Neonatal Anesthesia

Ain Shams Journal of Anesthesiology                                         Vol 4-1; Jan 2011

Neonatal Anesthesia 
Hany M. El-Zahaby, MD
Department of Anesthesia, Intensive Care and Pain Management, Faculty of
Medicine, Ain Shams University, Cairo, Egypt.
Safe and effective neonatal anesthesia is one of the most challenging tasks presented to anesthesiologists. Knowledge of  the neonate's unique features, great manual skills and continuous practice are required for the
anesthesiologist to perform such task.
Neonatal Physiology Related to Anesthesia
Nociceptive System and Stress Response
The central nervous system is incompletely developed at birth. However, studies in preterm and term
neonates reported a fully competent neuroendocrine stress reaction in response to surgical stimulation.
Neonatal pain is capable of producing a "pain memory" as a result of plasticity changes within the central
nervous system or a psychological process.
 This confirms that a nonanalgesic technique practice is no longer acceptable.  The potential incompletely developed autoregulation of cerebral blood flow together with fragile infant's cerebral blood vessels
are important factors in the development of intraventricular hemorrhage.
 The spinal cord extends to a lower segment of the spine in neonates than in older children and adults. The volume of cerebrospinal fluid and the spinal surface area are proportionally larger in neonates, whereas the amount of myelination is less than in older children and adults.
These factors explain the increased amount of local anesthetics (mg/kg) required for a successful spinal
anesthetic in infants.   Hyperoxia has been associated with retinopathy of prematurity (ROP).
 However, ROP has been reported in full-term infants, in preterm infants never exposed to greater than ambient oxygen, may affect retina of one eye only, and even in infants with congenital cyanotic heart disease who has low oxygen tension in their blood.



Airways
Beside the small size of the infant's airways, there are five cardinal anatomical features of clinical implication. The high larynx results in more acute angulation between the plane of tongue and the plane of glottis which makes exposure during laryngoscopy more difficult. The large tongue obstructing the airway favors nasal breathing in neonates and makes stabilization of endoscopic view during direct laryngoscopy more difficult and gives privilege for the paraglossal technique of intubation. The anterior attachments of vocal cords are lower than posterior attachments that results in difficulty in nasal intubations where “blindly” placed endotracheal tubeslodges in the anterior commissure rather than in the trachea. The infant's epiglottis is omega shaped and angled away from axis of trachea that makes it more difficult to lift an infant’s epiglottis with laryngoscopic blade.
Narrowest part of infant’s larynx is the cricoid cartilage and though tight fitting endotracheal tubes may cause
edema resulting in a common practice of using uncuffed endotracheal tubes for patients less than 8 years old.
Microcuff endotracheal tube is designed with low pressure distal cuff replacing the Murphy eye to fit the
anatomy of the pediatric larynx.
 Size 3 microcuff endotracheal tube is suitable for term neonates.
Cardiopulmonary
Respiratory Control and Mechanics The neonate has high metabolic rate (5-8 ml/kg/min) that needs sufficient amount of oxygen to be delivered by the cardiopulmonary system which explains the rapid decrease in blood oxygen levels during periods of hypoventilation. The tidal volume of a neonate (6-7 ml/kg/min) and other thoracic gas volumes relative to body weight are close to those of an adult. This makes high respiratory rate
(40-60 breaths/min) and hence high alveolar ventilation (130 ml/kg/min) -compared to 60 ml/kg/min in an adult- responsible for meeting the high rate of oxygen consumption. The neonatal lung compliance is less while chest wall compliance is more than those in adults. They are at increased risk of reduction of functional residual capacity (FRC) and development of atelectasis which can be counteracted by the application of a modest PEEP. Anesthesia negatively affects all respiratory muscles in the neonate increasing the risk of airway
obstruction and thoracoabdominal asynchrony. The diaphragm of the neonate is the dominating respiratory
muscle contains less of oxidative type I fibers making itself susceptible for fatigue. The work of breathing is
composed of compliance and resistive components. The compliance work relative to tidal volume is nearly the
same as in adults bearing in mind the highly compliant lungs on one hand and the low compliance chest wall on
the other hand. The resistive work, however, is nearly six times greater in the neonate. Breathing through an
endotracheal tube increases resistive work. Because the airway resistance is inversely proportional to the fifth
power of the radius and directly proportional to the length of the endotracheal tube, the relatively narrow and long endotracheal tubes through which neonates breathe can greatly increase their work of breathing.
