Treatment of acetaminophen ingestion with a superactivated charcoal-cola mixture.

STUDY OBJECTIVE: We evaluate the adsorptive capacity of a superactivated charcoal-cola mixture to acetaminophen compared with superactivated charcoal alone. METHODS: This was a triple-arm, prospective, unblinded study of 8 healthy adult human volunteers who ingested 80 mg/kg of acetaminophen. In the control arm of the study, participants ingested acetaminophen alone. In the next arm, acetaminophen was followed by 1 g/kg of superactivated charcoal mixed with water. In the final arm, acetaminophen was followed by 1 g/kg of superactivated charcoal mixed with caffeine-free diet cola. Serum acetaminophen concentrations over 6 hours for each arm were analyzed for area under the time-concentration curve (AUC), peak concentrations, and time to peak concentrations. RESULTS: AUCs were 298.5+/-82.5 mg-h/L (control), 77.1+/-85.2 mg-h/L (superactivated charcoal), and 81.3 +/- 71.8 mg-h/L (superactivated charcoal-cola). Comparison of AUCs by analysis of variance revealed mean square of 128,315.1 between treatments, and residual mean square of 6,405.0, yielding an F ratio of 20.03 (P <.0001). Student-Newman-Keuls pairwise multiple comparison procedure revealed a statistically significant difference in AUC for control versus superactivated charcoal (P <.05) and for control versus superactivated charcoal-cola (P <.05), but not for superactivated charcoal versus superactivated charcoal-cola (P >.05). Time-concentration curves for the 3 study arms were illustrated graphically. CONCLUSION: Combining superactivated charcoal with cola does not limit the adsorptive capacity of superactivated charcoal.

5-Year analysis of mushroom exposures in California.

OBJECTIVE: To evaluate outcomes following toxic mushroom ingestions. DESIGN: Retrospective data analysis. METHODS: We analyzed American Association of Poison Control Center data for California from 1993 through 1997. RESULTS: A total of 6,317 exposures occurred during the study period. Most (n = 6,229 [99.7%]) were acute exposures, and the rest (0.3%) were chronic; 87.6% (n = 5,536) were unintentional. Most (n = 4,235 [67.0%]) were in children younger than 6 years, and of these, only 6.0% experienced any clinical effects. The most common symptoms in patients aged 6 years and older were vomiting in 588 patients (28.2%), nausea in 307 patients (14.7%), diarrhea in 263 patients (12.6%), and abdominal pain in 221 patients (10.6%). No effects were seen in 3,131 (49.6% of all patients). Major effects were seen in only 17 patients (0.3%). Only 61 patients (1.0%) were admitted to a critical care unit. Death occurred in a 32-year-old adult who ate foraged mushrooms. Of all patients, 1,375 (21.8%) received no therapy or were observed only. CONCLUSIONS: Most mushroom exposures were acute and unintentional and occurred in children younger than 6 years. Major toxic reactions or death was uncommon.

Prospective evaluation of mild to moderate pediatric acetaminophen exposures.

STUDY OBJECTIVE: To determine whether pediatric patients with acute, mild to moderate acetaminophen exposures, treated with home monitoring alone, develop systemic signs of hepatic injury. METHODS: A prospective, observational study of calls to a regional poison center over a 25-month period was performed. Patients were eligible for the study if they were younger than 7 years and had an acute maximum possible acetaminophen exposure of up to 200 mg/kg. Exclusion criteria included previous decontamination measures, possibility of ingestion of an extended-release preparation, health or medication issues that could increase susceptibility to hepatotoxicity, current symptoms of hepatotoxicity, and indeterminable ingestions. Study protocol included reviewing the signs and symptoms of early and late acetaminophen toxicity, a 4- to 6-hour follow-up call, and a 72-hour follow-up call. Outcome measures were defined as a verbal report by the patient's parent or guardian of the presence or absence of signs or symptoms of hepatotoxicity. RESULTS: A total of 1,039 patients were enrolled in the study, including 519 girls and 520 boys, with exposures ranging from 20 to 200 mg/kg. Eighteen patients were lost to follow-up; data were incomplete for 2 patients. At 72-hour follow-up, the remaining 1,019 patients were all doing well, without signs or symptoms of hepatotoxicity. CONCLUSION: On the basis of these data, pediatric patients with acute acetaminophen exposures of up to 200 mg/kg, treated with home monitoring alone, do not develop signs or symptoms of hepatic injury.

Anaphylactoid reaction to rattlesnake envenomation.

The clinical manifestations of an anaphylactoid reaction are identical to true anaphylaxis; however, a previous exposure to the offending agent is not needed to manifest these symptoms. We present a case of an anaphylactoid reaction in a 62-y-o female following a first-time envenomation by a rattlesnake. The patient required s.c. epinephrine and i.v. diphenhydramine, methylprednisolone, and ranitidine. She had not been envenomated by a rattlesnake previously or received any horse-derived antivenins in the past.

Acute lindane poisoning in three children.

Lindane has been reported to cause central nervous system (CNS) toxicity including seizures after prolonged dermal contact and also after acute ingestions. Despite safer alternatives, lindane still remains a commonly used agent in the treatment of scabies and pediculosis. We present three cases of acute toxicity after the inadvertent oral administration of lindane in three siblings. A 17-month-old female suffered a single seizure. A 3-year-old male was listless, nauseated, pale, and had decreased responsiveness to verbal and tactile stimulation. A 4-year-old female became nauseated and required bag-valve-mask ventilation for hypoventilation. The three patients all recovered without sequelae.

Comparison of the toxicities of two iron formulations in a swine model.

OBJECTIVE: To describe the histopathologic and pharmacokinetic differences of acute iron poisoning between chewable multivitamins with iron and solid iron tablets in a swine model. METHODS: This was a prospective, randomized, unblinded toxicity study of iron poisoning of two iron formulations in male Yorkshire pigs. Eight swine were randomized to receive 60 mg/kg of iron in either solid iron tablets or chewable multivitamins with iron. Serum iron, arterial blood gases, and episodes of vomiting were recorded over a ten-hour period. Routine histologic evaluations of the esophagus, stomach, small intestine, large intestine, and liver were performed immediately after the study period. Pharmacokinetic analyses of area under the concentration-time curve (AUC), time to peak concentration, and peak serum iron concentration were performed. RESULTS: There was no significant difference between the serum iron levels except at three and four hours. There was a significant higher AUC in the chewable group compared with the solid group. Pathologic evaluation identified severe esophageal inflammation and focal erosion in the solid iron tablet group in two of the four animals, compared with no focal erosions and minimal esophageal inflammation in the chewable group. No significant change was identified in the liver, small intestine, or large intestine in either group. CONCLUSIONS: These results demonstrate increased local gastrointestinal toxicity following a large ingestion of solid iron tablets in a swine model, compared with chewable multivitamins with iron. Higher serum iron levels were identified in the animals that received chewable multivitamins with iron.

A review of selected seafood poisonings.

Seafood poisoning has been recognized as a problem in both coastal and inland populations for millennia. Many types of sea creatures from shellfish to the largest fish have been implicated. Severe cases of many different types of seafood poisonings can result in fatalities. While the pathophysiology of the toxins is well known in some cases, others, like ciguatera, remain somewhat confusing. As a result, the treatment of these conditions remains controversial, although supportive care continues to be the mainstay of therapy. In this manuscript, we review the pathophysiology, clinical presentation, and treatment of some of the most common and toxic varieties of seafood poisoning resulting from toxins.

The availability of activated charcoal and ipecac for home use.

Traditionally, ipecac has been used in the home; however, recently attention has focused on pre-hospital activated charcoal (AC) administration. In an effort to assess the availability of AC and ipecac, we conducted a telephone survey. One-hundred and 18 pharmacies were randomly selected from the 59 counties in California to assess availability of AC (liquid or powder) and/or ipecac. Ninety-four (80%) pharmacies participated. Seventy-nine of the pharmacies had ipecac compared to 8 which had AC. Three pharmacies had pre-mixed aqueous AC while 5 had AC in powder formulation. There was no difference between chains and community in AC or ipecac availability. The major limitations of effective GI decontamination are AC availability and rapidity in its administration. Our results identify a significant delay in the administration of AC if a parent was referred to a local pharmacy for home or pre-hospital decontamination. As more toxicologists and poison centers move towards pre-hospital and home AC much education of pharmacists as well as pediatricians and parents is required.

Elevated lithium level: a case and brief overview of lithium poisoning.

