Providing anesthetic care for infants and children poses unique challenges because of the profound differences in physiology, pharmacokinetics, and pharmacodynamics of anesthetic drugs, and the wide variety of procedures that these patients undergo, which are often very different from the adult population. The developmental physiology, pharmacology, fluid and transfusion therapy, and airway management in pediatric anesthesia will be defined. Anesthetic considerations and techniques in pediatric patients, especially in neonates, who are the most unique group of pediatric patients, will be reviewed. The new field of fetal surgery will be addressed, and finally, the growing area of anesthesia in remote locations for pediatric patients and anesthetic neurotoxicity in the developing brain will be discussed briefly.
Lung development begins in the fourth week of gestation, but extrauterine survival becomes possible only when terminal air sacs begin to form and the capillary network surrounding them is sufficient for pulmonary gas exchange around the 26th week. Alveolar formation begins by the 36th postconceptual week, but most alveoli form postnatally. Type II pneumocytes begin producing surfactant around the 24th week of gestation, and production of this mixture of phospholipids and surfactant proteins is critical for reducing surface tension and facilitating the inflation of alveoli.
Chest Wall and Respiratory Muscles
The ribs extend from the vertebral column horizontally in infants compared to a caudad angle in adults. This configuration renders the accessory muscles of respiration ineffective in infants. The rib cage also tends to move inward during inspiration because of the high cartilage content in the ribs of neonates and infants. This paradoxic chest wall movement occurs commonly under general anesthesia and is due to decreased tone of the intercostal muscles and upper airway obstruction. The diaphragm increases its work to maintain tidal volume, which can lead to fatigue.
The mature diaphragm has a low content of type I (slow twitch, high oxidative capacity) muscle fibers. Prior to 37 weeks’ postconceptual age, less than 10% of the diaphragmatic fibers are type I. A term infant has approximately 25% type I fibers, and an adult has approximately 50%. This means that the diaphragm is more likely to become fatigued in premature and term infants, leading to earlier respiratory failure.
Chest wall compliance decreases throughout childhood and adolescence owing to the ossification of the ribs and development of thoracic muscle mass. The elastic recoil pressure of the lung increases throughout this time from an increase in pulmonary elastic fibers.
There are some major differences in static lung volumes and respiratory variables between children of different ages and adults (also see Chapter 5 ). Table 34.1 illustrates the major differences in these and other variables between infants and adults. Total lung capacity (TLC) is much larger per kilogram in adults compared with infants. This is largely due to the relative efficiency and strength of adult muscles of inspiration and effort.
|50 ± 10
|30 ± 5
|24 ± 6
|24 ± 6
|23 ± 5
|20 ± 5
|18 ± 5
|12 ± 3
|Dead space/tidal volume ratio
|Functional residual capacity
|Total lung capacity
|Closing volume as percentage of vital capacity
|Number of alveoli
|Saccules × 10 6
|C l /FRC:mL/cm H 2 O/L
|Specific conductance of small airways
|mL/s/cm H 2 O/g
|55 ± 7
|37 ± 3
|35 ± 2.5
|40 ± 3
|40 ± 2
|40 ± 2
|42 ± 2
|Pa co 2
|Pa o 2
Functional residual capacity (FRC) is similar on a per kilogram basis among age groups. However, the mechanical reasons for this similarity differ. The FRC in adults is defined as the volume at which passive elastic forces of the chest wall are balanced by the recoil of the lung. This is the volume at end exhalation. In infants, both the elastic recoil of the chest and the recoil pressure of the lung are very small. This would predict an FRC of about 10% of TLC. However, the FRC is about 40% of TLC owing to a prolongation of the expiratory time constant by a process known as laryngeal braking .
In an apneic infant, the lung volume is smaller than the FRC. Thus, an apneic infant has a disproportionately smaller store of intrapulmonary oxygen than an adult, and hypoxemia will develop rapidly if the airway is poorly maintained.
In infants, the closing capacity (CC) is larger than the FRC, so during exhalation, small airways start to collapse and trap air. In adults, the closing capacity is smaller than the FRC.
