Oxygen Administration

Anatomy and Physiology

Oxygen administration requires a functional airway, effective breathing, and adequate circulation to meet the cellular demand for oxygen. These components, known as the "ABC" of emergency care, are essential for ensuring proper oxygenation by addressing the 3 critical elements required for delivering oxygen to the tissues.

Oxygen administration usually begins with a nasal cannula placed in the external nares. If nasal cannula use is not feasible due to specific factors, the oral cavity becomes the following option for oxygen delivery. However, the tongue is the most common cause of oral airway obstruction in unconscious patients. In infants, airway obstruction in the supine position may occur due to a disproportionately large occiput.

The face is then evaluated for evidence of trauma, as facial injuries may contraindicate oxygen administration via a face mask. Finally, the anterior neck is assessed for critical signs such as tracheal deviation, subcutaneous emphysema, crepitus, or an expanding hematoma, which can compromise the anatomical airway and render it nonfunctional. 

Selecting supplemental oxygen administration methods depends on the respiratory system's condition. Assessment involves inspecting chest wall movement, palpating for subcutaneous emphysema over the chest—often indicative of pneumothorax—and auscultating for breath sounds. 

Circulation is evaluated by assessing signs of adequate end-organ perfusion, such as warm skin, brisk capillary refill, and an alert mental state. Additional indicators include the presence of pulses, normal blood pressure, the absence of cyanosis and edema, and the lack of jugular venous distention. These criteria collectively help determine the integrity of the circulatory system during examination. 

Oxygen administration involves administering oxygen at a fraction of inspired oxygen(FiO₂) greater than 0.21, which exceeds the oxygen concentration in ambient air. The maximum achievable FiO₂ is 1.0. Delivering oxygen concentrations higher than this requires using a hyperbaric chamber, which provides 100% oxygen at pressures above normal atmospheric levels.

Cellular physiology begins with oxygen transport from inhaled air, driven by a diffusion gradient across the alveolar-capillary membrane into the pulmonary capillaries. The partial pressure of oxygen in the arterial blood (PaO₂) is directly influenced by the pressure of inhaled oxygen (PIO₂). This relationship is further described by the alveolar gas equation, which connects the alveolar pressure of oxygen (PAO₂) to the FiO₂, barometric pressure, and the partial pressure of carbon dioxide (PaCO₂).

Oxygen dissolves in plasma and binds to hemoglobin. Arterial oxygen content (CaO₂) directly reflects the total number of oxygen molecules in arterial blood, including those bound to hemoglobin (oxyhemoglobin) and those dissolved in plasma. Arterial oxygen saturation (SaO₂) represents the percentage of hemoglobin binding sites occupied by oxygen. The PaO₂ is a key determinant of SaO₂, and their relationship is depicted by the sigmoid-shaped oxygen–hemoglobin dissociation curve, first described by Archibald Vivian Hill (1886–1977) and later refined by John W. Severinghaus (1922-2021).[1] 

The administration of supplemental oxygen becomes critical when PaO₂ falls below 60 mm Hg, at which point the steep portion of the curve indicates a rapid decline in oxygen saturation, leading to inadequate oxygen delivery to tissues. The Haldane effect describes hemoglobin's property whereby oxygenation in the lungs facilitates carbon dioxide displacement from hemoglobin, enhancing carbon dioxide elimination. 

The cellular physiology of oxygen administration depends on the physiological relationship between oxyhemoglobin, PaCO_2, and hydrogen ion concentration (pH), as described by the Bohr effect. Key determinants of cellular oxygen physiology include PaO_2, SaO_2, and CaO₂. 

