Incident Atrial Fibrillation and Intoxicants

I remain very interested in the cardiac and brain complications of medications and substances that are commonly used to get high or create altered states.  I am also very interested in the popular trend to characterize cannabis as some previously undiscovered medication that can cure everything ranging from anxiety to obstructive sleep apnea.  I was naturally interested when I saw this paper (1) looking at the issue of incident atrial fibrillation and common intoxicants.

The authors examine a very large database in California that included anyone who had been seen in an emergency department, ambulatory surgery center, or hospital over a period of 10 years (2005-2015).  After they eliminate minors, subjects with persistent atrial fibrillation, and subjects with missing data they had a total of 23,561,884 people. 998,747 of those people had incident atrial fibrillation (defined as the first encounter for atrial fibrillation).  Since their study design is a retrospective observational study they also recorded substance use was considered present if Substance use was considered present if there was coding for any indication of use of methamphetamine, cocaine, opiates, or cannabis.  Knowing the atrial fibrillation and substance use diagnoses – the authors calculate the hazard ratio for each of the substances of interest.

Hazard ratios are basically the ratio of the people exposed to intoxicants who developed atrial fibrillation over the unexposed who developed atrial fibrillation.  So any number greater than 1 means that the population exposed to intoxicants had greater risk.  The corrected hazard ratios were noted to be 1.86 (methamphetamine), 1.74 (opioids), 1.61 (cocaine), and 1.35 cannabis. The authors adjusted for common atrial fibrillation risk factors and ran an additional negative control analysis and looked at the scatter of data pints for these 4 substances and hazard ratios of developing appendicitis, connective and soft tissue sarcoma, and renal cell carcinoma and showed no consistent pattern for these illnesses.

There are a couple of interesting considerations relevant to this study.  The first is the mechanism of action in each case. With stimulants there is a direct hyperadrenergic effects and depending on the individual and dose of the drug varying degrees of tachycardia, palpitations, and hypertension.  Long term users frequently end up with cardiomyopathy from these effects and in some cases ventricular arrhythmias and congestive heart failure. There can also be acute vascular effects like ischemia either due to the increased cardiac demand or pre-existing arteriosclerosis. Atrial fibrillation has not typically been placed in that group of morbidities from stimulant use. Patient with atrial fibrillation often notice emotional precipitants for discrete episodes or atrial fibrillation although a recent study showed that the only reliable precipitant was alcohol use (2). There were significant limitations with that study with attrition and length of the study although I generally agree that alcohol is a clear participant.  Precipitants need to be carefully approached and I suspect that attentive physicians have noted variable phenomenology on an individual basis. 

The high hazard ratio for opioids is a little puzzling. Hyperadrenergic states can occur with the euphorigenic effects and withdrawal effects as well. Direct comparison with stimulants may be difficult due to rapid dose escalation and some degree of tachyphylaxis.  Cannabis is not surprising to me at all. Many initial cannabis smokers notice that their heart is pounding and don’t know why.  They find it unexpected given the conventional wisdom that cannabis is supposed to be a benign substance. Many initial users also get increased anxiety and, in some cases, have a panic attack that may be due to the cardiac sensations. The primary heart pounding sensation is because cannabis causes hypotension and they are experiencing reflex tachycardia. The effects may be less predictable because cannabis use can affect both sympathetic and parasympathetic pathways that can potentiate arrhythmias. A case report of cannabis induced atrial flutter (3) was described as occurring in a woman with a history of hypertension that eventually had to be terminated by an intravenous antiarrhythmic.   

Atrial fibrillation and other cardiac arrhythmias are another good reason for avoiding intoxicants including alcohol (in the supplementary analysis alcohol had a Hazard Ratio of 2.37).  It could be argued that it is basically a numbers game – since most people who use these intoxicants do not develop incident atrial fibrillation.  As of this moment, even if you have had your DNA analyzed for what are known about atrial fibrillation genes – you can’t be certain that you are not susceptible to the problem. And as outlined above there are many additional cardiac problems and that are possible from using these compounds.  The safest path is to avoid these intoxicants all together.

 

George Dawson, MD, DFAPA

 

 

References:

1:  Lin AL, Nah G, Tang JJ, Vittinghoff E, Dewland TA, Marcus GM. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J. 2022 Oct 18:ehac558. doi: 10.1093/eurheartj/ehac558. Epub ahead of print. PMID: 36257330.

