Type I Respiratory Failure: Acute Hypoxic Respiratory Failure

Division of Critical Care Medicine University of Alberta

Outline
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Review of Pathophysiology Clinical presentation and differential diagnosis ARDS Reversible causes of ARDS Description and Treatment

Pathophysiology

Acute hypoxic respiratory failure (AHRF) is also called Type I Respiratory Failure. Marked by severe hypoxemia that is unresponsive to supplemental oxygen. This results from widespread flooding and collapse of alveoli that causes blood to flow past unventilated alveoli (V/Q ratio of zero). Also called shunt.

As can be seen above, blood passing through the right alveoli does not pick up any oxygen while the left is normal and fully saturated. The reduced oxygen content from the right mixes with the left and reduces the overall oxygen of the blood returning to the heart.

Pathophysiology

The intra-alveolar fluid and increased interstitial fluid decreases overall lung compliance. This imposes a larger elastic work of breathing resulted in increased respiratory muscle oxygen consumption. A vicious cycle of increased O2 demand, muscle fatigue and hypoxemia leads to respiratory arrest and death if mechanical assistance is not instituted.

Clinical Presentation

There are many causes of AHRF, however, the clinical presentation is remarkably similar. Almost all patients are tachypneic and dyspneic. Initial room air ABG show a PaO2 of 30-35 and SaO2 < 85%. If supplemental oxygen by mask or cannula is given and the SaO2 rises to >95%then a large intrapulmonary shunt is unlikely. The chest x-ray will provide further clues into the cause of the hypoxemia and only rarely will it be normal.

In this case, consider an error in the ABG, an intracardiac shunt or AVM malformation.

Differential Diagnosis of AHRF

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Acute lung injury or ARDS Acute cardiogenic pulmonary edema Bilateral aspiration pneumonia Lobar atelectasis of both lower lobes Severe unilateral lower lobe atelectasis, especially when the patient is receiving vasodilators such as nitrates, calcium channel blockers, or nitroprusside that blunt hypoxic vasoconstriction.

Differential Diagnosis of AHRF

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Main stem bronchus obstruction from mucous plug or blood clot. Bilateral or unilateral pneumothorax Large unilateral or bilateral pleural effusions Diffuse alveolar hemorrhage Massive pulmonary embolus Opening of patent foramen ovale with preexisting pulmonary hypertension.

Clinical Setting

Given the extensive differential for AHRF, the clinical setting and further investigations are invaluable in establishing the cause. Cardiogenic edema is usually accompanied by systolic left ventricular or valvular dysfunction and abnormal heart sounds or murmurs should be sought. ECG and biochemical evidence of ischemia should be considered as an obvious cause of cardiogenic edema.

Clinical Setting

Review of intravascular volume administration will often suggest an explanation for pulmonary edema in patients with left ventricular or renal dysfunction. ALI or ARDS commonly arises in a typical clinical context with direct and indirect causes (differential to be discussed soon).

Clinical Setting

The chest x-ray is not very accurate for distinguishing cardiogenic from non-cardiogenic causes. However, it can help sort out the other causes of AHRF. Essentially, the differential can be broken down into those causes that present with unilateral xray findings (i.e. lobar pneumonia, atelectasis, effusion) and bilateral findings (i.e.. ARDS, pulmonary edema, diffuse alveolar hemorrhage)

Clinical Setting

Echocardiography is helpful in distinguishing cardiogenic from noncardiogenic pulmonary edema. Echocardiography also helps identify left ventricular wall motion abnormalities, mitral valve dysfunction, and ventricular dilation. Early bronchoscopy is critical to identify reversible causes and guide therapy. Bronchoscopy can help diagnose some causes of AHRF including diffuse alveolar hemorrhage, pneumonia, and acute eosinophillic pneumonia.

Acute Respiratory Distress Syndrome (ARDS)

Acute lung injury (ALI) and ARDS are common causes of AHRF. Both are defined by acute onset, bilateral pulmonary infiltrates on chest x-ray consistent with pulmonary edema, hypoxemia and the absence of evidence of left atrial hypertension.

ARDS - Definition

The ratio of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2), also called the P/F ratio, reflects the degree of hypoxemia at different levels of FiO2. The syndrome is called ALI when the ratio is < 300 and ARDS when < 200. ALI was coined to identify those patients who are early in the course of their ARDS or have a form of AHRF that is milder than ARDS.

ARDS Precipitating Causes

ALI/ARDS is a syndrome diagnosis and should be considered a final common pathway reaction of the lung to a large variety of insults. Precipitating causes can be broken down into direct (pulmonary) and indirect (systemic).

