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41. Poisoning During Pregnancy: Observations from the Toxicology Investigators Consortium (ToxIC) Case Registry
Finkelstein Y1, Zelner I1, Hutson JR1, Matlow J1, Koren G1, Wax PM2
1Hospital for Sick Children, Toronto, ON, Canada; 2University of Texas Southwestern School of Medicine, Dallas, TX, USA
Background: Poisonings during pregnancy are a particular health concern because they may have serious, life-long implications for the mother and fetus.
Study Aim: To explore recent exposure trends in pregnant women in the United States.
Methods: We identified all cases involving poisoning during pregnancy that were catalogued in the 37 sites of the Toxicology Investigators Consortium (ToxIC) Case Registry of the American College of Medical Toxicology between Jan. 1, 2010 and Dec. 31, 2012. We recorded clinical data including volition, agents involved, management and outcome.
Results: Of 17,529 poisoning cases reported to the ToxIC Registry, 103 (0.6%) involved pregnant women. The most common type of encounter was deliberate self-overdose (54%, with a pharmaceutical agent [46%] and a non-pharmaceutical agent [8%]), followed by unintentional pharmaceutical exposure (10%), and withdrawal (9%). The most common classes of agents consumed were non-opioid analgesics (31%), sedative-hypnotics/muscle-relaxants (18%), opioids (17%), anticonvulsants (10%) and antidepressants (10%). Acetaminophen was ingested in 25% of all cases. Thirty-seven percent of cases involved exposure to multiple drugs and 32% involved exposure to more than one drug class. Seventy-nine patients (77%) were symptomatic. Twenty nine percent manifested a specific toxidrome, with sedative-hypnotic being the most common (13%), followed by a withdrawal toxidrome (5%), mostly from opioids. Central nervous system depression was present in 17% of cases (71% of whom involved sedative-hypnotic/muscle-relaxants). Tachycardia was present in 15% of cases, and 6% developed acetaminophen-induced hepatotoxicity. The most common antidotes administered were N-acetylcysteine (20%), sodium bicarbonate (9%), flumazenil (4%) and physostigmine (4%). All six patients with carbon monoxide therapy underwent hyperbaric oxygen therapy. Twenty-three percent of women did not receive any treatment, despite the fact that 42% of them were symptomatic.
Discussion: Most pregnant women presenting to hospital with acute poisoning were engaged in self-harm or suicidal behavior, and the majority were symptomatic. As roughly half of untreated pregnant women were symptomatic, prospective studies should explore whether pregnant patients are treated less aggressively than their non-pregnant counterparts and pregnancy outcomes.
Conclusion: Most acute poisoning cases in pregnant women are intentional (self-harm) and symptomatic.
42. Vilazodone May Cause Sodium Channel Blockade in Overdose
Fung BJ1, Yanta JH1, King, AM2, Pizon AF1, Menke NB1, Abesamis MG1
1University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Wayne State University, Detroit, MI, USA
Background: Vilazodone (VIIBRYD®), recently FDA approved in 2011 as an antidepressant, has enjoyed rapid popularity due to initial reports of a milder side effect profile. The few reported cases of toxicity of this 5-HT1A partial agonist and selective serotonin reuptake inhibitor (SSRI) have described symptoms consistent with serotonin syndrome. However, none provided confirmatory serum levels or mention cardiac sodium channel blockade as an adverse effect.
Hypothesis: Vilazodone toxicity can cause cardiac sodium channel blockade in overdose.
Methods: This is a single patient chart review. A 15-year-old adolescent boy intentionally ingested 780 mg of vilazodone in a suicide attempt. Three hours after ingestion, the patient exhibited signs of serotonin syndrome including severe agitation, bilateral five-beat ankle clonus, knee hyperreflexia with normal upper extremity reflexes, and tachycardia. An electrocardiogram obtained after transfer to a tertiary care center demonstrated evidence of sodium channel blockade with a QRS duration of 130 ms.
Results: Due to demonstrable sodium channel effects on the ECG, the patient was administered 200 mEq sodium bicarbonate IV bolus and started on an infusion (D5W + 150 mEq NaHCO3 + 40 mEq KCl) at 150mL per hour. Six hours after the initiation of the bicarbonate infusion, the QRS narrowed to 96 ms. At nine hours post ingestion, a serum level of vilazodone was found to be 830 ng/mL (reference normal < 156 ng/mL). The patient was extubated on hospital day (HD) two following return of baseline mental status. He was discharged without sequelae to an inpatient psychiatric hospital on HD three.
Discussion: There are only six cases of reported vilazodone toxicity. Serotonin syndrome has been previously reported, but no cases have reported cardiac toxicity or provided confirmatory vilazodone levels. The ECG changes seen in this case were similar to other known sodium channel blockers in the Vaughan Williams IA and IC anti-dysrhythmics classes. Based on experience with other sodium channel antagonists, we recommend sodium bicarbonate administration as a treatment for QRS widening due to vilazodone toxicity.
Conclusion: This case illustrates the clinical course of a confirmed vilazodone overdose, with emphasis on the development of cardiac toxicity and need for cardiac monitoring.
43. N-Acetylcysteine (NAC) Induced Hyponatremia caused by an EMR Order Set Error
Furmaga J1, Kleinschmidt KC2, Wax PM2
1Parkland Health and Hospital System, Dallas, TX, USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA
Background: Intravenous N-Acetylcysteine (NAC) causes few adverse drug events with anaphylactoid reactions being the most common. A case of hyponatremia from NAC’s hypoosmolar diluent was reported in 1967 but this occurred before electronic medication ordering was commonplace.
