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Biomedical subjects

Henry A Spiller

Publications and source records attributed to Henry A Spiller.

18 recordsLinked to original sources

Toxic effects from metformin exposure.

BACKGROUND: The major risk associated with metformin is lactic acidosis. The incidence of lactic acidosis is not clear. Hypoglycemia is not expected to be a major concern after metformin exposure. OBJECTIVE: This study assessed the demographics, toxic effects, and clinical syndromes of metformin exposures reported to poison centers nationally. METHODS: The Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers was searched for all metformin-only exposures occurring from January 1, 1996, through December 31, 2000. RESULTS: There were 10,958,526 total poisoning exposures reported to TESS during the study period. Of those, 4072 cases met the study criteria. Exposures occurred in 2421 (59%) women and were categorized in all patients as acute (3074; 75%), acute-on-chronic (767; 19%), chronic (200; 5%), and chronicity unknown (31; 1%). Children < or =12 years old experienced few adverse outcomes and no deaths. There were 20 moderate-effect outcomes (1.8%) and 2 major-effect outcomes (0.2%) in children <6 years old and 4 moderate-effect outcomes (2.3%) and no major-effect outcomes in children 6-12 years old. In the adult population, the adverse outcomes were distributed evenly across the age span, with a trend toward more serious outcomes in the elderly. There were 9 deaths (0.2%), 32 major-effect cases (0.8%), and 187 moderate-effect cases (4.6%). In all age groups, acidosis was rare (n = 68; 1.6%). Hypoglycemia is more common than previously reported (n = 112; 2.8%). Clinical effects associated with a major outcome or death were hyperglycemia, acidosis, elevated anion gap, elevated creatinine, hypotension, and coma. CONCLUSIONS: Severe adverse events after exposure to metformin are not common, occurring in approximately 1% of cases; this is in agreement with previous reports. The presence of hypotension, acidosis, elevated anion gap, hyperglycemia, and coma may be prognostic of severe or fatal outcome.

Acidosis, Lactic↗

Epidemiology of volatile substance abuse (VSA) cases reported to US poison centers.

Volatile substance abuse (VSA) is believed to be widespread. The Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Systems offers an opportunity to evaluate the epidemiology of volatile substance abuse using a data set that captures data from a large geographic area covering a wide-ranging group of socioeconomic strata, ethnic groups, and demographics. To utilize this potential we analyzed a data set of TESS for the 6-year period of 1996 through 2001 involving all cases of intentional inhalational abuse of nonpharmaceutical substances. Over the study period there was a mean annual decline of 9% of reported VSA with an overall decline of 37% from 1996 to 2001. Volatile substance abuse was reported primarily in children, with 6358 cases (54%) in children 13-19 yr and 1803 (15%) cases in children 6-12 yr. Fifty-two cases were reported in children < 5 or = 5 yr. A total of 2330 (20%) VSA cases had a serious outcome, defined as either moderate effect (n = 2000), major effect (n = 267), or death (n = 63). The top five categories of substances abused were gasoline (41%), paint (13%), propane/butane (6%), air fresheners (6%), and formalin (5%). Three categories were responsible for the majority of deaths: gasoline (45%), air fresheners (26%), and propane/butane (11%). While there was a decline in reported cases, there was no decline in major outcomes or fatalities. Volatile substance abuse was reported in all 50 states, with case distribution similar to population distribution. However, seven states had > 2 times the expected rate based on their population; three western states, two midwestern states, and two Appalachian states. The role of urban vs. rural population may possibly explain the difference in numbers, with a greater incidence of VSA cases reported in states with large rural populations. The mean monthly occurrence rate was 162 VSA cases/month (S.D. +/- 10.85). There were 4 months that were > 2 standard deviations from the mean, with two peak months (May, 192/month and March, 187/month) and two trough months (December, 126/month and January, 137/month). This report presents a broad picture of VSA in the United States. Volatile substance abuse, as reported to U.S. poison centers, appears to be on the decline, but continues to be an ongoing problem. Volatile substance abuse is reported throughout the U.S. in all areas of the country, with a higher incidence in states with large rural populations. A small group of substances appears responsible for the majority of deaths. It is imperative that we continue to educate the public and healthcare professionals regarding the risks of VSA and hopefully impact the incidence of VSA.

