Hypercalcemia Tuesday April 28th

Hypercalcemia

1.     asymptomatic routine evaluation  (most cases)

2.     symptoms: constipation, weakness, fatigue, depression, nephrolithiasis, osteopenia osteoporosis, polyuria

3.     altered mental status

90% will be from hyperparathyroid and malignancy. In the inpatient setting this will likely be related to cancer. In the outpatient setting, this will likely be related to hyperparathyroidism (an adenoma – a little tumor producing the hormone)

Symptoms of hypercalcemia (made this my self, it’s the best):

Kidney: nephrolithiasis, calcium oxalate, nephrocalcinosis, polyuria (DI – inhibits actions of ADH), AKI (afferent vasospasm)

GI: pancreatitis, constipation, ulcers (increased gastrin levels), increased alk phos

CVS: arrhythmias – shortens the qt, vascular calcification, AS, HTN (part of the workup)

Neuro: depression, decreased LOC, hypo-reflexia, band keratopathy in the eyes

MSK: weakness, bony pain, osteoporosis, fragility fractures, pseudogout

Skin: Calciphylaxis (calcific uremic arteriopathy) calcification of small to medium sized blood vessels of dermis and SC fat – ischemia and necrosis, associated with uremia, increased calcium and phosphate. IV sodium thiosulfate and parathyroidectomy controversial

**side note: Fatigue is a non specific primary physicians may be faced with which has a very large differential and a clear cause may not be found (high percentage of psychiatric illnesses). Consider calcium as part of your metabolic cause.

(in addition to consider a TSH, CBC, lytes, BUN, creat, liver enzymes, consider ECG – CHF?, OSA, etc.)

Different sources have different approaches to hypercalcemia, some refer to elevated PTH (or high normal) or low PTH.

Another way (my preference) is the following

1.     PTH related:

a.     primary hyperparathyroidism (consider MEN I and                                                                                                                                            MEN2A workup)

b.     secondary hyperparathyroidism (with calcium supplements)

c.      tertiary hyperparathyroidism

d.     lithium therapy (occurs in 10% of patients)

e.     familial hypocalciuric hypercalcemia (this always gets mentioned in every differential of hypercalcemia, I’ve never seen a case and don’t think I will, this can be considered after the most obvious causes are considered)

2.     hypercalcemia of malignancy

A.     PTH related peptide (squamous cell carcinoma, adenocarcinoma of lung pancreas, kidney)

B.     Osteolytic metastasis: breast, multiple myeloma

C.     Production of calcitriol (hodgkins lymphoma)

3.     Vit D related

A.     hypervitaminosis D

B.     granulomatous disease

C.      

4.     Other:

a.     milk alkali (patients with CKD on tums or patients with GERD taking tums)

b.     hyperthyroidism (increase bone turnover)

c.      immobility (prolonged bed rest)

d.     thiazide diuretics

e.     falsely elevated: hypergammaglobulinemia, hyperalbuminemia

Note: elevated calcium with a normal PTH is suggestive of primary hyperparathyroidism as in 10% of primary hyperparathyroidism PTH is inappropriately NORMAL.

Secondary hyperparathyroidism is when increased secondary to Vit D deficiency, usually in the setting of CKD. This causing elevated calcium is more rare as more commonly you would expect hypocalcemia. But we do know in the setting of CKD, we initially give calcium carbonate (tums) with meals to bind phosphate and get rid of it in gut, and if they absorb calcium while at it… great! It can be on the low side because of vit D deficiency because of CKD.  Patients may then become hypercalcemic from excessive PTH and all the calcium we are giving them! Subsequently we give them phosphate binders that DO NOT contain calcium such as sevalamer.

So how do we treat hypercalcemia? Below is the suspected cancer related hypercalcemia, typically with levels >3.

Treatment:

Fluids is are go to therapy first, NS 200-500 ml/hr. There are some case reports of giving Lasix but no good evidence. This  really is only considered after a patient is becoming overloaded but fluids and other meds  (to be discussed) may be enough.

*Lasix is more often considered in a patient who might have limited capacity to urinate, however, that paiient may be best suitable for dialysis.

