Neonatal Anaesthesia 1: Physiology Anaesthesia Tutorial of the Week 65

Metadata

• Author: WFSA Resource Library
• Full Title: Neonatal Anaesthesia 1: Physiology Anaesthesia Tutorial of the Week 65
• Category: #articles
• Document Tags: ../../../Knowledge/Medicine/Paediatrics
• URL: https://resources.wfsahq.org/atotw/neonatal-anaesthesia-1-physiology-anaesthesia-tutorial-of-the-week-65/

Highlights

• Infant: child less than 1 year of age (View Highlight)
• Full term neonate: born between 37-40 weeks and aged less than 1 month (View Highlight)
• Premature neonate: child born before 37 weeks gestation (View Highlight)
• Extreme preterm neonate: child born less than 28 weeks gestation (View Highlight)
• Development of the lung starts early in embryonic life, pulmonary surfactant is produced at 24-26 weeks; alveolar development begins at 32 weeks and is complete by 18 months of age (View Highlight)
• Extreme prems require pulmonary surfactant and CPAP or IPPV after delivery for survival and are susceptible to bronchopulmonary dysplasia and later chronic lung disease. (View Highlight)
• The newborn lung is small in relation to body size, tidal volumes small in absolute terms (7 ml/kg), the respiratory rate is high (30-40 breaths per minute) and there is little respiratory reserve. The deadspace and resistance of the breathing circuit should be kept to a minimum in infants who are breathing spontaneously, to minimise the work of breathing. (View Highlight)
• The tongue is relatively large, the occiput prominent so the head tips forward and the airway is easily obstructed. Airway patency is best maintained by chin lift, avoiding compression of the floor of the mouth, possibly with the use of an oropharyngeal airway. (View Highlight)
• The larynx is conical in shape, the narrowest portion at the level of the cricoid cartilage. Uncuffed tracheal tubes are commonly used in neonates to avoid airway oedema, also later subglottic stenosis. (View Highlight)
• Lung compliance is high and the ribs soft and elastic; chest wall compliance is higher compared with adults. Chest wall stability increases by about 1 year of life. The distending pressures on the lung are low and the newborn infant is prone to lung collapse, especially under general anaesthesia (View Highlight)
• Ventilation under anaesthesia should be at least assisted and infants should not be left to breathe spontaneously through a tracheal tube. CPAP or PEEP should be employed to avoid atelectasis. (View Highlight)
• Anaesthetic agents depress the pharyngeal dilator muscles leading to upper airway obstruction. Neonates should be intubated for all except the briefest of procedures and positive pressure ventilation should be used. (View Highlight)
• Neonates have a high metabolic requirement for oxygen (6-8 ml/kg/min vs 4-6 ml/kg/min in adults). (View Highlight)
• Tissue oxygen delivery is achieved by a relatively high cardiac output (300ml/kg/min vs 60-80 ml/kg/min in adults), high heart rate (120-180 beats per min) and respiratory rate (30-40 breaths per min); neonates do not tolerate bradycardia or interruption in ventilation for any length of time and become hypoxic very readily. Hypoxia may lead to profound bradycardia. (View Highlight)
• At birth, foetal haemoglobin (HbF) forms 70-80% of total haemoglobin. Foetal haemoglobin delivers oxygen effectively to the tissues in the hypoxic conditions found during foetal life but tends to ‘hold on’ to oxygen in normal conditions after birth (the oxygen dissociation curve for foetal haemoglobin is shifted to the left). This is compensated for by a relatively high haemoglobin concentration at birth, from 13-20 g/dl, depending on the degree of placental transfusion, increasing the availability of oxygen to be delivered to the tissues. (View Highlight)
• Adult haemoglobin, HbA2 increases from birth, being the dominant haemoglobin by the first few months of life. It is very efficient at delivering oxygen to the tissues, even more so during infancy than adult life (the oxygen dissociation curve is shifted to the right during infancy). This is because there are higher levels of 2,3 diphosphoglycerate (2,3 DPG) during infancy which helps ‘offload’ oxygen to the tissues. (View Highlight)
• Coupled with a relatively high cardiac output, tissue oxygen delivery is extremely efficient in infants compared to adults. These factors affect the triggers for transfusion or the haemoglobin level at which a child should be considered significantly anaemic. Equivalent haemoglobin concentrations for the same tissue oxygen delivery are 8g/dl, 6.5g/dl and 12g/dl for an adult, infant and neonate respectively. An infant tolerates anaemia fairly well, a neonate does not. (View Highlight)
• If a child does require transfusion, they should be transfused if possible from one donor unit. A useful formula for transfusion is:
