Handbook of Clinical Anesthesia

Chapter 44

Neonatal Anesthesia

The first year of life is characterized by an almost miraculous growth (body weight changes by a factor of three) in size and maturity (Hall SC, Suresh S: Neonatal anesthesia. InClinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1171–1205).

  1. Physiology of the Infant and the Transition Period

The newborn period has been defined as the first 24 hours of life and the neonatal period as the first month. The first 72 hours are especially significant for the cardiovascular, pulmonary, and renal systems.

  1. The Cardiovascular System (Fetal Circulation)(Fig. 44-1A
  2. Changes at Birth(Fig. 44-1B)
  3. Myocardial function is different in neonates because the cardiac myocytes have less organized contractile elements than in children and adults. The neonatal myocardium cannot generate as much force as in older children and is relatively noncompliant. Consequently, there is limited functional reserve in the neonatal period, and afterload increases are particularly poorly tolerated.
  4. Especially in the first 3 months of life, the influence of the parasympathetic nervous system on the heart is more mature than the influence of the sympathetic system, and the myocardium does not respond to inotropic support as well as in older children and adults.
  5. Even in the absence of stress, the neonatal heart has limited ability to increase cardiac output compared with the mature heart (Fig. 44-2).
  6. The Pulmonary System
  7. The airways and alveoli continue to grow after birth, with the alveoli increasing in number until about 8 years of age.


  1. With the initiation of ventilation, the alveoli transition from a fluid-filled to an air-filled state, and a normal ventilatory pattern with normal volumes develops in the first 5 to 10 minutes of life. Blood gases stabilize with the establishment of increased pulmonary blood flow (Table 44-1).
  2. Tidal volume is about the same in neonates as in children and adults on a volume per kilogram body weight measure, but the respiratory rate is increased in neonates (Table 44-2 and Fig. 44-3).

Figure 44-1. A. Schematic representation of the fetal circulation. B. Schematic representation of the circulation in the normal newborn. DA = ductus arteriosus.

  1. Increased minute ventilation mirrors the higher oxygen consumption in neonates (about double that seen in adults).
  2. The ratio of minute ventilation to functional residual capacity (FRC) is two to three times higher in newborns. As a result, anesthetic induction and emergence with a volatile anesthetic agent should be faster. In addition, the decrease in FRC relative to minute ventilation and oxygen consumption means that there is less “oxygen reserve” in the FRC than in older children and adults. There is a more


rapid decrease in arterial oxygen levels in newborns in the presence of apnea or hypoventilation.


Figure 44-2. Schema of reduced cardiac reserve in fetal and newborn animal hearts compared with adult hearts.

  1. Decreased surfactant production caused by prematurity or other conditions such as maternal diabetes can cause respiratory distress syndrome (RDS). Commercially


available surfactant is extraordinarily useful in treating and preventing RDS in susceptible patients.

  1. Neonates do not respond as well to hypercapnia as older children.

Table 44-1 Normal Blood Gas Values in Neonates



PO2 (mm Hg)

PO2 (mm Hg)


Fetus (term)

Before labor




Fetus (term)

End of labor




Newborn (term)

10 min




Newborn (term)

1 hr




Newborn (term)

1 wk




Newborn (preterm, 1500 g)

1 wk




  1. Persistent Pulmonary Hypertension of Newborns(Fig. 44-4)
  2. Hypoxia and acidosis, along with inflammatory mediators, may cause pulmonary artery pressure to persist at a high level or after initially decreasing to increase to pathologic levels (persistent fetal circulation).
  3. The elevated pulmonary vascular resistance causes both the ductus arteriosus and foramen ovale to remain open, with subsequent right-to-left (bypassing the pulmonary circulation) shunting.
  4. Treatment goals are to achieve a PaO2of 50 to 70 mm Hg and a PaCO2 of 50 to 55 mm Hg.


Table 44-2 Comparison of Normal Respiratory Values in Infants and Adults




Respiratory frequency



Tidal volume (mL/kg)



Dead space (mL/kg)



Alveolar ventilation (mL/kg/min)



Functional residual capacity (mL/kg)



Oxygen consumption (mL/kg/min)




Figure 44-3. Static lung volumes of infants and adults. CC = closing capacity; FRC = functional residual capacity; VC = vital capacity.


