In this episode, I’ll highlight the key points that set ketamine apart from other sedatives & analgesics and discuss how to use ketamine in the critical care setting.



There is a lot of buzz around the use of ketamine in the critical care setting, and for good reason. But a lot of providers are unfamiliar with and hesitant to use the drug.

What is ketamine?

Ketamine is a noncompetitive NMDA receptor antagonist that produces analgesia and dissociative anesthesia.

What makes ketamine different from other sedatives & analgesics used in critical care?

Ketamine’s analgesic effect is dose-dependent in the same manner as opioid analgesics. Give a little bit more ketamine, get a little more pain relief.

What sets ketamine apart is how it produces anesthesia / amnesia. Ketamine causes a dissociation of the cortex and limbic systems, with the result that the patient cannot perceive the surrounding environment. The key difference between ketamine and other agents such as etomidate, midazolam and propofol is that this dissociative state does not exist on a continuum. It is either on or off. I think of it like pregnancy – just like you can’t be “a little bit pregnant”, you can’t be “a little bit dissociated”.

When using it as a sedative, it is critical to keep in mind this on/off nature of ketamine.

What effects does ketamine produce besides analgesia and dissociative anesthesia?

Respiratory:

Ketamine does not suppress respirations, unless it is given too rapidly IV push (give over 1 minute, complications when given <30 seconds).

Rarely ketamine may cause laryngeal spasms.

Ketamine increases airway secretions.

Ketamine causes bronchodialation.

Cardiovasular:

Ketamine causes the release of endogenous catecholamines. This means in most patients ketamine has a neutral to positive effect on the cardiovascular system. Expect at most a few points increase on the systolic BP and HR. However if the patient is catecholamine depleted (such as in prolonged severe illness) ketamine may paradoxically cause hemodynamic collapse.

Neurological:

An emergence phenomenon may occur as the ketamine wears off. This is more common in adult patients. The patient may experience vivid dreams and be extremely agitated. IV midazolam can be used to treat or prevent this effect.

When used at sub-anesthetic doses some patients report feeling “weird” and this feeling can cause anxiety.

Ketamine carries a warning for use in the setting of elevated intracranial pressure (ICP). There is evidence that suggests any effects on ICP are not of consequence to the patient and the authors of Rosen’s Emergency Medicine and other tertiary drug references like UpToDate do not consider ketamine contraindicated in this state.

Musculoskeletal:

Hypertonic movements resembling seizures may occur – you can be assured ketamine is not causing a seizure in the patient.

What absolute contraindications does ketamine have?

The official contraindications to ketamine are allergy and any condition in which an increase in blood pressure would be hazardous. However an excellent review that is an American College of Emergency Physicians clinical practice guideline adds age <3 months (increased airway complications – anecdotal) and schizophrenia (may exacerbate condition) as absolute contraindications to ketamine use.

How can ketamine be used?

-Induction agent for intubation

-Procedural sedation

-Rescue analgesic

-Continuous sedation

-Status epilepticus

-Status asthmaticus

Induction agent for intubation

Make sure you use enough to dissociate the patient. Ketamine for this indication gets the Go Big Or Go Home dosing strategy. The recommended dose range is 1 to 2 mg/kg IV. A pediatric study showed that 95% of patients were adequately dissociated with 1.5 mg/kg, so I never go below this dose for induction purposes.

Ketamine has a 30 second onset and 10 to 15 minute duration when given IV for induction. All patients induced with ketamine should receive midazolam (I suggest 0.05mg/kg IV) after the airway is in but before the 10-15 minutes is up.

Procedural sedation

The same 1.5mg/kg IV dose can be given for this indication or it can be used IM at a dose of 4-5 mg/kg. Airway reflexes remain intact so this can be a great drug for procedures. Have at least 2 mg of midazolam in the room, especially with an adult patient in case emergence phenomenon occurs.

You may have heard about using “ketofol” for deep sedation procedures. This involves mixing propofol and ketamine (often in the same syringe) in varying proportions. The ketamine doses are always sub-dissociative and so this practice amounts to essentially using propofol and fentanyl. There have been some interesting pro vs con debates in Annals of Emergency Medicine on this topic. I am firmly on the side of it being ridiculously foolish to place two drugs with different effects and durations in the same syringe. What if you just need a little more analgesia? You are forced to give propofol to achieve that goal if the drugs are in the same syringe!

Rescue analgesic

I’ve had a few patients benefit from ketamine for rescue analgesia. In these patients I’ve used an infusion without a bolus. I start at 0.1mg/kg/hr and increase every 30 minutes to a max of 0.4 or 0.5 mg/kg/hr. The key is to keep the dose below dissociative levels.

One of the patients I used this on lost IV access and we converted him to oral ketamine at 0.5mg/kg every 6 hours. Oral ketamine is very bitter, so do your best to mask the taste (cherry syrup, etc…).

Some people give ketamine as a bolus for pain at 0.15 or 0.3 mg/kg. This is probably only reasonable in patients who have a high risk of respiratory depression from opioids. The 0.3mg/kg dose is probably more effective but comes with more side effects.

Continuous sedation

I’ve never used ketamine for this indication, although we have come close a couple of times at my hospital. Data is limited for this indication so that makes it a last line option in my opinion.

In one study of a few patients, the median duration of infusion was 1.5 days and the dose range was 0.3 to 2.8 mg/kg/hr. If I ever have to use this I will be starting with 1.5 mg/kg IV bolus and 1mg/kg/hr infusion.

Status epilepticus

Ketamine is an option for refractory status epilepticus. This is another time for the Go Big Or Go Home dosing strategy. I’d try at least 2mg/kg IV bolus followed by at least 2mg/kg/hr infusion. One review had loading doses at 1.5mg/kg (median), 5mg/kg (max) and infusion rates at 1mg/kg/hr (minimum), 2.75mg/kg/hr (median), 10mg/kg/hr (maximum).

Status asthmaticus

There is limited data using ketamine for this indication. The ketamine induced catecholamine release and possibly ketamine itself have bronchodilatory effects that may help in a severe asthma exacerbation. Give a one-time bolus of 0.75 mg/kg IV followed by continuous infusion of 0.75 mg/kg/hr.

Monitoring with continuous infusion

When using ketamine as a continuous infusion, I like Chris Pasero’s recommended monitoring frequency after each dose change: Vitals and neuro status q15 minutes x 4, then q2 hours x2, then q4 hours.

If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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