Toxicology

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

Most people who could benefit from FDA-approved medications for opioid use disorder do not receive them, and access to those treatments is not equitable, according to a new consensus study report from the National Academies of Sciences, Engineering, and Medicine.

“Methadone, buprenorphine, and extended-release naltrexone are safe and highly effective medications that are already approved by the U.S. Food and Drug Administration to treat OUD,” the report said. “These medications save lives, but the majority of people with OUD in the United States receive no treatment at all.”

The report, called “Medications for Opioid Use Disorder Save Lives,” said a critical factor in addressing the crisis is “confronting the major barriers” to using those medications. It also said additional research will be needed to address opioid use disorder among subpopulations in the United States, such as adolescents, older adults, people with comorbidities, racial and ethnic groups, and people with low socioeconomic status. The National Academies’ report was sponsored by NIDA and SAMHSA.

A few weeks before the release of National Academies report, the National Academy of Medicine (NAM) held a webinar providing details on its Action Collaborative on Countering the U.S. Opioid Epidemic. The collaborative, a partnership of public and private stakeholders, aims to address the opioid crisis through a multidisciplinary, cross-sector effort.

The collaborative is represented by federal agencies, state and local governments, health care systems, provider groups, nonprofits, payers, industry, academia, patient organizations, and communities across about 55 organizations, according to Victor J. Dzau, MD, chair of the Action Collaborative and current NAM president. Over a 2-year period, the collaborative’s goal is to accelerate progress in overcoming the opioid crisis by recognizing the challenges, research gaps, and needs of organizations involved in the crisis and “elevate and accelerate evidence-based, multisectoral, and interprofessional solutions,” he said.

“This is not a problem that can be solved by a single sector. It is truly a whole of society problem,” said Adm. Brett P. Giroir, MD, assistant secretary for health at the U.S. Department of Health and Human Services, said during the webinar. “And the only way that we are going to be able to begin making inroads to reverse the trends of this crisis is if we work together.” Dr. Giroir also serves as cochair of the steering committee for the collaborative.

In its overview of the collaborative, the NAM outlined four working groups developed through a series of surveys and planning meetings that would identify the resources that currently exist to combat the opioid epidemic and determine which resources still need to be developed. In the Health Professional Education and Training Working Group, for example, the objective is to examine what is being taught to health professionals about acute and chronic pain management at an accreditation, certification, and regulatory level to develop educational tools based around knowledge gaps in those areas and analyze how the new resources are affecting health professions after they have been adopted, said Steve Singer, PhD, vice president of education and outreach at the Accreditation Council for Graduate Medical Education and colead of the working group.“Our goal is really to provide guidance and resources across the continuum of health professions and education with an interprofessional – and patient-informed view,” he said.

The Opioid Prescribing Guidelines and Evidence Standards Working Group plans to address the disparities in prescribing and tapering guidelines for acute and chronic pain as well as identify where pain management guidelines in different specialties “cannot be justified,” based on available evidence.

“Further, we think it’s really important to not just have guidelines that will sit on a shelf, but we also want to think about how we can support implementation of these guidelines into practice ... ” said Helen Burstin, MD, MPH, executive vice president and CEO for the Council of Medical Specialty Societies and colead of the working group.

Alonzo L. Plough, PhD, MPH, vice president of research-evaluation-learning at the Robert Wood Johnson Foundation and colead of the Prevention, Treatment, and Recovery Services Working Group, explained that the goal of his group is to identify the “essential elements and components” and best practices of prevention, treatment, and recovery for OUD. He noted that, although the working group will not be able to reach all patient populations affected by OUD, it has discussed targeting vulnerable high-risk populations, such as those involved in the criminal justice system, homeless veterans, mothers, and children.

“This is an ecosystem that requires great concentration and effort to make sure that there are integrated approaches throughout the continuum that work for patients and clients from different walks of life, and I think that our overall guidance is how we can recognize and use evidence to find those approaches and build on them for guidance,” he said.

The Research, Data, and Metrics Needs Working Group is tasked with collaborating with the other groups to obtain currently available information and identify what barriers exist to greater transparency, sharing and interoperability of data as well as what gaps in research currently exist that would further the collaborative’s mission, said Kelly J. Clark, MD, MBA, of the ASAM. “It is simply critical for us to utilize the data that’s out there, to pool it into more actionable information – and then to act on it,” Dr. Clark said.

The NAM is seeking new organizations interested in joining the collaborative as a network organization, which would receive updates and provide input on the collaborative but would not be a part of the working groups.

The first public meeting of the Action Collaborative on Countering the U.S. Opioid Epidemic will take place on April 30, 2019, in Washington.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

SEATTLE – People with HIV are more likely to die from an opioid overdose than the general public, according to investigators from the Centers for Disease Control and Prevention.

M.Alexander Otto/MDedge News

“We looked into this because we know persons with HIV are more likely to have chronic pain and more likely to receive opioid analgesic treatments, and receive higher doses. In addition, they are more likely to have substance use disorders and mental illness than the U.S. general populations,” CDC epidemiologist Karin A. Bosh, PhD, said at the Conference on Retroviruses and Opportunistic Infections.

To see how that played out in terms of unintentional opioid overdose deaths, they turned to the National HIV Surveillance System and focused on overdose deaths during 2011-2015, the latest data available at the time of the work.

There were 1,363 overdose deaths among persons with HIV during that period, with the rate increasing 42.7% – from 23.2/100,000 HIV patients in 2011 to 33.1/100,000 in 2015.

Although the rate of increase was comparable to the general population, the crude rate was “actually substantially higher among persons with HIV,” Dr. Bosh said. Deaths were highest among persons aged 50-59 years (41.9/100,000), whites (49.1/100,000), injection drug users (137.4/100,000), and people who live in the Northeast (60.6/100,000).

Surprisingly, there was no increase in the rate of overdose deaths among HIV patients on the West Coast, possibly because heroin there was less likely to be cut with fentanyl.

Also, the rate of opioid overdose deaths was higher among women with HIV (35.2/100,000) than among men, perhaps because women are more likely to contract HIV by injection drug use, so they are more likely to be injection drug users at baseline, while the vast majority of men are infected through male-male sex, the investigators said.

The findings underscore the importance of intensifying overdose prevention in the HIV community, and better integrating HIV and substance use disorder treatment, they concluded.

M. Alexander Otto//MDedge News

That comes down to screening people for problems, especially in the subgroups identified in the study, and connecting them to drug treatment services. If HIV and substance disorder services were in the same clinic it would help, as would an increase in the number of buprenorphine providers, according to Sheryl B. Lyss, PhD, a coinvestigator and CDC epidemiologist.

