The influence of collection site and methods on postmortem morphine concentrations in a porcine model.

This study was to determine the relationship of antemortem to postmortem morphine concentrations in heart and femoral blood in a porcine model following acute intravenous opiate overdose. The study involved 20 swine; each was sacrificed 10 min after injection of 2 mg/kg body weight of morphine. Drug concentrations were assayed from vitreous humor and blood isolated from the femoral vein and artery and left and right ventricles at various times postmortem. Comparisons were made between antemortem and postmortem values to determine agreement and reliability. Both free and total postmortem values varied significantly among animals, sampling sites, and over time. Free postmortem values were generally higher in comparison with antemortem values, whereas postmortem total morphine values were similar to or slightly lower than antemortem values. The effect of time on postmortem values was small. These results demonstrate a significant amount of variability in free and total morphine measurements both over time and within and between sites. Furthermore, a comparison of antemortem to postmortem values demonstrates a lack of consistency relative to the dose of morphine administered. Concentrations of morphine in the femoral vein were typically the lowest observed. This observation is not surprising given the transformation that occurs prior to the drug reaching the femoral vein. Values associated with diffuse tissues, relative to femoral veins, demonstrate more stochastic variation.

The influence of site of collection on postmortem morphine concentrations in heroin overdose victims.

When assaying for postmortem morphine concentration, significant site sampling variability exists between central and peripheral sampling sites and even within sampling regions of the body. To study the variation, 76 suspected heroin overdoses were identified. Each had femoral artery (FA) and vein (FV), left and right ventricle and pooled heart blood samples obtained at autopsy. Forty-four tested positive for morphine. Morphine concentrations were determined by gas chromatography/mass spectrometry, with sampling site differences reported as log-transformed ratios and compared by signed rank test. The mean FA to FV ratio for total morphine was 1.2 (range 0-4.5). The ratio for left heart to right heart total morphine was 1.1 (range 0.4-3.2). Left ventricular to FV total morphine ratio was 2.0 (range 0.6-6.9). In these opioid overdose deaths, FA and FV morphine concentrations are usually similar, although up to 4.5-fold differences were noted. Centrally obtained morphine concentrations are on average twice as high compared with peripheral morphine concentrations. Left and right ventricular morphine concentrations were usually similar, although up to 3.2-fold differences were noted (left side higher).

Assessment of urinary metals following exposure to a large vegetative fire, New Mexico, 2000.

INTRODUCTION: In May 2000, a vegetative fire burned 47,000 acres in northern New Mexico, including 7500 acres of land administered by the Los Alamos National Laboratory. We evaluated potential human exposures from the fire. METHODS: We surveyed two populations (firefighters and the general population) in four cities for urine heavy metal concentrations. Reference concentrations were based on the Third National Health and Nutrition Examination Survey (NHANES III). Multivariate linear regression assessed the association of urinary metal concentrations with smoke exposure. We also performed isotopic analysis of uranium and cesium on a subset of specimens. RESULTS: A total of 92 firefighters and 135 nonfirefighters participated. In both populations, urinary nickel, cesium, chromium, and uranium concentrations were greater than expected compared with NHANES III reference values. No values required immediate medical follow-up. Regression analysis demonstrated that for National Guard members, arsenic and cadmium levels were significantly related to smoke exposure, and for firefighters, cesium and arsenic levels were significantly related to exposure; however, only for cesium in National Guard members was this association in the positive direction. Isotopic analysis demonstrated that the cesium and uranium were naturally occurring. CONCLUSIONS: Some people had spot urine metal concentrations above nationally derived reference values, and values for some metals were associated with smoke exposure. These associations had little public health or clinical importance. Studies of exposures resulting from vegetative fires are difficult, and careful consideration should be given to the technical and communication processes at the outset of a fire exposure investigation. Recommendations for future investigations include testing as soon as possible during or after a fire, and early clinical consultation with a medical toxicologist.

Do poison center guidelines adversely affect patient outcomes as triage referral values increase?

