Elephant-tranquilizer (carfentanil)-tainted heroin showing up in Ohio

4 out of 5 stars

Human Health Hazards of Veterinary Medications: Information for Emergency Departments. Lust EB et al. J Emerg Med 2011 Feb;40:198-207

Abstract

Yesterday, Canadian police announced that, earlier in the summer, they had seized one kilogram of carfentanil contained in a package labelled “Printer Parts” shipped from China and addressed to a man in Calgary.

Carfentanil is frequently, and accurately, referred to as an “elephant tranquilizer.” It is a fentanyl analog with a potency 10,000 times that of morphine (or 100 times that of fentanyl.) It is not approved for any medical indication in humans but is used by veterinarians to sedate large animals such as elephants and horses.

The lethal amount of carfentanil is reported to be about 20 μg in humans, which led the police in Canada to claim that the 1 kg seizure contained 50 million deadly doses. It’s unclear if the substance seized was actually pure carfentanil. If it was, that would present an extreme hazmat risk, since the drug can be absorbed after inhalation or through mucus membranes or broken skin.

I had missed this valuable article by Lust et al when it was published in 2011, but came across it when I found it was virtually the only paper available describing the toxicity of carfentanil. The authors note that in animals, the drug has rapid onset and undergoes hepatic metabolism and renal elimination. Manifestations of carfentanil exposure, consistent with opioid toxicity, include mitosis, altered mental status, and respiratory depression. Larger than usual doses of naloxone may be required to reverse the effects of the drug. Areas of mucus membrane or skin exposure should be irrigated abundantly with cool water. (Hot water will increase blood flow to the area and possibly accelerate absorption.)

Other veterinary medications discussed in this article are clenbuterol, ketamine, tilmicosin, testosterone, estradiol, dinoprost,  and cloprostenol.

By the way, recent news about carfentanil has not been limited to the seized shipment in Canada. As the news story from WKRC in Cincinnati at the top of this post reports, carfentanil has been identified in samples and specimens associated with a number of recent overdose cases in the Akron area. Carfentanil-laced heroin has also been associated with at least one fatality in Ohio.

Further reading:

Everything You Should Know About Carfentanil (Vice.com)

 

 

Seven cases of laboratory-confirmed exposed to the synthetic cannabinoid MDMB-CHMICA

sweetleafherbalbend3.5g-1-300x3003 out of 5 stars

Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB-CHMICA. A report from the Identification Of Novel psychoActive substances (IONA) study. Hill SL et al. Clin Toxicol 2016 Sep;54:638-643.

Abstract

MDMB-CHMICA is a synthetic cannabinoid receptor agonist (SCRA) with strong affinity for the CB1 receptor. It has to date not been banned in may localities, and is available on the street under labels such as “AK47 Loaded,” “Manga Hot,” “Black Diamond,” and “Sweet Leaf Obliteration.” It use has been associated with fatalities.

This case series, from the United Kingdom, describes 7 cases of laboratory-confirmed exposure to MDMB-CHMICA. The most interesting cases are the first three, which involve exposure to MDMB-CHMICA alone without any identified coingestants:

Case 1: A 41-year-old man collapsed after smoking a substance labelled “Sweet Leaf.” On arrival at hospital he was described as “drowsy,” with bradycardia and a respiratory acidosis. He did well with observation and supportive care only.

Case 2: A 16-year-old man lost consciousness at a bus station after smoking a product called “Sweet Leaf.” On presentation to the emergency department he had mildly depressed mental status and a respiratory acidosis. He also did well and was discharged after 18 hours observation

Case 3: A 33-year-old man was brought to the emergency department after being observed having a seizure. At the scene he had a Glasgow Coma Score of 3/15 and tachycardia (120 bpm.) On arrival at hospital his mental status had improved by he was described as agitated, paranoid, and violent. Laboratory work-up showed a respiratory acidosis. The patient improved over several hours and signed out against medical advice. Although he denied any recreational drug use,a blog sample tested positive for MDMB-CHMICA alone.

It’s hard to square these relatively mild cases of MDMB-CHMICA exposed with the occasional reports of fatalities that have appeared in the forensic literature. (For examples, click here and here.) It might be a matter of dose, undetected co-ingestants, or individual susceptibility.

The authors’ conclusions:

” . . . these analytically confirmed cases suggest that MDMB-CHMICA can cause a reduction of level of consciousness associated with hypercapnia, confusion, heart rate disturbances, mydriasis and in some cases convulsions and behavioral disturbances…

 

 

Counterfeit Norco containing fentanyl and the synthetic opioid U-47700

3 out of 5 stars

Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street “Norco” in Central California: A Case Report. Armenian P et al. Ann Emerg Med 2016 [Epub ahead of print]

Full Text

In a recent “Toxicology Rounds” column for Emergency Medicine News, I pointed out that designer opioids such as U-47700 are being identified in street drug specimens and overdose cases with increasing frequency. Knowing this, I was not really surprised when it was announced last week that the autopsy on music superstar Prince confirmed the presence of U-47700, as well as fentanyl.

U-47700 is a synthetic opioid analgesic developed by Upjohn almost half a century ago but never marketed. It is reported to be approximately 7-8 times a potent as morphine. There is at least one case reported in the literature describing a fatality associated with exposure to U-47700 and fentanyl.

