Pediatric anatomy, physiology & pharmacology

Pediatric anatomy, physiology & pharmacology

1. Pediatric Anatomy, Physiology & Pharmacology 848 th FST

2. Introduction Of primary importance to the pediatric anesthesia provider is the realization that infants and children are not simply a small adult. Their anesthetic management depends upon the appreciation of the physiologic, anatomic and pharmacologic differences between the varying ages and the variable rates of growth. Also of importance is a general knowledge of the psychological development of children to enable the anesthetist to provide measures to reduce fear and apprehension related to anesthesia and surgery.

3. Definitions Preterm or Premature Infant: < 37 weeks Term Infant: 38-42 weeks gestation Post Term Infant: > 42 weeks gestation Newborn: up to 24 hours old Neonate: 1-30 days old Infant: 1-14 months old Child: 14 months to puberty (~12-13 years)

4. Body Size The most obvious difference between children & adults is size It makes a difference which factor is used for comparison: a newborn weighing 3kg is 1/3 the size of an adult in length 1/9 the body surface area 1/21 the weight Body surface area (BSA) most closely parallels variations in BMR & for this reason BSA is a better criterion than age or weight for calculating fluid & nutritional requirements

5. Body Size

6. Fetal Development The circulatory system is the first to achieve a functional state in early gestation The developing fetus outgrows its ability to obtain & distribute nutrients and O2 by diffusion from the placenta The functioning heart grows & develops at the same time it is working to serve the growing fetus At 2 months gestation the development of the heart and blood vessels is complete In comparison, the development of the lung begins later & is not complete until the fetus is near term

7. Fetal Circulation Placenta Gas exchange Waste elimination Umbilical Venous Tension is 32-35mmHg Similar to maternal mixed venous blood Result: O2 saturation of ~65% in maternal blood, but ~80% in the fetal umbilical vein (UV) Low affinity of fetal Hgb (HgF) for 2,3-DPG as compared with adult Hgb (HgA) Low concentration of 2,3-DPG in fetal blood O2 & 2,3-DPG compete with Hgb for binding, the reduced affinity of HgF for 2,3-DPG causes the Hgb to bind to O2 tighter Higher fetal O2 saturation

8. Fetal Circulation P50 is 27mmHg for adult Hgb, but only 20mmHg for fetal Hgb This causes a left shift in the O2 dissociation curve Because the bridge between arterial & tissue O2 tension crosses the steep part of the curve, HgF readily unloads O2 to the tissue despite its relatively low arterial saturation

9. Fetal Circulation

10. Fetal Circulatory Flow Starts at the placenta with the umbilical vein Carries essential nutrients & O2 from the placenta to the fetus (towards the fetal heart, but with O2 saturated blood) The liver is the first major organ to receive blood from the UV Essential substrates such as O2, glucose & amino acids are present for protein synthesis 40-60% of the UV flow enters the hepatic microcirculation where it mixes with blood draining from the GI tract via the portal vein The remaining 40-60% bypasses the liver and flows through the ductus venosus into the upper IVC to the right atrium (RA)

11. Fetal Circulatory Flow The fetal heart does not distribute O2 uniformly Essential organs receive blood that contains more oxygen than nonessential organs This is accomplished by routing blood through preferred pathways From the RA the blood is distributed in two directions: 1. To the right ventricle (RV) 2. To the left atrium (LA) Approximately 1/3 of IVC flow deflects off the crista dividens & passes through the foramen ovale of the intraatrial septum to the LA

12. Fetal Circulatory Flow Flow then enters the LV & ascending aorta This is where blood perfuses the coronary and cerebral arteries The remaining 2/3 of the IVC flow joins the desaterated SVC (returning from the upper body) mixes in the RA and travels to the RV & main pulmonary artery Blood then preferentially shunts from the right to the left across the ductus arteriosus from the main pulmonary artery to the descending aorta rather than traversing the pulmonary vascular bed The ductus enters the descending aorta distal to the innominate and left carotid artery It joins the small amount of LV blood that did not perfuse the heart, brain or upper extremities

13. Fetal Circulatory Flow The remaining blood (with the lowest sat of 55%) perfuses the abdominal viscera The blood then returns to the placenta via the paired umbilical arteries that arise from the internal iliac arteries Carries unsaturated blood from the fetal heart The fetal heart is considered a “Parallel” circulation with each chamber contributing separately, but additively to the total ventricular output Right side contributing 67% Left side contributing 33% The adult heart is considered “Serial”