If calcium >3 consider bisphosphonate therapy (pamindronate 60 – 90 mg in 500 mL NS over 4 hrs) Or zoledronate 4 mg in 50 mL NS IV over 15 min, lowers bone pain from lytic lesions and bone mets.  Bisphosphonates take around 24-48 hours to take affect, also may cause ATN so caution with renal failure, no RUSH to give as this will take affect after. Also, they may cause hypocalcemia.. so be careful!

Malignancies may respond to steroids, pred 60 mg po daily x 10 days

Calcitonin 4-8 iU/kg IM/SC BID (tachyphylaxis so generally effective in the first 2-3 days.

Often patients with malignancy related hypercalcemia will have known malignancy at presentation, one small study suggested a 50% mortality rate with hypercalcemia related to malignancy.

The opposite end of the spectrum is primary hyperparathyroidism

Indications for parathyroidectomy?

Asymptomatic? Age <50, calcium >0.25 (normal is 2.5) GFR <60 ml/min, osteoporosis, or previous fragility fracture. Urine calcium >400 mg /24 hours is no longer an indication, but this will put them at higher risk of forming kidney stones.

Fragility fracture: vertebral fractures, fractures of the neck of the femur, and Colles fracture of the wrist

Another reason to consider surgery is issues with adherence or follow up, patients would need to get BMD every 2-3 years as well as follow up for calcium.  If you decide to go for surgery, a bisphosphonate or cinacalcet are drugs that can be used to lower calcium in the meantime, although encouraging po fluids may be sufficient. Dr. Kane pointed out that Cinacalcet may be quiet expensive (400 per month!) – may be covered by some insurance?

Is imaging recommended? Yes, as if imaging can identify a parathyroid adenoma, this will usually decrease the amount of time the ENT specialist spends searching for the tumor in the OR. It is also ideal to have a specialist perform the procedure (one that does parathyroidectomies on the regular). If imaging does not show a tumor… does this rule out primary hyperparathyroidism? NO!

Pamidronate maintains normocalcemia for approximately 2-3 weeks (up to 4 weeks), while zoledronic acid works slightly longer ( for about a month or more). If there is no tumor response to treatment, then patient may need regular infusions of bisphosphonates at approximately 2- to 4-week intervals to treat hypercalcemia. 4

This is an article on some rare causes

http://press.endocrine.org/doi/full/10.1210/jc.2005-0675

Pancreatitis April 24th

As I was away Friday for my rheumatology rounds, Dr. Gregor was nice enough to fill in. He talked about pancreatitis. Please refer to my post on March 12th. The one thing he brought up is genetic/inherited causes of pancreatitis, cystic fibrosis, hypertriglyceridemia (can be associated with diabetes though), IgG4 disease, and some more obscure ones.

So it never hurts to ask about family members with pancreatitis.

Seizure, April 23rd

As mentioned with syncope: consciousness  requires organized electrical acvitiy, glucose, oxygen, and blood pressure (and a conduit to get it there).

So when one here’s the word seizure – form nurse, patient, family member, always clarify what they mean.

Some classic questions you will and should have

Any witnesses? How did it start?

The last thing before they lost consciousness (if they did)

The first thing when they woke up

Déjà vu, nausea, dizziness odd smells (mesial temporal lobe seizure)

Bowel, bladder incontinence, tongue biting.

FYI: often times when a patient has had a seizure, juniors will start off by saying “seizure” and then mentioning that they did NOT have bowel or bladder incontinence. Always start by going over the pertinent positives FOR seizure, especially if that’s the story you are trying to sell.

So what do we do for a patient that is actively seizing in front of us?

ABCs, are they protecting their away?  Do they need to be sedated and intubated?

Ativan IV/IM, midaz IV/IM or diazepam per rectum are options.

Ativan 2 mg IV or IM is a standard starting dose and this should be repeated after 1-2 minutes, it has a quick onset.

An approach to seizure is actually similar to that of delirium!

DIMS! (drugs, infection, metabolic, structural)

Drugs – etoh withdrawal, TCAs, certain antibiotics lower seizure threshold, tox screen

Infection – mengintis and encephalitis are most feared ones,  blood cultures, +/- CT head, LP. Also note, an infection precipate a seizure in a previously controlled patients with epilepsy

Metabolic – hypoglycaemia, hyponatremia, cerebral edema from liver failure, hypocalcemia,

Structural – new stroke, brain mass, AV malformation, lowe threshold for CT head, and potentially MRI and EEG to localize an area.

