NEONATAL ANAESTHESIA
Special considerations in
the premature and
ex-premature infant
Geoff Frawley
Abstract
Ex-premature infants and children are a heterogenous population,
ranging from healthy children born at 36 weeks’ gestation to formerly
extremely premature children with significant medical issues that
affect anaesthetic care. Preterm birth is associated with perinatal mor-
tality, neurological disability (including cerebral palsy), severe
morbidity in the first weeks of life, prolonged hospital stay after birth,
readmission to hospital in the first year of life and increased risk of
chronic lung disease.
Around 3% of newborns have a major congenital physical anomaly
with 60% of congenital anomalies affecting the brain or heart and
around 1% having multiple anomalies. Individual congenital conditions
requiring surgical intervention in the neonatal period are rare. Gastro-
schisis is one of the most common abnormalities and has an incidence
of around 1 in 2500 live births. Outside of the neonatal period, the
most common surgical procedures performed in ex-premature infants
are inguinal hernia repair and ophthalmologic procedures for underly-
ing retinopathy of prematurity. After even minor surgical procedures,
ex-premature infants are at higher risk for postoperative complications
than infants born at term.
Keywords Apnoea; bronchopulmonary dysplasia; premature infant;
spinal anaesthesia
Royal College of Anaesthetists CPD Matrix: 2D02, 2G01
Definitions
The American Academy of Pediatrics defines gestational age
(GA) as time elapsed between the first day of the last menstrual
period and the day of delivery; chronological age (CA) as time
elapsed from birth and postmenstrual age (PMA) as GA plus CA.
These definitions replace older definitions such as post-
conception age (PCA). The World Health Organization (WHO)
further defines preterm birth (birth <37 weeks), extremely pre-
term (<28 weeks); very preterm (28 to <32 weeks); and mod-
erate to late preterm (32e37 weeks). In 2010 8.3% of babies
were born preterm with most of these births occurring at a
gestational age of 32e36 completed weeks. Preterm infants are
also classified by birth weight as low birth weight (LBW <2500
g), very low birth weight (VLBW <1500 g) or extremely low birth
weight (ELBW <1000 g).
Geoff Frawley MBBS, FANZCA is a Consultant Paediatric Anaesthetist
at Royal Children’s Hospital, Melbourne, Australia and a Clinical
Associate Professor, Department of Paediatrics, Melbourne
University, Australia. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
Please cite this article in press as: Frawley G, Special considerations in the premature and ex-premature infant, Anaesthesia and intensive care
medicine (2016), http://dx.doi.org/10.1016/j.mpaic.2016.11.001
Learning objectives
After reading this article, you should be able to:
C define the terms prematurity, extreme prematurity and post-
menstrual age
C list the consequences of prematurity
C explain the basic principles of anaesthetizing a premature
infant
Consequences of prematurity
Mortality and morbidity
Perinatal mortality is inversely proportional to gestational age
with the highest rates near the limit of viability (Table 1). In a
population-based British study (EPICure 2 study), the survival
and morbidity of 3378 extremely preterm infants (22e26 weeks)
born in 2006 were reported. The live birth rate was 60% with 83%
requiring admission to an intensive care unit (ICU) and active
resuscitation was withheld in 9%. The survival to discharge for all
live births was 51%, and the survival for infants admitted to ICU
was 62%. Among the infants who survived to discharge major
morbidities occurred in 59% including bronchopulmonary
dysplasia (68%), abnormal cerebral ultrasound (13%), laser
treatment for retinopathy of prematurity (ROP) (16%) and lapa-
rotomy for necrotizing enterocolitis (NEC) (8%). No major
morbidity was reported in 41% of survivors to discharge.
Chronic lung disease
Bronchopulmonary dysplasia (BPD) is a chronic lung disease
that remains one of the most prevalent long-term sequelae of
premature birth. For Infants born less 32 weeks BPD requiring
oxygen at 28 days of age BPD is defined as severe if an FiO2
greater than 0.3 is required at 36 weeks PMA. Most infants
currently developing BPD are born between 24 and 28 weeks’
gestational age, during the time of canalicular and saccular
development. BPD in the post-surfactant use era (‘New’ BPD) is
characterized by uniform arrest of lung development, with
simplified alveolar structures and dysmorphic capillaries. The
severity of BPD is related to ventilator-induced barotrauma or
volutrauma, oxygen toxicity, persistent patent ductus arteriosus
and other unknown variables. New neonatal ventilator strategies
such as high-frequency ventilation (HFOV) and nasal continuous
positive airway pressure (CPAP) may reduce the incidence.
Essentially BPD patients have a lifelong susceptibility to respi-
ratory complications of anaesthesia. BPD is associated with
bronchial hyper-reactivity and these infants have an increased
risk of perioperative bronchospasm and oxygen desaturation.
BPD also renders the pulmonary capillary network vulnerable to
pulmonary vasoconstriction in response to perioperative stimuli
such as hypothermia and pain.
Neurological injury
Ex-premature infants and children, especially those with severe
neonatal brain injury, are more likely than term infants and
children to have neurodevelopmental disabilities, including
impaired cognitive skills, motor deficits and cerebral palsy, vision
and hearing loss, and behavioural and psychological problems.
The risk of these impairments increases with decreasing GA.
1 Ó 2016 Published by Elsevier Ltd.
 NEONATAL ANAESTHESIA

