The Ketamine Brain Continuum

December 25th, 2013
by reuben in PSA & analgesia

K Brain Continuum

You’re cardioverting an otherwise healthy 100 kg 48 year old man with lone afib. Since cardioversion is a brief procedure, you decide on a smaller than usual dose of ketamine, 50 mg.  You push the ketamine and prepare the defibrillator. The patient develops a far off stare, seems like a good time to shock, and you’re about to do just that, when he starts screaming at the top of his lungs I’M DYING!! I’M DYING!! I CAN’T SEE ANYTHING!! HELP ME!! You try to reassure the patient but he seems unable to hear you, and is now shrieking with great emotion that his body has disappeared. Nearby patients and staff are visibly disturbed and your med student started to cry, then fled. What’s going on? How do you manage this distressing situation and prevent it from happening again?

 

Ketamine was developed in the 1960s in a successful effort to synthesize a dissociative anesthetic that didn’t make people as crazy as phencyclidine, PCP, which was developed in the 20s. Its effect on cognition is attributed to antagonism at the NMDA receptor; this action interferes with the transmission of information that starts outside the brain from getting into the brain. In high doses, NMDA antagonism leads to dissociation, a cataplectic state where the patient maintains airway reflexes and cardiorespiratory function but cannot perceive any external stimuli nor interact with the world in any way.

The ability of ketamine to produce dissociation is of great value to clinicians who perform painful procedures, and this practice is firmly entrenched in pediatric emergency practice. In the past decade, ketamine has seen an expanded role in general emergency medicine for a variety of indications, especially as mythical contraindications around intracranial pressure, intraocular pressure, and psychiatric disease have been debunked [1 2 3 4 5 6 7]. However, adults who receive ketamine are more likely than kids to develop emotional distress, which makes some providers reluctant to use ketamine in patients they cannot lift with one hand. This reluctance is unwarranted and, given the efficacy and safety advantages of ketamine over other agents for procedural sedation, not considering ketamine is suboptimal care. Understanding the effects of ketamine on the brain empowers you to use it fearlessly, even recklessly, to the benefit of your patients of all ages.

Analgesic dose (0.1-0.3 mg/kg) ketamine has minimal effect on perception or emotion but is a powerful analgesic. I use analgesic dose ketamine as a second line agent when opiates aren’t getting the job done or are poorly tolerated, or in cases when I don’t want to use opiates, for example the patient with concerning hypotension, or the patient with chronic pain whom I can’t discharge (although I prefer droperidol for this purpose). In a normal sized adult, a 10 mg bolus will usually have minimal psychiatric effect but may not have an adequate analgesic effect; a 20 mg bolus will usually produce terrific analgesia but many patients will slide into recreational dose and get loopy. You can get less recreation with equal analgesia by setting up a drip–pushing ketamine accentuates its effects on awareness. Using a drip also provides continuous therapy, whereas push-dose ketamine lasts only 15-20 minutes. In this dose range, ABCs are not a concern and patients do not require monitoring.

Recreational dose (0.2-0.5 mg/kg) ketamine will deliver excellent analgesia but also make your patient high. Patients will have distortions of perception that most will like (indeed ketamine is commonly used without physician supervision for this purpose), others will dislike, but at recreational dose, patients know what’s going on, they know where they are, they know who they are. Patients can converse with you and follow commands, but they are hallucinating and stoned. Few patients will require intervention for psychiatric discomfort and many will be disappointed that the effect is wearing off. An agitated patient will often become sedated in this range, but the effect on level of arousal is variable.

Partially dissociated dose (0.4-0.8 mg/kg) ketamine leaves enough synapses properly wired so that patients have some awareness and can make some purposeful actions but not enough to allow patients to be connected to the outside world, their bodies, or reality. Many will be unable see or hear, talk or move; these capabilities may fade in and out. Although most will tolerate this well, some will find it terrifying–partially dissociated is where you want your patients not to be.

Dissociative dose (>0.7 mg/kg) ketamine renders the patient isolated from all external stimuli, which is the desired state in most cases where ketamine is used to facilitate a procedure or endotracheal intubation. A dissociated patient perceives no sights, sounds or pain and cannot interact. Though nystagmus, random and reflexive movements are common, dissociated patients are incapable of volitional action. Unlike with conventional sedatives, the brain is on and patients are awake, cardiorespiratory function is preserved or stimulated, but the dissociated brain is unaware and does not build memories; patients generally do not recall this period. Dissociated is awake but unconscious.