“Obviously, when substance use is addressed, people can be much more adherent with their [HIV] medications,” she noted.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no relevant disclosures.

[email protected]

SOURCE: Bosh KA et al. CROI 2019, Abstract 147.

The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

[email protected]

The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

[email protected]

The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

[email protected]

In 2016, news reports warned the public of an opioid epidemic gripping the nation.

Karen Mower/iStockphoto

But Madeline Vaughn, then a lead clinical intake coordinator at the Houston-based addiction treatment organization Council on Recovery, sensed something different was going on with the patients she checked in from the street.

Their behavior, marked by twitchy suspicion, a poor memory, and the feeling that someone was following them, signaled that the people coming through the center’s doors were increasingly hooked on a different drug: methamphetamine.

“When you’re in the boots on the ground,” Ms. Vaughn said, “what you see may surprise you, because it’s not in the headlines.”

In the time since, it’s become increasingly clear that, even as the opioid epidemic continues, the toll of methamphetamine use, also known as meth or crystal meth, is on the rise, too.

The rate of overdose deaths involving the stimulant more than tripled from 2011 to 2016, the Centers for Disease Control and Prevention reported.

But unlike the opioid epidemic – for which medications exist to help combat addiction – medical providers have few such tools to help methamphetamine users survive and recover. A drug such as naloxone, which can reverse an opioid overdose, does not exist for meth. And there are no drugs approved by the Food and Drug Administration that can treat a meth addiction.

“We’re realizing that we don’t have everything we might wish we had to address these different kinds of drugs,” said Margaret Jarvis, MD, a psychiatrist and distinguished fellow for the American Society of Addiction Medicine.

Meth revs up the human body, causing euphoria, elevated blood pressure, and energy that enables users to go for days without sleeping or eating. In some cases, long-term use alters the user’s brain and causes psychotic symptoms that can take up to one year after the person has stopped using it to dissipate.

Overdosing can trigger heart attacks, strokes, and seizures, which can make pinpointing the drug’s involvement difficult.

Meth users also tend to abuse other substances, which complicates first responders’ efforts to treat a patient in the event of an overdose, said David Persse, MD, EMS physician director for Houston. With multiple drugs in a patient’s system, overdose symptoms may not neatly fit under the description for one substance.

“If we had five or six miracle drugs,” Dr. Persse said, to use immediately on the scene of the overdose, “it’s still gonna be difficult to know which one that patient needs.”

Research is underway to develop a medication that helps those with methamphetamine addiction overcome their condition. The National Institute on Drug Abuse Clinical Trials Network is testing a combination of naltrexone, a medication typically used to treat opioid and alcohol use disorders, and an antidepressant called bupropion.

And a team from the Universities of Kentucky and Arkansas created a molecule called lobeline that shows promise in blocking meth’s effects in the brain.

For now, though, existing treatments, such as the Matrix Model, a drug counseling technique, and contingency management, which offers patients incentives to stay away from drugs, are key options for what appears to be a meth resurgence, said Dr. Jarvis.

Illegal drugs never disappear from the street, she said. Their popularity waxes and wanes with demand. And as the demand for methamphetamine use increases, the gaps in treatment become more apparent.

Dr. Persse said he hasn’t seen a rise in the number of calls related to methamphetamine overdoses in his area. However, the death toll in Texas from meth now exceeds that of heroin.

Provisional death counts for 2017 showed methamphetamine claimed 813 lives in the Lone Star State. By comparison, 591 people died because of heroin.

The Drug Enforcement Administration reported that the price of meth is the lowest the agency has seen in years. It is increasingly available in the eastern region of the United States. Primary suppliers are Mexican drug cartels. And the meth on the streets is now more than 90% pure.

“The new methods [of making methamphetamine] have really altered the potency,” said Jane Maxwell, PhD, research professor at the University of Texas at Austin’s social work school. “So the meth we’re looking at today is much more potent than it was 10 years ago.”

For Ms. Vaughn, who works as an outpatient therapist and treatment coordinator, these variables are a regular part of her daily challenge. So until the research arms her with something new, her go-to strategy is to use the available tools to tackle her patients’ methamphetamine addiction in layers.

She starts with writing assignments, then coping skills until they are capable of unpacking their trauma. Addiction is rarely the sole demon patients wrestle with, Ms. Vaughn said.

“Substance use is often a symptom for what’s really going on with someone,” she said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In 2016, news reports warned the public of an opioid epidemic gripping the nation.

Karen Mower/iStockphoto

But Madeline Vaughn, then a lead clinical intake coordinator at the Houston-based addiction treatment organization Council on Recovery, sensed something different was going on with the patients she checked in from the street.

Their behavior, marked by twitchy suspicion, a poor memory, and the feeling that someone was following them, signaled that the people coming through the center’s doors were increasingly hooked on a different drug: methamphetamine.

“When you’re in the boots on the ground,” Ms. Vaughn said, “what you see may surprise you, because it’s not in the headlines.”

In the time since, it’s become increasingly clear that, even as the opioid epidemic continues, the toll of methamphetamine use, also known as meth or crystal meth, is on the rise, too.

The rate of overdose deaths involving the stimulant more than tripled from 2011 to 2016, the Centers for Disease Control and Prevention reported.

But unlike the opioid epidemic – for which medications exist to help combat addiction – medical providers have few such tools to help methamphetamine users survive and recover. A drug such as naloxone, which can reverse an opioid overdose, does not exist for meth. And there are no drugs approved by the Food and Drug Administration that can treat a meth addiction.

“We’re realizing that we don’t have everything we might wish we had to address these different kinds of drugs,” said Margaret Jarvis, MD, a psychiatrist and distinguished fellow for the American Society of Addiction Medicine.

Meth revs up the human body, causing euphoria, elevated blood pressure, and energy that enables users to go for days without sleeping or eating. In some cases, long-term use alters the user’s brain and causes psychotic symptoms that can take up to one year after the person has stopped using it to dissipate.

Overdosing can trigger heart attacks, strokes, and seizures, which can make pinpointing the drug’s involvement difficult.

Meth users also tend to abuse other substances, which complicates first responders’ efforts to treat a patient in the event of an overdose, said David Persse, MD, EMS physician director for Houston. With multiple drugs in a patient’s system, overdose symptoms may not neatly fit under the description for one substance.

“If we had five or six miracle drugs,” Dr. Persse said, to use immediately on the scene of the overdose, “it’s still gonna be difficult to know which one that patient needs.”

Research is underway to develop a medication that helps those with methamphetamine addiction overcome their condition. The National Institute on Drug Abuse Clinical Trials Network is testing a combination of naltrexone, a medication typically used to treat opioid and alcohol use disorders, and an antidepressant called bupropion.

