Case

76M pmh alcoholic cirrhosis, COPD presenting with altered mental status, vomiting, and diarrhea. Pt has been on a 3-day cocaine binge with increasing confusion and decreased oral intake. No fevers/chills, hematemesis.

Pt is hypotensive 80/40s despite 1 L. Pt is awake and alert but confused, aox0. Pt hypoglycemic to 45, received D50 with no improvement. K 2.8 but all other labs were normal. 

Pt was started on pressors but no significant improvement in BP.  The patient’s family stated said that the patient is in an out of hospitals for COPD and was recently discharged and has not been able to take his steroids.

The patient was treated with IV hydrocortisone for presumed adrenal crisis and admitted to MICU.  The patient’s mental status gradually improved after a few hours with resolving hypotension and was discharged the next day completely well.

Background

Adrenal glands produced mineralocorticoids, glucocorticoids, and androgens

Adrenal insufficiency affects 1-4/100,000 in the US, 80% from primary addison’s disease, other causes are trauma, drugs, infections, genetic disorders, sudden termination of prolonged glucocorticoid therapy, and pituitary disease (brain tumor/necrosis)

Adrenal insufficiency is extremely difficult to diagnosed in the ED, 44% of cases are diagnosed only after presenting in adrenal crisis

Stressors likely infection, surgery, trauma, emotional stress can exacerbate adrenal insufficiency

Presentation

Insufficiency: general dehydration, weakness, lethargy, AMS, delirium flank/back/abd pain, nausea, vomiting diarrhea, anorexia

Crisis: severe hypotension refractory to IV fluid and vasopressors

Diagnostic Studies

There are no great studies for adrenal insufficiency in the ED, random cortisol levels should not be drawn routinely, cortisol > 34 mcg/dL exclude adrenal crisis and < 15 is suggestive but this test is dependent on the patient’s corticosteroid binding globulin so free cortisol levels are very unreliable

Imaging in the ED is generally not necessary but if there are headaches suggestive of pituitary gland tumor or abdominal pain suggestive of secondary adrenal insufficiency, CTH and CTAP are options that can be used.

Treatment

If adrenal crisis is suspected, steroid should be given

Hydrocortisone 100 IV then 100 mg IV q 8h until acute crisis resolves, usually pt’s hypotension and clinical symptoms improves 1-2hrs after administration of hydrocortisone

50 mg for children 3-12 yo

25 mg IV for children < 3 yo

IVF up to 2-3 L

D5NS can be used as well for hypoglycemia, d50 for severe hypoglycemia

Vasopressors can be used but the patients are often unresponsive

Disposition

Admit to MICU for adrenal crisis

If patient is well appearing and just having weakness or fatigue, the patient can be discharged with followup with an endocrinologist/PMD who can do a normal serum cortisol level and ACTH stimulation tests as well as other extensive testing.

Steroid tapers for chronic steroid users I unfortunately there isn’t an optimal regimen verified by studies

For patients with short term glucocorticoid therapy (less than 3 weeks), you just stop and no taper needs to be given

For more chronic glucocorticoid therapy, it will depend on the dose the patient has been on, infection risk, duration of previous use, danger of underlying illness:

              Taper 5-10 mg/d every week from an initial dose > 40 mg prednisone or equivalent/day

              Taper 5 mg/d every week at prednisone doses 40-20 mg/d

              Taper 2.5 mg/d every two weeks at prednisone 20-10mg/d

              Taper 1 mg/d every 2 weeks at prednisone 10-5 mg/d

Generally we will only give 1-2 week course of medications from the ED, so make sure to do the calculations and give endocrine follow-up

Takeaways

For patients who are chronically on steroids often times for COPD, rheumatoid arthritis, crohn’s, etc. ask when the last time the patient had steroids; the patient might benefit from a steroid taper to prevent withdrawal.

Adrenal crisis is extremely rare and one should not wait for cortisol levels for a patient who is hypotensive and non-responsive to IVF/pressors. (often times, it’s just going to be that septic old patient that comes in with no clear history that’s unresponsive to pressors)

Neuroleptic Malignant Syndrome/Serotonin Syndrome

Let's talk about hyperthemia today, the weird kind. NMS and SS - I often get confused between the two, so this is as much as I can remember:

NMS is SLOW, it happens slowly and takes forever to resolve. Fever + rigidity.

SS is FAST, hyper reflexive and agitated, quick on and relatively quick off. Fever + clonus.

Both have fever/elevated temp. Treat both with benzos. For NMS, add on bromocriptine (SLOW down BRO). For SS, just use the other weird-sounding drug (cyproheptadine).

I think it's also important to learn to recognize potential offending agents when you are doing med recs on patients.

Definitely not a comprehensive list but here are some our patients might be taking (or you are giving them):

NMS

typical antipsychotics > atypicals. Classically, haldol, droperidol, thorazine, pheneragan. Metoclopramide. Less rare but atypicals like clozapine, olanzapine, risperidone, quetiapine, ziprasidone.

SS

sertraline, fluoxetine, citalopram, paroxetine, trazadone, buspirone, venlafaxine, valproate, tramadol, fentanyl, meperidine, ondansetron, metoclopramide, sumatriptan, linezolid, dextromethorphan, MDMA, LSD, St. John’s wort, ginseng.

Check this out for more details and some of the more nitty gritty:

http://www.emdocs.net/toxcard-differentiating-serotonin-syndrome-neuroleptic-malignant-syndrome/

Euglycemic DKA

What is it? 

DKA without the elevated glucose that usually triggers us to think about DKA in the first place. Patients often have blood glucose levels less than 250 mg/dl. 

Why do we care? 

Because untreated DKA can lead to cerebral edema, ARDS, renal failure, shock and death.

Why does it happen?

Euglycemic DKA can occur in any diabetic, but there is a rising incidence in those taking SGLT2 inhibtors (-gliflozins) (listed below). The pathophysiology behind this isn't totally clear yet though there are some theories. 

US approved: Dapagliflozin (Farxiga), Canagliflozin (Invokana), Empagliflozin (Jardiance)

It can also occur in those who have underlying disease that depletes the liver's ability to make glucose (putting those who are pregnant or have long bouts of nausea and vomiting under increased risk).

And of course, think of the usual triggers for DKA (ie infection, alcohol use, etc)

When to suspect it?

In any patient with a history of diabetes, including but not limited to those taking SGLT2 inhibitors, who come in for vomiting, generalized weakness, or SOB. Also consider euglycemic DKA in those who have a metabolic acidosis without other clear cause. Draw serum ketones or obtain urine ketones in these patients. 

Sounds a lot like alcoholic ketoacidosis--how to tell the difference?

History: history of heavy alcohol use vs a diabetic on an SGLT2 inhibitor.

Signs: those with alcoholic ketoacidosis tend to have a very low glucose. 

And maintain a high level of suspicion. 

How do we treat it differently than hyperglycemic DKA?

Overall, we treat it pretty similarly. A key difference is that you will need to start fluids with dextrose initially or much earlier than you would with hyperglycemic DKA. 

Sources

https://rebelem.com/euglycemic-dka-not-myth/

https://emcrit.org/ibcc/dka/#euglycemic_DKA

https://emergencymedicinecases.com/euglycemic-dka/

http://www.emdocs.net/diabetic-ketoacidosis-sneaky-triggers-clinical-pearls/