Anesthesia for ex-premature infants and children

INTRODUCTION — Prematurity is defined as a birth that occurs before 37 completed weeks (less than 259 days) of gestation. In ex-premature infants and children, there are high rates of long-term neurodevelopment impairment and chronic health problems, and an increase in conditions that require surgery and anesthesia compared with full-term infants.

Ex-premature infants and children include a heterogeneous population, ranging from healthy children born at 36 weeks gestation to children who are formerly extremely premature 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, ex-premature infants are at higher risk for postoperative apnea than infants born at term.

This topic will discuss the anesthetic management of ex-premature children who undergo surgical procedures outside of the neonatal period. Anesthesia for ex-premature neonates is beyond the scope of this topic.

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 "Bronchopulmonary dysplasia (BPD): Management and outcome" and "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth".)

Neurotoxic effects of anesthetics on the developing brain are also discussed separately. (See "Neurotoxic effects of anesthetics on the developing brain".)

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 ex-premature 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.)

In addition to the usual preoperative evaluation, we focus the assessment of ex-premature children on those conditions that are associated with prematurity and that have implications for anesthetic and postoperative care. In particular, preoperative risk factors for postoperative apnea 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 life-threatening events that required bag-mask ventilation or cardiopulmonary resuscitation [2-5].

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 [2-6].

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 ex-premature 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 12-hour monitoring period, the patient must be admitted to the intensive care unit (ICU) for more intensive observation.

Pulmonary disease — Prematurity itself is a dominant risk factor for lung injury and long-term impairment of pulmonary function. Children born prematurely are at higher risk than those born at term for bronchopulmonary dysplasia (BPD), reactive airway disease, pulmonary artery hypertension, chronic obstructive lung disease, and associated complications [9-18]. The definition, diagnosis, complications, and management of children with BPD are discussed more fully separately. (See "Complications and long-term 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 [22-24]. 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 long-term 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 full-term 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, which may require a smaller diameter endotracheal tube. In addition, airway obstruction may occur during induction of anesthesia. 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 — 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 behavioral and psychological problems [30-32]. The risk of these impairments increases with decreasing GA. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)

Intraventricular hemorrhage is common in premature infants and can result in posthemorrhagic hydrocephalus, periventricular hemorrhagic infarction, periventricular leukomalacia, and seizures. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome".)

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 very-low-birthweight infants, since necrotizing enterocolitis often occurs in these infants. (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 full-term 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 ex-premature infants who undergo procedures prior to 60 weeks postmenstrual age (PMA). Anesthesia management specifically related to ex-prematurity is discussed here.

Premedication — Ex-premature 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 age-appropriate 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, and children who have had multiple previous procedures or hospitalizations. 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 anesthesia can be used without sedative administration, ex-premature infants are at risk for postoperative apnea and require appropriate postoperative monitoring. (See 'Postoperative monitoring' below.)

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. There is a reported high rate of failure requiring conversion to general anesthesia and/or the need for supplemental opioid or sedative medication [5,34-36].

In a 2015 meta-analysis of seven small randomized trials of preterm infants who underwent inguinal hernia repair, the incidence of apnea/bradycardia was similar in infants who received spinal versus general anesthesia [36]. 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 that included 129 infants. However, there was a high technical failure rate with spinal anesthesia due to either inability to accurately place the spinal needle or drug failure.

Maintenance of general anesthesia — For most anesthetics and analgesics, there is a lack of data on safety and efficacy in ex-premature infants, and most such drugs are used "off label." . 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 short-acting 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 ex-premature 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 ex-premature infants should have extended cardiorespiratory monitoring is debated, as are the optimal duration and type of postoperative monitoring. Each institution that cares for ex-premature 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 ex-premature infants is designed to be simple and easily followed:

●For ex-premature infants with PMA ≤60 weeks, we monitor using continuous pulse oximetry, electrocardiography (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 ex-premature infants with PMA >60 weeks, we monitor using standard recovery room care.

Parameters that should be considered when deciding on postoperative monitoring for ex-premature infants include the following:

●PMA – The risk of postoperative apnea in ex-premature 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].

In a retrospective study of neonatal intensive care patients who underwent surgery and recovered in the post-anesthesia care unit, major postoperative respiratory events occurred in 9.1 percent of patients [38]. A birth weight of <1.58 kg and a PMA at the time of surgery of <41 weeks were strongly associated with an increased risk of a major postoperative respiratory event. The presence of both features was associated with a sevenfold increase in the risk.

●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 [2,3,5,39,40].

●Monitoring modalities – The incidence of detected apnea is related to the level of monitoring used [2], though there is no evidence that a specific form of monitoring reduces morbidity or mortality. A combination of nursing observation, continuous pulse oximetry and ECG, has been used most commonly to monitor these patients. Other monitors have included apnea impedance monitoring, impedance pneumograms, and pneumocardiograms [4,6,35,40].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric anesthesia".)

SUMMARY AND RECOMMENDATIONS

●Definitions – Gestational age (GA) is defined as the time elapsed between the first day of the last menstrual period and the day of delivery. Postmenstrual age (PMA) is defined as GA plus chronological age. (See 'Terminology' above.)

●Risk of postoperative apnea

•After even minor surgical procedures, ex-premature infants are at higher risk for postoperative apnea than infants born at term. (See 'Postoperative apnea' above.)

•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 ex-premature infants, we suggest delaying elective surgery until 60 weeks PMA (Grade 2C). (See 'Postoperative apnea' above.)

●Comorbidities

•Ex-premature 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.

•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.)

●Premedication – We use distraction techniques rather than sedative premedication in ex-premature children. (See 'Premedication' above.)

●Anesthetic management

•We use general anesthesia for most surgical procedures for ex-premature infants. For appropriate surgical procedures, spinal anesthesia may reduce the incidence of early postoperative apnea compared with general anesthesia, but it may 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 use inhalation anesthesia with sevoflurane for most ex-premature 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.)

●Postoperative monitoring – Guidelines for postoperative monitoring for ex-premature patients should be created on an institutional level. Our approach to postoperative monitoring is as follows:

•For ex-premature infants with PMA ≤60 weeks, we monitor using continuous pulse oximetry, electrocardiography (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 intensive care unit (ICU) for closer monitoring.

•For ex-premature infants with PMA >60 weeks, we monitor using standard recovery room care.