Michael D. Schwartz

Synthetic Cannabinoid–Related Illnesses and Deaths

Use of synthetic cannabinoids (SCs) in the United States is increasing, as are clusters of cases of serious adverse health effects, including death. Though SC intoxication can be difficult to identify, some steps can be taken to respond more quickly to future outbreaks.

Acute Metformin Overdose: Examining Serum pH, Lactate Level, and Metformin Concentrations in Survivors Versus Nonsurvivors: A Systematic Review of the Literature

STUDY OBJECTIVE Metformin is known to cause potentially fatal metabolic acidosis with an increased lactate level in both overdose and therapeutic use. No association between mortality and serum pH, lactate level, or metformin concentrations, though intuitive, has yet been described. This systematic literature review is designed to evaluate the association between mortality and serum pH, lactate level, and metformin concentrations in acute metformin overdose. METHODS We reviewed the literature by using the MEDLINE, EMBASE, CINAHL, and TOXNET databases for cases of metformin overdose with documented mortality data and values of serum pH, lactate level, and metformin concentrations. When available, patient age, patient sex, and whether patients received intravenous sodium bicarbonate therapy or hemodialysis were also analyzed. Cases meeting inclusion criteria were analyzed to determine whether a difference in distribution of nadir serum pH, peak serum lactate level, or peak serum metformin concentrations existed between overdose survivors and nonsurvivors. RESULTS We identified 10 articles that had 1 or more cases meeting our inclusion criteria. In total, there were 22 cases of metformin overdose (5/22 died) that met inclusion criteria. No intentional overdose patients died whose serum pH nadir was greater than 6.9, maximum lactate concentration less than 25 mol/L, or maximum metformin concentration less than 50 microg/mL (therapeutic range 1 to 2 microg/mL). Intentional overdose patients with a nadir serum pH less than 6.9 had 83% mortality (5/6), those with lactate concentration greater than 25 mmol/L had 83% mortality (5/6), and those with metformin concentration greater than 50 microg/mL had 38% mortality (5/12). Nadir serum pH and peak serum lactate and metformin concentration distributions in survivors and nonsurvivors revealed that survivors had a median nadir pH of 7.30, interquartile range (IQR) 7.22, 7.36; nonsurvivors, a median nadir pH of 6.71, IQR 6.71, 6.73; survivors, a median peak lactate level of 10.8 mmol/L, IQR 4.2, 12.9; nonsurvivors, a median peak lactate level of 35.0 mmol/L, IQR 33.3, 39.0; survivors, a median peak metformin level of 42 microg/mL, IQR 6.6, 67.6; and nonsurvivors, a median peak metformin level of 110 microg/mL, IQR 110, 110. CONCLUSION No cases of acute metformin overdose meeting the studys inclusion criteria were found in which patients with a nadir serum pH greater than 6.9, peak serum lactate concentrations less than 25 mmol/L, or peak serum metformin concentrations less than 50 microg/mL died. Patients with acute metformin overdose who died had much lower serum pH nadirs and much higher peak serum lactate and metformin concentrations than those who survived.

Intoxication From Smoking “Spice”

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A retrospective review of the relationship between facial fractures, head injuries, and cervical spine injuries

Facial fractures are common in the multiply-traumatized patient, and the results of previous studies that have examined the relationship between facial fractures, cervical spine injuries, and head injuries have produced conflicting results. A retrospective review of 1,050 blunt-trauma patients during a 40-month period at a regional trauma unit revealed 168 patients with facial fractures. The average injury severity score (ISS) of these patients with facial fractures was 31 compared with an average ISS of 25.6 for the entire group. There were 266 facial fractures in these 168 patients: mandible (n = 72), maxilla (n = 74), zygoma (n = 52), orbital (n = 46), nasoethmoidal (n = 20), and frontal (n = 2). There were seven (4%) cervical spine injuries, three of which were atlanto-occipital subluxations in patients who ultimately died. Of the four surviving patients, one had a cord injury. In contrast, 145 (85%) showed evidence of head injuries; 64 (38%) of these head injuries were serious and 17 of these patients required craniotomy. The relationship of facial fractures and cervical spine injuries may be over emphasized; head injuries, although frequently minor, are much more commonly associated with facial fractures.

