Brandon K. Wills

Intoxication From Smoking “Spice”

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The author has stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement.

Can acute overdose of metformin lead to lactic acidosis

INTRODUCTION Metformin-associated lactic acidosis (MALA) is well described in patients taking therapeutic metformin who develop renal failure or other serious comorbid conditions. Metformin-associated lactic acidosis from acute overdose has also been described in case series but is debated by some clinicians, arguing that metformin overdose does not cause lactic acidosis. Our aim was to perform a multicenter poison control database review to determine if MALA can occur in mono-overdose patients with no comorbid conditions. METHODS This was a retrospective chart review of the Illinois and Washington Poison Centers between the 2001-2006 and 1999-2006 periods, respectively. Metformin overdoses that were referred to health care facilities were categorized into mono-overdose with or with out MALA and polypharmacy overdose with or without MALA. RESULTS The overall prevalence of MALA was 14 (3.5%) of 398 cases referred to a health care facility. Metformin-associated lactic acidosis occurred in 9.1% of mono-overdose and in 0.7% of polypharmacy overdose patients referred to health care facilities and was 16% for intentional mono-overdoses. There was one death of 132 mono-overdoses referred to health care facilities. CONCLUSIONS Apparent metformin mono-overdose is associated with MALA. Dosages that place patients at risk for MALA will require additional study.

Sildenafil citrate ingestion and prolonged priapism and tachycardia in a pediatric patient

Introduction. Little is known about the toxicity of sildenafil overdose in the pediatric population. We present a case of prolonged priapism and tachycardia due to unintentional sildenafil overdose in a child. Case report. A 19-month-old male ingested up to six 50 mg Viagra tablets 45 minutes prior to presentation at the emergency department. Initial vital signs included temperature 98.2°F, blood pressure 90/58 mmHg, heart rate 140, respirations 20, and oxygen saturation of 100% on room air. The child weighed 10.4 kg. Physical exam revealed a happy, smiling, laughing toddler who was cooperative with all aspects of his exam. He had mild facial flushing and an erect penis which was normal in color and had a capillary refill of two seconds. Precordial palpation did not show evidence of increase dynamic force, his heart sounds were regular, and no ectopy was noted. His peripheral pulses were strong and regular in all four extremities. No gastrointestinal decontamination was performed. The patient was started on maintenance IV fluids and admitted to the pediatric floor for observation. The patient had a non-painful tumescent penis and mild tachycardia for about 24 hours post-ingestion. The child never had pain from the constant erection. Sildenafil concentration drawn approximately seven hours after ingestion was 3900 ng/ml (reporting limit 24 ng/ml) and N-desmethylsildenafil level was 1700 ng/ml (reporting limit 24 ng/ml). Conclusion. This case of pediatric sildenafil ingestion (up to 30mg/kg) initially resulted in facial flushing and priapism. The child had asymptomatic tachycardia and prolonged priapism that persisted until hospital discharge approximately 24 hours after ingestion. The erection was non-painful and required no urologic intervention, most likely representing a high flow state. In this ingestion, only supportive care was required.

Evaluation of a new nonnvasive device in determining hemoglobin levels in emergency department patients.

Introduction: The Masimo Radical-7 Pulse CO-Oximeter is a medical device recently approved by the US Food and Drug Administration that performs noninvasive oximetry and estimated venous or arterial hemoglobin measurements. A portable, noninvasive device that rapidly measures hemoglobin concentration could be useful in both austere and modern hospital settings. The objective of this study is to determine the degree of variation between the devices estimated hemoglobin measurement and the actual venous hemoglobin concentration in undifferentiated emergency department (ED) patients. Methods: We conducted a prospective, observational, cross-sectional study of adult patients presenting to the ED. The subjects consisted of a convenience sample of adult ED patients who required a complete blood count as part of their care in the ED. A simultaneous probe hemoglobin was obtained and recorded. Results: Bias between probe and laboratory hemoglobin measurements was –0.5 (95% confidence interval, – 0.8 to –0.1) but this was not statistically significant from 0 (t0.05,124 = 0.20, P > 0.5). The limits of agreement were –4.7 and 3.8, beyond the clinically relevant standard of equivalency of ± 1 g/dL. Conclusion: These data suggest that noninvasive hemoglobin determination is not sufficiently accurate for emergency department use.

