Reader response

Myron Yaster MD

From Andrew Davidson MBBS MD FANZCA FAHMS, Medical Director, Melbourne Children’s Trials Centre, Senior Staff Anaesthetist, Department of Anaesthesia, Royal Children’s Hospital, Professor, Departments of Paediatrics and Critical Care, University of Melbourne, Head of Anaesthesia Research, Murdoch Children’s Research Institute, Editor in Chief, Pediatric Anesthesia, Deputy Editor in Chief, Anesthesiology

This trial (Shen F, Zhang L, Wang W, et al. Effect of Intravenous, Inhalational, or Combined Anesthesia Maintenance on Postoperative Respiratory Adverse Events in Children Undergoing Adenotonsillectomy (AmPRAEC): A Multicenter Randomized Clinical Trial. Anesthesiology 2025;143(6): 1484-96. PMID: 40768554) has generated a rather large amount of controversy and many letters. I am glad we published it!

I completely agree with Lynn’s comments here. Indeed I would go further and consider recovery after tonsillectomy to be what is known as a “weak emergent phenomenon”. See editorial written by Annie Xin recently in Anesthesiology (in Xin A, Brasher C, Dünser MW, Gauss T: Insights from Modern Physics. Anesthesiology 2026, 144(1):17–18..)

An emergent phenomenon is something which cannot be explained by breaking it down into its various possible causal factors. The reductionist view of science and biology is that everything should be predictable if we understand the underlying mechanisms, laws of chemistry etc. This is what nearly all scientific research endeavours to do. Some things, like consciousness, cannot be understood with a reductionist view. That is a strong emergent phenomenon. Weak emergent phenomenon are when some causal factors can be identified but there are so many and so many interactions that the reductionist approach just gives you information that is of very little generalizable value. Tonsillectomy recovery is such a phenomenon. Outcome depends on type of anesthetic, dose of anesthetic, analgesia, dose and type and timing, premeds, use of alpha 2 agonists, surgical technique, skill of surgeon, airway management, extubation timing, temperament of the child and the way anesthesia discontinued and so on. These all interact.

There are three possible approaches to the problem. First is to do big multicentre pragmatic trials where you randomise just one element and hope that all the other elements will vary greatly so you gate a sample that represents the wider population. This tells you what to do at a population level where you can assume the better treatment will provide better outcomes on average. This only works if your population truly matches the broader population (they usually dont). It also means you miss out on identifying in which children the treatment works best and when it may, in a few do worse.

Second approach is to continue down the reductionist path in a series of tightly controlled populations. There are a very large number of small focussed trials looking at all sorts of aspects of recovery of tonsillectomy. These are however problematic for all the reasons mentioned above. Are they at all relevant to children with slightly different ways of managing tonsillectomy. They are probably of only marginal value to the broader community, but researchers still churn them out and we keep publishing them. Many rightly ignore these trials but then fret that they are not providing “evidence based care”.

The way “we” generally decide what is evidence is to tend to do a mix of both the above along with other indirect evidence or evidence form basic principles. It isn’t perfect but it is “best we have”. That’s the wonder of clinical anesthesia. How do you synthesise all that indirect evidence to manage the child in front of you?

The third approach is to consider your population as a closed system. In that closed system you will have some, but not a lot of variable practice. You then try different interventions to see which work best in your system. You have no interest in doing reductionist science and no interest in whether or not your tweak can be generalized beyond your closed system. This is of course QI. This is what you do so well in Seattle

From Matthias Koenig, MD, Children’s Hospital of the King’s Daughters, Children’s Specialty Group, Anesthesia Division, Norfolk, VA

Another interesting post here as usual, just wanted to add my 2 cents to it:

“I would like to point out another aspect that sometimes gets lost among advocates of relaxant-free intubations: quality of intubating conditions does actually matter. In a European paper by Mencke et al. (Anesthesiology 2003; 98(5), 1049-1056) the authors performed stroboscopic exams of the larynx of adult patients once before intubation and twice after extubation and also checked for symptoms of airway morbidity for several days post-extubation. The number needed to harm – by not using a relaxant and producing inferior intubating conditions – was frighteningly low, only 2.9! What they found was an inverse relationship between intubating conditions and airway morbidity. IMHO, a similar relationship appears more than likely in pediatric patients, and I would argue that our goal should therefore always be to produce “excellent” intubating conditions. Merely “getting the ETT in” is not an acceptable endpoint here.

From my reading of the literature, no relaxant-free intubation technique has ever been shown to achieve “excellent” intubating conditions more reliably than a relaxant-based technique. To my trainees I put it this way: skipping the relaxant means you are making a conscious decision for the 2^nd best option. All you can hope for now is to achieve similarly good – but not better - intubating conditions.

What I am seeing in my little corner of the pediatric anesthesia universe is that relaxant use is increasing quite a bit since sugammadex became available.”

From Charles Cote MD retired

I am a bit concerned with the recent review of succinylcholine administration here and the need or lack of need for concomitant administration of an anticholinergic agent. I have always recommended atropine prior to intravenous succinylcholine because of 3 cases I experienced over the years. Certainly this is not a case series but rather anecdotal events I have observed that have informed my 40+ years of practice.

