Only the A-E-I-O-U’s to start RRT and now we know “Y”! The Start-AKI Trial

In residency and med school we are always taught the indications for emergent CRRT as the mnemonic: AEIOU

metabolic acidosis with a pH < 7.1 Electrolytes hyperkalemia > 6.5 mEq/L refractory to treatment or rapidly rising levels in potassium
with dialyzable drug, including salicylates, lithium, isopropanol, methanol, and ethylene glycol (SLIME)
volume overload that does not respond to diuresis
especially with increased oxygen requirements
causing: uremic bleeding, encephalopathy, pericarditis, and neuropathy

However, in the ICU there has always been a question of how early should we start RRT in the setting of oliguria and BUN not causing symptoms. Initial thoughts were that earlier is better. Today’s infographic focuses on the latest RCT to determine the timing of CRRT. The Bottom Line here is that for the START-AKI TRIAL: Unless there is the emergent a-e-i-o-u’s to start CRRT doing it early does not appear to translate to a mortality benefit. There may be a signal of dialysis dependence at 90 days in this trial. Now we know “Y” we should wait until we have an indication other than the AEIOU’s.

Case Report: IV access in a dialysis patient: An Evidence free zone!

So the below is only my opinion! We are definitely in an evidence free zone and this is not meant to guide management! However this is my nightmare. 

A 53 yo ESRD is BIB EMS to a small community hospital. Her chief complaint: missed dialysis. She reports staying at her NH and not having been picked up for dialysis for the past week. She is on HD, Tues, thurs, and Saturday. Her last IHD was a week ago and her most recent one was unable to be continued because her graft had clotted off. She does not feel short of breath but does note her body is more swollen. SHe has no other symptoms. Past medical history includes (but not limited to): DM, HTN, ESRD on HD, and a right sided CVA with deficit on the right side. On exam her BP is 224/112, HR is 78, RR 20 (as usual), and afebrile. On exam she is in no acute distress and non-toxic appearing, she is morbidly obese, she speaks in full sentences, she has keloid formation on both sides of her neck and anterior chest wall. She has a moderate contracture on the right arm from her prior CVA, she has a Arteriorvenous graft (AVG) on the left arm with no palpable thrill or bruit. She further has bilateral above the knee amputations. Bilateral radial vessels are palpable no other findings. The nurses are unable to find a vein on the arm with the CVA and tell you they cannot do an IV on her arm with the graft. The lab tech is unable to obtain a blood draw given her skin changes and lack of venous access.  You are asked to obtain blood and you do so by radial arterial draw. Her ECG shows no peaked T waves and her Potassium (K) is 6.8.

So, to sum up this is a 53 yo female on dialysis with a clotted graft, no accessible veins peripherally by 2 different nursing attempts and the charge RN, no accessible EJ on the neck (visually or by US) due to keloid, no accessible mammary veins on the chest due to b/l keloid, no legs, an AV graft on the left arm and the right arm is fixed ADducted and held in flexion and cannot be straightened due to the stroke.

What do you do? Where and How do you get IV access? Do you put in a central line? If so where?


Where do we start?

As far as IV access goes, we are all aware that we “shouldn’t” use the arm with the AV graft (AVG) or fistula (AVF). But when we NEED blood and IV access as in the above case where do we start? Let’s look at this.

There are slim to none guidelines in this area. The only semblance of guidelines is from the 2006 KDOQI (Kidney Disease Outcomes Quality Initiative, In the section on “Clinical Practice Guidelines for vascular access”, pg 340 states “1.1 The veins of the dorsum of the hand should be the preferred site for IV cannulation.” And  under patient preparation for permanent access states “ In patients with CKD stage 4 or 5 forearm and upper-arm veins suitable for placement of vascular access should not be used for venipuncture or placement of IV catheters, subclavian catheters, or PICCs)

Does this mean both hands? Does this mean after or before placement of the AV access. No one will ever know…

The rationale for these recommendations are for PRESERVATION of the veins to create an AV fistula or graft, and maximize chances or successful fistula placement and maturation. Furthermore it is for prevention of thrombosis. These are the reasons for the PIV cautions. They report the incidence of central vein stenosis and occlusion after upper extremity placement of PICC and venous ports is 7% in 1 retrospective series of patients. PICCs are also associated with an incidence of upper extremity  varies between 11% and 85%. Thus PICCs should not be used in CKD.

And that sums up all the recommendations!

At, the housing site for the KDOQI guidelines, there is a post that states:

“Post date: February 10, 2014

I have permitted peripheral IV access in the back of the hand on the same side as the AV fistula. I do not permit IV access above the wrist on the same side as the fistula. I do not permit Peripherally Inserted Central venous Catheters (PICC) access to be placed in any dialysis patient with a fistula. I only permit centrally lines in the Right Internal Jugular position. The KDOQI guidelines recommend right sided central venous catheters, avoiding subclavian catheters and avoiding peripheral IV access in any dialysis patient or pre-dialysis patient. They also mention using the back of the hand veins for peripheral access but avoiding the arm veins for peripheral IV access.”

Obviously not high quality data…

The nurses were unable to obtain IV access or blood from either hand or veins on the chest wall.

Next step for me was to look for an EJ… sadly, no luck too much keloid formation over both sides of the neck nor could I find distended EJ’s visually  or by ultrasound.  Because of the left arm contracture and her soft tissue edema I had a very difficult time finding a deep brachial vein. In my own personal experience I feel the basilic vein is more likely to infiltrate whether you happen to “back wall” the vessel or not. However, after getting more help positioning the patient and have a few people hold her I was able to get a peripherally inserted 20 ga 1.88” (48mm) Angio catheter in the most anterior deep brachial at the level of the mid bicep. Now to find a new pair of underwear!

If that failed, I guess I would have done a right IJ since her graft is on her left arm and guidelines say to avoid Subclavian vessels. Also theoretically, an IO of the right humerus could be done emergently but being a renal patient I’m sure her bone strength is minimal.

So in summary, obtaining IV access in an HD patient would be in the following order:

  1. Dorsal veins in the hand
  2. Peripheral on the contralateral AVF/AVG side
  3. External Jugular (either
  4. IJ contralateral to the AVF/AVG; if CKD 3-5 then Right IJ preferred but either is Ok
  5. If PICC is needed substitute in a tunneled EJ/IJ catheter by IR


  1. Above the wrist on the AVF/AVG side
  2. Subclavian central line
  3. PICC

In case you were wondering what the steps are for accessing a fistula I found this wonderful article, by Manning, on how to do that:

Any gauge and type of needle may be used, although a large-bore (14, 16, or 18 gauge) needle is recommended in emergency circumstances. A needle is preferable to an angiocatheter because it is easier to secure with tape under the high pressure of the fistula. A tourniquet should be used when cannulating an AV fistula and removed immediately after cannulation. The tourniquet should be placed in the axilla area and applied lightly. These precautions will help prevent thrombosis, the most common cause of AV fistula and AV graft failure. One should scrub the skin at the puncture site with povidone-iodine, allow the skin to dry, and follow with a scrub using isopropyl alcohol.  The needle should be inserted into the AV fistula at an angle of 20 to 35 degrees until a flashback of blood is noted (The angle should be increased to 45 degrees if the nurse is cannulating an AV graft.) After the flashback, insert the needle up to 0.32 cm (1/8 inch) further and decrease the angle until the needle is flat with the skin. The needle or catheter should be advanced to the hub to prevent bleeding around the insertion site. If using an intravenous catheter, one should be prepared to attach intravenous or saline lock tubing quickly to avoid unnecessary blood loss. Blood flowing through the AV fistula travels at a high velocity, so fluids need to be infused under pressure. One must take care to tape the needle or catheter to the skin securely in a chevron fashion to prevent dislodging.

If the fistula has been accessed in the previous 24 hours and the needle puncture sites are visible, the nurse should take care to access the fistula at least 2.5 cm (1 inch), either proximal or distal, from the previous site to allow healing time and to avoid the formation of an aneurysm. Prior to and after cannulation, the emergency nurse should assess the AV fistula for a thrill and document its presence. The AV fistula can be de-accessed in the same manner as a peripheral intravenous line, with pressure applied after the needle or catheter has been removed. The nurse should take care to hold gentle, nonocclusive pressure for a full 10 minutes at the insertion site.


  1. Manning, M. Use of dialysis access in emergent situations.J Emerg Nurs 2008;34:37-40. Available online 18 October 2007. doi: 10.1016/j.jen.2007.03.018. PMID: 18237665
  3. February 2012 ASN kidney news. The PICC conundrum: Vein preservation and Venous Access.