Factors Affecting Respiration
In both infants and adults, Pa o 2 , Pa co 2 , and pH control ventilation. An increase in Pa co 2 increases minute ventilation by increasing respiratory rate and tidal volume. This response to hypercapnia is not enhanced by hypoxemia. In fact, hypoxia may depress the hypercapnic ventilatory response.
High inspired oxygen concentrations depress newborn respiratory drive, and low inspired oxygen concentrations stimulate it. However, continued hypoxia will eventually lead to respiratory depression. Hypoglycemia, anemia, and hypothermia also decrease respiratory drive.
Metabolic demand drives minute ventilation. As oxygen consumption increases, alveolar minute ventilation increases. Although tidal volume also increases, the increase in respiratory rate is the predominant variable that increases minute ventilation in infants.
Normal newborn breathing is periodic. There are pauses of less than 10 seconds and periods of increased respiratory activity. Periodic breathing is different from apnea, a ventilatory pause associated with desaturation and bradycardia. Apnea is associated with prematurity and is treated with respiratory stimulants and with tactile stimulation such as stroking or rocking. Postoperative apnea in former premature infants is an important consideration in the planning of outpatient surgery.
The fetal circulation is characterized by (1) increased pulmonary vascular resistance (PVR) with very little pulmonary blood flow, (2) decreased systemic vascular resistance (SVR) with the placenta as the major low resistance vascular bed, and (3) right-to-left blood flow through the ductus arteriosus and foramen ovale ( Fig. 34.1 ). At birth, three events change the circulation into its postnatal configuration. First, alveolar oxygen concentration increases, and alveolar carbon dioxide concentration decreases with the expansion of the lungs. This results in a decrease in PVR. Second, the low resistance placental bed is removed from the circulation when the umbilical cord is clamped. This results in an increase in SVR. The decrease in PVR leads to an increase in pulmonary blood flow and therefore an increase in blood return to the left side of the heart. The increase in left atrial pressure functionally closes the foramen ovale.
The three fetal channels that close after birth are the ductus arteriosus, ductus venosus, and foramen ovale. The ductus arteriosus is functionally closed in 98% of neonates at 4 days of life. It constricts because of an increase in arterial oxygen tension and a decrease in prostaglandins released from the placenta. Later, the constricted duct becomes fibrotic becoming the ligamentum arteriosum. The ductus venosus closes with the clamping of the umbilical vein. The portal pressure decreases, and the ductus venosus closes. Via the ductus venosus, an umbilical venous catheter enters the inferior vena cava and becomes a true central venous catheter. The foramen ovale is patent in many infants and is probe patent in 30% of adults.
If pulmonary artery vasoconstriction occurs in the first few days of life as a result of hypoxemia, acidosis, or pulmonary hypertension, blood can shunt right to left through the previously functionally closed foramen ovale or the ductus arteriosus, resulting in profound hypoxemia and acidosis. This is termed persistent fetal circulation and can be life threatening. Treatment is directed toward decreasing PVR.
The Neonatal Myocardium
The neonatal myocardium is characterized by poorly organized myocytes that contain fewer contractile elements than the adult myocardium, in which the myocytes are well organized in a parallel arrangement. The sarcoplasmic reticulum in the neonatal heart is immature with disorganized T-tubules. The neonatal myocardium depends heavily on the concentration of free ionized calcium for contractility. Transfusion of blood products to neonates may cause hypocalcemia and depressed cardiac function, which can be treated with calcium administration (also see Chapter 24 ).
Although the stroke volume of neonates is usually fixed and the cardiac output usually increases by increasing heart rate only, the neonate can increase stroke volume up to a point according to the Frank-Starling relationship if the afterload is kept low.
Autonomic Innervation of the Heart
The parasympathetic nervous system predominates early in life, while the sympathetic nervous system is still developing. This imbalance is clinically relevant and can be seen as marked bradycardia or even asystole during laryngoscopy, orogastric tube placement, or tracheal suctioning in the neonate or infant. Many anesthesia providers will pretreat with an anticholinergic, atropine or glycopyrrolate, prior to airway instrumentation.
