Dr. Gustin's Blog

Psychelic Drugs Used to Treat Depression and Anxiety-Toxicology

A very interesting study has recently been done on the effects of a psychedelic substance in a small mitigated-psychedelic dose in the treatment of resistant depression and anxiety. The following is a synopsis of the key points from a recent Medscape article.  The relevance of this study to toxicology is that psychelics can have severe side-effects, some even long-lasting or permanent, even in customary doses, as noted below. Practitioners who treat their patients with these substances should be aware of the medicolegal liability and health risks.

Read more: Psychelic Drugs Used to Treat Depression and Anxiety-Toxicology

Fluorquinolones can kill

New warning from the FDA-- a warning about Aortic Aneurysm Risk With Fluoroquinolones in patients being treated for common infections

The agency is urging healthcare providers to avoid prescribing the powerful antibiotics to patients with or at risk for an aortic aneurysm, such as those with peripheral atherosclerotic vascular disease, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and the elderly. This antibiotic is one of the most commonly prescribed antibiotics for braonchitis, sinusitis, bladder infections, and pneumonia.

"Although the risk of aortic aneurysm or dissection is low, we've observed that patients are twice as likely to experience an aortic aneurysm or dissection when prescribed a fluoroquinolone drug," FDA commissioner Scott Gottlieb, MD, said in the Drug Safety Communication.

"For patients who have an aortic aneurysm or are known to be at risk of an aortic aneurysm, we do not believe the benefits outweigh this risk, and alternative treatment should be considered."

The FDA reviewed adverse event reports and four recently published observational studies showing an increased risk of aortic aneurysm or dissection associated with fluoroquinolone use, which can lead to dangerous bleeding or even death.

The underlying reason for this increased risk cannot be determined, the statement notes. The background risk of aortic aneurysm also can vary depending on the population — from nine events/100,000 people/year in the general population to 300 events/100,000 people/year in the highest-risk individuals.

"For some patients, the benefits of fluoroquinolones may continue to outweigh the risks for treatment of serious bacterial infections, such as pneumonia or intra-abdominal infections, but there are other serious, known risks associated with these strong antibiotics that must be carefully weighed when considering their use," Gottlieb said. 

The FDA has issued several prior safety communications about fluoroquinolone use, including in  July 2018 (significant decreases in blood sugar and certain mental health side effects),  July 2016  (disabling side effects of the tendons, muscles, joints, nerves, and central nervous system),  May 2016 (restrict use for certain uncomplicated infections),  August 2013  (peripheral neuropathy), and  July 2008  (tendinitis and tendon rupture). 

 

Edible Marijuana is Potentially Dangerous

The number of cannabis-associated emergency department (ED) visits has risen sharply since marijuana was legalized in Colorado. New data show that although inhalable cannabis use accounts for most of these visits, edible cannabis is tied to a disproportionate number of visits, and patients present with different symptoms.

Although less frequent overall, edible cannabis products lead to more acute psychiatric events and cardiovascular symptoms than inhaled exposure. Researchers at the University of Colorado report their findings in an article published online recently in the Annals of Internal Medicine.

Edible cannabis has been considered to be more toxic than inhalable cannabis, particularly in light of accumulating poison center data on its associated adverse events (AEs) and anecdotal reports from adult users. In addition, the only deaths in Colorado that have been conclusively linked to cannabis use have involved edible products.

Nevertheless, the relative potential harms of inhalable and edible cannabis products have been poorly characterized.

With this in mind, Monte and colleagues conducted a study to compare adult ED visits related to edible and inhalable cannabis use. Using chart review, the researchers tracked 9973 ED visits to the University of Colorado Health emergency department from 2012 through 2016 that included an ICD-9 or -10 code for cannabis use. Of those, they found that 2567 (25.7%) of the visits were related to cannabis, with 238 of these (9.3%) linked to edible products.

The most common causes of cannabis-linked ED visits were gastrointestinal symptoms (30.7%), intoxication (29.7%), and psychiatric symptoms (24.7%).

