Comprehensive analysis of "bath salts" purchased from California stores and the internet.

STUDY OBJECTIVE: To analyze the contents of "bath salt" products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. METHODS: A convenience sample of "bath salt" products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. RESULTS: Thirty-five "bath salt" products were purchased and analyzed. Prices ranged from $9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. "bath salt" products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. CONCLUSION: Comprehensive analysis of "bath salts" purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. "bath salt" products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

[Polycystic ovary syndrome: what are the obstetrical risks?]. / Syndrome des ovaires polymicrokystiques: une pathologie à risque obstétrical?

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and the leading cause of female infertility. This condition is frequently associated with significant metabolic disorders, including obesity and hyperinsulinemia. Therefore, it seems essential to focus on the pregnancy of these patients and possible obstetric complications. Many studies suggest an increase in the risk of obstetric pathology: early miscarriage, gestational hypertension, preeclampsia, gestational diabetes mellitus diagnosed during early pregnancy, prematurity, low birthweight or macrosomia, neonatal complications and cesarean sections. However, it is difficult to conclude clearly about it, because of the heterogeneity of definition of PCOS in different studies. In addition, many confounding factors inherent in PCOS including obesity are not always taken into account and generate a problem of interpretation. However it seems possible to conclude that PCOS does not increase the risk of placental abruption, HELLP syndrome, liver disease, postpartum hemorrhage, late miscarriage and stillbirth.

Is apoptosis a regulatory mechanism during early canine pregnancy?

Fas is a membrane-bound protein which upon activation causes programmed cell death. Fas ligand (FasL) binds Fas on target cells. Both these factors are known to regulate apoptosis at implantation in different species and thus might be involved in the regulation of implantation in dogs. The aim of the study was to assess the expression of Fas and FasL in canine uterine tissue throughout pregnancy as well as in pre-implantation embryos using RT-PCR and RT-qPCR. Uterine tissues was collected from of 21 healthy pregnant bitches (group I: days 10-12, n = 5; group II: days 18-25, n = 6; group III: days 28-45, n = 6) and from 4 non-pregnant bitches (controls: days 10-12). Pregnancy stage was determined by days after mating, that is, 2-3 days after ovulation as determined by vaginal cytology and progesterone measurement. After ovariohysterectomy, uteri from group I bitches were flushed with PBS and the embryos washed and stored frozen at -80°. Tissues from the other groups were taken from the implantation and placentation sites, respectively, covered with Tissue Tek(®) and frozen at -80°. Extraction of RNA was performed with Trizol Reagent and RT-qPCR using SYBR green probes. In pre-implantation embryos, only FasL but not Fas could be detected. In all tissues from pregnant and non-pregnant bitches, both parameters were detectable. Before implantation (group I) expression of FasL resembled that of non-pregnant bitches in early dioestrus and decreased significantly during implantation and thereafter (p < 0.05). Expression of Fas did not change significantly until day 45. The relative expression of Fas exceeded that of FasL at each stage investigated, which is comparable to observations of other species; however, high standard deviations indicate high individual differences. These preliminary results point towards a regulatory function of the Fas/FasL system during early canine pregnancy.

Airway obstruction following canebrake rattlesnake envenomation.

We report an unusual case of canebrake rattlesnake (Crotalus horridus atricaudatus) envenomation whose major manifestation was orolingual edema and airway compromise. The likely source of swelling was mucosal absorption of venom following the first aid technique of cutting and sucking the bite site. Except for airway compromise, the patient had mild local bite site effects (swelling) and mild systemic findings (depressed fibrinogen and elevated creatinine phosphokinase). He was managed with fiberoptic nasotracheal intubation and Crotalid antivenin with good outcome.

Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning.

CASE REPORT: This case series documents the clinical courses of 4 patients after verapamil overdose and 1 patient after amlodipine-atenolol overdose. All subjects had hypodynamic circulatory shock (hypotension, bradycardia, and acidosis) that was not adequately responsive to conventional treatment. After initiation of insulin-dextrose infusion, the hemodynamic status of all 5 patients stabilized and all patients survived. Plasma drug concentrations are reported for all cases and verapamil levels were extremely high in 2 patients (3710 ng/mL and 3980 ng/mL). However, because patients were not treated according to a standard protocol, each patient received variable other supportive measures and inotropic agents, and the infusion rates of insulin were variable among patients. This report provides preliminary evidence toward a larger trial of insulin-dextrose to treat hypodynamic shock from calcium channel blocker overdose.

