Stockpiling antiviral drugs for the next influenza pandemic.

The threat of an influenza pandemic has been at the forefront of public health preparedness for more than 5 years. The national planning effort has included stockpiling antiviral drugs in the Centers for Disease Control and Prevention's Strategic National Stockpile (SNS). This article highlights the composition of the SNS before the 2009 H1N1 pandemic and includes considerations for future antiviral stockpile purchases, focusing on emergence of oseltamivir resistance and the need for additional pediatric supplies.

Challenges associated with creating a pharmaceutical stockpile to respond to a terrorist event.

The Centers for Disease Control and Prevention (CDC) was called into action to develop a National Pharmaceutical Stockpile (NPS). The NPS was created to respond to terrorism events involving blast, chemical and biological agents. There are many challenges associated with creating, managing and using such an asset. This paper provides a helpful background for clinicians and those planning to develop pharmaceutical and/or medical materiel stockpiles for national use. It also describes major challenges and offers suggestions for meeting those challenges.

Calcium channel blocker ingestions in children.

UNLABELLED: Limited data exists regarding toxicity of calcium channel blockers (CCBs) in children. The purpose of this study was to determine the frequency, the range of toxicity, the appropriate observation time, and to assess effective interventions for CCB ingestions in children. A 6-year retrospective review of CCB ingestions in children younger than 7 years of age reported to one regional poison center was undertaken. Patients with coingestants with recognized cardiovascular or central nervous system (CNS) effects were excluded. Two hundred eighty-three patients met criteria for review. The mean age was 27 months with 52% of all patients being boys. Nifedipine (38%), verapamil (34%), and amlodipine (14%) were most commonly ingested. Seventy-five percent of ingestions reportedly involved < or =1 pill. Symptoms occurred in 16/283 (6%): 4 had vomiting, and 12 had CNS or cardiovascular effects. The mean time to onset of symptoms for regular-release and for sustained-release (SR) CCB preparations were 1.5 hours (range 0.5 to 3 hr) and 4.5 hours (range 1 to 14 hr) respectively. OUTCOME: 74% of patients had no clinical effects, 4% minor effects, 2% moderate effects, and 20% other. No deaths or major effects were reported. TREATMENT: 88% of patients evaluated in an emergency department received gastric decontamination, usually one dose of charcoal. Calcium chloride was given in three verapamil SR cases. Five of six patients had reversal of hypotension with IV fluids and decontamination alone. Most pediatric CCB ingestions involve ingestions of small amounts of drug with no effects. Asymptomatic children in this study group who were known to have ingested <12 mg/kg of verapamil SR or <2.7 mg/kg of nifedipine SR could have been monitored at home. Of the children requiring evaluation and monitoring in a health care facility, an observation period for regular-release and SR-CCBs for 3 and 14 hours respectively would have been appropriate. There were insufficient cases with symptoms to draw conclusions for optimal therapeutic interventions.

Multi-center retrospective evaluation of oral benzocaine exposure in children.

On rare occasions benzocaine has produced methemoglobinemia from oral, rectal and dermal exposures. There is disagreement whether this is an idiosyncratic event or a dose-related event. To gain a better perspective on this problem we retrospectively reviewed cases at 4 large regional poison centers of children <18-y of age from 1993-1996. One hundred and eighty-eight benzocaine exposures were reported. Mean and median ingested dosage were 86.8 (+/- 89.5) mg/kg and 50 mg/kg, respectively. Fifty-eight patients (30%) were managed in the emergency department; 8 patients had methemoglobin levels determined. One child had a methemoglobin level of 19%; all others were <1%. One hundred and seventy-three patients (92%) remained asymptomatic. Other symptoms were minor: oral numbness (8), vomiting (3), and 1 each of oral irritation, dizziness and nausea. In this series of accidental ingestions of benzocaine-containing products cyanosis was rare and apparently not dose related. These cases may be safely managed at home with telephone follow up for at least 2 h. If there is evidence of cyanosis, dusky pallor, shortness of breath, or change in mental status direct medical evaluation should be recommended.

Multicenter case series of pediatric metformin ingestion.

OBJECTIVE: There are no large studies, case series, or case reports of metformin ingestion in children. This study summarizes the clinical course and outcomes of metformin ingestion in children reported to the American Association of Poison Control Centers-certified regional poison centers. METHODS: This was a case series of all metformin ingestions in patients <18 years of age reported to eight regional poison centers. Data collection included age, gender, dose ingested, co-ingestants, symptoms, vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required at least 24 hours of follow-up. RESULTS: Fifty-five cases were collected. Ages ranged from 15 months to 17 years, with a mean (+/- SD) of 42+/-4.4 years. The dose ingested, by history, ranged from 250 mg to 16.5 g, with a mean and median of 1710+/-3391 and 500 mg, respectively. Forty-one children (76%) ingested a maximum of two tablets (< or =1700 mg). In the children younger than six years, dosage ranged from 9 to 196 mg/kg, with a mean and median of 60+/-41.1 and 40 mg/kg, respectively. Thirty-seven children were evaluated in a healthcare facility. Clinical effects were limited to nausea (2), diarrhea (2), and dizziness (1). None of the 38 children who had serial glucose measurements experienced hypoglycemia. Arterial blood gas and electrolyte measurements were performed in three and 19 children, respectively. No evidence of acidosis was demonstrated. Two children had lactate concentrations measured and were determined to be in the normal range. Twenty-nine patients received activated charcoal. Five patients received parenteral glucose and one adolescent with a history of diabetes received insulin for hyperglycemia. CONCLUSIONS: Unintentional ingestion of < or =1700 mg of metformin in the healthy pediatric population does not appear to pose a significant health risk of hypoglycemia or detrimental outcome. In the 21 children who were tested for either blood glucose, electrolyte, or lactate concentrations, no evidence of lactic acidosis was seen.

Prospective multicenter study of sulfonylurea ingestion in children.

OBJECTIVE: Sixty-eight percent of pediatric sulfonylurea ingestions reported to poison centers do not result in laboratory or behavioral effects. Consequently, if all exposed children are admitted overnight or for 24 hours for these exposures, it will result in 600 to 700 hospital admissions per year of children who will remain free of symptoms. We prospectively studied exposures reported to 10 regional poison centers to determine if it were possible to differentiate those patients who would have symptoms from those who would remain symptom free. METHODS: We analyzed all sulfonylurea exposures in children < or = 12 years old reported to the participating poison centers. Hypoglycemia was defined as blood glucose (BG) concentration < 60 mg/dl. RESULTS: Hypoglycemia developed in 56 (30%) of 185 exposed patients. Fifty-four of the 56 (96%) hypoglycemic patients had development of hypoglycemia within 8 hours of ingestion. Eighty-seven of the patients were initially managed with oral supplementation only; in 13 cases, treatment advanced to intravenous administration of glucose or glucagon with the onset of hypoglycemia. There was no statistical difference in medical outcome between patients monitored during oral supplementation versus during intravenous infusion of dextrose. Ingestions analyzed by time of day did not predict risk of hypoglycemia. Sufficient data were available for 103 (58%) of the 177 patients who ingested glyburide or glipizide to calculate a toxic dose/weight ratio. Of these 103 patients, 31 of 36 patients who ingested < or = 0.3 mg/kg remained symptom free, whereas 31 of 67 who ingested more than 0.3 mg/kg had BG concentrations < 60 mg/dl (p < 0.005, 95% confidence interval 0.05 to 0.58; sensitivity 86%, specificity 46%). CONCLUSION: A lack of onset of hypoglycemia (BG > 60 mg/dl) in the first 8 hours after ingestion is predictive of a benign outcome in accidental pediatric sulfonylurea ingestion. Clinical observation of children for onset of hypoglycemia during oral feeding alone appears safe. Some children with symptoms of hypoglycemia need to receive intravenous dextrose therapy. Time of day of ingestion is not predictive of risk of hypoglycemia. Finally, at this time it appears inappropriate to use a milligram per kilogram body weight dose as a guide for management decisions.

Prospective multicenter evaluation of tramadol exposure.

BACKGROUND: Tramadol is a novel analgesic possessing both opiate and noradrenergic effects. Its low potential for abuse suggests increasing use, but there are limited data on the toxicity in overdose. METHODS: Multicenter prospective case series. All exposures from October 1995 through August 1996 reported to seven Poison Centers were evaluated. RESULTS: There were 126 cases of which 87 were tramadol alone. Of the tramadol alone cases, 51 were female (59%). Age ranged from 1 to 86 y with a mean and median of 26.8 y (SD 17.2) and 25 y, respectively. There were 15 cases of children less than 6 years old. Symptoms reported with overdose were: lethargy 26 (30%), nausea 12 (14%), tachycardia 11 (13%), agitation 9 (10%), seizures 7 (8%), 4 each (5%) of coma and hypertension, and respiratory depression 2 (2%). All seizures were brief. Naloxone reversed sedation and apnea in 4 of 8 patients. One patient experienced a seizure immediately after administration of naloxone. Other treatments were: diazepam (3 patients), and phenytoin, lorazepam and nifedipine (1 patient each). Tramadol 500 mg was the lowest dose associated with seizure, tachycardia, hypertension or agitation while 800 mg was the lowest dose associated with coma and respiratory depression. Urine drug screens performed on 19 patients were negative for opiates. All symptomatic cases exhibited effects within 4 h of ingestion. Mean hospital stay was 15.2 h (range 2-96 h, SD 15.8). Nineteen patients were admitted to an intensive care unit with a mean stay of 25 h (SD 20). DISCUSSION: Much of the toxicity in tramadol overdose appears to be attributable to the monoamine uptake inhibition rather than its opioid effects. Agitation, tachycardia, confusion and hypertension suggest a possible mild serotonin syndrome. No arrhythmias beyond tachycardia were seen. CONCLUSION: This study suggests significant neurologic toxicity from tramadol overdose. Serious cardiovascular toxicity was not seen.

Retrospective study of mistletoe ingestion.

BACKGROUND: There are limited data concerning accidental exposure to Phoradendron flavescens (Phoradendron serotinum, American Mistletoe). The only published reports include a review of 14 cases which revealed no symptoms and a single fatality from an intentional ingestion of an unknown amount of an elixir brewed from the berries. The risk of serious toxicity from accidental exposure to this plant appears to be minimal, yet it continues to be regarded as a dangerous plant. We reviewed charts for four years (1990-1993) from three poison centers where Phoradendron flavescens is indigenous. RESULTS: Ninety-two human cases were located. Age ranged from four months to 42 years, with a mean of six years (SD 8.8) and median of two years. There were 14 symptomatic cases of which 11 were determined to be related to mistletoe exposure. There were six gastrointestinal upset, two mild drowsiness, one eye irritation, one ataxia (21 months), one seizure (13 months). Treatments included gastrointestinal decontamination in 54 patients (59%), ocular irrigation in one and IV benzodiazepine in one. Decontamination did not appear to affect outcome. Amount ingested ranged from one berry or leaf to more than 20 berries or five leaves. In cases with a known amount ingested, eight of ten cases with > or = 5 berries remained symptom free. In the 11 cases with leaf-only ingestion (range 1-5 leaves), three patients had gastrointestinal upset. The one case with five leaves ingested remained asymptomatic. The infant with seizures was an unwitnessed exposure, found with both berries and leaves in the crib. No arrhythmias or cardiovascular changes were reported in any case. All symptomatic cases had onset of symptoms in < or = 6 hours. DISCUSSION: Symptoms are infrequent and in all but one case would not require direct medical supervision. Seizures have not previously been reported with Phoradendron flavescens exposure. CONCLUSION: Symptoms from Phoradendron flavescens exposure are infrequent, even with ingestion of 5-20 berries or 1-5 leaves, but may include seizures. Cardiovascular effects were not seen.

Streptococcal toxic shock-like syndrome presenting with hypoglycemia and reversible paralysis.

A patient with pharyngitis progressive to Toxic Shock-Like Syndrome presented to the emergency department with a chief complaint of lower extremity paralysis. This paraplegia was completely reversed with the administration of intravenous glucose. Hypoglycemia-induced paraplegia has not previously been reported in the medical literature, and this report emphasizes the importance of considering low-blood glucose as a potential etiology for patients who present with these neurological symptoms.