Recently, when talking about social media and medical education I have been comparing it to traditional medial education. Some media is locked into one camp or the other. Textbooks are a bastion of traditional medical education. The complexity of writing and publishing a physical book results in a cost structure so high that it can’t given away. Textbook costs for some corners of medicine have risen to absurd prices.
I had no idea pediatric nephrology text book prices were from another planet. pic.twitter.com/VbUE44VnK8
But I have a text book that has crossed over from traditional medical education to FOAMed. By making the Fluid, Electrolyte, and Acid-Base Companion a free download from this site I can get an idea of how much the price of a textbook is a barrier to wide adoption. The Companion went through one print run of 1200 books. We never did a second printing. All of them were sold. Any copies now available on Amazon are only available because of a robust secondhand textbook market. But since September of 2017, I have made the “Whole Enchilada” available for free on this site. The Companion is available as a simple PDF for anyone to download, redistribute, mark-up, and copy.
We sold 1200 printed copies. So how do we do with downloads? We get about half that number every month and have been averaging that for the last 5 years.
Download numbers from WordPress. I have been on WordPress for 46.5 months.
The Free in FOAMed is important. But I also think providing the document in a flexible, universal format like PDF that doesn’t require a specific reader app is also important. Remove as many barriers for the user as possible.
Why this post? Because I need a reference for a chapter I’m writing. I know it sounds circular, but a reference to a blog post seems better than “personal communication.” Look for this chapter on nephrology and social media to be published in a textbook in the next year or two.
The question: I am going through the real well made sodium and water guide you made and there is a concept I am having trouble with regarding ADH stimulation by decreased BP. In the text, one of the reasons that ADH release is triggered is:
Decrease in blood pressure: ADH is a potent vasoconstrictor. 10% drops in blood pressure are required to release ADH. This drop in pressure is usually due to a drop in the blood volume from volume loss but can also be due to heart failure or cirrhosis. ADH is relatively insensitive to changes in pressure, this is why it takes a full 10% drop in pressure to start to stimulate ADH.
I thought blood pressure goes up with heart failure as hypertension is a risk factor for heart failure. How do we get decreased blood pressure from heart failure?
The Answer: Hypertension can cause heart failure. Hypertension is a risk factor for hypertension. Heart failure can present with hypotension or hypertension. Regardless of the blood pressure, heart failure can cause poor perfusion, and stimulate ADH release, with or without a low blood pressure. Sometimes the heart pumps so poorly that blood backs up in the venous circulation, this venous congestion slows perfusion since the back pressure blocks flow, even though blood pressure it good.
So the important point is that heart failure, cirrhosis and volume depletion all stimulate ADH release through decreased perfusion/blood pressure predisposing to hyponatremia.
Lets do this number by numbers. This is an algorithm that will allow you to map out any acid-base question.
1. Primary disorder: pH is up (<7.4), pCO12 is down (< 40) and HCO3 is up (>24)The H-H variables are moving in discordant direction so this is an respiratory disorder, the pH is elevated so this is a respiratory alkalosis.
If you are really on the ball you will note that this breaks one of the fundamental guidelines of acid-base in that compensation is not in the same direction as the primary disorder (pCO2 and HCO3 almost always move in the same direction). This only happens when there are two primary disorders.
2. Is there a second primary acid-base disorder affecting compensation?Yes. In Respiratory alkalosis, for every 10 the pCO2 falls the bicarb falls 2 acutely and 4 chronically, so the target HCO3 is 22 for acute respiratory alkalosis and 20 for chronic respiratory alkalosis, well the bicarb did not drop at all, in fact it went up, so there is an additional primary metabolic alkalosis.
3. What is the anion Gap?148-(98+28)=22.So we did not talk about this, but the presence of an anion gap means there is an metabolic acidosis buried deep in the ABG.
4. Calculate the bicarb beforeBicarb before = HCO3 + (Anion gap -12)Bicarb before = 28 (22-12) = 38So without the anion gap the bicarb would be 38, revealing a pretty severe metabolic alkalosis, that is mostly hidden or covered up by the anion gap metabolic acidosis. The severity of the metabolic alkalosis by looking at the electrolytes without the anion gap.