14. Fetal Circulatory Flow

15. Fetal Circulatory Flow

16. Cardiac Malformations The parallel nature of the two ventricles enables fetuses with certain types of cardiac malformations to undergo normal fetal growth & development until term because systemic blood flow is adequate in utero Complete left to right heart obstruction does not impede fetal aortic blood flow The foramen ovale & ductus arteriosus provide alternate pathways to bypass obstruction

17. Fetal Circulatory Flow Summary: Ductus Venosus shunts blood from the UV to the IVC bypassing the liver Foramen Ovale shunts blood from the RA to the LA Ductus Arteriosus shunts blood from the PA to the descending aorta bypassing the lungs Fetal circulation is parallel Blood from the LV perfuses the heart & brain with well oxygenated blood

18. Fetal Pulmonary Circulation Fetal Lungs Extract O2 from blood with its main purpose to provide nutrients for lung growth Neonatal Lungs Supply O2 to the blood Fetal lung growth requires only 7% of combined ventricular output

19. Fetal Pulmonary Circulation Fetal pulmonary vascular resistance (PVR) is high & helps restrict the amount of pulmonary blood flow If not for the low resistance ductus arteriosus (DA) & adjoining peripheral vascular bed the RV would need to pump against a higher pulmonary resistance than the LV Instead, both ventricles face relatively low systemic vascular resistance established by the low resistance / high flow from the placenta

20. Transitional & Neonatal Circulation There are 3 steps to understanding transitional circulation 1. Foramen Ovale: ductus arteriosus & ductus venosus close to establish a heart whose chambers pump in series rather than parallel Closure is initially reversible in certain circumstances & the pattern of blood flow may revert to fetal pathways 2. Anatomic & Physiologic: Changes in one part of the circulation affect other parts 3. Decrease in PVR: The principal force causing a change in the direction & path of blood flow in the newborn

21. Transitional & Neonatal Circulation Changes that establish the newborn circulation are an “orchestrated” series of interrelated events As soon as the infant is separated from the low resistance placenta & takes the initial breath creating a negative pressure (40-60cm H2O), expanding the lungs, a dramatic decrease in PVR occurs Exposure of the vessels to alveolar O2 increases the pulmonary blood flow dramatically & oxygenation improves

22. Transitional & Neonatal Circulation Hypoxia and/or acidosis can reverse this causing severe pulmonary constriction The pulmonary vasculature of the newborn can also respond to chemical mediators such as Acetylcholine Histamine Prostaglandins **All are vasodilators

23. Transitional & Neonatal Circulation Most of the decrease in PVR (80%) occurs in the first 24 hours & the PAP usually falls below systemic pressure in normal infants PVR & PAP continue to fall at a moderate rate throughout the first 5-6 weeks of life then at a more gradual rate over the next 2-3 years Babies delivered by C-section have a higher PVR than those born vaginally & it may take them up to 3 hours after birth to decrease to the normal range

24. Transitional & Neonatal Circulation

25. Transitional & Neonatal Circulation

26. Persistent Pulmonary Hypertension (PPHN) In 1969 a syndrome of central cyanosis was observed in neonates who had no: Parenchymal pulmonary disease Abnormal intracardiac relationships Structural heart disease The syndrome was called persistent fetal circulation (PFC) & was identified by: Increased PVR Patent foramen ovale Patent ductus arteriosus

27. Persistent Pulmonary Hypertension (PPHN) A failure of the newborn’s circulation system to change from normal intrauterine to extrauterine patterns results in an abnormal shunting of blood from right to left via persistent fetal pathways However, because the placenta is no longer in continuity with the newborn’s cardiovascular system The condition is not really persistence of the fetal circulation Therefore, the syndrome is more accurately referred to as persistent pulmonary hypertension of the newborn (PPHN)

28. Persistent Pulmonary Hypertension (PPHN)

29. Persistent Pulmonary Hypertension (PPHN)

30. Persistent Pulmonary Hypertension (PPHN) Treatment Optimal oxygenation Hyperventilation Sedation Paralysis Extracorporeal membrane oxygenation (ECMO) Reserved for severe & persistent cases only