  1. An increase by 4-6-mmol/L [Na] is sufficient to reverse most serious manifestations of acute hyponatremia.
  2. Increase [Na] no more than 10 mEq/L in 24 hour period in pts with LOW RISK Osmotic Demyelination syndrome
  3. Increase [Na] no more than 8 mEq/L in 24 hour period in pts with HIGH RISK Osmotic Demyelination syndrome (ODS).
  4. PTS at HIGH RISK of ODS (mnemonic CHAMP):
    1. Cirhosis
    2. Hypokalemia
    3. Alcoholism
    4. Malnutrition
    5. Plasma Serum sodium <105


  1. For our purposes the only cause of cerebral edema and neurological causes of hyponatremia are the hypotonic (low osmolar) hyponatremia causes.
  2. IF neurological symptoms are present and hypotonic hyponatremia is presumed or confirmed then 150 ml of 3% (3ml/kg) over 20 min
  3. Check serum sodium after 20 min while repeating an infusion of 150 ml of 3% over 20 min IF symptoms persist.
  4. GOAL: Target goal of 5 mmol/L increase in serum Na is achieved


  1. As long as the patient is not hypovolemic AND the SEVERE symptoms are treated then
  2. Use the smallest volume of NS until specific causes are found
  3. Limit the increase in Serum Na to a total of 10 mEq/L[g]in the first 24hr and an additional 8 mEq/L during every 24hr there after until serum sodium reaches a goal of 130 mmol.
  4. Check Serum sodium concentration after 6 hour and after 12 hr and then daily until Na has stabilized.
  5. A sudden increase in urine output to >100ml/h signals increased risk of overly rapid rise in serum sodium concentration


To calculate the anticipated increase of Serum sodium by infused saline:

Screen Shot 2018-12-24 at 5.51.42 AMWhere:

  • Infused Na = 154 if Normal Saline or 513 if 3% hypertonic saline
  • Total Body water (TBW) = Wt x 0.6 if male
  • Total Body water (TBW) = Wt x 0.5 if female
  • Total Body water (TBW) = Wt x 0.5 if elderly (>65) male
  • Total Body water (TBW) = Wt x 0.45 if elderly (>65) female

Example: 70 kg young female with severe cerebral symptoms is given a 3 ml/kg bolus of 3% NaCl (Na=
513 mEq/L) and Serum Na = 108

Infuse Na                   = 513 mEq/L (hypertonic)

Volume infused         = 0.003 L/kg x 70 kg = 0.14 L

Serum Na                   = 108

TBW                            = 70×0.5 (young female) = 35L

Screen Shot 2018-12-24 at 6.33.33 AM

 Final serum Na = 111


  1. BEER POTOMANIA 15 (BOX 1 from algorithm)
    1. NPO except medications for 24 h
    2. No IVFs unless symptomatic
    3. Prescribe IVFs in finite amounts if needed
    4. Serum sodium every 2 h

    5. S Na increase < 10 mEq/L in first 24 h
    6. S Na increase < 18 mEq/L in first 48 h
    7. Re-lower serum sodium levels if necessary
    8. Give all IV medications in D5W

    9. If caloric intake is needed, use D5W.
  2. HYPERVOLEMIC causes (BOX 2 from algorithm)
    1. Recommend against treatment with the sole purpose of aim of increasing the serum sodium concentration in mild or moderate hyponatraemia.
    2. Fluid restriction (<1.5-1.0L/d or 500ml/d less than the Urine output) to prevent further fluid overload.
    3. Recommend against vasopressin receptor antagonists.
    4. Recommend against demeclocycline.
  3. HYPOVOLEMIC (BOX 3/4 from algorithm)
    1. It is recommended to restore volume with i.v. 0.9% saline or a balanced crystalloid solution at 0.5–1.0 ml/kg per h
    2. In case of hemodynamic instability, the need for rapid fluid resuscitation overrides the risk of an overly rapid increase in serum sodium concentration
    3. In these patients restoring volume will suppress vasopressin secretion causing electrolyte-free water excretion to increase. Therefore, these patients are at high risk of an overly rapid increase in serum sodium concentration. Sudden increases in urine output can act as a warning signal that overly rapid correction of hyponatremia is imminent.
  4. EUVOLEMIA HYPOTHYROIDISM (BOX 5 from algorithm)
    1. Unless severe (i.e. myexedma or TSH >50 mIU/mL), other causes of hyponatremia should be sought rather than hypothyroidism. 

    2. Unless the patient has hyponatremic encephalopathy, primary treatment of hyponatremia should consist of thyroid hormone replacement at standard weight-based doses; several days may be needed to normalize the serum Na. 

  5. SIADH (BOX 6 from algorithm)
    1. In moderate or profound hyponatraemia, restricting fluid intake should be first-line treatment.
    2. In moderate or profound hyponatraemia, the following are equal be second-line treatments: increasing solute intake with 0.25–0.50 g/kg per day of urea or a combination of low-dose loop diuretics and oral sodium chloride.
    3. In moderate or profound hyponatraemia, we recommend against lithium or demeclocycline.
    4. In moderate or severe hyponatraemia, we do not recommend vasopressin receptor antagonists.
  6. Cerebral Salt Wasting (Box 7 from algorithm)16 17
    1. CSW is a volume-depleted state
    2. Depending on the severity isotonic or hypertonic solutions are indicated.
    3. Additionally, sodium tablets up to 12 g/d may be used can be combined with the IVF
    4. Once euvolemia is achieved, the goal of therapy is to prevent volume depletion by matching the urinary output.
    5. Fludrocortisone has also been used for the treatment of CSW at doses of 0.1 to 1 mg/d (stimulating reabsorption of sodium and water)
    6. The most common adverse effect associated with fludrocortisone was hypokalemia in up to 73% of patients.


  1. Fluid restriction is first line treatment
  2. Urea[h]/loop diuretics are equal second line treatments


  1. Prompt intervention for re-lowering the serum sodium concentration if it increases >10 mmol/l during the first 24 h or >8 mmol/l in any 24 h thereafter
  2. We recommend discontinuing the ongoing active treatment.
  3. Consulting an expert to discuss if it is appropriate to start an infusion of 10 ml/kg body weight of electrolyte-free water (e.g. glucose solutions) over 1 h under strict monitoring of urine output and fluid balance.
  4. We recommend consulting an expert to discuss if it is appropriate to add i.v. desmopressin 2 mg, with the understanding that this should not be repeated more frequently than every 8 h.


Chances are if you are reading this you have probably seen a case or two of hyponatremia. Well, defining hyponatremia isn’t really hard. In fact treating acute symptomatic hyponatremia isn’t that hard either. So what makes this electrolyte disturbance so painful? It’s the over abundance of math, renal physiology and lack of organization that exists within the literature; enough to make doctors have flashbacks of their USMLE days. Fear not friends, we are going to make this simple and painless. Unless simple and painless are not your thing, then I have for you the sadist’s ball gag equivalent of math in the optional section to appease even the most vicious of IM attendings. No more google-ing 40 different articles to treat that hyponatremic patient, everything in one neat package! So lets get to it!

            First off some definitions:


Classification Definition Comment
Hyponatremia <136  
Moderate 125-135  
Severe/Profound <125 Profound in UK
Acute vs Chronic Time of development (48 hr cutoff)


Usually unknown
Tonicity Dealing with osmolarity There can be unaccounted osmoles (EtOH)
Hypotonic Hypo-osmolar Type of hyponatremia
Volemia Dealing with the pt volume status Difficult to asses clinically.

Table 1. Classification of Hyponatremia (US units: mEq/L) 1, 2

So far, not horrible; Right?


We need to talk about epidemiology not because every chapter on any disease starts out this way but because it will help us down the road. So lets push on. Hyponatremia is probably the most common electrolyte abnormality3.  Based on studies from the first half of the 2000’s the incidence[a]of hyponatremia is about 30-40% of admitted patients worldwide. The largest amount were found in the ICU with hyponatremia <125 mEq being an independent predictor of mortality. Values <126 mEq/L and < 116 mEq/L were found in about 6% and 1% of the patients, respectively4. In ED populations it is obviously lower than in admitted patients. ED based studies outside the US found a prevalence of  3-5% for all adults but 10-17% in those patients age 65 and older. These studies also found an increase in hyponatremia for both groups during the summer months 1-2% greater than the above numbers 5, 6. In the geriatric population 78% of episodes of hyponatremia were precipitated by increased fluid intake, administered orally or as intravenous hypotonic fluid. Finally, up to 17% of chronic alcoholic patients had hyponatremia secondary to Beer Potomania[b]

OPTIONAL: OsmolaLity or OsmolaRity?

