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Oxygen and COPD

Debunking the hypoxic drive theory.

In patients with chronic obstructive pulmonary disorder (COPD), inflammatory changes impact their ability to breathe properly. Patients will eventually retain carbon dioxide (CO2) as their efforts to maintain normal CO2 levels proves difficult. Experts have long debated whether chronically elevated carbon dioxide levels affect how a patient handles oxygen. As a result, a theory developed that administering oxygen obliterated the drive to breathe.

The problem with the Hypoxic Drive Theory is that it's a myth concocted on incomplete evidence and often elicits a controversial response, according to John Bottrell, RT, Spectrum Health Ludington Hospital, and COPD/asthma expert for

For hypoxemic patients with COPD, most medical experts now recommend administering the lowest amount of oxygen needed to maintain SpO2 of 88% to 92%, according to Bottrell.

The Controversy of Hypoxic Drive Theory
In hypoxic drive, Bottrell told ADVANCE, the peripheral chemoreceptors located at the bifurcations of the aortic arteries and the aortic arch monitor partial pressure of arterial oxygen (PaO2). This drive only becomes active when the PaO2 is less than 60 mmHg. "This hypoxic response is far slower than signals sent by central chemoreceptors, and therefore the hypoxic drive has only a minor role in breathing," he explained.

When patients with COPD need oxygen, healthcare practitioners should give it to them because doing otherwise will further compromise their health, Bottrell observed. "If the patient goes into respiratory failure, then he should be treated with either noninvasive ventilation or mechanical ventilation," he shared.

Spectrum Health Ludington Hospital tests include arterial blood gas (ABG) collection, pulse oximeter and end tidal CO2 monitor. End tidal CO2 monitor is a noninvasive device that can be connected to special nasal cannulas or endotracheal tubes. The test determines the ETCO2, which is an estimation of the amount of CO2 exhaled. This percentage can be used to estimate PaCO2. In a person with healthy lungs, the EtCO2 is about 2 to 5 mmHg less than PaCO2.

Oxygen and COPDHistorical Perspective on Hypoxic Drive Theory
Oxygen was first used for patients with COPD in the late 1940s and 1950s. Around that time, experts observed that some patients became lethargic or lapsed into a coma after receiving high levels of oxygen, Bottrell told ADVANCE. Initial studies showed a decrease in ventilation in 26 of 35 patients with COPD given oxygen therapy, with a rise in CO2 and a fall in pH. A further study showed that stopping and starting oxygen therapy led to a fall and rise in CO2 respectively.

The concern became so great that a study was performed in the 1950s that ultimately led Dr. EJM Campbell to give a lecture to pulmonologists in 1960 about the dangers of giving too much oxygen to COPD patients. "It was this lecture that forever linked hypoxic drive with COPD, and gave birth to the hypoxic drive theory," explained Bottrell.

"The hypoxic drive theory states that some patients with COPD develop chronically elevated arterial CO2 levels, and as a result, their hypercapnic drive becomes blunted, causing them to use their hypoxic drive to breathe instead," Bottrell said. "Therefore, giving high amounts of oxygen to these patients may blunt the hypoxic drive as well, thus completely blunting their drive to breathe."

This occurrence may cause PaCO2 levels to rise to critical levels, resulting in narcosis and possible death. For this reason, COPD patients with suspected CO2 retention are limited to 2 to 3 lpm by nasal cannula, or 40% by venturi mask.  

According to Bottrell, the study cited by Campbell included only four patients with COPD, and later studies failed to validate this theory. "Yet it has continued to be a gold standard theory when dealing with COPD patients," he observed.

"Under the guise of this theory, many patients who desperately need higher levels of supplemental oxygen to survive are deprived of it," Bottrell relayed. "Plus, as many respiratory therapists, nurses, and physicians have observed, when these patients are given the oxygen they need, rarely does this lead to complications."

Bottrell believes patients might go into respiratory failure regardless of how much oxygen they receive. "And while higher levels of oxygen may cause CO2 to rise, it's not due to oxygen blunting their hypoxic drive, which the hypoxic drive theory postulates, it's due to either the Haldane effect or V/Q mismatching," he said.  

The Haldane effect was postulated by John Haldane, a pioneer in oxygen therapy. He proved that the deoxygenation of arterial blood increases its ability to carry carbon dioxide. "In other words, as fewer oxygen molecules are attaching to hemoglobin, more CO2 are attaching to hemoglobin," Bottrell said.  

Oxygen is more soluble in water, and therefore, has a higher affinity for hemoglobin. "So if you increase oxygen in the blood, CO2 molecules are forced off hemoglobin and oxygen takes its place," Bottrell shared. "This causes an increase in PaCO2."

Out of respect for this theory, according to Bottrell, COPD patients should be maintained on the lowest level of oxygen required to maintain an oxygen saturation between 88% to 92%.

According to Bottrell, modern evidence suggests that the hypercapnic drive is never completely blunted, and therefore even COPD patients with chronically elevated PaCO2 will not stop breathing in the presence of higher oxygen levels. "There is such a thing as the hypoxic drive, but the hypoxic drive theory is a myth," he said.

Rebecca Mayer Knutsen is on staff at ADVANCE.

This article was one of our most popular of 2015. See the full list here.

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Been in the field for 36+ years now and have seen/treated Hypoxic Drive complications a few times personally. I agreed that it doesn't happen to everyone but for those that it does you have to know how to treat them

Rick K,  RCP,  ACUTE CARE HOSPITALJune 08, 2016

during my NMD training I took a course in statistical analysis and examined the validity of studies. It is truly amazing how many poor studies made public are believed by the less educated. Clinical observations are paramount. Anyone who don't listen to the pearls of wisdom from a seasoned clinician is a fool and another name that as a professional I cannot mention here.

Addison Taylor,  RRT NMD,  HSJanuary 31, 2016
Tucson, AZ

It would be a mistake to completely dismiss the hypoxic drive phenomenon as nothing but a myth. The problem is that it always was based on the wrong diagnosis. Back in the day, it was understood that there were two subgroups for COPD: Emphysema and Chronic Bronchitis. These were described according to their appearances (pink puffer/blue bloater). But I will skip ahead of a long argument and go straight to the punchline. The emphysematous patient never had a problem with hypoxic drive. It was the chronic bronchitic all along. Furthermore, they never had chronic bronchitis either! It was always obesity hypoventilation syndrome (before it was understood or had a name). Once OSA became a growth industry, the diagnosis of chronic bronchitis virtually disappeared overnight. The hypoxic drive phenomenon was real but exceptionally rare. Nowadays, it is unheard of and the result is that newer RT's think it never existed to begin with. Mysterious etiology notwithstanding, the phenomenon was real, witnessed, documented, and institutionalized - under the completely wrong diagnosis.

Fredric Ashton,  RRTDecember 11, 2015
Salt Lake City, UT

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