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Is a Raised Eucapnic Blood Bicarbonate Value a Bellwether of Preclinical Obesity Hypoventilation Syndrome?Bicarbonate Values and Obesity Hypoventilation Syndrome FREE TO VIEW

Brian N. Palen, MD; Erik R. Swenson, MD
Author and Funding Information

From the Puget Sound Veterans Administration Hospital, University of Washington.

CORRESPONDENCE TO: Brian N. Palen, MD, Puget Sound Veterans Administration Hospital, 1660 S Columbian Way, Seattle, WA 98108; e-mail: brian.palen@va.gov


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(2):282-284. doi:10.1378/chest.14-1970
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The obesity hypoventilation syndrome (OHS) is defined by obesity (BMI > 30 kg/m2) and awake arterial hypercapnia (Paco2 > 45 mm Hg) in the absence of other causes of hypoventilation and is generally associated with sleep-disordered breathing such as OSA, nocturnal hypoventilation, or both.1,2 Compared with eucapnic obese individuals, patients with OHS have a lower quality of life, greater health-care expenditure, greater risk for pulmonary hypertension, and higher mortality rate,3,4 thus emphasizing the importance of early disease recognition as a pathway to improved management outcomes. In this regard, the article by Manuel and colleagues5 in this issue of CHEST (see page 362) offers some direction toward that goal. They propose that obese eucapnic individuals with an isolated elevation in blood bicarbonate measured only several hours after awakening and not explained by diuretics, mineralocorticoids, or alkaline ingestion, may, in fact, be a patient population in the earliest stage of OHS.

It has been previously established that patients with OHS have a blunted response to hypoxia and hypercapnia.6 What is not clearly understood is why some obese individuals retain CO2 throughout the day to meet OHS criteria while other similarly obese individuals do not. The answer is likely multifactorial and further complicated by the broad, normal physiologic range of CO2 and bicarbonate values, which, in the absence of previous data, cannot reveal whether a patient has, for example, moved from a low-normal value to a high-normal value with the onset of disease.

The hypercapnia of OHS has previously been attributed to the cumulative effects of nocturnal sleep-disordered breathing, increased mechanical respiratory load, increased physiologic dead space, ventilation-perfusion mismatching, blunted respiratory chemoresponsiveness, and leptin resistance.7 A recent study by Javaheri and Simbartl8 further suggests increased CO2 production from enhanced sympathetic nervous system activation and/or obesity-related increases in basal metabolic rate, as a previously underestimated contributor. Sustained daytime hypercapnia is tolerated in patients with OHS due, in part, to the impact of elevated blood bicarbonate levels on central spinal-fluid hydrogen-ion concentration and subsequent effect on central respiratory-center responsiveness.

Thus, persistently elevated serum bicarbonate values play a critical role in the transition to sustained daytime hypercapnia in patients with OHS and are commonly misunderstood as a simple consequence of acid-base compensation. It remains unclear if elevated bicarbonate levels persist purely as delayed and incompletely resolved compensation for nocturnal hypercapnia, or if other processes are at play. Norman and colleagues9 previously demonstrated via computational modeling that intermittent nocturnal hypercapnia from sleep-disordered breathing could transition to chronic, sustained hypercapnia over a period of days if either renal bicarbonate excretion or ventilatory responsiveness to CO2 were decreased, with a synergistic effect seen when both were diminished.

The utility of blood bicarbonate values in diagnosis and assessment of treatment response in OHS has long been a source of confusion. A bicarbonate value ≥ 27 mEq/L has been shown to be a sensitive (92%) but not specific predictor of daytime hypercapnia in obese patients,10 since as discussed, other causes of mild, primary metabolic alkalosis may exist in these patients. Although Manuel and colleagues5 were careful to measure arterial blood gas values within a narrow time frame (8:00 am-10:00 am), blood drawn later in the day in these individuals may show further decline in bicarbonate level, possibly back into the normal range. Thus, the role of elevated serum bicarbonate level as a practical, reliable, and early predictor of decreased ventilatory responsiveness has yet to be clarified.

Manuel and colleagues5 suggest that obese eucapnic individuals with elevated serum bicarbonate levels constitute a patient population with diminished respiratory responsiveness. In this prospective observational cohort of 71 obese patients, they evaluated polysomnogram data as well as ventilatory response to daytime acute hypoxic and hypercapnic challenges. Eucapnic patients with isolated elevation of serum bicarbonate levels demonstrated similar percentages of nocturnal hypoxemia as well as response to daytime hypoxic and hypercapnic challenge as seen in patients with OHS.5 The conclusion from their article is that this patient population, in fact, represents a forme fruste of OHS.

Admitted limitations of the study include a self-selected, referred patient population, raising the question of compatibility within the general community. The authors also point out the expected decrease in ventilatory responsiveness of individuals may simply be a consequence of having an elevated bicarbonate levels regardless of the cause or underlying pathology.5 Full in-laboratory polysomnogram protocols including use of nocturnal CO2 monitoring would also be desirable in future studies.

This study strengthens the argument that our current definition, as well as general understanding, of OHS progression is inadequate. Whether the identified population will, in fact, progress to OHS as we currently know it remains unproven and will require data from longitudinal studies. Additional questions are raised by the study, including whether earlier recognition and or use of interventions such as respiratory stimulants would change clinical course and outcomes.

The physiologic questions raised by the study are also intriguing. Whether there is, in fact, a “critical mass” at which bicarbonate retention invokes blunted ventilatory response and subsequent refractory hypercapnia is chief among them. Although the study makes bicarbonate level more intriguing as a potential physiologic marker for diminished ventilatory responsiveness, the question remains as to why only certain individuals are susceptible. The answers to these questions are, no doubt, multifactorial and will likely remain a partially elusive combination.

In summary, the study offers evidence that elevated serum bicarbonate levels in eucapnic obese patients may be a practical and early identifier of a patient population with decreased ventilatory responsiveness similar to that found in patients with OHS. The question at hand is no doubt of value and should be further evaluated with longitudinal studies before polysomnograms are recommended for all in this group.

References

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22(5):667-689. [PubMed]
 
Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. 2007;132(4):1322-1336. [CrossRef] [PubMed]
 
Atwood CW Jr, McCrory D, Garcia JG, Abman SH, Ahearn GS; American College of Chest Physicians. Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1_suppl):72S-77S. [CrossRef] [PubMed]
 
Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004;116(1):1-7. [CrossRef] [PubMed]
 
Manuel ARG, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest. 2015;147(2):362-368.
 
Verbraecken J, McNicholas WT. Respiratory mechanics and ventilatory control in overlap syndrome and obesity hypoventilation. Respir Res. 2013;14:132. [CrossRef] [PubMed]
 
Shimura R, Tatsumi K, Nakamura A, et al. Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome. Chest. 2005;127(2):543-549. [CrossRef] [PubMed]
 
Javaheri S, Simbartl LA. Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it? Ann Am Thorac Soc. 2014;11(6):945-950. [CrossRef] [PubMed]
 
Norman RG, Goldring RM, Clain JM, et al. Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model. J Appl Physiol (1985). 2006;100(5):1733-1741. [CrossRef] [PubMed]
 
Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007;11(2):117-124. [CrossRef] [PubMed]
 

Figures

Tables

References

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;22(5):667-689. [PubMed]
 
Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. 2007;132(4):1322-1336. [CrossRef] [PubMed]
 
Atwood CW Jr, McCrory D, Garcia JG, Abman SH, Ahearn GS; American College of Chest Physicians. Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1_suppl):72S-77S. [CrossRef] [PubMed]
 
Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004;116(1):1-7. [CrossRef] [PubMed]
 
Manuel ARG, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest. 2015;147(2):362-368.
 
Verbraecken J, McNicholas WT. Respiratory mechanics and ventilatory control in overlap syndrome and obesity hypoventilation. Respir Res. 2013;14:132. [CrossRef] [PubMed]
 
Shimura R, Tatsumi K, Nakamura A, et al. Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome. Chest. 2005;127(2):543-549. [CrossRef] [PubMed]
 
Javaheri S, Simbartl LA. Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it? Ann Am Thorac Soc. 2014;11(6):945-950. [CrossRef] [PubMed]
 
Norman RG, Goldring RM, Clain JM, et al. Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model. J Appl Physiol (1985). 2006;100(5):1733-1741. [CrossRef] [PubMed]
 
Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007;11(2):117-124. [CrossRef] [PubMed]
 
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