Chapter 86

Management of the Neonate: 

Anesthetic Considerations 

Per-Arne Lönnqvist 

86 

CHAPTER 

INTRODUCTION 

Safe and effective anesthesia for the neonate undergoing surgery 

is one of the most challenging tasks presented to the anesthesio - 

logist. Great manual skills and continuous practice are required 

to perform successfully such essential tasks as vascular line place - 

ments and tracheal intubation. Additionally, to provide successful 

pediatric anesthesia, extensive knowledge of the neonate’s unique 

physiology is required. Neonatal anesthesia demands a wellplanned 

technique, based on a good understanding of pathophy - 

siologic conditions and surgical needs. In the past, both major 

surgery (e.g., thoracotomy for ductus arteriosus ligation) as well as 

minor operations (e.g., circumcision) were performed without 

analgesia. 1,2 This inhumane management can result in a measur - 

able and detrimental stress response associated with serious 

morbidity. 3 Furthermore, scientific evidence has suggested that 

the neonate’s nervous system could retain long-term pain memory 

with the consequences of causing modification of the response to 

future painful stimulation. 4 It is also well recognized that a com - 

petent nociceptive system already exists in the fetal period, 5 which 

confirms that a nonanalgesic practice is no longer acceptable. 

Anesthesia-related morbidity and mortality is higher in 

infants, 6,7 particularly in the neonate, compared to older children 

and adults. These increased risks are significantly reduced with 

proper training in pediatric anesthesia and regular exposure to 

pediatric anesthesia practice necessary to maintain skills 8,9 in 

neonatal care. These epidemiologic data have initiated an impor - 

tant debate and the regulation authorities of Great Britain cur - 

rently recommend transfer of all children ≤3 years of age requiring 

emergency surgical procedure to larger centers with adequate 

pediatric anesthesia staffing and facilities. 10 

Effects of Anesthetic Agents on the 

Premature and Neonatal Brain 

Although adequate anesthesia is to be considered mandatory for 

premature infants and neonates, recent studies have also provided 

evidence that being subjected to anesthesia at this early age may 

not be without important consequences to the child. 

The seminal publications by Ikonomidou 11 and Jevtovic- 

Todorovic, 12 showing a significant increase of apoptotic cell death 

by various anesthetic agents in the young rat, has sparked a vivid 

debate whether anesthesia in early life can be detrimental to the 

developing central nervous system. The increased apoptosis seen 

following the use of certain anaesthetics in rodents have also been 

linked to later developmental and cognitive deficits in the animals, 

showing that the increase in the normal apoptotic sequence of the 

neonate can have significant negative long-term effects. 

The main agents that have been targeted are N-methyl-Daspartic 

acid (NMDA) antagonists (e.g., ketamine) and -amino - 

butyric acid (GABA)-mimetic compounds (e.g., benzodiazepines, 

barbiturates, volatile agents), but nitrous oxide also has a potential 

for increased apoptosis if combined with other agents. It is clear 

that combinations of these drugs appear more potent with regards 

to the ability to induce apoptotic cell death than use of a single 

agent. The period of risk is associated with what is generally called 

the period of synaptogenesis or “brain-growth spurt.” Thus, 

interference by anesthetic drugs during this delicate developmen - 

tal period may lead to altered and maybe dysfunctional synaptic 

“hard wiring” of the maturing brain. 

Although the findings in animal studies are striking, there are 

a large number of problems with trying to translate this to the 

human preterm or neonate (e.g., doses, duration of exposure, 

species differences, nutritional issues). Another major issue in this 

context is the fact that neonatal surgery most often cannot be 

delayed until the child is out of the potential risk period without 

adding other risks and that previous research has clearly shown 

that insufficient anaesthesia and analgesia in neonates and prema - 

ture infants is associated with substantial harm, including negative 

long-term effects. 

The exposure to different anaesthetics during neonatal anaes - 

thesia is usually limited to a few hours and it is difficult to judge 

to what extent such limited exposure time may affect apoptotic 

cell death in the human neonate. Although the risks associated 

with neonatal anaesthesia should not be neglected due to this time 

limitation, it may possibly be seen as slightly less important 

compared to the prolonged exposure to very similar combinations 

of sedative and analgesic agents during the sometimes prolonged 

postoperative neonatal intensive care unit (NICU) stay (days– 

weeks). 

Despite the accumulating animal data, it is not currently pos - 

sible to know if one anaesthetic is better or worse than another 

and, thus, no recommendations have so far been issued. However, 

as stated above, there is absolute consensus that premature and 

neonatal infants always should receive adequate anaesthesia and 

postoperative analgesia. An approach based on opioids, regional 

anaesthesia, and a low concentration of volatile agent (e.g., 1% 

sevoflurane in oxygen-air) to counteract potential awareness does, 

in the author’s opinion, appear as a reasonable strategy, but 

adequate data to support this concept are currently lacking. 

Significant scientific effort is currently put into this field of 

research, both from individual research groups as well as from

1438 PART 5 ■ Anesthetic, Surgical, and Interventional Procedures: Considerations 

national bodies, for example, the U.S. Food and Drug Administra - 

tion (FDA), and more information will most likely be available 

within the next 5 to 10 years. For more in-depth information re - 

garding these issues the reader is referred to the reviews by 

Mellon 13 and Anand. 14 

This chapter aims at providing a comprehensive review of the 

theoretical aspects of neonatal anesthesia and at giving practical 

guidelines for the most frequently performed surgical interven - 

tions during the neonatal period. 

PHYSIOLOGIC PARTICULARITIES 

PRONE TO INFLUENCE 

ANESTHESIA MANAGEMENT 

Development of the Nociceptive 

System and Stress Response 

All structural components of the nociceptive system are already 

developed at the end of the second trimester, 15 as described in 

Chapter 4. In a pivotal study, Giannakoulopoulos and coworkers 

verified a competent stress reaction as well as behavioral 

signs indicative of a fully functional nociceptive system even in 

the fetus. 16 Two different groups of subjects were studied during 

fetal exchange transfusion due to fetomaternal blood group 

incom patibility. To achieve fetal venous access, the umbilical 

vein is usually punctured close to the insertion of the umbilical 

cord in the placenta under ultrasonographic guidance. Since the 

umbilical cord is uninnervated, such a procedure should not be 

associated with any pain or stress reaction. However, due to 

anatomic factors, this approach for fetal venous access is not 

always feasible, and in such cases the venous system of the fetus 

has to be accessed by puncture of the intrahepatic vein. This 

method, thus, involves perforation of the skin, muscle, and liver 

capsule, and if the fetus does have functionally intact stress and 

nociceptive systems, such a puncture would be associated with 

measurable signs of a neuro endocrine stress reaction as well as 

behavioral signs indicative of a pain reaction. As could be 

expected, puncture and exchange transfusion performed via 

the umbilical cord was not associated with any measurable 

stress reaction or behavioral signs of pain. However, in fetuses 

undergoing intrahepatic vein cannulation and transfusion, a 

distinct stress reaction could be observed (increase in cortisol and 

-endorphin). The stress response was also found to correlate with 

the duration of the needling and transfusion procedure in these 

fetuses. Moreover, during puncture of the abdominal wall and the 

liver capsule, the babies were found to start breathing rapidly 

(as well as starting to move the extremities vigorously). No 

such behavioral reactions were noted during puncture of the 

umbilical cord and the transfusion process itself did not induce 

any stress response. 

Neonatal pain is capable of producing a “pain memory,” either 

as a result of plasticity changes within the nervous system itself or 

due to a psychological process. A number of studies performed in 

neonatal rodents have investigated the maturational changes of 

the opioid system and the descending pain inhibitory control 

pathways. The main differences between the neonatal and adult 

rodent are summarized in Table 86–1. Although the current 

knowledge is almost exclusively based on the neonatal rodent 

studies, it is reasonable to assume the conditions may be similar in 

the human neonate. 

TABLE 86-1. Developmental Changes in the Nociceptive 

System of the Fetal and Newborn Rat 

1. High density of -receptors both in superficial and deeper 

layers of the gray matter in the spinal cord. A more adult 

localization of -receptors to the superficial layers of the 

dorsal horn are not achieved until postnatal day 14–28 

(P14–28) (approximately equal to a human toddler). 28 

2. Nociceptive A-fiber input predominates over C-fiber input 

in the neonatal period. 29 

3. Descending inhibitory control pathways from the brainstem 

to the spinal cord are not functional in neonates or during 

early infancy. 30 

4. Predominance of enkephalin over endorphin in the initial 

perinatal period. 31 

5. Enhanced intracellular calcium-release in response to 

NMDA (N-methyl-D-aspartate) stimulation compared to 

adults. 32 

6. A 40-fold increase in efficacy of morphine from P3 

(approx. human preterm baby) to P14 (approximately 

late infancy). 33 

Very interesting new knowledge currently exists regarding the 

growth factor effects of endogenous opioids in relation to normal 

neuronal development during the neonatal period. In rat models, 

endogenous opioids have, through a receptor mediated process, 

been found to have an inhibitory influence on dendrite and spine 

elaboration in 10-day-old rodents. 17 Suppression of astrocyte 

growth has also been shown in vitro following met-enkephalin 

administration. 18 Furthermore, morphine administration has been 

found to cause inhibition of DNA synthesis in the neonatal rat 

brain but not in older animals. This effect could be blocked by 

pretreatment with naloxone once again indicating receptor me - 

diated mechanisms. 19 

Despite the apparently normal development of most neonates 

following neonatal surgery, including significant postoperative 

administration of morphine or other opioids, further knowledge 

is required to delineate the potential problem of interference with 

normal neuronal development of the neonate if exposed to high 

doses of exogenous opioids. 20 A number of studies in preterm and 

term human babies reported the presence of a fully competent 

neuroendocrine stress reaction in response to surgical stimula - 

tion. 21,22 The neuroendocrine stress response has been found to be 

correlated with degree of surgical trauma 23 and can be beneficially 

modified by adequate anesthesia and analgesia. 24 The attenuation 

of the neuroendocrine stress response in both preterm and 

neonates by proper analgesia has been found to reduce morbidity. 

In the specific setting of neonatal cardiac surgery, high-dose 

sufentanil anesthesia and postoperative analgesia (n 30) have 

been shown to reduce the incidence of sepsis/necrotizing entero - 

colitis, disseminated intravascular coagulation, and metabolic 

acidosis by 20 to 25 percent 24 compared with a halothanemor 

phine based anesthetic technique (n 15). This study was 

also prematurely ended because of apparently lower mortality 

figures in the sufentanil group (0%) compared to the previous 

halothane-morphine based anesthetic technique (27%). 24 The 

reader should bear the small number of patients enrolled in this 

study in mind, but these results clearly point to a more favorable 

outcome for sick children if adequate intra- and postoperative 

analgesia is provided.

CHAPTER 86 ■ Management of the Neonate: Anesthetic Considerations 1439 

Cardiovascular System 

The physiology and main developmental stages of the cardiovas - 

cular systems are discussed in Chapter 3. 

Transitional Circulatory Adaptation 

Following birth, the circulation changes from a fetal parallel 

pattern characterized by both ventricle pumping the majority of 

their output into the systemic circulation (pulmonary blood flow 

10% of combined ventricular output 25 ) to an extrauterine series 

pattern with the right and left ventricles assuming responsibility 

for the pulmonary and the systemic circulations, respectively (see 

Chapter 3). The three embryological shunts close during the 

immediate postnatal period. The placenta circulation and the flow 

through the ductus venosus cease when the umbilical cord is 

clamped at birth. The foramen ovale will close within 1 to 2 hours 

after delivery, as the pressure in the left atrium will surpass that of 

the right atrium due to the rapid decrease in pulmonary pressures 

associated with initiation of breathing and the subsequent aeration 

of the lung. The foramen ovale will remain patent during the 

neonatal period and anatomic closure will often not take place 

until 1 year of age. Anatomic closure will not take place in all 

individuals and a patent foramen ovale can be present in up to 10 

to 20% of the adult population. The ductus arteriosus will start to 

close approximately 10 to 15 hours following delivery and is 

usually physiologically closed by the 2nd day of life. However, 

permanent anatomic closure with formation of the ligamentum 

arteriosus is not completed until about 3 weeks postnatally. During 

this period the ductus arteriosus might reopen if exposed to 

unfavorable neuroendocrine mediators or increasing pulmonary 

pressures. The main factors that modulate pulmonary vascular 

resistance and neonatal pulmonary resistance at birth and during 

the first days of life are summarized in Table 86–2. 

During certain circumstances in the early neonatal period, a 

relapse into the fetal circulatory pattern most often occurs due to 

pulmonary vasospasm with resulting pulmonary hypertension but 

can also be a consequence of, e.g., severe hypoxia or hypercarbia. 

Pulmonary vasospasm resulting in persistent pulmonary hyper - 

tension of the newborn (PPHN) is characterized by profound 

hypoxia due to right-to-left shunting through the fetal extrapul - 

monary shunts combined with right ventricular strain and 

circulatory compromise. A number of different neonatal condi - 

tions predispose to the development of PPHN, for example, con - 

genital diaphragmatic hernia, meconium aspiration syndrome, 

asphyxia, hypoxia and sepsis, all of which can coincide with the 

need for neonatal surgical intervention (Table 86–3). Thus, the 

neonatal anesthesiologist needs to be familiar with the pathophy - 

siology of PPHN, its diagnosis, and treatment. Conventional 

treatment consists of tracheal intubation and mechanical ven - 

tilation, induction of alkalosis by attempted hyperventilation, and 

acidosis correction, analgosedation, muscle paralysis, volume 

replacement, and inotropic/pressor support (dopamine, norepine 

phrine). 26 

More recent treatments include selective pulmonary vasodila 

tation by means of inhaled nitric oxide (iNO) or inhalation of 

nebulized prostacyclin and the use of high-frequency oscillatory 

ventilation. 27 Regarding iNO, the effective dose range appears to be 

within the 1 to 30 ppm dose range, although doses up to 80 ppm 

might be attempted in severe cases for brief periods of time. 28 Side 

effects of the treatment are few and mainly limited to the risk of 

methemoglobin formation and minor prolongation of bleeding 

time. The most dangerous complication of iNO treatment is severe 

rebound pulmonary hypertension in association with abrupt 

discontinuation of the iNO therapy either accidentally or during 

deliberate weaning. The risk of severe rebound necessitates the 

immediate option to reinstate therapy and to be able to handle an 

accidental delivery device malfunction situation; a back-up system 

needs to be available at the bedside. Since NO and especially 

concomitant and unavoidable nitrogen dioxide (NO 2 

) exposure at 

higher concentrations (100 ppm and 2 ppm, respectively) can 

be toxic it is imperative to use an approved delivery device and 

also to measure continuously the NO and NO 2 

levels in the in - 

spired gases. The anesthesiologist must be prepared to conduct 

the anesthetic without interrupting these new and effective treat - 

ments. If the anesthesiologist is not comfortable in this situation, 

help should be sought from an experienced neonatologist. 

TABLE 86-2. Factors That Modulate Pulmonary Vascular Resistance in the Near-Term and Term Transitional and 

Neonatal Pulmonary Circulation 

Endogenous mediators 

and mechanisms 

Mechanical factors 

Lowers Pulmonary Vascular Resistance 

Oxygen, nitric oxide 

PGI2, E2, D2 

Adenosine, ATP, magnesium 

Bradykinin, atrial natriuretic factor 

Alkalosis, K channel activation 

Histamine, acetylcholine 

Vagal nerve stimulation 

b-Adrenergic stimulation 

Lung inflation 

Vascular cell structural changes 

Interstitial fluid and pressure changes 

Shear stress 

PGI2, E2, D2 prostaglandins I2, E2, D2; ATP adenosine triphosphate; PGF2a prostaglandin F2a. 

Increases Pulmonary Vascular Resistance 

Hypoxia, acidosis 

Endothelin-1, leukotrienes, thromboxanes 

Platelet activating factor 

Ca channel activation 

a-Adrenergic stimulation 

PGF2a 

Overinflation or underinflation 

Excessive muscularization, vascular remodeling 

Altered mechanical properties of smooth muscle 

Pulmonary hypoplasia, pulmonary thromboemboli 

Alveolar capillary dysplasia 

Main pulmonary artery distention 

Ventricular dysfunction, venous hypertension


TABLE 86-3. Disorders Frequently Associated With Persistent Neonatal Pulmonary Hypertension 

Diagnosis Symptoms and Signs Investigations Treatment 

Congenital diaphragmatic 

hernia 

Meconium aspiration 

syndrome 

Birth asphyxia 

Septicemia 

Respiratory distress 

Displaced cardiac sounds, usually 

shifted to the right 

No breath sounds over one 

hemithorax, usually left side 

Scaphoid abdomen 

“Honeymoon” period 

History of intrauterine fetal 

distress 

Meconium stained amniotic fluid 

Meconium in pharynx and 

trachea 

Respiratory distress 

Chest wall retractions 

History of intrauterine fetal 

distress or difficult delivery 

Low APGAR scores 

Hyper- or hypotonicity 

Seizures 

Cardiovascular compromise 

Poor peripheral circulation 

Poor urine output 

Respiratory distress not always 

present 

Hypo- or hyperthermia 

Hypotonicity 

Cardiovascular compromise with 

poor peripheral circulation 

Poor urine output 

Respiratory distress not always 

present initially 

Chest x-ray diagnostic 

Meconium present at tracheobronchial 

suctioning 

Chest X-ray shows pachy 

bilateral infiltrates 

Cardiac and cerebral 

ultrasonography 

Cerebral function monitoring 

Elevation of liver enzymes 

Computed tomography on day 

3 for prognostic reasons 

C-reactive protein 

White blood cell count 

Bacterial cultures 

Chest x-ray may show fine 

granular infiltrates 

iNO inhaled nitrous oxide; HFOV high frequency oscillatory ventilation; ECMO extracorporeal membrane oxygenation. 

In more severe cases: 

Intubation 

Mechanical ventilation 

Analgo-sedation 

Vigorous acid-base correction 

Surfactant replacement 

iNO, HFOV, ECMO 

No emergency surgery! 

If possible thorough tracheobron - 

chial suctioning 

Possible indication for partial liquid 

ventilation 

(For further treatment please see 

Congenital diaphragmatic hernia) 

Endotracheal intubation 

Mechanical ventilation 

Inotropic support 

Diuretics 

Acid-base correction 

Pharmacologic seizure control 

Avoidance of hyperglycemia 

Adequate antibiotics 

Respiratory support as needed 

Volume replacement Inotropic 

support 

Diuretics 

Myocardial Function 

The neonatal cardiac myocyte contains more noncontractile ele - 

ments, has a disorganized intracellular arrangement of the con - 

tractile proteins, and its shape is less elongated than in the adult. 29 

This leads to a reduced capability of the neonatal myocardium to 

generate force. 30 The sarcoplasmatic reticulum and the T-tubular 

system are also immature, which leads to an increased dependence 

on extracellular calcium for contraction. 31 Developmental changes 

both in the cytoskeleton and the extracellular matrix make the 

neonatal myocardium less compliant, and both early diastolic 

relaxation and late diastolic filling are reduced compared to the 

adult. 32,33 While the overall number of ventricular myocytes is still 

increasing (hyperplasia) during the neonatal period, after that 

period further increase in ventricular mass depends only on 

physiologic hypertrophy. 34 Compared to adults, the neonatal 

myocardium is metabolically less effective in handling fatty acids, 

which makes carbohydrates and lactate its primary energy 

substrates. 35 It is also more resistant to hypoxia, 36 which might be 

explained by increased myocardial glycogen stores and higher rates 

of anaerobic glycolysis in the neonatal myocardium com pared to 

the adult. Better myocardial performance is also observed following 

an ischemic insult in the immature heart, 37 something which might 

be explained by less pronounced increase in resting tension during 

the ischemic insult compared to the adult myocar dium, thus, 

resulting in better preservation of myocardial energy stores. 