Morbidity and mortality of premature infants. Low-birth-weight infants are not necessarily low gestation and may have
suffered intrauterine growth retardation
Overall Late preterm Very preterm Very low birth Extremely low birth
weight (VLBW) weight (ELBW)

Definition Completed weeks’ gestation <37 weeks 32e36 weeks 28e31 weeks <1500 g <1000 g
Incidence % Live births 7.5% 6% 0.7% 1% 0.5%
Perinatal mortality Mortality rate per live birth 2:1000 7.2:1000 36:1000 40:1000 125:1000
Neurological injury IVH 2e5% 20% 45%
Cerebral palsy 1.9:1000 1:1000 33:1000 60:1000 74:1000
Blindness 0.1% 3%
Deafness 0.1% 2%
Chronic lung disease Mod severe BPD 12% 20% 30%
Home oxygen 0.3:1000 10% 4%
Congenital heart disease 8:1000 1.3% 4.4% 8.5%
Necrotizing enterocolitis 3.8:1000 5e10%

IVH, intraventricular haemorrhage; BPD, bronchopulmonary dysplasia. For infants less than 1500 g the incidences of mild, moderate and severe BPD were 13.5, 4.8 and
2.6% respectively.

Table 1

Cardiac abnormalities airway management, reliable intravascular access, maintenance of

There is a higher prevalence of cardiovascular malformations
among infants born prematurely (12.5 cases per 1000 preterm
infants vs 5.1 cases per 1000 full-term infants). The most com-
mon defects are pulmonary atresia with ventricular septal defect
(23%); complete atrioventricular septal defect (22%); and
coarctation of the aorta, tetralogy of Fallot, and pulmonary valve
stenosis (each 20%).
Retinopathy of prematurity
ROP is a developmental vascular proliferative disorder that oc-
curs in the retina of preterm infants with incomplete retinal
vascularization. The most important risk factor for developing
ROP is prematurity but more than 50 separate risk factors have
been identified including elevated arterial oxygen tension. ROP
typically begins at about 34 weeks PMA, but may be seen as early
as 30e32 weeks. It advances irregularly until 40e45 weeks PMA,
but resolves spontaneously in the majority of infants. ROP
screening is recommended in all infants with a birth weight of
1500 g or less, or a GA of less than 30 weeks.
Laryngotracheal abnormalities
Infants who require prolonged intubation can develop subglottic
stenosis or tracheomalacia. Airway obstruction may occur during
induction of anaesthesia, and a smaller-diameter endotracheal
tube may be needed. Infants who have had a procedure to relieve
airway obstruction may be at risk for chronic airway difficulty
and increased risk of aspiration related to limited motion and
decreased sensation of supraglottic tissue. The rate of aspiration
may be 6%, with the highest incidence occurring in the former
extremely preterm infant (<28 weeks GA).
Anaesthesia
General principles
All neonatal anaesthesia should occur in centres appropriate for
ongoing management (NHS directive E02/S/c 2013/14 Paediatric
Surgery: Neonates). The general principles include appropriate
temperature and metabolic homeostasis and adequate analgesia.
Most anaesthetic agents require modification to dose and duration
when used in infants (Table 2). Weiss has introduced the concept of
the 10-N quality paediatric anaesthetic where paediatric anaes-
thesia includes avoidance of fear and pain, maintenance of ho-
meostasis, normotension, normal heart rate, normovolaemia,
normoxaemia, normocarbia, normal electrolytes, normoglycaemia
and normothermia. There is a however a lack of normative data
describing optimal intraoperative anaesthetized blood pressure. In
premature infants a common rule is that the mean arterial pressure
(MAP) should not be less than the child’s postconception age in
weeks. A recent report suggests an MAP of more than 35 mmHg in
anaesthetized neonates and infants under 6 months preserves ce-
rebral oxygenation measured by near infrared spectroscopy (NIRS).
The optimal intraoperative FiO2 and PaO2 are also ill defined. Two
randomized controlled trials of supplemental oxygen for infants
with chronic neonatal lung disease support a target saturation of 91
e95%. The BOOST trial and the Supplemental Therapeutic Oxygen
for Pre-threshold Retinopathy of Prematurity (STOP-ROP) trial
suggest that infants in the higher SpO2 range had a greater incidence
of chest infections suggesting that even low-flow nasally delivered
oxygen may be toxic to respiratory epithelium.
Perioperative morbidity: the incidence of perioperative morbidity
is increased in ex-premature infants with the most frequent events
being upper airway obstruction, laryngospasm, apnoea and post-
intubation stridor. The initial perioperative cardiac arrest registry
(POCA) data suggest that the incidence of cardiac arrest in ex-
premature infants was much higher than older children. The
principal factor involved was drug related, especially halothane-
induced bradycardia. The most recent POCA data suggest the pri-
mary causes are now non-cardiac surgery in infants with congen-
ital cardiac disease. Two European Society of Anaesthesiology
prospective multicentre observational studies aiming to describe
perioperative risk in children (The APRICOT trial) and neonates
(the NECTARINE trial) are due to report their findings in late 2016.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 2 Ó 2016 Published by Elsevier Ltd.

Please cite this article in press as: Frawley G, Special considerations in the premature and ex-premature infant, Anaesthesia and intensive care
medicine (2016), http://dx.doi.org/10.1016/j.mpaic.2016.11.001
 NEONATAL ANAESTHESIA

Anaesthetic agents used for anaesthesia and analgesia and the dose modifications proposed from available
pharmacokinetic studies in neonates
Technique Agent Pharmacokinetics Dose modifications Comments Reference

General Volatiles MAC premature and newborn MAC Sevo 3.1% neonates Lerman J
anaesthesia half MAC 1e6 month old Anesthesiol 1994
Propofol Low clearance at birth 10-8-6 mg/kg/hour Allegeart K
(0.03 litres/minute) model over predicts Ped Anesth 2011
PNA-related increase clearance by 216%
Remifentanil 0.1 mg/kg/minute 43% apnoea at Shin SH et al.
0.25 mg/kg/minute Paediatric Crit
Care 2014
Dexmedetomidine Lower plasma clearance Bolus 0.5 mg/kg Chrysostomou C et al.
(0.3 vs 0.9 litres/hour/kg) Infusion 0.2e0.4 mg/kg/hour J Pediatrics 2014
T1/2 elimination
(7.6 vs 3.2 hours)
Regional Spinal Median unbound and total 1 mg/kg Frawley G
anaesthesia levobupivacaine 0.02 Ped Anesth 2016
and 0.3 mg/litre
Awake caudal 3 mg/kg bupivacaine Potential for local Hoelzle M et al.
0.25% adrenaline anaesthetic toxicity Ped Anesth 2010
Wound catheter Median unbound and total 0.125% at 0.2 mg/kg/hour Krylborn J et al.
levobupivacaine 0.02 and Eur J Anesthesiol 2015
1.3 mg/ml
Multimodal Paracetamol Clearance 51% lower preterm 28e32 weeks 10 mg/kg PMA adjusted Allegaert K et al.
analgesia Elimination T1/2 38% lower 32e36 weeks 12.5 mg/kg 6/24 dosing Arch Dis Child. 2016
36 weeks 15 mg/kg
NSAIDs PDA closure dose ibuprofen Not recommended Negative effects on Allegeart K
5 mg/kg or <3 months age diuresis, GFR, renal Pharmaceuticals 2010
indomethacin 0.2 mg/kg tubular function.
Ketorolac Clearance immature 1 mg/kg Single dose only Papacci P
in neonates Ped Anesth 2004
Tramadol Clearance 84% of the mature 1 mg/kg Target concentration Allegeart K
value by 44 weeks PMA of 300 mg/litre requires BJA 2005
bolus 1 mg/kg
and infusion of
0.18 mg/kg/hour at
40 weeks PMA

GFR, glomerular filtration rate; MAC, minimum alveolar concentration; T1/2, half-time; PNA, postnatal age; PMA, postmenstrual age; PDA, patent ductus arteriosus;
NSAIDs, non-steroidal anti-inflammatory drugs.

Table 2

Induction of anaesthesia: the incidence of difficult neonatal
intubation is highly dependent on the experience of the anaesthe-
tist. Difficult airway management may be anticipated (syndromes
such as Pierre Robin Sequence, TreachereCollins, cleft lip and
palate, Goldenhar syndrome) or unanticipated (e.g. subglottic
stenosis, laryngeal atresia, laryngeal or tracheal webs, glottic
oedema after extubation). Volatile induction is the preferred
neonatal induction technique when difficult intubation is expected.
Maintenance of anaesthesia: intravenous fluid replacement
with 10% dextrose solution in neonates and 4% dextrose 0.18%
saline solutions in infants has been associated with perioperative
hyponatraemia and the optimal perioperative fluid is still unre-
solved. Plasma glucose homeostasis is impaired in infants who
are small for gestational age, infants born to mothers who have
diabetes, and late-preterm infants and these infants require
glucose-containing maintenance fluids. The use of 10% dextrose
solutions at 2 ml/kg/hour however will only deliver 3.3 ml/kg/
hour or half the neonatal glucose requirement. The PIMS (Pae-
diatric Intravenous Maintenance Solution) study demonstrated
that the use of Plasmalyte 148 solution resulted in less significant
hyponatraemia than half normal saline in children.
Volatile anaesthesia: all inhalation agents have been used in
neonates. Neonates have a higher rate of uptake of inhalational
anaesthetic agents due to their high cardiac output and increased
minute ventilation. The minimum alveolar concentration (MAC)
is lower in neonates than in older infants and similar to older
children. Sevoflurane is the preferred volatile and the POCA data
suggesting that the decreased use of halothane reduced the

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 3 Ó 2016 Published by Elsevier Ltd.

Please cite this article in press as: Frawley G, Special considerations in the premature and ex-premature infant, Anaesthesia and intensive care
medicine (2016), http://dx.doi.org/10.1016/j.mpaic.2016.11.001
 NEONATAL ANAESTHESIA
incidence of cardiac arrest in infants. Time to emergence is faster
with desflurane than any of the other volatile anaesthetic agents;
this may be particularly beneficial in the neonate in whom
extubation is planned.
Total intravenous anaesthesia (TIVA): specific algorithms for
TIVA in neonates have not been designed and most regimens
involve adapting an adult dose scheme. Allegaert has reported that
neonatal propofol clearance is only 10% that of the mature value
at 28 weeks’ gestation, 38% at term and 90% of adult clearance by
70 weeks PMA. Postnatal age (PNA) may also have an additional
effect on maturation of propofol clearance above that predicted by
PMA. Predicted TIVA infusion rates (e.g. 24 mg/kg/hour for the
first 10 minutes in neonates) may cause delayed awakening, hy-
potension and an increased incidence of bradycardia in neonates
and infants. In addition common effect measures used to assess
depth of anaesthesia (spectral edge frequency, bispectral index,
entropy, cerebral state index) are validated in children older than 1
year but not in neonates. Propofol remifentanil anaesthesia has
been reported as a useful technique for screening and laser
photocoagulation of retinal vessels in infants with ROP.
Pain management: a multimodal approach to postoperative pain
control, which may include local anaesthetic infiltration, pe-
ripheral nerve blocks, neuraxial techniques, non-steroidal anti-
inflammatory drugs (NSAIDs), and paracetamol is appropriate.
When opioids are required, intensive monitoring or extended
respiratory support may be required in the postoperative period.
Opioids and sedatives: limited data exist about long-term neu-
rodevelopmental outcomes associated with sedatives and opioid
analgesics in preterm neonates. Large randomized controlled
trials in the Netherlands and the USA (NEOPAIN), and cohort
studies (EPIPAGE in France) have advocated against the routine
use of morphine infusions in mechanically ventilated preterm
infants. Fentanyl boluses have been recommended for analgesia
of ventilated preterm infants undergoing surgery or procedures in
the neonatal intensive care unit (NICU).
Regional anaesthesia: both single-shot and continuous central
neuraxial analgesia as well as peripheral nerve catheter tech-
niques are commonly used in neonatal anaesthesia. Awake spinal
and awake caudal anaesthesia have an established role in
reducing apnoea risk in ex-premature infants undergoing lower
abdominal surgery whereas local anaesthetic infusions through
wound catheters have been described for management of post-
thoracotomy pain in neonates. In all cases the potential for local
anaesthetic toxicity is increased as a result of reduced protein
binding and reduced metabolic capacity (especially cytochrome
P450 isoenzymes CYP1A2 for ropivacaine and CYP3A4 for levo-
bupivacaine). Continuous epidural infusion of bupivacaine in
neonates has demonstrated accumulation after 48 hours and it is
recommended that infusions are limited to no more than 72 hours.
Anaesthetic-induced neuroapoptosis
A relationship between the administration of general anaesthetics
and sedatives during periods of rapid brain growth and an in-
crease in neuronal apoptosis and subsequent long-term behav-
ioural impairment was first reported in 2003 by Jevtovic-
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
Please cite this article in press as: Frawley G, Special considerations in the premature and ex-premature infant, Anaesthesia and intensive care
medicine (2016), http://dx.doi.org/10.1016/j.mpaic.2016.11.001
Todorovic. Subsequent nonhuman research over the past
decade has established that fetal and neonatal exposure to N-
methyl-D-aspartate (NMDA) antagonists and g-aminobutyric acid
(GABA) agonist drugs leads to accelerated neuroapoptosis albeit
at doses not consistent with human exposure. NMDA receptor
antagonists include ketamine and nitrous oxide whereas GABA
agonists include benzodiazepines, barbiturates, propofol and all
volatile anaesthetics. Local anaesthetics and narcotics seem to be
free of concerns. Translation of these observations to humans has
proven much more difficult, and the clinical relevance remains
uncertain. A number of retrospective human clinical trials have
suggested there may be an association between multiple episodes
of anaesthesia and surgery and the subsequent development of
learning disabilities. The Boston Circulatory Arrest Trial sug-
gested that neonatal cardiac surgery poses a specific risk factor.
Retrospective studies have all been influenced by multiple un-
controlled factors making interpretation difficult and; recent
studies demonstrate effect in humans. The US Food and Drug
Administration and the International Anesthesia Research Society
have formed a public-private partnership entitled SmartTots
(www.smarttots.org) to promote prospective investigation of
anaesthesia effects on neurodevelopment and investigate agents
which may protect the neonatal brain. Three prospective studies
are under way to examine the influence of early anaesthetic
exposure on neurodevelopment. The GAS study used awake
regional anaesthesia as a control group and will report 2 and 5
year neurodevelopmental scores. The Pediatric Anesthesia &
Neurodevelopment Assessment (PANDA) project and the Mayo
Safety in Kids (MASK) study aims to examine two groups of
children e those who have been exposed to a single episode of
general anaesthesia during inguinal hernia surgery before age 3
years and those who are siblings of the first group who have not
and assess their neurodevelopment and cognitive functions be-
tween ages 8e15 years. Some studies of premature infants have
suggested behavioural and learning difficulties are more preva-
lent in infants treated surgically rather than medically for con-
ditions such as patent ductus arteriosus or NEC.
Surgery and the premature infant
Neonatal surgical emergencies
Congenital diaphragmatic hernia (CDH): this is a malformation
of the diaphragm that allows bowel to enter the thoracic cavity,
resulting in pulmonary hypoplasia and pulmonary hypertension.
Although the severity of pulmonary hypoplasia and hypertension
are the major determinants of overall survival for infants with
CDH, some mortality may be attributed to prematurity because of
an increase in associated anomalies. The incidence of CDH is
found to be 1: 2000e5000 live births.
Exomphalus, gastroschisis: exomphalus is a midline defect
where abdominal contents are covered by a thin peritoneal sac and
occurs in 1:4000 live births. Both are associated with chromosomal
abnormalities (trisomy 13, 14, 15, 18 and 21) and syndromes
especially VACTERL (vertebral anomalies, anal atresia, and car-
diac, tracheoesophageal, renal/radial, and limb anomalies).
Intestinal atresia: intestinal obstruction requiring neonatal sur-
gery occurs in 1 in 2000 infants. The morbidity and mortality
4 Ó 2016 Published by Elsevier Ltd.
 NEONATAL ANAESTHESIA
from malrotation and midgut volvulus are related to the loss of
intestine. Survivors may develop short-gut syndrome, with the
attendant complications of malabsorption and malnutrition.
Tracheo-oesophageal fistula: a tracheoesophageal fistula (TOF)
is a congenital or acquired communication between the trachea
and oesophagus occurring in 1:2000e4000 live births. The five
main categories of congenital TOFs include oesophageal atresia
(OA) with distal fistula (87%), OA without fistula (8%), isolated
TOF (4%), OA with proximal fistula (0.1%) and OA with prox-
imal and distal fistula (1%). The H-type fistula occurs with an
intact oesophagus.
Necrotizing enterocolitis: the incidence of NEC is 0.3e3/1000
live births and is inversely related to gestational age at birth. The
extremely premature infant is at greatest risk with nearly 12% of
infants under 1500 g developing NEC and mortality exceeding
30%. Multiple factors, including hypoxia, feeding, sepsis,
abnormal colonization of the bowel, and the release of inflam-
matory mediators stimulated by an ischaemic-reperfusion injury
in an immature gut, are thought to lead to NEC.
Patent ductus arteriosus: symptomatic patent ductus arteriosus
(PDA) is common in preterm neonates, occurring in about 30%
of VLBW infants. The PDA shunts blood flow from left to right
resulting in increased flow through the pulmonary circulation
and decreased perfusion of the systemic circulation. Significant
respiratory or cardiac failure may prompt medical (indometh-
acin) or surgical closure.
Operating in NICU
Critically ill neonates in the NICU often require surgical proced-
ures and the risks and benefits of surgical location need discus-
sion. Transferring critically ill neonates to the operating theatre
offers the best operating conditions but may increase perioper-
ative risk. Surgery in NICU is recommended for neonates who
require high-frequency oscillatory ventilation, inhaled nitric
oxide therapy or extracorporeal membrane oxygenation (ECMO).
Surgery in ex-premature infants
Inguinal hernia repair: the incidence of inguinal hernias is
approximately 3e5% in term infants and 13% in infants born at
less than 33 weeks of gestational age. Inguinal hernias in both
term and preterm infants are commonly repaired shortly after
diagnosis to avoid incarceration of the hernia. The most common
postoperative event in ex-premature infants undergoing lower
abdominal surgery is apnoea. Apnoea has been variably defined,
most commonly as a pause in breathing of 15 seconds or longer,
or a pause less than 15 seconds associated with bradycardia
(heart rate <80 beats/minute). Apnoeic events vary in severity
some resolve spontaneously, some require stimulation, and some
require bag-mask ventilation or cardiopulmonary resuscitation.
Cote identified that gestational age was inversely proportional to
the risk of postoperative apnoea in ex-premature infants. The
GAS study has demonstrated a much lower rate of apnoea with
sevoflurane anaesthesia and awake regional techniques. Signifi-
cant postoperative apnoea occurred in 4% of ex-premature in-
fants, with differences between regional (2.8%) and general
anaesthesia (4.2%). Early apnoeic episodes in the first 60
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
Please cite this article in press as: Frawley G, Special considerations in the premature and ex-premature infant, Anaesthesia and intensive care
medicine (2016), http://dx.doi.org/10.1016/j.mpaic.2016.11.001
minutes in the recovery room were more common with general
anaesthesia (3.4 vs 0.9%) whilst late apnoea (30 minutese12
hours postoperatively) was similar with regional (2.2%) and
general anaesthesia (2%). The most significant predictor of
postoperative apnoea was low gestational age. The PMA below
which ex-premature infants should have extended cardiorespi-
ratory monitoring is debated, as are the optimal duration and
type of postoperative monitoring. The most common are 50
weeks PMA and 12 hours apnoea free.
Awake regional anaesthesia for inguinal hernia repair reduces
both the risk of postoperative apnoea and exposure to volatile
anaesthetics. The Vermont Infant Spinal Study has extended the
use of awake spinal anaesthesia to a number of intraabdominal
procedures. High success rates have been reported in centres
where extensive experience exists. A
FURTHER READING
Costeloe K, Hennessy E, Draper ES. Short term outcomes after
extreme preterm birth in England: comparison of two birth cohorts
in 1995 and 2006 (the EPICure studies). Br Med J 2012; 345:
e7976.
O’Reilly M, Sozo F, Harding R. Impact of preterm birth and
bronchopulmonary dysplasia on the developing lung: long-term
consequences for respiratory health. Clin Exp Pharmacol Physiol
2013; 40: 765.
Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to
common anesthetic agents causes widespread neurodegeneration
in the developing rat brain and persistent learning deficits.
J Neurosci 2003; 23: 876e82.
Morriss F, Saha S, Bell E, et al. Surgery and neurodevelopmental
outcome of very low birth weight infants. J Am Med Assoc Pediatr
2014; 168: 746e54.
Byrne MW, Ascherman JA, Casale P, Cowles RA, Gallin PF,
Maxwell LG. Elective procedures and anesthesia in children:
pediatric surgeons enter the dialogue on neurotoxicity questions,
surgical options, and parental concerns. J Neurosurg Anesth 2012;
24: 396e400.
Bhananker SM, Ramamoorthy C, Geiduschek JM, et al.
Anesthesia-related cardiac arrest in children: update from the
pediatric perioperative cardiac arrest registry. Anesth Analg 2007;
105: 344e50.
Davidson AJ, Morton NS, Arnup SJ, et al. Apnea after awake regional
and general anesthesia in infants: the general anesthesia compared
to spinal anesthesia studydcomparing apnea and
neurodevelopmental outcomes, a randomized controlled trial.
Anesthesiol 2015; 123: 38.
Weiss M, Vutskits L, Hansen TG, Engelhardt T. Safe anaesthesia for every
Tot-the SAFETOTS initiative. Curr Opin Anesthesiol 2015; 28: 302e7.
Weber F, Honing G, Scoones G. Arterial blood pressure in anes-
thetized neonates and infants: a retrospective analysis of 1091
cases. Ped Anesth 2016; 26: 815e22.
Sottas C, Cumin D, Anderson BJ. Blood pressure and heart rates in
neonates and preschool children; an analysis from ten years of
electronic recording. Pediatr Anesth 2016; 26(11): 1064e70.
Long J, Joselyn AS, Bhalla T, Tobias JD, De Oliviera GS, Suresh S. The
use of neuraxial catheters for postoperative analgesia in neonates:
a multicenter safety analysis from the pediatric regional anesthesia
network. Anesth Analg 2016; 122: 1965e70.
5 Ó 2016 Published by Elsevier Ltd.