Gary S. Wasserman

TAC use and absorption of cocaine in a pediatric emergency department.

The topical anesthetic TAC (tetracaine 0.5%, adrenaline 0.05%, cocaine 11.8%) has been reported to be effective in pain control for local procedures. However, it has the potential for cocaine toxicity by absorption through an open wound. A study was undertaken to assess the systemic absorption of cocaine and its metabolites when TAC is used as a local anesthetic. Fifty-one children, 1 to 14 years of age, were enrolled in the study. Plasma for cocaine and/or its metabolite levels was available from 46 children and obtained 20 to 40 minutes after the topical anesthetic was applied. No plasma sample had detectable parent cocaine levels; however, 26 (56.5%) had cocaine metabolite levels. Ecgonine methylester levels were detected in plasma from six children and ranged from 59 to 985 ng/mL. Benzoylecgonine levels were detected in none of 19 specimens not preserved with sodium fluoride, and in 23 of 27 specimens to which sodium fluoride had been added. Benzoylecgonine levels ranged from 40 to more than 600 ng/mL. No clinical sign of cocaine toxicity was observed in any child.

Cytokines and Toxicity in Acetaminophen Overdose

Several cytokines have been reported to have hepatoprotective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme‐linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N‐acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity.

Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors.

OBJECTIVE This study was performed to determine the doses of midazolam used for sedation during procedures in children, and the frequency of adverse events. METHODS We performed a retrospective analysis of data collected for a prospective study of flumazenil in children who had received midazolam for a procedure (n = 91, 1-17 years). RESULTS Practitioners used a wide range of total midazolam doses (0.03-0.6 mg/kg); mean doses ranged from 0.09 +/- 0.06 mg/kg in adolescents to 0.26 +/- 0.13 mg/kg in toddlers (P < 0.001). Opioids were also used in 84% of patients. Twenty-six percent of children with normal lungs, most of whom had received relatively high opioid doses, developed decreased oxygen saturation (as low as 65%) after sedation. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). CONCLUSIONS The frequent choice of midazolam, usually combined with an opioid, indicates its wide acceptance. Midazolam doses were inversely related to age. The presence of vomiting, airway obstruction, and decreased oxygen saturation underlines the importance of appropriate personnel, equipment, and monitors during sedation.

24-Hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study

Introduction. The complementary and alternative medicine practice of prescribing chelators to children with autism is based on the premise that the chronic symptoms of autism can be ameliorated by reducing heavy metal body burden. However, there has not been definitive evidence, published to date, to support the assertion that children with autism are at increased risk of an excess chelatable body burden of heavy metals. The oral chelator meso-2,3-dimercaptosuccinic acid (DMSA) can be used diagnostically to mobilize heavy metals from extravascular pools, enhancing the identification of individuals who have a chelatable body burden. Methods. Seventeen children with autism and five typically developing children were enrolled in a pilot study to test for chelatable body burden of Arsenic (As), Cadmium (Cd), Lead (Pb), and Mercury (Hg). Evaluation included a questionnaire regarding potential exposure to heavy metals, diet restrictions, a baseline 24-hour urine collection, and a DMSA-provoked urine collection. Urine collections were sent for As, Cd, Pb, and Hg quantification by Inductively Coupled Plasma-Mass Spectrometry. Unprovoked reference ranges were used in the interpretation of all collections. Results. Fifteen autistic children and four typically developing children completed the study. Three autistic subjects excreted one metal in greater quantity during the provoked excretion than baseline. Two of these were very close to the limit of detection. In the third case, the provoked excretion of mercury was between the upper limit of normal and lower limit of the potentially toxic reference range. Fish was removed from this childs diet for greater than one month, and the provoked excretion test repeated. The repeat excretion of mercury was within the normal range. Conclusion. In the absence a proven novel mode of heavy metal toxicity, the proportion of autistic participants in this study whose DMSA provoked excretion results demonstrate an excess chelatable body burden of As, Cd, Pb, or Hg is zero. The confidence interval for this proportion is 0–22%.

