Good morning and welcome to another thrilling edition of Throwback Thursday! You know that weird phenomenon when something really emotional happens, like 9/11 or the assassination of JFK, and you remember the exact moment you heard about it and where you were? Well, that happened to me when I first stumbled upon this article while perusing the weekly Lancet. It was 1987, in the pediatrics library at Rainbow Babies & Children’s hospital in Cleveland where I did my pediatrics residency. I have no doubt this article influenced my decision to become a pediatric anesthesiologist (and boy, am I happy about that!).
Anand et al. randomized ventilated preterm infants who were about to undergo surgical PDA ligation to receive a traditional anesthetic consisting of 50% nitrous oxide and d-tubocurarine (the old Liverpool technique), with or without fentanyl (10 μg/kg). Postoperatively, they measured hormonal responses to surgery, such as blood glucose, lactate, adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, among others. These were measured at several time points up to 24 hours. They found that for nearly all measurements, indicators of metabolic stress were elevated in the non-fentanyl group, many of which persisted for many hours postop. Clinically, the group that received fentanyl had less circulatory and metabolic complications. These included (see their Table III) increases in ventilatory requirements, spontaneous bradycardias, and intraventricular hemorrhages, among others. Temperature instability, however, only occurred in the fentanyl group. The publication of this article received widespread attention because it showed that even premature infants maintained hemodynamic stability after administration of such a relatively high dose of fentanyl. Not to mention the anesthetic technique, very common at that time, of not giving any anesthetic other than nitrous oxide.
I was shocked to learn of this non-anesthetic technique, but I then understood why all my NICU babies came back from PDA ligation looking like crap – they were tortured! I remember it took us several days to stabilize them. And who says we should go back to the “good old days”? Progress is inevitable, and it is nearly always for the better, especially in medicine.
For those interested, later that year Anand published another landmark paper with Hickey in the NEJM and is a must-read for pediatric anesthesiologists and pain specialists. I believe these papers, in combination, changed the approach and practice of pediatric anesthesia forever.
Note: Both these articles are still behind a pay firewall. If you cannot access them, let me know (LitmanR@chop.edu) and I will gladly send you a copy. For free.
thank you Myron! Always great to have your perspective here. I forgot about the Robinson/Gregory paper, maybe because it was published before I took notice, or that the Anand paper had the cortisol etc measurements. As far as the neurotoxicity conundrum, see my previous post (polemic) here: https://ronlitman.substack.com/p/february-8-2021
typo in my comment: the newborn fentanyl dose should be 10-12.5 mcg/kg