2.5 out of 5 stars

Oxymorphone Insufflation Associated with Acute Sensorineural Hearing Loss: Case Files of the University of Massachusetts Medical Toxicology Fellowship. Boyle KL, Rosenbaum CD. J Med Toxicol 2013 Jun:9:179-183.

No abstract available

This case report describes a 37-year-old man who experienced transient partial hearing loss after snorting crushed Opana® (oxymorphone). The case itself isn’t much, but it provides the opportunity for the authors to present a good discussion of drug-induced ototoxicity.

Although opiate-associated hearing loss (OAHL) is well described, the authors state that this is the first such case involving oxymorphone. OAHL has occurred after both acute and chronic use. In all cases that have been thoroughly evaluated, the hearing impairment is sensorineural, apparently from drug effect on the cochlea. It is often permanent but can be successfully treated with cochlear implantation.

The authors note that other drug-related causes of hearing loss include:

• antibiotics (aminoglycosides, macrolides, vancomycin)
• anticonvulsants (valproic acid)
• non-steroidal antiflammatory drugs
• anti-hypertensives (enalapril)
• antimalarial (quinine)
• antineoplastics (cisplatin)
• heavy metals (cobalt, mercury)
• loop diuretics (furosemide)
• organic solvents )e.g., carbon disulfide, toluene)

For a more complete list of ototoxic drugs, click here.

Insufflation of oxymorphone has been associated with at least one fatality.

Related posts:

Methadone induces hearing loss

Neurotoxicity of cobalt

Deaths from Carbon Monoxide: WCNC in Charlotte, N.C. reports that on June 8, 11-year-old Jeffrey Williams died of carbon monoxide poisoning in the same Boone N.C. motel room where an elderly couple had died nearly 2 months before. On April 16, Shirley Mae Jenkins, 72, and her husband Daryl, 73, were found dead in the room. Laboratory tests available on June 1 revealed that both victims had carboxyhemoglobin levels > 60%. Apparently these results were not passed on to police and fire officials. The source of the carbon monoxide was traced to a faulty indoor pool water heater.

Ethylene glycol poisoning: On her blog at wired.com, Deborah Blum writes about the medical oncologist at M.D. Anderson Hospital in Houston who is accused of poisoning her colleague/lover using coffee spiked with ethylene glycol. In the post, Blum also reviews other recent episodes of ethylene glycol poisoning.

Speaking of toxic alcohols: ABC News in Australia reports that a 21-year-old man in Brisbane died after drinking home-made grappa contaminated with methanol.

Psychedelic Stamps: Erowid.org has posted a wonderful selection of postage stamps picturing psychotropic plants, as well as scientists who have researched mind-altering botanicals.

Must-read of the week: ion.com has a truly fabulous collection featuring images of bottles and ads from the days when cocaine and heroin were available over-the-counter in products claiming to cure toothache, cough, hay fever, and other ailments.

Strychnine: Also at io9.com, Esther Inglis-Arkell writes about strychnine as a performance-enhancing drug.

3.5 out of 5 stars

Acute Psychosis Associated with Recreational Use of Benzofuran 6-(2-Aminopropyl)Benzofuran (6-APB) and Cannabis. Chan WL et al. J Med Toxicol 2013 Jun 4 [Epub ahead of print]

Abstract

6-APB is a structural analogue of MDA that has characteristics of both phenethylamines and amphetamines. It is not yet scheduled or regulated in the United States. On June 10 2013, 6-APB was listed as a “Temporary Class Drug” in the United Kingdom, a move that outlawed its sale or import.

6-APB is available for purchase over the internet, often labelled as “Benzo Fury” and carrying a warning that it is “Not for Human Consumption”. Its use has been associated with fatality.

This case report describes a 21-year-old man who was brought to the emergency department after ingesting 6-APB and smoking marijuana. He was agitated and paranoid, stating that the emergency staff was “trying to read his mind”. He had multiple forearm lacerations from self-inflicted razor blade wounds. Interestingly, the remainder of his physical examination was unremarkable. There were no other manifestations of the sympathomimetic toxidrome. The patient continued to exhibit paranoia and agitation, treated with diazepam,  throughout his 5-day hospital course. After transfer to a psychiatric hospital, his psychotic manifestations resolved and he was discharged 8 days after presenting to the emergency department.

Toxicological testing of the patient’s urine revealed 6-APB (2,000 ng/ml) along with cannabinoids and a metabolite of the synthetic sannabinoid JWH-122. There were also small amounts of amphetamine, chloroquine, ketamine metabolite, and ephedrine.

In their discussion, the authors make the following points:

• 6-APB is a triple monoamine reuptake inhibitor.
• 6-APB is a potent agonist at the 5-HT_2C receptor, a property that has been associated with developement of anxiety.
• Some users on discussion forums such as Erowid report feelings of anxiety for up to 5 days after exposure to 6-APB.
• 6-APB can produce severe and prolonged neuropsychiatric manifestations.
• Patients who have used 6-APB and present with neuropsychiatric symptoms should be considered for prolonged observation.

3.5 out of 5 stars

Survival of Acute Hypernatremia Due to Massive Soy Sauce Ingestion. Carlberg DJ et al. J Emerg Med 2013 Jun1 [Epub ahead of print]

Abstract

This fascinating case report from the University of Virginia Medical Center describes a 19-year-old male who — apparently on a dare — ingested a quart of soy sauce (17-18% sodium chloride).

When brought to the emergency department 2 hours later he unresponsive (GCS = 3) and had possible seizure activity. His pulse rate was 147 bpm. Head CT was unremarkable. Labs were significant for a sodium of 177 mmol/L and glucose of 384 mg/dL. Four-and-a-half hours after ingestion his sodium was 191 mmol/L.

At that point, the treating physicians reasoned that since a sodium level this high has been strongly associated with fatality and the development of hypernatremia in this case was quite rapid, it would be reasonable to correct the electrolyte abnormality quickly.

The patient received 6 liters of 5% dextrose (D5W) over 30 minutes, followed by free water at a slower rate. His mental status gradually improved, and 32 hours after ingestion his sodium level was 145 mmol/L. At follow-up one month after the admission his mental status was reported as normal and he was “performing well on college examinations.”