Measurement of Acetaminophen‐Protein Adducts in Children and Adolescents with Acetaminophen Overdoses

Acetaminophen‐protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen‐induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen‐protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time ofrou‐ tine blood sampling for clinical monitoring. Six subjects developed “severe” hepatotoxicity (transaminase elevation > 1000IU/L), and 6 subjects had transaminase elevation of 100 to 1000 IU/L. Acetaminophen‐protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6000 IU/L) and high riskforthe development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen‐protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury.

Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents

Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin‐associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity.

Chloroquine poisoning in a child

Chloroquine poisoning in children, although infrequent, is extremely dangerous because of the narrow margin between therapeutic and toxic doses. Children clinically present with apnea, seizures, and cardiac arrhythmias. We present the case of a 12-month-old infant, the second-youngest patient reported in the US literature to die from chloroquine poisoning. A serum level of 4.4 mg/L (13.64 mumol/L) was obtained after the infant ingested only one tablet (300 mg). This establishes a new minimal lethal dose/blood level for children. Although some pediatric and adult pharmacokinetic and clinical similarities exist, the outcome is different. Pediatric mortality is 80%, whereas adult mortality is only 10%. Pediatric ingestion cases are primarily unintentional, and most adult cases are suicide attempts. Current treatment in adults includes a protocol of diazepam and epinephrine. Further studies involving children and these medications and other modalities are needed to improve survival.

Acetaminophen Intoxication During Treatment: What You Don't Know Can Hurt You

For over two decades, pediatricians have been made aware of the potential risk associated with the acute ingestion of large single and/or multiple doses of acetaminophen (APAP). Clearly, APAP-induced hepatotoxicity remains as a recognized medical emergency which, when treated promptly with appropriate gastrointestinal decontamination and when indicated, with the antidote N-acetylcysteine, has a uniformly good clinical outcome. Recently, the hepatotoxic potential associated with “therapeutic” APAP administration has been brought to the attention of the pediatric community. This review explores the issue of APAP toxicity with therapeutic intent by examining both the clinical literature and also, relevant information concerning the basic pharmacology and toxicology of this old and widely used nonprescription drug. A “risk profile” is developed with regard to factors that may predispose infants and children to this iatrogenic form of toxicity so that the awareness of physicians and other caregivers (including parents) can be heightened and preventative education administered. As is true for most all potentially beneficial medicines used in pediatrics, awareness of the actual amount of drug received from all sources and caution to not exceed the age-appropriate dosing guidelines (i.e., both amount and duration) contained in the approved labeling for all products containing APAP will insure safe and effective therapy.

Near-fatal caffeine intoxication treated with peritoneal dialysis.

Caffeine is generally regarded as a safe drug, as evidenced by its wide availability in “over-the-counter” preparations and beverages. However, it is capable of producing a lethal outcome in cases of intoxication. The case of a two-year-old girl, who suffered major poisoning from caffeine, is presented. Her care, including the use of peritoneal dialysis, is discussed. Previous cases of caffeine intoxication meriting hospital care or resulting in death which have been reported in the English language medical literature are summarized. It is suggested that drug-drug interactions and the use of peritoneal dialysis and hemoperfusion be given particular consideration in such patients.

Injuries associated with downhill sledding

During the winter season of 1985 to 1986, 30 children presented to the emergency department with injuries related to downhill sledding. All of the patients were seen and treated during December 1985, which was an unusually cold and snowy month. The age range of the patients was six to 16 years. Six patients required admission, and all were related to head and/or abdominal trauma. The special characteristics of the sled, the environment, and the rider work in concert to produce injuries. The injury is most likely to occur under cold, icy conditions. After analysis of this series of patients, it is concluded that downhill sledding injuries can be minimized. The factors that make this activity dangerous are defined, and safety precautions are suggested.