Figure 44-4. Correlation of mean pulmonary arterial pressure with age in 85 normal-term infants studied during the first 3 days of life.


  1. Meconium Aspiration
  2. Meconium aspiration may be a marker of chronic fetal hypoxia in the third trimester. This condition is different from the meconium aspiration that occurs during delivery, which is thick and mechanically obstructs the tracheobronchial system.
  3. Current recommendations for intubation and suctioning for newborns at delivery with frank meconium aspiration or meconium staining (approximately 10% of newborns) emphasize a conservative approach. Routine oropharyngeal suctioning of meconium is recommended immediately at the time of delivery, but tracheal intubation and suctioning should be performed selectively.
  4. If the newborn is vigorous and crying, no further suctioning is needed.
  5. If meconium is present and the newborn is depressed, the trachea should be intubated and meconium and other aspirated material suctioned from beneath the glottis.
  6. The Renal System
  7. At birth, the glomerular filtration rate (GFR) is low but increases significantly in the first few days and doubles in the first 2 weeks; however, it does not reach adult levels until about 2 years of age. The limited ability of newborns' kidneys to concentrate or dilute urine results from this low GFR and decreased tubular function.
  8. The half-life of medications excreted by means of glomerular filtration is prolonged in newborns. The relative inability to conserve water means that neonates, especially in the first week of life, tolerate fluid restriction poorly. In addition, the inability to excrete large amounts of water means that newborns tolerate fluid overload poorly.
  9. Fluid and Electrolyte Therapy in Neonates
  10. Total body water (TBW) decreases to about 75% of body weight for term infants at birth. Preterm infants have higher TBWs than term infants, often in the 80% to 85% range. TBW decreases during the first 12 months of life to about 60% to 65% of body weight and stays at this level through childhood.
  11. TBW is distributed between two compartments, intracellular fluid (ICF) and extracellular fluid (ECF). The ECF volume is larger than the ICF volume in fetuses and newborns, usually in the 40% (ECF) and 20% (ICF)


of body weight ranges. This is the opposite of the situation in infants and children.

  1. The ECF and ICF volumes (20% and 40% of body weight, respectively) approach adult values by about 1 year of age. This dramatic shift is beneficial to the child, especially in increasing the mobility of reserves in the face of dehydration.
  2. Fluid can be easily mobilized from ICF volumes to replenish intravascular volume that is lost from fasting, fever, diarrhea, or other causes. This means that non-neonates are better situated to maintain intravascular volume in these situations than neonates.
  3. The blood volume in normal full term newborns is approximately 85 mL/kg and approximately 90 to 100 mL/kg in the preterm newborns.
  4. Maintenance fluid requirements have been estimated to be 60, 80, 100, and 120 mL/kg/24 hours for the first 4 days of life, respectively. For the rest of the neonatal period, a maintenance rate of 150 mL/kg/24 hours is appropriate.
  5. Because of ongoing sodium loss secondary to the inability of the neonatal distal tubule to respond fully to aldosterone, intravenous (IV) fluids in neonates must contain some sodium (balanced salt solution such as lactated Ringer's solution or Plasmalyte).
  6. The other issues for fluid choice in neonates center on appropriate glucose administration. Neonates who are scheduled for surgery and have been receiving hyperalimentation fluids or supplementary glucose must continue to receive that fluid during surgery or must have their glucose levels monitored because of concerns of hypoglycemia.
  7. Blood Component Therapy in Neonates
  8. The indications in the perioperative period for red blood cells are similar to those in adults, but the target values in available guidelines are higher. Transfusion is indicated for a hemoglobin less than 10 g/dL for major surgery. The hemoglobin in transfused blood is hemoglobin A as opposed to hemoglobin F in neonates at birth. An advantage of the transfused blood is better release of oxygen at the tissue level from hemoglobin A.
  9. It is recommended that platelets be kept above 50,000/mL3for invasive procedures. These recommendations are based on expert consensus, not prospective studies.