Put it all together and you have: A respiratory alkalosis, likely from the respiratory stimulant effect of feverA metabolic alkalosis from vomiting and/or some antacids he may have taken to soothe his stomach. An anion gap metabolic acidosis from the sepsis.
Since the demise of TTKG I have had to retrain my brain to determine if hypokalemia is due to renal wasting or extra-renal potassium losses (as well as intracellular shift). The is not so important in the evaluation of hyperkalemia as persistent hyperkalemia is always due to decreased renal clearance of potassium.
There are two methods of looking at renal potassium wasting, the first is Fractional Excretion of Potassium. Super easy calculation.
The mean FEK+ in normal subjects was 8% (range 4-16%). FEK+ was positively correlated with serum potassium (r = 0.74, p < 0.0001) and inversely with serum creatinine (r = -0.51, p < 0.001). The mean FEK+ in patients with hypokalaemia of external origin was 2.8% (range 1.5-6.4%). On the contrary, the mean FEK+ in hypokalaemic patients in whom renal potassium loss was the main aetiologic factor for the pathogenesis of hypokalaemia was 15% (range 9.5-24%).
Even though the creatinine is measured in mg/dL and the potassium is measured in mEq/L the units don’t mess you up because the serum and urine creatinine units cancel each other out.
The other way to look at hypokalemia is urine potassium creatinine ratio. Just divide the urine potassium by the urine creatinine and if it is greater than 1.5 you have renal potassium wasting. But alas this only works if the urine creatinine is measured in mmol/L. I get urine creatinines in mg/dl, so to make this conversion you need to multiply urine creatinine by 88 to get micromol/L of creatinine and then divide it by 1000 to convert to mmol/L. In one step it looks like this:
I often get a call from a nurse saying something to the effect of, “Dr. Smith is ready to discharge this patient home as long as he is cleared by nephrology.”
I will tell you, that the pre-test probability that I will “clear” the patient for discharge is high. I want patients to go home and I feel that a lot of what we do in the hospital can be achieved as an outpatient. Send the patient home and I’ll see them in clinic. But one needs to be careful.
I didn’t discharge the patient, but received him when he was readmitted. The patient was admitted with bilateral pleural effusions and respiratory distress. Patient was diagnosed with COPD exacerbation and heart failure.
The patient was on furosemide 40 mg daily at home and this bumped to 80 mg IV twice a day on admission.
Nephrology was consulted to assist with diuretics and added some metolazone on day 2. That was a one time order and not repeated. Adding a thiazide, metolazone, to a loop diuretic part to increase diuresis is called sequential nephron blockade. One cause of diuretic resistance, is with chronic loop diuretic use, sodium resorption that occurs after the thick ascending limb can short circuit effective loop blockade. So by stacking diuretics that act distal to the loop increases the effectiveness of the loop diuretic.
The addition of a thiazide or K sparing diuretic to a loop diuretic is an example of sequential nephron blockade.
I would have been a bit nervous adding a thiazide in a patient who already had hyponatremia, but the following day the labs look okay.
The following day is the day of discharge. The morning potassium is replaced with a combination of oral and IV potassium as well as 2 grams of magnesium sulfate.
The nephrologist clears the patient for discharge as long as the potassium is normal. The potassium is almost normal and the patient is sent home. On a combination of furosemide and metolazone!
Three days later the patient collapsed at home and during resuscitation is found to have a cardiac arrhythmia and potassium of 1.6.
Know your diuretics. Respect the diuretics
Also keep in mind this propensity matched trial of metolazone in acute decompensated heart failure. They found a large fraction of the excess mortality found with metolazone could be explained by hypokalemia.
(and a gif for the people who want to rename this hyperhydronemia)
Chug Water GIF
Patient came to the hospital with abdominal pain, nausea, and vomiting. Patient has alcohol use disorder. Last drink was about a day prior to admission.
After arrival to the ER the patient has a seizure.
gross james van der beek GIF
Besides the weirdly elevated anion gap, and the hypokalemia, the initial labs just show some AKI. I don’t have an ABG but I suspect combined metabolic alkalosis and lactic acidosis.
This can be demonstrated by looking at the Delta Ratio which compares the change in bicarb to the change in anion gap. The ratio should be 1. If it is less than 1, there is an additional non-anion gap metabolic acidosis, > 2 additional metabolic alkalosis
A delta ratio of 6 is crazy high.
