Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

There are wide-ranging opinions on stress doses of corticosteroids (CS) in patients on chronic prednisone undergoing surgery, largely due to lack of adequately-sized randomized controlled studies.  Most experts seem to agree, however, that the age-old practice of routinely administering very high doses of hydrocortisone (eg, 100 mg IV every 8 hours) with prolonged taper postoperatively is excessive. 1-7

Couple of questions to consider before you decide on stress doses of CS for your patient with CS-induced (not primary) adrenal suppression. First, is your patient likely to have a suppressed adrenal function? And if so, what type of surgery is he or she about to undergo?

As for the first question, keep in mind that exogenous CS suppress the production of corticotropin (ACTH) and can induce adrenal atrophy that may persist for up to 12 months, an effect that’s dependent not only on their dose but also on their duration and may vary greatly from person to person. 2,4

Generally, a daily prednisone dose of 5 mg or less —irrespective of the duration— is considered unlikely to cause adrenal suppression (unless it’s given at bed time) and therefore should not require stress doses of CS.1 Conversely, clinical features of Cushing’s syndrome and prednisone doses of 20 mg or more daily for more than 3 weeks are likely to be associated with hyphothalamic-pituitary-adrenal (HPA) axis suppression.  Due to possible delay in the recovery of the HPA axis after discontinuation of exogenous CS, you should review not only your patient’s current dose and duration of CS but his or her regimen during the previous year. 2

When in doubt, particularly in patients receiving intermediate doses (eg, between 5 to 20 mg of prednisone daily) or duration of CS, testing the HPA axis (eg, by cosyntropin stimulation) has been suggested by some with the caveats that it’s a grade 2C (weak recommendation, low quality evidence) recommendation,7 and the results may not necessarily predict clinical adrenal insufficiency or be available before surgery. 4  

Once you have decided that your patient may be at risk of adrenal insufficiency during the perioperative period, the stress dose and duration of CS will likely depend on the type of surgery: “minor” (eg, inguinal herniorrhaphy); “moderate” (eg, total joint replacement, peripheral vascular surgery) and “major” (eg, pancreatoduodenectomy, cardiac surgery with cardiopulmonary bypass). 

A popular online resource suggests the following:4

  • Minor surgery or local anesthesia: Give only the morning maintenance dose of CS without any stress doses
  • Moderate surgery: Give the usual morning dose plus hydrocortisone IV 50 mg (or equivalent) just before the procedure followed by 25 mg IV every 8 hours for 24 hours, followed by the maintenance regimen
  • Major surgery: Give the usual morning dose plus hydrocortisone 100 mg IV before anesthesia induction, followed by 50 mg IV every 8 hours for 24 hours, tapering the dose by half each day to maintenance.

Alternatively, for minor and moderate procedures, other authors suggest usual daily dose plus hydrocortisone 50 mg IV before incision, followed by hydrocortisone 25 mg IV every 8 h for 24 h, then the usual daily dose.1  Yet others have recommended giving IV hydrocortisone 25 mg/day for 1 day for minor surgeries, 50-75 mg/day x 1-2 days for moderate surgeries, and 100-150 mg/day for 2-3 days for major surgeries.2-4 Whichever regimen you chose, make sure to give the morning maintenance dose.  

Why is less aggressive stress dosing being favored in these patients? Several reasons come to mind, including:

  •  In normal subjects, endogenous cortisol production rarely rises above 150-200 mg /day even in response to major surgery 2-4   
  • High doses of CS, particularly with long taper, may unnecessarily subject patients to adverse effects, such as hyperglycemia and poor wound healing 3,4
  • Published reports of CS-treated patients having complications such as hypotension or even death in the postoperative period have generally only implicated, not proven, adrenal insufficiency as a cause. 1-4

 

Bonus pearl: Did you know that the hypotension of secondary adrenal insufficiency in patients treated with CS is not caused by mineralocorticoid deficiency? Instead, it may in part be related to the action of CS in enhancing vascular responsiveness to vasopressors (eg, catecholamines).2 

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References

  1. Liu MM, Reidy AB, Saatee S, et al. Perioperative steroid management: Approaches based on current evidence. Anesthesiology 2017;127:166-72. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2626031
  2. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin N Am 2003;32:367-83. http://pggweb.com/doc/glucocorticoids.pdf
  3. Salem M, Tainsh RE Jr, Bromberg J, et al. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg 1997;219:416-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243159/
  4. Shaw M. When is perioperative ‘steroid coverage’ necessary? Clev Clin J Med 2002;69:9-11. https://www.ncbi.nlm.nih.gov/pubmed/11811727
  5. Urmson K. Stress dose steroids: the dogma persists. Can J Anesthe 2019;September 23. https://www.ncbi.nlm.nih.gov/pubmed/31549340
  6. Wax DB. One size fits all for stress-dose steroids. Anesthesiology 208;128:674-87. https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2672525
  7. Hamrahian AH, Roman S, Milan S. The management of the surgical patient taking glucocorticoids. Uptodate 2019, accessed October 21, 2019. https://www.uptodate.com/contents/the-management-of-the-surgical-patient-taking-glucocorticoids
Does my patient on chronic prednisone need stress doses of corticosteroids perioperatively?

Does the time of day matter when performing cosyntropin stimulation test on my patient with suspected adrenal insufficiency?

 

No, it doesn’t! Although there is a diurnal variation in serum cortisol level, time of the day does not have an appreciable impact on the synthetic ACTH, also known as cosyntropin (Cortrosyn), stimulation test results.

A 2018 retrospective cohort study found that outcomes from cosyntropin stimulation (CS) testing was not affected by time of the day (0800-1000 h vs 1001-1200 h vs after 1200 h).1

An experimental study involving healthy volunteers with normal adrenal function also found that the time of day of CS testing (250  mcg IV) did not influence the peak or the delta of cortisol levels when measured by immunoassay.2 Similarly, an experiment involving normal volunteers concluded that while compared to testing at 0800 h the afternoon (1600) cortisol response to CS was more pronounced at 5 and 15 min, there was no significant difference in cortisol levels at 30 min.3  Parenthetically, peak cortisol level is usually obtained at 1 h after IV cosynstropin administration.

So if you think your patient should undergo CS testing, there is no reason to wait until the next morning!

Bonus Pearl: Did you know that while the half-life of cortisol is between 70-120 min, the half-life of cosyntropin is only 15 min? 4

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References

  1. Munro V, Elnenaei M, Doucette S, et al. The effect of time of day testing and utility of 30 and 60 min cortisol values in the 250 mcg ACTH stimulation test. Clin Biochem 2018;54:37-41. https://www.ncbi.nlm.nih.gov/pubmed/29458002
  2. Jonklaas J, Holst JP, Verbalis JG, et al. Changes in steroid concentration with the timing of corticotropin stimulation testing in participants with adrenal insufficiency. Endocr Pract 2012;18:66-75. https://www.ncbi.nlm.nih.gov/pubmed/21856601
  3. Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effect of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 72:773-78. https://www.ncbi.nlm.nih.gov/pubmed/2005201
  4. Hamilton DD, Cotton BA. Cosyntropin as a diagnostic agent in the screening of patients for adrenocortical insufficiency. Clinical Pharmacology Advances and Applications 2010;2:77-82. https://www.ncbi.nlm.nih.gov/pubmed/22291489

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does the time of day matter when performing cosyntropin stimulation test on my patient with suspected adrenal insufficiency?