Sub Intern Curriculum 2019-2020 Electrolyte Disturbances

Resident Guide

Objectives:

1. Review hyperkalemia and its management, including the urgency required for treatment and the speed of various interventions.

2. Briefly touch on K repletion. 3. Review the diagnostic and management framework for hyponatremia.

Electrolytes

HYPERKALEMIA

During your night float rotation, you received the following sign out: “Mr. P came in with an NSTEMI and is 2 days out from a cath. He now has acute on chronic kidney disease, and his K was 5.3 this morning.” Overnight tasks include: “2000 BMP for K. IF K > 5.3, gives Kayexalate; last K 5.3 at 8AM.”

As you're scrolling through PM labs, you arrive on this patient and see a flagged result:

K 7.3 His brief overview reads: "64M w/ DM2, HTN, CKD admitted for NSTEMI, s/p cath 2d ago. Now w/ AoCKD (Cr 2.5 from b/l 1.8). ”

1. How urgently do you deal with this result? -Hyperkalemia is an emergency and requires immediate attention. -We worry most about patients with clinical signs & symptoms (see below - includes EKG

changes), K > 6.5 even without signs/symptoms, or moderate hyperK (>5.5) with renal impairment & ongoing source of elevated K (eg GI bleed, tumor lysis) or acidosis which could worsen hyperK

2. What are you most concerned about? Cardiac arrhythmias: high degree AV block, VT, VF, PEA arrest, VF arrest, asystole Can also see muscle weakness and paralysis that mimicks Guillain-Barre

3. When you call back the nurse, what do you ask for?

- Overall assessment (how the patient looks) - Complete set of vitals

- STAT 12-lead EKG, make sure the patient is on telemetry

You can also ask the nurse to hold any PO or IV KCl, tube feeds, or TPN (all contain KCl)

4. What potential etiologies of hyperkalemia? In this case, what do you suspect? Etiologies of Hyperkalemia:

Decreased renal excretion of K+ o AKI or CKD w/ missed dialysis o Hypoaldosteronism o Drugs: ACE-I, ARB, K-sparing diuretics, aldosterone antagonists, NSAIDs,

TMP-SMX, calcineurin inhibitors, etc. Excess endogenous K+ load

o Hemolysis o Tissue necrosis – rhabdomyolysis, trauma/burns, gut necrosis, XRT, hypothermia o Tumor Lysis Syndrome Excess redistribution of K+ from cells into blood

o Insulin deficiency (e.g. DKA): K cannot move into cells o Acidemia: excess H+ in cells is buffered, driving K+ out of cells o Drugs (B-blockers, digoxin, succinylcholine) Excess K+ intake (uncommon as sole etiology, but may contribute): PO or IV

In this case, the patient’s hyperkalemia is most likely due to AoCKD, probably due to contrast-induced nephropathy from his recent cath. He may also be taking ACE-inhibitors or ARBs for his HTN.

Important Note: If the labs are wildly different than all previous labs without any reasonable clinical explanation, consider pseudohyperkalemia, which can be caused by tourniquet use for venipuncture, clenched fist during lab draw, hemolysis of sample, extreme leukocytosis (>70,000) or thrombocytosis (>1,000,000). If there is doubt, obtain STAT repeat K , using ABG if needed (may be faster than BMP)

Upon arriving to bedside, you see the patient is not in cardiac arrest (yay!). In fact, he is responsive and is not in any acute distress. The nurse hands you the following EKG.

(EKG from lifeinthefastlane.com)

5. What worries you? What changes are you looking for? Possible EKG changes of Hyperkalemia

o Tall, peaked and symmetric T waves

o Prolonged PR interval

o Flattening (or disappearance) of P wave

o Widening of the QRS (can see RBBB, LBBB, or bifascicular block)

o Severely widened QRS, often called a “sine wave”

o VT w/ pulse

o Cardiac arrest (pulseless VT, VF, PEA arrest, asystolic arrest – all possible)

Importantly, the EKG changes of hyperkalemia DO NOT necessarily appear in a particular sequence. The first electrical manifestation of hyperkalemia can be cardiac arrest.

6. How do you approach treating this patient? Page your resident! And open the Hyperkalemia Order Set!

1. Immediate Myocardial Membrane Stabilization

• Calcium gluconate – 1-2g

• Calcium chloride – 500-1000mg (only via central access or if code situation)

Check serial EKGs q3-5min in order to monitor for resolution of EKG changes. If changes persist, continue to give calcium.

