Don't overlook obesity hypoventilation syndrome

The American Thoracic Society recently offered data and a guideline on obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is common, underdiagnosed, and dangerous, Babak Mokhlesi, MD, MSc, told attendees at the annual meeting of the American Thoracic Society (ATS), held in Dallas in May 2019.

“OHS is more common than what we think. We don't have a lot of data in the general population, but we've extrapolated that it's probably around 0.6%,” he said. “That gives you close to a million adults.”

The prevalence in the hospital, and especially the ICU, is probably much higher. A 2012 study, published in the Journal of Intensive Care Medicine, reviewed one ICU's admissions for eight months and found that 8% of the patients had a body mass index (BMI) above 40 kg/m2 and a partial pressure of carbon dioxide (PaCO2) greater than 45 mm Hg, and no explanation for the hypercapnia other than OHS.

Obesity and daytime hypercapnia are the two main criteria for OHS, said Dr. Mokhlesi, a professor of medicine and director of the Sleep Disorders Center at the University of Chicago and an author of a recent clinical practice guideline on OHS.

The patients in the ICU study had been admitted to the hospital an average of six times over two years. Three-quarters of them had been erroneously diagnosed with chronic obstructive pulmonary disease or asthma, and 86% had been treated for congestive heart failure.

Other research has found similar practice problems. An analysis of general ward patients published in the American Journal of Medicine in January 2004 found that almost a third of those with a BMI above 35 kg/m2 met the criteria for obesity hypoventilation syndrome, but most had been discharged home without therapy for the condition. “Many times it unfortunately gets misdiagnosed,” said Dr. Mokhlesi.

The consequences of misdiagnosis can be severe. “They have worse outcomes in terms of mortality, hospitalizations, ICU needs. It's not just a more severe form of obstructive sleep apnea,” he said. “OHS portends a significantly worse prognosis.”

Obstructive sleep apnea has been associated with mortality rates of around 3%. Recent data from the Pickwick Study, published by The Lancet in April 2019, found that after a median of 5.4 years, the mortality of patients with OHS was 13%, despite being adequately treated with continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV). Mortality is certainly higher in patients who are untreated or poorly adherent to positive airway pressure (PAP) therapy, Dr. Mokhlesi said.

How do you avoid having your patients become part of that statistic? Dr. Mokhlesi offered his advice on when to suspect OHS. “If you have a severely obese patient, I think it's important to think about it. If they have elevated total serum CO2 or serum bicarbonate levels, you should get concerned about that,” he said. “If they're hypoxemic on room air without any exertion, that should ring a bell. Why would that be? In these situations, a confirmatory arterial blood gas should be obtained.”

Total serum CO2 and serum bicarbonate are often used interchangeably in clinical practice despite not being exactly synonymous, Dr. Mokhlesi noted. “What we're really measuring is total serum CO2 in venous blood, but of that, 96% to 97% of it is bicarbonate in the blood.” Data reviewed by the ATS guideline panelists showed that these test results are most effective for ruling out OHS. “If the serum bicarbonate is below 27 [mmol/L], it's helpful to exclude. It's not helpful to rule in OHS if it's above 27 [mmol/L],” he said. “If serum bicarbonate level is above 27 [mmol/L], don't say, ‘Oh, you have OHS.’ You have to do a blood gas.”

Dr. Mokhlesi also cautioned that some medications, particularly loop diuretics, can increase serum bicarbonate. Transcutaneous carbon dioxide testing could also be useful for diagnosis during sleep studies, but it is not widely available. OHS is generally a diagnosis of exclusion, he noted, “So you have to rule out other causes of hypercapnia.”

Most OHS patients have concomitant obstructive sleep apnea. “In fact, 70% of them have severe sleep apnea defined by an apnea-hypoxia index above 30,” he said. However, sleep lab testing can help differentiate the two phenotypes of OHS (with or without significant obstructive sleep apnea). “Patients with OHS look different than those with classic obstructive sleep apnea patients in the sense that the hypoxemia tends to be more severe and more profound,” Dr. Mokhlesi said.

Sleep studies are a common way that OHS is diagnosed. Otherwise, patients may first present as ICU admissions for acute-on-chronic hypercapnic respiratory failure.

Unfortunately, diagnosis is only the first challenge in dealing with OHS. “What do I do if my patient is hospitalized with acute-on-chronic hypercapnic respiratory failure and I strongly suspect it's OHS, because I've ruled out other causes?” asked Dr. Mokhlesi. “There are no studies answering this question.”

Therefore, the ATS guideline panelists again did their own meta-analysis of the existing data, which consisted of observational studies with a total of more than 1,100 patients. The results showed that patients who left the hospital with a prescription for PAP had lower three-month mortality than those who didn't get PAP.

“The recommendation that we gave . . . is that these patients should probably be discharged on some form of PAP therapy, but we wrote in a way that we're very conservative because I think this area needs to be rigorously investigated,” said Dr. Mokhlesi. “Trying to discharge people and get them an empiric noninvasive positive airway pressure device can get quite complicated.”

There's also the question of what device to use. Studies have compared NIV and CPAP in ambulatory patients with stable OHS and found that both improve markers such as need for supplemental oxygen and dyspnea, he reported.

“This data suggests that at least in ambulatory patients who have severe obstructive sleep apnea and obesity hypoventilation and who are in steady state, we didn't see any difference between CPAP and NIV in outcomes that are most relevant,” Dr. Mokhlesi said.

NIV, which most commonly includes bilevel PAP and volume-targeted pressure support, should be the choice for patients who are decompensated in the hospital or who still have profound hypoxemia on CPAP, he advised. “If the patients have milder forms of sleep apnea, not severe, I think the jury is still out, we don't know, but most of us would recommend considering NIV.”

Another therapy to consider is weight loss. Unfortunately, diet and exercise are unlikely to achieve the necessary degree of change. “For patients to get resolution of OHS and real improvement, they need to lose around 25% to 30% of their actual body weight. With most intensive lifestyle interventions, people lose around 10 kg, so you know for these patients, it may not have a major impact,” said Dr. Mokhlesi.

Bariatric surgery may be a more effective means, but it has only a little evidence support as of now. “Believe it or not, there's not that much data when it comes to obesity hypoventilation syndrome and bariatric surgery,” he said. “I think more data is needed in relation to bariatric surgery in patients with OHS.”