31. Persistent Pulmonary Hypertension (PPHN) Implications for Anesthesia: Pathophysiologic mechanisms that trigger this condition Hypercarbia Acidosis Arterial Blood Sampling Right radial artery or temporal arteries More meaningful since these areas reflect the values in the blood reaching the brain & coronary arteries Left radial artery May be misleading because the left subclavian is very close to the ductus Pulse Oximeter Probes Should be placed on right upper limb or head

32. Closure of the Ductus Arteriosus, Foramen Ovale & Ductus Venosus

33. Ductus Arteriosus Closure occurs in two stages Functional closure occurs 10-15 hours after birth This is reversible in the presence of hypoxemia or hypovolemia Permanent closure occurs in 2-3 weeks Fibrous connective tissue forms & permanently seals the lumen This becomes the ligamentum arteriosum

34. Persistent Ductus Arteriosus Also referred to as Pathologic PDA Requires surgical closure & differs from the normal ductus in tissue structure The PDA in the preterm infant is due to a weak vasoconstrictor response to O2 and should be considered a normal not pathologic response This PDA may still need surgical correction A left to right shunt through the ductus can flood the lungs of the premature infant prolonging mechanical ventilation, eventually leading to pulmonary edema & right sided heart failure

35. Persistent Ductus Arteriosus Anesthetic Considerations Excessive fluids may reopen a ductus or permit excessive left to right shunting through an already open ductus Intraoperative short falls Strict fluid management Attention to acid base balance Oxygenation Ventilation All are very important in premature infants to avoid reopening the ductus & causing CHF

36. Persistent Ductus Arteriosus A PDA may also be beneficial In cyanotic congenital heart malformations with right to left & decreased pulmonary blood flow The PDA may be the major route by which the blood reaches the pulmonary arteries to receive O2 In this case closure of the DA causes severe cyanosis, tissue hypoxia & acidemia To keep the ductus open prior to palliative or corrective surgery of the heart malformation, PGE 1 (0.05-0.1mcg/kg/min) can be administered IV To help close the ductus prior to surgical intervention to ligate the PDA, Indomethacin (0.1-0.2mg/kg) can be administered This is an inhibitor of PGE synthesis

37. Foramen Ovale Increased pulmonary blood flow & left atrial distention help to approximate the two margins of the foramen ovale This is a flap like valve & eventually the opening seals closed This hole also provides a potential right to left shunt Crying, coughing & valsalva maneuver increases PVR which increases RA & RV pressure A right to left atrial & intrapulmonary shunt may therefore readily occur in newborns & young infants

38. Foramen Ovale Probe Patency Is present in 50% of children < 5 years old & in more than 25% of adults Therefore, the possibility of right to left atrial shunting exists throughout life & there is a potential avenue for air emboli to enter the systemic circulation A patent FO may be beneficial in certain heart malformations where mixing of blood is essential for oxygenation to occur such as in transposition of the great vessels Patients who rely on the patency of the foramen require a balloon atrial septoplasty during a cardiac cath or a surgical atrial septectomy

39. Ductus Venosus This has no purpose after the fetus is separated from the placenta at delivery

40. Cardiovascular Differences in the Infant There are gross structural differences & changes in the heart during infancy At birth the right & left ventricles are essentially the same in size & wall thickness During the 1 st month volume load & afterload of the LV increases whereas there is minimal increase in volume load & decrease in afterload on the RV By four weeks the LV weighs more than the RV This continues through infancy & early childhood until the LV is twice as heavy as the RV as it is in the adult

41. Cardiovascular Differences in the Infant Cell structure is also different The myocardial tissues contain a large number of nuclei & mitochondria with an extensive endoplasmic reticulum to support cell growth & protein synthesis during infancy The amount of cellular mass dedicated to contractile protein in the neonate & infant is less than the adult 30% vs. 60% These differences in the organization, structure & contractile mass are partly responsible for the decreased functional capacity of the young heart

42. Cardiovascular Differences in the Infant Both ventricles are relatively noncompliant & this has two implications for the anesthesia provider 1. Reduced compliance with similar size & wall thickness makes the interrelationship of the ventricular function more intimate Failure of either ventricle with increased filling pressure quickly causes a septal shift & encroachment on stroke volume of the opposite ventricle