Visits as a result of inhalable cannabis were more likely than those because of edibles to involve gastrointestinal symptoms, the most common of which was cannabinoid hyperemesis syndrome (18% vs 8.4%; mean difference, 9.6 percentage points; 95% confidence interval [CI], 5.7 - 13.5).

In contrast, visits due to edible cannabis more commonly involved acute psychiatric symptoms (18% vs 10.9%; mean difference, 7.1 percentage points; 95% CI, 2.1 - 12.1), intoxication (48.3% vs. 27.8%; mean difference, 20.5 percentage points; 95% CI, 13.9 - 27.1), and cardiovascular symptoms (8% vs 3.1%; mean difference, 4.9 percentage points; 95% CI, 1.4 - 8.4).

For patients using edible cannabis, the ED visits were also more likely to be shorter (2 hours vs 3 hours) and less likely to lead to hospitalization (18.9% vs 32.9%; P < .001) than they were for patients using inhalable cannabis.

The researchers also determined that, although edible cannabis accounted for just 0.32% of the states total cannabis sales (in kilograms of tetrahydrocannabinol [THC]) between 2014 and 2016, it was responsible for 10.7% of cannabis-related ED visits in Colorado during that period.

If inhalable and edible cannabis were equally toxic and resulted in the same number of ED visits, based on the study, 0.3% of cannabis-attributable visits would be due to use of edible products. The observed proportion of cannabis-attributable visits with edible exposure was about 33 times higher than expected (10.7% vs 0.32%) if both routes of exposure were equally toxic.

This data establishes that states considering cannabis legalization should take into account the relative toxicity of edible products. It may be best to limit edible products to medical indications in order to minimize pediatric exposures and mitigate the excessive rate of adult ED visits associated with these products. At the very least, users must be educated about the delayed kinetic profile and the increased risk for acute psychiatric and adverse cardiovascular events associated with edible ingestion.

Nora D. Volkow, MD, and Ruben Baler, PhD, from the National Institutes of Health, Bethesda, Maryland, highlight the important clinical and public health implications of these findings. There are several reasons why edible cannabis often leads to worse outcomes than inhalable cannabis. Because orally-ingested THC is absorbed more slowly than inhaled THC, people using the edible products find it harder to titrate the doses required to produce the desired effects. This is compounded by the slower clearance of orally-ingested THC from the body, which can result in accumulation in people who take extra doses in an attempt to achieve the desired drug effect more quickly.

In addition, the relatively harmless appearance of edibles and the variability in their labeling accuracy further contribute to overconsumption of these products.

Acknowledging that the complete range of potential adverse health consequences from cannabis consumption remain incompletely understood, the editorialists suggest that future research into the adverse effects of cannabis should focus on THC and content, route of administration, doses consumed, sex, age, body mass index, and the medical conditions for which it might be used.

The results of this recent study also underscore the urgent need for greater oversight of manufacturing practices, labeling standards, and quality control of cannabis products marketed to the public.

Ann Intern Med. Published online March 25, 2019.

 

EPA Alert: Methylene Chloride Banned

The Environmental Protection Agency (EPA) says it will issue a rule that bans the sale of methylene chloride to consumers but allows for its continued use in commercial products.

The deadly chemical is found in paint and furniture strippers. Many stores, including Lowe’s and Walmart, had already stopped selling products with methylene chloride. The ban includes the manufacturing, processing, and distribution of the chemical for consumers. Alexandra Dunn, the EPA’s assistant administrator for chemical safety, says in a press release: "This rule answers calls from many affected families to effectively remove these products from retail shelves and retail distribution channels, providing protection for the American public."

Environmental advocates say the rule doesn’t go far enough.  "They’ve excluded workers who are the most vulnerable population," says Lindsay McCormick, project manager, chemicals and health, for the Environmental Defense Fund in Washington, DC. "It’s a day late and a dollar short here."

