Is there an optimal dose of Ephedrine for the treatment of pediatric intraoperative hypotension?
Myron Yaster MD, Francis Veyckemans MD, and Justin L. Lockman MD, MSEd
Today’s PAAD is a discussion of the intraoperative management of hypotension in children < 6 months of age after the induction of anesthesia with sevoflurane. Hypotension? Hypotension after sevoflurane is expected, so what exactly is ABNORMAL and when does it need to be treated? One of my all time favorite movies, Mel Brooks’ Young Frankenstein has the perfect answer to the question of what is the difference between normal and abby normal. If you’ve never seen this movie you’ve missed one of the funniest comedies ever made… Myron Yaster MD
Original article
Szostek AS, Saunier C, Elsensohn MH, Boucher P, Merquiol F, Gerst A, Portefaix A, Chassard D, Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial. Br J Anaesth. 2023 May;130(5):603-610. PMID: 36639328
At the beginning of each new trainee rotation to pediatric anesthesia, invariably, there’s an overhead call for “Any anesthesiologist to room X!” On arrival to the room, you find the new trainee with a look of panic and a loaded syringe of ephedrine, epinephrine, or phenylephrine in preparation for treating hypotension. In the “voice of command” you say, “Put down that syringe!” and ask the trainee to open the PediCrisis V2 app which provides a table of normal blood pressures by age. Under the treatment tab, the app states that, “Hypotension is almost always treated by correcting hypovolemia and/or by decreasing the anesthetic agent.” [Note: if you haven’t downloaded the free app yet, what are you waiting for? Go to the SPA website or the Apple or Android app store today.] If a pressor is required, the app suggests dopamine or epinephrine as the first line catecholamines to use.
In today’s PAAD, Szostek et al.1 in an elegant prospective multi-centered, dose escalating trial determined that the optimal dose of ephedrine in children < 6 months of age who developed hypotension after induction of general anesthesia with sevoflurane was much higher, 1.2 mcg/kg, rather than the oft-quoted dose of 0.1 mcg/kg. Thus, if you plan on using ephedrine in this age group, the higher dose will be necessary. This is consistent with our [JLL and MY] own experience, which is that ephedrine does not work well enough, or fast enough, to satisfy us for treatment of shock in any patient. I [JLL] usually find myself asking my trainee (after they have given ephedrine ineffectively), “If you think the hypotension needs treatment, why not use a fast, direct acting, and effective medication: epinephrine.”
Thus, after reading this very well designed and conducted study, we were left wondering, “Why ephedrine?” And, “What is the threshold for treatment with ephedrine?” Finally, “When should anesthesiologists switch to epinephrine?” The authors state in their introduction that epinephrine (and norepinephrine) administration requires a “central venous line” for administration. Really? We 100% disagree. While all vasopressor infusions can be dangerous to administer for very long via peripheral IV, bolus dose epinephrine can be (and is) administered peripherally, intraosseously and even, albeit the least reliable route, via an endotracheal tube.2 There is a good reason why patients experiencing anaphylaxis are given IM epinephrine and not an “ephedra-pen” (if one existed). We believe that epinephrine by IV bolus and/or brief (<4-6 hours is the practice guideline at my [JLL] institution) infusion should be the first line pressor therapy and not the indirectly-acting drug ephedrine. As you recall, ephedrine acts on alpha-adrenergic and beta-adrenergic receptors and displaces norepinephrine from adrenergic terminals, which eventually increases HR and BP.
We do want to acknowledge that there are some cultural issues here. I [FV] note that in many French-European settings, while epinephrine and norepinephrine can be administered via a peripheral vein when a central access is not (yet) available, using these potent drugs for mild hypotension is considered excessive. We [JLL and MY] think the same cultural difference explains the ephedrine use phenomenon in the United States. But this is why language is so critical, and why it’s important to say “shock” instead of “soft blood pressure.” Keep in mind that in Szostek’ study, ephedrine was tested to treat hypotension following induction of anesthesia and not in a “shock” context, a situation where hypotension is usually a late sign in children and even “mild hypotension” is important to treat .
So… what should be the threshold to treat hypotension? Based on a survey of SPA members, Nafiu et al. found that most pediatric anesthesiologists consider a 20 or 30% fall in systolic arterial blood pressure from baseline a trigger to treat.3 The 20% fall is the trigger in the PediCrisis app and was the trigger used in today’s PAAD. An important confounder in pediatrics is also worth noting: determining the baseline blood pressure is challenging. As shown by Weber et al.4 MAP measured at induction is usually higher than when measured in the ward. We should probably be using the latter (ward) pressure as our baseline – when it is documented. Failure to do so could lead to overreaction to an otherwise tolerable fall in mean arterial blood pressure as induction-related anxiety wanes. Moreover, the reliability of the non-invasive measurement of blood pressure, even though used routinely, is problematic when compared with its invasive measurement: both under- and overestimation are possible.5
Ultimately, the effects of hypotension on cerebral hemodynamics may be most important. As we’ve discussed in previous PAADs, this is an area of much ongoing research. Finally, aside from providing more preload with an IV bolus of a balanced salt solution, turning down the sevoflurane may be the most important key in removing a negative inotrope/vasodilator and thereby improving contractility and BP. In this study, patients were induced with 6% sevoflurane and maintained with 3%. We think this is pretty standard practice. However, based on recent studies using EEG to guide anesthetic management, this may be too much.6
Regardless of what your current practice is, we do think this well-done study demonstrates that if you want to keep using ephedrine, you should likely be using more of it. What do you think? Please send your thoughts to Myron and we will publish in the Friday Reader Response.
References
1. Szostek AS, Saunier C, Elsensohn MH, et al. Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial. British journal of anaesthesia. May 2023;130(5):603-610. doi:10.1016/j.bja.2022.12.006
2. Vega RM, Kaur H, Sasaki J, Edemekong PF. Cardiopulmonary Arrest In Children. StatPearls. StatPearls Publishing
Copyright © 2023, StatPearls Publishing LLC.; 2023.
3. Nafiu OO, Voepel-Lewis T, Morris M, et al. How do pediatric anesthesiologists define intraoperative hypotension? Paediatric anaesthesia. Nov 2009;19(11):1048-53. doi:10.1111/j.1460-9592.2009.03140.x
4. Weber F, Koning L, Scoones GP. Defining hypotension in anesthetized infants by individual awake blood pressure values: a prospective observational study. Paediatric anaesthesia. Apr 2017;27(4):377-384. doi:10.1111/pan.13091
5. Dionne JM, Bremner SA, Baygani SK, et al. Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis. The Journal of pediatrics. Jun 2020;221:23-31.e5. doi:10.1016/j.jpeds.2020.02.072
6. Yuan I, Missett RM, Jones-Oguh S, et al. Implementation of an electroencephalogram-guided propofol anesthesia education program in an academic pediatric anesthesia practice. Paediatric anaesthesia. Jul 6 2022;doi:10.1111/pan.14520