Blood work to be done when a patient comes in would consist of BG (to look for hypoglycaemia) CBC (very high WBC in meningitis), lytes (hyponatremia, hypocalcemia), BUN/cre, drug levels if they are on seizure medications. Lactic acid if a patient came in with suspected seizure as it is often very high. CK to look for rhabdo

So now you’ve confirmed a seizure based on presentation, response to Ativan, consider the causes as above with DIMS. Consider stroke or bleed in people over 65 with new onset seizure, ask about family history in a child, look for neurocutaneous disease tuberous sclerosis, sturge weber.

O/E make sure patient is maintaining airway, often patients are drowsy in the post icatal period (or the benzos have kicked in). you can still examine pupils for asymmetry, can they localize with sternal rub? Response to nail bed pressure? Rigidity, reflexes? We may see a todd’s paralysis which is an are of brain that needs to wake up post seizure.

In someone with previously controlled seizure, always try to figure out what tipped them over this time, not JUST about controlling it. Similar to previously controlled afib, are they septic now, new heart failure, dehydrated, etc. So not JUST to give beta blockers and call it a day.

Driving: single unrpvodked seizure, normal eeg AND mri, NO REStricitons, usually no meds

So after you’ve controlled the new onset seizure, you then will consider loading them with phenytoin.

Phenytoin – 15 mg/kg, for a 70 kg man 1 g. Run it 50 mg /min, if faster lower BP (in fact if its low slow it down). Put them on a monitor, be careful of patients with cardiac arrhythmias, give with normal saline, it will precipitate if given with dextrose (nurse should have protocol for this). Nystagmus on lateral gaze, good sign they are taking the meds! Gait ataxia and lethargy signs of toxicity. Hirsutism, gingival hyperplasia, Metabolized by liver so not usually a problem in renal failure, megaloblastic anemia, osteomalacia, drug induced lupus. Be aware of hypotension from giving the med too fast, an expected response, just slow down the rate.

Carbamazepine:  600-1200 mg/day leucopenia, thrombocytopenia, hyponatremia, hepatic dysfunction

Dose of phenytoin is 300 to 400 mg /day. Drug level 10-20 albumin can alter it. Check level to see what level they are controlled at.

Status epilepticus, we used to say 30 minutes now we say 5 min. High mortality, adding agents, step up with valproic acid, then propofol (intubate) pressors, hook them up and look for burst suppression.

Risk of recurrence? structural brain, EEG with definite epileptiform pattern, history of prior brain insult, status epilepticus in first seizure

Discontinuing meds American Academy of Neurology suggest patients who were seizure free 2-5 with a single type of partial or generalized seizure, normal neuro exam, normal EEG. 60-70% chance of success.

http://m.neurology.org/content/84/16/1705.full some updated guidelins from American neurology fresh off the press!

AKI April 15th

On april 15th we talked about a patient with an elevated Creatinine of 600.

The discussion of acute vs chronic was brought up the day prior as well.

Some tips that MAY help us.

1. And old creatinine (easy enough), seeing a creatinine that was much lower 1 week prior.
2. Anemia - this is quite simply due to the fact that erythropoeitin is produced in the peritubular capillary cells in the kidneys, and with chronic damage, patient's become anemia. We generally target Hb between 100-110 in a patient with CKD. Trials have been done (although underpowered - CREATE and COIR) to try to demonstrate a benefit of increasing Hb levels - there was a trend to increasing mortality. Note** patients with polycystic kidney disease typically have EPO spared and so not as anemia!
3. Hypocalemia - the 1 alpha hydroxylase in vit D is produced in the proximal tubular cells of the kidney, hence patient may be low in activated Vit D.
4. Shrunken kidneys -  8 cm or less is generally used. This want be for ALL kidney disease but most commonly associated with hypertension.
5. Bone disease - are increased risk of bone disease because of high PTH and presumably high bone turnover. They may also be at risk of vascular calcification (within coronary arteries and even aortic stenosis - note KDIGO guidelines don't recommend to routinely screen for this, i.e. with echo)

Above is the classic breakdown of approach to acute renal failure. Thinking about the causes can seem overwhelming, best to start with the potentially easier things to diagnose and fix, and then some red flags to look for for RENAL causes.

Pre-renal is the majority of AKI we seen in the hospital in patients that are admitted. Looking for a history of dehydration, nausea/vomiting, diarrhea. A simple urine lyties and urine osm will put us in the right direction!