The parasympathetic innervation of the neonatal heart is 

considered to be more mature compared to the sympathetic 

system 38 and the expression of cholinergic receptors is maximal at 

birth and remains high during the neonatal period. 39 The time 

course for the maturation of the sympathetic nervous system is 

associated with great interindividual variability. At 3 months of 

age, the sympathetic nervous system can often be regarded as 

functionally developed but final maturation can be delayed until 

1 year of age in certain individuals. The adrenergic plexus system 

is less developed, 40 which might explain the pronounced response 

to norepinephrine simulating denervation supersensitivity. 41 

Circulating catecholamines are, thus, relatively more important 

for inotropic and chronotropic function in the neonate. The b- 

adrenergic receptors and the adenylate cyclase system are well 

developed in the neonate 38 but the coupling between the two 

might be reduced since direct activation of adenylate cyclase will 

produce a larger increase in inotropic response compared to 

b-receptor stimulation. 42 Birth is associated with very high levels 

of circulating catecholamine levels, 43 which most likely results in


Figure 86-1. Progressive reduction in cardiac output during 

the first days of life. LVO (n 16), SV(n 16), and ICBFV 

(a .20) in the first 72 h after birth in healthy term infants. Mean 

and 1 SD. Reproduced from Winberg 61 with permission. 

near maximal adrenergic stimulation of the myocardium imme - 

diately after parturition. During this time, the functional reserve 

of the myocardium is limited and the myocardium responds 

poorly to further increases in demand. 44 During the first days of 

life, there is a progressive reduction in cardiac output (Figure 

86–1) leading to an increase in functional reserve and an increased 

response to inotropic stimulation. 45 

Reactions to Changes in Preload, Afterload, 

Inotropy, and Heart Rate 

Recent scientific evidence has demonstrated that cardiac output 

is not unaffected by changes in preload. 46–48 A direct relationship 

between neonatal stroke volume and cardiac output exists already 

immediately following birth, whereas changes in heart rate does 

not appear to have the major influence on cardiac output in this 

setting as previously believed (Figure 86–2). 46 The increase in 

stroke volume in response to volume loading exists already 

immediately after birth but will be more prominent towards the 

end of the neonatal period. 45 The inflection point of the Frank– 

Starling relationship might be at a lower filling pressure (8 mmHg) 

compared to adults (12–15 mmHg). Because of the limited ability 

to generate force by the neonatal myocardium and the reduced 

compliance the neonatal heart tolerates increases in afterload 

poorly 46,49 (Figure 86–3). This is most pronounced regarding the 

right ventricle but applies to the left ventricle as well. Right 

ventricular strain often cause leftward interventricular septal shift, 

which can limit the filling of the left ventricle. 50 With the possible 

exception of the immediate period following parturition, the 

neonatal myocardium responds to inotropic stimulation with an 

increase in cardiac output. However, the response is usually less 

pronounced compared to adults. The choice of the optimum 

inotrope can be debated but, according to clinical experience, 

dopamine, dobutamine, epinephrine, isoproterenol, and norepine - 

phrine all increase cardiac output. Choosing agents with less 

effects on afterload might have a theoretical advantage since the 

neonatal myocardium tolerates increases in afterload poorly. Heart 

rate has previously been perceived as the major factor affecting 

cardiac output in the neonate. This is, as described above, only 

Figure 86-2. Left ventricular stroke volume (SV) versus left 

ventricular output (LVO) in 16 term infants during the first 72 h 

after birth. 

partially true. 46 Relative bradycardia obviously reduces cardiac 

output, but increases in heart rate above approximately 180 to 190 

bpm do not cause an increase in output, since higher rates limit 

diastolic filling time; hence, the stroke volume is reduced. Even at 

heart rates below 180 bpm, the supposed tight relationship 

between heart rate and cardiac output can be questioned in the 

early neonatal period (Figure 86–4). The optimal heart rate with 

regard to optimizing the hemodynamic situation will of course 

Figure 86-3. Left ventricular stroke volume (SV) versus systemic 

vascular resistance (SVR) in 16 term infants during the 

first 72 h after birth.


Figure 86-4. Heart rate (HR) versus left ventricular output 

(LVO) in 16 term infants during the first 72 hours after birth. 

vary between patients. After correcting and optimizing filling 

pressures, heart rates in the range of 120 to 180 bpm should be 

aimed for as a general rule. 

Changes in Heart Rate and Blood Pressure 

During the Neonatal Period 

The heart rate decreases and the blood pressure increases both in 

term neonates 47 and preterm infants 48 during the first 3 postnatal 

days (Figure 86–5). Adequate knowledge regarding the normal 

levels for these crucial parameters must be known to enable the 

pediatric anesthesiologist to adjust properly the depth of anesthesia 

in the neonate. 51 The main features of the neonatal circulation and 

myocardial functions are summarized in Table 86–4. 

Ventilatory Function and Control 

Control of Breathing 

During the neonatal period, control of breathing differs in some 

important aspects from what is normally seen in the older child or 

the adult. Neonates respond to hypercapnia (combined with hy - 

poxia) with an increase in ventilation but less than older subjects, 

as evidenced by a less steep CO 2 

response curve. 52 The ventilatory 

response to hypercapnia gradually matures both in relation to 

increasing gestational age and postnatal age. 52 In adults, hypoxia 

causes an increase in ventilation, whereas in the neonate hypoxia 

only briefly increases ventilation. This initial increase in ventila - 

tion is later followed by a sustained depression of ventilation. 53 A 

periodic breathing pattern is present in both preterm and term 

babies with an inverse relationship to gestational age. This ten - 

dency for periodic breathing decreases markedly following 44 

weeks postconceptual age but can be seen up to 1 year of age. 54 

The respiratory drive of the neonate is a complex interplay be - 

tween a number of various factors. Furthermore, the relative im - 

portance of different stimuli changes during the neonatal period. 

Thus, suprapontine drive dominates immediately after birth, 

together with the mechanosensory driving mechanism. The impor - 

tance of these systems, however, diminishes later on and the 

Figure 86-5. Mean (SD) left ventricular output, stroke volume, 

heart rate, and arterial blood pressure during postnatal circulatory 

adaptation in 16 healthy infants born at full term. 

chemoreceptor drive takes over as the most important system for 

maintaining the respiratory drive (Figure 86–6). 55 

Anesthetic Effects on Control of Breathing 

Apart from the well-known depressing effects of most anesthetics 

on respiration in both neonates and older subjects a specific 

situation exists in newborns and especially in ex-premature infants. 

General anesthesia increases the risk for postoperative apnea 

in this patient category until the age of 44 to 60 post concept- 

TABLE 86-4. Main Characteristics of the Neonatal 

Circulation and Myocardial Functions 

1. Myocardium less able to generate force. 

2. Myocardium relatively noncompliant. 

3. Myocardium more dependent on extracellular calcium. 

4. Myocardium more resistant to hypoxia and ischemia, at 

least immediately following birth. 

5. Limited functional reserve early in the neonatal period. 

6. Balance in favor of the parasympathetic nervous system. 

7. Changes in preload will significantly affect stroke volume 

and cardiac output. 

8. Tolerates increases in afterload poorly. 

9. Responds to inotropic support although less than the adult. 

10. Cardiac output less heart rate dependent than previously 

believed.


Figure 86-6. Schematic representation of the relative importance 

of different respiratory drive mechanisms after birth. 

Cooling of the skin and the increased arousal induced by labor 

and delivery are important for initiation of breathing at birth. 

Mechanosensory information constitutes a major drive to sustain 

regular and efficient breathing during the first few weeks of 

life. The importance of the peripheral chemoreceptor drive, as 

well as of the integration and modulation of various respiratory 

and nonrespiratory stimuli, increases after the newborn period. 

(Figure based on an original concept of P. Johnson, Oxford 

University, 1984.) 

ual weeks. 56,57 Anemia further increases this risk (Hct 30%) 57 

(Figure 86–7). Even after 56 postconceptual weeks, the risk for 

postoperative apnea can still be approximately 1%. 80 Since the risk 

for this potentially life-threatening event is above what is usually 

accepted in anesthetic practice (rates for significant morbidity and 

mortality in the range of 1/10.000 to 1/100.000) 58 these patients 

should be monitored in hospital for at least 12 to 24 hours after 

surgery in an environment with adequate staffing and resuscitation 

skills (i.e., recovery room, high dependency unit, neonatal ICU or 

step down unit). The minimum monitoring re quirements would 

be either an apnea monitor or preferably pulse oximetry. 

Figure 86-7. Predicted probability of apnea by weeks postconceptual 

age for all three models: model I (solid line) all infants; model 2 

(irregular line) all nonanemic infants; and model 3 (broken line) 

~ patients who were not anemic and did not experience apnea in recovery 

room. The risk for apnea decreases markedly when patients with 

anemia (model 2) are eliminated, and the risk diminishes further if 

patients with apnea in recovery room (model 3) also are eliminated. 

Reproduced from Coté et al 83 with permission. 

Anesthetic Effects on Respiratory Mechanics 

General anesthesia will impair the function of almost all muscular 

components of the respiratory system. The genioglossus muscle, 

which is very important for airway patency, is disproportionally 

sensitive to the depressant effects of anesthetics leading to an 

increased risk for airway obstruction. 59 Reduced tonus of the 

intercostal muscles will reduce the stability of the thoracic wall, 

increasing the risk for thoracoabdominal asynchrony resulting in 

less effective ventilation. 60 Although the diaphragm is more resis - 

tant to anesthetics compared to the genioglossus and intercostal 

muscle some interference with normal function still occurs. 61 The 

above-mentioned actions of anesthetics on the respiratory mus - 

cles, together with some other factors, will substantially increase 

the risk for detrimental reductions of functional residual capacity 

(FRC). Application of positive end-expiratory pressure (5–6 cm 

H 2 

O) will prevent the adverse effects on FRC and compliance in 

neonates and infants. 62 The main particularities of the respiratory 

control and respiratory mechanics in the neonate are summarized 

in Table 86–5. 

Hepatic Function 

The maturation process of the liver is a very complex interplay 

between different enzyme pathways, isoenzyme patterns, 

avail ability of cofactors, hepatic blood flow, and extraction 

characteris tics of the hepatocyte (see Chapter 7). During fetal life 

TABLE 86-5. Main Particularities of Neonatal Respiratory 

Control and Respiratory Mechanics 

1. Hypercarbia results in stimulation of respiration but to a 

lesser extent than in the adult. 

2. Hypoxia causes a transient increase in ventilation followed 

by a sustained respiratory depression. 

3. Neonates, and especially ex-premature infants, have a 

tendency for periodic breathing which is accentuated by 

anesthetics. Thus, these infants are at increased risk of 

postoperative apnea until approximately 60 weeks 

postconceptual age. 

4. The respiratory driving mechanisms are multifactorial 

during the neonatal period. 

5. Different types of afferent input and reflexes from the lung 

are important in respiratory control of the neonate. 

6. Newborns have higher oxygen consumption compared to 

older subjects. Tidal volume is relatively similar per kilo 

body weight but respiratory rates are higher. 

7. Lung compliance is lower whereas the chest wall 

compliance is higher compared to adults. 

8. The neonate is at increased risk of reduction of FRC and 

development of atelectasis. This can be counteracted by 

application of a modest PEEP. 

9. Anesthesia will negatively affect all respiratory muscles in 

the neonate, particularly the genioglossus and intercostal 

muscles. This leads to increased risk of airway obstruction 

and thoracoabdominal asynchrony. 

10. The diaphragm of the neonate is the dominating respiratory 

muscle. However, due to the relatively lower content of 

oxidative type I fibers the diaphragm of the neonate is 

susceptible to fatigue if subjected to increased ventilatory 

demands.


TABLE 86-6. Sulfation and Glucuronidation of 

Acetaminophen (AA) in Human Neonates and Adults 

(Formation Rate Constants, HR-1) 

Age Range AA-Sulfate AA-Glucuronide Sulfate/Glucuronide 

Neonates 0.099 0.025 4 

Adults 0.075 0.170 0.4 

Adapted from Levy et al. 96 

the liver is exposed to a very high blood flow due to the placenta 

circulation, which causes hepatic accumulation of anesthetic 

drugs. Addition ally, maternal metabolism is largely responsible 

for biotransfor mation and elimination of drugs, a pathway no 

longer available after birth. Elimination of many drugs such as 

diazepam is con siderably prolonged in the neonate. 63 The different 

metabolic pathways of the neonate mature at different rates. 

Conjugation by sulfation and acetylation are relatively mature, 

whereas glucuroni dation and conjugation with glutathione and 

glycine are less well developed. Whereas acetaminophen mainly 

undergoes glucuroni dation in the adult, it mainly undergoes 

sulfation in the neonate 64 (Table 86–6). 

A number of drugs display prolonged elimination half-lives in 

neonates compared to adults when they mainly undergo hepatic 

biotransformation (e.g., morphine). 65 Other factors responsible 

for the prolongation of elimination half-lives are the increased 

volume of distribution and the very limited, thus easily saturated, 

enzymatic capacity of the neonate. In the latter instance, elimina - 

tion may become virtually nil with increasing dosage. 66 On the 

other hand, certain drugs do not undergo prolonged elimination 

in neonates. The elimination rate of lidocaine does not signifi - 

cantly differ from that in adults because its clearance depends less 

on hepatic metabolism than on liver blood flow, which is fairly 

similar in neonates and adults. 67 The immature hepatic meta - 

bolism of certain drugs is to some extent ameliorated by a larger 

fraction of the drug being excreted unchanged. The urinary 

excretion of unchanged caffeine represents only 1% of the given 

dose in adults but may be as high as 85% in the neonate. 68 

The transition to extrauterine life as outlined above causes 

significant changes in hepatic function. With the cessation of the 

placental circulation the neonate’s liver faces a situation of reduced 

blood flow and oxygenation while becoming solely responsible for 

drug metabolism. However, parturition in itself might enhance 

the maturation of hepatic drug metabolism. Increased glucocorti - 

coid levels might beneficially affect different enzyme systems 69,70 

and the drastic decrease in plasma levels of the inhibitory maternal 

hormones (e.g., pregnenolone and progesterone 71 ) helps, increas - 

ing the biotransformation capacity of the liver. Glucocorticoid 

levels increase during late gestation and will influence the matura - 

tion of different hepatic enzyme systems. The normal increase in 

glucocorticoid levels during late gestation or treatment with 

steroids will affect the maturation of both the UDP-GT enzyme 

system 71 and certain P450-related activities. 72 Recent scientific 

evidence has suggested that exposure to drugs able to cause liver 

enzyme induction during the neonatal period could cause longlasting 

“imprinted” alteration of hepatic metabolism. 73 Short-term 

phenobarbital administration to neonatal rodents causes longterm 

enzymatic changes, still recognizable in adult rats compared 

to control animals. 74 Exposure to different drugs and other 

subs tances during the early neonatal period might influence 

the individual’s drug metabolic pattern later on in life. The 

implica tions of such neonatally induced hepatic changes in drug 

metabo lism or hepatic enzyme expression is unknown but raises 

both questions and concerns. Despite the lack of any obvious short 

term risks or side effects of medication administered in the 

neonatal period, further long-term follow-up studies are needed 

to show that this does not lead to unwanted consequences later on 

in adult life. 

Immature hepatic drug metabolism and elimination are likely 

to be responsible for the increased toxicity of a number of different 

drugs during early infancy. This is evidenced by lower LD 50 

values 

for many drugs in newly born versus adult animals. 75 This is not 

true, however, for some drugs such as acetaminophen, which 

undergoes reduced metabolism by the P-450 system with sub - 

sequent lower levels of the toxic reactive metabolite responsible 

for the hepatic toxicity; in this instance, neonates tolerate dosages 

of acetaminophen that would be hepatotoxic in adults. 76 The issue 

of the P-450 system in newborns is complex. Comparable total 

levels of the P-450 system are present before midgestation in 

human fetal liver 77 but the individual proportions of the various 

P-450 components differ considerably from adults and the 

maturation process differ between individual P-450 isoenzymes. 

Plasma protein binding of alkaline drugs, for example, synthetic 

opioids and local anesthetics, also differ substantially in neonates 

compared to adults. Higher free, unbound, and Pharmacologicly 

active fractions of these drugs will, thus be present in the neonate 

compared to adults. This in turn is due to much lower plasma levels 

of -1 acid glycoprotein, the protein mainly responsible for binding 

of such drugs, found in neonates. Alpha-1 acid glycoprotein levels 

will gradually increase during infancy and adult levels are reached 

at about 1 year of age. 78 Alpha-1 acid glycoprotein is one of the 

acute phase proteins and rapidly increasing levels of -1 acid gly - 

coprotein (0.1 g/L 24 h) will be seen in neonates following major 

activation of acute phase system (e.g., major surgery, sepsis or 

extracorporeal membrane oxygenation). The main issues of im - 

mature hepatic drug metabolism in the neonate is highly complex 

but have important clinical implications which are summarized in 

Table 86–7. 

Renal Function 

Formation of new nephrons are completed about 34 to 35 weeks 

of gestation and further renal growth during late gestation, 

infancy, and adulthood is caused by enlargement of already 

existing structures 79 (see Chapter 5). Due to low systemic blood 

pressure and high renal vascular resistance, the kidneys only 

receive about 3% of the cardiac output during the last trimester, 80 

which sharply contrasts to the situation in adults where 25% of 

cardiac output passes through the kidneys. After birth, renal 

vascular resistance decreases (like pulmonary vascular resistance) 

and perfusion pressures increase resulting in a fairly rapid increase 

in renal blood flow. Effective renal plasma flow increase from 

83 mL/min/1.73 m 2 in the term neonate to 300 mL/min/1.73 m 2 

by 3 months of age. 81 In the neonate, the inner cortical and the 

medullary zones will receive relatively more of the renal blood 

flow compared to the mature kidney. Autoregulation of renal 

blood flow is functioning in the neonate but the lower shoulder 

of this pressure–flow relationship is set at a lower level (approxi - 

mately 50 mmHg). 82 

The glomerular filtration rate is low in the term infant, then 

double within the first 2 weeks of life 83 but does not reach adult 

levels until 2 years of age. 84 The tubular function is also reduced in


TABLE 86-7. Clinical Implications of the Neonatal Immaturity of Hepatic and Renal Functions 

Hepatic Functions 

1. Dosing intervals and maintenance dosing needs to be 

adjusted. 

2. Administer small and repeated doses of intravenous drugs 

and titrate to effect in order not to cause an overdose or 

cause an unwanted prolongation of the effect of the drug. 

3. When possible monitor drug plasma levels (digoxin, 

antibiotics) to ensure effect and avoid overdose. 

4. Use drugs with a known neonatal pharmacokinetics 

(morphine, fentanyl, lidocaine, bupivacaine, 

acetaminophen) rather than new drugs which have not 

been evaluated properly in neonates. 

Renal Functions 

1. Neonates tolerate fluid restriction poorly. Keep fasting times 

to a minimum and start intravenous fluids early to avoid 

dehydration. 

2. Avoid excessive fluid administration. 

3. Restrict sodium administration in order not to cause 

hypernatremia. 

4. Outside the first 24 h after birth a urine output of less than 

1 mL/kg/h indicate hypovolemia or impeding renal failure. 

5. The neonate will respond to furosemide but larger doses 

compared to adults are needed in order to induce diuresis. 

6. Fluid requirements in a catabolic situation is substantially 

lower compared to a normal anabolic situation since the 

formation of new cells is very limited. A catabolic situation 

will also limit the neonate’s ability to excrete potassium and 

handle nitrogen waste products. 

7. The dosing of drugs which largely depend on renal excretion 

will have to be reduced and if possible the plasma 

concentrations should be closely checked in order to avoid 

accumulation and side effects 

the neonate with a decreased ability to concentrate the urine, 

which is the result of a relatively lower tonicity of the medullar 

interstitium. Fairly rapid maturation takes place during the 

neonatal period with an increased capacity of concentrating the 

urine from twice the osmolarity of plasma in the term baby to four 

times at 2 months of age. 85 The neonatal kidney has a welldeveloped 

system for sodium reabsorption 86 but a limited capacity 

for excreting a sodium load. 84 The neonate responds to furosemide 

administration with an increase in diuresis but larger doses 

(1 mg/kg) compared to adults are often needed. 

Urine output is low immediately after birth and the neonate 

might only void once during the first 24 hours. Diuresis then 

rapidly increases to a normal value of 1 to 2.5 mL/kg/h. Urine 

output less than 1 mL/kg/h indicate hypovolemia (most 

commonly) or impeding renal failure (usually due to asphyxia, 

hemorrhage, or septic shock). Growth, with the generation of new 

cells, reduces the excretory load on the renal system, since for - 

mation of new cells will require water, potassium and nitrogenmetabolites. 

The formation of new cells will take care of a 

considerable amount of the normal “waste products,” since water 

and potassium are sequestered to form new intracellular fluid and 

nitrogen metabolites are used to manufacture new membrane and 

intracellular proteins. Thus, growth has been termed “the third 

kidney” and will take care of a substantial part of the normal renal 

“waste load.” From a phylogenetic point of view it is also reason - 

able to assume that the neonates renal function is tailor-made to 

the normal requirements of the neonatal period and, thus, it would 

appear illogical if the newborn would be born with borderline 

renal failure. It should be remembered that the growth related 

unloading of the renal system will only be operational in an ana - 

bolic situation. In a catabolic situation, for example, the immediate 

postoperative period or during septicemia, no or very few new 

cells are being made, leaving the kidneys to handle the entire waste 

load. As a results of the above-mentioned renal considerations, 

the neonate cannot easily handle either fluid or sodium overload, 

and poorly tolerates fluid restriction since the concentration 

capacity is low. Meticulous attention must, thus, be focused on 

fluid and electrolyte balance during the neonatal period. The 

excretion of drugs too is affected, especially water soluble drugs 

which are dependent on renal excretion. The main clinical 

consequences of renal immaturity are summarized in Table 86–7. 

Fluid and Electrolyte Balance, Caloric 

Requirement, and Blood Volume 

The total body water is substantially higher in the normal neonate 

(75%) compared to the adult (60%), and preterm babies have a 

still higher total body water content (see Chapter 5). Intra- and 

extracellular water represents 30 to 35% and 40 to 45% of the 

neonate’s total body weight, respectively. This considerable 

expansion of the extracellular fluid compartment is even more 

pronounced in the premature infant. 87 The blood volume of the 

normal neonate is approximately 85 mL/kg and up to 90 to 100 

mL/kg in preterm infants, with consistent interindividual vari - 

ability (60 to 130 mL/kg) due to possible placenta-to-neonate 

transfusion. Since plasma volume is relatively constant (50 mL/ 

kg, 88 this variability depends mainly on hematocrit variability. 

