3.5 out of 5 stars

Common Hand Sanitizer May Distort Readings of Breathalyzer Tests in the Absence of Acute Intoxication. Ali SS et al. Acad Emerg Med 2013 Feb;20:212-215

Abstract

The goal of this clever study was to determine if use of ethanol-based hand sanitizer by an operator administering a breathalyzer test affected results. Participants reported not consuming ethanol in the previous 24 hours, and had initial breathalyzer readings of zero on an Alco-Sensor III breathalyzer device. There were 3 study groups of 25 subjects each:

• Group 1: Operator applied one pump (1.5 ml) Purell Hand Sanitizer (62% ethanol) to his/her hands and rubbed hands until dry.
• Group 2: Operator applied one pump Purell and performed test before it dried.
• Group 3: Operator applied two pumps (3.0 ml) Purell and performed test before it dried.

Results were as follows:

• Group 1: breathalyzer results ranged from 0.000 to 0.016 g/dL.(median 0.004)
• Group 2: breathalyzer results ranged from 0.020 to 0.109 g/dL (median 0.051)
• Group 3: breathalyzer results ranged from 0.020 to 0.166 g/dL (median 0.119)

The authors conclude:

The use of an alcohol-based hand sanitizer can cause false-positive readings of a breathalyzer when the operator uses the hand sanitizer correctly. The breathalyzer readings are further elevated if more sanitizer is used or if it is not allowed to dry appropriately.

This is useful information. Although the results in Group 1 would not be clinically significant, some of the subjects in Group 2 and most in Group 3 had false-positive results above the legal limit.

3 out of 5 stars

The Effect of Opioid Therapy on Endocrine Function. Brennan MJ. Am J Med 2013 Mar;126:S12-S18.

Abstract

In recent months, TPR has discussed recent medical literature detailing various averse effects of chronic opioid therapy, including narcotic bowel syndrome and opioid-induced hyperalgesia, Additional adverse effects include sedation, immune suppression, and worsening sleep apnea. This well done review article provides a helpful outline of yet another complication: depressed endocrine function.

The author notes that opioids affect 2 endocrine pathways. The first pathway is the hypothalamic-pituitary-gonadal axis. Opioids decrease secretion of gonadotropin-releasing hormone by the hypothalamus, directly depress pituitary function and also impair sex -hormone production by the ovaries and testes. The end result is diminished libido, fertility, sexual function, energy, bone density, and muscle mass.

The second pathway is the hypothalamic-pituiary-adrenal axis, where opioids reduce levels of corticotropin-releasing hormone, ACTH, cortisol, and adrenal sex-hormones such as DHEA. The resulting adrenal insufficiency can be clinically significant.

The author makes recommendations for monitoring and treating opioid-induced endocrine insufficiency. IMPORTANT NOTE: Dr. Brennan discloses financial relationships with a number of medical and pharmaceutical companies, some of which make endocrine monitoring tests and hormone replacement products. Tis should be kept in mind when reading his “Monitoring and Treatment” section.
 

Related posts:

Must-read article: everything you didn’t realize you wanted to know about narcotic bowel syndrome

Important new concept: opioid-induced hyperalgesia

Brown tree snake

ABC News reports that the U.S. Department of Agriculture Wildlife Service in planning to parachute dead mice stuffed with acetaminophen into the jungles of Guam in an attempt to poison the brown tree snake population that has taken over the area. First inttroduced into Guam after World War II, the snake has annihilated the bird population. Some experts fear it will come to Hawaii, devastating the wildlife there.

Each dead mouse will contain about 80 mg acetaminophen, a fatal dose of the snakes. It will be attached to a long paper stringer, meant to entangle the murine corpse in treetops, where the snake feeds. There have actually been scientific studies to determine the best way to deliver these airborne mouse treats.

[Photograph of brown tree snake from wikipedia.org]

4 out of 5 stars

Position paper update: gastric lavage for gastrointestinal decontamination. Benson BE et al. Clin Toxicol 2013 Feb18 [Epub ahead of print]

Abstract

The American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists published their initial position paper on gastric lavage in 1997, concluding that their was no good evidence supporting the use of the procedure in poisoned patients. A 2004 update  reached the same conclusion.

This paper reviewed medical literature appearing since 2003 and found there was no need to alter the groups’ previously stated recommendations. in the last decade, there have been additional papers demonstrating the risks and potential complications of lavage, but none convincingly demonstrating any clinical benefit. Although the groups didn’t completely throw lavage under the bus, they came as close to doing so as one could expect from expert panel consensus. It is important that all emergency practitioners be familiar with their conclusion:

At present there is no evidence showing that gastric lavage should be used routinely in the management of poisonings. Further, the evidence supporting gastric lavage as a beneficial treatment in special situations is weak, as is the evidence to exclude benefit in all cases. Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients. In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.

This is somewhat muddled, and the insertion of the word “routinely” is somewhat disingenuous — no one has argued that gastric lavage should be a routine procedure in toxicology cases, at least not in the last 3 decades. But if we take this conclusion as stated, lavage will — thankfully — disappear. Since lavage may be justified only in “rare instances”, even if it is considered there will be no one around with enough experience in the procedure to have developed “expertise”. Best to bite the bullet and say don’t do it, period.

