- Understand causes of hypoxia and hypoxemia (~10-15 min)
- Basic evaluation of acute onset dyspnea or hypoxia in a patient in the hospital (~10 min)
This webpage is meant to serve as the teaching platform for this chalk talk. However, this can talk can also be done on as a chalk talk on a whiteboard or chalkboard. Click here for Chalk Talk format teaching script. To abbreviate the teaching session by ~ 5 min, skip over the “Causes of Hypoxia” to the “Causes of Hypoxemia” section. Understanding the causes of hypoxia can be helpful in explaining why anemia or ACS can cause hypoxia in the absence of any pulmonary findings or with normal PaO2. Additionally, these patients do not respond to 100% FiO2.
This webpage is meant to serve as the teaching platform for this chalk talk. However, this can talk can also be done on as a chalk talk on a whiteboard or chalkboard. Click here for Chalk Talk format teaching script.
To abbreviate the teaching session by ~ 5 min, skip over the “Causes of Hypoxia” to the “Causes of Hypoxemia” section. Understanding the causes of hypoxia can be helpful in explaining why anemia or ACS can cause hypoxia in the absence of any pulmonary findings or with normal PaO2. Additionally, these patients do not respond to 100% FiO2.
Hypoxia and Hypoxemia
Causes of Hypoxia
While often used interchangeably, hypoxia and hypoxemia are not synonymous. Hypoxia refers to decreased oxygenation at a tissue level and can roughly be divided into “respiratory”, “cardiac” and “blood or tissue” causes of hypoxia1,2. Not all causes of hypoxia result in hypoxemia, which is a defined as decreased partial pressure of oxygen (PaO2< 60-80 mmHg) or percent bound to hemoglobin (SaO2 <90-95%)4.
Clinically, patients most commonly develop hypoxic hypoxia, stagnant hypoxia or anemia as a cause of hypoxia while in the hospital. However, cyanide poisoning and methemoglobemia can rarely occur while inpatient as a result of exposure to certain drugs. Sodium nitroprusside can result in cyanide poisoning and use of nitrates (including nitroglycerin), local anesthetics, and sulfonamides can result in methemoglobinemia.
Causes of Hypoxemia
There are five causes of hypoxemia (decreased PaO2 or SaO2). The A-a gradient and response to 100% FiO2 can be used to differentiate between these causes. The A-a gradient is the difference between the PaO2 and PAO2 (alveolar oxygenation). PaO2 is directly measured on an ABG, but PAO2 is calculated:
PAO2 = 0.21 (Patm– PH2O) – [PaCO2/RQ]
Patm – partial pressure of the atmosphere, at sea level is 760 mmHg
PH2O – partial pressure of the water, 47 mmHg
RQ – respiratory quotient, for most patients on a regular diet is 0.8
Normal A-a gradient is determined by age. An easy estimate is ~ 15, but is formally calculated as:
Expected A-a gradient = (age/4) + 4
V/Q mismatch, diffusion limitation and shunt are associated with an elevated A-a gradient; where as, hypoventilation and decreased FiO2 are associated with a normal A-a gradient.
Hypoventilation, V/Q mismatch and shunt are the main causes of hypoxemia that occur acutely in the hospital setting. Click to understand the relationship between shunt fraction and response to oxygen therapy (~ 1 min).
Basic Differential and Evaluation of Inpatient Dyspnea and Hypoxia
Dyspnea and hypoxia occur frequently in hospitalized patients. Dyspnea and tachypnea can occur without associated hypoxia such as patients with a metabolic acidosis or those with psychogenic causes of dyspnea (e.g. anxiety). The below diagram is a an anatomic way to organize different inpatient causes of dyspnea and hypoxia in the hospital (though should not be taken as a comprehensive list).
Draw the below diagram on the board or project the empty diagram. Primary causes can be separated into “respiratory”, “cardiac ” and “other” causes. The respiratory system can be further separate into pathology with the airways, the alveoli and the pulmonary vasculature. A blockage or narrowing at any of these levels results in dyspnea and/or hypoxia. To make it an interactive learning experience, have your learners walk through anatomically thinking about pathologies that result in blockages/narrowing at each level (e.g. upper airway, bronchioles, then alveoli, etc.).
Draw the below diagram on the board or project the empty diagram. Primary causes can be separated into “respiratory”, “cardiac ” and “other” causes. The respiratory system can be further separate into pathology with the airways, the alveoli and the pulmonary vasculature. A blockage or narrowing at any of these levels results in dyspnea and/or hypoxia.
To make it an interactive learning experience, have your learners walk through anatomically thinking about pathologies that result in blockages/narrowing at each level (e.g. upper airway, bronchioles, then alveoli, etc.).
Causes of hypoxia/dyspnea not related to the respiratory or cardiac systems can be simplified as the “3 A’s – anxiety, anemia, and acidosis.”
Evaluation of anyone with hypoxia or dyspnea should start with a physical exam (detailed physical exam findings). Vitals signs and work of breathing. In a patient with evidence of low oxygen saturations, response to 100% FiO2 can help differentiate a large shunt or anemia related hypoxia from other causes of hypoxia.
Initial work up (detailed work-up) could include CXR, EKG, BMP and CBC. Whether an ABG or VBG is truly needed depends on the clinical scenario. An ABG is particularly helpful if a hypoxemic patient has an unrevealing CXR. Calculation of an A-a gradient and pH/PCO2 may suggest hypoventilation driving hypoxemia (normal A-a gradient) or PE (elevated A-a gradient).
TAKE HOME POINTS:
- Shunt, V/Q mismatch and hypoventilation are the most common causes of inpatient hypoxemia.
- Hypoventilation can be differentiated by a normal A-a gradient.
- A large shunt can be differentiated by a blunted response to 100% oxygen.
Now you’re ready apply what you’ve learned with some practice cases!
Learn more about oxygen delivery systems here.
CHALK TALK TEACHING SCRIPT
Click on each diagram for the teaching script.
Board set up:
EXAMPLE CASES (~ 5 min each)
A 45 year old man admitted for AKI and management of back pain after recently diagnosed renal cell carcinoma, develops increased shortness of breath on POD2. He reports pleuritic bilateral chest pain and denies fevers, chills or cough. Vitals are notable for T 36.7, HR 125, BP 125/75, RR 24, 96% on 3L NC. On exam, he is tachypneic and uncomfortable but able to speak in full sentences. Lungs are clear to auscultation and JVD is 9 cm H2O.
What additional work-up do you want right now?
- ABG 7.50/30/68/22 on 3L NC
- CBC shows stable hct of 28 from earlier in the day
- ECG – sinus tachycardia without ischemic ST or T wave changes
- CXR below:
Above CXR image from http://images.radiopaedia.org/images/903193/063b041ff51e064424ba056806564a.jpg
How would you interpret his ABG?
He has an acute respiratory alkalosis and elevated A-a gradient.
What is your differential for his hypoxemic respiratory failure? How would you further evaluate your differential?
- Pulmonary embolus (PE)
- High suspicion based on history of malignancy and recent surgery
- Order a CT PE or VQ scan for evaluation
- Given that his Cr >2, he should be pre-hydrated prior to getting a CT PE
- If you have high suspicion and confirmatory testing cannot be obtained immediately, empirically anticoagulate while awaiting confirmatory testing
- Acute coronary syndrome (ACS)
- Lower suspicion given EKG without any ischemic changes
- Can be further evaluated with serial EKGs and troponins
- Heart failure exacerbation
- Lower suspicion given normal JVP and CXR without evidence of pulmonary edema
- BNP can further assess atrial stretch, though may be elevated in the setting of elevated Cr alone
Final Diagnosis and Teaching Points
CT the next day showed evidence of saddle embolus. He was continued on heparin gtt therapy. Troponin and BNP were both mildly elevated in the setting of a large/submassive PE.
Take Home Points:
- If you suspect PE and diagnostic imaging is going to be delayed, it is appropriate to initiate empiric anticoagluation, so long as there are no major contraindications to anticoagulation.