Maintenance fluid requirements increase regularly during the first 

days (60, 80, 100, and 120 mL/kg/24h at day 1, 2, 3, and 4, 

respectively), then remain stable for the rest of the neonatal period 

(approximately 150 mL/kg/24 h). Caloric consumption is about 

100 to 120 kcal/kg/24h, half of which is required for basal 

metabolic needs and the remaining for growth. 89 Since caloric 

requirements are closely linked to fluid intake (it is virtually 

impossible to supply fluid with a caloric content of more than 1 

calorie per milliliter), pathological conditions where cell growth is 

halted (severe sepsis, postoperative period following major 

surgery), are at risk of metabolic overload as well as fluid retention 

if fluid and caloric supply are not adjusted. Daily electrolyte 

requirements for maintenance of electrolyte balance in the neonate 

are 2.5 mmol/kg, 2.0 mmol/kg, and 0.5 mmol/kg for sodium, 

potassium, and calcium, respectively. It should be remembered 

that a negative sodium balance negatively affects the growth of the 

neonate and can also affect growth later in life. 90 In most cases a


maintenance infusion of 10% glucose containing 20 mmol/L 

sodium and 20 mmol/L potassium is usually satisfactory for the 

first 48 postnatal hours. If enteral feeding has not been established 

at this time, total parenteral nutrition should be started to ensure 

adequate nutrition of the baby. 

Temperature Control 

Thermoregulation in the neonate displays significant particulari - 

ties (see Chapter 10). Heat loss is favored by the comparatively 

larger body surface–to–body weight relationship, the poorly 

developed insulating subcutaneous fat layer, and the inability to 

use shivering thermogenesis. These limitations are partially 

compensated for by the unique thermal capacity for nonshivering 

thermogenesis (NST), which takes place in the neonate’s brown 

adipose tissue (see Chapter 10). Brown fat is mainly located be - 

tween the scapulae, around the blood vessels of the neck, in the 

axillae, in the mediastinum, and around the adrenal glands and 

kidneys. However, nonshivering thermogenesis is negatively 

influenced by the administration of volatile anesthetics. 91 Halo - 

thane, enflurane and isoflurane appear to cause an equipotent 

inhibition of thermogenesis. Concentrations of volatile anesthetics 

as low as 0.7% result in a 50% inhibition of the maximal thermal 

response 92 (Figure 86–8). Recent data also indicate that a fentanylpropofol–based 

anesthetic will interfere with NST. 93 Inadvertent 

intraoperative hypothermia has been found to cause a number of 

negative effects in adults, such as impaired immunologic function, 

increased rate of wound infections, negative influences on hepatic 

and renal function, and reduced drug metabolism. 94 Although no 

corresponding data are currently available in children, it is reason - 

Figure 86-8. The effects of halothane, isoflurane, and enflurane 

on the maximal norepinephrine-induced oxygen consumption 

in isolated brown adipocytes. The cells were preincubated with 

the indicated concentrations of the anesthetic agent, immediately 

transferred to an airtight oxygen electrode chamber, and 

then stimulated with successive additions of norepinephrine. In 

each of the control experiments, the maximal rate of oxygen 

consumption was defined. The highest rate of oxygen consumption 

that was reached for each concentration of each anesthetic, 

expressed as percent inhibition of the maximal rate of oxygen 

consumption, are the values shown. The results are the averages 

from two series of experiments. The values obtained were for 

cells treated with halothane: I max 

89 2%, IC 50 

0.7 

0.04%, r 0.997; with enflurane: I max 

79 4%, IC 50 

0.7 

0.07%, r 0.994; and with isoflurane: I max 

69 3%, IC 50 

0.6 0.06%, r 0.993. 

able to assume that these negative effects will occur also in the 

neonate, maybe at an ever greater degree, and hypothermia must 

be prevented during anesthesia and surgery in the neonate at all 

times (see “Prevention of Heat Loss” ). This fact is further under - 

scored by convincing evidence from adults pointing out that a 

reduction of as little as 2C will predispose to a number of post - 

operative complications and will also affect outcome. 95 

PREOPERATIVE INVESTIGATIONS 

Medical History and Physical Examination 

Hydration Status 

The anesthesiologist should screen every neonate for clinical signs 

of dehydration, for example, reduced fontanel tension, decreased 

skin perfusion, reduced skin turgor, and unexplained tachycardia 

(see Chapter 27). Special attention should be paid to any patho - 

logic fluid losses, most often occurring from the gastrointestinal 

tract. Also signs of hypovolemia (diaphoresis, tachycardia, hypo - 

tension, reduced capillary refill, oliguria) must be sought. All 

degrees of dehydration and/or hypovolemia will have to be fully 

corrected before going to the operating theater, the only exception 

being airway obstruction and other super-emergency conditions 

(e.g., threatening intestinal gangrene due to malrotation volvulus). 

Failure to correct a negative fluid balance or to miss pre-existing 

hypovolemia can cause severe problems during the course of the 

anesthetic. 

Respiratory Function 

The presence of any respiratory symptoms must be noted. Stridor 

is not infrequently mistaken as expiratory stridor. Since airway 

obstruction is very rare unless the neonate is infected with res - 

piratory syncytial virus, until proven otherwise, stridor is essen - 

tially inspiratory in nature and represents a symptom of upper 

airway obstruction. Its presence should lead to further investiga - 

tions and consultation with an otolaryngologist. Tachypnea, 

grunting, jugular and costal retractions, reduced peripheral oxy - 

gen saturation on room air, oxygen dependence or frank cyanosis 

are all signs of respiratory distress. Neonatal respiratory distress can 

be caused by a number of different pathologies and merits 

consultation with a neonatologist before anesthesia. 

Cardiovascular Function 

Cardiovascular abnormalities are usually known in neonates 

scheduled for surgery. However, the anesthesiologist should always 

check for the presence of any signs and symptoms indicative of 

cardiovascular problems, for example, poor or excessive weight 

gain, failure-to-thrive problems, hepatomegaly, tachypnea, cyano - 

sis, heart murmur, or weak or absent femoral pulses. If such symp - 

toms or signs of cardiovascular abnormalities are present further 

consultation with the pediatric cardiologist, including an echo - 

cardiographic examination, is mandatory before anesthesia and 

surgery. A liberal attitude towards pediatric cardiology consulta - 

tion should be the rule in order not to miss any significant 

cardiovascular abnormality. Neonates undergoing correction of 

any congenital malformation are at increased risk of having some 

associated syndrome. The anesthesiologist can not be expected 

to be knowledgeable regarding all rare congenital syndromes but 

signs suggestive of Down syndrome should always be sought. The


Pierre–Robin syndrome has anesthesiological implications and 

signs of micrognathia should be identified before going into the 

operating theater. 

Coagulation Disorders 

Coagulopathy is rare in neonates. However, since coagulation dis - 

orders can cause life-threatening bleeding intra- and postopera - 

tively, the anesthesiologist has to search for symptoms and signs 

(e.g., prolonged bleeding from skin puncture sites, spontaneous 

bleeding from the nasal or oral mucosa, presence of more signifi cant 

amount of blood during tracheal suctioning in already ventilated 

patients). The skin surface should also be inspected in order to 

identify any petechiae indicating a possible low platelet count. If the 

patient is suffering from uncontrolled sepsis, a coagulopathy should 

be suspected until proven otherwise. If coagulation problems are 

suspected, appropriate laboratory tests must be performed (see 

“Coagulation”). If these tests are not within the normal range, 

consultation with a coagulationist should be under taken. 

Laboratory Screening 

Hemoglobin, Blood Typing, 

and Compatibility Screening 

Neonatal hemoglobin values are considerably higher (150 to 240 

g/L) than in adults (see Chapter 9). It consists mainly of fetal 

hemoglobin (HbF) which has a higher oxygen binding capacity 

(P 50 

19.5 mmHg) than normal adult hemoglobin (HbA) (P 50 

 

27 mmHg); thus, the HbF oxygen dissociation curve is displaced 

to the left. Due to its higher oxygen binding capacity, HbF has a 

decreased potential for oxygen release to the tissues. In a situation 

where oxygen demand is high or oxygen transport is marginal 

(e.g., sepsis, hypoxemia, hypovolemia, and intraoperative 

hemorrhage), transfusion of HbA will be beneficial. Polycythemia 

(normal hemoglobin range in the newborn: 150–240 g/L) can be 

present in certain neonates (incidence approximately 4%) and 

hematocrit values above 65% increase blood viscosity, which 

negatively influences tissue blood flow. In such a situation, 

exchange transfusion (20–30 mL/kg of blood exchanged for the 

same amount of plasma) can be discussed before surgical 

intervention in order to optimize the conditions for the patient. A 

preoperative hemoglobin and hematocrit value should be taken 

in all neonates scheduled for surgery, with the exception of 

diagnostic or very minor procedures (e.g., inguinal hernia repair). 

If surgery is more extensive or if there is even a small risk of 

significant bleeding, blood typing and compatibility screening 

should be performed. Blood and plasma should be ordered 

according to the potential needs and should be readily available 

before induction of anesthesia. Indications for the ordering of 

plasma are mainly the anticipation of major blood loss where 

plasma will be needed to boost coagulation or in situations where 

substantial third space losses are likely (e.g., gastroschisis repair). 

In the neonate, blood typing and compatibility screening requires 

determination of the neonates blood type as well as blood typing 

and screening of the mother. The type and screen of the mother is 

acceptable if the baby is less than 6 weeks old. If irregular 

antibodies are found in the mother, cross-matching has to be 

performed. Screening tests do not need to be performed in the 

neonate, since the neonatal immune system is not capable of 

producing antibodies until 3 months of age. Thus, the antibodies 

present in the neonate only originate from placental transfer from 

the mother. 

Electrolytes and Acid-Base Balance 

If the patient is scheduled for more extensive surgery the patient’s 

electrolyte and acid-base status must be checked before induction 

of anesthesia. A standard screen should include sodium, potas - 

sium, chloride, calcium, pH, and base excess/standard bicarbonate 

levels. Any significant deviation from normal values should be 

corrected before anesthesia and surgery. It is worth remembering 

that the neonatal reference values for potassium are higher than in 

older children and adults (day 1–2: 4.5–7.0 mmol/L; 3rd postnatal 

day–3 months: 4.0–6.2 mmol/L). Values outside of the normal 

values might be associated with the same risk for cardiac 

arrhythmias as in older patients. 

Coagulation 

Coagulation parameters are quite different in neonates and pre - 

mature babies compared to adults (Table 86–8) and can be 

mistaken for a coagulopathy with an increased bleeding tendency, 

especially regarding activated partial thromboplastin time 96 

whereas neonates most often have an increased tendency for blood 

clotting. The theoretical background for this is still not entirely 

clear but can be a result of lower inhibitor levels. Thus, surgery 

does not have to be postponed or action taken merely on the 

grounds of coagulation tests outside normal adult limits. However, 

if coagulation parameters are outside the normal values for 

premature or term babies, especially also if clinical signs of coa - 

gulopathy are present, consultation with a coagulation expert 

should be undertaken. 

Platelet counts are similar to normal adult values in term 

neonates (250–300 10 9 /L) but are frequently lower in premature 

children (50–150 ( 10 9 /L). The function of the platelets are 

generally normal. The existence of thrombocytopenia should raise 

concern since this is often one of the initial signs of sepsis in 

neonates and a neonatologist should be consulted regarding the 

cause of a low platelet count. No specific knowledge is available 

for the lowest acceptable platelet count in association with 

neonatal surgery, but levels of at least 50 to 65 10 9 /L should most 

probably be required. Platelet transfusion of 5 mL/kg will increase 

the total platelet count by about 40 10 9 /L. In major surgery, 

intraoperative platelet transfusion is usually not needed until the 

patient has bled approximately two blood volumes, if the patient 

had a normal platelet count preoperatively. Due to limited reserves 

and a generally insufficient supply of vitamin K by breast feeding, 

neonates should receive supplemental vitamin K either by the oral 

or, preferably, by the intramuscular route (1 mg) immediately 

following birth. This will safeguard against the development of 

coagulopathy during the neonatal period. In emergent delivery 

situation or as a result of early transfer of the baby between 

hospitals, vitamin K administration can easily be forgotten. Before 

neonatal anesthesia and surgery it is prudent to check the patient’s 

notes to ensure that vitamin K has been administered. If not, 

coagulation parameters should be checked and vitamin K given 

(1 mg I.M. or I.V.). Intramuscular administration of vitamin K is 

preferable since I.V. administration is associated with an increased 

risk of side effects (mainly severe hemodynamic reactions). The 

effect of vitamin K is delayed (hours) and in an emergent situation 

transfusion of fresh frozen plasma will provide enough 

coagula tion factors to allow the start of the surgical intervention.


TABLE 86-8. Reference Values (Mean [Boundary]) for Coagulation Tests in Term and Premature (30–36 g.w.) Babies 

Coagulation test Day 1 Day 5 Day 30 Adult 

Premature infants 

PT (sec) 13.0 (10.6–16.2) 12.5 (10.0–15.3) 11.8 (10.0–13.6) 12.4 (10.8–13.9) 

APTT (sec) 53.6 (27.5–79.4) 50.5 (26.9–74.1) 44.7 (26.9–62.5) 33.5 (26.6–40.3) 

TCT (sec) 24.8 (19.2–30.4) 24.1 (18.8–29.4) 24.4 (18.8–29.9) 25.0 (19.7–30.3) 

Fibrinogen (g/L) 2.43 (1.50–3.73) 2.80 (1.60–4.18) 2.54 (1.50–4.14) 2.78 (1.56–4.00) 

Coagulation inhibitors 

AT III (U/mL) 0.38 (0.14–0.62) 0.56 (0.30–0.82) 0.59 (0.37–0.81) 1.05 (0.79–1.31) 

Protein C (U/mL) 0.28 (0.12–0.44) 0.31 (0.11–0.51) 0.37 (0.15–0.59) 0.96 (0.64–1.28) 

Term infants 

PT (sec) 13.0 (10.1–15.9) 12.4 (10.0–15.3) 11.8 (10.0–14.3) 12.4 (10.8–13.9) 

APTT (sec) 42.9 (31.3–54.5) 42.6 (25.4–59.8) 40.4 (32.0–55.2) 33.5 (26.6–40.3) 

TCT (sec) 23.5 (19.0–28.3) 23.1 (18.0–29.2) 24.3 (19.4–29.2) 25.0 (19.7–30.3) 

Fibrinogen (g/L) 2.83 (1.67–3.99) 3.12 (1.62–4.62) 2.70 (1.62–3.78) 2.78 (1.56–4.00) 

Coagulation inhibitors 

AT III (U/mL) 0.63 (0.39–0.87) 0.67 (0.41–0.93) 0.78 (0.48–1.08) 1.05 (0.79–1.31) 

Protein C (U/mL) 0.35 (0.17–0.53) 0.50 (0.22–0.78) 0.63 (0.33–0.93) 0.96 (0.64–1.28) 

PT prothrombin time; APTT activated partial thromboplastin time; TCT thrombin clotting time; AT III antithrombin III. 

Adapted from Andrew et al. 144 

When major surgery is planned a preoperative coagulation screen 

consisting of prothrombin time, activated partial thromboplastin 

time, and platelet count should be performed before surgery. 

The use of thromboelastography has recently been described 

also in neonates and infants. Using this technique, children with 

complex congenital heart disease have been found to have a 

functionally intact coagulation-fibrinolytic system working at a 

lower level than in healthy infants, indicating a reduction in the 

hemostatic potential with less reserve. 97 Using the same techno - 

logy, the effects of various colloid alternatives were analyzed in 

infants (3–15 kg). 98 In this investigation, the use of gelatins as an 

alternative to albumin was suggested since the use of hydroxyethyl 

starch affected the overall coagulation process the most. 

Diagnostic Investigations 

Special investigations can be required after taking the medical 

history and obtaining results from the laboratory testing. The most 

common preoperative investigations are chest radiography, 

echocardiography and ultrasonic head scans. 

Chest X-Rays 

Chest radiographs should be obtained in all patients with cardio - 

respiratory symptoms. Not only will this investigation provide the 

anesthesiologist with information regarding the severity of various 

conditions but it can also provide information if further treatment 

might optimize the patients condition before anesthesia and 

surgery. Thus, based on the chest radiograph, surgery might be 

postponed in order to re-expand atelectatic lung tissue or to 

reduce interstitial edema by intensifying diuretic treatment. 

Ultrasonographic Examinations 

Echocardiography should be performed liberally not only to search 

for associated congenital heart disease but also to more precisely 

estimate the intravascular volume status. Echocardiography is also 

useful in order to determine if the ductus arteriosus still remains 

open and to determine the possible presence of pulmonary 

hypertension and right-to-left shunting. 

Due to the existence of an open fontanel ultrasonic head scans 

provide the unique opportunity for investigating the intracranial 

contents of the neonate (for the vein of Galen for instance). In 

term neonates, this investigation rarely provides crucial infor - 

mation since intracranial hemorrhage is unusual in this group. 

However, premature infants have an increased risk for such 

hemorrhages with the highest risk seen in the most prematurely 

born babies. Before performing anesthesia in such premature 

infants, it might be wise to perform an ultrasonic head scan in 

order to document any pre-existing problem and, thus, escape the 

responsibility for any hemorrhages which have already occurred 

prior to the involvement of the anesthesiologist. 99 

PREANESTHETIC MANAGEMENT 

Premedication 

If the neonate is judged to be in pain preoperatively, low and 

titrated doses of morphine are appropriate. The response to 

morphine in this age group is variable and doses of 10 to 20 g/kg 

should be administered intravenously until adequate pain relief is 

achieved. In case of difficult venous access where an inhalational 

induction is planned, subcutaneous or intramuscular atropine 

(10–20 g/kg; minimum 100 g) is often useful to counteract 

parasympathetic reflexes before the placement of a reliable venous 

line. In case of intravenous induction, atropine can be given 

intravenously (10 g/kg; minimum 100 g) just before the start of 

the anesthetic. Apart from these specific situations, no preme - 

dication is usually required in the neonatal period. 

Parental Presence During Induction 

In older patients, parental presence can be helpful, although cer - 

tain practitioners still find this practice questionable. 100,101 

However, the neonate is not yet mentally capable of psychologic -


ally benefiting from parental presence, and contrary to the 

standard case in older children, where the children in most 

circumstances are otherwise healthy and the anesthetic and the 

surgical procedure are not expected to be hazardous, neonatal 

parents are often very anxious and scared for obvious reasons. 

Thus, parental presence does not provide any significant benefits 

to the neonate, may cause unnecessary stress on the parents, and 

can cause problems to the anesthetic team. The decision to allow 

or abstain from parental presence during induction of anesthesia 

can only be made on a case-by-case evaluation. 

Monitoring Requirements 

Overview 

Because of the small size of neonatal patients a number of 

advanced continuous monitoring options frequently used in adult 

patients undergoing major surgery or who are hemodynamically 

unstable (e.g., pulmonary artery catheterization, transesophageal 

echocardiography) cannot be used in the neonatal setting. 

However, the need for adequate and reliable monitoring is 

especially important in neonates since the patient will become 

more or less inaccessible to the anesthesiologist following surgical 

draping of the patient. The minimal monitoring required for 

neonatal anesthesia consists of the following: pulse oximetry, 

capnography, noninvasive blood pressure monitoring, electrocar - 

diogram, and body temperature measurement. The use of a 

precordial or an esophageal stethoscope is viewed as essential by 

some practitioners and is compulsory for medical–legal reasons 

in certain countries. Monitoring of anesthetic gases can obviously 

be incorporated into standard monitoring but the anesthesiologist 

must be aware of the caveats with the currently available 

systems resulting in problems with the interpretation of the 

generated data. 

If the patient is scheduled for more extensive surgery where 

substantial bleeding may occur or if the patient is unstable for any 

reason more invasive monitoring is required. Intra-arterial blood 

pressure monitoring should be performed liberally under these 

circumstances not only since it allows accurate and on-line 

measurement of the blood pressure even at very low blood 

pressure levels but also since it permits excellent monitoring of 

the intravascular volume status. Hypovolemia usually causes 

undulations of the blood pressure tracing synchronous with 

ventilation due to the variability in venous return caused by 

ventilation. Hypovolemia also causes a change in the up-stroke of 

the blood pressure curve due to inadequate filling of the heart. 

Compared to monitoring of central venous pressure intra-arterial 

blood pressure monitoring is superior in the setting of judging 

changes in filling pressures in the neonate. Intra-arterial access 

also allows repeated arterial blood gas sampling and other labo - 

ratory analyses (e.g., hematocrit, blood glucose, sodium, potas - 

sium, and ionized calcium). 

Insertion of a single lumen or multilumen central venous 

catheter might be a good option to get secure venous access and 

allow infusions of inotropic and vasoactive drugs. In any situation 

at risk of air embolism, precordial Doppler monitoring, together 

with an esophageal stethoscope, should be used to rapidly detect 

and treat this complication. Continuous measurement of urine 

output is obviously of great importance for the monitoring of the 

neonate undergoing major surgery. Urine output less than 1.0 mL/ 

kg/h is indicative of hypovolemia. However, sudden decreases in 

output should be viewed with suspicion and the catheter system 

should immediately be check for blockage or kinking before any 

therapeutic measures are taken. 

Specific Considerations Concerning 

Common Monitoring Options 

PULSE OXIMETRY: Neonatal probes should only be used since 

adult probes are not reliable when peripheral vascular perfusion is 

poor. It is preferable to place the probe on the hand so that its 

access is facilitated when it has to be checked or moved to a new 

location in order to obtain a good tracing again. The probe and 

cable should be protected from interference caused by electric 

cautery. Use of a pulse oximeter displaying the plethysmogram 

and indicating changes in skin perfusion is recommended since 

significant additional information regarding the cause of malfunc - 

tion and the development of peripheral vasoconstriction due to 

hypovolemia or hypothermia is provided. Pulse oximetry will not 

provide reliable readings in the presence of either pronounced 

polycythemia or methemoglobinemia. 

