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Boy, our fellows are smart!

The St. John Hospital and Medical Center has a nephrology fellowship where I am on the teaching staff. We currently have a particularly talented cohort of fellows but I had no idea how that talented compared on a national scale.

We just got the results of the Nephrology In-Service exam and our crew hit it out of the park. The average score was 69, only 4 programs (with five or more fellows) scored higher. Congratulations guys!

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Volume, a new target for dialysis and acute renal failure?

One of the major advancements in nephrology in the first decade of the 21ast century was the rejection of Kt/V as a treatment target in dialysis. In a field that is lacking in randomized clinical trials we had three well done randomized clinical trials designed to verify the mounds of observational data. In all three Kt/V as an expression of dose failed.

Chronic hemodialysis: HEMO

  • eKt/V of 1.05 vs 1.45 (or a spKt/V of 1.2 vs 1.6) 

Peritoneal dialysis: ADEMEX

  • Increase in PD dose such that they move from less than 40% at Kt/V of 2.0 to 83% at Kt/V of 2.0

Dialytic support for acute renal failure: VA/NIH ATN trial

  • 3 days a week dialysis versus 6 days a week all at a single-pool Kt/V of 1.2 to 1.4 per session
  • Hemodynamicly unstable patients were randomized to one of two levels of CVVH 20 or 35 ml/kg/hour of total CRT effluent
All three looked at variations on Kt/V tuned to the individual clinical scenario. Varying Kt/V in each of these clinical scanrio made not a whif of difference to the patients.

In the aftermath of such intellectual carnage nephrology is desperately seeking a replacement. My experience with nocturnal dialysis and the amazing work coming out of Canada makes home hemo look like the most appealing option. Getting results comparable to transplant makes it look like an entirely new modality compared to traditional in-center hemo.
One of the aspects that made Kt/V so appealing was how it was a useful in any situation involving dialysis. (The lessons from NCDS study on chronic in-center hemodialysis guided the definition of adequate dialysis for ARF in the ATN trial)

What lessons does home hemo have to teach acute renal failure in the ICU? What lessons does it have for peritoneal dialysis. One could argue that one of the central problems in modern dialysis is fluid management. Too many of my patients are chronically fluid overloaded leading to hypertension and over worked hearts. Home hemo corrects hypertension. Is solving that cardiovascular problem accounting for much of the improved clinical outcomes?

If that is the case, then there is a clear lesson that we can take from home hemo and apply to the ICU. 
Don’t let your patients get volume overloaded
We covered this in journal club last thursday: Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy

The study is a retrospective interpretation of registry data on children with acute renal failure receiving continuous renal replacement therapy. Each patient was given a fluid overload score by calculating a percentage overload:

They divided patients into three strata:

  1. <10% overload
  2. 10-20% overload
  3. ≥20% overload
They also used percentage overload as a continuous variable for the primary multivariate analysis.
The primary data is shown in table 2.
It should be immediatly obvious that the patients with more volume overload were sicker, they had signifigantly:
  • longer ICU stay
  • higher mortality
  • more multi-organ dysfunction
  • more likely to be intubated
  • more inotropes
  • more sepsis
  • higher PRISM score
For that reason I am not going to spend time discussing the univariate analysis and go straight to the multivariate analysis:

Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a 3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.

That is impressive. If the results hold up and aplies to adults it should scare the crap out of anyone who regularly rounds in the ICU. Think of a typical 80 kg adult who has total input of 2,400 mL (100 mL/hr) and has 1,600 mL of urine output, 67 mL/hour. That is a positive balance of 800 mL or 1% of body weight. If that goes on for 3 days and then the patient becomes oliguric with only 400 mL of urine output for two days (2,000 mL positive per day) before initiating CRT. That patient would be up 6,400 mL or 8% of bodyweight: Those relatively innocuous seeming numbers would represent a 24% increase in mortality compared to someone with matched ins and outs. Yowsa!
This is an observational study and it is important not to accept he results as truth but it is certainly a suggestive lead.
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Apple CEO Steve Jobs Live at D8

6:59 pm: Walt asks if Apple knew it would build a tablet before it built the iPhone.

Jobs: “I’ll tell you a secret. It began with the tablet. Jobs first charged his staff with developing a tablet, but after seeing their first efforts decided the way to go was a phone. “My God, I said, this would make a great phone … so we shelved the tablet and built the iPhone.”