 Additionally, resistive and compliance work are increased when a neonate breathes spontaneously through a circle system because of the inspiratory force required to open the one-way valves in the system.
Neonates and especially ex-premature infants have a tendency toward periodic breathing that is accentuated
by anesthetics increasing the risk of postoperative apnea until approximately 55-60 weeks postconceptual age. Apnea in a neonate is differentiated in terms of etiology into: (1) central apnea, due to immaturity or depression of the respiratory drive; (2) obstructive apnea, due to an infant's inability to maintain a patent airway; and (3) mixed apnea, a combination of both central and obstructive apnea.
Preterm infants are at greater risk of central apnea because of the responsiveness of chemoreceptors to
hypercarbia and hypoxia that develops with advancing conceptual age. Susceptibility to central apnea is
exacerbated by metabolic disturbances such as hypothermia, hypoglycemia, and hypocalcemia, anemia and sepsis.
Central apnea due to immaturity of the respiratory drive center is often treated with xanthine derivatives, such as caffeine and theophylline in addition to increasing the hematocrite and the fraction of inspired oxygen.
Because central apnea in neonates may be exacerbated by opioids, even patients treated with naloxone require continuous monitoring of blood oxygen saturation and apnea monitoring until 12-hours of apnea free
period. Severe premature infants who spent prolonged periods in neonatal intensive care units suffering chronic lung disease, sepsis, anemia and prolonged ventilator support may need postoperative apnea monitoring until the age of 6-12 months. Obstructive apnea may be due to incomplete maturation and poor coordination of upper airway musculature. These forms of apnea can be treated by changing the head position, inserting an oral or nasal airway, placing the infant in a prone position or by applying continuous positive airway pressure (CPAP).
The majority of apneic episodes in preterm infants are due to obstructive or mixed origin apnea.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants who have been born prematurely and are subjected to high levels of oxygen and ventilation therapy.
 BPD is diagnosed in infants with abnormal chest radiographs who require supplemental oxygen at 36 weeks' postconceptual age. Antenatal steroids, exogenous surfactant treatment, and advanced ventilator therapies has decreased the incidence of BPD. The treatment of BPD in infants often requires ventilation, bronchodilators, chronic diuretic and steroid therapies.
Oxygen Uptake and Circulation Fetal hemoglobin has a reduced affinity for 2,3-diphosphoglycerate and
hence a higher affinity for oxygen. Red blood cells containing fetal hemoglobin have an average half-life
of 100 days, compared with 120 days for those containing adult hemoglobin. This leads to a rapid turnover of red blood cells, increase in erythropoietin levels, and increased reticulocyte production.   Oxygen delivery to
systemic tissues in neonates is facilitated by a high cardiac output. At the lower end-diastolic volumes, mild
increases in preload in the neonate are associated with increased cardiac output. However, at greater enddiastolic volumes, due to poor ventricular compliance, cardiac output becomes more dependent on heart rate.