- Most common CXR finding in PE is a normal CXR.
A 64 year old man with HFrEF of 40% and severe COPD (FEV1 0.9L) presents to the ED with increased cough and SOB over the past three days. He denies fever or chest pain but reports sore throat, increased sputum production and “chest congestion”. He has been using his inhalers around the clock and he doubled his dose of diuretics for the past three days without improvement in his symptoms. On exam, he is afebrile, RR 32, has poor air movement on auscultation of his lungs but no appreciable wheezing.
What additional work-up would you want?
- ABG 7.25/92/35/100 on 6L NC
- BMP notable for Cr 2.1 (prev 1.0), HCO3 of 37
- EKG shows sinus tachycardia without evidence of
- CXR shows hyperinflation without evidence of focal infiltrates
- D-dimer negative
- BNP 250 (baseline BNP ~400s)
How would you interpret this ABG?
He has an acute on chronic (or partially compensated) respiratory acidosis and elevated A-a gradient.
What is the most likely diagnosis?
Most likely diagnosis is a COPD exacerbation. In patients with severe obstruction and bronchoconstriction, wheezing may not be audible because of poor air movement. The clinical signs and laboratory findings of COPD exacerbation can be difficult to distinguish from a PE, but this patient has a negative D-dimer and has low pre-test probability so is unlikely to have a PE.
How would you manage this patient?
- Initiate treatment of COPD: albuterol/ipratroprium nebulizers, steroids and consideration of antibiotics
- Initiate Bilevel for his acute hypercarbic and hypoxemic respiratory failure! He is the perfect population to initiate Bilevel in since he is still mentating well as long as his secretions do not limit his ability to tolerate the mask.
Take Home Points:
- Wheezing can be absent in severe airflow obstruction
- Initiate Bilevel in patients with acute hypercarbic and hypoxemic respiratory failure secondary to a COPD exacerbation
A 20 yo female with a history of developmental delay was admitted for acute hypoxemic respiratory failure requiring intubation for parainfluenza infection. She was extubated 3 days ago and has been stably on 3-4L NC. She has had thick secretions and weak cough but has not been aggressively suctioned because of agitation. She was found to be acutely hypoxic to 80% FiO2 with moderately increased work of breathing. On exam, her RR is ~ 25-30 with no accessory muscle use. She was placed on 100% NRB with improvement in her saturations to 90%. A CXR showed:
What is the differential for this finding?
Her CXR shows opacification of the L hemithorax. The differential for this is a large pleural effusion or lung collapse.
This can be differentiated by looking at the direction of tracheal deviation. A large pleural effusion will push the trachea away from the opacified hemithorax while lung collapse will cause the trachea to deviate towards the opacified hemithorax.
Final Diagnosis and Take Home Points:
She had a large mucus plug in her left mainstem bronchi which cause total collapse of her left lung. She was reintubated and underwent a bronchoscopy to remove her mucus plug. Her post-bronchoscopy CXR shows reinflation of her L lung with some persistent alveolar infiltrates.
Take Home Points:
- Opacification of a hemothorax is caused by a large pleural effusion or lung collapse
- Direction of tracheal deviation can help distinguish between these two diagnoses. In lung collapse, the trachea is pulled TOWARDS the opacified side. In pleural effusion, the trachea is PUSHED away from the opacified side.
A 75 year old woman with a history of mitral stenosis and atrial fibrillation is POD1 from cystoscopic resection of a bladder mass. Intraoperatively, she recieved 1U pRBCs and 3L of IVF for atrial fibrillation with rapid ventricular response (RVR) with heart rates in 150s. Immediately post-operatively, she continued to have heart rates in the 120s and was started on metoprolol. Over the past few hours, she has reported increasing shortness of breath and has had an increase in oxygen requirement from 1L NC to 60% high flow nasal cannula. She reports some mild chest tightness but no fevers, cough, or pleurisy.
What additional evaluation and work-up do you want?
