What Agent Should I Use For Procedural Sedation?
Reuben Strayer MD
Take Home Points
- Propofol can be used in conjunction with ketamine to minimize complications such as hypertension, muscle rigidity and emergency reaction.
- Patients may experience partial dissociation as they metabolize ketamine. This may be distressing to the patient.
- Dissociative dose ketamine may still cause hypoventilation and apnea.
- Elderly patients may require less propofol.
- Etomidate is likely to cause myoclonus as well as nausea/vomiting.
- Humanely performing painful procedures is one of the most satisfying aspects of emergency medicine. Over the last decade, we have emerged from the shadows of fentanyl/midazolam to enter the golden age of procedural sedation pharmacology. Most of us have a variety of better agents at our disposal so we don’t have to choose between agony and apnea. Ketamine, etomidate and propofol will give great results for just about every procedure about every time. To choose between them, you need to get to know them.
- This came into being in the 1960s when pharmacologists recognized the potential of dissociative anesthesia. The first commonly available agent in this class was phencyclidine (initially known as Sernyl and now as PCP). Dissociative anesthesia produces a state of unconsciousness that renders patients unaware and impervious to external stimuli while preserving other brain functions such as airway reflexes and cardiorespiratory tone.
- Sernyl had a prolonged and nasty recovery period where patients often became agitated and psychotic for hours upon emergence. A variant on phencyclidine was sought. The derivative that provided dissociation with the best emergence profile was a ketone with an amine; ketamine. Ketamine is used for analgesia, RSI, agitation, asthma, alcohol withdrawal, opioid withdrawal, depression, suicidality and everything else. Its best use is for procedural sedation.
- Ketamine has reliable pharmacokinetics from the intramuscular route which makes it of special value in veterinary and pediatric medicine.
- Use of ketamine in adult patients was avoided until recently for fear of psychiatric distress on emergence.
- Preventing and managing ketamine-related psychiatric distress requires an understanding of ketamine’s effects on the brain at different doses.
- At low doses (10 mg in a normal sized adult), ketamine has powerful analgesia properties and little effect on perception or emotions.
- As the dose is increased to 30 mg or higher, patients will develop psychoperceptual disturbances like hallucinations and feelings of unreality but they are fully aware of what is going on and conversant. This is the recreational phase of the continuum. Most will do fine and some will love it. Some will not like it, however. Patients can be reassured.
- At higher doses, 50-70mg, you get partial dissociation, which you don’t want.
- Full dissociation occurs at about 1 mg/kg IV or 4 mg/kg IM. Ketamine is less potent IM. The lights are on but nobody is home. The patient maintains their ABCs but is completely isolated from all external stimuli. Dissociated is awake but unconscious. This is the desired state for painful procedures.
- You can bypass the analgesic, recreational and partially dissociated stages by using a higher dose of 2mg/kg IV. However, you can’t prevent the patient from passing back through these states as they metabolize the drug on emergence, which is why psychiatric distress occurs on emergence. If you give an induction dose and the patient starts freaking out before the procedure, this means you haven’t achieved full dissociation and you should give more ketamine.
- How someone feels as they emerge from ketamine depends on how they feel going into it. Make them comfortable prior to induction. If the patient is in pain, treat it. Anticipatory guidance is essential. Pre-induction coaching effectively prevents psychiatric distress. Tell the patient they will have vivid dreams and that they can choose their dreams.
- Ketamine activates but disconnects the mind. You can’t reconnect the mind. You have to wait for the patient to metabolize through partial dissociation. However, you can deactivate the mind while the patient is metabolizing using a conventional sedative. A small dose of a benzodiazepine will work great. Strayer has moved to propofol for this indication.
- Propofol also helps with some of the other problems that can arise with ketamine like hypertension. Ketamine is a weak sympathomimetic. Some patients can’t tolerate this. A 58 year old patient with coronary artery disease and prior valve replacements receiving ketamine to facilitate wrist arthrocentesis had a jump in her blood pressure to 230. She then developed acute fulminant pulmonary edema and cardiac arrest. She was appropriately treated and recovered.
