Great New Toxicology Podcast

In the first episode of “The Dantastic Mr. Tox & Howard Show,” Drs. Dan Rusyniak and Howard Greller — formerly of the Journal of Medical Toxicology Podcast — have a superb discussion about the current expanding opioid crisis with Dr. David Juurlink from Sunnybrook Health Sciences Centre in Toronto. Topics covered include opioid-induced hyperalgesia, the key difference between relieving pain and relieving suffering, and why tramadol is generally such a poor drug. The episode is smart, succinct, and highly recommended. I look forward to future podcasts. To listen, click here. You can also subscribe through iTunes or your favorite podcast aggregator.

Episode #15: How easy is it to get addicted to opioids?




As has been well reported in medical papers, government studies and popular media, rates of overdose deaths from opioids have been increasing steadily over the last several decades. A recent article in the New York Times reported that there were likely more than 59,000 drug overdose deaths in 2016, an estimated 19% increase over the number in 2015. The total for 2017 is likely to be even higher.


Many deaths have been associated with prescription opioid analgesics, or have occurred among patients who became addicted to prescription opioid analgesics and then went on to use cheaper and more available forms such as heroin. As I detailed in my 2013 Emergency Medicine News column “The Dark Truth Behind Pain as the Fifth Vital Sign,” the trend towards increased use of opioid analgesics really took off in the 1990s, and was encouraged by some leading pain “specialists” who insisted that studies demonstrated that opioids were virtually never addictive when used to treat chronic pain. The sole basis for this claim was a one paragraph, five-sentence letter to the New England Journal of Medicine (often referred to as the Porter-Jick “study”) that described, not outpatients treated for chronic pain, but hospitalized in-patients. A recent excellent short paper by Zhang et al points out that this one letter was subsequently cited 608 times, often uncritically and often as evidence that long-term use of opioids for pain was associated with only minimal risk of addiction. Zhang et al is a must-read.


Rudd et al is loaded with statistics that illustrate the extent and reach of the opioid crisis in the United States. For example, they show that the relative increase in opioid deaths from 2010 to 2015 was 33%. In 2015, the number of overdose deaths in the U.S. — 52,400 — exceeded those from either motor vehicle accidents or firearms.


Shah et al searched records in a large managed care insurance database to identify adult patients who received at least one prescription for an opioid between 2006 and 2015 and were previously opiate naïve (no opioid prescription for the preceding 6 months before the index prescription.) Exclusion criteria included cancer (except for non-melanoma skin cancer) and history of substance abuse disorder.


The authors found that receiving the initial opioid prescription carried a high risk of long-term use. Six percent of patients prescribed at least one day of opioid medication were still receiving prescriptions for opioids 1 year later. Risk of continued use at one year markedly increased if the first use was for more than 8 days (13.5%) and for more than 31 days (30%.)


Brummett et al. found that opioid-naïve patients prescribed an opioid analgesic for post-operative pain from major or minor surgery had an incidence of persistent opiate use — evidenced by a script for opioid medication filled 90-180 days after surgery — of 6.0 – 6.5%. They conclude: “New persistent opioid use represents a common but previously underappreciated surgical complication . . .”



QUIZZLER: Last episode we discussed the assassination of Kim Jong-nam, the half-brother of North Korea’s leader Kim Jong-un. According to reports, the agent used in that killing was the nerve agent VX. We mentioned that the Aum Shinrikyo cult in Japan had also used VX as a murder weapon in the 1990s. Aum Shinrikyo was led by a half-blind former yoga instructor named Shoko Asahara. The Quizzler question was: According to Au Shinrikyo cult protocol, how were followers required to great Shoko Asahara when they came into his presence? The answer: they greeted the guru by kissing his big toe.


There were a number of correct answers submitted. The winner, picked at random, was Francis Manuel. Congratulations!