ARDS Direct Precipitating Causes

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Aspiration of gastric contents Bacterial pneumonia Chest trauma with pulmonary contusion Near drowning PCP pneumonia Toxic inhalations (i.e.. smoke, crack cocaine) Viral pneumonia

ARDS Indirect Precipitating Causes

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Pancreatitis Transfusion associated acute lung injury (TRALI) Post cardiopulmonary bypass Primary graft failure of lung transplant Severe sepsis and septic shock Toxic ingestions (i.e.. ASA, TCA) Trauma with multiple fractures and fat-emboli syndrome

ARDS/ALI Pathology

Early in the development, interstitial and alveolar edema, capillary congestion, and intraalveolar hemorrhage with minimal evidence of cellular injury appears. This is the early exudative phase of diffuse alveolar damage with inflammatory cell infiltration in the lung interstitium. Also during this phase, the pulmonary capillaries sequester neutrophils contributing further to the inflammation.

ARDS/ALI Pathology

Over the next days, hyaline membranes form in the alveolar spaces. These membranes contain condensed fibrin and plasma protein. Inflammatory cells become more numerous in the interstitium and there is extensive necrosis of type I alveolar cells.

ARDS/ALI Pathology

The late phase is dominated by disordered healing and begins to occur 7 to 10 days after initial injury. This is the fibroproliferative phase and is marked by increasing type II alveolar cells, fibroblasts and myofibroblast. Patients in this stage are typically left with a large dead space fraction, high minute ventilation requirement, progressive pulmonary hypertension, slightly improved pulmonary shunt, and reduction in lung compliance.

ARDS/ALI Treatment

A key step in treating patients with ARDS/ALI is to identify and treat the underlying cause. The ventilatory and other support of ALI is doomed to failure if the precipitant is not dealt with. ARDS/ALI is a syndrome diagnosis based on nonspecific criteria only, therefore, making the diagnosis of ALI/ARDS is not equivalent to diagnosing the patients underlying problem.

ARDS/ALI Ventilation Goals

After the underlying cause is identified, the focus is on ventilation goals:

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Maintain SaO2 < 88% and PaO2 < 55 Protect lung from further injury Maintain lung recruitment Maintain normal pH and PaCO2

ARDS/ALI Ventilation Goals

The primary problem in ARDS is that there is a large intrapulmonary shunt that is resistant to oxygen therapy. In order to meet oxygenation goals, sufficient PEEP needs to be given. PEEP works by recruiting collapsed and partially fluidfilled alveoli and therefore increasing FRC. It also redistributes alveolar fluid into the interstitium. By this approach, the patient should be able to avoid high levels of FiO2 (> 60%) which is toxic in itself. Higher levels of PEEP also prevents surfactant poor alveoli from repeatedly opening and collapsing which is also injurious to the lungs.

ARDS/ALI Ventilation Goals

Conventional ventilation strategy usually requires a tidal volume of 10-12 mL/kg in order to maintain minute ventilation and hence, normal PaCO2. However, in an injured lung, that volume causes excess stretch and perpetuates the injury. Therefore, the current goal is a low tidal volume strategy of 6 mL/kg. If this tidal volume is insufficient for minute ventilation (even at a higher respiratory rate) then the resultant elevated PaCO2 is tolerated as long as the pH is > 7.20. This is called permissive hypercapnia.

ARDS/ALI Other Adjuvant Measures

Prone Position Increases FRC, redistributes perfusion and better secretion clearance. Recruitment Maneuvers Open partially collapsed alveoli which is then kept inflated by a high level of PEEP. Other savage measures: NO Steroids during fibroproliferative stage High frequency oscillation EMCO Partial liquid ventilation Surfactant

Reversible Causes of ARDS/ALI

Bacterial pneumonia Viral pneumonia Fungal pneumonia PJP Diffuse alveolar hemorrhage Eosinophillic pneumonia Lupus pneumonitis Toxic drug reaction

Community Acquired Pneumonia

There are more than 100 microbes (bacteria, viruses, fungi, and parasites) that can cause CAP. Most cases of pneumonia are caused by 4 or 5 microbes. Bacteria are the most common cause of CAP and are divided into two groups:

Typical S. pneumoniae, H. influenzae, S. aureus, GAS, M. catarrhalis, anaerobes, and GNB. Atypical Legionella, Mycoplasma and Chlamydophila pneumoniae.

Community Acquired Pneumonia

A microbiological diagnosis is confirmed in only 20% of cases. There are a few clinical clues that must be considered for the etiology of CAP

Know your local epidemiology Be aware of outbreaks Never forget TB and PJP MRSA is an increasingly recognized cause of severe, necrotizing CAP

Community Acquired Pneumonia

Bacteria are the most common cause of CAP.