And a team from the Universities of Kentucky and Arkansas created a molecule called lobeline that shows promise in blocking meth’s effects in the brain.

For now, though, existing treatments, such as the Matrix Model, a drug counseling technique, and contingency management, which offers patients incentives to stay away from drugs, are key options for what appears to be a meth resurgence, said Dr. Jarvis.

Illegal drugs never disappear from the street, she said. Their popularity waxes and wanes with demand. And as the demand for methamphetamine use increases, the gaps in treatment become more apparent.

Dr. Persse said he hasn’t seen a rise in the number of calls related to methamphetamine overdoses in his area. However, the death toll in Texas from meth now exceeds that of heroin.

Provisional death counts for 2017 showed methamphetamine claimed 813 lives in the Lone Star State. By comparison, 591 people died because of heroin.

The Drug Enforcement Administration reported that the price of meth is the lowest the agency has seen in years. It is increasingly available in the eastern region of the United States. Primary suppliers are Mexican drug cartels. And the meth on the streets is now more than 90% pure.

“The new methods [of making methamphetamine] have really altered the potency,” said Jane Maxwell, PhD, research professor at the University of Texas at Austin’s social work school. “So the meth we’re looking at today is much more potent than it was 10 years ago.”

For Ms. Vaughn, who works as an outpatient therapist and treatment coordinator, these variables are a regular part of her daily challenge. So until the research arms her with something new, her go-to strategy is to use the available tools to tackle her patients’ methamphetamine addiction in layers.

She starts with writing assignments, then coping skills until they are capable of unpacking their trauma. Addiction is rarely the sole demon patients wrestle with, Ms. Vaughn said.

“Substance use is often a symptom for what’s really going on with someone,” she said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In 2016, news reports warned the public of an opioid epidemic gripping the nation.

Karen Mower/iStockphoto

But Madeline Vaughn, then a lead clinical intake coordinator at the Houston-based addiction treatment organization Council on Recovery, sensed something different was going on with the patients she checked in from the street.

Their behavior, marked by twitchy suspicion, a poor memory, and the feeling that someone was following them, signaled that the people coming through the center’s doors were increasingly hooked on a different drug: methamphetamine.

“When you’re in the boots on the ground,” Ms. Vaughn said, “what you see may surprise you, because it’s not in the headlines.”

In the time since, it’s become increasingly clear that, even as the opioid epidemic continues, the toll of methamphetamine use, also known as meth or crystal meth, is on the rise, too.

The rate of overdose deaths involving the stimulant more than tripled from 2011 to 2016, the Centers for Disease Control and Prevention reported.

But unlike the opioid epidemic – for which medications exist to help combat addiction – medical providers have few such tools to help methamphetamine users survive and recover. A drug such as naloxone, which can reverse an opioid overdose, does not exist for meth. And there are no drugs approved by the Food and Drug Administration that can treat a meth addiction.

“We’re realizing that we don’t have everything we might wish we had to address these different kinds of drugs,” said Margaret Jarvis, MD, a psychiatrist and distinguished fellow for the American Society of Addiction Medicine.

Meth revs up the human body, causing euphoria, elevated blood pressure, and energy that enables users to go for days without sleeping or eating. In some cases, long-term use alters the user’s brain and causes psychotic symptoms that can take up to one year after the person has stopped using it to dissipate.

Overdosing can trigger heart attacks, strokes, and seizures, which can make pinpointing the drug’s involvement difficult.

Meth users also tend to abuse other substances, which complicates first responders’ efforts to treat a patient in the event of an overdose, said David Persse, MD, EMS physician director for Houston. With multiple drugs in a patient’s system, overdose symptoms may not neatly fit under the description for one substance.

“If we had five or six miracle drugs,” Dr. Persse said, to use immediately on the scene of the overdose, “it’s still gonna be difficult to know which one that patient needs.”

Research is underway to develop a medication that helps those with methamphetamine addiction overcome their condition. The National Institute on Drug Abuse Clinical Trials Network is testing a combination of naltrexone, a medication typically used to treat opioid and alcohol use disorders, and an antidepressant called bupropion.

And a team from the Universities of Kentucky and Arkansas created a molecule called lobeline that shows promise in blocking meth’s effects in the brain.

For now, though, existing treatments, such as the Matrix Model, a drug counseling technique, and contingency management, which offers patients incentives to stay away from drugs, are key options for what appears to be a meth resurgence, said Dr. Jarvis.

Illegal drugs never disappear from the street, she said. Their popularity waxes and wanes with demand. And as the demand for methamphetamine use increases, the gaps in treatment become more apparent.

Dr. Persse said he hasn’t seen a rise in the number of calls related to methamphetamine overdoses in his area. However, the death toll in Texas from meth now exceeds that of heroin.

Provisional death counts for 2017 showed methamphetamine claimed 813 lives in the Lone Star State. By comparison, 591 people died because of heroin.

The Drug Enforcement Administration reported that the price of meth is the lowest the agency has seen in years. It is increasingly available in the eastern region of the United States. Primary suppliers are Mexican drug cartels. And the meth on the streets is now more than 90% pure.

“The new methods [of making methamphetamine] have really altered the potency,” said Jane Maxwell, PhD, research professor at the University of Texas at Austin’s social work school. “So the meth we’re looking at today is much more potent than it was 10 years ago.”

For Ms. Vaughn, who works as an outpatient therapist and treatment coordinator, these variables are a regular part of her daily challenge. So until the research arms her with something new, her go-to strategy is to use the available tools to tackle her patients’ methamphetamine addiction in layers.

She starts with writing assignments, then coping skills until they are capable of unpacking their trauma. Addiction is rarely the sole demon patients wrestle with, Ms. Vaughn said.

“Substance use is often a symptom for what’s really going on with someone,” she said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.

US DEA

“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.

The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.

The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.

Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)

However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.

The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).

In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).

“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”

Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.

“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”

The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.

There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.

Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.

“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”

Dr. Crystal reported no relevant disclosures.

SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.

New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.

US DEA

“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.

The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.

The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.

Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)

However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.

The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).

In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).

“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”

Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.

“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”

The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.

There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.

Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.

“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”

Dr. Crystal reported no relevant disclosures.

SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.

New federal statistics suggest that the opioid epidemic in the United States is evolving as physicians crack down on the use of prescription painkillers: Fatal drug overdose deaths rose by 12% from 2016 to 2017, boosted by a wave of fatalities linked to illicit synthetic opioids like fentanyl that are now linked to an estimated 60% of opioid-related deaths.

