Don't t-a-a-a-a-a-a-aze me bro!

April 16, 2010

A report in Popular Science (authored by Jeremy Hsu) points to a recent paper published in Academic Emergency Medicine. In this, Dawes and colleagues report on an investigation on the effects of TASER on sheep intoxicated with methamphetamine (MA). I was alerted to this by Damn Good Technician who wanted a little bit of context for what would seem to be a WTF? kind of study.
ResearchBlogging.orgThe study was conducted in Dorset sheep who were anesthetized, and administered 0, 0.5, 1.0 or 1.5 mg/kg of methamphetamine HCl (curiously from dissolved Desoxyn, the approved pharmaceutical product) in an IV infusion. The drug treatment was a between subjects factor (N=4 per group) and animals were monitored for “continuous blood pressure, heart rhythm (one-lead), pulse oximetry, and capnography… Arterial blood sampling was performed at baseline, 30 minutes after the administration of the methamphetamine, and after each exposure from a TASER X26”.
To answer the question of why?, and for appropriate background on the science try a PubMed search for “cardiac TASER“. I note a study in which 5 sec of TASER didn’t cause cardiac damage or symptoms in law enforcement trainees and another showing minimal cardiac effects on law enforcement volunteers after vigorous exercise. Also of interest are the case studies of atrial fibrillation in a previously healthy adolescent and recovery of a teen in TASER induced asystole. These, a mini-review by the Dawes group and other searched papers should give you some context and support from the feeling you might have from half-remembered MSM reports over the years that TASER is suspected of being somewhat less than “safe”.
What I’m not finding right away is very much about the drug intoxicated suspect who might be TASER’d by law enforcement. Remember this guy? My best estimate was that he was acutely intoxicated with 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) although that might be one of my blog interests talking. You might also wish to consider some papers found by searching PubMed for “methamphetamine cardiac toxicity“, “methamphetamine vetricular fibrillation” and “methamphetamine heart attack“.
Together this background would seem to identify a situation crying out for additional study.

It is worth noting right off the bat, given the comments following the Popular Science Article, that these studies were conducted (in the US) by research scientists under Institutional Animal Care and Use Committee approval and the usual Federal regulatory, and other, oversight mechanisms1.
Methodologically, the study examined four different TASER shock durations starting with a 5 sec continuous shock that seems to be the standard in human investigations. This study included 15, 30 and 40 sec intermittent shocks in which the longest continuous duration was 20 sec. If you watch the end of the Cochella video, these might seem to be more realistic conditions to test over the published studies in law enforcement volunteers I mentioned above. This consideration ties back into why we need to resort to animal models instead of just using law enforcement volunteers. The case reports identify some cases of serious harm to the TASee and the research literature reports essentially no (consistent?) harm. To cross this bridge we need to set up experimental conditions that seem more likely to get us closer to ones that will cause harm. That changes the ethical calculus for human subjects’ research versus animal research. Also, the combined effect of a stimulant drug and TASER might be presumed to be additive- again, problematic for human subjects research.
The MA doses were physiologically significant in this model, even though subjects were under anesthesia.

All animals given methamphetamine demonstrated signs of methamphetamine toxicity with tachycardia, hypertension, and atrial and ventricular ectopy … One smaller animal (animal 8, 30 kg, at 1.0 mg⁄ kg methamphetamine) had a supraventricular tachycardia (SVT) shortly (7 minutes) after methamphetamine administration requiring cardioversion. One animal (animal 11, 78 kg, at 1.5 mg⁄ kg methamphetamine) had
apparent seizure-like activity shortly (4 minutes) after methamphetamine administration that resolved spontaneously.

Effects of the ECD (Electronic control device, i.e.TASER) stimulus:

Smaller animals (n = 8, ≤ 32 kg, mean = 29.4 kg) had supraventricular dysrhythmias immediately after the
ECD exposures (including SVTs and frequent premature atrial contractions). Larger animals (n = 8, > 68 kg, mean = 72.4 kg) had only sinus tachycardia after the ECD exposures.

Note the bimodal size distribution, the authors accidentally ordered too-small animals in their first cohort but decided to go ahead with the study. This ended up being fortuitous as it identified possible age-related differences (interestingly the authors just focus on the size question, I’d like to know more about sheep development and whether these smaller animals were juveniles, adolescents, young adults or whatever). Unfortunately, however, that pushes the study right into trying to make something out of individual differences2. And that really compromises the ability to conclude much of anything definitive from a study.

One of the smaller animals had frequent episodes of ventricular ectopy after two ECD exposures, including runs of delayed-onset (2-5 minutes after the exposure), nonsustained, six- to eight-beat unifocal and multifocal ventricular tachycardias that spontaneously resolved. This animal had significant ventricular ectopy after the methamphetamine administration and prior to the exposures as well.

Now tachycardia (elevated heart rate) and hypertension (increased blood pressure) I more or less grasp but not being a cardiac physiologist I had to resort to the Googles for a couple of these.
Ventricular ectopy:

Ventricular ectopy leading to ventricular tachycardia (VT), which, in turn, can degenerate into ventricular fibrillation, is one of the common mechanisms for sudden cardiac death.

Supraventricular tachycardia:

..the heart rate is sped up by an abnormal electrical impulse starting in the atria.
-The heart beats so fast that the heart muscle cannot relax between contractions.
-When the chambers don’t relax, they cannot contract strongly or fill with enough blood to satisfy the body’s needs.
-Because of the ineffective contractions of the heart, the brain does not receive enough blood and oxygen. You can become light-headed, dizzy, or feel like fainting (syncope).

