[Health] Acetazolamide reduces central apneas, both altitude-induced and treatment emergent

[JoeyWallaby]

One treatment for central apneas at altitude is acetazolamide, a carbonic anhydrase inhibitor frequently used in the treatment of acute mountain sickness. Acetazolamide prevents central apneas at altitude through metabolic acidosis by its diuretic effects. Sleep of OSAS patients at 490 m and at 1630 to 2590 m with and without CPAP treatment was investigated in three previous studies, in which acetazolamide was shown to reduce central apneas compared to placebo during sojourns to moderate altitude. In addition, as observed in healthy subjects, acetazolamide in OSAS patients reduced the apnea/hypopnea index compared to placebo and increased oxygen saturation and improved sleep quality (sleep efficiency, arousals, slow-wave sleep).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977962/

[Geer1]

Not really related but about 7 years ago I hiked Volcan Tajumulco, the highest point in central america at 13,845 feet elevation. We started the day in Quetzaltenango which has elevation of around 7,640 feet and hiked up to a camping area at around 13,200 feet then the following morning hiked to the top for a neat sunrise. I hadn't even acclimated to Quetzaltenango as I had arrived the evening before from Panajachel which only has an elevation for 5,240 feet so my elevation increase was ~8,000 feet in a little over 24 hours. 

Almost everyone was feeling the effects of altitude sickness(headaches etc) and I remember sleeping very poorly that night. I was probably pretty lucky that I wasn't sicker (somehow was one of the least affected) since when I got back I did some research and found out that in order to avoid altitude sickness it is recommended to increase elevation by 1000 feet per night so that kind of trip should have been done in around 8 days instead of 1... 

It was a neat experience and quite the view though.

   

[Sleeprider]

Diamox or Acetazolamide has been used to help individuals traveling to higher elevations avoid high altitude sickness and even high altitude pulmonary edema (HAPE) for a long time. It is also being used in conjunction with EERS to treat CPAP emergent central apnea. Interesting stuff.

[sheepless]

maybe slightly off topic but related: I surmise without facts that diamox might help with elevation issues and treatment emergent ca but not necessarily for idiopathic ca.

they didn't have a treatment for central apnea when I was first diagnosed in 1987. after a night with oxygen failed to provide relief, we tried diamox and a couple other meds I can't remember. nothing helped my idiopathic (and perhaps plm induced) ca so I lived with it for almost 30 more years before getting cpap, and then only because I had developed equally severe oa on top of the ca.

[Sleeprider]

Sheepless, Acetazolamide is a carbonic anhydrase (CA) inhibitor sometimes used as a respiratory stimulant. It has well documented benefits in treatment of CSA and to stimulate respiration in COPD patients.

Acetazolamide is a carbonic anhydrase inhibitor that causes bicarbaturia and metabolic acidosis, which presumably shifts the apneic threshold of PaCO2 to a lower level. It has been shown to be effective therapy in primary central sleep apnea and CSB in patients with heart failure and in the treatment of high-altitude periodic breathing.

Effecto of Acetazolamide on CSA at high altitude https://www.ncbi.nlm.nih.gov/pubmed/28043212
CSA Improvement with Acetazolamide https://jamanetwork.com/journals/jamaint...act/602450

[sheepless]

news to me so thanks for that, although I'm not sure if what you've said contradicts my thought that diamox may be ineffective in (some types of?) idiopathic central apnea. all I know is nothing they offered me way back when, including diamox, helped at all. could be another factor suggesting maybe my ca has been driven by plm all along. remains to be seen.

[Sleeprider]

I think where CA is persistent rather than transient, and arises from PAP therapy or altitude, Diamox may have a role. It has been around for a long time for doctors working with athletes, skiers and hikers at altitude and in the anesthesiology profession. It appears to be a strategy for pulmonologists working with COPD and other forms of hypoventilation. I'm not expecting to see anything from sleep doctors for a very long time, if ever. I ofteh think it is a fraudulent specialty.

[JoeyWallaby]

AASM published this in 2012

https://www.aafp.org/afp/2012/1115/p968.html

Acetazolamide has limited supporting evidence, but may be considered for the treatment of primary central sleep apnea syndromes. (Option.) The overall quality of evidence for this recommendation is low. Use of acetazolamide has the potential to produce adverse effects, such as paresthesias, tinnitus, gastrointestinal symptoms, metabolic acidosis, electrolyte imbalance, and drowsiness.

Another study
https://respiratory-research.biomedcentr...017-0607-9

There was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.

[JoeyWallaby]

https://erj.ersjournals.com/content/45/2/408.long

Loop gain associated with increased OSA severity

We also observed a significant association between loop gain and OSA severity (LG1 versus AHI; r=0.72, p<0.001), the relative predominance of non-REM versus REM OSA (LG1 versus REM AHI minus non-REM AHI; r=−0.46, p=0.02) and the median duration from one adjacent apnoea/hypopnoea to the next (LG1 versus inter-event interval; r=−0.47, p=0.01). We observed no link indicative of a confounding relationship between measured loop gain and anatomy/collapsibility (online supplementary fig. S5).

Acetazolamide reduces loop gain

[JoeyWallaby]

Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837832/

This is, to our knowledge, the first study with a controlled design to compare the effect of AZT and CPAP, alone or in combination, on BP and respiratory disturbance in patients with HT and OSA. CA inhibition by AZT led to a reduction of BP and vascular stiffness, which was superior to that observed after CPAP. Conversely, CPAP was more effective than AZT in terms of OSA elimination, but this difference was reduced after adjustment for adherence to therapy. Our findings suggest that CA activity influences BP regulation and sleep-disordered breathing in patients with OSA. Larger placebo-controlled clinical trials addressing both effect and long-term outcome are warranted to fully explore the potential of CA-inhibitory drug therapies in OSA.