Benzodiazepines
Benzodiazepines, such as temazepam, may reduce the arousal frequency but do not appear to alter the apnea-hypopnea index (AHI). In one study, temazepam reduced high-altitude periodic breathing without adverse effect, but there was no real improvement in oxygenation or daytime symptoms.[80]Nickol AH, Leverment J, Richards P, et al. Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study. J Sleep Res. 2006 Dec;15(4):445-54.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2869.2006.00558.x
http://www.ncbi.nlm.nih.gov/pubmed/17118102?tool=bestpractice.com
Supplemental CO₂
Supplemental CO₂ decreases the AHI but does not reliably alter arousal frequency in primary CSA.[81]Thomas RJ, Daly RW, Weiss JW. Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing. Sleep. 2005 Jan;28(1):69-77.
http://www.ncbi.nlm.nih.gov/pubmed/15700722?tool=bestpractice.com
[82]Xie A, Rankin F, Rutherford R, et al. Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea. J Appl Physiol. 1997 Mar;82(3):918-26.
https://journals.physiology.org/doi/full/10.1152/jappl.1997.82.3.918
http://www.ncbi.nlm.nih.gov/pubmed/9074983?tool=bestpractice.com
There is anecdotal support for use in Cheyne-Stokes breathing (CSB).
Atrial overdrive pacing
Has been shown to only marginally reduce the AHI and cannot be recommended at this time as standard therapy for CSA.[83]Baranchuk A, Healey JS, Simpson CS, et al. Atrial overdrive pacing in sleep apnoea: a meta-analysis. Europace. 2009 Aug;11(8):1037-40.
http://www.ncbi.nlm.nih.gov/pubmed/19549678?tool=bestpractice.com
Cardiac valve replacement
In patients with congestive heart failure (CHF) secondary to valvular heart disease, improvement of CHF after valve replacement is associated with improved apnea-hypopnea index.[84]Abe H, Takahashi M, Yaegashi H, et al. Valve repair improves central sleep apnea in heart
failure patients with valvular heart diseases. Circ J. 2009 Nov;73(11):2148-53.
https://www.jstage.jst.go.jp/article/circj/73/11/73_CJ-09-0307/_pdf
http://www.ncbi.nlm.nih.gov/pubmed/19713650?tool=bestpractice.com
Phrenic nerve stimulation
Unilateral transvenous phrenic nerve stimulation (PNS) in patients with CHF and CSB showed a trend toward stabilization of breathing and improvement in respiratory events, oxygen saturation, and arousals at up to 12 months of follow-up. Favorable effects on quality of life and sleepiness were also noted. Furthermore, the beneficial effects of long-term PNS in patients with CSA appear to sustain for up to 36 months with no new safety concerns.[85]Fox H, Oldenburg O, Javaheri S, et al. Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea. Sleep. 2019 Oct 21;42(11):zsz158.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802564
http://www.ncbi.nlm.nih.gov/pubmed/31634407?tool=bestpractice.com
The therapy uses a pacemaker-like device that induces a breath by stimulation of the phrenic nerve when no impulse has been sent within a predetermined time.[86]Costanzo MR, Ponikowski P, Javaheri S, et al. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet. 2016 Sep 3;388(10048):974-82.
http://www.ncbi.nlm.nih.gov/pubmed/27598679?tool=bestpractice.com
[87]Jagielski D, Ponikowski P, Augostini R, et al. Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months' experience with the remedē(®) System. Eur J Heart Fail. 2016 Nov;18(11):1386-93.
http://www.ncbi.nlm.nih.gov/pubmed/27373452?tool=bestpractice.com
One such device was approved by the Food and Drug Administration in 2017 for patients with moderate to severe CSA. The approval was based on data from 141 patients. After 6 months, AHI was reduced by at least 50% in about half of patients with an implanted device. AHI decreased by 11% percent in patients without an implanted device.