The heart rate of a neonate is approximately 120 beats per minute and increases to 160 beats per minute
by 1 month of age. Parasympathetic control of heart rate matures earlier in gestation and to a greater extent than β-adrenergic control. For this reason, neonates may not respond to hypovolemia or an inadequate depth of anesthesia with tachycardia. Additionally, the vagotonic response caused by succinylcholine or its
metabolites (succinylmonocholine) and synthetic opioids may lead to bradycardia. These reflexes can be
offset by the vagolytic effects of atropine which is the only routine premedication.  With expansion of the lungs during the first breath, pulmonary vascular resistance decreases and blood flow to the lungs increases. Any factor that increases pulmonary vascular resistance (e.g., hypoxia, hypercarbia, or acidosis) may result in a return to the fetal-type of circulation with right-to-left shunt via the PFO or PDA. The presence of PDA
is diagnosed by bounding peripheral pulses, a harsh systolic ejection murmur at the left sternal border and a
large pulse-pressure. Blood flow through PDA from the pulmonary artery to the aorta causing right to left
shunt and deoxygenation. Persistent PDA after declining of pulmonary vascular resistance causes left to right
shunt with pulmonary hypertension and increased ventilatory support. PDA is treated by indomethacin, coiling or surgical ligation.
 Systemic perfusion may be improved in infants with PDA with dopamine infusion and judicious fluid administration.
Persistent pulmonary hypertension of Neonatal Anesthesia                                                                                    
the newborn (PPHN) is associated with sepsis and aspiration syndromes.
PPHN is suspected in severely hypoxic neonates when their postductal oxygen saturation does not improve on breathing 100% oxygen. A difference in preductal and postductal oxygen saturations supports the diagnosis because it reflects the extrapulmonary right-to-left shunting of deoxygenated blood via the PDA. PPHN is diagnosed when pulmonary hypertension and no other structural heart lesions are observed by cardiac ultrasonography.
Treatment of PPHN is directed at improving oxygenation and alkalosis to produce pulmonary vasodilation.
Selective pulmonary vasodilation can be induced by inhaled nitric oxide (NO).
Temperature Regulation
Neonates loose heat through four main physical pathways: radiation (to objects not in contact), convection (by currents of air or water), conduction (by direct contact objects) and evaporation (through skin,respiratory
tract, wounds and scrub solutions).
Heat loss by radiation and convection accounts for 75% of heat loss in neonates while conduction and
evaporation for 25%. The neonatal body habitus favors heat loss because of the large surface area of the head relative to that of the body of neonates and the poorly developed subcutaneous fat. Neonates do not shiver or sweat effectively to maintain body temperature and rely primarily on brown fat metabolism to maintain body heat (non-shivering thermogenesis) which is inhibited by anesthetics.
Brown fat cells begin to differentiate at 26 to 30 weeks' gestation and hence are not available in extremely preterm infants to provide fat for metabolism
and heat generation. A single layer of
covering over the head and nonoperative body areas dramatically reduce heat loss by radiation and convection. Warming the operating room to 85F (30C), using radiant warming units, forced-air heating pads,
adding humidity to the inspired gases, warming intravenous and irrigation fluids help maintain the neonate's
temperature in the neutral thermal range.
Metabolic Functions
Renal Function
At full-term birth, the glomerular filtration rate is only 15% to 30% of normal adult levels. Also, the kidneys'
tubular function is impaired and hence it's sodium-retaining ability. The immaturity of the kidney at birth also
affects the metabolism of many drugs in the neonate. The renal excretion of medications such as penicillin,
gentamicin, and some neuromuscular blocking agents such as pancuronium may be prolonged, resulting in
increased duration of action or the development of excessive blood concentrations. In the preterm infant
75% to 85% of body weight is water while in a term infant, 70% of body weight is water.
By 6 to 12 months of age, 50% to 60% of body weight is water. Differences in total body water and serum protein concentrations in a neonate affect the volume of distribution of most medications. The initial doses of some medications may be greater on a weight basis than for adults in order to achieve the desired blood concentration in the presence of high volume of distribution. In contrast, because of immaturity of renal function, the interval between dosages of some drugs may be increased.