HBO therapy involves pressurizing oxygen to 2 to 3 atmospheres at 100% concentration. The physiological effects of HBO are mediated by the positive pressure gradient in the inhaled air, which enables a higher oxygen concentration to diffuse from the alveoli into the bloodstream, thus increasing its concentration in tissues. This phenomenon, known as "hyperoxemia" and "hyperoxia," occurs through the dissolution of oxygen in the plasma, independent of hemoglobin. HBO also leads to generating reactive oxygen species (ROS) and reactive nitrite species (ROS), which promote the expression of growth factors, enhance neovascularization, and strengthen immunomodulatory properties.[2]

Indications

Hypoxemia, whether acute or chronic, is the primary indication for supplemental oxygen therapy, aiming to maintain oxygen saturation between 92% and 98% in otherwise healthy patients. Target oxygen saturation levels typically range from 88% to 92% for individuals with chronic hypercapnic conditions, the only evidence-based indication for oxygen administration.[3]

Oxygen administration can be delivered at standard atmospheric pressure, known as normobaric oxygen therapy (NBOT), or at pressures greater than atmospheric pressure, known as HBO therapy. HBO therapy is indicated to promote wound healing and angiogenesis, exert antimicrobial effects, and assist in specific medical emergencies, all based on increased oxygen dissolution in the bloodstream.[4] 

Oxygen therapy accelerates the resolution rate of primary spontaneous pneumothorax. However, the potential complications of hyperoxia should be carefully considered before routinely administering oxygen therapy for small pneumothoraces.[5]

Contraindications

Oxygen should be administered as a drug within its pharmaceutical window, ensuring effective hypoxia treatment while avoiding its associated risks.[6] Despite its essential role in medical care, oxygen therapy is not without risks and has specific contraindications that must be considered to prevent potential harm to patients. 

Acute Myocardial Infarction 

Historically, acute myocardial infarction (AMI) was treated using the well-known mnemonic MONA: morphine, oxygen, nitroglycerin, and aspirin. However, recent studies have demonstrated that routine oxygen administration does not benefit normoxic patients.[7] Supplemental oxygen is contraindicated in normoxic patients with myocardial infarction, as hyperoxia can generate free oxygen radicals, cause vasoconstriction, and lead to reperfusion injury, significantly reducing oxygen administration to cardiac patients with normal SaO2, may generate free oxygen coronary blood flow.[8][9] 

The Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction (AVOID) trial [10] further concluded that routine oxygen administration in normoxic patients does not improve symptoms or reduce infarct size. On the contrary, high-flow oxygen supplementation was associated with a significant increase in infarct size.

Hypercarbia

Hyperoxia can be harmful to patients with chronic obstructive pulmonary disease (COPD), particularly those with or at risk of hypercapnia.[11] Administering high FiO₂ levels is associated with a rise in PaCO₂ due to increased alveolar dead space and ventilation-perfusion (V/Q) mismatch. Studies have shown that patient-specific oxygen concentrations during prehospital transport for acute exacerbation of COPD (AECOPD) significantly reduce mortality compared to the delivery of consistently high oxygen concentrations.[12] Targeted oxygen therapy, titrated to maintain SpO₂ levels of 88% to 92%, has been shown to improve outcomes.[13] Notably, the idea that high FiO₂ worsens the hypoxic drive of respiration in COPD patients is a persistent and unfounded myth. This misconception can lead to reluctance to administer oxygen in cases of hypoxia during AECOPD, which may increase morbidity.[14] 

Retinopathy of Prematurity

In 1942, Dr. Terry published a seminal series of case reports on retrolental fibroplasia, the most severe stage of retinopathy of prematurity (ROP).[15] It was later discovered that unmonitored oxygen administration at birth was the primary cause of this condition. In recent years, the incidence of ROP has been rising in the United States, likely due to the improved survival rates of infants born prematurely at less than 25 weeks gestation, who are often treated with higher oxygen saturation targets. Despite advances in neonatal care, there remains no consensus on optimal oxygen levels to minimize the risk of ROP, highlighting the urgent need for refined oxygen administration strategies in preterm infants.[16][17]

Equipment

Oxygen administration equipment delivers life-saving therapy, from routine care to critical emergencies, across various clinical scenarios. These devices are designed to provide precise oxygen delivery tailored to individual patient needs, ranging from simple nasal cannulas to advanced systems like ventilators and hyperbaric chambers.  

