By: Hawnwan Philip Moy MD @pecpodcast
Expert Reviewed by: Minh Le Cong MD @ketaminh
It’s an unusually warm Halloween night and you, the medical director, are riding along with the EMS supervisor when you hear Medic 2 urgently request assistance on scene with a “bizarre behavior” patient. Your supervisor gives you a side long glance and says, “...And we were having such a good night!” He quickly puts his truck in gear and you both speed off to the scene.
On arrival...you find a large, athletic male patient in his 30s, who is only wearing purple, tattered pants, painted green, screaming, “Hulk Smash!!!” as he proceeds to...well...SMASH EVERYTHING!!!
You get a quick report from your exasperated paramedic: “This is a 30 year old male with no past medical history (we think) who took A LOT of...SOMETHING. We (2 fireman, 2 policeman, and his partner) pinned him down and tried to de-escalate him verbally...but he’s still Hulking out! What do we do?"
As the patient turns to you (UH OH!) and you ask yourself...is it time to use our Ketamine protocol? You remember reading that Ketamine can help sedate these patients...but is Ketamine safe to use in the prehospital environment? What are its pros and cons?!?!?
Fortunately, with your adrenaline-filled, razor sharp mind is firing on all cylinders... time slows down and you quickly recall the your most up to date research on Ketamine.
Excited Delirium (ExDS) is a syndrome described by the American College of Emergency Physicians (ACEP) as those patients with altered mental status who demonstrate severe agitation with combative and/or assaultive behavior. Also known as Agitated Delirium, Excited Derlium, or Sudden Death in Custody Syndrome, ExDS is characterized by the following [1, 2]:
Hyper-aggressive or Bizarre behavior
Lack of Sensitivity to Pain
Attraction to light or shiny objects
The scariest thing about ExDS is not just the harm it can do to our prehospital providers, but the harm it could cause to the patient himself. These patients can die with mortality rates of up to 10% with causes that are relatively unknown (click here to see ExDS from the beginning to the death of the patient) [1, 2]. Many prehospital providers are called to utilize a variety of medications (see below) to try to sedate the patient before harm to providers or harm to the patient himself can occur .
At present, the most popular medications for chemical restraint are Benzodiazepines with Antipsychotics. Unfortunately, Benzodiazepines have a relatively long onset (18 minutes) as do antipsychotics like Haldol (17 min)[4-7]. These prolonged times place prehospital providers at a higher risk of physical harm.
To attempt to ameliorate this inefficiency, researchers have decided to visit our old friend Ketamine as a potential treatment option.
the good, the bad, and the ugly
In 2014, Scheppke et al. retrospectively studied 52 agitated patients who were given 4mg/kg IM of Ketamine8. The average time to sedation was 2 minutes (yeah!).
However, 3/52 patients had significant respiratory depression with 2 of those 3 patients requiring intubation in the Emergency Department (ED). Should we be concerned? Maybe. On one hand, intubating is a high risk procedure and should make every medical director a little squeamish. However, those three respiratory depressed patients also received IV Midazolam to prevent an emergence reaction. As a result Scheppke et al. concluded that “Ketamine may be safely and effectively used by trained paramedics following a specific protocol.” A major limitation to this study is that the authors did not evaluate outcomes of these patients in the ED. However, so far so good for Ketamine in that 1) providers can provide it safetly and 2) it works pretty darn fast.
Earlier this year (2016), Cole et al. performed a prospective study in their urban/suburban midwest community that services approximately 1,000,000 citizens while transporting 70,000 patients a year . To minimize bias from seasonal changes, this service provided 10 mg of Haldol intramuscularly (IM) for severely agitated patients (defined as an altered mental status score of 2 or 3) for the first 3 months of the year. Subsequently, the authors changed the sedation medication to Ketamine 5mg/kg IM for the next 6 months. Afterwards, in the final three months of the year, they switched the sedative medications back to Haldol. So what did they observe? A total of 146 patients were treated with a median time for sedation of 5 minutes compared to Haldol’s 17 minutes to sedation. It appears that time to sedation using Ketamine was much faster in making the scene safe for our providers...but at what cost?!?!
It turns out that the Ketamine cohort had more side effects with more patients vomiting, more patients suffering laryngospasm (5% compared to 0.3%), and more patients being intubated (an intubation rate of 39% in the Ketamine cohort compared to 4% in the Haldol cohort).
Now, before we jump to any drastic conclusions about airway compromise, let’s take a little deeper dive into these intubated patients of this study. First, there was no association with the dosage of Ketamine and intubation rates. Next, the reasons for intubating these patients were documented as “Not Protecting Airway NOS.” Cole et al hypothesized that perhaps receiving physicians may be uncomfortable receiving patients in this dissociated state or may have, “misapplied the axiom ‘intubation for a GCS of 8.’” Certainly, those of us who are Emergency Physicians (EP), have had drunk patients arrive in the ED with a Glasgow Coma Scale (GCS) less than 8 and let them sleep it off without even a nasal cannula. Perhaps, when Ketamine is involved, EPs can also take this into account. However, is it because the EP wasn’t used to dealing with patients in the K-hole or was it truly an airway issue where the EP had to secure a compromised airway? Honestly, we can’t say for sure, but it is something to think upon when considering this manuscript for Ketamine in your system.
Finally, Olives et al. recently published their findings on the use of Ketamine (5mg/kg IM) for severely agitated patients in the prehospital environment . In this 2 year retrospective study, they studied a total of 135 patients who displayed “...active physical violence to himself/herself or others and usual chemical or physical restraints may not be appropriate or safely used.” Prehospital providers reported an initial improvement in agitation in 91.8% of ketamine treated agitated patients. Awesome news!