INTRODUCTION: We present the case of a minimally symptomatic patient found to have an elevated lithium level after a blood sample was inadvertently obtained in a green-top tube containing lithium heparin. CASE REPORT: A 33-year-old woman presented 8 hours after ingesting an unknown quantity of sustained-release lithium carbonate, venlafaxine, clonazepam, and valproic acid. The patient was noted to be slightly drowsy but could be easily aroused. No gastrointestinal symptoms or electrocardiographic changes were observed. The patient was admitted to the intensive care unit for observation. The patient's lithium level 21 hours after ingestion was 5.6 mEq/liter, but she was clinically asymptomatic. The disagreement between symptoms and lithium level led to the discovery that this blood sample had been collected in a lithium heparin tube, thereby falsely elevating the level. CONCLUSIONS: This case illustrates the wisdom of the old adage to "treat the patient, not the levels." Caution should be used by physicians, nurses, technicians, and other personnel when obtaining blood samples.

Ethanol analysis following consumption of "alcohol-free" beer.

Breath alcohol devices are routinely employed by emergency department personnel to reflect blood ethanol levels. No data have been published using these devices following the ingestion of "alcohol-free" beer that are required to contain < 0.5% alcohol. We performed a prospective, randomized, unblinded study on 8 healthy male volunteers that abstained from alcohol for 48 h and fasted for 10 h. Each subject ingested a 6-pack of alcohol-free beer over 1 h; breath alcohol determinations were made at 30, 60 and 120 min. Elevated breath alcohol levels were obtained at 30 and 60 min and decreased in all but 1 subject by 120 min. The elevated breath alcohol levels at 30 and 60 min may represent the previously reported "mouthwash" effect.

Recurrent and persistent coagulopathy following pit viper envenomation.

BACKGROUND: Coagulation abnormalities following crotaline (pit viper) snakebite have traditionally been considered short-lived, but laboratory studies have rarely been reported beyond the first few days of treatment for envenomation. During the course of an antivenom clinical trial, we observed coagulation defects as late as 2 weeks following envenomation. OBJECTIVES: To document and characterize the recurrence or persistence of coagulopathy among patients envenomed by pit vipers and treated with a Fab antivenom. METHODS: Patients with moderate pit viper envenomation were enrolled in a multicenter, prospective clinical trial. A Fab-based antivenom preparation, antivenom polyvalent crotalid (ovine) Fab, was administered in all cases. Platelet count, fibrinogen level, presence of fibrin split products, prothrombin time, and partial thromboplastin time were determined before treatment and at standard intervals during the following 2 weeks. RESULTS: Of 38 patients completing the study, 20 (53%) had recurrent, persistent, or late coagulopathy 2 to 14 days after envenomation. Thrombocytopenia occurred in patients with prior thrombocytopenia; hypofibrinogenemia occurred only in those with prior hypofibrinogenemia or positive fibrin split products. No patient experienced significant spontaneous bleeding. One patient with coagulopathy developed minor bleeding following minor surgery 12 days after envenomation. CONCLUSIONS: Prolonged or recurrent coagulopathy may occur after envenomation by North American pit vipers. Patients treated with Fab-based antivenom may benefit from periodic rather than single-bolus dosing. Patients with coagulopathy should undergo close monitoring during the first 2 weeks after snakebite.

Blood disposition and urinary excretion kinetics of methazolamide following oral administration to human subjects.

The pharmacokinetic disposition of methazolamide (MTZ) was studied in five healthy volunteers following administration of a single oral dose. Drug concentrations in blood, plasma, and urine were measured by HPLC. Over the range of plasma concentrations observed in vivo, MTZ free fraction (measured by ultrafiltration) was 0.28. Being a carbonic anhydrase inhibitor, MTZ would be expected to distribute into, and be sequestered by, red blood cells. For this reason, MTZ disposition was characterized utilizing blood concentrations as the reference. Using a two-compartment model, a series of differential equations were simultaneously fitted to blood concentrations and urinary excretion data generating estimates for k10 (0.035 +/- 0.019 h(-1)), k12 (0.200 +/- 0.036 h(-1)), k21 (0.077 +/- 0.046 h(-1)), k(a) (0.304 +/- 0.064 h(-1)), Vc (1.1 +/- 0.18 L) and f(r) (fraction excreted renally, 0.61 +/- 0.14). Total blood clearance was 0.037 +/- 0.020 L h(-1). The model estimate of elimination half-life (126 +/- 61 h) was consistent with drug binding to a high affinity carbonic anhydrase isozyme in the erythocyte. Estimates of MTZ renal clearance and renal excretion ratio were 0.021 +/- 0.010 L h(-1) and 0.16 +/- 0.06, respectively. Overall, the prolonged elimination of MTZ from the blood is the result of extensive erythrocyte distribution and tubular reabsorption by the kidney.