US DEA

“Overall, the overdose epidemic continues to worsen, and it has grown increasingly complex by coinvolvement of prescription and illicit drugs,” Lawrence Scholl, PhD, MPH, and his associates at the Centers for Disease Control & Prevention wrote in the Morbidity and Mortality Weekly Report.

The new statistics provide more evidence that 2017 marked “a sharp increase in what has characterized as the third wave of the opioid epidemic,” said drug and health policy researcher Stephen Crystal, PhD, of Rutgers University, New Brunswick, N.J., in an interview. He was referring to a wave that experts believe started in 2013 amid a spike in U.S. overdose deaths from fentanyl and other synthetic opioids.

The new report analyzes fatal drug overdose data from 2013 to 2017. According to the findings, the total number of those overdoses rose to 70,237 in 2017, up from 63,632 in 2016. The highest drug overdose death rates in 2017 were in West Virginia, followed by Ohio, Pennsylvania, and the District of Columbia.

Some statistics did not change much from 2016 to 2017: About two-thirds of the drug overdose deaths were linked to opioids in both years, and the death rate of cases linked to prescription drugs and heroin remained steady. (Death rates in the report were age adjusted.)

However, the percentage of fatal overdose cases linked to synthetic opioids grew 45% from 2016 to 2017. Overall, 60% of opioid-related fatal overdoses in 2017 involved synthetic opioids.

The report identifies increases in several areas from 2016 to 2017. Opioid-related drug overdose deaths among black people rose by 25%, and an analysis of data from 34 states and the District of Columbia found the highest increases in death rates in North Carolina (29%), Ohio (19%), and Maine (19%).

In regard to deaths linked to synthetic opioids specifically, the highest death rates in 2017 were in West Virginia (37 per 100,000), Ohio (32 per 100,000), and New Hampshire (30 per 100,000).

“Part of what we’re seeing in these increased numbers are individuals who have pain, can’t get prescribed opioids, and turn to street drugs,” Dr. Crystal said, adding that “abruptly cutting patients off is not good, and leaving patients with a lot of untreated pain is not good. If people are going to be discontinued [from opioids] or have their doses reduced, the taper needs to be done very slowly and carefully.”

Synthetic opioids were not the only drugs that are driving up fatal overdoses, as the death rates of cases linked to cocaine and psychostimulants (such as methamphetamine) jumped by more than a third in 2017.

“The most important thing these numbers are telling me is that it’s becoming more and more attractive to drug dealers to put fentanyl in the heroin, cocaine, and other drugs they sell,” Dr. Crystal said. “When that happens, dependence on street drugs becomes much more deadly. It’s almost impossible to get the dose right. Every time you shoot up, you’re taking a chance that you’ll overdose.”

The report had limitations, including the fact that details about drug use were missing from 12% (2016) and 15% (2017) of death certificates in fatal overdose cases. By state, the percentages of those death certificates that included drug information ranged from as little as 55% to 99%.

There’s some possible positive news: The report points to preliminary data from 2018 suggesting that the number of annual drug overdose deaths may be leveling off – although it says more analysis is needed to confirm the trend.

Dr. Crystal, however, is not celebrating. “I don’t see this as a good news story, really,” he said, adding that there’s “a little too much of people patting themselves on the back” because they’re proud of cutbacks in opioid prescriptions.

“This doesn’t have to do with the huge number of people who got started with opioids years ago” and are now at risk of using street drugs, he said. “We haven’t engaged that population at the rate we need to. And flattening out at 70,000 drug overdoses a year is not a good news story.”

Dr. Crystal reported no relevant disclosures.

SOURCE: Scholl L et al. MMWR. 2019 Jan 4;67(5152):1419-27.

It used to be the stuff of stoner comedies and “Just Say No” campaigns. Today, marijuana is becoming mainstream as voters across the country approve ballot questions for legalization or medical use.

JasonDoiy/iStock/Getty Images Plus

In response, state governments are testing ways to ensure that the integration of this once-illicit substance into everyday life doesn’t create new public health risks. These efforts are sparking a difficult question: At what point is someone too high to get behind the wheel?

The answer is complicated. Brain scientists and pharmacologists don’t know how to measure if and to what extent marijuana causes impairment.

The reason: Existing blood and urine tests can detect marijuana use, but, because traces of the drug stay in the human body for a long time, those tests can’t specify whether the use occurred earlier that day or that month. They also don’t indicate the level at which a driver would be considered “under the influence.”

“It’s a really hard problem,” said Keith Humphreys, a psychiatry professor and drug policy expert at Stanford University (Calif.), the first state to legalize medical marijuana and where recreational pot use among adults became legal in 2016. “We don’t really have good evidence – even if we know someone has been using – [to gauge] what their level of impairment is.”

Marijuana is now legal for recreational use in 10 states and the District of Columbia – including Michigan, where a ballot initiative passed in November 2018 took effect Dec. 6. In New York, the governor said Dec. 17 that legalization would be a top priority for 2019. And nearly three dozen states have cleared the use of medical cannabis.

For alcohol, there is a clear, national standard. If your blood alcohol content is 0.08% or higher, you’re considered cognitively impaired at a level that is unsafe to drive. Extensive research supports this determination, and the clarity makes enforcement of drunken-driving laws easier.

Setting a marijuana-related impairment level is a much murkier proposition. But states that have legalized pot have to figure it out, experts said.

“You can’t legalize a substance and not have a coherent policy for controlling driving under the influence of that substance,” said Steven Davenport, an assistant policy researcher at the nonprofit Rand Corporation, who specializes in marijuana research.

Marijuana, after all, weakens a driver’s ability to maintain focus, and it slows reflexes. But regulators are “playing catch-up,” suggested Thomas Marcotte, a psychiatry professor at the University of California, San Diego, and one of a number of academics around the country who is researching driving while high.

States have put forth a bevy of approaches. At least five have what’s called a “per se” law, which outlaws driving if someone’s blood level of tetrahydrocannabinol, or THC, exceeds a set amount. THC is marijuana’s main intoxicant.

Colorado, where voters approved legalization of recreational marijuana in 2012, has this type of driving law on the books. It took 3 years to pass amid fiery debate and deems “intoxicated” any driver who tests higher than 5 ng of THC per milliliter of blood.

Indiana, Pennsylvania and Rhode Island are among states that forbid driving at any THC level. Still others say drivers should be penalized only if they are impaired by the chemical – a standard that sounds reasonable but quickly gets difficult to measure or even define.

None of these approaches offers an ideal solution, experts said.

“We’re still definitely evaluating which policies are the most effective,” said Ann Kitch, who tracks the marijuana and driving issue for the National Conference of State Legislatures.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

It used to be the stuff of stoner comedies and “Just Say No” campaigns. Today, marijuana is becoming mainstream as voters across the country approve ballot questions for legalization or medical use.

