CroFab reconstitution – a faster method

June 29, 2010, 3:07 pm


Improving Crotalidae polyvalent immune Fab reconstitution times. Quan AN et al Am J Emerg Med 2010;28:593-595.


The package insert for Crotalidae polyvalent immune Fab (CroFab [Protherics Inc.]) recommends that each vial be reconstituted with 10 mL of Sterile Water for Injection USP (SWI) and mixed by continuous gentle swirling (to avoid foaming).  The insert goes on to recommend that administration of the antivenom be initiated  “as soon as possible after crotalid snakebite in patients who develop signs of progressive envenomation”.  The recommended initial dose is 4 to 6 vials, mixed with 250 mL normal saline.

The authors of this study (from Banner Good Samaritan Medical Center in Phoenix AZ) note that in their experience preparation of 4 to 12 vials may require an hour or more.  They compared the effect of the volume of SWI used to reconstitute each vial (10 mL or 25 mL) and mixing technique (mechanical v. hand swirling) on time to complete dissolution of the product.

They found that using 25 mL SWI and manual swirling produced a time to dissolution (median 1.1 min) significantly shorter than using 10 mL SWI and 10 mL SWI and manual swirling (median 4.5 min).  All other combinations were radically slower.  The authors recommend  using 25 mL of SWI per vial and hand mixing when reconstituting CroFab, especially for the initial dose.

I found these results interesting, with one caveat. The authors measured the time to complete dissolution from when SWI was introduced into the vial.  However, when 25 mL SWI was introduced, air had to be removed to avoid pressure buildup.  It is not clear how much time this added to preparation of each vial.  Starting the clock when SWI injection was begun would have clarified this point.


  1. john Says:

    as a CSPI who regularly also works on a trauma floor Ive had mix crofab on a few occasions, I have found it almost impossible to get the crofab into solution with only 10 ml of SWI

  2. Leon Says:

    Thanks for the comment, John. Have you ever tried preparing the product with a higher volume of SWI?

  3. john Says:

    yes we used 25-30 ml because the crofab was in a hard ball and would not go into solution

  4. Michelle Says:

    As the air at the top of the vial inhibits further injection of fluid into the vial you just withdraw the air with the same syringe. Doesn’t add any time at all really. It wouldn’t make any noticeable difference.