Addisonian crisis prevention
Myron Yaster MD
Before reading today’s PAAD and my introductory comments, I need to give you a pre-pre-introduction explanation. When I wrote the first draft of today’s PAAD on perioperative steroid prophylaxis for adrenal insufficiency,1 I knew my comments would be very controversial. So, I wrote to Britta von Ungern-Sternberg the lead author of the paper to ask her whether she either agrees or completely disagrees with my thoughts. Although, I’ve never met Britta in person, I’ve been an avid admirer of her work and almost always try to feature her articles in the PAAD whenever I see a new one in print. Perhaps as expected, Britta and her colleagues strongly disagreed with my thinking. Rather than publishing the PAAD and waiting for the Friday reader review for their response, I am trying something completely new and presenting both viewpoints today…sort of a PRO CON debate. Depending on your reader responses over the next 2 weeks, I’ll suggest this to the SPA education committee for their consideration. Myron Yaster MD
OK, here goes:
I’m pretty sure you’ve all received the panicked/stressed phone call from the resident/fellow/attending pediatric endocrinologist requesting/demanding hydrocortisone stress hormone coverage for your pediatric patient with either primary or secondary adrenal insufficiency coming for anesthesia for surgery or diagnostic imaging studies. Have you ever wondered why, particularly in the modern era when we give 4 mg or more of dexamethasone to ALL of our patients for PONV prophylaxis? After all, dexamethasone is 25 times more potent than hydrocortisone as a glucocorticoid (100 mg of hydrocortisone = 4 mg dexamethasone) so we are really giving stress steroid doses to ALL of our patients already!. And yes I know that dexamethasone does not have mineralocorticoid activity but does that matter when we are providing or being requested to give hydrocortisone primarily for its glucocorticoid activity? To my mind, giving hydrocortisone on top of dexamethasone was/is, well, nuts. When I received these phone calls, I explained to the resident/fellow/attending endocrinologist that dexamethasone is given routinely to virtually all of our patients, which is usually followed by stunned silence on the other end of the phone. To the endocrinologist steroids are dangerous and overused drugs and should not be given willy-nilly. My explanation that dexamethasone significantly reduces PONV almost never changed the mind of the endocrinologist who requested that a stress dose of hydrocortisone be given anyway. Why?
Further, it’s not even really clear to me if the stress dose is required in the first place, particularly if the patient has continued to receive his/her usual daily dose of corticosteroid.2 Thus, when I read today’s PAAD1 and a previous paper on this topic by the same authors3 I was intrigued. The authors of today’s PAAD disagree and their comments follow.
Original article
Heath C, Johnston A, Siafarikas A, Price G, von Ungern-Sternberg BS. Perioperative steroid prophylaxis for adrenal insufficiency, a single-centre experience. Paediatr Anaesth. 2024 Mar;34(3):274-276. doi: 10.1111/pan.14797. Epub 2023 Nov 10. PMID: 37947252.
Original article
Heath C, Siafarikas A, Sommerfield A, von Ungern-Sternberg BS. Peri-operative steroid management in the paediatric population. Acta Anaesthesiol Scand. 2021 Oct;65(9):1187-1194. doi: 10.1111/aas.13952. Epub 2021 Aug 4. PMID: 34263943.
“Patients with adrenal insufficiency are at risk of adrenal crisis, a potentially life-threatening emergency in the peri-operative period. Historically, this risk has driven the practice of prescribing stress-dose glucocorticoids. However, there is a lack of standardisation regarding peri-operative stress dose glucocorticoids in pediatric and adult clinical practice.”1,3 In today’s PAAD, Heath et al. provide some guidance.
But first, let’s do a lightning review of the hypothalamic-pituitary-adrenal-axis (HIPPA) pathway, which is activated by acute stress, both physiological and psychological. “Corticotropin-releasing hormone (CRH) produced by the hypothalamus stimulates the release of adrenocorticotropic hormone (ACTH) in the anterior pituitary gland, subsequently signalling glucocorticoid (cortisol) release from the adrenal glands.”1,3 And as we hope you remember, “cortisol has many physiological roles including activation of gluconeogenesis, immune system modulation, catecholamine production, maintenance of cardiac output and enhancement of vascular tone.”1,3 “In the anaesthetized patient and in the immediate peri-operative period, the cardinal feature of adrenal crisis is hypotension which is poorly responsive to fluid or vasopressor therapy.”1,3 If untreated, this can lead to shock which may be fatal. “The mechanisms of HPAA activation in the perioperative period include hypovolemic stimulation of baroreceptors, direct afferent stimulation, cytokine release from traumatized tissue and psychological stress from postoperative pain and fear.”1,3 Finally, as discussed in Myron’s introduction, it’s not really clear if the stress dose is required at all, particularly if the patient continues to receive his/her usual daily dose of corticosteroid.1
So, if you are going to treat with hydrocortisone or prophylax who should get it and what dose should you use? “The authors recommend perioperative stress dose glucocorticoids in all pediatric patients with known diagnosis of primary or secondary adrenal insufficiency undergoing any sedation or general anesthesia irrespective of procedural invasiveness. Furthermore, the authors would suggest no peri-operative stress dose steroids should be considered in pediatric patients on glucocorticoid therapy for a period of less than 4 weeks, for an indication other than adrenal insufficiency, undergoing any sedation or general anesthetic. In these cases, emergency steroid medication should be readily available. The risk benefit approach is particularly applicable to the management decision regarding perioperative stress dose glucocorticoids for pediatric patients undergoing sedation or general anesthesia for any procedure who have been on glucocorticoid therapy for a period greater than 4 weeks at a dose equivalence of greater than 10 mg/m2 hydrocortisone. In all these patient groups, in addition to the clinical decision regarding perioperative stress dose glucocorticoids, the other key management issue is ensuring appropriate clinical monitoring continues into the peri-operative period, in particular the first 48 h postoperatively when cortisol levels have been shown to be higher than baseline and patients remain at risk for an adrenal crisis.”1
On the other hand, in patients receiving dexamethasone for PONV prophylaxis, which is just about everyone, I (MY) disagree and think it is completely unnecessary to provide additional hydrocortisone.
Reply from Aris Siafarikas, Chloe Heath & Britta von Ungern-Sternberg
While Myron’s is a very valid point of view, we would like to highlight the following: Practice varies widely across countries and institutions, so we believe it is going too far to generalize that ALL patients routinely get 4 mg of dexamethasone. While it is indeed commonly prescribed in the institutions we are working in or have worked in, it is not administered to everyone. In fact, with the increasing choice of TIVA, the indication for a second PONV modality is not necessarily evidence-based for a lot of patients, and the use of dexamethasone will be even more varied. Furthermore, variation is even more increased by the standard paediatric practice of weight-based dosing of drugs. Particularly in our youngest patients, who tend to be those at highest risk, dosing with hydrocortisone is a much more accurate choice than an approximate dose with dexamethasone for PONV prophylaxis.
This clearly shows that it would be a dangerous idea to stop following the evidence-based practice to give hydrocortisone to children at risk of adrenal crisis on the basis of a mere assumption that anaesthetists will routinely give a drug for a completely separate indication.
In response to the second argument of the merit of dexamethasone vs hydrocortisone based on the different potency and glucocorticoid activity. We have to remember, in crisis, the electrolyte derangement and hemodynamics are influenced by the mineralocorticoid activity which is only provided by hydrocortisone. In the absence of sufficient crystalloid replacement and electrolyte management, increased renal sodium excretion and dysregulation of potassium can be problematic. The substitution of hydrocortisone is a much better physiological profile compared with dexamethasone administration. Additionally, the shorter half-life for hydrocortisone leads to more flexibility in dosing and a reduced concern about accumulation and staggering, thus improving safety.
So what’s the verdict? We agree, we should not give dexamethasone on top of hydrocortisone, but instead we should be using hydrocortisone for this population in line with the available evidence. Why should our patients settle for an inferior option just because it might fix some issues related to adrenal insufficiency? With regards to PONV, there are other choices of anti-emetic agents one could administer if required. So let’s go with the evidence and treat our patients with the optimal agent.
What do you think? What do you do in your practice? Send your responses to Myron who will post in a Friday reader response.
References
1. Heath C, Johnston A, Siafarikas A, Price G, von Ungern-Sternberg BS. Perioperative steroid prophylaxis for adrenal insufficiency, a single-centre experience. Paediatric anaesthesia 2024;34(3):274-276. (In eng). DOI: 10.1111/pan.14797.
2. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Archives of surgery (Chicago, Ill : 1960) 2008;143(12):1222-6. (In eng). DOI: 10.1001/archsurg.143.12.1222.
3. Heath C, Siafarikas A, Sommerfield A, von Ungern-Sternberg BS. Peri-operative steroid management in the paediatric population. Acta anaesthesiologica Scandinavica 2021;65(9):1187-1194. (In eng). DOI: 10.1111/aas.13952.