Acute Dyspnea: Try Physiologic Approach in Differential Diagnosis

DENVER – If you presume that a patient who comes to the emergency department with acute dyspnea primarily has a pulmonary cause, you’ll almost always be right. Those few other cases, though, take a bit of detective work.

In the approximately 5% of cases in which dyspnea is not easily referable to the lungs, the culprit may be a cardiac problem (usually in a very young child) or, rarely, other problems – hemoglobinopathies, diseases that cause metabolic acidosis, or neurologic disorders, Dr. Jeffrey Sankoff said at the annual meeting of the American College of Emergency Physicians.

Take a physiologic approach that can guide you through the differential diagnosis, he suggested. "As somebody who trained in critical care, everything boils down to physiology," said Dr. Sankoff of the University of Colorado, Denver, and director of quality and patient safety at Denver Health Medical Center.

To begin, think of diseases that cause hypoxemia, hypercapnia, or metabolic acidosis, which lead to dyspnea.

Hypoxemia

The most common cause of hypoxemia is ventilation-perfusion (V-Q) mismatch, in which blood flows in the lungs but areas are not getting oxygen. Diffusion abnormalities, in which oxygen gets into alveoli but oxygen transit to the bloodstream is impaired, also cause hypoxemia. These occur in primary pulmonary disease.

But extrapulmonary disease processes create four causes of hypoxemia: a shunt, low mixed venous oxygen saturation (MVO₂), decreased fraction of inspired oxygen (FiO₂), and alveolar hypoventilation.

A V-Q mismatch at its most extreme is a shunt, in which blood bypasses the lungs altogether, he said. Disease processes that cause blood to go directly from the right to the left side of circulation result in hypoxemia. A shunt is almost always intracardiac, rarely intrapulmonary.

In children, shunts are seen at characteristic times for the development of cyanotic congenital heart disease, most commonly patent ductus arteriosus in an infant.

Look for a shunt by its hallmark – oxygen saturation will not improve when you give the patient oxygen. "This is the test for any young child under the age of 6 weeks who comes to the emergency department hypoxemic," Dr. Sankoff said.

Adults with shunts will have a murmur as well as dyspnea. "Adults don’t develop shunts de novo. This is going to be happening as part of some acute process," he said. The chest x-rays in adults with shunts often are normal.

The second cause of hypoxia – low MVO₂ – occurs mainly when blood flows too slowly through the capillary bed, allowing excess oxygen extraction, and blood returns to the heart in a deoxygenated state. When you see this, focus on right ventricular impairment to identify the etiology. Left ventricular impairment will show up on x-ray as pulmonary edema. A right-sided infarction or cor pulmonale from pulmonary embolism will impair right ventricular function. Cardiac tamponade from infectious, inflammatory, or neoplastic processes also can cause low MVO₂ and dyspnea, though nobody really understands why, he added.

The third cause of hypoxia– decreased FiO– usually is a problem relegated to people at high altitudes or industrial workers in enclosed spaces, where hypoxemia (low partial pressure of oxygen in blood) causes hypoxia (low oxygen levels in tissues). But Dr. Sankoff uses this category to remind himself to look for diseases that are not associated with lower FiO₂ and hypoxemia but still are associated with hypoxia – primarily hemoglobinopathies.

"If a patient has 100% oxygen saturation yet is hypoxic, they have a problem with hemoglobin," Dr. Sankoff said. It may be a severe or acute garden-variety anemia causing the dyspnea, or occasionally a hereditary hemoglobinopathy such as thalassemia or sickle cell disease. To diagnose these, have a high index of suspicion. You’ll see no patient improvement on oxygen therapy, and some diseases create a characteristic appearance of the blood.

Alveolar hypoventilation may be the most insidious cause of hypoxemia, and dyspnea and may be a flag for impending respiratory compromise if the patient has peripheral weakness. The most common acquired causes of peripheral neuromuscular weakness are Guillain-Barre syndrome, amyotrophic lateral sclerosis, and Colorado tick paralysis.

Make the diagnosis in context with other findings, he said. Expect an abnormal motor exam. Check the negative inspiratory force; if it isn’t at least –20 cm H₂O, it’s abnormal and the patient likely will need respiratory support.

