A few weeks ago the Sunday New York Times had an op ed by Randall Stross
regarding Steve Jobs. Stross suggested that Jobs’ leaving Apple in 1985 was instrumental in him becoming the capable executive that he is today rather than “the worst personnel decision
In 1993, Stross released a book, Steve Jobs and the Next Big Thing, chronicling the NeXT computer company and its struggles. The book is out of print but I found an old copy and read it a few years ago. The book is well researched and Stross provides ample evidence to to support his conclusion that Jobs was an immature brat, a terrible leader, a liar, and a poor manager. The picture he paints of Steve Jobs is the classic story of the entrepreneur conquring the world, becoming egocentric and then failing miserably when attempts to replicate his initial success. When I read the book, in 2007, I was in possetion of invaluable data not available to Stross in 1993. Jobs masterful turn around of Apple.
So everytime I read a chapter I had to accept the anecdotes Stross recounted while rejecting his thesis and attempt to fit the data to a different conclusion. It was a fun reading experience.
In another recent bit of news on Steve Jobs, take a look at John Scully’s interview
with Leander Kahney. Its a fascinating view of their relationship and what Steve meant to Apple.
On Monday night I was called by one of our fellows regarding a patient in the ED with a potassium of 8.5. They had already given insulin, glucose and kayexalate and the follow-up potassium was 8.1. This is not much improvemnt and less than you typically see. The patient was in acute renal failure with a creatinine of 3 and was anuric.
I asked if the patient had any EKG changes and according to the ER doc the patient had just a touch o’QRS widening. What do you think?
|Peaked symmetric T’s
Link for more on EKG changes in hyperkalemia
That night his CPK was 5,000. The next day it rose to 341,680.
Now dat’s a spicy meatball!
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A few weeks ago while on acetazolamide for altitude sickness prophylaxis
the whole group noted tingling and paresthesias. What was curious is that the symptoms were most pronounced in the morning. The paresthesias were primarily on the hands and feet with a rare complaint of symptoms on the face.
I suspected that these symptoms are due to hyperventilation induced hypophosphatemia and the high carbohydrate breakfast (oatmeal) caused a bolus of insulin that further lowered the phosphorous. Does anyone know the etiology? Does hyperventilation cause hypophosphatemia if the increase in ventialtion is compensatory for metabolic acidosis?
FYI: the acetazolamide taste alteration makes carbonated beverages inedible.
One of the inherent truths in transplant is that the longer someone is on dialysis the worse the outcome after transplant. Patient with higher dialysis vintage prior to transplant are more likely to lose their graft and die following transplant. This was first shown by Cosio Et al. and subsequently verified by other researchers.
|Cosio’s primary figure showing dramatically increased mortality with increasing time on dialysis
Though Cosio et al. was the first (?) to find this association the most elegant data comes from Meier-kreiesche, Et al. who looked at graft survival when a paired sets of cadaveric kidneys is donated to recipients with differing duration of dialysis. By looking at paired kidneys they were able to neutralize any confounding factors from the donor. The primary analysis looked at kidneys that were split between one recipient with less than 6-months of dialysis and another with more than 2-years of dialysis. The end-point was graft survival:
They also calculated patient survival and they likewise found a significant splay based on time on dialysis:
Five- and ten-year unadjusted overall patient survival for paired kidneys was 89% and 76%, respectively, in the group on dialysis less than 6 months compared to 76% and 43%, respectively, in the group on dialysis for more than 2 years (P<0.001 each).
The obvious implication was that dialysis was bad for you. The longer you were on dialysis the more baggage you were carrying at the time of transplant and that baggage comes back to haunt the recipient with a shorter life and shorter kidney survival. From the conclusion:
…the longer patients wait on dialysis for a transplant the longer patients are exposed to the chronic effects of end-stage renal failure and dialysis. It is well documented that patients on dialysis have alterations in the concentration of a number of substances (e.g., homocysteine, advanced glycosylation end products, and lipoproteins) that may predispose these patients to both cardiovascular and renal allograft vascular damages. In addition, the poor nutrition, chronic in- flammatory state, altered immunologic function, and inade- quate clearance that often accompanies patients with ESRD on dialysis may predispose these patients to poorer toler- ance to the immunosuppressive agents after transplantation.
