Tox Tunes #93: Lithium (Evanescence)

As with the Nirvana song of the same title, the lyrics are not completely clear as to whether the singer is describing the experience of the drug, or using it as a metaphor for emotional ambivalence. (We should note that in fact Nirvana’s “Lithium” never mentions the drug in its lyrics.)

I thought of this song after reviewing the new paper from the EXTRIP workgroup paper on extracorporeal treatment of lithium toxicity.

Saturdays with SMACC: Hinds & May debate cricoid pressure

At the 2014 smaccGOLD conference in Australia, two motorsport enthusiasts, Drs. Brent May (@DocBrent) and John Hinds (@DocJohnHinds) engaged in a very amusing debate about the efficacy of cricoid pressure in managing airways. Taking the pro side, Dr. May argued that applying cricoid pressure is superior (or at least non-inferior) to not doing so in preventing aspiration. Dr. Hinds’ position was that  . . . well, it’s best summed up in this graphic:

Screen Shot 2015-01-24 at 1.18.11 PM

The combatants were introduced by Minh Le Cong (@ketaminh).

By the way, SMACC is giving away several free student registrations to the smaccUS Chicago conference taking place June 23-26, 2015. Be among the first 3 students to answer correctly a 12-question quiz and the registration is yours. Questions for the first round will be posted tonight (Saturday) exactly at midnight Chicago time (CST). For more information and to see the questions when they are posted, click here. An additional similar opportunity will be available February 24.

Hemodialysis in lithium poisoning: what is the evidence?

0Lithium Carbonate, 300mg, 1,000 Capsules per Bottle McGuffMedical.com3.5 out of 5 stars

Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Decker BS et al. Clin J Am Soc Nephrol 2015 Jan 12 [Epub ahead of print]

Abstract

The purpose of this review, from the Extracorporeal Treatments in Poisoning (EXTRIP) workgroup, was to give evidence-based recommendations related to use of hemodialysis and other extracorporeal modalities in the treatment of lithium toxicity.

The goal of enhanced elimination in lithium poisoning is to avoid the syndrome of irreversible lithium-effectuated nerutoxicity (SILENT), which causes persistent cerebellar dysfunction after prolonged exposure of the CNS to high levels of lithium.

Using elaborate methodology, the EXTRIP group reviewed relevant literature, identifying 166 papers (describing 228 patients) in multiple languages that merited inclusion. Most of these were case reports yielding, in the words of the authors, “a very low quality of evidence for all recommendations.” In other words, there is no real evidence, and the recommendations and (weaker) suggestions are based mostly on the opinions of the workgroup members.

Now, the EXTRIP group is comprised of some various smart clinicians from a variety of specialties, including medical toxicology, nephrology, and intensive care. Their opinions are definitely worth reading and considering carefully. For example, this is a summary of their proposed indications for extracorporeal treatment (ECTR – read hemodialysis) in lithium poisoning:

  • ECTR is recommended
    • if kidney function is impaired [serum creatinine > 2.0 mg/dL in adults or 1.5 mg/dL in the elderly] and lithium > 4.0 mEq/L
    • if there is decreased level of consciousness, seizures, or life-threatening dysrhythmias regardless of lithium level
  • ECTR is suggested:
    • if lithium level > 5.0 mEq/L
    • if there is confusion
    • if the expected time to reach lithium level < 1.0 mEq/L with optimal management is greater than 36 h

There are a number of problems with this list. Most importantly, I think, is that it considers hemodialysis in isolation without integrating the modality in the total care of the patient and other possible treatments. For example, if an adult took an acute lithium overdose and presented with a serum lithium level of 4.1 mEq/L and at serum creatinine of 2.1 mg/dL, but without signs or symptoms of toxicity, would it not be reasonable to administer fluids, observe carefully, and recheck levels in several hours? And if that makes sense, what if the lithium was 4.2 and the creatinine 2.2? Would the speculative potential benefit of hemodialysis in this situation outweigh the small change of possible risks? Clinical judgment is still required, and strict cut-off criteria seem artificial — and certainly not evidence-based.

Some toxicologists have objected that the recommendations seem not to make a distinction between acute, chronic, and acute-on-chronic exposure. i think the authors would argue that inclusion of symptoms in their recommendations (if not in their weaker “suggestions”) corrects for not considering the pattern of exposure, and that the most important thing is whether the drug is in the CNS, not how it got there.

In any case, there are many pearls about lithium toxicity in this article, and it is well worth reading. Just take the recommendations with a grain of salt — but not a salt substitute.
Related posts:

Lithium-induced nephrotoxicity

Evidence does not support use of long-term opioid therapy for chronic pain

RxOpioids1703.5 out of 5 stars

The Effectivenss and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Chou R et al.  Ann Intern Med 2015 Jan 13 [Epub ahead of print]

Abstract

Although prescription opioids have been advocated and used for long-term treatment of chronic non-cancer pain, there is scant literature supporting such use. Most studies have been limited to a time period of 3 months or less. The purpose of this literature review was to assess the evidence pertaining to safety and effectiveness of long-term (> 1 year) opioid therapy for pain.

The authors point out that when evaluating this question, in addition to potential benefits of pain relief, known risks of opioid therapy must be considered, including falls, fractures, motor vehicle accidents, and endocrinopathy. In addition, level of function and quality of life must be assessed.

The authors searched several databases for relevant English-language literature published between January 2008 and August 2014. Among their findings:

  • “No study of opioid therapy versus placebo, no opioid therapy, or nonopioid therapy evaluated long-term (> 1 year) outcomes related to pain, function, or quality of life.”
  • “No randomized trial evaluated opioid abuse, addiction, or related outcomes with long-term opioid therapy versus placebo or no opioid therapy.”
  • “One good-quality case-control study (5300 case patients) found that MEDs [morphine equivalent doses] of at lest 20 mg/d were associated with increased odds of road trauma among drivers.”
  • “No study evaluated risk for falls; infections; or psychological, cognitive, or gastrointestinal harms among patients with chronic pain who were receiving long-term opioid therapy versus placebo or no opioid therapy.”

In addition, the authors found that: “Evidence on the accuracy and effectiveness of risk assessment instruments for predicting opioid abuse or misuse in patients before initiation of  long-term opioid therapy was sparse . . .”

Their conclusion:

In summary, reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date. Accumulating evidence supports the increased risk for serious harms associated with long-term opioid therapy, including overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction; for some harms, the risk seems to be dose-dependent.

In a related development, last week’s issue of MMWR reported that although the rate of increase in drug fatalities related to opioid analgesics has levels off some, the rate of such increased from 199 to 2013 by almost a factor of 4:

Screen Shot 2015-01-21 at 10.03.52 PM

[Chart from MMWR 2015 Jan 16;64:32]

Tox Tunes #92: Born in Chicago (Paul Butterfield)

This is my favorite live version of Paul Butterfield’s blues classic “Born in Chicago” (written by Nick Gravenites.) It also features Rick Danko on bass and Blondie Chaplin on guitar. Although this visceral and gritty song does not specifically mention drugs, they are certainly alluded to in the lyrics:

Well, my first friend went down
When I was 17 year old
Well, my first friend went down
When I was 17 years old

Well, there’s one thing I can say about that boy
He gotta go

Well, my second friend went down
When I was 21 years of age
Well, my second friend went down
When I was 21 years of age

Well, there’s one thing I can say about that boy
He gotta pray.

As Steve Huey writes in his biography of Butterfield on allmusic.com:

Paul Butterfield was the first white harmonica player to develop a style original and powerful enough to place him in the pantheon of true blues greats. It is impossible to overestimate the importance of the doors Butterfield opened: before he came to prominence, white American musicians treated the blues with cautious respect, afraid of coming off as inauthentic. . . . [Butterfield’s] storming sound was a major catalyst in bringing electric Chicago blues to white audiences who’d previously considered Delta blues the only really genuine article.

Speaking of Paul Butterfield, the follow clip where he is the mystery guest on the 1960s quiz show To Tell the Truth is absolutely surreal:

 

Tox in the news: 72 die in Mozambique from poisoned beer

Mozambique

Mozambique

In a very strange story that’s been developing all week, the Washington Post reported that at least 72 people died in Mozambique after consuming poisoned beer offered at a funeral gathering. Details are scarce and the poison (or poisons) has not yet been identified, but a limited clinical scenario can be gleaned from reading news coverage.

Apparently, the funeral was an all-day affair. The beer was brewed in and served from a 210 liter container. People who drank the beer only in the morning were not affected. However, those who had the beer in the afternoon were sick by the next morning, with diarrhea and muscle pain. Among the 72 fatalities was Olivia Olocane, the woman who provided the beer for the funeral.

Originally,  residents and some authorities thought that the poison used was “crocodile bile” (“nduru”), a substance known in local lore to be extremely toxic, useful for mass poisonings and use as an arrow poison. The possible toxicity of “nduru” has been investigated in the medical literature in a 1984 article by Professor N.Z. Nyazema in the Central Africa Journal of Medicine. In that paper Dr. Nyazema points out:

It is widely believed that the bile from the gall bladder of a crocodile is very poisonous. The bile nduru is used as poison which is added to beer or stiff porridge, sadza, of an unsuspecting victim. It is not easy to buy this poison neither is it easy for anyone to kill a crocodile solely for the purpose of obtaining the bile. But with a good fee one can obtain some of the poison from a special n’anga At times the n’anga may undertake to poison the victim thus adding mystery to the ingredients of the poison. It is reported that the poisoning occurs at special occasions like beer drinking. The nduru is said to be introduced into the beer by dipping the finger or nail where a small amount is placed. This will suffice for the purpose. The unfortunate victim is supposed to die within 24 hours. The poison is supposed to manifest itself when the patient develops pains mainly in the abdomen.

By far the best coverage of this event has been from David Kroll (@davidkroll), who blogs about pharmacology and health care for forbes.com. In a superbly reported blog post, Kroll took the trouble of tracking down Dr. Nyazema, who now works in South Africa at the University of Limpopo. Dr. Nyazema told Kroll that the notion crocodile bile caused the deaths was “a lot of nonsense . . . [c]rocodile bile is not poisonous whatsoever.”

In his studies on crocodile bile from 3 decades ago, Dr. Nyazema fed it to mice without producing any toxicity whatsoever. In addition, as he pointed out to Kroll, some populations use crocodile bile as an aphrodisiac, contradicting its reputation for extreme toxicity.

Nazema thinks the poison used was more probably a cardiac glycoside (foxglove and other similar plants are abundant in that area of Africa) or an organophosphate pesticide. Whatever it turns out to have been, it must have been extremely potent to fatally poison 72 people she mixed in a 210 liter vat. Unfortunately, that vat — which would have been a crucial clue in this tragedy — seems to have disappeared.

[Map of Mozambique from wikipedia.org]