Oxygen administration methods span a spectrum from the most commonly used noninvasive approaches to more intensive and less frequently employed techniques. These include nasal cannulas, simple face masks, face tents, nonrebreather masks, Venturi masks, high-flow nasal cannulas, noninvasive positive-pressure ventilation (eg, continuous positive airway pressure [CPAP] and bilevel positive airway pressure [BiPAP]), closed-system respiration via an endotracheal tube, and HBO. Venturi masks, equipped with high-flow Venturi valves, operate based on the Bernoulli principle, where oxygen jet velocity entrains ambient air to deliver a precise and consistent oxygen concentration.[18][19]

Oxygen administration devices are commonly categorized by flow type. Low-flow oxygen therapy devices, also known as variable performance devices, deliver oxygen at a rate that varies with the patient's minute ventilation, resulting in fluctuating FiO2 levels. The oxygen flow rate is typically adjusted using a flow-meter connected to the oxygen source.

In hospitals, oxygen is supplied through a gas pipeline or cylinders. In nonhospital settings, oxygen is typically provided through an oxygen concentrator or cylinder. 

Humidifiers are commonly used in oxygen administration equipment because oxygen is a dry, irritant gas that can damage the respiratory mucosa.[20] Humidifiers help prevent dryness and irritation by adding moisture to the oxygen, improving patient comfort, and protecting the airways from potential injury. 

Equipment used to monitor oxygen administration can be noninvasive, such as pulse oximeters, which measure the oxygen saturation in the blood. However, pulse oximeters cannot differentiate between hemoglobin bound to CO or methemoglobin from hemoglobin bound to oxygen.

Carbon monoxide (CO) oximeters monitor CO levels noninvasively, but they may not provide highly accurate estimates of carboxyhemoglobin or reliably confirm CO poisoning.[21] This limitation is particularly concerning in cases where prompt, accurate diagnosis of CO poisoning is crucial for appropriate treatment. 

Invasive oxygen monitoring is performed through ABG analysis. The equipment used for ABG analysis includes a puncture needle and ABG syringe or an indwelling catheter and blood gas analyzers. Automated blood gas analyzers directly or indirectly measure or calculate specific components of the arterial blood gas. The PaO₂ is measured, but a reduced PaO2 is a nonspecific finding and not diagnostic.  

Personnel

Oxygen is considered a drug and must be prescribed and administered by healthcare practitioners who have the appropriate knowledge, training, clinical experience, and the ability to implement necessary skills and make competent judgments. The healthcare team usually includes physicians, subspecialists such as pulmonologists or intensivists, nurses, and respiratory therapists. In out-of-hospital settings, when oxygen is administered, caregivers and family members must also possess a level of competency commensurate with the inherent risks, monitoring requirements, and safety precautions associated with oxygen administration.[22]

Preparation

The first step in administering oxygen is to determine the indications for its use, such as hypoxia, an unconscious state induced by general anesthesia, or exposure to CO. The healthcare provider must assess the severity of the condition and ensure that oxygen therapy is appropriate for the patient's specific needs and clinical situation. 

The second step is to identify the optimal route of administration. For example, a conscious patient with intact reflexes may receive oxygen via a nasal, while an unconscious patient may require airway protection and oxygen delivery through endotracheal intubation.

The third step is to evaluate the required FiO₂ to achieve the target oxygen saturation levels. This decision should consider the patient's respiratory physiology, underlying pathology, and the desired oxygenation target while also accounting for the potential consequences of hyperoxia.

The fourth step in preparation is to select and use the appropriate equipment for oxygen delivery, administration, and monitoring. When equipment is calibrated correctly, functional, and suitable for the patient's condition, complications during oxygen therapy can be avoided. 

The fifth and final step is adopting an interprofessional approach that involves collaboration with the patient, family, and caregivers, especially when oxygen therapy is administered in out-of-hospital settings. Patients and families should be educated to ensure proper understanding and adherence to safety protocols.