  1. The Hepatic System
  2. The functional capacity of the liver is immature in newborns, especially synthetic and metabolic functions. Because of this immaturity, some drugs that undergo hepatic biotransformation, such as morphine, have prolonged elimination half-lives in newborns. Up to 85% of unmetabolized caffeine may be found in the urine in newborns compared with 1% in adults.
  3. Decreased metabolism of a drug may actually increase its safety profile. Acetaminophen undergoes less biotransformation by the cytochrome P450 system in newborns, producing less reactive metabolites that are toxic.
  4. Anatomy of the Neonatal Airway (Fig. 44-5)
  5. The majority of neonates are preferential nose breathers, and anything that obstructs the nares may compromise the neonate's ability to breathe.

Figure 44-5. Complicating anatomic factors in infants.


  1. The large tongue occupies relatively more space in the infant's oropharynx, promoting both soft tissue obstruction of the upper airway and increasing the difficulty of laryngoscopic examination and intubation of the infant's trachea.
  2. In adults, the narrowest aspect of the upper airway is at the vocal cords, but in neonates, there is further narrowing until the level of the cricoid ring. (This is susceptible to trauma from intubation or placement of too large an endotracheal tube.)

III. Anesthetic Drugs in Neonates (Table 44-3)

The pharmacokinetics of drugs in neonates are different than in older children and adults. Factors affecting the metabolism of drugs in neonates include a larger volume of distribution, decreased protein binding, and decreased fat stores and immature renal and hepatic function.

  1. Anesthetic Management of Neonates

Effective evaluation, preparation, and anesthetic management of neonates are dependent on appropriate knowledge, clinical skills, and vigilance by the anesthesiologist. The anesthesiologist needs to develop a detailed plan that encompasses the issues of anesthetic equipment and monitoring, airway management, drug choice, fluid management, temperature control, anticipated surgical needs, pain management, and postoperative care.

  1. Preoperative Considerations
  2. Preanesthetic Evaluation: History.The preanesthetic planning process starts with an evaluation of the course of intrauterine growth followed by labor and delivery and the immediate postpartum course.
  3. The World Health Organization definition of prematurity is less than 37 weeks gestation at birth. The greater the degree of prematurity, the more physiologic abnormalities will be expected (variability of responsiveness to anesthetic agents, fluids, cardioactive drugs, and the stress of the surgical procedure) (Table 44-4).
  4. Low birth weight is defined as a birth weight of 2500 g or less.
  5. Preanesthetic Evaluation: Physical Examination.Physical examination of newborns is focused by the condition requiring surgical intervention.


Table 44-3 Anesthetic Drugs for Use in Neonates

Intravenous Agents Anticholinergics (atropine and glycopyrrolate are used frequently in neonates to decrease secretions and the vagal response to intubation)
Midazolam (used for premedicating infants before surgery)
Thiopental (should be avoided in neonates with congenital heart disease)
Ketamine (used frequently in neonates with congenital heart disease; based on animal data, there is a question of neurodegenerative changes)
Fentanyl (mainstay in newborns for sedation and analgesia; even the use of small doses may result in respiratory depression)
Neuromuscular Blocking Agents
Succinylcholine (increased dose requirement; used to treat laryngospasm)
Nondepolarizing agents (variable and unpredictable duration of action)
Rocuronium (alternative to succinylcholine)
Vecuronium (long acting in infants younger than 1 year of age)
Reversal Agents
Edrophonium (rapid onset)
Volatile Agents
Halothane (still used outside North America)
Sevoflurane (most commonly used agent; rapid induction and awakening)
Desflurane (pungent)
Local Anesthetic Solutions
Bupivacaine (most commonly used)
Topical Anesthesia

EMLA = eutectic mixture of local anesthetic; LMX-4 = 4% liposomal lidocaine solution.


Table 44-4 Abnormalities Associated with the Preterm Infants: Common Anesthetic Concerns

Respiratory distress syndrome
Pneumothorax, pneumomediastinum
Pulmonary hemorrhage
Bronchopulmonary dysplasia
Patent ductus arteriosus
Pulmonary hypertension
Persistent transitional circulation
Congenital heart disease
Central Nervous System
Intraventricular hemorrhage
Hypoxic-ischemic encephalopathy
Drug withdrawal
Metabolic acidosis
Poor urine output
Poor feeding
Necrotizing enterocolitis
Intestinal obstruction
Vitamin K deficiency
Retinopathy of prematurity
Sepsis and infections