JasonDoiy/iStock/Getty Images Plus

In response, state governments are testing ways to ensure that the integration of this once-illicit substance into everyday life doesn’t create new public health risks. These efforts are sparking a difficult question: At what point is someone too high to get behind the wheel?

The answer is complicated. Brain scientists and pharmacologists don’t know how to measure if and to what extent marijuana causes impairment.

The reason: Existing blood and urine tests can detect marijuana use, but, because traces of the drug stay in the human body for a long time, those tests can’t specify whether the use occurred earlier that day or that month. They also don’t indicate the level at which a driver would be considered “under the influence.”

“It’s a really hard problem,” said Keith Humphreys, a psychiatry professor and drug policy expert at Stanford University (Calif.), the first state to legalize medical marijuana and where recreational pot use among adults became legal in 2016. “We don’t really have good evidence – even if we know someone has been using – [to gauge] what their level of impairment is.”

Marijuana is now legal for recreational use in 10 states and the District of Columbia – including Michigan, where a ballot initiative passed in November 2018 took effect Dec. 6. In New York, the governor said Dec. 17 that legalization would be a top priority for 2019. And nearly three dozen states have cleared the use of medical cannabis.

For alcohol, there is a clear, national standard. If your blood alcohol content is 0.08% or higher, you’re considered cognitively impaired at a level that is unsafe to drive. Extensive research supports this determination, and the clarity makes enforcement of drunken-driving laws easier.

Setting a marijuana-related impairment level is a much murkier proposition. But states that have legalized pot have to figure it out, experts said.

“You can’t legalize a substance and not have a coherent policy for controlling driving under the influence of that substance,” said Steven Davenport, an assistant policy researcher at the nonprofit Rand Corporation, who specializes in marijuana research.

Marijuana, after all, weakens a driver’s ability to maintain focus, and it slows reflexes. But regulators are “playing catch-up,” suggested Thomas Marcotte, a psychiatry professor at the University of California, San Diego, and one of a number of academics around the country who is researching driving while high.

States have put forth a bevy of approaches. At least five have what’s called a “per se” law, which outlaws driving if someone’s blood level of tetrahydrocannabinol, or THC, exceeds a set amount. THC is marijuana’s main intoxicant.

Colorado, where voters approved legalization of recreational marijuana in 2012, has this type of driving law on the books. It took 3 years to pass amid fiery debate and deems “intoxicated” any driver who tests higher than 5 ng of THC per milliliter of blood.

Indiana, Pennsylvania and Rhode Island are among states that forbid driving at any THC level. Still others say drivers should be penalized only if they are impaired by the chemical – a standard that sounds reasonable but quickly gets difficult to measure or even define.

None of these approaches offers an ideal solution, experts said.

“We’re still definitely evaluating which policies are the most effective,” said Ann Kitch, who tracks the marijuana and driving issue for the National Conference of State Legislatures.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

It used to be the stuff of stoner comedies and “Just Say No” campaigns. Today, marijuana is becoming mainstream as voters across the country approve ballot questions for legalization or medical use.

JasonDoiy/iStock/Getty Images Plus

In response, state governments are testing ways to ensure that the integration of this once-illicit substance into everyday life doesn’t create new public health risks. These efforts are sparking a difficult question: At what point is someone too high to get behind the wheel?

The answer is complicated. Brain scientists and pharmacologists don’t know how to measure if and to what extent marijuana causes impairment.

The reason: Existing blood and urine tests can detect marijuana use, but, because traces of the drug stay in the human body for a long time, those tests can’t specify whether the use occurred earlier that day or that month. They also don’t indicate the level at which a driver would be considered “under the influence.”

“It’s a really hard problem,” said Keith Humphreys, a psychiatry professor and drug policy expert at Stanford University (Calif.), the first state to legalize medical marijuana and where recreational pot use among adults became legal in 2016. “We don’t really have good evidence – even if we know someone has been using – [to gauge] what their level of impairment is.”

Marijuana is now legal for recreational use in 10 states and the District of Columbia – including Michigan, where a ballot initiative passed in November 2018 took effect Dec. 6. In New York, the governor said Dec. 17 that legalization would be a top priority for 2019. And nearly three dozen states have cleared the use of medical cannabis.

For alcohol, there is a clear, national standard. If your blood alcohol content is 0.08% or higher, you’re considered cognitively impaired at a level that is unsafe to drive. Extensive research supports this determination, and the clarity makes enforcement of drunken-driving laws easier.

Setting a marijuana-related impairment level is a much murkier proposition. But states that have legalized pot have to figure it out, experts said.

“You can’t legalize a substance and not have a coherent policy for controlling driving under the influence of that substance,” said Steven Davenport, an assistant policy researcher at the nonprofit Rand Corporation, who specializes in marijuana research.

Marijuana, after all, weakens a driver’s ability to maintain focus, and it slows reflexes. But regulators are “playing catch-up,” suggested Thomas Marcotte, a psychiatry professor at the University of California, San Diego, and one of a number of academics around the country who is researching driving while high.

States have put forth a bevy of approaches. At least five have what’s called a “per se” law, which outlaws driving if someone’s blood level of tetrahydrocannabinol, or THC, exceeds a set amount. THC is marijuana’s main intoxicant.

Colorado, where voters approved legalization of recreational marijuana in 2012, has this type of driving law on the books. It took 3 years to pass amid fiery debate and deems “intoxicated” any driver who tests higher than 5 ng of THC per milliliter of blood.

Indiana, Pennsylvania and Rhode Island are among states that forbid driving at any THC level. Still others say drivers should be penalized only if they are impaired by the chemical – a standard that sounds reasonable but quickly gets difficult to measure or even define.

None of these approaches offers an ideal solution, experts said.

“We’re still definitely evaluating which policies are the most effective,” said Ann Kitch, who tracks the marijuana and driving issue for the National Conference of State Legislatures.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

The dangers of synthetic drugs and heroin, and the opioid epidemic, are hitting emergency departments hard. A lack of guidelines and poor presentation to follow-up care make treatment decisions difficult. Pockets of outbreaks emerge when dangerous toxins are added to already dangerous drugs. One such regional outbreak occurred in March 2018 when synthetic cannabinoids laced with superwarfarin were led to 150 patients presenting to hospitals with severe coagulopathy in Illinois.

ACEP18 will feature a plethora of toxicology presentations and workshops, such as “Emergency Toxicology: Emerging Trends – Cases in Poisoning Management” on Tuesday, Oct. 2 at 8 am, led my Patrick M. Lank, MD, FACEP. Dr. Lark, an emergency medicine specialist in Chicago, will also be leading  “Critical Update in Toxicology 2018" on Monday, Oct. 1, at 12:30 pm and “FAST FACTS: High-Yield Toxicology,” on Monday, at 4:30 pm.

Synthetic cannabinoids laced with superwarfarin were behind a recent outbreak of severe coagulopathy in Illinois.

In most cases, vitamin K replacement therapy alleviated symptoms, but four patients died after developing intracranial bleeding, said Amar H. Kelkar, MD, of the University of Illinois at Peoria.

Experts continue to look for how and why superwarfarin ended up in synthetic cannabinoids, whose street names include spice and K2, wrote Dr. Kelkar and his associates. Their report is in the New England Journal of Medicine.

Starting in March 2018, more than 150 patients across Illinois presented to hospitals with bleeding diathesis that involved persistent coagulopathy, the investigators explained. Early inquiries revealed that patients had consumed synthetic cannabinoids. Serum tests identified vitamin K antagonists, including brodifacoum, bromadiolone, and difenacoum. During arrests of suspected distributors, police confiscated synthetic cannabinoids that also tested positive for brodifacoum.

To help characterize the outbreak, the investigators reviewed admissions to Saint Francis Medical Center in Peoria, Ill., between March 28 and April 21, 2018. They identified 34 cases in which patients with vitamin K–dependent factor coagulopathy reported recent exposure to synthetic cannabinoids.

Fifteen of these patients underwent confirmatory anticoagulant testing, which universally confirmed superwarfarin poisoning. Brodifacoum was detected in all patients, difenacoum in five patients, bromadiolone in two patients, and warfarin in one patient.

Common presenting symptoms included gross hematuria (56% of patients) and abdominal pain (47%). Computed tomography identified renal abnormalities in 12 patients.

All patients received oral vitamin K₁ (phytonadione). Red cell transfusions, fresh-frozen plasma infusions, and 4-factor prothrombin complex concentrate, or a combination of these treatments, were also used in some patients.

Among the four confirmed deaths in this outbreak, one occurred in a patient in this case series. The patient, a 37-year-old woman presenting to the emergency department with markedly reduced consciousness, was reported by her friends to have recently used synthetic cannabinoids and methamphetamine. She had no personal or family history of coagulopathy.

Computed tomography of the head without contrast material revealed severe acute intraparenchymal hemorrhage of the right basal nuclei and insula with intraventricular extension, a 10-mm left-sided midline shift, and herniation.

She met criteria for brain death 15 hours after hospital admission despite treatment with 10 mg of intravenous vitamin K₁, four units of fresh frozen plasma, and 2,300 units of Kcentra.

Treating these patients after hospital discharge was difficult because of a lack of consensus guidelines and access to follow-up care, Dr. Kelkar and his associates noted. Some patients were quoted $24,000 to $34,000 per month for oral vitamin K1 therapy, which also made caring for them difficult and highlighted the need for confirmatory laboratory testing of suspected cases of superwarfarin poisoning.

Dr. Kelkar reported having no conflicts of interest. Two coinvestigators reported relationships outside the submitted work with Shire, CSL Behring, HEMA Biologics, and other companies.

SOURCE: Kelkar AH et al. N Engl J Med. 2018;379:1216-23.

Synthetic cannabinoids laced with superwarfarin were behind a recent outbreak of severe coagulopathy in Illinois.

In most cases, vitamin K replacement therapy alleviated symptoms, but four patients died after developing intracranial bleeding, said Amar H. Kelkar, MD, of the University of Illinois at Peoria.

Experts continue to look for how and why superwarfarin ended up in synthetic cannabinoids, whose street names include spice and K2, wrote Dr. Kelkar and his associates. Their report is in the New England Journal of Medicine.

Starting in March 2018, more than 150 patients across Illinois presented to hospitals with bleeding diathesis that involved persistent coagulopathy, the investigators explained. Early inquiries revealed that patients had consumed synthetic cannabinoids. Serum tests identified vitamin K antagonists, including brodifacoum, bromadiolone, and difenacoum. During arrests of suspected distributors, police confiscated synthetic cannabinoids that also tested positive for brodifacoum.

To help characterize the outbreak, the investigators reviewed admissions to Saint Francis Medical Center in Peoria, Ill., between March 28 and April 21, 2018. They identified 34 cases in which patients with vitamin K–dependent factor coagulopathy reported recent exposure to synthetic cannabinoids.

Fifteen of these patients underwent confirmatory anticoagulant testing, which universally confirmed superwarfarin poisoning. Brodifacoum was detected in all patients, difenacoum in five patients, bromadiolone in two patients, and warfarin in one patient.

Common presenting symptoms included gross hematuria (56% of patients) and abdominal pain (47%). Computed tomography identified renal abnormalities in 12 patients.

All patients received oral vitamin K₁ (phytonadione). Red cell transfusions, fresh-frozen plasma infusions, and 4-factor prothrombin complex concentrate, or a combination of these treatments, were also used in some patients.

Among the four confirmed deaths in this outbreak, one occurred in a patient in this case series. The patient, a 37-year-old woman presenting to the emergency department with markedly reduced consciousness, was reported by her friends to have recently used synthetic cannabinoids and methamphetamine. She had no personal or family history of coagulopathy.

Computed tomography of the head without contrast material revealed severe acute intraparenchymal hemorrhage of the right basal nuclei and insula with intraventricular extension, a 10-mm left-sided midline shift, and herniation.

She met criteria for brain death 15 hours after hospital admission despite treatment with 10 mg of intravenous vitamin K₁, four units of fresh frozen plasma, and 2,300 units of Kcentra.

Treating these patients after hospital discharge was difficult because of a lack of consensus guidelines and access to follow-up care, Dr. Kelkar and his associates noted. Some patients were quoted $24,000 to $34,000 per month for oral vitamin K1 therapy, which also made caring for them difficult and highlighted the need for confirmatory laboratory testing of suspected cases of superwarfarin poisoning.

Dr. Kelkar reported having no conflicts of interest. Two coinvestigators reported relationships outside the submitted work with Shire, CSL Behring, HEMA Biologics, and other companies.

SOURCE: Kelkar AH et al. N Engl J Med. 2018;379:1216-23.

Synthetic cannabinoids laced with superwarfarin were behind a recent outbreak of severe coagulopathy in Illinois.

In most cases, vitamin K replacement therapy alleviated symptoms, but four patients died after developing intracranial bleeding, said Amar H. Kelkar, MD, of the University of Illinois at Peoria.

Experts continue to look for how and why superwarfarin ended up in synthetic cannabinoids, whose street names include spice and K2, wrote Dr. Kelkar and his associates. Their report is in the New England Journal of Medicine.

