Oxygen was employed in the acute care setting for the first time in 1885; but it was not until the twentieth century that discoveries related to its physiological effects and technological advances enabled its clinical application.
Oxygen was employed in the acute care setting for the first time in 1885; but it was not until the twentieth century that discoveries related to its physiological effects and technological advances enabled its clinical application.1
Oxygen therapy is the administration of oxygen at a higher concentration than room air (21%) with the aim of treating or preventing hypoxaemia and the resulting tissue hypoxia.2 Although it is one of the most commonly prescribed treatments, especially in critical care medicine, it has side effects and costs which must be considered. Physicians, nurses and respiratory therapists require training in the operation and handling of oxygen supply devices, as well as in indications and risks of oxygen therapy. The expression ‘if something is good, more is better’ should not be applied to oxygen therapy.3
Pregnant patient management represents a challenge to healthcare workers due to the presence of a fetus, diseases specific to pregnancy and an altered maternal physiology. Although the general approach for pregnant patients requiring oxygen therapy is similar to non-pregnant patients, the above-mentioned aspects must be taken into consideration before implementing supplemental oxygen.4,5
In this chapter, we will describe the physiological aspects of oxygen, indications and risks related to its utilization, oxygen delivery systems and oxygen therapy monitoring, as well as specific features related to pregnancy.
Physiology of Oxygen
Oxygen serves as the terminal electron acceptor in the electron transport chain, generating the energy to preserve cell structure and function. Physiological changes of pregnancy can modify some aspects of oxygen delivery to tissues (please refer to Chapter 4). Briefly, hypoxaemia develops faster in pregnant patients than in non-pregnant patients due primarily to their higher oxygen consumption and lower oxygen reserve; this is related to a reduced functional residual capacity.5 During pregnancy, minute ventilation rises by approximately 40%, resulting in respiratory alkalosis with normal arterial carbon dioxide partial pressure (PaCO2) levels of 26–30 mmHg. These lower PaCO2 levels result in lower alveolar PCO2 (PACO2), which in turn, increases alveolar oxygen partial pressure (PAO2) and consequently arterial oxygen partial pressure (PaO2) up to 106 mmHg.6 The theoretical background of this statement comes from the alveolar gas equation7:
where PAO2 = alveolar oxygen pressure (mmHg)
PIO2 = partial pressure of oxygen in inspired gas (mmHg)
PACO2 = alveolar carbon dioxide pressure (mmHg); this value is often assumed to be equal to arterial PCO2 (PaCO2).
RQ = respiratory quotient (molar ratio of carbon dioxide production to oxygen consumption)
Breathing room air at sea level
where FiO2 = fractional concentration of inspired oxygen
PB = barometric pressure (mmHg)
PH2O = water vapor pressure (47 mmHg at 37 °C)
In summary, upon reviewing the alveolar gas equation again and inserting the normal values for pregnancy (PAO2 = 150 mmHg – PaCO2 (28 mmHg)/0.8), it is clear that when PaCO2 decreases, PAO2 and PaO2 increase, resulting in PaO2 values falling between 106–115 mmHg.6 Thereafter, oxygen is delivered to tissues mainly via the haemoglobin in arterial blood, which requires adequate tissue perfusion and oxygen diffusion from capillaries to intracellular sites. Finally, oxygen partial pressure in mitochondria is 1 mmHg8; this assures a constant diffusion gradient and is sufficient to accomplish satisfactory cell functioning.9
As indicated above, oxygen delivery (DO2) to tissue depends mainly on both arterial oxygen content (CaO2) and cardiac output (CO), as follows:
As noted earlier, the oxygen content in arterial blood is determined primarily by the oxygen transported via the haemoglobin (Hb), while the oxygen dissolved in blood is negligible (0.003 ml of O2/100 ml blood):
(1 g of Hb transports 1.36 ml of O2 × 100 ml of blood normally contains 15 g of Hb = 100 ml of blood transports 20.4 ml of O2)
Resting oxygen consumption in pregnant patients is higher than in non-pregnant patients. Accordingly, these higher metabolic demands are met by increased minute ventilation and cardiac output. However, studies comparing twins vs singleton pregnancies showed that the higher basal metabolic rates in the former group were accompanied by increases in cardiac output without changes in minute ventilation.10 Therefore, when dealing with pregnant patients, healthcare workers must bear in mind the importance of cardiac output in addition to respiratory function in order to preserve appropriate oxygen tissue levels.