Technique or Treatment

Oxygen administration should follow a stepwise approach, starting with the most physiological and minimally invasive methods and progressing to higher concentrations or more invasive techniques, as clinically indicated by the severity of hypoxia and the care setting. Proper monitoring and regular reassessment of the patient's oxygenation status are essential to ensure the chosen method remains effective and appropriate. 

The simplest oxygen administration techniques are the nasal cannula and the simple face mask, both of which are effective first-line methods for preventing hypoxemia.[23] The flow rate of nasal oxygen does not correspond to a specific FiO_2, as FiO₂ depends on the patient's breathing rate and tidal volume due to the mixing of supplemental oxygen with room air.

Nasal cannulas, the most commonly used technique, deliver oxygen at flow rates of 1 to 6 L/min, providing an FiO₂ of approximately 24% to 40%. Simple face masks, which cannot deliver 100% oxygen without a tight seal, are low-flow systems that provide oxygen at rates of 5 to 10 L/min, achieving a FiO₂ of approximately 40% to 60%. Without unstable or falling oxygen saturation levels, oxygen doses are typically maintained for 5 minutes before any upward or downward adjustment. 

A face tent delivers humidified oxygen through a loose-fitting tent that covers the nose and mouth. With a flow rate of up to 15 L/min, it can achieve a FiO₂ of approximately 50%. 

High-flow nasal oxygen (HFNO) is administered through a high-flow nasal cannula(HFNC), using an air and oxygen blender and humidified oxygen at flow rates of up to 60 L/min. Flow rates and FiO₂ can be independently adjusted to achieve the target SaO₂.[24] HFNC improves oxygenation by reducing anatomical dead space and increasing PEEP.[25][26][27]

A nonrebreather mask, classified as a high-flow system, is commonly used in critical care settings for short-term use when high levels of supplemental oxygen (FiO₂ 0.6-0.8 are required). This device comprises a simple mask connected to a small reservoir bag through one-way valves. During inspiration, the patient inhales oxygen exclusively from the reservoir bag, while the one-way valves prevent exhaled gases from entering the bag. The flow rate is typically set between 10 to 15 L/min.  

Based on the Bernoulli principle, Venturi masks are another high-flow oxygen delivery option. These air-entrainment masks deliver oxygen at a flow rate exceeding the patient's peak inspiratory flow rate, effectively minimizing the possibility of inhaling ambient air.

In critically ill patients, oxygen is delivered directly into the trachea primarily through oral and, less commonly, nasal endotracheal intubation. Oxygen can also be administered via a tracheostomy using a tracheal mass. These methods facilitate oxygen delivery and enable invasive ventilatory support through mechanical ventilators. Notably, 100% oxygen can be delivered using only a mechanical ventilator or a tight-fitting face mask. 

Oxygen Administration with Positive Pressure and Ventilation Support

After HFNC, the subsequent escalation in oxygen therapy is noninvasive positive pressure ventilation (NIPPV), including BiPAP and CPAP. Noninvasive ventilation (NIV) augments tidal volume (VT), supporting adequate alveolar ventilation. Since hypoventilation is a common cause of hypoxemia, NIPPV effectively improves oxygenation[28][29][30][31]

Prone positioning, including awake proning and semi-proning is another stepwise escalation technique for oxygen administration. Prone positioning improves oxygenation through multiple mechanisms, including enhanced ventilation-perfusion (V/Q) matching and reduced physiological shunting. Prone positioning also increases lung volume, redistributes perfusion, recruits dorsal lung regions, and promotes a more uniform ventilation distribution.[32]

Strategies consistent with acute respiratory distress syndrome network (ARDSnet) that can be implemented to improve oxygenation include ventilation with a low tidal volume of 4 to 8 mL/kg of predicted body weight, maintaining a plateau pressure of less than 30 cm H₂O, and utilizing recruitment maneuvers. These approaches aim to optimize lung mechanics, minimize ventilator-induced lung injury, and improve overall oxygenation while preventing further lung damage in patients with ARDS.

As patients' oxygenation needs escalate, a stepwise approach includes rescue techniques for oxygen administration, such as using neuromuscular blocking agents (NBMA), inhaled pulmonary vasodilators, and extracorporeal membrane oxygenation (ECMO). Additionally, the use of steroids has emerged as another tool to manage hypoxia.[25]

Oxygen, one of the most commonly used therapies in the neonatal intensive care unit, can be delivered through various techniques. Methods for infants not on a ventilator or receiving positive pressure include using an oxygen hood, nasal cannula, face mask, and "free flow" oxygen or "incubator flooding" oxygen.[33]

Oxygen Saturation Targets in Patients with Hypoxemia and COVID-19

While the ideal oxygen saturation for patients with hypoxemia and COVID-19 remains unclear, the suggested target is typically 92% to 96%.[34] This target range aims to balance adequate oxygenation while minimizing the risk of potential complications associated with hyperoxia, especially in critically ill patients.

Techniques for Oxygen Administration in Cardiac Arrest

Current Advanced Cardiac Life Support (ACLS) guidelines recommend using either a supraglottic airway or an endotracheal tube for oxygen delivery during out-of-hospital or in-hospital cardiac arrest. The guidelines emphasize bag-mask ventilation (BMV) or an advanced airway strategy. Rescue breathing, which involves mouth-to-mouth or BMV, is used for oxygen administration in unconscious patients without spontaneous breathing.[35] However, caution is required when administering oxygen administration in these settings, as hyperoxemia may negatively impact neurological recovery following cardiopulmonary resuscitation (CPR). 

Additionally, chest hyperinflation or the use of positive airway pressure during CPR may have adverse effects on hemodynamics.[28] During CPR, the highest possible oxygen dose is typically delivered, which is then reduced to maintain a target saturation range of 94% to 98%.

Complications

Oxygen administration, while critical in treating hypoxia and supporting patients with respiratory distress, can also lead to complications if not carefully managed. Potential risks include infection, hyperoxia, and ventilator-induced lung injury, which can adversely affect patient outcomes. Understanding and mitigating these complications is essential for optimizing oxygen therapy and ensuring patient safety.

Respiratory equipment represents a critical vector for transmitting nosocomial or healthcare-associated infections.[20] Pathogenic microorganisms, including bacteria, viruses, and fungi, can colonize respiratory devices such as ventilators, endotracheal tubes, oxygen delivery systems, and nebulizers. Inadequate cleaning, disinfection, or sterilization of these devices can lead to the introduction of infections such as ventilator-associated pneumonia (VAP) and other lower respiratory tract infections. To mitigate the risk of healthcare-associated infections, implementing stringent infection control measures is essential, including routine decontamination of equipment, appropriate handling practices, and adherence to protocols for aseptic techniques. 

Oxygen is not flammable or combustible, but it promotes combustion by enhancing the flammability of other materials. Leaks in oxygen delivery equipment can elevate oxygen levels in the surrounding air, creating an environment that actively supports the ignition and burning of combustible materials. Incidents of facial burns and fatalities in patients who smoke while using oxygen are well-documented and highlight the significant risks associated with oxygen use in such settings.[36]

Approximately 5% of oxygen not consumed for energy production is converted into activated oxygen or reactive oxygen species (ROS). These metabolites are highly reactive and can generate free radicals. Oxidative stress occurs when the production of ROS and other oxidants surpasses the body's antioxidant capacity. Oxidative stress has been linked to the pathogenesis of various diseases, contributing to cellular damage and inflammation.[37][38]

Hyperoxia, resulting from hyperoxemia due to oxygen administration, can lead to oxygen toxicity, particularly affecting the lungs.[39][40] Prolonged exposure to a FiO₂ greater than 0.60, even for just 1 day, may cause severe and irreversible pulmonary fibrosis.[41][42]

