Respiratory failure differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vellayat Ali M.B.B.S[2] Karina Zavaleta, MD [3] M. Khurram Afzal, MD [4]


As respiratory failure manifests in a variety of clinical forms, differentiation must be established in accordance with the particular type of respiratory failure. Type I respiratory failure must be differentiated from other disease that cause hypoxia, such as acute decompensated heart failure, adult respiratory distress syndrome, high altitude pulmonary edema, neurogenic pulmonary edema, pulmonary embolism, pneumonia and idiopathic chronic lung fibrosis. In contrast Type II respiratory failure must be differentiated from other diseases that cause hypercapnia, such as COPD, status asthmaticus, opioid toxicity, myasthenia crisis, Guillain-Barré syndrome. As well as Type III preoperative respiratory failure and Type IV respiratory failure.

Differentiating Respiratory Failure from other Diseases

Type of respiratory failure Causes/Etiology Onset Clinical manifestations Investigations Gold standard Other features
Symptoms Physical exam
Dyspnea Cough Fever Others findings Imaging Labs
Hypoxic respiratory failure (Type 1 respiratory failure) Cardiogenic pulmonary edema Acute decompensated heart failure[1][2] [3]
  • Acute
+ + with frothy expectoration +/-
  • nausea and anorexia
  • confusion
  • headaches
  • Pulse oximetry
  • Assays for BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro-B-type natriuretic peptide)
  • Cardiac troponin levels
  • ST and T waves abnormalities in ECG
  • Clinical diagnosis
  • History of heart disease, hypertension
Non cardiogenic pulmonary edema Adult respiratory distress syndrome (ARDS) [4]
  • Acute
+ +/- +/-
  • Diffuse, bilateral, alveolar infiltrates without cardiomegaly in chest radiograph
  • Bilateral opacities in CT
  • Clinical diagnosis with supportive test

According to Berlin definition:

  • One week of new or worse respiratory symptoms or clinical insult
  • Symptoms can not be explained by cardiac disease
  • Bilateral opacities in chest X-Ray or CT
  • Compromised oxygenation
High-Altitude Pulmonary edema (HAPE) [5]
  • Acute
+ + with frothy expectoration +
  • Chest X-ray may show patchy alveolar infiltrates, predominantly in the right central hemithorax, which become more confluent and bilateral as the illness progresses
  • Clinical diagnosis with supportive test
  • Occurrs over 2500 m
  • Descent is mandatory in >4000 m
Neurogenic pulmonary edema [6] [7]
  • Acute
+ +/- with frothy expectoration +/-
  • Diagnosis of exclusion
  • A proposed criteria is as follows
    • Bilateral infiltrates
    • PaO2/FiO2 ratio < 200
    • No evidence of left atrial hypertension
    • Presence of CNS injury
    • Absence of other common causes of acute respiratory distress or ARDS
Pulmonary embolism [8] [9]
  • Acute
  • Sub-acute
  • Chronic
+ + +/-
  • Hamptom and Westermark sign may be seen in chest X-Ray
Pneumonia[10] [11]
  • Acute
+ + with sputum production +
  • Pleuritic chest pain
  • Clinical manifestations and infiltration chest X-Ray with or without microbiological test
Idiopatic chronic lung fibrosis[12] [13] [14] [15]
  • Chronic
+ + without any sputum production +/-
  • symptoms suggestive of rheumatic diseases may be present
  • Reticular or nodular pattern in chest X-Ray
  • HRCT may show reticular opacities, including honeycomb changes and traction bronchiectasis
  • Serological tests e.g. ANA, RF for underlying rheumatological diseases
  • Clinical presentation in combinations with HRCT findings
  • Lung biopsy when lab, imaging and PFT do not yield enough evidence
  • History of cigarette smoking
Hypercapnic respiratory failure (Type 2 respiratory failure) COPD [16] [17]
  • Acute
  • Chronic
  • Acute-on-chronic
+ + +/-
  • Exercise intolerance
  • Acute exacerbation may affect CNS, ranging from irritability to decreased responsiveness
  • Clubbing
  • Tachypnea
  • Barrel shaped chest
  • Decreased breath sounds with prolonged expiration
  • Rhonchi and Wheeze
  • Use of accessory respiratory muscles
  • Increased JVP, peripheral edema may manifest with right ventricular overload during an acute exacerbation
  • Chest X-ray may show hyperinflation, flattened diaphragm, rapid tapering of vascular markings 
  • CT scan helps to correlate with COPD prognosis
  • PFTs: (FEV1/FVC) <70% of predicted   
  • Clinical diagnosis with supportive test
  • CNS symptoms may be the only manifestation in elderly with baseline hypercapnia
Severe Asthma/Status Asthmaticus [18] [19]
  • Acute
+ + -
  • Chest tightness
  • Audible wheeze
  • Chest X-ray not required in acute conditions, may show hyperinflation
  • PEF <40 percent predicted or personal best
  • Clinical diagnosis
Drug Overdose (opioid toxicity) [20] [21] [22]
  • Acute
+ - -
  • Nausea and vomiting
  • Constipation
  • Seizures
  • Classic triad suggesting opioid toxicity consist of respiratory depression, pinpoint pupils, and altered mental state 
  • Conjunctival injection,
  • Decreased bowel sounds
  • Euphoria
  • Urine toxicology screen: may reveal polysubstance abuse
  • Clinical diagnosis with supportive test
Myasthenic crisis [23] [24] [25] [26] [27]
  • Acute
+ +/- +/-
  • Inability to cough
  • Bulbar weakness: dysphagia, nasal regurgitation, a nasal quality to speech, staccato speech, jaw weakness, bi-facial paresis, and tongue weakness
  • Pulse Oximetry
  • ABGs
  • CBC: Infective cause precipitating the crisis may be observed
  • Tensilon (edorphonium) test
  • Clinical diagnosis with supportive test
Guillain-Barré syndrome [28] [29] [30] [31] [32] [33]
  • Acute
+ - +/-
  • Difficulty walking (ascending symmetric muscular weakness)
  • Back pain
  • Pain in extremities
  • Diminished or absent deep tendon reflexes
  • Limb weakness (first lower then upper limbs)
  • Facial droop (Facial nerve palsy)
  • Ophthalmoparesis (3rd & 6th nerve palsies)
  • Decreased breath sounds
  • Decreased bowel sounds
  • CSF analysis: Albuminocytologic dissociation
  • Nerve conduction studies may show conduction block, slowed motor conduction velocities and delayed latencies
  • PFTs: Vital Capacity, maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) should be followed to determine appropriate timing of intubation and mechanical ventilation
  • Clinical diagnosis with supportive test
  • Signs depicting respiratory failure occur late, early manifestations are tachypnea, tachycardia, air hunger, broken sentences, and a need to pause between sentences
  • Use of the accessory respiratory muscles, paradoxical breathing, and orthopnea indicate severe diaphragmatic weakness
Perioperative respiratory failure (Type 3 respiratory failure) Post-operative atelectasis [34] [35] [36] [37] [38]
  • Acute
+ +/- +/-
  • Tachypnea
  • Tachycardia
  • Decreased movement in the affected lung area
  • Dullness percussion note
  • Absent breath sounds Tracheal deviation to affected side
  • Chest X-ray may show increased density and reduced volume
  • CT chest accurately shows the involved segment
  • Pulse oximetry
  • ABGs
  • Clinical diagnosis with support of radiographic findings
  • History of abdominal or thoracic surgery
Type 4 respiratory failure Shock[39] [40]
  • Acute
+ - +/-
  • Clinical diagnosis with supportive test


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