An examination of serial urinalyses in patients with North American crotalid envenomation.

STUDY OBJECTIVE: To examine the incidence of abnormal urinalyses after rattlesnake envenomations and its association with bite severity and antivenom administration. METHODS: A retrospective review of data collected in a prospective manner for an experimental crotalid antivenom trial. Subjects were individuals with minimal to moderate North American crotalid envenomations. Incidence and characterization of abnormal urinalysis after crotalid envenomation is presented. Additionally, the relationship of abnormal urinalysis to bite severity is examined. A preliminary test of antivenom protein urinalysis interference was also conducted. RESULTS: Forty-three percent of the urinalyses reported prior to antivenom treatment had abnormalities. Thirty-three of 41 subjects (80%) had an abnormal urinalysis, defined as the presence of cells, blood, glucose, or protein, at some time during the 2-week period following envenomation. All but 3 of these subjects had urinalyses which returned to normal by 2 weeks postenvenomation. Fifteen of 22 subjects (68%) with minimal envenomations had an abnormal urinalysis at some time following envenomation, while 18 of 19 subjects (95%) with moderate envenomations had abnormal urinalyses (p < 0.05). In addition, high concentrations of antivenom added to urine were found to produce a positive urine dipstick test for protein. CONCLUSION: In our study of patients with minimal to moderate North American crotalid envenomations, there was a high incidence of abnormal urinalyses. The urine abnormalities tended to be more common with increased bite severity and more frequent during the first few hours following envenomation. Antivenom appearance in the urine could be responsible for some of our findings.

Clarithromycin induced digoxin toxicity.

A case of digoxin poisoning following the co-administration of digoxin and clarithromycin in a 28 year old male is described. Since the aetiology of chronic digoxin poisoning is often unclear, clinicians should be aware of the potential drug-drug interaction between digoxin and clarithromycin.

Resource-use analysis of a medical toxicology consultation service.

STUDY OBJECTIVE: To evaluate the impact of a medical toxicology consulting service (MTCS) on resource use and efficiency of care in patients hospitalized with a diagnosis of tricyclic antidepressant (TCA) poisoning. METHODS: We conducted a retrospective, case-controlled medical-records review at two urban tertiary care teaching hospitals. The study population comprised patients who presented to the emergency department with a diagnosis of TCA poisoning, in two phases. The first phase was longitudinal; we evaluated cases over 4 years before and after inception of an MTCS at one institution. In the second phase we compared consecutive cases of TCA poisoning treated at two urban teaching hospitals located within a mile of each other with similar patient populations, one with and one without MTCS backup. Inclusion criteria consisted of complete medical records, ingestion of first- and second-generation TCAs, and age greater than 16 years. Patients were excluded if history, physical examination, or laboratory analysis suggested that multiple substances had been ingested. Extensive demographic data were collected in each case. Clinical information obtained from each patient included admission vital signs, pupil size, QRS and corrected QT duration, and the presence of markers of severe TCA toxicity such as hypotension, seizures, pulmonary edema, respiratory insufficiency necessitating intubation, and the occurrence of antimuscarinic signs and symptoms. Information regarding treatment was also collected from each case, including laboratory tests, decontamination procedures, administration of sodium bicarbonate, and use of other medications and therapies. RESULTS: We identified a total of 88 patients in both phases of the study. Comparison groups were similar with respect to age, sex, presenting vital signs, presenting QRS and corrected QT duration, and incidence of recorded antimuscarinic signs, hypotension, seizures, and respiratory insufficiency requiring intubation. Total length of stay in a monitored hospital bed was also similar between groups. One fatality was recorded, but all other patients were discharged home or to a psychiatric facility. Patients seen by the MTCS consumed fewer health care resources in the form of less decontamination and fewer laboratory tests. CONCLUSION: The MTCS may provide a resource-efficient means of treating patients with TCA poisoning. A larger, multicenter study of a variety of poisoned patients should be undertaken to further investigate this issue.