4 out of 5 stars

The Clinical and Forensic Toxicology of Z-drugs. Gunja N. J Med Toxicol 2013 Feb 13 [Epub ahead of print]

Abstract

This well done article is the most comprehensive discussion I’ve seen about the pharmacology and toxicology of the so-called Z-drugs: zolpidem (Ambien), zopiclone (Imovane), and zaleplon (Sonata). It also touches on eszopiclone (Lunesta), the active enantiomer of zopiclone.

All these drugs are non-benzodiazepine sedative-hypnotic agents that act as agonists at the GABA_A receptor. These drugs tend to have relatively short durations, making them effective at inducing but not necessarily maintaining sleep. Zopiclone is the longest acting. Zaleplon is described as ultra-short acting, with a half life of about 1 hour.

These drugs are generally well tolerated. Elderly patients are more susceptible to adverse effects, which include residual sedation, imbalance and falls, parasomnias, bizarre behavior, hallucinations, and psychosis. In January 2013, the FDA advised lowering standard zolpidem doses — especially in women and those taking extended-release products — to minimize the chance of next-day drowsiness and mental clouding. (Much praise to the author and editors for including this late-breaking development in both the article and the references.)

Treatment of Z-drug overdose is generally supportive. Activated charcoal should be avoided because sedation may result in an unprotected airway. Flumazenil will reverse the sedative effects of all Z-drugs, but should be used with caution — if at all — in cases of multidrug overdose and/or unclear history.

Z-drugs should not be confused with ZDogg.

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

     Well what you gonna do when your troubles they get like mine
     Well what you gonna do when your troubles they get like mine
You take a mouthful of sugar, drink a bottle of turpentine 

The blues-rock band Canned Heat took their name from Tommy Johnson’s 1928 classic “Canned Heat Blues“, the only tune I can think of that is about methanol poisoning.  Their song “Amphetamine Annie” — with its repeated admonition “Speed Kills!” — was one of the earliest anti-drug songs of the 1960s.

“Turpentine Moan” appeared on the band’s first album “Boogie with Canned Heat”. Chicago blues pianist Sunnyland Slim is on keyboards.

At least two band members on this track subsequently died of drug-related causes. Alan “Blind Owl” Wilson (slide guitar) died of a barbiturate overdose in September 1970 at age 26. Bob “The Bear” Hite (vocals) died in April 1981, probably of causes related to a heroin overdose.

3 out of 5 stars

Enhanced Poison Elimination in Critical Care. Ghannoum M, Gosselin S. Adv Chronic Kidney Dis 2013 Jan;20:94-101.

Abstract

This survey of methods available for enhanced elimination in toxicology cases gives a good overview, but unnecessarily wastes time discussing modalities that now are never used (e.g., forced diuresis and urine acidification). The information would have been more accessible if it had been streamlined to reflect current practice. For instance, the authors list 20 poisons “amenable” to multidose activated charcoal, but in fact the indications for this treatment are limited and can be remembered by using the mnemonic ABCDQ: aminophylline /theophylline, barbiturates (phenobarbital), carbamazepine, dapsone, and quinine.

The authors don’t delve into specific indications for these modalities, deferring to the EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup which is expected to publish consensus guidelines in the near future. Actually, this project has become somewhat controversial, since some toxicologists and other clinicians do not believe there is enough evidence to make firm recommendations in many types of poisoning. My own feeling is that the lack of evidence makes the availability of consensus guidelines even more important, as long as the document clearly states that the suggestions are not mandates and in no way constitute a standard of care.

Related posts:

Superb review of hemodialysis and other enhanced elimination techniques

Management of poisonings from a nephrologist’s point of view

Another must-read article on hemodialysis and other enhanced-elimination techniques

Hemodialysis and other extracorporeal modalities in toxicology cases

4.5 out of 5 stars

Acute Kidney Injury Associated with Synthetic Cannabinoid Use — Multiple States, 2012. MMWR 2013 Feb 15;62:93-98.

Full Text

About a year ago, TPR posted that several cases of acute renal failure following the use of synthetic cannabinoids had been reported in Wyoming. After this, the story seemed to drop off the map, and we were unable to obtain any additional information despite several calls to the Wyoming Department of Health.

The current issue of MMWR contains at important update. Following an alert issued after the 4 Wyoming cases were reported, 12 additional cases were detected in several states: Oregon (6 cases), New York (2), Oklahoma (2), Rhode Island and Kansas (1 each). The most common presenting symptoms were nausea and vomiting (15/16 cases) and abdominal, flank, and/or back pain (12 cases). The highest recorded serum creatinine was 21.0 mg/dL (normal 0.6-1.3 mg/dL). Renal biopsy in 8 patients revealed acute tubular injury (6) and acute interstitial nephritis (3). Although all patients recovered, 5 patients required hemodialysis.

Synthetic cannabinoids (SC) products associated with these cases included those labelled with the names “Phantom Wicked Dreams”, “Mr. Happy”, “clown Loyal”, and “Lava”. Toxicological analysis of products consumed and biological specimens were possible in 7 cases. Although no single SC compound was identified in all these cases, six of seven had biological and/or product specimens positive for XLR-11 or its metabolites. This compound is a fluorinated derivative of UR-144, a drug that has been previously identified in SC products sold over the internet. The authors point out that it is not clear whether or not XLR-11 caused the kidney injury in these cases, or was just commonly found in SC products at the time they were reported.

