Dilantin (Phenytoin) Loading: IV vs. 4 hour oral load, or is there another way? by Dr. Carly Darr

Dilantin (Phenytoin) Loading: IV vs. 4 hour oral load, or is there another way?

You have a breakthrough seizure patient on Dilantin whose level came back undetectable (or really low), and you plan to load them and then discharge them.  Reference guidelines for oral phenytoin loading recommend about 1g in 3 divided doses spaced by 2hrs each.  This is usually done with 400mg, waiting 2hrs, 300mg, waiting 2hrs, then a final 300mg, resulting in a total of 1g after 4 hours.  Alternatively, some people will load phenytoin IV while the patient is on a cardiac monitor for 20 minutes (a GIGANTIC waste if the patient can tolerate PO meds).  So, why can’t we give patients 1g orally all at once?  The short answer is that we CAN give 1g oral load all at once.  ALIEM has a nice summary of the research behind this and the link is included below.   The long answer is that the side effects of nausea and vomiting were believed to be less and the absorption higher with the divided dosing, but research shows these effects are minimal.  Several small studies in which patients were given about 1g oral load and then serum levels tested at varying time points after the load have shown that therapeutic range (10 mcg/mL) is reached within 3-5 hours.  Furthermore, there have been only a handful with vomiting or severe nausea. So, go ahead and give them 1g orally, maybe consider a dose of antiemetic, and remember that they won’t be therapeutic for the first few hours with any type of oral loading.  Or, if that makes you nervous, try 2 doses of 500mg and/or more rapid spacing between doses.  Please note that these are small studies, and our DMC reference recommends the 4 hour load, so discuss with your attending.

ALIEM article on single oral load: https://www.aliem.com/2013/04/trick-of-trade-rapid-oral-phenytoin-loading/

Teaching in the Emergency Department by Zeid K.

The challenges of effective teaching in Emergency Medicine are well documented. The ED is not a comfortable learning environment. Time is limited and this creates a significant barrier to education. There are books, blogposts, tweets, research papers and podcasts that all attempt to answer one question: How do I become a more effective teacher in the Emergency Department? My recently concluded teaching elective was an attempt to experience these challenges first-hand. My month was cut short by a vacation as well as being scheduled for 5 shifts in the department by everyone’s least favorite chief resident, Christopher Sponaugle. This blog post will discuss some of the more important aspects of bedside teaching and the tools that we have at our disposal.

Whatever your motivation might be, accepting your role as a clinician-educator is extremely important. This role is not limited to those of us pursuing academic interests post-graduation. Regardless of what environment you will be practicing in, you will have some degree of teaching responsibilities; as an educator, you have a professional and ethical obligation to your learners.

Successful teaching in emergency medicine (EM) begins with enthusiasm and a desire to positively influence the learner. Learner-centered teaching has been repeatedly shown to be the most effective method of teaching in EM. Taking a few minutes at the beginning of your shift to get to know your learner is key. This helps to establish your relationship, determine their goals and set expectations. One of the most powerful questions that you as a teacher possess is, “What are you hoping to get out of this shift today?”

One of the more useful tricks to being an effective teacher comes from Amal ‘put the mess in Messman’ Mattu. Something he likes to do, which I see a lot of attendings do as well, is play the “what if” game. Playing this game can make routine patient encounters become a productive conversation that allows you to explore differential diagnosis, pathophysiology and treatment options for a variety of diagnoses. Every case can provide a teaching point. Train yourself to ask questions that promote critical thinking in a non-threatening fashion. Make an effort to deliver a clear, concise and focused message. Avoid “over-teaching” or providing an excessive amount of information that obscures the original teaching point.

There are several, widely adopted frameworks that educators use in emergency medicine. One- Minute Preceptor is a 5-step model of clinical teaching that acknowledges the hectic nature of Emergency Medicine. The acronyms SPIT and SNAPPS are other teaching methods that have been adopted quite widely. These were featured during our MedEd Grand Rounds and discussing them in further detail would be beyond the scope of this blog post. A quick Google search and review of the references at the end of this post will provide everything you need to know about these and other teaching techniques.

Providing feedback is just as vital to the educational process as effective teaching. Feedback should be provided consistently, objectively and in real-time. We have all received the proverbial “shit sandwich” during the course of residency and while this is a well-known method to provide feedback, there are other important aspects of providing effective feedback. Allowing self-evaluation at the initiation of the feedback process can provide valuable information to the educator regarding the effectiveness of their teaching methods. Similar to over-teaching, avoid giving too much feedback as this can diminish the effectiveness of your message. Always finish the conversation with a positive or encouraging summary.

“I desire no other epitaph… than the statement that I taught medical students in the wards, as I regard this as by far the most useful and important work I have been called upon to do.” While asking you to uphold yourselves to the lofty standards set by the great Sir William Osler in the above quote is impossible, I only ask you all to take a more methodical and refined approach to teaching your learners. This will serve you well for not only the rest of residency, but for the entirety of your careers.



Berger, Todd J., et al. “The impact of the demand for clinical productivity on student teaching in

academic emergency departments.” Academic emergency medicine 11.12 (2004): 1364-1367


Practical teaching in emergency medicine / chief editor, Robert L. Rogers; associate editors,

Amal Mattu … [et al.].–2nd ed


https://www.aliem.com/2016/09/idea-series- asynchronous-curriculum- for-resident- as-




Zeid Kalarikkal, Chief Resident Extraordinaire

Picture this; you have a previously healthy 14-week-old boy who is brought by his very concerned first-time parents. The mother notes that the infant had an episode where he went blue and was not breathing. She quickly picked him up, tapped on his back and maybe 30 seconds later the baby was noted to be awake and breathing comfortably.

You note that the child was born at-term with an uncomplicated birth history. He has been doing well since and they follow up regularly with their pediatrician. Parents deny any history of fever, URI symptoms, cough, vomiting or diarrhea. Vital signs and physical are normal and the baby is noted to feeding from the bottle during your evaluation.

You complete your evaluation and conclude that this child had an Acute Life Threatening Event or ALTE.

ALTE was previously defined as “an episode that is frightening to the observer and that is characterized by some combination of apnea, color change, marked change in muscle tone, choking, or gagging”

You return to the room to explain this to the parents. While your gestalt tells you that the child is and probably will be fine, you start explaining your diagnosis. At the mere mention of the word ‘Life-Threatening’, the father collapses to the ground and the mother starts sobbing. You curse yourself for picking up the chart and start consoling the parents.

In most cases, this case had an obvious disposition – Transfer to a Pediatric hospital.  Previously, there was no data to identify a subset of ALTE patients that could be safely discharged home. While some do get discharged home, it depended heavily on provider gestalt, comfort and degree of risk aversion.

Enter BRUE

Brief Resolved Unexplained Event or BRUE has replaced ALTE in the most recent guidelines from the American Academy of Pediatrics.

BRUE brings some clarity to the definition of ALTE by specifying that:

  • The term only applies to infants less than 1 year old
  • Episode must be less than 1 minute and have resolved
  • Patient must have a reassuring history, physical exam and vitals during evaluation
  • Episode must be unexplained

First thing to do with a child meeting the definition of BRUE is to classify them as low or high risk.

Features that have been defined as low risk are age greater than 60 days, a lack of prematurity (gestational age > 32 weeks and post-conceptual age > 45 weeks), a first and isolated event, duration of less than one minute, no need for CPR provided by a trained medical provider and no concerning historical features or physical exam findings. 

