Susan C. Smolinske

Adverse events associated with dietary supplements: an observational study

BACKGROUND Adverse events associated with dietary supplements are difficult to monitor in the USA, because such products are not registered before sale, and there is little information about their content and safety. METHODS In 1998, 11 poison control centres in the USA recorded details of 2332 telephone calls about 1466 ingestions of dietary supplements, in 784 of which patients had symptoms. We used a multitiered review process (kappa 0.42) to select 489 cases for whom we were at least 50% certain that their negative events were associated with dietary supplements. We aimed to assess the effects of multiple ingredients and long-term use, and collated data for patterns of use and information resources. FINDINGS A third of events were of greater than mild severity. We noted both new and previously reported associations that included myocardial infarction, liver failure, bleeding, seizures, and death. Increased symptom severity was associated with use of several ingredients, long-term use, and age. Paediatric exposures were more often unintentional than were adult ingestions, and treatment of disease was the reason for supplement use in at least 28% of reports. Most products and ingredients were not identified in the information database (Poisindex) used by poison control centres, and specific adverse events were reported variably among five additional sources. INTERPRETATION Dietary supplements are associated with adverse events that include all levels of severity, organ systems, and age groups. Associations between adverse events and ingredients are difficult to verify if a product has more than one ingredient, and because of incomplete information systems. Research into hazards and risks of dietary supplements should be a priority.

The severity of toxic reactions to ephedra: comparisons to other botanical products and national trends from 1993-2002.

Objective. Ephedra is a botanical product widely used to enhance alertness, as a weight loss aide, and as a decongestant. Its reported adverse effects led the Food and Drug Administration (FDA) to ban ephedra-containing products in the United States in 2004. This studys purpose was to compare toxicity from botanical products containing ephedra to nonephedra products. Methods. The Toxic Exposure Surveillance System (TESS), a national poison center database, was utilized to determine the number and outcomes of cases involving botanical products reported from 1993–2002. Cases listing both a botanical product and any other drugs or chemicals were excluded a priori. Ten-year hazard rates (moderate outcomes + major outcomes + deaths per 1000 exposures) were used to compare botanical product categories. Results. There were 21,533 toxic exposures with definitive medical outcomes reported over the 10 yrs where a botanical product was the only substance involved. Of these, 4,306 (19.9%) had moderate or major medical outcomes and there were two deaths, for an overall hazard score of 200 per 1000 exposures. The number of ephedra reports to poison centers increased 150-fold over the 10-yr period. The hazard rate for products that contained only ephedra was 250 per 1000 exposures and 267 per 1000 exposures for products that contained ephedra and additional ingredients; whereas the hazard score for only nonephedra botanical products was 96 per 1000 exposures. The rate ratios for multibotanical products with ephedra (RR 1.33; 95% C.I. 1.27–1.40) and for single-ingredient ephedra products (RR 1.25; 95% C.I. 1.11–1.40) were both two to six times higher than those of other common botanical products. Yohimbe-containing products had the highest hazard score (417) and rate ratio (2.08; 95% C.I. 1.59–2.80). Conclusion. Ephedra-containing botanical products accounted for a significant number of toxic exposures with severe medical outcomes reported to poison centers. Hazard rate analysis suggests poison center–reported events involving ephedra-containing botanical products were much more likely to result in severe medical outcomes than those involving nonephedra-containing botanical products. These data support recommendations by policymakers that the sale of ephedra should be prohibited to protect consumers. Our data suggest that the botanical product, yohimbe, may also be associated with unacceptably high risks of toxicity and should receive close scrutiny from health policymakers.

A case of MAO inhibitor/MDMA interaction: agony after ecstasy

After ingesting 3,4-methylene-dioxy-methamphetamine (MDMA) and the monoamine oxidase (MAO) inhibitor phenelzine, a 50 year old male developed marked hypertension, diaphoresis, altered mental status, and hypertonicity lasting 5-6 hours. This clinical course is typical of interaction between MAO inhibitors and some sympathomimetics including amphetamines. Such interaction has not previously been described involving MDMA. Sympathomimetic-MAO inhibitor interactions can cause excessive release of endogenous bioactive amines (e.g. norepinephrine, serotonin). Hypertensive crisis, intracranial hemorrhage, hypertonicity, and severe hyperthermia have occurred due to sympathomimetic-MAO inhibitor interactions. MDMA shares structural and pharmacologic features with other agents capable of causing this interaction, and this case suggests that MDMA can cause significant toxicity in patients taking MAO inhibitors.

Foxy methoxy: A new drug of abuse

IntroductionIn 1999, a new synthetic tryptamine, 5-MeO-DIPT, became known as a street drug, with the street name of “Foxy” or “Foxy Methoxy”. By February 2003, the DEA reported law enforcement seizures and/or reports of abuse in 12 states. We report a case along with an analysis of poison center data on this new drug of abuse.Case reportA 19-year-old male was brought to the emergency department following ingestion of a larger than his usual dose of Foxy. Upon arrival, he had hallucinations, hypertension, tachycardia, mydriasis, and catalepsy. Symptoms resolved within two hours after administration of lorazepam and he recovered uneventfully.DiscussionThe AAPCC TESS database contained 41 exposures to “Foxy” between April, 2002 and June, 2003; 26 had moderate or major effects, indicating this drug has significant toxic potential. Given the expanding use of this and other club drugs, the spectrum of toxicity from this new agent will continue to be elucidated.

Probable Gastrointestinal Toxicity of Kombucha Tea: Is This Beverage Healthy or Harmful?