To jump back a bit we should define osmolaLity and osmolaRity. Osmolality (with an “L”) is a measure of the osmoles per kilogram (Osm/Kg),  osmolarity (with an “R”) is defined as the number of osmoles per liter (L) (Osm/L). Don’t worry we don’t have to know how many kg our patients are to calculate their osmolality. If the L and the R were flipped it would probably be easier to remember but lets just remember that the L is for weight and the R is for volume. This is important because we calculate osmolaRity but measure osmolaLity so we should keep track of the units. If you want to not be accurate then you don’t have to worry because we are dealing with water in the body, so we can approximate osmolaLity to equal the osmolaRity[c].


Figuring out the differential our patients have for their hyponatremia is probably the most difficult part of this diagnosis. However, here is where I am going to try (or at least try to try) to simplify it.

Click Here for the Hyponatremia Algorithm: Hyponatremia 2.0-3

In order to decide the reason for the hyponatremia in our patients we need to have a starting point. We used to talk about volume status as the starting point but this makes things too difficult furthermore the reliability of volume status by clinical exam is less than accurate. Instead we are going to start with the osmolality.



The first branch point into our differential diagnosis is figuring out what is the serum osmolality (tonicity). We can do this two ways: order an extra lab value of serum osmoles (not usually part of “first round of orders”) or we can estimate (oh thank god!) a serum olsmolarity. To do this we us the formula:

Serum Osm [mmol/L]= 2[Na+] + Glucose + Bun               (Equation 1)

This probably looks a bit strange to US doctors since it’s missing some numbers. That’s because we don’t use [mmol/L] in the US, instead we use the crazy units of  [mEq/L]. So to go from mmol to mEq (or mg same thing for our purposes) we have to divide the molecules by their molecular weight. In fact, any good British child will tell you to convert their glucose to US values by dividing by 18![d]So now our formula becomes the familiar:

Serum Osm [mEq/L]= 2[Na+] + Glucose/18 + Bun/2.8    (Equation 2)


To estimate the serum osmolarity [mEq/L] use the formula:

2[Na+] + Glucose/18 + Bun/2.8


How good is this formula for estimating serum osmoles? When equation 1 (also referred to as the Smithline-Gardner formula) is compared to the mean measured osmolality in healthy patients it gives an osmolal gap (OG, i.e the difference between calculated and measured Osm) close to zero and an SD of 4 mmol/L. When applied to patients in which an osmolality was clinically indicated (i.e where it would theoretically matter) the variability in the OG is approximately +/- 7 mmol/L. This held true as long as ethanol was not adulterating the sample7. Remember that ethanol will contribute to serum osmolarity and will need to be divided by 3.78. Thus equation 2 (in the US) is proposed to be adopted by all clinicians and laboratories along with a “fudge” factor of +/- 10 mmol/L for the gap7. To really get the most accurate answer here you would likely have to order a serum osmoles but it would appear that this estimation holds up pretty well to start treatment.


Only true (hypotonic) hyponatremia matters so exclude other causes.

The normal human plasma osmolality is 275-300 mOsm/Kg9. Therefore, we need to see if we have hypertonic or isotonic hyponatremia. Hypertonic (also called Translocational or redistributive hyponatremia) causes include: hyperglycemia[e], mannitol, and sometimes a contrast load.  Isotonic (also called Pseudo or normo-osmolal hyponatremia) causes include: hyperlipidemia and hyperproteinemia. Once we have excluded these causes by a value of <275 mOsm/kg then we can say that we have a true hypotonic or hypo-osmolar hyponatremia.


Calculate the serum osmolarity. If it is <275 mOsm/Kg then the causes are “true” or hypotonic causes1which can truly cause symptomatic hyponatremia.


The normal response to hyponatremia is marked suppression of ADH secretion, resulting in the excretion of maximally dilute urine with an osmolality below 100 mOsm/kg and a specific gravity ≤1.003. Vasopressin (ADH) levels are what really differentiates the type of hyponatremia at this point. The first type will have high vasopressin levels and high urine Osm with low Na.  Here high vasopressin causes inability to excrete water and consists of the classic 3 groups of hyponatremia: hypovolemic, euvolemic and hypervolemic. The second type will have low serum vasopressin levels and typically low urine osmolality. Thus, mechanisms other than vasopressin are responsible. These types includes: chronic renal failure, psychiatric disorders, potomania, and low solute load excreted in the urine. However we can’t measure Vasopressin (ADH) so we use low osm and low sodium to represent this group. Values above 100 mOsm/kg indicate an inability to normally excrete free water, most commonly because of persistent secretion of ADH. Therefor the urine osmolality can help us. Once again we have 2 options to determine osmolality: order it or to estimate it. 


To jump back a bit to med school physiology lets understand what ADH does. ADH (Vasopressin) is released from the posterior pituitary. It does this in response to 2 motivating factors: 1. Low Blood pressure via Angiotensin II released from the kidney and activating the V2 receptor; 2. High plasma osmolality (Hypertonicity) either by too little water or too many solutes. Once ADH is release it works on the principal cells in the collecting duct to stimulate aqauporin-2 channels to be inserted on the collecting duct to reabsorb more water back into the blood. So ADH “ADDs H20″ to the plasma. Thus in the algorithm when there is low URINE osmolality this must mean that ADH is not working and is “ADH independent”


The normal response to hyponatremia causes a urine osmolality below 100 mOsm/kg. To estimate the urine Osm from the urine we can use the Urine specific gravity (USG) and the following equation:

            UOsm = (USG -1) x 25,000                         Equation 311.


So if the urine Osm are calculated and less than 100 mOsm/kg then it is likely that a relative excess water intake is the umbrella cause of the hypotonic hyponatremia1. Thus the differential includes: Primary polydipsia, beer potomania, water dilution in formulas of infants, tap water enemas in infants, or very low sodium intake. Again this is because the normal response to hyponatremia is suppression of ADH, resulting in the excretion of a very dilute urine If that’s the case you are done and all you need to do is fluid restrict! We will speak more about beer potomania later on since it deserves special attention.

            TAKE HOME POINT: UOsm <100 implies water excess


If urine osmolality > 100 mOsm/kg then likely there is impairment of the renal concentrating ability. Now, it gets a little more complicated. *At this point more lab testing will likely be needed. My feeling is if you are going to order a urine sodium, you might as well order everything at once[f]. At this point I recommend ordering:

Serum:  cortisol, Osmoles, TSH, Uric acid

Urine:  creatinine, potassium, sodium, Uric acid,


In a study by Imran, 504 urine specimens from patients on whom a simultaneously drawn USG and an osmolality were available were examined. They found good linear correlation between USG and Urine Osm when measured either by reagent strip or refractometry. Urine samples were divided into ‘‘clean’’ and ‘‘pathological’’ urines. Pathologic urines on reagent strip included: glucose, ketones, urobilinogen, bilirubin, and protein and ketones, bilirubin, and urobilinogen, for samples measured using refractometry. The study found that pathological urines did not correlate as well to urine Osm as the non-pathological12.  In another study of only hyponatremic patients it was found that USG has a linear relationship with measured urine osmolality in patients with hyponatremia. A multiplying factor of 20-33 is better than 30-40 in predicting urine osmolality of most patients with hyponatremia11. The commonly used formula to predict UOsm from USG uses a multiply of 30 but from the above two studies it would appear that multiplying by 25 gives a closer approximation and less likely to overestimate.  Hence equation 3.

STEP 4: URINE Na <30 mEq/L

If urine sodium concentration ≤ 30 mmol/L, then most likely low effective arterial volume (see below optional section on What the hell does “low effective arterial volume” mean) is the cause of the hypotonic hyponatraemia. Really what we have to focus on here is whether the patient has HYPERvolumic or HYPOvolemic causes. The cutoff of urine sodium of 30 is randomly picked based on studies and is used by guidelines2. Using a cutoff of <30 suggests the above diagnoses and diuretics wont affect this diagnosis1.

OPTIONAL: What the hell does “low effective arterial volume” mean

Early observations in patients with cardiac failure demonstrated renal sodium and water retention that resulted in an increase in extracellular fluid (ECF) volume and edema. This degree of sodium and water retention in normal individuals would lead to an increase in renal sodium and water excretion, yet the reverse occurs in patients with heart failure. A similar sequence of events occurs in patients with cirrhosis and pregnancy. Renal sodium and water retention in edematous disorders continued to be perplexing. A term for sodium and water retention in edematous disorders was proposed to be due to a decrease in “effective blood volume” rather than “total blood volume”. For many years, however, this enigmatic term, which was used to explain sodium and water retention in patients with heart failure or cirrhosis, was never defined.  Use of the term “decreased effective blood volume” can be considered outdated and be replaced by “arterial under-filling.” However, use of the term persists in clinical medicine, as “decreased effective arterial blood volume”13.