  • 4 ml/kg packed cells raises the Hb by 1g/dl
  • 8ml/kg whole blood raises the Hb by 1 g/dl (View Highlight)
• The control of ventilation is immature at birth and neonates are at risk from postoperative apnoeas, especially if born prematurely, anaemic or exposed to opiates. (View Highlight)
• The ventilatory response to hypercapnia is blunted in the first few weeks of life. (View Highlight)
• Neonates respond to hypoxia by a brief increase in ventilation followed by apnoea. The apnoeic response to hypoxia is probably due to respiratory muscle fatigue or upper airway obstruction. (View Highlight)
• Control of respiration matures by three weeks of age in the term baby. (View Highlight)
• Anaesthetic agents depress ventilation in a dose dependent manner. (View Highlight)
• Term neonates are probably not at risk of postoperative apnoea after routine minor surgery (avoiding opiates) from 1 month of age (i.e. 44 weeks PCA) (View Highlight)
• Premature neonates are at low risk of postoperative apnoeas after 60 weeks post conception. (View Highlight)
• Heart rate is an important determinant of cardiac output and the heart rate should be maintained in the normal range (120-180 bpm, term neonate). (View Highlight)
• The Frank-Starling relationship regulates cardiac output as in adults but is limited; neonates increase cardiac output with careful volume loading (fluid bolus 5-10ml/kg), but they do not tolerate fluid overload. (View Highlight)
• Contractility in neonates is high due to high sympathetic tone, especially around the time of birth, and this also explains the high resting heart rate of neonates. (View Highlight)
• Cholinergic innervation is well developed at birth and vagally mediated cardiac reflexes are obvious, even in premature infants. Hypoxia and laryngoscopy lead to profound bradycardia. (View Highlight)
• Afterload is also a major determinant of cardiac output. The neonatal heart is exquisitely sensitive to increases in systemic or pulmonary vascular resistance which will reduce the cardiac output. (View Highlight)
• The myocardium is dependent on extracellular calcium for contraction and ionised hypocalcaemia is poorly tolerated. Hypocalcaemia may occur after large volume blood or blood product transfusion or in a child who is septic. (View Highlight)
• Neonates are more sensitive to the negative inotropic effects of anaesthetic agents than older children; the effect is more marked with halothane than isoflurane or sevoflurane. Avoid deep anaesthesia, especially ventilation with high concentrations of volatile agents (View Highlight)
• Atropine may counteract the reduction in cardiac output seen with volatile agents and will protect against vagally mediated reflexes, especially those associated with laryngoscopy and intubation. It is useful as premedication, although no longer routinely used, but should always be drawn up ready. (View Highlight)
• When the umbilical cord is clamped and the low resistance placental circulation is lost, there is a sudden rise in systemic vascular resistance (View Highlight)
• With the first breath and expansion of the lungs there is an increase in pH and increased oxygenation, the pulmonary vascular resistance decreases and pulmonary blood flow increases. The increased pulmonary venous return to the left atrium raises the left atrial pressure above the right and as a result the flap valve of the foramen ovale closes. (View Highlight)
• The duct closes in response to oxygen, prostaglandins, bradykinin and acetylcholine. Anatomical closure by constriction occurs at 6hrs, complete occlusion usually occurs at 6 weeks of age. (View Highlight)
• The pulmonary vascular resistance may increase in response to hypoxia, hypercarbia or acidosis. Severe pulmonary hypertension may ensue, with reopening of the foetal shunts, causing profound hypoxia and cardiovascular compromise. (View Highlight)
• The liver in the newborn contains 20% of the hepatocytes found in adults and continues to grow until early adulthood. (View Highlight)
• Phase I processes (metabolic, e.g. the cytochrome P450 system) are significantly reduced at birth whilst phase II processes (conjugation) may be well developed (sulfation) or limited (glucuronidation). Paracetamol is useful in neonates as it is excreted by sulfation (rather than glucuronidation as in adults). (View Highlight)
• In general, drug effects are prolonged in neonates and drugs should be titrated to effect, given by bolus rather than infusion, or plasma levels monitored as appropriate. (View Highlight)