The four stages of the ketamine brain continuum have overlapping dose ranges that are highly variable among patients. At small analgesic dose (<0.1 mg/kg) or large dissociative dose (>2 mg/kg), effects are consistent; anything in between is unpredictable. A feature of ketamine’s dose-response that accounts for its remarkable margin of safety is the dissociation threshold, above which higher doses do not produce any further effect: a dissociated patient does not become more dissociated with more ketamine, higher doses only prolong duration of action.

You can skip the analgesic, recreational and partially dissociated phases of the continuum and deliver immediate dissociation with an ample dose, however, you cannot avoid the patient traversing back through these phases as brain levels more slowly fall and the patient emerges from dissociation. This is why psychiatric distress–emergence phenomenon–is generally observed as the patient emerges from dissociation and starts to reintegrate external stimuli while passing through the partially dissociated phase of the spectrum.

Managing psychiatric distress caused by ketamine is straightforward and much less dangerous than managing the cardiorespiratory adverse events seen routinely with conventional sedatives. If the patient develops distress shortly after an initial dose, the patient is not fully dissociated and the best maneuver is usually to give more ketamine. More commonly, the patient develops distress on emergence, after the procedure is over; the mind is activated but disconnected. You can’t reconnect the mind, but you can deactivate the mind with a sedative such as midazolam or propofol while it metabolizes through partial dissociation.

The incidence of emergence reactions can be greatly reduced by pre-induction comfort (aggressive analgesia prior to the procedure if the patient is in pain) and pre-induction coaching (explaining to the patient that they will have vivid dreams; that they should choose a pleasurable destination for their ketamine trip). I describe these strategies in more detail here and here.

A patient who can hear and talk to you but is still tripping and anxious can often be reassured: “Mr. Lee, you’re in the emergency room because you broke your ankle. We gave you a drug that makes you feel weird and just fixed the ankle and everything went great. In a few minutes you’re going to be feeling like your normal self.” However, verbal reassurance to a partially dissociated patient is useless; reassure with midazolam or propofol, or push the patient back into full dissociation with more ketamine.

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Three part screencast covering the essentials of procedural sedation and analgesia for emergency clinicians.

Part one covers how to think about and prepare for PSA, including a discussion of fasting guidelines. 13 minutes.

Part two describes how patients are harmed during PSA and how to prevent patients from being harmed during PSA. 29 minutes.

Part three discusses contemporary PSA pharmacology. 16 minutes.

References

Slideset

Emergency Department PSA Checklist

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Designed to be used as a single, double-sided page. 

pdf for printing

pdf vector image for screen viewing

for PSA mastery, see the PSA screencast trilogy

If you’d like to modify the checklist for your institution, I can send you the original layout (omnigraffle format) and tables (excel format).

Newborn: Kyan James

Guest post by Greg Press

 

The second perimortem C-section of my career happened last week. The first was almost ten years ago. While I’m hardly an expert (takes three to be an expert), I have some pointers worth sharing.

The first case happened on the first day of my first job, in Houston, having just completed my ultrasound fellowship in New York. The night started with a guy shot in the right chest: intubation and chest tube. His girlfriend was brought in next, pregnant, shot in the head: perimortem c-section and neonatal intubation.

The second was just the other day. It was my first code at my new job at a small hospital in Wellington, New Zealand. A young girl hanged herself, was found by family who called EMS. They found in her VFib, defibrillated, started CPR, intubated and called to warn us of her arrival. They reported she was in asystole, a bad sign for mom. They reported she was 22 weeks pregnant, a bad sign for baby.

There have been a few PMCS reviews circulating recently in the EM world and I agree with most of their recommendations. But I have differing thoughts on a few points.

Do not memorize the number 24. Or 23. Or 25, or whatever the gestational age your neonatologists say they can currently save premies. You are unlikely to know the precise age–the mother is generally the most reliable source for this information, but generally not in this circumstance. We understood the hanged woman to be 22-weeks pregnant; post-mortem estimates placed the baby at 26 weeks. More importantly, you are not doing this procedure for the baby: PMCS is a resuscitative intervention for the mother. You’re trying to save mom, first and foremost, and then baby, maybe. So, whether the gestational age is 22, 24, or 26 weeks is irrelevant.

