Unlabeled amphetamine isomer in sports supplement “probably” caused hemorrhagic stroke

Jacked_Power-300x3003.5 out of 5 stars

Hemorrhagic Stroke Probably Caused by Exercise Combined With a Sports Supplement Containing β-Methylphenylethylamine (BMPEA): A Case Report. Cohen P et al. Ann Intern Med 2015 May 12 [Epub ahead of print]

Reference

Last month, the FDA sent letters to 5 companies that manufacture so-called “dietary” or “sports” supplements, warning them that their products were mislabeled because they contained an unlisted ingredient.

That ingredient, β-methylphenylethylamine (BMPEA), is an isomer of amphetamine. Although the effects of BMPEA in humans have not been well studied, it has been shown to increase heart rate and blood pressure in an animal model. Although BMPEA is a synthetic compound, it is sometimes mistakenly thought to be a natural component of the shrub Acacia rigidula. Manufacturers of products containing BMPEA often list A. rigidula as one of the ingredients, possibly in an attempt to obscure the fact that they are being spiked with a synthetic amphetamine isomer. A paper last year analyzed 21 supplements labeled as containing A. rigidula, and found that over half contained BMPEA.

This case report describes a previously healthy 53-year-old woman who developed a right parietal hemorrhagic stroke 45 minutes into a “vigorous exercise routine” that she had performed regularly without incident for several years. Shortly before starting the routine, she had ingested for the first time 13 g of the supplement “Jacked Power” as recommended on the label. During the workout she experienced “numbness and clumsiness” of the left hand.

On presentation to hospital the next day, her blood pressure was 163/58 mm Hg and her pulse rate 90/min and she had subtle left upper extremity sensory/motor deficits. Head Ct showed a right parietal hemorrhage. Cerebral angiography did not demonstrate evidence of vasculitis, aneurysm, or vascular malformation.

Analysis of the product the patient consumed found that the only unlabeled drug it contained was BMPEA (290 mg per dose.)

The authors claim that based on the World Health Organization’s Adverse Reaction Terminology,  causality in this case is “probably/likely.” Using the more familiar Naranjo algorithm, this case would also be classified as a “probable” adverse drug reaction.

The paper notes that suspected adverse drug reactions should be registered at the FDA’s Safety Reporting Portal.

 

 

ED sedation with droperidol is relatively safe and effective

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The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Calver L et al. Ann Emerg Med 2015 Apr 11 [Epub ahead of print]

Abstract

Before the Food and Drug Administration issued a black box warning in 2001 regarding the relationship between droperidol and risk of QTc prolongation, the drug had been used for decades — often to provide sedation in agitated emergency department patients — with a good history of safety. At the time, many physicians and pharmacologists raised doubts that the warning had any scientific basis.

The goal of this prospective observational Australian study was to evaluate the safety and efficacy of high-dose droperidol in treating acute behavioral disturbance in the emergency department. The authors collected data on adult ED patients with behavioral abnormalities treated according to the following clinical protocol:

  • 10 mg droperidol IM or IV
  • repeat 10 mg droperidol in 15 minutes if response inadequate
  • additional sedation as needed at discretion of treating physician

The primary outcome was the percentage of patients who had an abnormal QTc interval within 2 hours of the last droperidol dose, as determined by the QT nomogram. Secondary outcomes included occurrence of adverse effects including torsades de pointes.

Over a period of 43 months in 6 emergency departments, the authors identified 1,403 eligible patients. Of the 13 patients had abnormal QT intervals, 7 had other possible or contributing causes, including QT-prolonging medications (methadone, escitalopram, amiodarone). There were no episodes of torsades de pointes.

The authors conclude:

“This study has shown that droperidol is relatively safe and effective for the management of violent and aggressive patients in the ED and that there was no increased risk of QT prolongation and torsades de points according to a large cohort of cases.”

