Hypoxia in the ED Setting: Systematic Approach and Management

Authors: Michael Andrew Tandlich, MD (EM Resident Physician, Northwestern University) and Timothy M. Loftus, MD, MBA (EM Attending Physician, Northwestern University) // Edited by: Bryant Allen, MD (EM Attending Physician, Carolinas Medical Center): Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case 1:

An 87-year-old male with history significant for chronic obstructive pulmonary disease, myelodysplastic syndrome complicated by anemia of chronic disease, obstructive sleep apnea, coronary artery bypass grafting, and percutaneous coronary interventions for coronary artery disease, with over a one-year history of exertional dyspnea, presented to the ED with one to two weeks of worsening dyspnea on exertion. Patient states he would feel his dyspnea worsen with any movement. In the ED, his vital signs were stable, and there was no hypoxia at rest, but upon standing upright, he was noted to have an abrupt oxygen desaturation on a pulse oximeter to 86% on room air. Laboratory studies were remarkable for a hemoglobin level of 8.2 g/dL, down from 9.6 g/dL two weeks prior. Chest x-ray and ECG showed no acute processes. The patient was transfused one unit of packed red blood cells and admitted to the hospital medicine floor for further management.

Case 2:

A 2-year-old female previously healthy with up-to-date immunizations presents to the ED with two days of lethargy, fever, rhinorrhea, and difficulty breathing. On exam, the patient appeared normal color with no increased work of breathing. Vitals notable for HR 137, RR 23, T 37.8, SpO₂ 65% on room air, improved to 78% on 15L NRB. Exam was notable for normal breath sounds and respiratory effort, normal heart sounds without auscultated murmurs, and an otherwise normal exam. An arterial blood gas was performed, demonstrating a true oxygen saturation of 96 percent.

What is hypoxia?

Hypoxia is the condition when body tissues receive inadequate oxygen. This leads to disruption in cellular function. There may be a switch to anaerobic metabolism and subsequent lactic acidosis. While low blood oxygen content, also known as hypoxemia, is a major cause of hypoxia, it is not the only cause.

What are the major etiologies of hypoxia?

Hypoxia can best be broken down into four major categories:

• Hypoxemia
• Anemic Hypoxia
• Ischemic/Stagnant Hypoxia
• Histotoxic Hypoxia

Hypoxemia

Hypoxia which refers to the state of low oxygen concentration in the blood itself, and largely depends on five key factors:

• Altitude: As one moves to higher altitudes, the barometric pressure drops, resulting in the amount of oxygen content inspired to be decreased despite a stable FiO₂. At the extremes of altitude, an otherwise healthy lung would not see enough oxygen in the inspired air to adequately supply metabolism of the body tissues.

• Ventilation: Ventilation refers to the supply of gases to the alveoli and is directly tied to clearance of CO₂. Hypoventilation leads to CO₂buildup, decreased CO₂ clearance, and subsequent decreased concentration of alveolar oxygen. In many disease processes, an increase in CO₂ itself may drive increased work of breathing and is correlated with lung compliance and airway resistance. For example, a patient with acute asthma exacerbation will have high airway resistance which will exacerbate work of breathing.

• Oxygen Diffusion: This is the ability of oxygen to cross the alveoli and surround capillary membranes effectively. Transport may be impaired because of a primary tissue disease process, such as in pulmonary fibrosis.

• Ventilation/Perfusion (V/Q) Matching: There is a balance between oxygenation of alveoli and blood flow through their capillaries. Mismatch between these two factors will occur when blood flows through alveoli with inadequate ventilation, or when blood does not reach alveoli that do have adequate ventilation. Examples of this is include pulmonary embolism, in which perfusion is obstructed, and status asthmaticus, in which airway collapse causes air trapping and ventilation obstruction. Mismatch may be corrected when excess oxygen is inhaled, since even poorly ventilated areas of the lung will receive adequate flow of oxygen. It is important to note that ventilation and perfusion matching is heterogeneous throughout different areas of the lung in normal state and is exacerbated by certain conditions affecting V/Q mismatch (e.g. asthma, pneumonia).

• Blood Shunting: Shunting of blood refers to the bypassing of the process by which blood receives oxygenation. In other words, blood enters systemic circulation before receiving adequate oxygenation. Classic examples of blood shunting occur with anatomic defects such as intracardiac septal defects. Mucus plugging of one mainstem bronchus is another example of shunt physiology. In either case, an increase fraction of inspired oxygen will not fill alveoli which are receiving blood, and classically will not correct hypoxemia.

Anemic hypoxia

Hypoxia may occur if there is a critically low blood oxygen carrying capacity. Acute changes in hemoglobin level (such as from acute blood loss anemia and hypovolemic shock) may result in decreased transport of oxygen to tissues. Hypoxia may also result from changes in the hemoglobin functionality such as during acute carbon monoxide poisoning, where there are plenty of hemoglobin molecules which simply are not able to bind oxygen.

Ischemic/stagnant hypoxia

Hypoxia may result from a critical decrease in the flow of oxygenated blood to peripheral tissues. Systemic conditions such as cardiogenic shock may lead to decrease oxygenation of blood during pulmonary gas exchange as well as inadequate global delivery of blood to central and peripheral organs. Localized conditions may impede cellular diffusion of oxygen (such as with severe tissue edema) or focally impede flow of oxygenated blood (such as with arterial damage or obstruction).

Histotoxic hypoxia

Hypoxia may result from low tissue utilization of oxygen. This may occur with direct cellular poison (cyanide, colchicine overdose) or abnormally high tissue oxygen demand (malignancy).

When should hypoxia be suspected?

While there is no single lab value to directly measure hypoxia, it should be suspected in any patient with anxiety, confusion, and restlessness, which may be early signs of hypoxia and may precede changes in vital signs³. Low SpO₂ is the hallmark of hypoxemia, one of the main causes of hypoxia, and may be suspected in any patient with oxygen saturation less than 90 percent (or less than 88 percent in patients with chronic lung disease). Lactic acidosis may develop in response to anaerobic metabolism from tissue hypoxia or from increased catecholamine surge and may be detected on blood gas⁴.

Approach to Hypoxia

1-Patient Stability – check general appearance, ABCs, vital signs

In the assessment of any patient in the ED, it is the cornerstone of our decision making as EM physicians to do a quick yet thorough “sick or not sick” assessment.

General appearance

How does the patient appear? Is the patient comfortable or in acute distress? Does the patient exhibit any behaviors which may be clinical signs however subtle of “badness?”

ABCs

Airway, Breathing, and Circulation assessment is the right place to start in any patient who may be experiencing critical illness, including from hypoxia.

Is the patient protecting her airway? Although rare, hypoxia may result from critical airway narrowing that can be audibly detected as stridor. In pediatric patients, laryngeal stridor should prompt a thorough evaluation of upper airway obstruction⁵. Hypoxia may be seen with severe smoke inhalation injury, which may present with rales and rhonchi and lead to imminent airway compromise⁶.

Are breath sounds present bilaterally? While tension pneumothorax is associated with classic symptoms of respiratory distress and tracheal deviation, only half of cases may present with frank hypoxia⁷. Does the chest rise and fall equally? Patients with significant rib fractures causing an unstable chest wall may become inadequately ventilated and develop hypoxia as well as hypercapnia and acidosis⁸.

Is the patient tachycardic? Are distal pulses present? Thready pulses may indicate intravascular volume loss. In the patient with blunt trauma, this may be a manifestation of hemorrhagic shock, in whom resuscitation is vital to prevent tissue hypoxia⁹. In the patient with severe infection, tachycardia may be the manifestation of inflammatory-mediated fluid shifts and subsequent end-organ hypoperfusion and ischemic damage¹⁰.

Vital Signs

Especially in any unstable patient, it is crucial to obtain a full set of vitals, which are likely to be abnormal and may help to elucidate an underlying etiology of the patient’s instability. Acute hypoxia is most likely to manifest with increased respiratory rate (RR>24) and increased heart rate (HR>100), but normal respiratory rate and heart rate should not exclude the possibility of hypoxia¹⁰. In diseases with hypoxemia and hypercarbia, the body will try to increase tidal volume in addition to respiratory rate, with the goal of increasing alveolar ventilation¹¹. Patients with brisk intravascular volume loss may develop tachycardia and hypotension, and as the hypovolemia worsens, the body compensates for the subsequent tissue hypoxia by increasing respiratory rate¹². Patients with hypotension may have hypoxia from malperfusion and warrants a prompt investigation of the underlying cause. Patients hypoxic from septic shock may be hyperthermic or hypothermic, and this may best be identified using core temperature measures such as rectal temperature. Pulse oximetry reading is prone to inaccuracies, especially in the unstable patient, and it should always be considered in a clinical context.

2-History and Physical Exam

In the unstable patient, the history may be limited. Yet, in the stable patient it is important to obtain a thorough history and physical exam. Taking a clear and thorough history is the first important step.

Does the patient have a history of cardiac disease or pulmonary disease? Patients with preexisting cardiovascular disease are more likely to develop dysfunctional perfusion of end organs and a subsequent hypoxic state¹³. Patients with underlying lung disease are prone to developing physiologic changes that increase the risk of hypoxemia and subsequent hypoxia, including decreased ventilatory drive, airway obstructive processes, intra-alveolar exudates, alveolar septal thickening, inflammation and fibrosis, and alveolar capillary damage¹⁴.

Any history of smoking? Cigarette smoking is well known for its detrimental effects on normal body physiology and is associated with increased risk of hypoxia. Carbon monoxide blood levels are often elevated in chronic smokers in whom severe elevations and symptoms of hypoxia have been reported.¹⁵

Recent surgeries? Patients in the post-operative period are generally more prone to atelectasis, pneumonia, and pulmonary embolism, all pathologies that may present with hypoxia¹⁶.

Review of Systems: Many patients with hypoxia will report dyspnea or increased work of breathing. Patients may also note confusion or feeling sluggish. Headache may the only symptom of hypoxia in patients with acute CO poisoning¹⁷.

Physical Exam

General appearance of a patient may give clues to underlying etiology. Cyanosis may first show on lips and distal fingertips and may be a sign of severe hypoxemia. Diffuse, dull, red skin discoloration may be a sign of cyanide toxicity. Pale appearance may be a sign of acute blood loss anemia. Crackles on auscultation of lung parenchyma may point to heart failure if bilateral or a lobar pneumonia if focal and unilateral. Absent breath sounds may point to an effusion or a collapsed lung. Distal extremities may be warm in distributive shock or cold and clammy in a patient with hemorrhage. Cherry red skin and mucous membranes are usual post-mortem findings in carbon monoxide poisoning which are in fact uncommon at presentation¹⁸. Patient may be altered and restless on neurologic exam. Rectal exam with gross blood may point to acute blood loss anemia.

3-Further Evaluation

Arterial oxygen saturation (SaO₂)

SaO₂ describes the amount of oxygen bound to hemoglobin, and normal values range between 95 and 100 percent¹⁹. A rapid means of evaluating this is with pulse oximetry. Based on the known absorption of light at particular wavelengths of oxygenated and deoxygenated blood, pulse oximetry uses spectrophotometry to calculate an estimated SaO₂ (SpO₂)²⁰. The accuracy of this measurement relies in part on accurate signal strength, which is demonstrated as a waveform and which should normally be sharp with a clear, dicrotic notch²⁰. Low perfusion states will have sinus wave forms with low amplitude; SpO₂ measurements must be taken with caution in these patients (such as those with low cardiac output, peripheral vasoconstriction, or hypothermia)²⁰. SpO₂readings should also be taken with caution in patients with nail polish, which may interfere significantly with light absorption at the wavelengths used by pulse oximetry, as well as in patients with darker skin pigmentation^21,22. It is also important to note that SpO₂ is often inaccurate in patients with carbon monoxide poisoning²³. In fact, since oxyhemoglobin and carboxyhemoglobin have similar absorptive properties for red light, pulse oximetry will often estimate true SaO₂ as normal or falsely elevated in patients with CO poisoning; this absorptive property is also the reason patients with CO poisoning would appear cherry red²⁴. Methemoglobinemia is another disease in which its absorptive properties of red light will make pulse oximetry unreliable and is the reason significant toxicity will often shift pulse oximetry estimations of SaO₂ toward approximately 85 percent²⁴. Also be cautious when using pulse oximetry to trend oxygen saturation in critically ill patients, in whom the effects of acidosis and amenia have been shown to interfere with the correlation of pulse ox estimates and true SaO2²⁵. New, multi-wavelength pulse oximeters designed to measure methemoglobin and carboxyhemoglobin may improve future oxygen monitoring capabilities²⁶.

Arterial Blood Gas (ABG)

Blood gas analysis provides information on alveolar ventilation, oxygenation, and acid-base balance²⁷. In the evaluation of these key physiologic processes, ABG analysis measures arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2), and compared with pulse oximetry, it is a more definitive tool in evaluating oxygenation and ventilation^28,29. Normal PaO₂is considered 80-100 mmHg, and lower values may indicate hypoxemia as the cause of hypoxia. Knowledge of its value also is useful in managing patients on ventilatory support³⁰.  Normal PaCO₂ is considered 35-45 mmHg, and its levels may be elevated in either situations of increased metabolism or decreased ventilation; in either case, acuity of the hypercapnia can be evaluated by assessing for any concurrent change in HCO₃³⁰. Elevations from baseline of PaCO₂ in respiratory distress with increased work of breathing may signal respiratory failure and serve as an indication for ventilatory support³¹. While most ABG analyses measures pH and PaCO₂ directly, HCO₃ and base changes are indirectly calculated; especially in critically ill patients, these latter calculations may be highly variable and should be interpreted with caution³². This prompt direct measurement of pH may be critical in patients with metabolic derangements, such as in severe sepsis, diabetic and alcoholic ketoacidosis, trauma, acute respiratory failure, cardiac arrest, and COPD; in these situations, venous blood gas (VBG) analysis, one which may be clinically preferred for numerous reasons, is also reliable³³.

It is imperative to always interpret ABG within the clinical context of the patient. Accuracy of the data collected with an ABG sample is particularly susceptible to errors, and care must be taken to confirm the blood sample is truly arterial in nature (and not venous), completely and promptly rid of any air bubbles, inspected for any clots, and analyzed within thirty minutes of the collection time³⁴. ABG samples are even more prone to error in patients with high PaO₂ such as those with high levels of supplemental oxygen or in whom shunt physiology is suspected, as well patients with leukocytosis or thrombocytosis, and should have ABG analysis performed within five minutes³⁴.

Venous Blood Gas (VBG)

Compared with ABG, the VBG puncture is often quicker to perform, less painful, and carries a lower risk of complications such as arterial injury and arterial thrombosis^35,36. Given these potential benefits, VBG should be considered in establishing acid-base state and assessing respiratory function, two key purposes for which blood gas analysis is used in the ED. VBG is noninferior in its ability to screen for acid-base abnormalities in critical illnesses such as DKA and acute COPD exacerbations^34,35. Numerous studies and meta-analyses have confirmed this^35,37,38. Caution should be taken in severe hemodynamic compromise such as in severe shock or cardiac arrest, when VBG analysis of lactate and pH has been shown to be less reliable^38,39. Furthermore, while VBG may be helpful in screening for arterial hypercarbia, it has poor correlation with ABG results in pO₂ and pCO₂ analysis and is too clinically unpredictable³⁹.

Imaging

Imaging studies of the chest can aid in determining the underlying cause of hypoxia. Chest x-ray can be useful in diagnosing focal airway abnormalities, such as pneumonia, acute respiratory distress syndrome, lung hyperinflation, and pulmonary edema. An initial chest x-ray may not always elucidate an underlying etiology. Chest computed tomography (CT) can be useful in giving more detail. Evidence of smoke inhalation injury may be absence on initial chest x ray imaging but nonetheless will serve as a baseline evaluation in such cases⁴⁰.

Differential Diagnosis of Hypoxia

HYPOXEMIC:

– High altitude: high altitude, high altitude pulmonary edema

– Hypoventilation: central nervous system depressants (opioids), hypothyroidism, neuromuscular (myasthenia gravis, Guillain-Barre syndrome), nerve disease (cervical spine injuries, phrenic nerve injuries), chest wall injury (flail chest)

– Low Diffusion: pulmonary edema, pulmonary contusion, chronic obstructive pulmonary disease, interstitial lung disease

– V/Q Mismatch: pulmonary embolism, chronic obstructive pulmonary disease, asthma, mucus plugging, pulmonary hypertension

– Shunt: Intracardiac, arteriovenous malformation, pneumonia, atelectasis, acute respiratory distress syndrome

ANEMIC:

acute blood loss anemia, hemorrhagic shock, carbon monoxide poisoning, methemoglobinemia

ISCHEMIC:

global: cardiogenic shock (STEMI, ADHF), distributive shock (anaphylaxis, severe sepsis), obstructive shock (tamponade, tension pneumothorax), increased demand (seizure, shivering)

local: arterial obstruction, interstitial edema

HISTOTOXIC:

cyanide poisoning, hydrogen sulfide

4-Management

Maintain Patent Airway

The first step in managing an airway is to evaluate whether the airway is patent. Hypoxic patients with respiratory failure or altered consciousness may not be able to protect their airway patency in which endotracheal intubation may be warranted⁴¹. Patients in respiratory failure exhibiting signs of fatigue (such as lethargy, increasing use of accessory muscles, decreased rate and depth of respiration) may decompensate without ventilatory support in whom intubation may also be warranted⁴². Airway management is particularly important in inhalation injuries and thorough evaluation and risk stratification for impending airway compromise may be performed with fiberoptic bronchoscopy⁴³.

Increase Oxygen Content of Inspired Air

Supplemental oxygen is the cornerstone of therapy for many cases of hypoxia and can be divided into devices which provided low flow of oxygen, high flow of oxygen, and positive pressure ventilation. Supplemental oxygen at 100% FiO2 should be administered to any patient with suspected inhalation injury in whom the physiologic goal is to quickly reverse and displace carbon monoxide from hemoglobin binding sites⁴⁴.