Hypothesis: We hypothesize that a poorly constructed electronic medical record (EMR) order set for IV NAC may result in seizures from hyponatremia due to excess free water administration.
Methods: This is a single patient chart review of a 13 month old female with no past medical history who presented to a hospital after ingesting Tylenol Extra Strength. The 4 hour acetaminophen level was 343 mcg/mL and she was started on IV NAC. Twelve hours later, she developed a tonic-clonic seizure with sodium at that time measuring 124 mEq/Liter, a decrease from 142 mEq/Liter at the time of admission. She was treated with hypertonic saline, lorazepam, levetiracetam and had no further seizures. A brain MRI and EEG were normal.
Results: The EMR ordering system did not allow for volume adjustment of NAC for a young child. The NAC dose was correct, however, the diluent volume was a standard amount for an adult but not an 8 kg child, the 1st bag contained 150 mg/kg of NAC in 200 mL of D5W, the 2nd contained 50 mg/kg in 500 mL of D5W, and 3rd contained 100 mg/kg in 1000 mL of D5W (with total of 900 mL given at the time of seizure).
Discussion: Because the 21 hour IV NAC administration involves preparation of 3 different bags, an order set was developed to reduce ordering errors. With the exception of patient's weight, no other aspect of this order set was adjustable (including diluent choice or volume of preparation). These preset values caused the pharmacist to prepare a solution that contained too much free water, decreasing patient’s intravascular sodium and resulting in a seizure.
Conclusion: Development of an order set intended to reduce ordering errors may lead to an adverse drug error if volume of diluent cannot be adjusted for pediatric patients.
44. Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: A Retrospective Cohort Study
Gashlin LZ, Groth CM, Wiegand TJ, Dodds Ashley ES
University of Rochester Medical Center, Rochester, NY, USA
Background: Phenobarbital is a long-acting barbiturate with evidence for use in the treatment of alcohol withdrawal including planned detoxification and symptomatic control during acute withdrawal syndromes. Patients with severe withdrawal or delirium tremens are clinically challenging, requiring high doses of benzodiazepines for prolonged periods placing them at risk for oversedation, mechanical ventilation, and benzodiazepine-induced delirium. Rapid control using phenobarbital loading doses may reduce these risks and improve symptom management.
Research Question: Does the addition of phenobarbital to benzodiazepine therapy improve symptom control and decrease duration of withdrawal?
Methods: This was a retrospective cohort study of patients admitted to an academic medical center. Subjects were identified through electronic medical record reports for intravenous phenobarbital or intravenous/oral benzodiazepine orders for alcohol withdrawal from March 1st, 2011- October 31st, 2012. Included subjects had a diagnosis of alcohol withdrawal, at least 1 Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar ) score > 10, received 1 dose of phenobarbital in the phenobarbital group, and 3 doses of 20 mg diazepam equivalents within 6 hours in the benzodiazepine group. Exclusion criteria included ICU admission for initial treatment and positive urine toxicology screen. The primary endpoint, the proportion of patients 24 hours after initial treatment with a CIWA-Ar score < 10, was compared using Fisher’s Exact. Duration of withdrawal and cumulative doses were analyzed via Mann-Whitney U.
Results: 7 patients in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. 40% in the phenobarbital group versus 23.8% in the benzodiazepine group met the primary endpoint (p = NS, Fisher’s Exact). Secondary objectives appear in the table.
Discussion: Although symptom control at 24 hours was not statistically different between groups, diazepam equivalent doses were significantly decreased with adjunctive phenobarbital treatment. The phenobarbital dose requirement was similar to previously reported doses. Limitations include potential selection bias due to differences in withdrawal severity in the phenobarbital group and small sample size.
Conclusions: Phenobarbital appears to be a safe and effective alternative to benzodiazepines for the treatment of alcohol withdrawal in non-critically ill patients and may be benzodiazepine-sparing.
45. Massive Atenolol and Lisinopril Overdose Treated with Hemodialysis, Impella® Heart Pump Device, ECMO and Endoscopic Decontamination
Heise CW, Graeme KA, Bosak AR
Banner Good Samaritan Medical Center, Phoenix, AZ, USA
Background: Atenolol is a cardioselective beta antagonist. We present a case of a massive atenolol overdose and lisinopril treated with multiple modalities, resulting in an excellent outcome.
Case:A healthy 44 year old woman with a history of depression ingested 90 tablets of atenolol 50 mg/chlorthalidone 25 mg and an unknown quantity of 40 mg lisinopril tablets. These medications were prescribed to her boyfriend. In the ED, SBP was 59 mmHg, HR 49 bpm. She remained hypotensive despite fluid boluses, a glucagon bolus and drip, and a norepinephrine drip. She required intubation for declining mental status. Phenylephrine and epinephrine drips were started upon transfer. Three hours after ingestion, HR was 45 bpm and BP 62/43 mmHg. Examination was otherwise unremarkable. Initial bedside ECHO revealed good contractility. The infusions included: epinephrine at 50 mcg/min, norepinephrine at 100 mcg/min, phenylephrine at 200 mcg/min, and glucagon at 10 mg/hr.She was started on CVVHD. An Impella® LD device and intravenous pacemaker were placed. MAP increased from 60 mmg Hg to 75 mm Hg. EGD was done 16 hours post-ingestion and revealed a large load of pill fragments (picture), which were suctioned and removed. Twenty hours after ingestion, her cardiac output decreased to only that provided by the Impella® device.Five days after admission, the Impella® device was weaned, but the patient was unable to be oxygenated and was placed on ECMO for ARDS. ECMO was used for two days to support her oxygenation. Beta-blockade effects appeared to resolve 5 days into her hospitalization. Vasopressors and mechanical ventilation were weaned by day 7 and 11, respectively. Full renal function and good recovery were complete in 30 days.