The authors conclude that:

Physicians caring for otherwise healthy adolescents and young adults with unexplained AKI [acute kidney injury] should inquire about SC use, and cases of suspected SC poisoning should be reported to both the regional poison center and the appropriate state health department.

Related posts:

Blueberry ‘spice” in Wyoming linked to cases of renal failure

2.5 out of 5 stars

The effect of prehospital nebulized naloxone on suspected heroin-induced bronchospasm. Tataris KL et. Am J Emerg Med 2013 Feb 1. [Epub ahead of print]

Abstract

Heroin can induce bronchospasm, probably through the release of histamine. This very brief observational study — from Chicago EMS services — reports on prehospital patients treated with nebulized naloxone for suspected heroin-induced bronchospasm. Data was extracted from paramedic run sheets.

Eligible patients had spontaneous respiration and were treated with nebulized naloxone, 2 mg in 3 ml normal saline. Nineteen cases were identified. Of these, 13 had documented clinical improvement, 4 had no response, and 2 patients deteriorated. No patient needed intubation. Of the 13 patients who improved, 1 received only nebulized naloxone and 1 received naloxone and albuterol combined. Presumably, the others who improved received a range of additional therapies.

The authors admit that this report is limited, but it does suggest that nebulized naloxone may have a role in treating these patients. Of course, it doesn’t seem wise to use only nebulized naloxone. Clarification of what role nebulized naloxone might have as adjunctive treatment for heroin-induced bronchospasm will have to await additional data.

Related posts:

Nebulized naloxone in opiate intoxication

Prehospital naloxone given by nebulized inhaler

http://www.youtube.com/watch?v=cP4zgb9H3Cg

Very funny stand-up routine by Brian Regan about going to the emergency room, and trying to ace the multiple choice question: What is you pain on a scale of 1 to 10?  I give this clip four enthusiastic smiley-faces.

Tip o’ the Hat to Rick Bukata and Mel Herbert. I learned of Regan’s routine when they mentioned it on a recent edition of Emergency Medical Abstracts.

3.5 out of 5 stars

Botulism From Drinking Prison-Made Illicit Alcohol — Arizona, 2012. MMWR 2013 Feb 8;62:88.

Full Text

Last October, MMWR reported 8 cases of foodborne botulism diagnosed in inmates at a maximum security prison in Utah. All 8 patients gave a history of ingesting pruno, an alcoholic concoction made surreptitiously in prisons by combining fruit, vegetables, sugar and water and allowing the mixture to ferment in a plastic bag. The resulting beverage has been described as looking and smelling just like vomit.

The current issue of MMWR reported 8 additional cases of botulism in inmates of an Arizona maximum security prison. All these cases developed symptoms starting one to three days after drinking from the same batch of pruno. Seven patients required intubation. All tested positive for botulinum toxin type A — as did a sample from the batch of pruno — and were treated with heptavalent botulinum antitoxin.

Significantly, the ingredients used to make the implicated batch of pruno included potato, as did batches involved in previously reported outbreaks in California (5 cases, 2004-2005), Utah (8 cases, 2011), and Arizona (4 cases, 2012). Since this latest outbreak, the prison involved has banned potatoes from the prison kitchen.

Related post:

Case series: foodborne botulism from home-made prison hooch

http://www.youtube.com/watch?v=RTKj-hgFhE0

At Academic Life in Emergency Medicine, Dr. Rahul Patwari has posted a very good series of whiteboard lectures that can serve as a basic introduction to medical toxicology for rotating medical students or interns. The four lectures — about 10 minutes each — cover general supportive management, toxidromes, laboratory testing, and gastrointestinal decontamination.

I especially appreciated Dr. Patwari’s uncompromising approach to gastric lavage: “We don’t do that anymore”. The entire lecture series is full of common sense advice.

There are some areas in which I’d add to Dr. Patwari’s points. As noted in some of the comments to the series, many toxicologists are now using a starting dose of naloxone lower than that used in the past to manage possible opioid overdose. Dr. Patwari recommends 0.4 mg; some recommendations go as low as 0.04 mg. The lecture also might have mentioned administration of nebulized naloxone by inhalation, or even not using naloxone at all unless absolutely necessary.

Also, in the discussion of the Rumack-Matthew nomogram in acetaminophen overdose, a more careful distinction could have been made between acute ingestion (generally within 8 hours, with the time of ingestion being when last taken) — in which the nomogram can be applied, and chronic ingestion where it can not be used.

2.5 out of 5 stars

The Toxic Trio: Valproic Acid, Lithium, and Carbamazepine. Karydos H et al. Am J Ther 2013 Jan 23. [Epub ahead of print]

Abstract

Frequently, emergency practitioners are called upon to manage patients with altered mental status. In many of these cases, history is unavailable, incomplete, or unreliable. Overdose with an unsuspected medication should be on the differential diagnosis in these cases.

In this situation, qualitative urine drug screen may be misleading because of potential for false negative or false positives. However, quantitative levels of specific drugs may be more valuable. Most clinicians in these cases would obtain an acetaminophen level. This paper suggests that other drug levels should be considered.

