A.A. Kreshak

A Poison Center's Ten-year Experience with Flumazenil Administration to Acutely Poisoned Adults

BACKGROUND The frequency of seizures among acutely poisoned adults who are administered flumazenil has not been well established. STUDY OBJECTIVE The objectives of the study were: to determine the frequency of seizures among acutely poisoned adults administered flumazenil; to identify factors associated with seizures; and to determine the mental status of subjects before and after administration of flumazenil. METHODS This study was a historical case series of acutely poisoned adults reported to a poison control system from 1999 to 2008. Included cases were those involving administration of flumazenil to subjects who were ≥ 18 years of age. Both genders were included. Variables collected included: presence of seizure or death, exposure to a pro-convulsant drug, and mental status before and after flumazenil administration. RESULTS Over the 10-year period studied, 904 cases were identified that met inclusion criteria. Thirteen subjects (1.4%) developed seizures after flumazenil was administered. One death occurred. There were 293 subjects exposed to a pro-convulsant drug, and 8 of these had seizures after flumazenil administration. Development of seizures after flumazenil administration was significantly associated with exposure to a pro-convulsant drug (odds ratio 3.41; 95% confidence interval 1.13-10.72). Mental status before and after flumazenil administration was available for 546 subjects (60.3%). Of these, 291 (53.3%) became awake after administration of flumazenil. CONCLUSIONS Flumazenil administration to acutely poisoned adults resulted in a low frequency of seizures and death. Development of seizures was associated with exposure to a pro-convulsant drug. More than half of the subjects for whom mental status was recorded became awake after receiving flumazenil.

Flumazenil administration in poisoned pediatric patients.

Objective The goal of this retrospective cohort study of pediatric patients exposed to flumazenil was to identify the frequency of seizures. Methods Included patient were those aged 12 years or younger who received flumazenil, who had evidence of clinical poisoning as defined by an altered mental status, and who were reported to the California Poison Control System for the period 1999 to 2008. Data variables were age, sex, seizure, death, acute exposure to a benzodiazepine, drugs of exposure, long-term use of benzodiazepines, history of a seizure disorder, mental status before flumazenil administration, and poison center recommendation of flumazenil (yes/no). Results Eighty-three patients were included. Forty-eight (58%) of this subset were female. Median age was 2 years (range, 3 months–12 years). Seventy (84%) patients were younger than 5 years. Of the 83 patients, 68 (82%) were allegedly exposed to a benzodiazepine; whereas, 12 (15%) had been allegedly exposed to a proconvulsant drug. No flumazenil-related seizures occurred (0% with 95% confidence interval, 0%–4%). The California Poison Control System recommended flumazenil use in 60 (72%) of the 83 cases, and 48 of these had been allegedly exposed to a benzodiazepine. Conclusions No flumazenil-associated seizures occurred among allegedly benzodiazepine- and non–benzodiazepine-poisoned pediatric patients aged 12 years or younger.

Transient vision loss in a patient with metformin-associated lactic acidosis.

Metformin-associated lactic acidosis (MALA) can occur when renal function is impaired and metformin accumulates in the body. Symptoms of MALA are varied and have rarely included vision loss. The objective of the study was to describe a case of MALA-associated vision loss. A 67-yearold woman presented to an emergency department (ED) with a complaint of acute vision loss. She was taking metformin for treatment of type 2 diabetes mellitus. In the ED, the patient had a temperature of 32.3°C (90.1°F), a heart rate of 55 beats per minute, a blood pressure of 117/94 mmHg, and respiratory rate of 34 breaths per minute, with a pulse oximeter reading of 98% on room air. On neurologic examination, she was awake and alert and was answering questions. She had no visual acuity, visual fields were not intact, her fundoscopic examination result was unremarkable, and her pupils were midsized and slow to react. Laboratory evaluation revealed a severe lactic acidosis (pH 6.65; lactate, 19.9 mmol/L). Creatinine concentration was 7.0 mg/dL (baseline creatinine, 1.3 mg/dL). Her metformin concentration was 28 μg/mL. Methanol and formic acid concentrations were negative. Result of her head computed tomographic scan was unremarkable. She underwent dialysis and had resolution of her metabolic acidosis with full return of her vision. This patient experienced transient vision loss associated with severe acidosis due to metformin. Treatment of the acidosis was effective in restoring vision in this patient. Metformin, a biguanide oral antihyperglycemic, was approved for use in the United States in 1992 for treatment of type 2 diabetes mellitus. Since its introduction, metformin-associated lactic acidosis (MALA) has become a wellrecognized adverse event. This case describes the occurrence of MALA-associated vision loss. A 67-year-old woman presented to the emergency department (ED) complaining of acute painless bilateral vision loss. The patients vision loss occurred over the course ☆ This work was presented in abstract form at the North American Congress of Clinical Toxicology in September 2009. 0735-6757/