The authors state that, to their knowledge, the corrected sodium level of 196 mmol/L is the highest ever reported from acute salt ingestion in a patient who survived.

Chronic hypernatremia should be corrected slowly, since the brain adapts over time to a high sodium level by producing idiogenic osmoles. In this situation, reversing hypernatremia too rapidly can cause cerebral edema, seizures, or herniation. In the case reported here, the sodium level increased so acutely there was no time for this adaptive mechanism to occur.

There are many videos on YouTube of adolescents and young adults taking the so-called “soy sauce challenge.” This seems even less wise than enduring the “cinnamon challenge,” which TPR has reported on before.

Tip o’ the hat to @ToxTalk, who alerted me to this article.

Philosophy students on drugs:  A recent survey in The Tab — a student newspaper at Cambridge (U.K.) University — found that the “druggiest” university in the U.K. is Leeds, whose students prefer marijuana, ecstasy, ketamine, and nitrous oxide (laughing gas). The druggiest subject, according to their data, was philosophy, with 87% of students in this field admitting to use. At the bottom of the list of 22 subjects was medicine, with only 57% of respondents revealing prior use. (Of course, this type of survey is far from scientific, but never mind.)

A blog post on the website for The Guardian (U.K.) newspaper asks the question: why do philosophy students to the most drugs? It notes that the philosopher William James expanded the variety of his religious experience by taking nitrous oxide, and that the Greek philosopher Epicurius recommended using a concoction called tetrapharmakos as way to peace of mind and the happy life. Since tetrapharmakos was made of wax, resin, pitch and tallow, one shouldn’t be surprised that it has gone out of fashion. Unfortunately, the post never quite answers the question about why philosophy majors are the most zonked.

Fentanyl-related deaths: In just a 2-week stretch, the city of Lebanon PA (population 25, 477) has seen 6 overdoses — including one death — attributed to fentanyl. Authorities believe that at least some of these cases the victims had purchased what they believed was heroin and used their usual amounts of drug, not realizing that they were dealing with the much more potent fentanyl.

No soy sauce: a 19-year-old Virginia man is recovering following a 1-week coma caused by hypernatremia after he ingested a quart of soy sauce.

Smoking alcohol: Time magazine’s “Health and Family” blog reports that the practice of “smoking” alcohol has gained some traction. In this practice, ethanol is vaporized either mechanically, or by heating it or pouring it over dry ice. This method is used as an alternative route to intoxication, or by dieters who want to experience the effects of ethanol without the calories. It seems to me that this route for ethanol consumption would be very inefficient, since most of the intoxicant would go up in smoke. (I should point that ethanol does contain calories, however it gets into the system.) In 2004, Slate posted a very good discussion of vaporized ethanol. To read it, click here.

Finally, the podcast “ToxTalk” has posted part 2 of their interview with Earth and Fire Erowid,  creators and curators of erowid.org, the massive psychoactive drug information site.

Tide laundry pod

3.5 out of 5 stars

Laundry Detergent “Pod” Ingestions: A Case Series and Discussion of Recent Literature. Beuhler MC et al. Pediatr Emer Care 2013;29:743-747.

Abstract

In 2011, laundry “pods” were introduced into the United States market. These colorful products are formulated by sealing concentrated liquid detergent inside a water-soluble casing (polyvinyl alcohol). Pods look somewhat like pieces of candy, and can be enticing to young children. Although ingestion of laundry powder or liquid by toddlers usually causes only mild symptoms such as vomiting or mucosal irritation, exposure to the contents of a laundry pod may result in more severe toxicity.

This case series describes four young children who developed significant toxicity after biting into laundry pods. All patients presented with some degree of mental status depression and respiratory distress. Three were intubated, and two required hospitalization for at least one week. Other findings included vomiting, metabolic acidosis, elevated lactate,  epiglottic swelling, difficulty swallowing, and evidence of aspiration.

In their discussion, the authors note that caustic injuries from these products are likely caused by surfactants, and metabolic acidosis with elevated lactate by propylene glycol (which is metabolized to lactic acid).  It is not clear what component is responsible for the presence of decreased or waning-and-waning mental status.

The authors conclude that in these cases “practitioners should be vigilant for rapid onset of neurological impairment and inability to protect the airway in addition to [the] caustic effects.”

The June issue of Pediatric Emergency Care contains two other articles about laundry detergent “pod” ingestion. A case report by Schneir et al. from UC-San Diego describes a 15-month-old girl who required intubation for 5 cays because of bronchospasm and oxygen desaturation after ingesting part of a “pod”. Heppner and Vohra fro UCSF-Fresno present a similar case, and point out that exposure to laundry detergent pods can affect the following systems:

• Gastrointestinal: nausea, vomiting, mucosal lesions
• Pulmonary: coughing, stridor, aspiration, bronchospasm, oxygen desaturation, acute respiratory distress syndrome
• Metabolic: metabolic acidosis, increased lactate
• Ocular: keratitis
• CNS: sudden and profound decreased mental status

The authors note that the deterioration in mental status — not usually seen after ingestion of laundry powders or liquids — can occur as early as 20 minutes after exposure.

Related posts:

Just when you thought it was safe to go back to the laundry room , , ,

Look-alike tox: is it a laundry detergent, or a piece of candy?

3.5 out of 5 stars

Pediatric Marijuana Exposures in a Medical Marijuana State. Wang GS et al. JAMA Pediatr 2013 May 27 [Epub ahead of print]

Abstract

In October 2009, the US. Justice Department decided not to prosecute medical marijuana users and suppliers who were conforming to state laws. As a result, in Colorado the use of medical marijuana skyrocketed. The effects of this change — especially on children — are not yet completely understood.

The goal of this paper, from the Rocky Mountain Poison Center and the University of Colorado School of Medicine, was to compare the number of children seen in a tertiary-care pediatric emergency department for exposure to marijuana in the years before and after October 2009.

The authors did a retrospective study covering January 2005 through December 2011 to identify children < 12 years old who had specific ICD-9 codes and a urine toxicology screen positive for marijuana. They found identified no such patients before October  1 2009, but 14 patients after that date. They conclude that after the Justice Department’s policy change, there was a “new appearance of unintentional marijuana ingestions by young children”.