Hypoxaemia: defined as partial pressure of oxygen in arterial blood less than 60 mmHg breathing room air, which corresponds to an arterial oxygen saturation (SaO2) of 90%. Normal oxygen saturation (SO2) among adults under 64 years of age at sea level is 96–97%, while normal PaO2 ranges between 90 and 100 mmHg.11 Normal PaO2 varies with age and body position. The supine position in pregnant patients is associated with a PaO2 drop of approximately 5 mmHg and 7 mmHg at the end of the second and third trimesters, respectively, compared to the sitting position.12 Upward diaphragmatic displacement resulting from a gravid uterus reduces functional residual capacity, which in turn can reduce PaO2 levels in pregnant patients in the supine position even more. In addition, oxygen delivery decreases further due to inferior vena cava compression with resulting lower venous return.13
Hypoxia: refers to reduced levels of tissue oxygenation.2,14,15 Tissue hypoxia is frequently caused by hypoxaemia; however, it can also be associated with other conditions compromising haemoglobin functioning (carbon monoxide poisoning), oxygen delivery (cardiogenic shock), oxygen utilization (sepsis) or a combination of these mechanisms (septic shock).16 Patients under supplemental oxygen whose PaO2 is greater than 60 mmHg should still be evaluated for signs and/or symptoms of hypoxia if PaO2 levels are lower than expected.14 Physiological risks associated with acute hypoxia are illustrated in Table 23.1.2
|Ischaemia/infarction of other critically perfused organs|
|Renal||Acute tubular necrosis|
Hyperoxaemia: refers to high oxygen partial pressure in blood, usually over 120 mmHg. It is commonly associated with the use of FiO2 > 21%, for example when patients are administered oxygen but do not need it. Although supplemental oxygen therapy is indicated in non-hypoxaemic patients in some specific clinical situations, such as carbon monoxide poisoning or patients with pneumothorax, to hasten resolution, it produces direct physiological damage and indirect toxicity through liberation of reactive oxygen species with the risk of potential damage to lungs and other tissues.2 Some risks associated with hyperoxia are presented in Table 23.2.
|Respiratory||Worsening ventilation/perfusion (V/Q) matching|
|Cardiovascular||Myocardial ischaemia (under anemic conditions)|
|Reduced cardiac output|
|Reduced coronary blood flow|
|Increased peripheral resistance|
|Metabolic||Increased reactive oxygen species|
|Renal||Reduced renal blood flow|
In neonates, deleterious effects associated with the use of high concentrations of oxygen are well known,17 while in adults the utilization of supplemental oxygen in non-hypoxaemic patients with myocardial infarction could worsen patient outcomes.18 Damaging effects of hyperoxia post cardiac resuscitation and in mechanical ventilation contexts are controversial. Therefore, the current recommendation for oxygen usage is not to exceed physiological thresholds.19
There is no general consensus regarding the upper limit of the fraction of inspired oxygen to prescribe; however, to avoid oxygen toxicity, it appears that FiO2 <40% is safe for long periods of time and FiO2 ≥80% should be avoided. As a rule, the lower the fraction of oxygen utilized, the lesser the adverse effects.3,19 There is controversy as to the role of maternal oxygen supplementation for intrauterine fetal resuscitation,20 although this practice remains common.21
Respiratory indices refer to formulas that are useful in evaluating gas exchange, and mechanisms and severity of hypoxaemia. In addition, they can be valuable in monitoring patient evolution.7
Alveolar–arterial oxygen partial pressure gradient (A–a gradient) results from the difference between alveolar and arterial oxygen partial pressure, which increases due to any pathology involving the alveolocapillary membrane. It also estimates the degree of intrapulmonary shunt. However, this formula gives a qualitative estimate of the degree of shunting and varies with changes in cardiovascular status and inspired oxygen concentration. A–a gradient increases with age, approximately 10 mmHg for young people and 30 mmHg for elderly people, due primarily to progressive V/Q mismatch.
is measured by dividing PaO2 by PAO2. It is more stable than the A–a gradient when taking into consideration the changing values of FiO2.
Oxygenation ratio (PaO2/FiO2)is easier to calculate than the above-mentioned indices. It results from the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen; the latter is expressed by a decimal (30%= 0.3). Although a ratio of ≤200 correlates with a shunt of 20% or more, it is generally a crude indicator of shunt. Moreover, it does not take into account arterial carbon dioxide partial pressure.
OI = FiO2 × MAP × 100/PaO2
Examples of the some of the indices mentioned for a patient with and without respiratory disease can be found below. It is necessary to obtain the PaO2 figures from the arterial blood gases (ABG) and to understand how to calculate PAO2 from the alveolar gas equation (please see previous section):
Patients without respiratory disease (e.g. PaO2 = 95 mmHg)
Normal values breathing room air (FiO2 = 21%) = 10–15
Abnormal = >20
A–a = 100 mmHg – 95 mmHg = 5
Normal values = 0.75–1
a/A = 95 mmHg/ 100 mmHg = 0.95
Normal values = 340–470
Abnormal values = <300
PaO2/FiO2 = 95 mmHg/0.21= 452.38
Patients with respiratory failure requiring supplementary oxygen (e.g. PaO2 = 55 mmHg, PCO2 = 40 mmHg, FiO2 = 40%)
PIO2 = FiO2 × (Pb – PvH2O) = 0.40 × (760 mmHg – 47 mmHg) = 285.2 mmHg
PAO2 = 285.2 mmHg – 40 mmHg/0.8 = 235.2
A–a = PAO2 – PaO2
A–a = 235.2 mmHg – 55 mmHg = 180.2
a/A = PaO2/PAO2
a/A = 55 mmHg/235.2 mmHg = 0.23
PaO2/FiO2 = PaO2/ FiO2
PaO2/FiO2 = 55 mmHg/0.4 = 137.5
It should be noted that some indices are influenced by body position; for example, the ‘A–a’ gradient increases in pregnant patients in the supine position due to lower PaO2 levels related to diminished functional residual capacity.20,22
Mechanisms of Hypoxaemia
Dealing with hypoxaemic patients requires understanding the mechanisms of hypoxaemia (Table 23.3), assessing and interpreting ABGs and evaluating cardiovascular and haematological systems, as well as patient response to supplementary oxygen.
|1. Low ambient oxygen levels|
|1. V/Q mismatching|
|3. Diffusion abnormalities|
Main mechanisms of hypoxaemia can be categorized into two groups: (1) those presenting with a normal A–a gradient, such as with hypoventilation or low ambient air pressure, and (2) those presenting with a high A–a gradient, such as with V/Q mismatch, diffusion limitation or shunt.15
Mechanisms of hypoxaemia
Low ambient PO2 occurs when barometric pressure decreases, causing a proportional reduction in PO2 without changes in FiO2 (e.g. high altitude or air travel), or when the inspired oxygen is mixed or contaminated by other gases, reducing FiO2 (e.g. inert gas asphyxia – nitrogen, methane, carbon dioxide excess). Low inspired PO2 can be related to incorrect implementation of oxygen therapy causing air reinhalation (e.g. expiratory obstruction, using low flow for partial rebreathing systems).
In this context, a normal patient response consists of increasing minute ventilation in order to reduce PaCO2, which in turn increases PAO2, causing respiratory alkalosis. Therefore, the A–a gradient is normal. Treatment for this mechanism of hypoxaemia is supplemental oxygen.
Hypoventilation occurs when alveoli are inadequately ventilated, causing elevated arterial PCO2, which in turn increases PACO2 and consequently reduces PAO2. It can be caused by an impaired central drive (narcotics, stroke), weakness of respiratory muscles (e.g. Guillain–Barré syndrome, residual neuromuscular blockade, high spinal block), defects in the chest wall (kyphoscoliosis), increased work-of-breathing and/or high CO2 production without a compensatory rise in alveolar ventilation. The A–a gradient is normal and supplemental oxygen can correct hypoxaemia. However, the appropriate treatment consists of increasing alveolar ventilation (e.g. using mechanical ventilation).
Ventilation/perfusion inequality is the most common cause of hypoxaemia. It refers to a mismatch between alveolar ventilation and perfusion. Respiratory disease presents with some lung regions having poor ventilation and good perfusion (low V/Q) and some other regions with adequate ventilation but poor perfusion (high V/Q). Some examples of V/Q mismatch are pneumonia, COPD, atelectasis, pleural effusion, pulmonary embolism, amniotic fluid embolism, acute respiratory distress syndrome (ARDS), etc. In these settings, the A–a gradient is high and hypoxaemia improves with supplemental oxygen. However, oxygen therapy in patients with a profound V/Q mismatch may induce or worsen hypercapnia due to the inhibition of hypoxic vasoconstriction.
Pulmonary shunt occurs when venous blood returning from tissues passes through unventilated alveoli (collapsed or filled with fluid, pus, or another liquid) and ends in the systemic arterial circulation without performing a gas exchange. It is associated with a high A–a gradient, and since shunted blood does not make contact with ventilated alveoli, oxygen therapy does not improve hypoxaemia. Some disorders causing pulmonary shunt are ARDS and pneumonia. Extrapulmonary shunt also occurs when venous blood passes into arterial circulation without any gas exchange; however in this case, it is caused by the presence of an abnormal intracardiac septal defect (atrial or ventricular) or intrapulmonary anatomic pathway (pulmonary arteriovenous fistula).
Impairment of diffusion is the least frequent cause of hypoxaemia and usually plays a marginal role in its development, acting mostly to aggravate other mechanisms. Oxygen equilibration between capillary blood and alveoli normally occurs in 0.25 seconds, although available pulmonary capillary transit time is 0.75 seconds; therefore, gas exchange normally requires only one-third of the available time. A thickened alveolar wall, such as in asbestosis or diffuse interstitial fibrosis, and/or a reduced time available for oxygen diffusion, such as during exercise or in septic conditions, would be needed to generate hypoxaemia in these settings. Again, the A–a gradient is high and hypoxaemia could be improved by increasing PAO2 with supplemental oxygen.