TPR Podcast Episode #13: Naloxone in the Age of Carfentanil

In this “Lucky 13” episode of the TPR podcast, Steven and Leon discuss naloxone, and address the following issues:

 

  • Does the concept of a “heroin overdose patient” have meaning anymore in this age of U-47700, fentanyl, and carfentanil?
  • Given the adulteration of both heroin and counterfeit prescription medications with extremely potent synthetic opioids, do we have to reconsider our entire approach to opioid overdose patients?
  • Can past medical literature guide us in our management of these patients?(Hint: the answer is no.)
  • What medical toxicology paper do Steve and Leon — in an unusual state of agreement — feel was the best to appear in 2016?

 

Here are links to some of the articles discussed in the podcast:

 

 

Fentanyl Outpaces Heroin as the Deadliest Drug on Long Island. New York Times Dec 28, 2016

 

Do heroin overdose patients require observation after receiving naloxone? Willman MW et al. Clin Toxicol 2017 Feb;55:81-87.

 

Fatal Fentanyl: One Pill Can Kill. Sutter ME et al. Acad Emerg Med 2017 Jan;24:106-113.

 

Experts weigh minimum naloxone dose as opioid crisis evolves. Traynor I. Am J Health Syst Pharm 2016 Dec 1;73:1892-1894.

 

The Rising Price of Naloxone — Risks to Efforts to Stem Overdose Deaths. Gupta R et al. N Engl J Med 2016 Dec 8;375:2213-2215.

 

Fentanyl epidemic in Chicago, Illinois and surrounding Cook County. Schumann H Erickson T, Thompson TM et al. Clin Toxicol 2008 Jul;46: 501-6.

 

 

Quizzler:

 

From TPR Podcast #12: Question – What branch of yoga features the drinking of one’s own urine?

 

Answer: Amaroli Yoga

 

The winner was Dr. Angela Regina (New York). Congratulations!

 

This episode’s Quizzler: During World War II, Sir Winston Churchill and his cabinet worked from the underground Churchill War Rooms in London. Those who tour the rooms today can see that a tox-related method of putting out fires was used. (Hint: it does not involve spray fire extinguishers.) What is that method?

 

All entries should be submitted to: toxtrivia@gmail.com. Deadline is 10 pm CST (Chicago time) February 2, 2017. The winner will be chosen randomly from all correct answers, and will receive a$10 gift certificate to Amazon.com as well as a TPR tee-shirt.

 

 

References:

 

Guide to Practical Amaroli (Yoga Magazine)

 

Drink to Your Health — Urine Therapy (Agama)

 

 

The 7th Annual Alexander Awards: The Best Tox Reading of 2016

 Alexander Gettler

Alexander Gettler

When TPR began giving out the annual Alexander Awards for best long-form writing in the field of toxicology, the eligibility criteria included the requirement that “entries must be fully and freely accessible” on the web. After 2016 — a remarkably truth-impaired year scarred by fake news and unchallenged mendacity — supporting aggressive, unbiased, fearless journalism appears to us to be a civic duty. A number of our selections this year come from sources such as the New York Times and Los Angeles Times that have much of their content behind a paywall. Often they allow access to a certain number of free articles each month, but after that limit easy accessibility to subscribers.

Of course, it’s usually possible to cheat by doing a Google search for the title of the article — most often the link will lead directly to the desired piece. But these institutions are more important now than ever, and deserve financial backing from readers. TPR subscribes online to the New York TimesWashington PostLos Angeles TimesBoston GlobeWall Street Journal, and Milwaukee Journal-Sentinel. All of these publications have had superb coverage of toxicology, the pharmaceutical industry, and the opioid catastrophe over the last several years.

The Alexander Awards was inspired by David Brooks’ Sidney awards, a yearly compilation of that New York Times columnist’s pick of the best essays of the year. Brooks’ picks appeared in two columns this week and can be found here and here.

The Alexander Awards are issued in honor of Alexander Gettler (1883 – 1968,) New York City’s chief toxicologist in the early twentieth century whose work helped establish the field of forensic toxicology.

Going through the last year’s essays and reporting in the field of toxicology was a somewhat grim business — so many of the pieces dealt with lives lost and ruined by the opioid crisis. In the news of 2016, the number of deaths and overdoses from OxyContin and heroin was surpassed by those attributed to fentanyl, carfentanil, and U-47700. the Wall Street Journal recently published a heartbreaking compilation of pictures and short biographies of people — mostly young, in their teens, 20s, and 30s — who overdosed and died from opioid overdose in recent years. An amazing number of them started on the road to addiction when they were prescribed opioid analgesics by often minor injuries.