Although I said before that determining clinical volume status is more difficult at this stage the causes of hyponatremia from hypovolemic and hypervolemic reasons should be more obvious. Hypervolemic causes would include: CHF, Cirrhosis, and Nephrotic syndrome. Hypovolemic causes would include: Diarrhea and vomiting, third spacing, diuretics. It should be noted that a third cause of low urine sodium is very low sodium intake but this is rare in western diets. Also know there are insufficient data to suggest that increasing serum sodium concentration improves patient-important outcomes in moderate hyponatraemia with expanded extracellular fluid volume, in cirrhosis or heart failure.



If the urine sodium is >30 mEq/L then one needs to consider if the patient is on diuretics. When I say diuretics I’m mostly refering to Thiazide and Thiazide-like diuretics. Potassium sparing diuretics can contribute to hyponatremia but less so. Loop diuretics are much less likely to cause hyponatremia.  In fact diuretics can cause a urine sodium of <30 mEq/L also but we will touch on how to differentiate this as well.  If the patient is NOT on diuretics then again we must decide if the patient has hypovolemia or Euvolemia


Determining volume status in this category may be more subtlebut hypovolemia should be more obvious than euvolemia in this group. Thus, if by clinical exam, the patient is hypovolemic then the causes include: vomiting, primary adrenal insufficiency and renal/cerebral salt wasting.Determining euvolemia is much more subtle, however, if the ECF is normal by clinical exam then the causes include: SIADH, secondary adrenal insufficiency, and hypothyroidism (realistically unless hypothyroidism is severe such as myxedema or TSH >50 mIU/mL, then other causes of hyponatremia should be considered10). 


As I said above the big problem at this branch point is that determining whether a patient is euvolemic or not can be very difficult. Additionally the treatments of SIADH and salt wasting are differentbecause of fluid restricting patients with SIADH as opposed to administering salt and water in salt wasting14. One way to differentiate this is by the fractional excretion of uric acid (urate). FEurate is normally 4%–11%and will stay normal in the excess water states with low urine osmoles because the concentrating ability is preserved (BOX 1 conditions). If the FEurate is <4%, it is consistent with pre-renal (BOX 2,3,4 conditions) including volume depleted states or edematous states such as CHF, cirrhosis, nephrotic syndrome,and pre-eclampsia.


Distinguishing these two can be very different because the only real difference is that in salt wasting there is a decrease in volume. However, the treatments are very different. The FEurate is especially helpful in distinguishing these two entities. In SIADH and Salt wasting (either cerebral or renal) FEurate is increased to >11% while the sodium is low. However, they can be differentiated after correction of the sodiumto >130. In SIADH, correction of hyponatremia will normalize FEurate to <11%, however in salt wasting the FEurate will still be inceased to>11%. One important caviat is that for the FEurate to be valid the patients serum creatinine must be <1.5 mg/dL14.


Essential criteria

  • Effective serum osmolality < 275 mOsm/kg 

  • Urine osmolality > 100 mOsm/kg at some level of decreased effective osmolality

  • Clinical euvolaemia 

  • Urine sodium concentration > 30 mmol/L with normal salt and water intake 

  • Absence of adrenal, thyroid, pituitary or renal insufficiency 

  • No recent use of diuretic agents 

Supplemental criteria

  • Serum uric acid < 0.24 mmol/L (< 4 mg/dL) 

  • Serum urea < 3.6 mmol/L (< 21.6 mg/dL)

  • Failure to correct hyponatraemia after 0.9% saline infusion 

  • Fractional sodium excretion > 0.5% 

  • Fractional urea excretion > 55% 

  • Fractional uric acid excretion > 12%
Correction of hyponatremia through fluid restriction


Fractional Excretion Of Sodium FENa

It is calculated byScreen Shot 2018-12-24 at 5.51.21 AM         

In patients with normal renal function and hyponatremia cut off for FENa is <0.1%.

<0.1%- hypovolemic hyponatremia

>0.1%- hypervolemic and normovolemic hyponatremia.


In hyponatremia due to SIADH, the blood urea nitrogen (BUN) is usually less than 5 mg/dL. However, as urea excretion decreases with aging the absence of a low BUN cannot be used to exclude SIADH in older patients10.

 Fractional Excretion of Uric Acid14

This is calculated as:   Screen Shot 2018-12-24 at 5.51.28 AM     

FEUrate <4% implies: Volume Depletion Addison’s Disease Edematous states, CHF

  Cirrhosis, Nephrotic syndrome

FEUrate 4-11% implies: psychogenic polydipsia

FEUrate >11% implies: HCTZ, Salt Wasting

After normalization of Na to >130 FEurate will be <11% in SIADH and >11% in Salt wasting


Cases of a hypoosmolal (Hypotonic) syndrome in beer drinkers were first described in 1972. Up to 17% of chronic alcoholic patients had hyponatremia.  Although not consistently reported in patients with beer potomania, low urine osmolality on admission laboratory test results was not a consistent finding. In addition to the history of excess beer drinking, often a recent history of binge drinking or illness was present.  This may potentially precipitate a rapid decrease in serum sodium levels. The maximum urinary dilution capability is 50 mOsm/L, a large amount of water (>20 L) must be ingested under normal situations to overwhelm the capacity for urinary dilution. For example, if the patient excretes only 100 mOsm/d, greater than 2 L of fluid intake with a urinary dilution capability of 50 mOsm/L will result in net water retention and subsequently hyponatremia. Patients with beer potomania have a history of significant beer drinking, often long term, in conjunction with a poor diet. The net result is very low osmole intake because beer has very little sodium and no protein, but has some calories that prevent endogenous protein breakdown (urea generation). Because the obligatory solute loss in a day is approximately 250 mOsm in these patients, with a urinary dilution capability of 50 mOsm/L, water intake greater than 5 L (or 14 cans of beer) results in hyponatremia. The net effect is an excess of free water without the solute for diuresis. ADH levels are expected to be suppressed in patients with beer potomania. The low ADH levels limit free-water reuptake in the collecting tubules of the kidney and explain why these patients have brisk diuresis when solute is presented. Sodium chloride in IV fluids is a common source of the solute load while hospitalized. Urine osmolality on recheck after the solute is introduced is low in these patients because of the low ADH levels. Based on a solute concentration of 308 mEq/L (154×2) in 0.9NaCl solution and the kidney’s diluting ability of 50 mOsm/L, significant diuresis can occur with 1 L of NS solution in the setting of a low-ADH state. This water diuresis can produce large increases in serum sodium levels in a short period. Attempting to replace this with electrolyte-free water to prevent a rapid increase in sodium levels can be difficult. Beer potomania is unusual because the cause of hyponatremia is multifactorial, including low osmole intake. Furthermore, as these patients convert to a low ADH state, the rate of correction may be dramatic.  One study found that 18% of patients presenting with beer potomania developed ODS. Three large retrospective reviews of patients who presented with symptomatic severe hyponatremia found no benefit to aggressive correction of chronic hyponatremia. If the patient is asymptomatic, fluid restriction and monitoring the patient despite the degree of hyponatremia is the recommended approach. If the serum sodium level increase occurs at a rate that will exceed the desired goal, D5W infusion should be started to match urine output. The D5W rate can be adjusted every 2 hours based on serum sodium level change. If serum sodium levels increase to greater than either the 24- or 48-hour goals, D5W rate should be increased to decrease the serum sodium level to the recommended goal. Desmopressin may be considered if diuresis occurs at an excessive rate that the infused D5W is unable to match; based upon the current rate of serum sodium level change, the goal will be exceeded despite D5W; the goal has been already been exceeded; or last, symptoms of ODS develop15. A large rise in serum Na after infusion of a test volume of isotonic saline suggests the presence of hypovolemia. 