This case report, from UCSF-Fresno,  describes a laboratory-confirmed case of overdose following ingestion of illicitly purchased pills that looked like, and were believed by the victim to be, Norco tablets. The patient had ingested 3 of these pills 90 minutes before presentation.On arrival, the serum fentanyl level was 15.2 ng/ml (therapeutic, 1-2 ng/ml.) The patient was described as minimally responsive on presentation but responded to 0.4 mg naloxone and was discharged 4 hours later.

Several months ago, MMWR reported a series of 7 overdoses in the San Francisco Bay area from counterfeit Norco in the San Francisco-Fresno area. Fentanyl was detected in the serum of all these patients.

We should note that despite the attention paid to a “new” synthetic opioid, U-47700 is much less potent than fentanyl and thus most likely presents less of a threat at this time.

 

 

All bleeding stops — but does idarucizumab (Praxbind) make it stop faster?

PraxBind3.5 out of 5 stars

Persistent life-threatening hemorrhage after administration of idarucizumab. Alhashem HM et al. Am J Emerg Med 2016 June 30 [Epub ahead of print]

Reference

Dabigatran (Pradaxa) is a direct thrombin inhibitor approved for stroke and embolism prophylaxis in patients with non-valve-related atrial fibrillation. When it was first released in 2008, a major disincentive to widespread use was the lack of a reliable reversal agent to treat major bleeds, or to administer before necessary invasive procedures.

In October 2015, the U.S. Food and Drug Administration approved idarucizumab (Praxbind), a monoclonal antibody that avidly binds to dabigatran. under its accelerated approval program. As described by an FDA release, this program:

. . . allowed drugs for serious conditions that filled an unmet medical need to be approved base on a surrogate endpoint.”

In the case of idarucizumab, the surrogate end-points involved normalization of laboratory parameters of anticoagulation. As far as I can determine, there have been no studies that demonstrate convincingly any clinical patient-oriented benefit. In fact, in the major study addressing this issue,  it took a median of 11.4 hours to restore hemostatis after administration of idarucizumab. There was not control group, so we have no idea if this is better than simple watchful waiting. Clearly, it seems far too long to be useful in true life-threatening hemorrhage.

This case report illustrates the point.

A 65-year-old man recently started on dabigatran for atrial fibrillation presented to the emergency department weakness and dyspnea that started approximately 1 hours before. He gave a history of melena for 3 days. On arrival he ws tachycardia (122 ppm) and hypotensive (BP 74/52 mmHg.)

Digital rectal examination confirmed the presence of melena, and a nasogastric tube returned 300 ml bright red blood that did not clear with irrigation. The patient remained unstable despite administration of fluids and packed red blood cells.

The authors note that a markedly elevated thrombin time (120 sec, reference 15-19 sec) indicated significant dabigatran activity. After idarucizumab (5 gm) was administered intravenously. the coagulation tests improved but the patient remained unstable. Upper endoscopy revealed ongoing hemorrhage from a vessel in the duodenum. Several attempts to control the site of bleeding failed, and the patient ultimately underwent angiography with embolization of the gastroduodenal artery. This successfully stopped the bleeding and the patient was discharged after a 4-day hospital stay.

According to Wikipedia, the hospital acquisition cost of a 5 gm dose of idarucizumab is $3500. Although it clearly improves coagulation lab values, it is not clear if if stops significant or life-threatening hemorrhage, or allows for safer procedures such as hemodialysis.

An excellent post at REBEL EM discussed many of the problems with the major study of idarucizumab mentioned above, including industry sponsorship, lack of power, dicey inclusion criteria, and poor study design without blinding or randomization.

Bottom line: idarucizumab had accelerated approval by the FDA as a reversal agent for dabigatran because of biological plausibility. There is still no real proof of its effectiveness. However, in cases of truly life-threatening hemorrhage, many clinicians will no doubt administer the drug if no other treatment options seem available.

Related points:

Case report: hemodialysis for dabigatran overdose

The many potential problems with using dabigatran

Case series: four patients with dabigatran-associated bleeding

Review: the bleeding patient on dabigatram

Dabigatran and the elderly

 

 

 

 

A normal (or negative) anion gap does NOT rule out salicylate toxicity

Aspirin_Tabs-300x2363 out of 5 stars

Salicylate toxicity in the absence of anion gap metabolic acidosis. Bauer S, Darracq MA. Am J Emerg Med  2016 Jul;34(7):1328.e1-3

Reference

Moderate-to-severe salicylate toxicity typically presents with a combined metabolic acidosis and respiratory alkalosis. Often, the arterial blood gas shows a pH quite near the normal 7.4, but with decreased pCO2 and decreased bicarbonate.

However, occasional case reports have shown that in these cases the anion cap may, rarely, but normal or even negative. This seems to be related to specific electrodes that measure chloride level loosing selectivity as they age, and mistaking the salicylate ion for chloride. This artifactual hyperchloremia lowers or abolishes the anion gap.

No need to go into the details of this case, which again illustrates this phenomenon. The key take-home lesson: If you suspect salicylate toxicity in a patient with a metabolic acidosis, the absence of an elevated anion gap does not rule-out the diagnosis.

Related posts:

Pearl: falsely normalized anion gap in salicylate overdose

Salicylate toxicity can present with a normal anion-gap metabolic acidosis