Refractory Hypoxemia

Refractory hypoxemia is a hallmark of COVID-19. Patients can quickly develop severe breathing problems, which can profoundly impact their bodies. Refractory hypoxemia can happen. And regardless of the level of hypoxemia, restoring adequate oxygen delivery remains a top priority. 

COVID-19 is not the only thing that can lead to such a problem. For example, refractory hypoxemia can also result from acute lung injury. In addition, acute respiratory distress syndrome (ARDS) is a typical and severe type of acute lung injury. 

It can occur due to indirect (i.e., sepsis) and direct (i.e., pneumonia) pulmonary insults. It’s a typical reason for ICU admissions for hypoxemic respiratory failure and the need for mechanical ventilation. In some cases, ARDS can lead to severe refractory hypoxemia, putting the patient’s life in danger. (1)

Although the strategies for alleviating hypoxemia can vary, the goal is to maintain proper oxygenation using conventional mechanical ventilation. This is a detailed overview of what refractory hypoxemia does to the human body. 

What Is Refractory Hypoxemia?

Refractory hypoxemia is a common problem found in mechanically ventilated patients for acute respiratory failure. Severe hypoxemia can happen in 20% to 30% of patients with ARDS and often has high mortality rates. Roughly 10% to 15% of ARDS deaths occur because of refractory hypoxemia. (2)

ARDS is the reason for around 10% of ICU (intensive care unit) admissions. To better understand hypoxemia, it’s essential to take a closer look at how it affects the system. When refractory hypoxemia develops, the alveoli collapse or become flooded. (3)

The excess debris or fluid won’t let inspired gas pass through the alveolar-capillary membrane. As a result, despite the increase in inspired oxygen, the lungs still have trouble functioning properly. This results in a continuous blending of deoxygenated blood, which leads to arterial hypoxemia. 

Causes of Refractory Hypoxemia

Many health complications can be a trigger. Clinical problems that are considered the causes of refractory hypoxemia include:

● pneumonia

● significant trauma

● sepsis

● drowning & pulmonary aspiration

● massive blood transfusions

● burns & inhaling smoke

● poisoning

● radiation

● air, fat, and amniotic fluid embolism

But, the most significant trigger for this kind of health problem is serious acute lung injury from ARDS. There are physiological causes as well, such as:

● intrapulmonary right-to-left shunt lesions 

● ventilation-perfusion (V/Q) mismatch because of pulmonary embolism, atelectasis, and pulmonary edema 

● hypoventilation after machine leakage, failure, or calibration error 

● other factors such as intracardiac shunts, anemia, reduced cardiac output, etc.

How Do Nurses Recognize Refractory Hypoxemia?

The oxygenation index (OI) is an efficient tool for evaluating refractory hypoxemia. When OI is less than 40, this can indicate refractory to conventional ventilation, which means rescue therapy is necessary to improve oxygenation. 

Shortness of breath (dyspnea) is a predominant symptom. It gets worse in the next couple of hours and days. The lungs are getting stiff, and the alveoli sac has collapsed; oxygen can’t flow through and down to the sac to go into that capillary and replenish the body. 

In the very early stages, for the body to try and compensate for the low oxygen, patients experience increased respiratory rate and low O2 levels. So oxygen can’t get in, but carbon dioxide can still cross over.

As the patient progresses through the different phases, continual development makes it even harder for CO2 to cross over. As a result, the patient’s respiratory muscles are worn out. Then, the patient can enter into respiratory acidosis. They are in need of mechanical ventilation. (4)

Therefore, refractory hypoxemia symptoms can appear, such as cold extremities, confusion, reduced urine output, and altered mental status. Nurses recognize the problem with careful physical examination and a detailed history of the patient’s health state. 

Physical examination reveals low blood oxygen saturation in the system, abnormally rapid breathing, irregular heart rhythm, and peripheral or central cyanosis. Cyanosis occurs when the fingertips, hands, or feet turn blue due to the lack of oxygen-rich blood. 

At times, a lung exam could be necessary. This can be used to reveal the plummeting air entry and bilateral rales. Next, experts may suggest a focused cardiac exam. But, this can vary from person to person. Overall, the shock of hypoxemia is easy to recognize. A trained expert can identify the symptoms and act accordingly to try and get the patient’s breathing back on track. 

How Is Refractory Hypoxemia Managed?

Many treatment modalities can be used to manage this problem. Non-ventilatory and ventilatory strategies have been incorporated as “rescue” therapies in patients with refractory hypoxemia. Mechanical ventilation is the cornerstone of managing refractory hypoxemia.

If the problem persists despite the use of lung-protective ventilation, then doctors will use additional therapies to curb the issue. Management of refractory hypoxemia in ARDS can include: (5)

● prone positioning

● recruitment maneuvers

● extracorporeal membrane oxygenation

● high-frequency oscillatory ventilation 

● inhaled vasodilators

● neuromuscular blockade (NMB)

All rescue therapies currently being used improve oxygenation in patients. According to recent research, none show a specific superiority that would topple the rest. As a result, experts use the best viable opportunity to aid their patients. (6)

Prone ventilation and NMB are key management strategies that curb mortality rates. But, refractory hypoxemia in COVID is a lot more complex than that. It comes with high mortality rates and can encompass an advanced process of ARDS.

A COVID-19 infection attacks the lungs in an unprecedented way. Some viruses that affect the throat, nose, and upper airways, like the common cold, typically infect a smaller section of the lung. However, COVID-19 packs a vicious double punch, infecting the whole respiratory system, including the alveoli (small air sacs). There aren’t that many respiratory pathogens that go as far as the upper and lower respiratory regions. And the coronavirus is one of them. As a result, it is making people sicker and low on oxygen. 

As a result, respiratory management will vary based on the severity of the health issue. Supplemental oxygen therapy is necessary for patients with silent hypoxemia (mild to moderate). Given that SpO2 (oxygen saturation) stays over 80%. 

In those with symptomatic moderate/severe hypoxemia, using supplemental oxygen therapy through HFNCs or reservoir masks may help. But, more research is necessary to confirm the outcome and overall improvement. 

The decision to intubate and use mechanical ventilation is based on multiple parameters. Refractory Hypoxemia mechanical ventilation is used when there is a severe problem with pulmonary opacities. Intubation can save a person’s life, and it’s mainly used when serious complications occur. (7)

That said, prone positioning and some rescue therapies require skilled healthcare practitioners and respiratory therapists. Managing the problem is a labor-intensive process that comes with numerous technical challenges. 


Refractory hypoxemia is a severe breathing problem that can happen in patients with mechanical ventilation and acute respiratory failure. ARDS is the most well-known cause. But, COVID-19 can also lead to such a complication. Skilled healthcare practitioners can manage the issue. However, the mortality rates are high.