- Burmon, C et al. Acute pulmonary edema associated with ketamine-induced hypertension during procedural sedation in the ED. Am J Emerg Med. 2017 May;35(3):522. PMID: 28277252
- If you don’t like how high the blood pressure or heart rate is going during procedural sedation with ketamine, give a dose of propofol. This is a sympatholytic and direct vasodilator. Propofol is great for muscle rigidity which may be seen occasionally. Ketamine also occasionally causes hypersalivation or a confluent truncal rash that is not allergic and does not require treatment. Nausea is common and effectively treated with ondansetron.
- Do emerging patients become unconscious with propofol? They usually just chill out with small dose. They may lapse into brief unconsciousness but rapidly recover. The duration of action is at most 5 minutes.
- What dose of propofol does Strayer use? 30-40 mg below 50 years old and decrease with advancing age.
- Dissociative dose ketamine can cause hypoventilation and apnea by a variety of mechanisms. If ketamine is pushed rapidly as an intravenous bolus, you will often see a transient period of apnea that usually lasts 10-20 seconds and resolves without treatment. Give ketamine slowly. This may be done by putting your dissociative dose in a bag of 50 mL normal saline and dripping it in over 1-2 minutes. There is some evidence that psychiatric distress is less likely with longer infusion times.
- Dissociated patients may develop hypoventilation due to airway malpositioning, excessive salivation and laryngospasm. These patients must be monitored by an airway capable provider. Most tolerate it well.
- Propofol is so adept at causing hypotension, hypoventilation and apnea that these physiologic derangements are the norm when propofol is used for deep sedation. However, propofol when used properly confers a high degree of safety from its vanishingly short duration of action.
- There are multiple ways to use propofol. You can start a drip and titrate the rate to the depth of sedation desired. However, this requires patience. You may give repeated small boluses (about 20-30 mg in a normal sized adult) and hope to achieve an anesthetic homeostasis. However, propofol disappears so quickly that it becomes challenging to get and keep your patients sedated. If you give repeated doses, you are pushing the patient in and out of very deep levels of unconsciousness. Be careful with repeated doses of propofol.
- Propofol should be reserved for brief procedures and administered in a single dose. Tank the patient up with oxygen and quickly push a bolus of propofol that is likely to lead to deep unconsciousness and possible apnea. Then the patient rapidly regains consciousness.
- For patients under age 50, you can give a push of 1 mg/kg followed by a quick flush and have the patient slowly count to 20. If this doesn’t get you where you to need to be in 60 seconds, give a second push of 0.5 mg/kg. If you need more than that or the procedure is longer than expected, you can give subsequent doses of 0.25-0.5mg/kg. If you are pushing the patient to deep sedation, be careful with more than 2-3 doses of propofol.
- Patanwala, AE et al. Age-related differences in propofol dosing for procedural sedation in the Emergency Department. J Emerg Med. 2013 Apr;44(4):823-8. PMID: 23333181
- They found that on average, lower doses were needed with advancing age. Younger patients on average needed more. Patients between 18-40 years needed 2 mg/kg. 41-64 year olds needed 1.7 mg/kg. Patients 64 and over needed 1.2 mg/kg. These probably won’t be the starting doses but may be the ending doses.
- Propofol does not have analgesic properties but rapidly and effectively causes coma where patients feel no pain. While giving opiates or pain medication prior to sedation with propofol may decrease the amount of propofol necessary, giving opiates along with propofol does not help and increases the likelihood of adverse events.
- Older patients can be remarkably sensitive to propofol. Use small doses for the small, frail elderly patient. Start with 20-30mg.
- Ketamine and propofol play well together. Propofol causes hypotension and ketamine causes hypertension. Ketamine causes hypertonicity and nausea while propofol causes flaccidity and is an anti-emetic. Because of this synergy and the prospect of using lower doses of both agents, using them together is a great idea. There is increasing evidence supporting the safety and efficacy of ketofol. Most of literature shows that combining ketamine and propofol in the same syringe does no better than either one alone.
- Dosing ketamine and propofol together in a fixed ratio doesn’t make much sense pharmacokinetically. Propofol is metabolized in minutes while ketamine accumulates. Depending on how you mix them, the propofol effects dominate for short procedures and the ketamine effects dominate for long procedures. No one has figured out the right ratio. It is better to dose them independently.
- Unlike ketamine which is hemodynamically stimulating and propofol which is hemodynamically depressing, etomidate is hemodynamically neutral. This is very attractive for sicker patients who are less likely to tolerate hypertension or hypotension. The dose in RSI is 0.3 mg/kg and the procedural sedation dose is about half that. 0.1-0.2 mg/kg.
