive voice response systems (IVR) have traditionally been used by banking and credit card industries to rapidly process information requests for their customers. Today IVR technology is being used in clinical medicine to randomize patients in clinical studies, to collect patient data, and to follow-up on recently discharged patients. Use of IVR systems by poison centers is relatively new. This commentary explores the advantages and disadvantages of applying IVR technology to the medication identification requests in poison centers.

Cause of death conundrum with methadone use: a case report.

Deaths caused by a methadone intoxication or overdose are becoming more frequent. We report a case involving a patient who had extremely high methadone blood concentrations but whose cause of death may have been unrelated to the drug. A 51-year-old woman was found deceased in bed by her daughter. At the scene were numerous bottles of methadone, with the chronic dosage of 240 mg 3 times a day. There was no history of prior suicide attempts, there were no reports of suicidal ideation having been voiced and there was no suicide note. At autopsy, there were no pills found in the stomach. Microscopic tissue examination revealed lobar pneumonia of the right lower lobe. Postmortem lung cultures grew out Streptococcus pneumoniae. Femoral blood contained methadone, 5.7 mg/L; EDDP, 2.1 mg/L; oxycodone, 0.017 mg/L; doxylamine, 0.022 mg/L; and ethanol, 13.0 mg/dL. The postmortem methadone concentration was consistent with her known dose, plausible pharmacokinetics and conditions of discovery. Various causes of death, such as a methadone-related arrhythmia from QTc prolongation or the contribution of methadone to the development of the pneumonia, cannot be ruled out and may well have caused or contributed to death, but the pneumonia was felt to be a competent cause of death. Ultimately, the most likely cause(s) of death, is a decision left to the individual medical examiner. This case is illustrative of the growing number of similar cases facing forensic pathologists. The cause of death cannot be solely based on drug concentrations and it may not be possible to come to a conclusion as to "the" cause of death and the forensic pathologist must be content with "a" cause of death.

Diphenhydramine dose-response: a novel approach to determine triage thresholds.

CONTEXT: It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. METHODS: We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves. RESULTS: There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5). CONCLUSION: Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.

Determinants of U.S. poison center utilization.

CONTEXT: High poison center utilization has been associated with decreased emergency department usage and hospitalization rates. However, utilization requires awareness of the poison center. Penetrance, defined as the number of human poison exposures reported to a poison center per 1,000 population, has been used as a marker of poison center awareness. OBJECTIVES: To identify factors that influence poison center penetrance to optimize the life- and cost-saving benefits of poison control centers. METHODS: Human poison exposures that were reported to the National Poison Data System in 2001 were analyzed to identify and rank factors affecting poison center penetrance. RESULTS: Overall penetrance correlated with pediatric penetrance (R(2) = 0.75, p < 0.01). As pediatric penetrance increased, there was a significant decline in the percent of children reported to a poison center that were already in or en route to a healthcare facility at the time of the call to the poison center (R(2) = 0.41, p < 0.01). Larger poison center service populations were associated with lower penetrance (R(2) = 0.23, p < 0.01). Inverse predictors of penetrance included inability to speak English well, Black/African American race, and distance from the poison center (multiple regression). Positive predictors included the percentage of the population younger than 5 years, the percentage of the adult population with a bachelor's degree, poison center certification, poison center educator FTEs (full time equivalents), Asian population percentage, and population density. DISCUSSION: The inverse correlation between pediatric penetrance and healthcare facility utilization supports prior observations of excessive healthcare utilization when a poison center is not called. Since race, language and distance are barriers to poison center utilization, and since healthcare utilization increases when poison center penetrance declines, low penetrance suggests a lack of awareness of the poison center rather than a low incidence of poisonings. CONCLUSION: Strategies to raise penetrance should be informed by an understanding of the barriers to utilization - language, Black/African American race, distance from the poison center, poverty, and lower education levels.

Amlodipine toxicity in children less than 6 years of age: a dose-response analysis using national poison data system data.

