Calcium Channel Blockers and Sepsis Outcomes

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I read with interest the article in a recent issue of Critical Care Medicine by Lee et al (1), which investigated whether preadmission use of calcium channel blockers (CCBs) was associated with improved outcomes in patients with sepsis. They found that the use of CCBs before sepsis development was associated with reduced mortality. I agree that more research is needed to validate this finding and would add that future studies should also evaluate the effects of administering calcium for the treatment of hypocalcemia in patients with sepsis. Previous experimental and clinical studies have suggested not only that calcium antagonism may improve sepsis outcome (1, 2) but also that calcium administration may be harmful (3, 4). Taken together, the results of these studies raise several important questions about patients who are admitted to the ICU with sepsis. For example, would patients with the worst outcomes be those not receiving CCBs prior to admission and then given calcium supplementation in the ICU? Would the administration of parenteral calcium during critical illness attenuate the beneficial effect of CCBs? And would prior use of calcium antagonists mitigate the deleterious effects of calcium supplementation?
The available data to date on CCBs and calcium supplementation in sepsis are either animal studies or observational clinical studies, and prospective randomized trials are needed to validate these findings. In addition to an interventional study with CCBs in patients who are at high risk of developing sepsis, there is a need for a randomized placebo-controlled trial of calcium supplementation. I agree with Lee et al (1) that a sufficiently powered interventional study with CCBs would be a challenging task because the incidence of sepsis in the general population is low. However, since hypocalcemia is extremely common in critically ill patients with sepsis (5), a randomized controlled trial of calcium supplementation should be feasible to conduct.

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