Newborn Cardiovascular Assessment
The newborn cardiovascular examination should focus on the hemodynamics, including heart rate and arterial blood pressure (in all extremities) and oxygen saturation measurements. Other parts of the examination include capillary refill, peripheral pulses, respiratory status, and the possible presence of a murmur or third or fourth heart sound on auscultation. Urine output trends should be assessed. Analysis of arterial, venous, or capillary blood gases should be performed if acidosis is suspected. If performed, results of a chest radiograph, electrocardiogram, or echocardiogram should be reviewed. Normal cardiovascular variables are displayed in Table 34.2 .
|Heart Rate (beats/min)
|Systolic Blood Pressure a (mm Hg)
|Neonate (<30 days)
The Renal System
Postnatally, the kidneys replace the placenta in maintaining metabolic homeostasis. The glomerular filtration rate (GFR) is 15% to 30% of adult values at birth and increases to 50% at 5 to 10 days of life. Adult values are reached by 1 year of age. The low GFR affects the neonate’s ability to excrete sodium, water loads, and some drugs. Tubular function develops after 34 weeks of gestation. The tubules are immature and have a reduced threshold at which bicarbonate is no longer completely reabsorbed by the kidney. This is associated with the inability of young infants to respond to an acid load and the slightly reduced values of pH (7.37) and plasma bicarbonate (22 mEq/L). Infants also have decreased concentrating ability and a low level of production and excretion of urea. Blood urea nitrogen (BUN) remains normal because less urea is being produced. Creatinine immediately postnatally equals the maternal value and decreases in the first 48 hours to levels of 0.5 mEq/L or less if renal function is normal.
The Hematologic System
The blood volume in the newborn ranges from 82 to 93 mL/kg for the term newborn to 90 to 105 mL/kg for the preterm newborn. After the first year of life, blood volume declines to approximately 70 to 80 mL/kg. The normal newborn hemoglobin is 14 to 20 g/dL. Fetal hemoglobin (HgF) makes up 70% to 80% of the hemoglobin at birth. HgF has a higher affinity for oxygen than does adult hemoglobin. The higher affinity of HgF for oxygen shifts the oxyhemoglobin dissociation curve to the left. The P 50 of HgF is 18 to 20 mm Hg, and the P 50 of adult hemoglobin is 27 mm Hg. The difference in P 50 between the two types of hemoglobin facilitates the uptake of oxygen by the fetus at the placental interface.
The physiologic nadir in hemoglobin occurs at 9 to 12 weeks of life and is 10 to 11 g/dL in the term infant. The decreased hemoglobin values do not affect oxygen delivery because of a shift in the oxyhemoglobin dissociation curve to the right. The rightward shift is caused by an increase in 2,3-diphosphoglycerate (2,3-DPG) and the replacement of HgF by adult hemoglobin and facilitates the unloading of oxygen in the tissues. The hemoglobin concentration stabilizes at 11.5 to 12 g/dL until 2 years of age, after which it increases gradually to adult values during puberty.
At birth, the vitamin K–dependent coagulation factors (II, VII, IX, X) are present at 20% to 60% of adult levels. This may lead to a prolonged prothrombin time. It can take several weeks for these factors to reach normal values owing to synthesis in an immature liver. Prophylactic intramuscular (IM) vitamin K is given to all newborns. In addition, maternal ingestion of some drugs including anticonvulsants and warfarin can cause vitamin K deficiency in the newborn.
Protein binding of drugs is different between infants and adults. Some of this difference is due to a lower concentration of serum protein/albumin in younger children. There is also a lower affinity of protein-bound drugs for serum proteins in neonates compared with adults. With decreased protein binding, the concentration of free drug is increased, resulting in an increase in drug effect. The effect of decreased protein binding is most apparent in highly protein-bound drugs such as phenytoin, bupivacaine, barbiturates, and diazepam (also see Chapter 4 ).