Incidence of aspiration pneumonia in intubated patients receiving activated charcoal.

Several case reports and animal studies raise concerns over the risk of aspiration pneumonia when administering activated charcoal (AC) to intubated patients. Therefore, we sought to determine the incidence of aspiration pneumonia in intubated overdose patients who then received AC. We conducted a retrospective review from January 1994 to April 1997 of intubated patients who then received AC. Patients were transferred to, or primarily treated at, an 843-bed tertiary medical center with an annual emergency department volume of 100,000 patients. Objective evidence of infiltrate on chest radiograph during initial 48 h of hospitalization was used to determine the incidence of aspiration pneumonia. Patients with known preexisting pneumonia or with administration of AC before intubation were excluded. There were 64 patients identified. Fourteen were excluded for clinical aspiration before intubation, receiving activated charcoal before intubation, or abnormal immediate post-intubation chest radiographs. The remaining 50 patients, ages 1-64 years, 33% male, overdosing on a large variety of substances, required acute intubation and then received AC. Only two patients of these 50 (4%) with initial negative radiographs developed a new infiltrate after intubation and AC. Administration of AC to intubated overdose patients is associated with a low incidence of aspiration pneumonia.

Rapid-sequence intubation at an emergency medicine residency: success rate and adverse events during a two-year period.

OBJECTIVES: Rapid-sequence intubation (RSI) is an active airway intervention used frequently in emergency medicine (EM). The authors hypothesized that RSI can be performed safely in the setting of an EM training program at a tertiary care center. METHODS: Observational study of RSI at an urban ED/Level 1 trauma center with annual census of 100,000 patients. Consecutive patients who underwent RSI during a two-year period were studied. Data included age, gender, type of patient (medical/trauma), indication for intubation, number of intubation attempts (laryngoscope passes), training level of operator, and major immediate adverse events (clinical deterioration within 10 minutes of RSI). RESULTS: RSI was used in 417 of 596 (70%) critically ill patients requiring emergent intubation. The patient demographic distribution was the following: adults 89.7%, male 58%, and trauma 44%. Primary indications for intubation among RSI patients were as follows: mechanical ventilation 57.4%, airway protection 41.3%, and cardiac arrest 1.3%. Distribution of intubations by level of EM training was PGY1, 5%; PGY2, 52%; PGY3, 40%; and attendings, 3%. Intubations were successfully completed within two attempts in 97% of the patients. Major immediate adverse events were encountered in six patients (1.4%) (hypotention=2, hypoxemia=1, dysrhythmia=3). There was no death attributable to RSI. The rate of intubations requiring two or fewer attempts and without major immediate adverse events was 96%. Three patients required cricothyrotomy. CONCLUSION: In the setting of an EM residency at a tertiary care ED, RSI can be performed successfully with few major immediate adverse events.

Carbon monoxide poisoning. Early awareness and intervention can save lives.

Each year, particularly during the heating season, thousands of people are poisoned by carbon monoxide, with potentially devastating outcomes. Initial diagnosis can be difficult because symptoms closely resemble those of influenza and are often misinterpreted. Dr Tomaszewski discusses diagnosis and treatment, including the benefits and risks of hyperbaric oxygen therapy.

Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group.

OBJECTIVE: Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. METHODS: Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) +/- hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t1/2, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. RESULTS: Ten patients, mean age 49 years (range 28-73 years), presented a mean of 10.5 hours (range 3.5-21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8-62.2 mmol/L) (115 mg/dL; range 5-386 mg/dL) and glycolate was 17.0 mmol/L (range 10.0-23.7 mmol/L). Nine of 10 underwent hemodialysis. Nonhemodialysis (n = 4) elimination rate was 1.08 +/- 0.67 mmol/L/h (mean +/- SD) and t1/2 was 626 +/- 474 minutes. Elimination t1/2 during hemodialysis (n = 8) was 155 +/- 42 minutes. Hemodialysis clearance (n = 5) was 170 +/- 23 mL/min with flow rates 250-400 mL/min. Pearson correlation coefficients were: anion gap vs glycolate r2 = 0.65 (p = 0.005), bicarbonate vs glycolate r2 = 0.10 (NS) and pH vs glycolate r2 = 0.06 (NS). CONCLUSION: Glycolate has a slow elimination rate and long half-life. Hemodialysis effectively clears glycolate. An increased anion gap correlates with the presence of glycolate. Hemodialysis is projected as useful for ethylene glycol-poisoned patients with anion gap acidosis and low ethylene glycol blood levels.

The effect of hypertonic sodium and dantrolene on propranolol cardiotoxicity.

OBJECTIVE: To evaluate whether measures that lower cytosolic calcium (Ca) can reverse propranolol (PROP) toxicity in the isolated, perfused rat heart. METHODS: Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit-bicarbonate (KHB) buffer solution. Toxicity was produced by perfusing the hearts with PROP (5 micrograms/mL) for 30 minutes. Subsequently, the hearts were treated for 30 minutes with buffer containing PROP plus experimental treatment. Three treatments were chosen: hypertonic sodium (Na) (160 mmol), to stimulate Na-Ca exchange, dantrolene (DAN) (10 mumol), to inhibit Ca release from sarcoplasmic reticulum, and combined hypertonic Na and DAN. The hearts were paced after 20 minutes of treatment. Heart rate (HR), left ventricular peak systolic pressure (LVP), the first derivative of LVP (dP/dt), and coronary flow were measured. RESULTS: PROP decreased HR and rendered the hearts refractory to pacing. PROP did not alter dP/dt. PROP increased LVP consistent with increased cytosolic Ca. Combined hypertonic Na and DAN treatment restored the ability to pace PROP-toxic hearts to the basal HR. Individually, hypertonic Na or DAN treatment partially restored the ability to pace toxic hearts. As experimental treatments increased HR, dP/dt and LVP decreased, consistent with decreased cytosolic Ca availability. CONCLUSION: These data are consistent with the hypothesis that bradycardia during beta-blocker cardiotoxicity is mediated by altered Ca homeostasis.

Insulin improves survival in a canine model of acute beta-blocker toxicity.

STUDY OBJECTIVE: To compare the efficacy of a novel antidote, insulin, with standard treatments, glucagon and epinephrine, in a canine model of acute beta-blocker toxicity. METHODS: Anesthetized dogs were fitted with instruments by means of thoracotomy and vascular cutdown for multiple cardiodynamic, hemodynamic, metabolic, and electrical measures. After basal measurements were taken, animals received intravenous propranolol (.25 mg/kg/minute) continuously for the remainder of the experiment. Toxicity was defined as a 25% decrease in the product of heart rate times mean blood pressure. Thirty minutes after the development of toxicity, toxic measures were taken (treatment 0 minutes), and then the animals (n = 6 each group) received either sham (saline solution), insulin (4 IU/minute with glucose clamped), glucagon (50 micrograms/kg bolus, then 150 micrograms/kg/hour infusion), or epinephrine (1 microgram/kg/minute). Animals were monitored until death or for 240 minutes. RESULTS: Propranolol decreased contractility, left ventricular pressure, and systemic blood pressure, and resulted in death of all sham-treated animals by 150 minutes. Six of six insulin-treated, four of six glucagon-treated, and one of six epinephrine-treated animals survived. Survival was greater for insulin-treated animals, compared with either glucagon-treated (P < .05) or epinephrine-treated animals (P < .02) by the log-rank test. Insulin-treated animals were characterized by improved cardiodynamics and hemodynamics, increased myocardial glucose uptake, and decreased serum potassium. CONCLUSION: Insulin is a superior antidote compared with glucagon or epinephrine in an anesthetized canine model of acute beta-blocker toxicity.

Prophylaxis against middle ear barotrauma in US hyperbaric oxygen therapy centers.

The most common complication of hyperbaric oxygen (HBO) treatment is middle ear barotrauma, which can lead to permanent hearing loss and vertigo. Unconscious patients and infants present a special diagnostic challenge because of difficulties in communicating pain and equalizing pressure across the ears. This study involved a phone survey to all hospital-based HBO centers in the United States concerning routine practice for middle ear barotrauma prophylaxis. Results indicate that more than a fifth of centers always do routine prophylactic myringotomies on intubated patients (30 of 126) and infants (19 of 86). Less than half of centers never performed the procedure as routine prophylaxis. A third of centers (49 of 145) routinely administered prophylactic drugs before HBO treatment. Topical nasal decongestants, particularly oxymetazoline, were preferred to systemic oral medications (chi2 = 20.8, P<.001). These results show that there is great variance in clinical practice with regard to middle ear barotrauma prophylaxis among US HB0 centers. Many centers are using unproven therapies such as topical nasal decongestants.

Spontaneous hemoperitoneum from brodifacoum overdose.

Brodifacoum is a 4-hydroxycoumarin derivative that is commonly used as a rodenticide. Human exposures have produced severe coagulopathies resulting in hematuria, gastrointestinal bleeding, intracranial hemorrhage, and death. This is the first report of spontaneous hemoperitoneum secondary to brodifacoum ingestion. The patient was successfully managed with fresh frozen plasma, packed red blood cells, and vitamin K1. No surgical intervention was performed. The patient required ongoing daily vitamin K1 therapy for longer than 6 months.

The effects of extracellular ions on beta-blocker cardiotoxicity.

The mechanism of beta-blocker induced cardiotoxicity is poorly understood. One possible explanation is that beta-blockers induce ion dyshomeostasis, resulting in cardiac hyperpolarization. The intent of this study was to determine if modifying extracellular ions would reverse cardiotoxicity from two beta-blockers: propranolol (PROP) and atenolol (ATEN). Two treatments were studied: low extracellular K+ and high extracellular Na+. Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit- Bicarbonate buffer (KHB) solution. Toxicity (Tox) was induced by perfusing hearts for 30 min with KHB + PROP [5 microgram/ml] or KHB + ATEN [2.5 mg/ml]. Subsequently, hearts were perfused with KHB containing either PROP or ATEN, but modified by lowering K+ [2.3 mM] or raising Na+ [160 mM] for a 30-min treatment (Tx) period. Hearts were paced near the end of treatment. Cardiodynamics were monitored via a balloon-tipped catheter in the left ventricle. The first derivative of LV pressure (dP/dt) with respect to time served as our index of myocardial performance. Tx groups were as follows: (1) KHB only, (2) PROP only, (3) PROP + K, (4) PROP + Na, (5) ATEN only, (6) ATEN 4 K, and (7) ATEN + Na. PROP induced negative chronotropic effects and rendered the hearts refractory to pacing. ATEN demonstrated similar chronotropic toxicity plus decreased myocardial contractility. Tx with low extracellular K+ and high extracellular Na+ increased HR and restored the ability to pace, thereby reversing toxicity. These data suggest that beta-blocker toxicity is mediated via hyperpolarization.

Urine toxicology screens in drivers suspected of driving while impaired from drugs.

OBJECTIVE: Police departments, in conjunction with the National Highway Traffic Safety Administration, have developed a standardized evaluation aimed at identifying drivers impaired by drugs other than ethanol. These evaluations are performed by specially trained police officers known as Drug Recognition Experts. METHODS: We retrospectively reviewed the evaluations of 242 drivers detained for driving while impaired in the City and County of Denver from January 1, 1988 to June 30, 1990. RESULTS: All drivers had urine toxicology screens performed, which were positive for a mean 1.2 +/- 0.9 SD (range zero to four) for drugs having the potential for causing driving impairment. The 193/242 urine screens (79.8%) testing positive showed the following drugs: cannabis 162 (66.9%), stimulants (including cocaine metabolites) 80 (33.1%), depressants (benzodiazepines and barbiturates) 24 (9.9%), narcotics 12 (5.0%), inhalants (toluene) 1 (0.4%), hallucinogens (LSD) 1 (0.4%), and other 3 (1.2%). Drug Recognition Experts, based on their initial evaluation, were able to predict correctly some or all of the drugs found on the urine screens in 178/242 (73.6%) of cases. Overall agreement between the Drug Recognition Experts opinions and urine screen results had a kappa value (p < 0.05) of 0.41. CONCLUSIONS: There was a high rate (79.8%) of positive urine toxicology screens in drivers suspected of nonethanol drug impairment. In most cases, Drug Recognition Experts were able to reliably predict the results of these screens.

Effect of acute ethanol ingestion on orthostatic vital signs.

STUDY OBJECTIVE: To determine the effect of acute ethanol intoxication on the results of orthostatic tilt testing. DESIGN: Prospective, randomized crossover study. Subjects received ethanol (1.1 gm/kg) or an equal volume of water added to nonalcoholic beer. Orthostatic vital signs, ethanol concentration, and relative volume status were checked initially and hourly for 8 hours. PARTICIPANTS: Twenty healthy human volunteers, 10 men, and 10 women. RESULTS: Peak ethanol concentration was 116 +/- 18 mg/dL (mean +/- SD) 1 hour after ingestion. ANOVA for repeated measures revealed a significant difference in orthostatic pulse change and relative volume deficit between the ethanol and placebo groups (P < .05). Post hoc testing revealed significant differences between the two groups at two, five, seven and eight hours post ingestion for pulse change, and two to eight hours for volume status (Bonferroni's corrected t test, P < .0055). At 2 and 5 to 8 hours, there were significantly more positive tilt tests (+/- 30 beat/minute increase) in the ethanol group than in the placebo group (P < .05). Starting at 2 hours, the ethanol group had a statistically significant relative fluid deficit averaging .5 L by 3 hours. There was no difference in postural blood pressure changes between the two groups. CONCLUSION: In healthy volunteers, ethanol intoxication resulted in exaggerated postural pulse changes and in a greater proportion of positive orthostatic tilt test results than in a placebo group. These changes were accompanied by significant relative fluid deficits.

Methamphetamine toxicity prevented by activated charcoal in a mouse model.

STUDY OBJECTIVE: To determine the effectiveness of activated charcoal in preventing toxicity from oral methamphetamine HCI. DESIGN: Randomized, prospective, nonblinded, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: CD-1 male mice. INTERVENTIONS: Mice were given 100 mg/kg methamphetamine HCI (lethal dose 60) in water by oral gavage. Within 1 minute of methamphetamine administration, mice received either 1 g/kg activated charcoal or an equivalent volume of water as control. MEASUREMENTS AND MAIN RESULTS: Mice were observed for time to onset of symptoms (piloerection, agitation, and tremor) and mortality at 1, 24, and 48 hours. Activated charcoal delayed onset of symptoms (5.53 +/- 1.25 minutes versus 4.27 +/- 1.22 minutes, P < .002) and decreased mortality compared to controls at 1 hour (1 of 20 versus 10 of 20, P < .003) and 24 hours (five of 20 versus 12 of 20, P < .05). There was no difference between groups in mortality at 48 hours. CONCLUSION: A single dose of activated charcoal given after oral methamphetamine delayed onset of toxicity and decreased early mortality in mice. There was no effect on overall mortality.

Use of hyperbaric oxygen in toxicology.

HBO has become recognized as a potential treatment for a variety of toxins. HBO is helpful because it provides an excess of dissolved oxygen, which not only can sustain life in the absence of hemoglobin, but in some cases can actually increase the clearance of toxins. In addition, it is now apparent that HBO serves more complex roles in toxicological injuries, such as modifying PMN-endothelial interactions and preventing oxidative tissue injury. The major drawback of HBO therapy is the lack of controlled clinical trials, partly due to the rarity of most of the toxins discussed. In fact, the field of hyperbaric medicine has come under increasing criticism for this failure. There is a physiologic basis for use of HBO in the toxins discussed. Unfortunately, only for CO is patient volume adequate for studies to document efficacy. Regarding the other toxins mentioned, the use of HBO should be reserved for carefully selected cases in which patients have failed routine care or are at risk for delayed effects.

Prevention of toxicity from oral cocaine by activated charcoal in mice.

STUDY OBJECTIVE: To study the effectiveness of activated charcoal in preventing toxicity after an enterally administered cocaine hydrochloride overdose in mice. DESIGN: A prospective, randomized, controlled animal laboratory investigation. INTERVENTIONS: Fasted mice were given aqueous cocaine hydrochloride (0.8% final concentration) 100 mg/kg body weight orally by gavage tube. One minute later, animals received one of three treatments by gavage: 1 g activated charcoal/kg body weight, 2 g activated charcoal/kg body weight, or an equivolume of water (control). All treatments consisted of 20 mL/kg body weight of an activated charcoal slurry with water. MEASUREMENTS: After 24-hour observation, proportions of seizures and deaths between each group were compared using Pearson chi 2 test followed by Fisher's exact test (P < .017 for significance after Bonferroni's correction). MAIN RESULTS: There were 20 seizures and 16 deaths in the control group (20 mice). There were four seizures (P = .0004) and one death (P = .0004) in the 1-g activated charcoal/kg group (ten mice) and five seizures (P = .0018) and three deaths (P = .015) in the 2-g activated charcoal/kg group (ten mice). CONCLUSION: In this mouse model, activated charcoal decreased the incidence of seizures and death after an enteral cocaine hydrochloride overdose.