BACKGROUND: Amlodipine is a long-acting calcium channel blocker capable of producing hypotension and dysrhythmia in overdose. The toxic doses of amlodipine in children are unclear. OBJECTIVES: The purposes of this study were to describe amlodipine poisoning in children and to determine whether a dose-response relationship could be detected in this population using standardized call data from United States (US) poison centers. PATIENTS AND METHODS: 1251 amlodipine-only ingestions in children < 6 years of age were reviewed. Cases with doses coded as "Exact" or "Estimated" and with dose, age, and medical outcome were analyzed (n = 678). Ingestions reported as a "taste or lick" (n = 53) were included as a dose of 1/10 of the dosage form involved. A clinically important response was defined as bradycardia, hypotension, dysrhythmia, conduction disturbance, or hyperglycemia. The risk of such responses was examined over four dosage intervals (< 2.5 mg, 2.5-5 mg, 5.1-10 mg, and > 10 mg). RESULTS: The median estimated dose ingested was 5 mg (range 0.25-200 mg). Clinically important responses developed in 27 patients (3.98%), and the prevalence of such response significantly increased from 0% for the lowest to 11.1% for the highest dose interval (p = 0.001). The smallest dose to produce a clinically important response was 2.5 mg (0.15 mg/kg). Children who ingested > 10 mg were 4.4 times more likely to develop clinically important responses than those ingesting < or = 5 mg. CONCLUSION: Hypotension may occur in children with amlodipine doses as low as 2.5 mg. The National Poison Data System might provide useful insights regarding dose-response.

Toxicity from a clonidine suspension.

BACKGROUND: Clonidine is frequently prescribed to children. Clonidine overdose in children has resulted in major clinical effects and deaths. CASE REPORT: A 3.5-year-old male with a history of a seizure disorder and night terrors presented following difficulty walking, excessive sleeping, agitation when awake, and possible seizure activity. Chronic medications were valproic acid (VPA) and clonidine. On presentation, he alternated between poor responsiveness and agitation, with initial vitals: blood pressure, BP 144/76 mmHg; heart rate, 65 bpm; respiratory rate, 18 bpm; temperature 99.5 degrees F; and pulse oximetry 96% on room air. VPA level was 35 microg/mL. A toxicology consult the next day noted a dry mouth, 2-mm pupils, intermittent gasping, and central nervous system (CNS) depression, with a diagnostic impression of clonidine overdose. The caregiver had been giving 1 mL (0.1 mg) qd of a pharmacy-compounded clonidine suspension by a provided syringe. The pharmacy procedure record agreed with the physicians order. The amount dispensed was a 30-day supply but the bottle was empty on day 19, leading us to suspect a possible accelerated dosing error. The concentration in the bottle thus could not be confirmed. The child slowly returned to his baseline state over 48 hours. A serum clonidine level drawn approximately 18 hours after his last dose later returned at 300 ng/mL (reference range = 0.5-4.5 ng/mL). CASE DISCUSSION: Compounding and liquid dosing errors are common in children and may result in massive overdoses. There was an accelerated dosing error, but whether a compounding or suspension error or even an acute overdose occurred as well is unknown. CONCLUSION: Particular care should be taken with medications that have low therapeutic indices, that are extemporaneously compounded, and are prepared as liquids, where medication errors are more likely.

The impact of bittering agents on pediatric ingestions of antifreeze.

BACKGROUND: Legislation requiring bittering of antifreeze enables assessment of the impact on frequency, volume, and severity of pediatric antifreeze ingestions. METHODS: US poison control data for antifreeze ingestions in children younger than 5 years were analyzed comparing 232 ingestions occurring in states after enactment of bittering requirements with 6218 cases occurring in states (or at times) where bittering was not required. RESULTS: The frequency of pediatric antifreeze ingestions was unchanged after implementation of bittering in Oregon and California. The medical outcome distribution, median volume ingested, and observed clinical effects were no different in bittered compared with nonbittered groups. Likewise, the rates of hospital admission, critical care treatment, and use of alkalinization, hemodialysis, or intubation showed no differences with bittering. CONCLUSION: Despite the appealing logic of limiting the ingested volume and thereby the severity of poisonings by adding aversive agents, and despite promising results in volunteer studies, bittering agents do not decrease the frequency or severity of pediatric antifreeze poisonings. The addition of bittering agents to household products cannot be justified based on actual poisoning data.

AAPCC database characterization of native U.S. venomous snake exposures, 2001-2005.

BACKGROUND: Differences in victim demographics, clinical effects, managements, and outcomes among native viperid (rattlesnake, copperhead, and cottonmouth) and elapid (coral snake) species have not been systematically characterized. METHODS: The database of the American Association of Poison Control Centers from 2001 through 2005 was analyzed. RESULTS: Between 2001 and 2005, there were 23,676 human exposures (average = 4,735/year) to native venomous snakes in the United States reported to U.S. poison centers in all states except Hawaii: 98% were to viperid snakes and 2% to elapids. Overall, 77% of victims were male, 70% were adults >20 years, and 12% were aged less than 10 years. Sixty-five cases involved pregnant women, with rattlesnake bites resulting in moderate or greater effects in over 70%. The overall hospital admission rate was 53%. Outcomes were generally more severe with rattlesnake and copperhead envenomations and in children <6 years of age. The fatality rate of reported cases was 0.06%. CONCLUSIONS: Native U.S. venomous snakebite results in considerable morbidity and mortality. Rattlesnake and copperhead envenomations, and those in children <6 years of age, produce the most severe outcomes, but coral snakebites result in similar hospital admission rates.

The impact of bittering agents on suicidal ingestions of antifreeze.

BACKGROUND: Legislation requiring the addition of bittering agents to antifreeze enables assessment of the impact on frequency, volume and severity of suicidal antifreeze ingestions. METHODS: U.S. poison control data were analyzed comparing 130 suicidal antifreeze ingestions occurring in two states after enactment of bittering requirements with 3,493 cases occurring in states (or at times) where bittering was not required. RESULTS: The frequency of suicidal antifreeze ingestions was unchanged after implementation of bittering. The volume implicated, medical outcome distribution, and use of antidotes, hemodialysis, intubation, or critical care, showed no significant difference between bittered and non-bittered groups. Bittering was not a significant contributor (positively or negatively) in predicting lethal or life-threatening medical outcomes. CONCLUSION: The addition of bittering agents to antifreeze for the purpose of limiting the frequency or severity of suicidal ingestions could not be justified using U.S. poison control data.

Prospective observational multi-poison center study of ziprasidone exposures.

BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (>0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.

TESS-based dose-response using pediatric clonidine exposures.

OBJECTIVE: 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. METHODS: 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). RESULTS: The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P = 0.0000) and Certainty (P = 0.045). CONCLUSION: TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.

Do poison center guidelines adversely affect patient outcomes as triage referral values increase?

BACKGROUND: The purpose of this study was to determine whether patient outcomes were adversely affected as healthcare referral values increased for two common poisonings: acute, unintentional acetaminophen (APAP) poisonings and acute, unintentional iron (Fe) poisonings. We hypothesized that symptom rates would increase with high referral values. METHODS: Qualifying 1997 exposures were separated by substance (APAP or Fe) and then further stratified into three healthcare referral value ranges. Symptomatic and asymptomatic patients were totaled for each stratum. Expected vs. observed distributions of symptomatic and asymptomatic patients across triage referral strata for a given substance and treatment location were compared using chi-square test for independence. The Wilcoxon-Mann-Whitney test was used to compare the distribution of patients across referral strata for home vs. healthcare facility locations for a specific substance. RESULTS: There were no statistically significant differences in the distribution of symptomatic patients within referral value strata for APAP or for Fe. There was also no difference in distribution of symptomatic patients across strata when comparing home vs. healthcare facility for APAP and Fe. CONCLUSION: Referral values as high as 201 mg/kg for APAP and 61 mg/kg for Fe do not appear to adversely affect patient outcomes.