Acute Respiratory Failure

Definition, Etiology, Pathogenesis Top

Acute respiratory failure develops suddenly (usually over hours or days to a few weeks) and is potentially reversible. This definition pertains to the timing of development rather than its cause, which may be due to any of the processes discussed in the chapter on respiratory failure.

Anatomical approach to acute hypoxemia:

1) Diffuse lung parenchymal disease:

a) Pulmonary edema caused by increased hydrostatic pressure in the pulmonary vessels (left ventricular failure, fluid overload), increased permeability of the alveolar-capillary barrier (acute respiratory distress syndrome [ARDS]), drowning, lung reperfusion [after lung transplant or arterial embolectomy]); of unclear or complex mechanism (decompression [eg, pneumothorax], postobstructive [following the elimination of the cause of atelectasis], neurogenic, following stroke, after tocolytic therapy).

b) Alveolar bleeding: Vasculitis and connective tissue diseases (including anti-glomerular basement membrane disease [formerly known as Goodpasture syndrome]), disorders of hemostasis (particularly disseminated intravascular coagulation).

2) Focal lung parenchymal disease: Severe pneumonia, atelectasis (resulting from airway obstruction by a foreign body, tumor, or exudate), pulmonary contusion.

3) Pleural disease: Pneumothorax (particularly tension or large pneumothorax), massive pleural effusions.

4) Reduced pulmonary perfusion: Pulmonary embolism, shock.

Clinical Features and Natural History Top

1. Symptoms: Dyspnea is a relatively uniform finding in acute respiratory failure. Depending on the cause, the following may also occur: cough, fever, chest pain, hemoptysis, and other symptoms.

2. Signs include signs of acute hypoxia (cyanosis, tachycardia, tachypnea) and acute hypercapnia (headache, altered mental status) as well as signs of the underlying condition. In more advanced states the use of accessory respiratory muscles and paradoxical movements of the chest wall and abdomen may be observed. Paradoxical abdominal indrawing on inspiration suggests that respiratory collapse is imminent. Untreated acute respiratory failure can be fatal.

Diagnosis Top

1. Exclude other causes of dyspnea not related to respiratory failure (see Dyspnea).

2. Determine the cause of acute respiratory failure:

1) Assess the respiratory system: Inspect, palpate, and auscultate, looking for signs of upper airway obstruction, or parenchymal or pleural disease.

2) Assess the cardiovascular system: Assess for signs of cardiogenic pulmonary edema (see Table 1 in Acute Heart Failure), pulmonary embolism, or anaphylaxis.

3) Exclude or confirm sepsis (see Sepsis and Septic Shock), and if confirmed, determine its cause.

