Respiratory failure in confirmed synthetic cannabinoid overdose.

CONTEXT: Synthetic cannabinoids (SCs) are a structurally heterogenous synthetic class of drugs of abuse. The objective was to describe the incidence of acute respiratory failure in Emergency Department (ED) patients with confirmed SC exposure, and to investigate the association between SC overdose with respiratory failure compared to non-SC overdose. METHODS: This was an observational cohort of ED patients ≥18 years with suspected cannabinoid overdose between 2015 and 2020 at two tertiary-care hospitals. Patient serum was analyzed via liquid chromatography/quadrupole time-of-flight mass spectrometry using a library with >800 drugs including novel psychoactive substances. The primary outcome was acute respiratory failure. DISCUSSION: Of 83 patients with suspected cannabinoid overdose, there were 29 confirmed SC overdoses: 5 F-MDMB-PICA (n = 18) and its metabolite 5OH-MDMB-PICA (n = 16), ADB-FUBINACA (n = 4), AB-CHIMINACA (n = 4), AB-FUBINACA (n = 1), AB-PINACA (n = 1), MDMB-4en-PINACA (n = 1), and 4 F-MDMB-BINACA (n = 1). Overall, incidence of acute respiratory failure was 31.3% (95%CI 21.6-42.4). Compared to non-SC overdose, confirmed SC overdose was significantly associated with respiratory failure (25.0% SC vs. 4.2% non-SC, p = 0.05). CONCLUSION: This study demonstrates that SCs are associated with respiratory failure. Since respiratory depression is a potentially lethal adverse effect of SC overdose, future research is warranted.

Prior use of medications for opioid use disorder in ED patients with opioid overdose: prevalence, misuse and overdose severity.

OBJECTIVES: Medications for opioid use disorder (MOUD) reduce opioid overdose (OD) deaths; however, prevalence and misuse of MOUD in ED patients presenting with opioid overdose are unclear, as are any impacts of existing MOUD prescriptions on subsequent OD severity. METHODS: This was a prospective observational cohort of ED patients with opioid OD at two tertiary-care hospitals from 2015 to 19. Patients with confirmed opioid OD (via urine toxicology) were included, while patients with alternate diagnoses, insufficient data, age < 18, and prisoners were excluded. OD severity was defined using: (a) hospital LOS (days); and (b) in-hospital mortality. Time trends by calendar year and associations between MOUD and study outcomes were calculated. RESULTS: In 2829 ED patients with acute drug OD, 696 with confirmed opioid OD were included. Overall, 120 patients (17%) were previously prescribed any MOUD, and MOUD prevalence was significantly higher in 2018 and 2019 compared to 2016 (20.1% and 27.8% vs. 8.8%, p < 0.05). Odds of MOUD misuse were significantly higher for methadone (OR 3.96 95% CI 2.57-6.12) and lowest for buprenorphine (OR 1.16, p = NS). Mean LOS was over 50% longer for methadone (3.08 days) compared to buprenorphine and naltrexone (both 2.0 days, p = NS). Following adjustment for confounders, buprenorphine use was associated with significantly shorter LOS (IRR -0.44 (95%CI -0.85, -0.04)). Odds of death were 30% lower for patients on any MOUD (OR 0.70, 95%CI 0.09-5.72), but highest in the methadone group (OR 0.82, 95%CI 0.10-6.74). CONCLUSIONS: While MOUD prevalence significantly increased over the study period, MOUD misuse occurred for patients taking methadone, and OD LOS overall was lower in patients with any prior buprenorphine prescription.

The effect of succinic acid on the metabolic profile in high-fat diet-induced obesity and insulin resistance.

Obesity, insulin resistance, and poor metabolic profile are hallmarks of a high-fat diet (HFD), highlighting the need to understand underlying mechanisms. Therefore, we sought to determine the effect of succinic acid (SA) on metabolism in high-fat diet (HFD)-induced obesity. Animals were randomly assigned to either low-fat diet (LFD) or a high-fat diet (HFD). Mice consumed their respective diets for 4.5 months and then assigned to the following groups: (LFD)+vehicle, LFD + SA (0.75 mg/ml), HFD + vehicle, or HFD + SA. Body weight (BW), food, and water intake, were tracked weekly. After 6 weeks, insulin, glucose, and pyruvate tolerance tests were completed, and spontaneous physical activity was assessed. Epididymal white adipose tissue (EWAT) mass and in vitro measurements of oxidative skeletal muscle (soleus) respiration were obtained. Expectedly, the HFD increased BW and EWAT mass, and reduced glucose and insulin tolerance. SA significantly reduced EWAT mass, more so in HFD (p < .05), but had no effect on any in vivo measurements (BW, insulin, glucose, or pyruvate tolerance, nor physical activity, all p > .05). A significant (p < .05) interaction was observed between mitochondrial respiration and treatment, where SA increased respiration, likely owed to greater mitochondrial content, as assessed by complex IV activity in both LFD and HFD. In HFD-induced obesity, coupled with insulin desensitization, we found no favorable effect of succinic acid on glucose regulation, though adiposity was attenuated. In oxidative skeletal muscle, there was a tendency for increased respiratory capacity, likely owed to greater mitochondrial content, suggestive of a succinic acid-induced mitochondrial biogenesis.

Exercise performance and physiological responses: the potential role of redox imbalance.

Increases in oxidative stress or decreases in antioxidant capacity, or redox imbalance, are known to alter physiological function and has been suggested to influence performance. To date, no study has sought to manipulate this balance in the same participants and observe the impact on physiological function and performance. Using a single-blind, placebo-controlled, and counterbalanced design, this study examined the effects of increasing free radicals, via hyperoxic exposure (FiO2 = 1.0), and/or increasing antioxidant capacity, through consuming an antioxidant cocktail (AOC; vitamin-C, vitamin-E, α-lipoic acid), on 5-kilometer (km) cycling time-trial performance, and the physiological and fatigue responses in healthy college-aged males. Hyperoxic exposure prior to the 5 km TT had no effect on performance, fatigue, or the physiological responses to exercise. The AOC significantly reduced average power output (222 ± 11 vs. 214 ± 12 W), increased 5 km time (516 ± 17 vs. 533 ± 18 sec), suppressed ventilation (VE; 116 ± 5 vs. 109 ± 13 L/min), despite similar oxygen consumption (VO2; 43.1 ± 0.8 vs. 44.9 ± 0.2 mL/kg per min), decreased VE/VO2 (35.9 ± 2.0 vs. 32.3 ± 1.5 L/min), reduced economy (VO2/W; 0.20 ± 0.01 vs. 0.22 ± 0.01), increased blood lactate (10 ± 0.7 vs. 11 ± 0.7 mmol), and perception of fatigue (RPE; 7.39 ± 0.4 vs. 7.60 ± 0.3) at the end of the TT, as compared to placebo (main effect, placebo vs. AOC, respectively). Our data demonstrate that prior to exercise, ingesting an AOC, but not exposure to hyperoxia, likely disrupts the delicate balance between pro- and antioxidant forces, which negatively impacts ventilation, blood lactate, economy, perception of fatigue, and performance (power output and 5 km time) in young healthy males. Thus, caution is warranted in athletes taking excess exogenous antioxidants.