Evan S. Schwarz

Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation

Synthetic cannabinoids have been popular recreational drugs of abuse for their psychoactive properties. Five of the many synthetic cannabinoids have been recently banned in the United States because of their unknown and potentially harmful adverse effects. Little is known about these substances. They are thought to have natural cannabinoid-like effects but have different chemical structures. Adverse effects related to synthetic cannabinoids are not well known. We provide clinical effects and patient outcome following K9 use. In addition, we briefly review synthetic cannabinoids. We present a 17-year-old adolescent boy with chest pain, tachycardia, and then bradycardia associated with smoking K9. Two synthetic cannabinoids, JWH-018 and JWH-073, were confirmed on laboratory analysis. In addition to the limited current data, we demonstrate harmful adverse effects related to toxicity of 2 synthetic cannabinoids. Further studies are needed.

Synthetic cannabinoid and marijuana exposures reported to poison centers

Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38–2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87–1.51), 40.2% and 56.6% age ≤19 years (RR 0.71, 95% CI 0.52–0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02–1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28–1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03–2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.

Synthetic Cannabinoid Exposures Reported to Texas Poison Centers

ABSTRACT Synthetic cannabinoid abuse is increasing in the United States. Synthetic cannabinoid exposures reported to Texas poison centers in 2010 were identified, and the distribution of exposures by selected factors was determined. There were 464 total cases. The number of exposures increased each month during January-July, then remained relatively constant for the next 5 months. The patients were 73.9% male and 57.3% were 20 years or older. Moderate or major effects or potentially toxic outcome occurred in 59.9% of the exposures. The most frequently reported clinical effects were tachycardia (37.3%), agitation (18.5%), drowsiness (18.5%), vomiting (15.7%), hallucinations (10.8%), and nausea (9.9%).

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

Abstract Context. Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. Objective. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. Methods. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms (“oxoproline” OR “pyroglutamic acid” AND “paracetamol” OR “acetaminophen”). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Results. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients with quantified 5-oxoproline concentrations. The cases varied widely in paracetamol dose, duration and circumstances of paracetamol exposure, presence, and degree of elevation in transaminase activities, and when reported observed blood, serum, or urine 5-oxoproline concentrations. Concomitant use of flucloxacillin, another medication associated with oxoprolinemia or oxoprolinuria, confounded several of the cases. No clear dose–response relationship existed between the quantity of paracetamol ingested and the observed concentrations of 5-oxoproline. Clinical outcomes, including mortality, varied with no clear relationship to 5-oxoproline concentrations. Conclusions. In rare cases, HAGMA in the setting of paracetamol exposure is attributable to 5-oxoprolinemia. Clinicians should first exclude commoner and treatable causes of HAGMA, such as lactic acidosis, co-ingested drug administration, and ketoacidosis. It is likely that the propensity for HAGMA following paracetamol exposure may be genetically determined. The effects of acetylcysteine on 5-oxoproline concentrations or clinical outcome are unknown. When HAGMA is diagnosed, the 5-oxoproline concentration and the glutathione synthetase activity should be measured.

Two cases of disseminated intravascular coagulation due to "bath salts" resulting in fatalities, with laboratory confirmation.

Synthetic cathinones are phenylalkylamines developed for both medicinal use and as substances of abuse referred to as “bath salts.” The rapid emergence of these bath salts over the recent years has been concerning to the medical community and law enforcement. Widespread availability, legality, and desired amphetamine-like effects have dramatically increased sales of these compounds. Only recently has regulations on specific derivatives been enacted in the United States. The acute sympathomimetic toxidrome associated with bath salts by virtually any route can result in harmful effects. The mechanism of action of these various derivatives is not well understood. There is no specific antidote for these agents. Aggressive supportive care, including sedation with benzodiazepines, fluid administration, and cooling measures, should be provided early in the toxidrome. The media and poison centers have tracked similarities in the acute toxicity from these agents, including neurologic, cardiovascular, and psychiatric effects. Multiorgan failure and deaths have recently been reported with both mephedrone and methylenedioxypyrovalerone. We report 2 fatalities presenting with hyperthermia, delirium, and disseminated intravascular coagulation. Both patients had laboratory confirmation of recent exposure to methylenedioxypyrovalerone. Cathinone is a naturally occurring amphetamine analogue found in the leaves of the Catha edulis plant [1]. The leaves are chewed for their stimulant effects, which primarily include increased alertness, insomnia, and hyperactivity. Synthetic cathinone derivatives were developed for both medicinal use and as substances of abuse. Bupropion is a clinically used synthetic cathinone. Other derivatives such as methcathinone and pyrovalerone were investigated for medicinal purposes before being used recreationally. Recently, ☆ This article has never been presented. 0735-6757/