If your patient does not meet all of these criteria, they are now high risk and the guidelines offer no further recommendation.

For low-risk patients, the guidelines offer further recommendations.

  • Parent/caregiver education regarding these events and use shared-decision making for further testing, discharge and follow-up.
  • You may consider pertussis testing, EKG and cardiorespiratory monitoring.
  • You do not need obtain viral panels, CBC, CSF/blood cultures, electrolytes, CXR, EEG or other advanced testing.
  • You DO NOT need to admit these patients for the event alone and they can be discharged home with close outpatient follow-up within 24 hours.

Remember, BRUE is only used when no other condition can be found as the etiology of the event. It only represents a constellation of symptoms and you should use your history and physical examination skills to determine a more precise diagnosis before labeling it a BRUE. The biggest strength of these updated guidelines is that you now have some support for discharging a low risk patient.



Tieder JS, Bonkowsky JL, Etzel RA, Franklin WH, Gremse DA, Herman B, Katz ES, Krilov LR, Merritt JL 2nd, Norlin C, Percelay J, Sapién RE, Shiffman RN, Smith MB; SUBCOMMITTEE ON APPARENT LIFE THREATENING EVENTS. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016 May;137(5). PMID: 27244835.




Ryan Ernst’s trauma lecture summary

Trauma, VS, and Shock

Here is a brief summary of my 30-minute presentation:

No single vital sign is reliable to determine severity of injury or degree of traumatic shock. There have been papers that indicate correlation of mortality/injury severity with increased HR, RR > 25, BP <90, and GCS < 14.[i]

Location of palpable pulse does not correlate accurately with estimated BP, is no longer taught in ATLS, and should not be used as a surrogate to estimate blood pressure. It can be useful to assess improvement or decline in a single patient over time.[ii],[iii]

When automated BP measurements have been studied, they significantly overestimate BP in hypotensive trauma patients. Consider using a manual cuff if there is any question of the accuracy of the BP. Definitely cycle the initial BP two or three times to verify.[iv]

ATLS guidelines for degree of shock are not based on firm literature, and will tend to underestimate the degree of shock based on HR and BP. Do not rely on this to assess stability of your trauma patient – take the entire picture into account.[v],[vi],[vii],[viii],[ix]

Shock Index is also not completely reliable, but may be more sensitive than HR or BP alone to assess severity of injury and degree of shock. SI is calculated as HR/SBP. Results > 0.9 suggest increased level of injury and shock.[x],[xi],[xii],[xiii]

SBP < 110mmHg may be a more sensitive indicator of severity of injury, level of hemorrhagic shock, and impending mortality than the traditional 90mmHg. This previous cutoff is not based in any specific literature, and is used by arbitrary convention, likely based on estimated needs for cerebral and renal perfusion.[xiv],[xv],[xvi],[xvii]

If you’re in the mood for some easy listening on the topic of trauma resuscitation, I suggest the following:





Disclaimer: My lecture and EMSGH blog post are a summary of my personal opinions, based on extensive literature review, well-vetted online podcast and blogs, training I have received both within and outside of SGH/DMC, and personal experience. Any implementation into your personal practice should be thoroughly discussed with your attending, and if any question persists, with ED and hospital administration.

[i] Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, Gülmezoglu AM. A systematic review of the relationship between blood loss and clinical signs. PLoS One. 2013;8(3):e57594. doi: 10.1371/journal.pone.0057594. Epub 2013 Mar 6. Review. Erratum in: PLoS One. 2013;8(6). PMID: 23483915

[ii] Deakin CD, Low JL. Accuracy of the advanced trauma life support guidelines for predicting systolic blood pressure using carotid, femoral, and radial pulses: observational study. BMJ. 2000 Sep 16;321(7262):673-4. PMID: 10987771

[iii] Poulton TJ. ATLS paradigm fails. Ann Emerg Med. 1988 Jan;17(1):107. PubMed PMID: 3337405

[iv] Davis JW, Davis IC, Bennink LD, Bilello JF, Kaups KL, Parks SN. Are automated  blood pressure measurements accurate in trauma patients? J Trauma. 2003 Nov;55(5):860-3. PubMed PMID: 14608157

[v] Guly HR, Bouamra O, Little R, Dark P, Coats T, Driscoll P, Lecky FE. Testing the validity of the ATLS classification of hypovolaemic shock. Resuscitation. 2010 Sep;81(9):1142-7. PMID: 20619954

[vi] Guly HR, Bouamra O, Spiers M, Dark P, Coats T, Lecky FE; Trauma Audit and Research Network. Vital signs and estimated blood loss in patients with major trauma: testing the validity of the ATLS classification of hypovolaemic shock. Resuscitation. 2011 May;82(5):556-9. PMID: 21349628

[vii] Mutschler M, Nienaber U, Brockamp T, Wafaisade A, Wyen H, Peiniger S, Paffrath T, Bouillon B, Maegele M; TraumaRegister DGU. A critical reappraisal of the ATLS  classification of hypovolaemic shock: does it really reflect clinical reality? Resuscitation. 2013 Mar;84(3):309-13. PMID: 22835498

[viii] Mutschler M, Paffrath T, Wölfl C, Probst C, Nienaber U, Schipper IB, Bouillon  B, Maegele M. The ATLS(®) classification of hypovolaemic shock: a well established teaching tool on the edge? Injury. 2014 Oct;45 Suppl 3:S35-8. PMID: 25284231

[ix] Mutschler M, Hoffmann M, Wölfl C, Münzberg M, Schipper I, Paffrath T, Bouillon B, Maegele M. Is the ATLS classification of hypovolaemic shock appreciated in daily trauma care? An online-survey among 383 ATLS course directors and instructors. Emerg Med J. 2015 Feb;32(2):134-7. doi: PMID: 24071947

[x] Bruijns SR, Guly HR, Bouamra O, Lecky F, Lee WA. The value of traditional vital signs, shock index, and age-based markers in predicting trauma mortality. J Trauma Acute Care Surg. 2013 Jun;74(6):1432-7. PMID: 23694869

[xi] Schafer K, Van Sickle C, Hinojosa-Laborde C, Convertino VA. Physiologic mechanisms underlying the failure of the “shock index” as a tool for accurate assessment of patient status during progressive simulated hemorrhage. J Trauma Acute Care Surg. 2013 Aug;75(2 Suppl 2):S197-202. PMID: 23883908

[xii] McNab A, Burns B, Bhullar I, Chesire D, Kerwin A. An analysis of shock index as a correlate for outcomes in trauma by age group. Surgery. 2013 Aug;154(2):384-7. PMID: 23889965

[xiii] Mutschler M, Nienaber U, Münzberg M, Wölfl C, Schoechl H, Paffrath T, Bouillon B, Maegele M; TraumaRegister DGU. The Shock Index revisited – a fast guide to transfusion requirement? A retrospective analysis on 21,853 patients derived from the TraumaRegister DGU. Crit Care. 2013 Aug 12;17(4):R172. PMID: 23938104

[xiv] Eastridge BJ, Salinas J, McManus JG, Blackburn L, Bugler EM, Cooke WH, Convertino VA, Wade CE, Holcomb JB. Hypotension begins at 110 mm Hg: redefining “hypotension” with data. J Trauma. 2007 Aug;63(2):291-7; discussion 297-9. PMID: 17693826

[xv] Edelman DA, White MT, Tyburski JG, Wilson RF. Post-traumatic hypotension: should systolic blood pressure of 90-109 mmHg be included? Shock. 2007 Feb;27(2):134-8. PMID: 17224786

[xvi] Hasler RM, Nuesch E, Jüni P, Bouamra O, Exadaktylos AK, Lecky F. Systolic blood pressure below 110 mm Hg is associated with increased mortality in blunt major trauma patients: multicentre cohort study. Resuscitation. 2011 Sep;82(9):1202-7. PMID: 21632168

[xvii] Hasler RM, Nüesch E, Jüni P, Bouamra O, Exadaktylos AK, Lecky F. Systolic blood pressure below 110 mmHg is associated with increased mortality in penetrating major trauma patients: Multicentre cohort study. Resuscitation. 2012  Apr;83(4):476-81. PMID: 22056618

Analeptics – Quinn’s Toxicology Post

Analeptics: The Modern Coma Cocktail


I had never actually heard this term analeptic before and it seems somewhat old fashioned.