2: Marcus GM, Modrow MF, Schmid CH, Sigona K, Nah G, Yang J, Chu TC, Joyce S, Gettabecha S, Ogomori K, Yang V, Butcher X, Hills MT, McCall D, Sciarappa K, Sim I, Pletcher MJ, Olgin JE. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol. 2022 Feb 1;7(2):167-174. doi: 10.1001/jamacardio.2021.5010. PMID: 34775507; PMCID: PMC8591553.

3: Fisher BA, Ghuran A, Vadamalai V, Antonios TF. Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg Med J. 2005 Sep;22(9):679-80. doi: 10.1136/emj.2004.014969. PMID: 16113206; PMCID: PMC1726916. [full text] 

Abstract Attack Journal Article Presentation Format

 

I recently participated in an Addiction Medicine Journal Club where the presenter used a novel presentation technique called Abstract Attack. The result in terms of group process was so good – I thought I would present it here for further exposure and comment.  As a qualifier I would add that I have not spoken directly to the creators and base this post on my direct participation in the format and the PowerPoint from the creators (1) and the presentation I attended (2).

Standard presentations in medicine and other academic fields typically consist of a single presenter charged with presenting data or techniques for information and some discussion.  The expertise of the presenter and role of the audience varies considerably.  For example, in my Biochemistry course in medical school the seminars were focused on techniques and concepts. The course instructor would typically choose a paper or two on a clear topic like diphtheria or cholera toxin.  The presenter was responsible for presenting those two papers at the minimum with additional papers as necessary. That was in 1978 – well before the Internet and online resources. All papers had to be obtained as hard copies from the medical library.  We would have two or three biochem seminars per week – so there were always a number of presentations to prepare for and the information content was variable.  My pharmacology course used a similar format but slide presentations were allowed. Since there was no digital presentation software – the slides had to all be shot on 35 mm film and projected.  That was the standard until well after I completed residency and started working. Eventually presentation software was developed making the job much easier.

Microsoft PowerPoint eventually evolved into the standard presentation format but it is not without controversy.  In the past 15 years there have been numerous presentations and papers written about everything that people consider to be wrong with PowerPoint.  That criticism is highly variable such as too little to too much information, being more boring that an extemporaneous lecture, problematic graphics and format on the slides, reading the slides, and competing software that claims to produce a better presentation.  The competition angle is an interesting one because in the beginning I bet on (and paid for) two competing products before it became apparent that PowerPoint would be the winner. It is difficult to win against a product that is installed on most business computers in the country.

My person bias is that I like the PowerPoint format.  The product is greatly improved in the past decade and can also be used to produce graphics for other applications.  I have attended seminars and courses on this to improve the approach with PowerPoint from a graphical standpoint and my slide making has improved considerably. I think it is very useful to put up graphics and texts that provide more information to the audience while I am free associating to the slides. To me the main difference between a verbal only lecture and a PowerPoint presentation is the greater informational content.  Consider that TED Talks are supposed to present a great idea in 18 minutes.  I am supposed to be presenting many ideas and facts in 50-50 minutes. That is what a PowerPoint presentation is for.

The doesn’t mean that all high information PowerPoints are successful. The speaker still has to be fairly good in both presentation style and engaging the audience. The audience has to be well behaved and focused on the content. I was giving a fairly detailed lecture on alcohol use and the latest World Health Organization (WHO) report on the scope of the problem.  There was a student in the audience checking the data on my slides (taken directly from the report) about what he could find on his phone and arguing about it. There are always unexplained emotional reactions in the crowd and in some cases, people get up and leave – even when nothing presented is really controversial. We have all attended presentations when the discussion starts with the dreaded: “I don’t have a question but I would like to comment……” followed by a 10 minute long irrelevant digression.  

When you experience all of those occurrences at conferences and lectures, you can’t help thinking: “Is there a better way to keep all of this on track?” Limiting the discussion, not taking questions, or having all of the questions submitted and moderated are certainly possibilities that I have seen used successfully. But I was recently exposed to a presentation format that structured the responses right in PowerPoint and that led to a focused high-quality discussion.  I will explain the format and hopefully provide a good example of how to approach the problem.