So it appears that Ketamine is safe for our providers and easy to provide. But...wait for it...endotracheal intubation was performed on 85 patients (63%) in which 4 patients (2.96%) were intubated by prehospital providers. Of note, laryngospasm, hypersalivation, and pulmonary edema were not listed as any complications and there was no difference (p=0.68) in the dosage of ketamine for those intubated (5.25 mg/kg IM) and those not intubated (5.14 mg/kg IM). :(
Again, before jumping to any conclusions, let’s look at Olives et al’s analysis of those intubated patients. Among the four patients in whom prehospital intubation was undertaken, one experienced post ketamine vomiting and jaw clenching resulting in intubation and another suffered severe hypoxemia. Fair enough. The other two patients were combative, altered on scene, and required both physical and chemical restraints. After sedation both patients went into cardiac arrest and died. The medical examiner determined that cause of death was Citalopram and Amphetamine toxicity for one patient and seizure disorder, sub therapeutic dose of valproic acid, hypertension and history of substance abuse for the other patient. Essentially, Ketamine nor hypoxia was not deemed to be the cause of the patient’s death. However...did Ketamine exacerbate the situation or help? Again hard to say. Now for the other 81 patients intubated in the ED. Olives et al. found that intubation had a higher association if they were male and presented to the ED overnight. More interestingly, among the 31 staffed EPs at that facility, two providers accounted for 50.9% (28/55) of overnight encounters, but 65.9% (27/41) of overnight intubations. The same two providers comprised just 7.5% (6/80) of daytime encounters, but 11.4% (5/44) of all daytime intubations. So could this be physician practice, resource availability associated with time of day, or staffing that justified intubation? Again, it is hard to say, but certainly something to consider when looking at these numbers. Of note, arterial PH of those intubated versus those not intubated were similar (7.33 v. 7.32), lactate was slightly higher in the non intubated group (5.6 v. 7.05), and ethanol levels were similar as well (0.18 g/dL v. 0.19 g/dL). At least physiologically, intubated versus nonintubated groups appeared to be very similar, suggesting that intubation was more of a clinical decision. Again this is hard to tell as this is sometimes difficult to articulate in medical charts.
Overall, ExDS is dangerous for both our patients and our providers in the field. Ketamine is one shield that we can use to help sedate our patients and keep our providers safe.
It has a great treatment profile, especially for prehospital care in that it sedates quickly, can be administered in a safe manner, and has a relatively short duration of action. However, the sweet ain’t as sweet without the sour. There are those side effects that you have to watch out for...mainly airway issues that are up for debate, but should be considered. That being said, there is always a risk-benefit assessment in everything we do in medicine. In a prehospital environment, the benefits of Ketamine administration for quick and safe sedation in a truly chaotic, dangerous environment does appear to outweigh the risk to your providers. More importantly, Ketamine's quick sedation profile protects your patients from themselves and the harms of physical restraint. Thus, if you decide to use Ketamine in your system, ensure that you have adequate safeguards within your protocols to monitor airways (i.e. ETCO2 & paramedic training) as well as assuage receiving facility's discomfort by informing them that Ketamine may be provided in the prehospital environment, careful monitoring of these patients is important, and GCS <8 may not always indicate intubation (i.e. we do not intubate every inebriated patient in the ED).
For your entertainment, here is a video of when I had to be procedurally sedated with Ketamine and Propfol. I suffered a nasty open left subtalar ankle dislocation (there are pics, ask me about them via email or at the NAEMSP Conference and I'll show them to you!). I have no recollection of this at all...but man...what a video! We swear there no editing was done :)! Enjoy and Happy Holidays!
1. Vilke, G. M., DeBard, M. L., Chan, T. C., Ho, J. D., Dawes, D. M., Hall, C., ... & Bozeman, W. P. (2012). Excited delirium syndrome (ExDS): defining based on a review of the literature. The Journal of emergency medicine, 43(5), 897-905.
2. Vilke, G. M., Payne-James, J., & Karch, S. B. (2012). Excited delirium syndrome (ExDS): redefining an old diagnosis. Journal of forensic and legal medicine, 19(1), 7-11.
3. Vilke, G. M., Bozeman, W. P., Dawes, D. M., DeMers, G., & Wilson, M. P. (2012). Excited delirium syndrome (ExDS): treatment options and considerations. Journal of forensic and legal medicine, 19(3), 117-121.
4. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med. 2004; 11(7):744-749.
5. Spain D, Crilly J, Whyte I, Jenner L, Carr V, Baker A. Safety and effectiveness of high-dose midazolam for severe behavioral disturbance in an emergency department with suspected psychostimulant-affected patients. Emerg Med Australas. 2008; 20(2):112-120.
6. Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med. 2010;56(4):392-401.c1.
7. Takeuchi A, Ahern TI, Henderson SO. Excited Delirium. West J Emerg Med. 2011;12(1):77-83.
8. Scheppke, K. A., Braghiroli, J., Shalaby, M., & Chait, R. (2014). Prehospital use of IM ketamine for sedation of violent and agitated patients. Western Journal of Emergency Medicine, 15(7), 736.
9. Cole, J. B., Moore, J. C., Nystrom, P. C. et al. (2016). A Prospective study of ketamine versus haloperidol for severe prehospital agitation. Clinical Toxicology, 54(7), 556-562.
10. Olives, T. D., Nystrom, P. C., Cole, J. B., Dodd, K. W., Ho, J. D. (2016). Intubation of Profoundly Agitated Patients Treated with Prehospital Ketamine. Prehospital and Disaster Medicine, 31(6), 1-10.