Human Toxicity Caused by Indole and Indazole Carboxylate Synthetic Cannabinoid Receptor Agonists: From Horizon Scanning to Notification.

BACKGROUND: The emergence of novel psychoactive substances (NPS), particularly synthetic cannabinoid receptor agonists (SCRA), has involved hundreds of potentially harmful chemicals in a highly dynamic international market challenging users', clinicians', and regulators' understanding of what circulating substances are causing harm. We describe a toxicovigilance system for NPS that predicted the UK emergence and identified the clinical toxicity caused by novel indole and indazole carboxylate SCRA. METHODS: To assist early accurate identification, we synthesized 5 examples of commercially unavailable indole and indazole carboxylate SCRA (FUB-NPB-22, 5F-NPB-22, 5F-SDB-005, FUB-PB-22, NM-2201). We analyzed plasma and urine samples from 160 patients presenting to emergency departments with severe toxicity after suspected NPS use during 2015 to 2016 for these and other NPS using data-independent LC-MS/MS. RESULTS: We successfully synthesized 5 carboxylate SCRAs using established synthetic and analytical chemistry methodologies. We identified at least 1 SCRA in samples from 49 patients, including an indole or indazole carboxylate SCRA in 17 (35%), specifically 5F-PB-22 (14%), FUB PB-22 (6%), BB-22 (2%), 5F NPB-22 (20%), FUB NPB-22 (2%), and 5F-SDB-005 (4%). In these 17 patients, there was analytical evidence of other substances in 16. Clinical features included agitation and aggression (82%), reduced consciousness (76%), acidosis (47%), hallucinations and paranoid features (41%), tachycardia (35%), hypertension (29%), raised creatine kinase (24%), and seizures (12%). CONCLUSIONS: This toxicovigilance system predicted the emergence of misuse of indole and indazole carboxylate SCRA, documented associated clinical harms, and notified relevant agencies. Toxicity appears consistent with other SCRA, including mental state disturbances and reduced consciousness.

MDMA toxicity: management of acute and life-threatening presentations.

Since the 1980s, methylenedioxymethamphetamine (MDMA) has been a popular recreational drug, used particularly among those who attend raves and nightclubs. Over the past 3 years, the popularity of this drug has once again increased and there has been an associated rise in deaths. The pathophysiology of MDMA toxicity is complex and much remains to be understood. This article aims to increase readers' knowledge of patient presentations, the pathophysiology behind life-threatening toxicity, current treatments and the use of extracorporeal membrane oxygenation as a potential future treatment.

Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB-CHMICA. A report from the Identification Of Novel psychoActive substances (IONA) study.

CONTEXT: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects. OBJECTIVE: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA. MATERIALS AND METHODS: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE REPORTS: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine. CONCLUSIONS: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions.

The role of venous blood gas in the emergency department: a systematic review and meta-analysis.

The aim of this study is to provide a systematic review of the literature reporting agreement between arterial and venous pH, partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3⁻), base excess and lactate; and to perform a meta-analysis of the differences. Medline and Embase searches using Eduserv Athens from 1950 to present were conducted using the terms 'VBG', 'ABG', 'arterial', 'venous', 'blood', 'gas', 'lactate', 'emergency' and 'department'. References of the published papers were hand searched and full-text versions of those deemed helpful to the question were obtained. Mean difference (MD) and 95% limits of agreement (LOA) were either reported or calculated from the published data. Pooled MDs with 95% confidence intervals (CIs) were calculated for differences between arterial and venous pH, PCO2, bicarbonate and lactate. Thirteen articles relevant to pH, 12 relevant to PCO2, 10 relevant to bicarbonate and three relevant to lactate were found. The pooled MD (venous-arterial) for pH was -0.033 pH units (95% CI -0.039 to 0.027) with narrow 95% LOA, the pooled MD for PCO2 was 4.41 mmHg (95% CI 2.55-6.27) with 95% LOA ranging from -20.4 to 25.8 mmHg, the pooled MD for bicarbonate was 1.03 mmol/l (95% CI 0.56-1.50) with 95% LOA ranging from -7.1 to 10.0 mmol/l and the pooled MD for lactate was 0.25 mmol/l (95% CI 0.15-0.35) with 95% LOA ranging from -2.0 to 2.3 mmol/l. Venous and arterial pH and bicarbonate agree reasonably at all values, but the agreement is highest at normal values. Arteriovenous agreement for PCO2 is poor and PvCO2 cannot be relied upon as an absolute representation of PaCO2. However, normal peripheral PvCO2 has a good negative predictive value for normal arterial PCO2, and a normal PvCO2 can be used as a screen to exclude hypercapnic respiratory disease. There may be a poor agreement between arterial and venous lactate at abnormal values; however, if the venous lactate is normal, it is likely the arterial values of this parameter will also be normal.

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death.

2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.

Sparkle lamp ingestion: a rare cause of death.

A 51-year-old man was brought to the emergency department after he had drunk 200 mL of fluid from a decorative sparkle lamp. His calcium level was 4.99 mmol/L with a blood gas pH of 7.21. His calcium levels were corrected and his acidosis improved, but his stay in the intensive care department was complicated on day 10 by upper gastrointestinal hemorrhage because of caustic erosions in his stomach. Ten days after admission, he had an emergency right hemicolectomy during which residual luminescent particles were found to have eroded through his cecal mucosa. He eventually died 15 days after admission because of disseminated intravascular coagulopathy and refractory septic shock. This case demonstrates the potential for fatal toxicity associated with ingestion of a common household item.