Is Ketamine Really Sympathomimetic?

[frozenborderline]

https://www.pharmacytimes.com/contr...md/2015/09/is-ketamine-really-sympathomimetic

Is Ketamine Really Sympathomimetic?
2015-09-17 02:25:29

Ketamine is a popular yet polarizing drug in emergency medicine.

For some, it's the drug of choice for any and every indication in the emergency department (ED). For others, it's avoided at all costs.

Health care providers often believe that ketamine should never be used in patients with cardiovascular disease (CVD) because it is common knowledge that ketamine is a sympathomimetic drug.

However, this shared belief is not referenced in the American College of Emergency Physicians’ guidelines for ketamine use in the ED, for instance, so it is not actually true. In fact, this misguided principle is based on data from the 1960s and 1970s that has been quoted for decades.

...

While the cardiovascular effects of ketamine reported in historical literature suggest a cardiovascular neutral or depressant effect at above-normal therapeutic dosing, review articles may also state that ketamine increases norepinephrine transport into the peripheral circulation by inhibiting uptake and reuptake, thereby increasing the concentration in the neuronal synapse—an argument also supported by historical data.7.8

The human and animal models tested did not demonstrate clinical response to the increase in plasma norepinephrine (NE) or epinephrine. Furthermore, current attitudes toward plasma NE levels suggest they are meaningless.9

The ultimate concern of sympathomimetic effects in a patient with CVD is that a drug such as ketamine would lead to an increase in myocardial oxygen demand and possibly lead to ischemia/necrosis.

...

The prevailing theory is that ketamine acts on voltage-gated calcium channels in a manner similar to calcium channel blockers (CCBs).11

Nevertheless, the available evidence makes it difficult to draw conclusions. While some evidence suggests that ketamine is a sympathomimetic drug, the evidence against it is of equally poor quality.

Should ketamine be contraindicated in patients with CVD? Perhaps. Is it still often given to patients with an unknown history of such disease? Absolutely.

References
1. Mion G, Villevieille T. Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings). CNS Neuroscience & Therapeutics. 2013;19(6):370–80.
2. Traber DL, et al. Involvement of the sympathetic nervous system in the pressor response to ketamine. Anesth Analg. 1969;48(2):248-252.
3. Bidwai AV, et al. The effects of ketamine on cardiovascular dynamics during halothane and enflurane anesthesia. Anesth Analg. 1975;54(5):588-592.
4. Savege TM, et al. A comparison of some cardiorespiratory effects of althesin and ketamine when used for induction of anaesthesia in patients with cardiac disease. Br J Anaesth. 1976 Nov;48(11):1071-81.
5. Waxman K, et al. Cardiovascular effects of anesthetic induction with ketamine. Anesth Analg. 1980 May;59(5):355-8.
6. Dewhirst E, et al. Cardiac arrest following ketamine administration for rapid sequence intubation. J Intensive Care Med. 2013 Nov-Dec;28(6):375-9.
7. Baraka A, et al. Catecholamine levels after ketamine anesthesia in man. Anesth Analg. 1973; 52(2):198-200.
8. Miletich DJ, et al. The effect of ketamine on catecholamine in the isolate perfused rat heart. Anesthesiology. 1973;39(3):271-277.
9. Goldstein DS, et al. Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans. JPET. 2003 Jun;305(3): 800-11.
10. Smith G, et al. The effects of ketamine on the canine coronary circulation. Anesthesia. 1979;34:555-61.
11. Baum, VC, et al. Ketamine inhibits transsarcolemmal calcium entry in guinea pig myocardium: direct evidence by single cell voltage clamp. Anesth Analg. 1991;73:804-807.

 

[frozenborderline]

This might be interesting for anyone who, like me, has some level of hypertension but also pain and is prescribed ketamine

 

[valentinelynx]

Well, it sure as heck acts like a sympathomimetic in the OR at high doses—elevated BP and heart rate. However, the very low doses used for pain control it really doesn't affect heart rate and BP much if at all, in my experience.

Compare the dosages:
For induction of anesthesia (which is the same as the Emergency physicians would use for intubation): (1-4 mg/kg: translate that to an "average" 70 kg male and you get 70 to 280 mg.
For chronic pain control 5-20 mg (0.05-0.2 mg/kg) if injected or about 1/20th the dose.

Ketamine is still a "new kid on the block" for use in pain and especially chronic pain, although it's been used as an anesthetic since 1963. When I was in my anesthesia residency there were still faculty (and not old faculty, either) who were terrified of it, despite its obvious benefit in certain situations. But it was well known as a good choice of anesthetic if you didn't want to drop the blood pressure. It was more often used in children. The "sympathomimetic" label made it relatively undesirable in patients with heart disease, although I knew some cardiac anesthesiologists that used it in an induction "cocktail" that avoided the sharp blood pressure drop you get with the more common induction agents.

For pain and chronic pain, I find or no useful little literature discussing it's effects on blood pressure and heart rate. There's one or two case studies where a patient developed hypertension on home doses of ketamine that resolved when they stopped taking it. From experience, I would say that it generally has little effect at the very low doses used for home pain control.

 

[frozenborderline]

For chronic pain control 5-20 mg (0.05-0.2 mg/kg

A lot of times the dose is higher than that for chronic pain but it is still way lower than in anesthesia

 

[valentinelynx]

A lot of times the dose is higher than that for chronic pain but it is still way lower than in anesthesia

Is the higher dose an oral one? Ketamine is not very effective orally. For example, I use oral troches (lozenges that dissolve slowly between cheek and gum) that cause some transmucosal absorpton, but much of it ends up in the GI tract. That's a 50 mg dose. Trust me, if you injected 50 mg, you'd be in another world!

 

[frozenborderline]

No, I mean up to 50 mg nasally. I know ketamine sn't orally effective.

But in periodic treatments for chronic pain higher doses are used iv. They still don't get into the range of anesthesia though.