Who needs to be on stress dose steroids and how do you taper them?

This post is about perioperative stress dose steroids, for adult patients, only. 

Who is at risk for perioperative adrenal insufficiency? The goal of stress dose steroids is to prevent hypotension and adrenal crisis/shock. The Society of Hospital Medicine (in one of their great learning modules), states: 

  • Low risk: <5 mg prednisone daily or ❤ weeks of prednisone over the past year
  • Moderate risk: >5 mg prednisone for >3 weeks in the past year
  • High risk: >20 mg prednisone daily for >3 weeks in the past year
  • Obviously, someone with primary adrenal insufficiency is the highest risk. 

What kind of steroid should be used? IV hydrocortisone is the most physiologic (+mineralocorticoid effect) and should be used until the patient can be transitioned back to prednisone/oral steroids. This letter makes an argument for dexamethasone that is interesting–I myself have never seen dexamethasone used for this indication, though. 

Does the kind of surgery affect whether someone should get stress dose steroids? Yes. 

  • Low stress: local anesthesia, ophthalmologic procedures, some small joint or hernia surgeries <1 hour
  • Moderate stress: general anesthesia, open procedures (hysterectomy, hemicolectomy)
  • High stress: lengthy, complex surgeries (CABG, pancreatectomy)
  • Patients at moderate-high risk undergoing moderate-high stress surgeries should be given stress dose steroids in the perioperative period. (Take this with a grain of salt–the objective evidence is very limited and there are good arguments for being even more conservative and only giving steroids to patients at high risk.)
    • Should you test for HPA axis suppression prior to surgery? If the patient is at moderate risk and undergoing moderate or high stress surgery, and you have the time to wait on results, then sure, you can. What test should you use? You can probably get away with an AM cortisol, although the cort stim test is more accurate

How the heck do I taper stress dose steroids? Stress dose steroid tapers, like ALL steroid tapers, are made up. We as a medical community prescribe tapers based on what “sounds reasonable.” What is usually reasonable is something along the lines of: 

  • Moderate stress surgery: 50 mg IV hydrocortisone x1 –> 25 mg Q8H x24-48 hours –> 10 mg prednisone x3-4 days –> usual dose
  • High stress surgery: 100 mg IV hydrocortisone x1 –> 50 mg Q8H x24-48 hours  –> 20 mg prednisone x3-4 days –> 10 mg prednisone x3-4 days –> usual dose 

Some people would advocate going straight from IV hydrocortisone back to the home dose, which is fine if the patient looks clinically well. Patients at higher risk of complications from steroids (hyperglycemia, fluid retention, agitation) should be tapered more quickly and patients at higher risk of adrenal insufficiency should be tapered more slowly.

Medications used to treat hypercalcemia

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Some notes:

Fluids (normal saline) are the first-line treatment for hypercalcemia!

Cinacalcet (brand name: Sensipar) is used for hyperparathyroidism, whether caused by primary hyperparathyroidism or that related to CKD.

Calcitonin is used most often for moderate-severe hypercalcemia (such as in emergent situations when a patient with multiple myeloma comes in with symptomatic hypercalcemia), Paget disease, and postmenopausal osteoporosis. When being used for emergent situations, note that onset of action is ~2 hours and the effect lasts for 6-8 hours. It comes in injection and subcutaneous forms. It also comes in an intranasal form; the pharmacokinetics of that are highly variable/not reliable, but it’s much cheaper.

Bisphosphonates are a class of medication, and can be used for a wide range of indications including moderate-severe hypercalcemia, osteoporosis, adjuvant treatment for aromatase inhibitor-induced osteoporosis (in breast cancer patients), bone metastases, Paget disease, and osteogenesis imperfecta. In acute hypercalcemia, bisphosphonates (usually zoledronic acid or Zometa) are more potent than calcitonin, but take longer to work, reaching max efficacy in 2-4 days. Bisphosphonates are renally cleared so must be used with caution–and may even be contraindicated–in patients with CKD.

Not pictured is denosumab, a RANK-ligand inhibitor that increases bone mineralization and is used to treat osteoporosis. It is not traditionally used to treat hypercalcemia, and there are no formal guidelines on its dosing to treat hypercalcemia, but there are case reports of its use. Unlike bisphosphonates, it is not renally cleared so there are no restrictions for patients with CKD.

How much sliding scale insulin should I give?

The American Diabetes Association goals for inpatient management of diabetes can be found here. The goal fingerstick for non-critically ill patients is 140-180 mg/dL. Even though we don’t always do it (read: rarely do it), it is ideal to calculate a patient’s inpatient insulin regimen based on body weight. Sliding scales should not be the sole form of insulin administration as there is actually no evidence to support their use!

Sliding scale insulin is extra coverage and usually consists of short-acting insulin like lispro (Humalog) or insulin aspart (Novolog). These forms of insulin start working in 15-60 minues and peak in 1-3 hours.

