Doc in the Bay: Ketamine
Howie Mell MD
- Ketamine is perhaps the most misunderstood drug that is out there. We are using it a lot in the out-of-hospital setting, but we aren’t using it nearly as much in the in-hospital setting, outside of procedural sedation. This should change.
- Ketamine was developed in the 1960s to create a synthetic dissociative anesthetic that didn’t make people as crazy as PCP did. It is an antagonist to the NMDA receptors and interferes with any transmission of information originating outside the brain, from getting into the brain. Think of it like internet hubs and fiberoptic cables; some of them get disconnected.
- In high doses, ketamine leads to a complete dissociation or cataleptic state, where the patient has good airway reflexes and cardiorespiratory function but can’t perceive external stimuli or interact with the world in any way. This makes it a great drug for procedural sedation.
- There is more to this drug. We need to consider it for analgesia, facilitating rapid sequence intubation (RSI), and patients suffering from excited delirium.
- Some are concerned that ketamine causes increased intracranial pressure, increased intraocular pressure or psychiatric disease. These concerns have been debunked; ketamine does not cause any of these problems.
- Ketamine has one of the best safety profiles out there. Once you bind all of the NMDA receptors with ketamine, there is nowhere else to go. Increased dosing does not lead to more dissociation but increased length of dissociation. Adults who receive ketamine are more likely than children to develop emotional distress.
- Ketamine is dosed along a continuum with four stages.
1. The analgesic dose is 0.1 to 0.3 mg/kg IV. At this dose, ketamine has a minimal effect on perception or emotion but is a powerful analgesic. In a normal-sized adult, a 10 mg bolus will usually have minimal psychiatric effect but doesn’t always give adequate analgesia. A 20 mg bolus gives terrific analgesia, but some patients will slide into the recreational dosing zone and get a little bit loopy. Administering fentanyl first can work synergistically.
2. The recreational dose, of about 0.2-0.5 mg/kg, gets you high. This provides great analgesia but makes the patient high and can result in distortions of perception. These patients can converse with you and follow commands but are hallucinating. They may require interventions, such as gentle redirection, to relieve psychiatric discomfort.
3. The next level of dosing is the partially dissociated dose between 0.4-0.8 mg/kg. There are enough synapses left unaffected that patients have some awareness and can make some purposeful actions, but they are not fully connected to the outside world. Some may tolerate it but others will find it terrifying. Emergence reactions occur when patients are partially dissociated.
4. The dissociative dose is generally anything greater than 0.8 mg/kg IV. The patient is isolated from all external stimuli. This is the desired state to facilitate a procedure or endotracheal intubation. You may see nystagmus and random reflexive movements. The brain is on, but the patient is not in our reality. The patient’s cardiorespiratory function is preserved or stimulated, but the dissociated brain is unaware. Patients won’t recall this period. This can be used for RSI, procedural sedation, and excited delirium.
- The four stages of the ketamine dosing continuum have overlapping dose ranges. At these doses, the effects are variable among patients. The effects are more consistent at very small doses, around 0.1 mg/kg, or large dissociating doses greater than 2 mg/kg IV. Higher doses just prolong the duration of action; this makes it an incredibly safe drug to use for things like RSI or procedural sedation.
- As patients begin to metabolize the drug, they may enter the part of the continuum where they are partially dissociated and they may have psychiatric distress. Managing this is very straightforward.
- If the patient develops distress shortly after the first dose, even though they are not fully dissociated, the best move is to give them more ketamine and get them fully dissociated.
- More commonly, the patient develops distress on emergence. You can administer a sedative, like midazolam, that will metabolize. Alternatively, you can talk them through what is going to happen.
- As they enter the recreational dose level, they can hear and talk to you but are still tripping. You can say, “Mr. Smith, you’re in the ambulance because you broke your ankle. We gave you a drug that makes you feel weird but in a few minutes, you’re going to start feeling like your normal self.”
- Mell had a patient who was ice-skating and fractured his tibia and fibula right at the edge of his hockey boot. Hockey boots are extremely difficult to remove easily. The patient received 1.5 mcg/kg of fentanyl, followed by 0.1 mg/kg of ketamine. He sat up, looked at his ankle and said, “That looks bad. Tell me when you are done.” He then laid back down. The boot was removed, and the patient tolerated it very well.
- Excited delirium syndrome is a recognized condition. Vilke GM, et al. Excited Delirium Syndrome (ExDS): defining based on a review of the literature. J Emerg Med. 2012 Nov;43(5):897-905.PMID: 21440403
- One of the authors of the paper, Mark DeBard, has said that he believes ketamine is the best drug to use in this setting. You can give a 5mg/kg IM dose of ketamine. It has rapid onset and resolves the issue. The patient is sedated with preservation of airway reflexes using a single dose of the medication. Mell monitors these patients with capnography and has airway equipment available, but case series do not report problems or unmanageable adverse effects.