Hypercapnia

Diseases that cause hypercapnia can cause dyspnea. Three things cause carbon dioxide levels in the blood to rise: increased metabolic rate (which tends to be seen in the ICU, not in the emergency department), decreased minute ventilation, and increased pulmonary dead space. All can be diagnosed by checking arterial blood gases.

Metabolic Acidosis

Acidosis, usually due to high levels of lactate, stimulates respiratory drive to try and balance pH. Sepsis is the most important cause of acidosis. When sepsis is developing, dyspnea frequently is a subtle sign. Have a high index of suspicion for sepsis, and be wary of a normal oxygen saturation level in a patient with dyspnea, he said. Other causes of metabolic acidosis that lead to dyspnea include diabetic or alcoholic ketoacidosis.

Putting this physiologic approach to dyspnea into context, consider three scenarios, Dr. Sankoff suggested. A patient with dyspnea who responds to oxygen therapy and has an abnormal chest x-ray has a primary pulmonary problem. A patient who responds to oxygen but has a normal chest x-ray may have sepsis, another cause of acidosis, or alveolar hypoventilation; their response to oxygen may be transient. They will respond to oxygen but continue to be tachypneic.

The third scenario – normal x-ray, but the patient does not respond to oxygen therapy – raises a broad differential diagnosis including sepsis, other causes of acidosis, hypercapnia, cardiac causes, and hemoglobinopathies. Narrow the differential by recalling the history and physical findings and getting arterial blood gas tests.

Only after everything else has been excluded should you consider anxiety or pain as the cause of dyspnea, he said.

Dr. Sankoff reported having no financial disclosures.

DENVER – If you presume that a patient who comes to the emergency department with acute dyspnea primarily has a pulmonary cause, you’ll almost always be right. Those few other cases, though, take a bit of detective work.

In the approximately 5% of cases in which dyspnea is not easily referable to the lungs, the culprit may be a cardiac problem (usually in a very young child) or, rarely, other problems – hemoglobinopathies, diseases that cause metabolic acidosis, or neurologic disorders, Dr. Jeffrey Sankoff said at the annual meeting of the American College of Emergency Physicians.

Take a physiologic approach that can guide you through the differential diagnosis, he suggested. "As somebody who trained in critical care, everything boils down to physiology," said Dr. Sankoff of the University of Colorado, Denver, and director of quality and patient safety at Denver Health Medical Center.

To begin, think of diseases that cause hypoxemia, hypercapnia, or metabolic acidosis, which lead to dyspnea.

Hypoxemia

The most common cause of hypoxemia is ventilation-perfusion (V-Q) mismatch, in which blood flows in the lungs but areas are not getting oxygen. Diffusion abnormalities, in which oxygen gets into alveoli but oxygen transit to the bloodstream is impaired, also cause hypoxemia. These occur in primary pulmonary disease.

But extrapulmonary disease processes create four causes of hypoxemia: a shunt, low mixed venous oxygen saturation (MVO₂), decreased fraction of inspired oxygen (FiO₂), and alveolar hypoventilation.

A V-Q mismatch at its most extreme is a shunt, in which blood bypasses the lungs altogether, he said. Disease processes that cause blood to go directly from the right to the left side of circulation result in hypoxemia. A shunt is almost always intracardiac, rarely intrapulmonary.

In children, shunts are seen at characteristic times for the development of cyanotic congenital heart disease, most commonly patent ductus arteriosus in an infant.

Look for a shunt by its hallmark – oxygen saturation will not improve when you give the patient oxygen. "This is the test for any young child under the age of 6 weeks who comes to the emergency department hypoxemic," Dr. Sankoff said.

Adults with shunts will have a murmur as well as dyspnea. "Adults don’t develop shunts de novo. This is going to be happening as part of some acute process," he said. The chest x-rays in adults with shunts often are normal.

The second cause of hypoxia – low MVO₂ – occurs mainly when blood flows too slowly through the capillary bed, allowing excess oxygen extraction, and blood returns to the heart in a deoxygenated state. When you see this, focus on right ventricular impairment to identify the etiology. Left ventricular impairment will show up on x-ray as pulmonary edema. A right-sided infarction or cor pulmonale from pulmonary embolism will impair right ventricular function. Cardiac tamponade from infectious, inflammatory, or neoplastic processes also can cause low MVO₂ and dyspnea, though nobody really understands why, he added.