Case Series Of Selenium Toxicity From A Nutritional Supplement

Introduction. Selenium is an essential trace element, but can be toxic in excess. In May 2008, US FDA reported 201 individuals with adverse reactions to liquid nutritional supplements containing excess selenium and chromium resulting in the largest epidemic of selenosis in the history of the United States. Objective. To describe the clinical features, biomonitoring data of selenium levels, and the estimated total dose of selenium ingestions of nine patients with selenium toxicity who presented after use of a liquid dietary supplement with a formulation error. Methods. A retrospective observational case series was performed on nine patients presenting to our medical toxicology clinic between March 2008 and May 2008 with symptoms of selenosis after consuming a nutritional supplement. Institutional IRB approval was obtained for this case series. Results. Supplement testing revealed almost 200 times the reported amount of selenium. There were 5 males and 4 females and their ages ranged from 15 to 57 years (median 46 years, mean 44.2 years). The mean estimated cumulative dose of selenium ingested in our patients was 1.3 gram over a mean period of 37.5 days (10–60 days). In each case, the symptoms of selenium toxicity manifested within 1 week from the start of ingestion. Initial symptoms included alopecia, dystrophic fingernail changes, GI symptoms, and memory difficulties. The initial whole blood selenium concentrations ranged from 150 to 732 mcg/L (reference mean range 123–193 mcg/L) at an average of 27 days post cessation of the formula. The urinary selenium concentrations ranged from 41 to 220 mcg/g Creat (reference < 25 mcg/g Creatinine). None of the patients required more than supportive care for symptoms and none required hospitalization. Conclusion. Selenium is an essential element, which can result in significant toxicity if ingested in large amounts.

An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA.

Background: Synthetic cannabinoid containing products are a public health threat as reflected by a number of outbreaks of serious adverse health effects over the past 4 years. The designer drug epidemic is characterized by the rapid turnover of synthetic cannabinoid compounds on the market which creates a challenge in identifying the particular etiology of an outbreak, confirming exposure in cases, and providing current information to law enforcement. Results: Between 28 May 2014 and 8 June 2014, 35 patients were evaluated and treated at the University of Florida Health Medical Center in Gainesville following reported exposure to a synthetic cannabinoid containing product obtained from a common source. Patients demonstrated acute delirium (24) and seizures (14), and five required ventilator support and ICU-level care; none died. The presence of N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA), or one of its predicted metabolites was confirmed in 15 of 21 cases. A rapid public health response and aggressive public messaging prevented further morbidity, identified the source, and led to law enforcement seizure of the implicated product. Discussion: The significance of this outbreak lies as much in the rapid occurrence of unpredictable, life-threatening adverse health effects from a newly identified synthetic cannabinoid compound as it does in the multidisciplinary investigation and novel partnership between local public health, the laboratory, and the chemical industry, resulting in termination of the outbreak. Conclusion: A coordinated response and collaboration between law enforcement, the local public health, emergency medical services and Health Center staff, were all key interventions in preventing a more substantial public health outbreak resulting from use of a novel synthetic cannabinoid compound. Real time collaborations between toxicology laboratories, suppliers of analytical standards and the public health system may be useful in the face of future novel chemical exposures.

Cardiotoxicity after Massive Amantadine Overdose

IntroductionAmantadine hydrochloride is an antiviral medication used as therapy for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute ingestion of amantadine hydrochloride confirmed with serial serum levels.Case ReportsA 47-year-old woman presented to the emergency department (ED) 30 minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the ED, the patient sustained a pulseless cardiac arrest and the monitor revealed ventricular tachycardia. She was successfully defibrillated. Postdefibrillation ECG showed a sinus rhythm (rate = 82 bpm), QRS of 236 msec, and QTc of 567 msec. The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300 cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the hypertonic saline infusion, the patient’s ECG abnormalities resolved and the QRS was 88 msec. Her potassium was repleted over the next 11 hours postpresentation, and she also received an IV bolus of 4 g of magnesium sulfate immediately after the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or ectopy was noted during the patient’s hospital stay. The second case involved a 33-year-old female patient who presented 1 hour after ingesting 100 tablets of amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia with a QRS of 113 msec, an R wave in lead aVR of 4–5 mm and a QTc of 526 msec. Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at initial presentation. The patient was intubated for airway protection, and her potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities improved 8 hours after initial presentation and normalized at approximately 14 hours postingestion. The patient was discharged home 11 days after her ingestion.ConclusionAcute amantadine toxicity manifests with life-threatening cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the administration of sodium bicarbonate in the management of cardiac dysrhythmias.