• Maturation of enzymatic processes increases over the first few weeks of life and the half-life of drugs such as morphine reaches adult levels at 2 months of life. Neonates require significantly less morphine than older children, especially in the first week of life. Morphine should be given as a bolus dose of 10 mcg/kg; beware, the half-life may be up to 8 hours (double that of older children). (View Highlight)
• Plasma protein binding is reduced in neonates (low levels of α1-acid glycoprotein) and drugs that are plasma protein bound (such as local anaesthetics) may demonstrate increased toxicity in infants. (View Highlight)
• Neonates have reduced hepatic stores of glycogen and immature gluconeogenic enzyme systems. Coupled with a high metabolic rate, this makes them susceptible to hypoglycaemia following starvation. Neonates should not be starved excessively (breast milk feed 4 hours preoperatively, clear fluids 2 hours preoperatively), and if possible, blood sugar should be measured during surgery. Glucose should be added to the intraoperative fluids, for instance, add 25ml of 50% dextrose to 500ml of Ringers Lactate to give a solution of 2.5% dextrose in Ringers Lactate. (View Highlight)
• Nephrogenesis is completed at 36 weeks gestation and no further nephrons are produced (impaired nephrogenesis in premature infants has been related to hypertension in adult life). Further increase in renal mass is due to the growth of tubules. (View Highlight)
• The glomerular filtration rate at term is low and reaches adult indexed values only at 2 years of age. Creatinine at birth reflects the mother’s creatinine and falls to reflect renal function of the baby by 1 week of age. (View Highlight)
• Tubular function matures over the first few months of life; infants usually produce urine that is isotonic to plasma, but if required, can concentrate their urine to achieve an osmolality of 500-700 mOsmol/kg H2O. Adult values (urinary osmolality typically 1200-1400 mOsmol/kg H2O) are reached by a year of age. Infants tolerate fluid restriction poorly and become dehydrated quickly. (View Highlight)
• The neonate’s limited renal function is appropriate to the period of rapid growth after birth – growth has been termed the ‘third kidney’. However, in the postoperative (catabolic) infant, renal insufficiency may become apparent and the neonate does not handle fluid or sodium overload. (View Highlight)
• The extracellular fluid compartment is expanded in neonates, with total body water representing 85% of body weight in premature babies, 75% of body weight in term babies, compared to 60% body weight in adults. (View Highlight)
• The expanded extracellular fluid compartment results in an increased volume of distribution of commonly used drugs and increased dose requirements, despite increased sensitivity (muscle relaxants, intravenous induction agents). (View Highlight)
• Contraction of the extracellular fluid compartment and weight loss in the first few days after birth is a normal physiological process, due in part to a diuresis induced by atrial naturetic peptide (ANP) secondary to increased pulmonary blood flow and stretch of left atrial receptors. After this period of negative water and sodium balance, water and sodium requirements increase to match those of the growing infant. (View Highlight)
• Fluids should therefore be restricted until the postnatal weight loss has occurred. Liberal fluid regimens in the first few days of life have been shown to be associated with worse outcomes in premature infants (increased patent ductus arteriosus, necrotising enterocolitis and death). Fluid requirements increase incrementally from day 1 of life (60ml/kg/day) to 150ml/kg/day at 1 week of life (up to 180ml/kg/day in a premature neonate with high evaporative losses) (View Highlight)
• Heat production is limited and there is a greater potential for heat loss (high body surface area to body weight ratio, increased thermal conductance, increased evaporative heat loss through the skin). The newborn infant is able to increase heat production through brown fat metabolism (non shivering thermogenesis, inhibited by volatile agents), however this is at the expense of increased oxygen consumption. (View Highlight)
• Hypothermia is associated with hypoxia, impaired wound healing, prolonged coagulation with reduced platelet function, reduced drug metabolism, cerebral depression, myocardial depression, acidosis, decreased immunity, patient discomfort. (View Highlight)
• The lower limit for cerebral autoregulation in neonates is not known, but is thought to be around a cerebral perfusion pressure of 30 mmHg. Appropriate mean arterial blood pressures for extreme premature neonates are controversial but it generally accepted that the mean arterial pressure equates to the gestational age of the child during the first day of life, rising to a minimum of 30mmHg by 3 days. (View Highlight)
