Recently, I had the opportunity to perform a rapid sequence intubation on a patient who presented in compensated(ish) traumatic shock, with an altered mental status, and ventilatory compromise. The patient was treated per our protocols with 1.5 mg/kg ketamine and 1.5 mg/kg rocuronium. Unfortunately, the patient decompensated after the intubation, eventually coded, and died. The question was raised whether the intubation drugs that were given could have contributed to his abrupt decompensation.
This patient encounter coincidentally took place shortly after a lengthy discussion with some of my coworkers on the flight team about traumatic shock resuscitation, RSI, and our protocols vs. what other teams do and what is “en vogue” on the lecture circuit and in various education forums. In thinking about this discussion and this particular unfortunate patient outcome, I decided to do some research and do some extracurricular writing on the topic. Please note, I am not an academic. I am a simple paramedic and I guess you could say that this is an, at best, a quasi-academic discussion.
Obviously, we perform RSI procedures for various reasons. As Walls described in his Manual of Emergency Airway Management, emergency intubation is indicated for failure of airway maintenance, failure of oxygenation and/or ventilation, and poor anticipated clinical course. As per our protocols, we administer a dissociative dose of ketamine for sedation and follow with rocuronium for paralysis.
Ketamine is a rather ideal agent for the RSI situations we encounter because of its hemodynamic stability. It preserves spontaneous ventilation and the airway remains unobstructed as it activates the adductor muscles to open the larynx which preserves upper airway patency and muscle activity (Canet & Castillo, 2012). Ketamine is also a preferred sedative agent in critically ill patients because it is well-known to stimulate catecholamine reserves which causes a rise in BP and heart rate and even produces some vasopressor effect on cardiovascular dynamics (Young-Yeob, et al, 2008).
The benefits of ketamine allows the provider to achieve dissociation with hemodynamic stability that provides the benefits of effective dissociation and patient comfort during an incredibly uncomfortable and physiologically taxing procedure while rendering the pt sedate to facilitate an intubation.
However, I have heard repeatedly in lectures, read in literature and medical blogs, and heard on podcasts by renown experts in the field that while yes, ketamine is effective and has these benefits; your patient still has a real risk of crashing peri and post-intubation because the sedative and analgesia effect is blunting the sympathetic response of trauma and pain. As Richard Dutton, director of trauma anesthesia at the University of Maryland Shock Trauma said in a lecture (and I’m paraphrasing here), it really doesn’t matter what agents you use for a patient in severe traumatic shock. What matters is the dose. He advocates reducing the dose of induction agents to 1/10th of the full intubating dose to avoid causing your patient to crash by blunting the sympathetic response (Weingart, 2010).
One-tenth of the full intubating dose? What the heck? What about achieving full dissociation and making your patient comfortable? After all, sub-dissociative doses of ketamine have been believed to cause agitation (Nickson, 2020), which we definitely don’t want. However, I’ll refer back to Richard Dutton. He argues that he has probably intubated more traumatic shock patients “than anyone else on the planet” and that shock is actually quite effective intrinsically as an anesthetic. While his assertion about his intubatory prowess seems pompous, his credentials and reputation are nothing to turn one’s nose up at.
Obviously we want our patients to be comfortable and preferably, fully dissociated. We certainly don’t want these patients to become agitated for obvious reasons. This begs the question: if administering ketamine for induction in the patient with traumatic shock, is it safe and appropriate to give a smaller dose?
Aside from anecdotal accounts, there doesn’t seem to be a plethora of research out there specifically studying whether sub-anesthetic doses of ketamine actually causes agitation in the prehospital patient. I think that it is worth mentioning that many services have moved to employing sub-anesthetic doses of ketamine (commonly 0.2-0.5 mg/kg) first-line for pain management. As prevalent as ketamine is in today’s prehospital world, I speculate that you would be hearing about many more case reports of adverse effects of ketamine administration. In fact, according to Lebin, et al (2019) few studies have examined ketamine associated behavioral outcomes in the ED or prehospital setting.
In the prehospital setting, we perform RSIs for two reasons that are closely interwoven. First and foremost, we want to prevent our patients from dying from whatever insult they have suffered. Second, some patients require “total control” to safely facilitate manage and transport them in a cramped space with limited resources in a transport environment that has time and again been shown to be fraught with risk. The patient experience and their comfort are absolutely important however, I submit that patient stability and provider safety are the essential and fundamental priorities in a prehospital RSI performed by our flight team. The priority is to keep the patient alive. I will refer to Nickson’s Heirarchy of Resuscitation Airway Needs as published by Weingart (2013).
Stated simplistically, is it safe to give full doses of ketamine for induction to patients in traumatic shock? Perhaps not according to Dewhirst et al (2013): “The sympathomimetic effects of ketamine result in an enhanced cardiovascular stability make it an extremely useful anesthetic agent. However, in patients with an exhausted endogenous catecholamine reserve, the unopposed direct negative inotropic effects of ketamine may lead to cardiovascular compromise.” Rezaie (2018) highlighted this in More Evidence for Starting with Lower Doses of Ketamine in the Shock Patient Requiring RSI by citing a retrospective cohort study by Heffner, et al (2013) that showed that 1 out of every 25 patients undergoing emergency intubations (n=410) suffered cardiac arrest after emergency intubation. 2/3 of these arrests occurred within 10 minutes after induction drugs were pushed.
Despite its certainly laudable properties of catecholamine stimulation and resultant blood pressure and heart rate increases; could ketamine be a culprit in worsening patient outcomes in prehospital RSI? Well, perhaps. Krebs, et al (2021) performed a retrospective study of adults (n=80) undergoing RSI with ketamine as an induction agent. They reported with confidence (p < 0.5) that even in younger and healthier trauma patients, higher induction doses of ketamine were associated with, among other problems, hypotension. In fact, it found that even despite standard vs. higher dosing of ketamine, 33.7% of patients suffered hypotension, and 13.5% of total patients (not just the ones who became hypotensive) coded sometime after induction. Interestingly enough, adult patients undergoing RSI with ketamine had agitation requiring “rescue meds” at higher rates (1.6% vs. 17%). As one would expect due to commonly held beliefs about ketamine dissociation at higher doses, the authors of the study were confounded and wrote that it seemed counterintuitive because one would expect a higher dose of ketamine to provide a longer period of dissociation and were unable to find any definitive causation between higher doses of ketamine and agitation.
So, one must ask; do higher doses of ketamine in RSI really do the job better than subanesthetic doses? Maybe? Probably? From what you read in the FOAMed blogs, hear about on the lecture circuit, and read in pharmacology texts: yes. Higher doses of ketamine equals higher sedation and dissociation — which is obviously what we want to occur when we push ketamine. But isn’t it cruel to give a patient a “less than” dose of ketamine during an RSI procedure? After all, I’d want my brain shut off if I had just been in a horrible accident and now some flight paramedic was going to shove a laryngoscope down my throat.
The question of whether it is appropriate to sacrifice patient comfort for hemodynamic stability and avoidance of agitation may very well be a moot point because recall, shock acts as a potent anesthetic. Therefore, smaller (and more hemodynamically stable doses) are sufficient to achieve the necessary sedation desired in RSI. Rezaie (2016) described that ketamine for induction in adult shock patients should be dosed at 0.5 mg/kg. Subsequent doses of 0.5 mg/kg can be administered prior to pharmacologic paralysis if needed to ensure complete sedation. However, the need for further ketamine dosing would likely not be needed because smaller doses are sufficient for therapeutic value in shock patients.
I would also argue that concerns about agitation and crew safety are put to rest because we are administering a paralytic after the induction dose of sedative.
But back to shock and hypotension. Caro (2018) described that one must use caution in shock patients who have depleted catecholamine stores. He wrote “patients who are depleted of catecholamines due to their underlying disease or otherwise at increased risk of shock have a blunted sympathetic response, and may even develop hypotension, following administration of ketamine for RSI.”