The effect of amifostine, a cytoprotective agent, on paraquat toxicity in mice

BackgroundParaquat (PQ) is a highly poisonous herbicide with a variety of toxic effects, most notably pulmonary fibrosis. In alveolar epithelial cells, it is converted to a PQ radical and subsequently generates other reactive species resulting in lipid peroxidation and cell destruction. Amifostine is a thiophosphate prodrug approved by the FDA for the prevention of toxicities associated with cisplatin and therapeutic radiation. When amifostine is converted to an active metabolite (WR-1065), it functions as an oxygen and DNA radical scavenger that has been shown to protect against lipoperoxidation. The aim of this study was to determine whether amifostine improves survival or lung injury resulting from PQ toxicity.MethodsSwiss mice (n = 23 per group) were given an approximate LD75 dose of PQ intraperitoneal (60 mg/kg). Thirty minutes prior to PQ injection, group 1 was pretreated with 200 mg/kg of amifostine subcutaneously (s.c.). Subsequent doses of amifostine at 75 mg/kg were administered 4 hours after PQ injection, and injections continued every 8 hours for a total of 6 doses (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 2 received 200 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 75 mg/kg were administered every 8 hours (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 3 received 100 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 30 mg/kg were administered every 8 hours (cumulative dose: 250 mg/kg). Group 4 received equivolume injections of sterile 0.9% saline s.c. at the same time intervals. We removed lungs from all mice for histologic analysis and injury scoring.ResultsThe number of surviving mice in groups 1, 2, 3, and 4 were 17, 18, 17, and 17 respectively. The Kaplan-Meier with log rank analysis showed no differences in survival. Lung injury scores did not differ between treatment groups and the control group for either dead or surviving mice.ConclusionAmifostine does not appear to improve survival or lung injury due to PQ toxicity at the doses administered.

Factitious lithium toxicity secondary to lithium heparin-containing blood tubes.

IntroductionLithium concentrations analyzed from blood collected in inappropriate tubes may lead to misdiagnosis and lead to unnecessary hospitalization and intervention. We sought to assess the magnitude of falsely elevated lithium levels in green top lithium heparin-containing blood tubes.MethodsSerum lithium concentrations from two types of commonly used standard green top tubes were evaluated against a control tube. Blood samples obtained from 5 healthy volunteers who have never ingested pharmaceuticals containing lithium were aliquoted into a control serum separator tube (SST), a light green heparin-containing tube, and a dark green heparin tube at the following volumes: full draw, 2cc, and 1cc. Serum lithium levels in lithium heparin blood tubes were compared to standard blood tubes.ResultsAll levels are reported as mmol/L. Mean serum lithium level for the control was 0.16 [range: 0.1–0.2]. Levels for the light-green tubes at full-draw, 2cc, and 1cc were 1.05 [1.0–1.1], 1.99 [1.68–2.3], and 3.31 [2.8–4.2] respectively. Levels for the dark-green tubes at full-draw, 2cc, and 1cc were 1.07 [1.0–1.14], 2.35 [2.1–2.55], and 4.04 [3.8–4.4] respectively.ConclusionsFalsely elevated lithium levels may occur when using green-top lithium containing blood tubes and may contribute as much as 4 mmol/L to the level in tubes not completely filled.

A continuing black hole? The FDA boxed warning: An appeal to improve its clinical utility

The boxed warning is increasingly utilized by the Food and Drug Administration (FDA) as a clinical warning to prescribers of dangerous adverse drug reactions. As these warnings have expanded, we feel the utility and application of boxed warnings are becoming more nebulous. The use of drugs following issuance of a boxed warning has been variable. Droperidol sales decreased 10-fold in the year following the warning, yet there has been essentially no change in the methadone usage over a similar time period after its boxed warning. Including more information, such as estimation of incidence for the adverse drug reaction, would be more clinically useful to the prescriber. Reasonable standards using supplemental databases outside of the FDA (such as national poison center data) could be helpful in developing an integrated and balanced approach to boxed warnings.

Compliance with poison center fomepizole recommendations is suboptimal in cases of toxic alcohol poisoning.