BACKGROUND: The purpose of this study was to determine whether patient outcomes were adversely affected as healthcare referral values increased for two common poisonings: acute, unintentional acetaminophen (APAP) poisonings and acute, unintentional iron (Fe) poisonings. We hypothesized that symptom rates would increase with high referral values. METHODS: Qualifying 1997 exposures were separated by substance (APAP or Fe) and then further stratified into three healthcare referral value ranges. Symptomatic and asymptomatic patients were totaled for each stratum. Expected vs. observed distributions of symptomatic and asymptomatic patients across triage referral strata for a given substance and treatment location were compared using chi-square test for independence. The Wilcoxon-Mann-Whitney test was used to compare the distribution of patients across referral strata for home vs. healthcare facility locations for a specific substance. RESULTS: There were no statistically significant differences in the distribution of symptomatic patients within referral value strata for APAP or for Fe. There was also no difference in distribution of symptomatic patients across strata when comparing home vs. healthcare facility for APAP and Fe. CONCLUSION: Referral values as high as 201 mg/kg for APAP and 61 mg/kg for Fe do not appear to adversely affect patient outcomes.

Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution.

A 29-year-old woman ingested 8 g of nortriptyline and presented to the emergency department with coma, hypotension, and widened QRS interval. After intubation, gastric lavage, hyperventilation, and therapy with intravenous normal saline solution, sodium bicarbonate boluses (rapid intravenous push), and high doses of norepinephrine and dopamine, she transiently improved, only to deteriorate on arrival to the ICU. Because her arterial pH was alkalemic at 7.5 at this point, she was given additional sodium in the form of 200 mL of 7.5% NaCl by means of rapid intravenous infusion (intravenous push) to treat hypotension and widening QRS interval with ventricular ectopy. A continuous 12-lead ECG documented narrowing of her QRS interval with concomitant improvement of hypotension within 3 minutes of hypertonic saline solution infusion. Hypertonic saline solution should be considered for wide complex QRS and hypotension caused by tricyclic antidepressant-induced cardiotoxicity that is unresponsive to standard therapies.

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.

Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom.

Allergic reactions are the most commonly reported adverse events after administration of antivenoms. Conventional horse serum-based crotalid antivenom used in the United States (Antivenin [Crotalidae] polyvalent) can lead to both immediate and delayed hypersensitivity reactions. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) has recently been approved for use in the United States. Experience from premarketing trials of this product and in the administration of other types of Fab, such as in digoxin poisoning, has demonstrated these fragments to be safe and effective, with a low incidence of sequella; however, allergic reactions can occur when any animal-protein derivatives are administered to human subjects. We report in detail the nature and course of allergic reactions that occurred in 4 patients treated with FabAV. Cases of anaphylaxis, acute urticaria, angioedema, and delayed serum sickness are described. All reactions were easily treated with some combination of antihistamines, epinephrine, and steroids, with prompt resolution of signs and symptoms enabling further dosing of antivenom as required. Several of these cases may have resulted from batches of antivenom contaminated with Fc fragments. The overall incidence of immediate and delayed allergic reactions to this product appears so far to be lower than that reported with conventional whole-immunoglobulin G (IgG) antivenom, but postmarketing surveillance is warranted.

Octreotide: an antidote for sulfonylurea-induced hypoglycemia.

STUDY OBJECTIVES: Sulfonylurea agents are widely used as therapy for hyperglycemia in type 2 diabetes mellitus. In overdose, these agents can produce sustained and profound hypoglycemia that is refractory to treatment with dextrose alone. Our objective was to determine whether treatment with octreotide decreases glucose requirements and the number of hypoglycemic episodes in patients with sulfonylurea-induced hypoglycemia. METHODS: We retrospectively reviewed the charts of patients treated with octreotide for sulfonylurea-induced hypoglycemia from 1995 through 1998. The study took place in a large urban teaching hospital in the United States. We measured the number of episodes of hypoglycemia reported and the amount of dextrose used before and after treatment with octreotide. Using a failure time analysis, we compared the risk of hypoglycemia before and after octreotide administration. RESULTS: The age range of the 9 patients was 20 to 65 years. Six patients ingested glyburide and 3 ingested glipizide. The number of hypoglycemic events recorded per patient before octreotide (mean 3.2) was greater than the number of hypoglycemic events recorded per patient after octreotide (mean 0.2, P =.008). Similarly, the number of ampules of 50% dextrose administered per patient before octreotide (mean 2.9) was greater than the number of ampules administered per patient after octreotide (0.2, P =.004). The risk of recurrent hypoglycemia before octreotide treatment was 27 times the risk of the group after octreotide treatment (P <.001). Stabilization of blood glucose concentration and cessation of rebound hypoglycemia occurred immediately after the administration of octreotide in all 9 patients. CONCLUSION: Octreotide appears to be safe and effective in preventing rebound hypoglycemia after sulfonylurea ingestion. Octreotide in combination with dextrose should be considered for first-line therapy in the treatment of sulfonylurea-induced hypoglycemia.