The method is called Abstract Attack and it was apparently devised by members of the University of Minnesota North Memorial Family Medicine Program.  Rene Crichlow, MD, FAAFP is credited with the concept and in the PowerPoint I acquired her co-presenters were Tanner Nissly, DO, and Jason Ricco, MD, MPH (1).  I first experienced this approach in a journal club teleconference (2) that was presented by Ian Latham, MD a resident from the UMN program on an article about lorazepam versus phenobarbital for alcohol detoxification based on a 2021 paper (3).

The overall goals for this presentation format are from family practice curriculum.  In the initial presentation the authors use the Accreditation Council for Graduate Medical Education (ACGME) requirements for scholarship to develop the Abstract Attack approach.  Those scholarship requirements can be found in the document on common requirements for all residency programs. Interested readers can find the specifics in a box graphic on page 26 of this document.  It is an elaboration of the way all physicians are trained to critique scientific and clinical studies and the application of the studies to clinical work.  The primary goals of Abstract Attack (1) are cited as:

1.  "Abstract Attack", a method to provide uniform acquisition of skills and knowledge

2.  Sufficient for a practicing clinician to confidently, participate in efficient and effective Evidence Based critique of the medical literature at the point of care

 The secondary goal is “Eschew Obfuscation”.

The overall process is described as patient rather than disease oriented and adhering to a critical appraisal pathway that answers the questions:   Pertinent to your patients’ care?  Consistent or Inconsistent?  Valid or Invalid?  The structured order of presentation is given in the slide below:

  

In the session I attended (2) the author discussed the overall goal of being able to present journal articles with the assumption that nobody else has read it.  He proceeded to illustrate how the presented information could be discussed at the level of every slide by the following prompts (that he incorporated in every slide):

What is interesting about this?

What is concerning about this?

What do I need to know more about?

I will illustrate with a few slides from a recent JAMA paper (5).  The slides cueing the discussion might look something like this.

   

Additional slides are provided on the methods and results.  That is followed by a slide with questions exploring how the study potentially impacts clinical practice and what additional information or studies may be needed.  Supplemental slides can contain information on the scientific and statistical concepts used in the paper.  The emphasis is clearly proceeding from the clinical trials to clinical practice.

My direct experience with this format is that there was timely discussion every step of the way.  Senior clinicians and physicians can add commentary early in the process about what they see are being important about the study.  The audience is clearly engaged without every reading the paper. The presenter can add critical information in supplementary slides at the end after the discussion on how impactful the information is on clinical practice and what else might be needed.

Overall, I thought this was a breakthrough in how to make these presentations efficiently when everyone’s time is at a premium. Dr. Crichlow and her colleagues are to be congratulated.  I have made a comparison slide below.

 

George Dawson, MD, DFAPA

 

References:

1:  Crichlow R, Nissly T, Ricco J.  Trans-formative Journal Club Experience as a Basis for a Longitudinal EBM Curriculum.  PowerPoint Presentation.  Accessed on October 16, 2022.

2:  Latham I. Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study Addiction Medicine Journal Club.  PowerPoint Presentation. August 2, 2022.

3:  Hawa F, Gilbert L, Gilbert B, Hereford V, Hawa A, Al Hillan A, Weiner M, Albright J, Scheidel C, Al-Sous O. Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study. Cureus. 2021 Feb 11;13(2):e13282. doi: 10.7759/cureus.13282. PMID: 33728215; PMCID: PMC7949711.

4:  Accreditation Council for Graduate Medical Education (ACGME).  Common Requirements Currently In Effect.  7/1/2022:  https://www.acgme.org/what-we-do/accreditation/common-program-requirements/  Accessed on 10/19/2022.

5:  Florian J, van der Schrier R, Gershuny V, Davis MC, Wang C, Han X, Burkhart K, Prentice K, Shah A, Racz R, Patel V, Matta M, Ismaiel OA, Weaver J, Boughner R, Ford K, Rouse R, Stone M, Sanabria C, Dahan A, Strauss DG. Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial. JAMA. 2022 Oct 11;328(14):1405-1414. doi: 10.1001/jama.2022.17735. PMID: 36219407.

Supplementary Info:

Any slide above can be enlarged by clicking on it.