This study retrospectively identified cases from a regional poison center database involving patients with supra therapeutic levels of valproic acid (VPA), lithium (Li), or carbamazepine (CZN)  and “altered mental status and an unclear history of psychiatric diseases or seizure disorder and . . . an unknown medication history regarding the use of VPC, Li, or CZN.” They identified 26 cases over a 3 year period: 8 in the VPA group (113-247 μg/ml), 9 in the Li group (1.9-5.2 mEq/L), and 9 in the CZN group (13.4-38,8 μg/ml).

Although it is completely unclear what, if any, clinical significance was indicated by these levels, the authors note that one patient with a lithium level of 5.2 mEq/L (reference range < 1.2 mEq/L) underwent hemodialysis. Since they do not describe this case in detail, it is impossible to know if the dialysis was likely to improve patient outcome. The authors conclude by stating that their toxicology group will continue the practice of drawing levels for VPA, Li, and CZN in patients with altered mental status of unknown etiology.

This small study leaves many questions unanswered. How many empirical levels would have to be determined to find one that was clinically significant. What’s the NNT (number needed to test)? Would this practice improve clinical outcomes, or result in unnecessary therapeutic interventions? What would be the cost of all these screening tests? They call for a prospective study, but since relevant cases seem so infrequent I doubt that any such study would provide these answers.

A superb piece in this Sunday’s New York Times tells in gripping and heartbreaking detail how casual prescribing of Adderall and other stimulant drugs can lead to catastrophe. The article is structured like a Greek tragedy, with the reader — like the victim’s family — seeing where the narrative is leading but powerless to do anything to derail it.

The author, Alan Schwarz, lets us in on what to expect from the beginning:

The story of Richard Fee, an athletic, personal college class president and aspiring medical student, highlights widespread failing in the system through which five million Americans take medications for A.D.H.D. (attention deficit hyperactivity disorder), doctors and other experts said.
Medications like Adderal can markedly improve the lives of children and others with the disorder. But the tunnel-like focus the medicines provide has led growing numbers of teenagers and young adults to face symptoms to obtain steady prescriptions for highly addictive medications that carry serious psychological dangers. These efforts are facilitated by a segment of doctors who skip established diagnostic procedures, renew prescriptions reflexively and spend too little time with patients to accurately monitor side effects.

The elements leading to Richard Fee’s death are familiar: rapid and glib diagnosis, inadequate follow-up, failure to screen for abuse potential, failure to utilize available resources such as prescription databases to determine if a patient is doctor shopping or filling scripts for excessive amounts of dangerous medications.

Also, at the end, without being too explicit, the article highlights an enormous problem we’ve seen before in relation to chronic opioid abuse: drug company-sponsored physician education sessions that overstate potential benefits of these drugs, while grossly understating the severity of potential adverse effects and the risk of becoming addicted.

It’s only the beginning of February, but I doubt there will be a more riveting or important article about prescription drug abuse all year. Absolutely essential reading.

http://www.youtube.com/watch?v=cYIN-b8qjmo

This toxicology-themed Bud Light commercial was banned from airing during the 2007 Super Bowl.

My Emergency Medicine News column on the ability of chronic opioid use paradoxically to increase pain sensation has just been posted. To read it, click here.

3.5 out of 5 stars

Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication. Baumann BM et al. Am J Emerg Med 2013 Jan 21.  [Epub ahead of print]

Abstract

The use of intravenous naloxone to reverse opiate effects is associated with many potential adverse events, some well-known and others not sufficiently recognized. Even relatively small doses of IV naloxone can cause acute withdrawal, severe agitation, and emesis. If the patient has another CNS depressant on board — such as ethanol — he may vomit but not be alert enough to protect the airway. In addition, acute withdrawal is sometimes associated with catecholamine surge, hypertension, and pulmonary edema.

If severe respiratory depression is evident, the prehospital or emergency team must be prepared to perform endotracheal intubation and assisted ventilation, or quickly administer adequate doses of antidote. However, the majority of opiate-affected patients do not present with incipient respiratory failure, and may not need naloxone at all. However, often the clinician feels that he or she “must do something”, and administers IV naloxone. This is an intervention often regretted as the patient — who had been slightly obtunded but stable and manageable — becomes extremely agitated uncooperative, and very very unappreciative.

In this situation, nebulized naloxone may be the preferred route which, as a previous report claimed, can “gently and effectively” reverse opioid-induced respiratory and CNS depression. Often this gradual reversal results in self-titatration, since as soon as the patient is alert enough she removes the mask. Unfortunately, existing literature about nebulized naloxone is scarce, consisting of a case report, a volunteer study, and one retrospective review of prehospital cases.

This prospective observational study reports on a convenience sample of emergency department patients treated with nebulized naloxone to reverse opiate effects. Patients were eligible if they were “18 years and older, had not received naloxone in the prehospital setting, and received naloxone in nebulized form in the ED for the purpose of reversing suspected opioid intoxication”. Opioid intoxication was defined by respiratory and/or CNS depression AND historical evidence of opioid use. Eligible patients also had to have a respiratory rate > 6 breaths per minute.

Patients were given a nebulized solution of 2 mg naloxone in 3 ml normal saline. The side ports of the face mask were partially covered with tape to increase drug delivery. Primary outcomes were changes in the Glascow Coma Scale and the Richmond Agitation Sedation Scale (RASS).

Twenty-six patients were entered into the study. Eleven patients required repeated doses of naloxone. These cases were usually associated with overdose of multiple drugs or methadone. The authors report “few adverse effects”. Three patients were described as developing ” moderate-severe agitation after the first dose. No patient vomited.

The authors conclude that “nebulized naloxone reduces the need for supplemental oxygen and results in improvements in GSC and RASS scores”.

Two points: First, the authors state in their introduction that the “endotracheal route may also be utilized” for naloxone administration. This seems nuts. Why would anyone consider this. If the patient is intubated, the airway is protected and ventilation can be assisted. Why ask for trouble?

Second, I wonder how many of these patients would have done well on observation alone. If they were arousable and breathing adequately and protecting the airway, did they actually need naloxone. Most opiates will wear off rather quickly on their own. Avoiding the antidote may have avoided some or all three of the cases of moderate-severe agitation (which I wish had been described in more detail.)

In any case, this is a paper well worth reading, especially for those inexperienced or unacquainted with the concept of nebulized naloxone.

Related posts:

Prehospital naloxone given by nebulized inhaler

Nebulized naloxone

3.5 out of 5 stars

Ciguatera Fish Poisoning — New York City, 2010-2011. MMWR 2013 Feb 1;62:61-65.

Full Text

In the year-long period between August 2010 and July 2011, New York City reported several outbreaks of ciguatera poisoning.  A total of 28 patients were stricken, more than had been reported in NYC during the previous 10 years. This paper documents the city’s Department of Health investigation into these cases.

Patients gave a history of having ingested barracuda (13 cases) or grouper (15 cases). Manifestations of ciguatera poisoning affected three systems: gastrointestinal (abdominal pain, nausea, vomiting, diarrhea); neurological (perioral and peripheral paresthesias, cold-hot temperature reversal, and itching); and cardiovascular (symptomatic bradycardia and hypotension). Some patients experienced weakness and difficulty walking.

This paper gives us the opportunity to review ciguatera poisoning. Let’s do it in the form of a quiz. (Click on the following questions to reveal the answer.)

What causes ciguatera poisoning?

What is the mechanism of ciguatoxin?

What are the manifestations of ciguatera poisoning?

Can ciguatera poisoning be a sexually transmitted disease?

What clinical laboratory test can diagnose ciguatera poisoning?

What is the treatment for ciguatera poisoning?

2 out of 5 stars

Tramadol Induced Paradoxical Hyperalgesia. Lee SH et al. Pain Physician 2013;16:41-44.

Full Text

This paper presents 2 cases of patients who developed increased sensitivity to pain (hyperalgesia) as a paradoxical reaction to being chronically on tramadol. We’ve talked before about opioid-induced hyperalgesia, a still under-recognized phenomenon in which chronic opioid use increased pain perception. This is the first report I’m aware of describing hyperalgesia as a result of long-term tramadol use.

Tramadol has only weak affinity for the opioid μ receptor. (A metabolite binds somewhat more strongly.) In addition, it inhibits reuptake of serotonin and norepinephrine. Opioid-induced hyperalgesia has generally been reported  in association with stronger narcotics, and unfortunately these case descriptions are not detailed enough to be completely convincing. (For instance, what steps were taken to rule-out increased pain caused by progression of disease?)  Nevertheless, the paper serves as a reminder to consider paradoxical hyperalgesia when a patient on opioids develops increased pain, more generalized that usual, that does not respond or even worsens when analgesic dose is increased.

Related post:

Important new concept: opioid-induced hyperalgesia

Dr. Mehmet Oz

Michael Specter’s long, nuanced and mesmerizing portrait of Dr. Mehmet Oz in the current issue of The New Yorker is an absolute must-read. Specter highlights all the facets of Oz’s personality: fierce competitor, TV personality, masterful communicator, skilled cardiac surgeon, compassionate physician, snake-oil promoter, and — at home — Mr. Oz, apparently mightily influenced by his wife, herself the daughter of a famous heart surgeon. As for the topics presented on Oz’s TV show, Specter writes:

“Much of the advice Oz offers is sensible, and is rooted solidly in scientific literature. That is why the rest of what he does is so hard to understand.”

No matter what one thinks about Oz’s work on television, he is a fascinating, larger-than-life character. But certainly read this piece before going to stock up on “miracle” green coffee beans or red palm oil.

Related posts:

Is apple juice poisoning our children? Update

More on Dr. Oz and Applegate

 Is apple juice poisoning our children? Dr. Oz v Dr. Besser smackdown 

[Photograph of Dr. Mehmet Oz from wikipedia.org]

http://www.youtube.com/watch?v=FLRF9LKU-iA

Tom Rush was one of my favorite folk singers in college, when I wore out the grooves on the LP listening to his cover versions of Joni Mitchell’s “The Circle Game” and “Urge for Going” .

This somewhat jaunty version of Rev. Gary Davis’s “Cocaine Blues” is, frankly, a little too cheerful for my taste. I much prefer Keith Richards’ spare and haunting version.