The third cause of hypoxia– decreased FiO– usually is a problem relegated to people at high altitudes or industrial workers in enclosed spaces, where hypoxemia (low partial pressure of oxygen in blood) causes hypoxia (low oxygen levels in tissues). But Dr. Sankoff uses this category to remind himself to look for diseases that are not associated with lower FiO₂ and hypoxemia but still are associated with hypoxia – primarily hemoglobinopathies.

"If a patient has 100% oxygen saturation yet is hypoxic, they have a problem with hemoglobin," Dr. Sankoff said. It may be a severe or acute garden-variety anemia causing the dyspnea, or occasionally a hereditary hemoglobinopathy such as thalassemia or sickle cell disease. To diagnose these, have a high index of suspicion. You’ll see no patient improvement on oxygen therapy, and some diseases create a characteristic appearance of the blood.

Alveolar hypoventilation may be the most insidious cause of hypoxemia, and dyspnea and may be a flag for impending respiratory compromise if the patient has peripheral weakness. The most common acquired causes of peripheral neuromuscular weakness are Guillain-Barre syndrome, amyotrophic lateral sclerosis, and Colorado tick paralysis.

Make the diagnosis in context with other findings, he said. Expect an abnormal motor exam. Check the negative inspiratory force; if it isn’t at least –20 cm H₂O, it’s abnormal and the patient likely will need respiratory support.

Hypercapnia

Diseases that cause hypercapnia can cause dyspnea. Three things cause carbon dioxide levels in the blood to rise: increased metabolic rate (which tends to be seen in the ICU, not in the emergency department), decreased minute ventilation, and increased pulmonary dead space. All can be diagnosed by checking arterial blood gases.

Metabolic Acidosis

Acidosis, usually due to high levels of lactate, stimulates respiratory drive to try and balance pH. Sepsis is the most important cause of acidosis. When sepsis is developing, dyspnea frequently is a subtle sign. Have a high index of suspicion for sepsis, and be wary of a normal oxygen saturation level in a patient with dyspnea, he said. Other causes of metabolic acidosis that lead to dyspnea include diabetic or alcoholic ketoacidosis.

Putting this physiologic approach to dyspnea into context, consider three scenarios, Dr. Sankoff suggested. A patient with dyspnea who responds to oxygen therapy and has an abnormal chest x-ray has a primary pulmonary problem. A patient who responds to oxygen but has a normal chest x-ray may have sepsis, another cause of acidosis, or alveolar hypoventilation; their response to oxygen may be transient. They will respond to oxygen but continue to be tachypneic.

The third scenario – normal x-ray, but the patient does not respond to oxygen therapy – raises a broad differential diagnosis including sepsis, other causes of acidosis, hypercapnia, cardiac causes, and hemoglobinopathies. Narrow the differential by recalling the history and physical findings and getting arterial blood gas tests.

Only after everything else has been excluded should you consider anxiety or pain as the cause of dyspnea, he said.

Dr. Sankoff reported having no financial disclosures.

DENVER – If you presume that a patient who comes to the emergency department with acute dyspnea primarily has a pulmonary cause, you’ll almost always be right. Those few other cases, though, take a bit of detective work.

In the approximately 5% of cases in which dyspnea is not easily referable to the lungs, the culprit may be a cardiac problem (usually in a very young child) or, rarely, other problems – hemoglobinopathies, diseases that cause metabolic acidosis, or neurologic disorders, Dr. Jeffrey Sankoff said at the annual meeting of the American College of Emergency Physicians.

Take a physiologic approach that can guide you through the differential diagnosis, he suggested. "As somebody who trained in critical care, everything boils down to physiology," said Dr. Sankoff of the University of Colorado, Denver, and director of quality and patient safety at Denver Health Medical Center.

To begin, think of diseases that cause hypoxemia, hypercapnia, or metabolic acidosis, which lead to dyspnea.

Hypoxemia

The most common cause of hypoxemia is ventilation-perfusion (V-Q) mismatch, in which blood flows in the lungs but areas are not getting oxygen. Diffusion abnormalities, in which oxygen gets into alveoli but oxygen transit to the bloodstream is impaired, also cause hypoxemia. These occur in primary pulmonary disease.

But extrapulmonary disease processes create four causes of hypoxemia: a shunt, low mixed venous oxygen saturation (MVO₂), decreased fraction of inspired oxygen (FiO₂), and alveolar hypoventilation.

A V-Q mismatch at its most extreme is a shunt, in which blood bypasses the lungs altogether, he said. Disease processes that cause blood to go directly from the right to the left side of circulation result in hypoxemia. A shunt is almost always intracardiac, rarely intrapulmonary.

In children, shunts are seen at characteristic times for the development of cyanotic congenital heart disease, most commonly patent ductus arteriosus in an infant.

Look for a shunt by its hallmark – oxygen saturation will not improve when you give the patient oxygen. "This is the test for any young child under the age of 6 weeks who comes to the emergency department hypoxemic," Dr. Sankoff said.

Adults with shunts will have a murmur as well as dyspnea. "Adults don’t develop shunts de novo. This is going to be happening as part of some acute process," he said. The chest x-rays in adults with shunts often are normal.

The second cause of hypoxia – low MVO₂ – occurs mainly when blood flows too slowly through the capillary bed, allowing excess oxygen extraction, and blood returns to the heart in a deoxygenated state. When you see this, focus on right ventricular impairment to identify the etiology. Left ventricular impairment will show up on x-ray as pulmonary edema. A right-sided infarction or cor pulmonale from pulmonary embolism will impair right ventricular function. Cardiac tamponade from infectious, inflammatory, or neoplastic processes also can cause low MVO₂ and dyspnea, though nobody really understands why, he added.

The third cause of hypoxia– decreased FiO– usually is a problem relegated to people at high altitudes or industrial workers in enclosed spaces, where hypoxemia (low partial pressure of oxygen in blood) causes hypoxia (low oxygen levels in tissues). But Dr. Sankoff uses this category to remind himself to look for diseases that are not associated with lower FiO₂ and hypoxemia but still are associated with hypoxia – primarily hemoglobinopathies.

"If a patient has 100% oxygen saturation yet is hypoxic, they have a problem with hemoglobin," Dr. Sankoff said. It may be a severe or acute garden-variety anemia causing the dyspnea, or occasionally a hereditary hemoglobinopathy such as thalassemia or sickle cell disease. To diagnose these, have a high index of suspicion. You’ll see no patient improvement on oxygen therapy, and some diseases create a characteristic appearance of the blood.

Alveolar hypoventilation may be the most insidious cause of hypoxemia, and dyspnea and may be a flag for impending respiratory compromise if the patient has peripheral weakness. The most common acquired causes of peripheral neuromuscular weakness are Guillain-Barre syndrome, amyotrophic lateral sclerosis, and Colorado tick paralysis.

Make the diagnosis in context with other findings, he said. Expect an abnormal motor exam. Check the negative inspiratory force; if it isn’t at least –20 cm H₂O, it’s abnormal and the patient likely will need respiratory support.

Hypercapnia

Diseases that cause hypercapnia can cause dyspnea. Three things cause carbon dioxide levels in the blood to rise: increased metabolic rate (which tends to be seen in the ICU, not in the emergency department), decreased minute ventilation, and increased pulmonary dead space. All can be diagnosed by checking arterial blood gases.

Metabolic Acidosis

Acidosis, usually due to high levels of lactate, stimulates respiratory drive to try and balance pH. Sepsis is the most important cause of acidosis. When sepsis is developing, dyspnea frequently is a subtle sign. Have a high index of suspicion for sepsis, and be wary of a normal oxygen saturation level in a patient with dyspnea, he said. Other causes of metabolic acidosis that lead to dyspnea include diabetic or alcoholic ketoacidosis.

Putting this physiologic approach to dyspnea into context, consider three scenarios, Dr. Sankoff suggested. A patient with dyspnea who responds to oxygen therapy and has an abnormal chest x-ray has a primary pulmonary problem. A patient who responds to oxygen but has a normal chest x-ray may have sepsis, another cause of acidosis, or alveolar hypoventilation; their response to oxygen may be transient. They will respond to oxygen but continue to be tachypneic.

The third scenario – normal x-ray, but the patient does not respond to oxygen therapy – raises a broad differential diagnosis including sepsis, other causes of acidosis, hypercapnia, cardiac causes, and hemoglobinopathies. Narrow the differential by recalling the history and physical findings and getting arterial blood gas tests.

Only after everything else has been excluded should you consider anxiety or pain as the cause of dyspnea, he said.

Dr. Sankoff reported having no financial disclosures.