I’m sure they’re correct, but the explanation for the increased number of cases may partially involved heightened awareness on the part of clinicians, and a lower threshold for ordering toxicology screen on children with suggestive but nonspecific signs and symptoms. The main value of this paper, however, is in the brief descriptions of their 14 cases. Some key points:

• Seven patients had a history of exposure to marijuana cookies, cakes, or candy.
• Ten patients were described as lethargic or somnolent.
• One patient was admitted to the pediatric intensive care unit because of respiratory insufficiency.
• One patient was ataxic; another complained of dizziness.

As the 60 Minutes piece at the top of this page suggests, in some states THC  is becoming available in palatable form such as brownies, cookies, soft drinks etc.  As both medical and recreational use of marijuana become legal and more widespread, inadvertent pediatric exposure will definitely go up. The diagnosis should be considered in children who present with unexplained lethargy, ataxia or dizziness, and parents questioned about possible sources at home. In 4 of these cases, the source was a grandparent’s medical marijuana.

In an accompanying editorial, Hurley and Mazor point out that signs and symptoms of marijuana intoxication may include:

• anxiety
• hallucinations
• panic attacks
• dyspnea
• chest pain
• nausea
• vomiting
• dizziness
• somnolence
• CNS depression
• respiratory depression
• coma

Note: Although Wang’s abstract and paper states that the study population included children less than 12 years of age, one of the fourteen patients was 12.

The new Smart FOAM app for the iPhone and iPad is now available. It contains several tools that will make it easier to follow individual blogs and podcasts and specific topics that are posted as part of the ever-growing Free Open Access Medical education movement. These tools include:

• Updated links to new posts.
• An updated list of tweets that contain the hashtag #foamed.
• Links to brief cases and images uploaded by the Global Medical Education project.
• The GoogleFOAM search engine, a tool that searches FOAM resources on the Web.
• Links to 2608 sets of guidelines.

This is a trial version of the app, which was created by Dr. Tessa Davis. It’s free, and is available at the iTunes app store.

With the discovery of new letters this week said to contain “ricin” and mailed to public figures such as President Obama and New York City Mayor Michael Bloomberg, news media have had further opportunities to embarrass themselves by misreporting the actual risks that toxin, which is derived from castor beans. The Washington Post ran an AP story , suggesting in the headline that ricin was “the perfect poison,” while burying in the 9th paragraph that at most only one person has ever actually been killed by ricin. The Los Angeles Times does much better. Their great science reporter David Willman notes that the letters are more frightening than dangerous, and that not a single person has ever been affected — let alone killed — by ricin sent through the mail. Willman mentions that although initial reports stated several police officers exposed to the letters developed “minor symptoms”, in face they seem not to have been affected at all. For my take on what is, in my opinion, an overblown ricin hysteria, read my Emergency Medicine News column by clicking here.

In a special guest episode, Matt Zuckerman at the podcast ToxTalk interviews Earth and Fire Erowid, the founders and directors of the Erowid Center, a compendium of information related to psychoactive plants and chemicals, as well as the frequently consulted online library erowid.org. In Part 1 of the interview, Earth and Fire reveal that all the “first-person” accounts of correspondents using various psychoactive substances have been reviewed and vetted. Unfortunately, they are not asked more detail about this. What is the review process? How do they determine if an individual has actually been exposed to the psychoactive drug he or she claims to be describing, or possibly just made up the experience. Perhaps Dr. Zuckerman will ask follow-up a questions along these lines in part 2, which will be posted shortly.

At The New Yorker magazine, Gideon Lewis-Kraus reviews White Out: The Secret Life of Heroin,Michael W. Clune’s memoir of his heroin addiction, calling it “sensual and hilarious”. The review has some great lines. Two of my favorites:

• “What most drug books don’t do is make the reader, upon closing the book, feel as though he or she really out to think more seriously about experimenting with drugs.”
• “Anybody who’s read ‘Being and Nothingness’ can agree that there’s such thing as too many drugs.”

444

http://www.youtube.com/watch?v=2yj-8fgFkM8

3 out of 5 stars

Pharmacology of Kratom: An Emerging Botanical Agent with Stimulant, Analgesic and Opioid-Like Effects. J Am Osteopath Assoc 2012 Dec;112:792-799.

Abstract

Kratom is a psychoactive leaf from the southeast Asian tree mitragyna speciosa, a species related to the coffee and gardenia plants. Because the leaf contains over 20 active substances and its effects are dose-related, ingesting the leaf in pill or tea form has been associated with a variety of effects.

At low doses, the leaves produce a stimulant effect that can be perceived as pleasant and energizing, but can also result in anxiety, irritability and aggression. At high doses, kratom is active at the opioid μ and δ receptors, causing opioid-like effects such as analgesia, sedation, nausea and constipation. Seizures have been reported. Like opiates, kratom has a significant potential for addiction that is often not recognized by users. Because of of these addictive properties, kratom has been banned by a number of countries in Southeast Asia, including Thailand.

Kratom is easily available over the internet, and frequently self-administered as a “legal” opiate to treat chronic pain and opiate withdrawal. It is also used recreationally. To this date, kratom has not been regulated by the U.S. federal government.

Since kratom is so readily available, emergency practitioners and toxicologists should be aware of its properties and adverse effects. This review article is a good place to start.

Related posts:

Kratom: a unique leaf with stimulant and opiate-like effects

Comprehensive review of new designer drugs

Hepatotoxicity from abuse of kratom: first reported case

3 out of 5 stars

Aminorex poisoning in cocaine abusers. Karch SB et al. Int J Cardiol 2012 Jul 26;158:344-346.

Abstract

The drug aminorex was introduced in several European countries as an appetite suppressant in 1965, but quickly withdrawn when its use was associated with cases of pulmonary hypertension (PH) and a high fatality rate.

Starting in 2004, a large percentage of cocaine batches tested have been shown to contain levamisole. Recent investigations have demonstrated that levamisole is metabolized to aminorex in humans.

