This is a fellow level lecture. I built it off an old lecture from 2003 or 2004. It is remarkable how much data has emerged since then. Of coarse the IDEAL Trial has put a dagger in the heart of early initiation but the observational data in agreement with abandoning early initiation has also turned.
A drop in hemoglobin on 9 grams brings to mind the old surgical maxim “all bleeding stops” but I just had a case of a drop that big that includes three other confounding factors:
He is a dialysis patient
He didn’t died
He didn’t required a transfusion
He is a 58 year old patient with ADPKD, as part of this disease he had polycythemia and the day he was admitted with a chief complaint of dyspnea he had a hemoglobin of 19 g/dL. He had been advised that this was dangerous and he should go for phlebotomy. Sure enough he had a bilateral PE and multiple DVTs.
We started unfractionated heparin and ordered phlebotomy. So the next morning when we saw the decrease in the hemoglobin from 19 to 14 I was satisfied that he had a good response to phlebotomy. In reality, he never received the phlebotomy.
On that next hospital day he reported worsening flank pain. We ordered a CT to evaluate this and to help evaluate why his PD was failing. Turns out the pain and falling hemoglobin were due to a large bleeding renal cyst and renal hematoma. We stopped the heparin. The hemoglobin fell to 10 g/dL, a tidy 9 gram drop. We transferred him to the MICU. The initial plan was to embolise the bleeding kidney but the hemoglobin stabilized after stopping the heparin. After a few days of expectant testing and nervous observation we resumed the heparin and the hemoglobin held.
While we initially attributed the DVT solely to the erythrocytosis, he has a troubling family history (in addition to the ADPKD) that suggests thrombophilia.
Hi, I am a patient with IgA nephropathy, (current serum creatinine around 3.7, eGFR around 18ish). I also have an MD from the University of Washington in seattle.
I love your blog. I was wondering if you could recommend books or review-type journal articles on two topics of interest to me. With my MD background I can read fairly technical material, although sometimes get a bit lost in some journal articles. Wanting some overview material to bone up on a few topics.
I just haven’t been able to find book titles that seem spot-on. I have a great nephrologist here in Seattle who is very busy at the moment and I can’t seem to get his attention via email, etc. to provide these kinds of recommendations. I thought you might be able to help.
1. IgA nephropathy – overview of pathological mechanism, current research areas, etc.
2. A good article/book on reading kidney biopsy results.
Any information would be very much appreciated.
I didn’t have anything to suggest. Anyone have any good sources to recommend?
Giles Brindley, the man who gave whole new meaning to
PowerPoint.
In 1983 Professor Brindley presented his findings on papaverine injection and erectile dysfunction. His presentation was a bit unconventional as recounted by (PDF) Laurentz Klotz, a senior resident who attended the presentation.
…four or five of the women in the front rows threw their arms up in the air, seemingly in unison, and screamed loudly. The scientific merits of the presentation had been overwhelmed, for them, by the novel and unusual mode of demonstrating the results.
Those are not glucoses. They are Sodiums. And, except for maybe an infant with congenital adrenal hyperplasia when I was a resident, those are the highest sodiums I have ever seen.
The primary management concern was the speed of correction. The first Na at 188 was drawn at 4:32 pm. Four hours later it was 177, a change of 11 mEq. Too fast. Here is the salient section from UpToDate:
Rate of correction in chronic hypernatremia — There are no definitive clinical trials, but data in children (particularly infants) suggest that the maximum safe rate at which the serum sodium concentration should be lowered in patients with chronic hypernatremia is 12 meq/L per day. To be safe, we suggest a maximum rate of correction of the serum sodium of 10 meq/L per day in patients who have had hypernatremia for at least 24 hours. The following findings provide support for this conclusion:
A retrospective case control study included 97 children with hypernatremia and dehydration; the mean baseline serum sodium was 165 meq/L. The rate of reduction in serum sodium was significantly faster in the children who developed cerebral edema compared with children who had no complications following correction of the hypernatremia (1.0 versus 0.5 meq/L per hour).
Similar findings were noted in another report in which the rate of reduction in serum sodium was 1.0 meq/L per hour in the nine infants who developed seizures compared with 0.6 meq/L per hour or less in 31 infants who did not develop seizures.
So Bud Rose, the dean of electrolytes, says 12 mEq per day.
Burton Rose
My patient moves 11 mEq in 4 hours after receiving 500 mL of normal saline. Now what? I was convinced that continuing normal saline would perpetuate the overly rapid correction of the sodium and put the patient at risk of cerebral edema. But since the patient was still in hypovolemic shock, I couldn’t just stop the fluids.
I ordered 3% saline. I ran it at 100 mL/hour and 5 hours later the sodium was back up to 186. I was going in circles. I then changed back to normal saline and over the subsequent 48 hours we corrected the sodium at roughly 0.5 mEq/l/hr. The whole time I was going through this I was wondering is it all necessary? Is rapid correction of hypernatremia as dangerous as Rose said it was? Is half a miliequivalent/L/hr a real evidence based speed limit?
I put this question to a fourth year medical student and he did an excellent job diving into the evidence (or lack there of) on the topic. Here is his analysis:
I think he is a little hard on Rose’s guidelines. The student’s analysis criticizes one of 4 references that are provided in UpToDate (though his criticism is appropriate and is the sole reference in Rose’s landmark Clinical Physiology of Acid Bas Disorders) to support of the 0.5 mEq/L/hr speed limit.
The section in Rose’s text is very similar to the UpToDate card. The relevant paragraph is on page 777 in my 5th edition (black cover). The sole reference in this paragraph, is the 1986 Blum article (number 4 from the above list).
iPhone, a surprisingly effective photocopier.
Kahn retrospectively looked at the care of infants. They used half normal saline and gave it at 160 mL/kg/day (6.7 mL/kg/hr). All of the patients were 0-5 months, so maintenance fluids would have been 4 mL/kg/hr.
What book did this great page on maintenance fluids come from?
Nine of the first 47 patients developed seizures that could not be explained by other etiologies (fever, hypocalcemia, hypoglycemia) and so were ascribed to rapid fluid restoration, Group I. They matched these nine to 22 age-matched children who were treated contemporaneously but did not have a seizure, Group II. The investigators then changed the protocol for treating infants with hypernatremia to 120 mL/kg/day and included data on 9 patients under 5 months who were treated this way, Group III.
Here is the primary data on the three groups:
All three groups had similar sodiums but Group I had significantly higher BUNs than Group II, with I +II vs III and I vs III being non-signifigant.
The protocol called for patients in Group I and II to get only 160 mL/kg/day. Both groups significantly exceeded this. Group III hit its fluid goal nearly on the nose. They blamed the excess fluid on oral replacement and volume resuscitation with sodium bicarbonate.
The net result was a wide spread in the rate of correction of sodium:
The kids that seized: 1.02 mEq/L/hr
The kids that did not seize but were on the same treatment protocol: 0.62 mEq/L/hr
The kids on the conservative protocol, also without seizures: 0.35 mEq/L/hr
Fang looked at 97 children with hypernatremia. Mean sodium was 164.5. Mean age 13 months. He performed a case-control study with the cases being patients who developed cerebral edema. Manifestations included seizures, eyelid edema, papilledema in all the patients and bulging fontanel in 36 and pupillary abnormalities in 9 cases.
The data shows cerebral edema was more common with bolus therapy, especially when the bolus was faster, higher sodiums were associated with cerebral edema but much of that disappeared in multivariate analysis as higher sodiums were also associated with increased rate of correction and ind increased bolus rates. Using ROC the investigators found a rate of fluid administration of 6.8 ml/kg/hr was safest. And the average decrease in serum sodium in the cerebral edema group was 1 mEq/L/hr and 0.5 mEq/L/hr without cerebral edema.
The final reference is Blum’s study of oral rehydration, this is the reference my med student was upset with. As he outlined, this was a study of oral rehydration rather than a study of rates of treatment. The cohort was composed of eighteen infants, 6 months or younger admitted with hypernatremia (Na > 150) and treated with oral fluid resuscitation. They compared the hypernatremia outcomes to a second cohort of 26 infants who received IV rehydration for hypernatremia. Average sodium for both groups was 160.
In both groups the reduction of sodium was slow (0.3 mEq/L/hr) and no patient developed seizures.