  1. If there are clinical signs of dehydration, efforts should be made to correct the deficits before surgery except in extreme, life-threatening situations.
  2. Physical examination also focuses on the respira-tory and cardiovascular systems.
  3. Preanesthetic Evaluation: Laboratory Tests
  4. Most newborns should have a blood count and glucose level drawn.
  5. Electrolyte determinations and coagulation profiles are indicated in specific patients. Unexplained hypotension, irritability, or seizures can be presenting signs of hypocalcemia.
  6. Preanesthetic Plan(Table 44-5)
  7. Premedicationis not commonly used for neonatal anesthetics (atropine may be used because of the dominance of the parasympathetic nervous system and bradycardia on induction or in response to inhalational agents).
  8. Intraoperative Considerations
  9. Monitoring.Neonatal patients are at a disadvantage when it comes to perioperative monitoring because of their small size. Pulse oximetry is one of the most important monitors in neonatal anesthesia. Electrocardiography is useful primarily to assess heart rate and rhythm. Blood pressure measurements are important in the management of all newborns. An effective alternative to a conventional blood pressure cuff is to use a manual cuff and place a Doppler probe over the brachial or radial artery.
  10. Anesthetic Systems.There is a long tradition in pediatric anesthesia of using semi-open, non-rebreathing systems for general anesthesia in newborns (Jackson-Rees


adaptation of the Ayre's t-piece, Bain circuit). As the use of these circuits has diminished, familiarity with their use and application has decreased in favor of the semi-closed rebreathing circle systems used in adult patients.

Table 44-5 Major Factors to Consider in Planning the Anesthesia for Neonates

Need to have blood and blood products available
Need for invasive monitoring
Need for additional equipment for securing the airway or establishing vascular access
Need to transport the neonate to and from the operating room
Likelihood of postoperative ventilation
Plan for postoperative pain relief

  1. Induction of Anesthesia.There is no one method of induction and maintenance of anesthesia that is best for all patients.
  2. Airway Management.Most newborns' tracheas are intubated after a rapid sequence induction. A Miller #1 blade is commonly used for full-term newborns and a Miller #0 in preterm newborns. Uncuffed tubes have traditionally been used in newborns to minimize cuff pressure on the subglottic larynx, especially at the level of the cricoid. It is prudent to use the depth markers at the end of the tube to ensure under direct vision that the tip is advanced 2 or 3 cm past the vocal cords.
  3. Anesthetic Dose Requirements of Neonates.Neonates and premature infants have lower anesthetic requirements than older infants and children. The reasons for the lower minimum alveolar concentration (MAC) requirements are believed to be an immature nervous system, progesterone from the mother, and elevated blood levels of endorphins coupled with an immature blood–brain barrier.
  4. Regional Anesthesia(Table 44-6)
  5. Postoperative Pain Control(Table 44-7)

Table 44-6 Regional Anesthesia Techniques That Are Useful in Neonates

Central Neuraxial
Epidural (lumbar, thoracic, caudal)
Peripheral Nerve Blocks
Infraorbital block
Brachial plexus block (axillary, infraclavicular)
Lateral femoral cutaneous block
Penile block
Ilioinguinal block
Scalp blocks

Table 44-7 Postoperative Pain Control for Neonates and Infants

Opioids: Morphine, fentanyl, methadone
NSAID: Ketorolac
Regional and Local Anesthesia

NSAID = nonsteroidal anti-inflammatory drug.


  1. Postoperative Ventilation
  2. If the surgical procedure or the neonate's condition is such that postoperative ventilation is likely, the prolonged respiratory effects of opioids or any other drug are of little concern.
  3. If the surgical procedure will be relatively short and by itself does not require postoperative ventilation, the clinician should carefully select drugs, as well as doses of anesthetic drugs and relaxants, that will not necessitate prolonged postoperative ventilation or intubation.
  4. Postoperative ventilation places the neonate at added risk because of the problems associated with mechanical ventilation, trauma to the subglottic area, and potential development of postoperative subglottic stenosis or edema.
  5. Special Considerations
  6. Maternal Drug Use During Pregnancy.Maternal drug use (cocaine, marijuana) during pregnancy may result in premature birth; intrauterine growth retardation; and cardiovascular abnormalities, including low cardiac output.
  7. Temperature Control and Thermogenesis
  8. Newborns are at risk for significant metabolic derangements caused by hypothermia. (Newborns do


not shiver, increase activity, or effectively vasoconstrict like older children and adults do in response to cold.)

  1. Placing the patient on a forced-air warming blanket may dramatically reduce conductive heat loss.
  2. Anesthetic agents may reduce or eliminate thermogenesis, removing any ability to compensate for cold stress.
  3. Respiratory Distress Syndrome
  4. Exogenous surfactant has been widely used in premature infants of low birth weight either to prevent or to treat RDS.
  5. One of the long-term consequences of RDS is bronchopulmonary dysplasia. Many patients improve as they age, but reactive airways, recurrent pulmonary infections, and prolonged oxygen requirements are seen in some patients.
  6. Anesthetic concerns in these patients include baseline oxygenation and the potential presence of active bronchoconstriction.
  7. These patients often benefit from an additional bronchodilator before induction. Although postanesthetic tracheal intubation is not usually required, a high index of suspicion should be used if there is significant clinical evidence of poor lung function before surgery.
  8. Postoperative Apnea
  9. Apnea and bradycardia are well-recognized, major complications that are possible during and after surgery in neonates. The infants at highest risk are those born prematurely, those with multiple congenital anomalies, those with a history of apnea and bradycardia, and those with chronic lung disease. Hypothermia and anemia can also contribute to the development of postoperative apnea.
  10. Infants with life-threatening apnea and bradycardia before surgery may be taking central nervous system stimulants (caffeine, theophylline [metabolized to caffeine]). Administering caffeine (10 mg/kg) prophylactically to infants at risk of postoperative apnea to ensure adequate serum levels may prevent the need for prolonged periods of postoperative ventilatory support.
  11. Spinal anesthesia without sedation decreases the incidence of postoperative apnea and bradycardia in


high-risk infants, but this advantage is lost if supplemental sedation is used.

  1. Retinopathy of Prematurity (ROP)
  2. Very preterm infants, especially those weighing less than 1200 g, are at highest risk for ROP, with an incidence of significant disease of about 2%.
  3. The most common cited cause of ROP is hyperoxia from administered oxygen, but hypoxemia, hypotension, sepsis, intraventricular hemorrhage, and other stresses have also been implicated.
  4. The primary anesthetic challenge in these patients is related to their extreme prematurity and small size. Adequate monitoring, vascular access, and thermal stability are common challenges to management. Use of supplemental oxygen at pulse oximetry saturations of 96% to 99% does not cause additional progression of prethreshold ROP.
  5. Neurodevelopmental Effects of Anesthetic Agents
  6. Studies have shown that prolonged exposure (equivalent to several weeks of continuous exposure in humans) of animal models to anesthetic agents can lead to neurodegenerative changes in the developing brain of neonatal rats.
  7. Currently, no conclusive evidence demonstrates the deleterious effect of inhaled or IV anesthetics on neurocognitive function in neonates and infants.
  8. Surgical Procedures in Neonates

Surgical procedures in neonates are functionally divided into those performed in the first week and those performed in the first month of life. Emphasis of presurgical stabilization before taking the newborn to the operating room has reduced the emergent nature of newborn surgeries


(congenital diaphragmatic hernia, omphalocele). Exceptions include gastroschisis, which is usually attended to within 12 to 24 hours; airway lesions such webs that are causing significant airway obstruction; and acute subdural or epidural hematomas from traumatic delivery.

Table 44-8 Surgical Procedures Performed in the First Week of Life

Congenital diaphragmatic hernia
Tracheoesophageal fistula
Intestinal obstruction

Table 44-9 Surgical Procedures Performed in the First Month of Life

Exploratory laparotomy for necrotizing enterocolitis
Inguinal hernia repair
Correction of pyloric stenosis
Patent ductus arteriosus ligation
Shunt procedure for hydrocephalus
Placement of a central venous catheter

  1. Surgical Procedures in the First Week of Life(Table 44-8). Two confounding factors in neonatal surgery are prematurity and associated congenital anomalies. The presence of one congenital anomaly increases the likelihood of other congenital anomalies.
  2. Surgical Procedures in the First Month of Life(Table 44-9)

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine

Title: Handbook of Clinical Anesthesia, 6th Edition

Copyright ©2009 Lippincott Williams & Wilkins

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