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Happy birthday PBFluids

PBfluids.com turned 2 years old on May 30th.
283 posts with another 24 drafts that have not yet seen the light of day.
283 posts in 730 days is one post every two and a half days. Not bad.
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Abacavir and methanol poisoning

About a month ago, Nephron Power wrote about a great electrolyte case in AJKD. The case regarded a patient who drank a liter of methanol but was asymptomatic. The reason the patient was apparently resistant to a toxic methanol slug of methanol (The quantity of methanol that produces toxicity ranges from 15 to 500 ml of a 40% solution to 60 to 600 ml of pure methanol) was protective powers of abacavir. Abacavir is a nucleoside reverse transcriptase inhibitor and apparently, is a potant inhibitor of alcohol dehydrogenase, the critical enzyme which converts methanol into formaldehyde. Formaldehyde is then converted into the lethal formic acid by formaldehyde dehydrogenase.

After reading this I started to wonder if abacavir was such an effective inhibitor of alcohol dehydrogenase what happens when patients get exposed to say a more common substrate of alcohol dehydrogenase such as whiskey. Shouldn’t we hear about people on abacavir going on alcohol benders after a single shot of ethanol?

A couple of cracks at PubMed and I sure didn’t find much. Barber, Marrett et al. looked for two types of alcohol reactions from abacavir, either a disulfaram-like reaction or reduced alcohol tolerance. The authors found three cases of in 173 patients starting abacavir. They found one disulfarem reaction (nausea, tachycardia, flushing with a single shock of vodka) and two cases of decreased alcohol tolerance

After three glasses of wine he felt as though he had a bottle and a half, with memory loss.

The only other paper I could find was by McDowell, Chittick, et al. who looked at increased abacavir levels with alcohol intake. The reverse of what I was looking for, but at least it was related. They gave a single dose of abacavir and 0.7 g/kg of ethyl alcohol to 25 HIV positive men. They found a 26% increase in the half life of abacavir with alcohol but…

This study did not demonstrate any alteration in the pharmacokinetic parameters of ethanol by abacavir coadministration; blood ethanol median profiles following ethanol administration in the presence and absence of abacavir were essentially superimposable. There was no evidence that co-administration of abacavir interferes with ethanol metabolism. There were no disulfiram-type reactions in any subject who received coadministration of abacavir and ethanol.

This study tested the effects of a single dose of abacavir, chronic dosing may result in a different effect on alcohol dehydrogenase.

Interesting case nonetheless.

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The dangers of high dose vitamin D

Back in November I posted on a patient who had a dramatic improvement in her PTH following correction of her vitamin D deficiency. One of the comments was:

Anonymous said…
Why wait one entire year to correct the Deficiency. I would have treated with 100,000 units po qd for 5-10 days.

I responded…
Regarding the time to treat the patient. This patient had almost no appreciable renal disease outside of the SHPTH. I was not going to schedule frequent visits to monitor therapy I just put them on a safe and familiar vitamin D dose and followed up every six months. I don’t think I harmed the patient with slow therapy. The one time I had a patient on 50,000 units daily (resident error) they were readmitted within 2 weeks with hypercalcemia.

What I was really thinking was I never considered a more aggressive replacement regimen. This weeks JAMA provides some insight in the potential dangers of rapid and high dose vitamin D replacement. It is a randomized, placebo-controlled study looking at whether giving half a million units of oral cholecalciferol once a year can reduce the number of falls and fractures. Surprising, at least to me, was the higher risk of falls in the experimental group.
The investigators did a post-hoc analysis on the timing of the falls and found they were more likely to occur right after the vitamin D and the risk attenuated as more time passed after the dose. Thus implicating the drug itself as the cause.

The accompanying editorial is quite good and provides references for additional studies that also point to higher fall risk with high doses of vitamin D.
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The sugar in soda

From a pretty good article in Fast Company of all places:

But come on, are sodas really so bad? Even coffee drinkers like to use a little sugar. Should we demonize coffee, too? Well, as a thought experiment, imagine that you’re in the office kitchen as a colleague adds some sugar to his coffee. As you watch, he adds a teaspoon. And then another. And another. And another. And another. And another. And another.And another. And another. And another. And another. And another. And another. And another. And another. And another. (Dude, want some coffee with your sugar?)