• Survival of extreme preterm infants has improved considerably in recent years, but this has been associated with high levels of disability. A major determinant of cerebral impairment is intraventricular haemorrhage (IVH) which usually occurs within the first few days of life. Steroids are thought to interfere with the development of the brain in the newborn and avoidance of postnatal dexamethasone is currently the single most important factor to improve neurological outcomes in premature infants. (View Highlight)
• Neonates, including premature neonates, show well developed responses to painful stimuli. The foetus shows a stress response (and behavioural changes) to painful stimulation from 18-20 weeks gestation, which can be attenuated by the administration of fentanyl. Attenuation of the stress response to surgery improves postoperative morbidity and mortality in neonates. (View Highlight)
• There is a great deal of neuronal fine tuning of pain pathways during early neonatal life which may be influenced by the activity of endogenous opioids (and by implication, administered opioids). (View Highlight)
• Atropine is a muscarinic acetylcholine antagonist. It causes vagal blockade at the AV and sinus node in the heart and increases heart rate. A dose of 40 mcg/kg PO or 20 mcg/kg IM/IV is used to prevent reflex bradycardia, for instance from hypoxia, deep volatile anaesthesia or from reflex vagal stimulation with intubation/laryngoscopy. Bradycardia results in a marked fall in cardiac output. Atropine also dries secretions, including after ketamine anaesthesia; secretions might obstruct the airway or cause laryngospasm. (View Highlight)
• A PDA results in left to right shunting from the aorta to the pulmonary artery and increase in pulmonary blood flow. In the premature neonate this will result in cardiac failure. There is a low diastolic blood pressure which may cause gut hypoperfusion, resulting in necrotising enterocolitis, or intraventricular haemorrhage. In an older child, persistence of a PDA may cause mild cardiac failure presenting as frequent chest infections. If a child has a PDA for many years, this may eventually cause pulmonary hypertension and result in flow reversal across the duct (Eisenmenger circulation). There are a few conditions where patency of the arterial duct is required for survival: for instance, duct dependent systemic circulation in critical coarctation (blood flow to the lower body is from the pulmonary artery, via the duct), or duct dependent pulmonary circulation in pulmonary atresia (blood flow to the lungs is from the aorta, via the duct). Such children collapse about a week after birth as the duct closes and require a prostaglandin infusion to maintain the duct until a definitive procedure is undertaken (e.g. coarctation repair or a systemic to pulmonary artery shunt in pulmonary atresia, known as a modified Blalock Taussig shunt (mBT shunt). (View Highlight)
• The neonate is prone to upper airway obstruction so anaesthesia is best managed by intubation. The work of breathing is high and breathing through the high resistance of a tracheal tube further adds to the work of breathing and the neonate will tire rapidly. The neonate is prone to atelectasis and small airway collapse as the ribs are soft and lack elastic recoil to maintain lung volumes. In addition, the diaphragm is the principle muscle of respiration and tires easily; abdominal distension will further interfere with diaphragmatic movement. (View Highlight)
• Neonates should therefore be intubated and ventilated for anaesthesia, using low pressure ventilation (<20cmH2O), to achieve the appropriate small tidal volumes (7ml/kg), with the application of a small amount of PEEP (4cmH20). If the neonate is breathing spontaneously under volatile anaesthesia on a facemask, an oropharyngeal airway should be considered with the application of a small amount of CPAP (4cmH20). A neonate breathing spontaneously under ketamine anaesthesia should have the airway supported by a chin lift and supplemental oxygen administered. (View Highlight)
• Neonates have reduced renal function and produce dilute urine. They are unable to tolerate dehydration; similarly, they cannot handle a high fluid load or sodium load in the first few days of life. They undergo a diuresis after a few days of life. If a baby requires intravenous fluids from birth, they should be given as 10% dextrose in the following volumes. Sodium 3 mmol/kg/day and potassium 2 mmol/kg/day should be added after the postnatal diuresis or if the baby becomes hyponatraemic:
  1. Fluid volume (ml/kg/day)
  2. Day 1 – 60
  3. Day 2 – 90
  4. Day 3 – 120
  5. Day4 – 150
  6. Day 5 – 150 (View Highlight)
• A premature neonate may require an additional 30 ml/kg/day because of increased insensible fluid losses and may also require additional sodium supplements (4 mmol/kg/day). (View Highlight)