The administration of N-acetylcysteine may improve outcome in a subset of diabetic foot patients but there is no randomised evidence in this paper.

Clinical Bottom Line:

1. NAC administration improved in-chamber oxygenation of the wound area in those who could only achieve poor PtcO2 (<200 mmHg) during HBOT. This is not a randomised result.
2. Randomised outcomes not given in this paper.

Citation/s:1. Efrati S, Gall N, Bergan J, Fishlev G, Bass A, Berman S, Hamad-Abu R, FeigenzonM, Weissgarten J. Hyperbaric oxygen, oxidative stress, NO bioavailability and ulcer oxygenation in diabetic patients. Undersea Hyperb Med. 2009 Jan-Feb;36(1):1-12.
Lead author's name and fax: No contact given

Three-part Clinical Question:When treating diabetic ulcers with hyperbaric oxygen, does the co-administration of N-acetylcholine (NAC) improve clinical outcome?
Search Terms: Diabetes; NAC; antioxidant

The Study:Non-blinded randomised controlled crossover trial (unclear purpose of randomisation).
The Study Patients: Patients with Type-II diabetes mellitus with non-healing foot ulcers and no surgically treatable major arterial disease.
Control group (N = 26 ; 25 analysed): Planned course of at least 20 HBOT treatments for 90 mins daily. For 5 days (either day 1 to 5 or 6 to 10) breathing air at 1 ATA (30 mins), then 100% oxygen at 1 ATA for 30 minutes and finally 30 minutes breathing 100% oxygen at 2 ATA while tissue oxygenation was measured using transcutaneous PO2 (PtcO2).
Experimental group (N = 26 ; 25 analysed): As above but had 5 days of NAC (600 mg twice daily) on the alternate period of 5 days (600mg twice daily) then HBO exposure as above with extra NAC (total 1800mg) while breathing the same sequence as above.

End of crossover:After 10 days, all patients were classified as responders to HBOT with PtcO2 in-chamber of >200 mmHg, or as poor responders with PtcO2 <200 mmHg and the poor responders were kept on NAC (I think!). No results given at that point so no randomised results.

The Evidence:Nil

1. Patients had eight weeks of convential wound therapy before this trial
2. NAC (N-acetylcysteine is a thiol-containing antioxidant previously demonstrated to decrease reactive oxygen species and increase nitric oxide bioavailability.
3. This was a crossover study but it seems some patients continued with NAC for the rest of the HBO course and some did not – based on their PtcO2 response.
4. Results are given for the comparison between groups in each arm that did and did not receive NAC on the basis of whether or not they achieved a target PtcO2 in the chamber. In the group achieving the target PtcO2, NAC did not further improve this figure. In the group with low PtcO2 in the chamber at 2 ATA, NAC improved that figure - but this is not a randomised result.
5, I am not sure why the patients were randomised to NAC/not NAC in the crossover manner described.

Appraised by:Mike Bennett m.bennett@unsw.edu.au ; Monday, 6 September 2021
Kill or Update By: Sept 2024