The nonprofit group Safer Chemicals, Healthy Families says at least 64 people have died from exposure to methylene chloride since 1980. Many of those deaths were among workers who were refinishing bathtubs. Bathtub refinishers often work in poorly ventilated spaces. Methylene chloride is heavier than air, so it sinks and collects in low places like bathtubs, right where refinishers hold their heads as they work.

Methylene chloride is metabolized to carbon monoxide and replaces and blocks oxygen in the blood. When inhaled, it can cause headaches, nausea, dizziness, seizures, coma, and death. Over the long term, it increases the risk of cancer, and may alter cognitive function permanently. 

The EPA has estimated that as many as 32,000 workers use methylene chloride on the job. Yet the EPA will continue to allow the use of the compound for workers even though they are at risk for adverse health events.

The EPA says it will take public comments for the next 90 days. Those comments will inform a future rule that could establish a training, certification, or limited-access program for methylene chloride for commercial uses.

FENTANYL OVERDOSES AND DEMOGRAPHIC DISPARITIES

Fentanyl overdoses are increasing at a dramatic rate in the United States.  Visits to Emergency Rooms are far more frequent now than they were just a few years ago.  Fentanyl is a synthetic opiate that when blending with heroin becomes a life-threatening toxic cocktail as it is 50-100 times more potent than morphine.  Physician in the ER when treating cardiorespiratory complications from an assumed heroin overdose must be mindful of the possibility that Fentanyl may have contaminated the ingested drug.  The Narcan reversal agent requirements may be higher for Fentanyl.  Here are three recent newspaper articles describing the scourge.

The Washington Post (3/20, Achenbach) reports that “the synthetic opioid fentanyl has been driving up the rate of fatal drug overdoses across racial and social lines in the United States, with the sharpest increase among African Americans, according to a new analysis by the Centers for Disease Control and Prevention.” Data show the African American death rate “from fentanyl-involved drug overdoses rose 141 percent each year, on average, from 2011 to 2016, the study showed.” Meanwhile, the overdose death rate “for Hispanics rose 118 percent in that period every year on average, and 61 percent for non-Hispanic whites.”

The Washington Time  (3/20, Healy) reports that during the study period, 2011 to 2016, “more than 36,000 Americans died with fentanyl in their systems” and the “majority of those deaths – 18,335 – occurred in 2016 alone.” The Times adds that “fentanyl was first approved by the Food and Drug Administration back in 1968.”

NPR (3/21, Bebinger) reports that the study also indicates “men are dying after opioid overdoses at nearly three times the rate of women,” and there is “an especially steep rise in the number of young adults ages 25 to 34 whose death certificates include some version of the drug fentanyl.”

Intoxication and Death from Synthetic Cannabinoids-Missed Dx

Nearly half of patients with suspected synthetic-cannabinoid-receptor agonist (SCRA) intoxication test negative for an SCRA, and many test positive for another substance, researchers report.  Clinicians caring for patients with reported synthetic-cannabinoid exposures must have a high index of suspicion for other drugs of abuse, trauma, or other medical conditions, and should evaluate and treat accordingly,

Additionally, for patients that are exposed to synthetic cannabinoids, it is essential to look out for new or different symptoms and complications, as the chemical composition of these agents is rapidly evolving.

SCRAs, sometimes referred to as "K2" or "Spice," have become popular recreational drugs due to their easy availability, legal ambiguity, inability to be detected by current drug screens, and the potent high associated with their use. Acute SCRA intoxication presents with a wide range of symptoms and poses significant challenges to emergency medicine clinicians seeking to identify and manage these patients.

Dr. Mazer-Amirshahi and colleagues sought to characterize and confirm the constituents of reported or suspected SCRA exposures presenting to two academic emergency departments in Washington, D.C.  Among the 128 unique patients included in the study, only 71 (55.5%) tested positive for an SCRA. Most (40/71) were positive for an SCRA alone, but 31 were positive for an SCRA and another substance.  Among those testing positive, 12 were positive for two SCRAs, four were positive for three SCRAs, and two were positive for four SCRAs, the researchers report in the American Journal of Emergency Medicine, online December 24.

Of the 57 patients who tested negative for an SCRA, 28 (21.9% overall) tested positive for another substance, the most common being tetrahydrocannabinol (THC) and phencyclidine (PCP). The rest (22.7% of patients overall) tested negative for SCRAs and toxicology screens.

The most commonly detected SCRAs were AB-fubinaca (39.4%), ADB-fubinaca (21.1%), AB-chminaca 3-methyl-butanoic acid (21.1%), ADB-chminaca (19.7%) and 5-flouro-PB-22 (11.3%).  There was a significant shift in the chemical constituents from prior studies, which is a known trend to avoid legal regulation.

Synthetic cannabinoids are part of a group of drugs called new psychoactive substances (NPS). NPS are unregulated mind-altering substances that have become newly available on the market and are intended to produce the same effects as illegal drugs. Some of these substances may have been around for years but have reentered the market in altered chemical forms, or due to renewed popularity.

Individuals reported acquiring the contaminated synthetic cannabinoid products (i.e., K2, spice, synthetic marijuana, and legal weed) from convenience stores, dealers, and friends, in counties across the state.   

Synthetic cannabinoids are human-made, mind-altering chemicals that are either sprayed on dried, shredded plant material so they can be smoked or sold as liquids to be vaporized and inhaled in e-cigarettes and other devices. They are sold for recreational drug use with claims they will provide the user the effects of cannabis. These products are also known as herbal or liquid incense and have brand names such as K2, Spice, Black Mamba, Bombay Blue, Genie, and Zohai, but may be packaged under other brand names also.

These chemicals are called cannabinoids because they are similar to chemicals found in the marijuana plant. Because of this similarity, synthetic cannabinoids are sometimes misleadingly called "synthetic marijuana" (or "fake weed"), and they are often marketed as safe, legal alternatives to that drug. In fact, they are not safe and may affect the brain much more powerfully than marijuana; their actual effects can be unpredictable and, in some cases, more dangerous or even life-threatening.

Deaths from synthetic cannabinoids have occurred from ingesting too much of the drug.  Also, deaths from synthetic cannabinoid-related motor vehicle accidents are now widely reported in the news.

 

SOURCE: https://bit.ly/2RqfTU1

Am J Emerg Med 2018.  Intoxication From Synthetic-Cannabinoid-Receptor Agonists Often Missed - Medscape - Jan 15, 2019.

Melatonin is Over-rated as a Sleeping Aid

 

Experts say that other issues pertaining to poor sleep quality, such as light exposure and certain behaviors, should be tackled ahead of resorting to use of the hormone melatonin to regulate sleep.  But if it is used, an individual's daily onset of natural melatonin production should be taken into account before deciding on an appropriate dose to supplement, they say. 

Melatonin, which is available over-the-counter in the United States but restricted in other developed countries, is typically recommended acutely for sleep schedules thrown off by, for example, jet lag or chronically for certain circadian rhythm disorders.  It has also been touted as something close to a panacea, with some even suggesting it can treat cancer, cognitive dysfunction, and obesity.  However, it is the explosion in the use of melatonin to regulate general sleep in otherwise healthy individuals that has led to US consumers reportedly spending more than $400 million on melatonin supplements in 2018.

This has raised concerns over its safety among healthcare professionals and led to questions as to whether the hormone should be taken for jet lag at all and whether its use should be restricted in children.  This ongoing debate led the American Chemical Society to recently produce a video produce a video that debunks many of the myths around melatonin and its effects, including the magnitude of its benefits in improving sleep.  

Now, José Cipolla-Neto, MD, PhD, Institute of Biomedical Sciences, University of São Paulo, and Fernanda Gaspar do Amaral, PhD, a professor at the Federal University of São Paulo, Brazil, have conducted an in-depth review of the literature on melatonin and its uses.  Moreover, they have produced a series of recommendations, published in the December issue of Endocrine Reviews, that set out how best to use the hormone, including advice on the most effective dosage and timing.