2. K+ redistribution into cells

**One way to remember these

changes is to imagine a hook under

the T wave pulling the whole tracing

up and to the right – the T wave

peaks, the QRS widens, PR interval

stretches out, and P wave flattens.

• IV Insulin – 10U regular insulin + 1-2 amps D50

o Must be IV, not SC

o Acts in 15-30 minutes, lasts 1-2 hours

o Remember to check FSBG 1 hr after!

• Albuterol nebulizer – Requires 10-20mg (normal albuterol neb is 2.5mg)

• NaHCO3 – 1-3 amps IV

o Works best if concomitant acidemia, and should never be sole therapy

3. Elimination of K+ from the body

Generally, excretion from urine is more effective. Total K balance is minimally affected by stool K losses in most patients. ESRD patients a notable exception due to upregulated K excretion in stool.

• Urine: furosemide (can give with IV fluids if worried about hypovolemia)

• Stool:

o Lactulose 15-30mL PO o Kayexelate 15-30g PO (cation-resin exchanger)

Warning: May cause intestinal ischemia. Risk higher in post-op patients, pts with ileus/receiving opiates, bowel obstruction, underlying bowel disease (eg C diff/IBD)

7. How do you follow the patient now? • Telemetry

• Follow serial EKGs

• Check K again in ~2 hours – Use ABGs if cannot get reliable blood draws in the middle of the night.

8. What is the next step if K is not decreasing? Page the renal fellow! Dialysis is the definitive treatment for controlling hyperkalemia, if all other measures fail.

If you think the patient will need dialysis, page the Phys. The patient will need an ICU bed for urgent/emergent dialysis.

1. Repolarization Abnormality (peaked T waves)

Changes of Hyperkalemia (DO NOT necessarily occur in a particular order)

(all EKGs from lifeinthefastlane.com)

2. Atrial paralysis (long, flat P wave → PR lengthening → P waves disappear) 3. Conduction abnormalities and bradycardia (wide QRS, high grade AV block, conduction

block, sinus brady)

4. Sine wave (preterminal rhythm)

Learning points:

• Hyperkalemia should be treated as an emergency with rapid acting treatments when there is the presence of EKG changes, K is rapidly rising or if the patient has any symptoms.

• Calcium antagonizes the membrane effects of hyperkalemia and restores normal cardiac membrane excitability within 1-2 minutes.

• Potassium can be shifted over 15-30 minutes into cells with insulin (most commonly used), bicarbonate or albuterol. This temporarily lowers the serum value but this does NOT fix the underlying cause nor decrease total body K.

• Maneuvers designed to shift potassium into cells must be repeated every 2-3 hours if total body potassium levels have not returned to normal in that time.

• A strategy designed to reverse the underlying cause of the hyperkalemia (e.g. IV fluids to a patient with pre-renal AKI) or to remove total body K stores must be instituted to prevent recurrence of hyperkalemia once initial therapies have worn off.

• Consider calling the Phys for possible ICU transfer in severe cases that cannot be managed easily on the floor and may need dialysis.

HYPONATREMIA

You are on call on GMS and receive a new admission from the ED. The ED resident informs you that Mr. Saltpore is an 85 year-old male who presents with several days of cough productive of yellow sputum and subjective fevers. The resident was unable to obtain a complete history because the patient was “a little confused,” but CXR showed a RLL consolidation. Labs were significant for WBC of 18K. As you hang up the phone, you scroll through the patient’s labs and notice that his serum sodium is 123 mEq/L.

1. How should you begin to think about this patient’s sodium?

First, look at serum osmolarity. Hypo-osmolar hyponatremia is the most common form.

Serum osmolality can be measured directly, and can be added on to a BMP. You can also estimate serum osmolality with the following equation:

Osm = 2 x Na + glucose/18 + BUN/2.8

But keep in mind, this equation may not be accurate in all cases.

HYPO-OSMOLAR HYPONATREMIA (Osm <280)

• Caused by an excess of free water relative to sodium

• Most commonly seen type of hyponatremia

HYPEROSMOLAR HYPONATREMIA (Osm >295)

• Caused by an excess of another osmotically active molecule in the serum

• Glucose (e.g. HHS or DKA): for each 100 mg/dL that Glc is elevated above 100 mg/dL, add 1.6 mEq/L to measured Na

• Hiller et al. (1999) suggested adding 2.4 mEq/L to Na for every 100 that the glucose is elevated above 100 – either can be used

• This is not “pseudohyponatremia”. The Na concentration is truly as low as measured.