Discussion: Atenolol is almost entirely renally excreted. We present levels demonstrating removal with CVVHD. This is the first case reported of using the Impella® device for this overdose. This is the first report of EGD decontamination of atenolol overdose. The large pill fragments burden found and removed from this patient at 16 hours after ingestion is somewhat surprising.
46. Phytophotodermatitis Resulting From Citrus Exposure: A Pediatric Case Series From Central California
Heppner JD, Lee H, Armenian P
University of California San Francisco, Fresno, CA, USA
Background: Psoralens belong to the furocoumarin family, and cause phytophotodermatitis when coupled with ultraviolet light exposure. This phenomenon has been described in case reports from Sweden, Italy, Brazil, United Kingdom and the United States after exposures to wild parsnip, fig leaf tea, hogweed, carrot and citrus.
Methods: This is a consecutive-patient case series of five girls aged 7-11 transferred from an outside facility for specialty burn center evaluation. Symptoms developed 24 hours after playing with limes and lemons near a backyard swimming pool.
Results: The girls had skin findings of large flaccid bullae on an erythematous base over sun-exposed areas, not following any dermatomal distribution. Initially, parents were questioned regarding possible pool chemical exposure and abuse. Two girls required admission to the intensive care burn unit, one was admitted to the floor and two were discharged from the emergency department. Initial treatment for patients 1-3 included pain control with intravenous opioids, use of bacitracin ointment and non-adherant Xeroform® and Adaptic® dressings. Clobetasol ointment was started on hospital day 2 on patients 1-3 and applied during dressing changes. Procedural sedation was required for dressing changes and debridement for patients 1, 2 and 3. Patients 4 and 5 were discharged home with bacitracin ointment and Xeroform® dressings. Following discharge, return visits were required for dressing changes in all 5 patients. Over the next 3 weeks, erythematous areas gradually became hyperpigmented. Plant specimens were identified by local botanists as Key Lime (Citrus aurantifolia) and Lisbon Lemon (Citrus limon).
Discussion: Few phytophotodermatitis outbreaks demonstrate such severity in multiple pediatric patients, requiring transfer to a burn center for management. Optimal management of severe psoralen toxicity is not well established. In these cases, supportive care and topical steroids were used with good result. Oral steroids and silver impregnated dressings may also be considered.
Conclusion: Psoralen phytophotodermatitis diagnosis requires a high index of suspicion and may be initially misdiagnosed as herpes zoster, lymphangitis, chemical burns, poison oak or jellyfish envenomation. Although potential abuse or pool chemical burns was considered in these cases, it became clear that the lesions were actually due to citrus exposure.
47. A Haddon Matrix Model for Prevention of Iatrogenic Opioid Overdose
Janicki AJ1, Beaudoin FL1, McKaig D1, Babu KM2
1Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA; 2University of Massachusetts Medical School, Worcester, MA, USA
Background: Iatrogenic in-hospital opioid toxicity results in a range of adverse drug effects, from sedation to potentially life-threatening CNS and respiratory depression. In order to prevent this avoidable cause of morbidity and mortality, a structured approached is required to identify risk factors for iatrogenic opioid overdose. This investigation aims to identify patient, provider, and systematic factors associated with iatrogenic opioid toxicity in the emergency department (ED).
Research Question: Can the Haddon Matrix, a well-defined injury prevention paradigm, be applied to in-hospital opioid toxicity?
Methods: A case series of iatrogenic opioid overdose from a large urban academic ED was identified through query of ED electronic medical records for ED visits during 10/1/10-12/31/11. Naloxone was used as a surrogate marker of overdose. Cases where prehospital naloxone was given were excluded. Cases of iatrogenic overdose in the ED were identified by naloxone administration after in-ED opioid administration. A committee consisting of a medical toxicologist, emergency physician, and patient safety pharmacist reviewed each case to determine category of harm and root cause of error. Cases were assigned a category of harm based on the National Coordination Council for Medication Error Reporting and Prevention Index [NCC MERP] classification scheme. Cases where harm resulted were used to construct a Haddon Matrix,
Results: A total of 63 cases of iatrogenic opioid overdose were identified. The median age was 57 (Range: 14 – 97), 60% were female, and 42 (67%) were determined to have experienced harm (NCC MERP categories E – H). Contributory factors were discussed for each case, and recorded. Identified patient, provider (vector), and system factors were then used to construct the Haddon Matrix displayed in Table 1.
Conclusions: We describe a Haddon matrix for iatrogenic in-hospital overdose, which identifies several modifiable factors. Focused interventions for high-risk patient populations and clinical settings, and pre-/post-event provider education could be effective at reducing iatrogenic opioid overdose in the ED setting.
48. Improvement and Evolution of a Toxicology Consultation Billing Service
Kamali M, Montante R, Loveland T, Wratni R, Crane PW, Wiegand TJ
University or Rochester Medical Center, Rochester, NY, USA
Background: The University of Rochester Medical Center (URMC) Toxicology Consult Service (TCS) began on January 1, 2010. Adult and pediatric patients receive bedside consultation at two URMC hospitals. All consults are billed under a single board-certified Medical Toxicologist and include inpatient and outpatient (ED and clinic) encounters. We have previously described reimbursement over a one year period (July, 2011 – June, 2012) including average monthly charges, revenue sources and billing codes. Since presenting this data, billing charges and encounter types have increased. In July, 2013, the total one month charges billed by the TCS were $94,508.00.
