A 55-year-old woman with diabetes, hypertension, obesity (BMI 45 kg/m2), and obesity hypoventilation/obstructive sleep apnea (OHS/OSA) presented to an Emergency Department with dyspnea and somnolence of 2 days duration. Arterial blood, sampled while she breathed 50% oxygen via face mask at a rate of 22 breaths per minute, revealed a pH 7.26; PCO2 80 mmHg; PO2 150 mmHg ; [HCO3] 35mEq/l; BEecf 8.3 mEq/l. She was intubated for hypercapnic respiratory failure and admitted to the intensive care unit.
Questions regarding the pathophysiology and hospital-based management of obesity hypoventilation syndrome addressed by Drs. Roberta Goldring, Kenneth Berger and Beno Oppenheimer at New York University School of Medicine. Last blog, these experts reviewed their research suggesting the mechanism for chronic hypercapnia with OHS/OSA. This installment they explore implications of their research for patient care.
- Might this patient have benefitted from a trial of breathing ambient air or a lower concentration of supplemental oxygen before a decision was made to intubate her?
The initial FiO2 may have been too high because inhaled oxygen can exacerbate a pre-existing hypercapnia or even produce hypercapnia due to a combination of reduction in hypoxic drive, alteration in V/Q relationships and/or offloading of CO2 from hemoglobin (i.e. Haldane effect). Deciding how far to reduce the FiO2 requires consideration. While reduction to room air would eliminate the effect of supplemental oxygen on PaCO2, in this patient it could be detrimental with respect to blood oxygenation. If the PaCO2 remains at 80 mmHg, indicating that the hypercapnia was not exacerbated by the oxygen therapy, an obligate hypoxemia would ensue with a maximal PaO2 = 50 mmHg (assuming a zero A-a gradient which is unlikely in this patient with acute cardio-respiratory failure / OHS.) Therefore, a practical approach would be to gradually lower the FiO2 while monitoring the patient with a goal of producing an oxygen saturation ~90%. This target would minimize the contribution of oxygen administration to hypercapnia while maintained adequate delivery of oxygen to the tissues.
- Do opiates and tranquilizers exacerbate chronic daytime hypercapnia in OHS-OSA? And for acute-on-chronic hypercapnia, when should we consider a trial of naloxone or flumazenil?
Yes! These medications blunt respiratory drive even in the absence of somnolence. The effects are manifest by an increase in nocturnal as well as the daytime PaCO2.
Naloxone and/or flumazenil can be used diagnostically if there is a history of relevant medication and/or drug use to assess the contribution of these agents to the hypercapnia. The agents would not reverse the underlying OHS and the chronic component of the hypercapnia and, therefore, would probably not play a role in the chronic management of these patients. (Caution in patients habituated to benzodiazepines where flumazenil can cause seizures).
- Loop diuretics are often used both chronically and acutely in these patients. Does the metabolic alkalosis promoted by these agents exacerbate hypercapnia?
Loop diuretics may exacerbate hypercapnia by further elevating bicarbonate levels (metabolic alkalosis) with associated blunting of respiratory drive as described above. The development of metabolic alkalosis can be mitigated by adequate chloride repletion. Optimally, chloride supplements should be administered simultaneously with the loop diuretic to prevent development of the metabolic alkalosis.
- What is the role of acetazolamide in correcting the acid-base derangement of chronic and acute-on-chronic hypercapnia in OHS-OSA?
Use with caution. While it would effectively reduce the bicarbonate level and increase respiratory drive, it may not reduce the PaCO2 unless the patient is capable of increasing minute (and alveolar) ventilation. Thus, a metabolic acidosis would occur simultaneous with the pre-existing respiratory acidosis producing worsening acidemia. Moreover, even if ventilation increases during wakefulness, acute episodes of acidemia will occur during sleep if the sleep disordered breathing is not adequately treated.
It should be noted that appropriate treatment of the sleep disordered breathing (CPAP for OSA or Bilevel for central hypoventilation) will result in normalization of both acute and chronic hypercapnia. In some patients, persistently elevated bicarbonate levels will be noted (i.e. post hypercapnic alkalosis). Even in this circumstance, acetozolamide would not be indicated because reduction of the bicarbonate level will not persist following discontinuation of the acetazolamide. Effective therapy of the post hypercapnic alkalosis is best accomplished by chloride repletion.
Drs. Goldring, Berger, and Oppenheimer comprise the André Cournand Pulmonary Physiology Laboratory at Bellevue Hospital. Their interests center on study of normal physiology and pathophysiologic derangements in numerous diseases as a basis to guide clinical diagnosis and determine optimal management.