It means something that is restorative and invigorating, in this context, used to wake up someone with a decreased level of consciousness.

First, a quick practice case:

A middle-aged man presents to your hospital obtunded with poor respiratory effort. Which of the below treatments/Medications do you administer?

  1. Place patient in Ice bath
  2. Strychnine
  3. Camphor.
  4. Picrotoxin
  5. Caffeine

Of course all of these answers seem ridiculous, if not downright dangerous. However, depending on the where and when of your medical practice, any one of these may have been the standard of care.

At one time or another, these have been treatments of choice for decreased levels of consciousness. And some of them even work… In a fashion.  Strychnine for example might even wake you up so hard that you are totally conscious for the painful muscle convulsions that may eventually cause you do die of anoxia. Ew. But at least you woke up, so that’s good.

Granted, these are from a time where mechanical ventilation was not really a thing, so you would go to great lengths to avoid deep coma. No matter the cost.

The risk benefit here is a little different than most things we deal with nowadays and was basically “probably dead vs possibly dead”

Such is the dubious history of Analeptics and the “coma cocktail,” which is still evolving and is argued about to this day.

The coma cocktail:

In the modern era, say for the past 20 years or so, this contains dextrose, thiamine, naloxone, and flumazenil.

The concept for this when it was first devised is that it was something you could just reflexively give to people with decreased levels of responsiveness, to rapidly address reversible causes of depressed consciousness while reducing permanent neurological injury.

You are probably quite familiar with the medications listed above, although you may not use all of them, and may not use any of them in the reflexive manner that this concept was designed for.

The prevailing practice attitudes now have shifted against indiscriminate administration of this cluster of potentially harmful medicines, so it is probably most appropriate to break it down and look at each component individually.


Dextrose is a sugar, used to treat hypoglycemia.

Hypoglycemia is a common endpoint that may result from a drug or toxin exposure, nutritional deprivation, or numerous nontoxic events.

Hypoglycemia is common. The rate of hypoglycemia in patients with altered mental status of any cause is approximately 8.5%. This means that about 1 in 12 of your altered mental status patients have a hypoglycemic component. This is extremely significant because prolonged hypoglycemia can result in permanent brain damage, and mortality in hypoglycemic patients ranges from 11-27%.

This alone might be enough to persuade you administrate this in your altered patients. You would use D50 in adults, and D25 or D10 for pediatric patients.

In the end, the dosage that is required is “enough” because every patient is different, and have their own thresholds at which they become symptomatic. Dosing for pediatric patients is as follows. D10W: 2.5ml/kg,    D25 4ml/kg. In adults, starting with 1-2 ampules of D50 is appropriate, each ampule contains 25g of dextrose.

What if they get too much?

Concerns for making the blood sugar too high are generally not demonstrated clinically.  Renal losses alone keep it from going way too high, which is something we routinely take advantage of in patients with DKA and HHS. And anyway, one ampule of D50 only generally raises blood glucose by 60mg/dL.

What if it wasn’t hypoglycemia at all?

If their altered mentation is from something nontoxic, like an ICH, there has been no demonstrated long term change in survival or functional ability.

The solution to these concerns is to be able to reliably detect hypoglycemia right?

Well, if we accept that treatment should be administered as fast as possible to reduce hypoglycemia, then bedside testing might be completely impractical.

On the flip side, and in defense of standard bedside testing, a potentially very high number of patients (up to 25!) are misdiagnosed based on purely clinical findings, as many appear agitated instead of somnolent, and for this reason their blood glucose may not be tested, so maybe we should just test everyone.

Dangers of relying on a number:

Keep in mind though that lots of people become altered at blood levels above the “definition” of hypoglycemia of a glucose below 60. If a person lives their life at a serum level of 300mg/dL, the normal lab values become less useful.

This justifiably seems like a tough balance. The clinical need to make a rapid decision in a busy or hostile environment vs a documentable objective measurement.

Hoffman and Goldfrank recommend a stratification system for your altered pts:

  1. If they have numerical hypoglycemia, treat. Problem solved.
  2. If they have nonfocal neuro exams, and have borderline glucose levels. Give dextrose.
  3. If you don’t have ability to test a patient in the above scenario, give dextrose anyway.
  4. So what do you do if they are altered and have a localizing exam: This is admittedly rare in cases caused by low sugar, 2.5%. So for these patients, if you go strictly by the numbers, you will get 90% of those rare patients. And even if you are wrong, the extra sugar won’t hurt.

So, with this method, you will admittedly over treat a large number of patients, but you probably won’t delay a single person with real hypoglycemia. Which is important, because the cost of an amp of D50 is like 5$. But the economical and physical cost of not treating it is massive.


Right off the bat, empirical use seems less complicated than with dextrose.

Thiamine (Vitamin B1) functions as a cofactor for pyruvate dehydrogenase, which links anaerobic glycolysis to the krebs cycle, as well as an enzyme in the krebs cycle itself, and the pentose phosphate pathway. It’s important.

One interesting, and possibly problematic aspect of thiamine is that the amount needed is dependent on total energy intake. More energy=more thiamine needed.

Dietary thiamine becomes decreased  in chronic liver disease, folate deficiency, malabsorption, malnutrition like with TPN/post op patients, or those juice cleanses your facebook friends from high school like to use and/or sell.

The prime example of people who take in calories without other nutrients (like thiamine!) are alcoholics. Liquor has lots of energy but not so many vitamins. The most notable result of low thiamine is everyone’s old friend Wernicke-Korsakoff.

The characteristics of Wernicke encephalopathy includes oculomotor abnormality, ataxia, and confusion. It carries a mortality rate of 10-20%, and up to 80% of survivors develop the other half of the odd couple- Korsakoff psychosis with that fun, permanent short term memory damage. Confabulation is all fun and games until you need a reliable medical history from a patient besides a lifetime of drinking.

So, this is rare. But it is very bad.

Including the 100mg IV of thiamine treats/prevents the encephalopathy. And it costs like 1$. That’s what we in the biz like to call a steal.

But what about that thing with glucose I learned about in medical school that I also had to know for step 1 and 2!?!

And of course the other benefit you may hear, is that it prevents the precipitation of the encephalopathy by the dextrose loading these people will get too, as thiamine requirement is calorie dependent.

So that part sounds right and almost makes sense from a basic physiology standpoint, but the evidence for this is very lacking. The cases that drive this are most likely people who had the encephalopathy already, or who got dextrose in large volumes for a long time (hours to days) without other nutrition.

