Doc in the Bay - Ketamine

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.