Do heroin overdose patients require observation after receiving naloxone

– see front matter. Published by Elsevier Inc. substances sold under the name of “bath salts” have become popular among recreational drug users [2]. These drugs are injected, inhaled, ingested, or smoked. Bath salts in the United States were found to contain mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), all of which are synthetic cathinones [3]. These synthetic cathinones also have the ability to modulate serotonin, which can result in psychoactive effects [1]. The media have devoted a lot of attention to this problem because the drugs are widely available in the United States, and the use of these agents seems to have exponentially increased in the past few years [1]. Both emergency department visits and poison center calls have grown significantly in the past 3 years [4,5]. In 2010, the American Association of Poison Control Centers reported 304 calls related to bath salts; the number increased to 6138 calls in 2011 [5]. Many of the patients presenting for emergency care have tachycardia, hypertension, and hallucinations. Multiorgan failure and deaths have recently been reported [4,6-8]. We report 2 deaths of patients who presented with hyperthermia, delirium, and disseminated intravascular coagulation (DIC) with laboratory confirmation of exposure to MDPV. A 20-year-old man was witnessed fleeing from the police after sniffing bath salts when he started seizing. When emergency medical services arrived on the scene, the patient was unresponsive. Emergency medical services administered naloxone 0.4 mg IV and adenosine 6 mg IV for narrow complex tachycardia, without effect. At the initial health care facility, the initial rhythm was narrow complex tachycardia with a heart rate (HR) of 165 beats per minute. The patient had spontaneous respirations at a rate of 24 per minute and an oxygen saturation of 100% on room air. He was intubated for airway protection using succinylcholine 90 mg IV and midazolam 2 mg IV. Rocuronium 50 mg IV, midazolam 4 mg IV, and ceftriaxone 1 g IV were given after intubation. The narrow complex tachycardia was again treated with 12 mg of adenosine IV without effect. Cardioversion at 150 J was also ineffective. Two liters of IV normal saline were infused. Despite this, the patient remained with an HR of 160 to 188 beats per minute for an hour at the initial hospital. During this period, the blood pressure (BP) was reported between 120/55 and 80/35 mm Hg. Acetaminophen 650 mg suppository was given for a temperature (T) of 39.6°C. The

Successful resuscitation of a patient in asystole after a TASER injury using a hypothermia protocol

Abstract Context: Heroin use in the US has exploded in recent years, and heroin overdoses requiring naloxone are very common. After awakening, some heroin users refuse further treatment or transport to the hospital. These patients may be at risk for recurrent respiratory depression or pulmonary edema. In those transported to the emergency department, the duration of the observation period is controversial. Additionally, non-medical first responders and lay bystanders can administer naloxone for heroin and opioid overdoses. There are concerns about the outcomes and safety of this practice as well. Objectives: To search the medical literature related to the following questions: (1) What are the medical risks to a heroin user who refuses ambulance transport after naloxone? (2) If the heroin user is treated in the emergency department with naloxone, how long must they be observed prior to discharge? (3) How effective in heroin users is naloxone administered by first responders and bystanders? Are there risks associated with naloxone distribution programs? Methods: We searched PubMed and GoogleScholar with search terms related to each of the questions listed above. The search was limited to English language and excluded patents and citations. The search was last updated on September 31, 2016. The articles found were reviewed for relevance to our objective questions. Eight out of 1020 citations were relevant to the first 2 questions, 5 of 707 were relevant to the third question and 15 of 287 were relevant to the fourth question. In the prehospital environment, does a heroin user revived with naloxone always require ambulance transport and what are the medical risks if ambulance transport is refused after naloxone? The eight articles were all observational studies done either prospectively or retrospectively. Two studies focused on heroin overdoses and included 1069 patients not transported to the hospital. No deaths occurred in this group. In counting the patients from all eight studies, some of which included non-heroin opioid overdoses, there were 5443 patients treated without transport and four deaths from rebound opioid toxicity. The number needed to transport to save one life (NNT) is 1361. Adverse effects were mostly related to opioid withdrawal. If a heroin user is treated in the ED, how long must the patient stay under observation before being safe for discharge? Five articles addressing the duration of ED observation required for patients treated with naloxone for opioid overdoses. Although a wide range of observation durations were reported, one study supported observing patients for one hour. If after this period the patient mobilizes as usual, has normal vital signs, and a Glasgow Coma Scale of 15, they can be discharged safely. What are the likely risks in heroin users following naloxone use by lay bystanders or first responders? Of the 15 relevant papers, a systematic review reported a 100% survival rate in eleven studies and a range of 96–99% survival in the remaining four. Two other studies suffered from poor follow-up and had lower success rates of 83% and 89%. Few if any risks were associated with opioid overdose prevention programs in which lay people were trained to administer naloxone. Conclusions: Patients revived with naloxone after heroin overdose may be safely released without transport to the hospital if they have normal mentation and vital signs. In the absence of co-intoxicants and further opioid use there is very low risk of death from rebound opioid toxicity. For those patients treated in the ED for opioid overdose, an observation period of one hour is sufficient if they ambulate as usual, have normal vital signs and a Glasgow Coma Scale of 15. Patients suffering opioid toxicity can be administered naloxone safely by first responders and trained lay people. Programs that train these individuals are likely safe and beneficial, however further research is necessary.

Life-threatening diphenhydramine toxicity presenting with seizures and a wide complex tachycardia improved with intravenous fat emulsion.

New studies have shown the benefit of initiating a hypothermia protocol in the survivors of cardiac arrest. Although the data have shown an improved neurologic end point in patients initially in ventricular fibrillation or pulseless ventricular tachycardia, there is still debate about whether patients initially in other rhythms would benefit from hypothermia after return of spontaneous circulation. This is a report of a 17-year-old male found to be in asystole after sustaining a TASER injury, who was treated with a hypothermia protocol after return of spontaneous circulation and left the hospital with intact neurologic function.

Emergency department patients with diabetes have better glycemic control when they have identifiable primary care providers.

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of IFE after a confirmed sole ingestion of diphenhydramine is not previously reported. We present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after IFE administration.

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series

OBJECTIVES The objective was to determine if emergency department (ED) patients with diabetes mellitus (DM) who have primary care providers (PCPs) have better control of their DM than patients with no PCPs. METHODS This was a prospective, cross-sectional, observation study at a large, adult, urban, academic ED with 85,000 annual visits. ED patients with a history of DM were eligible. Patients with severe systemic disease, diabetic ketoacidosis (DKA), sepsis, active steroid use, pregnancy, or cognitive impairment were excluded. Consenting patients had hemoglobin A1c (HgbA1c) analysis and completed a questionnaire regarding demographics, lifestyle, medication usage, educational level attained, and health care access, including whether or not they had PCPs. HgbA1c levels were compared between subjects with and without PCPs using medians with interquartile ranges (IQRs). A continuous plot was developed to demonstrate the proportion of patients without PCPs (PCP-) compared to those with PCPs (PCP+) at every level of %HgbA1c across the entire measured range. Multivariate logistic regression analysis was used to determine which clinical and demographic factors obtained from the questionnaire were associated with improved glycemic control (increased relative risk [RR] of having a %HgbA1c < 8%). RESULTS A total of 284 patients were screened; 227 were enrolled, had HgbA1c analysis performed, and had complete PCP, race, and sex information. Complete demographic data (insurance status, employment status, etc.) were available on 209 subjects. Sixty-four of the 227 patients (28.2%) denied having PCPs. Median HgbA1c was 7.7% (IQR = 6.5% to 9.68%) in PCP+ versus 8.9% (IQR = 6.8% to 11.3%) in PCP- patients (p = 0.01). Ninety-one of 163 (55.8%) PCP+ subjects had a median HgbA1c < 8% versus 25 of 64 (39.1%) in the PCP- group (p = 0.02). After adjusting for multiple clinical and demographic variables, having a PCP remained significantly associated with a median HgbA1c value less than 8% (RR = 1.43; p = 0.04). CONCLUSIONS Diabetes control was significantly better in patients with PCPs, even after adjusting for a number of potentially confounding social and demographic factors.