Withholding dextrose until thiamine doesn’t do much. Thiamine uptake is way slower than glucose anyway, something like 6 hours.  So even giving them together wouldn’t even help that much if you were truly worried about Wernicke’s. Which again, you shouldn’t be.

So in that case you would basically just be withholding dextrose from a patient that may desperately need it to avoid something that is probably theoretical at best. Don’t be that person.

Now you have me all fired up to give thiamine!

You can give it oral, IM, or IV. People who need the coma cocktail probably won’t be getting it orally if they are really that altered. At least they shouldn’t. Most medications are less effective if aspirated. And if they are really malnourished, they might not have good muscle mass to take an IM injection. You can do it that way, but you will have an IV in these people anyway.

Thiamine is cheap, safe, and since you can’t measure it in a patient, this has a good place in the modern coma cocktail. At worst, it just reminds us to address nutrition, right?


Probably the best known and most talked about. It is a pure opioid antagonist used for reversal of acute intoxication. It rapidly counteracts sedation, respiratory depression, miosis, analgesia, bradycardia, and GI stasis caused by exogenous opioids through your 3 different opioid receptors.

It also fights your endogenous opioid peptides too. Which may explain why it works a certain degree on some intoxications with things that are not opioids, such as some antiepileptic medications.

Naloxone can be given IV, IM, through an ET tube, and intranasally.

There are risks like pulmonary edema and hypertension, and risk to you through precipitation of violence. However, these risks to the patient are generally considered rare. Approx 1% or less.

Except for extremely unpleasant opioid withdrawal. We know it does that. That’s the whole point. You can do that every time if you really wanted to. The effects of withdrawal are not life threatening, but it can cause other problems to arise in the setting of a polydrug intoxication. You don’t want your newly opiod-free patient vomiting from withdrawal while their benzodiazepine co-ingestion is keeping them nice and asleep.

On the other side of the same coin, you could uncover dangerous and more threatening sympathomimetic symptoms from something like cocaine, like seizure and arrhythmia.

Are there any agitated people this might help with? Like dextrose does?

This differs from the case of dextrose possibly helping agitated people. People on opioids won’t be rowdy like that. You aren’t gonna help, and will probably make things worse.

What is the best metric for giving this?

This is something you want to consider giving right away to someone with decreased consciousness. In the Hoffman/Goldfrank paper, they reference prior works by Hoffman that show a respiratory rate of 12 of less predicted a naloxone responder 80% of the time. So this is where you want to focus your attention if you are thinking about opiods. Respiratory depression is what kills these people, so treat the respiratory depression. A PCO2 from a blood gas is better, but that takes a lot more time than checking out the respiratory rate.

But the PUPILS. People on opioids have miosis!

But what if they aren’t miotic? Certain opioids have a much more dramatic effect on respiration than pupils. They could die of anoxia with normal pupils. Our old friend Demerol was particular well known for that. Pupils are nice, but you can’t breathe through your pupils, to quote Dr. King.

So how much do you use?

Conventional dosing ranges from .4 to 2mg. If you reach 10mg, isolated opioid toxicity is unlikely.

The Hoffman paper suggests that you lower the dose to .2mg as a first dose. That was in 1995.

This new publication in the British Journal of Pharmacology suggest that even that may be unnecessarily high, and that a first dose of 40 micrograms is more appropriate. This way you can titrate to their breathing, which is what the lethal issue, not the sleepiness. They can be sleepy and breathe, as long as they are protecting their airway.

And what if they DO need the full 2mg to breathe? Naloxone acts so fast that you can titrate it up .04mg at a time, and it won’t keep you in the resuscitation bay for an hour. It will still be fast. They can be bagged or intubated during this of course.

Go slow. Don’t hit them with 2mg right away. If you need it, work up to it. You avoid getting punched and pooped on, and the patient doesn’t leave AMA only to have their naloxone wear off 3 blocks away.

The recommendations for naloxone drip remain the same, with an hourly infusion rate around half of what you needed to give them initially.


Last and probably least, is flumazenil. While naloxone got a WHO classification as an essential medicine, flumazenil got a black box warning.

This is no longer a standard, and essentially only exists in the coma cocktail as a historical item.

It reverses sedation from benzodiazepines, but will also precipitate withdrawl in patients dependent on them, or alcoholics.

Compared to opioids, this is less on the gross side, and more on the potentially fatal side. It can precipitate dangerous withdrawal seizures which you would then treat with benzos… which you just nullified the effectiveness of.

To be fair, it was developed for conscious sedation reversal before it was added to the coma cocktail. Which it still has a valid use for- If you have a clear history, and a low suspicion of benzo/ETOH dependence it may have a role in reversal of conscious sedation from benzos. OR… you could just intubate them and let them get better on their own.

If you are curious, Initial dosing is .2mg for adults, slowly given/titrated. In kids it is 10ug per kilogram with a max of .2mg.

You essentially want to give this the same time you perform gastric lavage. AKA basically never.

Probably best to avoid without advice from a toxicologist



  1. Hoffman, Robert S. “The Poisoned Patient With Altered Consciousness.” Jama 274.7 (1995): 562. Web
  2. Sivilotti, Marco L.a. “Flumazenil, Naloxone and the ‘coma Cocktail’.” British Journal of Clinical Pharmacology Br J Clin Pharmacol 81.3 (2015): 428-36. Web.




Zeid’s Critical Care Post – Chest Compressions in CPR

Hands off? Never!!

We have all heard that tweeter go off, “60 year old male, cardiac arrest with downtime of 20 minutes. No shocks advised and coming in a BLS unit.” As your airway and vascular access pathways run through your head, EMS comes in through Resus 4 bagging your patient while performing chest compression. They start giving you their prehospital report and while unfastening the patient from the EMS stretcher and transferring him to the hospital bed, compressions stop. Anywhere from 5-15 seconds later the patient is now on the bed and the designated team member resumes compressions.

The importance of high quality CPR is stressed during our BLS/ACLS courses. The trend continues during any high-level resuscitation lecture that you might have heard. The AHA repeats this point several times in their guidelines;

“Increased emphasis has been placed on high-quality CPR using performance targets (compressions of adequate rate and depth, allowing complete chest recoil between compressions, minimizing interruptions in compressions, and avoiding excessive ventilation).”

Of the many interventions we do, the intervention shown most to correlate with survival and positive neurological outcomes is high quality chest compressions. A lot of resuscitation research is based off animal models, for obvious reasons. Berg et all described a significant drop in coronary perfusion pressure when chest compressions are interrupted. This is depicted in the image below:

Click here for graph

An important take away point is not only the significant and sudden drop in coronary perfusion pressure when chest compressions are interrupted but also the additional time required after resumption to reach previously achieved levels of perfusion. This time period has been estimated to be anywhere from 40-45 seconds during animal studies and were shown to be associated with worsening outcomes. The red arrow in the graph above highlights this period.

Paradis et all highlighted this point when they showed that ROSC is associated with higher initial and maximal coronary perfusion pressure during CPR in humans. Christenson et all also found that patients who receive longer periods of uninterrupted chest compressions are more likely to survive. These studies are in the references for further reading.

Other significant barriers to uninterrupted compressions include pulse checks and airway management. This is difficult to avoid but attempts should be made to minimize pulse check during CPR and this is reflected in the AHA guidelines as well. In the appropriate situation, EtCO2 monitoring can serve as a useful surrogate for determining ROSC. A sudden increase of >10mm Hg has shown to be an indicator of ROSC and thus allowing you to minimize interruptions for pulse checks. Obviously, this requires endotracheal intubation and represents a limitation of this method.

This brings forward the next reason for interruption in chest compressions: endotracheal intubation. In our EMS system, a majority of cardiac arrest patients come in with BVM or a supraglottic airway such as a combi-tube or King airway in place. While there is some debate regarding the timeliness of endotracheal intubation during cardiac arrest, there is no doubt that should be achieved with minimal interruptions in chest compressions. Some studies suggest that passive oxygenation (i.e. nasal cannula or non-rebreather mask) may be superior to BVM ventilation. The literature also suggests that ET intubation may be deferred till ROSC with no significant differences in outcomes. Endotracheal intubation, if attempted, should be performed by an experienced provider since the incidence of esophageal intubation is estimated to be 3-15%. This results in worsening hypoxia and hypercarbia. Additionally, Wang et all found that the median duration of all endotracheal intubation associated interruptions is about 105 seconds and represents about 23% of all interruptions in chest compressions. In summary, there is not a lot of definitive evidence regarding airway management in cardiac arrest patients but use your clinical judgment to ensure first-pass success and minimize interruptions in compressions.

In conclusion, when that cardiac arrest patient is wheeled in to your resuscitation room you should assign someone to take over compressions from EMS immediately. We already have dismal survival rates for out of hospital cardiac arrest in the metro Detroit area and it is your obligation to provide your patient with the best possible chance of survival.


  1. Berg RAR. Circulation (New York, N.Y.): Adverse hemodynamic effects of interrupting chest compressions for rescue breathing during cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest. American Heart Association, etc; 11/2001;104:2465.
  2. Cardiopulmonary resuscitation for cardiac arrest: the importance of uninterrupted chest compressions in cardiac arrest resuscitation, Cunningham, Lee M. et al. The American Journal of Emergency Medicine , Volume 30 , Issue 8 , 1630 – 1638
  3. Christenson J,Andrusiek D, Everson-Stewart S, et al. Chest compression fraction determines survival in patients with out-of-hospital ventricular fibrillation. Circulation 2009;120(13):1241-7.
  4. Paradis NAN. JAMA : the journal of the American Medical Association: Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. American Medical Association; 02/1990;263:1106.
  5. Wang CC. Resuscitation: The association between timing of tracheal intubation and outcomes of adult in-hospital cardiac arrest: A retrospective cohort study. Elsevier; 08/2016;105:59.

July 28 Lectures

As promised, here are further references/reading/podcasts pertinent to this past week’s grand rounds.

From Dr. Ernst, here is further information regarding chest trauma, particularly chest tubes:

EMRAP September 2007 – Penetrating Chest Trauma (Kenji Inaba)

EMRAP April 2016 – More Penetrating Chest Trauma (Chris Hicks)

EMCrit December 2011 – Discusses Needle Decompression, Finger Thoracostomy (Weingart)

Podcast 62 – Needle vs. Knife II: Needle Thoracostomy?

Ultrasound Podcast July 2016 – Airway/Breathing in Trauma

Airway & Breathing Ultrasound in Trauma with @ultrasoundmd. #FOAMED

From Dr. Fellows, here is information regarding cardiac amyloidosis and ventilator management:

EMCrit Lecture – Dominating the Vent: Part I

EMCrit Lecture – Dominating the Vent: Part II

Here is a link that with the Echo and EKG findings of Amyloid:


The Unnecessary Pelvic Exam – Dr. Smith

I don’t want to disappoint you, but…

We don’t need to be performing pelvic exams for the sole purpose of cervical sampling in women we suspect of having simple chlamydia or gonorrhea infections. Although we’ve been taught that women presenting for an STD check need a pelvic exam, the cervical swabs we obtain are entirely unnecessary.

Self-collected vulvovaginal swabs are performed by the patient, who is instructed to insert the swab in the vagina and rotate for roughly 10 seconds. This uses the same nucleic acid amplification testing (NAAT) swabs that we already use in the Emergency Department during pelvic exams. Rather than perform a pelvic exam – something that ties up nurses, physicians, and rooms – we can simply hand patients these swabs and quickly instruct them on how to perform the test.

But how do self-collected vulvovaginal swabs perform compared to physician-collected endocervical samples? One prospective study of 3859 women was performed comparing self-collected, vulvovaginal NAAT testing to an otherwise identical physician-collected endocervical sample.1,2 Patients were responsible for packaging the sample, which was then tested against the traditionally collected (pelvic exam) endocervical sample. Patients were considered ‘true positives’ if GC/Chlamydia NAAT was confirmed using an additional NAAT with a different nucleic acid target – the authors do not explain the characteristics of this test any more than that. There are issues with the last part of this methodology.*

However, since physician-collected endocervical sampling is effectively our ‘gold-standard’ in the ED, we really only care about one data point. That is, what sample technique found more GC/chlamydia infections that were ‘confirmed’ by a second NAAT assay – endocervical or vulvovaginal? The paper does effectively answer this question.

In the case of chlamydia, the sensitivity of self-collected vulvovaginal swabs was 97% (NPV 99.7) compared to 88% for physician-collected endocervical swabs (p<0.00001). Only 0.13% of samples were ‘indeterminate’, meaning there was some form of disagreement in the NAAT results.1 In the case of gonorrhea, the sensitivity of vulvovaginal swabs was 99% compared to 96% for endocervical swabs, (p=0.375).2

So what do these data mean? Self-collected, vulvovaginal testing produced essentially the same sensitivity characteristics in diagnosing gonorrhea infections. If you’re looking for gonorrhea, you’re equally likely to find it with an endocervical or vulvovaginal swab. In the case of chlamydia, however, vulvovaginal swabs actually revealed more infections than endocervical swabs. The authors conclude that endocervical samples missed 9% of chlamydia infections, or one out of every 11 infections. The authors hypothesize that this is due to chlamydia infections harbored in the urethra that are missed by endocervical sampling. Furthermore, the authors identified 12 previously published studies making similar comparisons to vulvovaginal and endocervical sampling in chlamydia. 10 of those found vulvovaginal swabs to be more sensitive (median 5.1% difference) while 2 of them found a higher sensitivity with endocervical samples (median 1.8% difference).1 If you’re looking for chlamydia, you’re more likely to find it with a vulvovaginal swab than with an endocervical swab.

Detroit Medical Center uses the BD ProbeTec Qx Amplified DNA assays. This is an NAAT assay similar to the one used in the studies outlined above. According to the manufacturer, this assay remains effective when the vulvovaginal self-collection technique is used.3 In fact, BD provides patient instructions for how to do so.4 Additionally, patients prefer this method of non-invasive testing, and 94% state that they’d be tested more often if a self-collected vaginal swab was used.5

In light of all of the above data, the CDC’s recommendations state:

For female screening, specimens obtained with a vaginal swab are the preferred specimen type. Vaginal swab specimens are as sensitive as cervical swab specimens, and there is no difference in specificity. Self-collected vaginal swabs are equivalent in sensitivity and specificity to those collected by a clinician. Cervical samples are acceptable when pelvic examinations are done, but vaginal swab specimens are an appropriate sample type, even when a full pelvic exam is being performed.6

Clearly, this doesn’t obviate the need for a pelvic exam in all patients. But for a patient with a history and symptoms suggestive of GC/chlamydia infection – or those patients who simply request an STD test and deny any bleeding or pain – the pelvic exam is an antiquated and unnecessary procedure.