ISO-OSMOLAR HYPONATREMIA (Osm 280-295)

• Caused by high protein (e.g. multiple myeloma) or lipid levels (e.g. hypertriglyceridemia) that interfere with lab assays for sodium.

• This is “pseudohyponatremia.” Very rare.

The rest of his metabolic panel is as follows:

2. What is the next step in assessing the patient’s hyponatremia?

Assess the patient’s volume status (to determine etiology) and mental status (to determine triage and urgency of treatment).

3. What will you look for on physical exam when you go see your new patient?

Mental status: Lethargy, confusion, obtundation. o If present, treatment of the hyponatremia should begin immediately. o Severe hyponatremia can cause seizure, coma or death if untreated. o If altered mental status, think about triage (e.g. floor vs. ICU)

Volume status: Dry mucous membranes, poor skin turgor, lack of axillary sweat (highly sensitive for hypovolemia), JVD, edema, ascites, crackles. Orthostatics should also be checked.

4. Why do both hypovolemia and hypervolemia lead to hyponatremia?

If a patient is euvolemic, what are possible causes of hyponatremia?

Hypo and hyper-volemia cause poor effective circulating volume to the kidneys. The kidneys are relatively hypoperfused, leading to appropriately increased ADH to try to increase circulating volume, causing retention of free water in excess of sodium. In hypovolemia, this results from low total body fluid volume. In hypervolemic states, this results from excessive fluid accumulating in tissues instead of the intravascular space.

On the other hand, hyponatremia with euvolemia is NOT a kidney perfusion problem.

On physical exam he is a well-developed, thin male in moderate respiratory distress. Blood pressure (supine) 120/86, pulse 74, blood pressure (standing) 115/85, pulse 70, respirations 24 and labored. Temperature is 101.2 F. He is alert, but oriented only to self and is unable to tell you why he is in the hospital. HEENT exam was unremarkable. Cardiopulmonary exam demonstrated decreased breath sounds at the base of the right lung. The skin turgor is normal, and the mucous membranes are moist. His abdomen is thin without flank dullness, and his lower extremities are warm and without edema. The remainder of his physical exam is within normal limits.

5. Based on your physical exam, what type of hyponatremia does this pt have?

Euvolemic hyponatremia

Ddx:

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Malignancies (especially small cell lung cancer)

Pulmonary processes (pneumonia, abscesses, TB)

CNS processes (trauma, hemorrhage, space-occupying CNS lesions)

Pain

Nausea

Surgery

Trauma

Medications (opiates, antipsychotics, SSRIs, TCAs, some chemotherapy agents)

…Lots of Other Things Too!

Other possibilities (rare):

- Endocrinopathies:

• glucocorticoid deficiency

increased CRH release → increased ADH production

• hypothyroidism (really has to be myxedema coma to cause hyponatremia)

- Psychogenic polydipsia: Extreme water intake ( > 12-20 L /day) overwhelms the kidneys’ ability to excrete free water.

- Reset osmostat –ADH reset to regulate lower serum Na concentration.

6. What lab tests could you order to determine the cause of hyponatremia?

Urine osmolality is the most important. Urine sodium may also help.

Urine osmolality

- When a normal person is euvolemic and hyponatremic, their body should be trying to excrete free water → dilute urine

- If a patient has Uosm > 100 (i.e. not maximally dilute), this confirms SIADH. Most cases actually have Uosm > 300.

- If a patient has Uosm < 100, this means the kidneys are appropriately diluting the urine, suggesting excessive free water intake (polydipsia).

Urine Sodium

- >40 mEq/L in SIADH (inappropriately concentrated urine)

- <40 mEq/L in most cases of hypovolemic or hypervolemic hyponatremia, o BUT you should already suspect this from your volume exam!

Consider TSH or AM cortisol to rule out hypothyroidism and adrenal insufficiency (though generally not necessary if patient has an obvious cause for SIADH – e.g. lung cancer) Another way to consider teaching this topic is with the following algorithm, which relies less heavily on volume status:

This patient’s labs are as follows: Urine osmolality = 635 mOsm/kg

Urine Na 85 = mmol/L

TSH and AM cortisol levels are within normal limits

7. Why does the patient have hyponatremia? Does this explain his altered mental status?

The patient has hypo-osmolar euvolemic hyponatremia with an elevated urine osmolality and high urine sodium. Thus, the patient has SIADH, likely secondary to pneumonia.

Hyponatremia (Na<130)

Serum Osm

Low (<280)

Urine Osm

Low (<100)

Tea and Toast

Polydipsia

Urine Osm

Normal-High (>100)

Urine Sodium

Low (<20)

USE VOLUME STATUS

Dehydration

TBV up, intravasc dry

(Cirrhosis, CHF, Nephrotic)

Urine Sodium

High (>40)

SIADH

Serum Osm

High (>280)

Paraprotein Hypertriglyceridemia

Hyperglycemia Mannitol

Low serum osmolality results in the movement of free water into cells by osmosis. In severe (typically acute) cases, cerebral edema can develop, but even in more mild cases, intracellular electrolyte contents and protein function are disturbed. In chronic hyponatremia, brain cells adapt by producing “idiogenic osmoles,” counteracting the excess intracellular water.

8. What are the treatment options for this patient? What would be best?

Fluid restriction, salt tablets, loop diuretics, normal saline, and hypertonic saline.

Important Point: If a patient is asymptomatic, no matter the level of Na, there is no rush to correct Na! The lack of symptoms suggests chronicity, and the risk of CPM is highest in chronic hyponatremia that is too rapidly corrected.

Management of a patient with SIADH should be done in a stepwise fashion with frequent sodium checks to determine that the sodium is rising and at a safe rate of change.

• Treat the underlying cause or remove the offending agent!

• Free water restriction (800cc to 1.5L depending on the severity of the hyponatremia). It is also vital to look for other iatrogenic forms of free water that may prevent adequate treatment, including:

o D5W IV medications—page pharmacy and ask them to concentrate IV meds or formulate in NS instead, if possible

o Free water in G- or J-tube flushes—use normal saline instead

• Salt tablets

o In a patient with SIADH, the urine osmolality is a fixed value. Thus, urine output (and excretion of free water) can only be increased by increasing solute intake.

o Can start salt tabs at 1g tid (though some patients with very high urine osmolality require up to 3g tid)

• Loop diuretic

o Abolishes the medullary gradient which decreases the concentrating ability of the kidneys.

o Start with very low-dose furosemide (e.g. 20mg PO) as high doses have the potential for overcorrection.

• Normal Saline

o Only helpful if UOsm < 308.

o The osmolality of NS is 308. If patients where UOsm < 308, infusion of NS results in net retention of NaCl. However, in patients where UOsm > 308, infusion of NS results in net retention of free water.

• Hypertonic Saline (3%)

o Indicated for severe MS changes

o Almost always requires ICU care, q2h labs (consider a-line)

o Call the PHYS for ICU transfer

9. At what rate can you safely correct this patient’s hyponatremia? What is the risk of correcting too quickly?

Unless it is definitively known that the patient’s hyponatremia is acute (e.g. has been present for <24 hours), it should be assumed that the hyponatremia is chronic and therefore the patient is susceptible to central pontine myelinolysis (osmotic demyelination syndrome).

CPM results from rapid correction of hyponatremia, especially of chronic hyponatremia. The brain makes idiogenic osmoles to compensate for excess intracellular water in the setting of hyponatremia. When the serum Na suddenly corrects, free water rushes back out of brain cells, resulting in shrinking of brain cells and demyelination.

Important point: CPM manifests clinically 4-5 days after the overcorrection has occurred!

An upper limit on the rate of correction is an increase of serum sodium of no more than 12 mEq/L in 24 hrs (or 0.5 mEq/L per hour), and no more than 18 mEq/L in 48 hours. But remember, if a patient is asymptomatic, there is no rush! Better to go even slower (e.g. 8 mEq/L in 24 hrs) and minimize the risk of CPM.

If correction is occurring too quickly, you can drop the serum sodium with either D5W or ddAVP (1-2 micrograms IV or subQ).

Resources: Approach to lab diagnosis of hyponatremia: CMAJ. 2002 Apr 16; 166(8): 1056–1062. A guide to SIADH: Ellison DH, Berl T. NEJM 2007; 356:2064-2072