History

The diagnosis of acute or chronic respiratory failure begins with clinical suspicion of its presence. Confirmation of the diagnosis is based on arterial blood gas analysis (see Workup). Evaluation of an underlying cause must be initiated early, frequently in the presence of concurrent treatment for acute respiratory failure. The cause of respiratory failure is often evident after a careful history and physical examination.

Cardiogenic pulmonary edema usually develops in the context of a history of left ventricular dysfunction or valvular heart disease. A history of previous cardiac disease, recent symptoms of chest pain, paroxysmal nocturnal dyspnea, and orthopnea suggest cardiogenic pulmonary edema. Noncardiogenic edema (eg, acute respiratory distress syndrome [ARDS]) occurs in typical clinical contexts, such as sepsis, trauma, aspiration, pneumonia, pancreatitis, drug toxicity, and multiple transfusions.

A study by Canet et al, examining acute respiratory failure in kidney transplant recipients, determined that 200 of 6,819 kidney transplant recipients required admission to the intensive care unit (ICU) for acute respiratory failure, which was associated with high mortality and graft loss rates.^[6]Early ICU admission and increased bacterial and Pneumocystis prophylaxis may improve outcomes.

Physical Examination

The signs and symptoms of acute respiratory failure reflect the underlying disease process and the associated hypoxemia or hypercapnia. Localized pulmonary findings reflecting the acute cause of hypoxemia (eg, pneumonia, pulmonary edema, asthma, or chronic obstructive pulmonary disease [COPD]), may be readily apparent. In patients with ARDS, the manifestations may be remote from the thorax, such as abdominal pain or long-bone fracture. Neurologic manifestations include restlessness, anxiety, confusion, seizures, or coma.

Asterixis may be observed with severe hypercapnia. Tachycardia and a variety of arrhythmias may result from hypoxemia and acidosis.

Cyanosis, a bluish color of skin and mucous membranes, indicates hypoxemia. Visible cyanosis typically is present when the concentration of deoxygenated hemoglobin in the capillaries or tissues is at least 5 g/dL.

Dyspnea, an uncomfortable sensation of breathing, often accompanies respiratory failure. Excessive respiratory effort, vagal receptors, and chemical stimuli (hypoxemia and/or hypercapnia) all may contribute to the sensation of dyspnea.

Both confusion and somnolence may occur in respiratory failure. Myoclonus and seizures may occur with severe hypoxemia. Polycythemia is a complication of long-standing hypoxemia.

Pulmonary hypertension frequently is present in chronic respiratory failure. Alveolar hypoxemia potentiated by hypercapnia causes pulmonary arteriolar constriction. If chronic, this is accompanied by hypertrophy and hyperplasia of the affected smooth muscles and narrowing of the pulmonary arterial bed. The increased pulmonary vascular resistance increases afterload of the right ventricle, which may induce right ventricular failure. This, in turn, causes enlargement of the liver and peripheral edema. The entire sequence is known as cor pulmonale.

Criteria for the diagnosis of ARDS include the following:

Clinical presentation - Tachypnea and dyspnea; crackles upon auscultation
Clinical setting - Direct insult (aspiration) or systemic process causing lung injury (sepsis)
Radiologic appearance - 3-quadrant or 4-quadrant alveolar flooding
Lung mechanics - Diminished compliance (< 40 mL/cm water)
Gas exchange - Severe hypoxia refractory to oxygen therapy (ratio of arterial oxygen tension to fractional concentration of oxygen in inspired gas [PaO₂/FiO₂] < 200)
Normal pulmonary vascular properties - Pulmonary capillary wedge pressure lower than 18 mm Hg

Complications

Complications of acute respiratory failure may be pulmonary, cardiovascular, gastrointestinal (GI), infectious, renal, or nutritional.

Common pulmonary complications of acute respiratory failure include pulmonary embolism, barotrauma, pulmonary fibrosis, and complications secondary to the use of mechanical devices. Patients are also prone to develop nosocomial pneumonia. Regular assessment should be performed by periodic radiographic chest monitoring. Pulmonary fibrosis may follow acute lung injury associated with ARDS. High oxygen concentrations and the use of large tidal volumes may worsen acute lung injury.