Starting in March 2018, more than 150 patients across Illinois presented to hospitals with bleeding diathesis that involved persistent coagulopathy, the investigators explained. Early inquiries revealed that patients had consumed synthetic cannabinoids. Serum tests identified vitamin K antagonists, including brodifacoum, bromadiolone, and difenacoum. During arrests of suspected distributors, police confiscated synthetic cannabinoids that also tested positive for brodifacoum.

To help characterize the outbreak, the investigators reviewed admissions to Saint Francis Medical Center in Peoria, Ill., between March 28 and April 21, 2018. They identified 34 cases in which patients with vitamin K–dependent factor coagulopathy reported recent exposure to synthetic cannabinoids.

Fifteen of these patients underwent confirmatory anticoagulant testing, which universally confirmed superwarfarin poisoning. Brodifacoum was detected in all patients, difenacoum in five patients, bromadiolone in two patients, and warfarin in one patient.

Common presenting symptoms included gross hematuria (56% of patients) and abdominal pain (47%). Computed tomography identified renal abnormalities in 12 patients.

All patients received oral vitamin K₁ (phytonadione). Red cell transfusions, fresh-frozen plasma infusions, and 4-factor prothrombin complex concentrate, or a combination of these treatments, were also used in some patients.

Among the four confirmed deaths in this outbreak, one occurred in a patient in this case series. The patient, a 37-year-old woman presenting to the emergency department with markedly reduced consciousness, was reported by her friends to have recently used synthetic cannabinoids and methamphetamine. She had no personal or family history of coagulopathy.

Computed tomography of the head without contrast material revealed severe acute intraparenchymal hemorrhage of the right basal nuclei and insula with intraventricular extension, a 10-mm left-sided midline shift, and herniation.

She met criteria for brain death 15 hours after hospital admission despite treatment with 10 mg of intravenous vitamin K₁, four units of fresh frozen plasma, and 2,300 units of Kcentra.

Treating these patients after hospital discharge was difficult because of a lack of consensus guidelines and access to follow-up care, Dr. Kelkar and his associates noted. Some patients were quoted $24,000 to $34,000 per month for oral vitamin K1 therapy, which also made caring for them difficult and highlighted the need for confirmatory laboratory testing of suspected cases of superwarfarin poisoning.

Dr. Kelkar reported having no conflicts of interest. Two coinvestigators reported relationships outside the submitted work with Shire, CSL Behring, HEMA Biologics, and other companies.

SOURCE: Kelkar AH et al. N Engl J Med. 2018;379:1216-23.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.

Case

An 86-year-old woman, who recently had been seen in the same facility after a ground level fall, presented to the ED with to a 2- to 3-day history of vague abdominal pain, increasing weakness, nausea, and dry heaves.

Upon examination, the patient was unable to stand due to generalized weakness She arrived at the ED via emergency medical services. Her vital signs at presentation were significant for a systolic blood pressure (BP) of 90 mm Hg with a wide complex tachycardia concerning for ventricular tachycardia. The patient’s other vital signers were: heart rate, 136 beats/min; respiratory rate 20 breaths/min; and pulse oximetry was 94% on 4 liters/min of oxygen via nasal cannula.

The patient’s medical history was significant for atrial fibrillation and an indwelling pacemaker, for which she was chronically on flecainide and anticoagulation therapy with apixaban.

The initial electrocardiogram (ECG) revealed a wide complex rhythm with pacemaker spikes (Figure 1). Based on these findings, electrodes were placed on the patient in the event she required cardioversion. The patient was started on an amiodarone intravenous (IV) drip for presumptive ventricular tachycardia.

Discussion

Flecainide acetate was approved by the Food and Drug Administration in 1984.¹It is a Vaughan-Williams class IC antiarrhythmic with a sodium channel blocker action used to treat supra ventricular arrhythmias. The CAST trial in 1989 investigated the efficacy of this class of antiarrhythmics, which resulted in a revision of its role.² Based on this study, flecainide is not recommended for patients with structural heart disease or coronary artery disease.^2,3 However, it is recommended as a first-line therapy for pharmacologic cardioversion and maintenance of normal sinus rhythm in patients with atrial fibrillation and supraventricular tachycardia^4,5 without the above caveats.

Class IC agents produce a selective block at the sodium (Na+) channels, resulting in the slowing of cardiac conduction.^6,7 This high affinity for Na+ channels combined with slow unbinding kinetics during diastole explain the slowing of recovery time and prolongation of the refractory period.^6,8,9 These electrophysiologic properties all can increase the PR, QRS, and QT interval duration. The QT interval is not significantly affected, as most of the QT prolongation is due to the QRS widening.^6,10,11 Widening of the QRS by greater than 25% as compared to the baseline value is used as the threshold to decrease dosing or discontinue the use of flecainide.³The toxic effects of flecainide on cardiac conduction can produce prolonged QRS duration of up to 50%, and PR interval up to 30%, especially in rapid heart rates. Signs of intoxication are difficult to discern owing to its nonspecific presentation. A well-documented, but under-recognized, presentation of flecainide toxicity is the transformation of atrial fibrillation to atrial flutter.^5,7,9,11-13 The reported rate of this pro arrhythmic effect can be as high as 3.5% to 5%.^14,15Flecainide toxicity can occur secondary to chronic ingestion and may be precipitated in mild renal failure. The majority of flecainide is renally excreted and the half-life is 20 hours. Maximum therapeutic effect is seen between levels of 0.2 to 1 mcg/mL with levels greater than 0.7 to 1 mcg/mL associated with adverse effects.⁹ Systemic effects include dizziness and visual disturbances. A high degree of suspicion for flecainide toxicity is required when the patient’s initial presentation is nonspecific. In this circumstance, real-time bedside interrogation of the pacemaker is invaluable. Early diagnosis and treatment minimizes the risk for adverse sequelae, including death. Treatment includes increasing the excretion of flecainide, symptomatic support (including pacemaker placement, intravenous fat emulsion, or extracorporeal circulatory support) and administration of sodium bicarbonate, to transiently reverse the effect of the sodium channel blockade, in severe cases.^15-17

Case

An 86-year-old woman, who recently had been seen in the same facility after a ground level fall, presented to the ED with to a 2- to 3-day history of vague abdominal pain, increasing weakness, nausea, and dry heaves.

Upon examination, the patient was unable to stand due to generalized weakness She arrived at the ED via emergency medical services. Her vital signs at presentation were significant for a systolic blood pressure (BP) of 90 mm Hg with a wide complex tachycardia concerning for ventricular tachycardia. The patient’s other vital signers were: heart rate, 136 beats/min; respiratory rate 20 breaths/min; and pulse oximetry was 94% on 4 liters/min of oxygen via nasal cannula.