CAPNOGRAPHY: Mainstream analysis will give more reliable 

readings that sidestream analysis for rapid ventilatory rates. At 

ventilatory rates above 50/min, the accuracy of both types of 

analyzers is substantially affected. However, it is usually possible to 

decrease the ventilatory rate intermittently briefly to 15 to 20/min 

to obtain a more reliable reading. The probe of mainstream 

analyzers will generate heat, thus, care must be taken to avoid 

contact of the probe with the skin. The advantages with main - 

stream analysis will, however, to a substantial extent be offset by 

the problems of mixture and dilution of the expired gases by the 

fresh gas flow. 102 A major issue in this respect is that it is impossible 

to use a measuring point distal to the tracheal tube connector with 

mainstream analysis. To obtain more reliable readings, sidestream 

analysis with a sampling point distal to the elbow connector 

should be used, with the ideal point being distal to the point where 

the tube connector narrows to the diameter of the tracheal tube 103 

(Figure 86–9). In summary, very useful trend information can be 

generated both by mainstream and sidestream analyzers but the 

clinician must be aware of the limitations of the techniques and, 

when clinically indicated, control the end-tidal readings against 

conventional blood gas analysis. 

NONINVASIVE BLOOD PRESSURE MONITORING: The cuff must 

be appropriately sized and the arterial indicator arrow has to be 

in the correct place. Measurement intervals shorter than every 

third minute should not be routinely used, since this can cause 

venous stasis and petechial formation, especially in preterm 

babies. The calf can be used instead of the arm, depending on the 

circumstances. Noninvasive blood pressure monitoring provides 

sufficiently accurate readings in most cases and at least allows for 

trend observations. 

ELECTROCARDIOGRAPHIC TRACINGS: Cleaning the skin with an 

alcohol solution improves the quality of skin contact with electro - 

des and provides a high quality signal throughout the operation. 

The derivation providing the best P-wave tracing should be 

preferred, as it makes easier the diagnostic of nodal arrhythmia 

which is frequent in pediatric anesthesia. Electrocardiogram pads 

must be carefully removed especially in preterm infants, to avoid 

skin damage.


Figure 86-9. The site of mixing of fresh gas flow and expired 

gas is always proximal to the endotracheal tube connector. At 

an expired gas flow of 500 mL/min-1, the influence of fresh 

gas flow rate on the site of mixing and the degree of dilution 

is significantly greater. 

ANESTHETIC GAS ANALYSIS: Most available monitors aspirate gas 

volumes of approximately 150-200 mL/min which is con siderable 

if compared to the tidal volume of the neonatal child. The gas is 

also most frequently sampled close to the Y-piece of the ventilatory 

tubing. This invariably causes mixing of inspired and expired gases 

and also distorts the end-tidal CO2 tracing. The values derived in 

this setting are, thus, not accurate but trend changes are still 

detectable. 

INTRA-ARTERIAL BLOOD PRESSURE MONITORING: Maintenance 

of functional arterial lines throughout the operation is not an easy 

task during neonatal surgery. Pre-existing arterial lines must be 

checked before draping or a new line should be estab lished. The 

wrist should be splinted when using a radial approach. The 

insertion site should be protected from electrical interference 

(electrical cautery). Extension lines should be long enough when 

a femoral approach is planned, otherwise there is a risk that the 

catheter kinks or becomes dislodged (small gauge central venous 

lines are good options in this setting). The arterial line must be 

continuously flushed with a dilute heparin solution (1 U/mL) to 

prevent clotting. If flushing the system is necessary, it must be 

done over a short period of time to limit the injected volume; the 

distance from the wrist to the aortic arc is short and even small 

saline boluses may cause systemic and cerebral embolism. 

NEAR-INFRARED SPECTROSCOPY: This relatively new method 

to continuously assess cerebral oxygenation, displayed as cerebral 

tissue oxygenation index (cTOI), has gained widespread use 

in pediatric cardiac anesthesia and is able to give a fast but 

unspecific warning of cerebral ischemia. A sensor, similar in size 

compared to the bispectral (BIS)-monitor, is put on one or both 

sides of the forehead of the child (unilateral monitoring is usually 

sufficient in most instances) and is then attached to a relatively 

small moni tor. 104 The cTOI value has also been shown to 

correlated to central venous oxygenation (SvO 2 

) in neonates and 

infants. 105 This new modality of monitoring will definitely gain 

widespread use both in adults and children and will in the future 

most likely be considered standard of care for all cases of major 

surgery in the neonate. 

ANESTHETIC DEPTH MONITORING: BISPECTRAL INDEX 

MONITORING (BIS), SPECTRAL ENTROPY AND AUDITORY 

EVOKED POTENTIALS (AEP): This electroencephalography 

(EEG)-derived monitoring device has gain popularity in adult 

anesthesia as an indicator of anesthetic depth and safeguard 

against awareness. However, there is widespread skepticism with 

regards to the fact that this monitor in fact has anything to do with 

anesthetic depth, although there is a clear covariation between the 

BIS value and anesthetic depth in adults. Due to the differences 

in EEG patterns between adults and neonates and small children, 

the BIS monitor cannot be recom mended in these age groups. 106 

A different concept of attempting to assess anesthetic depth is 

the so-called Spectral Entropy that is based on the EEG power 

spectrum. Although this method appears comparable to BIS in 

adults and older children spectral entropy has not been properly 

validated in neonates and small infants. 107 

A third monitoring system in this category is Auditory Evoked 

Potentials (AEP). Despite measuring the response to an active 

auditory stimulus this method does not appear to have any 

advantage over the other two systems described above. 108 Thus, at 

present the various option for anesthetic depth monitoring that 

are widely used in adults cannot be recommended in the context 

of neonatal anesthesia. 

ANESTHETIC MANAGEMENT 

Pharmacokinetic Data for 

Commonly Used Drugs 

Because of the lack of interest and incentive for drug companies to 

register drugs for use in neonates and small infants, there has been 

a substantial knowledge gap regarding fundamental pharmaco - 

kinetic data for a large number of analgesic and anaesthetic drugs 

that are frequently used in the context of neonatal anaesthesia. 

However, a significant scientific effort from various research 

groups during the last few years have provided valuable informa - 

tion regarding pharmacokinetic data in this field, often using the 

approach of population pharmacokinetics, nonlinear mixedeffects 

modelling (NONMEM) and allometric scaling ( 3 / 4 

power 

modeling). The provision of the new data provide a basis for more 

appropriate dosing as well as minimising the risk for accumulation 

and undesired side effects. A summary of pharmacokinetic data 

are given below in Table 86–9. 

Preoxygenation 

The median time necessary to achieve an end-tidal oxygen 

concentration of at least 90% using a tight fitting mask and 6 L/ 

min oxygen flow is 40 seconds (range: 20–50 sec) and a preoxy - 

genation period of 60 seconds is, thus, recommended up to 5 years 

of age. 115 However, even after a 2-minute period of preoxygenation 

by manual ventilation with 100% oxygen following anesthesia 

induction and muscle relaxation oxygen, desaturation (SpO 2 

90%) occurs after about 80 to 90 seconds of apnea in neonates. 116 

Induction Techniques 

Neonates undergoing surgery usually already have intravenous 

access with an infusion running. In this setting, intravenous 

induction obviously is the first option. Pharmacologic properties


TABLE 86-9. Pharmacokinetic Values for Some Analgesic and Anesthetic Drugs Commonly Used in Neonates and Infants 

Drug Clearance Volumes of Distributions Volumes of Distributions PK Model Used/Age Groups 

Ketorolac 109 Central volume Peripheral volume Two compartment/Infants 

R()isomer 7.5 mL min-1 1.2 L 0.83 L 6–18 mo 

S() isomer 45.3 mL min-1 3.2 L 0.22 L 

Midazolam 110 157 mL min-1 Central volume 3.8 L Peripheral volume Two compartment/ 

30.2 L Infants 3–24 mo 

Morphine 111 71 L h-1 (70 kg)-1 Volume of distribution One compartment/ 

136 L (70 kg)-1 0–3 yr 

Proparacetamol 112 55 L h-1 (70 kg)-1 Central volume Peripheral volume Three compartment/ 

24 L (70 kg)-1 30 L (70 kg)-1 Premature babies–14 yr 

Propofol 113 442 mL min-1 Apparent volume of distribution Three comparment/ 

(70 kg)-1 at steady state 259 L (70 kg)-1 Neonates 

Tramadol 114 17.5 L h-1 Central volume 228 L (70 kg)-1 Peripheral volume Two compartment/ 

(70 kg)-1 0.6 L kg-1 0–6 yr 

of intravenous agents are fully evaluated in Chapter 14. Thiopental 

has withstood the test of time and is a good routine induction 

agent in hemodynamically stable patients. It should, however, be 

remembered that the terminal half-life of thiopental is very long 

in premature and newborn babies 117 and can result in prolonged 

emergence from anesthesia as well as an increased tendency for 

the development of postoperative apnea. Recently, the pharmaco - 

kinetic profile of propofol has been outlined in small children and 

infants 118 ; propofol might prove to be a useful alternative to 

thiopental also in the neonate. Based on clinical experience larger 

doses than normally recommended are often required to induce 

anesthesia with thiopental (4–8 mg/kg) or propofol (3.0–3.5 

mg/kg) in neonates compared to adults. In hemodynamically 

unstable patients ketamine (1.5–3 mg/kg) is the drug of choice for 

intravenous induction. 

In patients with a compromised airway or if intravenous access 

appears difficult, an inhalational induction should be used. The 

newer volatile agent sevoflurane tends to replace halothane as the 

induction agent of choice in these situations due to its relative lack 

of hemodynamic depression. 119 In the setting of inhalational 

induction with sevoflurane the anesthesiologist should be aware of 

one unique characteristic of sevoflurane compared to the other 

volatile anesthetics. Contrary to the other volatile agents, the 

minimum alveolar concentration (MAC) value of sevoflurane is 

not reduced in preterm and newborn babies compared to older 

children (see Chapter 13). Thus, the MAC for sevoflurane in the 

neonate is approximately 3.2%, which is similar to the MAC values 

for 1 to 6 months old infants 119 (Figure 86–10). A drawback with 

sevoflurane is the slightly more pronounced depression of 

ventilation compared to halothane above 1.4 MAC, 120 but this is 

not believed to be of clinical importance. 121 

Airway Management 

General Considerations 

Preservation and protection of a patent airway is fundamental to 

the practice of neonatal anesthesia. Due to practical problems and 

the vulnerability of the newborn infant, tracheal intubation should 

be used liberally to avoid unnecessary ventilatory problems. This 

is particularly true if the anesthesiologist in charge has a limited 

experience with neonates. A face mask anesthetic can be consi - 

dered for very brief procedures. However, even during short 

procedures ventilation should at least be assisted, since most 

anesthetics will cause a significant degree of respiratory depression 

in the neonate. If, despite a good mask seal, the anesthesiologist is 

experiencing difficulties with keeping a clear airway, the use of an 

oropharyngeal airway or the application of 3 to 4 cm H 2 

O of 

continuous positive airway pressure are often helpful. If the 

situation is still not satisfactory at this point, the use of a laryngeal 

mask airway (LMA) can be used even in very small neonates. 122 

Should problems still persist, tracheal intubation must be 

performed without any further delay. 

Laryngeal Mask Airway 

The number 1 size LMA can be used successfully even down to 

approximately 1.0 kg. 122,123 To have a good LMA fit in such small 

patients, injection of a muscle relaxant is helpful to allow adequate 

relaxation of the pharyngeal muscles during the insertion 

procedure. Due to the relatively large dead space of the LMA often 

associated with high end-tidal CO 2 

concentrations, ventilation 

should at least intermittently be assisted in order to avoid hyper - 

capnea and atelectasis formation. To avoid gastric overdistension, 

Figure 86-10. The mean ( standard deviation) end-tidal concentration 

of sevoflurane in oxygen for each of the six age 

groups from neonates to older children up to 12 y of age. The 

data for MAC at 30 y of age were obtained from reference 9.


a nasogastric tube should be inserted before placement of the 

LMA and left open to vent the stomach. Use of the LMA allows the 

anesthesiologist to avoid unnecessary tracheal intubation in expremature 

babies with bronchopulmonary dysplasia where 

extubation has just recently been achieved with great difficulty. 

The LMA with preserved spontaneous ventilation can be used for 

selected cases with an anticipated anesthetic duration of less than 

30 to 45 minutes. If longer interventions are planned, tracheal 

intubation should be performed. 

The LMA has also been advocated in the resuscitation situation 

immediately after delivery in asphyxiated term babies. If an 

experienced anesthesiologist performs the placement of the LMA 

in this situation, successful placement of the LMA is virtually 

always achieved at the first attempt. 124 If the position of the LMA 

is checked by fiberscopy, the epiglottis is visible in about 50% of 

cases. The clinical relevance of this finding is still open to question 

since only 2% of the children had complete airway obstruction. 125 

The clinician should also be aware that end-tidal CO 2 

readings 

will underestimate the PaCO 2 

by as much as about 10% of the 

correct arterial value if the child is allowed to breath sponta - 

neously. 126 However, if ventilation is controlled, end-tidal CO 2 

values are as accurate as if a tracheal tube were used. 127 This, 

together with the high prevalence of hypercapnea associated with 

the use of the LMA in spontaneously breathing neonates and 

infants, further underscores the necessity of at least intermittently 

assisting the ventilation manually. 

Tracheal Intubation 

As discussed above, tracheal intubation should be considered the 

standard method for airway management in the neonate. A 

number of points deserve attention: 

1. Awake tracheal intubation has previously been recommended 

in neonates as a safe and practical method. Currently, this 

practice is no longer acceptable since tracheal intubation is a 

very stressful and painful stimulus which can definitely cause 

harm to the patient both in the short and long-term pers - 

pective. Additionally, the technique is also very stressful for the 

anesthetic team since the intubation conditions are far from 

optimal compared to the situation following a controlled 

anesthetic induction. 128 

2. Different measures exist to achieve the appropriate degree of 

muscle relaxation to allow easy intubation. Succinylcholine 

should mainly be reserved for rapid sequence intubation and 

nondepolarizing muscle relaxants should be preferred under 

more ordinary circumstances. However, the use of nonde - 

polarizing muscle relaxants will cause a reduction in FRC 

associated with decrease dventilatory homogeneity. This can 

be counteracted by the use of 3 cm H 2 

O of positive endexpiratory 

pressure (PEEP) and, thus, the use of this level of 

PEEP is recommended in anesthetized and paralyzed 

neonates. 129 

Sufficient muscle relaxation can be achieved also by deeper 

inhalational anesthesia, but, due to the increased risks for 

cardiopulmonary complications, this will require quite exten - 

sive neonatal anesthesia experience. Since sevoflurane causes 

substantially less cardiovascular depression compared to 

halothane, sevoflurane is preferable when available. However, 

the slightly more pronounced respiratory depression caused by 

sevoflurane compared to halothane should be borne in mind. 

When intubation is performed during deeper inhalational 

anesthesia only, the use of muscle relaxants might also be 

completely avoided in most cases of neonatal surgery. Inspira - 

tory concentrations of sevoflurane and halothane necessary to 

achieve good intubating conditions will, however, cause a 

certain degree of hypotension and great caution should be 

observed in the unstable neonate regarding the use of deeper 

levels of inhalational anesthesia. However, in more stable 

neonates intubation during sevoflurane inhalation was found 

to achieve more stable hemodynamics compared to the 

outdated technique of awake intubation. 130 

3. Since the neonatal larynx is located more anteriorly and more 

cephalad, with the epiglottis tending to be much floppier and 

to drop down over the laryngeal entrance like a theater curtain, 

use of a straight laryngoscope blade is recommended to gain 

good visualization of the vocal cords in neonates (see Chapter 

38). The tip of the blade should not be placed in the vallecula as 

in older subjects but should lift the epiglottis. This is most easily 

achieved by first inserting the laryngoscope so that the tip of 

the laryngoscope is in the entrance the esophagus and then 

gently withdraw the laryngoscope until the laryngeal entrance 

“pops” in view. Visibility is regularly enhanced by gentle external 

pressure on the larynx which can be accom plished either by the 

anesthesiologist’s own little finger or by an assistant. 

4. Several equations are available to help determine the optimal 

depth to which the tracheal tube should be inserted in order 

to avoid unintentional dislodgment of the tube or intubation of 

one of the mainstem bronchi (term neonate; oral intubation: 

9 cm at teeth; nasal intubation: 11 cm at nose). Although 

helpful, such equations and guidelines are not completely 

reliable and the anesthesiologist must still carefully look how 

much of the tube is inserted during the intubation procedure 

and then confirm equal breath sounds and chest wall move - 

ments bilaterally as well as adequate end-tidal CO 2 

readings 

before being satisfied with the positioning of the tracheal tube. 

5. Due to the very compliant chest wall and the slightly stiffer 

lung, the neonate is prone to develop atelectasis following 

intubation or other situation involving muscle relaxation and 

cessation of manual or mechanical ventilation. In order to reexpand 

the atelectatic lung, a vital capacity maneuver should be 

performed. Based on animal experiments, a vital capacity 

maneuver (VCM; inflation pressure 40 cm H 2 

O for 15 sec) 131 

or a timed re-expansion inspiratory maneuver (TRIM; inflation 

pressure 30 H 2 

O for 10 sec) 132 has been suggested. 

6. Adequate fixation of the tracheal tube is of course very 

important. Since nasal intubation provides better opportunities 

to accomplish reliable fixation, nasal intubation should be 

performed in all situations with limited access to the head or if 

the patient is in the lateral or prone position. 

7. By tradition, uncuffed tracheal tubes are used in neonates and 

infants and an air leak should be present at an airway pressure 

of approximately 20 cm H 2 

O to prevent laryngotracheal 

trauma. With the introduction of newer materials and designs 

of the tracheal tubes, this traditional view is now questioned. 133 

However, more data are necessary before changing the classical 

recommendation of using uncuffed tracheal tubes in neonates. 

8. Use of an atraumatic technique and appropriate size of the 

tracheal tube is of paramount importance since the risk of 

laryngeal damage with long-term sequelae otherwise is high. 134 

9. A number of diseases and syndromes are associated with 

difficult intubation in the neonate too (see companion 

textbook, Bissonnette B, Luginbuehl I, Marciniak B, editors.


Syndromes: Rapid Recognition and Perioperative Implications. 

New York: McGraw-Hill; 2006.). In such a situation an 

individualized preinduction strategy should be formed to deal 

with this potential problem. 135 

Use of Muscle Relaxants for Intubation 

The dose necessary to achieve adequate muscle relaxation with 

succinylcholine is substantially larger in neonates compared to 

older children and adults 136 (see Chapter 16). The most likely 

explanation for this larger dose requirement in neonates is the 

larger extracellular fluid volume (responsible for a larger volume 

of distribution) present in the newborn. Thus, an effective intubat - 

ing dose of succinylcholine in the neonate will be approximately 

3 mg/kg. 136 

Neonates have increased sensitivity to nondepolarizing muscle 

relaxants due to their reduced capacity for release of acetylcholine 

at the motor end-plate in neonates. 137 This increased sensitivity 138 

(Figure 86–11) is, however, offset by the increase in extracellular 

fluid volume. Thus, the actual dose requirements per kg body 

weight is similar to the doses used in adults. 138 Neonates also 

display a faster onset time and a prolonged duration of action of 

these agents. 139 At present neonatal pharmacokinetic data only 

exists for atracurium, 138 vecuronium 140 and pancuronium, 141 mak - 

ing these drugs the first line choices. Of these agents only atra - 

curium is of intermediate duration since both vecuronium 142 and 

pancuronium cause long-acting muscular relaxation in neonates. 

Further data are necessary before the routine use of rocuronium 

or mivacurium can be recommended in the neonatal population. 

With the variable duration of the nondepolarizing muscle 

relaxants in neonates monitoring of neuromuscular transmission 

is clearly advisable. However, such monitoring is not easily 

accomplished in this age group. Adequate reversal of muscle 

relaxation should, therefore, be the rule in all neonates. In this 

respect it can be discussed whether nondepolarizing muscle re - 

laxants should be used routinely since the judicious use of halo - 

genated agents and regional anesthetic techniques can produce 

adequate muscle relaxation in most clinical situations without the 

concomitant use of nondepolarizing muscle relaxants. 

Ventilation 

Ventilation should almost constantly be controlled in neonates, 

either by manual ventilation or with the aid of a ventilator. 143 A 

number of pediatric anesthesia breathing circuits have been 

described 144 (see Chapter 23) and one of the most commonly used 

intraoperatively is still the Jackson–Rees modification of the Ayres 

T-piece system. Although very versatile, this traditional system 

does have certain disadvantages compared to circle absorber 

systems. The use of low-flow (600 mL/min) semiclosed circle 

ventilation has been found possible also in neonates using modern 

anesthesia machines. 145 

A number of patients undergoing neonatal surgery have various 

degrees of pulmonary problems, and during surgery the need for 

more advanced means of mechanical ventilation might become 

necessary. Thus, the ventilator used during the anesthetic must be 

as sophisticated as the ventilator in the NICU and, at the same time, 

be able to deliver anesthetic gases. With the latest developments 

within neonatal intensive care, the neonatal anes thesiologist 

must also be prepared and equipped to perform anesthesia and 

surgery during administration of inhaled nitric oxide and/or high 

frequency oscillatory ventilation (HFOV). These new demands will 

place a great deal of responsibility on the anesthesiologist and the 

operation unit to learn and acquire new and sophisticated 

ventilators in order to meet the needs of the sick neonate. 

