Obesity Hypoventilation Syndrome (OHS) is defined by the following triad.
The diagnosis requires exclusion of other causes of hypoventilation (e.g., neuromuscular disease, chest wall disease, pulmonary parenchymal disease)1)2).
In 1956, Burwell et al. named the condition in patients with extreme obesity and somnolence “Pickwickian syndrome” after a Dickens novel1). However, for decades thereafter, the distinction between OHS and OSA remained unclear. In 1999, the American Academy of Sleep Medicine (AASM) classified the causes of daytime hypercapnia into “upper airway obstruction predominant (OSA)” and “hypoventilation predominant (OHS)”, establishing the formal definition of OHS1).
Approximately 90% of OHS patients have comorbid OSA, while the remaining 10% exhibit sleep hypoventilation without obstructive events2).
The estimated prevalence of OHS in the general US population is approximately 0.15–0.3% 1). The prevalence increases markedly with rising BMI.
The prevalence of OHS in the OSA patient population is reported to be 10–20% 2). Diagnosis is often delayed, and it is typically first diagnosed in the 40s to 60s. Approximately 75% are misdiagnosed with chronic obstructive pulmonary disease (COPD) 2).
The exact mechanism of visual impairment associated with OHS is not fully understood, but associations with papilledema and central retinal vein occlusion (CRVO) have been reported. Additionally, ocular diseases associated with OSA, which is closely related to OHS, include floppy eyelid syndrome (FES), glaucoma, keratoconus, non-arteritic anterior ischemic optic neuropathy (NAION), and central serous chorioretinopathy (CSCR).
OSA is characterized by repetitive apnea and hypopnea due to upper airway collapse during sleep. OHS differs in that, in addition to OSA, hypercapnia (PaCO₂ >45 mmHg) persists even during wakefulness. Approximately 90% of OHS patients have comorbid OSA, but about 10% have a hypoventilation type without OSA.
The systemic symptoms of OHS are as follows.
Ocular subjective symptoms include the following.
Papilledema
Bilateral optic disc swelling: Accompanied by hemorrhages and venous engorgement. The main mechanism is hypercapnia → cerebral vasodilation → increased intracranial pressure → increased venous pressure in the optic disc.
Another hypothesis: It has also been proposed that intermittent hypoxia during apnea in OSA causes increased intracranial pressure during sleep, and compression of the transverse sinus leads to elevated intracranial pressure.
CRVO
Central retinal vein occlusion: Presents with venous tortuosity and dilation, flame-shaped hemorrhages, and mild optic disc edema and macular edema in one or both eyes.
Proposed mechanism: Hypoxia-induced dilation of the central retinal artery compresses the adjacent central retinal vein. Local increased blood viscosity associated with optic disc edema may also contribute.
FES
Floppy eyelid syndrome: A condition in which the upper eyelid easily everts upward. It is found in 2–33% of OSA patients. Caused by weakening of the tarsal muscle, it typically occurs on the side the patient sleeps on.
Bilateral cases: Suggest alternating lateral decubitus or prone sleeping positions.
Nonarteritic Anterior Ischemic Optic Neuropathy
Nonarteritic anterior ischemic optic neuropathy: Characterized by sudden painless monocular vision loss, optic disc edema, and relative afferent pupillary defect (RAPD).
Association with OSA: Patients with OSA have a 16% higher risk of developing nonarteritic anterior ischemic optic neuropathy, involving combined effects of hypoxia, oxidative stress, and increased intracranial pressure during apnea.
In the early stage, there are often no subjective symptoms other than transient visual obscurations (in both eyes) lasting a few seconds. When intracranial hypertension persists for several months, visual field defects appear in the inferonasal or concentric pattern, followed by visual acuity loss. Bilateral abducens nerve palsy may also occur.
Compared to non-hypercapnic obese patients, OHS patients have a significantly higher risk of the following complications 2).
The diagnosis of OHS requires all three of the following conditions to be met.
| Test | Purpose | Notes |
|---|---|---|
| Arterial blood gas analysis | Confirm awake PaCO₂ | Essential for definitive diagnosis |
| Polysomnography | Diagnosis of sleep-disordered breathing | Assessment of nocturnal hypoventilation |
| Serum bicarbonate level | Screening | ≥27 mmol/L: sensitivity 92%, specificity 50%1) |
When papilledema is present, differentiation from idiopathic intracranial hypertension (IIH) is important. IIH commonly occurs in young obese women, with elevated intracranial pressure but normal PaCO₂. In contrast, OHS is associated with hypercapnia, which increases intracranial pressure through cerebral vasodilation. CT or MRI is used to exclude space-occupying lesions and hydrocephalus, and MRV is used to confirm stenosis or occlusion of the cerebral venous sinuses.
In obese patients (especially BMI >40) presenting with excessive daytime sleepiness, morning headache, and dyspnea, OHS should be suspected when serum bicarbonate is ≥27 mmol/L. Confirm diagnosis with arterial blood gas analysis showing PaCO₂ >45 mmHg.
The mainstays of OHS treatment are positive airway pressure therapy (PAP therapy) and weight loss.
CPAP
Continuous Positive Airway Pressure: First-line treatment for OHS with severe OSA (AHI≥30). Maintains constant positive pressure during sleep to prevent upper airway collapse.
Efficacy rate: Respiratory events are eliminated in 57% of patients. For non-responders, consider switching to BiPAP.
NIV (BiPAP, etc.)
Non-invasive ventilation: First-line treatment when OSA is mild or absent. Also indicated for CPAP non-responders.
Success rate in acute phase: The success rate of NPPV for acute hypercapnic respiratory failure (AHRF) is approximately 84%4).
Long-term NIV and CPAP have equivalent efficacy. CPAP can be prescribed regardless of baseline PaCO₂ severity, but if hypercapnia does not improve after 2–3 months, switching to NIV is recommended2).
Significant weight loss through conventional methods or bariatric surgery improves lung function, respiratory muscle strength, and sleep-disordered breathing.
In a study by Sugerman et al., 61 OHS patients who underwent bariatric surgery showed improvement in PaO₂ from 53 to 73 mmHg and PaCO₂ from 53 to 44 mmHg one year postoperatively. However, at 5-year follow-up, PaO₂ decreased to 68 mmHg, PaCO₂ increased to 47 mmHg, and BMI increased from 38 to 40 kg/m², indicating challenges in maintaining long-term effects2).
Since the widespread use of CPAP, tracheostomy is less commonly performed but remains a last resort when other treatment options fail. It can improve alveolar ventilation by bypassing the upper airway, but does not affect CO₂ production or the muscle weakness specific to OHS.
For papilledema, management of the underlying OHS (PAP therapy, weight reduction to lower intracranial pressure) is most important. Drug therapy to lower intracranial pressure includes acetazolamide (Diamox, off-label) and mannitol. If intracranial pressure is reduced early, papilledema resolves quickly without visual impairment. However, delayed treatment can lead to irreversible visual dysfunction.
For CRVO, treatment follows general CRVO management (e.g., anti-VEGF therapy), but management of OHS as the underlying disease is essential.
For OHS with severe OSA (AHI≥30), CPAP is first-line. If OSA is mild or absent, or if hypercapnia does not improve after 2–3 months despite adequate CPAP adherence, consider switching to BiPAP (NIV).
The pathophysiology of OHS involves multiple interacting mechanisms.
Hypercapnia dilates cerebral blood vessels, leading to increased intracranial pressure (ICP). This elevates venous pressure at the optic disc, causing papilledema. In OSA patients, it is hypothesized that hypoxia during apnea episodes also raises ICP during sleep. Additionally, compression of the transverse sinus is proposed to increase ICP.
Multiple mechanisms are thought to be involved in the development of CRVO.
These changes act in combination to increase the risk of CRVO in patients with OHS.
OHS currently lacks a widely used severity scale. The ERS task force has proposed a system classifying hypoventilation in obesity into five stages (stages 0–4) 1). Additionally, Cabrera Lacalzada and Diaz-Lobato proposed a classification of mild, moderate, and severe based on awake PaCO₂, PaO₂, BMI, and AHI 1). However, neither has been validated in large prospective studies, and their clinical utility remains unestablished.
Incretin therapies such as GLP-1 receptor agonists have shown significant weight loss in obesity treatment, but weight regain and reversal of cardiometabolic improvements after discontinuation have been reported. Their efficacy for OHS remains largely unclear 2).
In a French retrospective cohort by Gachelin et al. (102 obese children, mean age 10.5 years), OHS was diagnosed in 3.9% 7). Pediatric OHS is currently managed by extrapolating from adult data, and there is an urgent need to establish pediatric-specific prevalence, diagnostic criteria, and treatment protocols.
Digital health technologies such as remote monitoring and feedback systems are being considered for use in improving adherence to PAP therapy and comprehensive management of OHS.
