Jonathan B. Ford

Is It Prime Time for Alpha2-Adrenocepter Agonists in the Treatment of Withdrawal Syndromes?

The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.

Acute, Sustained Chorea in Children After Supratherapeutic Dosing of Amphetamine-Derived Medications

Amphetamine-derived medications are being prescribed with increasing frequency to younger pediatric patients to treat attention deficit hyperactivity disorder. Although choreiform movements were reported in adults with amphetamine abuse and in those under therapeutic treatment for attention deficit hyperactivity disorder, previous literature concerning the pediatric population is spare. We describe two children who developed chorea after ingesting amphetamine-derived medications prescribed to treat attention deficit hyperactivity disorder. Patient 1, a 10-year-old boy, accidently received an extra dose of lisdexamfetamine dimesylate the night before the onset of acute chorea involving his arms, legs, and trunk. Patient 2, an 8-month-old boy, accidentally ingested his stepbrothers mixed amphetamine salts (Adderall XR) and developed acute chorea. Benzodiazepines, diphenhydramine, benztropine, and opioids did not suppress the chorea in either case. The 10-year-old received haloperidol, which significantly improved his abnormal findings, and he returned to baseline in approximately 48 hours. The 8-month-old was observed in the pediatric intensive care unit, and his signs resolved by 72 hours. Our cases demonstrate that choreiform movements of sustained duration can occur in children with acute supratherapeutic ingestions of amphetamine-derived medications.

Blood leak alarm interference by hydoxocobalamin is hemodialysis machine dependent

Context. Hydroxocobalamin has been reported to interfere with the blood leak alarm on hemodialysis machines making it difficult to use this treatment modality after hydroxocobalamin infusion. Objective. The objective was to determine if this interference with hydroxocobalamin occurs across hemodialysis machines by different manufacturers. Additionally, we aimed to see if this represented a colorimetric interference alone or if it is the optical properties of hydroxocobalamin. Materials and methods. Hydroxocobalamin was reconstituted per package insert. Food coloring was added to 0.9% saline to create the colors of the visual spectrum. Optical properties of absorbance and transmittance were measured. Hydroxocobalamin and the saline solutions were infused into the Fresenius 2008K™ and the Gambro Phoenix X36™ machines. Times were recorded from the start of the machine until the solution finished or the alarm triggered. Results. When evaluating the Gambro Phoenix X36™ machine and dialysis circuit; the alarm did not trigger. In contrast, the blood leak alarm on the Fresenius 2008K™ machine was tripped by both the red solution and hydoxocobalamin infused per the package insert. The alarm stopped the machine between 128 and 132 seconds for the red solution and between 30 and 35 seconds with the hydroxocobalamin. Membranes of the circuits where the alarm tripped were examined and remained intact without blood. Results were validated on different machines with new circuits. Discussion. Hydroxocobalamin infusion per package insert and the red saline solution prepared with Red Dye 40 both triggered the blood leak alarm and stopped the Fresenius 2008K™ machine. However, this was not true for the Gambro Phoenix X36™ machine as the alarm never triggered. The interference with the Fresenius 2008K™ appears colorimetric due to normal saline with Red Dye 40 triggering the alarm. Conclusion. We alert physicians to become familiar with the properties of individual dialysis machines prior to use of hydroxocobalamin. When facing difficulties with hemodialysis after the administration of hydroxocobalamin, consider attempting with a different manufactures machine or model if available or contact the manufacturer directly.

An 11-year review of bupropion insufflation exposures in adults reported to the California poison control system

Abstract Background. Seizures of both immediate and delayed onset after ingestion of bupropion SR and bupropion XL formulations are well documented, but are less well characterized after insufflation. Bupropion is crushed and insufflated to experience a high similar to that from amphetamines and cocaine. We sought to characterize the abuse of bupropion via insufflation in cases reported to the California Poison Control System (CPCS) and the incidence of seizures. Methods: An 11-year (2002–2012) retrospective observational case series of insufflated bupropion exposures evaluated in a health care facility (HCF) were reviewed after searching our database for all bupropion insufflation exposures. Patients with coingestants, multiple exposure routes, or age less than 18 were excluded. Data included age, gender, estimated bupropion dose, occurrence of pre-HCF seizures, symptoms and vital signs reported to the CPCS, treatments, and adverse events that occurred until time of discharge. Results: 74 cases were identified (1 excluded due to age, 5 excluded due to additional oral ingestion of bupropion, and 1 excluded due to being unable to follow). A total of 67 cases met inclusion criteria. The median age was 36 (range, 18–65) years. The total dose of bupropion insufflated was reported in 52 pts; median dose of 1500 (range, 100–9000) mg. Eighteen cases (27%) involved staggered or chronic exposures. Of the 67 patients, 20 (30%) experienced a seizure prior to arrival at the HCF. Of these, 19 patients (95%) presented with tachycardia. None of these patients had a second seizure in the emergency department. There were no major medical outcomes and no deaths. Of the 67 patients, 9 patients received benzodiazepines and 6 patients received single-dose activated charcoal. Conclusion: The abuse of bupropion by crushing and insufflating through the nose is uncommon (67/2270 or 3.0%) compared with that by oral bupropion exposures reported to CPCS. Seizures are common but are self-limited. Delayed seizures (more than 8 h after exposure) appear to be rare. Tachycardia is present in almost all patients who have seizures.

Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

ABSTRACT The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

Intracranial hemorrhage after prehospital administration of intramuscular epinephrine

BACKGROUND The administration of epinephrine by the intramuscular route can be life-saving in cases of anaphylaxis or severe allergic reactions. However, the use of this drug can lead to a rapid rise in blood pressure, which theoretically could lead to deleterious effects in patients of any age, with elderly patients at greatest risk. OBJECTIVES To present a rare case of intracranial hemorrhage potentially resulting from the administration of intramuscular epinephrine in an elderly patient with an allergic reaction. CASE REPORT We present a case report of a 65-year-old woman who developed an intracranial hemorrhage after a single, therapeutic, intramuscular dose of epinephrine for a wasp sting to the tongue. The patient underwent successful craniotomy with evacuation of the intracranial hematoma. CONCLUSIONS In circumstances where the severity of the allergic reaction remains unclear (lack of airway compromise, cardiovascular collapse, or true anaphylaxis), careful consideration of the potential risks of intramuscular epinephrine, such as a rapid rise in blood pressure leading to intracranial hemorrhage, should be undertaken when using this medication in elderly patients.

Altered Mental Status and End Organ Damage Associated with the use of Gacyclidine: A Case Series

IntroductionOver the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.Case ReportsDuring a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.DiscussionThis is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Elimination Kinetics of Ethanol in a 5-Week-Old Infant and a Literature Review of Infant Ethanol Pharmacokinetics

Primary ethanol metabolism occurs through alcohol dehydrogenase, but minor metabolic pathways such as the P450 enzymes CYP2E1 and CYP1A2 and the enzyme catalase exist. These enzymes have distinct developmental stages. Elimination kinetics of ethanol in the infant is limited. We report the elimination kinetics of ethanol in a 5-week-old African-American male who had a serum ethanol level of 270 mg/dL on admission. A previously healthy 5-week-old African-American male was brought to the ED with a decreased level of consciousness. His initial blood ethanol level was 270 mg/dL. Serial blood ethanol levels were obtained. The elimination rate of ethanol was calculated to be in a range from 17.1 to 21.2 mg/dL/hr and appeared to follow zero-order elimination kinetics with a R 2 = 0.9787. Elimination kinetics for ethanol in the young infant has been reported in only four previously published reports. After reviewing these reports, there appears to be variability in the elimination rates of ethanol in infants. Very young infants may not eliminate ethanol as quickly as previously described. Given that there are different stages of enzyme development in children, caution should be used when generalizing the elimination kinetics in young infants and children.

Transaminase and creatine kinase ratios for differentiating delayed acetaminophen overdose from rhabdomyolysis

Introduction Rhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) can differentiate acetaminophen hepatotoxicity from rhabdomyolysis. Methods A retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis was performed. Subjects were classified into three groups: rhabdomyolysis, acetaminophen overdose (all), and acetaminophen overdose with undetectable serum acetaminophen concentrations [acetaminophen(delayed)]. Ratios of AST, ALT, and CK were compared using non-parametric statistical methods. Results 1,353 subjects were identified and after applying our exclusion criteria there were 160 in the rhabdomyolysis group, 68 in the acetaminophen overdose (all) group, and 29 in the acetaminophen (delayed) group. The AST/ALT ratio for the rhabdomyolysis group was 1.66 (Interquartile range: 1.18–2.22), for the acetaminophen overdose (all) group was 1.38 (1.08–1.69, statistically lower than the rhabdomyolysis group, p = 0.018), and for the acetaminophen (delayed)group was 1.30 (1.06–1.63, p = 0.037). CK/AST ratios were 21.3 (12.8–42.2), 5.49 (2.52–15.1, p < 0.001), and 3.80 (1.43–13.8, p < 0.001) respectively. CK/ALT ratios were 37.1 (16.1–80.0), 5.77 (2.79–25.2, p < 0.001), and 5.03 (2.20–17.4, p < 0.001) respectively. Increasing CK to transaminase ratio cutoffs resulted in increasing test sensitivity but lower specificity. Conclusion AST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.

Monitoring the corrected QT in the acute care setting: A comparison of the 12-lead electrocardiogram and bedside monitor

Introduction: Prolongation of the QT interval is a well‐recognized complication associated with many commonly used medications. Emergency Department monitoring of the corrected QT (QTc) both before and after medication administration is typically performed using the 12‐lead electrocardiogram (ECG). The purpose of this study is to compare the QTc reported on the 12‐lead ECG to that reported by single brand of bedside monitor. Methods: A convenience sample of emergency department patients over the age of 18 undergoing bedside monitoring and who had an ECG ordered by their treating physician were enrolled. These patients underwent simultaneous ECG and monitor QTc calculation. The primary outcome of interest was the correlation between the monitor and ECG QTc. Secondary outcomes included ability of each method to identify patients with a QTc > 500 ms and the ability of each method to identify patients with a QTc < 450 ms. Results: A total of 125 patients had simultaneous ECG and monitor QTc measurements recorded. There was moderate correlation between the monitor and ECG QTc (Pearsons correlation coefficient = 0.55). The median difference between the ECG QTc and the monitor QTc (ECG QTc minus monitor QTc) was − 7 ms (IQR − 23 to 11 ms). Conclusion: We found that there was moderate correlation between the QTc reported on the 12 lead ECG and that reported by the bedside monitor. This correlation is not strong enough to support the use of the bedside monitor as a substitute for the 12‐lead ECG when evaluating a patients QTc.