We sought to examine hospital compliance with poison center antidotal alcohol dehydrogenase inhibition recommendations in cases of ethylene glycol (EG) and methanol (ME) ingestion. A 2-year analysis of all potential EG and ME ingestion cases reported to a regional poison center was conducted. Excluded from analysis were exposures without an ingestion, without a confirmatory EG or ME serum assay, or without complete medical charting. During the study period, 579 EG or ME exposures were reported to the poison center: 133 cases met study eligibility as an ingestion. Of the 133 cases, 102 (77%) had complete data and were included in the analysis. Immediate alcohol dehydrogenase inhibition was recommended by the poison center in 79 of the 102 cases. Fomepizole was recommended in 61/79 (77%); ethanol was recommended as an alternative therapeutic choice in 32/61 (52%) of these cases if fomepizole was not immediately available. Ethanol alone was recommended in 18/79 (23%). Fomepizole was eventually administered in 39/61 (64%) cases where recommended. The mean time to antidote administration was 3 times longer in cases where a choice in antidote was given [57 min (95% confidence interval, 43-70) vs. 146 min (95% confidence interval, 93-200)]. Despite its ease of administration, fomepizole is used less frequently than recommended by poison center staff. Delays to antidote administration occurred more commonly in cases where the poison center gave a choice in antidotal therapy.

Airway compromise in children exposed to single-use laundry detergent pods: a poison center observational case series.

INTRODUCTION Single-use laundry detergent pods (LDPs) were introduced to the United States in 2010 but had been available in Europe as early as 2001. Case reports of unintentional exposures noted vomiting, ocular injuries, respiratory depression, and central nervous system depression. We summarize clinical effects from unintentional LDP exposures reported to a single poison center over 15 months. METHODS Electronic poison center records were searched using verbatim field and both product and generic codes to identify laundry pod exposures from January 1, 2012, through April 9, 2013. Clinical effects were abstracted to a database and summarized using descriptive statistics. RESULTS We identified 131 cases between March 2012 and April 2013. Median (interquartile range) age was 2.0 (1.5) years with 4 adult cases; all were coded as unintentional. The most common route was ingestion (120) followed by ocular (14) and dermal (6). Some patients had multiple routes of exposure. Of ingestion exposures, 79 (66%) were managed at home; and 41 (34%) were evaluated in a hospital, of which 9 patients were admitted. The median (interquartile range) age of admitted patients was 1.4 (1.1) years. Relevant findings in these admitted children included emesis (78%), central nervous system depression (22%), upper airway effects (56%), lower respiratory symptoms (33%), seizure (n = 1), and intubation (67%). One child with emesis initially managed at home was subsequently intubated for respiratory distress. DISCUSSION Exposure to LDP can cause significant toxicity, particularly in infants and toddlers. Compared to traditional detergents, clinicians should be aware of the potential for airway compromise following exposure to LDP.

Analysis of suspicious powders following the post 9/11 anthrax scare.

BackgroundFollowing the 9/11 terrorist attacks, SET Environmental, Inc., a Chicago-based environmental and hazardousmaterials management company received a large number of suspicious powders for analysis.MethodsSamples of powders were submitted to SET for anthrax screening and/or unknown identification (UI). Anthrax screening was performed on-site using a ruggedized analytical pathogen identification device (R.A.P.I.D.) (Idaho Technologies, Salt Lake City, UT). UI was performed at SET headquarters (Wheeling, IL) utilizing a combination of wet chemistry techniques, infrared spectroscopy, and gas chromatography/mass spectroscopy. Turnaround time was approximately 2–3 hours for either anthrax or UI.ResultBetween October 10, 2001 and October 11, 2002, 161 samples were analyzed. Of these, 57 were for anthrax screening only, 78 were for anthrax and UI, and 26 were for UI only. Sources of suspicious powders included industries (66%), U.S. Postal Service (19%), law enforcement (9%), and municipalities (7%). There were 0/135 anthrax screens that were positive.ConclusionsThere were no positive anthrax screens performed by SET in the Chicago area following the post-9/11 anthrax scare. The only potential biological or chemical warfare agent identified (cyanide) was provided by law enforcement. Rapid anthrax screening and identification of unknown substances at the scene are useful to prevent costly interruption of services and potential referral for medical evaluation.