- Ketamine is also useful for rapid sequence intubation. Some providers in the aeromedical field deliver a cocktail called, “three, two, one.” They administer 3mcg/kg of fentanyl, followed by 2mg/kg of ketamine, followed by 1mg/kg of rocuronium. Although you may see some drop in the blood pressure due to release of the adrenergic tone, these medications do not affect the hemodynamics themselves.
Paul W. - May 15, 2015 10:47 AM
Its a skate - not a hockey "boot", eh?
Randal R. - May 19, 2015 9:46 AM
Ever use the 321 formula for rsi with Succinylcholine@1.5mg/kg.instead or Roc ? Any issues? This dinosaur prefers the former.
Howard M. - May 22, 2015 5:27 AM
I've very rarely used Sux in the formula, but when I have, it's been closer to 1mg/kg (rounding up). There is no issue with it.
Jeff - May 27, 2015 8:39 PM
Our paramedics use ketamine and succs. Not because I think succs has any real benefit but because I couldn't get roc. Damn national backorders.
Great discussion, Howie.
David H., M.D. (@BritFltDoc) - June 9, 2015 3:39 AM
Great segment, thanks.
So this has me wondering about Ketofol for procedural sedation. If it is better with Ketamine to either use "a little" (0.1-0.2mg/kg) for analgesia, or "a lot" (1mg/kg) for full dissocation, then I wonder if the traditional 0.5mg/kg cited at the Ketofol dose can be refined. Perhaps the ideal combination would be usual Propofol dose of 1mg/kg and then a pain dose of Ketamine with it (0.1-2mg/kg). No need for Fentanyl. Probably better analgesia than fentanyl, and a low dose of Ketamine that avoids any emergence problems. After listening to your talk, I wonder if this might be the ideal combination and ratio ? Any thoughts ?
Howard M. - June 13, 2015 7:25 PM
David, sorry for the delayed response. I agree, the analgesic properties of ketamine make it an ideal agent to combine with propofol. I've always used 0.75 mg/kg of both agents when I've used Ketofol. As far as a lower dose, my concern would be the rapid metabolism of the ketamine not offering a lasting analgesia. That is why I've always leaned toward higher dose if I'm dissociating the patient anyway.
Alex F. - June 20, 2015 8:02 AM
Howard and David, I was also wondering about Ketamine's dose in Ketofol. In traditional dosing of 1 mg/kg Ketofol, the patient would get 0.5 mg/kg of ketamine, putting them in the partial dissociation dose. And your increased dosing of 0.75 mg/kg of both ketamine and propofol would also fall under partial dissociation. In this case, is the propofol acting almost like the midazolam-rescue in preventing partial dissociation effects?
Thanks for the discussion on the beauty that is Ketamine.
[I don't have as much experience with Ketofol or ketamine in adults, but will be graduating residency in a couple weeks and will finally have free reign over sedation choice!]
Mitchell L. - July 20, 2015 5:08 AM
I second this question! The pharmacologic basis of this doesn't make much sense. 1mg/kg of each might make a little more sense to me if you want to get a full dose of each and counter one another's side effects.. not sure what to think
drmtv - July 3, 2015 12:53 PM
Dr Mel...Question any literature on the use of Ketamine to sedate patients suffering from delirium from FLAKKA?
Jennifer M. - July 14, 2015 4:28 PM
great seeing you at smacc :)
Thanks for the ketamine tips. I understand when you give for procedural sedation, it is a very slow push. When used for RSI, how fast can you push the ketamine? Thanks.
Howard M. - July 21, 2015 1:24 PM
Drmtv - I don't know of any literature specifically to FLAKKA. However, Dr.Keseg's study of prehospital ketamine did include drug induced delirium. http://www.ncbi.nlm.nih.gov/pubmed/25153713
Jennifer M. - I don't push Ketamine slowly in any setting. If you have premedicated the patient and prepared them well, I've not seen problems with speed of the push. In RSI, I do push it "quickly"...
A. Terry - October 8, 2015 12:27 AM
For analgesia dosed ketamine, our hospital pharmacy has started mixing the ketamine with 50 mL NS and then running it into the pt over 20-30 minutes. Haven't seen anybody start getting to the recreational level since starting to do this.
Gar - January 5, 2016 7:45 PM
I hear these dose ranges for anlagesia, recreational, partial dissociation & full dissociation cited very commonly but I can't figure out where they come from? Do you have a reference?