But others question whether people should look to melatonin to regulate sleep at all, suggesting that, instead, individuals should be looking at controlling night-time light exposure and even regulating light levels in shops.  The sheer amount of research that has been conducted into melatonin in recent years is staggering. Cipolla-Neto and Amaral point out more than 4000 studies have been published in the last 20 years, of which 200 were randomized controlled trials and 195 systematic reviews.

Melatonin has been shown to affect a number of physiological processes, including downstream effects on the cardiovascular, reproductive, immune, respiratory, and endocrine systems, alongside energy metabolism.  Melatonin synchronizes our organism's temporal order both daily and on the seasonal time scale.  Consequently, multiple modes of action should be taken into account both when performing laboratory experiments and conducting clinical studies into melatonin's use as a treatment.

Melatonin's effects depend not just on the route of administration and concentration but also on the time of administration, among other factors.  Additionally, the daily variation in melatonin levels varies between individuals.  For example, those who prefer to get up early start daily melatonin production earlier than those who prefer to stay up later, while long sleepers tend to produce the hormone for longer periods than those who sleep less.

A given dose of melatonin may, moreover, result in different plasma levels between individuals, owing to pharmacokinetic differences in the way that it is absorbed, distributed, metabolized, and eliminated.  These processes can themselves be affected by an individual's age and clinical condition, the presence of pathological conditions, and the physiological performance of the gastrointestinal tract, liver, and kidneys.  If these factors are not adequately considered, they say that the clinical efficacy of melatonin will be altered.

How Should Melatonin Be Best Used?

The first recommendation is to determine the start of melatonin production, known as the dim light melatonin onset (DLMO), and its duration in each patient, and use that to guide prescribing. This is because, without using the DLMO as an indicator of the timing of administration, melatonin could advance, delay, or even have no effect on the timing of endogenous circadian rhythms.

However, is not typically feasible to determine the DLMO in everyday clinical practice.  A more practical surrogate is to take the time at which the patient usually goes to sleep at night.  Because of bioavaiability, melatonin should be taken around an hour before the usual bedtime at exactly the same time every day.

In terms of the dose, there is no consensus in the literature.  What is known is that young people who take approximately 0.1 to 0.3 mg of melatonin will have a plasma concentration in the range of 100 to 200 pg/mL, which is considered to be within the physiological range.

 

A dose of 1.0 mg would result in a plasma concentration of approximately 500 to 600 pg/mL, which is far higher than the physiological concentration.  For example, if the outcome is an acute phase displacing, as it is desired for jet lag treatment, a fast-release pulse correctly timed is perfectly adequate.  However, if the desired effect is a sustained phase displacement as, for example, in non-24-hour sleep disorder or circadian dysfunction in totally blind people, the synchronizing effect requires chronic continuous daily intake of melatonin.  For this purpose, a slow-release or dual-release formulation is the most appropriate."

 Should Melatonin Be Taken at All?

A question nevertheless remains as to whether melatonin should be taken at all by individuals who do not have a recognized clinical condition, or indeed whether it is the most appropriate treatment in those who do.

Satchidananda Panda, PhD, and his colleagues at the Salk Institute for Biological Studies, La Jolla, California, published a study in mice showing how the protein melanopsin in retinal cells continually responds to light. Melanopsin, which is tuned to blue light, is essentially checking whether it's daylight still out there and, if there is daylight, then it will tell the brain to avoid sleeping and stay awake.  It does that by two ways, one is increasing the circadian clock, telling that it's still daytime, and the second is it tells the pineal gland to slow down production of melatonin.  Melatonin, threfore, has a big impact on sleep and it should not be seen as a panacea, and should be heavily regulated, which it's not.  At the present time melatonin is the only hormone produced in the human body that's not heavily regulated.

Not Harmful, But Not That Effective

That said, currently, there isn't any hard  evidence to say that taking melatonin on a daily basis is harmful; there aren't large-scale multicenter clinical trials to really test that.  Most of the ongoing research is now being focused on reduction of light exposure in the hours prior to bedtime.  