The mode of ventilation differs slightly depending on the age 

of the neonate and the type of surgery. Generally, pressure con - 

trolled ventilation is preferred in premature infants, in newborns 

with respiratory distress or any other pre-existing pulmonary 

pathology, and also during the first days of extrauterine life. Out - 

side the above mentioned patient categories, volume controlled 

ventilation can be used successfully and is especially useful in 

situations where surgical manipulations will interfere with 

intraoperative ventilation. Due to high compliance of the thoracic 

cage, lower compliance of the lung and higher closing volume, 

neonates are particularly prone to develop atelectasis during sur - 

gery. 146 In order to counteract this tendency for regional lung 

collapse, a positive-end expiratory pressure of 3 to 5 cm H 2 

O 

should routinely be used in this setting. For shorter procedures, 

manual ventilation is an option. A false sense of security might be 

associated with this mode of ventilation, since even experienced 

practitioners cannot reliably sense a change in compliance only by 

the tactile feel of the bag. 147 

Figure 86-11. Log dose-probit response regression lines for 

neonates (N), infants (I) and children (C). The points along the 

lines represent mean responses from subgroups of five patients. 

Maintenance of Anesthesia 

Volatile Agents 

In babies given a regional block as part of the anesthetic plan, or 

who are otherwise stable and not subjected to major or very 

painful procedures, a volatile agent is often a good choice for 

maintenance. Three different volatile anesthetics are commonly 

used: sevoflurane, isoflurane, and halothane. All of these agents 

negatively affect the baroreceptor reflex with halothane having the 

most pronounced effect. 148 The drop in blood pressure is similar 

for all three agents but the mechanism for this differs for halothane 

compared to isoflurane and sevoflurane. Halothane depresses 

myocardial contractility to a greater extent than isoflurane and


sevoflurane, and is also associated with a decrease in heart rate. 

With isoflurane and sevoflurane, a reduction of peripheral 

vascular resistance is the main cause of the reduced blood pressure 

and the heart rate will be maintained or even slightly increased. 149 

Most often, the degree of hypotension caused by the inhalational 

agents can be tolerated. However, if treatment is deemed necessary, 

a bolus administration of 5 to 10 mL/kg of crystalloid in the case 

of sevoflurane and isoflurane, 119,148 or administration of atropine if 

halothane is used, often suffices to correct the situation. 150 The 

concomitant administration of N 2 

O has different effects on 

the MAC requirements for the three volatile anesthetics 

mentioned above. The addition of 60% N 2 

O decreases the MAC 

values by 60%, 40%, and 25% for halothane, 151 isoflurane, 152 and 

sevoflurane, 119 respectively. To use N 2 

O together with halothane 

in an attempt to minimize the negative cardiovascular effects of 

halothane appears reasonable. However, whether supplemental 

use of N 2 

O is of significant value when isoflurane or sevoflurane 

is used can be debated. 

The preconditioning effect of sevoflurane is currently an area 

of great interest, and recent data has shown a myocardial pre - 

conditioning effect of sevoflurane in a neonatal rodent model. The 

mechanism behind this preconditioning effect of sevoflurane 

appeared to be a blockage of mitochondrial K ATP 

channels. 153 

The effect of inhalational agents on cerebral autoregulation is 

also an important topic in the context of neonatal anesthesia. 

Recent data suggest that cerebral autoregulation is preserved up 

to 1.5 MAC sevoflurane as assessed by the transient hyperemic 

response measured by transcranial Doppler. 154 

Opioids 

The use of moderate to high doses of opioids for maintenance of 

anesthesia is associated with a high degree of hemodynamic 

stability. This is especially useful in unstable patients or in the case 

of major surgery in the neonate. The use of fentanyl (10–50 g/kg) 

or sufentanil (35 g/kg) has been found capable of attenuating the 

neuroendocrine stress response and reducing morbidity; a reduc - 

tion in mortality has even been suggested in neonates undergoing 

corrective surgery for congenital heart defects. 15,24 Synthetic 

opioids are high clearance drugs and the metabolism is not so 

dependent on the maturation of the hepatic biotransformation 

system 155 (see Chapter 15). The terminal half-lives of fentanyl and 

sufentanil in the neonate are approximately 5 and 13 hours, 

respectively. 156 Because these drugs have a high clearance, their 

elimination is substantially prolonged in situations of compro - 

mised liver blood flow, for example, high abdominal pressure 

following closure of an omphalocele or gastroschisis. In this 

situation the terminal half-life of fentanyl has been reported to 

increase to 1.5 to 3 times the normal average value. 155 

When a regional anesthesia has not been performed for 

intraoperative analgesia, the repeat injection of small boluses of 

fentanyl (1–2 g/kg) can be used together with a volatile agent as a 

balanced anesthesia technique. 157 Some caution is recommended 

regarding the intraoperative doses of opioids in patients having 

received a regional anesthetic block. If there is intraoperative need 

to increase the depth of anesthesia, this should preferentially be 

accomplished by temporarily increasing the dose of volatile agent. 

Otherwise the patient will be exposed to the risk of a prolonged 

emergence with respiratory depression, possibly necessitating 

postoperative ventilation, since at the time of emergence the patient 

will have good analgesia from the regional block and, thus, will have 

no stimulatory effects of any pain. Such a situation can be overcome 

by the administration of naloxone, but the staff in the recovery 

room or NICU should be aware of the risks of renarcotization if a 

prolonged infusion of naloxone has not been started. 

5.6. Use of Regional Anesthesia 

Techniques 

The modern concept of a combination of a light general volatile 

anesthetic and a central or peripheral nerve block has proved to be 

of great benefit in neonatal surgery. 157,158 Apart from offering 

excellent intra- and postoperative analgesia, frequently making 

the perioperative administration of opioids unnecessary, regional 

anesthetic techniques provide muscle relaxation, making unnecessary 

the use of muscle relaxants except to facilitate tracheal 

intubation. A regional block also attenuates the magnitude of the 

surgically induced stress response 159 which is highly likely to be 

beneficial to the recovery of the patient. Retrospective data also 

indicate that a thoracic epidural block reduces the need for posto - 

perative ventilation compared to children receiving more tradi - 

tional postoperative analgesia with opioids. 157 A further advantage 

may also be earlier return of peristalsis following abdominal 

surgery in premature babies and neonates. 160 The use of epidural 

blocks has been found adequately safe in children, as shown in a 

large prospective audit (10,000 children), including more than 

500 epidurals performed in neonates. 161 

Although regional blocks offer considerable benefits in neo - 

nates compared to more traditional techniques, care must be taken 

regarding the dosing of local anesthetics in order to avoid toxi - 

city. 162 Generally accepted guidelines restrict a maximum bolus 

injection of bupivacaine to 1.5 (up to 2.0) mg/kg and a subsequent 

continuous infusion to maximum 0.2 mg/kg/h 163 and these dosage 

recommendation have recently been found to result in safe plasma 

levels in neonates, at least up to 48 hours postoperatively. 158 

Bupivacaine plasma levels of 2 to 4 g/L are generally believed to 

represent the threshold for CNS toxicity in children, but signi - 

ficantly lower plasma levels are associated with pretoxic symptoms 

in awake ex-premature infants receiving a caudal block. 164 Since 

the metabolism of lidocaine is relatively mature in neonates this 

local anesthetic might be an even better option than bupivacaine 

in neonates if a continuous infusion technique is con sidered. 

Determinations of plasma levels of lidocaine are usually readily 

available at most laboratories, making monitoring of the treatment 

possible and steady state conditions following conti nuous infusion 

will be reached within approximately 12 hours. 165 This provides a 

sharp contrast to bupivacaine infusion, where plasma concentra - 

tions of bupivacaine are still increasing in a significant portion of 

neonates following 48 hours of infusion. 158 Neonates receiving 

continuous regional blockades postoperatively should be cared for 

in the NICU or in a high dependence environ ment with appro - 

priate monitoring, for example, ECG, pulse oxi metry, respiratory 

rate, pain scoring, and general behavior of the neonate. 

Prevention of Heat Loss/Maintenance 

of Normal Body Temperature 

Every possible effort must be made to prevent perioperative 

hypothermia in the neonate (see Chapter 10). This can be 

accomplished by combining a number of different measures (Table 

86–10). If hypothermia still occurs despite precautions, attempts


TABLE 86-10. Measures to Prevent Neonatal 

Perioperative Hypothermia 

1. Avoid unnecessary exposure of the patient. Cover the baby 

as much as possible during anesthesia induction and line 

placement. 

2. Use warm preparation solutions and the smallest amount 

necessary 

3. Keep the incubator plugged in and warm during the 

operation. 

4. Increase the operating room temperature to at least 25–26C. 

5. Use an active humidifier or a heat-moisture exchanger to 

prevent heat and water losses from the exhaled air. 

6. Active heating blanket with a prewarmed gel mattress 

7. Forced convective air heating system. Do not use the 

highest temperature setting to avoid hyperthermia and/or 

skin burns. 

8. Open bed incubator with overhead radiant heaters. 

Preferably use servocontrol mode with skin temperature 

probe. 

9. Warm intravenous fluids. Coaxial devices are more efficient 

to warm fluids. 

10. If intraoperative irrigation is necessary in the surgical 

wound, warm solutions should be used. 

to normalize body temperature should be undertaken as soon as 

possible. In order to be in control of temperature homeostasis, it 

is crucial to measure body temperature in all neonatal patients as 

part of routine monitoring. The best site for measurement of true 

core temperature during normal clinical conditions can be debated 

but convenient sites are the axilla, esophagus, rectum, and naso - 

pharynx. To gain further information any of the above monitoring 

sites can be complemented by measurement of the skin tem - 

perature in order to determine the degree of difference between 

the peripheral and the core temperature. 

With regards to the operating room temperature, it has recently 

been reported that using a room temperature of more than 23C 

is beneficial but will not prevent hypothermia in neonates as a 

single measure. 166 

Intraoperative Fluid Requirements and 

Volume Replacement During Anesthesia 

Caloric, Fluid, and Electrolyte Requirements 

Caloric, fluid, sodium, and potassium requirements have been 

defined during minor surgery performed under halothane 

anesthesia (Table 86–11). 167 These requirements are close to those 

associated with the basal metabolic rate. 168 Depending on the 

degree of surgical trauma basal infusion rates during neonatal 

surgery can be set as follows: 

TABLE 86-11. Intraoperative Energy and Fluid 

Requirements 167 

Intraoperative Requirements 

Caloric 

Fluid 

Sodium 

Potassium 

Calculated Maintenance Value 

1.5 kg 5 kcal/h 

2.5 kg 10 mL/h 

0.045 kg 0.16 mmol/h 

0.03 kg 0.10 mmol/h 

1. minor surgery (e.g., inguinal hernia repair): 5 mL/kg/h; 

2. moderate surgery (e.g., duodenal atresia repair): 7.5 mL/kg/h; 

3. major surgery (e.g., gastroschisis repair): 10 mL/kg/h. 

These infusion rates will cover fluid losses due to evaporation 

from the wound and “third spacing” losses. These infusion rates 

should be viewed as guidelines only; individual adjustments will 

have to be made in each separate case. 

Glucose Administration 

To include or abstain from intraoperative glucose administration 

has been a highly debated topic during recent years. In the majo - 

rity of neonates it is possible to use only Ringer solutions during 

the operation without risking the development of hypoglycemia. 169 

However, in newborns less than 48 hours ols, in babies born to 

diabetic mothers, following interruption of a continuous glucose 

infusion, and in premature or small-for-date babies, there is a 

definite risk of intraoperative hypoglycemia. Since the risks 

associated with intraoperative glucose administration are small 

(excluding cardiac and neurosurgical anesthesia) most practitio - 

ners include some amounts of glucose in the intraoperative 

infusion in order to safeguard against intraoperative hypoglyce - 

mia. Frequent intraoperative measurements of blood glucose are, 

however, of value regardless of infusion strategy in order to 

monitor glucose levels. 

Fluid Replacement and Suitable Solutions 

The composition of the intraoperative infusion fluid varies greatly 

between centers. A solution containing 2.5% glucose with sodium 

70 mmol/L represents an acceptable standard solution for most 

cases. Volume replacement will mainly be governed by clinical 

signs such as blood pressure, urine output, and time for capillary 

refill, since attempts at measuring carefully the amount of 

intraoperative blood loss in neonates are associated with great 

difficulties. Neonates tolerate hypovolemia poorly and substitution 

with crystalloids and colloids (Ringer solution 3 mL/mL of blood 

loss; 5% albumin 1 mL/mL of blood loss) should be started very 

early to compensate for ongoing losses due to oozing from the 

wound edges and transudation. Substitution with packed red cells 

and plasma (aliquots of 5–10 mL/kg of packed red cells or plasma 

are given according to the estimated blood loss and the blood 

pressure response) should also be started early and if the child is 

not polycythemic at the outset of surgery, the author suggests that 

transfusion should be started when the blood loss exceeds 10% of 

the estimated blood volume. 

Administration of a 4 to 5% albumin solution has traditionally 

been the colloid of choice in the neonatal setting to treat hypo - 

volemia, whereas it has been strongly questioned in adults. 170 

Albumin solutions contain quite large amounts of sodium. After 

significant administration of albumin the occurrence of hyper - 

natremia is exceedingly rare in the authors experience, even if 

surgery is performed immediately postpartum. Successful use of 

gelatin solutions (maximum dose of Haemaccel 40 mL/kg) in 

neonatal surgery has recently been reported. 171 Currently, albumin 

is still the colloid of choice for use in neonatal surgery until further 

data are available. 

Major hemorrhage, fortunately, is a rare event during neonatal 

surgery due to the meticulous hemostasis technique practiced by 

most pediatric surgeons. If confronted with major bleeding, rapid 

transfusion can most often be accomplished by rapid injection


with a normal syringe attached to the infusion line. If very 

substantial blood loss is anticipated preoperatively, the use of a 

rapid transfusion device might be indicated. 172 If transfusion is 

given, it is necessary to make sure that the infused components 

are warmed. Supplementary intravenous calcium administration 

might also be needed in the setting of larger transfusions of packed 

red cells (calcium chloride 10 mg/kg (0.05 mmol/kg) I.V., might 

need to be repeated. Rule of thumb: 1 mg calcium chloride/ 

transfused mL of packed red cells or plasma). 173 

Intraoperative Complications 

The most frequently encountered intraoperative complications are 

listed in Table 86–12. Whatever the presenting symptom, airway 

problems should always be ruled out first, even including rein - 

tubation of the patient. Tachycardia and hypotension are usually 

indicative of hypovolemia. Bradycardia and hypotension can 

either be caused by anesthetic overdose, especially if halothane is 

used, or represent a late and very ominous sign of an unobserved 

complication about to escalate. However, if a thoracic epidural 

block has been performed, relative bradycardia and modest 

hypotension can be caused by blockade of the sympathetic cardio - 

accelerator fibers. Bradycardia and hypertension is rarely seen 

except in the case of an abrupt increase in afterload, as can be seen 

during aortic clamping/compression or following the ligation of a 

large patent ductus arteriosus, but in neurosurgical patients can 

also be a sign of increasing intracranial pressure. In this setting, the 

hemodynamic response is caused by a partially operative baro - 

receptor reflex. Tachycardia and hypertension in the absence of 

catecholamine producing tumors most frequently indicate 

insufficient levels of anesthesia (Table 86–13). 

Venous air embolism is always a risk in neonatal anesthesia and 

utmost care must be observed not to allow injection of small air 

bubbles or to cause air entrainment at three-way stopcocks. It must 

be remembered that the fetal extrapulmonary shunts might still 

be open or can reopen during the course of the anesthetic. Inter - 

mittent increases in pulmonary artery pressure due to intense 

surgical stimulation combined with insufficiently light anesthesia 

can set the stage for devastating systemic embolization due to 

right-to-left shunting of air bubbles through the oval foramen or 

the ductus arteriosus. 

Low urine output is a frequent problem during lengthy pro - 

cedures. Most commonly this is due to prerenal causes which can 

easily be corrected by fluid and/or volume replacement. If this 

does not return the urine output to an acceptable level, then a renal 

cause for the problem might be present. Although the neonatal 

TABLE 86-12. Intraoperative Complications 

Ventilatory 

Circulatory 

Complications Complications Miscellaneous 

1. Dislodgment of 1. Hypotension 1. Hypothermia 

tracheal tube 

2. Tracheal tube 2. Bradycardia 2. Low urine output 

obstruction 

3. Bronchial intubation 3. Tachycardia 3. Coagulopathy 

4. Pneumothorax 4. Hypertension 

5. Failure of the 5. Venous air 

anesthetic equipment embolism 

TABLE 86-13. Differential Diagnosis of Intraoperative 

Hemodynamic Events 

Any Major Hemodynamic 

Event 

Tachycardia 

hypotension 

Bradycardia 

hypotension 

Tachycardia 

hypertension 

Bradycardia 

hypertension 

First Exclude Any Problems Related 

to Hypoxia or the Airway: 

1. Ventilator circuit 

2. Tracheal tube kinked or blocked by 

secretions 

3. Dislodgment of the tracheal tube 

4. Intubation of a main stem bronchus 

5. Unilateral or bilateral pneumothorax 

Hypovolemia 

Reduced venous return due to surgical 

manipulations 

Overdose of volatile anesthetic 

Late ominous sign—collapse imminent 

Insufficient level of anesthesia 

Hypercapnea 

Clamping or compression of the aorta 

Ligation of a large ductus arteriosus 

Increasing intracranial pressure 

kidney is far from mature (see “Renal Function”) it is still capable 

of responding to stress induced increases of antidiuretic hormone 

and aldosterone. If fluid and volume replacement is believed to be 

accurate, then a small dose of furosemide (0.25–0.5 mg/kg) is 

indicated to try to enhance renal urine production. Probably the 

most common cause for insufficient urine output is postrenal in 

nature and is caused by obstruction or kinking of the Foley 

catheter. In this case, urine output often completely ceases or the 

urine production is very variable over time. Checking the patency 

of the Foley catheter should, thus, be the first action taken if urine 

output is less than anticipated. 

Termination of Anesthesia—Emergence 

Reversal of Muscle Relaxation 

Although adequate time is believed to have elapsed since the last 

dose of intermediate acting nondepolarizing muscle relaxant, 

all neonates should be subjected to the administration of 

neostigmine (50 g/kg) and glycopyrrolate (10 g/kg) in order to 

reverse any residual muscle relaxation. Because of inherent 

problems with neonatal application of nerve stimulators (e.g., type 

and placement of the stimulating electrodes, size of the stimulating 

current) monitoring of train-of-four does often not provide 

reliably infor mation regarding the status of the neuromuscular 

blockade, since almost all such monitors will not function 

optimally in the neonate. However, if the neonate displays any type 

of spontaneous muscular response, reversal can be performed 

without risk. 

Should the Trachea Be Extubated or 

Kept Intubated? 

The answer to this question is complex and should be decided 

individually for each patient. However, if the neonate has stable 

vital signs, is normothermic without any major residual effects of 

the anesthetic, and has good quality pain relief without any 

concomitant respiratory depression, tracheal extubation can often 

be successfully performed if the patient fulfills certain criteria:


1. regular spontaneous breathing 

2. vigorous movements of the limbs 

3. gagging 

4. eye opening or pronounced grimacing 

5. stable hemodynamics, good oxygen saturation 

6. Absence of significant hypothermia 

In any other case, the patients should be ventilated in the NICU 

at least overnight before extubation is attempted. However, one 

should remember that controlled mechanical ventilation is not 

without significant risks for the patient and these risks must be 

carefully weighed against the risk for respiratory depression/ 

insufficiency after attempted early extubation. 

Anesthetic Aspects Associated With 

Laparoscopic and Thoracoscopic Surgery 

Still, a traditional surgical technique is most often used, but lapa - 

roscopic surgery is becoming increasingly popular 174 and may 

soon be the method of choice in many institutions. If a laparosco - 

pic approach is used, the anesthesiologist must pay special 

attention to the various issues associated with the use of pneumo - 

peritoneum. 

Pneumoperitoneum 

Laparoscopic techniques or robotic surgery require the use of gas 

insufflation into the abdominal cavity. The insufflation will lead to 

physiologic alterations, especially if the abdominal pressure is 

allowed to be more than marginally increased. The choice of 

insufflation gas may also influence these physiologic changes, as 

will the choice of body positioning necessary for surgical access 

(e.g., extreme head-up or head-down positions). 175,176 

Carbon dioxide is the most frequently used gas, since if 

inadvertently insufflated into the blood vessels it will be rapidly 

absorbed, and thus the risk of serious pulmonary gas embolism is 

minimized. A certain amount of the CO 2 

will be absorbed via the 

peritoneum itself and this will cause an increased CO 2 

load for the 

patient. By using advanced mass spectrometry, it has been shown 

that 10 to 20% of exhaled CO 2 

after 10 minutes of pneumoperi - 

toneum is derived from exogenous CO 2 

. 177 An increase in alveolar 

minute ventilation by approximately 25 to 30% is needed during 

normal circumstances in order to counteract the increased CO 2 

load. 175 Further adjustment of minute ventilation may be needed 

due to cranial displacement and splinting of the diaphragm if 

abdominal pressures are unduly raised and/or if the patient is 

placed in a head-down position. Thus, in some patients the preser - 

vation of adequate ventilation during laparoscopic surgery can be 

quite challenging. 

Increased abdominal pressure and cranial displacement of the 

diaphragm will also increase the risk for atelectasis formation. To 

prevent undue atelectasis formation the use of volume controlled 

ventilation and a slightly elevated PEEP is recommended. 

Endotracheal intubation represents standard airway manage - 

ment in children undergoing laparoscopic procedures. The 

combined use of pneumoperitoneum and a head-down tilt will, 

however, produce a downward movement of the tip of the endo - 

tracheal tube that may result in endobronchial intubation. De - 

pending on the size of the child the shift of the tip can range 

between 1.2 to 2.7 cm. 178 

Pneumoperitoneum can also cause hemodynamic instability, 

but if intra-abdominal pressures are maintained in the lower range 

(10 mmHg) the impact on hemodynamics is usually minor. In 

this situation, venous return will be enhanced due to displacement 

of blood from the splanchnic bed as well as an overall increase in 

systemic vascular resistance. 175 However, if intra-abdominal pres - 

sures are allowed to increase to about 12 mmHg, then cardiac 

function will be directly affected as evidenced by septal dyskine - 

sia 179 and furthermore preload will be reduced due to compression 

of the inferior vena cava. 175 

Since the hemodynamic consequences of pneumoperitoneum 

is so closely related to the intra-abdominal pressure, it is absolutely 

essential to monitor the intra-abdominal pressure during the 

surgical procedure. The maximum tolerable intra-abdominal 

pressure level during laparoscopic surgery should be 6 to 8 mm 

Hg. 180 If greater pressures occur or are necessary for surgical access 

one may have to abandon the procedure and instead convert to an 

open approach due to safety concerns for the child. 

Both volatile and total intravenous anesthesia can be used for 

laparoscopic surgery. However, the use of nitrous oxide is sub - 

optimal based on the fact that nitrous oxide will easily diffuse into 

gas filled spaces and thereby increase the volume and/or pressure 

of trapped gas (cf. pneumothorax and intracranial air). Further - 

more, the use of nitrous oxide can both obscure the visibility for 

the surgeon due to expansion of the bowel as well as causing 

unwanted increases of the intra-abdominal pressure. 

All the problems listed above will obviously be more prominent 

in neonates and infants compared to older children. 

Thoracoscopy 

There is currently a surgical trend at certain major centres to 

perform tetralogy of Fallot (TOF) repair as a thoracoscopic pro - 

cedure. This is of cause associated with very specific anaesthetic 

considerations. A number of issues are similar to the situation of 

pneumoperitoneum but there are also some specific issues asso - 

ciated with thoracoscopy in neonates. 181 

CONSIDERATIONS REGARDING ENDOTRACHEAL INTUBATION: 

Although endotracheal intubation following an inhalational in - 

duction with preserved spontaneous ventilation is preferred by 

many clinicians (in order to avoid the risk of potential gastric 

distension) an intravenous induction can also be used safely in 

most cases. 

It is important to place the tip of the endotracheal tube distal 

to the fistula, but even more important is that the tip has a 

reasonable safety margin to the carina. The latter is paramount 

since intuba tion of the right mainstem bronchus, either during 

intubation or secondary to movement during the positioning of 

the patient, will make ventilation impossible once gas has been 

insufflated into the right pleural cavity causing right lung collapse. 

It is therefore necessary to confirm the position of the tube 

tip both following intubation as well as after placing the patient 

in the final position with the right side slightly elevated for 

surgical access. 

ONE-LUNG VENTILATION (OLV): Insufflation of CO 2 

into the 

right pleural cavity will cause the right lung to collapse, even when 

using the recommended insufflation pressure of 5 to 6 mmHg. 

This will in turn result in an increase in pulmonary vascular 

resistance secondary to hypoxic vasoconstriction in the right lung. 

The positive pressure in the right hemithorax will also cause a 

decrease in venous return by compression of the vena cava and 

may also cause direct compression of the right ventricle. Thus,


reductions in cardiac output and blood pressure are likely to occur 

during the case. 

Ventilation during surgery can be achieved either by mechani - 

cal ventilation or by hand ventilation by the anesthesiologist. Even 

if mechanical ventilation is used, periods of manual ventilation 

are often necessary. 

PROBLEMS WITH GAS EXCHANGE: Insufflation of CO 2 

com bined 

with a limited possibility to maintain adequate alveolar ventilation 

will result in serious CO 2 

retention combined with pronounced 

respiratory acidosis (pH 7.0). This situation is further 

compounded by the fact that the measurement of end-tidal-CO 2 

is notoriously unreliable and the CO 2 

tracing may even become 

absent during parts of the procedure. A well-functioning arterial 

line is, thus, a prerequisite in this situation. Desaturation episodes 

can be considered the rule, and to counteract this as much as 

possible ventilation with 100% oxygen is recommended during 

the period of OLV. 

The combination of hypoxia, hypercapnea and acidosis will of 

cause add to the increase in pulmonary vascular resistance caused 

by the atelectasis of the right lung. Due to the substantial altera - 

tions that take place both regarding hemodynamics and gas 

exchange it is very useful to use cerebral near-infrared spectros - 

copy (Invos) to monitor cerebral oxygenation throughout the 

procedure. 182 

Requirements for monitoring and vascular access are: 

1. normal noninvasive monitoring 

2. arterial line for repeated blood gas analysis and invasive blood 

pressure monitoring 

3. at least two peripheral venous lines or if deemed necessary a 

femoral or central venous catheter 

4. cerebral near-infrared spectroscopy (Invos) 

Even if it is clearly possible to perform TOF repair as a thora - 

coscopic procedure, the combination of neonatal anesthesia with 

periods of hypoxia, pronounced hypercarbia, and substantial 

acidosis may raise concern regarding the risk for brain cell 

apoptosis with potential long-term cognitive and behavioral 

problems (see “Effects of Anesthetic Agents on the Premature and 

Neonatal Brain” above). Despite this, there are case reports where 

this technique at least initially has been used successfully, even in 

TOF cases with significant concomitant congenital heart disease 

(e.g., pulmonary atresia with single ventricle physiology). 182 

POSTOPERATIVE CARE 

Pain Scoring 

The use of appropriate pain scales for monitoring of postoperative 

pain is fundamental to the provision of optimal pain relief. 

Im plementation of regular pain assessment has a number of 

advan tages: 

1. regular pain assessment and charting of the results increases 

the awareness of the care providers regarding the problem of 

postoperative pain in neonates and children 

2. assessment performed before and after an intervention aimed 

at reducing pain will provide the care providers with feedback 

regarding the efficacy of the intervention 

3. pain assessment will provide a tool for evaluation of different 

analgesic techniques and allows for a more structured and 

scientific analysis of the treatment of postoperative pain 

The problem with pain assessment in the neonatal period is 

that existing pain scales are only designed and validated for shortterm 

procedural pain (e.g., heel lancing). Frequently used pain 

scales which has been developed and validated for ongoing 

postoperative pain in neonates and infants are the CHIPPS scale 183 

and the CRIES score. 184 An advantage with the CHIPPS scale is 

that the intention with this scale is not only to assess pain but also 

to identify a score which will predict the need for administration 

of supplemental analgesia. However, a recently published com - 

parison of neonatal pain scores did find that the neonatal infant 

pain scale may be a preferable pain evaluation tool in the setting 

of neonatal surgery. 185 

Analgesia 

A plan for treatment of postoperative pain should be available in 

all neonates. The metabolism of paracetamol (acetaminophen) is 

reason ably well developed in the neonate and, thus, this drug 

should be regularly administered. Rectal dosages of 20 to 40 mg/kg 

have been reported to result in safe plasma concentrations in the 

preterm and term baby. 186,187 Whenever possible, regional anesthe - 

tic techniques should also be utilized due to the excellent quality 

of pain relief combined with the low risk for unwanted side 

effects. 188 If regional techniques are not applicable or are insuf - 

ficient, continuous low-dose infusions of opioids are often helpful 

(e.g., morphine 10–20 g/kg/h) 189 and with careful titration of the 

infusion the risk for respiratory depression is very small. However, 

more complicated analgesic regimens should be carried out under 

closed supervision in the NICU or high dependency unit. 

Fluid Balance/Nutrition 

If the neonate has been subjected to anything but a minor proce - 

dure or pure diagnostic examination, there will be a postsurgical 

stress reaction inducing a state of catabolism and fluid retention. 

Although the period of catabolism and fluid retention is shorter in 

newborns and infants it is not possible to resume full nutrition or 

normal fluid volumes immediately following surgery. Ignoring the 

effects of the postsurgical stress reaction will lead to unnecessary 

strain on the neonates metabolism and cardiorespiratory system 

and will also lead to unwanted fluid retention and edema. Thus, 

during the first 12 to 24 hours postoperatively it is generally wise 

to restrict the fluid volume to approximately 80 to 100 mL/kg 

24 h and give only a glucose solution, for example, 10% glucose 

with sodium 40 mmol/L and potassium 20 mmol/L. Early 

supplementation with lipid emulsions can, however, be used in 

neonates requiring additional caloric support. 190 

This traditional approach has recently been challenged by data 

showing that neonates undergoing major gastroschisis surgery are 

able to achieve a positive protein balance if given parenteral amino 

acids (2.5 g kg-1 24 h-1) immediately postoperatively without 

signs of protein intolerance. 191 However, further prospective 

randomized trials including the full variety of neonatal surgical 

procedures are needed before changing the more traditional 

approach described above. 

Antibiotics 

Although mainly a surgical concern the anesthesiologist should 

check that appropriate antibiotic coverage has been order for


the patient. If not, or if any doubts exist regarding the need for or 

the choice of antibiotic, the anesthesiologist should contact the 

surgeon to discuss this matter. 

Radiographic Examinations 

A postoperative chest radiograph is frequently performed follow - 

ing a number of interventions in order to check for adequate line 

and tube placing and to rule out pneumothorax. Radiographic 

control of the location of epidural catheters should also be 

performed if the catheters have been threaded via the caudal or 

lumbar epidural route to a more cephalad position. The suspicion 

of partial intravenous injection through the epidural catheter also 

warrants postoperative radiographic control. The necessity for 

other investigations will have to be individualized and is most of 

the times the responsibility of the surgeon. 

Postoperative Complications 

Complications during the immediate postoperative period in 

neonates is dominated by ventilatory problems. The most 

common problems encountered are the following: opioid-induced 

hypoventilation, postoperative apnea in the ex-premature, residual 

muscle relaxation, postextubation stridor, inadequate ventilation 

due to insufficient pain relief, and upper airway obstruction. The 

frequency of these potentially life-threatening events merits close 

supervision of the neonate for at least 24 hours postoperatively 

before being returned to an ordinary ward. 

The anesthesiologist is often confronted with questions regard - 

ing postoperative diuresis. In this situation, it is important to 

remember that the normal newborn child does not always pass 

urine until 12 to 24 hours after birth and that the surgically 

induced stress response leads to water conservation and reduced 

diuresis. It is, thus, not reasonable to expect a hourly urine output 

in excess of about 1 mL/kg/h in the immediate postoperative 

phase. If the patient is believed to be truly oliguric, the anes - 

thesiologist has to decide whether this is due to hypovolemia or if 

diuresis should be enhanced by the administration of loop 

diuretics. It should be remembered that patients can be hypovole - 

mic despite showing signs of peripheral edema, for example, 

on the dorsum of the hand and feet and eye lids. Although 

postoperative hemorrhage is unusual following neonatal surgery, 

additional volume replacement is frequently necessary following 

major operations due to ongoing losses through drains or due to 

developing tissue edema and “third spacing.” If postoperative 

hemorrhage or hypovolemia of other causes do occur the clinical 

signs will be usual: diaphoresis, reduced peripheral circulation, 

prolonged capillary refill, tachycardia, oliguria, and hypotension. 

SPECIFIC NEONATAL CONDITIONS 

REQUIRING SURGICAL 

INTERVENTION 

Airway Obstruction 

Stridor 

A variety of different conditions can cause the presence of inspi - 

ratory stridor with jugular and intercostal/subcostal retractions in 

the neonate: 192 (1) bilateral choanal atresia, (2) Pierre–Robin 

syndrome, (3) cystic hygroma, (4) laryngomalacia, (5) laryngeal 

web or adhesion of the vocal cords, (6) vocal cord paralysis, (7) 

subglottic hemangiomas, (8) tracheomalacia. It should be 

remembered that in a significant number of neonates outside the 

immediate newborn, period the cause for the stridor can be ac - 

quired and, thus, a sequelae of previous intubation. 193 If the 

inspiratory stridor is more severe in nature or if it tends to be 

progressive causing respiratory distress the cause of the obstruc - 

tion needs to be clarified. In the case of bilateral choanal atresia, 

the diagnosis is made by trying to pass a suction catheter through 

each of the nostrils (see Chapter 63). In more severe cases of cystic 

hygroma, the condition will be obvious from observing the 

swelling in the neck. Apart from these conditions, a diagnostic 

bronchoscopy will have to be performed to identify the cause of 

the problem as well as determining the degree of obstruction. 

Depending on the finding made during the bronchoscopy further 

action may need to be undertaken (e.g., tracheal intubation or 

tracheotomy). How to approach this problem will obviously 

depend on the severity of the condition. If the stridor is only slight 

or moderate, a preoperative workup can be performed in a normal 

fashion, whereas if the symptoms are judged to be life-threatening, 

immediate action needs to be taken. It is of vital importance 

both for the well-being of the patient and for diagnostic purposes 

that spontaneous ventilation is preserved during the anesthetic. 

The main steps of anesthetic management are summarized in 


Cleft Lip Repair 

Neonatal surgical intervention in these conditions is now perfor - 

med in certain centers in order to improve the cosmetic and 

functional outcome. 194 Cleft lip/palate can be associated with other 

malformations, but frequently patients are otherwise healthy and 

normal. The main steps of anesthetic management are sum - 

marized in Table 86–15. 

Thoracic Surgery 

Esophageal Atresia With 

Tracheoesophageal Fistula 

The incidence of the malformation is approximately 1/3000. The 

lesion is classified I to V depending on the anatomic configuration 

of the tracheoesophageal fistula. In the majority of cases the upper 

esophageal segment ends in a blind pouch with the lower esopha - 

geal segment connecting to the trachea close to the carina via a 

fistula. This abnormality makes the neonate unable to swallow its 

own pharyngeal secretions and the baby will cough or even choke 

when breastfed. More serious aspiration into the airways can also 

occur through the fistula, which is in direct continuum with the 

stomach. Acid aspiration of gastric secretions can cause significant 

chemical pneumonitis. In order to minimize the risks of pulmo - 

nary aspiration, surgery should be performed without undue 

delay. Surgery can be deferred until the next morning and since 

available expertise and infrastructure is usually superior during 

daytime this is often preferable compared to the on-call nighttime 

setting. The main steps of anesthetic management are summarized 

in Table 86–16. 

Tracheoesophageal Cleft 

Tracheoesophageal cleft is a very rare syndrome with an estimated 

incidence of approximately 1/100,000. The extent of the cleft


TABLE 86-14. Typical Anesthetic Management of a Neonate Presenting With Stridor 

Symptoms 

Preoperative investigations 

(if time allows) 

Monitoring 

Suggested anesthetic and 

recommendations 

Recommended Examinations and Management 

Inspiratory stridor, jugular and intercostal/subcostal retractions, cyanosis 

1. Arterial blood gas, routine laboratory 

2. Chest radiograph 

3. Transthoracic echocardiography (can help to diagnose vascular ring abnormality) 

Routine monitoring only 

1. No premedication 

2. Establish I.V. access before induction, preferably in the neonatal intensive care unit 

3. I.V. atropine (10 g/kg), preoxygenation 

4. Inhalational induction sevoflurane or halothane in oxygen 

5. Deep anesthesia needed to avoid laryngospasm, coughing or breath-holding. The more severe the 

obstruction the longer the time necessary to reach the appropriate level of anesthesia 

6. Apply a continuous positive airway pressure (3–5 cm H 2 

O). This helps distending the airways and 

prevent laryngospasm 

7. Depending on the ear-nose-throat technique used, continuous supply of O 2 

and volatile agent is 

provided through a bronchoscope attachment or holding the fresh gas tubing within the mouth; jet 

ventilation can be used (delivery of volatile agent usually not possible) 

8. If the airway is left unintubated and tracheotomy is not performed, administration of I.V. 

hydrocortisone (1–2 mg/kg) may help counteracting postoperative airway edema (postoperative 

inhalation of epinephrine might be useful in this regard too) 

9. Even if the airway obstruction is judged to be only minor to moderate, e.g., with a number of 

patients suffering from laryngotracheomalacia, the patient should be cared for in an NICU or high 

dependency area for the first postoperative 12–24 hours 

varies. In less severe cases there is only a cleft present in 

the posterior parts of the larynx with no involvement of the 

trachea and the esophagus. However, in the most extensive cases 

(Type IV) the cleft extends from the larynx to the carina. The 

existence of the cleft creates the possibility for regurgitation and 

aspiration of both saliva and stomach contents with repeated 

cyanotic episodes and pneumonias. Occasionally the diagnosis 

is suspected following repeated tracheal tube dislodgment. The 

final diagnosis is made at bronchoscopy. The anesthetic plan for 

later closure of the defect has to be individualized since the 

TABLE 86-15. Typical Anesthetic Management of a Neonate Undergoing Cleft Lip/Palate Repair 

Symptoms 


Monitoring 




Usually apparent on inspection. Isolated palate lesion requires palpation of the palate 

1. Search for other malformations 

2. Echocardiography to search for associated cardiac anomalies 

3. Blood type and compatibility tests 

4. Order 1 unit blood 

Routine monitoring 


2. I.V. atropine (10 g/kg) 

3. Preoxygenation 

4. Induction technique according to the preference of the anesthesiologist 

5. Tracheal intubation can be difficult (blade of the laryngoscope sliding into the cleft); packing the 

cleft with a small wet sponge will circumvent this problem 

6. RAE tubes are useful. Careful that the distance from the tip of the tube to the preformed “knee” 

may be wrong and lead to bronchial intubation. If too long, cut appropriately before intubation or 

fixe the “knee” lower on the mandible 

7. Throat packing is recommended to protect airway from blood and secretions; the end of the pack 

should be left outside the mouth to remind to remove it at the end. 

8. Local anesthetic block of the infraorbital nerves will provide excellent intra- and immediate 

postoperative analgesia 

9. Extubation should only be performed after the removal of the throat pack and following careful 

suctioning of the mouth and pharynx. Because of blood oozing following surgical reconstruction, 

extubation in the lateral position is preferable and when fully awake. If edema or bleeding and 

concern regarding the airway, the patient should be returned to NICU until safe extubation can be 

achieved


TABLE 86-16. Typical Management of a Neonate Presenting With Tracheoesophageal Fistula 

Symptoms 


Monitoring 




Coughing or choking when swallowing. Drooling. Can’t pass a nasogastric tube into the stomach 

1. Chest radiograph with radio-opaque catheter or nasogastric tube inserted into the upper 

esophageal segment. Avoid use of radio-opaque dye to prevent aspiration 

2. Echocardiography to search for associated cardiac anomalies 

3. Routine laboratory and arterial blood gas 

4. Blood type and compatibility tests 

5. Order 1 unit blood and 1 unit plasma 

1. Routine monitoring 

2. Invasive blood pressure monitoring 

3. Foley catheterization 


2. Establish venous access before induction of anesthesia if not yet in place 

3. I.V. atropine (10–20 g/kg) 

4. Evacuate any secretions from the upper esophageal pouch by aspirating the catheter 

5. Preoxygenation 

6. Rapid sequence induction with succinylcholine (1–2 mg/kg) for relaxation. Cricoid pressure is not 

meaningful since aspiration can still occur through the fistula 

7. Avoid gastric distention. Gas insufflation of the stomach is greater in patients with decreased lung 

compliance. Bronchoscopy prior to tracheal intubation is occasionally used to identify the fistula 

and seal it with a small balloon tipped catheter. If severe gastric distention, rapid decompression 

(needle aspiration gastrostomy) is requested 

8. Maintenance depends on the condition of the neonate and the postoperative ventilatory strategy. 

In the unstable neonate an opioid anesthetic (fentanyl 10–25 g/kg) is often preferable. Stable 

term neonates will benefit of inhalational agents. Low dose volatile agents is also a good choice if 

analgesia is provided by an epidural technique. Certain surgeons require that the patient be kept 

sedated, paralyzed and ventilated in the early postoperative period to “protect” the anastomosis, a 

high-dose opioid anesthetic is most indicated 

9. Insertion of an arterial catheter for the unstable neonate 

10. Placement of a continuous thoracic epidural regional block, either via the caudal approach or 

directly (by experienced anesthesiologists only) 

11. During surgery, the lung, the trachea and the large veins will be compressed leading to 

desaturation, reduction of venous return and cardiac output. The surgeon must be alerted when 

this happens but must be given reasonable time to perform the different stages of the procedure. 

Brief periods of desaturation or blood pressure changes must be accepted without alarming the 

surgeon 

12. Manipulation and ligation of the fistula leads to minor bleeding and secretions. Repeated 

suctioning of the tracheal tube might be needed to avoid partial or complete obstruction 

13. Before the closure of the thoracic wound the lung should be carefully re-expanded in order to 

avoid unnecessary postoperative atelectasis 

procedure is a significant surgical and anesthetic ordeal. 195,196 

Below are only some guidelines for the initial bronchoscopy. 



Congenital Lobar Emphysema 

This congenital malformation consists of pathologic enlargement 

of one of the lung lobes, which can be caused by bronchomalacia, 

a vascular anomaly, or an intrabronchial obstruction. Depending 

on the size of the lesion, it can compress healthy lung tissue and 

also create an intrathoracic volume lesion with mediastinal shift 

and impeded venous return. Such patients will present with 

a combination of respiratory distress and cyanosis. Surgical 

intervention due to this condition will be undertaken either on a 

semiemergent basis or as an elective procedure. The condition 

is also frequently (35%) associated with congenital heart disease. 



Patent Ductus Arteriosus 

In the neonatal period this is almost exclusively a disease of the 

premature baby. The presence of a patent ductus arteriosus (PDA) 

causes a left-to-right shunt across the ductus resulting in two 

different unfavorable situations. First, the resulting pulmonary 

overcirculation puts significant volume strain on the left side of 

the heart and causes enlargement of the left atrium and ventricle 

and causes high-output cardiac failure. Second, in severe cases 

the left-to-right shunting may become so pronounced that there 

can be reversal of the diastolic aortic blood flow in the descending 

aorta. In this situation, the blood supply to the lower body 

is jeopardized and patients with PDA are at increased risk of 

developing necrotizing enterocolitis as a result of splanchnic


TABLE 86-17. Typical Management of a Neonate Presenting With Tracheoesophageal Cleft 

Symptoms 


Monitoring 




Recurrent episodes of cyanosis, frequently associated with feeding. Repeated tracheal tube 

dislodgment 

1. Nasogastric tube for continuous suction. Can be very difficult. Check x-ray for position 


3. Echocardiography 

4. Routine laboratory 

5. Blood type and compatibility test 




1. No premedication, I.V. atropine (10 g/kg), preoxygenation 

2. Inhalation induction and spontaneous ventilation. Keep the nasogastric tube on suction 

3. If symptoms are mild and complete cleft unlikely, bronchoscopy can be handled as usual. In severe 

cases, ventilation and oxygenation may be difficult due to reduced lung compliance and repeated 

aspiration. This is accentuated if positive pressure ventilation is attempted 

4. If cleft is complete (down to the carina), securing the airway with a tracheal tube is not possible. 

Selective bronchial intubation might become the only option available. If necessary, use a normal 

tracheal tube for each main bronchus and two separate ventilation circuits for each tube. This will 

avoid many problems 

hypoperfusion. Pharmacologic closure of the PDA (I.V. indo - 

methacin) is often successful but if this treatment has failed, in 

longstanding cases or if the size of the PDA is judged to be very 

large, surgical ligation of the PDA is required. The anesthesiologist 

should be aware that one of the cornerstones of the conservative 

treatment of a PDA is fluid restriction and the use of diuretics 

(usually furosemide). Thus, these patients are regularly on the 

border of hypovolemia and can also have significant potassium 

deficits, two conditions that have serious implications for the safe 

administration of anesthesia. Even if unsuccessful in accomplish - 

ing closure of the PDA, I.V. indomethacin will regularly cause 

transient renal dysfunction with a reduction in urine output and 

a fall in platelet number and activity due to the effects of indo - 

methacin on prostanoid synthesis in the kidney and the platelet. 

Thus, it is wise to wait until urine output has normalized and there 

is no clinical or laboratory signs of platelet dysfunction before 

accepting the neonate for surgery. The main steps of anesthetic 

management are summarized in Table 86–19. 

TABLE 86-18. Typical Management of a Neonate With Congenital Lobar Emphysema 

Symptoms 


Monitoring 




Tachypnea. Moderate to severe respiratory distress. Tachycardia and/or hypotension. Cyanosis. 

Lateral shift of cardiac sounds. Accidental finding on chest radiograph 


2. Echocardiography 

3. Routine laboratory, arterial blood gas, blood type and compatibility test 






2. Inhalational induction, maintain spontaneous ventilation to limit enlargement of the lobar 

emphysema by positive pressure ventilation while securing the airway. If the patient is in 

distress ketamine is preferred to thiopental to prevent hemodynamic deterioration 

3. Selective bronchial intubation might be necessary if positive pressure ventilation needed. 100% 

O 2 

helps reduce the size of the emphysema (resorption of the nitrogen) 

4. Maintenance depends on severity. Total intravenous anesthesia or volatile techniques are 

suitable 

5. Inotropic support may be needed and a dopamine infusion should be at hand 

6. Re-expand the lungs before thoracic closure to limit postoperative atelectasis 

7. If possible, the trachea should be extubated at the end of procedure. Spontaneous breathing 

reduces the strain on the bronchial stump and decrease the risk for significant air leak or 

development of a bronchopleural fistula. Regional anesthetic techniques are very helpful (e.g., 

continuous paravertebral or thoracic epidural blockade)

TABLE 86-19. Typical Management of a Neonate With Patent Ductus Arteriosus 

Symptoms 


Monitoring 





Cardiac failure with fluid retention, poor weight gain, tachypnea, ventilator dependence. 

Bouncing femoral pulses or wide pulse pressure due to the left-to-right shunting (cf. aortic 

insufficiency). Echocardiography will give final diagnosis 


2. Echocardiography (ask for signs of hypovolemia and degree of cardiac failure) 

3. Ultrasonic head scan to document any pre-existing intracranial pathology 

4. Routine laboratory including potassium 

5. Blood type and compatibility test. Platelet count 


8. Check last 24 h urine output and diuretic use to judge body fluid status 

Routine monitoring; invasive blood pressure monitoring if patient is unstable 

1. No premedication, IV atropine (10 g/kg), preoxygenation 

2. Induction of anesthesia depends on the degree of cardiac failure. If moderate (failure to wean the 

patient from the ventilator), standard IV induction and maintenance with low dose sevoflurane 

(less myocardial depression than halothane); if severe (poor contractility on preoperative 

echocardiography or digitalization), opioid anesthetic and small doses of midazolam or a very low 

dose of sevoflurane 

3. Nasal intubation is preferred to reduce the risk of dislodgment of the tube due to limited access to 

the patient, right lateral positioning and low weight 

4. During surgery, lung compression is inevitable; periods of desaturation must be tolerated to allow 

progress of the surgery. If bradycardia develops, immediate re-expansion is needed 

5. Hypotension occurs frequently; if not due to surgical impairment of venous return, this requires 

lightening anesthesia first, then give plasma expander (most patients are hypovolemic). If 

moderate expansion (10–15 mL/kg of 5% albumin solution) fails to restore the blood pressure, 

inotropic support is necessary (dopamine 5–10 g/kg/min) 

6. Before closing the wound the surgeon should be encouraged to place either a multilevel intercostal 

block or a paravertebral block under direct vision 

7. Weaning from the ventilator may requires several days despite the correction of the pathology due 

to edema and atelectasis of the right lung, necessity to administer fluids to stabilize 

hemodynamics and improve cardiac function 

Abdominal Surgery 

Congenital Diaphragmatic Hernia 

The incidence of congenital diaphragmatic hernia (CDH) is 

approximately 1/5000 live births. Most often it is left-sided, but 

right-sided cases do occur. The severity of the malformation 

depends on the amount of herniation of the abdominal contents 

that as occurred during fetal life. In minor herniation, the patient 

can be asymptomatic at birth and is only diagnosed by a chest 

radiograph often performed for other reasons. In severe cases, the 

baby has immediate symptoms of severe respiratory distress and 

hypoxic respiratory failure combined with life-threatening pulmo - 

nary hypertension. The ventilatory problems are not due solely to 

an intrathoracic mass lesion, as previously believed, but are instead 

also due to the associated pulmonary hypoplasia and pulmonary 

hypertension. Thus, there is no need for immediate reduction 

of the abdominal viscera as previously practiced. This can in fact 

be regarded as absolutely contraindicated and should be preceded 

by preoperative stabilization. In the case of more pro nounced 

intrauterine herniation not only will the ipsilateral lung be 

hypoplastic but the contralateral lung is also affected to some 

degree by hypoplasia. 197 Most of the children with CDH are term 

infants and normally developed regarding most organ systems 

except for the lungs. Not only are both lungs affected by varying 

degrees of hypoplasia depending on the severity of the intrauterine 

herniation, but they are also immature. 

Recent research has found CDH lungs in more severe cases to 

be surfactant deficient 198 and surfactant replacement has been 

reported to be successful in certain cases. 199 Thus, the CDH patient 

can be described as being term with the lungs of a premature. The 

associated pulmonary hypertension is due both to a reduction in 

the number of pulmonary vessels and also due to an exaggerated 

pulmonary vasoreactivity capable of causing life-threatening 

episodes of pulmonary vasospasm leading to profound extrapul 

monary right-to-left shunting. The vasoreactivity in CDH 

will occasionally produce what has been termed a “honeymoon 

period.” In these cases, the patient will have a period of acceptable 

gas exchange immediately after birth without the use of any 

more extreme ventilatory settings or adjuvant treatments. This 

is later followed by very severe pulmonary hypertension associated 

with profound hypoxic respiratory failure. Conventional 

treatment for the treatment of this situation has been prophylaxis 

consisting of deep analgo-sedation, inotropic support, moderate 

hyperventila tion if possible, and meticulous control of the 

patient’s acid-base status. Previous attempts to treat this situation 

with intravenous vasodilators has been abandoned due to the 

risk of hypotension, since systemic hypotension can be lifethreatening 

in this setting. More modern treatment consists of 

surfactant replacement, high frequency oscillatory ventilation, 

inhaled nitric oxide, and extracorporeal membrane oxygenation. 

The neonatal anesthesio logist might, thus, be faced with 

the situation of administering anesthesia to patients either on


inhaled nitric oxide 199 or extra corporeal membrane oxygenation 

(ECMO). 200 

Improved outcome has been reported following preoperative 

stabilization of the patient and treatment of pulmonary hyperten - 

sion. 201 An interesting phenomenon with the pulmonary hyper - 

tension experienced by CDH patients (and some other neonatal 

disorders as well, e.g., meconium aspiration syndrome and 

idiopathic persistent pulmonary hypertension of the newborn) is 

that the tendency to react with severe vasospasm appears to be 

time limited and once the patient is through this period pulmo - 

nary hypertension will not reappear for the rest of the patient’s life. 

However, some patients with pronounced pulmonary hypoplasia 

will never come through this period and will develop chronic 

pulmonary hypertension as a result. Before this period has passed 

the patient can respond with vasospasm to almost any kind of 

stressful stimulus and it is readily apparent that emergency surgery 

with the release of cytokines and other neuroendocrine stress 

factors is not helpful. If on the other hand the patient is stabilized 

and has been so for “a hundred hours” without signs of deterio - 

ration or episodes of pulmonary vasospasm surgery can be 

performed without a stormy intra- and postoperative period. 201 

Most patients will eventually fulfill these modern criteria but a 

small subsegment will not and will have to be operated on despite 

the lack of full stabilization. Such patients are often on advanced 

adjuvant treatments (e.g., high-frequency oscillatory ventilation, 

inhaled nitric oxide or ECMO), which put very specific demands 

on the surgical and anesthetic teams. 

One key issue in the treatment of CDH patients is to try to 

predict which patients have enough lung tissue to survive with 

maximum medical treatment and which patients have pulmonary 

hypoplasia of such severity that extrauterine life is not possible. 

No specific tests or observations can yet define this with 

satisfactory sensitivity and specificity but some indications can be 

achieved from the immediate postpartum situation and also 

examination of the patient’s red blood cells. If the baby presents 

with immediate symptoms and has never shown an acceptable 

blood-gas analysis as an indicator of sufficient amount of lung 

tissue to sustain gas exchange (lack of “honeymoon period”), this 

is a strong indicator of poor prognosis. In severe cases of intrau - 

terine herniation, cardiac output will be compromised, leading to 

a compensatory erythropoesis. This will cause the occurrence of 

significant amounts of immature nucleated erythrocytes at birth. 

If the CDH patient displays ≥2.0 10 9 /L of nucleated red blood 

cells in the blood stream, this is an significant indicator of a poor 

prognosis, and if ≥0.5 10 9 /L ECMO is frequently needed. 202 The 

main steps of anesthetic management are listed in Table 86–20. 

Omphalocele 

The incidence of the malformation is 1/5000. This abdominal wall 

defect can range from minute to very significant with herniation of 

parts of the intestine, spleen and the liver. Contrary to gas troschisis, 

the herniated viscera will be covered by a hernia sac or mem - 

brane. 203 If this membrane has ruptured, the situation might look 

very similar to gastroschisis, but a closer inspection of the abdo - 

minal wall will disclose the true nature of the condition. Although 

they present similar appearances, omphalocele is quite different 

from gastroschisis from an embryologic standpoint. Omphalocele 

is also much more often associated with other malformations 

(mainly cardiac) than gastroschisis, which only represents a 

midline fusion failure. Small omphaloceles can be closed without 

any problems, whereas larger herniation can cause significant 

problems. This is mainly due to the increase in intra-abdominal 

pressure resulting from forcing the herniated viscera into an abdo - 

minal cavity which is too small. This increase in intra-abdominal 

pressure will cause a cephalad shift of the diaphragm, interfering 

with ventilation, and will also affect organ blood flow. 204,205 In this 

situation, both renal and hepatic function will be impaired. Due to 

a reduction in renal perfusion transient oliguria or even anuria tend 

to occur and reductions in liver blood flow will reduce the capacity 

for hepatic drug clearance. In this situation the terminal half-life 

of both renal and hepatic dependent drugs can be significantly 

prolonged (e.g., fentanyl, local anesthetics). Forceful closure of the 

abdominal defect will also cause significant tension of the skin and 

the abdominal wall and necrosis with secondary infection are 

frequent complications. To avoid the above the surgeons on 

occasion will opt to create a “tent” by artificial material and suspend 

this contraption in order to allow gravity to reduce the herniated 

viscera gradually by distending the abdominal cavity over a period 

of 4 to 7 days. During this period, the tent will be reduced slowly 

in the same manner as rolling the end of a tube of tooth paste. The 

omphalocele can then usually be closed without any major pro - 

blems. Drawbacks with this approach are the risk for infection and 

the risk of suture disruption at the wound edges. 

Although not an absolute emergency, surgery should be per - 

formed as soon as convenient. Proper preoperative stabilization 

and investigation must take precedence, but surgery should not 

be postponed until the next working day due to the risk of 

infection and fluid balance problems. To avoid fluid loss and 

evaporative heat loss, the omphalocele should be covered by wet 

sponges and a plastic wrap during the preoperative period. Despite 

this, close attention has to be paid to preserving body temperature 

and an optimal volume and electrolyte status. The main steps of 

anesthetic management are summarized in Table 86–21. 

Gastroschisis 

The incidence of gastroschisis is 1/10,000. In this condition, the 

abdominal wall defect is located in the midline between the 

umbilicus and the xiphoid process. Most parts of the gut will 

usually be herniated and not covered by any membrane. The gut 

does not appear entirely normal but will instead be edematous and 

partly covered by fibrin. This malformation is rarely associated 

with any other congenital birth defects but a routine search for 

mainly cardiac malformations should nevertheless be undertaken. 

The diagnosis of this condition is obvious from inspecting the 

patient. An intact umbilicus, the location of the herniation and 

the lack of any covering membrane/hernia sac distinguishes this 

lesion from omphalocele. Clinical handling of this condition will 

not in any major way differ from the handling of patients with 

more pronounced forms of omphalocele. Thus, for guidelines 

please see Table 86–21. 

Intestinal Obstruction 

The gastrointestinal tract can be affected by mechanical obstruc - 

tion at any location between the pylorus and the anus. The 

handling of the more frequent of these disorders will be discussed. 

Pyloric Stenosis 

This lesion is caused by pathologic hypertrophy of the pyloric 

smooth muscle. Neonates rarely display any symptoms of this 

condition since the very characteristic forceful projectile type of 

vomiting will usually not occur until 4 to 6 weeks of age. 206


TABLE 86-20. Typical Management of a Neonate With Congenital Diaphragmatic Hernia 

Symptoms 


Monitoring 



ECMO extracorporeal membrane oxygenation. 


Tachypnea, various degrees of respiratory distress and cyanosis, absent breath sounds over one 

hemithorax, lateral displacement of cardiac sounds, scaphoid abdomen 

1. Check that the patient fulfills the golden criterion of 100 hours of stability before surgery, 

otherwise request that surgery be postponed until completion of this delay 

2. Check the presence of a nasogastric tube allowing decompression of the stomach (prevention of 

further respiratory distress caused by a distended intrathoracic stomach) 

3. Chest radiograph and echocardiography 

4. Routine laboratory, including test for the presence of nucleated erythrocytes 

5. Blood type and compatibility test; order 1 unit blood and 1 unit plasma 

1. Routine monitoring, invasive blood pressure monitoring in most severe cases 


3. Monitor SpO 2 

simultaneously on the right hand and one foot to estimate the severity of 

extrapulmonary right-to-left shunting 

4. Place a multilumen central venous line (administration of inotropes, sampling of venous blood 

gases and for volume infusion) 


2. Tracheal intubation should be performed after induction if not yet done. Keep spontaneous 

ventilation (positive pressure ventilation yields gastric distention and respiratory distress). 

3. Inhalational anesthetic is suitable for very stable patients. In unstable patients, opioid anesthetic 

(fentanyl 25–50 g/kg) is most appropriate. 

4. To optimize analgesia intra- and postoperatively, a continuous regional block is often indicated. If 

an epidural technique is used the tip of the catheter must be closed to the dermatome of the skin 

incision. If the epidural puncture is not performed at the appropriate thoracic level but threaded 

from a caudal or lumbar approach the location of the tip needs to be confirmed by fluoroscopy. 

Since the incision is usually a left-sided subcostal incision an ipsilateral T 6–7 continuous thoracic 

paravertebral block is an excellent alternative 

5. Surgical repair is usually uneventful; hypotension may be due to venous return impairment, if so 

give a volume bolus or increase inotropic support. If pneumothorax on the contralateral side, 

must be drained. Finally, consider acute episode of pulmonary hypertension with right ventricular 

strain and impeded venous return (left heart) and right-sided septal shift (reducing diastolic 

volume of left ventricle). Increasing gap between the SpO 2 

of the right hand and the foot (increase 

in extrapulmonary right-to-left shunt). In this event, give additional bolus of opioid to deepens 

anesthesia, increase ventilation and FiO 2 

(to improve oxygenation and reduce pCO 2 

) and check 

acid-base status (correct any acidosis). If this fails, consider administering inhaled nitric oxide. 

After reduction of the hernia and closure of the diaphragm, ventilation may be affected (probably 

due to changes in anatomic geometry of the diaphragm and lack of space for the content). Ventilation 

must be maintained and surgeons informed 

6. If the patient is judged to be at risk of sustained pulmonary hypertension, use a ventilator allowing 

nitrous oxide administration; however, these ventilators do not allow delivery of volatile agents. 

Total intravenous anesthesia is an excellent option. With patient on ECMO, problems with 

bleeding will be important due to anticoagulation with heparin 

7. Occasionally extubation is possible at the end; most often, ventilation will be needed 

Although rare, some patients will present during the late neonatal 

period. If the diagnosis has been delayed the patient will become 

dehydrated and will also have a combined electrolyte/acid base 

disorder. Due to the loss of primarily hydrogen, chloride, and 

potassium ions with protracted vomiting the patient will develop 

a hypochloremic, hypokalemic alkalosis. Before these patients are 

accepted for anesthesia and surgery, they must be rehydrated and 

have normal electrolytes and acid-base parameters. Providing 

intravenous access and starting the correction of the fluid balance 

has a very high priority in these patients. Thus, surgery can and 

must wait until the fluid balance has been corrected and can be 

delayed without any problems and should be performed during 

normal day time. The main steps of anesthetic management are 

summarized in Table 86–22. 

Duodenal Obstruction 

This is most often caused by duodenal atresia. Depending on 

the exact location of the atresia, the vomiting or the drainage 

from the nasogastric tube will be discolored by bile. Duodenal 

atresia is frequently associated with Down syndrome and the 

patient should be checked for physical stigmata associated 

with this syndrome. Cardiac malformations are also often 

associated with this condi tion, most commonly as part of a Down 

syndrome. Other causes of duodenal obstruction are annular 

pancreas and choledochal cysts. Due to the nature of the con - 

dition, diagnosis is usually made at an early stage and patients 

will, thus, not be allowed to develop fluid or electrolyte distur - 

bances. The main steps of anesthetic management are listed in 

Table 86–23.


TABLE 86-21. Typical Management of a Neonate Presenting With Omphalocele 

Symptoms 


Monitoring 




30–40% have congenital heart defects. Midline defects 

1. Nearly all patients have paralytic ileus. Nasogastric tube allows decompression of stomach 

2. Chest radiograph and echocardiography 

3. Routine laboratory with special attention regarding electrolyte status 

4. Make sure the patient is not hypovolemic 

5. Blood type and compatibility test; Order 1 unit blood and 1 unit plasma 

1. Routine monitoring healthy neonates 

2. Invasive blood pressure monitoring and Foley catheterization 

3. If available, monitor stomach or bladder pressure if primary closure of the defect is expected. 

Pressures 20 mmHg significantly reduce cardiac output and hepatic blood flow 205 


2. Aspirate nasogastric tube and perform a rapid sequence induction 

3. Closure of a minor defect and creating a “tent” are usually uneventful; primary closure of a larger 

defect is accompanied by a number of problems 

4. Maintenance depends on hemodynamic stability. Inhalational or opioid technique indicated. Pain 

relief can be provided with epidural which also provide abdominal wall muscle relaxation. 

Remember that high intra-abdominal pressure reduces clearance of local anesthetics. Lidocaine 

provides better muscle relaxation than bupivacaine and plasma levels are easier to monitor 

5. Large insensible water loss (often in excess of 10 mL/kg/h). Volume replacement with albumin or 

plasma. Fluids must be warmed. Overhead or convective warming are needed 

6. Despite adequate volume replacement hypotension may persists and dopamine infusion is often 

needed to achieve normal blood pressure and urine output (severe presentation) 

7. Overenthusiastic attempts by the surgeon to close the defect inevitably cause a decrease in blood 

pressure and cardiac output and may interfere with ventilation. The surgeon must be alerted and 

use an alternative approach (Gortex patch, Silastic tent) 

8. Postoperative ventilation support might be needed in the more severe presentation 

Intestinal Obstruction 

This is most commonly caused by single or multiple atresia of the 

small intestine. The symptoms present somewhat later than 

duodenal obstruction and an abdominal radiograph will show 

classic signs of mechanical ileus. If diagnosed properly patients 

rarely deteriorate regarding fluid and electrolyte balance to any 

significant degree. The main steps of anesthetic management are 


Malrotation of the Gut 

In this condition, the mesentery of the gut has failed to develop in 

a normal way. Instead of attaining the normal broad base of the 

mesenterium, reaching from the ligament of Treiz to the right iliac 

fossa, rotation of the gut will be incomplete, leaving the gut sus - 

pended in a mesenterial base which is very narrow at the root of the 

superior mesenteric vessels. This sets the stage for the possibility of 

rotation of the gut around its own base with concomitant strangula - 

TABLE 86-22. Typical Management of a Neonate Presenting With Pyloric Stenosis 

Symptoms 


Monitoring 




Forceful projectile vomiting after feeding. Look for signs of dehydration. Palpable olive-like 

resistance to the right in the epigastrium. Ultrasonographic examination will usually provide the 

final diagnosis 

1. A nasogastric tube should be passed at the same time the diagnosis is made 

2. Make sure signs of dehydration are not present. Check or inquire about urine output during the 

last couple of hours. Inspect the diaper 

3. Routine laboratory with special attention regarding electrolyte and acid-base status. Sodium, 

potassium, and chloride values should be normal. Do not accept base excess values above 2 

Routine monitoring 


2. Reduce stomach volume and content by aspirating the nasogastric tube 

3. Rapid sequence induction. Maintenance with volatile agents. Relaxation indicated during 

pyloromyotomy to avoid duodenal tears 

4. Infiltration of the wound edges with a long acting local anesthetic (bupivacaine or ropivacaine) 

will ensure high quality pain relief in the immediate postoperative period. Narcotics should not 

be used for risk of postoperative hypoventilation or apnea

TABLE 86-23. Typical Management of a Neonate Presenting With Duodenal Atresia 

Symptoms 


Monitoring 





Classic signs of intestinal obstruction. An abdominal radiograph is usually diagnostic due 

to the presence of the “double bubble” signs, which consists of two large air-filled structures 

(stomach and proximal duodenum separated by the pylorus) in the epigastric region 

1. Check the presence of a nasogastric tube 

2. Make sure signs of dehydration are not present 

3. Routine laboratory (electrolyte and acid-base status) 

4. Blood type and compatibility test and order 1 unit blood 




2. Try to empty the stomach by aspirating the nasogastric tube 

3. Rapid sequence induction 

4. Since the patient will be subjected to fairly extensive upper abdominal surgery a continuous 

epidural block supplemented by a light volatile agent maintenance anesthetic is often a good 

choice 

5. Central venous catheter placement might be mandatory, not for anesthetic purposes but for 

postoperative total parenteral nutrition since enteral nutrition will usually be delayed 

tion of the mesenteric vessels. This will lead to an ischemic 

paralysis of the gut which does not have to have any mechanical 

obstructive component associated. If prolonged the gut ischemia 

will cause a combined situation of ileus, hypovole mia, and sepsis/ 

endotoxemia from translocation of intestinal bacteria. Thus, these 

patients will often present in an unstable state. However, this 

represents one of the very few real emergen cies within neonatal 

surgery, since failure to treat this condition rapidly can cause severe 

harm to the patient. Either necrosis of almost the entire small 

intestine will occur and leave the patient and the family with the 

lifelong problems associated with the short bowel syndrome or the 

condition might become fatal or require a very long period of 

intensive care due to overwhelming sepsis/endotoxemia. The 

emergency nature of this condition cannot be overemphasized and 

stabilization of the circulation, correction of fluid and electrolyte 

deficits and other necessary measures needs to be performed 

simultaneously with starting and maintainin the anesthetic! The 

main steps of anesthetic management are listed in Table 86–25. 

Anal Atresia 

This malformation should be identified as part of the routine 

examination of each newborn baby. The atresia can be classified as 

low, intermediate, or high. If an adequate fistula (most often 

rectovaginal fistula in females) is not present the baby will need 

some surgical intervention to allow reasonable drainage of the 

gastrointestinal tract. In the case of a low, membranous atresia 

definitive correction is possible but in the case of a higher atresia 

final repair will be deferred until later, and drainage will be 

accomplished by the formation of a colostomy. Since diagnosis is 

usually made early, the neonate will almost always be in good 

clinical condition for the anesthesia. 

TABLE 86-24. Typical Management of a Neonate Presenting With Intestinal Obstruction 

Symptoms 


Monitoring 




Classic signs of intestinal obstruction. An abdominal radiograph is usually diagnostic showing 

traditional signs of mechanical obstruction 


2. Make sure signs of dehydration are not present 

3. Routine laboratory with special attention regarding electrolyte and acid-base status 

4. Blood type and compatibility test and order 1 unit blood 

1. Routine monitoring. Invasive blood pressure monitoring when indicated 



3. Rapid sequence induction 

4. Since the patient will be subjected to extensive upper abdominal surgery a continuous 

epidural block supplemented by a light volatile agent maintenance anesthetic is a good 

choice 

5. Contrary to duodenal atresia the surgical procedure will most often involve resection of the 

bowel. Due to third spacing within the mesenterium volume replacement with 5% albumin 

or plasma is usually required to maintain adequate intravascular volume 

6. As with duodenal atresia, a central venous catheter might be mandatory for postoperative 

nutritional purposes (parenteral nutrition)


TABLE 86-25. Typical Management of a Neonate Presenting With Malrotation of the Gut 

Symptoms 


Monitoring 




Sicker aspect than “ordinary” intestinal obstruction: dehydration, frank hypovolemia and sepsis. 

Pain and discomfort is more intense than in other neonatal occlusion due to bowel ischemia. 

X-rays will often not show any signs of mechanical obstruction but instead a picture of 

paralytic ileus 


2. Electrolyte and acid-base status. Coagulation profile is needed since coagulopathy is not 

infrequent. Do not wait for the results before going to the operating theater 

3. Blood type and compatibility test 

4. Order 2 units of blood and 2 units of fresh frozen plasma 

5. Check that adequate antibiotic prophylaxis/treatment is started immediately 


2. Invasive blood pressure monitoring in severe presentations 

3. Foley catheterization with hourly urine output measurements 



3. Rapid sequence induction. Maintenance depends on patient’s hemodynamic status and clinical 

presentation. Opioid and/or inhalational anesthesia techniques appropriate 

4. In presence of coagulopathy, epidural anesthesia should be denied or postponed until the end of 

the surgery 

5. Two large bore venous access. A central venous line might be useful 

6. Administer syringe boluses (5% albumin, plasma or packed red cells) according to blood pressure. 

If hypotension persists consider dopamine infusion 

7. Check regularly blood glucose, hematocrit, electrolytes and ionized calcium, arterial blood gas 

analysis and coagulation parameters 

8. Untwisting of the gut release vasoactive substances and lactic acid into the circulation yielding 

hypotension. Volume, inotropic support and correction of acid-base status 

9. Most patients will require postoperative ventilatory support in the NICU 

Inguinal Hernia Repair 

Repair of a inguinal hernia is most often delayed until the baby is 

passed the neonatal period. (see Chapter 54) However, if the size 

is very significant and give raise to pain or intermittent episodes 

of incarceration surgery might be necessary in the first few weeks 

of life (for inguinal hernia repair in the ex-premature baby please 

see below). 

Necrotizing Enterocolitis 

This is a severe complication seen almost exclusively in premature 

children. The cause of this complication is most likely 

multifactorial, but intestinal ischemia with secondary bacterial 

overgrowth appears as a key factor. The premature baby will 

present with abdominal distention, increasing gastric aspirates and 

micro- or macroscopic gastrointestinal bleeding. Signs of general 

sepsis are also frequently present. Withholding enteral feeding and 

starting parenteral nutrition and antibiotic treatment will usually 

handle the situation, but in severe cases perforation of the gut 

might supervene, which necessitates surgical intervention. 

However, patients with an intestinal perforation are generally very 

sick and unstable and will present the anesthesiologist with a 

significant challenge. Crucial to success is preoperative circulatory 

support by volume replacement and inotropic agents as well as 

appropriate antibiotic treatment. The current surgical trend is to 

insert only one or more abdominal drainage tubes and refrain 

from performing acute intestinal resections and enterostomies. 

This is a significant advantage from an anesthetic perspective and 

is likely to increase the baby’s chances of surviving. Further 

surgery can be performed at a later stage when the patient has 

recovered. The main steps of anesthetic management are 


Bladder Exstrophy 

In this malformation, there is a defect midline fusion of the uri - 

nary bladder, the symphysis, and the urethra. The interior of the 

bladder will be exposed and the mucosa and the ureteral orifices 

can be observed. Care should be taken to cover the area with wet 

sponges in order not to cause secondary injury and infection due 

to drying of the mucosa. Prophylactic antibiotics should be started 

and the patient should be scheduled for operative repair as soon 

as possible during normal working hours. The surgery is often 

associated with moderate blood loss and transfusion is almost 

always necessary in these patients. In order to close the symphysis, 

a inferior pubic ramus osteotomy is frequently required. Posto - 

peratively the legs are often suspended, similar to patients with 

bilateral femoral fractures, in order not to cause undue stress on 

the symphysis. A specific concern in these patients is the risk for 

the subsequent development of latex allergy. Care should be taken 

not to expose these babies to latex (e.g., surgical gloves, tapes, face 

masks) 207 (see Chapter 45). The main steps of anesthetic manage - 

ment are summarized in Table 86–27. 

Myelomeningocele 208,209 

Myelomeningocele (MMC) is associated with an incomplete 

closure of the neural tube (see Chapter 58). This will obviously be

TABLE 86-26. Typical Management of a Neonate With Necrotizing Enterocolitis 

Symptoms 


Monitoring 





1. Abdominal distention, feeding problems associated with increased gastric aspirates, micro- or 

macroscopic gastrointestinal bleeding 

2. Hypovolemic/septic appearance. Laboratory signs of infection/sepsis 

3. Abdominal x-rays: paralytic ileus with gas in the intestinal wall and, in severe cases, the portal vein. 

If perforation has occurred, free intra-abdominal gas is present 


2. Routine laboratory panel including C-reactive protein and white cell count 

3. Coagulation parameters, arterial blood gas analysis. Correct any degree of acidosis 

4. Determine degree of dehydration and hypovolemia and correct accordingly 

5. Echocardiography (look for signs of hypovolemia and decreased myocardial contractility). Check 

for signs of pulmonary hypertension 

6. Chest radiograph. Look for signs of acute respiratory distress syndrome and bronchopulmonary 

dysplasia 



3. Foley catheterization with measurement of hourly urine output 


2. Most babies are already intubated and mechanically ventilated in the NICU. If not, rapid sequence 

induction should be performed. If the baby is severely septic or hemodynamically unstable, 

ketamine should be used as induction agent. Opioid maintenance anesthetic is often preferred in 

order to maintain hemodynamic stability 

3. Dopamine or dopexamine infusion will be used to improve cardiac output and splanchnic 

perfusion before anesthesia and surgery. If not, it should be readily available. High infusion rate 

should be used (10–15 mL/kg/h) and volume supported with 5% albumin, fresh frozen plasma and 

packed red cells. Epinephrine infusion might be needed to support cardiac output and systemic 

blood pressure 

4. If urine output remains low despite volume loading and a low-dose dopamine infusion, administer 

iteratively small doses of furosemide (0.5 mg/kg) 

5. Due to the risk of coagulopathy, avoid epidural techniques despite potential benefits. Postoperative 

analgesia can be achieved by continuous morphine infusion 

associated with a varying degree of neural dysfunction below the 

level of the MMC and will also predispose to early infection 

unless rapid surgical closure is undertaken and appropriate 

antibiotic coverage provided. This lesion is often associated with 

hydrocephalus and the later development of an Arnold–Chiari 

type II syndrome. Large MMCs or MMCs at a higher level are 

often more complex to handle. Due to the risk of secondary 

infection and to improve the handling of the patients surgical 

closure should be performed as soon as convenient. Before surgery 

the MMC should be covered by wet sponges to counteract drying 

of the tissues and an attempt at assessing the neurologic function 

below the lesion should be performed. Antibiotic coverage must 

be instituted at once. Special issues with these patients are how to 

position the patient during tracheal intubation in order not to put 

undue pressure on the MMC. These patients also are very likely to 

develop latex allergy. 207 The main steps of anesthetic management 

are summarized in Table 86–28. 

Surgery on the NICU Graduate 

Overview 

These patients do most often belong to one of two groups. Either 

the neonatal period has been relatively uneventful despite the 

baby being born preterm, thus, leaving the child almost completely 

healthy or with only minor residual medical problems. In this 

case, anesthesia is relatively straightforward. On the other hand, 

the preterm baby might have been on ventilatory support for 

extended time periods, complicated by, e.g., repeated sepsis 

episodes, cerebral hemorrhage, patent ductus arteriosus, and/ 

or necrotizing enterocolitis. Patients in the latter group will often 

be on multiple medications (e.g., diuretics, digoxin, antiepileptics, 

inhaled steroids, and b2-agonists). Such babies will frequently 

have developed a moderate to severe degree of bronchopulmonary 

dysplasia/chronic lung disease of the newborn and tracheal 

extubation has often been accomplished with great difficulty. 

Most of these ex-premature babies will still be on a continuous 

positive airway pressure device or will receive supplemental 

oxygen by nasal prongs. Postoperative apnea is a cause of concern 

in this patient category and the time period during which 

the infants are at risk will be significantly longer than 44 to 

60 postconceptual weeks (see “Ventilation Function and Control”) 

and often the risk for postoperative apnea is still present up to 

6 to 12 months of age. Since the neonatologists so often have 

had great difficulty in extubating these children, both the neona - 

tologists and the parents are reluctant to have the child reintubated 

if surgery and anesthesia becomes necessary. The anesthesiologist 

should try to respect these concerns and when ever possible 

try to use alternative but safe techniques in order to try to 

avoid tracheal intubation. Below the two most frequent situation 

where the anesthesiologist will meet the NICU graduate will be 

outlined.


TABLE 86-27. Typical Anesthetic Management of a Neonate Presenting With Bladder Exstrophy 

Symptoms 


Monitoring 




Obvious from looking at the baby 

1. Routine laboratory panel 

2. Cardiac echocardiography 

3. Blood type and screen 


5. Check that adequate antibiotic prophylaxis/treatment is started immediately and that the defect is 

covered by wet sponges 



1. Make sure the patient is not exposed to latex 


3. Intravenous or inhalational induction appropriate. Tracheal intubation is indicated due to 

prolong surgery. No special requirement for maintenance. 

4. Due to extensive surgical reconstruction and postoperative need for some immobility of the 

lower limbs, a lumbar epidural block should be considered. 

5. Hemodynamically stable and normothermic patients can be extubated following emergence from 

anesthesia. 

Retinopathy of the Premature (ROP) 

The cause for this condition was previously believed to be hypero - 

xia secondary to overenthusiastic administration of oxygen during 

the early neonatal period. Increasing degrees of prematurity and 

repeated sepsis episodes are currently seen as more fundamental 

predisposing factors for the development of ROP than hyperoxia. 

Briefer episodes of hyperoxia, as often happens during anesthesia 

of these infants, is currently not believed to be so dangerous in 

this regard. The retinal lesions will be treated with a laser or with 

a cryothermic probe (or a combination). The ophthalmologists 

will need free access to the patients eyes and will, thus, interfere 

with the anesthesiologists possibilities to handle the airway. Thus, 

face mask ventilation is usually not practical since the anesthe - 

siologists hands need to be out of the operating field. Despite the 

often small size of these infants (1–2 kg body weight) the use of the 

laryngeal mask airway will often avert the need for tracheal 

intubation. 122 Crucial for the successful return to the previous level 

of respiratory support prior to the anesthetic, is to expose the 

patient to as few medications as possible and to use only drugs 

with a very short effect duration. 122 The use for example of 

thiopental should be considered contraindicated since the halflife 

is excessively long in these babies. 117 

Inguinal Hernia Repair 

Awake caudal or spinal anesthesia can successfully be performed 

in the ex-premature infant 210–212 and will circumvent the problem 

of general anesthesia and tracheal intubation. The risk for 

postoperative apnea will also be reduced with these methods 

compared to general anesthesia. However, supplementation of 

these blocks by any sedative drugs, including ketamine, 213 will 

TABLE 86-28. Typical Anesthetic Management of a Neonate Presenting With Myelomeningocele 

Symptoms 


Monitoring 

Suggested anesthetic 

and recommendations 

Recommended examinations and management 

Obvious from routine inspection of the patient 

1. Routine laboratory panel. 

2. Blood type and screen. Order 1 units of blood and 1 units of plasma. 

3. Check that adequate antibiotic prophylaxis/treatment is started immediately and that the 

defect is covered by wet sponges 


2. If large undermining of the skin needed for closure, invasive blood pressure monitoring 

might be indicated. 

1. Make sure the patient is not exposed to latex 

2. No premedication, IV atropine (10 g/kg) and preoxygenation 

3. Intravenous or inhalational induction and maintenance per choice 

4. If general anesthesia is used tracheal intubation is mandatory because of the duration of 

surgery and the prone position. To minimize the risk for accidental dislodgment of the 

tracheal tube nasal intubation is recommended. To avoid pressure damage of the nervous 

structures within the MMC, tracheal intubation can be performed in the lateral position. 

Custom made support pads with a hole cut for the MMC can also be used for tracheal 

intubation in the supine position. 

5. Most patient will be extubated at the end of the procedure.


increase the risk for the development of apnea in the postoperative 

period. Although the risk for apnea will be reduced by an awake 

regional technique these patients should still be closely supervised 

overnight. 214 The limited duration of both caudal and especially 

spinal blocks in this age group will make it difficult to perform 

bilateral inguinal hernia repairs with these techniques without 

intravenous or volatile supplementation at the end of the 

procedure. Clonidine will significantly prolong the duration of 

caudal blocks 215 and co-administration of 1 g/kg of clonidine 

together with bupivacaine will usually prolong the duration in expremature 

babies sufficiently to allow bilateral repair. In the 

author’s experience the use of adjuvant clonidine administration 

in this setting has not been associated with any noticeable increase 

of postoperative apneic episodes although this still needs to 

be verified scientifically. Although awake caudal anesthesia is 

advantageous compared to general anesthesia in this patient 

category it should be remembered that the bolus dose of 

bupivacaine needed to provide an adequate block might produce 

signs of early central nervous system toxicity due to systemic 

absorption of the local anesthetic. 164 In this respect an awake spinal 

block might be preferable, since a lesser amount of local anesthetic 

is needed to accomplish an adequate block with this technique. If 

by some reason awake regional techniques are not appropriate the 

same method described above (see “Retinopathy of the Prema - 

ture”), complemented by either a caudal or ilioinguinal block for 

intra- and postoperative analgesia, should be considered in an 

attempt to avoid tracheal intubation. 

Circumcision 

Circumcision is often performed in the neonatal period due to 

religious beliefs or parental preference. Adequate anesthesia or 

regional anesthesia is obviously an obligatory part of this minor 

procedure. Failure to do so in not only inhumane and represents 

unacceptable clinical practice but will also cause long-term altera - 

tions in pain perception. 4 A brief face-mask volatile anesthetic or 

a penile block are acceptable options. A eutectic mixture of local 

anesthetics (EMLA cream) is used by some practitioners in this 

setting but this method does not provide sufficient analgesia in 

most cases. 

CONCLUSION 

In the current era of changing demographics, with a rapidly in - 

creasing number of older and sicker patients, the anesthesio logist 

might occasionally question the ethical and moral value of the 

medical work at hand. In this situation, pediatric anesthesia in 

general, and neonatal anesthesia in particular, will provide the 

anesthesiologist with an unique opportunity to make a true 

difference in patients with their entire life span ahead of them. 

However, this is an endeavor that should not be undertaken lightly 

but instead with the utmost care and professionalism. The 

successful performance of neonatal anesthesia will depend on a 

combination of a thorough understanding of the specific charac - 

teristics of perinatal physiology and pharmacology, adequate basic 

training and maintenance of manual skills as well as the availability 

of proper equipment and perioperative facilities. If lacking in any 

of the above aspects necessary for the safe and successful conduct 

of neonatal anesthesia the practitioner should not hesitate to 

consult more experienced colleagues or transfer the patient to a 

center better equipped to take care of small babies. 

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