- Etomidate works immediately and lasts somewhere between propofol and ketamine depending on the dose. However, etomidate is messier than propofol or ketamine. If you use it regularly, you will see a lot of myoclonus. This may be disruptive or mistaken for a seizure. Etomidate lowers the seizure threshold. This is the induction agent preferred by anesthesiologists to prolong seizures for electroconvulsive therapy.
- Etomidate may cause severe muscle rigidity including jaw rigidity as well as apnea. This is not a problem if given prior to a paralytic for RSI but is a problem for procedural sedation.
- Etomidate is the most emetogenic agent. Post-procedural nausea-vomiting are common and may be severe with etomidate.
- However, many providers love etomidate and use it routinely and effectively.
- Many providers continue to use a combination of fentanyl and midazolam. However, the onset is 3-5 minutes. This is much longer than expected. When doctors are not comfortable with these agents, they push dose after dose and then do the procedure with the patient screaming. They walk away just as the fourth dose hits its peak effect. Fortunately, there is a reversal agent. If this is all you have, go slow, have a time set to four minutes and have naloxone and flumazenil on the ready.
- There is evolving literature on newer agents such as remifentanil or dexmedetomidine. Most of this is not based in emergency medicine.
- Remifentanil is an ultra short-acting, non-accumulating opioid that produces moderate sedation and analgesia. Optimal dosing strategies and indications for ED based sedation have not been established. Remifentanil may have a role for less painful procedures when deep sedation is not required or to facilitate propofol PSA, allowing smaller doses of propofol. In the anesthesia literature, it has relatively high rate of adverse effects. Be careful.
- Dexmedetomidine is a sympatholytic alpha-2 agonist similar to clonidine but much more sedating. This produces sedation and analgesia without respiratory depression but with predictable bradycardia and sometimes hypotension. This may have its best role facilitating non-painful procedures in kids like radiology studies or as an adjunct to ketamine. As monotherapy, its more complicated dosing, slower onset and price have limited its role downstairs in the ED.
- How do you choose an agent?
- Physiologic reserve. Propofol should be avoided when hypotension and respiratory depression are a concern. Ketamine should be avoided when hypertension or tachycardia are a concern. If your patient is brittle and you need hemodynamic neutrality, chose etomidate. Although you should always be prepared for RSI with procedural sedation, be particularly ready if using etomidate. If you are very concerned about the patient’s reserve, don’t forget to ask yourself if you should be doing the procedure in the emergency department at all.
- Duration of the procedure. Propofol for very brief procedures, especially where muscle relaxation is required. Propofol is terrific for cardioversions or lancing an abscess. For longer procedures, use ketamine. Strayer uses full dissociative dosing at least 1.5 mg/kg IV or 5 mg/kg IM and draws up 100 mg of propofol in a syringe so you can deliver a small bolus to manage hypertension, muscle rigidity or psychiatric distress.
Suneth J. - December 16, 2017 4:48 PM
I am an emergency physician working in Australia. I really enjoyed Rueben Strayer/ Rob Orman s segment on procedural sedation. Any thoughts about the best agent/ dose to sedate a conscious patient for DC cardioversion of an unstable tachyarrhythmia? (e.g rapid AF with hypotension/ Conscious VT). Propofol isn't ideal due to risk of hypotension. Ketamine not ideal, as could worsen the tachyarrhythmia. We don't have etomidate in Australia. Is this a time when the old Fent/Midaz has a role? Or is Ketamine safe in patients with tachyarrhythmia? Or would a small dose of propofol be ok? Thank you!
Reuben Strayer (@emupdates) - December 16, 2017 9:19 PM
Hi Suneth. This is one of the classic PSA questions and you've framed it nicely.
If very unstable, peri-arrest - just shock.
If unstable/hypoperfused/very hypotensive, etomidate is probably the best option but if you don't have it, ketamine. ketamine is unlikely to cause trouble here (at least from a hemodynamics perspective) because it does not cause significant catecholamine effect in patients who already have high catecholamine tone. you can't use propofol in this scenario, and these patients are too sick to be messing around with fentanyl/versed, which will also cause a significant sympatholysis which these patients may not tolerate.
if stable or semi-stable, propofol is the right drug, because of its super-brief duration of action. if you're concerned about the BP, you can push some phenylephrine or titrate up a drip to get their MAP up before giving the propofol, but in a well patient with arrhythmia-induced hypotension, since you're going to solve the cause of the hypotension with cardioversion, in my opinion you're generally safe to push propofol.
Suneth J. - December 18, 2017 3:15 AM
Thanks so much for the quick reply!
I have pondering this question for a while, and you have summarised a fantastic approach. I think its one of those situations where its good to have a pre-planned approach. So my options are from sickest to least sick - 1. nothing, 2 Ketamine, 3 phenylephrine (or metaraminol as we use commonly here) + propofol.
Any comment on the doses? Particularly for ketamine for the very hypotensive.. would you go for 0.5mg/kg (or less) or stick with 1mg/kg? I imagine a sub-dissociated state with people shouting "all clear" followed by an electric shock may not be very pleasant! However I imagine the full 1mg/kg may result in further instability from sympatholysis.
ps - loving the sense of humour in your segments
pps - Rob Orman's Kenny G joke had me laughing out loud!
Reuben Strayer (@emupdates) - December 18, 2017 11:08 AM
Suneth - Ketamine acts differently than a conventional sedative and using a subdissociative may not be any safer than using a dissociative dose. Since the sedation efficacy of subdissociative dose is unpredictably inferior to the dissociative dose(might be equal, might be tremendously inferior/dangerous, and how inferior cannot be predicted), I recommend a dissociative dose, which is ≥1 mg/kg IV or ≥5 mg/kg IM.
Reuben Strayer (@emupdates) - December 19, 2017 11:18 AM
This meta analysis with James Miner editorial at the end endorse ketofol in this group. https://goo.gl/bmzTdV
Ed B. - December 29, 2017 8:10 PM
Thanks for an excellent podcast!
I totally agree with your approach to procedural sedation, especially the use of low-dose Propofol to mitigate the adverse effects of Ketamine. I’ve been doing this for a few years now and I would highly recommend it.
My procedural sedation cocktail is very similar to yours:
- Reassurance and explanation to patient and family re what to expect from ketamine. I encourage family presence in the room if they are a calming influence. I also close the doors / curtains and try to lower noise levels to minimise over-stimulation.
- Fentanyl 1mcg/kg around 3-5 mins prior to the procedure. The analgesic, euphoric and anxiolytic effects of the opiate give a nicer “trip” with ketamine.
- Ketamine 20-40mg as a test dose. Some patients (eg. elderly patients) may have adequete sedation in this “recreational” dose range for minor procedures. Allows me to pick up patients who are unusually sensitive to the ketamine before I commit to the full dose.
- For everyone else, I titrate the ketamine up to 1-1.5mg/kg to achieve full dissociation.
- I use low-dose Propofol boluses (20mg) to manage agitation, hypertension or muscle rigidity during the procedure. I use Propofol for top-up sedation during the final stages of the procedure to smooth out emergence reactions and for its amnestic and antiemetic effects. I’ve found that the quick-on/ quick-off pharmacokinetics make it superior to midazam for controlling emergence reactions. I have also used Propofol in higher doses (50-100mg) to successfully manage ketamine-induced laryngospasm.
Having had some disastrous emergence reactions from ketamine as a single agent I now always pre-load with fentanyl and keep a vial of Propofol in my back pocket.
Hopefully after listening to your podcast, more people will start using this approach!
Reuben Strayer (@emupdates) - December 30, 2017 7:26 AM
thanks Ed. the pearl re: laryngospasm is an interesting one. I don't have the patience to titrate ketamine and have found that a fully dissociative dose is safe and effective for everyone, but many swear by the incremental approach you describe.
Ed B. - December 29, 2017 8:27 PM
Hi Suneth -
For the unstable patient with AF/flutter/VT and low BP (eg. 70-80 systolic), I would recommend:
- Take 5-10 mins to optimise the patient. You rarely need to shock them “right now” if they have a BP of 70-80 and are still conscious.
- 500ml saline bolus to boost preload.
- Fentanyl 0.5-1mcg/kg in small increments around 5 mins prior to the procedure. Fentanyl is very cardio-stable and doesn’t usually drop BP by much in these doses.
- Ketamine 0.5-1mg/kg (less than the 1-1.5mg/kg used in non-shocked patients). Give it slowly and stop as soon as you get dissociation.