The “Editor’s Capsule Summary” that accompanies the article is even more emphatic*:

How this is relevant to clinical practice
Droperidol is safe even with the high doses used in this study.

The authors note that the study does not rule out that droperidol may be associated with rare cases of torsades. But the agitated, delirious ED patient may be a danger to himself, staff, and other patients, and may have underlying serious medical problems that must be addressed emergently. The need to get control of the situation by using chemical restraints is crucial, and certainly trumps what is clearly a very small risk of prolonging the QT interval.

*The original post was updated to include the “Editor’s Capsule Summary” conclusion.

Related post:

 

FDA Warnings: Black Box, or Black Hole?

 

Lipid rescue therapy and ECMO in the poisoned patient — can they be used together?

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What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient? Lee HM et al. Clin Toxicol 2015;53:145-150.

Abstract

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is often used in the neonatal and pediatric intensive care units on children who are also receiving intravenous lipid emulsion (LE) for nutritional support. Complications reported in patients receiving both interventions include lipid agglutination, clogging, occurrence of blood clots, and cracking of parts of the ECMO circuit.

There is increasing interest in treating critically ill poisoned patients with VA-ECMO to support failing cardiac and pulmonary function. The idea is that this support will be a “bridge to recovery” until the body can eliminate the poison or poisons impairing key organs. In toxicology cases, ECMO is still considered a “last-ditch” effort in patients who have failed standard therapy, often including lipid rescue therapy.

Will toxicology patients develop the same complications seen in the pediatric population receiving both VA-ECMO and nutritional support with LE? This paper shows that the data is scarce. The authors did a literature search and found reports of 9 overdose patients treated with both LE and VA-ECMO. In 2 reports, it was specifically stated that no complications were observed. In 7 reports, the presence or absence of complications was not commented on. Although in many cases the time relationship between administration of LE therapy and initiation of VA-ECMO was not clear, it is likely that ECMO was started after LE (and other interventions) failed.

Obviously, this question requires much more study and experience with using both modalities. Given the state of our knowledge at this time, in my opinion the following conclusions are reasonable:

  • Lipid emulsion therapy should be withheld in the poisoned patient actively receiving VA-ECMO
  • Failed lipid emulsion therapy should not be an absolute contraindication to the use of VA-ECMO in the poisoned patient

Obviously, these suggestions are based on very limited evidence. This is a rapidly growing field. Stay tuned.
 

 

Hemodialysis in metformin poisoning

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Extracorporeal Treatment fo Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workshop. Calello DP et al. Crit Care Med 2015 Apr 9 [Epub ahead of print]

 

Abstract

Metformin is now the oral drug most commonly prescribed to treat non-insulin-dependent diabetes in the United States. The drug is large eliminated by the kidneys. Toxicity presents with severe lactic acidosis, and can occur when decreasing renal function causes accumulation of therapeutic doses, or in the case of acute deliberate overdose. According to some reports metformin poisoning, though rare, is associated with a morality rate of 30%.

Metformin is a small molecule that is not protein-bound, making it amenable to dialysis despite having an appreciable volume of distribution (1-5 L/kg.) This paper, from the Extracorporeal Treatments in Poisoning (ExTRIP) Workgroup, aimed to review systematically literature relevant to the use of extracorporeal methods to treat metformin poisoning, and present recommendations for using such methods.

The authors identified 175 relevant articles, including case reports and observation studies. Unfortunately, as in this group’s previous papers regarding different poisons, the quality of the evidence was so poor that all of their recommendations were rated 1D (1=strong recommendation, D=very low level of evidence). As we’ve pointed out in discussing the group’s earlier papers, this makes their conclusions opinions rather than evidence-based recommendations. However, given the expertise and experience of members of the group, their opinions must be reckoned with.

The paper concludes that metformin is dialyzable and that extracorporeal treatment (ECTR) is recommended in “severe” metformin poisoning. Specific suggested indications are as follows:

  • ECTR is recommended if:
    • Lactate > 20 mmol/L
    • Blood pH < 7.0
    • Treatment with supportive care and bicarbonate fails

The group’s “suggestions” are less strong than their “recommendations,” reflecting less of a consensus among the members:

  • ECTR is suggested if:
    • Lactate > 15-20 mmol/L
    • Blood pH < 7.0-7.1

The group also suggests that presence of the following conditions should lower threshold for starting ECTR:

  • shock
  • renal insufficiency
  • liver failure
  • decreased level of consciousness

The group recommends that intermittent hemodialysis should be the initial ECTR method of choice if available, but that continuous renal replacement therapy (CRRT) may be helpful if it is not. Subsequent ECTR can involve either hemodialysis or CCRT. The end point should be lactate < 3 mmol/L and pH > 7.35. Since the metformin level can rebound and increase after ECTR is stopped, patients’ acid-base status should be followed closely until it is clearly stable.

Again, all of these recommendations and suggestions are based on very poor evidence — so poor, in fact, that the authors describe their analysis as somewhat of a “guess.” But the paper is well worth reading and represents a good starting point for thinking about ECTR in metformin poisoning. Recommended.

Related posts:

Hemodialysis in acute methanol poisoning: is there really good evidence?

Hemodialysis in lithium poisoning: what is the evidence?

Must-read: consider hemodialysis in cases of massive acetaminophen overdose

What enhanced elimination techniques are useful in critical toxicology patients?

Hemodialysis and other extracorporeal modalities in toxicology cases

 

 

Severe reactions to “Spice” on rise, some associated with drug MAB-CHMINACA

AB-CHMINACA

AB-CHMINACA

3 out of 5 stars

In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA Erratico C et al. Drug Test Analysis 2015 Apr 12 [Epub ahead of print]

Abstract

The New York Times reported today on the recent dramatic increase in emergency department visits related to use of synthetic cannabinoids (call colloquially, but somewhat inaccurately, “Spice”). This phenomenon has been seen in many states, especially Mississippi, Pennsylvania, and New York.

According to reports, patients often present with agitation, delirium, and hallucinations. Medical complications have included rhabdomyolysis and acute kidney injury, including that of a soldier at Fort Hood.

Preliminary media reports indicate that at least some of these cases may be associated with the synthetic cannabinoid MAB-CHMINACA (also known as ABD-CHMINACA.) This chemical seems to be a strong agonist at the CB-1 receptor, with a reported 10 times the affinity of the synthetic cannabinoid JWH-018.

This paper is mainly concerned with identifying metabolites of the structurally similar compound AB-CHIMINACA with an eye on developing screening tests. However, in their introduction the authors discuss the indazole-carboxamide (INACA) class of synthetic cannabinoids. Adverse effects include:

  • seizures
  • coma
  • agitation
  • altered mental status
  • loss of consciousness
  • dyspnea
  • death

Many INACA chemicals are now classified as schedule I substances by the U.S. Drug Enforcement Administration. At this point, MAB-CHMINACA is not.*

To read the 2014 DEA announcement temporarily classifying MAB-CHMINACA and similar drugs as schedule I, click here.

*The original post erroneously stated that MAB-CHMINACA had been classified as a schedule I substance by the DEA. A tweet from @forensictoxguy informed me that although it has been banned in Louisiana, it is not listed as schedule I on the federal level. To read @forensictoxguy’s take on MAB-CHMINACA on his blog “Dose Makes the Poison,” click here.

Even Dr. Oz can’t rebut John Oliver

Dr. Oz’s rebuttal yesterday to the letter from ten self-described “distinguished physicians” who demanded that Columbia Medical School cancel his faculty appointment was absolutely brilliant — recasting the narrative from the selling of snake oil to standing up for free speech and against the juggernaut agricultural-industrial complex.

But there’s no rebuttal to John Oliver.

See also Michael Specter’s New Yorker blog post on this issue, as well as his superb profile of Dr. Oz in the magazine.