Kate Mckinnon Snl GIF by Saturday Night Live
A related calculation, called the “bicarb before” can tell you the serum bicarb without the anion gap acidosis, so if the patient has two disorders it allows you to look at the metabolic alkalosis (or non-anion gap metabolic acidosis) without the anion gap metabolic acidosis.
The “bicarb before” comes to a mostly unbelieable serum bicarb of 60.
But the reason I was intrigued by the case are the next two labs that come 10 and 20 hours after the initial labs…The sodium drops to 125 despite getting 150 an hour of 0.9% NS and the patient making 3600 ml of urine.
Additionally the full force of the metbolic alkalosis is revealed with the bicarb shooting from 29 to 41. I suspect this is due to vomiting. The urine chloride < 20 is consistent with this. This is Cl responsive metabolic alkalosis. It will (eventually) respond to the NS.
The urine also has a massive anion gap, around 90. What is the unmeasured anion?
(BTW the answer is bicarbonate)
But what is driving down the sodium? The patient appears volume depleted, and the steadily improving serum creatinine points to a patient with pre-renal AKI.
In volume depletion hyponatremia, giving fluid improves the serum sodium, it doesn’t make it worse. Also these patients do not typically make 3600 ml of urine
In it is highly unusual to make that much urine and have the sodium fall, usually that kind of urine output is associated with arising sodium. A hint to what is happenning can be found in the electrolyte free water clearance (Clefw).
The high urine sodium and really high urine potassium makes the urine essentially isotonic to plasma. Even though the patient is making 3.6 liters, it is like taking ladles of soup from a big pot, no matter how many ladles you take out it doesn’t change how salty the soup is.
pot wo GIF
Because the electrolyte free water is close to zero, those 3.6 liters of urine are not afffecting the serum sodium at all. So why is the sodium falling? I suspect this is due to the patient drinking (unrecorded) water.
So what would you do if faced with a falling sodium in a volume depleted patient?
I chose Tolvaptan plus continued 0.9% NS at 150/hr. The following day, the labs look…better.
I think this patient had nausea induced ADH in addition to severe metabolic alkalosis and volume deficiency. I found it interesting.
What I loved about it is that the full lab interpretation required six different equations:
Anion Gap
the rare case of a relevant anion gap despite an increased serum bicarb
Gap Gap analysis
First the Delta Ratio
Then the Bicarbonate Before
Urine chloride in metabolic alkalosis
<20 mEq/L is chloride responsive
Urina anion gap
People think it is just for RTAs…not true
Electrolyte free water clearance
And I got great comments from Twitter. Some highlights:
Great thread! Given the magnitude of the metabolic alkalosis, did you ask the patient if they were chronically ingesting sodium bicarb (generally to treat alcohol-induced gastritis)? Most of my 50+ mEq/L bicarbs have been associated with this.
Wild case. Thanks 4 sharing. With the high Ca on admission and unexplained low sNa, I thought u were going 2 show us Normal serum Osm and a pseudohypoNa picture from light chains/myeloma. But yes it does look like a transient inappropriate ADH release, but even then 3L UOP is odd
— Juan Carlos Q Velez (@VelezNephHepato) July 30, 2021
Daniel Coyne is one of my heroes in nephrology. Starting in fellowship and for the first decade of being a nephrologist, I was suckered into the normalization of hemoglobin delusion. The idea that we could heal our patients’ hearts by treating the ubiquitous anemia of CKD was seductive. The theory made sense. The retrospective data looked amazing. Many really smart nephrologists promoted the idea. Living through the medical reversal of CHOIR, CREATE, and finally TREAT was both academically traumatic and a profoundly formative moment in my career. One of the major components of the CKD-anemia delusion was the role that KDOQI played in promoting the high hemoglobin targets before the clinical data showed the folly of this strategy. Dr. Coyne is one of the first nephrologists to ring the warning bells. We highlighted his story in NephMadness 2016. So when Dr. Coyne criticized the nutrition guideline my ears were perked.
The thread highlighted above is convincing and I amplified it.