- You can use 0.5-1mg boluses of metoraminol at any stage if the BP is falling below your comfort zone. This may not be necessary though.. the shock is a potent stimulus and many patients end up hypertensive once their rhythm is corrected.
- If they are tense and agitated after the shock you can use 20mg Propofol for additional sedation and amnesia (provided adequete BP).
I don’t usually worry about the sympathomimetic effects of ketamine driving up the heart rate. Most of these patients are already sympathetically maxed out, so you’re not going to be able to drive the HR much higher by using ketamine (you might get a BP spike though).
Also, for re-entrant rhythms like VT, the heart rate is determined by the length of the re-entrant circuit rather than by the degree of sympathetic tone, so the ketamine shouldn’t increase the heart rate.
Reuben Strayer (@emupdates) - December 30, 2017 7:27 AM
Great points Ed. The heart rate pearls are key.
Suneth J. - January 9, 2018 5:45 AM
Thanks Reub and Ed! The case that comes to mind was an elderly lady who presented a few years ago with AF broadish QRS and very fast HR - around 220. I was concerned at the time about AF with WPW (but later discovered it was AF with Ashmann's phenomenon - which I had never heard of before). She was hypotensive (~80 systolic), but conscious. The added issue was that I wasn't sure that the cardioversion would work (unlike VT for example). and indeed it didn't - despite 3 x shocks, and we ended up rate controlling with amiodarone.
For the cardioversion - I ended up sedating her with fentanyl and small boluses (0.5mg titrated) of midazolam - but didn't feel that the sedation went as smoothly as I would have liked, and there was probably some awareness, which I understand isn't the most important thing, but I would have liked to avoid if possible.
Would a fentanyl/ ketamine/ metaraminol combination have been safe in this situation as well? (given the non re-entry circuit tachyarrhythmia). Also any thoughts about the concern of using ketamine in an elderly patient with CVS disease?
Thanks to both of you so much for your valuable input!
Reuben Strayer (@emupdates) - January 11, 2018 10:24 AM
unstable elderly person requiring cardioversion is tough PSA scenario. i think you are unlikely to effect adequate analgesia/sedation in an elderly woman needing an extremely painful procedure like cardioversion using fentanyl/versed without flirting with apnea/worsening hypotension. etomidate is probably the best option. if you don't have access to etomidate, I would use ketamine monotherapy. No reason to add fentanyl if you're using dissociative-dose ketamine. Be ready with vasopressors and be prepared to intubate.
ThanhVan T. - February 26, 2018 4:37 PM
I am an emergency medicine physician and medical director in a busy ED in a small, rural hospital. Before our group started in this hospital, the hospital had a procedural sedation policy that required 2 providers to be present during a procedural sedation if propofol was to be used. That is, there needed to be a provider present to do the sedation, and another provider (whether it's a CRNA, another physician, etc) to do the procedure (like a joint reduction, laceration repair, etc). We thus used mainly etomidate, ketamine, etc at this small hospital. Our group of 20 physicians also mainly practices in a larger hospital, in a nearby larger town. Many of the physicians expressed an interest in being able to use propofol in the this smaller ED as we are allowed to do so in the larger one. The 2 hospitals are not affiliated.
So, in my efforts to change the sedation policy regarding propofol at the smaller hospital, the administration (who are not physicians) have decided that all procedural sedations, regardless of agents used, require 2 providers. This puts us in a pickle as we are single coverage. As a result, we need to call in the CRNA to do the sedation, who are not always in house. I've provided the administration with the ACEP guidelines, and have provided guidelines similar to our larger hospital, which is similar to other hospitals that I have practiced. (I've also been on the coreem.net site.) We are all board certified emergency physicians, and do this routinely at our other hospital.
Are there a lot of hospitals that are requiring this 2 provider policy? Is this the future?
Reuben Strayer (@emupdates) - February 27, 2018 11:00 AM
I'm hoping this is more of the past than the future.
Perhaps the best way to address this is, after providing the data/guidelines demonstrating that one-provider PSA is safe and accepted practice, document cases where patients suffered harm because a second provider wasn't available.
Another tactic is to propose that one-provider PSA be implemented provisionally, and every case will be reviewed, for 6 months, and at that time it can be decided whether or not there is a safety concern and the practice should be extended.
Can be very difficult to affect change in these ways; the hospital administrators are responding to their own incentives which are often not patient- or physician-oriented.