Respiratory failure: diagnosis

Respiratory failure is a condition in which the respiratory system fails to provide adequate gas exchange, meaning the body is not receiving enough oxygen, is not removing carbon dioxide, or both. In clinical diagnosis, it is important to distinguish between "shortness of breath" as a subjective symptom and "respiratory failure" as an objective disorder confirmed by measurements. [1]

In practical work, two basic biological benchmarks are most often used: hypoxemia usually corresponds to a partial pressure of oxygen in arterial blood below 60 mmHg, and hypercapnia to a partial pressure of carbon dioxide above 45 mmHg. These thresholds do not replace clinical judgment, but they help standardize decisions when it comes to respiratory failure, rather than “just severe shortness of breath.” [2]

The diagnosis should answer three questions. 1) How severe is the condition and is there a risk of respiratory arrest? 2) What is the underlying cause: oxygen deficiency, carbon dioxide retention, or both? 3) What is the underlying cause: lung parenchyma, bronchi, heart and blood vessels, central nervous system, respiratory muscles, or metabolic factors. [3]

The main mistake in managing such patients is starting with "pretty tests" instead of stabilization and basic assessment. Current guidelines for the initial assessment of respiratory distress in the emergency department emphasize the priority of clinical signs of severity, respiratory rate, and oxygen saturation, followed by selective studies, which actually change the approach. [4]

Table 1. Types of respiratory failure and basic criteria used in diagnosis

Type	Leading violation	What is most often seen in blood gases?	Frequent mechanisms
Hypoxemic	Lack of oxygen	PaO2 below 60 mmHg, carbon dioxide may be normal or decreased	Pneumonia, pulmonary edema, atelectasis, acute respiratory distress syndrome
Hypercapnic	Carbon dioxide retention	PaCO2 above 45 mmHg, often with acidosis in the acute process	Exacerbation of chronic obstructive pulmonary disease, respiratory depression, weakness of the respiratory muscles
Mixed	Both mechanisms	Both oxygen and carbon dioxide are low.	Severe exacerbation of chronic obstructive pulmonary disease, severe pneumonia due to hypoventilation

Source for thresholds and types: NCBI Bookshelf. [5]

Step 1: Initial examination and assessment of severity

The initial assessment begins with clinical signs, as respiratory failure can progress faster than testing can be performed. Airway patency, verbal ability, level of consciousness, the severity of intercostal retractions, and the involvement of accessory muscles are assessed immediately. [6]

Respiratory rate is one of the strongest "danger signals." Guidelines for the initial assessment of respiratory distress indicate that tachypnea greater than 25 breaths per minute and signs of respiratory fatigue (thoracoabdominal asynchrony, inability to speak in full sentences) should be actively identified during initial contact and triage. [7]

Signs of decompensation are assessed separately: severe sweating, peripheral cyanosis, confusion, bradycardia due to hypoxia, and increasing drowsiness. An important clinical detail: upper airway obstruction can produce loud respiratory sounds and heavy work of breathing even before overt hypoxemia occurs, so "normal oxygen saturation at the time of examination" does not always rule out a threat. [8]

The level of monitoring is determined based on severity. In severe cases, continuous monitoring of vital signs is required, including respiratory rate, oxygen saturation, blood pressure, and level of consciousness. Guidelines specifically emphasize the need to measure respiratory rate over at least 30 seconds, not just by eye, as errors in respiratory rate measurement are common and lead to risk underestimation. [9]

Table 2. Signs of severity that require accelerated diagnosis and increased monitoring

Sign	Why is it important?	What does it usually mean?
Respiratory rate greater than 25 per minute	High risk marker for deterioration	Increasing respiratory load
Inability to speak in complete sentences	Sign of severe respiratory distress	Lack of ventilation and fatigue
Thoracoabdominal asynchrony	A sign of fatigue of the respiratory muscles	Risk of respiratory exhaustion
Confusion, drowsiness	Hypercapnia or hypoxia is possible	Risk of respiratory depression
Peripheral cyanosis, profuse sweating	Markers of severe hypoxia and stress	Risk of decompensation

Source: Guidelines for the initial assessment of respiratory distress in the emergency department. [10]

Step 2: Assess oxygenation at the bedside

Pulse oximetry is the primary rapid tool for assessing oxygenation because it is noninvasive and provides a continuous trend. Guidelines for the initial assessment of respiratory distress note that peripheral blood oxygen saturation is often sufficient for an initial assessment of oxygen status and the need for further intervention. [11]

There is a practical guideline useful for diagnosis: in a patient breathing room air, a saturation above 96% makes it unlikely that PaO2 will fall below 60 mmHg. For patients with chronic obstructive pulmonary disease, a saturation above 92% also makes significant hypoxemia unlikely. These thresholds help determine when arterial blood sampling for oxygen alone can be avoided if the clinical picture is stable. [12]

It's important to interpret oxygen saturation in conjunction with the patient's oxygen status and the risk of hypercapnia. Emergency oxygen guidelines recommend aiming for a saturation of 94%-98% for most acutely ill patients and 88%-92% for those at risk of hypercapnic respiratory failure. This is diagnostically useful because "too much oxygen" can sometimes mask deteriorating ventilation in vulnerable patients. [13]

Pulse oximetry has limitations that are important to understand, particularly in diagnostics. Saturation may be falsely elevated in carbon monoxide poisoning and not reflect actual oxygen delivery to tissues. In methemoglobinemia, a characteristic gap between pulse oximetry saturation and co-oximetry saturation may occur. Perfusion, motion artifacts, and skin pigmentation also affect accuracy, as highlighted by modern reviews and recommendations on oxygen therapy. [14]

Table 3. How to use pulse oximetry in diagnostics and when it cannot be trusted

Situation	What does saturation look like?	Why is it dangerous?	Which confirms the problem
Carbon monoxide poisoning	It may be "normal"	Does not reflect true tissue hypoxia	Co-oximetry and clinical context
Methemoglobinemia	There may be a gap between dimensions	Error in oxygenation assessment	Co-oximetry
Shock, cold extremities	Unstable or low values	Poor signal due to low perfusion	Arterial blood gases, clinical
Strong motion artifacts	Jumping numbers	Incorrect trend assessment	Repeat measurement, different sensor
Severe respiratory distress with "good" oxygen saturation	Saturation may be acceptable	There may be a ventilation problem or obstruction.	Capnography, blood gases, examination

Source: Reviews of the limitations of pulse oximetry and clinical commentary on the 'saturation gap'.[15]

Step 3: Assess ventilation and acid-base balance

If the key question is "is ventilation adequate?", pulse oximetry is insufficient. Blood gas analysis is used to assess carbon dioxide and acid-base balance, as it reveals hypercapnia and respiratory acidosis, which can develop during exacerbations of chronic obstructive pulmonary disease, respiratory depression, respiratory muscle weakness, and severe respiratory fatigue. [16]

Current guidelines suggest a more pragmatic approach to venous and arterial testing. Venous blood gas is not suitable for assessing the degree of hypoxemia, but it can help rule out severe hypercapnia: a normal venous partial pressure of carbon dioxide below 45 mmHg makes an arterial value above 50 mmHg unlikely. However, arterial analysis remains the "standard" in complex situations. [17]

It is important that arterial blood gas analysis should not be performed "automatically" for everyone. Guidelines for the initial assessment of respiratory distress note that arterial sampling should be considered selectively: when oxygen saturation is unreliable or unmeasured, when hypercapnia and respiratory acidosis need to be confirmed and quantified, or when the result genuinely influences decisions about respiratory support and routing. [18]

Blood gas interpretation must be standardized, otherwise it's easy to misinterpret mixed disorders. A stepwise approach is often used for this: assessing blood acidity, determining the respiratory or metabolic nature of the disorder, checking compensation, and then clinically linking it to the cause. The American Thoracic Society publishes a training algorithm for blood gas interpretation that is easily adapted for clinical practice. [19]

Table 4. When arterial blood gases are needed and what exactly is looked for in them

Clinical question	What is enough to do first?	When is an arterial blood test needed?
Is there significant hypoxemia?	Pulse oximetry and clinic	If saturation is unreliable, if an accurate oxygen assessment is required in a critical condition
Is there hypercapnia?	Venous blood gas as a screening test for carbon dioxide	If venous carbon dioxide is elevated, if there is drowsiness, respiratory depression, or suspected respiratory acidosis
Is respiratory support needed?	Clinical presentation, respiratory rate, saturation, signs of fatigue	If the decision depends on the degree of acidosis and carbon dioxide
Is this a purely respiratory disorder or a mixed one?	Step-by-step interpretation of acid-base balance	Almost always with severe respiratory failure, intoxication, shock

Source: Guidelines for the initial assessment of respiratory distress and educational materials on blood gas interpretation.[20]

Step 4: Visualization and express methods for finding the cause

After the initial assessment and understanding of the type of gas disturbance, the next step is to quickly find the cause, because "respiratory failure" is almost always secondary. In typical emergency department scenarios, the most common causes of respiratory distress are pneumonia, acute heart failure with pulmonary edema, pulmonary embolism, exacerbation of chronic obstructive pulmonary disease or bronchial asthma, and pneumothorax. [21]

Chest radiography remains the basic initial imaging tool, but in cases of doubt and severe cases, computed tomography (CT) is increasingly used because it better differentiates edema, inflammation, atelectasis, interstitial processes, and complications. Guidelines for the initial evaluation of respiratory distress specifically discuss imaging strategies and reassessment of the diagnosis after CT scanning in suspected pneumonia. [22]