 

Drug Overdose Deaths Increasing in U.S.

Deaths from drug overdose in the United States increased by 54% from 2011 to 2016 — with opioids, benzodiazepines (benzos), and stimulants the most commonly used drug classes involved, a new report released today by the Centers for Disease Control and Prevention's National Center for Health Statistics (NCHS), shows.

 The report notes that there were 41,340 drug overdose deaths in 2011 vs 63,632 such deaths in 2016.

 Although the opioid oxycodone was the most cited drug in overdose death records in 2011, heroin took the top spot from 2012 to 2015.

The story around fentanyl may be even more troubling. The rate of overdose deaths involving it or one of its analogs doubled each year from 2013 through 2016, when it finally took the lead in becoming the most mentioned drug. In 2016, 29% of all overdose deaths involved fentanyl (n = 18,335).

In addition, cocaine was the second or third most cited drug in the overdose death records throughout the entire study period.

The CDC's list of the 10 most frequently mentioned drugs also included the opioids, methadone, morphine, and hydrocodone;  the benzos, alprazolam and diazepam; and the stimulant methamphetamine.

Of all 10 drugs, only methadone was associated with a decreasing overdose death rate from 2011 to 2016.

"While the ranking changed from year to year, the top 10 drugs involved in overdose deaths remained consistent throughout the 6-year period," note the investigators, led by Holly Hedegaard, MD, NCHS.

"This report identifies patterns in the specific drugs most frequently involved in drug overdose deaths…and highlights the importance of complete and accurate reporting in the literal text on death certificates," they write.

The data were published online in the December 12 issue of the National Vital Statistics Reports.

Rise in Overdose Death Toll

An NCHS report released last year showed the age-adjusted rate of US drug overdose deaths increased dramatically from 1999 (6.1 per 100,000 population) to 2016 (19.8 per 100,000).

Although several previous studies on drug overdoses have used National Vital Statistics System-Mortality (NVSS-M) information, this data is coded using the International Classification of Diseases, Tenth Revision(ICD-10); and these ICD-10 codes focus on broad drug categories rather than on individual drugs, note the investigators.

In answer to this, the NCHS and the US Food and Drug Administration "collaboratively developed methods to search the literal text from death certificates to identify mentions of specific drugs and other substances, and to search contextual terms to identify involvement of the drug(s) or substance(s) in the death," the researchers write.

They defined "literal text" as written information from the medical certifier on cause or circumstances related to a death.

For the current report, they examined NVSS-M data from 2011 through 2016. These data were linked to electronic files containing death certificate information.

In addition to the top 10 drugs involved in overdose deaths, drugs that held the number 11 through number 15 ranking throughout the 6-year study period included diphenhydramine, acetaminophen, citalopram, carisoprodol, oxymorphone, tramadol, amitryptyline, clonazepam, gabapentin, and amphetamine. 

Threefold Increase in Heroin Deaths

The involvement of heroin in overdose deaths rose threefold from 4571 deaths in 2011 to 15,961 deaths in 2016. This made it the second-most mentioned drug in 2016, behind fentanyl.

Mentions of cocaine increased from 5892 overdose deaths in 2014 to 11,316 deaths in 2016, giving it that year's number 3 ranking.

The fourth most mentioned drug in overdose deaths in 2016 was methamphetamine. Its 6762 related deaths signified a sharp increase from the 1887 related deaths in 2011.

"An analysis of trends…showed that, for several drugs, the age-adjusted rate of drug overdose deaths increased considerably within a relatively short period," the investigators write.

Heroin, cocaine, and methamphetamine all showed significant increasing trends for age-adjusted rates of drug overdose deaths between 2011 and 2016 (1.5 vs 5.1 per 100,000 population; 1.6 vs 3.6 per 100,000; and 0.6 vs 2.1 per 100,000, respectively; all, P< .05).