S. pneumoniae: Most common cause overall H. influenzae: Important in the elderly, COPD and CF. M. pneumoniae: The most common cause of atypical pneumonias. C. pneumoniae: Accounts for 5-10% of cases. Most common in the elderly. Legionella: Causes 2-8% of cases either sporadically or outbreaks. Klebsiella: Should be considered as a cause in patients who have significant underlying diseases such as COPD, diabetes, and alcohol abuse.

Community Acquired Pneumonia

Pseudomonas: Community acquired Pseudomonas occurs mainly in immunocompromised patients or those with structural lung abnormalities such as CF or bronchiectasis. Acinetobacter: Typically seen in hospitalized patients but starting to emerge in the community. S. aureus: Usually seen in the elderly and young who are recovering from influenza. GAS: Can cause a fulminant pneumonia with early empyema formation even in healthy patients.

Community Acquired Pneumonia

Anaerobes: May be the cause of aspiration pneumonia and lung abscesses. Role is not clear since detection in routine cultures is not possible. N. meningitidis: An uncommon cause of CAP but is reportable to public health and prophylaxis must be given. TB: Missed diagnosis is common and many patients are initially treated for presumed CAP.

Community Acquired Pneumonia Treatment

The selection of specific antibiotics for empiric therapy is based on a number of principles:

The most likely pathogen Clinical trials proving efficacy Risk factors for the presence of resistance Presence of medical co-morbidities

Community Acquired Pneumonia Treatment

Antibiotic recommendations for hospitalized patients are divided between ICU and non-ICU and whether the patient is admitted from a long term care facility. When the etiology of CAP is identified, treatment regimen must be simplified and directed to that pathogen.

Community Acquired Pneumonia Treatment

Not in the ICU

Cefotaxime 1 g q8h and azithromycin 500 mg daily Levofloxicin 750 mg daily or moxifloxacin 400 mg daily Pipericillin/tazobactum 4.5 g q6h or imipenem 500 mg q6h or meropenem 1 g q8h or cefepime 2 g q8h or ceftazidime 2 g q8h PLUS Ciprofloxicin 400 mg q12h or levofloxicin 750 mg daily or aminoglycoside Penicillin allergy use aztreonam, an aminoglycoside, and levofloxicin If initial gram strain suggests S. aureus then add vancomycin 15 mg/kg q12h

Admitted to ICU (high risk for resistant organisms)

Viral Pneumonia

Viruses are estimated to cause adult CAP in 10 to 31% of cases. Influenza A or B occurs in outbreaks and epidemics. They can cause pneumonia although they are more likely to cause a URTI and then predispose to a secondary pneumonia. High risk patients include patients with heart and lung disease, diabetes, renal diseases, immunosuppression, nursing home residents and over 65.

Viral Pneumonia

Parainfluenza are important in the immunocompromised patients causing life threatening lower respiratory tract infections. RSV is more common in children but can cause CAP in elderly. Adenovirus presents with fever, cough, and peribronchial markings with patchy alveolar infiltrates. Metapneumovirus is an emerging pathogen and causes disease in young children and the elderly.

Viral Pneumonia

SARS is a coronavirus that caused an outbreak after it jumped species in 2002. Currently quiescent. Hantavirus is spread from the feces of infected mice. The illness is preceded by prodromal flu-like symptoms followed by ARDS. The virus does not cause pneumonia and the ARDS is from the host response. Avian influenza currently causes sporadic outbreaks but WHO and CDC consider it to be a potential source for the next global pandemic. Varicella pneumonia is the most frequent complication of varicella infection in healthy adults with a case fatality rate of 10-30%.

Fungal Pneumonia

Fungal infections are an unusual cause of CAP in immunocompetent patients but should be considered in those with neutropenia, organ transplant, and HIV. Cyptococcus is mostly asymptomatic and usually discovered incidentally on CXR in normal patients. It is usually symptomatic in immunocompromised patients. Histoplasma proliferates in soil contaminated with bird and bat droppings. Symptomatic patients present with flu-like illness and radiographic abnormalities such as bronchopneumonia and interstitial pneumonitis. Coccidioides typically presents with chest pain, cough, and fever with a normal CXR in up to 50% of patients. It is endemic in the deserts of southwestern North America.

PJP Infection in HIV Patients

Most common opportunistic infection in patients with HIV. Frequently presents as the first manifestation of HIV infection. 75% of the population are infected by age 4. The primary infection is asymptomatic and remains latent throughout life unless the patient becomes immunosuppressed. PJP does not occur until the CD4 count falls below 200 cells/mL.