43. Cardiovascular Differences in the Infant 2. Decreased compliance makes it less sensitive to volume overload & their ability to change stroke volume is nearly nonexistent CO is not rate dependent at low filling pressures but small amounts of fluid rapidly change filling pressures to the plateau of the Frank-Starling length tension curve where stroke volume is fixed This changes the CO to strictly being rate dependent Additional small amounts of fluid can push the filling pressure to the descending part of the curve & the ventricles begin to fail The normal immature heart is sensitive to volume overloading

44. Cardiovascular Differences in the Infant Functional capacity of the neonatal & infant heart is reduced in proportion to age & as age increases functional capacity increases The time over which growth & development overcome these limitations is uncertain & variable When adult levels of systemic artery pressure & PVR are achieved by age of 3 or 4 years the above limitations probably no longer apply

45. Autonomic Control of the Heart Sympathetic innervation of the heart is incomplete at birth with decreased cardiac catecholamine stores & it has an increased sensitivity to exogenous norepinephrine It does not mature until 4-6 months of age Parasympathetic innervation has been shown to be complete at birth therefore we see an increased sensitivity to vagal stimulation

46. Autonomic Control of the Heart The imbalance between sympathetic & parasympathetic tone predisposes the infant to bradycardia Anything that activates the parasympathetic nervous system such as anesthetic overdose, hypoxia or administration of Anectine can lead to bradycardia If bradycardia develops in neonates & infants always check oxygenation first

47. Autonomic Control of the Heart Atropine may inhibit vagal stimulation Is always given prior to, or at the same time, that Anectine is given or anytime that vagal stimulation will be present such as in an awake intubation Dose of Atropine is 20mcg/kg where the minimum dose for children is 0.1mg Anything less than 0.1mg can cause paradoxical bradycardia which may occur secondary to a dose dependent (low dose) central vagal stimulating effect of the drug

48. Circulation The vasomotor reflex arcs are functional in the newborn as they are in adults Baroreceptors of the carotid sinus lead to parasympathetic stimulation & sympathetic inhibition There are less catecholamine stores & a blunted response to catecholamines Therefore neonates & infants can show vascular volume depletion by hypotention without tachycardia

49. Cardiovascular Parameters Parameters are much different for the infant than for the adult Heart rate: higher Decreasing to adult levels at ~5 years old Cardiac output: higher Especially when calculated according to body weight & it parallels O2 consumption Cardiac index: constant Because of the infants high ratio of surface area to body weight O2 consumption: depends heavily on temperature There is a 10-13% increase in O2 consumption for each degree rise in core temperature

50. Circulation Variables in Infants

51. Respiratory System Neonatal adaptation of lung mechanics & respiratory control Takes several weeks to complete Beyond this immediate period the lungs are not fully mature for another few years Formation of adult type alveoli begins at 36 weeks postconception Represents only a fraction of the terminal air sacs with thick septa It takes more than several years for functional and morphologic development to be complete

52. Respiratory System Neural & chemical controls of breathing in older infants & children are similar to those in adolescents & adults A major exception to this is found in neonates and young infants, especially in premature infants less than 40-44 weeks postconception In these infants, hypoxia is a potent respiratory depressant, rather than a stimulant This is due either to central mediation or to changes in respiratory mechanics These infants tend to develop periodic breathing or central apnea with or without apparent hypoxia This is most likely because of immature respiratory control mechanisms

53. Respiratory System During the early years of childhood, development of the lungs continues at a rapid pace This is with respect to the development of new alveoli By 12-18 months the number of alveoli reaches the adult level of 300 million or more Subsequent lung growth is associated with an increase in alveolar size

54. Respiratory System Lung volumes of infants is disproportionately small in relation to body size Since the infant’s metabolic rate, in relation to body weight, is twice that of the adult, more marked differences are seen in respiratory frequency and in alveolar ventilation The higher level of alveolar ventilation in relation to FRC makes the FRC a less effective buffer between inspired gases & pulmonary circulation Any interruption of ventilation will lead rapidly to hypoxemia & the function of anesthetic gases in the alveolus will equilibrate with the inspired fraction more rapidly than occurs in adults

55. Respiratory System Functional Residual Capacity (FRC) Determined by the balance between the outward stretch of the thorax & the inward recoil of the lungs In infants, outward recoil of the thorax is very low They have cartilaginous chest walls that make their chest walls very compliant & their respiratory muscles are not well developed Inward recoil of the lungs is only slightly lower than that of an adults