Reid K Smith, M.D.
Sinai-Grace Emergency Medicine


  1. Schoeman SA, et. al. Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study. BMJ 2012; 345:e8013. PMC3520545.
  2. Stewart CM, et. al. Assessment of self taken swabs versus clinician taken swab cultures for diagnosing gonorrhea in women: single center, diagnostic accuracy study. BMJ 2012; 345:e8107.
  3. Fine, P, et. al. Vaginal swab performance on the BD Viper System with XTR technology (extracted mode) for detection of Chlamydia trachomatis and Neisseria gonorrhea at family planning/OB/GYN collection sites – perspectives in clinical care. Presented at 25th clinical virology symposium. Daytona Beach, FL, April 2009. Available at https://www.bd.com/ds/technicalCenter/whitepapers/lr222943.pdf.
  4. Available at https://www.bd.com/ds/technicalCenter/charts/ch_1_222801.pdf
  5. Chernesky, MA, et. al. Women find it easy and prefer to collect their own vaginal swabs to diagnose Chlamydia trachomatis or Neisseria gonorrhea infections. Sex Transm Dis. 2005 Dec;32(12):729-33. PMID 16314768.
  6. Rapp, JR et. al. Recommendations for the Laboratory-Based Detection of Chlamydia trachomatis and Neisseria gonorrhea. MMWR 2014; 63(RR02);1-19. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6302a1.htm

* The primary issue with these studies is the use of the term ‘sensitivity.’ With a ‘gold-standard’ (although the authors rightfully avoid using the term), that is essentially a different version of the tested NAAT assay, these papers cannot really be used to make any population-based assumptions on GC/chlamydia testing/symptomatology. The authors do so anyway. In other words, when using two tests with similar characteristics in a population with very low disease prevalence, assigning a sensitivity to one of those tests is rather arbitrary – or, at least, it’s different than what we typically think of as ‘sensitivity’. In fact, the true sensitivity is really determined by the NAAT assay manufacturers. However, GC/chlamydia swabs are the prototypical screening test that doesn’t even require a confirmatory assay in practice. We desire higher sensitivity at nearly all costs. Always keep in mind that even high sensitivities begin to fail in populations with a low prevalence of disease. There are a lot of implications here – again, sensitivity is a misleading term if not understood correctly. The reality is that all of the above is purely academic for an ED practice, where we tend to treat prior to results – which are never reflexed to any confirmatory test.

Low Dose Ketamine for Analgesia – Dr. Smith


Synthesized at Wayne State in 1962, ketamine is a non-competitive NMDA antagonist used most often for moderate sedation and as part of rapid sequence induction (RSI). When used at such doses – generally greater than 1mg/kg IV – ketamine has amnestic, sedative, and profound analgesic properties. Ketamine is used extensively on the battlefield by US forces for analgesia in combat-ineffective troops requiring medical evacuation.1 One review of combat analgesia characterized ketamine as “an almost ideal analgesic because of its profound pain relief, its potentiation of opioids, its role in preventing opioid hyperalgesia, and its large margin of safety.”2

This discussion and review will be limited to IV, low dose ketamine (LDK) given for analgesia – although it can also be given IM and IN (especially helpful in the prehospital, pediatric, or agitated patient setting). LDK has been evaluated for all variants (MSK, abdominal, trauma) of acute and chronic pain encountered in the ED. Ketamine affects several other neurotransmitters (including opioid mu receptors) in addition to NMDA receptors, which remain largely unaffected at LDK doses. This may explain why dissociation does not occur at LDK doses, while analgesia and opiate potentiation remain.

LDK is sometimes termed “sub-dissociative dose” ketamine (SDDK). This is somewhat improper; all LDK falls within the sub-dissociative dose range, but not all sub-dissociative ketamine is LDK. As an example, 0.7mg/kg of ketamine may not dissociate your patient, but it will do far more than provide anesthesia.3 At present, many hospitals limit the use of ketamine to procedural sedation, as most systems classify it as a general anesthetic.

What is the evidence for efficacy of analgesia?

LDK has been very successfully shown to decrease pain scores, both in conjunction with morphine4,5,6,7 and as a standalone treatment.3,8,9,10 It appears to be non-inferior to morphine when used alone at doses of 0.15 or 0.3mg/kg. Onset usually occurs in 1-3 minutes and effects are observed for approximately an hour and a half, with peaks observed in the earlier portion of that time period.8,9 Ketamine has been shown to potentiate the effects of morphine, and has been uniformly shown to reduce required doses of morphine when administered together.5 Two studies that asked patients whether they would like to receive LDK for similar pain in the future found 67% and 85% patients answering in the affirmative.7,10

One recent literature review of four randomized-controlled trials of LDK did discuss two trials with somewhat equivocal results. The first of these showed LDK to be non-inferior to fentanyl.11 The second found that patients pre-medicated with 0.1mg/kg of morphine who then received 0.2mg/kg ketamine required significantly fewer rescue doses of 3mg morphine (1.0 vs. 2.3), but showed no change in their VSAS scores – a finding that is difficult to explain.12

Bottom Line: LDK plus morphine provides better pain relief than morphine alone and reduces opiate consumption. Because high-quality evidence for this indication is more numerous, most new ED LDK policies may limit LDK to opiate-refractory pain or combination therapy. However, LDK alone certainly provides efficacious analgesia, certainly potentiates and decreases subsequent opiate requirements, and is likely non-inferior to morphine when used alone.

A truly large-scale, DB-RCT is needed to more convincingly elucidate whether LDK analgesia is superior to morphine when used alone. Miller (2015) and Beaudoin (2014) provide good templates for a larger-scale trial.

Which doses are best supported by evidence?

LDK doses range from 0.1-0.4mg/kg. Anecdotally, many physicians support a starting dose of roughly 0.1-0.2mg/kg. Side effects appear to be dose-dependent.5 Ketamine should be pushed slowly over at least one minute, which some authors feel reduces the likelihood of immediate side effects such as disorientation.

Most controlled studies dose ketamine at 0.15 or 0.3mg/kg, as these are the well-studied doses in post-op anesthesia literature.5 Ahern (2015) followed initial doses with a 20mg/hr infusion with good results, increasing analgesia duration to 120 minutes with pain scores that appear superior to push-dose only LDK, although with no control group.7

‘Recreational’ dosing traditionally starts around 0.4mg/kg, so dosing higher than that runs the risk of placing your patient in the recreational “K-hole”.

Bottom line: Dosing of LDK has been effectively studied from 0.1-0.3mg/kg, with some studies using a uniform 10mg or 15mg dose.

A large-scale, DB-RCT is still needed to effectively determine an optimal dose, whether weight-based dosing is required, and what rate should be used. LDK infusions have a theoretical advantage, but require more research.

What side effects/ADE will not occur?

Anticipation of emergence reactions is the number one reason why physicians fear use of LDK in the ED.10 However, emergence reactions are nearly impossible with properly dosed LDK, and none were reported in any study.3,4,5,6,7,8,9,10,13 Ketamine does not increase ICP.14 It does not inhibit respiratory drive to the point of apnea at any dose.14,15,16 Up to 100-fold (50mg/kg) overdoses have been reported with no adverse events other than prolonged, otherwise typical sedation.8,16 

What side effects/ADE will occur?

