Agitated with a head injury: Will Ketamine make it worse?

You are a second-year emergency medicine resident physician doing a ride along with a helicopter-based EMS (HEMS) agency. You are dispatched to the scene of a golf cart versus tree. The air crew successfully identifies a safe landing place near where the ambulance is staged. You deboard the helicopter and head over to the waiting ambulance to find a man in his 60’s laying on an EMS stretcher on a backboard with a c-collar in place. The paramedic on scene states that the man was the driver of a golf cart traveling at “high speeds” when it struck a tree. The golf cart was mangled around the man, and it took several minutes to extricate him from the wreck. When they did, they found the patient very confused and asking repetitive questions. He also had a large area of swelling to his left cheek, left temple, and left parietal/occipital region. The EMS ground crew confirmed that he is somewhat altered, oriented only 1-2, and had a loss of consciousness after the crash. He is not currently on blood thinners and is otherwise healthy. You and the HEMS crew load the patient onto the helicopter gurney and start to move toward the helicopter. During this time, the patient is stating that he wants to refuse transport and does not want to go, all while asking the same questions repeatedly: “Where am I? What happened? What’s going on?” After getting in the helicopter, the pilot starts to take off while the patient simultaneously keeps trying to sit up and is pulling at the c-collar and ear protection one of the flight crew is trying to put on him. After takeoff, the patient continues this behavior and one of the flight crew pulls out Ketamine to give the patient. He gives what he calls a “pain dose” of ketamine at 20mg. The patient does somewhat calm down and tolerates the rest of the flight. When you transfer care of the patient to the awaiting care team at the Trauma Center, they voice frustration that Ketamine was given to a patient likely suffering a Traumatic Brain Injury.

Literature Review:

Although ketamine has been in use for over 50 years, it is still somewhat controversial and has only gained true popularity within emergency medicine and acute care within the last decade [1]. Additionally, it has known side effects of transient blood pressure increase along with bradycardia [2]. Given these effects, it was long thought that Ketamine should be avoided in head injuries due to concerns that the medication would raise intracranial pressure (ICP). However, this theory has not been shown to be true in the literature and Ketamine can be an excellent form of anesthesia for combative patients such as in this case.

Ketamine is thought to work as an antagonist at the NMDA receptor and has a dose dependent response [1]. At higher doses (1-1.5mg/kg IV or 3-4 mg/kg IM), ketamine can have a dissociative effect where sensory inputs may reach cortical receiving areas, but these inputs are not perceived, meaning the patient might still feel what is going on, but they will have no memory of it and are not truly processing the sensory input as pain [1][2]. This dissociative effect can be great for rapid sequence intubation or conscious/procedural sedation [2]. Ketamine can also be used at a lower dose (0.1-0.3mg/kg IV) where there is not a dissociative effect but more of an analgesic effect [2]. At these lower doses or “pain dose,” Ketamine can be used for pain management, treatment-resistant depression, suicidal ideation, as well as treating refractory status epilepticus [2]. Additionally, at these lower doses, Ketamine can be an excellent tool to calm a combative patient [2].

Given the mixed beliefs regarding Ketamine, a recent joint position statement was issued by The American College of Surgeons Committee on Trauma, the American College of Emergency Physicians, the National Association of State EMS Officials, the National Association of EMS Physicians, and the National Association of EMTs. Among their recommendations, they state that Ketamine “…may be given to the trauma patient when acute control of agitation is required…or when rapid control is necessary to reduce the risk of injury to staff, bystanders or the patients themselves” [3]. Additionally, they state that Ketamine “…can be safely administered to the trauma patient with a head injury as it has minimal effects on intracranial pressure and has no adverse effect on cerebral perfusion pressure or neurologic outcomes” [3]. This consensus likely comes from some of the many studies that have investigated this concern. A 2014 literature review looked specifically into published studies that measured the effects of Ketamine on ICP in traumatic brain injured patients. This review found that Ketamine administration did not increase ICP and in fact, three of the studies had a reported decrease in ICP after ketamine bolus [4].   

Ultimately, low-dose Ketamine is a safe and effective agent for agitation, even for patients suffering from traumatic head injuries. Ketamine is likewise safe as an induction agent for RSI at dissociative doses in trauma patients. Ketamine has not been shown to rise ICP and is not associated with worsened outcomes in this patient demographic. Thus, Ketamine should be a go-to agent in calming combative trauma patients.

References:

1. Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013 Jun;19(6):370-80. doi: 10.1111/cns.12099. Epub 2013 Apr 10. PMID: 23575437; PMCID: PMC6493357.
2. Rosenbaum SB, Gupta V, Patel P, et al. Ketamine. [Updated 2024 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470357/
3. Margaret M. Morgan, Debra G. Perina, Nicole M. Acquisto, Mary E. Fallat, John M. Gallagher, Kathleen M. Brown, Jeffrey Ho, Aaron Burnett, Julio Lairet, Dennis Rowe & Mark L. Gestring (2021) Ketamine Use in Prehospital and Hospital Treatment of the Acute Trauma Patient: A Joint Position Statement, Prehospital Emergency Care, 25:4, 588-592, DOI: 10.1080/10903127.2020.1801920
4. Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014 Aug;21(1):163-73. doi: 10.1007/s12028-013-9950-y. PMID: 24515638.