Point-of-care ultrasound has become an important adjunct because it helps quickly differentiate cardiogenic pulmonary edema from pneumonia and identify pleural effusions, pneumothorax, and signs of right heart strain. Studies and reviews of point-of-care ultrasound suggest that the combination of ultrasound and blood gas analysis can expedite the clarification of the etiology of acute respiratory failure in intensive care and emergency departments. [23]

When pulmonary embolism is suspected, it's not "intuition" that's important, but following a validated algorithm. Guidelines for the initial assessment of respiratory distress indicate that the YEARS and PEGeD strategies help safely rule out the diagnosis and reduce unnecessary testing. Most importantly, the chosen algorithm should be followed to ensure diagnostic safety. [24]

Table 5. Visualization and rapid methods: what they provide specifically for the diagnosis of respiratory failure

Method	What does it reveal best?	When it is especially useful
Chest X-ray	Large infiltrates, edema, pneumothorax, effusion	The first step in most acute scenarios
Computed tomography of the chest	Accurate differentiation of the causes of infiltration and complications	Severe and unclear cases, discrepancy between clinical and X-ray findings
Computed tomography angiography	Pulmonary embolism	According to a validated algorithm for suspected embolism
Ultrasound of the lungs and pleura	Pulmonary edema, effusion, pneumothorax	Rapid bedside screening, treatment dynamics
Echocardiography	Left and right ventricular function, pulmonary artery pressure	Suspected cardiac cause, right ventricular overload

Source: Guidelines for the initial assessment of respiratory distress and reviews of bedside ultrasound. [25]

Step 5: Functional tests and clarifying diagnostics after stabilization

Functional respiratory testing is important, but it's usually reserved for patients after stabilization. Spirometry helps confirm obstruction or restriction and assess the severity of chronic lung diseases. However, in acute respiratory distress, it may be technically impossible and potentially dangerous due to severe shortness of breath, cough, and the risk of deterioration. Therefore, functional testing should be included in the algorithm only when the patient is able to perform a maneuver and this will change the management plan.

For patients with chronic obstructive pulmonary disease, assessing hypercapnia and acidosis during an exacerbation is diagnostically important, as these parameters determine the severity and need for respiratory support. The GOLD 2025 report emphasizes the role of noninvasive ventilation as the first mode of ventilatory support for acute respiratory failure in such patients in the absence of contraindications, making early assessment of carbon dioxide and blood acidity a clinically significant part of the diagnostic pathway. [27]

If imaging and blood gas data suggest acute respiratory distress syndrome, the Berlin definition criteria are used: acute onset, bilateral opacities on imaging, no explanation for cardiogenic edema, and severity grading based on the PaO2 to FiO2 ratio in the presence of positive end-expiratory pressure. This is diagnostically important because the syndrome requires a separate management protocol and search for causes, including sepsis, aspiration, severe pneumonia, and trauma. [28]

Finally, laboratory diagnostics are needed not "to confirm respiratory failure," but to identify the cause and complications: anemia, metabolic acidosis, inflammatory markers in infection, lactate in shock and tissue hypoperfusion. The Surviving Sepsis Campaign guidelines emphasize the clinical significance of lactate dynamics as part of the assessment of the severity and effectiveness of therapy in patients with sepsis and shock, which is often directly related to respiratory failure as an organ dysfunction. [29]

Table 6. What is usually added after initial stabilization to clarify the cause and phenotype of respiratory failure

Task	Research	What clarifies
Confirm chronic obstruction or restriction	Spirometry, bronchodilator test as indicated	Type of ventilation defect and initial reserve
Assess diffusion	Carbon Monoxide Diffusion Test	Alveolar-capillary component
Determine the infectious cause	Microbiology, inflammatory markers in clinical practice	Etiology of pneumonia and the need for antibacterial therapy
Assess systemic hypoperfusion	Lactate, hemodynamics, echocardiography as indicated	Shock as a cause of tissue hypoxia
Rule out rare causes	Toxicology tests, co-oximetry	Poisoning and oxygen transport disorders

Source: Guidelines for sepsis and definitions of acute respiratory failure phenotypes. [30]

A short "practical" diagnostic algorithm

1. First, clinical severity: respiratory rate, work of breathing, consciousness, ability to speak, saturation. [31]
2. Then determine what the leading problems are: oxygen, carbon dioxide ventilation, or both. [32]
3. Next, a quick search for the cause: X-ray or ultrasound at the bedside, then computed tomography according to indications and algorithms, including pulmonary embolism. [33]
4. After stabilization, functional tests and extended laboratory diagnostics are performed to clarify the phenotype and prevent relapses.