Overview of the PRN

The Perioperative Care PRN represents a diverse group of clinical pharmacists engaged in the spectrum of care for surgical patients. PRN membership includes clinical pharmacists involved in optimizing preoperative medications, emergency medicine pharmacists caring for presurgical patients, perioperative clinical pharmacists, and surgical or critical care pharmacists focusing on postoperative care. You can read more about the current scope and responsibilities of the perioperative care clinical pharmacist in a recent publication of the Journal of the American College of Clinical Pharmacy.¹

The Perioperative Care PRN has numerous opportunities for clinical pharmacists, fellows, residents, and students to become involved. In addition to travel awards provided for both students and residents to the ACCP Annual Meeting, the PRN leadership cultivates the PRN’s growth at the student and resident level. Opportunities include resident journal clubs, student-provided clinical pearls, and development of the student/resident outreach committee.

Follow the Perioperative Care PRN on social media.

Twitter: @AccpPeriopPRN                           

Facebook: ACCP Perioperative Care PRN

Current PRN Officers:

Chair: Eric Johnson, Pharm.D., BCCCP

Chair-Elect: Gourang Patel, Pharm.D., FCCM, BCPS, BCCCP

Secretary: Amanda Giancarelli, Pharm.D., BCCCP, CNSC

Treasurer: Laura Ebbitt, Pharm.D., BCCCP

Research Liaison: Marian Gaviola, Pharm.D., BCCCP

Board Liaison: Suzanne Nesbit, Pharm.D., BCPS, CPE

Current Clinical Issue

Perioperative Steroids and HPA Suppression

Patients receiving chronic steroid therapy may present as a challenge in the perioperative area. Depending on their steroid dose and therapy duration, these patients are at risk of developing adrenal insufficiency or adrenal crisis during surgical intervention. This is remedied by the preoperative administration of supplemental steroids; however, dosing and optimal patient selection for steroid administration are less clear in the literature.

Secretion of the stress hormone cortisol from the adrenal glands is mediated by a negative feedback pathway initiated by the hypothalamus. Corticotropin-releasing hormone, which is released from the hypothalamus in response to stress, acts on the anterior pituitary. This releases adrenocorticotropic hormone (ACTH), which acts on the adrenal cortex. This, in turn, causes the adrenal cortex to secrete cortisol. Exogenous steroid supplementation and a rise in plasma cortisol provide negative feedback to each step of this pathway. Two groups of at-risk patients are those receiving chronic steroid supplementation and those with severe hepatic disease who may have undiagnosed adrenal insufficiency.² Patients may have HPA suppression and be at risk of perioperative complications such as vasodilation and persistent hypotension during and after the surgical procedure.

Physiologic cortisol release is around 8–10 mg daily. In response to stress, illness, or surgical procedures, this amount increases to 50–200 mg daily, depending on complexity and severity.³ Early symptoms of adrenal insufficiency may manifest as altered mental status, abdominal pain, nausea/vomiting, and hypotension. With the progression to adrenal crisis, hypotension often becomes refractory to fluids or vasopressors.⁴

No consensus exists about the exact timeline of onset for HPA suppression. One commonly documented causative regimen is prednisone 20 mg/day (or steroid equivalent) for greater than 3 weeks.⁵

Alternatively, the usefulness of measuring cortisol concentrations to identify patients at risk of symptomatic adrenal suppression has not been shown. In a study by Kehlet and colleagues,⁶ patients receiving preoperative steroids of up to 80 mg of prednisone or equivalent daily were monitored for hypotension. Seven of the 73 patients were hypotensive because of bleeding, sepsis, or anaphylaxis. However, when corticol concentrations were measured, only three of these patients had concentrations less than 15 mcg/100 mL. The study also showed that patients with empirically low preoperative cortisol concentrations were not likely to have hypotension.

Studies using cosyntropin (synthetic ACTH) to stimulate cortisol release have failed to definitively show its effectiveness as a diagnostic tool. A study of 18 patients receiving prednisone for 2 months were given 250 mcg of cosyntropin, after which their plasma cortisol concentrations were measured. The patients were randomized to 100 mg of cortisol versus normal saline before the procedure. No difference was found in hemodynamic parameters, though the study was likely underpowered because of low enrollment.⁷

A 2012 Cochrane review concluded that evidence was inadequate to support the use of supplemental perioperative steroids in patients with adrenal insufficiency. The authors stated that the “daily maintenance dose of corticosteroid may be sufficient.”⁸ However, this review was later retracted after the eligibility criteria and interpretation of the evidence summarized in the review were challenged.⁹

The treatment pendulum continues to swing, with some literature recommending continuing the home steroid dose on the day of surgery and maintaining a high vigilance/awareness for signs of adrenal crisis intraoperatively to trigger treatment.^10,11

Countering this recommendation is the 2016 Endocrine Society clinical practice guideline on adrenal insufficiency.⁴ This guideline places a distinct value on preventing adrenal crisis rather than using a watch-and-treat approach, recommending empiric treatment instead of mitigating the potential adverse effects of short-term overtreatment.

Ultimately, the decision of whether to preemptively treat or defer to symptom presentation is made by the surgical team and anesthesia provider. If the decision is to treat with perioperative steroids, appropriate dosing and duration should be a point of emphasis. A recent review by Liu et al.¹² provides recommendations for steroid dosing on the basis of procedure. Shown below is an adaption of that chart.

HCT = hydrocortisone; IV = intravenous(ly); NaCl = sodium chloride.

References:

1. Patel GP, Hyland SH, Birrer KL, et al. Perioperative clinical pharmacy practice: responsibilities and scope within the surgical care continuum. JACCP 2019 Oct 21. [Epub ahead of print]. Available at https://accpjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jac5.1185. Accessed November 20, 2019.

2. Fede G, Spadaro L, Tomaselli T, et al. Adrenocortical dysfunction in liver disease: a systematic review. Hepatology 2012;55:1282-91.

3. Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am 2003;32:367-83.

4. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016;101:364-89.

5. Jabbour SA. Steroids and the surgical patient. Med Clin North Am 2001;85:1311-7.

6. Kehlet H, Binder C. Adrenocortical function and clinical course during and after surgery in unsupplemented glucocorticoid-treated patients. Br J Anaesth 1973;45:1043-8.

7. Glowniak JV, Loriaux DL. A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency. Surgery 1997;121:123-9.

8. Yong SL, Coulthard P, Wrzosek A. Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev 2012;12:CD005367.

9. Yong SL, Coulthard P, Wrzosek A. WITHDRAWN: Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev 2013;10:CD005367.

10. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg 2008;143:1222-6.

11. Brown CJ, Buie WD. Perioperative stress dose steroids: do they make a difference? J Am Coll Surg 2001;193:678-86.

12. Liu MM, Reidy AB, Saatee S, et al. Perioperative steroid management: approaches based on current evidence. Anesthesiology 2017;127:166-72.