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Wednesday, February 12, 2014

#Dream RCT: Ca-HIL Study ( diuretic use in hypercalcemia)


#DreamRCT: Ca-HIL Study

Dream RCT is a project that many of us online are involved in. The assignment is to target the most important question you see in nephrology today and design a trial to answer it. Per Dr Topf, “Money no object, forget about pesky IRBs, let your mind free and create the trial which will meaningfully push back the walls of knowledge.

After you post your entry at your site of choice, UKidney will host a summary with a link for each entry and gather votes for the best. Check out what others have proposed. This is a novel project on ideas online for nephrology projects.
Here is my entry.
















My idea for a dream RCT is very simple. There are many simple questions unanswered in nephrology.
Hypercalcemia is a common problem we encounter in the hospital setting. The most common cause usually is malignancy. While the long term treatment is dependent on the cause, the initial treatment is usually IV fluids and diuretics, calcitonin and so forth.  The data to give IVF followed by diuretics have been questioned. The initial observational experiences of many physicians have driven this practice.

 Usually aggressive IV hydration is warranted sometimes even at 150-200-250 CC/HR. 
Once volume depletion is addressed, a loop diuretic MAY be used for augmentation of calcium excretion.
A recent review and analysis published in Annals of Internal Medicine sheds some light about use of loop diuretic in this setting.

The review suggests the following points:

1. Aggressive hydration is necessary
2. Use of diuretics without aggressive hydration might be harmful
3. Found only 9 articles documenting the use of furosemide in hypercalcemia and latest one published in 1983 and total was only 37 patients.
4. Average dose was 1120mg over 24 hours ( really??)
5. Normalization of Ca occurred in only 14 of 39 cases
6. Study with lower doses didn't achieve normalization ( and what do we use????)
7. Complications of other electrolyte disorders ensued
8. Finally, recommended against the use of this agent routinely except for cases of volume overloaded with hypercalcemia.
I think the tile of the paper listed below nicely puts it:- Furosemide in hypercalcemia is an unproven but common practice ( really not evidence based)
·                     My suggestion is we study this in a standardized fashion: Hypercalcemia IVF and Lasix  ( HIL study)

Venue: Multi Center
Design: Randomized control trial
Primary end point:   1. AKI  2. Need for HD
Secondary end points: 1. Length of stay, 2. Mortality
Monitor closely other electrolyte disorders in both cohorts.

·                     Inclusion Criteria
o                  Age >18
o                  Sex males and females
o                  Primary known history of a malignancy related hypercalcemia


·                     Exclusion Criteria
o                  Other causes of hypercalcemia
o                  Hypercalcemia requiring dialysis at first visit with nephrologist
o                  History of known CHF requiring diuretics on a chronic basis.

Enroll all patients with acute hypercalcemia that are inpatient setting that are initially evaluated for treatment with aid of a nephrologist. To make it a uniform setting, perhaps only hypercalcemia of malignancy should be considered ( most common cause anyway). 

Randomize to IVF ( normal saline) alone for 48 hours followed by long term therapy with bisphosphanates, steroids or denosunab.
Or IVF (normal saline) for 48 hours and furosemide ( dose dependent escalation) followed by long term therapy with similar agents


I think this study or a variant of this concept should answer the question of need and use of diuretics in treatment of hypercalcemia.  Problem is who is going to fund this? 

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