The first case occurred when I was a fellow involving a 2-year-old for rapid sequence induction. Immediately after 2 mg/kg of succinylcholine he developed bradycardia and then asystole within about 10-15 seconds. He rapidly responded to chest compressions and atropine. While I was in the Navy, I also had a healthy 42-year-old healthy male develop asystole after a single dose of succinylcholine.

The third case occurred several years later when I was a junior faculty and working with a new resident on our pediatric anesthesia service. His plan was to use succinylcholine for a 12-year-old (this was prior to the black box warning about its routine use). I asked him if he was going to also administer atropine because I had seen asystole following a single dose of succinylcholine. His response was “I don’t need to”. I said “OK but please pay attention.” He proceeded with his thiopental/succinylcholine induction and, being a good resident, he was using his ear-piece to continuously auscultate heart tones. I observed the EKG go from bradycardia to asystole on one screen. I don’t know what got into me but before doing anything I asked him if he heard heart tones. His response was NO with panic in his eyes. I said “OK you press the chest and I will give the atropine”. The patient’s oxygen saturation never went below 100%. He then asked me “How did you know this was going to happen?” and I responded “I have no idea, just experience.”

It is well known that bradycardia is common after a second dose of succinylcholine and exceedingly rare after intramuscular injections. Thus, atropine is surely indicated if a second dose is needed and not indicated if the drug is administered IM. However, the clinical experiences I describe above have informed my practice to always administer atropine even before the first dose of succinylcholine. In a healthy child with a normal cardiovascular system there is virtually no harm with a little prevention so I do not even understand this discussion about avoiding atropine. What is the risk of giving an anticholinergic vs the risk of not giving one?

Fortunately, with the advent of rocuronium and sugammadex, as well as the black-box warning against the routine use of succinylcholine, the incidence of life-threatening events such as hyperkalemia from rhabdomyolysis in male children with undiagnosed muscular dystrophy and malignant hyperthermia, particularly associated with the combination of succinylcholine and halothane, are now quite rare. The indications for the use of succinylcholine are thus now quite limited as well described in the PAAD but it still has a role in our practice for select cases and indications.

Am I the only pediatric anesthesiologist to have ever witnessed asystolic events associated with a single dose of succinylcholine? I am curious about how many others have seen this in their practices.

From Francis Veyckemans MD

Regarding the controversial use of etomidate here in children, I would like to add the following information taken out of two studies.

The first study illustrates the remarkable hemodynamic stability provided by etomidate. This was nicely illustrated in a study published by N Dennhardt [Dennhardt N, Elfgen-Schiffner F-D, Keil O, Beck CE, Heiderich S, Sumpelmann R, Nickel K. Effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease: a prospective observational study. Pediatr Anesth 2020; 30:984-989]. In 50 neonates and infants with a congenital heart disease, there was almost no change in the hemodynamic parameters up to 10 min after induction with sufentanil 0.5 mcg/kg and etomidate 0.4 mg/kg. This is an important issue in children with congenital heart disease, intracranial hypertension or severe trauma, populations in which post-induction hypotension can have deleterious effects.

The second study involved 80 children 3-12 years old undergoing elective urological surgery. The children were randomized to receive either etomidate 0.3 mg/kg or propofol 2 mg/kg. All inductions started around 11 am to take the circadian secretion of cortisol into account. Salivary cortisol was measured in both groups up to 48h after surgery, and compared with the same data in unoperated children. They found that the cortisol levels were lower in the etomidate group than in the propofol and control groups up to 20h after induction. [Du Y, Chen Y-J, He B, Wang Y-W. The effects of single dose etomidate versus propofol on cortisol levels in pediatric patients undergoing urological procedures: a randomized controlled trial. Anesth Analg 2015; 121:1580-1585]. Although this has to the best of my knowledge not been studied in children this effect is probably similar to the one of dexamethasone 0.15 mg/kg (= 4 mg/kg hydrocortisone) that most children receive nowadays in prevention of PONV.

From my point of view, etomidate iss the first choice (in balance with ketamine) if a fragile child needs an IV induction.

From Professor PA Lönnqvist

Here is a little feedback to the PAAD on Etomidate. It says in two places that etomidate is causing injection pain. It is true that older preparations of etomidate did cause frequent injection pain. However, the modern lipid emulsion from B Braun (Etomidate-Lipuro) cause significantly less injection pain than propofol with added lidocaine, as we did show in a RCT in 2006, published in British Journal of Anaesthesia.

Nyman Y, Von Hofsten K, Palm C, Eksborg S, Lönnqvist PA. Etomidate-Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine. Br J Anaesth. 2006 Oct;97(4):536-9. doi: 10.1093/bja/ael187. Epub 2006 Aug 16. PMID: 16914464.

Furthermore, since a lot of children currently are given dexamethasone for PONV prevention, they will be well covered from any minor and time restricted “adrenal suppression” by an induction dose of etomidate.

I agree that it is unlikely that etomidate will replace propofol in routine care but we should not refrain from using a single induction dose when indicated by the clinical circumstances.

For the Beatles loving colleagues I here also provide a recent comment on etomidate use, also published in BJA.

Nyman Y, Lönnqvist PA. Etomidate and its derivatives: time to say goodbye? You say goodbye and I say hello. Response to Br J Anaesth 2025; 134: 11-3. Br J Anaesth. 2025 May;134(5):1561-1562. doi: 10.1016/j.bja.2025.02.016. Epub 2025 Mar 19. PMID: 40113483.