The new Quizzler is revealed at the end of this episode’s podcast. Answers can be submitted to: Deadline for submissions is midnight Chicago time, Sunday June 25. The winner’s name will be selected at random from among all those submitting correct responses. The prize again will be a $25 Amazon gift certificate, and a choice of either a TPR tee shirt or hoodie. Good luck!








Addiction Rare in Patients Treated with Narcotics. Porter J, Jick H. N Engl J Med 1980;302:123


The One-Paragraph Letter from 1980 That Fueled the Opioid Crisis. Zhang S. The Atlantic Jun 2, 2017


A 1980 Letter on the Risk of Opioid Addiction. Leung PTM et al. N Engl J Med 2017;376:2194-5.


Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010-2015, Rudd RA et al. MMWR Morb Mortal Wkly Rep 2016 Dec 30;65:1445-1452.


Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006 – 2015. Shah A et al. MMWR Morb Mortal Wkly Rep 20017 Mar 17;66:265-269.


Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use. Barnett ML et al. N Engl J Med 2017 Feb 16;376:663-673.


New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. Brummett CM et al. JAMA Surgery 2017 Apr 12 [Epub Ahead of Print]






Lipid rescue therapy for local anesthetic toxicity: is less more

2.5 out of 5 stars

Adverse events associated with a large dose of intravenous lipid emulsion for suspected local anesthetic toxicity. Corwin DJ et al. Clin Toxicol 2017 Jul;55:603-7.


The key word in the title of this case report is “associated” — a.though the authors do not emphasize the point, it’s not at all clear that all of the adverse events described were actually caused by the IV lipid emulsion. Nonetheless, there are some important take-home lessons here.

CASE: An 11-year-old girl presented to hospital with confusion and somnolence 15 minutes after receiving local anesthesia with 54 mg mepivacaine for a dental procedure. She had facial twitching and 2 brief episodes of possible seizure activity that resolved spontaneously.

The local poison center was contacted and recommended that lipid emulsion therapy be given to treat local anesthetic toxicity:

The suggested dosing [20%] was to be given in three 1 mL/kg boluses spaced every five minutes, followed by an infusion of 0.25 mL/kg/min for one hour if symptoms persisted.

After the 3 bolus doses were given, the patient continued to have self-limited episodes of unresponsiveness and abnormal muscular activity, lasting seconds each. The 1-hour infusion dose was started. After transfer, the receiving hospital continued the infusion at 0.25 mL/kg/hr for an additional 4 hours. The reported total 20% lipid dose was 3670 mL (66 mL/kg) over 7 hours.

Neurological symptoms continued overnight after lipid infusion was stopped. Head CT was unremarkable; MRI showed enhanced signal in the dural venous sinuses, consisted with elevated serum lipid levels. EEG was consistent with presence of sedating medications but did not show seizure activity.

Not surprisingly, the patient’s serum was lipemic and her triglyceride level markedly elevated. Although she had episodes of tachycardia and tachypnea, workup did not reveal evidence of ARDS or fat emboli. Lipemia interfered with some laboratory tests.

On discharge after 3 days in hospital,  the patient’s neurological exam and laboratory results were normal.

DISCUSSION: Most of the “adverse events” associated with lipid rescue therapy have occurred after administration of relatively high doses. Although there have been no good studies demonstrating the maximum “safe” dose of intralipid for lipid rescue therapy, many authors recommended limiting the dose to that recommended by the FDA for nutritional support: 12.5 mL/kg (lean body mass) per day total. In specific cases it may be reasonable to consider extending the infusion beyond this, but such situations are likely rare. In this patient, who did not appear to have cardiovascular instability, it is not clear if the high dose administered was the result of careful consideration or lack of attention to total dose received as the patient was transferred and treated at a new hospital.

By the way, if the reader goes by Figure 1 in the paper, the total dose received would have been not 66 mL/kg but approximately 110 mL/kg. the authors do not explain the discrepancy.

To read my recent Emergency Medicine News column on lipid rescue therapy, click here.

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