Administration, Inhalation↗

Evaluation of the effect of a public educator on calls and poisonings reported to a regional poison center.

There are few studies that use measurable outcomes to gauge the effect of a public educator on the mission of the poison center. Human exposures, penetrance and total call volume from 2 regional poison centers for 7y (1996-2002) were evaluated. In poison center 1 a dedicated educator was employed for the final 4y of data (1999-2002). Poison center 2 data acted as a control with no dedicated educator for the 7-y period. The 2 centers were comparable in a number of ways: similar demographic rural and urban populations; similar geographic and economic region; and served the entire state. Human exposures in poison center 1 increased 4.3 % after employment of a dedicated educator, while exposure continued to decline at center 2 (1.7%). A steep decline in penetrance in poison center 1 was reversed after employment of a dedicated educator. Human exposures and penetrance for poison center 2 continued to decline during the study years. Total calls to center 1 increased 13.8% while total calls to center 2 remained flat (0.2%). This is the first study to use measurable outcomes to evaluate the impact of a public educator on the mission of a poison center. The addition of a public educator was associated with a positive impact on human exposures and penetrance reported to a regional poison center.

Hotlines↗

Use of dosage as a triage guideline for unintentional cyclic antidepressant (UCA) ingestions in children.

Triage guidelines for unintentional cyclic antidepressant (UCA) ingestions vary widely, with limited supportive evidence. All records of UCA ingestion reported to 4 certified regional poison centers were evaluated for the years 1998 through 2000. Inclusion criteria included age </=6 years patients with a known outcome and known ingested dose by history. Exclusion criterion was polydrug ingestion. Two hundred forty-six cases were evaluated. The mean age was 2.4 years (standard deviation, +/-1.2 y). One hundred thirty-six patients (55%) were managed in a hospital. One hundred ten patients were managed at home with observation and telephone follow up. Symptoms reported were drowsiness (n = 59), tachycardia (n = 4), agitation (n = 2), coma (n = 2), respiratory depression (n = 1), and ataxia (n = 1). Medical outcome was reported as no effect (n = 185; 75%), minor effect (n = 57; 23%), moderate effect (n = 2; 1%); and major effect (n = 2; 1%). Mean dosage of patients with and without symptoms was 6.3 mg/kg (+/- 9.3) and 2.9 mg/kg (+/- 3.1), respectively. Forty-three of 57 patients (75%) with minor symptoms reported a dosage of <5 mg/kg. All patients with a moderate or major outcome (n = 4) reported a dosage of >5 mg/kg. The majority of UCA ingestions produced limited or no symptomatology. In this series, all children with ingestions of <5 mg/kg developed no or minor effects. Home monitoring might be appropriate in such cases.

Antidepressive Agents, Tricyclic↗

Intermediate syndrome after exposure to chlorpyrifos in a 16-month-old girl.

We describe a case of intermediate syndrome after chlorpyrifos ingestion in a toddler, despite a continuous pralidoxime infusion. A 16-month-old girl ingested a pesticide containing chlorpyrifos. She was brought to an Emergency Department where she became lethargic and tachycardic, and subsequently developed pulmonary edema requiring mechanical ventilation. Pralidoxime 150 mg i.v. was administered twice, and an infusion begun at 15 mg/kg/h. At 24.5 h post-ingestion the child had a normal neurologic examination, showed no signs of cholinergic excess, and was extubated successfully. At 27.5 h post-ingestion the child became flaccid, bradycardic and apneic. She was emergently re-intubated. The child's delayed onset of respiratory arrest and flaccid paralysis after an asymptomatic period is consistent with Intermediate Syndrome. This is an unusual case in that it occurred in a young child, was related to chlorpyrifos, and occurred despite continuous and adequate oxime therapy.

Chlorpyrifos↗

Prospective study of morbidity associated with snakebite envenomation.