Fentanyl showed a significant increasing trend between 2013 and 2016 (0.6 vs 5.9 per 100,000; P< .05).

The only decrease for a specific drug came from methadone, which was mentioned in 4545 overdose deaths in 2011 vs 3493 deaths in 2016 (1.4 vs 1.1 per 100,000). Still, it was the eighth most mentioned drug in 2016.

 For the 2016 top 10 drugs, "the proportion of deaths involving both the referent drug and at least one other concomitant drug ranged from 50% for methamphetamine to 96% for alprazolam or diazepam," the researchers report.

Finally, drugs most frequently recorded in unintentional overdose deaths in 2016 were fentanyl, heroin, and cocaine. The most frequently cited drugs in suicide by overdose were oxycodone, diphenhydramine, hydrocodone, and alprazolam.

NCHS National Vital Statistics Reports. Published December 12, 2018. Full text

Narcan and ER Treatment of Opiate Overdose

Recently published in the Acad. Emerg. Med. December 28, 2018

Most patients who overdose on opioids can be safely discharged from the emergency department (ED) as early as an hour after prehospital administration of the opioid antagonist naloxone, the study has found.

Opioid-related ED visits nearly doubled in the United States from 2005 to 2014. 

The researchers conducted a prospective study to validate the early discharge rule practiced at St. Paul's Hospital, Vancouver, Canada, which allows for discharge after 1 hour for those in whom the following six criteria are within normal limits: ambulation, oxygen saturation (> 95%), respiratory rate (>10 and <20 breaths/min), temperature (>35.0° C and <37.5° C), heart rate (>50 and <100 beats/min), and Glasgow Coma Scale score (15).

The study included 538 adult patients who presented by ambulance to the ED from 2016 to 2017, who had been administered at least one dose of naloxone before entering the hospital, and who underwent evaluation by an emergency medicine provider 1 hour after naloxone administration. (The typical observation period at the hospital is 4 hours.) The mean age of the patients was 33.4 years, and 69.5% were male.

The researchers examined whether clinical judgment, the St. Paul's Early Discharge Rule, or both, when utilized 1 hour after prehospital administration of naloxone, could predict who would have an adverse event (AE) within 24 hours.

AEs occurred in 82 patients (15.4%), but none died within 48 hours. The most common AEs were need for supplemental oxygen (11.3%), repeat naloxone for hypoventilation (3%), and assisted ventilation (2.6%).

Overall, the rule had a sensitivity of 84.1% (95% confidence interval [CI], 76.2 - 92.1), a specificity of 62.1% (95% CI, 57.6 - 66.5), and a negative predictive value of 95.6% (95% CI, 93.3 - 97.9). The inability to mobilize normally had the greatest sensitivity (58.0%) for predicting AEs; an abnormal temperature had the greatest specificity (99.1%). The rule failed to predict AEs in just 13 of 538 cases (2.4%).

These results are in line with the derivation study by the rule's originators, which found that the AE rate was 16% and the negative predictive value was 99%.

Only one patient in the study whose 1-hour evaluation results were normal subsequently needed additional naloxone following another presumed heroin overdose.

When used in tandem with healthcare provider judgment, the rule had a sensitivity of 87.8% (95% CI, 80.7% - 94.9%), a specificity of 53.0% (95% CI, 48.4% - 57.7%), and a negative predictive value of 96.0% (95% CI, 93.5 - 98.4%). Used together, provider judgment and the St. Paul's Early Discharge Rule predicted AEs in all but 10 of 529 patients (1.9%) .

 "Applying the prediction rule for patients for whom providers have a low clinical suspicion for AEs is a reasonable approach for risk stratifying patients for early discharge following naloxone administration for suspected opioid overdose," the authors write. They add, however, that the rule should be used with caution in cases of known oral or mixed overdose. They also call for further study to determine the rule's effectiveness in the context of overdoses of different drugs, drug combinations, and routes of administration.

Acad Emerg Med. Published online December 28, 2018. Full text

 

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