1A evidence for protein restriction? KDOQI is embarrassing itself. This makes a mockery of the whole organization. Disgraceful. https://t.co/EbisUKhi1o
Subsequently,` I received a polite email from one of the guideline authors suggesting I may have gone too far in criticizing the guideline. Time to put up or shut up. Here are my thoughts, at longer than tweet-length, regarding the protein restriction guideline. Much of this comes from Dr Coyne’s thread, so read that first, so you know where the smart stuff comes from.
Guidelines should only express certainty when there is certainty. When guidelines flip-flop with each new edition doctors lose credibility while taking care of patients. Consistency is important. Because of this I want guidelines to be late adopters rather than on the cutting edge, and for guidelines to be humble about the frailties of human knowledge.
The Detailed Justification of this guideline provides this guidance
Research reports a beneficial effect of protein restriction (0.55-0.6 g/kg per day) on ESKD/death in adults with CKD. In adults with CKD, 5 RCTs reported findings on the effect of protein restriction on survival/deaths. Three studies clearly indicated a beneficial effect of moderate restriction in dietary protein on the development of ESKD/death.153,164,168
So there are 5 RCT that looked at protein restriction for the development of ESRD/Death. Of these 5 studies (of which I could only find 4), 3 were positive, but one of them, Locatelli, is only positive if you consider a P value of 0.06 as significant.
It is so strange to see this reported as a positive trial, because when I would answer questions about low protein diets for my patients with relatively early kidney disease, I would say, this has been looked at in a number of studies but there were two big studies, one in Italy (this one) and one in the US (MDRD) and neither were able to show improvement in outcomes. But here, I guess, this is good enough to qualify for “clearly indicated a beneficial effect.”
The second reference is a small 82 person study by Henrik Hansen. I find this troubling because even though the KDOQI guideline specifically excludes people with diabetes, Hansen restricted enrollment to patients with diabetic nephropathy.
The last of the triplets is Rosman. I could not find Reference 168. This sounds like a study that was presented at a conference, Proceedings of the European Dialysis and Transplant Associations, European Renal Association 1985. Here is the pubmed listing. The abstract is pretty thin. I am particularly concerned because a later publication that seems to be long-term follow-up this cohort (no I don’t know how they picked up an additional 50 patients) and it spins a different tale. The title says it all:
I also highlighted a concerning line from the abstract, “The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet.” If this is the case this is something that should have given pause to the authors trying to generalize this recommendation for all people without diabetes and CKD 3-5 not on dialysis.
The three “positive” trials were published in 1991, 2002, and 1989. This means the cohorts were pre-ACEi/ARB. In fact, Locatelli’s study actively discouraged the use of ACEi.
Lastly, of the two negative trials (of the five that looked at ESRD/death) the authors brush off Cianciaruso for being, “a relatively small sample size.” Let’s take a look at the trials.
Cianciaruso had an N of 423, twice the size of Rosman’s study and five times the size of Hansen’s. The only study in the group of 5 larger was Locatelli with 456. Relatively small sample size? Come on. We are currently in the midst of a revolution in evidence based nephrology with the data emerging about the effects of SGLT2i. One of the compelling findings with each subsequent blockbuster study is how consistent the data is regardless of how the outcome is assessed:
Change in GFR? Yup, the SGLT2i is better
Change in GFR slope? Check, SGLT2i again
Fraction of patients that reach death or dialysis? SGLT2i still got you covered.
This is not the case for this guideline. The authors trumpet guideline 3.0.1 claiming a reduction in need for dialysis, but this benefit appears to be fragile because if instead we look at low protein diets (LPD) through the lens of the change in GFR, the data no longer points to a benefit. From the guideline:
This mismatch between the 1A conclusions about development of ESRD or death and the lack of biologic plausibility that one can prevent ESRD without preventing loss of GFR should be addressed in the guideline mentioned and probably should have forced the guideline committee to rethink the 1A grade they awarded to protein restriction.
Coyne’s first tweet was in response to this
It is amazing to still read the term « risks » for low protein diets when in 2020 kdoqi recommend LPD with highest evidence level (1A). This is unfair to patients #stoplpdbash
Dr Fouque expresses outrage that someone would question the safety of low protein diets. Well safety is a concern. As I wrote on this blog (see this and the follow up here). These posts are regarding long term follow-up of the MDRD cohort. MDRD is famous for not showing any difference in ESRD or death with either a low or very low protein diet, the long term follow up revealed that among people that did progress to dialysis, the patients randomized to the very low protein had nearly a two times higher risk of death (HR 1.92). So Dr. Fouque, with all due respect, I do think it is quite reasonable to question the risks of a low protein diet.