Research Purpose: Describe the encounter types, billing codes and reimbursement profiles from a TCS.
Methods: A review of consultation service billing records for July 2013 was performed. Encounter types, billing codes, diagnoses and charge profiles, as well as payer breakdown were reviewed. Information is compared to overall fiscal-year 2012-2013.
Results: July 2013 total charges were $94,508 (62% inpatient, 38% outpatient) compared to FY12-13 monthly averages of $50,340 (57% inpatient, 43% outpatient). 597.6 work RVUs were generated. Net collection rate was 86.5% in July 2013 (88.3% average in FY12-13). There were 156 inpatient and 63 outpatient encounters and 15 procedures billed in July 2013 versus 79 inpatient, 39 outpatient and 11 procedures on monthly average FY12-13. A total of 15 different billing codes were used in July 2013. Net collection rate for July 2013 was 86.5% of claims submitted.
Discussion: Over the past several years, URMC has evolved its TCS to a point where significant income is being generated through inpatient and outpatient consultation, as well as clinic visits. However, it should be noted that at our institution this work has been conducted by a single toxicologist who has committed significant time and effort towards success.
Conclusion: A TCS can be supported financially with the appropriate support and structure. This service, when optimally operated can be of great benefit to patients, the community, as well as its associated medical center.
49. Clear and Preventable Danger?: A Haddon Matrix Safety Analysis of Injuries Sustained by Students Working in University Chemistry Laboratories
Koh CH1, Dissanayake VL1,2, Thompson TM1,2
1University of Illinois Hospital & Health Sciences System, Chicago, IL, USA; 2Toxikon Consortium, Chicago, IL, USA
Background: Recent media reports have highlighted the potential danger of working in an academic chemistry laboratory, most memorably with the stories of two students’ deaths at UCLA and Yale. Despite the awareness raised by these events, our own Toxicology service has noted a recent increase of patients presenting with laboratory-related injuries. It is not known what factors are contributing to this.
Hypothesis: A Haddon matrix analysis may reveal potential areas of vulnerability regarding safe laboratory practices among academic laboratory investigators, particularly students.
Methods: This is a case series of incidents wherein laboratory workers were inappropriately exposed to a chemical hazard. The consultation logs of our academic Toxicology service from 4/8/2008 to 10/3/2013 were reviewed to compile a list of these cases, which were then cross-referenced with our electronic medical record. We collected variables regarding the characteristics of each incident (e.g. the name of the chemical, the safety equipment used, and medical outcome on follow-up). These variables were then used to construct a Haddon matrix (Table 1).
Results: Six different cases were identified, routes of exposure ranged from inhalation to ocular. Time of exposure ranged from seconds to 60 minutes, symptoms ranged from irritation to chest discomfort. The majority took place without the use of PPE, although two incidents happened despite use of safety equipment. There were no known long-term sequelae of these exposures.
Discussion: The utility of Haddon matrices is to analyze hazardous circumstances to determine prevention and mitigation strategies for future implementation. Examination of the Haddon matrices constructed from each of these cases yields common areas amenable to intervention: lack of personal protective equipment, improper storage conditions, lack of worker vigilance, improper spill containment/area clean-up, incongruous risk perception, incomplete adherence to existing safety practices, inadequate initial decontamination prior to ED arrival, and lack of witnesses during the exposure.
Conclusion: This data will be used to improve education materials and instruction for students in laboratory research and to support a culture of safety and prevention in our university laboratories.
50. The ToxIC International Registry: Initial Glimpses from Medical Toxicology Consultation Services in Russia, Thailand, and Mexico
Kopec KT1, Vohra R2, Brusin K3, Santos J4, Otong R5, Smith E6, Brent J7,Wax PM6
1Duke University, Durham, NC, USA; 2UCSF Fresno Medical Center, Fresno, CA, USA; 3Sverdlovsk Regional Clinical Psychiatric Hospital, Ekaterinburg, Russia; 4Hospital Pediatrico Peralvillo, Mexico City, Mexico; 5Navamindradhiraj University, Bangkok, Thailand; 6University of Texas Southwestern Medical Center, Dallas, TX, USA; 7Toxicology Associates, University of Colorado Health Sciences Center, Denver, CO, USA
Background: The international toxicology community has limited communication and collaboration mechanisms.
Research Question: Is it feasible to develop an international registry of poisoned patients parallel to the American College of Medical Toxicology (ACMT) Toxicology Investigator’s Consortium (ToxIC) Registry, an internet-based, multicenter toxicosurveillance network active in the USA since 2010?
Methods: We identified international colleagues with an interest or need in developing a registry of poisoned patients via online surveys and interviews. A web-based data entry form was developed to capture anonymized demographic, clinical, and management details of patients seen in bedside consults by international ACMT members. All entries was de-identified locally prior to registry enrollment, with periodic feedback via email or videoconference encounters provided to address logistical issues.
Results: The International ToxIC Registry has been active since 2/1/2013. ToxIC Investigators in urban settings in Russia, Thailand, and Mexico entered a total of 235 cases involving 43 agents. One hundred ninety six (83%) patients presented with clinical signs of toxicity, while 39 were asymptomatic. The most common clinical presentations were: confusion, CNS and respiratory depression, agitation/delirium, or anticholinergic toxidrome. GI decontamination was performed on 44 patients: 37 received gastric lavage and 10 received activated charcoal. Medical treatments, given to 55 patients, were: benzodiazepines (44 patients), antipsychotics (11 patients), atropine (7 patients), as well as NAC, calcium, glucose, vasopressors, high dose insulin euglycemic therapy, and intralipid (1 to 4 patients for each). The most common intoxicants (and number of cases) were: synthetic cathinones (42), ethanol (30), antipsychotics (20), sedatives (19), carbon monoxide (12), cannabinoids (12), acid/corrosives (11), and opioids/heroin (6).