In the European experience, onset of symptoms of PH began after six to nine months of aminorex use, with average daily doses of 10 -40 mg. Although it is not know how much aminorex would be produced after exposure to cocaine contaminated with levamisole, the authors of this article speculate that cocaine users may be at increased risk for PH. Although PH has been associated with cocaine use, the literature on this predates 2004.

Because the symptoms of PH are nonspecific and develop slowly, the diagnosis can be difficult to make. This article is valuable in alerting clinicians cocaine users may be at risk for the condition. I expect future studies will determine just how much aminorex is produced from exposure to typical amounts of contaminated cocaine.

Remember, there are two known conditions that can be caused by levamisole-tainted cocaine: agraulocytosis and necrotizing vasculitis.

Tip o’ the hat to Dr. Jerry Hoffman, who alerted me to this possible connection. I had not heard of it before.

Related posts:

Cocaine-associated hyponatremia: is levamisole the culprit?

Levamisole-adulterated cocaine: an excellent review

Cocaine, levamisole, and the white blood count 

Dramatic pictures: vasculitis caused by levamisole-contaminated cocaine

Scrotal gangrene after smoking crack

Unusual complication of cocaine abuse

Case reports: neutropenia associated with levamisole-adulterated cocaine

Why is the antihelminthic drug levamisole used to adulterate cocaine?

Cocaine adulterated with levamisole implicated in 21 cases of agranulocytosis

SHISHA

The Guardian (U.K.) has a feature describing that use of the drug shisha is increasing in Greece at a rate that parallels the unravelling of that country’s economy and increasing desperation, especially among the poorest segments of the population.

Much of the article seems to come from a vice.com documentary. (For more on vice.com, read this fascinating article published recently in The New Yorker.

Sisha seems to be a derivative of methamphetamine, easy to make and available at low prices (1-2 € per hit).  It is often contaminated with precursor ingredients such as battery acid, and is quite dangerous. One user is quoted in the article:”It is a killer but it also makes you want to kill. You can kill without understanding that you have done it … And it is spreading faster than death. A lot of users have died.”

Recreational Marijuana: is it dangerous?

Scientific American has posted an article cautioning that we still don’t really know the acute or chronic risks of legalizing recreational marijuana and making it more readily available. There is evidence that a blood marijuana level of 5 nm/ml can cause driving impairment similar to that associated with a blood alcohol level of 0.08 gm/mL, but that enforcing this will be difficult. In addition, marijuana may have detrimental effects on lung function and concentration.

Datura poisoning from frozen vegetables

Nine people in Finland have developed anticholinergic poisoning after eating a frozen vegetable product contaminated with seeds from the Datura plant. Presenting signs and symptoms included tachycardia, dry mouth, and decreased vision. One patient was hospitalized for a week with hallucinations and amnesia. To read a report of this incident, click here. 

“Crack babies”: another example of media-fueled hysteria

The New York Times “Retro Report” series posted a video examining the furor over “crack babies” — a somewhat misleading term that generally referred to infant born of mother who had been exposed to cocaine. Despite predictions of vast numbers of severely impaired children — suffering from a wide range of problems including seizures, cerebral palsy, addiction, and low birth rate, as well as significant social and emotional deficits — the envisioned nightmare scenario did not occur. The report makes the point that fetal exposure to alcohol is a much more serious problem. The view the video, click here.

3 out of 5 stars

Digoxin Toxicity with Normal Digoxin and Serum Potassium Levels: Bewre of Magnesium, the Hidden Malefactor. Rao MPR et al. J Emerg Med 2013 May 16 [Epub ahead of print]

Abstract
This case report from Oman describes at 66-year-old woman (inexplicably described as “elderly”) who presented to hospital with one day of nausea, vomiting, abdominal distress, and palpitations. Her medications included furosemide, spironolactone, digoxin, carvedilol, lisinopril, metformin, and calcium. Initial EKGs showed evidence of junctional tachycardia and digoxin effect.

The treating physicians initially considered digoxin toxicity, but were nonplussed when testing showed that both the digoxin and the serum potassium levels were “normal”. [Digoxin = 2.4 nmol/L; potassium = 3.9 mmol/L]  However, further testing revealed significant hypomagnesemia. [Serum magnesium = 0.39 mmol/L, with normal = 0.65-1.25]  After magnesium repletion with 2 g given over 60 minutes, the increased automaticity resolved, and her EKG showed a sinus rhythm at a rate of 70 beats per minute. No digoxin immune Fab was administered.

In the discussion of this case, the authors touch on the following important points:

• Enhanced automaticity and impaired conduction are hallmarks of digoxin toxicity.
• Hypokalemia and hypomagesemia sensitize the myocardium to digoxin
• Digoxin toxicity can be precipitated by conditions such as hypokalemia, hypomagnesemia or hypothyroidism, even if the digoxin level is “normal”.
• Administration of magnesium is contraindicated in patients with bradycardia, AV block, or severe renal failure.

Note that although a serum digoxin level of 2.4 nmol/L is technically “therapeutic” [reference level 1.9-2.6 nmol/L], some recent commentators have recommended lowering the upper therapeutic level by about 50%.

The key take-home lessons:

1. Do not depend solely on laboratory values to diagnose digoxin toxicity.
2. If digoxin toxicity is suspected, check the magnesium level.

3.5 out of 5 stars

The New Crisis in Confidence in Psychiatric Diagnosis. Frances A. Ann Int Med 2013 May 17 [Epub ahead of print]

Full Text

Allen Frances, professor emeritus and former chairman of the Department of Psychiatry at Duke, has long argued that the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) would be a seriously flawed product. He much credibility on this issue — perhaps along with potential bias — since he chaired the task force that produced the previous edition, DSM-IV, in 1992.

In this short but interesting article, appearing just as DSM-5 is becoming available, Dr. Frances summarizes his objections. Basically, he argues that DSM-V will accelerate the already alarming trend of psychiatric diagnosis inflation, resulting in an epidemic of false-positive diagnoses and use of unnecessary, potential harmful medications. He points out that this process has been happening at least in the 2 decades since DSM-IV was published:

In the past 20 years, the rate of attention-deficit disorder tripled, the rate of bipolar disorder doubled, and the rate of autism had a more than 20-fold increase.

DSM-5, Frances contends, will make things much worse:

The DSM-5, the recently published firth-edition of the diagnostic manual, ignored this risk and introduced several high-prevalence diagnoses at the fuzzy boundary with normality. With DSM-5, patients worried about having a medical illness will often be diagnosed with somatic symptom disorder, normal grief will be miidentified as ajor depressive disorder, the forgetfulness of old age will be confused with ild neurocognitive disorder, temper tantrums will be labeled disruptive mood dysregulation disorder, overeating will become b eating disorder, and the already overused diagnosis of attention-deficit disorder will be even easier to apply to adults thanks to criteria that have been loosened further.

In addition, Frances charges that the entire process that produced DSM-5 was corrupt:

I found the DSM-5 process secretive, closed, and disorganized. Deadlines were consistently missed. Field trials produced reliability results that did not meet historical standards. I believe that the American Psychiatric Association (APA)’s financial conflict of interest, generated by DSM publishing profits needed to fill its budget deficit, led to premature publication of an incompletely tested and poorly edited product. The APA refused a petition for an independent scientific review of the DSM-5 that was endorsed by more than 50 mental health associations. Publishing profits trumped public interest. . . .

The issues surrounding DSM-5 have potentially enormous consequences for the field of medical toxicology, since diagnostic inflation may very well result in an exponential increase in prescribing psychotropic drugs such as stimulants and antidepressants.

For those interested in this important topic,  Dr. Frances’s lecture “Diagnostic Inflation: Does Everyone Have a Mental Illness”,  given last year at the University of Toronto, is worth checking out:

http://www.youtube.com/watch?v=yuCwVnzSjWA

http://www.youtube.com/watch?v=OkvjhWirED8

In a recent post titled “Hashville Skyline”, Slate describes the way that references to marijuana has infiltrated into country music tracks over the last decade or so. In this single, from the Pistol Annies‘ new album Annie Up, one of the singers describes how she relieved the tension surrounding a drunken family Christmas dinner by sneaking out for some weed:

So I snuck out behind the red barn
And I took myself a toke
Since everybody here hates everybody here
Hell I might as well be the joke

In future editions of “Tox Tunes”, we’ll visit some of the other country songs in which pot makes an appearance.

Tricyclic Antidepressant Overdose – Over at EMCrit Blog, Scott Weingart has posted a superb podcast discussing the presentation and treatment of TCA overdose. In severe cases not responding to standard therapy, lidocaine, lipid rescue, or ECMO may be indicated. Gastrointestinal lavage — I’m not so sure. Both the podcast and the show notes are well worth your attention.

Was Toronto mayor Rob Ford caught on film smoking crack? 

http://www.youtube.com/watch?v=IaOerRnp4KU

Two journalists from the Toronto Star report that they have seen a video apparently showing mayor Rob Ford smoking from a crack pipe. The mayor has issued what appear to be non-denial denials. New York Magazine has chronicled 20 instances of bizarre behavior exhibited by the mayor, at least several seeming drug related. And in an hilarious feature, Slate challenges the reader to identify whether each of 20 different quotations were uttered by Mayor Rob Ford of Toronto or Mayor Diamond Joe Quimby of the Simpsons’ hometown Springfield.

Toxic Beer – A Florida man is suing a Dallas-area Red Lobster for caustic injuries apparently sustained after drinking a draft beer ordered at the restaurant.  The Dallas Observer reports that Justin Grogg, in town from Florida on a business trip, developed severe pharyngeal and gastrointestinal pain immediately after downing the beer. Gregg’s lawsuit claims that the restaurant had cleaned in beer’s keg and tubing with potassium hydroxide earlier that day, but neglected to rinse system adequately. The suit is seeking compensation for mental and physical pain, as well as medical expenses.

4 out of 5 stars

Critical Care Management of Verapamil and Diltiazem Overdose with a Focus on Vasopressors: A 25-Year Experience at a Single Center. Levine M et al. Ann Emerg Med 2013 May 1 {Epub ahead of print]

Abstract

This uncommonly interesting and thought-provoking study comes from the Department of Medical Toxicology at Banner Good Samaritan Medical Center in Phoenix. The authors note that in recent years, many toxicologists have suggested that hyperinsulinemic euglycemic therapy (HIT) is superior to vasopressors in the treatment of calcium channel blocker (CCB) toxicity. However, there have been no studies comparing the two modes of treatment.

At the authors’ institution — one that includes an in-hospital toxicology service — administration of high-dose vasopressors is a mainstay of treating these cases, and HIT apparently somewhat de-emphasized. To evaluate their perception that patients who present with CCB overdose almost always respond well to vasopressors, the authors retrospectively reviewed their experience of 25 years (1987 through 2012) with patients > 14 years of age who had laboratory-confirmed overdose to verapamil or diltiazem.

They identified 48 eligible patients, half with exposure to verapamil. Three patients received HIT, along with multiple vasopressors. In total, 33 patients received vasopressors (median 2 drugs, range 1-5). Maximum infusion rates included norepinephrine 100 μg/min, dopamine 100 μg/kg/min, epinephrine 150 μg/min, and phenylephrine 250 μg/min.

There was 1 death which apparently was caused by over-sedation for alcohol withdrawal and respiratory arrest, rather than the primary effects of CCB overdose. There were 8 possible or probable ischemic complications in 5 patients, all or most of which could be attributed to hypoperfusion from CCB overdose, rather than the effects of vasopressors. Except for the one patient who died, all the others survived neurologically intact.

The authors conclude that:

. . . management with high-dose vasopressors without hyperinsulemic euglycemic is not detrimental, given complete recovery in all but 1 patient. . . we recommend the use of initial fluid challenges and vasopressors as first choices in supporting blood pressure and treating shock caused by verapamil and diltiazem toxicity.

As the authors note in their “Limitations” section, these results may not be generalizable beyond their institution, which has extensive in-house toxicology resources. However, the paper makes one reconsider the effectiveness of vasopressors in these cases, especially when given in high doses. This is important reading, especially for toxicologists.

4 out of 5 stars

Critical Care Management of Verapamil and Diltiazem Overdose with a Focus on Vasopressors: A 25-Year Experience at a Single Center. Levine M et al. Ann Emerg Med 2013 May 1 {Epub ahead of print]

Abstract

This uncommonly interesting and thought-provokeng study comes from the Department of Medical Toxicology at Banner Good Samaritan Medical Center in Phoenix. The authors note that in recent years, many toxicologists have suggested that hyperinsulinemic euglycemic therapy (HIT) is superior to vasopressors in the treatment of calcium channel blocker (CCB) toxicity. However, there have been no studies comparing the two modes of treatment.

At the authors’ institution — one that includes an in-hospital toxicology service — administration of high-dose vasopressors is a mainstay of treating these cases, and HIT apparently somewhat de-emphasized. To evaluate their perception that patients who present with CCB overdose almost always respond well to vasopressors, the authors retrospectively reviewed their experience of 25 years (1987 through 2012) with patients > 14 years of age who had laboratory-confirmed overdose to verapamil or diltiazem.

They identified 48 eligible patients, 24 with verapamil exposure.

Sous Influences. DOCU. by lamaisonrouge

Just returned from a short stay in Paris, where I saw the art exhibit Sous Influences (Under Influences: Artists and Psychotropics) at the Maison Rouge. Although somewhat disjointed and often lacking sufficient context, the show had a number of fascinating works, including Bryan Lewis Saunders‘ series of self-portraits done under the influence of different psychotropic drugs. Also mind-blowing — and somewhat reminiscent of the surrealist motion pictures of Luis Buñuel and Salvador Dali — was the film Images du Monde visionnaire, commissioned by the drug company Sandoz in 1963 to demonstrate the effects of LSD:

http://www.youtube.com/watch?v=VKXZGETIgxo

Sous Influences closes this week, but is worth a visit.

3 out of 5 stars

Metformin overdose-induced hypoglycemia in the absence of other antidiabetic drugs. Al-Abri SA et al. Clin Toxicol 2013 Apr 1 [Epub ahead of print]

Abstract

Hypoglycemia association with metformin overdose has been reported but is distinctly unusual. In cases published previously, it has not been clear if factors other than metformin toxicity — such as co-ingestion of other hypoglycemic agents or poor nutrition — have been present.

This case report describes a 15-year-old girl who ingested an estimated 75 g of metformin and 3 g of quetiapine (Seroquel). On arrival at hospital, her glucose level was normal but she was drowsy, possibly due to the effects of quetiapine. Initial metformin level was 267 mg/L (therapeutic 0.465 – 2.5 mg/L). Several hours after arrival, she developed lactic acidosis and profound hypoglycemia (serum glucose 15 mg/dL) treated with dextrose infusion and hemodialysis.

By the second hospital day, her mental status improved and hypoglycemia resolved. Extensive laboratory testing did not reveal the presence of any other hypoglyeemic agents. The authors conclude that:

Metformin overdose can cause hypoglycemia in the absence of other glucose-lowering drugs, and blood glucose levels should be monitored closely.

They are probably right, but I wish they had discussed the possibility that quetiapine could have caused or contributed to the hypoglycemia. This has been described before.

Police are suspecting that the death of a prominent Pittsburgh neurologist was related to cyanide poisoning. Dr. Autumn Klein collapsed at her home in late April and died 3 days later. Although initial tests detected cyanide, both false positive and false negative results are possible. Final test results may not be available for weeks.

A post on the Scientific American site reports that high lead levels in children and adults in some communities along the Amazon river in Brazil have been traced to the use of lead strips to improvise fishing sinkers, which are often molded by mouth. So far, this practice has proved difficult to eradicate.

The ToxTalk podcast has a recent episode on the methanol poisoning disaster in Libya, which has to date resulted in more that 90 fatalities and sent about 1000 patients to hospital. Matt Zuckerman and the team from the University of Massachusetts discuss methanol poisoning in general, as well as some options when standard interventions such as administering 4-MP or hemodialysis are in short supply. Some take-home lessons:

• isopropanol can falsely elevate serum creatinine
• when determining the osmolal gap, specimens for measured osmolality as well as for electrolytes, glucose, creatinine, and ethanol must be drawn at the same time
• in cases of severe methanol toxicity when hemodialysis is not available, peritoneal dialysis case be considered

3.5 out of 5 stars

Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review. Neavyn MJ et al. J Med Toxicol 2013 Apr 30 [Epub ahead of print]

Abstract

Sodium bicarbonate is used frequently to treat specific overdoses, including those from salicylates, as well as tricyclic antidepressants and other sodium channel blockers that increase the QRS interval. Goals of therapy with this antidote can include alkalinizing the urine or serum, and providing a sodium load.

In 2012, the FDA confirmed that there was a shortage of sodium bicarbonate, and clinicians began looking for alternative preparations that could safely accomplish he goals listed above. Despite a paucity of clinical data, sodium acetate was proposed as a suitable replacement.

The goal of this paper was to review the English-language medical literature relating to the pharmacology of sodium acetate, and to apply what is known to its potential use in place of sodium bicarbonate during times of shortage.

The authors note that the metabolism of sodium acetate is more complex than that of sodium bicarbonate. When given too rapidly, the amount of sodium acetate infused may saturate metabolic pathways, leading to buildup of both acetate and nitric oxide.This can cause hemodynamic instability, with myocardial depression, decreased systemic vascular resistance and hypotension. Because of this potential complication, the authors recommend that when using sodium acetate to treat toxicology-related widened QRS intervals,  1 mEq/kg should be given over 15-20 minutes, rather than a bolus over several minutes.

Take-home lesson: Clinicians should be aware of possible problems involved with substituting sodium acetate for sodium bicarbonate when treating overdoses, and seek consultation fro a toxicologist or poison control center when shortages make such an adjustment necessary.

3 out of 5 stars

Exposures to Discarded Sulfur Mustard Munitions — Mid-Atlantic and New England States 2004-2012. MMWR 2013 Apr 26;62:315-316.

Full Text

Prior to 1970, the U.S. military commonly dumped chemical munitions at sea. Among these munitions are those containing sulfur mustard, a vesicant or blistering agent.  Manifestations of sulfur mustard exposure include burning, irritation or blistering of the skin or mucous membranes, eye irritation, and dyspnea. In the last decade, there are been several reported incidents of  patients developing symptoms after exposure to these munitions:

•  In 2004, two workers developed chemical burns and large blisters after a “black, tar-like substance” leaked from an artillery shell in a driveway that had been paved with crushed clamshells.Tests confirmed sulfur mustard exposure.
• In 2010, fishermen  dredging for clams off Long Island retrieved a munition that leaked a black liquid. Two crew members became symptomatic. Chemical analysis detected sulfur mustard.
• In 2012, a munition containing sulfur mustard was found at a Delaware clam processing plant. The projective was recovered and no person became symptomatic.

Incidents involving symptoms caused by these discarded munitions have affected workers engaged in clam fishing or sea dredging, as well as military ordnance disposing personnel. An important take-home lesson from these cases is that sulfur mustard causes delayed symptoms, with blisters and burning typically starting several hours after exposure.

The article lists several numbers clinicians can call for further information or consultation in case of suspected exposure to sulfur mustard:

CDC Chemical Weapons Elimination Program:      770-488-7100

U.S. Army Chemical Material Activity Programs:   800-488-0648

Related posts:

Great case report of fisherman exposures to sulfur mustard

Sulfur mustard exposure in Massachusetts

[U.S. Army World War II mustard poster from wikipedia.org]

25I-NBOMe

3.5 out of 5 stars

A case of 25I-NBOMe (25I) intoxication: a new potent 5-HT2A agonist designer drug. Rose SR et al. Clin Toxicol 2013;51:174-177.

Abstract

The designer drug 25I-NBOMe is an extremely potent serotonin agonist. Since it is so new, there have been few case reports of toxicity reported in the medical literature. However, there have been several fatalities associated with use of 25I described in the lay press. The website erowid.org has posted a summary of fatalities related to 25I.

This case report, from the Virginia poison Center, describes a 25-year-old man who was brought to the emergency department after jumping out of a moving car. The patient admitted to using 25I, an exposure later confirmed on laboratory testing. He was agitated and reportedly hallucinating, and had a clear-cut sympathomimetic syndrome: tachycardia, hypertension, and mydriasis. He was not hyperthermic. Although manifestations improved after treatment with fluids and a benzodiazepine, agitation persisted and required pharmacologic treatment for 3 days.

Although the details of this case are spotty and seem to have been extracted from a poison center database, it is good to have a laboratory-confirmed case of 25I toxicity in the medical literature.

By the way, Dallas Morning News investigative report @brooksegerton has tweeted about the recent death of a Texas teenager, that has been linked to the related designer drug 25C-NBOMe (25C).

Related posts:

Review of 2C hallucinogenic stimulants

Seizures, hyperthermia and serotonin syndrome following use of designer drug 2C-I (“Smiles)”

25I-NBOMe: a dangerous new hallucinogen

 2C-I:designer hallucinogen linked to North Dakota deaths

Caster beans and ricin: At the ToxTalk podcast, Matt Zuckerman, Jen Carey, and Ed Boyer from the University of Massachusetts toxicology program have a level-headed discussion as to whether or not one should panic if an envelope filled with ricin arrives in the mail. I was especially interested to hear about their recent case of a suicidal man who put 30 castor beans through a blender and swallowed the slurry. Tests for urine ricinine were strongly positive. Consistent with TPR‘s long-held belief that the furor about ricin is much ado about (mostly) nothing, the ensuing nausea, vomiting, and abdominal discomfort quickly resolved. Recommended. To listen to the episode, click here.

Calcium Channel Blocker and Beta Blocker Poisoning: At the PEM ED Podcast, Andy Sloas posted a detailed discussion of clinical issues involved in identifying and treating these overdoses. I agree with most of the points he makes, but I’m just not enthusiastic about his recommendation to start whole bowel irrigation (WBI) in beta-blocker overdose. Either the ingestion is not significant — in which case WBI will not provide benefit — or it’s potentially lethal, and one may end up with a hypotensive patient with a belly full of polyethylene glycol. Not a good situation.To listen to the podcast, click here.

Hitler’s Food Taster: The Associated Press has an interview with 95-year-old Margot Woelk, who says she was one of 15 young women who, during World War II, tasted Hitler’s food for poison.

Gila Monster: Slate’s informative piece about the gila monster contains the following interesting tidbits:

• The diabetes drug Byetta (exenatide) is a synthetic version of exendin-4, a compound found in gila monster salive.
• The gila monster delivers its venom by biting down on an enemy and chewing . . . and chewing  . . . and chewing.
• The “gila monster” depicted in the 1959 film “The Giant Gila Monster” is actually a Mexican beaded lizard (Heloderma horridum):

http://www.youtube.com/watch?v=_3b0NWljlPw

3 out of 5 stars

Hemodialysis for the Treatment of Pulmonary Hemorrhage from Dabigatran Overdose. Chen BC et al. Am J Kidney Dis 2013 Apr 15 [Epub ahead of print]

Abstract

Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved in the United States for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Although dabigatran has certain advantages over coumadin related to issues of dosing and testing, there is no readily available test to measure its anticoagulation effect, and there is no antidote to reverse bleeding.

Recommendations for treating a patient with dabigatran-associated hemorrhage include local control of bleeding, and hemodialysis (HD). Although dialysis may be difficult in a patient with critical bleeding — such as intracranial hemorrhage — this case report, from NYU and the NYC Poison Control Center, suggests that HD may be useful in some cases.

An 80-year-old man presented with hemoptysis and pulmonary hemorrhage. Increasing dyspnea required intubation and mechanical ventilation. History revealed that some dabigatran pills (150 mg) were missing from his supply. INR, aPTT, and thrombin time were all abnormal. The initial dabigatran level was 1,100 ng/ml, over 8 times therapeutic. The patient underwent 4 hours of HD. During dialysis his coagulation studies improved and pulmonary aspirates cleared. Dabigatran levels measured before, during, and after dialysis demonstrated significant drug clearance, although there was some rebound.

The source of hemorrhage was found to be a tuberculous lung abscess.

Related posts:

The many potential problems with using dabigatran

New York times on dabigatran

Case series: four patients with dabigatran-associated bleeding

Guidelines for reversing overdose of dabigatran (Pradaxa) and other new anticoagulants

Care Report: fatal GI bleed 6 days after one dose of dabigatran (Pradaxa)

Dabigatran: is laboratory monitoring really unnecessary?

Dabiagtran and the trauma patient

Dabigatran Toxicity: The Top 10 Questions

Review: the bleeding patient on dabigatran

Dabigatran and the elderly

Dabigatran etexilate: a new challenge for emergency physicians and toxicologists

3.5 out of 5 stars

Ingesting and Aspirating Dry Cinnamon by Children and Adolescents: The “Cinnamon Challenge” Grant-Alfieri A et al. Pediatrics 2013 Apr 22 [Epub ahead of print]

Full text

There are thousands of videos on YouTube of individuals attempting the “Cinnamon Challenge“, which involves ingesting one tablespoon of ground cinnamon without the aid of water or fluids to wash it down. Cinnamon — a spice derived from the bark of certain trees — contains cellulose, fibers that once inhaled persist in the respiratory tree and are not biodegraded.

Cinnamon is a caustic irritant that can cause a hypersensitivity reaction or trigger an asthma attack. Most individuals who attempt to swallow a dry tablespoon-full experience coughing and gagging, along with burning of nasopharyngeal mucus membranes. Pneumothorax has occurred in a number of cases.

As the authors of this helpful article point out, rat studies indicate that inhaling cinnamon dust and cellulose fibers can lead to pulmonary fibrosis, alveobronchiolitis and granulation.Aspiration pneumonia can occur. Although symptoms from undergoing the cinnamon challenge are usually self-limited, children and adults with respiratory diseases such as asthma or cystic fibrosis may be at increased risk.

I am not pleased to report that my very own governor, Pat Quinn of Illinois, is on YouTube taking the “Cinnamon Challenge” and setting an appalling example. By the way, he cheats, washing the cinnamon down with water and, to my eye, ingesting much less than a tablespoon-full:

http://www.youtube.com/watch?v=-Of5BdKZD5o

http://www.youtube.com/watch?v=DZ-yxs8n2aI

Thanks to Rich Warren and The Midnight Special on WFMT in Chicago for playing this song last week. I had not heard it before.

2.5 out of 5 stars

Lithium poisoning: the value of early digestive tract decontamination. Bretaudeau Deguigne MB et al. Clin Toxicol 2013 May;51:243-248.

Abstract

Although whole bowel irrigation is being used less and less as a means of gastrointestinal decontamination in cases of overdose, one possible remaining indication is a potentially significant ingestion of a poison that is not well absorbed to activated charcoal. Practically, this applies to ingestion of heavy metals, including lithium, iron, and the occasional lead chip. The objective of this French study was to . . . well, I’m not sure I can tease out a convincing objective.

The authors state that:

The objective of this study was to evaluate the effects of early digestive tract decontamination on the severity of acute-on-chronic lithium poisoning (acute poisoning in patients under long-term therapy).

Without specifying specific outcome measures, the authors open up the possibility for all sorts of data dredging and post hoc analysis. But this is just the start of the problems with the paper.

The authors retrospectively searched the records of the Angers Poisons and Toxicovigilance Centre for cases of acute-on-chronic lithium overdose. They identified 59 patients. Fifteen patients had received early GI decontamination and 44 had not. (“Early GI decontamination” was defined as whole bowel irrigation (WBI) and/or administration of sodium polystyrene sulphonate (SPS) within 12 h of ingestion).

The two groups were similar as to mean age, estimated dose ingested and documented poisoning severity score (PSS) during the first 12 h after ingestion. A higher percentage of “early decon” patients had ingested a sustained-release preparation.

Although the authors claim their statistical analysis found that early decon was significantly associated with a lower risk of severe poisoning, their criteria for determining this were so vague that I thought the claim unconvincing. It would be a good journal club exercise to list all the design flaws in this paper. One could start with these:

• Being an observational study, there was no standardization as to which patients received early GI decontamination, who received WBI or SPS, or who underwent hemodialysis.
• The study population was small, and was not analyzed with regard to what type of early devon — WBI, SPS, or both — was administered.
• No information is provided as to how long after ingestion the lithium level was drawn, or PSS determined.
• While the definition of severe poisoning seems to have been based on a PSS > 2, a PSS of 2 is actually considered moderate, and I wonder if this definition was decided on post hoc.

The authors conclude that:

Our results, nevertheless, highlighted the possible usefulness of early digestive tract decontamination [in acute-on-chronic lithium toxicity]. . . . Randomized, controlled and prospective studies will now be necessary to enable a separate assessment of these two techniques for digestive tract decontamination.

Look, one might argue, despite the flaws inherent in a retrospective observational study this paper is valuable to generative a hypothesis that, as the authors suggest, can be subject for further study. Nonsense. It is clear to me that a good randomized control trial of this question will never be carried out — neither the will nor the funds to support such a study exists. While there are theoretical reasons to think that early WBI in these cases improves outcome, and the intervention is recommended in many texts, in my opinion we will never demonstrate this scientifically. It will continue to be a matter of faith.

Castor beans

A Mississippi man was arrested today under suspicion of sending letters to President Obama and Senator Roger Wicker (R-Miss) that gave a positive preliminary test for ricin. Further, more conclusive tests are under way.

In the wake of the bombings at the Boston Marathon, it is understandable that this revelation would be unsettling, inevitably brining to mind the deadly anthrax letters that were sent shortly after 9/11. Yet, in my opinion, the concern is overblown. False positive tests for ricin are common — after all, castor beans are common and often present in and around homes. In addition, although ricin is theoretically a powerful toxin, it is extremely difficult to turn it into an effective bioweapon. For reasons I explained almost a decade ago in a column in Emergency Medicine News, ricin has never been proven to have killed anyone, and has never been successfully deployed as a biological weapon. (The Washington Post made a similar point in an article posted today.)

Ricin is a toxin extracted from the castor bean, Ricinus communis. It consists of two peptide chains linked by a disulfide bridge. The A chain enters cells and shuts down protein synthesis, causing cell death. The B chain facilitates this process by binding to receptors on the cell’s surface.

[Photograph of castor beans from wikipedia.org]