BACKGROUND: The morbidity associated with snakebite envenomation has not been well documented. METHOD: Using a standardized questionnaire all patients with snakebite reported to a regional poison center during the year 2001 were followed after hospital discharge by telephone until resolution of symptoms. RESULTS: One hundred and twenty-eight snakebite cases were reported, of which 16 (12.5%) were lost to follow-up and 31 (24.2%) reported no progression of symptoms beyond puncture and were deemed "dry bites." Eighty-one (63.3%) patients were followed for the duration of symptoms. Age ranged from 1 to 86 years with a mean of 32 years. There were 64 males (79%). The snakes were identified as copperhead (n = 57), unidentified venomous (n = 17), timber rattlesnake (n = 6), and cottonmouth (n = 1). All patients were initially evaluated in a hospital emergency department of which 51 were admitted. Nine patients received antivenin. Of the 37 patients who had a job, 33 lost a mean of 14 days of work (SD +/- 18.1). Mean duration of edema was reported as 11.4 days (S.D +/- 12). Recurrent edema frequently occurred with limb activity. Pain was scored on a scale of 1 to 10, with a mean score of 4.8 (SD +/- 2.7). Mean duration of pain was reported as 7.8 days (SD +/- 6.4). Thirty patients required accommodation for ambulation including crutches (n = 11), limp (n = 11), and no shoes or loose shoes (n = 14). Of the 26 patients bitten on the hand or finger, duration of reduced function persisted for a mean of 14.3 days (SD +/- 10.4) and reduction of hand strength persisted for a mean of 22 days (SD +/- 25.5). Five patients had poorly healing wounds at the bite site which persisted from 14 to 77 days with a mean of 45 days (SD +/- 22.8) CONCLUSION: In this study snakebite resulted in significant duration and extent of morbidity in a majority of patients.

Adolescent↗

Skin breakdown and blisters from senna-containing laxatives in young children.

BACKGROUND: At the direction of the Food and Drug Administration, phenolphthalein was removed from all over-the-counter laxatives in 1999. Phenolphthalein was then replaced in most laxative products with the natural product senna from Cassia acutifolia Delile, which contains various anthraquinones. No data are available on the safety of senna use in children <6 years of age. OBJECTIVE: To describe the clinical outcomes of exposure to unintentional ingestion of senna-containing laxatives in young children. METHODS: All ingestion exposures of senna-containing laxatives in children <5 years of age from 6 poison centers over a 9-month period were evaluated. Inclusion criteria required 24-hour follow-up and the presence of diarrhea to confirm ingestion. Parents were told routinely that severe diaper rash was possible and to protect the perianal area with frequent cleansing and a barrier ointment if the child was wearing diapers. RESULTS: During the study period, 111 cases were reported: 19 children experienced no diarrhea, 4 were lost to follow-up, and 88 exposures were evaluated. Fifty-two children (59%) were </=2 years old. Fifty children remained in diapers, 28 children were fully toilet trained, and 10 wore diapers (pull-up pants) overnight. Twenty-nine children (33%) experienced severe diaper rash. The mean +/- SD time to recognition of the diaper rash was 15.6 +/- 8.6 hours. Ten children (11%) had blisters and skin sloughing. There was a significant increase in severe diaper rash (p < 0.05) and onset of blisters and skin breakdown (p < 0.05) in children wearing diapers versus those who were fully toilet trained. The mean time to onset of blisters was 14.5 +/- 6.8 hours. Skin burns and loss were seen primarily on the buttocks and perineum, loosely following the diaper area. CONCLUSIONS: Unintentional ingestion of senna-containing laxatives in young children may potentially cause severe diaper rash, blisters, and skin sloughing.

Blister↗

Postmortem oxycodone and hydrocodone blood concentrations.

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.

Adult↗

Fatal cyclobenzaprine overdose with postmortem values.

There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.

Adult↗

Dermal absorption of a liquid diphacinone rodenticide causing coagulaopathy.