Common cardiovascular complications in patients with acute respiratory failure include hypotension, reduced cardiac output, arrhythmia, endocarditis, and acute myocardial infarction. These complications may be related to the underlying disease process, mechanical ventilation, or the use of pulmonary artery catheters.

The major GI complications associated with acute respiratory failure are hemorrhage, gastric distention, ileus, diarrhea, and pneumoperitoneum. Stress ulceration is common in patients with acute respiratory failure; the incidence can be reduced by routine use of antisecretory agents or mucosal protectants.

Nosocomial infections, such as pneumonia, urinary tract infections, and catheter-related sepsis, are frequent complications of acute respiratory failure. These usually occur with the use of mechanical devices. The incidence of nosocomial pneumonia is high and associated with significant mortality.

Acute renal failure and abnormalities of electrolytes and acid-base homeostasis are common in critically ill patients with respiratory failure. The development of acute renal failure in a patient with acute respiratory failure carries a poor prognosis and high mortality. The most common mechanisms of renal failure in this setting are renal hypoperfusion and the use of nephrotoxic drugs (including radiographic contrast material).

Nutritional complications include malnutrition and its effects on respiratory performance and complications related to administration of enteral or parenteral nutrition. Complications associated with nasogastric tubes, such as abdominal distention and diarrhea, also may occur. Complications of parenteral nutrition may be mechanical (resulting from catheter insertion), infectious, or metabolic (eg, hypoglycemia, electrolyte imbalance).

Differential Diagnoses

Khan NA, Palepu A, Norena M, et al. Differences in hospital mortality among critically ill patients of Asian, Native Indian, and European descent. Chest. 2008 Dec. 134(6):1217-22. [QxMD MEDLINE Link].
Moss M, Mannino DM. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979- 1996). Crit Care Med. 2002 Aug. 30(8):1679-85. [QxMD MEDLINE Link].
Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000 May 4. 342(18):1301-8. [QxMD MEDLINE Link].
Phua J, Badia JR, Adhikari NK, et al. Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review. Am J Respir Crit Care Med. 2009 Feb 1. 179(3):220-7. [QxMD MEDLINE Link].
Noveanu M, Breidthardt T, Reichlin T, Gayat E, Potocki M, Pargger H, et al. Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study. Crit Care. 2010 Nov 3. 14(6):R198. [QxMD MEDLINE Link]. [Full Text].
Canet E, Osman D, Lambert J, et al. Acute respiratory failure in kidney transplant recipients: a multicenter study. Crit Care. 2011 Mar 8. 15(2):R91. [QxMD MEDLINE Link].
Peek GJ, Elbourne D, Mugford M, Tiruvoipati R, Wilson A, Allen E, et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010 Jul. 14(35):1-46. [QxMD MEDLINE Link].
Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13. 359 (20):2095-104. [QxMD MEDLINE Link].
Girault C, Briel A, Benichou J, Hellot MF, Dachraoui F, Tamion F, et al. Interface strategy during noninvasive positive pressure ventilation for hypercapnic acute respiratory failure. Crit Care Med. 2009 Jan. 37(1):124-31. [QxMD MEDLINE Link].
Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010 Mar 3. 303(9):865-73. [QxMD MEDLINE Link].
Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19. 372 (8):747-55. [QxMD MEDLINE Link].
[Guideline] Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). European Society of Intensive Care Medicine. Available at https://www.esicm.org/wp-content/uploads/2020/03/SSC-COVID19-GUIDELINES.pdf. 2020; Accessed: April 7, 2020.
Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995 Sep 28. 333(13):817-22. [QxMD MEDLINE Link].
Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000 Jun 3. 355(9219):1931-5. [QxMD MEDLINE Link].
Vitacca M, Clini E, Rubini F, Nava S, Foglio K, Ambrosino N. Non-invasive mechanical ventilation in severe chronic obstructive lung disease and acute respiratory failure: short- and long-term prognosis. Intensive Care Med. 1996 Feb. 22(2):94-100. [QxMD MEDLINE Link].
Confalonieri M, Potena A, Carbone G, Porta RD, Tolley EA, Umberto Meduri G. Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation. Am J Respir Crit Care Med. 1999 Nov. 160(5 Pt 1):1585-91. [QxMD MEDLINE Link].
Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med. 1998 Aug 13. 339(7):429-35. [QxMD MEDLINE Link].
[Guideline] Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. 2017 Aug. 50 (2):[QxMD MEDLINE Link]. [Full Text].