  1. Spasovski G, Vanholder R, Allolio B et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014; 29 Suppl 2, i1-i39.
  2. Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol 2017; 28, 1340-1349.
  3. Anderson RJ, Chung HM, Kluge R, Schrier RW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 1985; 102, 164-168.
  4. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med 2006; 119, S30-5.
  5. Giordano M, Ciarambino T, Castellino P et al. Seasonal variations of hyponatremia in the emergency department: Age-related changes. Am J Emerg Med 2017; 35, 749-752.
  6. Imai N, Osako K, Kaneshiro N, Shibagaki Y. Seasonal prevalence of hyponatremia in the emergency department: impact of age. BMC Emerg Med 2018; 18, 41.
  7. Choy KW, Wijeratne N, Lu ZX, Doery JC. Harmonisation of Osmolal Gap – Can We Use a Common Formula. Clin Biochem Rev 2016; 37, 113-119.
  8. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med 2001; 38, 653-659.
  9. Plasma osmolality. Wikipedia
  10. Sahay M, Sahay R. Hyponatremia: A practical approach. Indian J Endocrinol Metab 2014; 18, 760-771.
  11. Sumethkula V, Choojitaromb K, Ingsathitc A, Radinahamed P. The Correlation between Urine Specific Gravity and Urine Osmolality in Patients with Hyponatremia. nternational Journal of Sciences: Basic and Applied Research (IJSBAR) 2017; 31, 181-189.
  12. Imran S, Eva G, Christopher S, Flynn E, Henner D. Is specific gravity a good estimate of urine osmolality. J Clin Lab Anal 2010; 24, 426-430.
  13. Schrier RW. Decreased effective blood volume in edematous disorders: what does this mean. J Am Soc Nephrol 2007; 18, 2028-2031.
  14. Maesaka JK, Imbriano L, Mattana J, Gallagher D, Bade N, Sharif S. Differentiating SIADH from Cerebral/Renal Salt Wasting: Failure of the Volume Approach and Need for a New Approach to Hyponatremia. J Clin Med 2014; 3, 1373-1385.
  15. Sanghvi SR, Kellerman PS, Nanovic L. Beer potomania: an unusual cause of hyponatremia at high risk of complications from rapid correction. Am J Kidney Dis 2007; 50, 673-680.
  16. Momi J, Tang CM, Abcar AC, Kujubu DA, Sim JJ. Hyponatremia-what is cerebral salt wasting. Perm J 2010; 14, 62-65.
  17. Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am 2010; 21, 339-352.
  18. Filippatos TD, Liamis G, Christopoulou F, Elisaf MS. Ten common pitfalls in the evaluation of patients with hyponatremia. Eur J Intern Med 2016; 29, 22-25.


[a]Incidence Incidence is the rate of new cases of the disease. Prevalence is the actual number of cases alive or the accumulation of the incidences over a period of time. 

[b]Poto – drinking alcohol; mania – excessively

[c]Well really Osmolarity = Osmolality x 0.995 but who is counting.

[d]I was literally once told this by one of my really smart 8 yo Type I diabetic patient from the UK who told me how to convert mEq/L to mmol/L for his glucometer readings!

[e]Remember: each mg increase in blood glucose above 100 mg/dl decreases the serum sodium by 1.6 meq/l. This is negligible when blood sugar is less than 300 mg/dl. When serum triglycerides are above 100 mg/dl, for every 500 mg/dl rise in serum triglycerides, fall in serum sodium will be about 1.0 mEq/L. When serum protein is above 8 gm/dl, for every 1 gm/dl rise in serum protein, fall in serum sodium will be about 4.0 mEq/L10.

[f]This is the Shriki-EM Mantra

[g]US guidelines recommend a limit of 6-8 but this is based on limited data.

[h]As a means of increasing solute intake, daily intake of 0.25–0.50 g/kg urea can be used. The bitter taste can be reduced by the following recipe in Sachets:  10 g urea + 2 g NaHCO3 + 1.5g citric acid + 200 mg sucrose to be dissolved in 50–100 ml water.  Alternately using a commercially available urea powder drink mix (Ure-Na by Nephcentric)2

Hyper K, The EBM Way: Protect, Push, and Purge

As we all know hyperkalemia is a life threatening condition. But how can something so basic be shrouded in such confusion? So many choices and everyone has their own recipe to fix it. Along with all the treatment choices, come pitfalls and side effects. Thus, we need to know what is the best way to treat this without giving our patients further problems! Enter “The Algorithm”. I hold before you an approach (evidenced based of course) for treating this life threatening condition. Remember, as always this is only one option and not THE ONLY option for treatment. If your hospital has a guideline or best practice then best stick to that. Otherwise, feel free to enter into a deep forest overgrown with evidence and lush with literature about the treatment of hyperkalemia.


Hyperkalemia can be tricky. We all learn the basic ECG patterns for hyperK as it goes through stages on its way to a “sine wave” and eventual flat line. However, experience teaches that hyperK comes in many forms. The most devious is the severe symptomatic bradycardia. All too often a patient will come in for bradycardia and hypotension, then get started on the path to a pacer, only to find out their K was 10! Don’t let this happen to you! Remember the mantra:

O WATA GOO SIAM… wait no not that one this one:

Bad Brady? Give Gluconate”(Ca+2that is)

Let me repeat that “Bad Brady? Give Gluconate”( Ca+2 that is). That’s right for BAD BRADYcardia GIVE calcium GLUCONATE. Or maybe better:


Whatever it takes for you to remember, check that K when you see symptomatic bradycardia and if you don’t have time for it to result give a trial of calcium gluconate before you put in that pacer!



While we are on the topic of electricity, how good is the ECG for detecting hyperK? It depends what you are calling “ECG Changes”. Studies looking at this topic have shown that hyperK can present without any ECG findings. One study found peaked T-waves in only 34% of ECG’s and potassium levels >6.5 mEq/L1. There are also case reports of patients with potassium levels >10 mEq/L and ECG’s non-diagnostic for hyperkalemia2.  In another study it was not until the serum K > 8 that they found 100% concordance between hyperkalemia and ECG change3. So what are some predictors of hyperkalemia in the ECG? This study3suggests the best predictors by Risk Ratio (RR) for hyperkalemia are QRS prolongation (RR 4.74), junctional rhythm (RR 7.46), and bradycardia less than 50 bpm (RR 12.29) (See Table 1). Importantly, these were the ECG changes that were predictive of adverse events in hyperkalemia. Interestingly peaked T-waves in this study had an RR of 0.77[a]3.


Table 1. ECG changes associated with Hyerkalemia3

ECG Finding Risk Ratio, 95% Confidence interval
Bradycardia (HR<50) 12.3, 95% CI [6.69-22.57]
Junctional rhythm 7.46, 95% CI [5.28-11.13]
QRS prolongation >111 4.74, 95% CI [2.01- 11.15]
Peaked T-waves 0.77, 95% CI [0.35-1.70]



We all have that picture in our mind of who gets hyperkalemia but I want to talk about one group in particular that can be at a special risk. Patients with cardiac devices (pacemakers/AICDs) in addition to the typical cardiovascular collapse can have additional problems. Hyperkalemia can precipitate pacemaker problems specifically widening of the QRS, failure to capture, and delay of the interval from the pacemaker stimulus to the onset of depolarization 4.



OK, So now on to the good stuff! The treatment can be divided essentially into 3 phases, which I have dubbed: PROTECT, PUSH, PURGE (mostly because I enjoy  the alliteration[b]).

Hyper K algorithm

PDF VERSION: Hyper K algorithm-2


The first commandment of treating hyperkalemia is to PROTECT(and don’t covet) this myocardium! Calcium is the mainstay of treatment to protect the cardiac cells from the electrical disaster that is hyperkalemia. Calcium gluconate is typically the first line treatment given the fact that there is less elemental calcium than its partner calcium chloride. This becomes both its advantage and hindrance. The gluconate will not likely sclerose the veins given its concentration. Furthermore, it wont cause tissue necrosis (the opposite of helping) or thrombophlebitis unlike the chloride form. However, it may need to be repeated since it contains a third less the calcium than the chloride form. Strangely enough even in the year 2018, the optimal dose of calcium gluconate isn’t known5, however usually recommended is 10mL or 1g IV. There used to be some lore that the gluconate would require liver activation however both animal and human studies have shown that this is not the case even in liver failure5. Therefore, this is unlikely an issue. Due to the potential for harm, the chloride form is only recommended in the case of cardiac arrest or in the presences of a central line.  Calcium may be re-dosed twice based upon expert consensus5, 6.


The second commandment of the algorithm; thou shalt PUSH thine K into thine cells. By pushing the K back into the cells you are merely hiding the K from the now excited myocardium. Remember, this is only a temporary fix. Potassium is pushed into the cell using a beta-2 agonist such as albuterol. Catecholamines work on the sodium-potassium ATP-ase pump. There is nothing special about albuterol (sorry albuterol), any catecholamine will do. However, albuterol is probably the safest and the easiest to administer. Epinephrine could do the same but would have too many side effects so its not really used. The does of albuterol is big however 10-20mg nebulized. These doses can cause a decrease of serum K+ by 0.6 mEq/L within 30 min and 1.0 mEq/L 1 h after administration for 10mg and 20 mg, respectively5. Tell your patient to expect a few jitters with this and consider that up to 40% of patients on oral beta-blocker therapy may be resistant to this therapy. However, predicting who gets this is impossible. The second drug to accomplish this PUSH is insulin given with glucose to prevent hypoglycemia. Insulin can decrease K+ by 0.6–1.2 mEq/L 5, with an onset of action about 15 min, peak around 30-60 min, and last about 4 hours6.  Insulin/glucose combined with albuterol appear to have a synergistic effect5. The last treatment is controversial. The use of 8.4% Bicarbonate has long been held as the go to treatment. Recently, however, the thrill is gone. There is insufficient data showing benefit for bicarb. Several studies reported that sodium bicarbonate did not lower serum potassium significantly or promptly. In one (poorly done) study 1 mEq (1 amp) of bicarb decreased serum K only by 0.15 mEq/L 5. No study has found immediate reductions in serum K+ and the effects may be not be observed until 4-6 hours later5–7. Sodium bicarbonate may expose patients to a large fluid load, hypernatremia, and metabolic acidosis. Therefore, sodium bicarbonate should no longer be the first line therapy for hyperkalemia6. Bicarb may be useful when patients are acidotic or hypovolemic requiring a fluid load given its large amount of sodium6, 7. Table 2 is a summary of the PUSH therapies.

Table 2. Therapies to PUSH K intracellularly.

Calcium (either) 10 ml Immediate 30 min N/A
Albuterol 10mg 25-30 min 1 hr 0.6
Albuterol 20mg 30 min 2 hr 1.0
Insulin 10-20 mg 15 min 4 hr 0.6-1.2
Bicarbonate 4-6 hrs 4-6hrs 0.15?


Obviously, giving doses of insulin can result in a decrease in blood glucose and even life threatening hypoglycemia. Therefore glucose is given in conjunction with insulin. The question is how much insulin and how much glucose? No one knows the answer to this question. Many different schemas have been suggested. Altering the insulin dose has been suggested; from ultra short acting insulin to infusions of insulin. Additionally, altering the amount of glucose; using a continuous infusion vs. bolus has also been suggested. There is no consensus between expert panels on the dose or route of insulin or glucose. Frequent monitoring for hypoglycemia is definitely recommended. One poorly done before and after study suggested 5 units of insulin in ESRD patients (see my post on that study here). One conservative dosing regimen is given below in table 3.  


TABLE 3. Insulin/Glucose Dosing options

Insulin Options Glucose Dose Glucose Re-Dose Lab Monitoring
Regular 5 U

(Consider in ESRD)

25g D50

(1 amp)

None BS q 1 hr x3

BMP 1 hr post insulin

Regular 10 U 25g D50

(1 amp)

25g D50 @ 1 hr post insulin BS q 30 min x 6

BMP 2hr post insulin

Regular 10 U

(Consider if glucose <100 mg/dL)

D10W gtt @

200 ml/h infusion

None BS q 1hr x3

BMP 2hr post insulin

ESRD = End Stage Renal Disease, BMP = Basic Metabolic Panel, glucose mg/dL


This phase will depend on whether or not the patient has working kidneys. In the case that the kidneys are not working, there is a post obstructive uropathy, or there is oliguria; hemodialysis (HD) is the answer (or CRRT). This means placing a call to your friendly neighborhood nephrologist and dialysis nurse and getting them to come out. HD is also the gold standard treatment. Although there are no definitive studies on the timing or dose of HD. Recommendations for initiation can include: persistent ECG changes, poor response to treatments, and severe AKI. Kayexalate (Sodium PolyStyrene/SPS), once the mainstay of treatment, has fallen out of favor. Multiple consensus panels have endorsed not using it 6, 7.  One such panel recommended “that all other treatment options be exhausted prior to using this [SPS] potentially harmful therapy with little evidence of efficacy”6. Subsequently, the FDA has added a warning for colonic necrosis to the Kayexalate labeling when co-administered with sorbitol8. If, on the other hand, the kidneys are working then loop diuretics may be used at a dose of 20 mg (naive and CKD stage <3) or 40 mg (not naive or CKD stage ≥3).


On the horizon are new potassium binding medications. One expert consensus panel[c]recommended using Patiromir in the acute setting7despite ZERO studies performed in the ED.  Patiromer is an FDA approved new potassium binder that exchanges calcium for potassium for treatment of chronic hyperkalemia.  Side effects include binding oral medications, constipation, and hypomagnesaemia.  Furthermore, its effect is not reached until about 7 hours. Another possibility is the yet unapproved Sodium zirconium cyclosilicate (ZS-9). In a study of 45 patients with serum potassium concentrations of at least 6 mEq/l, 10 g of ZS-9 reduced the serum K by 0.4 mEq/l at 1 hour, by 0.6 mEq/l at 2 hours, and by 0.7 mEq/l at 4 hours9.


One last item to tackle is the “Stone Heart” condition. The “stone heart” theory ascribes calcium as the precipitating condition in which the heart is unable to contract. This occurs when a patient with hyperkalemia is given calcium while currently taking digoxin. The thought is that this may be due to the failure of diastole from calcium binding to troponin and the heart freezes like a stone. This has been “romanticized” into lore. Besides how can one deny a sexy name like “Stone Heart”, it rings of truth! Thus far however, not animal studies, case reports, nor retrospective reviews have found an association of mortality with administration of calcium for hyperkalemia in occult digoxin toxicities 10–12.  The romance may be gone. It was a good run “Stone Heart”. I’ll miss you most of all.


How bad is Hyperkalemia? That question can be seen in the graph below from a study by  Einhorn in archives of internal medicine 2009. This study looked at 66,259 Hyperkalemia events (not patients) in a VA population. They found a 2.4% incidence of death WITHIN ONE DAY (yes one day!). The found that in the patient with no chronic kidney disease a serum K between 5.5 and 6.0 had an OR of death within 24 hours of 10 and above 6.0 had an OR of death of almost 32! Those are huge numbers. In actual cases the group with no CKD had an inpatient mortality of 3.2% for K 5.5 to 6.0 meq/L and 8.6% for those with K greater than 6! For the CKD group (as a whole) it was 1.8% for K between 5.5 and 6.0 and 4.8% for those with a k >6.0. Those numbers while about half of these with chronic kidney disease still represents a very high mortality! Thus Hyperkalemia should be taken very seriously and both treated and admitted unless they are very reliable or have good follow up. Screen Shot 2019-03-19 at 10.29.59 PM



  1. Freeman K, Feldman JA, Mitchell P et al. Effects of presentation and electrocardiogram on time to treatment of hyperkalemia. Acad Emerg Med 2008; 15, 239-249.
  2. Szerlip HM, Weiss J, Singer I. Profound hyperkalemia without electrocardiographic manifestations. Am J Kidney Dis 1986; 7, 461-465.
  3. Durfey N, Lehnhof B, Bergeson A et al. Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events. West J Emerg Med 2017; 18, 963-971.
  4. Barold SS, Herweg B. The effect of hyperkalaemia on cardiac rhythm devices. Europace 2014; 16, 467-476.
  5. Long B, Warix JR, Koyfman A. Controversies in Management of Hyperkalemia. J Emerg Med 2018; 55, 192-205.
  6. Rossignol P, Legrand M, Kosiborod M et al. Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future. Pharmacol Res 2016; 113, 585-591.
  7. Rafique Z, Weir MR, Onuigbo M et al. Expert Panel Recommendations for the Identification and Management of Hyperkalemia and Role of Patiromer in Patients with Chronic Kidney Disease and Heart Failure. J Manag Care Spec Pharm 2017; 23, S10-S19.
  8. Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective. J Am Soc Nephrol 2010; 21, 733-735.
  9. Sterns RH, Grieff M, Bernstein PL. Treatment of hyperkalemia: something old, something new. Kidney Int 2016; 89, 546-554.
  10. Hack JB, Woody JH, Lewis DE, Brewer K, Meggs WJ. The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model. J Toxicol Clin Toxicol 2004; 42, 337-342.
  11. Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med 2011; 40, 41-46.
  12. Van Deusen SK, Birkhahn RH, Gaeta TJ. Treatment of hyperkalemia in a patient with unrecognized digitalis toxicity. J Toxicol Clin Toxicol 2003; 41, 373-376.