 

Minnesota Medical Cannabis Program Petitions

 

I have written about this program in the past.  In Minnesota, we have a medical cannabis program that allows for the prescription of specific forms of cannabis for a list of what are seen as indications.  To get on that list is basically a review of opinions and the Commissioner. Even though this program runs like a mini-FDA, it does not have a standard for approving conditions for medical cannabis use.  And let’s face it - that is because the supporting evidence for using medical cannabis is very weak and in many if not most instances – non-existent. And as I have pointed out in the past – the evidence collected by the program is also weak.  As far as I know the program does not produce any detailed adverse drug effect information and a lot of that advice depends on the pharmacists dispensing the medical cannabis.

This year the conditions up for placement on the list of indications include opioid use disorder, obsessive compulsive disorder, and irritable bowel syndrome. I restricted my comments to the first two conditions and the rationale is very clear. In the case of opioid use disorder (OUD), it is a widespread drug epidemic at this point fueled by widespread availability of opioids and synthetic opioids. Even though physician prescriptions have decreased overdose deaths continue to increase on a year-to-year basis. The pattern of overdoses has also changed substantially since OUD has spread from metropolitan to rural areas. Thirty years ago, OUD and overdose deaths were practically unheard of in rural areas and now they are commonplace. There are effective treatment for OUD as listed in the letter that follows.  There is a problem with access to substance use disorder treatment.  Most states have practically no detoxification facilities.  Access to physicians who are prescribing medication assisted treatment (MAT) for OUD (MOUD) is also very limited.

Like most political movements in the country – there is no critical analysis of the various cannabis initiatives.  To me – it was obvious from the start that medical cannabis was a way to start building political consensus for legalization of cannabis. Adding more intoxicants to the environment is never a good idea – but the practical issue is that the lesson of alcohol prohibition was that it could not be done without increasing crime, corruption, and the health dangers of unregulated alcohol. So a medical cannabis initiative is really not a genuine attempt to treat medical conditions with cannabis.

On that basis – it is not surprising that there is significant overreach in finding conditions where medical cannabis can be used. OUD and OCD are just two more diagnoses on that list. I was informed that my comments will be added but the vast majority of comments are not by physicians and are basically testimonials to cannabis. The FDA receives a lot of criticism and they also elicit public commentary but there is a core body of scientific decision makers.

With the writing of this post President Biden just came out with a statement that he is going to pardon people who are incarcerated for simple possession of marijuana and encourage governors to do the same (1).  That may be easier said than done since there was also a news report that the majority of these people have additional complicating charges.  He also initiated a review process by Secretary of Health and Human Services and the Attorney General on the way marijuana is listed in the Control Substance Act schedule.  It is currently a Schedule I drug making it the most dangerous and without medical applications according to this ranking. That results in a large grey zone when it is legally prescribed in some states and approved for recreation use in others.  There are associated problems with banking due to the federal scheduling but in an election year when any number of people from both parties are tripping over each other to legalize it – it seems like a foregone conclusion that it will be rescheduled at the minimum.

The Minnesota legislature approved low dose cannabis edibles earlier this year. There is a question about whether that was done by mistake. This is another step toward the eventual legalization of cannabis in Minnesota and will probably lead to the extinction of the Medical Cannabis program.  This story also illustrates the confusion among legislators about the basic differences between raw materials and cannabinoid derivatives. My viewpoint is legalization of cannabis was the goal all along and the users of medical cannabis have objected to higher fees for the medical product and many prefer smoking cannabis rather than using other forms.

 

George Dawson, MD, DFAPA

 

1:  Statement from President Biden on Marijuana Reform October 7, 2022 Link.

2:  Miranda S.  Minnesota lawmakers voted to legalize THC edibles. Some did it accidentally.  July 2, 2022 Link.

The letter not in support of indications for opioid use disorder or obsessive compulsive disorder:

October 3, 2022

Office of Medical Cannabis
PO Box 64882
St. Paul, MN 55164-0882

To Whom It May Concern:

I am a Minnesota psychiatrist who recently retired from clinical practice. I continue to research and write about psychiatry.  I worked at one of the largest substance use disorder treatment facilities in the United States. Every person I saw had a substance use disorder (SUD) that was significant enough to need residential treatment. Alcohol use disorder was the most common followed by opioid use disorder (OUD).  I was also an adjunct professor and lectured on the epidemiology, assessment, and treatment of substance use disorders. Areas of focus included the neurobiology of SUD, opioid use disorders, chronic pain, and Attention Deficit~Hyperactivity Disorder. I did research on medication assisted treatment of alcohol use disorder and depression. 