The patient’s medical history was significant for atrial fibrillation and an indwelling pacemaker, for which she was chronically on flecainide and anticoagulation therapy with apixaban.

The initial electrocardiogram (ECG) revealed a wide complex rhythm with pacemaker spikes (Figure 1). Based on these findings, electrodes were placed on the patient in the event she required cardioversion. The patient was started on an amiodarone intravenous (IV) drip for presumptive ventricular tachycardia.

Discussion

Flecainide acetate was approved by the Food and Drug Administration in 1984.¹It is a Vaughan-Williams class IC antiarrhythmic with a sodium channel blocker action used to treat supra ventricular arrhythmias. The CAST trial in 1989 investigated the efficacy of this class of antiarrhythmics, which resulted in a revision of its role.² Based on this study, flecainide is not recommended for patients with structural heart disease or coronary artery disease.^2,3 However, it is recommended as a first-line therapy for pharmacologic cardioversion and maintenance of normal sinus rhythm in patients with atrial fibrillation and supraventricular tachycardia^4,5 without the above caveats.

Class IC agents produce a selective block at the sodium (Na+) channels, resulting in the slowing of cardiac conduction.^6,7 This high affinity for Na+ channels combined with slow unbinding kinetics during diastole explain the slowing of recovery time and prolongation of the refractory period.^6,8,9 These electrophysiologic properties all can increase the PR, QRS, and QT interval duration. The QT interval is not significantly affected, as most of the QT prolongation is due to the QRS widening.^6,10,11 Widening of the QRS by greater than 25% as compared to the baseline value is used as the threshold to decrease dosing or discontinue the use of flecainide.³The toxic effects of flecainide on cardiac conduction can produce prolonged QRS duration of up to 50%, and PR interval up to 30%, especially in rapid heart rates. Signs of intoxication are difficult to discern owing to its nonspecific presentation. A well-documented, but under-recognized, presentation of flecainide toxicity is the transformation of atrial fibrillation to atrial flutter.^5,7,9,11-13 The reported rate of this pro arrhythmic effect can be as high as 3.5% to 5%.^14,15Flecainide toxicity can occur secondary to chronic ingestion and may be precipitated in mild renal failure. The majority of flecainide is renally excreted and the half-life is 20 hours. Maximum therapeutic effect is seen between levels of 0.2 to 1 mcg/mL with levels greater than 0.7 to 1 mcg/mL associated with adverse effects.⁹ Systemic effects include dizziness and visual disturbances. A high degree of suspicion for flecainide toxicity is required when the patient’s initial presentation is nonspecific. In this circumstance, real-time bedside interrogation of the pacemaker is invaluable. Early diagnosis and treatment minimizes the risk for adverse sequelae, including death. Treatment includes increasing the excretion of flecainide, symptomatic support (including pacemaker placement, intravenous fat emulsion, or extracorporeal circulatory support) and administration of sodium bicarbonate, to transiently reverse the effect of the sodium channel blockade, in severe cases.^15-17

Case

An 86-year-old woman, who recently had been seen in the same facility after a ground level fall, presented to the ED with to a 2- to 3-day history of vague abdominal pain, increasing weakness, nausea, and dry heaves.

Upon examination, the patient was unable to stand due to generalized weakness She arrived at the ED via emergency medical services. Her vital signs at presentation were significant for a systolic blood pressure (BP) of 90 mm Hg with a wide complex tachycardia concerning for ventricular tachycardia. The patient’s other vital signers were: heart rate, 136 beats/min; respiratory rate 20 breaths/min; and pulse oximetry was 94% on 4 liters/min of oxygen via nasal cannula.

The patient’s medical history was significant for atrial fibrillation and an indwelling pacemaker, for which she was chronically on flecainide and anticoagulation therapy with apixaban.

The initial electrocardiogram (ECG) revealed a wide complex rhythm with pacemaker spikes (Figure 1). Based on these findings, electrodes were placed on the patient in the event she required cardioversion. The patient was started on an amiodarone intravenous (IV) drip for presumptive ventricular tachycardia.

Discussion

Flecainide acetate was approved by the Food and Drug Administration in 1984.¹It is a Vaughan-Williams class IC antiarrhythmic with a sodium channel blocker action used to treat supra ventricular arrhythmias. The CAST trial in 1989 investigated the efficacy of this class of antiarrhythmics, which resulted in a revision of its role.² Based on this study, flecainide is not recommended for patients with structural heart disease or coronary artery disease.^2,3 However, it is recommended as a first-line therapy for pharmacologic cardioversion and maintenance of normal sinus rhythm in patients with atrial fibrillation and supraventricular tachycardia^4,5 without the above caveats.

Class IC agents produce a selective block at the sodium (Na+) channels, resulting in the slowing of cardiac conduction.^6,7 This high affinity for Na+ channels combined with slow unbinding kinetics during diastole explain the slowing of recovery time and prolongation of the refractory period.^6,8,9 These electrophysiologic properties all can increase the PR, QRS, and QT interval duration. The QT interval is not significantly affected, as most of the QT prolongation is due to the QRS widening.^6,10,11 Widening of the QRS by greater than 25% as compared to the baseline value is used as the threshold to decrease dosing or discontinue the use of flecainide.³The toxic effects of flecainide on cardiac conduction can produce prolonged QRS duration of up to 50%, and PR interval up to 30%, especially in rapid heart rates. Signs of intoxication are difficult to discern owing to its nonspecific presentation. A well-documented, but under-recognized, presentation of flecainide toxicity is the transformation of atrial fibrillation to atrial flutter.^5,7,9,11-13 The reported rate of this pro arrhythmic effect can be as high as 3.5% to 5%.^14,15Flecainide toxicity can occur secondary to chronic ingestion and may be precipitated in mild renal failure. The majority of flecainide is renally excreted and the half-life is 20 hours. Maximum therapeutic effect is seen between levels of 0.2 to 1 mcg/mL with levels greater than 0.7 to 1 mcg/mL associated with adverse effects.⁹ Systemic effects include dizziness and visual disturbances. A high degree of suspicion for flecainide toxicity is required when the patient’s initial presentation is nonspecific. In this circumstance, real-time bedside interrogation of the pacemaker is invaluable. Early diagnosis and treatment minimizes the risk for adverse sequelae, including death. Treatment includes increasing the excretion of flecainide, symptomatic support (including pacemaker placement, intravenous fat emulsion, or extracorporeal circulatory support) and administration of sodium bicarbonate, to transiently reverse the effect of the sodium channel blockade, in severe cases.^15-17