56. Respiratory System The FRC of young infants in conditions such as apnea , under general anesthesia and/or in paralysis decrease to 10-15% of TLC Total Lung Capacity (TLC) is normally ~50% of an adults 10-15% TLC is incompatible with normal gas exchange because airway closure, atelectasis & ventilation/perfusion imbalance result Awake infants are normally as capable of maintaining FRC as older children & adults This is important because it limits O2 reserve during apnea and greatly reduces the time before you see a drop in oxygen saturation

57. Respiratory System Breathing Patterns of Infants Less than 6 months of age Predominantly abdominal (diaphragmatic) and the rib cage (intercostal muscles) contribution to tidal volume is relatively small (20-40%) After 9 months of age The rib cage component of tidal volume increases to a level (50%) similar to that of older children & adolescents, reflecting the maturation of the thoracic structure By 12 months Chest wall compliance decreases The chest wall becomes stable & can resist the inward recoil of the lungs while maintaining FRC This supports the theory that the stability of the respiratory system is achieved by 1 year of age

58. Anatomic Differences in the Respiratory System Anatomic Airway Differences are Many Upper Airway: the nasal airway is the primary pathway for normal breathing During quiet breathing the resistance through the nasal passages accounts for more than 50% of the total airway resistance (twice that of mouth breathing) Except when crying, the newborns are considered “obligate nose breathers” This is because the epiglottis is positioned high in the pharynx and almost meets the soft palate, making oral ventilation difficult If the nasal airway becomes occluded the infant may not rapidly or effectively convert to oral ventilation Nasal obstruction usually can be relieved by causing the infant to cry

59. Anatomic Differences in the Respiratory System The Tongue: is large & occupies most of the cavity of the mouth & oropharynx With the absence of teeth, airway obstruction can easily occur The airway usually can be cleared by holding the mouth open and/or lifting the jaw An oral airway may also be helpful

60. Anatomic Differences in the Respiratory System Pharyngeal Airway: is not supported by a rigid bony or cartilaginous structure Is easily collapsed by: The posterior displacement of the mandible during sleep Flexion of the neck Compression over the hyoid bone Chemoreceptor stimuli such as hypercapnia & hypoxia stimulate the airway dilators preferentially over the stimulation of the diaphragm so as to maintain airway patency

61. Anatomic Differences in the Respiratory System Laryngeal Airway: this maintains the airway & functions as a valve to occlude & protect the lower airway In the infant the larynx is located high (anterior & cephlad) opposite C-4 (adults is C-6) The body of the hyoid bone is between C2-3 & in the adult is at C-4 The high position of the epiglottis & larynx allows the infant to breathe & swallow simultaneously The larynx descends with growth Most of this descent occurs in the 1st year but the adult position is not reached until the 4 th year The vocal cords of the neonate are slanted so that the anterior portion is more caudal than the posterior

62. Anatomic Differences in the Respiratory System Laryngeal Reflex: is activated by stimulation of receptors on the face, nose & upper airways of the newborn Reflex apnea, bradycardia & laryngospasm may occur Various mechanical stimuli can trigger response including: Water Foreign bodies Noxious gases This response is very strong in newborns

63. Anatomic Differences in the Respiratory System

64. Anatomic Differences in the Respiratory System

65. Anatomic Differences in the Respiratory System

66. Anatomic Differences in the Respiratory System Narrowest area of the airway Adult is between the vocal cords Infant is in the cricoid region of the larynx The cricoid is circular & cartilaginous and consequently not expansible An endotracheal tube may pass easily through an infants vocal cords but be tight at the cricoid area The limiting factor here becomes the cricoid ring This is also frequently the site of trauma during intubation 1mm of edema on the cross sectional area at the level of the cricoid ring in a pediatric airway can decrease the opening 75% vs. 19% in an adult There should be an audible air leak at 15-20cm H2O airway pressure when applied

67. Anatomic Differences in the Respiratory System

68. Anatomic Differences in the Respiratory System Trachea Infant: the alignment is directed caudally & posteriorly Adult: it is directed caudally Cricoid pressure is more effective in facilitating passage of the endotracheal tube in the infant