Even for a paramedic like myself, who requires concepts to be broken down into the most simplistic terms that even a caveman could understand; it makes sense. Put it into the format akin to an old geometry proof from ninth grade (that I never thought I’d have to bust out again):
Catecholamine response = preserved HR and BP in shock
Ketamine = stimulates catecholamine stores
Higher levels of shock = subpar or non-existent catecholamine stores
Therefore, in higher levels of shock: Ketamine does not or may not really stimulate those catecholamine stores
Ketamine = sedation and analgesia
Sedation and analgesia = reduction of catecholamine response
Reduction of catecholamine response = hypotension
Hypotension = Bad
THEREFORE…
Ketamine, while still an ideal agent, may not be as great as one might think in patients with higher degrees of shock
So what’s a flight crew member to do? Is it still safe to use ketamine for induction in patients with high degrees of shock? Probably. I’ll once again refer back to Dutton. I’m sorry to keep beating the proverbial dead horse by referring back to him but it is very important. At least the published experts who are much smarter and accomplished than I seem to think so. Anyway, a reiteratory paraphrase of Dutton is: Shock is intrinsically a potent anesthetic. Therefore, you need much less levels of the full intubating dose.
Let’s look at some recent research to highlight the point I’m trying to make. An oft cited paper is Miller, et al (2016)’s Hemodynamic Response After Rapid Sequence Induction With Ketamine in Out-of-Hospital Patients at Risk of Shock as Defined by the Shock Index. The researchers conducted a prospective observational study of (n=112) patients undergoing prehospital RSI. Subjects were grouped into high shock index (HSI) patients (SI > 0.9) and low shock index (LSI) patients (SI < 0.9). The mean dose of ketamine administered was 1.7 mg/kg. I’ll directly quote their conclusion: "After ketamine induction, HSI patients exhibited blunted hypertensive responses and more frequent hypotension, whereas LSI patients had sustained increases in pulse rate and SBP.”
In the spirit of not just blindly copying and pasting a conclusion from PubMed, I’ll provide some analytics from the study. Of the 112 subjects who were included in the study, 9% experienced hypotension after induction — regardless of whether they were in the HSI or LSI group. While the rate of hypotension was low overall, patients with a HSI had more episodes of hypotension (26%) than the LSI group (2%) which supports postulations that sedative agents, regardless of pharmacologic profile and “hemodynamic stability” put patients with HSI at risk of further hypotension after induction. The researchers concluded that in HSI patients, the 1.7 mg/ kg (pretty similar to our 1.5 mg/kg) was not hemodynamically protective and that administration in patients with depleted catecholamine states (i.e., shock) less substrate is available for the ketamine to maintain the hemodynamic stability the prehospital providers seek which puts the patient at risk for hypotension.
Anectdotally, I’ve heard providers ranging from respected co-workers to physician medical directors (not at Cooper mind you — I’ve never had this discussion with any of them) that rocuronium (or any paralytic we administer for that matter) will cause the hypotension that leads to the big crash that is so oft seen post-RSI. However, what I’m learning from some self-education on the topic is that it’s really the sedative and not the paralytic that leads to the hypotension post-RSI.
French (2016) outlined best practice for rocuronium administration. Recall that rocuronium is a long acting non-depolarizing neuromuscular blocker. It has no sedative or analgesic property. French asserted that in reviewing lessons from case reviews and research that in hypotensive patients requiring RSI, paralytic doses should actually be increased while induction sedatives should be decreased. This practice was also advocated by Scott Weingart in his lecture series that went viral (among medical nerds like myself) entitled The Laryngoscope as a Murder Weapon — Hemodynamic Kills. I spent a good deal of time researching PubMed, Science Direct, CINHAL, et cetera, et cetera for this quasi-academic paper and I could find nothing that supports that rocuronium is the culprit that causes a blood pressure crash peri or post-intubation. I did find repeatedly that it can increase heart rate which I suppose could cause some drop in blood pressure after some time elapses but it doesn’t directly drop blood pressure and now I’m rambling so I’ll stop and get to my point.
When it comes to traumatic shock, it may be worth considering adjusting our doses of ketamine based upon the patient’s shock index. Obviously we want to resuscitate these patients before we intubate them but that is somewhat limited due to a myriad of factors like not carrying blood products (which is currently logistically prohibitive as per our last staff meeting), not using vasopressors to increase blood pressure, and a logical upright zeal for minimizing scene times. Add that to the fact that we are not encountering these patients in Trauma Admitting where there are residents, surgeons, fellows, respiratory therapists, nurses, techs, pharmacists, wandering med students, and of course, the ubiquitous old lady with a hip fractures moaning in the next-door bed readily available to lend their expertise and technical skill. It’s a flight paramedic and a flight nurse on a scene or in the back of an ambulance with an ALS or BLS crew that’s — let’s be honest — a coin toss whether they are going to be exceptional partners who synergistically maximize our response to the patient or whether we’re going to get a deer in a headlight stare and 17.3% of a SAMPLE history for a report.
(Note: I am of the mindset that using pressors in active hemorrhagic shock is kind of useless and I agree that we shouldn’t necessarily be doing it just to get a “fake” BP. Please don’t think that I’m griping about that).
Judiciously modifying ketamine doses for this patient population may be an (and I hate this term because it’s overused and often inappropriately) evidence based tool in our arsenal to try and mitigate the incidence of life threatening hypotension after RSI.
And that’s what I’ve got. Thanks for reading.
References
Brown, Sakies, & Mick. (2017). The Walls Manual of Emergency Airway Management (5th Ed.). New York: LWW.
Jaume Canet, Jorge Castillo; Ketamine: A Familiar Drug We Trust. Anesthesiology 2012; 116:6– 8 doi: https://doi.org/10.1097/ALN.0b013e31823da398
David Caro. (2018). Induction agents for rapid sequence intubation in adults outside the operating room. Up to Date. Available at [https://www.uptodate.com/contents/induction-agentsfor-rapid-sequence-intubation-in-adults-outside-the-operating-room].
Dewhirst E et al. Cardiac Arrest Following Ketamine Administration for Rapid Sequence Intubation. J Intensive Care Med 2013. PMID: 22644454
James French. RSI Drugs Summary. Published on December 15, 2016. Accessed on July 22, 2021. Available at [http://sjrhem.ca/rsi-drugs/]. Heffner AC, Swords DS, Nussbaum ML, Kline JA, Jones AE. Predictors of the complication of postintubation hypotension during emergency airway management. J Crit Care. 2012 Dec;27(6):587-93. doi: 10.1016/j.jcrc.2012.04.022. Epub 2012 Jul 2. PMID: 22762924.
Heffner AC et al. Incidence and Factors Associated with Cardiac Arrest Complicating Emergency Airway Management. Resuscitation 2013. PMID: 23911630
Ko YY, Jeong YH, Lim DY. Influence of ketamine on catecholamine secretion in the perfused rat adrenal medulla. Korean J Physiol Pharmacol. 2008;12(3):101-109. doi:10.4196/ kjpp.2008.12.3.101
Jacob A. Lebin, Arvin R. Akhavan, Daniel S. Hippe, Melissa H. Gittinger, Jagoda Pasic, Andrew M. McCoy, Marie C. Vrablik. Psychiatric Outcomes of Patients With Severe Agitation Following Administration of Prehospital Ketamine. Academic Emergency Medicine 2019; 26: 889– 896.
Krebs W, Werman H, Jackson J, Swecker KA, Hutchison H, Rodgers M, Fulton S, Brenna CC, Stausmire J, Buderer N, Paplaskas AM. Prehospital Ketamine Use for Rapid Sequence Intubation: Are Higher Doses Associated With Adverse Events? Air Med J. 2021 JanFeb;40(1):36-40. doi: 10.1016/j.amj.2020.11.007. Epub 2020 Dec 4. PMID: 33455623.
Chris Nickson. Intubation, Hypotension, and Shock. Life in the Fast Lane Blog. Published on November 3, 2020. Accessed on July 21, 2021. Available at [http://www.lifl.com/intubationhypotension-and-shock]. Salim Rezaie. Critical Care Updates: Resuscitation Sequence Intubation - Hypotension Kills. REBEL EM Blog. Published on September 26, 2016. Accessed on July 22, 2021. Available at [https://rebelem.com/critical-care-updates-resuscitation-sequence-intubation-hypotension-killspart-1-of-3/].
Salim Rezaie. Dosing Sedatives Low and Paralytics High in Shock Patients Requiring RSI. REBEL EM Blog. Published on May 6, 2018. Accessed on July 22, 2021. Available at [https:// rebelem.com/dosing-sedatives-low-and-paralytics-high-in-shock-patients-requiring-rsi/].
Scott Weingart, MD FCCM. EMCrit Podcast 30 – Hemorrhagic Shock Resuscitation. EMCrit Blog. Published on August 15, 2010. Accessed on July 21st 2021. Available at [https:// emcrit.org/emcrit/trauma-resuscitation-dutton/ ].