Sinus Tachycardia: a heart rhythm with elevated rate of impulses originating from the sinoatrial node, defined as a rate greater than 100 beats/min in an average adult.

cardioversion: a medical procedure by which an abnormally fast heart rate or cardiac arrhythmia is converted to a normal rhythm, using electricity or drugs.

For some reason the authors don’t make much of a stab at inferential statistics to deal with the main quantitative measures of heart rate, blood pressure, etc. The MA group (N=4) means are presented for each of the doses and stimulus-duration conditions, as are the stats for a nonparametric comparison with the control no-drug group. The didn’t even specify any correction for multiple comparisons. I would have like to have seen some analysis of the main effects for drug dose and the duration of the TASER stimulus to see if heart rate and blood pressure increases depended on either factor or an interaction of the two. Doing a very rough scan of the table it doesn’t look like there are systematic effects of the drug dose or the duration of the shock on either measure. This latter would seem to be a particularly important analysis. As I mentioned, it seems to me that the human studies use just the single 5 sec shock…it would be nice to provide evidence to address concern over administration of a longer shock duration or multiple closely spaced shocks.
Nevertheless, as the authors conclude, there was no obvious smoking gun here.

Methamphetamine intoxication was associated with both supraventricular and ventricular irritability. In small sheep, electronic control device exposures did exacerbate this irritability, but this did not occur in the larger sheep. There was no ventricular fibrillation after electronic control device exposure.

This is just an initial study (as far as I can find) of the interaction between a stimulant drug and shock such as would be produced by a TASER. It appears to be essentially negative in that there were no consistent effects in the life-threatening line followingTASER stimulus. It did point to a possible age- or size- related difference that might be interesting to follow up on.
The major caveat to this study is the fact that they used an anesthetized preparation. Some physiologists seem to think the brain is a huge confounder of your study and it is okay to get it out of the experiment. I disagree. In a body of literature that I talk about all the time on the blog, if you anesthetize laboratory animals you prevent thermoregulatory, locomotor and cardiac effects of MDMA that are seemingly most relevant to studying the causes of medical emergency and death in the human user. The present study is presumably directed at the suspect who dies after being TASER’d by law enforcement so….hmm. An experimental model in which the animal was awake and allowed to express normal behavior, more or less, would have been much superior.
As one final caveat the researchers acknowledge that the study was supported (research funding and consulting agreements) by TASER International. (This blogger is not, btw). Thus an additional consideration for my readers is the usual Conflict of Interest one where it comes to research conducted by academics with funding from a private, for-profit company. My uninformed view would be that these present findings would be viewed as positive by the company. One wonders how they would feel if the study showed that TASER stimulus that was safe in the undrugged individual caused increased risk if the individual was intoxicated with methamphetamine.
1See the Speaking of Research page on research oversight for additional details.
2This is not necessarily a bad thing. If a drug interaction with TASER was a consistent thing, presumably we’d have more evidence from human arrests. Since TASER is considered to be generally safe and suspects are not dropping like flies, we might conclude that what we are most interested in would be relatively rare circumstances. I.e., individual differences in susceptibility to develop cardiac complications of a TASER shock when on methamphetamine (or other drug).
Dawes DM, Ho JD, Cole JB, Reardon RF, Lundin EJ, Terwey KS, Falvey DG, & Miner JR (2010). Effect of an electronic control device exposure on a methamphetamine-intoxicated animal model. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 17 (4), 436-43 PMID: 20370784

No Responses Yet to “Don't t-a-a-a-a-a-a-aze me bro!”

  1. znz Says:

    Oh yeah. Meth sheep are the worst.


  2. Anonymous Says:

    “One wonders how they would feel if the study showed that TASER stimulus that was safe in the undrugged individual caused increased risk if the individual was intoxicated with methamphetamine. ”
    I would imagine that they would be thrilled. Field ready diagnostics seem to be something law enforcement would love to get their hands on.


  3. Neuroskeptic Says:

    Most anaesthetics cause hypo-tension, a fall in body temperature etc. Depending on the anaesthetic it might directly interfere with the effect of meth too e.g. xylazine fairly obviously since it blocks noradrenaline signalling, but you can’t rule it out with others.


  4. whimple Says:

    Worth it just for the picture of the sheep alone.


  5. Jason Says:

    This is exactly the kind of reason that this kind of animal research is important:


  6. DrugMonkey Says:

    Related thoughts from Dr. Isis who criticized the selection of isoflurane which interferes with L-type calcium channels in the heart. These are regulating contractile function so you might expect this to be a big old confound in the study under discussion.


  7. thomas Says:

    The results of these studies have a number of implications, but the most pertinent for me regards whether I need to get an ECG when a tazed suspect rolls into the emergency department. Based on very little data, the policy in my municipality requires recently apprehended suspects (who happen to have been tazed) to undergo a medical evaluation before booking. What is the evaluation?
    1) ECG.
    2) Tazer barb removal.
    My review of the relevant literature showed exactly one case report of an abnormal human ECG status post tazing. So we get an ECG on everyone. As far as #2, I never realized how useful my fishing experience would be in medicine.
    But as the article alludes to, most tazed suspects are also under the influence of some special sauce. They are generally young, strong and agitated. I am glad that the investigators are trying to challenge the conception of medical danger to the procedure.
    In the interim, I’ll do the ECG, put a band-aid on the wound and move on to the next patient.


  8. Jason Says:

    It really is a shame that anesthetic was used, and the brain knocked out, given the fact that the brain regulates cardiac function. But it is even *more* a shame since new research shows clearly that meth decreases brain size by like 200%, suggesting that an intact brain may be especially important for understanding meth x tase interactions.


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