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Special considerations in the premature and ex-premature infant

After reading this article, you should be able to: define the terms prematurity, extreme prematurity and list the well-known complications of premature infants explain the basic principles of anaesthetizing a RDS may be complicated by air leak (pneumothorax, pneu- Mean survival rates for babies born at 24 weeks and 27 weeks are momediastinum, pulmonary interstitial emphysema) and lead to currently 50% and 90% respectively, although levels of morbidity for bronchopulmonary dysplasia (BPD) and chronic lung disease the most premature infants may be high. This article describes the clinical conditions unique to the premature and ex-premature infant, and some BPD is defined as oxygen dependency for more than 28 days common surgical procedures and special considerations for the conduct after birth and an abnormal chest radiograph. The chest radio- of anaesthesia in this vulnerable population.
graph changes in early BPD may be indistinguishable from theground glass appearance of RDS, but later radiographs show Keywords Apnoea; pain; premature infant; respiratory distress patchy atelectasis and cystic changes with hyperexpansion and The course of RDS has been greatly ameliorated by modern neonatal intensive care practice. Exogenous surfactant isadministered prophylactically within hours of birth. Nasal continuous positive airway pressure (nCPAP) is the method of choice for ventilatory support, and results in an increase in Full-term neonate: 37e42 weeks’ gestation and aged less than functional residual capacity (FRC), reduction in atelectasis and improved work of breathing. Intermittent positive pressure Premature neonate: less than 37 weeks’ gestation.
ventilation (IPPV) increases the risk of BPD and is used only if Extreme preterm neonate: less than 28 weeks’ gestation.
necessary (e.g. for the administration of surfactant, for VLBW Post-conceptional age: gestational age plus post-natal age.
infants at <28 weeks, and if oxygenation with nCPAP is inade- Low birth weight (LBW): less than 2500 g.
quate with a fraction of inspired oxygen (FiO Very low birth weight (VLBW): less than 1500 g.
Babies are extubated to nCPAP as soon as possible.
Extremely low birth weight (ELBW): less than 1000 g.
Different ventilation modes are used to reduce volu/baro- trauma. These include various forms of patient-triggered venti- lation (such as pressure support and proportional assist The neonatal period is one of major physiological changes, with ventilation) and minimization of excessive tidal volumes transition from intrauterine to extrauterine life. The premature (volume targeted ventilation and high frequency infant has to undergo these same changes, but in the context of The use of strategies to allow permissive hypercapnia may also reduce the risk of ventilator-induced injury.
Steroids have an adverse effect on development of the brain Respiratory distress syndrome and chronic lung disease and are no longer used to facilitate weaning from long-term Respiratory distress syndrome (RDS) results from immaturity of the lungs, particularly the production of surfactant in the CLD occurs in 15e50% of VLBW infants. The severity of CLD premature infant. RDS is typified by tachypnoea, dyspnoea, is estimated from the duration of nCPAP and oxygen depen- cyanosis and ‘grunting’, non-compliant lungs, widespread atel- dency, rather than the duration of ventilation.
ectasis on chest radiograph and the presence of hyaline Ex-premature babies are susceptible to respiratory infection in membranes in terminal airways (previous terminology: hyaline childhood, particularly in the first year of life. Reversible obstructive airway disease is common and they may have RDS is invariable in infants born at less than 28 weeks’ acquired subglottic stenosis as a consequence of prolonged Antenatal corticosteroid administered to mothers in preterm labour induces surfactant production and reduces the incidence Apnoea is a pause in breathing of more than 20 seconds or one ofless than 20 seconds associated with bradycardia and/orcyanosis.
Guy Bayley MB BS MRCP MRCPCH FRCA is a Consultant Paediatric Apnoea of prematurity is commonly seen in neonatal units, Anaesthetist at Bristol Royal Hospital for Children, Bristol, UK. Conflicts and may be classified as central (brainstem, peripheral chemo- receptor immaturity), obstructive (reduced tone, asynchrony of Ó 2010 Elsevier Ltd. All rights reserved.
diaphragm/upper airway activity, excessive neck flexion, struc- signs progressing to apnoea with shock and disseminated intra- tural abnormalities) or of mixed cause.
vascular coagulation (DIC). Intestinal perforation may cause In adult life, hypoxia and hypercapnia increase ventilation.
a localized mass and the abdominal wall may be reddened in the Premature and newborn term babies respond to hypoxia by presence of peritonitis. NEC is associated with pneumatosis (gas a brief increase in ventilation followed by apnoea and have within the bowel wall), and a characteristic appearance on a blunted response to hypercapnia. In the term infant, normal a radiograph of dilated thickened loops of bowel with intramural responses to hypercapnia and hypoxia are seen by 3 weeks of gas. Free gas may be visible on horizontal shoot-through in the age, but this is delayed in premature infants.
presence of a perforation. Investigations may also reveal low Apnoea in premature infants is exacerbated by hypoxia, platelet count, raised C-reactive protein and metabolic acidosis.
sepsis, intracranial haemorrhage, metabolic abnormalities, Babies with severe disease may have exposed T antigen on red hypo/hyperthermia, upper airway obstruction, heart failure, blood cells, which leads to haemolysis in the presence of trans- anaemia, vasovagal reflexes and drugs, including prostaglandins fused blood products containing anti-T antibodies. Blood prod- ucts with low-titre anti-T antibodies will be required for Apnoeas are treated by stimulation, bag-mask ventilation, T-antigen-positive infants (packed cells reconstituted in SAG-M addressing underlying abnormalities, the use of respiratory stimulants such as caffeine or aminophylline, nCPAP or Treatment of NEC consists of general supportive measures, antibiotics, and resting the gut with 7e10 days of total parenteral Term neonates are at low risk of postoperative apnoea after nutrition. Half the infants with NEC require surgery for intestinal routine minor surgery at 44 weeks post-conception. However, in perforation or following failure of medical treatment. Surgical premature neonates the probability of postoperative apnoeas options include: laparotomy for resection of necrotic bowel and decreases to less than 1% only at 60 weeks post-conception.
formation of a proximal stoma and distal mucous fistula; gutresection and primary anastomoses; placement of a peritoneal drain in those unsuitable for laparotomy; or for infants with The arterial duct is one of the fetal shunts and is closed in 3e4 inoperable disease, proximal defunctioning jejunostomy and days in 90% of term and ‘well’ premature babies. The duct closes ‘second look’ laparotomy at 24 hours if the baby survives.
in response to a rise in oxygen tension after birth and a fall incirculating prostaglandins. Patent ductus arteriosus (PDA) is seen in 50% of VLBW infants due to low oxygen tension, Survival of extreme preterm infants has improved considerably continuing high prostaglandin levels, or abnormal stimuli such in recent years. However, 21% of babies born at less than 25 as acidosis and expansion of the circulating volume.
weeks’ gestation have severe disability, and 41% have significant Aorto-pulmonary shunting though the PDA causes high cognitive impairment. A major determinant of cerebral impair- pulmonary blood flow, worsening RDS, cardiac failure and low ment is germinal matrix intraventricular haemorrhage (IVH), diastolic pressure. PDA is a risk factor for intraventricular hae- particularly complicated by ventricular enlargement, paren- morrhage, necrotizing enterocolitis and CLD. PDA typically chymal infarction or cystic periventricular white-matter injury.
becomes symptomatic at 5e10 days as pulmonary vascular Major IVH usually occurs within the first few days of life and is resistance falls; it presents with worsening respiratory function, bounding pulses, a continuous murmur and chest radiograph Factors that have been shown to increase the incidence of IVH that shows cardiomegaly and increased lung shadowing. Diag- or later neurodevelopmental delay include RDS, hypotension or nosis is confirmed by echocardiography.
fluctuating blood pressure, the use of hypertonic infusions and Conventional treatment for symptomatic PDA is fluid restric- tion, diuretics (furosemide) or medical closure with indometh- The normal lower limit of mean arterial blood pressure (MAP) is roughly equivalent to the gestational age on the first day of life, (NSAIDs) may worsen renal function, and have been associated with a MAP of at least 30 mmHg for all infants by day 3 of life.
with gastrointestinal haemorrhage and perforation. These agents Management of hypotension requires judicious use of volume are contraindicated in the presence of thrombocytopenia.
expansion (crystalloid or colloid) and the early use of inotropic Surgical closure of symptomatic PDA is indicated for failed agents such as adrenaline, dopamine or dobutamine. Aggressive medical treatment or when NSAIDs are contraindicated.
volume expansion should be avoided, especially in the first fewdays of life.
Periventricular leukomalacia describes histological changes in Necrotizing enterocolitis (NEC) occurs mainly in preterm infants, periventricular white matter seen in premature infants. The with an incidence of about 7% and a mortality of 15e30%. It has pathogenesis of periventricular leukomalacia is associated with a multifactorial aetiology, but common features include prema- hypoxic-ischaemic or toxic injury, infection, impaired cerebral turity and poor mucosal integrity, hypoxia, early feeding with autoregulation, cerebral ‘steal’ due to a large PDA and severe formula milk and colonization with pathogenic bacteria.
hypocarbia. Bilateral occipital cystic periventricular leukomalacia NEC causes inflammation and transmural necrosis and can is a very strong predictor of cerebral palsy.
affect any part of the intestine, typically the terminal ileum,caecum and ascending colon. The classical presentation is of Retinopathy of prematurity and oxygen toxicity abdominal distension, bloody stool and bile-stained aspirates, Retinopathy of prematurity (ROP) is seen in LBW infants less but signs of sepsis may predominate, with vague non-specific than 32 weeks’ gestation. Hyperoxia in the first weeks of life Ó 2010 Elsevier Ltd. All rights reserved.
causes vasoconstriction of retinal vessels, which leads to retinal the infant. Disadvantages include limited access and light for ischaemia and a subsequent vasoproliferative phase. Good surgeons. Laparotomy for NEC may be difficult because of neonatal care, ophthalmic screening and treatment can prevent hypovolaemia, significant third-space losses, bleeding and coa- gulopathy. Extreme care should be taken if transporting the There is concern that even brief exposure to high oxygen neonate to theatre, in particular not to displace intravenous lines levels is associated with increased morbidity and mortality in VLBW infants; fluctuations in oxygen levels should be avoided  Anaesthesia monitoring should be as standard for any oper- and oxygen saturation maintained between 88e95%, not ating room. Ventilator dead-space should be minimized but end exceeding 95%. Newborn resuscitation should be carried out tidal carbon dioxide may still significantly under-read. A T-piece with room air rather than 100% oxygen.
should be available for hand ventilation with an air/oxygenmixer. Oxygen saturation should not exceed 95%.
 Invasive arterial monitoring is useful in the septic patient Thermoregulation in the neonate is limited and easily over- receiving inotropes, or when cardiovascular stability is antici- whelmed by environmental conditions. There is a great potential pated. An umbilical arterial catheter may be present from birth; for heat loss (high body surface area to body weight ratio, its distal end should be sited above the diaphragm between the increased thermal conductance, increased evaporative heat loss sixth and tenth vertebrae. Peripheral arterial cannulation (radial, through the skin) and limited heat production through brown fat posterior tibial, dorsalis pedis) is aided by a ‘cold’ light. The metabolism. The preterm baby is particularly vulnerable as the femoral or axillary artery may be used. The brachial artery immature skin is thin and allows major heat (and evaporative should be avoided because it is an end artery with poor collateral fluid) losses. The principle of anaesthesia in these infants is for minimal handling in a warm environment.
 Central venous access may be useful if large-volume trans- fusions are anticipated or inotropes are required. An umbilical venous catheter may be present from birth and is useful for the Pain pathways develop during the second and third trimester. By first week of life. The tip of the umbilical venous catheter should 26 weeks’ gestation premature neonates respond to tissue be in the inferior vena cava at the level of (but not in) the right damage by withdrawal reflexes and activation of the stress atrium. Ultrasound guidance may be useful to aid in femoral response. Pathways between the thalamus and somatosensory cortex function by 29 weeks’ gestation. The precise gestational  Blood for transfusion and a means for warming infused fluids age when a neonate is able to perceive pain is unknown.
 The temperature of the operating room should be raised to Anaesthetic agents in the premature infant 25 C and there should be a means of warming the baby (overhead Recent work has investigated the effects of exposure of the developing brain to anaesthetic drugs such as midazolam,  The surgical drapes should be lightweight, ideally transparent nitrous oxide, isoflurane and ketamine. In animal experiments plastic, so that the baby (and the tracheal tube) can be clearly prolonged exposure to these agents were found to cause wide- seen. Drapes should not be stuck to the fragile skin. The surgeons spread apoptosis with persistent memory/learning impairments.
must not rest their hands on the infant.
The mechanism appears to be due to blockade of glutamate and  Anaesthesia should be induced only when all are fully g-aminobutyric acid receptors. The relevance to clinical practice prepared. The baby is intubated orally, either with an uncuffed is unclear, but only essential surgery should be performed in tracheal tube (2.0e3.0 mm internal diameter (ID)). The tracheal tube should be carefully strapped in place (not tied to a bonnet),and the position rechecked every time the infant is moved.