Neonates treated with high FiO2 are at increased risk for developing ROP.[43][44] Therefore, it is crucial to carefully monitor and adjust oxygen therapy in neonates, particularly those born prematurely

Absorption atelectasis can occur during mechanical ventilation or general anesthesia, even after short periods of preoxygenation with FiO₂ at 1.0. A high FiO₂ displaces nitrogen in the alveoli, and oxygen absorption reduces alveolar volume, leading to atelectasis. This condition can result in increased physiological shunting and hypoxemia.[23][45][46][47] 

Dry, non-humidified oxygen can increase insensible water losses, particularly at high flow rates. Additionally, using cool or cold oxygen can elevate the risk of hypothermia.

Oxygen administration in AECOPD is associated with the complication of hypercapnia.[14] Additionally, hyperoxemia may negatively impact neurological recovery following CPR.

Clinical Significance

Oxygen administration is a critical component of patient care, frequently used in acute medical settings to address a wide range of acute and chronic conditions. Understanding the various methods of oxygen delivery, along with their pathophysiological effects and potential complications, is essential for healthcare professionals. In patients experiencing severe hypoxia, oxygen therapy can be life-saving.

Hypoxemia is a common consequence of many serious illnesses, including pulmonary injuries caused by conditions such as pneumonia or significant trauma. Additionally, diseases that do not directly affect the lungs, such as hemodynamic insufficiency in sepsis, shock, or cardiac arrest, can also lead to hypoxemia. In some cases, hypoxemia arises from ventilation-perfusion mismatch, as seen in pulmonary embolism. Hypoxia, which may result from various factors impairing ventilation, underscores the importance of identifying and addressing the underlying causes to ensure effective management.

Oxygen is the primary metabolic fuel for cellular processes. Consequently, a significant reduction in tissue oxygen levels can cause rapid and severe injury to multiple organs, with the brain being the most susceptible to hypoxia.

The majority of patients in critical care units require mechanical ventilation, which typically involves the use of supplemental oxygen. This intervention is essential for maintaining adequate oxygenation in patients with respiratory failure or compromised pulmonary function.

Patients with medical emergencies and hypoxemia have higher mortality rates.[48][49] However, it is unclear if the increased risk of death is directly caused by low blood oxygen levels or if hypoxemia serves as a marker of severe disease. Historically, oxygen was used routinely and prophylactically, often without strong evidence supporting its benefit. Current evidence does not support the administration of supplemental oxygen in patients with SaO₂ levels above 90%. Moreover, there is evidence of harm associated with hyperoxemia due to excessive oxygen supplementation. Although the consequences of hyperoxemia are less immediate or apparent than those with acute hypoxia, they can still result in significant adverse effects. 

Enhancing Healthcare Team Outcomes

Oxygen is essential for normal cell function, and its absence can result in severe complications, including death due to cardiac arrest. Early identification and management of hypoxia is critical in reducing morbidity and mortality. The management of patients with hypoxia necessitates a collaborative, interprofessional approach to ensure patient-centered care and optimal outcomes. Pulmonologists, emergency medicine physicians, critical care physicians, advanced practitioners, nurses, respiratory therapists, emergency medical technicians, other healthcare professionals, and family members involved in patient care must possess the necessary clinical skills and knowledge to diagnose and manage oxygen administration.

Proficiency in recognizing diverse clinical presentations of hypoxia and understanding monitoring techniques, such as pulse oximetry and arterial blood gas analysis, is essential. Interprofessional care teams have demonstrated improved outcomes through early detection of hypoxia and prevention of complications related to oxygen therapy. Educating patients and caregivers on the factors influencing oxygen use, safety measures, and recognition of symptoms related to hypoxia and hyperoxia is also vital in minimizing the risks associated with oxygen administration.  

By adhering to principles of skill, strategy, ethics, responsibilities, interprofessional communication, and care coordination, healthcare teams can deliver high-quality patient-centered care. This approach enhances clinical outcomes and fosters interprofessional collaboration in oxygen therapy management.