BTW, one of the first music videos produced was made by the record company Elektra to illustrated Rush’s great song “No Regrets”:

Related posts:

Tox Tunes #47: Cocaine Blues (Nick Drake)

Tox Tunes #1: Cocaine Blues (Keith Richards)

1.5 out of 5 stars

Cannabis-related Stroke: Myth or Reality? Wolff V et al. Stroke 2013 Feb;44(2):558-63. doi: 10.1161/STROKEAHA.112.671347. Epub 2012 Dec 27.

No abstract available

There have been scattered reports in the literature claiming an association between the use of cannabis and ischemia and/or hemorrhagic stroke. Although no convincing mechanism has been postulated, some suggest that use of marijuana or hashish and the occurrence of stroke may stem from the ability of cannabis to cause orthostatic hypotension, or possibly vasoconstriction.

If such an association is real, it must be exceedingly rare. The purpose of this paper, from the University of Strasbourg in France, was to “analyze the different aspects of neurovascular complications in cannabis users as described in the literature”. This stated purpose is so vague as to be useless, and, in fact, the entire paper is a mess.

The authors searched PubMed for articles association stroke OR ischemic stroke with cannabis OR marijuana. The say they identified 59 cases. But how were these chosen? What was the case definition? Did the case descriptions rule out other known causes of stroke, such as cocaine or amphetamine use? The authors don’t bother to discuss this. I do agree with their recommendation that young patients with unexplained stroke by asked in detail about their drug consumption.

Milk thistle

2.5 out of 5 stars

Amanita phalloides poisoning and treatment with silibinin in the Australian Capital Territory and New South Wales. Roberts DM et al. Med J Aust 3013 Jan 21;198:43-47

Abstract

In one of his published works, the second-century Roman physician Galen related an anecdotal method of treating mushroom poisoning:

I have heard of a physician of Mysia who administered Fowl’s dung to persons suffering form fungus poisoning, and I myself have experimented with the remedy. I have used finally powdered dung mixed with water or mixed with honey and vinegar The patients immediately on drinking the mixture vomited and recovered. One must observe that the dung of a fowl at liberty is more efficacious than one in confinement.

Unfortunately, in the two millennia since Galen advocated the therapeutic benefits of ingesting chicken shit (and free-range chicken shit at that!) we really haven’t discovered any specific antidotes with proven efficacy. Not that possible candidates have not been put forward.  High-dose penicillin-G, thioctic acid, dexamethasone, cimetidine, N-acetylcysteine (NAC), silymarin, and silibinin have all been tried; none has been proven to improve clinical outcomes.

Silibinin and silymarin are extracts of the milk thistle plant (Silybum marianum). It is thought that silibinin may inhibit entry of amatoxin through cell membrane receptor sites.

This observational retrospective case series looked at patients admitted to certain Australian hospitals for suspected Amanita phalloides poisoning  over a 12-year period. Of the 12 patients identified,  10 received silibinin. Four died of fulminant hepatic failure and shock. Additional treatments included IV fluids, multidose activated charcoal, penicillin, cimetidine, and silymarin.

Unfortunately, there is nothing of value one can deduce from this type of observational study, whick looked at only a small number of patients managed with non-standardized treatment. Certainly, silibinin didn’t prevent the sickest patients from dying: all patient who died — but none of the survivors — had lactate levels > 10 mmol/L. Despite this, the authors recommend “treatment with supportive care, multiple doses of activated charcoal, intravenous silibinin, and acetylcysteine, as well as consideration of liver transplantation.” All of these suggestions seem reasonable except for the IV silibinin, which is not stocked by many hospitals and is often difficult to obtain. It seems to me there are more important things to do when taking care of these sometimes very sick patients.

Surprise quiz! Here are some questions about A. phalloides toxicity touch on in the article. (Click on the question to reveal the answer.)

What are the stages of A. phalloides poisoning?

Why may multidose activated charcoal be effective in A. phalloides toxicity?

What is a Meixner test?}

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3.5 out of 5 stars

Dabigatran: Uncharted Waters and Potential Harms. Radecki RP. Ann Intern Med 2012;157:66-68.

No abstract available

The Institute for Safe Medication Practices has reported that soon after its approval in October 2010,  the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa) was associated with a higher incidence of adverse events than almost any other drug.

In this opinion piece, Ryan Radecki — curator and author  of the essential blog Emergency Medicine Literature of Note — reviews some of the factors contributing to this alarming alarming association:

• Dabigatran etexilate is available in the United Sates in doses of 75 and 150 mg, and it is unclear which dose is safer and/or more effective.
• Drug interactions — including those with proton-pump inhibitors, amiodarone, and verapamil — complicate dosing.
• There is no readily available laboratory test that can be used to monitor patients on dabigatran.
• In cases of dabigatran-associated bleeding, there is no antidote effective in reversing the anticoagulant effect.
• The drug is often prescribed for off-label uses.
• Unanticipated adverse events — such as increased relative risk for myocardial infarction or acute coronary syndrome — have been discovered after dabigatran came on the market.

This short review is well worth reading. In a recent letter to the Annals of Internal Medicine, Patricio Pazmiño points out that the largest study to date of dabigatran — the RE-LY Trial — excluded patients with creatinine clearances < 30 ml/1.73 m³,  a laboratory value that is rarely measured clinically. Since dabigtran is eliminated through the kidneys and is often used in the elderly who may have covert renal insufficiency, frequent complications can be anticipated.

Related posts:

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

4 out of 5 stars

Powerful Cocaine-Like Actions of MDPV, a Principal Constituent of Psychoactive ‘Bath Salts’ Products. Baumann MH et al. Neuropsycho- pharmacology 2012 Oct 17. doi: 10.1038/npp.2012.204. [Epub ahead of print]

Abstract

This article, from the National Institute on Drug Abuse, is complementary to another similar article we recently reviewed, and by some of the same authors.

Even though the paper gets super-granular about molecular mechanisms and contains more than most people want to know about how bath salt components — the synthetic cathinones MDPV, methylone, and mephedreone — act at the cellular level, there are some important points to be gleaned from among the weeds:

• MDPV is the most prevalent synthetic cathinone identified in ER admissions because of bath salt exposure.
• MDPV is a powerful blocker of dopamine and norepinephrine re-uptake, with only weak action on serotonin and no  effect on releasing neurotransmitters.
• Methylone and mephedrone promote increased release of dopamine, norepinephrine, and serotonin.
• Drugs that increase release of neurotransmitters, unlike those that purely block re-uptake, can cause depletion and wash-out.
• Recent experiments in rats have found that MDPV produces results on behavior similar to those of methamphetamine, while mephedrone is more similar to MDMA (ecstasy).

Related posts:

MDPV can give a false positive test for phencyclidine (PCP)

Vivid Navy video depicts horrors of bath salts

Death from methylone ingestion

Agitation and hallucinations from bath salts containing MDPV and flephedrone

Bath Salts (MDPV): another possible cause of serotonin syndrome

Review of synthetic cannabinoids and bath salts

Comprehensive review of bath salts

Multiorgan failure after injection of “bath salts” (MDPV)

Comprehensive review of new designer drugs

Death from MDPV-associated excited delirium

Bath salts and necrotizing fasciitis: a case report

All bath salts are not mephedrone 

“Legal Highs”: new psychoactive drugs

Toxicology of Synthetic Cathinones

The science of designer drugs: essential review

Baths salts: calls to poison centers in Louisiana and Kentucky

New York Times on bath salts

NBC’s Dateline goes undercover to investigate the “bath salt” industry

“Bath salts” in Michigan

Dr. Oz on bath salts (MDPV)

NBC’s Today show reports on “bath salts” (MDPV)

3.5 out of 5 stars

Psychoactive “bath salts”: Not so soothing. Baumann MH et al. Eur J Pharmacol 2013;698:1-5.

Abstract

This article, from the Medicinal Chemistry Section of the National Institute on Drug Abuse, is an up-to-date review of certain aspects of “bath salts”, specifically the synthetic cathinones: MDPV, mephredrone, and methylone. Although much of the material the authors cover is well known and has been discussed here before, the following are some take-home points I was glad to be reminded of, or didn’t known the first place:

• MDPV, a potent uptake blocker of at the dopamine and norepinephrine receptors, with little effect on the serotonin receptor.
• The effect of synthetic cathinones on dopamine suggests high abuse potential.
• Recent evidence shows that MDPV can give a false positive test for phencyclidine (PCP).

Related posts:

Vivid Navy video depicts horrors of bath salts

Death from methylone ingestion

Agitation and hallucinations from bath salts containing MDPV and flephedrone

Bath Salts (MDPV): another possible cause of serotonin syndrome

Review of synthetic cannabinoids and bath salts

Comprehensive review of bath salts

Multiorgan failure after injection of “bath salts” (MDPV)

Comprehensive review of new designer drugs

Death from MDPV-associated excited delirium

Bath salts and necrotizing fasciitis: a case report

All bath salts are not mephedrone 

“Legal Highs”: new psychoactive drugs

Toxicology of Synthetic Cathinones

The science of designer drugs: essential review

Baths salts: calls to poison centers in Louisiana and Kentucky

New York Times on bath salts

NBC’s Dateline goes undercover to investigate the “bath salt” industry

“Bath salts” in Michigan

Dr. Oz on bath salts (MDPV)

NBC’s Today show reports on “bath salts” (MDPV)

3.5 out of 5 stars

Thrombotic Thrombocytopenic Purpura (TTP)-Like Illness Associated with Intravenous Opana ER Abuse — Tennessee, 2012. MMWR 2013 Jan 11;62:1-4.

Full Text

This paper describes a 2012  CDC investigation into a cluster of 15 cases of thrombotic thrombocytopenic purpura (TTP)-like illness in the state of Tennessee. TTP-like illness was defined as microangiopathic hemolytic anemia (hemolytic anemia anemia based on haptoglobin and lactate dehydrogenase with schistocytes and an admission platelet count < 50,000/μL. Typical TTP-like signs and symptoms included nausea (11 patients), abdominal pain (11), fatigue (10), and fever (6).

Drugs previously associated with secondary TTP include quinine, platelet aggregation inhibitors such as ticlopidine and clopidogrel, and some immunosuppressants including cyclosporine.

The strongest common thread shared by 14 of these patients was a history of injecting new formulation Opana ER (extended-release oxymorphone). In Feburary 2012, Opana ER was reformulated to discourage abuse by crushing or dissolving the tablets. Among the new inactive ingredients in the tablets were polyethylene oxide (PEO) and polyethylene glycol (PEG). OxyContin was also reformulated in recent years with the addition of PEO (but not PEG). There have been no cases of TTP-like illness in patients who have snorted or injected the new Oxycontin.

Significantly, 9 of 28 control patients without TTP-like manifestations also reported a history of injecting Opana ER, including 7 who abused the new formulation.

The paper recommends that patients with TTP-like illness and no apparent cause be asked about IV drug use. Patients prescribed Opana ER should be warned that the drug should be taken only as directed, and informed of the risk of abuse.

Tabernanthe iboga

1.5 out of 5 stars

Life-threatening complications of ibogaine: three case reports. Paling FP et al. Neth J Med 2012 Nov;70:422-424.

Abstract

Ibogaine is a psychoactive alkaloid found in the bark of the root of the iboga plant (Tabernanthe iboga), a shrub that grows in the rain forests of western Central Africa. The plant  is an important adjunct to Bwiti religious ceremonies in Gabon. Ibogaine causes hallucinations that apparently are mediated, not through serotonin receptors, but rather muscarinic cholinergic pathways involved in dreaming and memory.

In the mid-twentieth-century, ibogaine was marketed in France under the name “Lambarene” for dieting and as a stimulant. Ibogaine is banned as a Schedule I substance in the United States, but is used in some areas to treat addiction to opiates and other drugs.

This paper describes three patients who developed potentially life-threatening complications  — ventricular dysrhythmias, CNS depression  — after exposure to ibogaine. One case had been previously published. Unfortunately, the details provided are so sketchy that it’s impossible to make much of these cases. In addition, the reason patient 3 was unresponsive is completely unclear, and I believe the authors mis-applied the Naranjo algorithm in determining that ibogaine was the probable cause.

Nevertheless, the paper does serve to remind us that ibogaine has been associated with — and probably causes — a prolonged QT interval and torsade de pointes.

Related post:

Ibogaine — an hallucinogen that was NOT a factor in the 1972 presidential campaign

methylmethaqualone

methaqualone

3.5 out of 5 stars

Acute neurotoxicity associated with recreational use of methylmethaqualone confirmed b liquid chromatography tandem mass spectrometry. Ceschi A et al. Clin Toxicol 2013;52:54-7.

Abstract

Methylmethaqualone (MMQ) is a designer drug made by adding a methyl group to the long-restricted sedative-hypnotic molecule methaqualone (Quaalude). This paper represents the first case report describing a confirmed case of methylmethaqualone toxicity.

A 24-year-old man presented to the emergency department approximately 2-3 hours after washing down several MMQ tablets with wine. Shortly after this, he was found at home somnolent but suddenly became extremely agitated with urinary incontinence and generalized clonic muscle contractions.

When paramedics arrived the patient was agitated and confused, but improved with 10 mg IV midazolam. In the ED, he was confused but not agitated. Vital signs were unremarkable except for a heart rate of 115/min. He had a mild resting tremor but no nystagmus. EKG was normal. Urine drug screen was negative.

A serum sample — analyzed by liquid chromatography tandem mass spectrometry — was positive for MMQ but no other medications or drugs of abuse.

The patient was observed overnight and discharged the next day.

Ten days later the patient again came to the ED with a similar presentation after ingesting MMQ. He responded to midazolam, and was discharged after 2 hours of observation.

The authors note that methaqualone is an addictive quinazolone derivative that acts as a sedative-hypnotic, anticonvulsant, and anxiolytic. It acts on GABA-A receptors.

The authors note that another designe qualones is mebroqualone. Methaqualone itself is addictive and can cause a withdrawal phenomenon similar to delirium tremens.

Methaqualone overdose usually causes ataxia, lethargy, and CNS depression, although limb hyperreflexia, myoclonia, seizures, coma, and other non-neurological symptoms such as respiratory and cardiac failure have been described after severe poisoning. Psychomotor agitation was observed in a life-threatening intoxication, and, at lower doses, recreational users have reported a euphoriant effect.

MMQ users describe similar effects to those of methaqualone, and the symptoms and signs observed in our patient (CNS depression followed by psychomotor agitation, muscle hyperactivity, and tachycardia) are compatible with methaqualone-induced adverse effects.

The authors conclude: “MMQ appears to have a similar acute toxicity profile to methaqualone, with marked psychomotor stimulation. Symptoms of acute toxicity can be expected to resolve within hours with supportive care.” Of course, all expectations may go out the window in cases of massive overdose.

For extra credit, what popular culture figure had a boat named after methaqualone? For the answer, click here

http://www.youtube.com/watch?v=DgyuBWN9D4w

Several weeks ago, TPR posted about a Wall Street Journal article describing the genesis of the “Pain: the 5th Vital Sign” meme over the last decade or two. The article focused on one pain specialist — Dr. Russell Portenoy — who was instrumental in the movement to destigmitize opioid use for chronic pain and push for more general use. In an interview, Dr. Portenoy now says: “Clearly, if i had an inkling of what I know now then,I wouldn’t have spoken in the way that I spoke. It was clearly the wrong thing to do”.

Portions of that interview are included in this short video, posted by the group Physicians for Responsible Opioid Prescribing. In the context of the WSJ article and a similar recent piece in the Washington Post, it is startling and infuriating to hear the words actually come out of Dr. Portenoy’s mouth.