UKidney Toxicology Series

Check out the Nephrology Social Media interns discuss an up to date information on Toxico-Nephrology.

http://ukidney.com/nephrology-resources/toxicology/toxicology-posts-by-agent

Topic Discussion: Novel ways to combat Intradialytic hypotension

Intradialytic hypotension(IDH) during hemodialysis(HD) is a challenging clinical concern and often hard to treat.  After one has ruled out cardiac disorder ( especially diastolic dysfunction), common medications and ideas attempted are: midodrine pre dialysis, low temperature during dialysis, daily short dialysis sessions, florinef use, steroids in the right clinical setting, and sodium and or calcium profiling.  Switching to peritoneal dialysis can be an option as well.  The KDOQI guidelines recommends most of these above mentioned changes.

What are some other novel mechanisms that can be used?

1.Carnitine:  Carnitine deficiency has been associated with IDH and trial of L-carnitine at 20mg/kg with dialysis might help reduce IDH


2.Sertraline: This anti- depressant has shown improvement in orthostatic hypotension. Both retrospective and prospective studies in small number of patients demonstrated that treatment with sertraline hydrochloride was associated with an improvement in the hemodynamic parameters in patients with IDH. A recent randomized control trial from Iran also showed good benefit with this agent in IDH. The dose one can usually start is 50mg once a day and then max at 100mg daily per most trials when used for IDH.

Some good references:

https://www.ncbi.nlm.nih.gov/pubmed/26174461
https://www.ncbi.nlm.nih.gov/pubmed/15012700
https://www.ncbi.nlm.nih.gov/pubmed/9531178

3.DDAVP

Rho et al nicely demonstrated in a CJASN paper in 2008 that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients compared with controls despite hypotensive episodes. As a result, many have tried to use DDAVP as a treatment option for IDH.
As early as 1990s, vasopressin was tried in 6 patients to help IDH in one single center study with success.  The largest study(17 patients) using this was from Iran. In that study, the treatment arm received intranasal DDAVP (two puffs) 30 minutes before all HD.  Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). This might be another interesting option to consider in IDH.  Risk of  thrombotic events might be something to think about.

4.Droxidopa

This agent has been approved by FDA for autonomic neuropathy.. The trade name is Northera. Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine. Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier. Why in IDH? Well recently published trial that was a placebo controlled, phase 2 study looked at efficacy and safety of this agent in IDH.  The investigators looked at placebo vs 400mg vs 600mg dose.  Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with -4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Treatment of both dosages were well tolerated. This might be an interesting option as well. The most common side effects noted were GI related.