The difference in body composition also has an effect on pharmacokinetics. Preterm and term neonates have a larger percentage of total body water compared with older children and adults. This is reflected in an increase in the volume of distribution (Vd). A larger initial dose of drug is needed to reach the same therapeutic serum level and pharmacologic effect when the Vd is increased. Larger initial doses are required for digoxin, succinylcholine, and antibiotics in neonates. Fentanyl is an important example of a commonly used anesthetic in neonates that requires larger initial doses. Also, neonates and infants may be more sensitive to the effects of certain drugs and need lower serum blood levels to achieve the same effects. Medications should be given slowly and titrated to predetermined effects.
There is also a decreased percentage of fat and muscle in small infants compared with older children and adults. Drugs that rely on redistribution to these tissues for the termination of clinical effects may last longer in small infants. Thiopental and propofol, for example, depend on redistribution for awakening after a single dose.
Hepatic metabolism of drugs changes lipid-soluble, pharmacologically active drugs into usually inactive, nonlipid-soluble drugs for excretion. The activity of most hepatic enzymes is reduced in neonates, as is blood flow to the liver. This can result in a longer duration of effect of some pharmacologic drugs. Again, fentanyl is an important example. Hepatic metabolism of drugs approximates 50% of adult values at birth in a full-term neonate, rapidly increases during the first month of life to near adult values, and is fully mature by 1 or 2 years of age.
Neonatal kidneys become more efficient with age. Owing to immature glomerular and tubular function, drugs that depend on the kidney for excretion such as aminoglycosides have prolonged elimination half-times in neonates. Glomerular and tubular function is nearly mature at 20 postnatal weeks and is fully mature at 2 years.
Pharmacology of Inhaled Anesthetics
F a /F i is the ratio of concentration of alveolar (F a ) to inspired (F i ) anesthetic. At the beginning of an inhaled induction of anesthesia, F a is zero, and F i is large. As the F a /F i increases toward 1, induction of anesthesia occurs. The F a /F i ratio increases more rapidly in neonates compared to adults, which means that anesthesia can be induced more rapidly than in adults. There is a larger alveolar ventilation to FRC ratio (V a /FRC) in neonates compared to adults and thus a more rapid increase in F a /F i . The ratio is 5:1 in neonates and 1.5:1 in adults (also see Chapter 7 ).
Infants and small children may have an increased cardiac output during an inhaled induction via a mask because of preoperative anxiety. Increased cardiac output is associated with increased pulmonary blood flow and higher uptake of anesthetic from the lungs, which decreases F a and slows the increase in F a /F i . Therefore, as a result of uptake, the rate of anesthetic induction would slow down. However, the increased cardiac output also increases anesthetic delivery to the vessel-rich group (VRG), and the partial pressure of anesthetic in the VRG equilibrates with F a . The partial pressure of anesthetic in the venous blood approaches the partial pressure in the alveoli and speeds the increase in F a /F i .
In neonates, there are also reduced tissue/blood solubility and reduced blood/gas solubility. Blood solubility of the higher solubility inhaled anesthestics (isoflurane) is 18% lower in neonates. Therefore, there is less uptake from the alveoli, and the increase in F a /F i is more rapid. The blood solubility of the less soluble inhaled anesthetics, such as sevoflurane and desflurane, does not differ between infants and adults, and F a /F i does not increase as rapidly. The reduced tissue solubility of isoflurane also contributes to a more rapid increase in F a /F i in neonates compared with adults.
Effect of Shunt on an Inhaled Induction of Anesthesia (Also See Chapter 26 )
Left-to-right shunts are mostly intracardiac (ventricular or atrial septal defects) and are associated with increased pulmonary blood flow. These have no real effect on the rate at which induction of anesthesia occurs. Right-to-left shunts involve a portion of the systemic venous return that bypasses gas exchange in the lungs and is circulated systemically. Right-to-left shunts can be either intracardiac (tetralogy of Fallot) or intrapulmonary (endobronchial intubation, atelectasis). Right-to-left shunts slow the rise in F a /F i and delay induction of anesthesia. This is more pronounced with less soluble anesthetics such as sevoflurane and desflurane.
Minimum Alveolar Concentration
Minimum alveolar concentration (MAC) varies with age. The MAC of inhaled anesthetic drugs is highest in infants 1 to 6 months old. The MAC is 30% less in full-term neonates for isoflurane and desflurane. Sevoflurane MAC at term is the same as at age 1 month. The presence and degree of prematurity decrease MAC. This may be due to immaturity of the central nervous system or neurohumoral factors. Cerebral palsy and developmental delay also reduce the MAC by 25%.
Fluids and Electrolytes
Intraoperative Fluid Administration
Intravenous (IV) fluid given to children in the operating room serves one of four purposes: replacement of a deficit, maintenance fluids, balancing ongoing losses, and treatment of hypovolemia (also see Chapter 23 ). Although hypotonic solutions such as 0.2% normal saline with added dextrose and potassium are often used outside the operating room for maintenance fluid administration, generally, nonglucose-containing isotonic solutions are given in the operating room in order to avoid hyponatremia and abnormalities of serum potassium concentrations. Lactated Ringer solution and Plasma-Lyte A are the most commonly used isotonic solutions in pediatric patients. Administration of 5% albumin is the most common colloid used in pediatric patients, but disagreement exists as to the efficacy of this therapy versus isotonic crystalloid administration.
Replacement of Preoperative Fluid Deficits
The preoperative deficit is the number of hours that a patient has had no oral intake or has been nil per os (NPO) multiplied by the hourly maintenance fluid requirement of the patient ( Table 34.3 ). Generally, 50% of the deficit is replaced in the first hour of anesthesia, and the remaining 50% is replaced during the following 2 hours.
|Basis for Replacement
|Replacement of Ongoing Losses a
a Replacement for ongoing losses with crystalloid must always be integrated with the patient’s current cardiorespiratory status, status as evaluated during the surgical procedure, estimated blood loss with plans for blood product replacement, and baseline medical problems.
Patients presenting for emergency surgery may have larger fluid deficits from vomiting, fever, third-space fluid loss, or blood loss that needs to be taken into account. The use of warmed fluids should be considered to avoid hypothermia with administration of large amounts of intravascular volume replacement.
The hourly maintenance rate should be calculated using the “4-2-1 rule” and should be administered in the form of isotonic solution throughout the case.
Ongoing Fluid Losses
Ongoing losses can be characterized as whole blood loss, third-space loss, and evaporation. When blood or colloid is used to replace blood loss, a ratio of 1:1 is used. When crystalloid is used to replace blood loss, a ratio of 3:1 is used. Third-space and evaporative losses vary with the invasiveness of the procedure from noninvasive such as a strabismus repair to very invasive such as an exploratory laparotomy for necrotizing enterocolitis (NEC) (see Table 34.3 ). Third-space losses can be replaced with isotonic crystalloid.
Treatment of Hypovolemia
Intravascular volume can be monitored in pediatric patients by assessing the hemodynamic variables for the age group. Tachycardia and decreased arterial blood pressure suggest hypovolemia. Monitoring of urine output or central venous pressure can provide other information about intravascular volume status. If hypovolemia is suspected, a 10 to 20 mL/kg bolus of crystalloid or colloid can be given.
Glucose-containing solutions should not be used routinely in pediatric patients intraoperatively. They should not be used to replace intravascular fluid deficits, third-space losses, or blood loss. In children older than 1 year of age, the stress and catecholamine release associated with surgery usually prevent hypoglycemia. Glucose is commonly given to patients who are younger than 1 year of age or less than 10 kg. Pediatric patients at greater risk for developing hypoglycemia include premature and term neonates and any patient who is critically ill or who has hepatic dysfunction. Patients receiving total parenteral nutrition with high dextrose concentrations preoperatively can either be continued on a reduced rate of the same infusion or can be converted to a 5% or 10% dextrose-containing infusion to maintain the administration of glucose. An infusion pump should be used for high-concentration dextrose solutions to avoid bolus administration. Blood glucose concentration should be monitored closely in patients with risk of glucose instability.
Maximum Allowable Blood Loss
Before anesthesia, the maximum allowable blood loss (MABL) should be calculated for a given case and to prepare for possible transfusion of red blood cells (also see Chapter 24 ). The estimated blood volume (EBV) is dependent on the age of the child and hematocrit (Hct):