Dr. Fouque comment also highlights what is so dangerous about the 1A grade for protein restriction, it says this is settled science, we no longer need to investigate this. A 1A guideline insulates protein restriction from questions that need to be asked. This is not settled science. Not even close.
If you find this curious, I advise you to listen to Freely Filtered #27 where Ian de Boer describes the logic for that 1B grade. Whether or not you find that admirable or absurd it is clear that the authors of the diabetic kidney disease guideline respect a score of 1A. They hold it in reverence and reserve it for only the most rigorous evidence. This argument came from the mind of Nayan Arora:
Crazy in it’s own right, more so when ACEi/ARB for DKD isn’t even 1A
Robert Schrier was a giant in nephrology. I met him a couple of times at Kidney Week but he was well past his prime and it was hard to make out the lion that he must have been. I didn’t know Dr. Schrier but I do know someone who knew how quite well.
Ever since I left fellowship I have worked at Saint Clair Specialty Physicians. It was originally a multi-specialty practice with internists, surgeons, hematologists and nephrologists. But things change and we are now a couple dozen nephrologist and one vascular surgeon. The practice is one of the oldest nephrology practices in Michigan. It was started by Joe Beals in the 70’s.
Joe was a Hoosier and went to DePauw where he was roommates and fraternity brothers with Robert Schrier. When you think of how small the field of nephrology was in the 60’s, it’s incredible to imagine that college roommates would both independently navigate to the same field. Here is Joe in his own words after I told him that Schrier had passed.
Thanks Joel, no I hadn’t heard. So sad! One of the smartest guys I ever knew. Was a fraternity brother, Sigma Nu, at DePauw University in Greencastle, IN. He was on the DePauw basketball team and baseball team. Worked his way through college working in the kitchen at a sorority house. He sold Fuller Brushes with me one summer in Indianapolis. Has 5 kids, all names starting with “D.” Most if not all also attended DePauw. Wife was a Theta at DePauw. A Fulbright Scholar. Will be missed.
Joseph Beals
Joseph and Mary Beals
Joe is a great doctor and has been a good friend. Strange to realize that I’m the youngest partner at St Clair that worked with the founder.
I have been thinking about the role of social media in the pandemic. This is the first medical crisis not the age of the public physician and social media. It has resulted in some some fascinating developments. Some of the changes that came about because of the pandemic will indelibly change medicine and most of them are for the better.
I started thinking about it this past August as part of an invited essay on the topic by Blood Purification. I worked this paper with The Curbsiders’ Paul Williams. We looked at the role of public physicians this time of intense public interest.
We leaned into the definition of public physician created by Bryan Vartabedian. Take a look at the manuscript (PDF link).
I used that paper as a jumping off point for a talk I gave on Social Media and the Pandemic for the Renal Research Institute. I started focused talk on the changes in medical education, looking at how traditional medical education fell apart in the face of social distancing while FOAMed took off.
I'm recording a lecture in 2 hours. The premise is the COVID-19 pandemic is the greatest Med Ed challenge ever.
The RRI is the research arm of Fresenius and they run a top notch nephrology meeting every year. This year, the meeting is in May but they had a few speakers record their talks for release in January. Mine just came out.
I recorded that lecture in mid-late December.
The most recent thinking on this topic was for Innovations in Media and Education Delivery (iMED) Initiative at Beth Israel Deaconess Medical Center first annual conference. I had the honor of presenting the keynote talk. Here I continued my focus on the impact the pandemic had on medical education and the role FOAMed played. A lot of the bones of the talk were there in the RRI talk but the connective tissue is much stronger.
There is no public recording of the talk, but you can take a look at my slides:
PowerPoint: The Pandemic blows up #FOAMed (251 MB) Note: I create, rehearse and deliver the presentation in Keynote. The PowerPoint version is a simple export of the Keynote presentation and often looks like garbage. If you want to see the presentation as it was meant to be, use Keynote.