[a]For those of you keeping score you might say with an RR of 0.77 peaked T-waves are PROTECTIVE of adverse events of hyperkalemia but this is probably because we are used to looking for peaked T-waves so physicians were more likely to recognize these and treat earlier rather then it being protective of adverse events in hyperK

[b]I always get confused between alliteration, consonance and assonance. So FYI, the difference is in where the rhyme occurs. Alliteration it’s the beginning (e.g. Larry likes Laurie), consonance it’s the end (frog on a log), and assonance its the middle (e.g. rock in a box was locked)

[c]This panel discussion was funded by Relypsa and facilitated by Magellan Rx Management. Relypsa is the manufacturer of Veltassa (patiromer). Rafique is a principal investigator for Relypsa and serves as a consultant for Instrumentation Laboratory, Magellan Health, Relypsa, and ZS-Pharma. Butler serves as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CardioCell, Janssen, Merck, Novartis, Relypsa, and ZS-Pharma. Lopes and Farnum are employed by Magellan Rx Management. Rafique designed the management protocol for this panel discussion and contributed to the writing and editing of this report document. The other authors report no conflicting interests.


Quick Hit Article #6:  How much insulin to give ESRD patients with Hyper K?

One of the most physiologically complicated yet overly simplified “set it and forget it” protocols in emergency medicine just might be the acute treatment of hyperkalemia. We all have the protocol in our head and can write it up in our sleep (hopefully) but how effective is it? How safe is it? How evidenced based is it? So many questions so little time. To think that we can still improve on this time-tradition sequence tells me that we still don’t, “K”-now it all.. Mmm .. “K”…. (see what I did there? Lol)

Today’s Quick hit article is on this topic of how much insulin is needed in the treatment of hyperkalemia in dialysis patients. I think this may be the only method lacking, retrospective, observational, chart review that has or ever will change my practice (with all due respect to the authors). This is a before and after study of the amount of insulin given to patients who are hyperkalemic AND have ESRD (end stage renal disease).

McNicholas. Treatment of Hyperkalemia With a Low-Dose Insulin Protocol Is Effective and Results in Reduced Hypoglycemia.  Kidney Int Rep. 2017 Oct 24;3(2):328-336.


The Bottom Line:
This was a single center before and after trial of an intervention to decrease the amount of hypoglycemia by decreasing the amount of regular insulin given IV to treat hyperkalemia. The big flaw here? This study lacks methods necessary for statistical rigor (see Table 1).  The treatment of hyperkalemia with the use of insulin in ESRD patients may be decreased from 10 units of regular insulin IV down to 5 units of regular insulin IV. This decreased the amount of hypoglycemia (12% vs 6%) induced while still appropriately lowering the potassium by 0.5 to 1 meq/L. Despite the high risk of bias and very small sample size used, it seems to make sense to lower the insulin dose in ESRD patients to 5 with minimal(?) harm. I will continue to order frequent point of care glucose checks since hypoglycemia was not abolished. I will also repeat the K at appropriate intervals in the case that a repeat dose of insulin or other treatment is needed. Therefore, although I don’t think this study is evidence for using lower insulin in ESRD patients I do think they came up with the right answer anyway.

The Shout out:

I want to give a big shout out to an amazing mentor Dr. Paul Blackburn. We discussed this article and he told me this has always been his practice. Dr. Blackburn never stop teaching, you have and always will have something to teach us young (and not so young) docs! Thank you!


K chart review-2

The Details:

This was a single center, before and after trial, of an intervention to decrease the amount of hypoglycemia by decreasing the amount of regular insulin given to treat hyperkalemia. The study was performed in an urban academic ED in Seattle. They noticed a significant amount of hypoglycemia, including hypoglycemia to <40 in the ESRD patients. Therefore, they undertook an intervention using education to recommend lowering the dose of IV insulin given form 10 units down to 5 units. They called the pre-intervention “audit 1” and the post intervention “audit 2”. We will get into the details but first let’s go over the methods using my chart review checklist (See my post on Chart reviews). By looking at Table 1 you can see that very few of the methods necessary to validate a chart review were followed. Therefore, this chart review is at extremely high risk of bias. Fortunately, the authors do mention a number of significant limitations. One noteworthy limitation is the very small numbers. What is strange is the number of cases of hyperkalemia decreased in the after period for an unknown reason. Another issue is that some of the patients weren’t treated with insulin at all! They also noted that although compliance with their new protocol of decreased amount of insulin improved (25% getting 10 units vs 2% getting 10 units) they still did not have complete compliance. The way they organized their data actually makes it quite difficult to discern differences. In fact you can’t really tell how many of the ESRD patients were hypoglycemic in audit 1 vs audit 2. Nor can you tell in audit 2 if the K dropped to an appropriate level. A sample size calculation was not given so we don’t even know if these numbers were either clinically or statistically significant. The most glaring example is when they say that they noticed in the pre-audit a “large” amount of hypoglycemia. However, they note that “There was a trend for ESRD patients who were treated with 10 units versus 5 units of insulin to develop hypoglycemia (9 of 32 patients [28%], 5 units, vs. 6 of 11 patients (54%), 10 units i.v. insulin, P = 0.1).” So is this a even a real difference? Clinically it sounds like it however they state there were “fewer patients being treated for hyperkalemia between the 2 audit periods”.  There are certainly a lot of holes in this swiss cheese. On the other side however, this seems like it is an intervention that makes sense and in their small sample size they did have few cases of hypoglycemia and still a reduction (I think?) in the K. Therefore, even though this study isn’t evidence for using lower insulin in ESRD patients they came up with the right answer anyway.

Table 1.

The Checklist:
1.     Investigator bias
        a.     Question appropriate for chart review? Yes
        b.     Financial/Intellectual disclosures supplied? Yes
2.     Charts bias
        a.     Methods of Chart Identification (CC vs ICD-10) No
        b.     Sufficiently sampled? Unknown
        c.     Was a power calculation supplied? No
        d.     A priori inclusion criteria? No
        e.     A priori exclusion criteria? No
        f.      Table of clinical characteristics? Yes
        g.     Flow diagram delineating how the study population was derived? Abbreviated
3.     Data bias
        a.     Defined A priori? No
        b.     Coding guide for abstractors? No
        c.     Coding guide provided? No
        d.     Standardized Data Collection tool (DAT)? No
        e.     Was the DAT pilot tested? No
        f.      Was the DAT provided? No
        g.     Is there missing or conflicting data? Unknown
        h.     How is missing data handled (sensitivity analysis)? unknown
4.     Abstractor bias
        a.     Blinded to study hypothesis? Unknown
        b.     Trained appropriately? Unknown
        c.     Monitored? Unknown
        d.     Inter-rater Reliability? Unknown
        e.     Intra-rater reliability? Unknown
5.     Reliability bias
        a.     Kappa and percent agreement calculated for the data? No
        b.     What level of reliability and why was that level chosen? Unknown
        c.     Which of the collected variables were checked for reliability? Unknown
        d.     What percent of the data was checked for reliability? Unknown

The ABC’s of ABG’s or How to read a blood gas without the Hassel(bach)

A blood gas interpretation is often a fear inducing “pimp” question. Probably because there is a so much packed into them and at some point, some basic math is needed. So, let’s try to unpack it a little so we have more method and less madness. I’m going to divide this up into 4 parts: The explanation (Part I), The calculation of the ABG (Part II), The Differential Diagnoses (Part III), The Practice (Part IV)


Blood gases are ruled by the often cited but never remembered: Henderson-Hasselbach equation:Screen Shot 2018-07-08 at 5.30.47 PMI think its easier to remember written in the ABCD form:

Screen Shot 2018-07-08 at 5.30.52 PM

There are only FIVE RULES to understanding ABG’s

  1. The primary disorder causes the pH
  2. The primary disorder is moves with the pH in the resulted direction
    1. Metabolic disorders are like a boy band…They always changes in ONE DIRECTION (i.e pH goes in the same direction as the primary disorder)
    2. Credit to Joel Topf of the curbisders podcast for that dad joke…
  3. Compensation occurs in the same direction as the primary disorder
  4. The body can’t make a large number of anions so an anion gap always means a primary metabolic acidosis is present
  5. A second primary disorder exists when the compensation doesn’t completely correct for the problem


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The 4 steps in reading an ABG:

Step I: Determine the pH and Primary disorder:

–      If pH, HCO3, and pCO2 are ONE DIRECTION then primary disorder is metabolic

e.g. All down:    <7.40, CO2 <40, HCO3 <24 = metabolic acidosis

e.g. All up:     >7.40, CO2 >40, HCO3 >24 = metabolic alkalosis

–    If pH, pCO2, HCO3 are in opposite directions then primary disorder is respiratory

Step II: Determine if there is a gap acidosis. If there is, then a  gap acidosis must be present

  • Gap = Na (corrected for glucose) – (Cl + HCO3)
  • PEARL: Remember to use the bicarb from the BMP/CMP not the ABG!
  • An AG of >30 is very likely to have an AGMA
  • An AG 20-29 then clinically 1/3 will not have metabolic acidosis
    • The Bicarb is CALCULATED in the ABG and MEASURED in the BMP
      • The pCO2/HCO3 ratio should always be checked
        • H+ = 24 x pCO2/HCO3-
    • Na is falsely low in hyperglycemia and must be corrected to get the correct Na. To correct do the following: For every 100 over 100 glucose add 1.6 to Na
    • Some people correct the  gap for albumin but you probably don’t need to. However, if you did it would be:
      • Corrected gap = AG + [2.5x(4-albumin)]

Step III: Determine Compensation (occurs in the same direction as the primary disorder)

  • Remember pH is inversely related to pCO2 and directly proportional to HCO3
  • If the HCO3 is low then the PCO2 should lower to compensate
  • See Compensation question below
    • Some say if the last two digits of the pH = pCO2 then NO respiratory disturbance occurs (eg. pH = 7.40 and pCO2= 40 then no respiratory disturbance)

Step IV:  Calculate the excess (or Delta) Gap (that is take out the GAP):

  • (Anion Gap – 12) + HCO3
  • If Excess > 25 then underlying Metabolic Alkalosis
  • If Excess < 23 then underlying Non-gapacidosis


Delta Gap =∆AG-∆HCO -=Na+-(Cl++HCO -)-12-(24-HCO -)

=Na+-Cl – 36

If the DG is significantly positive (>+6), a metabolic alkalosis  (IN ADDITION TO AGMA) is present because the rise in AG is more than the fall in HCO3-.

Conversely, if the DG is significantly negative (<-6), then a hyperchloremic (non-gap) acidosis (IN ADDITION TO AGMA) is present because the rise in AG is less than the fall in HCO3-.

*You could stop at the above step at get most of the way there*


Step IVa: Calculate “correction equations” to find the second primary disorder

  • Is there ENOUGH compensation to make up for the primary disorder (Is there a SECOND PRIMARY disorder?) ∆= Delta = Change
  • Correction equations can be made into a mnemonic (not a great one but kinda) if you remember things alphabetically (metabolic then respiratory, acidosis then alkalosis, acute then chronic) and the numbers  1.5 – 8 = 7, 1,2,3,4:
    • Metabolic acidosis:           pCO2 =  1.5 × HCO+ 8 ± 2 (Winter’s formula)
    • Metabolic alkalosis:           ∆ pCO2 = 9[∆ HCO3] OR                                         (pCO2 =0.9x HCO3+9±5) [Narins]
    • (Acute) Respiratory acidosis:   pCO2:HCO3 changes 10:1
    • (Acute) Respiratory alkalosis:  pCO2:HCO3 changes 10:2
  • (Chronic) Respiratory acidosis:         pCO2:HCO3 changes 10:4
  • (Chronic) Respiratory alkalosis:       pCO2:HCO3 changes 10:3
  • Alternately remembered as: The RESPIRATORY corrections table 
  pCO2 : HCO3
  Acidosis Alkalosis
Acute 10:1 10:2
Chronic 10:4 10:3


STEP I:   LOOK AT THE PH (>7.40 is alkalosis, <7.40 is acidosis)
if >6 there is a metabolic alkalosis)



         Old: CAT MUDPILES                                                       New: GOLDMARK

C CO, CN   G Glcyols (ethylene and propylene)
A AKA   O 5-oxoproline (Pyroglutamic Acid) [from chronic acetaminophen toxicity]
T Toluene   L L-Lactic acidosis
M Methanol   D D-Lactic acidosis (short gut syndromes)
U Uremia   M Methanol
P PARALDEHYDE, Pyroglutamic Acid, Phenphormin, Paraquat, Propylene Glycol   R Renal Failure
I INH, Fe, Ibuprofen (large doses)   K Ketosis (DKA/AKA)
L Lactate      
E Ethylene glycol      
S Salicylates      

H Hyperchloraemia
A Acetazolamide, Addison’s
D Diarrhea from ileostomies, fistulas


Use urinary anion gap [= (Na+ + K+) – Cl-] to differentiate between GI and renal causes

The remaining significant ions are NH4+ or  HCO3-

Renal causes increase HCO3- excretion thus increased urinary AG

GI causes increase NH4+ excretion thus decreased urinary AG



Screen Shot 2018-07-08 at 5.30.21 PM

3-L Lytes (Ca,K, Na, Mg), Lipids, Lithium
A Albumin
M Multiple Myeloma (IgG – cationic; IgA is anionic)
B Bromide, polymyxin B
  • Analytical errors like increased Na+ (most common), increased viscosity, iodide, increased triglycerides)
  • Decrease in anions (albumin, dilution)
  • Increase in cations (multimyeloma (IgG – is a cation; IgA is an anion), hyperkalemia, hypercalcemia, hypermagnesemia, lithium, polymixin B)
  • Bromide OD (causes falsely elevated chloride measurements)


Alkaline Input

  • Bicarbonate Infusion
  • Hemodialysis
  • Calcium Carbonate
  • Parenteral Nutrition

Proton Loss

  • GI Loss (vomiting, NG suction)
  • Renal loss
  • Diuretics
  • Mineralocorticoids


C CO2 overproduction (Malignanty Hyperthermia) or CNS Depression (Trauma or Toxins)
L Lung obstruction/injury (Upper or Lower)
I Inadequate ventilation
M Myopathies
B OBesity – Pickwickian syndrome

 6. RESPIRATORY ALKALOSIS: (Only 2 general causes)

Stimulated Respiratory Drive

– Hypoxemia



Step I: Determine the pH and Primary disorder:

  • If pH, HCO3, and pCO2 are ONE DIRECTION then primary disorder is metabolic

Step II: Determine if there is a gap acidosis.

  • Gap = Na (corrected for glucose) – (Cl + HCO3)

Step III:  Calculate the excess (or Delta) Gap:

  • Na – Cl – 36
  • If Excess > 6 then underlying Metabolic Alkalosis
  • If Excess < 6 then underlying Non-AGMA

Step IV: Determine Compensation (same direction as the primary disorder)


Practice Problems:

  1. pH 7.50 / pCO2 20 / HCO3 15 / Na 140 / Cl 103
  2. pH 7.40 / pCO2 40 / HCO3 24 / Na 145 / Cl 100
  3. pH 7.10 / pCO2 50 / HCO3 15 / Na 145 Cl 100
  4. pH 7.37 / pCO2 18 / HCO3 10
  5. pH 7.50 / pCO2 48 / HCO3 36
  6. pH 7.35 / pCO2 56 / HCO3 30
  7. pH 7.56 / pCO2 22 / HCO3 23
  8. pH 7.14 / pCO2 18 / HCO3 8 / Na 134 / Cl 104
  9. pH 7.45 / pCO2 17 / HCO3 12 / Na 139 / Cl 114

Practice Answers (Primary disorder is listed first)

  1. Respiratory Alkalosis and Anion Gap Metabolic Acidosis (e.g. aspirin overdose)
  2. Gap Acidosis AND metabolic alkalosis (e.g. A vomiting renal failure patient)
  3. Primary Respiratory alkalosis, Gap Acidosis AND metabolic alkalosis
  4. Metabolic acidosis, predicted pCO2 = 23, Respiratory alkalosis
  5. Metabolic alkalosis, pCO2 48
  6. Respiratory acidosis HCO3 acute: 26, HCO3 chronic 29, Metabolic alkalosis
  7. Respiratory alkalosis, HCO3 acute: 20, HCO3 chronic 16, Metabolic alkalosis
  8. Metabolic acidosis that is a gap acidosis with an additional non-gap acidosis
  9. Respiratory alkalosis with both a gap and non-gap metabolic acidosis.


1: Narins RG, Emmett M. Simple and mixed acid-base disorders: a practical
approach. Medicine (Baltimore). 1980 May;59(3):161-87. PubMed PMID: 6774200.

2:  Baillie JK. Simple, easily memorised ‘rules of thumb’ for the rapid assessment of physiological compensation for respiratory acid-base disorders. Thorax 2008;63:289-290 doi:10.1136/thx.2007.09122

3. Haber RJ. A practical approach to acid-base disorders. West J Med. 1991
Aug;155(2):146-51. Review. PubMed PMID: 1843849; PubMed Central PMCID: