During normal respiration in an individual with healthy lungs, the body identifies the need to stimulate increased respirations by monitoring changes in the carbon dioxide (CO2) levels in the peripheral chemoreceptors. These changes are very minor and occur very early if the person is experiencing any hypoxia.
The hypoxic drive however, is a late homeostatic system designed to increase respiration rate and depth (tidal volume) when the body’s arterial oxygen levels (SaO2) decreases significantly. This is why patients who are somewhat dependent on an hypoxic drive to breath normally only saturate at around 90-92% oxygenation.
The hypoxic drive only accounts for a very minimal amount of the body’s desire to breath (approximately 10-15%) and generally, this is so low, that most people would literally become unconscious before their body’s hypoxic drive will trigger the need to increase tidal volume and rate of ventilation.
However, in patients who have chronic airway limitations (also known as chronic obstructive pulmonary disease), their body is continuously surviving on a much higher than normal blood CO2 level, and the body eventually “gives up” attempting to correct this diversion from normal homeostatic CO2 parameters within the peripheral chemoreceptors.
It should be noted however, that currently theories regarding the need for the hypoxic drive in patients who have had prollonged periods of high CO2, such as those with chronic respiratory diseases/ or disorders, under the headings of COPD and CAL are currently under review and there is some discourse on the topic amongst medical professionals and scientists alike.
EDUCATION/TRAINING
Busting Top Trauma MythsBY KEVIN T. COLLOPY, BA, FP-C, CCEMT-P, NREMT-P, WEMT, SEAN M. KIVLEHAN, MD, MPH, NREMT-P,SCOTT R. SNYDER, BS, NREMT-P ON MAR 2, 2015In 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 healthcentral.com.
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 CO2exhaled. 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.
Historical 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.
By Rebecca Mayer Knutsen: December 7, 2015
Original/source article: //bit.ly/1ZMS46E
- Access through your institution
Volume 35, Issue 4, July–August 2016, Pages 210-211
//doi.org/10.1016/j.amj.2016.03.006Get rights and content
View full text
Clinically interesting and yet not well understood, hypoxic-drive theory holds that people who chronically retain carbon dioxide lose their hypercarbic drive to breathe.
By William A. French, MA, RRT
One of the most clinically interesting and least understood theories in respiratory medicine is the hypoxic-drive theory. This holds that people who chronically retain carbon dioxide lose their hypercarbic drive to breathe. Thus, according to the theory, since the brain no longer responds to hypercarbia, the only remaining autonomic drive is hypoxemia. It then follows that, should patients in this condition be given enough supplemental oxygen to drive their PaO2 levels much higher than 60 mm Hg, they will also lose their hypoxemic drive to breathe.
Periodically, this theory is challenged, with the challenges based primarily on clinical observations that patients who exhibit the typical arterial blood gas (ABG) pattern suggestive of carbon dioxide retention do not simply stop breathing when their PaO2 levels climb.
SUBSCRIBE TO DAILY RT NEWS
A recent challenge1 approaches the question primarily from the standpoint of gas transport and the Haldane effect, as well as clinical observation. The neurophysiology of ventilatory control itself, however, can account for the theory as well as seemingly contradictory clinical observations.
Central Control of Ventilation
Neurological control of ventilation begins in the medulla, with the central controller. As part of the central nervous system, the central controller is isolated from the rest of the body by the cerebrospinal fluid (CSF). Although the exact mechanism involved is not fully understood,2 the central controller is primarily responsive to changes in the pH of CSF. At the same time, the blood/brain barrier is selectively permeable to carbon dioxide. Thus, when the carbon dioxide content of the blood increases, more carbon dioxide diffuses into the CSF. The pH of the CSF decreases due to the hydration of the carbon dioxide and the subsequent creation and release of hydrogen ions.
If the increase in carbon dioxide becomes chronic (lasts more than 24 hours), bicarbonate will begin to diffuse into the CSF and restore the CSF pH to its baseline level (7.326). At this point, the medulla is receiving a signal that the blood PCO2 is normal. Whether this restoration of the CSF pH at a higher blood PCO2 blunts the sensitivity of the central controller, or merely shifts the baseline for response upward, is not clear.
Although the central controller does not respond directly to hypoxia, it is known that medullary hypoxia can trigger respiratory depression. Likewise, it is known that high concentrations of carbon dioxide can cause narcosis; however, the PaCO2 must generally reach a level above 90 mm Hg for this to occur.
Peripheral Chemoreceptors
In addition to the central chemoreceptors in the medulla, the body also has peripheral chemoreceptors.2 Two are located near the bifurcation of the common carotid artery. Another is located in the ascending aorta. The carotid chemoreceptors are most active in ventilatory control. Each is a complex mass of tissue having a volume of about 6 mm. The principal cell type is the glomus, which can secrete dopamine as well as (possibly) noradrenaline, serotonin, acetylcholine, and polypeptides. The carotid bodies are innervated by both afferent and efferent branches of the glossopharyngeal (or ninth cranial) nerve.
The primary function of the carotid bodies is to sense and respond to changes in Pao2 levels. In the presence of normal PaCO2 and pH, the response of the carotid body begins a dramatic increase when the Pao2 decreases to less than 60 mm Hg. A number of factors can, however, shift the sensitivity (and, thus, the point of maximal response) of the carotid body. Among these are pH (in particular, acidemia), PaCO2 (principally hypercarbia), hypoperfusion, and increased body temperature. For example, if a person experiences a sudden metabolic acidosis (due to lactic or ketonic acid release), the sensitivity of the peripheral chemoreceptors would shift to a higher hypoxemic threshold, thus stimulating an increase in ventilation at higher Pao2 levels. The same shift would occur at increased PaCO2 levels, although whether there is an upper limit to this response is unclear.
Clinical Implications
It should be clear that patients who experience chronic hypercapnia will eventually readjust the pH of their CSF. Whether this blunts the central chemoreceptor response to pH change or simply shifts the CSF’s carbon dioxide baseline is unclear. Thus, patients who have been labeled carbon dioxide retainers or hypoxic-drive breathers may still be operating with some amount of hypercarbic drive.
Likewise, it should be clear that, under normal circumstances, the peripheral chemoreceptors become most active when the PaO2 drops to less than 60 mm Hg. Patients who have chronic hypercapnia are not in normal circumstances, however, and it may be that their peripheral chemoreceptors become most active at higher PaO2 levels.
From clinical observations, it is apparent that patients who exhibit the ABG pattern of compensated respiratory acidosis will not suddenly become apneic once their PaO2 rises to more than 60 mm Hg. Thus, over-oxygenating a patient under these conditions carries little risk.
A particular pattern, however, has been observed many times; its components are a pH of 7.29, a PaCO2 of 76 mm Hg, a PaO2 of 84 mm Hg, a bicarbonate level of 36 mEq, and a fraction of inspired oxygen (FiO2) of 0.3. Clinically, patients exhibiting this pattern often can be aroused, but are sleepy; they are also observed to be breathing more shallowly than normal. Given these conditions, simply lowering the FiO2 usually results in an increase in ventilation and a subsequent decrease in PaCO2.
Whether this phenomenon is caused by a blunting of the ventilatory drive or some other mechanism is not known, but this pattern is usually observed in patients who are relaxed and unstimulated. Certainly, most respiratory clinicians have observed that similar patients who experience transient increases in PaO2 (for example, through aerosol treatments powered by oxygen or through the use of an FiO2 of 1.0 during pulmonary function testing) do not demonstrate a similar decrease in ventilatory drive or level of consciousness.
In addition, the foregoing addresses only the role of the chemoreceptors in driving ventilation. In order to complete the picture, other potential ventilatory stimuli such as joint and muscle receptors and exogenous chemicals (for example, theophylline) should also be considered.
Case Report
A 63-year-old male was admitted to a hospital in Cleveland, with an acute exacerbation of chronic obstructive pulmonary disease (COPD). His admitting ABG levels (based on sampling while the patient breathed room air) were: pH, 7.41; PaCO2, 66 mm Hg; bicarbonate, 40 mEq; and PaO2, 49 mm Hg. His oxygen saturation level was 84%.
After admission and review by the attending physician, the patient began to use supplemental oxygen, delivered via nasal cannula, at a flow rate of 4 LPM. Approximately 8 hours later, an RCP drew arterial blood for routine ABG analysis. The results showed a pH of 7.36, a PaCO2 of 77 mm Hg, a bicarbonate level of 41 mEq, and a PaO2 of 74 mm Hg. The patient’s oxygen saturation level was 94%.
Clinically, the patient was reported to be alert, but drowsy. He was breathing shallowly, but was in no respiratory distress. Subsequently, the RCP recommended lowering the flow from the nasal cannula to 2 LPM, which was the flow rate that the patient had been using at home. The patient’s ABG levels stabilized, and he became less drowsy.
Summary
The neurological drive to breathe is complicated and is not fully understood. From a clinical standpoint, the injudicious and uncontrolled administration of supplemental oxygen to patients with compensated respiratory acidosis, although probably less risky than implied in the clinical literature, is not a good idea. The deliberate under-oxygenation of a patient with compensated respiratory acidosis (or a diagnosis of COPD) because of fear of hypoventilation or apnea, however, creates the greater risk of inducing prolonged tissue hypoxia.
RT
William A. French, MA, RRT, is clinical director and assistant professor, Respiratory Therapy Program, Lakeland Community College, Kirtland, Ohio.
References
- Whitnack J. Why the hypoxic drive theory sucks wind. Available at: //www.jeffsplace.com. Accessed: December 1, 1999.
- Nunn JF. Applied Respiratory Physiology. 4th ed. Oxford, UK: Butterworth-Heinemann; 1993.