Rare cases of coagulaopathies from dermal absorption of hydroxycoumarin derivatives have been reported. We report the first case of dermal absorption of an indandione derivative rodenticide causing severe coagulopathy. An 18-y-o male worker at a pest exterminating company spilled a concentrated liquid preparation of 0.106% diphacinone in his boot. He did not remove the boot or wash the area for 6 to 8 h. Seven days later he presented to the emergency department with flank pain, hematuria and epistaxis. Laboratory values were PT > 40 sec, PTT > 90, Hb 16.2, and platelets 273. Urinalysis reported gross hematuria with RBCs too numerous to count. Prolonged bleeding was noted at i.v. puncture sites. Initial therapy included i.m. injection of vitamin K and nasal packing. The patient's religious beliefs precluded the use of blood products. The patient was admitted for observation until PT was controlled. He was discharged on high dose vitamin K p.o. dose titrated to the international normalized ratio measured every 48 h. After 2 w, a dose of 100 mg vitamin K/d was set and the patient was followed as an outpatient for 3 mo. Vitamin K therapy was tapered and discontinued 60 d post-exposure with no further elevation in PT. Diphacinone was detected in a serum sample drawn 60 d post-exposure using gradient and isocratic HPLC methods with fluorescence and UV detection. Factors increasing the dermal absorption of the diphacinone were: prolonged skin contact in a confined area and exposure to a concentrated solution.

Accidents↗

Status epilepticus after massive carbamazepine overdose.

We report two patients who experienced status epilepticus after carbamazepine overdose. The first patient was an 18-year-old female with a history of epilepsy. She experienced 4 hour of persistent and prolonged seizures resistant to sodium amytal therapy. The status epilepticus ended with her death. The second patient was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour of persistent and prolonged seizures that appeared to be resistant to diazepam, phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam. This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.

Adolescent↗

The Delphic oracle: a multidisciplinary defense of the gaseous vent theory.

Ancient historical references consistently describe an intoxicating gas, produced by a cavern in the ground, as the source of the power at the oracle of Delphi. These ancient writings are supported by a series of associated geological findings. Chemical analysis of the spring waters and travertine deposits at the site show these gases to be the light hydrocarbon gases methane, ethane, and ethylene. The effects of inhaling ethylene, a major anesthetic gas in the mid-20th century, are similar to those described in the ancient writings. We believe the probable cause of the trancelike state of the Priestess (the Pythia) at the oracle of Delphi during her mantic sessions was produced by inhaling ethylene gas or a mixture of ethylene and ethane from a naturally occurring vent of geological origin.

Amnesia↗

Multi-center retrospective evaluation of carbonyl iron ingestions.

There is limited published data concerning carbonyl iron ingestion and no data on overdose. A retrospective chart review of all patients with carbonyl iron ingestion reported to 5 regional poison information centers from January 1998 to April 2000 was done. Thirty-three patients with carbonyl iron ingestion were reported. Twenty-seven patients (82%) were managed without referral to a health care facility. The mean and median age of these patients was 3years and 20 months, respectively. The mean dose ingested was 11.2 mg/kg (range of 2.2 to 34.5 mg/kg) with no effects noted. Six patients evaluated in the emergency ingested a mean of 34 mg/kg (range of 12 to 72 mg/kg). The mean peak serum iron concentrations in 4/6 were 82 microg/dL (range of 36 to 177 microg/dL). One child with a history of flu-like symptoms reported diarrhea, fever and lethargy and had a serum iron concentration of 36 microg/dL; symptoms were believed unrelated to the exposure. In this limited first case series of iron carbonyl ingestion, serious toxicity did not occur.

Adolescent↗

Massive gabapentin and presumptive quetiapine overdose.

Previous reports of gabapentin overdose have described mild symptoms of somnolence, ataxia and slurred speech. Quetiapine has produced a false positive for cyclic antidepressants on immunoassay drugscreens. Quetiapine overdose is associated with coma, QTc prolongation and hypotension. We report a case of massive gabapentin and presumptive quetiapine overdose with the highest recorded serum gabapentin concentration (104.5 u/ml) associated with coma, respiratory depression requiring mechanical ventilation, and hypotension.

Acetates↗

Envenomations as a novel drug-seeking method.

Drug seekers have often sought narcotics and benzodiazepines through subjective reports of severe pain. We report 2 patients who claimed repeated envenomation to receive narcotic administration; 1 claimed black widow bite on 8 occasions at 7 separate healthcare facilities, the other claimed to have been bitten by a copperhead snake on 7 occasions at 4 separate healthcare facilities. A 3rd patient complained of lionfish envenomation with no tissue reaction and was refused analgesia. Inconsistent clinical presentations of envenomations may signal drug-seeking behaviors.

Adult↗