But you don’t want to do this procedure for a first-trimester pregnancy, so when do you do it?

  1. When you have a reported gestational estimate anywhere near viability. Or…

  2. When the tummy is big. If the fundal height is above the umbilicus, great. If this assessment escapes your mind in the chaos of the moment, just recognize that the tummy is big. Or…

  3. When the baby looks big on ultrasound. Ultrasound does not need to be performed routinely, particularly if the mother is bursting with baby. But if you’re not certain, put the probe on the belly, not to measure biparietal diameter, just to see is this a big baby? You will probably not be able to resist the urge to look for a fetal heartbeat, but do not delay the intervention of interest.

Do not memorize the number 4. This is the supposed number of minutes after maternal arrest when we see a precipitous decline in fetal neurologic outcome and survival. The number 4 is even more irrelevant than the number 24, because, again, the procedure is done primarily for the mother. And the procedure is done as soon as possible. As soon as possible is the only time consideration.

So what is most important to know? There are two things you must do and a few nuances to keep in mind.

Assuming you have some forewarning, the two things you must do are GET HELP and GET STUFF.

Call the obstetrician.  Call the NICU, or PICU, or whomever can help you take care of the baby.

Get stuff for mom. Get a kit. You may only have a thoracotomy kit or some other all purpose ED kit – get it. If you don’t have a kit, get a scalpel, real surgical scissors, towels, and clamps for the cord.

Get stuff for baby. Get a baby warmer. Get a neonatal BVM. Get a neonatal intubation kit, and an IO, and the dose of epinephrine.

Assign someone to manually displace the uterus to the left. Tell this person she must do this nonstop until the scalpel hits the skin. And then she must immediately shift focus to assure CPR continues until all efforts cease. There will be others responsible for CPR, ideally a line of people performing CPR, but it’s easy to neglect once scalpel hits skin, and so it is important to have someone assigned as insurance just at the moment when this oversight is most likely to occur.

Forget the mommy-tilting ramp. It will be hard to find the ramp, harder to jerry-rig one, and harder still to perform CPR and the procedure on a tilt. Assign a tummy-pusher.

The patient will arrive, and if she’s arrested you will have to secure the airway, perform CPR, obtain IO or IV access, give drugs, possibly defibrillate. This will seem simple because you do it all the time.

And then you will have to perform the perimortem C-section. Perhaps an obstetrician has by now arrived. If not, two thoughts might cross your mind: there’s very little to gain and I’m not going to be a hero. Erase both of those thoughts; there’s even less to lose and it’s time to be a hero.

Cut a vertical incision from the top of the belly’s curve to the pubis. With an earlier pregnancy and heftier mother, there may be fat to get through to the peritoneal wall – you can use your fingers as claws to bluntly dissect a parting to the peritoneum. Then cut through the peritoneum vertically, ideally with scissors (you can use the scalpel to initiate an opening inferiorly). Pull out the big uterus and cut it open vertically in the same manner until you get the baby out. Be careful not to cut the baby.

When the baby comes out it will be very alarming. If it is very premature, it will look like a purple alien. The first time I saw this it was disturbing. The second time I was quite aware how disturbing it was for everyone else in the room. The cord will have to be clamped twice and cut in between. Grab the baby, wrap it in a warm towel, bring it to the warmer you have prepared. Most likely you will immediately start bagging the neonate, unless it is near-term and crying. Look for signs of life such as attempts to breathe, cry or move. Both times for me there have been none. If there is no heartbeat or signs of life, start CPR. To determine if there is a heartbeat, listen with your stethoscope over the chest or feel for umbilical pulsations. If there is a heartbeat and it is slow (<60 bpm) just bag the baby, if it doesn’t improve quickly (30 seconds) start CPR. If the eyelids are fused it is probably too premature to be viable. If the baby is an early premie and bagging and CPR do not resuscitate the child I would stop efforts. If it is a full or near-term baby that cannot be resuscitated by bagging and compressions, intubate, obtain IO/UV access and start in with epinephrine and advanced neonatal life support.

Once more: the delivery is a resuscitative intervention for the mother first and foremost. Make sure maternal CPR and resuscitation continue throughout and after delivery. Don’t let the splayed open belly and uterus concern you, just pack them with towels, it will bleed less than you anticipate. Mom is likely young and healthy. After a few minutes our mother had a strong pulse and a good blood pressure. She is alive in the ICU as of this writing.

Despite having read this and feeling prepared, expect a shit storm. The unique scenario of your case will bring unanticipated events. Get help and get stuff (mommy and baby stuff) early. Assign the tummy-pusher-turned-CPR-advocate. Cut the tummy, cut the uterus, cut the cord. Expect to bag the baby and perform compressions unless near term and breathing. Continue efforts with mom until after the procedure.

Finally, I would like to comment on a dramatic difference between the Houston and New Zealand experiences. Following the case in New Zealand, there have so far been two debriefing sessions. Both have been held to address the clinical and emotional aspects of such a difficult case. In Houston, ten minutes after PMCS we moved on to the next case, another critically injured patient, and that was that. Everybody involved in the New Zealand case was invited to the second debriefing session, from the ambulance crew to the students to the doctors and nurses from the ED, obstetrics and the ICU. A psychologist ran the session, and though I was skeptical, she was quite good. Was very interesting to hear how students, pregnant nurses, old cranky doctors and everyone in between felt about the experience. It was just as important to air out clinical concerns and perspectives unique to each specialty, to avoid frustrations and move closer to optimal care for next time. I suggest you try to make this happen for the next once-in-a-lifetime case you experience.

Greg Press

A correspondence from New Zealand

Awake Intubation: A Very Brief Guide

July 7th, 2013
by reuben in airway

 

 

Awake intubation is placing an endotracheal tube in the trachea while the patient continues to breathe. The principle advantage over RSI is that you do not take away the patient’s respirations or airway reflexes, which makes the process safer in many circumstances. The disadvantages are that the patient’s personality and movements, as well as the patient’s airway reflexes, must be managed, which takes time, and even when done well, the view you get won’t be as good as in a paralyzed patient.  Instrumenting the back of the throat may cause gagging and possibly vomiting, though this is quite unlikely to lead to clinically significant aspiration (because the patient is awake).  The more difficult airway features, and the less urgent the intubation, the more likely you should intubate awake. Patients who are at high risk to vomit are not good candidates for an awake technique.

The two arms of awake intubation are local anesthesia and systemic sedation. The more cooperative your patient, the more you can rely on local; perfectly cooperative patients can be intubated awake without any sedation at all. More commonly in the ED, patients will require sedation. Ketamine is the agent of choice in most circumstances, as it sedates without depressing respiration or airway reflexes. In somewhat cooperative patients, 20 mg boluses, titrated to effect, work very well. In very uncooperative/agitated patients, a full dissociative dose (1.5 mg/kg) is an effective strategy though a brief period of apnea is usual if dissociative doses are delivered as a bolus, and laryngospasm is a possible complication. For those patients where raising heart rate or blood pressure is undesirable, benzodiazepine sedation will have a less effective but still salutary effect. Dexmedetomidine is probably a better agent in these scenarios, but is a little tricky to use and not available in most EDs.

Even if using full dissociative dose ketamine, do your best to anesthetize the airway, using the steps listed in the box above, excerpted from the ED intubation checklist. Local is much facilitated by a dry mucosa, so the first step, if possible, is to dry the mucosa with glycopyrolate or atropine, followed by suction and dabbing with gauze. Once this is done, anesthesia is delivered by nebulization, atomization (ideally using a purpose-built atomizer like a MAD device), and drip techniques.

Once the patient is adequately anesthetized/sedated, you gently proceed with your intubation method of choice. When you see the cords, you can pass the tube without paralysis, place the bougie and then paralyze, or paralyze before placing the bougie/tube. I recommend the second option, and I also recommend that you prepare to do a full RSI, with whatever equipment and drugs you would use in an RSI case.

When done well, awake intubation is quite anticlimactic, as the patient simply continues to breathe, and saturation is maintained, for as long as needed. While RSI is terrific and will work very well in most cases, if you perform RSI on a patient who was a good candidate for an awake technique, and it doesn’t go well, you have made a consequential mistake. Awake technique requires little additional skill; it is under-utilized in emergency medicine because it requires what emergency providers often lack: patience. In this case, however, patience is well rewarded.