In this month’s Annals of Emergency Medicine, Sener et al report on their nicely blinded study where 182 adult subjects were randomized to one of four groups – IV or IM ketamine (at dissociative doses), with or without IV midazolam (.03 mg/kg). They conclude that midazolam reduces the incidence of recovery agitation based on their results:

Green and Krauss provide an accompanying editorial where they caution that the treatment effect as reported by Sener might be exaggerated and conclude:

“Given this compelling evidence from Sener et al, many clinicians will choose to ‘tame’ ketamine in adults by routinely coadministering midazolam. Others, according to the caveats above, will just as reasonably elect to individualize such prophylaxis, using a subjective assessment of a given patient’s risk. After all, should their prediction fail and an unpleasant reaction result, it can readily be quelled with midazolam. Regardless of these approaches, the ketamine ‘tiger’ may not be as ferocious as some fear.”

In my 2008 catalog of ketamine adverse events in adults, I describe three strategies for dosing midazolam–predissociation, preemergence, and PRN. I use the PRN strategy, and in hundreds of sedations of adults, I’ve needed to use it once. Here is my accumulated wisdom on how to use ketamine.

* Use ketamine. No other agent matches its safety, efficacy, and reliability. The only patients who should not receive ketamine are patients in whom an increase in heart rate or blood pressure would really concern you. All the other variously reported contraindications, including oral procedures and especially the concerns around ICP (this is more of an issue for RSI than PSA), can be ignored*. For very quick procedures like cardioversion, propofol is probably a better choice. Propofol also provides better muscle relaxation for ortho procedures, but these procedures often take a while, and propofol is hard to use for longer procedures. Ketofol is sexy but really offers no advantage over propofol alone for very brief procedures or ketamine alone for longer procedures.

* Be prepared to intubate. This goes for all PSA agents and procedures. Full intubation setup, paralytic in vial. In PSA, airway and breathing are everything; have all your tools ready. Laryngospasm is rare but it happens – if you’re ready for it, it’s no big deal, if not, it’s a big deal.

* Use it IM in pediatrics. Starting an IV for ketamine PSA in a child who is already suffering some other painful condition is unnecessary and therefore cruel. The best approach is to immediately treat the painful condition with atomized intranasal fentanyl, get your xrays or whatever, then give IM ketamine, 4 mg/kg. Once dissociated, you can start an IV easily and painlessly, or you can skip the IV completely and do your procedure.

* Make the patient comfortable before ketamine PSA. The response to ketamine is largely emotional. When the patient goes down agitated and in pain, she is more likely to have bad dreams and a scary emergence.

* Coach the patient pre-induction. Tell your patients that you are giving them a drug that will make them have vivid dreams, but that they can choose their dream and it can be very enjoyable, and that when they wake up, their wrist is going to feel a lot better. Offer some suggestions as you’re pushing the drug; I like describing a pleasant beach scene.

* Give them a dose of ondansetron before or during PSA. Ketamine causes post-procedure nausea and vomiting frequently. There is no literature evaluating this strategy, but in my opinion zofran works, and my opinion matters. To me.

* If giving ketamine IV, give it over 60 seconds. If you give IV ketamine in a quick bolus, you will often see apnea. This resolves by itself, but it’s really hard to watch a patient not breathing for 30 seconds. Slowing the infusion makes apnea much less likely. In order to give a slow infusion, you have to

* Either dilute the ketamine or draw it into a very small syringe. Most EDs stock 50 mg/ml and 100 mg/ml preparations (some EDs stock more than one concentration – be careful). You cannot slowly give 2 cc in a 10 cc syringe.

* Have the midazolam ready and don’t hesitate to use it if the patient appears to be experiencing psychological distress. You will rarely need it if you follow the steps above, but I’ve read some firsthand reports of bad ketamine emergence reactions and they sound truly terrifying. However, the fear of an emergence reaction is a silly reason to avoid using ketamine. Unlike the adverse reactions associated with most other PSA agents, emergence reactions are not dangerous, and are very easily treatable.

* You don’t always need to use a full dissociative dose. 1-2 mg/kg IV causes dissociation; once you’re dissociated you can’t be any further dissociated and larger doses just prolong duration of action (which can be a good thing, e.g. an intubated, hypotensive but still thrashing about patient). For a quick, only moderately painful procedure, 20 mg boluses work great. The ketamine continuum starts with analgesia (note the analgesic dose ketamine drip), to loopy (giggling, responding to questions and tolerating pain), to partly dissociated (sort of responsive to questions but indifferent to pain) to fully dissociated (awake but unresponsive to any external stimuli). That said, don’t hesitate to give a full dissociative dose if you’re not in the mood to get fancy. Dissociated is da bomb.

Sener S et al. Ketamine With and Without Midazolam for Emergency Department Sedation in Adults: A Randomized Controlled Trial. Ann Emerg Med. 2011;57:109.

Green S and Krauss B. The Taming of Ketamine— 40 Years Later. Ann Emerg Med. 2011;57:115.

Strayer RJ and Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. American Journal of Emergency Medicine, Volume 26 Issue 9, November 2008, pages 985-1028.

* Here are the contraindications as reported in the 2011 ACEP Clinical Policy.
Absolute: Age less than 3 months; schizophrenia.
Relative: “Major” procedures stimulating the posterior pharynx; history of airway instability, tracheal surgery, or tracheal stenosis; active pulmonary infection or disease including URI or asthma; known or suspected cardiovascular disease; CNS masses, abnormalities, or hydrocephalus; glaucoma or acute globe injury; porphyria, thyroid disorder, or thyroid medication.

From his PaACEP resident lecture. For children who are undergoing painless imaging studies and would not otherwise require an IV.

Dose: 25 mg/kg

Typically comes in powder form for IV use, one vial = 500 mg.

Directions suggest that you reconstitute with 50 cc NaCl, which would = 10 mg/cc.

Chudnofsky method is to reconstitute with 5 cc NaCl, mix well to get all powder into solution, now you have 100 mg/cc.

Attach to syringe an 18g angiocath without needle.

Insert into rectum, not very far (1-2 cm in small child), inject slowly to keep fluid in rectum.

Close the buttocks together, hold with 3 inch cloth tape.

According to his study (PMID 10790471), average time to sedation = 7 minutes, average time to awake = 60 minutes. Note that of 100 patients, “Six had brief oxygen desaturations that responded to repositioning, although 3 of these also were given brief bag-valve- mask ventilation per institutional protocol. One developed a continuous cough. All had complete recovery and none required intubation.” So these patients have to be on a pulse oximeter and someone has to be ready to adjust airway, provide O2, and BMV as needed. I would round down the dose to closer to 20 mg/kg.

Conscientious Sedation

Patients who scream usually get my attention and things go something like this. Bypassing the protocol on a technicality (narcotics alone without sedatives are not “conscious sedation”), I administer rapid boluses of fentanyl (150 to 200 mcg usually suffice in total). Within a minute or two, the patient enters the most euphoric experience of her recent memory, closing her eyes and beginning to smile. I signal the surgeon who starts the procedure while the patient lazily registers the discomfort, but when offered more pain medication claims “it’s OK.” I hang out in the room during the procedure, adding fentanyl if needed and catching up on paperwork. Meanwhile, content surgeons, who despite their hard shells do prefer a nonsuffering patient, wrap it up in style. When all is done, the patient looks at me with immeasurable gratitude, and I recall all the reasons for which I became a physician. My term for it: “conscientious sedation.”

It uses up ED attending time, but for all the right reasons. I start with half the intended final dose for the rare hyperresponder. There is naloxone in my pocket and I’ve never had to use it. I am ready to intubate should the need arise, but I doubt it will. I memorized side effects of fentanyl and consider risk-benefit beforehand. And yes, I think it is an adequate approach to procedural pain for most ED interventions on typical adult patients, especially when local anesthetics are appropriately used.

from: Veysman, Boris D. Annals of Emergency MedicineVolume 56, Issue 4, October 2010, Page 430

Photo: http://www.flickr.com/photos/fimbrethil/387068341