Short-acting insulin vs. regular insulin for a sliding scale? Studies have found that there is no significant difference in outcomes, but generally regular insulin should be used for patients who are NPO, on TPN or continuous tube feeds.

To create an insulin sliding scale, calculate your patient’s “insulin sensitivity factor.”

ISF = 1700/total daily dose of insulin

For example: if someone takes 20 U insulin glargine (Lantus) and 2 U insulin lispro (Humalog) with meals, their total daily dose of insulin is 20 + 2*3= 26. 1700/26=65, so 1 U Humalog for sliding scale would be expected to lower their fingerstick glucose by 65.

The University of Pittsburgh put out a patient safety study with a preset protocol for low, moderate, and high-risk patient sliding scales that can be found here.

Important note: bedtime or “QHS” sliding scales should, generally speaking, be more gentle than mealtime sliding scales, as there is a risk for overnight hypoglycemia.

Testing for adrenal insufficiency: random cortisol level versus cort stim test

Let’s say a patient presents to the medical floor with hypotension and hyperkalemia, and generalized fatigue and weakness. Adrenal insufficiency might be on your differential. What’s the most accurate way to test for it? Can you get away with using doing a random cortisol level?

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Reference

A random serum cortisol level must always be in the context of what time of day it was taken. There are different laboratory cutoffs depending on what time of day the sample was taken. Typically, a morning cortisol level is most helpful. An AM cortisol level >15 mcg/dL is very reassuring that someone doesn’t have adrenal insufficiency. But any level <15 does not exclude adrenal insufficiency! As this case report shows.

A cort stim test (also called ACTH/cosyntropin stim test) involves measuring an AM serum cortisol, injecting 250 mcg of ACTH or cosyntropin, waiting 30 minutes, and then measuring serum cortisol again. An “adequate response” ruling out adrenal insufficiency is  ≥18 to 20 mcg/dL before or after ACTH injection. If there is an inadequate response, you may consider directly measuring ACTH levels or doing other tests to further evaluate for primary vs. secondary adrenal insufficiency.

Note 1: patients with higher levels of cortisol-binding globulin (like cirrhotics or those with nephrotic syndrome) may have lower levels of cortisol, and may be incorrectly diagnosed with adrenal insufficiency using normal cut-off ranges.

Note 2: this doesn’t apply to patients who are really, really sick in the ICU. As this review discusses, critically ill patients are probably relatively adrenally insufficient because they need tons of cortisol to maintain perfusion and create an inflammatory response.

One point that this review makes is:

Our belief is that adrenal insufficiency appears to be unlikely when a random cortisol measurement is greater than 34 μg per deciliter. Conversely, adrenal insufficiency is likely if the serum cortisol level is below 15 μg per deciliter during acute severe illness. For persons with cortisol levels between these two values, a poor response on a corticotropin test would indicate the possibility of adrenal insufficiency and a need for supplemental corticosteroids.

What’s the difference between D2 and D3 for supplementation? And when should you supplement?

I have to look this up myself every time:
D2=ergocalciferol
D3=cholecalciferol

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precisionnutrition.com

One study, albeit small, looked at the effects of vitamin D3 versus D2 supplementation and found that D2 potency is less than 30% of that of D3 and that it has a markedly shorter duration of action. Because the 1,25 form is metabolized in the kidney, D2 is not recommended for patients with CKD or ESRD (D3 should be used). One paper even argues that vitamin D2 should not be sold as a supplement anymore.

Random fact: vitamin D supplementation is a USPSTF grade B recommendation for elderly adults for fall prevention.

Prescribing vitamin D for vitamin D-deficient patients is surprisingly controversial. There are gray areas like what truly counts as “low vitamin D,” racial differences in vitamin D levels (most discussions of vitamin D supplementation are based on evidence in Caucasians), and who should be screened in the first place.

However, here are the quick and dirty guidelines from UpToDate:

Generally, vitamin D deficiency is a serum 25 (OH)D level <20 ng/ml. A couple of specialty societies suggest that a level <30 ng/ml is cause for supplementation in pts >age 65. However people are usually not at risk for osteomalacia unless <10 ng/ml.

Normal adults do NOT need to be screened, but the elderly, those with poor sunlight exposure and malabsorptive disease, should be.

D3 (cholecalciferol) is thought to be more efficacious than D2 (ergocalciferol). Although you will often see someone prescribed 50,000 U weekly followed by 600-800 U daily, there is no evidence behind the 50,000–so you might as well just start them on 600-800 U daily. Vitamin D levels should be monitored every 3-4 months until the target level is met. If someone has malabsorptive disease or isn’t responding to initial treatment, they may require increase of their dose.

How does the cosyntropin test work?

The cosyntropin test is used when adrenal insufficiency is suspected.

At T0, a baseline cortisol level is drawn.

250 mcg of cosyntropin (an ACTH derivative) is administered.

30 minutes later, a repeat cortisol level is drawn.

If the cortisol response is inappropriately low, this suggests adrenal insufficiency.

Further reading: a brief review of the pharmacokinetics of cosyntropin and adrenal insufficiency