Conclusion: These initial data indicate that emerging drugs of abuse, prescription agents, and alcohol are well represented intoxicants in urban toxicology practice settings worldwide. The increased use of gastric lavage over charcoal represents a trend which markedly differs from the US and warrants further research. Our experience suggests that an international, web-based registry of bedside medical toxicology consultations is feasible. This project can create opportunities for global collaborative research and education among toxicologists with the ultimate goal of improving the care of poisoned patients worldwide.
51. Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome
Southern California Permanente Medical Group, San Diego, CA, USA
Background: Cannabinoid hyperemesis syndrome (CHS) is described as cyclical episodes of nausea, vomiting, and abdominal pain associated with chronic and heavy cannabinoid use. The pathophysiology of CHS is poorly understood and published theories fail to explain the involvement of the endogenous cannabinoid system in the development of reported symptoms.
Hypothesis: Topical capsaicin will improve symptoms associated with CHS.
Methods: Prospective, non blinded, non placebo controlled trial of topical capsaicin preparation (0.075%) in two patients with CHS. Case one: A 19 year-old female presents to the emergency department for the third time in one week complaining of nausea, vomiting, and severe generalized abdominal pain. She previously underwent negative CT of the abdomen and pelvis, negative transvaginal ultrasonography, negative pelvic exam, and with the exception of mild hypokalemia, negative laboratory values. Further history revealed the patient has frequent and heavy use of marijuana. Her pain completely resolved when placed in a hot shower in the emergency department. She was treated for hypokalemia and when her pain and nausea returned a trial of topical capsaicin cream was initiated. Her pain decreased from 8/10 to 4/10 and she was subsequently discharged home. Case two: A 28 year-old man with history of cyclical nausea, vomiting, and abdominal pain for 3 years presents to the emergency department with return of his symptoms. His previous work up includes negative CT of abdomen and pelvis, negative EGD, and cholecystectomy. History revealed frequent and heavy marijuana smoking with improvement of symptoms upon exposure to hot water. A trial of topical capsaicin cream was initiated and the patient reported improvement in symptoms from 8/10-3/10. He was then discharged home.
Discussion: Capsaicin’s only known receptor, TRPV1, is known to interact with endocannabinoids and plays a role in pain transmission. The results here suggest TRPV1 may play a role in the pathophysiology of CHS as well as indicate a safe and convenient therapeutic option for these often challenging cases.
Conclusion: Topical capsaicin therapy for CHS has potential as both a therapeutic modality and mechanistic probe that merits further investigation.
52. Intravenous Lipid Emulsion Therapy use in the Toxicology Investigators Consortium (ToxIC)
Levine M1,2, Iwanicki J3, Leikin JB4,5, Donovan JW6, McKay CA7, Hernandez S8, et al., for the Management with Intravenous Lipid in Overdose (MILO) investigators
1University of Southern California, Los Angeles, CA, USA; 2Good Samaritan Medical Center, Phoenix, AZ, USA; 3Rocky Mountain Poison and Drug Center, Denver, CO, USA; 4NorthShore University Health Systems – OMEGA, Chicago, IL, USA; 5University of Chicago Pritzker School of Medicine, Chicago, IL, USA; 6Pinnacle Health, Harrisburg, PA, USA; 7Hartford Hospital, Hartford, CT, USA; 8Mt Sinai Medical Center, New York, NY, USA
Background: In May 2012, the Intravenous Lipid Emulsion (ILE) sub-registry was created as part of the ToxIC registry. The purpose of this sub-registry is to prospectively collect detailed information regarding the use of ILE by toxicologists.
Objective: The primary objective of this interim analysis is to describe the patient characteristics for which ILE is being administered.
Methods: Retrospective review of prospectively collected data.
Results: Between 1 May 2012 through 30 October 2013, 44 patients received ILE. The sub-registry analysis was complete on 34 of these patients. The 34 cases were derived from 17 different institutions. Males accounted for 13/34 (38.2%) of subjects. The median (IQR) age was 48 (34.5-56) years, with the youngest patient being 13 months. ILE was administered most often for non-dyhydropyrine calcium channel blockers (n=9), followed by dihydropyridine-class calcium channel blockers (n=5), or the combination of a beta blocker and a calcium channel blocker (n=4). ILE was administered for beta blockers alone in 5 subjects. Local anesthetics accounted for only 3 cases of ILE administration. Various other medications accounted for the remaining cases. Bradycardia (HR < 50 bpm) was observed in 11/34 (32.3%), while hypotension (SBP < 90 mmHg) occurred in 29/34 (85.3%). Three patients experienced a high grade AV block prior to ILE administration. Six (17.6%) patients experienced cardiac arrest prior to implementation of ILE. In total, 10/34 (29.4%) patients died. Acute kidney injury (creatinine > 2.0 mg/dL) was present in 7/34 (20.6%), while metabolic acidosis (pH < 7.2) was present in 14/34 (41.7%)
Conclusion: In this series of patients who received ILE, the majority of cases involved non-local anesthetics. Most patients were in shock and had evidence of abnormal tissue perfusion.
53. Prevention of Neonatal Abstinence Syndrome in the Setting of Intrauterine Baclofen Exposure
Lin HH, Barton N, Wiegand TJ
University of Rochester Medical Center, Rochester, NY, USA
Background: Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a muscle relaxant in the treatment of spasticity. Baclofen is occasionally necessary to continue during pregnancy due to preexisting neurological conditions. Neonatal abstinence syndrome (NAS) including seizures in a benzodiazepine-refractory case has been reported with baclofen and additional information regarding optimal treatment is needed.