Fluid Management
The highly variable body fluid composition, degree of renal maturity, neuroendocrine control of intravascular
fluid status, and insensible fluid loss with age make precise estimates of fluid requirements in neonates very
difficult. Urine volume and concentration may be difficult to determine intraoperatively and may not always correlate with volume status. Moreover, blood pressure and heart rate may not correlate with intravascular volume status in preterm infants and anesthetics may mask subtle cardiovascular responses that occur with changes in intravascular volume. Maintenance fluid requirements increase regularly during the first days (60, 80, 100, and 120 ml/kg/day at days 1, 2, 3, and 4 respectively) before remaining stable for the rest of the neonatal period at approximately 150 ml/kg/day. Caloric consumption is about 100-120 Kcal/kg/day. Daily electrolyte requirements are 2.5, 2.0, and 0.5 mmol/kg for sodium, potassium, and calcium respectively.
Glucose Homeostasis
In full-term infants, a glucose infusion rate of 5 to 8 mg/kg/min is required to prevent hypoglycemia.
Full-term infants who have been excessively fasted, small for gestational age (SGA) infants and
infants of diabetic mothers are particularly prone to develop hypoglycemia. The signs and symptoms of hypoglycemia (apnea, cyanosis, seizures, tremors, highpitched cry, irritability, limpness, lethargy, eye rolling, poor feeding, temperature instability, and sweating) in infants are often blunted and nonspecific. Plasma glucose values less than 45 mg/dL should be considered abnormally low and treated with bolus of 3 to 4 mL/kg of D10W (0.1 to 0.2 g/kg of glucose) and an increase in the basal glucose infusion.
Infants undergoing surgical procedures often require less glucose supplementation because of hormonal
responses that decrease glucose uptake as a result of catecholamine release in excess of insulin activity, as well as a decrease in metabolic demand owing to the effects of the anesthetic agents.
Nevertheless, it is important to administer glucose-containing solutions using a constant infusion device to avoid large fluctuations in blood glucose values and to monitor blood glucose values in critically ill
newborns.  All other fluids replaced (third-space losses, blood loss, deficits) should be glucose free to
avoid hyperglycemia.
 In infants receiving total parenteral nutrition (TPN), it is important to continue these infusions (possibly at a slightly reduced rate) during surgery and to check the serum glucose level to avoid hypoglycemia.
Gastrointestinal and Hepatic Function
Gastric emptying in neonates is prolonged and lower esophageal sphincters are incompetent and hence
reflux of stomach contents is common. After birth, increased levels of unconjugated serum bilirubin carry the
risk of kernicterus (bilirubin encephalopathy), particularly in infants who are preterm, hypoxemic, and acidotic and have low serum protein levels.
 High protein bound agents such as furosemide and sulfonamides may displace bilirubin and increase the
possibility of kernicterus. Hepatic metabolism is immature in neonates, particularly in preterm infants, which
may affect drug metabolism. Any factor that further compromises hepatic blood flow (e.g., increased intraabdominal pressure) may have profound adverse effects on hepatic drug metabolism. Therefore, careful
titration of all hepatically metabolized drugs (e.g., opioids, barbiturates, benzodiazepines, muscle relaxants) is
required to optimize therapeutic effects and prevent toxicity.
Preoperative Investigations
Guidelines for preoperative investigation are usually institutionbased. A preoperative hemoglobin and             hematocrit value should be taken in all neonates scheduled for surgery. If significant bleeding is anticipated,
blood typing and compatability screening should be performed. If more extensive surgery, the patient's electrolyte (sodium, potassium, chloride and calcium) and acid-base status (pH, base excess and standard
bicarbonate) should be determined. Coagulation parameters are quite different in neonates and premature
babies compared with adults. Activated partial thromboplastin time (APTT) at day 1 averages at 42compared to 33 in adults. Platelet counts are similar to normal adult values in term neonates. The lowest acceptable platelet count for surgery in neonates is not specifically known, but levels of 50-65 x 109/L should probably be required.
Due to limited reserves and insufficient supply of vitamin K by breast feeding, intramuscular vitamin K (1 mg) is usually given.
Premedication
The only routine premedication in neonates is atropine 10-20µg/kg IV.
Morphine in the same dose is used for pain in the preoperative period.
Parental presence during induction does not provide significant benefits to the neonates.
Monitoring
Routine standard any monitoring equipment includes an electrocardiograph, precordial or esophageal
stethoscope, blood pressure monitor, temperature probe, pulse oximeter, and a carbon dioxide (CO2) analyzer. A pulse oximeter probe placed in a preductal position (right hand) can be compared with one placed in a postductal position (foot or left hand) to determine the severity of extrapulmonary shunting of
deoxygenated blood via the PDA. This device can diagnose hypoxemia but not hyperoxia; however, maintaining the oxygen saturation at 93% to 95% (preductal) places most infants on the steep portion of the oxygenhemoglobin dissociation curve and avoids severe hyperoxia.
   Expired CO2 can be measured using capnography. However, dilution of the exhaled gases with those of the dead space of the endotracheal tube or by the fresh gas may underestimate the CO2 levels in the exhaled gases. If desired, a more accurate estimate of expired CO2 levels may be obtained by using special endotracheal tubes that have a sample port located at its tip or by using a needle introduced through the side wall of the endotracheal tube 2 to 3 cm distal to the tube's 15-mm connector
 Using a circle system may allow reasonably accurate measurement of expired CO2 values.
However, regardless of the circuit configuration, the value obtained by the capnograph may not accurately
reflect PaCO2 in the presence of congenital heart disease or significant intrapulmonary shunting.
   In neonates, changes in blood pressure, heart rate, and the intensity of heart sounds are excellent indicators of cardiac function, intravascular volume status, and depth of anesthesia. Under most circumstances, a urinary catheter permits adequate determination of urine output and aids in the monitoring of fluid balance during prolonged operations. Neonates with significant underlying cardiovascular instability should have an intra-arterial catheter placed for continuous monitoring of blood pressure and to provide the means to obtain arterial blood samples for determination of blood pH and gas levels and serum glucose and
electrolyte levels. Many neonates arrive in the operating room from the intensive care unit with an umbilical
artery line in place. Because of the risk for renal artery thrombosis with these lines, it is important to verify the
location of the tip of the umbilical artery catheter. Infrahepatic umbilical venous lines may not be reliable under
operative conditions because they may become wedged in the liver. In this position, infusion of hypertonic
solutions may lead to parenchymal necrosis and, ultimately, fibrosis.
Anesthetic Circuits
Non-rebreathing (open) circuits are simple and effective for delivering anesthetic agents to infants weighing
less than 10 kg. The system must have provisions for a humidifier to warm and hydrate the cold, dry anesthetic gases. There is, however, a trend away from the use of non-rebreathing circuits in order to save money and reduce air pollution. Pediatric circle systems should be used only if the provider has a clear understanding of the marked increase in compression volume/compliance volume losses compared with non-rebreathing circuits and should not be used for spontaneous breathing.
Preoxygenation
Preoxygenation with 6L/min for 60 seconds is recommended up to 5 years old. Desaturation occurs after 80-
90 seconds of apnea even with longer periods of preoxygenation.
Induction Techniques
In neonates with intravenous access, thiopental, propofol or ketamine induction may be an option depending on hemodynamic status.
However, delayed emergence and increased tendency for postoperative apnea especially for short procedures is a disadvantage. Inhalation induction is preferred if no intravenous access and in patients with compromised airway using sevoflurane which has gradually replaced halothane induction for its rapid onset and more hemodynamic stability. The MAC value for sevoflurane in oxygen in neonates is approximately 3.2%. Nitrous oxide 60% reduces MAC of halothane, isoflurane, and sevoflurane by 60%,
40%, and 25% respectively.