Diagnostic Tests

1. Pulse oximetry: Low oxygen saturation of hemoglobin (SpO2).

2. Blood tests:

1) Arterial blood gas analysis: Hypoxemia, hypercapnia (respiratory acidosis), and metabolic acidosis may be present in various combinations. Blood gas analysis provides measurement of blood pH, oxygen tension (PaO2), carbon dioxide tension (PaCO2), bicarbonate concentration, as well as SaO2, allowing interpretation of oxygenation, ventilation, and acid-base balance. While an arterial blood gas (ABG) sample accurately reflects oxygenation and pulmonary gas exchange, central venous blood is more accurate at detecting the acid-base status and hypercapnia at the tissue level if severe hypoperfusion is present (ie, circulatory failure).Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to data coming from a case series of 105 patients with consistent findings of acid-base status in patients with hemodynamic compromise. Adrogué HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE. Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood. N Engl J Med. 1989 May 18;320(20):1312-6. PubMed PMID: 2535633. Peripheral venous blood gas (VBG) analysis is a simpler, less painful, and more convenient alternative to ABG. While it is likely sufficient to estimate arterial pH, VBG may not be sufficient to estimate arterial pCO2, especially at highly abnormal values.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to heterogeneity of findings in a systematic review of 20 eligible studies. Byrne AL, Bennett M, Chatterji R, Symons R, Pace NL, Thomas PS. Peripheral venous and arterial blood gas analysis in adults: are they comparable? A systematic review and meta-analysis. Respirology. 2014 Feb;19(2):168-75. doi: 10.1111/resp.12225. Epub 2014 Jan 3. PubMed PMID: 24383789. Byrne AL, Bennett MH, Pace NL, Thomas P. Peripheral venous blood gas analysis versus arterial blood gas analysis for the diagnosis of respiratory failure and metabolic disturbance in adults (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD010841. DOI: 10.1002/14651858.CD010841. In the absence of circulatory failure or shock, venous pH, bicarbonate, and base excess have sufficient agreement with arterial values and, while the relationship between venous and arterial pCO2 remains to a degree unpredictable, it may still be of value as a screening test for arterial hypercapnia or to monitor changes in respiratory function.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision. Kelly AM. Review article: Can venous blood gas analysis replace arterial in emergency medical care. Emerg Med Australas. 2010 Dec;22(6):493-8. doi: 10.1111/j.1742-6723.2010.01344.x. Review. PubMed PMID: 21143397. Bloom BM, Grundlingh J, Bestwick JP, Harris T. The role of venous blood gas in the emergency department: a systematic review and meta-analysis. Eur J Emerg Med. 2014 Apr;21(2):81-8. doi: 10.1097/MEJ.0b013e32836437cf. Review. PubMed PMID: 23903783.

2) Complete blood count (CBC) and biochemical tests: Abnormalities may suggest specific etiologies (eg, leukocytosis, anemia, or eosinophilia; elevated serum brain natriuretic peptide or troponin, elevated D-dimers).

3. Microbiology: Because acute respiratory failure is frequently caused by infections, attempt to identify the etiologic agent (microbiologic tests of respiratory secretions [eg, during flexible bronchoscopy], blood, or other clinically relevant material).

4. Imaging studies:

1) Plain chest radiography: Specific abnormalities may suggest the etiology (eg, various patterns of interstitial or air-space opacification in the lungs, volume loss, pneumothorax, pleural effusion).

2) Chest ultrasonography or computed tomography (CT) may further help in delineating the etiology of acute respiratory failure.

5. Electrocardiography (ECG) may reveal features of myocardial ischemia or pulmonary hypertension.

Diagnostic Criteria

Diagnostic criteria: see Respiratory Failure.

Treatment Top

1. Clearing the upper airway, as the situation requires: Noninstrumental (see Cardiac Arrest); insertion of an oropharyngeal tube or other device; intubation; cricothyrotomy; tracheostomy (the procedure of choice in patients with massive laryngeal edema or prolonged mechanical ventilation).

2. Oxygen therapy (see Oxygen Therapy) with a fraction of inspired oxygen (FiO2 100%) as required. Consider the possibility of hypoxic respiratory drive in chronic lung diseases. Consider oxygen supplementation with a lower FiO2 or a lower target of arterial oxygenation, because a higher FiO2 or higher target of oxygenation may increase the rates of mortality and serious adverse events.

3. High-flow nasal cannula compared with conventional oxygen therapy in the setting of acute hypoxemic respiratory failure decreases the need for noninvasive or invasive ventilation.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and the risk of bias. Rochwerg B, Granton D, Wang DX, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019 May;45(5):563-572. doi: 10.1007/s00134-019-05590-5. Epub 2019 Mar 19. Review. PubMed PMID: 30888444. Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. 2020 Jun 4;324(1):1–12. doi: 10.1001/jama.2020.9524. Epub ahead of print. PMID: 32496521; PMCID: PMC7273316. There is some evidence that it may be preferred to noninvasive ventilation maneuver in such situations.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and the risk of bias. Frat JP, Thille AW, Mercat A, et al; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17. PubMed PMID: 25981908. Barbateskovic M, Schjørring OL, Russo Krauss S, et al. Higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Cochrane Database Syst Rev. 2019 Nov 27;2019(11):CD012631. doi: 10.1002/14651858.CD012631.pub2. PMID: 31773728; PMCID: PMC6880382.

The ratio of SpO2 measured by oximeter to FiO2 (higher levels indicate less hypoxia) divided by RR is known as the ROX index and may be of some use in estimating risk of failure of therapy. A ROX of ~5 provides the best cutoff.Evidence 6Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirctness). Roca O, Messika J, Caralt B, et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016 Oct;35:200-5. doi: 10.1016/j.jcrc.2016.05.022. Epub 2016 May 31. PMID: 27481760.

4. Treatment of the underlying condition: Pharmacologic (eg, epinephrine for anaphylaxis, bronchodilators, antibiotics) or invasive (eg, decompression of pneumothorax, thoracentesis).

5. Mechanical ventilation:

1) Noninvasive positive pressure ventilation should be an early consideration for patients with an acute exacerbation of COPDEvidence 7Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Evidence includes a systematic review of 16 randomized controlled trials within a clinical practice guideline. Trials showed large, precise reductions in the rate of endotracheal intubation as well as in the risk of mortality across a range of COPD populations. Keenan SP, Sinuff T, Burns KE, et al; Canadian Critical Care Trials Group/Canadian Critical Care Society Noninvasive Ventilation Guidelines Group. Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2011 Feb 22;183(3):E195-214. doi: 10.1503/cmaj.100071. Epub 2011 Feb 14. PubMed PMID: 21324867; PubMed Central PMCID: PMC3042478. or cardiogenic pulmonary edema (in the absence of shock or an acute coronary syndrome).Evidence 8Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Evidence includes a systematic review of 20 randomized controlled trials within a clinical practice guideline. Trials showed large and precise reductions in the rates of treatment failure and hospital mortality across a range of populations. Keenan SP, Sinuff T, Burns KE, et al; Canadian Critical Care Trials Group/Canadian Critical Care Society Noninvasive Ventilation Guidelines Group. Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2011 Feb 22;183(3):E195-214. doi: 10.1503/cmaj.100071. Epub 2011 Feb 14. PubMed PMID: 21324867; PubMed Central PMCID: PMC3042478. It may also be beneficial in other situations of acute respiratory failure.Evidence 9Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the heterogeneity of populations and risk of bias. Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. 2020 Jun 4;324(1):1–12. doi: 10.1001/jama.2020.9524. Epub ahead of print. PMID: 32496521; PMCID: PMC7273316.

2) Invasive mechanical ventilation may be required.

3) When a patient no longer requires invasive mechanical ventilation, there is some evidence that the use of high-flow nasal cannula alternating with noninvasive ventilation may prevent postextubation respiratory failure in patients at high risk of extubation failure (aged >65 years, with underlying chronic heart or lung disease).Evidence 10Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence decreased due to indirectness and imprecision. Thille AW, Muller G, Gacouin A, et al; HIGH-WEAN Study Group and REVA Research Network. Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial. JAMA. 2019 Oct 2;322(15):1465-1475. doi: 10.1001/jama.2019.14901. Epub ahead of print. Erratum in: JAMA. 2020 Feb 25;323(8):793. PMID: 31577036; PMCID: PMC6802261.

6. Respiratory physiotherapy, including postural drainage.

7. Nutrition support to prevent malnutrition: see Chronic Respiratory Failure.

Complications Top

Consequences of hypoxemia and hypercapnia. More severe complications following intubation and mechanical ventilation: upper gastrointestinal tract bleeding due to stress ulcers or hemorrhagic gastritis (prevention: see Acute Hemorrhagic/Erosive Gastropathy), venous thromboembolism (prevention: see Primary Prevention of Venous Thromboembolism).