The Role of Obstructive Sleep Apnea in Hypercapnic Respiratory Failure Identified in Critical Care, Inpatient, and Outpatient Settings

Abstract

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single "cause" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia.

Keywords: Hypercapnia; Hypercapnic respiratory failure; Hypoventilation; Non-invasive ventilation; Positive airway pressure; Respiratory insufficiency; Sleep apnea.

Figure 1:. Determinants of the arterial blood CO₂ tension

The efficiency of ventilation refers to the portion of ventilation (air moved by the respiratory system) that participates in gas exchange. Deadspace (Vd) is synonymous with “wasted ventilation” that does not participate in gas exchange. Therefore, the unwasted ventilation is one minus the deadspace fraction (Vd/Vt, Vt refers to the overall tidal volume). The production of CO₂ (${\stackrel{.}{\mathrm{V}}\text{CO}}_2$) depends on the overall metabolic rate, and the portion of that is aerobic vs anaerobic. Each condition can contribute to hypercapnia through multiple mechanisms (e.g. COPD may result in elevated deadspace, resistive respiratory system loads, and mechanical disadvantage from hyperinflation) and multiple diseases can contribute to each physiologic abnormality. (From Sleep Med Clin 9 (2014) 289–300 http://dx.doi.org/10.1016/j.jsmc.2014.05.014 Berger et al., but originally appearing in the Journal of Applied Physiology.)

Figure 2:. CO₂ Loading During Apneas and Hypopneas

Apneas and hypopneas can lead to an accumulation of CO₂ in the arterial blood, particularly if the inter-event ventilation is not able to increase because metabolic CO₂ production continues while alveolar ventilation drops. According to this model, more frequent events (a higher Apnea-Hypopnea Index), longer events, or a limited ability to increase the amount of ventilation between obstructions will lead to progressive nocturnal CO₂ accumulation. In combination with any underlying respiratory system abnormalities, bicarbonate retention by the kidneys to minimize the change to blood pH is then hypothesized to lessen the tendency to normalize the nocturnal loading, eventual leading to daytime hypercapnic respiratory failure. From Berger et al J Appl Physiol 88:257-264 (2000)^,; with permission.

Figure 3:. Spatial Representation of the “Inverse Problem” of Conditional Probability

The probability of having a disease among patients identified with hypercapnia [represented as: P(disease ∣ hypercapnia) in statistical notation] may be much different from the probability that a patient with a disease develops hypercapnia [P(hypercapnia ∣ disease)]. This is an important difference because clinicians often recognize hypercapnia before knowing the cause, and thus, P (disease ∣ hypercapnia) is the expected rate for finding that disease in subsequent investigations. In this case, only 1 in 5 cases of “Disease A” develop hypercapnia, while 1 in 2 cases of “Disease B” do. However, because Disease A is much more common, the likelihood of hypercapnia being caused by Disease A is double that of Disease B. It has been suggested that Obesity Hypoventilation Syndrome is the most common current cause of hypercapnia (see Table 3), despite most patients with obesity and OSA not developing hypercapnia. Figure generated using ‘eulurr’ package.