Hypothesis: The administration of a baclofen taper shortly after birth will help prevent NAS from intrauterine baclofen exposure.
Methods: A single patient chart review and review of the literature regarding baclofen exposure during pregnancy and NAS was performed. A 43 year-old female with history of spasticity secondary to a spinal cord injury gave birth to a healthy full-term infant male via spontaneous vaginal delivery. Throughout pregnancy the mother had received oral baclofen 80 mg daily. In order to mitigate NAS a baclofen taper was planned after a multidisciplinary meeting. The initial dose was 0.1 mg/kg/day for four days, followed by a daily decrease of 0.01 mg/kg/day until discontinuation of the baclofen on the 13th day of life. Daily assessment for NAS was performed using the modified Finnegan NAS scoring system.
Results: 82 modified Finnegan NAS scores were obtained in the first 16 days of life with a mean score of 2.0 ± 2.4. A max NAS score of 9 was observed on the 13th day of life. At no point were there three consecutive NAS scores ≥8, indicating no need for further pharmacological intervention. The infant was discharged 3 days after the taper ended.
Discussion: This study demonstrates the absence of NAS in an infant who received a baclofen taper after intrauterine baclofen exposure from a mother taking 80 mg/day. In addition to the taper the baby received baclofen through breast milk as well. In fact, baclofen concentrations in milk ranged from 0.28 to 0.38 mcg/mL which provided an additional approximate dose of 0.02 mg/kg/day (1/3 diet breast milk).
Conclusion: The administration of a baclofen taper can prevent NAS in the setting of intrauterine baclofen exposure.
54. Baclofen Distribution into Breast Milk – A Potential for Toxicity?
Lin HH, Barton N, Wiegand TJ
University of Rochester Medical Center, Rochester, NY, USA
Background: Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a muscle relaxant in the treatment of spasticity. Baclofen may be used by pregnant and lactating patients but may cause serious toxicity in infants. Other than one case report there is little data regarding distribution of baclofen into breast milk.
Hypothesis: Nursing infants may be exposed to clinically significant amounts of baclofen when the mother is on oral baclofen.
Methods: A single patient chart review was conducted. A 43 year-old female with spasticity secondary to a spinal cord injury began supplying breast milk for her baby shortly after giving birth to a healthy full-term infant male. During-and-after pregnancy the mother received oral baclofen, 20 mg QID at evenly spaced intervals, between 0600 and 2200 daily. For three consecutive days, breast milk samples were collected at estimated trough (0530) and peak (2400) times. Using high performance liquid chromatography and tandem mass spectrometry, baclofen concentrations were determined for each sample.
Results: Baclofen mean trough levels were 0.297 ± 0.021 mcg/mL and mean peak levels were 0.343 ± 0.033 mcg/mL (Table 1).
Discussion: Our patient was taking 80 mg of oral baclofen (20 mg QID) daily and had breast milk concentrations ranging from 0.28 to 0.38 mcg/mL. A 3 kg infant consuming 750 mL of breast milk per day would be ingesting approximately 0.075 mg/kg/day, approximately 1/4th the weight-based dose of baclofen (0.29 mg/kg/day) in an average 70 kg adult consuming 20 mg baclofen daily. Infants, however, may have longer elimination half-lives and accumulate baclofen at greater concentrations. Infants may also be more sensitive to the effects of baclofen and exposure to lower amounts of baclofen over time could cause significant toxicity. In our infant-mother pair the breast milk was initially limited to 1/3 amount of total daily diet (2/3 formula), only after observing for clinical effects and obtaining levels in milk did we increase the ratio to 50%.
Conclusion: This report adds to the data on baclofen distribution in breast milk. Nursing mothers may have to limit amount of breast milk intake as distribution may be significant.
55. Aspirin Associated Fanconi Syndrome: Is it an Occult Phenomenon?
Lopez AM, Hatten BW, French LK, Hendrickson RG
Oregon Health & Science University, Portland, OR, USA
Background: Fanconi syndrome is a generalized transport defect within the proximal renal tubules which leads to inappropriate urinary losses of glucose, amino acids, bicarbonate, uric acid, phosphate, potassium and other organic compounds. It may be inherited or acquired following exposure to certain xenobiotics. The medical literature has a few case reports of aspirin (ASA) intoxication leading to its development.
Research Question: In cases of ASA toxicity, what proportion of patients develop laboratory findings consistent with Fanconi syndrome?
Methods: This is a retrospective review at a tertiary care hospital in an urban setting. All cases from 2001-2011 with ASA concentrations >30 mg/dL were reviewed for proximal tubule renal dysfunction (either elevation of creatinine on presentation that resolved prior to discharge or development of an elevation during hospital stay), an associated glucosuria (within the renal threshold level of 160-180mg/dL or greater than expected based on serum glucose levels), and proteinuria.
Results: One hundred and three patients in 108 independent encounters had ASA levels >30mg/dL and were analyzed for elevations in creatinine, proteinuria and glucosuria. Nine cases were identified to meet the study criteria. The average age was 25.8±9.9 years. Women accounted for 66.7% of all identified cases. Mean ASA concentration was 59.8±20.4 mg/dL. The mean maximum serum glucose was 142.6±30.1 mg/dL, while the the mean maximum urinary glucose was 237.5±174.7 mg/dL. Mean proteinuria was 128.6±75.6 mg/dL, while mean pH was 7.4±1.1.
Discussion: A proposed mechanism for Fanconi syndrome involves covalent bonding of salicylate or its metabolites to the mitochondria of the proximal tubular cells, altering its function and leading to energy-dependent dysfunction of active transporters. Though the study was limited by the retrospective design, restriction to a single center and a small number of events fitting the definition of Fanconi syndrome, the findings consistent with Fanconi syndrome in patients with ASA overdoses suggests ASA’s role in the development of renal tubular dysfunction.
Conclusion: Fanconi syndrome was found in 8.7% of patients, but further studies in a larger scale may provide better understanding regarding the frequency or risk factors for the development of this syndrome following ASA overdose.
56. Transient Fanconi Syndrome Following Salicylate Overdose
Lopez AM, French LK
Oregon Health & Science University, Portland, OR, USA
Background: Fanconi syndrome is a generalized transport defect within the proximal renal tubules leading to inappropriate urinary losses of glucose, amino acids, bicarbonate, uric acid, phosphate, potassium and other organic compounds. It may be inherited or acquired following exposure to certain xenobiotics.
Hypothesis: We hypothesized that salicylates may lead to Fanconi syndrome.
Methods: This is a single patient chart review. A 15 year-old previously healthy female reportedly ingested 65g of aspirin in a self-harm attempt. Within five hours, she experienced nausea, vomiting, abdominal pain and decreased hearing. Her initial vital signs were a heart rate of 118 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 137/93 mmHg and a temperature of 36.1°C. She was empirically started on an infusion of 5% dextrose containing 150mEq of sodium bicarbonate at 200mL/hour. Activated charcoal was also given. Initial laboratory values included: creatinine (1.06 mg/dL), potassium (3.3 mmol/L), bicarbonate (21 mmol/L), a pH of 7.47, and an initial salicylate concentration of 72 mg/dL. Over the next 3 days, she developed acute renal failure.
Results: Creatinine peaked at a level of 1.21 mg/dL. Her urinalysis was notable for elevated protein at 100 mg/dK, glucose was greater than 500 mg/dL despite normal serum glucose concentrations, rising urinary pH and the presence of red blood cells.
Discussion: There is limited data on the role of salicylate intoxication as a cause of proximal tubular dysfunction in humans and it is not previously described in the toxicology literature. Salicylate effects on renal function are ill-defined, but in large exposure, salicylate may lead to a reversible, generalized, tubular dysfunction and acute tubular necrosis. Proposed mechanisms involve the covalent bonding of salicylate or its metabolites to the mitochondria of the proximal tubular cells, altering function and causing dysfunction of the active transporters. In this case, there was no alternative explanation for the etiology of this transient Fanconi syndrome other than the salicylate exposure.
Conclusion: We present a case of transient Fanconi syndrome following a significant aspirin overdose. Further studies may provide better understanding regarding the frequency or risk factors for its development following salicylate overdose.
57. Twittering Toxicology: Use of MicroBlog for Asynchronous Teaching of Toxicology to Emergency Medicine Residents
Lung D1, Armenian P2, Vohra R2, Lin M1
1University of California, San Francisco, CA, USA; 2UCSF Fresno, Fresno, CA, USA
Background: Learning toxicology is an asynchronous process. Clinically severe or novel toxicities are infrequent. The expected breadth of knowledge in toxicology for Emergency Medicine (EM) residents is much larger than what is typically experienced during a residency. When medical toxicologists are available faculty, they are not ubiquitously available to reinforce salient learning points. In order to more uniformly teach toxicology, we used the social media platform Twitter to broaden our reach and accessibility. We attempt to measure the effectiveness of social media as a teaching tool among a select group of EM residents.
Methods: This is an observational study of 3 EM-Toxicologists and 7 EM residents from 2 EM residency programs. We used qualitative descriptions of teaching content and a pre- and post-intervention survey during a five-month period.
Results: EM-toxicologists posted an average of 25 separate topics per month. Residents posted about 2 questions or replies per month. At the onset, all residents were using social media for personal purposes. The few (3/7) that were using any social media for education were viewing context less than once per day. By the conclusion, the majority (5/6) residents were using social media for educational purposes; half daily. Content felt to be most “useful” were “teaching pearls” (5/6), followed by “clinical cases” (4/6) and “news” (4/6). Barriers to use included content (“my questions are so base . . . it’s way easier to just google it”), unfamiliarity or distrust (“I’m resistant . . . to social media”), and lack of routine use (“I'm not used to opening up Twitter like I am with opening my gmail”).
Conclusions: Our small study suggests that social media can be used as an educational platform for residency education, but for a selected group of learners. Once using Twitter for education, our residents generally continued to use it. We also observe that our group of residents preferred to be passive consumers of educational content. Self-described barriers to use included content level and ease of use of the platform.
58. Trends in Opioid Prescribing Based on Provider Specialty in U.S. Ambulatory Clinics
Mazer-Amirshahi M1, Mullins PM1, Perrone J2, Nelson LS3, Pines JM1
1The George Washington University, Washington, DC, USA; 2Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 3New York University School of Medicine, New York, NY, USA
Background: In recent years, there have been significant increases in opioid analgesic (OA) prescribing. Trends in opioid prescribing based on the specialty of the care provider are less well characterized.
Research Question: To assess trends in OA prescribing by different health care provider specialties in U.S. ambulatory clinics (ACs).
Methods: A retrospective review of data from the CDC’s National Ambulatory Medical Care Survey (NAMCS) 2006-2010 was performed. All AC visits that were potentially pain-related were included. Trends in AC prescribing of all opioids categorized by provider specialty were evaluated. The proportion of visits during which an OA was prescribed was tabulated and trends were analyzed using survey-weighted logistic regression.
Results: The weighted estimate of pain-related AC visits increased from 148.6 million in 2006 to 173.4 million in 2010 and the proportion of pain-related visits during which an OA was prescribed by any provider specialty did not increase significantly (10.4% to 11.6%), p=0.277. Overall opioid prescribing for pain-related visits was the greatest for family medicine visits (13.7%). There was considerable variation within individual specialties during the study period, but no statistically significant trends over time between 2006 and 2010 were identified (Table).
Discussion: Trends in overall opioid prescribing did not significantly change for pain-related visits in ACs from 2006 to 2010. These findings suggest that more acute visits, such as in emergency departments, or following inpatient hospitalizations may be major contributors to the increased rates of opioid prescribing in the U.S. Our study was limited in that there was not adequate data to evaluate all specialties and small sample size for some specialties in certain years may have contributed to increased variability in the data.
Conclusion: Opioid prescribing in ACs across several US specialties did not change significantly from 2006-10.
59. Symptoms and Exposure Histories of Chronically Ill Gulf War Veterans Presenting to a Medical Toxicology Clinic After 20 Years
Meggs WJ, Brewer KL, Mainhart AL
Brody School of Medicine at East Carolina University, Greenville, NC, USA
Background: Approximately 30% of the US veterans serving in the 1991 Gulf War developed a chronic illness that persists twenty years after the conflict that has been resistant to treatment.
Objective: To report the symptom profile on presentation and exposure histories of ill Gulf War Veterans evaluated by a medical toxicology clinic for an ongoing treatment protocol.
Methods: A modified Kansas case definition of Gulf War Illness was used to screen veterans of the 1991 Gulf War. Veterans were contacted through veterans organizations, web postings, and mailings from a Department of Defense manpower database. After informed consent, a screening telephone interview was conducted. Veterans meeting inclusion criteria were scheduled for an initial clinic visit at a medical toxicology clinic. A standardized history and physical examination was performed, an exposure history was taken, and symptoms were scored using a visual analogue scale. Other data obtained but not reported here included completion of the SF-36 health assessment questionnaire and the Connors Continuous Performance test. Means + standard errors of visual analogue scores were calculated.
Results: 42 Gulf War veterans were enrolled. Most troubling symptoms were sleep disturbance, chronic fatigue, arthralgias, myalgias, irritability, difficulty with memory, headaches, difficulty concentrating, inappropriate anger, and nasal congestion. Visual analogue scores are given in the table. The only consistent finding on physical examination was rhinitis (100%). Treatment histories included a variety of psychotropic, analgesic, and antiflammatory medications which were reportedly not helpful. Reported exposure histories were oral pyridostigmine bromide (95%), vaccines including anthrax (88%), SCUD missile attacks with chemical alarms sounding (76%), smoke from oil well fires (69%), and pesticide sprays in living spaces (50%). 7% reported exposure to depleted uranium. 4% reported being in the vicinity of the demolition of the sarin ammunition site at Khamsieh. 3% reported being in the vicinity of other ammunition sites.
Conclusion: Twenty years after the 1991 Gulf War, chronically ill veterans presented to a medical toxicology clinic with a consistent illness consisting of chronic fatigue, chronic pain, and neuropsychological disabilities. Exposures to cholinesterase inhibitors and smoke from oil well fires were reported.
60. Volume of Vodka Absorbed in Commercially Available Tampons
Nordt SP1, Vivero LE1, Rangan C2
1University of Southern California, Los Angeles, CA, USA; 2Los Angeles County Department of Health, Los Angeles, CA, USA
Background: Ethanol use is commonplace amongst adolescents and young adults. Much attention in the popular press to “recent phenomenon” of this group utilizing “tampons soaked in vodka” as a clandestine means for ethanol intoxication either vaginally or rectally. Whilst concerning, it is unclear if ethanol intoxication could be achieved through this technique.
Research Question: How much volume of ethanol can standard tampons absorb utilizing vodka?
Methods: Four different types of commercially available tampons were purchased, Tampax® regular (A), super absorbent (B), Kotex® regular (C) and super absorbent (D). Standard 80 proof (40 percent) vodka 250 milliliters was measured with graduated cylinder. Each tampon submerged separately in 250 mL of vodka in beaker for 10 minutes each using stopwatch whilst still in applicator. After 10 minutes, tampon was removed and volume remaining in beaker was measured with graduated cylinder calibrated to one mL increments. Each tampon type underwent three separate experiments i.e., triplicate. Mean volume and standard deviation of each type were calculated. In addition, a separate tampon of each type was removed from applicator and placed in 250 mL vodka and volume absorbed measured after 10 minutes. This was done once per each tampon.
Results: The Tampax® A group absorbed 9±1 mL, Tampax® B group absorbed 7±2 mL, Kotex® C group absorbed 11±1.5 mL and Kotex® D group absorbed 10±5 mL. The maximum absorbed by any of type was 15 mL in one of Kotex® D group. Without applicator, amount absorbed was 31 mL, 30 mL, 25 mL, 29 mL, in groups A, B, C, D, respectively.
Discussion: Our results demonstrate minimal amounts of vodka are absorbed following submersion for 10 minutes of intact tampons in applicators. The amount of vodka did increase to approximately 30 mL without applicator, however, physical inspection of the expanded tampons suggests it would be difficult if not impossible to successfully insert the expanded tampons outside of the applicator. Attempts would likely extrude a considerable amount of the ethanol.
Conclusion: Our data suggests minimal amounts of vodka are absorbed by various types of tampons and clinical intoxication would be unlikely if applied from intact applicators.
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