Hypoxia: Critical but Often Poorly Understood Concepts

Arterial hypoxemia almost always points to either a reduction of the inspired oxygen tension or to a lung problem. When troubleshooting a hypoxemic patient, it sometimes helps to investigate the problem by breaking it down in an organized and stepwise fashion:

1. Hardware and access issues: these are more or less obvious plumbing problems which can generally be fixed with straightforward mechanical means such as endotracheal intubation, repositioning of the endotracheal tube, or cranking up the inspired oxygen pressure (FiO₂). Hardware issues are, in a sense, nonbiological: you need to get oxygen to flow from point “A,” which is either the atmosphere or an oxygen tank, to Point “B,” which is the alveolus. Frequently, these airway management issues take precedence over all other aspects of patient management.
2. Shunting: shunting occurs when deoxygenated blood from the pulmonary circulation enters the systemic circulation without first abutting against functioning alveolocapillary membranes.  A chest radiograph is usually the first test done here because it is fast and cheap, and because it reveals many of the more common and fixable causes of shunting such as pulmonary edema, pneumonia, and atelectasis. You can fix a shunt by increasing the PEEP (positive end expiratory pressure), and by getting rid of whatever substance or condition is causing the shunt. So basically, to fix shunting, you will give diuretics, antibiotics, good pulmonary hygiene–whatever the case may be.
3. Pulmonary embolism. If the hardware is in place and functioning appropriately and the chest radiograph is clear, then a pulmonary embolism should be the next thing you think about in a hypoxemic patient. The test of choice here is, of course, a CT angiogram of the chest. In addition to picking up pulmonary emboli, a CT angiogram of the chest has the added benefit of being able to pick up other more subtle forms of shunting that cannot be visualized well on a chest radiograph. Specifically, the chest CT will be able to pick up various forms interstitial lung disease, arteriovenous malformations, and milder forms of pulmonary edema. (Incidentally, therefore, when ordering a PE study, don’t write, “rule out PE.” Rather, write “hypoxemia.” That way, you might get a lot more useful information from your radiologist.)
4. Arterial hypercarbia: a high PCO₂, or partial pressure of carbon dioxide, will “crowd out” oxygen and cause an automatic drop in PaO₂, the partial pressure of oxygen in the arterial circulation. Why does this happen? This is called Dalton’s law of Partials Pressures. If you remember from you physics and biochemistry days, Dalton’s law states that the sum of all partial pressures of gasses in a closed system is constant. So when the PCO₂ goes up, the PaO₂ will go down, even in the absence of an independent cause for the hypoxemia. If you are inclined to prove the diagnosis of arterial hypercarbia, the best way to do so is with an arterial blood gas. You order an ABG, and you look for two things: (1) acute acidosis and (2) a very high PCO₂. If both of these are present in a patient with a reasonably high pretest probability, then the diagnosis is almost surely acute hypercarbic respiratory failure. You fix arterial hypercarbia with improving ventilation, for example, with endotracheal intubation, or with BiPAP.

The above approach will enable you to figure out, in almost every instance, why your patients are hypoxemic, and will help you initiate the best tests and treatments for them.

 

The SaO₂

While the PaO₂ is the most accurate test and the reference standard for hypoxemia, it is a relatively invasive, painful and time-consuming test because it requires skilled puncture of an artery.  Instead, the percent oxygen saturation of hemoglobin  (SaO₂) can serve as good surrogate test because it can be determined noninvasively with a pulse oximeter.

There are, however, situations where a patient can have a falsely low SaO₂, despite a normal PaO₂. These include:

• Shocky patients with poor peripheral circulation
• The presence of barriers (e.g., nail polish)
• Tricuspid regurgitation, and
• Mechanical failure of the pulse oximeter device itself.

Conversely, a falsely high SaO₂ is also possible in patients with carbon monoxide poisoning and methemoglobinemia (see below).

Anemic Hypoxia

The critical concept here is that when the PaO₂ is well within normal limits, small drops in PaO₂ will cause only tiny drops in the blood’s total oxygen content. This is due to hemoglobin’s incredible oxygen-carrying capacity and the sigmoidal shape of the oxygen-hemoglobin dissociation curve.  A transfusion of packed red blood cells will add oxygen carrying capacity to an anemic patient and will improve total oxygen content, but it will not improve a poor PaO₂. Again, a low PaO₂ points squarely to a reduction of the inspired oxygen tension (FiO₂) or to a lung problem. The PaO₂ needs to be fixed separately but concomitantly.

Circulatory Hypoxia

Poor systemic or local circulation. The PaO₂ and hemoglobin may be normal, but oxygen is still not getting where it needs to go because of poor cardiac output or vascular supply.

Toxic Hypoxia

The most important causes of toxic hypoxia are carbon monoxide, methemoglobin, and cyanide. Carbon monoxide binds to hemoglobin, while methemoglobin is a hemoglobin derivative. They both prevent normal oxygen delivery to cells and cause a falsely-normal pulse oximeter reading. Therefore, if carbon monoxide poisoning or methemoglobinemia are suspected, ditch your regular pulse oximeter and get an arterial blood gas with cooximetry or perform a pulse cooximetry. A cooximeter will measure the relative concentrations of various forms of hemoglobin, including oxyhemoglobin, carboxyhemoglobin, and methemoglobin.

Cyanide poisoning is called histotoxic hypoxia because cyanide does not bind hemoglobin to a significant degree. Rather, it poisons tissues (mitochondria) directly and thereby prevents them from utilizing oxygen. Thus, in patients with cyanide poisoning, oxygen will float right past the capillaries and enters the venous circulation, instead of getting dropped off at the capillary level for cellular respiration. Cells are then forced to undergo anaerobic respiration and produce lactic acid in the process.

As with carbon monoxide poisoning and methemoglobinemia, the pulse oximeter will often be normal in cyanide poisoning. However, unlike patients with carbon monoxide poisoning and methemoglobinemia, patients with cyanide poisoning will frequently have a normal cooximetry reading as well. The key to clinching the diagnosis is to look for:

• Hemodynamic instability
• Profound, persistent, anion gap metabolic acidosis (from lactic acid), and
• Red (hyperoxic) venous blood, either on venipuncture or on funduscopic examination.

Summary Table

 

Resources

• Fishman, Alfred, Fishman’s Pulmonary Diseases and Disorders (2008)
• Terry Des Jardins, Clinical Manifestations & Assessment of Respiratory Disease, 6e (2010)