Do rapid comprehensive urine drug screens change clinical management in children?

CONTEXT: Multiple studies have concluded that urine drug screens rarely change clinical management. The rapid comprehensive urine drug screen (RCUDS) at our institution detects over 300 substances using a combination of EIA and GC/MS and typically takes 2-5 h for completion. OBJECTIVE: We sought to determine whether this RCUDS altered management in the pediatric population. METHODS: All patients >1 month and <18 years of age in which a RCUDS was completed from 1 January 2012 to 31 December 2012 were eligible for the study. Assuming that clinical management would not be altered in at least 90% of cases with a confidence interval of 95%, an alpha error of 5%, we calculated a sample size of 122 cases to ensure adequate study power. Four board-certified medical toxicologists reviewed 160 cases. Cases were assigned to the toxicologists based on a random-number generator. In addition, each toxicologist reviewed 12 random cases from the other three toxicologist's cases to determine inter-rater reliability. All four toxicologists reviewed any case in which a RCUDS was believed to have changed management. RESULTS: A total of 908 RCUDS were performed during the study period, and 160 were selected for study. Mean age was 10.5 years; male = 83, female = 77. Most were ordered from the ED (101/160 = 63%), followed by the inpatient unit (36/160 = 23%), outpatient (14/160 = 9%), and ICU (9/160 = 6%). 111/160 (69%) had a history of ingestion. Of the 160 randomly chosen cases, only three cases were found in which overall clinical management was altered based on the results of the RCUDS. All three cases were children <3 years old with a RCUDS positive for amfetamines. In all the three cases, police, Division of Family Services (DFS), and social work were involved. In no case did the acute clinical management change occurred due to the results of the RCUDS. CONCLUSIONS: The RCUDS rarely changed management in patients at our institution. Further study is warranted.

Evaluation of an Alternative Intravenous N-Acetylcysteine Regimen in Pediatric Patients.

OBJECTIVE: Conventionally, intravenous N-acetylcysteine (IV-NAC) administration is a 3-bag regimen administered over the course of 21 hours, which increases the risk of reconstitution and administration errors. To minimize errors, an alternative IV-NAC regimen consists of a loading dose (150 mg/kg) followed by a maintenance infusion (15 mg/kg/hr) until termination criteria are met. The aim was to determine the clinical outcomes of an alternative IV-NAC regimen in pediatric patients. METHODS: A retrospective review of pharmacy dispensing records and diagnostic codes at a pediatric hospital identified patients who received alternative IV-NAC dosing from March 1, 2008, to September 10, 2012, for acetaminophen overdoses. Exclusion criteria included chronic liver disease, initiation of oral or other IV-NAC regimens, and initiation of standard IV-NAC infusion prior to facility transfer. Clinical and laboratory data were abstracted from the electronic medical record. Descriptive statistics were utilized. Clinical outcomes and adverse drug reaction incidences were compared between the alternative and Food and Drug Administration (FDA)-approved IV-NAC regimens. RESULTS: Fifty-nine patients (mean age 13.4 ± 4.3 years; range: 2 months-18 years) with acetaminophen overdoses were identified. Upon IV-NAC discontinuation, 45 patients had normal alanine transaminase (ALT) concentrations, while 14 patients' ALT concentrations remained elevated (median 140 units/L) but were trending downward. Two patients (3.4%) developed hepatotoxicity (aspartate transaminase/ALT > 1000 units/L). No patients developed hepatic failure, were listed for a liver transplant, were intubated, underwent hemodialysis, or died. Two patients (3.4%) developed anaphylactoid reactions. No known medication or administration errors occurred. Clinical outcome incidences of the studied endpoints with the alternative IV-NAC regimen are at the lower end of published incidence ranges compared to the FDA IV-NAC regimen for acetaminophen overdoses. CONCLUSIONS: This alternative IV-NAC regimen appears to be effective and well tolerated among pediatric patients when compared to the FDA-approved regimen. It may also result in fewer reconstitution and administration errors, leading to improved patient safety.

Buyer Beware: Pitfalls in Toxicology Laboratory Testing.

Urine drug screens are commonly used in various clinical settings and situations. Immunoassays are the most commonly available method of testing for urine drug screens in hospitals. Although convenient, immunoassays are prone to false positive and false negative results. It is important for the health care provider to understand the principles of the laboratory methods involved with urine drug screens as this will help guide appropriate result interpretation and therefore improve clinical care.

Acute acepromazine overdose: clinical effects and toxicokinetic evaluation.

INTRODUCTION: Acepromazine is a phenothiazine that is used exclusively in veterinary medicine for multiple purposes. Human overdoses are rarely reported and toxicokinetic data has never been reported. We present a case of intentional acepromazine overdose resulting in central nervous system and cardiovascular toxicity with confirmatory toxicokinetic data. CASE REPORT: A 54-year-old woman intentionally ingested 950 mg of her dog's acepromazine. Within 3 h of ingestion, she developed central nervous system and respiratory depression along with hypotension requiring non-invasive ventilation and vasopressors. Clinical toxicity resolved over the following 8 h. Serial plasma acepromazine levels were determined using gas chromatography/mass spectrometry. The initial acepromazine level (1-h post-ingestion) was 63 ng/ml. Follow-up levels at 8-, 10.5-, and 13.5-h post-ingestion were 8.9 ng/ml, 7.6 ng/ml, and 6.3 ng/ml, respectively. DISCUSSION: Human acepromazine toxicity is rarely reported but results in clinical toxicity (central nervous system depression, respiratory depression, hypotension) are similar to other phenothiazines. Compared to other phenothiazines, it appears to have a short elimination half-life that may account for the brief duration of clinical toxicity with relatively rapid improvement. No significant human cardiac toxicity has been reported. Treatment is supportive. CONCLUSION: This case highlights the unique toxicity of acepromazine in demonstrating rapid improvement of severe toxicity within 8 h consistent with a short elimination half-life.

Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

BACKGROUND: During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. METHODS: Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. RESULTS: Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 µg/ml (n = 91, range <0.002-0.051 µg/ml) and 0.02 µg/ml (n = 32, range <0.004-0.069 µg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %). CONCLUSION: Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Two successive necrotic lesions secondary to presumed loxosceles envenomation.

Brown recluse spider (Loxosceles reclusa) envenomations with subsequent necrotic skin lesions occur infrequently, and systemic loxoscelism is rarer still. We report a case of 2 successive developing necrotic lesions, each on adjacent medial aspects of the legs, secondary to presumed Loxosceles envenomation. A 31-year-old man with no significant past medical history presented to the emergency department with 2, large, necrotic lesions, 1 on each medial thigh. They had progressed over the course of 1 month from small blisters to large necrotic lesions with eschar. He underwent surgical debridement without skin grafting with no further complications. Bites from recluse spiders that progress to necrosis usually present as single lesions. The differential diagnoses for a necrotic skin lesion is large. The presence of more than 1 lesion argues against Loxosceles envenomation; however, in the absence of underlying infection, systemic diseases, immunodeficiency, or malignancy, the diagnosis must be considered if the case presents in an endemic area. Brown recluse spiders rarely bite multiple times, thus confounding the diagnosis of an already nonspecific clinical finding.

Bilateral patellar tendon ruptures without predisposing systemic disease or steroid use: a case report and review of the literature.

Simultaneous bilateral patellar tendon rupture occurs rarely and is even rarer in patients without systemic disease or predisposing conditions. We present a case of bilateral, midsubstance patellar tendon ruptures along with a partial anterior cruciate ligament tear from a fall from a standing height in an otherwise healthy adult without any predisposing conditions. Most patients that sustain a tendon rupture have risk factors for tendonopathy including chronic renal disease, systemic lupus erythematosus, rheumatoid arthritis, or exposure to medications (such as corticosteroids or fluoroquinolones). Currently, there are approximately 50 reported cases of bilateral patellar tendon rupture in the scientific literature; however, only a small minority occurred in patients without any predisposing factors. Most of the reports of a bilateral tendon rupture without systemic disease occurred in the inferior pole of the tendon, with only a few of these occurring in the midsubstance. Because of the rarity of this event in a patient without systemic disease, this condition is often misdiagnosed. Emergency physicians should maintain a high degree of suspicion in those patients with concerning clinical and/or radiographic findings.

Transportation-related hazardous materials incidents and the role of poison control centers.

BACKGROUND: Department of Transportation (DOT) mandates reporting of all serious hazardous materials incidents. Hazardous material exposures may result in secondary contamination of emergency departments, or delayed clinical effects. Poison control centers specialize in the management of patients exposed to toxic substances; however, poison control center notification is not required. PURPOSE: The objective is to determine the frequency of poison control center notification after serious hazardous materials incidents when patients were transported to a hospital. METHODS: A retrospective analysis was conducted of serious hazardous materials incidents as reported by DOT, matched with data from the American Association of Poison Control Centers from 2002 through 2006 that involved patient transport. Incidents were divided into four groups: those reported to a poison control center within 0-360 minutes of the incident; those reported within 361-1440 minutes of the incident; those reported within 1441-4320 minutes of the incident; and no poison control center notification. Analyses were performed on variables including date, time, substance, and time to notification. Data were received in January 2008. RESULTS: One hundred fifty-four serious incidents met inclusion criteria. One hundred thirty-four incidents (87%) occurred without poison control center notification. Poison control centers were notified in 20 incidents (12.9%); 15 incidents (9.7%) were reported within 0-360 minutes of the incident (M=115 minutes, range=5-359 minutes); four incidents (2.6%) were reported within 361-1440 minutes of the incident (M=652 minutes, range=566-750 minutes); and one incident (0.7%) was reported after 4320 minutes following the incident. CONCLUSIONS: Most serious hazardous materials incidents involving patient transport are not reported to poison control centers. Opportunities exist to increase utilization of poison control center resources without increasing financial burdens of the hazardous materials incident.

The role of a poison control center in identifying and limiting an outbreak of foodborne botulism.

Many poison control centers partner with public health agencies to handle weekend and after-hours consultations and emergencies. This event describes the effective use of poison control center capabilities in identifying and limiting an outbreak of foodborne botulism. On September 8, 2006, the poison control center received a call regarding a man aged 77 years admitted to a hospital neurology service with dysarthria, dysphagia, and weakness. The poison control center was contacted regarding a concern for botulism. Further information revealed that the patient's wife and a friend had similar symptoms and had eaten together on the previous night. All three sought treatment at different hospitals. The poison control center successfully located the other two patients and provided information regarding the treatment of botulism. In addition, the poison control center notified the on-call local public health official and the CDC for the release of botulinum antitoxin. Public health officials were informed of our concerns for a foodborne outbreak given the common meal. Their investigation determined that the source of botulism was carrot juice.

Metformin overdose with a resultant serum pH of 6.59: survival without sequalae.

Metformin, widely used in the treatment of diabetes mellitus, is known to cause lactic acidosis in both therapeutic use and after an overdose. We report the case of a 40-year-old woman who claimed to have ingested between 75 and 100 grams of metformin and subsequently developed severe lactic acidosis. She eventually developed a peak serum lactate level of 40.0 mmol/L and a serum pH nadir of 6.59 and became obtunded, hypotensive, and hypothermic. After aggressive supportive therapy with mechanical ventilation, vasopressor agents, sodium bicarbonate, and hemodialysis, her metabolic derangements steadily improved and she made a complete recovery without any residual sequelae. Her admission serum metformin concentration was later determined to be 160 microg/mL (therapeutic range is 1-2 microg/mL). There are several case reports and case series describing lactic acidosis secondary to metformin ingestion, although the exact mechanism remains unclear. The overall management of metformin overdose is reviewed. This case represents the largest reported amount of ingested metformin, the lowest serum pH, and the highest serum lactate concentration in any intentional metformin overdose survivor in the literature. Despite potentially lethal metabolic derangements, such patients can survive with aggressive supportive care.

Management of the poisoned patient.

Poisoning is common and results in significant morbidity and mortality. The emergency physician should approach the evaluation and management of the poisoned patient with an unknown exposure in a stepwise fashion. Clues from the history, physical exam, and laboratory studies can often lead the emergency physician to the correct diagnosis. Gastrointestinal decontamination should not be performed routinely and its use should be individualized in each patient. Poison centers and toxicologists can serve as a valuable resource in the management of the poisoned patient.

Populations at risk for intubation nonattempt and failure in the prehospital setting.

OBJECTIVES: Pediatric cardiac arrest patients and adult traumatic arrest patients are perceived as more difficult to endotracheally intubate than adult cardiac arrest patients. The study hypothesis was that these populations were at higher risk of endotracheal intubation failure compared with adult cardiac arrest patients and that paramedics would more frequently defer attempts to intubate these patients. METHODS: This was a retrospective, observational study analyzing oral endotracheal intubations on pediatric cardiac arrest, adult traumatic arrest, and adult cardiac arrest patients over 66 months. Homogeneity of intubation nonattempt and endotracheal intubation failure was studied with chi-square analysis. Relative risks (RRs) with 95% confidence intervals (CIs) were used to compare pediatric cardiac arrest with adult traumatic arrest with adult cardiac arrest nonattempt rates and endotracheal intubation failure rates. RESULTS: 2,669 oral endotracheal intubations were included. There was a significant difference in intubation nonattempts and intubation failure between the combined pediatric cardiac arrest and adult traumatic arrest groups and the adult cardiac arrest cohort (RR 7.24, 95% CI 5.73, 9.16 for nonattempt; RR = 2.33, 95% CI 1.93, 2.83 for intubation failure). Both groups individually showed significant risk for intubation nonattempt and endotracheal intubation failure compared with adult cardiac arrest, with the pediatric cohort at higher risk for failure and the adult traumatic arrest cohort at higher risk for nonattempt. CONCLUSIONS: There was significant risk of intubation nonattempt and intubation failure in the pediatric cardiac arrest and adult traumatic arrest cohorts compared with the adult cardiac arrest population, with the pediatric cohort being at particularly high risk for intubation failure and the adult traumatic arrest cohort at higher risk for nonattempt.