Setting: ED
CC: confusion, lethargy, and constipation
VS: R: 12 breaths/minute; BP: 145/94 mm Hg; P: 86 beats/minute; T: 97.8°F
HPI: A 34-year-old man is brought to the ED by his family because of lethargy. He lives alone and was not answering the phone for several days. His father has to have the lock broken to get into the house. He was found on the floor disoriented and awake only enough to say he is constipated and has abdominal pain.
PMHX: none
Medications: none
“Altered mental status of unclear etiology”: These orders should be written even before doing the physical examination because the physical examination moves the clock forward. Legal drugs (e.g., opiates) kill far more people than illegal drugs, so immediately give the patient naloxone as an opiate antagonist.
Give naloxone (it is always safe in patients with acute altered mental status).
Give thiamine.
Start dextrose.
Order calcium, sodium, glucose, magnesium levels; oximeter; computed tomography (CT) of the head; urine toxicology screen.
Acute opiate withdrawal will not kill the patient!
PE:
Neurological: lethargic, unable to follow commands
Cardiovascular: normal
Abdominal: decreased bowel sounds
Extremities: decreased skin turgor
Do not give flumazenil! Benzodiazepine withdrawal causes seizures.
Initial Orders:
Naloxone, thiamine, dextrose IV stat
NS bolus, then continuous
CHEM-7
CBC, UA, head CT scan
LFTs
Urine toxicology screen
Sodium alters brain neural transmission; potassium does not.
Both renal and liver failure cause encephalopathy.
Order BUN, creatinine, and transaminases levels.
With acute confusion, move the clock forward only 5 to 10 minutes. On CCS, although everything you order is considered to be done instantly, you cannot see the effect of it unless you move the clock forward. For example, if you order naloxone, it is given instantly, but you cannot determine on CCS that it is effective unless you move the clock and do an “Interval History” or occasionally get a spontaneous nurse’s note telling you an update on the status.
You move the clock forward 5 minutes. There is no effect from either the glucose or the naloxone. The bolus of NS is given because the patient is extremely dehydrated. You move the clock forward another 15 minutes to get the results of the serum chemistry, CT, and UA.
One of the great magical things about the Step 3 examination on CCS is that the patient can be in multiple places at the same time. The blood tests, CT, and urine sample will all be listed as obtained at the exactly same time.
Laboratory Test Results:
Total calcium: 16 mg/dL (normal 9−10.5 mg/dL)
BUN: 70 g/dL (normal 7−20 g/dL)
Creatinine: 2.2 mg/dL (normal 0.7−1.2 mg/dL)
Bicarbonate: 21mEq/L
CBC, transaminases, head CT, and urine toxicology: normal
What is the mechanism of altered mental status in this patient?
a. Dehydration
b. Hypokalemia
c. Sepsis
d. Metabolic acidosis
Answer a. Dehydration
Severe hypercalcemia is routinely associated with massive volume depletion. This is why the BUN-to-creatinine ratio is so high. Potassium does not alter CNS neural activity. Potassium will alter cardiac conduction, but not neural conduction. Although there is a slight metabolic acidosis, it does not cause altered mental status.
Acidosis can be caused by renal insufficiency or parathyroid hormone (PTH) inhibiting bicarbonate absorption at the proximal tubule.
Reorder a fluid bolus and run IV fluids continuously. The most important management of severe hypercalcemia is restoring fluid balance. NS by itself increases calcium excretion from the kidney.
Do NOT give furosemide before giving liters of fluid!
Never use thiazides in hypercalcemia: Thiazides increase calcium levels.
What is the mechanism of thiazides in increasing calcium levels?
a. They increase calcium reabsorption at the distal tubule.
b. They decrease calcium filtration at the glomerulus.
c. They increase PTH effect at the bone.
d. They block phosphate metabolism.
Answer a. They increase calcium reabsorption at the distal tubule.
Calcium is reabsorbed at the distal tubule. Phosphate is usually absorbed at the proximal tubule.
As soon as you confirm the presence of hypercalcemia, you should hydrate the patient and give bisphosphonates, as well as look for the cause.
Orders:
PTH level
Phosphate level
Pamidronate
Re-bolus NS
You move the clock forward 1 hour. Move this patient with acute, unresolving mental status changes to the ICU and give him more fluids. Bisphosphonates, such as pamidronate or zoledronic acid, will take 1 to 3 days to work, so any effect you see on improvement of the calcium level in the first few hours is entirely due to NS increasing the excretion of calcium at the kidney.
What is the mechanism of massive volume depletion in hypercalcemia?
a. Blockage of ADH production in the hypothalamus
b. Blockage of ADH release from the posterior pituitary gland
c. Blockage of ADH effect on the collecting duct in the kidney
d. Constriction of the afferent arteriole
Answer c. Blockage of ADH effect on the collecting duct in the kidney
ADH stimulation of the kidney needs normal calcium and potassium levels. Hypercalcemia causes nephrogenic diabetes insipidus (NDI).
Hypokalemia and hypercalcemia cause nephrogenic NDI.
After 2 hours, the patient wakes up somewhat but is still lethargic. He complains of abdominal pain.
Laboratory Test Results:
Calcium: 14.7 mg/dL
Phosphate: 1.5 mg/dL (normal 2.4−4.1 mg/dL)
PTH: elevated
Bisphosphonates inhibit osteoclasts in the bone.
What is the mechanism of high calcium causing lethargy and constipation?
a. Inhibition of acetylcholine reuptake at the neuromuscular junction
b. Somatostatin release
c. Raising the threshold for depolarization of neural tissue
d. Blockade of β-receptors
Answer c. Raising the threshold for depolarization of neural tissue
High calcium levels inhibit neural hyperexcitability. High calcium levels move the threshold for depolarization higher and farther away from the resting membrane potential.
High Calcium Level = Short QT on ECG
Low Calcium Level = Prolonged QT on ECG
Because of the continued high calcium level and the persistence of symptoms despite hours of hydration, you give calcitonin. Calcitonin works much faster than bisphosphonates, but will wear off.
Calcitonin rapidly inhibits osteoclast activity.
After giving calcitonin, move the clock forward 2 to 4 hours. Continue to give NS in large volumes. You will only give furosemide if the person is not producing urine. This is entirely possible because hypercalcemia can create severe prerenal azotemia. It can also be associated with CHF.
Loop diuretics increase calcium excretion at the loop of Henle.
By the second hospital day, massive volume replacement of 4 to 8 L should have improved the patient’s mental status. His abdominal pain has improved and he is able to have a bowel movement. Hyperparathyroidism is confirmed again.
Orders:
Consult endocrinology.
Move the patient to a hospital ward.
Continue hydration and bisphosphonates.
Order a nuclear sestamibi parathyroid scan.
Repeat calcium, BUN, creatinine, and phosphate levels.
A nuclear sestamibi scan is to localize which of the four parathyroid glands has to be removed.
Hyperparathyroidism—85% occurs from a solitary adenoma.
Remove it!
PTH:
• Reabsorbs calcium from bone
• Reabsorbs calcium at the distal tubule
• Increases activation of vitamin D
• Blocks phosphate absorption at the proximal tubule
When asymptomatic, you do not need to remove the parathyroid gland unless:
• There is bone disease (osteoporosis).
• There are kidney stones.
• There is decreased renal function.
• Calcium levels are more than 1 point above normal when the patient is younger than 50 years old.
Your case may go as far as rechecking the calcium and phosphate levels after removal of the adenoma. Most cases of hyperparathyroidism present as asymptomatic elevation in the calcium level. This case was to help you understand the key basic science foundations of severe hypercalcemia.