Vancomycin Dosing

When to use vancomycin

The most common use for vancomycin is in invasive Gram positive infections

You need to consider

  • Infection site
  • Patient weight
  • Kidney function
  • Pathogen susceptibility

Pharmacokinetics

  • Vancomycin has bad oral bioavailability so it’s almost never used as a pill
    • Occasionally it is orally to supplement C. diff infections (because that’s going on in the GI tract)
  • Volume of distribution: IV serum 0.4-1 L / kg
  • Normally vancomycin doesn’t cross the blood brain barrier very well, but in the setting of meningitis the inflamed meninges increases permeability

Adverse effects

  • Redman syndrome: A histamine-like flushing during or immediately after dose. Occurs mostly on the face and neck. This is NOT life threatening
    • Treatment: anti-histamine, pause infusion, then restart at a slower rate
    • If the reaction is severe, stop the infusion, give antihistamines, wait until symptoms resolve before restarting. When you restart, give the infusion reaaaalllllly slooooooowly (over more than 4 hours)
  • Nephrotoxicity

Dosing

This is where vancomycin can get tricky, because you are aiming for a target trough (between dose) serum concentrations.

  • Generally the target is 10 mcg/ml, but this may need to be higher for treating MRSA or osteomyelitis
  • Trough concentrations should be measured 30 minutes before the 4th dose any time a course of vanco is started or the dose is changed
  • Monitor creatinine at least once a week (remember that whole nephrotoxicity bit)

Starting dose should be 15-20 mg/kg (based on actual not ideal body weight) every 12 hours. This usually works out to 1-2 g IV Q12H. If the kidneys are not working well, reduce the dose.

References

  • UpToDate.com “Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults”

Renal replacement therapy (dialysis)

Renal replacement therapy (RRT) is a process of removing waste products and excess free water from the blood during renal failure and critical illness.
Common indications for RRT can be remembered with the mnemonic AEIOU:
  • (Metabolic) Acidosis
  • Electrolyte abnormalities (especially severe hyperkalemia)
  • Ingestions/toxins (aspirin, lithium, methanol, ethylene glycol)
  • (Volume) Overload
  • Uremia

There are many different variations of RRT, but the main principles behind it can be quite simple.

In hemodialysis, diffusion is responsible for removing unwanted solutes and water. The setup involves a semipermeable membrane that can allow water and some water-soluble molecules to pass. Blood will flow on one side of the membrane, under pressure, while the dialysate (contains glucose and some electrolytes) generally flows on the other side in the opposite direction. This creates a suitable concentration gradient for unwanted molecules to pass into the dialysate, while excess water is forced across the membrane based on the amount of pressure is applied by the dialysis circuit.

In hemofiltration, blood is pushed across a semipermeable membrane, under pressure. Most of the plasma water is able to pass through the membrane, while unwanted molecules get stuck in the membrane (convection). A substitution fluid may be added back to the blood, in order to dilute out waste molecules (e.g., urea), replace useful molecules (e.g., bicarbonate), and to avoid losing too much fluid from the patient’s circulation.
Some modes of RRT will involve both hemodialysis and hemofiltration. Others only use one of these mechanisms.

References

  • Butcher BW, Liu KD. 2013. Renal replacement therapy and rhabdomyolysis. In: Critical Care Secrets (Parsons and Wiener-Kronish, Eds.) Mosby, Philadelpia PA.
  • Hoste E, Vanommeslaeghe. 2017. Renal replacement therapy. In: Textbook of Critical Care (Vincent, Abraham, Moore, Kochanek, and Fink, Eds.) Elsevier, Philadelphia PA.
  • Ricci Z, Romagnoli S, Ronco C. 2015. Extracorporeal support therapies. In: Miller’s Anesthesia (Miller, Ed.) Elsevier/Saunders, Philadelphia PA.

Where diuretics work in the nephron

The nephron is composed of distinct areas that are specific to regulating different electrolytes.

An overview of nephron anatomy

Loop diuretics: blocks the sodium/potassium/chloride transporter in the ascending loop of Henle, potassium-wasting
Thiazide diuretics: blocks the sodium/chloride transporter in the distal tubule, potassium-wasting
Amiloride: directly blocks sodium channels in the collecting duct, potassium-sparing
Spironolactone: blocks the aldosterone receptors in the cortical collecting duct. This causes a decrease in sodium and water reabsorption and decreases potassium secreting (therefore is potassium-sparing)

Anatomy of a nephron

The nephron is divided into 6 distinct parts

  1. Proximal (covoluted) tubule
  2. Descending loop of Henle
  3. Ascending loop of Henle
  4. Distal (convoluted) tubule
  5. Cortical collecting duct
  6. Distal collecting duct

Each of these sections has a main function in adjusting the amount and kind of solutes in the urine. Different drugs and diuretics work at distinct areas, which is why some diuretics are potassium sparing while others (like Lasix/furosemide) are potassium wasting.

Acid/Base (alkalosis vs acidosis, metabolic vs respiratory)

This is the general way to approach an acid-base disturbance. They’re not really as bad as they seem at first. You just need to remember that CO2 is acidic and HCO3- is basic. So an increase in CO2 makes the body acidotic and an increase in HCO3- makes the body alkalotic.

It’s also good to remember to calculate the anion gap when doing these calculations.

AG = Na – (Cl- + HCO3-) it’s just the cations minus the anions. If this gap between the cations and anions is large, it means that the anions are stacking their team and have an extra anion helping out.

The classic mnemonic is MUDPILES

  • Methanol
  • Uremia
  • Diabetic ketoacidosis
  • Paraldehyde
  • Isopropyl alcohol
  • Lactic acidosis
  • Ethylene glycol
  • Salicylates

If the anion gap is big, it’s good to look at the ratio between the change in the gap and the change in the HCO3-.

  • Increase in AG < decrease in HCO3- = coexisting non-anion gap metabolic acidosis
  • Increase in AG > decrease in HCO3- = coexisting metabolic alkalosis

Determinants of Glomerular Filtration Rate (GFR)

GFR should be ~100 mL/min

Calculating GFR
(140 – age) x lean body weight (kg) / sCr (umol/L)

What determines GFR

  1. Renal blood flow: effective circulating volume, cardiac output
  2. Resistance to flow: vascular tone of afferent and efferent arterioles
  3. Permeability of glomerular basement membrane

Drugs that increase GFR

  • Prostaglandin: vasodilator (afferent > efferent)
  • Angiotensin II: vasoconstrictor (efferent > afferent)
  • Norepinephrine: vasoconstrictor, increases blood pressure
  • ANP: afferent vasodilator, efferent vasoconstrictor

Drugs that decrease GFR

  • NSAIDs: afferent vasoconstriction
  • ACE Inhibitors: decrease efferent vasoconstriction
  • Angiotensin Receptor Blockers (ARBs): decrease efferent vasoconstriction

Calcium homeostasis, parathyroid and vitamin D

Calcium homeostasis is largely controlled by the parathyroid glands (tucked away underneath the thyroid). I’ve included a little bit of the vitamin D synthesis pathway as well, though D3 (the form that is absorbed in the intestines) is also synthesized in the skin as long as you’re getting a little bit of sunlight.

Hypercalcemia

  1. Hyperparathyroidism: usually an adenoma
  2. Malignancy: PTH-related peptide released by tumor (squamous cell, renal, breast, bladder)
  3. Vitamin D excess: granulomas (sarcoidosis, TB, Wegener’s)
  4. Increased bone turnover: hyperthyroidism, Paget’s
  5. Familial hypocalcuric hypercalcemia: mutation in the calcium-sensing receptor in parathyroid and kidney

Hypocalcemia

  1. Hypoparathyroidism: sporadic, caused by thyroid surgery, Wilson’s, hypomagnesemia
  2. Pseudo-Hypoparathyroidism: PTH end-organ resistance
  3. Vitamin D deficiency: no sunlight, GI disease
  4. Chronic renal failure: decreased 1,25(OH)D production, increased phosphate
  5. Calcium sequestration: acute phosphate increase

Causes of Acute Kidney Injury (AKI)

Acute kidney injury can be caused by problems directly in the kidney, before the kidney or after the kidney. If you think about it that way, it’s much easier to develop a differentiate and establish a treatment.

The RIFLE criteria define the relative damage to the kidney and the outcome.
RIF = Severity in terms of serum creatinine (sCr), glomerular filtration rate (GFR) and urine production. Though for simplicity I only included serum creatinine since that is most likely what you’ll be looking at on initial blood work.
LE = Outcome variables (temporary or permanent)

Causes of hyponatremia

First – look to see what the person’s sodium is
Second – what is their volume status

The most important thing about hyponatremia is don’t correct more than 8 to 12 mmol/L per day!!!

Also, the paper titled “The Syndrome of Inappropriate Antidiuresis” by Ellison and Berl (N Engl J Med 2007;356:2064-72) is very useful.

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