As an SUD develops, there are several associated biases that lead to chronicity. The first is the euphorigenic effect or “high” that occurs with all substances. That becomes a permanent memory that all subsequent episodes of use are compared against. Tolerance to drug effects limits the ability to experience that same degree of euphoria.  That leads to attempts to use more or more powerful versions of the same drug. In the case of OUD, that has led to the use of more powerful opioids like fentanyl. A second bias is the idea that all emotions and reactions to stress can be controlled by external substances.  Cannabis, alcohol, and benzodiazepines are used for that purpose. In that situation, withdrawal symptoms are misinterpreted as anxiety or depression.   That leads to an additional substance being taken. Detoxification is required to determine a person’s baseline state and whether there is a treatable anxiety or depressive disorder. A third bias is that “I have a lot of time to quit.” Young people with severe SUD will often tell themselves: “I am only in my 20s, I can quit later and at that time go to work or school.” That prolongs their risk exposure and the associated morbidity and mortality. A fourth bias is people with SUD are not risk averse. In other words, if they knew a substance contained fentanyl and were risk averse, they would avoid it. This is not true. Many will seek out fentanyl products or products they know contain fentanyl in pursuit of getting high. That pursuit can get to the point that greater amounts of substances or more novel substances are used and they do not care what the outcome is. They are willing to risk a fatal outcome in pursuit of getting high.  Finally, withdrawal symptoms from substances create a negative reinforcement bias – substances need to be taken to avoid withdrawal symptoms.

Easy access to opioids is a major factor in the continuing opioid crisis and the “three waves” of this epidemic that are described by the CDC (1). There were several papers (3) published that suggested that medical cannabis use was associated with less opioid use. Those findings have not been validated over time.   There has been a study done showing that opioid use was more likely to increase rather than decrease (4) with cannabis use. That study is consistent with what I have seen in the clinic.  

To summarize:

1.  We are still in the midst of a 2 decades long opioid use epidemic that has produced significant overdose mortality and morbidity. 

2.  There are current FDA approved treatments (10 drugs in 3 categories) that have demonstrated ability to prevent opioid overdoses and treat opioid use disorder (2). 

3.  Suggesting that Minnesota residents with an opioid use disorder use cannabis with no proven treatment efficacy over the FDA approved medications that have efficacy presents a clear ethical problem considering the level of mortality associated with this disorder.

For these reasons medical cannabis should not be approved for opioid use disorder.

I am also recommending that medical cannabis not be approved for the treatment of obsessive-compulsive disorder. The bulk of my argument rests on the information that I submitted last year recommending no medical cannabis approval for generalized anxiety disorder. In that submission, I pointed out that for many people cannabis use leads to anxiety and panic attacks rather than alleviating them. Obsessive-compulsive disorder (OCD) has effective psychotherapies and medical therapies. In fact, psychotherapy is the primary treatment modality. We currently have a healthcare system that rations access to both psychotherapy and medical treatment. When the lack of clinical trials of cannabis in OCD is considered, the same ethical dilemma presents as in the case of opioid use disorder. Is cannabis approved for OCD because health care systems and government regulators refuse to provide access to proven methods of treatment?

In both the case of opioid use disorder and obsessive-compulsive disorder, neither should be an indication for medical cannabis for the above stated reasons.

Sincerely,

George Dawson, MD, DFAPA

Lino Lakes, MN

 

 

References:

1:  CDC.  Understanding the Epidemic:

https://www.cdc.gov/opioids/basics/epidemic.html

 

2:  FDA Information about Medication-Assisted Treatment (MAT):  https://www.fda.gov/drugs/information-drug-class/information-about-medication-assisted-treatment-mat

3. Bachhuber MA, Saloner B, Cunningham CO, et al. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999–2010. JAMA Intern Med. 2014;174:1668–1673.

4:  Olfson M, Wall MM, Liu SM, Blanco C. Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States. Am J Psychiatry. 2018 Jan 1;175(1):47-53. doi: 10.1176/appi.ajp.2017.17040413. Epub 2017 Sep 26.