At birth, the lungs must transition rapidly to become the site for gas exchange or else hypoxia and cyanosis (see Color Plate) will rapidly develop. For the lungs to exchange gas adequately after birth, the airways and the alveoli must be cleared of fetal lung fluid, and an increase in pulmonary blood flow must occur. In utero, fetal pulmonary vascular resistance is high and the fetal systemic vascular resistance is low; most of the cardiac output is shunted away from the lungs and is directed to the placenta where fetoplacental gas exchange occurs. Within minutes of delivery, the newborn’s pulmonary vascular resistance may decrease eight- to tenfold, causing a corresponding increase in neonatal pulmonary blood flow. Effective transition requires that the lung fluid be expelled or quickly absorbed to allow effective gas exchange. In fact, the decrease in lung fluid begins during labor (3). As a consequence of increased catecholamine levels, during labor, there is also an increase in lymphatic drainage. The absence of these physiologic events accounts for the increased incidence of transient tachypnea of the newborn after a cesarean section without labor. The first breath must generate a high transpulmonary pressure to overcome the viscosity of the lung fluid and the intraalveolar surface tension. It also helps to drive the alveolar fluid across the alveolar epithelium. Lung expansion and aeration also stimulate surfactant release with the resultant establishment of an air-fluid interface and development of functional residual capacity (FRC) (4). Normally, 80% to 90% of FRC is established within the first hour of birth in the term neonate with spontaneous respirations.

At birth, the clamping of the umbilical cord increases the systemic vascular resistance with a resultant increase in left ventricular and aortic pressures. Lung aeration and subsequent
gas exchange result in increased PaO₂ and pH, which result in pulmonary vasodilation. These physiologic changes increase flow of blood to the left atrium via the pulmonary veins, so that left atrial pressure exceeds right atrial pressure, resulting in functional closure of foramen ovale. When pulmonary vascular resistance decreases to a level lower than the systemic vascular resistance, the ductus arteriosus closes functionally. As a result of the cessation of umbilical venous return, clamping of the umbilical cord also leads to the closure of the ductus venosus.

Asphyxia has the potential to set in motion a series of responses that can not only impair the normal feto/neonatal transition, but may, in fact, reverse this process and lead to the persistence of the fetal circulatory state. Hypoxia keeps the ductus arteriosus open and causes pulmonary vasoconstriction leading to right-to-left flow across the ductus. Tissue hypoxia causes metabolic acidosis worsening the pulmonary vasoconstriction. The pulmonary hypertension leads to tricuspid insufficiency, raising right atrial pressure, which leads to right-to-left shunting of blood through the foramen ovale, causing further tissue hypoxia. However, in the majority of instances, with timely and appropriate resuscitation, the changes leading to a persistent fetal circulation like state can be reversed quickly.

Asphyxia occurs when the organ of gas exchange fails. When this happens, arterial carbon dioxide partial pressure (PaCO₂) rises, and PaO₂ and pH fall. Despite the low PaO₂, tissues continue to consume O₂, although at a lower rate in some organs. When the PaO₂ is very low, anaerobic metabolism sets in, producing large quantities of metabolic acids. These are buffered partly by the bicarbonate in the blood (5).

The human infant is particularly vulnerable to asphyxia in the perinatal period. During normal labor, transient hypoxemia occurs with uterine contractions, but the healthy fetus tolerates this well. There are five basic events that lead to asphyxia during labor and delivery:

The umbilical cord blood pH, partial pressure of oxygen (PO₂), partial pressure of carbon dioxide (PCO₂), and calculated base excess are standard measures of fetal asphyxia (6,7,8). With fetal acidosis, the pH can vary over a wide range. Consequently, it is important to remember that pH is a logarithmic function of hydrogen ion concentration. A decrease of 0.3 pH units from 7.40 to 7.10 indicates only a 40 nmol/L increase in hydrogen ion (i.e., from 40 to 80 nmol), whereas a 0.3 decrease from 7.10 to 6.80 indicates an increase of 80 nmol/L (i.e., from 80 to 160 nmol). The gradient in blood gas tensions between umbilical artery and vein gives some indication of placental perfusion at the time of birth. The slower the flow of fetal blood through the placenta, the more complete the equilibration of gas tensions between fetal and maternal blood. For example, an arterial PO₂ of 25 mm Hg with a venous PO₂ of 32 mm Hg suggests good placental blood flow. An arterial PO₂ of 12 mm Hg with a venous PO₂ of 45 mm Hg suggests very slow flow. Metabolic acidosis suggests asphyxia, although some of the increased lactic acid in the blood may be a result of reduced uptake of lactate by the asphyxiated liver rather than increased lactate production from anaerobic metabolism (6,9). If asphyxia occurred just before birth, there may be lactic acid in the tissues that has not yet reached the central circulation. This will be detected only by blood gas measurements a few minutes after birth. If the fetus was asphyxiated an hour before delivery and recovered, that event may not be reflected in the umbilical cord blood gases at birth. Other indicators of asphyxia include plasma hypoxanthine, which increases because of lack of aerobic metabolism, plasma erythropoietin, which increases in response to fetal hypoxia, increased plasma levels of several lipid mediators, such as platelet-activating factor, and increased cerebrospinal fluid levels of several proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-8 (10,11,12).