Kombucha tea is a health beverage made by incubating the Kombucha “mushroom” in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association.

Review of Parenteral Sulfite Reactions

Sulfiting agents are commonly used in parenteral emergency drugs, including epinephrine, dexamethasone, dobutamine, dopamine, norepinephrine, phenylephrine, procainamide, and physostigmine. Published anaphylactic or asthmatic reactions have been associated with sulfited local anesthetics, gentamicin, metoclopramide, doxycycline, and vitamin B complex. The reactions differ from those caused by foods, in that they have a rapid onset, have no predilection for steroid-dependent asthmatics, and do not always coincide with a positive oral challenge. The mechanism is unknown, but may involve a dose-related reaction with disulfide bonds on sympathetic and parasympathetic receptor membranes. Patients with a history of positive oral challenge to 5-10 mg of sulfite may be at increased risk of developing a reaction to parenteral sulfites. Despite documentation of sensitivity, sulfites should not be withheld from patients experiencing a life-threatening emergency. Non-sulfited alternatives are often available, and should be used preferentially.

IBUPROFEN OVERDOSE IN ADULTS

A prospective study of 63 ibuprofen overdose cases in adults (14 years or older) reported to the Rocky Mountain Poison and Drug Center between March 1987 and February 1988 was done to determine the incidence of renal injury and utility of timed plasma levels. No serious toxicity was noted. No CNS or other significant toxicity was seen with ingestion of less than 3 g. Two patients with normal serum creatinines had minor elevations of the blood urea nitrogen after ingesting 4 and 4.8 g. Timed plasma levels (125 total) from patients without coingestants from this study (48) and previously published reports (77) were compared with a previously described nomogram. The resulting nomogram revision may be useful in determining which initially asymptomatic patients are likely to remain so. Renal function tests are not routinely required for patients ingesting less than 6 g. Four h of observation is sufficient for asymptomatic patients not requiring psychiatric admission. Plasma ibuprofen levels are not required for proper patient management.

Pulmonary toxicity following exposure to waterproofing grout sealer

IntroductionWe report a large number of cases of pulmonary toxicity from 6 regional poison control centers associated with the use of a waterproofing-grout sealer. The identification of this illness occurred by means of the poison control center (PCC) national automated toxicosurveillance.Materials and MethodsThis is a retrospective case review of all cases of pulmonary toxicity following exposure to a waterproofing grout sealer from 6 regional PCCs including Michigan, Kentucky, Utah, Maine, Arizona, and Nebraska. The study period extended from June 1, 2005 to December 1, 2005.ResultsThe vast majority of patients used the product at home (80%). Over half the patients presented within 3 hours of exposure. The most common presenting symptoms were shortness of breath (63%), cough (60%), and chest pain (44%). Wheezing (33%) and rales (23%) were the most common signs of clinical toxicity. One patient required endotracheal intubation. Thirty-seven percent of patients had signs of acute pneumonitis on initial chest x-ray. The mean presenting oxygen saturation was 89.5%. The most common treatment measures used were supplemental oxygen, bronchodilator therapy, oral steroids, and antibiotics. Over half of the study group required hospital admission.ConclusionThe majority of patients in this study were adults using the product at home. Over one-third of patients had an abnormal x-ray upon presentation. Over half of the study group required hospital admission following exposure to this product. Medical professionals should be aware of the potential for pulmonary toxicity due to waterproofing aerosols.

Demand for poison control center services “surged” during the 2003 blackout

Background. Beginning 8/14/03, for 24 hours, the largest geographic power failure in U.S. history occurred. Our Poison Control Center (PCC) catchment area was one of the most severely affected, with most of the population left without electricity, fuel, water pressure, or municipal potable water. The paucity of reports on the impact of disasters on PCC operations led us to summarize our experience. Method. Data sources included 1) Toxicall® human exposures during 8/03 (with comparison to 2002 and to national trends) and 2) an after-action report completed by Specialists-in-Poison Information (SPIs) on duty during the disaster. Results. The average call volume for 8/03 increased by 7.8 %. Significant increases in human exposure and information calls occurred in four categories: gasoline, carbon monoxide, food poisoning, and water contamination. After-action report findings included: vulnerability of PCC operations to interruptions in power supply; lack of redundant communication methods; staffing challenges; and exclusion of PCC staff from hospital disaster plans despite co-location. Conclusion. During the blackout of 2003, there was a measurably increased demand for poison center services. PCC disaster plans should address increased staffing needs during the time of disaster, communication system redundancy, back-up power supply, and SPI needs (food, water, transportation, environmental safety, and rest/rotation).

Consumer perception of household hazardous materials

We evaluated consumer perception of household hazardous materials (HHM) to identify links between storage of HHMs and consumer perception. Methods. 357 telephone surveys were conducted within one county to determine home storage location (high, low, unknown) of 10 substances common to pediatric poisoning. Questions addressed look-alikes, poison information resources, disposal/recycling practices, and the transfer of cleaning products to other containers. Results. Prescription medications were stored in lower elevations than vitamins with iron and OTC ibuprofen or acetaminophen. Products common in poisoning were often stored at low elevations. Poison center (PCC) awareness was modest; 35% stated the PCC would be first choice; 43% chose 911. Nineteen percent indicated they transferred cleaning items to other containers, usually bleach (6.7%), but 29% transferred prescription medications. Conclusion. Results will be utilized to develop a community-specific educational campaign targeted toward lack of awareness of the poison center and reinforcement of proper storage and disposal practices.