Urine sodium <20

urine osm >500 

Signs of a kidney that is trying to reabsorb sodium (and water to follow) and where ADH is increased hence concentrating the urine. Urine specific gravity is a simple way to pick up pre-renal and when the story for pre-renal is a good one a urinalysis would probably all that needed. 

How do we treat it? with fluids! The most important thing to consider is what will kill the patient first which is hyperkalemia, but those reading the blog are already pros at that!

As we see prenreal most commonly in hospital: and we order urine lytes quite often, its important to think of some situations that can cause a false negative result; high urine sodium in the setting of prerenal

1. Diuretic use, there job is prevent sodium reabsoption, thereby possibly elevated the urine sodium results.. keeping in mind that the lasix may have done this in the first place

2. underlying CKD: patients may have baseline poor abilities to reabsorb sodium

3. After IV fluids; this has been reported and may be related to a large sodium and maxing out our kidneys ability to reabsorb all of it

4. Glucosuira - osmotic pull telling water and electrolytes with it

5. Salt wasting disorders: adrenal insufficiency - lack of aldosterone will prevent sodium reabsorption in the DCT.

The above discussion although interesting, may be impractical. If someone comes in tachycardic, hypotensive, with dry mucous membranes, flat neck veins, low cap refill in the setting of nausea and vomiting from a partial bowel obstruction - screaming at you "I'm thirsty!"...they are dehydrated, the urine lytes wouldn't really matter.

Post renal causes: anything post kidney is a post renal cause - including renal pelvis, but remember we need bilaterally obstruction. So when do we go searching for this? when patients aren't making sufficient urine, 0.5ml/kg/hr (<500 per day) despite fluids, we need to consider obstructive causes. The easier thing is to insert a foley (with plans to remove it within 24 hours if things go accordingly) or a bladder scan. 

Seeing no urine with the above may move one to consider higher up obstruction. The reason this is important to pick up sooner than later is because we can do something about it! Whether this is by-passing the prostate with a suprapubic catheter, or bilateral nephrostomy tubes in the renal pelvices.

Renal causes:

Acute tubular necrosis: muddy brown casts are pathognomonic and something we do not want to see. >10 per high power field has the best specificity. This happens in response to prolonged ischemia (pre-renal for a long time) and toxins!

endogenous - uric acid (tumor lysis), lytes chains in multiple myeloma, and rhabdo!

exogenous - drugs, aminoglycosides, contrast

The urine sodium will be elevated as the kidney has lost its concentrating ability. This may take 2-3 weeks to recover, but some patients may go on to develop CKD.

AIN: most commonly associated with drugs, infection, may see eosinophiluria in the urine although not very sensitive, or sterile pyuria. Remove the agent.. treat the infection, debatable about using steroids.

RBC casts:This is something you need to look for, but do not want to see. This leads us down the pathway of glomerulonephritis, is this a type of vasculitis and that's when a detailed review of systems will be considered.

TTP/HUS: schistocytes, increased creatinine, and thrombocytopenia the dreaded renal disease as the mortality is extremely high without PLASMAPHERESIS, which essentially filters out antibodies to ADAMTS13. Which is though to be deficient in these individuals.

Does everyone with increased creatinine need an ultrasound?

NO

think about what will be done with that information, if you believe this is all pre-renal, see how they recover it maybe useful to consider in the future for assessing for CKD if there creatinine doesn't recover. 

However, if you think there is obstruction this should get done - potentially overnight.

Commonly we would be looking for hydro on the renal ultrasound acutely

be aware of some false negatives!

4 settings!

1. with very early obstruction <8 hours

2. when the patient has obstruction but is also volume depleted - may consider repeating the test after fluids

3. retroperitoneal fibrosis, may cause hydronephrosis without ureteral dilatation; the hydro and fibrosis is best seen on CT scan

4.  with mild obstruction, as to not impair renal function.

The classic clerk question: what are the indications for dialysis?

AEIOU

acidosis - refractory to medical therapy, i.e. shifting

electrolyte (hyperkalemia) - refractory to medical therapy

ingestions - aspirin, lithium are common ones

overload - someone who is on dialysis or is not making uring and is volume overloaded

uremia - pericarditis, encephalopathy 

Hyperkalemia April 14th 2015

Hyperkalemia

Potassium is often found mostly  intracellular, majority of it is reabsorbed, about 10% of our potassium losses is through our GI tract. The reason we talk about high potassium is that it can kill us via cardiac arrhythmia, low potassium can do the same so we need it just right!

