Ketamine can cause rapid cardiovascular collapse

[Kris Thompson]

Be careful with ketamine! Even though it normally provides for good hemodynamics, patients that are critically ill may rapidly decompensate when you give it. I have seen several patients become hypotensive and two go into cardiac arrest during RSI with ketamine. It is my understanding that ketamine relies on upregulation of catecholamines to maintain hemodynamic stability. In the critically ill patient who may already be "running low" on catecholamines (or already at the highest level of response to them), ketamine may cause rapid deterioration.

If the patient doesn't need emergent airway management or can wait a moment for it (while using BLS techniques), it is best to deal with the shock first. Infuse some blood or fluids for hypovolemia, treat obstructive shock (pleural decompression, pericardiocentesis, thrombolytics), and perhaps give some push-dose epinephrine or start a norepinephrine drip prior to induction.

Remember to dose induction agents low (and based on ideal/lean body weight) and paralytics high (based on actual body weight), especially in the critically ill patient. Ketamine is probably still the drug of choice for this patient population but it, like all induction and paralyzing agents, must be used with caution.

Here is a paper that demonstrates that patients with a high shock index (HR/BP>0.9 or, basically, HR>BP) are more likely to experience hypotension during pre-hospital RSI with ketamine.

Miller, M., Kruit, N., Heldreich, C., Ware, S., Habig, K., Reid, C., & Burns, B. (2016). Hemodynamic Response After Rapid Sequence Induction With Ketamine in Out-of-Hospital Patients at Risk of Shock as Defined by the Shock Index. Annals of emergency medicine. www.ncbi.nlm.nih.gov/pubmed/27130803

[Tony Held]

Do you think this is due to dissociative dosing and the mind's loss of the need for sympathetic response?  Similar to heavy-handed Fentanyl dosing?

Or do you think it's a direct pharmacologic impact?

[Kris Thompson]

Jan 12, 2017 10:01:35 GMT -6 Tony Held said:

Do you think this is due to dissociative dosing and the mind's loss of the need for sympathetic response?  Similar to heavy-handed Fentanyl dosing?

Or do you think it's a direct pharmacologic impact?

Direct pharmacological impact, based on what I've read.

Ketamine has known direct cardiac depressant effects. We know this from dog and human studies, both in and ex vivo. Contractility of the heart decreases when clinical range doses of ketamine are given. Ketamine only maintains cardiovascular stability by sympathomimetic effects, which are poorly understood. From what I've read, it appears to be centrally mediated and some believe it is related to inhibition of norepinephrine reuptake. However, there is also often significant tachycardia which I believe is unlikely from norepinephrine reuptake inhibition alone.

In patients who are critically ill, catecholamine or adrenocorticosteroid depletion may prevent ketamine from exerting its secondary sympathomimetic effects. In the same way, patients that have been chronically ill may have significant resistance to catecholamine and adrenocorticoid stimulation.

In any patient undergoing RSI, especially those that are critically ill, you should:

-Adequately volume resuscitate with fluids or blood products, as appropriate, prior to RSI
-Treat other causes of shock (PE, tamponade, pneumothorax, etc.)
-Start vasopressors prior to induction to maintain blood pressure (push dose epinephrine is great here)
-Dose induction agents low and based on lean body weight
-Ventilate with appropriate tidal volumes and respiratory rate to match the patient's clinical presentation and pH

Here is some of the literature on the hemodynamic effects of ketamine:

Gelissen, H. P., Epema, A. H., Henning, R. H., Krijnen, H. J., Hennis, P. J., & den Hertog, A. (1996). Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle. The Journal of the American Society of Anesthesiologists, 84(2), 397-403. anesthesiology.pubs.asahq.org/article.aspx?articleid=1949119

Pagel, P. S., Kampine, J. P., Schmeling, W. T., & Warltier, D. C. (1992). Ketamine depresses myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs with autonomic nervous system blockade. Anesthesiology, 76(4), 564-572. anesthesiology.pubs.asahq.org/article.aspx?articleid=1951263

Waxman, K., Shoemaker, W. C., & Lippmann, M. (1980). Cardiovascular effects of anesthetic induction with ketamine. Anesthesia & Analgesia, 59(5), 355-358. journals.lww.com/anesthesia-analgesia/Abstract/1980/05000/Cardiovascular_Effects_of_Anesthetic_Induction.7.aspx

Here is a paper from long ago (1976!) that shows that a second dose of ketamine decreases HR and BP. It doesn't get to the mechanism, but is interesting nonetheless. I think this supports the idea that ketamine's hemodynamic stability is catecholamine-dependent.

Savege, T. M., Colvin, M., Weaver, E. J. M., Bond, C., Drake, J., & Inniss, R. (1976). A comparison of some cardiorespiratory effects of althesin and ketamine when used for induction of anaesthesia in patients with cardiac disease. British journal of anaesthesia, 48(11), 1071-1081. bja.oxfordjournals.org/content/48/11/1071.long