Airway Management
Preservation of patent airway is of crucial importance to the practice of neonatal anesthesia. In clinical
practice, especially with anesthesiologist with limited experience, tracheal intubation should be used liberally to avoid ventilation problems. A well sealed face mask with oropharyngeal airway and 3-4 cmH2O positive airway pressure (CPAP) and assisted ventilation should be considered for short procedures.
Laryngeal mask airway is used successfully for spontaneous breathing in neonates with careful monitoring of
ventilation with capnography for procedures less than 30 minutes with experienced anesthesiologists. If
assisted ventilation is used, a nasogastric tube is inserted prior to LMA and left open to avoid gastric
overdistension. Awake tracheal intubation used by some anesthesiologists is very stressful to neonates and intubation condition is usually suboptimal with high chance of airway trauma. Tracheal intubation may be done using inhalation anesthesia with the potential of cardiopulmonary complications.
Succinylcholine should mainly be reserved for rapid sequence induction where non-depolarizing muscle
relaxants should be used under normal circumstances. Due to the very compliant chest wall and slightly
stiffer neonatal lungs, atelectasis is common after intubation. This requires a pressure of 30-40 cmH2O for
seconds after intubation to be overcome.
 Nasal intubation should be used for procedures done on lateral or prone position and in situation with
limited access to the head. For diseases and syndromes with anticipated airway difficulty, individualized preinduction strategy should be planned with proper preparation of resources.
Ventilation
Ventilation should almost constantly be controlled in neonates whether by manual or ventilator assistance. Pressure controlled ventilation adjusted to produce expired tidal volume of 7-10 ml/kg is preferred in premature infants, newborns with respiratory distress and during the first few days of life. Volume-controlled
ventilation can be used successfully especially when surgical manipulations will interfere with intraoperative
ventilation. Positive end expiratory pressure (PEEP) of 3-4 cmH2O should routinely be used with any mode of ventilation.
Maintenance of Anesthesia
All inhalation anesthetics depress baroreceptor reflex. Halothane depresses the myocardium and heart rate more than sevoflurane and isoflurane. Hypotension due to halothane is treated by atropine while hypotension due to sevoflurane and isoflurane responed to 5-10ml/kg fluid bolus. Opioids are used with half the
recommended dosed until 60 weeks of postconceptual age if no regional blocks were performed. More liberal use of narcotics is allowed for surgeries with planned postoperative ventilation.
Use of Regional Anesthesia Techniques
The use of light general volatile anesthetic with a central or peripheral nerve block has proved to be of great
benefit in neonatal surgery.
Fluid Replacement during Anesthesia
A solution containing 2.5% glucose with 70 mmol/L sodium represents an acceptable standard solution for most cases. However, if not available, Ringer's solutions or 0.9% Saline are acceptable alternatives. Isotonic fluid administration is of crucial importance to maintain normal fluid status of the neonate by replacing the loss of isotonic fluids during surgery. Volume replacement will be governed by clinical signs such as blood pressure, urine output, and capillary refill.
Emergence
Reversal of muscle relaxant is done after spontaneous movement even with adequate time after last dose.
Extubation requires regular spontaneous breathing, vigorous movements of all limbs, gagging, eye opening or pronounced grimacing, stable hemodynamics, good oxygen saturation and absence of significant hypothermia.
Pain Scoring and Analgesia
The use of perioperative pain scales for monitoring of postoperative pain is crucial for optimal pain relief,
increasing the awareness of the care givers regarding the problem, and for evaluation of different analgesic
techniques. CRIES(cry, requires O2, increased vital signs, expression, sleeplessness), CHIPPS (children's
and infants' postoperative pain scale) and NIPS (neonatal infant pain scale)are good examples of such
tools.Paracetamol metabolism is well developed in neonates and is commonly administered as 10-15
mg/kg PO q4-6 h with maximum doses of 100 mg/kg/day. Whenever possible, regional anesthetic techniques should be utilized for its high quality of pain relief. If regional blocks are not applicable, continuous low dose of opioids as morphine 10µ/kg/h should be carefully titrated with little risk of respiratory depression.