- Physical exam – JVP 11 cm H2O, new 1+ bilateral LE edema, crackles on lung auscultation bilaterally up to mid-lung fields
- CBC with hct of 24% after 1U of pRBCs
- BMP shows normal Cr and HCO3 of 21
Above image courtesy of Dr Jeremy Jones, from the case”https://radiopaedia.org/cases/6463″>rID: 6463.
What is the most likely diagnosis?
The CXR shows bilateral diffuse alveolar infiltrates and cephalization consistent with pulmonary edema. In the setting of recent transfusion this could represent a transfusion reaction – either TRALI (transfusion related acute lung injury) or TACO (transfusion associated circulatory overload). More likely, she developed acute cardiogenic pulmonary edema from AF with RVR in the setting of pre-existing mitral stenosis.
Patients with mitral stenosis are reliant on a sufficient long diastole and atrial contraction to adequately fill the left ventricle. Tachycardia decreases diastolic filling time and atrial fibrillation eliminates effective atrial contraction.
How do you want to manage the patient?
- Start CPAP or Bilevel! Positive pressure from either CPAP or Bilevel results in decrease in venous return (decreases preload) and decreased afterload.
- Get an ABG before initiation of CPAP/Bilevel and re-evaluate with a repeat ABG in 20-30 min.
- Start diuresis for acute cardiogenic pulmonary edema
- In this patient in particular, aggressive attempts should be made at rate control (increase AV nodal blockade with beta-blockers or calcium channel blockers). Strong consideration should be given rhythm control in this patient because of underlying mitral stenosis.
Take Home Points:
- Non-invasive positive pressure ventilation (CPAP or BiPAP) should be used in acute hypoxemic respiratory failure from
- Tachycardia and atrial fibrillation are poorly tolerated in patients with mitral stenosis because of the lack of atrial contraction and decrease in left ventricular filling time
A 68 yo woman with metastatic breast cancer admitted for cancer-related back pain was found to be acutely hypoxemic to 70% FiO2 and RR in the 30s. She was placed on 100% NRB with improvement in her saturations to 85%. On exam, she has wet upper airway sounds that are transmitted throughout all lung fields. There is little airway movement at the L base. She is unable to respond to any questions because of respiratory distress. She is DNR/DNI.
What is your differential diagnosis?
Failure to respond to 100% oxygen suggests the presence of a large shunt. A CXR will be helpful in identifying causes including:
- Large aspiration event
- Mucus plugging with lobar collapse
- Flash pulmonary edema (that may be precipitated by ACS)
- Large PTX or pleural effusion causing lobar collapse
What additional evaluation would you want?
- An ABG was deferred, but a VBG showed a signs of hyperventilation 7.45/30/-/21
- BMP is stable with HCO3 of 21
- CBC shows hct of 36, stable from prior
- EKG shows sinus tachycardia without any ischemic changes and troponin was 0.04
- A CXR is shown below
Final Diagnosis and Take Home Points:
Her hypoxemia was related to mucus plugging from thick secretions. Her CXR shows evidence of L basilar consolidation and elevation of the L hemidiaphragm consistent with left lower lobe collapse.
Take Home Points:
- Failure to respond to 100% FiO2 indicates presence of a large shunt
- Pittman RN. Regulation of Tissue Oxygenation. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. Chapter 7, Oxygen Transport in Normal and Pathological Situations: Defects and Compensations. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54113/
- Chapter 8. Acid-Base Balance. In: Levitzky MG. eds. Pulmonary Physiology, 8e New York, NY: McGraw-Hill; 2013. http://accessmedicine.mhmedical.com.offcampus.lib.washington.edu/content.aspx?bookid=575§ionid=42512986. Accessed July 10, 2017.
- Sarkar M, Niranjan N, Banyal P. Mechanisms of hypoxemia. Lung India : Official Organ of Indian Chest Society. 2017;34(1):47-60. doi:10.4103/0970-2113.197116.
- Johannes, J & Saggar R. Arterial Hypoxemia. In: Vincent, JL et al, eds. Textbook of Critical Care. 7th ed. Philadelphia, PA. Elsevier Inc. 2017.