By far, the two most common side effects are dizziness and mild dysphorias, sometimes referred to as ‘psychomimetic reactions’ and including ‘disorientation’ or ‘negative feelings’. Mild dysphoric events are far shorter and less severe than true emergence reactions.13 The incidence of these ranges from 3-15%, depending on the study’s definition and reporting, as well as dose.5,8,9,13 They typically occur immediately after administration and quickly resolve. They appear to be dose-dependent, but that dose may differ per patient.5 An approach where you literally prepare and coach the patient through the experience prior to giving the medication has, anecdotally, been shown to reduce the incidence of the patient experiencing an emergence or psychomimetic reaction.10,13

Dizziness is, by far, the most common ADE, reported in roughly 20% of patients in RCTs polling patients on side effects.8,9 Another study showed dizziness in 45% and 53% of patients immediately after receiving .3mg/kg; of note, 31% of patients receiving morphine had the same complaint.5,9

In one large (n=530), retrospective chart review, the following notable findings were shown; 6% of patients experienced an adverse event documented in the chart. 7 patients (1.5%) developed transient hypoxia – 4 of those also received hydromorphone and all but 1 (COPD requiring BiPAP) resolved with 2L NC. 18 patients (3.5%) developed “psychomimetic/dysphoric disturbances” which included dizziness or bad dreams; only 3 of those received benzos and disposition was unaltered in all of them. 5 patients (1%) experienced emesis, with no cases of documented or concern for aspiration.13 While this study was limited by its retrospective design and lack of dosing protocol, its strength is that, presumably, only clinically apparent ADEs were documented. This, in addition to the fact that lower doses tended to be used, likely account for the decrease in ADEs. Most importantly, any incidents of true emergence phenomenon, laryngospasm, apnea, or cardiac arrest would certainly have been detected if they occurred. None did.13

Multiple studies comparing ketamine to morphine find adverse event rates to be similar; these events are dizziness and dysphoria in ketamine, nausea and respiratory depression in morphine, thereby highlighting the superior safety profile of ketamine as compared to morphine.

Bottom line: LDK is most certainly safe, and all of the common side effects appear to be benign. There were no incidences of emergence reaction, laryngospasm, apnea, cardiac arrest, or anything requiring alteration of disposition documented in any study. Dizziness and mild dysphorias – also termed disorientation, feelings of unreality, negative feelings, or psychomimetic reactions in various studies – are the most common side effects. When compared head-to-head with morphine, adverse event rates tend to be similar. Obviously, side effects for opiates are neither uniformly benign nor uncommon.

When is LDK indicated?

LDK should be considered any time your patient is in pain. It should be considered for patients who do not want to receive narcotics (i.e., previous addicts), patients who are hypotensive or have a tenuous respiratory status, patients with difficult-to-control pain (i.e., chronic opiate-tolerant, sickle cell, oncologic), or patients in whom opiates would worsen their condition (i.e., constipation).3,8 Furthermore, there is some evidence that ketamine prevents the “wind up” phenomenon seen in chronic pain, and may have long-lasting analgesic effects in patients with chronic pain.10

Additionally, LDK can be used in concert with opiates in patients who might require more opiates – either due to tolerance or injury – than could be safely administered without concern for respiratory depression in poorly monitored areas of the ED.1

I hope this provides some good evidence to you for the practice of using low dose ketamine for analgesia.

Reid K Smith, M.D.
Sinai-Grace Emergency Medicine


  1. Dickey N, Jenkins D, Butler FK. Prehospital use of Ketamine in Battlefield Anesthesia 2012-2013. 2012. Available at http://www.specialoperationsmedicine.org/documents/TCCC/06%20TCCC%20Reference%20Documents/DHB%20Memo%20120308%20Ketamine.pdf
  2. Black IH, McManus J. Pain Management in current combat operations. Prehosp Emerg Care 2009; 13(2):223-7. PMID:19291561
  3. Beik N, Sylvester K, Rocchio M, and Stone MB. Evaluation of the Use of Ketamine for Acute Pain in the Emergency Department at a Tertiary Academic Medical Center. Pharmacology & Pharmacy 2016; 7:19-24. http://dx.doi.org/10.4236/pp.2016.71003
    – Retrospective chart review, n=25. Many patients received opiates as well. Poor, retrospective methods, however no significant ADE.
  4. Jennings PA, et. al. Morphine and Ketamine Is Superior to Morphine Alone for Out-of-Hospital Trauma Analgesia: A Randomized Controlled Trial. Ann Emerg Med 2012; 59(6):497-503. PMID:22243959.
    – Pre-hospital, open label RCT, n=135, MS 5mg followed by initial 10-20mg LDK and 10mg LDK q3m until resolution (mean 40.6mg), vs. 1-5mg MS q5m. MS + LDK was superior.
    – “Emergence phenomenon was reported by paramedics in 4 of the ketamine group… which included symptoms such as dysphoria, agitation, and hallucinations.” These sound like mild, dysphoric events. Given the overwhelming evidence in other trials where no such reactions were found, and the fact that these are not described as true emergence reactions and required no medications, I’ve not characterized them as such. It should also be noted that the mean amount of ketamine administered in this trial was likely higher than the total administered to any single patient in any other study reviewed here.
  5. Beaudoin FL, et. al. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med 2014; 21(11):1193-1202. PMID:25377395
    – DB-RCT, n=60, 0.1mg/kg MS vs. MS + 0.15mg/kg LDK vs. MS + 0.3mg/kg LDK.
    – Reviewed at recent SGH journal club. LDK + MS superior to MS alone for pain reduction. No emergence reactions.
  6. Lester L, et. al. Low-dose ketamine for analgesia in the ED: a retrospective case series. Am J Emerg Med 2010; 28(7):820-7. PMID:20837262
    – Retrospective chart review, n=35, early (2004-2006) case study in which LDK was primarily used for abscess drainage in opiate-tolerant patients in conjunction with opiates. No significant adverse events.
  7. Ahern TL, et. al. Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain. Pain Med 2015; 16(7):1402-9. PMID:25643741
    – Descriptive observational, n=40. LDK IVP of 15mg, followed by 20mg/hr infusion. 436 of 456 observed sedation scores were minimal sedation, 20 were mild sedation. No deep sedation. No ADE beyond dizziness, ‘feelings of unreality’. 85% of patients were satisfied.
  8. Miller JP, et. al. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med 2015; 33(3):402-8. PMID:25624076.
    – DB-RCT, n=45, MS 0.1mg/kg vs. LDK 0.3mg/kg
    – Found nearly no difference between 2 groups, with onset of relief faster with LDK. ADEs were equal by incidence, none severe.
  9. Motov S, et. al. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med 2015; 66(3):222-9. PMID:25817884
    – DB-RCT, n=90, 0.1mg/kg MS OR 0.3mg/kg LDK. No serious ADEs. There were essentially no differences between groups.
  10. Richards JR, Rockford RE. Low-dose ketamine analgesia: patient and physician experience in the ED. Am J Emerg Med 2013; 31(2):390-4. PMID:23041484
    – Descriptive observational, n=24, study of patients receiving LDK, pain reduced from 8.9 to 3.9 and 67% of patients would receive it again. No emergence reactions.
  11. Sin B, Ternas T, Motov SM. The Use of Subdissociative-dose Ketamine for Acute Pain in the Emergency Department. Acad Emerg Med 2015; 22(3):251-7. PMID:25716117
    – Review of 4 LDK RCTs. The trials were very heterogeneous with entirely different methods and outcomes; this was not a meta-analysis. In their discussion, the authors admit that “the review suggests… limited evidence to either support or refute” LDK, however they acknowledge that the reviewed studies had “small sample sizes” and “various methodologic flaws” including unclear documentation and missing data.
  12. Galinski M, et. al. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med 2007; 25(4):385-90. PMID:17499654
    – DB-RCT, n=65. All patients given 0.1mg/kg MS, followed by 0.2mg/kg LDK or placebo. The mean number of 3mg MS rescue doses was significantly decreased (1.0 vs. 2.3) in the LDK group, however, the average VSAS between the two groups showed no difference. Poor ADE reporting.
  13. Ahern TL, et. al. The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED. Am J Emerg Med 2014; 33(2):197-201. PMID:25488336
    – Retrospective chart review, n=530, of patients receiving LDK under LDK protocol. “Most” patients received 10-15mg LDK.
  14. Cohen L, et. al. The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review. Am J Emerg Med 2015; 65(1)43-51. PMID:25064742.
  15. Tobias JD, Leder M. Procedural Sedation: A review of sedative agents, monitoring, and management of complications. Saudi J Anaesth 2011; 5(4):395-410. PMC3227310
    – This is an excellent review of procedural sedation agents.
  16. Green SM, et. al. Inadvertent ketamine overdose in children: clinical manifestations and outcome. Ann Emerg Med 1999; 34(4):492-7. PMID:10499950
    – Solicited case reports of 9 cases where peds received 5-, 10-, or 100-fold overdoses of Ketamine. 100-fold OD was a 16kg child who received 800mg of Ketamine. He was prophylactically intubated but at no point showed signs of respiratory depression and his sats remained at 100%. Sedation lasted 9 hours and he was discharged 17 hours after administration.

As a reminder, you can easily access almost any article from any computer by navigating to https://library.wayne.edu/resources/journals/, logging in with your WSU access ID (usually two letters followed by 4 numbers), and searching for the article by PubMed ID (PMID).

Tox Takedown: Tachy with a Good Night’s Rest – Dr Ajani

History and Physical:

It is nearing 10:45pm on New Year’s Eve as you work your swing shift and are dreading being in the ‘hot seat’ for the next resuscitation that might be tweeted in the next 15 minutes. A patient is on his way in with altered mental status, with a last known well of approximately 4 hours prior to arrival. A family member accompanies the patient to the ER who mentions that the patient always gets depressed during the holiday seasons.

H&P pertinent details:

Further history, review of medical record and physical exam findings reveal the patient has a history of hypertension, diabetes, polysubstance abuse and overdose in the past. You determine the patient has 4mm pupils which are reactive and he is not bradypneic. Patient does not have any needle tracks on his arm. Family member did bring his medications to the hospital, which include:

  • Norvasc 10mg po qd,
  • Lopressor 25mg po bid,
  • Lantus 18 units qhs,
  • Lispro 7 units tidac,
  • Seroquel 75mg po qd,
  • Cogentin 1mg po bid, and
  • Aspirin 81mg po qd.

Physical exam reveals:
VS 37.5, 120, 132/89, 18, 95% 2L NC
General: confused, depressed LOC
Neuro: pupils 4mm and reactive, localizes to pain, opens eyes to pain, and mumbles incomprehensible words. Currently controlling secretions.
Skin: no obvious signs of IVDA, non-diaphoretic

The EKG is obtained:



Differential Diagnosis:

As you decide to cancel your post-work night-cap with your man squeeze, you consider the pharmacologic differential diagnosis for this patient. Let’s consider the adverse drug events for this patient’s medication list:

  • beta blocker: bradycardia, hypotension, altered mental status (from tissue hypoperfusion), bronchospasm, hypoglycemia (relative to stress level), vasoconstricted (cool to touch)
  • calcium channel blocker: bradycardia, hypotension, altered mental status (from tissue hypoperfusion), diaphoresis/warm to touch (vasodilation), ileus
  • anticholinergic: hot/bilnd/red/dry/mad, tachycardia. (Classic pimping question: how do you differentiate
  • sympathomimetic overdose vs anticholinergic overdose? From the skin exam! Sweat glands need acetylcholine to work)
  • alpha blocker: hypotension, reflex tachycardia, erection, small pupils (sometimes)

The next thing of course is to measure a glucose level. Can hypoglycemia present this way? Of course it can! Often, patients who are hypoglycemic have a surge of sympathetic activity and can be tachycardic, diaphoretic, and obtunded. However, the nurse in the resuscitation bay tells you that the fingerstick glucose measurement is 70.

You look at a sleepy patient that is breathing and tachycardia and the pupils are small. You look up at your attending and say “I don’t know WTF is going on!” but then you remember THIS tox takedown. This is classic sleepy-tachy. You look at the med list for any potential culprits (all the anti’s antihistamine, anticholinergica, antidepressant, antipsyhotic) and find the likely suspect: QUETIAPINE.

EKG findings of isolated atypical antipsychotic overdose:
Prolonged QT = 6g of quetiapine
Prolonged QTc => risk of Torsades de Pointes, though unlikely if patient gets proper supportive care
Torsades risk increases with bradycardia (due to relative prolongation of QTc)


Antipsychotic medications are largely classified as:
Typical (1st generation). Table 1.

Table 1

  • high or low potency based on binding to D2 receptor
  • good for positive symptoms, not good for negative symptoms
  • can have cross-reactivity with M1 cholinergic receptor (olanzapine/quetiapine/colazpine)
  • peripheral tissue effects (block alpha-1 receptor leading to hypotension
  • block K channel in heart leading to prolonged QT).

Table 2

Atypical (2nd generation)

  • Often affect multiple neurotransmitter subtypes


First, the obvious. Focus on ABC’s. The fingerstick glucose was 70, and you’re unsure if this is a relatively low value for the patient, so you offer him an amp of D50 without any change. He is a gentleman, so he accepts. You also consider naloxone.

To effectively treat anti-psychotic overdose, you must first understand how antipsychotics work. As many antipsychotic medications have cross-reactivity with multiple neurotransmitter subtypes, often the clinical picture is not a clear one. Blockade of histamine receptors and acetylcholine receptors centrally often causes patients to present with a decreased level of mentation (sleepy) and elevated heart rate (tachy). As with anticholinergic overdoses, the patient may also have low-grade hyperthermia (not necessarily ‘fever’) due to ineffective mechanisms of heat dissipation. The etiology of the tachycardia is often multifactorial, from elevated temperature, reflex sympathetic response from hypotension, and anticholinergic effect.

Treatment highlights:

  • IV fluids
  • Temperature control
  • Replete electrolytes
  • Ride out the tachycardia (bradycardia increases QTc relatively, increased risk of Torsades)
  • AC (single-dose activated charcoal) – single dose AC can usually be effective, even if given after one hour of ingestion (delayed gut motility from anti-cholinergic effect)
  • Torsades – treat per ACLS (Mg, overdrive pacing)
  • Physostigmine (reversal of anticholinergic effect) – the ONLY acetyl-cholinerase that crosses blood-brain barrier – for treatment of refractory altered mental status/hyperthermia – Not to be used in patients with prolonged QRS, any heart block, arrhythmia


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