In Burton Rose’s Clinical Physiology of Acid-Base and Electrolyte Disorders this observational study with no seizures is the sole reference behind the recommendation for a slow restoration of normal sodium. Weak sauce. Of note Androgue’s review of hypernatremia in the NEJM from 2000 references the same Blum and Khan articles to support its recommendation of slow treatment.
So in the end, the recommendation for slow normalization of sodium is based on a handful of studies in infants with no randomized or even prospective studies. What is unbelievable to me is no one references a study that reviews the functional/neurological outcomes of patients with the highest sodiums admitted to a large hospital based on the speed of correction. Seems like an easy study and in its absence we are left to trust in the physiology of babies.
Last year I published a list Apple predictions and I will post a complete score card. However, some of my predictions can not be judged until Apple announces its first quarter results on January 24th. I will however provide my 2012 predictions now.
iPad The iPad 3 will be announced February 28th and released March 16th. The iPad 3 will include a Retina Display with a resolution of 2048×1536. The case will largely look like the current iPad but Apple will introduce colors (again) like the iPod Nano and possibly patterns like the old Flower Power and Blue Dalmatian iMacs.
The cellular equipped iPad 3 will come with LTE radios in addition to the 3g and 2g radios they currently have. The large battery capacity of the iPad will make this luxury a possibility even though the iPhone 5 will lag behind with 3g.
The iPad 3 will also have the new quad-core A6 processor and get the same battery life as the current iPad except when using the LTE radio.
The memory options will remain16, 32, and 64 gb. This will be the last iOS device to include the 30 pin dock connector. The iPad 3 will get Siri. Prices will remain the same.
The current iPad 2 will continue as a discount model to fight the Kindle Fire and what-ever 7 inch piece of crap Eric Schmidt is talking about. The iPad 2 will only be available in 16 gb, but will still be available with WiFi or WiFi +cellular. The iPad 2 will be priced at $349 for the WiFi version and $479 for the WiFi +cellular
In addition to Verizon and AT&T, Sprint will get both iPads. Sprint will introduce a discounted price that bundles the wireless internet for your phone and iPad in order to solidify its position as the bargain wireless plan.
Last year I estimated cumulative sales of 65 million iPads (total of 2010 and 2011 iPad sales). Barring a total sales frenzy over this past Christmas I’m was a wee bit optimistic, with cumulative sales coming in closer to 54 million (that assumes iPad sales of 14 million in the Christmas quarter, 90% more than last Christmas, and 30% more than previous quarter). I am going to predict sales of 60 million iPads in 2012.
iPhone The iPhone 5 will be introduced in September and go on sale two weeks later. The message of the design is durability. Apple will use the same nano-coating that Motorola used on the RAZR to make it more water repellant. Apple will brand this with a unique name and claim it to be a major breakthrough.
Continuing with the theme of durability, Apple will abandon the 30-pin dock connector and seal the entire body of the phone. All data connections will need to be done wirelessly. A new MagSafe-like connector will be introduced for charging. Additionally the iPhone will lose the glass back, and it will be replaced with an aluminum one like on the iPad.
NFC will be added to go along with an electronic wallet system called iCash. This will be linked to your iTunes account.
The phone will be slightly thinner than the iPhone 4, but will largely have the same form factor. There will not be a tear-drop shaped design. The screen size remains 3.5 inches. Like the iPad 3, it will be released in multiple colors. The rear camera gets better, the device gets thinner, the phone receives the quad core A6.
With the introduction of the iPhone 5, the iPhone 4S is only offered with 16 gb and moves down to $99. The 8 gb iPhone 4 becomes the free offering in developed countries and the 3GS soldiers on as the price leader in emerging economies.
Last year I predicted Apple would sell 65 million iPhones. As of September 1, Apple has sold 56 million and analysts are expecting 30 million in the Christmas quarter, for a total of 86 million iPhones. So I blew that. 86 million represents an increase of 181% over 2010, which was an 189% increase over 2009 which was an increase of 183% over 2008. I’m going to guess that iPhone sales continue this incredible streak and grow by 180% in 2012 so that is 154 million. My official guess is 160 million iPhones in 2012 (that seems totally insane given that Apple has cumulative sales of 146 million iPhones as of September 2011).
After a stale year with no changes besides a white iPod touch the iPod line gets a significant revision.
In October, a month after the iPhone announcement, Apple will unveil the new iPod lineup. It’s tag line will be something like “Something big. Something small.” The iPod Nano is the something small. It adopts iOS and becomes the smallest general purpose computer. Like the iPhone it will lose the 30-pin doc connector while gaining WiFi and bluetooth. Apple will open the Nano to a specialized corner of the App with simple single function apps that incorporate voice control and feedback. The Nano will also gain a front and rear facing camera. Yes I know this is exactly what I predicted a year ago, but in the grand-tradition of Apple prognostication, I wasn’t wrong, just a year too early.
The iPod touch goes big. It gains a 4 or 4.5 inch screen and is marketed as a game machine and Kindle competitor. It bumps up to the A5 processor and remains just as thin as the current device. The front face gains multiple colors but the back remains polished stainless steel. It also loses the 30-pin dock connector. All of those sightings of a teardrop shaped, 4-inch screened iPhone 5 from last summer were actually early proto-types of the 2012 iPod Touch.
Apple offers an iPod Touch with a cellular radio for the first time, just like in the iPad. The data rates are also identical to the iPad. No LTE option. Prices:
8 gb WiFi $229
32 gb WiFi $329 WiFi + Cellular $399
64 gb WiFi $429 WiFi + Cellular $499
iOS
iOS 6 is announced at WWDC in June and roles out to all iOS devices in September a week before the introduction of the iPhone 5. The marque feature of iOS6 is Siri which becomes available on the iPhone 4, iPod 4th Generation and all three iPads. Siri leaves beta and opens up to allow limited third party software access to new voice and speech APIs. TV shows and movies get the iCloud experience and can be downloaded repeatedly. FaceTime over 3g.
Macintosh
The big story of 2011 is the repositioning of the MacBook Pro line. After the MacBook Air displaced the MacBook in 2011, it will set its sights on the iconic MacBook Pro. The MacBook Pro 13 inch will disappear entirely. The 15 and 17 inch will remain.
The Macbook Air line will add a 15 inch model. The MacBook Airs will begin to offer a cellular modem option.
MacPro will get updated without fanfare in March. Despite much handwringing, this will not be the final update of the tower mac which continues to serve a small, but influential, sliver of the Macintosh family.
Apple will introduce a cloud back up service which will move Time Machine from a spare drive on your desk to one of Apple’s data centers. This will be a pay-to-play service: one year of back-up will be provided with new machines and it will be $100 per year after that.
Throughout 2012 there is not a peep about the next version of OS X.
Apple TV
Apple introduces a revamped Apple TV at WWDC and it goes on sale in September. It remains the little iOS box that is currently sold with a bigger processor and a new version of the OS and Siri. An iOS device running iOS 6 will be required to act as the microphone for Siri. It will also gain the ability to add apps from the iTunes App Store. The Apple TV Set will also be introduced in June for a September or October role out. The Apple TV set (iPanel?) will not offer any significant feature beyond the Apple TV. However, it will come bundled with a 7 inch iPad to act as a remote control, game controller and auxiliary screen. Additionally, any iPhone, iPad and iPod running iOS will be able to duplicate the functions of this uber-remote.
Apple
Apple will spill some of their massive war chest to lock-up exclusive content deals. This will include sports, movies and original content. They will continue to purchase small engineering-focussed companies but no other major merger.
Tim Cook will remain the CEO and there will be a steady trickle of VPs leaving the company for other CEO positions. Names that will stay include Cook, Cue, Ive and Schiller. Forstall, Mansfield are among the Veeps who may move on.
A lot of companies might try to entice the architect of the iPhone to be their top guy and with a young Tim Cook (born 1960) secure as CEO, an ambitious Forstall might make the jump. Can you imagine Scott Forstall being tapped to replace Ballmer at Microsoft?
With the release of the new Apple TV the stock will be seriously goosed. I expect a 52-week high of $667 and the stock to close 2012 at $605.
I spilled an entire cup of coffee on my laptop. Dead laptop.
Last back-up, 7 weeks old.
Lost blogging momentum.
I have a pile of half written posts and should be out of the funk soon.
I have also purchased a dropbox account and will not be caught with two-month old back-ups again. That’s a pretty good new years resolution, though better would be to not spill cups of coffee into my laptop.