Public Health Investigation After the Discovery of Ricin in a South Carolina Postal Facility

OBJECTIVES In October 2003, a package containing ricin and a note threatening to poison water supplies was discovered in a South Carolina postal facility, becoming the first potential chemical terrorism event involving ricin in the United States. We examined the comprehensive public health investigation that followed and discuss the lessons learned from it. METHODS An investigation consisting primarily of environmental sampling for ricin contamination, performance of health assessments on affected personnel, and local, regional, and national surveillance for ricin-associated illness. RESULTS Laboratory analysis of 75 environmental sampling specimens revealed no ricin contamination. Health assessments of 36 affected employees were completed. Local surveillance initially identified 3 suspected cases, and national surveillance identified 399 outliers during the 2-week period after the incident. No confirmed cases of ricin-associated illness were identified. CONCLUSIONS A multifaceted and multidisciplinary approach is required for an effective public health response to a chemical threat such as ricin. The results of all of the described activities were used to determine that the facility was safe to reopen and that no public health threat existed.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential diagnosis of delirium.

Abstract Background. Medical toxicologists are frequently consulted when young patients present with delirium attributed to suspected poisoning. Medical toxicologists should be aware of non-toxicological mimics of delirium. We describe two patients ultimately diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis for which a toxicological consultation was requested to evaluate for neuroleptic malignant syndrome (NMS). Case 1. A 21 year old male was sent from a psychiatric facility for new, worsening psychotic symptoms. He had autonomic instability, confusion, and hyper-reflexia. He was treated for NMS without improvement, and after an extensive workup was unrevealing, he was discharged home with significant cognitive dysfunction. Stored CSF later tested positive for anti-NMDAR antibodies. Case 2. A 27 year old female was sent from a psychiatric facility for a seizure and new psychiatric symptoms. She was agitated and had violent, alternating extremity flexion and extension along with autonomic instability. She was treated for NMS, rhabdomyolysis, and rabies before analysis of CSF demonstrated anti-NMDAR antibodies. Treatment included surgical resection of a suspicious ovarian cyst, steroids and IVIG, with moderate improvement. Discussion. Autoimmune syndromes of the central nervous system result from receptor dysfunction after an antibody response to extracellular or intracellular antigens, such as subunits of the NMDA receptor. The NMDA subunits NR2b and NR2a, in addition to the N-terminal region of the glycine binding NR1 subunit, have been implicated. Typical features such as memory loss, movement disorders, and hallucinations reflect the density and distribution of neuronal NDMA receptors. As young people, particularly young women, are predominantly affected, initial symptoms may be attributed to encephalopathy from drug abuse or schizophrenia. Toxicologists may be consulted as many features mimic NMS. Serum and cerebrospinal fluid can be checked for anti-NMDAR antibodies as part of a paraneoplastic or meningioencephalitis panel. Effective treatments have been described and include surgical resection and immunosuppressive medications.

Aripiprazole (Abilify™) Overdose in a Child

Aripiprazole, 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl] butyloxy}-3,4-dihydro-2(1H)-quinolinone, is an atypical antipsychotic medication inaugurating the newest class of atypical antipsychotics: the partial dopamine agonist. It has a particularly long half-life of elimination and variable metabolism secondary to genetic polymorphism. We report an unintentional overdose of 195 mg (17.1 mg/kg) of aripiprazole in a 2.5 year-old child. This patient exhibited CNS depression not requiring respiratory support and without significant cardiovascular effects. CNS effects persisted for almost 2 weeks postingestion.