Media Gallery

Bilateral airspace infiltrates on chest radiograph film secondary to acute respiratory distress syndrome that resulted in respiratory failure.
Extensive left-lung pneumonia caused respiratory failure; the mechanism of hypoxia is intrapulmonary shunting.
A 44-year-old woman developed acute respiratory failure and diffuse bilateral infiltrates. She met the clinical criteria for the diagnosis of acute respiratory distress syndrome. In this case, the likely cause was urosepsis.
This patient developed acute respiratory failure that turned out to be the initial presentation of systemic lupus erythematosus. The lung pathology evidence of diffuse alveolar damage is the characteristic lesion of acute lupus pneumonitis.
A Bilevel positive airway pressure support machine is shown here. This could be used in spontaneous mode or timed mode (backup rate could be set).
Headgear and full face mask commonly are used as the interface for noninvasive ventilatory support.
Bilevel positive airway pressure (BiPAP) and inspiratory positive airway pressure (IPAP) settings are shown. IPAP or expiratory positive airway pressure (EPAP) and frequency can be preset.
Noninvasive ventilation with bilevel positive airway pressure for acute respiratory failure secondary to exacerbation of chronic obstructive pulmonary disease.
Wave forms of a volume-targeted ventilator: Pressure, flow, and volume waveforms are shown with square-wave flow pattern. A is baseline, B is increase in tidal volume, C is reduced lung compliance, and D is increase in flow rate. All 3 settings lead to increase in peak airway pressures. Adapted from Spearman CB et al.
The cause of respiratory failure may be suggested by spirometry.
A 65-year-old man developed chronic respiratory failure secondary to usual interstitial pneumonitis. Loss of normal architecture is seen upon biopsy. Also seen are varying degrees of inflammation and fibrosis.
Lung biopsy from a 32-year-old woman who developed fever, diffuse infiltrates seen on chest radiograph, and acute respiratory failure. The lung biopsy shows acute eosinophilic pneumonitis; bronchoscopy with bronchoalveolar lavage also may have helped reveal the diagnosis.
Lung biopsy on this patient with acute respiratory failure and diffuse pulmonary infiltrates helped yield the diagnosis of pulmonary edema. Therefore, cardiogenic pulmonary edema should be excluded as the cause of respiratory failure prior to considering lung biopsy.
Pressure-volume curve of a patient with acute respiratory distress syndrome (ARDS) on mechanical ventilation can be constructed. The lower and the upper ends of the curve are flat, and the central portion is straight (where the lungs are most compliant). For optimal mechanical ventilation, patients with ARDS should be kept between the inflection and the deflection point.
Surgical lung biopsy was performed in the patient described in Image 3. The histology shows features of diffuse alveolar damage, including epithelial injury, hyperplastic type II pneumocytes, and hyaline membranes.

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Author

Ata Murat Kaynar, MD Associate Professor, Departments of Critical Care Medicine and Anesthesiology, University of Pittsburgh School of Medicine

Ata Murat Kaynar, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Chest Physicians, American Society of Anesthesiologists, Society of Critical Care Medicine, Society of Critical Care Anesthesiologists

Disclosure: Nothing to disclose.

Coauthor(s)

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Thoracic Society, European Society of Intensive Care Medicine, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Baxter Medical, Exostat, LiDCO<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED.

Acknowledgements

Cory Franklin, MD Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment