Lt Col Dara D. Regn, USAF, MC, FSa; Lt Col Anh H. Davis, USAF, MC, FSb; Lt Col William D. Smith, USAF, MC, FSa; Maj Catherine J. Blasser, USAF, MC, FSa; Lt Col Caelan M. Ford, USAF, MC, FSa
Correspondence: Dara Regn (drregn@hotmail.com)
aUnited States Air Force School of Aerospace Medicine, Wright-Patterson Air Force Base, Ohio
bDepartment of Aerospace Medicine, McConnell Air Force Base, Kansas
Author disclosures
The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Treatment-emergent CSA (TECSA, also known as complex sleep apnea) has been defined by the ICSD-3 by the following criteria: (1) diagnostic PSG with ≥ 5 events per hour of predominantly obstructive events; (2) resolution of obstructive events with PAP without a backup rate and CSA index (CAI) ≥ 5 per hour with central events ≥ 50% of the AHI; and (3) CSA not better explained by another disorder.8 Patients with TECSA can be further classified into those who have transient events that resolve within weeks to months, those with persistent events, and those with delayed events that may develop weeks to months after initiating PAP therapy.14
PAP treatment can decrease the PaCO2 below the AT due to removal of flow limitation in previously obstructed upper airways, resulting in TECSA.15,16 PAP therapy has not been the only treatment where new CSA has been identified on initiation. A 2021 systematic review identified patients who developed new-onset CSA with mandibular advancement device (MAD), hypoglossal nerve stimulator, tongue protrusion device, and nasal expiratory PAP device use, as well as after tracheostomy, maxillofacial surgery, and other surgeries, such as nasal and uvulopalatopharyngoplasty.17
The prevalence of TECSA has been noted to range between 0.6% and 20.3%, but Nigam and colleagues estimated a prevalence of 8.4% in their systematic review.11,14 The variability in prevalence between studies could be due to differences in study design (retrospective vs prospective vs cross-sectional), diagnostic and inclusion criteria, patient population, and type of study used (full-night vs split-night vs both).18,19 Risk factors for TECSA include male sex; older age; lower body mass index; higher baseline AHI, CAI, and arousal index; chronic medical issues such as CHF and coronary artery disease; opioid use; higher CPAP settings; excessive mask leak; and bilevel PAP (BiPAP) use.20 Identifying these risk factors is important, as patients with TECSA are at higher risk of discontinuing therapy and of developing PAP intolerance.15,20
Most patients with TECSA can continue CPAP therapy with resolution of events over weeks to months, but treatment of comorbid conditions should be optimized as they could be contributing factors. Zeineddine and colleagues recommend continuation of CPAP for 3 months if the patient has minor or no symptoms.19 A 2018 systematic review noted that 14.3% to 46.2% of TECSA patients will have persistent TECSA and some will develop TECSA after at least 1 month of PAP therapy.14 For these patients and those with severe symptoms in spite of therapy, a switch to BiPAP spontaneous/timed (BiPAP-S/T) or ASV should be considered, if not contraindicated based on comorbidities.21 Medications such as acetazolamide, oxygen therapy, and CO2 supplementation have also been discussed as alternative treatments, but these options should not be first-line therapies and should be used on a case-by-case basis as adjuncts to PAP therapy.16,17
Altitude-Induced CSA
Also known as CSA due to high-altitude periodic breathing (CSA-HAPB), this form of CSA occurs in nearly all lowlanders at altitudes above 3000 m, with severity increasing with altitude.15 The exact altitude at which it occurs varies based on an individual’s physiology. CSA-HAPB occurs in response to the low barometric pressure at altitude, combined with stable fraction of oxygen, resulting in decreased inspired partial pressure of oxygen and hypoxia. The normal physiologic response to hypoxia is increased ventilation, which can cause hypocapnia, suppressing respiratory drive and resulting in CSAs. The instability of the respiratory response results in cyclical CSAs followed by hyperventilation. This periodic breathing then causes arousals from sleep, driving further sleep fragmentation and exacerbation of baseline desaturation and instability in the cyclical respiratory response. There is individual variability in hypoxic chemoresponsiveness (loop gain). Compensatory mechanisms are most robust when an individual routinely dwells at high altitude, resulting in acclimatization, rather than traveling there for a brief stay. Genetics and cardiac output also contribute to the effectiveness of compensation to altitude.