There are no specific symptoms of high potassium – fatigue, weakness, decrease reflexes (but one of our approach to fatigue is checking lytes to look for high potassium).

To be honest, I’ve yet to find a nice and neat all encompassing approach to hyperkalemia.

However my approach is as follows:

Firstly make sure its real! (hemolysis of the sample: often with PICC lines, clenched fists, can be seen in CLL with high lymphocytes!)

** tip: if you REALLY need to know you can do lytes via ABG, comes back quick and accurate, this also helps you distinguish pseuduohyponatremia in the setting of multiple myeloma.

***tip: If you really uncertain whether the potassium of 7 is real, you could do a stat ECG

Decreased secretion: in the setting of decreased perfusion to the kidneys, also less sodium delivery prevents potassium secretion because of a N+/K+ exchange in the distal convoluted tubule. Remember angiotensin II gets unregulated in dehydration, it works on the cortex of the kidney to excrete aldosterone, hence why ACEI can effect potassium. ALWAYS check creatinine when checking potassium as it gives context (AKI?).

 Anything that effects aldosterone which also gets rid of H+ and K+ can cause potassium to increase – addisons, ACEI/ARBS/ spironolactone which will effect potassium secretion. Septra inhibits secretion at DCT and needs to be considered when putting patients on potassium sparring diuretics.

Type IV RTA is a rare cause of hyperkalemia  and is most commonly seen in diabetics, aldosterone is not as effective on the DCT.

Increased body production: This is where scary things like tumor lysis syndrome, Rhabdo, and intravascular hemolysis need to be considered.

Shift out of cells:  acidosis and lack of insulin are the two big things! Acidosis is because the blood wants to balance pH above everything, when there is an increased amount of H+ (acidosis) from sepsis, a loss of bicarb with diarrhea, etc. H+ will be buffered out of the vasculature to try and balance pH. As the H+ moves out, K+ moves intravascular to balance the charge. HENCE Acidosis = Hyperkalemia. Insulin shifts potassium inside cells as well as glucose so a lack of it will cause hyperkalemia… and if you remember, when treating DKA we GIVE potassium when the patient’s labs are high normal 5.2 because we know it will drop with insulin therapy.

*More obscure causes – beta blockers (makes sense because we USE beta agonists to shift high potassium), and heparin is also associated with high potassium in hospital.

Increased production: Rare, but maybe patients with renal impairment were just left on IV potassium replacement or there are certain foods (noni juice>) etc. may contain high amounts, also some patients maybe taking high amounts of potassium supplementation for alternative medical therapy.

ECG findings is peaked T waves, and potentially heart block or wide QRS. That’s why we always check lytes in the setting of heart block!

Treatment is outlines in the

1.      Most sources will use potassium >6.5 as severe, if you believe it to be true or ECG shows peaked T waves, give calcium gluconate 1 gram (1 amp) IV to protect the heart. Caution with dig toxicity.

2.      Shift with 1 amp of D50 (25-50 g of glucose), followed by 10 units of regular insulin IV which will last around 2-6 hours.

3.      Consider beta agonist salbutamol with 10-20 mg nebs

4.      Ensure urine output! Foley catheter, Normal saline, can give IV boluses of 500. Be aware of resp function, are they in AKI and building up fluid?

5.      Kayexlate 30 g followed by lactulose 30 mL po. Need a bowel movement! Has been associated with necrosis bowel so avoid in ileus, post op, or patients on heavy doses of narcotics.

6.      Sodium Bicarb – in patients with CKD, this functions two fold. By making an alkalotic environment, it shifts potassium into cells, and by increasing sodium delivery to distal nephron, it will activate the N/K+ exchanger to kick out more potassium.

7.      Nephrology consult? If patient not urinating, or unable to shift potassium, or the patient is severely overloaded and worried about giving fluids to pee it out, dialysis may be the best option.

Be aware that all this shifting is fine and dandy but if they can’t urinate you have yourselves a problem! If they can urinate, giving them lots of fluids may be the best thing… if they get overload, Lasix can be given which will ALSO lower potassium.