PJP Infection in HIV Patients

PJP is generally gradual n onset and characterized by fever, cough, and progressive dyspnea and tachypnea. The most common radiographic abnormalities are diffuse, bilateral interstitial or alveolar infiltrates. Other less common presentations include: Pneumothoraces Lobar infiltrates Cysts Nodules Pleural effusions Infection is also associated with a high LDH.

PJP Infection in HIV Patients

Unlike CAP, establishing the diagnosis before starting therapy is important

PJP is less common and may have atypical presentation Therapy may have complications such as steroids with undiagnosed TB

BAL is the procedure of choice for diagnosis with a yield of 97 to 100%

PJP Infection in HIV Patients

Patients with a PaO2 < 70 or a-A gradient > 35 should receive prednisone 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days. TMP/SMX is the preferred treatment, 2 DS tablets q8h but convert to IV if respiratory failure occurs. Continue treatment for 21 days. Start HAART therapy after therapy completion, patients already on treatment should be continued.

Diffuse Alveolar Hemorrhage

Hemoptysis is usually due from the bronchial circulation but DAH causes alveolar bleeding from injury to the alveolar-capillary membrane. Even severe DAH may not have hemoptysis.

Diffuse Alveolar Hemorrhage

One of three histological patterns may be seen:

Pulmonary capillaritis Neutrophillic infiltration of the alveolar septa then capillary necrosis Bland alveolar hemorrhage Characterized by hemorrhage into the alveolar space without inflammation Diffuse alveolar damage The underlying lesions of ARDS can occasionally cause hemorrhage.

Diffuse Alveolar Hemorrhage

The onset of DAH is often abrupt. Hemoptysis can be absent at presentation in a third of DAH cases. The CXR commonly demonstrates new patchy or diffuse alveolar opacities. Recurrent episodes can lead to fibrosis. BAL demonstrates progressive hemorrhagic return and hemosiderin laden macrophages.

Diffuse Alveolar Hemorrhage Clues to the Cause

Exposure history to drugs and chemicals History of BMT and cytotoxic drugs History of systemic vasculitis, collagen vascular disease, or mitral valve disease C-ANCA positive = Wegeners Disease P-ANCA positive = Microscopic Polyarteritis or ChurgStrauss syndrome Anti-GBM = Goodpastures syndrome Hypocomplementemia, ANA+, or anti-DNA+ = SLE Idiopathic pulmonary hemosiderosis is a diagnosis of exclusion and is established by lung biopsy

Diffuse Alveolar Hemorrhage Treatment

Steroids are the mainstay for DAH due to systemic vasculitis, collagen vascular disease and isolated pulmonary capillaritis. Start with Solu-medrol 500-2000 mg daily for 5 days followed by gradual tapering and maintenance on an oral preparation. Do not delay therapy, especially in the face of renal dysfunction, as the renal injury is more likely to be irreversible than the lung disease.

Diffuse Alveolar Hemorrhage Treatment

Cyclophosphamide or azathioprine is added based on the response to steroids or if Wegeners disease is the etiology. Start with a single dose of 0.75 gm/m2 and follow the WBC Plasmapheresis is used in Goodpastures disease although its role may expand in other vasculitis syndromes Treatment for massive hemoptysis is covered in a separate lecture

Idiopathic Eosinophillic Pneumonia

Characterized by eosinophillic infiltration of the pulmonary parenchyma. The cause remains unknown but thought to be an acute hypersensitivity reaction to an unidentified inhaled antigen. Patients present with an acute febrile illness of < 3 weeks, tachypnea, and inspiratory crackles. 63% develop respiratory failure and need mechanical ventilation.

Idiopathic Eosinophillic Pneumonia

The WBC is elevated with a high eosinophil fraction. If measured, the IgE level is high. In addition, eosinophils are found in the pleural fluid and BAL. CT scan demonstrates bilateral, random, and patchy ground glass or reticular opacities. Treatment is with steroids only and usually there is a dramatic (12 to 48 hours) response with no relapse.

Summary
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ARDS/ALI is marked by inflammation and edema in the lungs. ARDS is a syndrome diagnosis and, therefore, any reversible underlying cause must be sought.
Bacterial pneumonia Viral pneumonia Fungal pneumonia PJP Diffuse alveolar hemorrhage Eosinophillic pneumonia Lupus pneumonitis Toxic drug reaction

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Supportive therapy includes a low tidal volume, high PEEP lung protection strategy.