A descriptive regional study of drug and alcohol use in pregnant women using results from urine drug testing by liquid chromatography-tandem mass spectrometry

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Crotaline Fab Antivenom Reverses Platelet Dysfunction Induced by Crotalus scutulatus Venom: An In Vitro Study

ABSTRACT Background: Patterns of drug use during pregnancy may be changing. Identifying changes in pregnant women’s drug use may help to target prevention and treatment. Objective: To determine the regional prevalence of drug and alcohol use among pregnant women in Southern California. Methods: This was a prospective, descriptive study conducted at a university health system’s urban and suburban ambulatory obstetric offices. Included were pregnant women of all ages and trimesters. Excluded were non-pregnant women and women who had previously presented for an obstetric appointment during the data collection time period. Women provided a urine sample as part of routine care. Liquid chromatography-tandem mass spectrometry analysis of urine was performed for detection of a pre-selected sample of drugs and for alcohol. Descriptive statistics were performed. Results: A total of 295 urine samples were included. All trimesters were represented. A total of 14.2% of urine samples were positive for at least one of the tested drugs or alcohol. Alcohol was detected in 6% of the urine samples and was the most frequently identified substance. Prescription opioid analgesics (3.7% detection rate) and marijuana (4% detection rate) were the other most frequently detected substances. Conclusions: Compared with older reports, our detection rates of prescription opioid analgesics were increased while rates of urinary alcohol detection were relatively unchanged, and detection rates of marijuana were decreased. Provider awareness of these substance detection rates may facilitate the identification of patients using these substances during pregnancy and ultimately help promote potential prevention and treatment.

A Retrospective Poison Center Review of Varenicline-Exposed Patients

BACKGROUND Patients sustaining rattlesnake envenomation often develop thrombocytopenia, the etiology of which is not clear. Laboratory studies have demonstrated that venom from several species, including the Mojave rattlesnake (Crotalus scutulatus scutulatus), can inhibit platelet aggregation. In humans, administration of crotaline Fab antivenom has been shown to result in transient improvement of platelet levels; however, it is not known whether platelet aggregation also improves after antivenom administration. OBJECTIVES The objective was to determine the effect of C. scutulatus venom on platelet aggregation in vitro in the presence and absence of crotaline Fab antivenom. METHODS Blood was obtained from four healthy male adult volunteers not currently using aspirin, nonsteroidal anti-inflammatory drugs, or other platelet-inhibiting agents. C. scutulatus venom from a single snake with known type B (hemorrhagic) activity was obtained from the National Natural Toxins Research Center. Measurement of platelet aggregation by an aggregometer was performed using five standard concentrations of epinephrine (a known platelet aggregator) on platelet-rich plasma over time, and a mean area under the curve (AUC) was calculated. Five different sample groups were measured: 1) blood alone, 2) blood + C. scutulatus venom (0.3 mg/mL), 3) blood + crotaline Fab antivenom (100 mg/mL), 4) blood + venom + antivenom (100 mg/mL), and 5) blood + venom + antivenom (4 mg/mL). Standard errors of the mean (SEM) were calculated for each group, and paired t-tests were used to measure differences between groups. RESULTS Antivenom administration by itself (group 2) did not significantly affect platelet aggregation compared to baseline (103.8%, SEM ± 3.4%, p = 0.47). Administration of venom (group 3) decreased platelet aggregation (72.0%, SEM ± 8.5%, p < 0.05). Concentrated antivenom administration in the presence of venom (group 4) normalized platelet aggregation (101.4%, SEM ± 6.8%) and in the presence of diluted antivenom (group 5) significantly increased aggregation (133.9%, SEM ± 9.0%; p < 0.05 for both groups when compared to the venom-only group). To further assess the effects of the venom and antivenom, each was run independently in platelet-rich plasma without epinephrine; neither was found to significantly alter platelet aggregation in the absence of epinephrine. CONCLUSIONS Crotaline Fab antivenom improved platelet aggregation in an in vitro model of platelet dysfunction induced by venom from C. scutulatus. It is unclear at this time whether this improvement in platelet dysfunction translates into improved clinical outcomes in envenomated patients.

Effect of a Computerized Alert on Emergency Department Hepatitis A Vaccination in Homeless Patients During a Large Regional Outbreak

Background: Varenicline was approved by the Food and Drug Administration (FDA) as a prescription smoking cessation aid in May 2006. Varenicline is both a partial nicotine agonist and an antagonist. Recent reports by the Institute of Safe Medication Practices identified safety problems associated with varenicline use, and the FDA recently issued a boxed warning. These safety concerns regarding varenicline use prompted this study. Objective: To characterize varenicline-exposed patients as reported to a poison control system. Methods: We performed a retrospective search of the California Poison Control System electronic database from August 2006 through August 2008, using the term varenicline or Chantix. Cases matching these results were reviewed. All ages were included. Excluded were patients with coingestants and unknown outcomes. Clinical parameters and medical outcomes were extracted from the database. Results: Thirty-six cases met inclusion criteria and 17 cases were excluded, Ten cases involved nonpediatric patients; 9 cases involved patients less than 6 years old, which were defined as pediatric patients. The median duration of poison center follow-up for pediatric patients was 253 minutes; median duration of follow-up for nonpediatric patients with unintentional exposures was 28.5 minutes. The majority of exposures were unintentional and included all the pediatric patients and 6 nonpediatric patients who had unintentional medication errors, Gastrointestinal and neuropsychiatric adverse events were most frequently reported. The majority of these patients were managed at home. Among those evaluated at a healthcare facility, only 1 pediatric patient was admitted. Of the remaining patients, 1 nonpediatric patient reported a deliberate exposure and 3 nonpediatric patients experienced adverse effects at therapeutic doses. Median duration of follow-up for these patients was 308 minutes. Conclusions: Patients exposed to varenicline in our study had favorable outcomes. Gastrointestinal and neuropsychiatric effects were the most commonly reported adverse events. A dose-response relationship could not be determined and triage criteria to a healthcare facility remain undetermined.

A 3-Year-Old Boy with Fever and Oral Lesions

BACKGROUND While the overall incidence of hepatitis A has declined markedly since the introduction of a vaccine, sporadic cases and outbreaks of the disease continue to occur. OBJECTIVE Our aim was to evaluate the effectiveness of an electronic health record (EHR) provider alert as part of an outbreak-control vaccination program implemented in the emergency department (ED). METHODS We conducted a retrospective study assessing the impact of a Best Practice Alert (BPA) built into an EHR to prompt providers when a patient was homeless to consider hepatitis A vaccination in the ED. Data were collected over three 6-month time periods: a historical control period, a pre-intervention period, and an intervention period. RESULTS There were no vaccinations given in the ED in the historical period, which increased to 465 after the implementation of the BPA. During the implementation period, there were 1,482 visits identified among 1,131 patients that met the inclusion criteria. Of these, there were 1,147 (77.5%) visits where the patient either received the vaccine in the ED, had already received the vaccine, or it was not indicated due to the current medical issue. There were also 333 (22.5%) visits where the BPA was active for potential vaccination eligibility, but did not receive it in the ED. CONCLUSIONS We leveraged an informatics tool developed within our EHR to identify high-risk patients and remind providers of the availability of vaccination in the ED. Using these tools enabled providers to increase vaccination efforts within our ED to help control the community-wide outbreak.