Asphyxia in the fetus or newborn infant (including a preterm infant) is a progressive and reversible process. The speed and extent of progression are highly variable. Sudden, severe asphyxia can be lethal in less than 10 minutes. Mild asphyxia may progressively worsen over 30 minutes or more. Repeated episodes of brief, mild asphyxia may reverse spontaneously but produce a cumulative effect of progressive asphyxia. In the early stages, asphyxia usually reverses spontaneously if its cause is removed. Once asphyxia is severe, spontaneous reversal is unlikely because of the circulatory and neurologic changes that accompany it. Other sources provide a more detailed review of these phenomena (13,14).

Figure 18-1 schematically represents the sequence of pathophysiologic changes that accompany asphyxia. Although there are some quantitative differences between the changes that occur in the fetus and those in the newborn infant, the scheme generally applies to both. It is useful to consider the changes in both fetus and newborn infant together, because many cases of neonatal asphyxia
begin in the fetus and continue after birth. Cardiac output is maintained early in asphyxia, but its distribution changes radically. Selective regional vasoconstriction reduces blood flow to less vital organs and tissues such as gut, kidneys, muscle, and skin (15). Blood flow to the brain and myocardium increases, thereby maintaining adequate oxygen delivery despite reduced oxygen content of the arterial blood. Other organs and tissues must depend on increased oxygen extraction to maintain oxygen consumption (16,17). Pulmonary blood flow is low in the fetus. It is decreased further by hypoxia and acidosis (18). As a consequence of these adaptations, fetal oxygen consumption decreases (19).

Early in asphyxia, newborns make vigorous attempts to inflate their lungs. If successful, the lungs become adequately ventilated and perfused, but the mere presence of gasping does not ensure that this will happen. As asphyxia becomes more severe, the respiratory center is depressed, and the chances of an infant spontaneously establishing effective ventilation and pulmonary perfusion diminish.

If asphyxia progresses to the severe stage, oxygen delivery to the brain and heart decreases. The myocardium then uses its stored reserve of glycogen for energy. Eventually, the glycogen reserve is consumed and the myocardium is exposed simultaneously to progressively lower values of PO₂ and pH. The combined effects of hypoxia and acidosis lead to decreased myocardial function and decreased blood flow to the vital organs (20,21). Brain injury begins late during this phase (13,14).

This sequence of cardiovascular events is manifested by changes in heart rate and aortic and central venous pressures (see Fig. 18-1), all of which are measured easily in the newborn immediately after birth. The early bradycardia and hypertension are caused by the reflexes that shunt blood away from nonvital organs. Early in asphyxia, central venous (i.e., right atrial) pressure may rise slightly, owing to pulmonary hypertension and constriction of systemic capacitance vessels. As the myocardium fails, central venous pressure rises further, aortic pressure decreases, and heart rate is reduced further.

The initial adaptations of the systemic circulation to asphyxia are mediated by various physiologic reflexes (22). There also are major hormonal responses to asphyxia, including elevations in plasma corticotrophin, glucocorticoids, catecholamines, arginine vasopressin, renin, and atrial natriuretic factor, and a decrease in insulin (23,24). Some of these are important in maintaining the circulatory adaptations to asphyxia. Catecholamines, which come mainly from the adrenal medulla, maintain myocardial function in the presence of asphyxia, thereby increasing survival (25,26). Arginine vasopressin helps maintain the hypertension, bradycardia, and redistribution of systemic flow (27). Increased hepatic glycogenolysis helps maintain plasma glucose concentrations (9).

The physiology of resuscitation is essentially a reversal of the pathophysiology of asphyxia. In Fig. 18-1, which illustrates both processes, asphyxia proceeds from left to right, and resuscitation from right to left. It is crucial to determine where the infant is in this sequence of pathophysiologic events when resuscitation is started. If asphyxia has proceeded to myocardial failure, resuscitation must include restoration of cardiac output as well as establishment of effective ventilation and perfusion of the lungs. Generally, myocardial failure does not occur until both pH and PaO₂ are extremely low, approximately 6.9 and 20 mm Hg, respectively. Cardiac output is reestablished through rapid correction of the severe hypoxia and acidosis. Until this is done, output must be maintained by cardiac massage. As soon as pH is raised to approximately 7.1 and PaO₂ to 50 mm Hg, the myocardium responds rapidly, heart rate rises, aortic pressures rise, and pulse pressure widens, whereas central venous pressure falls. These changes indicate that cardiac massage can be stopped. At this point, the infant may be hypertensive because the vasoconstriction in nonvital organs is still present. This vasoconstriction is relieved only by continued adequate oxygenation and correction of acidosis. Pressures then will fall toward normal. The vasoconstriction also is manifested by intense pallor of the skin. As the vasoconstriction is relieved, the skin becomes pink and well perfused, with rapid capillary refilling (i.e., less than 2 seconds) when blanched by pressure. As peripheral flow improves, lactic
acid sequestered in these tissues enters the central circulation and a large base deficit, which may have been corrected earlier, now reappears.

If asphyxia is only moderately severe, resuscitation begins in the middle of the sequence depicted in Fig. 18-1. There is hypertension, indicating that the myocardium has not yet failed. Effective ventilation of the lungs with a high oxygen concentration may correct acidosis by lowering the PaCO₂, oxygenating the blood, and adequately dilating the pulmonary vascular bed. If significant acidosis persists after alleviation of the hypercarbia, alkali might be needed to correct the metabolic component of the acidosis, relieve pulmonary vasoconstriction, and establish good pulmonary perfusion. Generally, raising pH to 7.25 is sufficient for this purpose, but there are some important exceptions (discussed below) in which a higher pH is needed to dilate the pulmonary vascular bed.

When the effects of asphyxia are alleviated, spontaneous respiratory efforts return. The duration between the onset of resuscitation and reappearance of spontaneous respiratory efforts is directly proportional to the amount of brain injury that has occurred (13).

Onset of spontaneous respiratory efforts is not necessarily an indication to withdraw assisted ventilation. Often, there is residual atelectasis and the infant does not have strong, regular respiratory efforts. PaCO₂ may be normal, and PaO₂ may rise to a high level with assisted ventilation. But when assisted ventilation is withdrawn, effective ventilation may decrease and the whole process of asphyxia recurs. Therefore, assisted ventilation and supplemental oxygen should be only gradually withdrawn.

The blood volume of the asphyxiated infant may be abnormal. Asphyxia during labor usually shifts blood from the placenta to the fetus. There are certain situations, however, in which the infant’s blood volume may be reduced. The most obvious of these is hemorrhage from the fetoplacental unit, which is manifested by vaginal bleeding. Three other conditions that shift blood volume from the fetus to the placenta are compression of the umbilical cord, in which umbilical venous flow is reduced selectively more than arterial flow; severe hypotension in the mother; and asphyxia occurring only at the end of labor (28).

Initially, it may be difficult to determine whether or not blood volume is adequate in the asphyxiated newborn. There are two reasons for this. First, many of the circulatory responses to asphyxia are similar to those associated with loss of blood volume. Either asphyxia or hypovolemia may cause bradycardia, metabolic acidosis, poor peripheral perfusion indicated by pallor and slow capillary filling, and a large difference between core and skin temperature. A low aortic pressure could be a result of either the end stage of asphyxia or to shock. Only changes in central venous pressure are in the opposite direction, and even here the coexistence of the two processes can have offsetting effects. Second, the circulatory changes during asphyxia and resuscitation may determine the adequacy or inadequacy of the circulating blood volume. If an infant is moderately asphyxiated and has systemic and pulmonary vasoconstriction (see Fig. 18-1, center) and a small blood volume, aortic and central venous pressures will be nearly normal. Administration of a blood volume expander at this point would only overload the circulation. The effects of volume expansion would be even worse if the asphyxia were more severe and myocardial failure were present. Correction of asphyxia (see Fig. 18-1, going from right to left) relieves the vasoconstriction of resistance and capacitance vessels, and the small blood volume now becomes inadequate to support the circulation. Reperfusion of asphyxic and ischemic tissues also increases loss of intravascular water from these capillary beds, leading to edema and reduced plasma volume.

During recovery from asphyxia, several metabolic abnormalities appear. There may be hypoglycemia caused by depletion of carbohydrate reserves during the asphyxia. Hypoglycemia must be prevented because it can cause myocardial failure in a heart recently subjected to asphyxia (29). Hyperglycemia caused by excessive glucose administration similarly is dangerous during asphyxia because it worsens the acidosis by increasing lactic acid production (30). Hypocalcemia also develops, possibly as a result of increased calcitonin release during asphyxia (31), and can lead to myocardial failure.

Hyperkalemia occurs during asphyxia, when, in the process of buffering acidosis, H⁺ enters the erythrocytes and K⁺ is displaced from them. Although this increases plasma K⁺ while the patient is asphyxiated, total body K⁺ decreases as some of the K⁺ is excreted by the kidney. On relief of asphyxia, the buffering processes are reversed and K⁺ leaves the plasma and reenters the erythrocytes, leading to hypokalemia.

Certain situations during pregnancy, labor, or delivery carry an increased risk of intrapartum asphyxia. If these high-risk deliveries are identified before birth, their progress during labor and delivery should be closely monitored and resuscitation can be initiated at birth. Tables 18-1 and 18-2 list some of the factors that alert the physician to a high-risk delivery. Optimal management of these cases requires good communication between the obstetrician, anesthesiologist, and pediatrician.

If a severely asphyxiated infant is expected, a resuscitation team must be present at delivery. In the majority of instances, good communication between the obstetrician and pediatrician will provide timely notice of the impending delivery of an asphyxiated infant. The actual extent of resuscitation needed can be determined only after someone with considerable clinical experience evaluates the infant’s condition. It is helpful to assign the responsibility of each member of the resuscitation team before delivery.
The following is an example of outlining the responsibilities of each member of the resuscitation team.

Member A:

Member B:

Member C: