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Anesthesia for ex­premature infants and children
Author: Leila M Pang, MD
Section Editor: Lena S Sun, MD
Deputy Editor: Marianna Crowley, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2018. | This topic last updated: Feb 27, 2018.
INTRODUCTION — Prematurity is defined as a birth that occurs before 37 completed weeks (less than 259
days) of gestation. In ex­premature infants and children, there are high rates of long­term neurodevelopment
impairment and chronic health problems, and an increase in conditions that require surgery and anesthesia
compared with full­term infants.
Ex­premature infants and children include a heterogeneous population, ranging from healthy children born at
36 weeks gestation to formerly extremely premature children with significant medical issues that affect
anesthetic care.
Outside of the neonatal period, the most common surgical procedures performed in these children are
inguinal hernia repair and ophthalmologic procedures (often due to underlying retinopathy of prematurity).
After even minor surgical procedures, ex­premature infants are at higher risk for postoperative apnea than
infants born at term.
This topic will discuss the anesthetic management of children who undergo surgical procedures outside of the
neonatal period. Neonatal management, the acute and chronic complications of prematurity, and medical care
of formerly preterm infants are discussed separately. (See "Care of the neonatal intensive care unit graduate"
and "Management of bronchopulmonary dysplasia" and "Short­term complications of the preterm infant" and
"Long­term complications of the preterm infant".)
TERMINOLOGY — In this topic, we follow the American Academy of Pediatrics policy statement on the
recommended terminology regarding the length of gestation and age for neonates [1], as follows:
Gestational age (GA): time elapsed between the first day of the last menstrual period and the day of
delivery
Chronological age: time elapsed from birth
Postmenstrual age (PMA): GA plus chronological age
Corrected age: Chronological age reduced by the number of weeks born before 40 weeks of gestation
(should only be used for children up to three years of age who were born preterm)
Many studies of ex­premature patients refer to postconceptual age (PCA). The PMA (which is used
throughout this topic) can be estimated by adding two weeks to the PCA.
PREANESTHETIC EVALUATION — A thorough preanesthetic evaluation should be performed to allow for an
individualized plan for management of anesthesia and postoperative care. (See 'Postoperative management'
below and 'Anesthesia management' below.)
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In addition to the usual preoperative evaluation, we focus the assessment of ex­premature children on those
conditions
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care. In particular, preoperative risk factors
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should be identified.
Postoperative apnea
Incidence and severity of postoperative apnea — The incidence of postoperative apnea/bradycardia in
preterm infants is unclear but significant. Apnea has been variably defined, most commonly as a pause in
breathing ≥15 seconds, or one <15 seconds associated with bradycardia (ie, heart rate <80 beats per
minute). Apneic events vary in severity; studies have reported episodes that resolved spontaneously, others
that resolved with stimulation, and some life­threatening events that required bag­mask ventilation or
cardiopulmonary resuscitation [2­5].
Based on both retrospective and prospective studies including heterogeneous patient populations, anesthetic
techniques, and monitoring methods, the risk of having at least one postoperative apneic episode has been
reported at between 5 and 49 percent [2­6].
Risk factors for postoperative apnea — Risk factors for postoperative apnea include the following:
• Postmenstrual and gestational ages – Postmenstrual age (PMA) is the most important risk factor
for postoperative apnea in ex­premature infants, with gestational age (GA) as the next most
important variable. A combined analysis of data from eight prospective studies reported that
postoperative apnea was strongly and inversely related to PMA and, to a slightly lesser degree, GA
[2]. As PMA increases, the probability of apnea decreases, holding GA constant. Likewise, as GA
increases, the probability of apnea decreases, holding PMA constant. However, the effect of
increasing GA is slightly more than half the effect of increasing PMA. Thus, the risk of apnea in the
preterm infant without anemia or apnea in the immediate postoperative period decreases to less
than 5 percent at a PMA of 50 weeks with a GA of 35 weeks, or a PMA of 52 weeks with a GA of 32
weeks.
• Apnea at home – Episodes of apnea at home seem to predispose patients to postoperative apnea
[2]. Infants with a variety of medical conditions associated with prematurity may be monitored for
apnea at home (eg, persistent apnea of prematurity, neurologic or metabolic disorders affecting
respiratory control, and chronic lung disease). (See "Use of home cardiorespiratory monitors in
infants", section on 'Monitoring decisions'.)
• Other risk factors – Other risk factors for postoperative apnea include anemia, neurologic disease,
and a complicated postnatal history [7,8].
Timing of surgery — The optimal timing of surgery (ie, the PMA at which the risk of postoperative apnea
is acceptably low) is unclear. The timing of elective surgery for these patients should reflect the risks
associated with delay of the procedure, additional patient risk factors for postoperative apnea, and the
institutional resources for perioperative care and postoperative monitoring. (See 'Postoperative monitoring'
below.)
Our approach to the timing of surgery for these patients is as simple and understandable as possible:
We recommend delaying elective procedures until 60 weeks PMA for infants born prior to 37 weeks
gestation.
When semielective or urgent surgery is performed before 60 weeks PMA, the infant is monitored for
apnea and bradycardia with nurse observation, pulse oximetry, and electrocardiography (ECG) overnight.
If apnea occurs during the first 12­hour monitoring period, the patient must be admitted to the intensive
care unit (ICU) for more intensive observation.
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Pulmonary disease — Prematurity itself is a dominant risk factor for lung injury and long­term impairment of
pulmonary
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bronchopulmonary dysplasia (BPD), reactive
Continue
airwayordisease,
find outpulmonary
more. artery hypertension, chronic
obstructive lung disease, and associated complications [9­18]. The definition, diagnosis, complications, and
management of children with BPD are discussed more fully separately. (See "Complications and long­term
pulmonary outcomes of bronchopulmonary dysplasia".)
Complications of bronchopulmonary dysplasia that may affect anesthetic management include the following:
Pulmonary function abnormalities – Abnormalities in pulmonary function tests (PFTs) are commonly
found in children and adults with BPD [9,10,19,20]. PFTs frequently show decreased forced expiratory
volume in one second (FEV1) and decreased ratios of FEV1 to forced vital capacity (FVC) (FEV1:FVC),
consistent with airflow limitation and small airway obstruction. Many children with BPD also have a
reactive component to their obstructive lung disease as demonstrated by their clinical response to
steroids and bronchodilators or hyperreactivity to challenge [11,21]. Induction and maintenance of
anesthesia, and airway management, may require modification for these children. (See "Anesthesia for
the child with asthma or recurrent wheezing".)
Pulmonary hypertension – Pulmonary artery hypertension (PAH) is increasingly recognized as an
important complication associated with moderate to severe BPD [22­24]. Children with PAH are at risk for
PAH crisis and death during general anesthesia [23,25]. Risk factors for PAH include extremely low GA at
birth, birth weight <1500 g, small for GA birth weight, prolonged mechanical ventilation, prolonged oxygen
therapy, and anatomic cardiac abnormalities [13,22,26,27]. Children with these risk factors should be
evaluated by a pediatric cardiologist and screened with ECG prior to surgery and anesthesia; a
multidisciplinary decision should be made to determine the timing of surgery. (See "Complications and
long­term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary hypertension'
and "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Epidemiology
and natural history'.)
Sleep hypoxemia – Infants, especially premature infants, have periodic breathing. Premature infants
spend more time breathing periodically and have more periods of oxygen desaturation (SaO2 <90
percent) than full­term infants. Infants with a history of BPD spend more total time at SaO2 <80 percent,
especially during feeding but also to a lesser extent while awake and during active and quiet sleep [28],
and may require nighttime supplemental oxygen. Thus, these children may require supplemental oxygen
postoperatively until fully awake.
Neuropsychiatric conditions – Children who survive with BPD have a higher occurrence of
neurosensory problems such as cerebral palsy and movement disorders than comparable children
without BPD [9]. They also have more than double the incidence of cognitive and motor delays, have
lower IQs, have more severe attention impairments, and exhibit more behavioral problems than
comparable children without BPD. Such children may require sedative premedication before anesthesia.
(See 'Premedication' below.)
Laryngotracheal abnormalities – Infants who require prolonged intubation can develop subglottic
stenosis or tracheomalacia. Airway obstruction may occur during induction of anesthesia, 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 percent, with the
highest incidence occurring in the former extremely preterm infant (<28 weeks GA) [29].
Neurodevelopmental disabilities — Ex­premature 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 behavioral
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and psychological problems [30­32]. The risk of these impairments increases with decreasing GA. (See
"Long­term
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Intraventricular hemorrhage is common in premature infants and can result in posthemorrhagic
hydrocephalus, periventricular hemorrhagic infarction, periventricular leukomalacia, and seizures. (See
"Germinal matrix hemorrhage and intraventricular hemorrhage (GMH­IVH) in the newborn: Prevention,
management, and complications".)
Gastrointestinal disorders
Gastroesophageal reflux – Gastroesophageal reflux (GER) is common during infancy, especially in
preterm infants. For most infants, GER remains asymptomatic, requires no evaluation or intervention,
and resolves on its own by one year of age. (See "Gastroesophageal reflux in premature infants".)
The degree of GER and the effects of medical management may influence decisions regarding airway
management for anesthesia, including intravenous (IV) versus inhalation induction and the choice of
supraglottic airway (SGA) versus endotracheal tube (ETT). (See "Airway management for induction of
general anesthesia".)
Short bowel syndrome – Short bowel syndrome (SBS) is more common in premature and very­low­
birthweight infants, and is often associated with necrotizing enterocolitis. (See "Management of short
bowel syndrome in children".)
Infants with SBS may require enteral feeding and are at risk for electrolyte abnormalities and
dehydration. Perioperative care, including hydration, preoperative oral intake, and laboratory evaluation,
should be coordinated with the patient's medical care providers.
Cardiac abnormalities — There is a higher prevalence of cardiovascular malformations among infants born
prematurely (12.5 cases per 1000 preterm infants versus 5.1 cases per 1000 full­term infants) [33]. The most
common defects are pulmonary atresia with ventricular septal defect (23 percent); complete atrioventricular
septal defect (22 percent); and coarctation of the aorta, tetralogy of Fallot, and pulmonary valve stenosis
(each 20 percent).
ANESTHESIA MANAGEMENT — We suggest that a pediatric anesthesiologist should care for ex­premature
infants who undergo procedures prior to 60 weeks postmenstrual age (PMA). Anesthesia management
specifically related to ex­prematurity is discussed here.
Premedication — Ex­premature infants and children should receive their usual medications preoperatively,
as would children born at term (eg, anticonvulsants, inhaled bronchodilators).
We do not routinely premedicate infants or young children with sedatives. We prefer to use age­appropriate
distraction techniques (eg, parental presence, toys, video games, stickers) prior to anesthesia for most
pediatric patients, rather than sedatives. Premedication with midazolam, a benzodiazepine commonly used in
this setting, may be associated with a higher risk of respiratory complications during and after anesthesia.
(See "Anesthesia for the child with a recent upper respiratory infection", section on 'Premedication' and
"Anesthesia for the child with asthma or recurrent wheezing", section on 'Premedication'.)
However, sedative premedication may be required, particularly for children with behavioral, cognitive, or
anxiety disorders. If sedative medication is administered, the child should be monitored with pulse oximetry by
skilled nursing or anesthesia personnel. Midazolam (0.5 mg/kg orally, maximum dose 15 to 20 mg) is the
most commonly used sedative in this setting. Duration of sedation is prolonged in children <1 year of age
because of hepatic immaturity. Therefore, young children who receive midazolam may require a longer period
of postoperative monitoring until fully awake.
Regional versus general anesthesia — There appears to be no difference in the risk of postoperative
apnea and/or bradycardia between infants who undergo spinal and general anesthesia. Even if regional
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anesthesia can be used without sedative administration, these patients are at risk for postoperative apnea
and
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Regional anesthesia (ie, spinal, epidural, or caudal) is possible for some surgical procedures (eg, inguinal
hernia repair) and could theoretically reduce the incidence of postoperative apnea by avoiding the need for
sedatives, opioids, and general anesthetic medication. However, neuraxial anesthesia in infants is technically
difficult and the duration of block may be insufficient, resulting in high rates of failure, the need to convert to
general anesthesia, and the need for supplemental opioid or sedative medication [5,34,35].
A systematic review of studies comparing regional with general anesthesia for inguinal hernia repair in
preterm infants included seven small randomized studies [36]. There was no difference in the risk of
postoperative apnea/bradycardia between infants receiving spinal compared with general anesthesia. When
infants who had received sedatives were excluded, there was a reduction in the risk of postoperative apnea in
the spinal group (relative risk [RR] 0.53), based on four studies including 129 infants. There was a high
technical failure rate with spinal anesthesia due to either inability to accurately place the spinal needle or drug
failure.
A prospective multi­institutional study randomized infants <60 weeks PMA to regional or general anesthesia
for inguinal herniorrhaphy [5]. Postoperative apnea occurred in 6.1 percent of ex­premature infants, with no
difference between regional and general anesthesia. Apneic episodes in the first 30 minutes in the recovery
room were more common with general anesthesia (3 versus 1 percent). The incidence of apnea between 30
minutes and 12 hours was the same with regional and general anesthesia. In this study, 96 percent of infants
with apnea were ex­premature.
Maintenance of general anesthesia — Randomized trials comparing various general anesthetic regimens
have not been done. The choice of anesthetic agents will necessarily be multifactorial, depending on the
surgical procedure and patient factors. In general, we use short­acting anesthetic medications during surgery
and avoid opioids and neuromuscular blocking agents (NMBAs) when possible.
Sevoflurane (and halothane outside the United States) is the least noxious and therefore the most commonly
used inhalation anesthetic in children. In general, drugs that depend on hepatic clearance have a prolonged
duration of action in ex­premature infants, including sedatives, opioids, and NMBAs. Clearance of propofol is
slower in formerly premature children compared with older children and adults [37]. (See "Anesthesia for the
patient with liver disease", section on 'Effects of liver disease on anesthetic drug administration'.)
When possible, drugs should be titrated to effect.
POSTOPERATIVE MANAGEMENT
Pain management — We follow a multimodal approach to postoperative pain control, which may include
local anesthetic infiltration, peripheral nerve blocks, neuraxial techniques, nonsteroidal antiinflammatory drugs
(NSAIDs), and acetaminophen. When opioids are required, intensive monitoring or extended respiratory
support may be required in the postoperative period (eg, in the intensive care unit [ICU]).
Postoperative monitoring — The postmenstrual age (PMA) below which ex­premature infants should have
extended cardiorespiratory monitoring is debated, as are the optimal duration and type of postoperative
monitoring.
PMA – The risk of postoperative apnea in ex­premature infants without other risk factors is markedly
diminished after 43 weeks PMA but does not reliably decrease to a level of <1 percent until a PMA of 56
weeks with a gestational age (GA) of 35 weeks, or a PMA of 58 weeks with a GA of 32 weeks [2]. While
the risk is decreased at later times, it is not eliminated. Apnea requiring intervention has been reported in
infants up to 54 weeks PMA [5].
Duration of monitoring – Early apnea (within the first 30 minutes) is a strong predictor of late apnea (30
minutes to 12 hours after surgery), but its absence does not exclude the possibility of late apnea
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[2,3,5,38,39].
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Monitoring modalities – The incidence
of detected
is related to the level of monitoring employed
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[2], though there is no evidence that a specific form of monitoring reduces morbidity or mortality. Nursing
observation, in addition to continuous pulse oximetry and electrocardiography (ECG), have been used
most commonly to monitor these patients. Other monitors have included apnea impedance monitoring,
impedance pneumograms, and pneumocardiograms [4,6,35,39].
Each institution that cares for ex­premature infants and children should create guidelines for postoperative
monitoring and ensure availability of personnel experienced with the care of these patients. Our approach to
postoperative monitoring for ex­premature infants is designed to be simple and easily followed:
For ex­premature infants with PMA ≤60 weeks, we monitor using continuous pulse oximetry, ECG, and
recovery room level of nursing care overnight. If apnea occurs during the first 12 hours after surgery, the
patient is admitted to the ICU for closer monitoring.
For ex­premature infants with PMA >60 weeks, we monitor as for standard recovery room care.
SUMMARY AND RECOMMENDATIONS
Ex­premature infants and children include a heterogeneous population, ranging from healthy children
born at 36 weeks gestation to formerly extremely premature children with significant medical issues that
affect anesthetic care.
After even minor surgical procedures, ex­premature infants are at higher risk for postoperative apnea
than infants born at term. (See 'Postoperative apnea' above.)
Gestational age (GA) is defined as the time elapsed between the first day of the last menstrual period
and the day of delivery. Post menstrual age is defined as GA plus chronological age.
The most important risk factor for postoperative apnea is postmenstrual age (PMA). Other risk factors
include GA, apnea at home, anemia, neurologic disease, and a complicated postnatal history. For
otherwise healthy ex­premature infants, we suggest delaying elective surgery until 60 weeks PMA
(Grade 2C). (See 'Postoperative apnea' above.)
Prematurity may be associated with a number of comorbidities that can affect anesthetic management,
including bronchopulmonary dysplasia, neurodevelopmental disabilities, gastrointestinal disorders, and
cardiac abnormalities. (See 'Preanesthetic evaluation' above.)
We use distraction techniques rather than sedative premedication in ex­premature children. (See
'Premedication' above.)
We administer general anesthesia for most surgical procedures for ex­premature infants. For appropriate
surgical procedures, spinal anesthesia may reduce the incidence of early postoperative apnea compared
with general anesthesia, but it does not reduce the overall incidence of apnea and need for postoperative
monitoring, and is associated with a high failure rate. (See 'Regional versus general anesthesia' above.)
We administer inhalation anesthesia with sevoflurane for most ex­premature infants and avoid long­
acting opioids and neuromuscular blocking agents (NMBAs). (See 'Maintenance of general anesthesia'
above.)
We use a multimodal approach to postoperative pain control, which may include local anesthetic
infiltration, peripheral nerve blocks, neuraxial techniques, nonsteroidal antiinflammatory drugs (NSAIDs),
and acetaminophen. (See 'Pain management' above.)
Guidelines for postoperative monitoring for ex­premature patients should be created on an institutional
level. Our approach to postoperative monitoring is as follows:
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• For ex­premature infants with PMA ≤60 weeks, we monitor using continuous pulse oximetry,
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Contributor Disclosures
Leila M Pang, MD Nothing to disclose Lena S Sun, MD Consultant/Advisory boards: Merck [Anesthesia
care (Sugammadex)]; Neuorprorexeon. Employment: Partial salary support to be the Medical Director of
SmartTots, a public-private partnership between FDA and International Anesthesia Research
Society. Marianna Crowley, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
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