On our journal club last week we looked at a study by Schold, et al. that analyzed time on dialysis prior to transplant by dividing it into time prior to wait list and time after being listed. They found that all of the risk from prolonged dialysis comes from the time prior to being placed on the transplant wait list:
The data was more dramatic for graft loss than for mortality. The intersting part of this is trying to explain this discrepancy. Why would time on dialysis prior to wait listing be any different that time on dialysis after wait listing? There is no biological difference so the authors conclude that the difference must be in a subtle, previously unmeasured difference in co-morbidity or access to care. The authors go on to pre-suppose that efforts to reduce patient exposure to dialysis may not yield the benefits one might expect if these other factors are not also corrected.
My camping club, Aggressive Deer Adventures had a great trip to Kings Canyon National Park. The group consisted of 7 men, all 40-something who lived at around 600 feet above sea level. The whole trip took place between eight thousand and twelve thousand feet.
Every one started on low dose acetazolamide (125 mg bid) 36 hours before we left home.
Not one of us developed anything more than a small headache on travel day. Complete success.
The patient had SIADH due to viral encephalitis. We started tolvaptan 30 mg and his SIDAH rapidly reversed with the sodium rising from 124 to 128 overnight and up to 136 in the following week. Along with his improved sodium the patients mental status improved. I attribute that more to improvement in the encephalitis than the normalized osmolality but the association is there.
I stopped the Tolvaptan after 8 days and the next morning here are his urine chemistries:
Urine sodium 20, urine osmolality was 614. Somehow, I got a urine chloride rather than the urine potassium I ordered. The sodium nudged up to 137 off the tolvaptan. It looks like the SIADH has resolved with the urine sodium falling from 148 prior to the drug to 70 after the first dose to 20 off the drug completely.
Also note that even though the urine osmolality (614) is greater than serum osmolality, the serum sodium can still rise. This is because the electrolyte free water is still positive, despite a negative solute free water.
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I am going to Kings Canyon National Park at the end of the month. I will leave Detroit, elevation 600 feet and will travel via planes, trains and automobiles to 9,000 feet for the first night. Then we will begin out hike and cross passes over 12,500 feet.
In the past, I have developed modest altitude sickness going from 600 to 8,000 feet. So, I am nervous about the same problem on this trip. Acetazolamide is supposed to ameliorate altitude sickness.
The body acclimates to decreased oxygen and is so effective that people can function at the top of Mt. Everest without supplemental oxygen. The partial pressure of oxygen at the summit is 43 mmHg which is equivalent to breathing 6% FiO2.
|From NEJM 2009, 360: 140-9
The primary means of improving oxygenation is hyperventilation. Hypoxia stimulates ventilation. There is also an increased ventilatory response to carbon dioxide so that that the normal respiratory response to carbon dioxide is exaggerated so that one gets more ventilation at lower CO2 levels. The reason that increased ventilation improves oxygenation has to do with the effect carbon dioxide in the blood has on oxygen transfer in the alveoli. During respiration CO2 leaving the blood dilutes the incoming oxygen at the alveoli, increased respiration, lowers the pCO2 and hence minimizes this dilution.
Antagonizing the hyperventilatory response is respiratory alkalosis. Central chemoreceptors detect alkalosis in the CSF and slow respiration. This is one of the key factors preventing the essential hyperventilation.
Acetazolamide (Diamox) is a carbonic anhydrase inhibitor. Carbonic anhydrase catalyzes the reaction converting bicarbonate to carbon diaoxide and water:
This is the fundamental buffer reaction in the body and it is amazing to me that blocking this essential acid-base reaction is not lethal. Acetazolamide works in the proximal tubule by blocking the reabsorption of filtered bicarbonate.
Acetazolamide induces a proximal renal tubular acidosis (RTA 2). This results in metabolic acidosis. The metabolic acidosis stimulates compensatory hyperventilation. This metabolic acidosis antagonizes the respiratory alkalosis which normally occurs with hyperventilation.
Their maybe additional advantages of acetazolamide including decreased CSF production and antagonizing fluid retention.
I gave the patient from yesterday 30 mg of tolvaptan. The repeat sodium was 128, up from 124 and urine sodium was down to 70, from 148 and the potassium was 40, down from 48. Urine output rose to 3425 mL.
The electrolyte free water clearance went from negative 1,364 to positive 481 mL.
The SIADH is due to West Nile Virus induced encephalitis.
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Check out that urine sodium. The guys pissing normal saline. That’s the highest urine sodium I have ever seen.
Urine sodium 148
Urine potassium 48
Serum sodium 124
Urine output 2350
Electrolyte free water clearance:
Interpretation: with those urine electrolytes, when urinates 2,300 mL it is as if he actually drank nearly a liter and a half of tap water. And that is why fluid restriction fails in dense SIADH.
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