Respiratory failure differential diagnosis

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]

Overview

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

• 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.

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	Acute	+	+ with frothy expectoration	+/-	nausea and anorexia confusion headaches	Wheezing Increased pulse rate Crackles Pedal edema Elevated JVP Obtundation Enlarged liver	Cardiomegaly and interstitial edema in chest radiograph Echocardiography	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)	Acute	+	+/-	+/-	Cyanosis	Tachypnea Tachycardia Diffuse crackles	Diffuse, bilateral, alveolar infiltrates without cardiomegaly in chest radiograph Bilateral opacities in CT	Hypoxemia with acute respiratory alkalosis in arterial blood gases	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)	Acute	+	+ with frothy expectoration	+	Chest tightness Decreased exercise performance	Wheezing	Chest X-ray may show patchy alveolar infiltrates, predominantly in the right central hemithorax, which become more confluent and bilateral as the illness progresses	High levels of white blood cell count Decreased of oxygen saturation	Clinical diagnosis with supportive test	Occurrs over 2500 m Descent is mandatory in >4000 m
		Neurogenic pulmonary edema	Acute	+	+/- with frothy expectoration	+/-	Hemoptysis	Rales Bilateral crackles	Bilateral hyperdense infiltration in chest X-Ray	CBC may show Leukocytosis Bilateral hyperdense infiltrations on chest X-Ray	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	Major causes of NPE are epileptic seizures, cerebral hemorrhages and brain injury
		Pulmonary embolism	Acute Sub-acute Chronic	+	+	+/-	Chest pain Orthopnea	Wheezing Tachypnea Edema Decreased breath sounds Tachycardia	Hamptom and Westermark sign may be seen in chest X-Ray	Leukocytosis, elevated erythrocyte sedimentation and lactic acid in complete blood count Hypoxemia in arterial blood gas D-dimer to rule out other diseases Tachycardia and abnormalities in ST-segment and T waves are observed in ECG VQ scan	Computed tomography pulmonary angiogram (CTPA) or catheter based pulmonary angiography	Venous thromboembolism (VTE)
	Pneumonia		Acute	+	+ with sputum production	+	Pleuritic chest pain	Egophony Crackles Tactile fremitus Bronchial breath sounds	Infiltration in chest X-Ray	Leukocytosis Sputum culture & sensitivity	Clinical manifestations and infiltration chest X-Ray with or without microbiological test	Community-acquired pneumonia Hospital-acquired pneumonia Healthcare-associated pneumonia Ventilator-associated pneumonia Aspiration pneumonia
	Idiopatic chronic lung fibrosis		Chronic	+	+ without any sputum production	+/-	symptoms suggestive of rheumatic diseases may be present	Clubbing of the digits Bibasilar Crackles	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 Reduced FEV1 and FVC on spirometry	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		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    ABGs: Mild to moderate hypoxemia, hypercapnia with progression of disease, pH is around normal, < 7.3 points to respiratory acidosis	Clinical diagnosis with supportive test	CNS symptoms may be the only manifestation in elderly with baseline hypercapnia
	Severe Asthma/Status Asthmaticus		Acute	+	+	-	Chest tightness Audible wheeze	Tachypnea Tachycardia Wheezing Use of accessory respiratory muscles Unable to speak full sentences Orthopnea Pulsus paradoxus	Chest X-ray not required in acute conditions, may show hyperinflation	PEF <40 percent predicted or personal best Pulse oximetry ABGs	Clinical diagnosis	History of bronchial asthma
	Drug Overdose (opioid toxicity)		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	Chest X-ray usually not required, may show signs of acute lung injury	Urine toxicology screen: may reveal polysubstance abuse	Clinical diagnosis with supportive test	Toxicity from antipsychotics, anticonvulsants, ethanol, and sedatives can result in miosis and altered mentation, but respiratory depression is usually absent
	Myasthenic crisis		Acute	+	+/-	+/-	Inability to cough Bulbar weakness: dysphagia, nasal regurgitation, a nasal quality to speech, staccato speech, jaw weakness, bi-facial paresis, and tongue weakness	Expressionless face with droopy eyelids and mouth Use of accessory muscles of respiration i.e. external intercostal muscles, sternocleidomastoid, scalene muscles Rapid and shallow breathing	Chest X-ray findings depicting bacterial pneumonia and/or aspiration may be observed	Pulse Oximetry ABGs CBC: Infective cause precipitating the crisis may be observed Tensilon (edorphonium) test	Clinical diagnosis with supportive test	Known case of Myasthenia Gravis In some cases, respiratory failure may be the presenting symptom
	Guillain-Barré syndrome		Acute	+	-	+/-	Difficulty walking (ascending symmetric muscular weakness) Paresthesias in hands and feet Back pain Pain in extremities	Dysautonomia (tachycardia/bradycardia, hypertension/hypotension, urinary retention) 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	MRI Spine: thickening of intrathecal spinal nerve roots and cauda equina	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		Acute	+	+/-	+/-	Asyptomatic or increase work of breathing	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		Acute	+	-	+/-	Oliguria Abnormal mental status Clammy skin Cool extremities	Hypotension Tachycardia Tachypnea Rales Gallop rythm	Visible congestion in chest X-Ray	Electrocardigogram Increased levels of lactic acid Low levels of Bicarbonate Echocardiography to identify any cardiac dysfunction	Clinical diagnosis with supportive test	Cardiac index decreased Troponin leves, chemestry screen, complete blood count Cardiogenic shock Septic shock Hypovolemic shock