Conduct of anaesthesia in the premature infant  Avoid hyperventilation, oxygen saturation greater than 95%, General considerations: anaesthesia and surgery in the prema- high-peak inspiratory pressures and barotrauma. Permissive ture neonate is high risk, require careful collaboration with the neonatal intensive care unit (NICU), and close attention to detail  Isotonic fluids should be used during surgery (0.9% saline, Hartmann’s or Ringer’s lactate), given as boluses of 10e20 ml/kg  Consent should be discussed with the parents and questions and titrated to blood pressure, heart rate, capillary refill time and base excess if available. Avoid swings in blood pressure and  A full history should be taken, with particular note of excessive volume loading. Blood should be transfused to main- cardiorespiratory status, acidebase balance, full blood count tain a haematocrit of 36% in the newborn infant (high levels of (including platelet count), coagulation, urea, and electrolytes, fetal haemoglobin) and 30% in the chronically transfused infant.
 Blood glucose should be monitored and glucose-containing  The baby should be carefully examined. Identify the site and maintenance fluids continued during surgery (e.g. 10% dextrose state of intravenous lines. If intubated, assess bilateral air entry, size and length of the tracheal tube, recent chest radiograph and  Multimodal analgesia should be used for pain relief (e.g.
regional anaesthesia, local anaesthetic infiltration, paracetamol  Surgery can take place in the NICU (PDA ligation is frequently and opioids, most commonly fentanyl). Epidural catheters can be performed in the NICU). The advantages are a thermoneutral inserted via the caudal route. Sucrose analgesia may be useful in environment, use of neonatal ventilator and minimal handling of the NICU for painful interventions such as cannulation.
Ó 2010 Elsevier Ltd. All rights reserved.
 The child may have CLD, reduced lung compliance, reversible  Regional anaesthesia (spinal or caudal anaesthesia) may be obstructive airway disease, gastro-oesophageal reflux, impaired suitable in experienced hands and may reduce postoperative renal concentrating ability, chronic anaemia, failure to thrive, apnoeas, provided supplemental sedation is avoided.
neurodevelopmental delay and/or seizures, subglottic stenosis Anaesthesia for ventriculoperitoneal shunt  Prolonged exposure in a cold theatre may result in  The child will be susceptible to postoperative apnoeas up to 60 weeks post-conception and may require postoperative nCPAP  May require morphine for postoperative analgesia or ventilation; oral caffeine may be considered, particularly if (in combination with paracetamol and ibuprofen); the child is at  Careful preoperative resuscitation and correction of acidebase balance and coagulopathy. Platelet transfusion and fresh-frozen 1 Greenough A, Premkumar M, Patel D. Ventilatory strategies for the extremely premature infant. Pediatr Anaesth 2008; 18: 371e7.
 Fluid shifts during surgery may be significant, requiring up to 2 Tan A, Schulze A, O’Donnell CPF, Davis PG. Air versus oxygen for 60e80 ml/kg of volume resuscitation.
resuscitation of infants at birth. Cochrane Database Syst Rev 2004; 3.
 Careful positioning for left thoracotomy and placement of clip Bingham R, Lloyd Thomas A, Sury M, eds. Hatch and Sumner’s textbook of Place pulse oximeter or arterial line on lower half of the body to paediatric anaesthesia. Edinburgh: Churchill Livingstone, 2007.
detect accidental ligation of descending aorta; persistent desatu- Cote C, Lerman J, Todres D. A practice of anesthesia for infants and ration after reinflation of the lung indicates accidental ligation of children. 4th edn. Saunders Elsevier, 2010.
pulmonary artery. Correct placement of clip is indicated by rise in Dalens B. Anesthesia at early ages. Best Pract Res Clin Anaesthesiol blood pressure, particularly diastolic blood pressure.
Intercostal nerve block by surgeon is useful (under direct Management of the neonate: anaesthetic considerations. In: Bissonnette B, Dalens B, eds. Principles and practice of pediatric anaesthesia. Philadelphia: McGraw-Hill, 2003.
 Caudal anaesthesia or ilioinguinal nerve block and para- Rennie J, ed. Roberton’s textbook of neonatology. 4th edn. Oxford: cetamol for postoperative analgesia can be used.
Ó 2010 Elsevier Ltd. All rights reserved.



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