In a well-reported article, the Los Angeles Times traced how black-market OxyContin imported from Los Angeles devastated the Seattle suburb of Everett, Washington. In another superbly detailed long piece entitled “Dope Sick,” the essential health news website STAT exhaustively examines the story of DJ Shanks, a 21-year-old man in Toledo Ohio of overdosed from fentanyl despite all the efforts of his family and friends and multiple attempts to detox. The article includes an amazing video showing Mr. Shanks terminal event as he passes out face down in tray of donuts in his workplace after snorting fentanyl (he thought it was heroin), while fellow workers go about their jobs not realizing or ignoring the fact that something is terribly wrong:

The DJ Shanks story involves the death of just one individual, but multiply that by 300,00, the number of American who have died from opioid overdose since that late 1990s.

In May, the Los Angeles Times published probably the finest investigative piece of medical journalism I’ve ever read. The title was: “‘You Want a Description of Hell?’ OxyContin’s 12-hour Problem.” In this explosive and masterfully written article by Harriet Ryan, Lisa Girton and Scott Glover, the authors amass an overwhelming amount of supportive evidence of back their claim that in the majority of patients the duration of OxyContin’s analgesic effect is far short of the advertised 12 hours, and that this discrepancy may bear a large part of the blame for the current crisis of opioid-related overdoses and deaths. TPR discussed this must-read article when it was first published. But every health-care provider should read the original.

There were good articles in 2016 about drugs other than opioids. In the New York Times Magazine, Casey Schwartz described her experience getting hooked on Adderall, first at college as an aid for studying, then simply to socialize in Los Angeles where Adderall was the “currency” of friendship. Schwartz points out that the effects of Adderall nicely match the age of the internet, an era when distracted attention is the norm. In the end Schwartz was able to recover from her addiction to Adderall, but doing so was remarkably difficult.

Speaking of drugs that are a perfect match for their time, Ariel Levy’s New Yorker piece “The Drug of Choice for the Age of Kale” writes about how the South American shamanistic ritual ayahuasca — a ceremony centered around the psychedelic tryptamine DMT, is spreading to hip areas in the U.S. such as Brooklyn and the San Francisco Bay area. My guess is that Levy’s description of her experience with ayahuasca — involving vomiting and confronting one’s darkest thoughts — will not appeal to many readers.

Finally, just yesterday the Washington Post published a story about potential medical uses for cannabidiol (CBD,) a non-psychoactive component of cannabis that has shown promise as treatment for a number of conditions, especially some forms of epilepsy. Unfortunately, CBD, like THC itself, is still classified as a Schedule I drug, making it difficult to perform research on its therapeutic possibilities.

 

 

Severe respiratory depression after snorting U-47700

3.5 out of 5 stars

Two cases of intoxication with new synthetic opioid, U-47700. Domanski K et al. Clin Toxicol 2017 Jan;55:46-50.

Abstract

U-47700 was first synthesized by Upjohn in the 1970s — hence the “U”. The company was seeking to develop an analgesic as effective as morphine but not addictive. Work on this compound was abandoned when the addictive properties of the drug became apparent.

U-47700 is a μ-receptor agonist that is approximately 7.5 times as potent as morphine. This paper reports two patients who presented to hospital after insufflating U-47700 (confirmed on laboratory testing.) One patient was minimally symptomatic on presentation. The other case was much more dramatic.

Patient one: A 26-year-old man was brought to hospital approximately 3 hours after snorting a powder he had purchased on the internet believing it was “synthetic cocaine.” He was found lying face down, cyanotic with agonal breathing. He was intubated in the field. On arrival he had a Glasgow Coma Scale of 3 and pinpoint pupils. Arterial blood gas showed severe respiratory acidosis with PCO2 > 90. Urine drug screen was negative and serum ethanol level was 55 mg/dL.  He recovered with supportive care. His exam was reported as “normal” on discharge 3 days later.

GC-MS testing of the patient’s urine revealed U-47700 but no other opioids.

The authors note that this patient’s presentation was consistent with an opioid toxidrome, featuring coma, miosis, and respiratory depression.

The video above, from KPIX in the San Francisco Bay Area, is 3 months old. Last month, the U.S. Drug Enforcement Agency classified U-47700 — along with another synthetic opioid, furanyl fentanyl — as Schedule I.

Related post:

Counterfeit Norco containing fentanyl and the synthetic opioid U-47700

 

Lipid therapy in oral poisoning: a not-so-systematic review

intralipid-161x3002 out of 5 stars

No support for lipid rescue in oral poisoning: A systematic review and analysis of 160 published cases. Forsberg M et al. Hum Exp Toxicol 2016 Nov 24 [Epub ahead of print]

Abstract

The authors’ goal was “to present a systematic review and case analysis of practically all published reports on humans treated with lipid rescue for LAST [local anesthetic systemic toxicity] or oral poisoning.”

The focus of the paper is on oral poisonings. The authors report that they identified 94 reported cases of oral poisoning with “alleged” positive response to lipid rescue therapy (LRT.) Two authors reviewed each case and rated causality (that is, LRT -> positive response) using a modified WHO-UMC scale. (As the authors note, the WHO-UMC scale was actually designed to determine causality in adverse drug reactions, not antidote response.) If the two authors disagreed as to the causality score, “consensus was obtained through discussion.”

The authors report that all 94 oral poisonings received scores of 2 (probable causality,) 3 (possible causality,) and 4 (unlikely causality.) in fact, 86% received a score of 3 or 4. They note that 91% of these cases received other treatment modalities at approximately the same time they received LRT.

The authors conclude:

“Considering the findings of the present study, the weak and contradictory scientific evidence for lipid rescue being an effective antidote and its increasingly reported adverse effects, it is reasonable to strictly limit its use in clinical practice. We would not recommend its use at all in cases of oral poisoning.”

There are several significant problems with this conclusion:

  1. Because of the nature of case reports, it is most often impossible to determine causality, especially using a scale that was not designed for this purpose. There are few methods describe as to how the authors assigned a score to each case. One could go back to original cases and make one’s own conclusions, but the reference list has only 22 citations and does not include all or most of the relevant papers. The paper says this information is contained in online appendices at http://het.sagepub.com/supplemental, but my efforts to reach that material through the link came back with either a blank page or an error message. This is really inexcusable. While it’s true that this paper was posted online before it appears in print, it should not in my opinion have been posted until the crucial supplemental material was available.
  2. It is completely unclear how the “discussions” of disputed cases were handled. Was one author more pessimistic and more persuasive than the other?
  3. Of course many of these patients received multiple, nearly simultaneous, treatment modalities. This certainly would make determining causality more uncertain, but not to the extent of concluding that LRT should not be used at all in oral poisoning.

I would add that the Cochrane Review states that a systematic review “summarizes the results of available carefully designed healthcare studies (controlled trials) and provides a high level of evidence on the effectiveness of healthcare interventions.” Case reports are not “carefully designed healthcare studies.” This is no systematic review, and this paper totally misappropriates the term.
Related posts:

Effect of lipid rescue therapy on laboratory tests

Excellent review of lipid rescue therapy

Lipid rescue therapy can interfere with critical lab values

 

Synthetic cannabinoid AMB-FUBINACA responsible for July 2016 “zombie” episode

ak-47-24-karat-gold4 out of 5 stars

“Zombie” Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York, Adams AJ et al. N Engl J Med 2016 Dec 14 [Epub ahead of print]

Abstract 

On July 12, 2016, the New York Times reported that in the course of one day, in the Bushwick and Bedford-Stuyvesant areas of Brooklyn, 33 people had been transported to hospitals after apparently overdosing on a synthetic cannabinoid.

The major manifestations shown by the victims were altered mental status and lethargy. One observer described what he say at the scene:

“’It’s like a scene out of a zombie movie, a horrible scene’ said Brian Arthur, 38, who watched three people collapse as he made his way to work in the morning and began live-streaming the episode on Facebook. ‘This drug truly paralyzed people.’”

The video above was taken by Mr. Arthur at the scene, posted it to Facebook, and according to a report in the  Guardian (U.K.) said that the scene as looking like “Zombieland.”

This paper describes the outbreak and subsequent investigation:

“The clinical features in this outbreak were typified by the index patient, a man who was 28 years of age and who was described by EMS providers at the scene as being slow to respond to questioning and as having a ‘blank stare.’ . . .He had intermittent periods of ‘zombielike’ groaning and slow mechanical movements of the arms and legs.”

This patient’s vital signs were unremarkable, as was his physical exam except for “sweating” and a Glasgow Coma Scale of 13. His lethargy and altered mental status resolved after 9 hours of observation.

Extensive laboratory investigation identified the synthetic cannabinoid involved in all these cases as AMB-FUBINACA which was labelled, in at least some cases, as “AK-47 24 Karat Gold.” The authors note that exposure to AMB-FUBINACA seems to be unusual in that “extreme CNS depression is not accompanied by the tachycardia, arrhythmias, seizures, hyperthermia, cardiotoxicity, and acute kidney injury that are usually found in association with potent or high doses of synthetic cannabinoid.”

The paper cites laboratory studies suggesting that AMB-FUBINACA is 85 times more potent than THC as an agonist at the CB-1 receptor.

Related posts:

5F-ADB-PINACA and other extremely potent new synthetic cannabinoids

Serious toxicity and fatalities from synthetic cannabinoids