69. Anatomic Differences in the Respiratory System Newborn Trachea Distance between the bifurcation of the trachea & the vocal cords is 4-5cm Endotracheal tube (ETT) must be carefully positioned & fixed Because of the large size of the infant’s head the tip of the tube can move about 2cm during flexion & extension of the head It is extremely important to check the ETT placement every time the baby’s head is moved

70. Anatomic Differences in the Respiratory System

71. Anatomic Differences in the Respiratory System

72. Anatomic Differences in the Respiratory System Tonsils & Adenoids Grow markedly during childhood Reach their largest size at 4-7 years & then recedes gradually This can make visualization of the larynx more difficult

73. Anatomic Differences in the Respiratory System The compliant nature of the major airways of the infant are also different than adults The diameter of infant airways changes more easily when exposed to distending or compressing forces With obstruction at the level of the larynx, stridor will be heard mainly on inspiration With obstruction at the level of the trachea (foreign body), stridor may be heard during both inspiration & expiration In contrast, during lower airway obstruction (asthma or bronchiolitis), most of the collapse occurs during expiration thus producing expiratory wheeze

74. Anatomic Differences in the Respiratory System The configuration of the thoracic cage differs in the infant & adult Infant: ribs are horizontal & do not rise as much as an adult’s during inspiration The diaphragm is more important in ventilation & the consequences of abdominal distention are much greater As the child grows (learns to stand) gravity pulls on the abdominal contents encouraging the chest wall to lengthen Now the chest cavity can be expanded by raising the ribs into a more horizontal position

75. Anatomic Differences in the Respiratory System Lower Airway Diaphragmatic & intercostal muscles of infants are more liable to fatigue than those of adults This is due to a difference in muscle fiber type Adult diaphragm has 60% of type I: slow twitch, high oxidative, fatigue resistant Newborns diaphragm has 75% of type II: fast twitch, low oxidative, less energy efficient The same pattern is seen in intercostal muscles The newborn is more prone to respiratory fatigue & may not be able to cope when suffering from conditions that result in reduced lung compliance (RDS)

76. Anatomic Differences in the Respiratory System Ventilation/Perfusion Ratio (V/Q) Infants & children: the distribution of pulmonary blood flow is more uniform than adults Adults changes from base to apex because of gravity Infants & children PAP is relatively high & the effect of gravity is less

77. Anatomic Differences in the Respiratory System V/Q changes in anesthesia General anesthesia (GA) FRC & diaphragmatic movements are reduced Airway closure tends to be exaggerated & the dependent parts of the lung are poorly ventilated Hypoxic pulmonary vasoconstriction, which diverts blood flow from areas of the lung that are under ventilated, is abolished during GA This increases the hypoxic tendency

78. Anatomic Differences in the Respiratory System In General: Rate & depth of respiration are regulated to expend the least amount of energy At their given rates, both the infant & the adult expend about 1% of their metabolic energy in ventilation

79. Anatomic Differences in the Respiratory System Periodic Breathing Can be observed in the normal newborn infant & frequently occurs during REM sleep Manifested as rapid ventilation followed by a period of apnea of less than 10secs During this period arterial oxygenation tension remains in the normal range Usually not seen in healthy infants after 6 weeks of age

80. Anatomic Differences in the Respiratory System Apneic spells longer than 20secs are frequently seen in premature infants & are frequently associated with arterial desaturation & bradycardia Episodes of apnea increase in frequency during stressful situations such as respiratory infection or the postanesthetic & postsurgical states Apneic spells can be central (originating in the CNS) or obstructive (d/t upper airway obstruction) Treatment with caffeine & theophylline has been show to be effective in reducing both types in preterm infants

81. Anatomic Differences in the Respiratory System Tidal Volume 7-10ml/kg Dead Space 2-2.5ml/kg These two measures remain constant between infants & adults

82. Oxygen Transport Blood volume of a healthy newborn is 70-90ml/kg Hemoglobin tends to be high (approx. 19g/dl) Consisting primarily of HgF Hgb rises slightly in the first few days because of the decrease in extracellular fluid volume Thereafter, it declines & is referred to as physiologic anemia of infancy HgF has a greater affinity for oxygen than HgA After birth, the total Hgb level decreases rapidly as the proportion of HgF diminishes (it can drop below 10g/dl at 2-3 months) creating the anemia

83. Oxygen Transport The P-50 rapidly increases at the same time the HgF is replaced by HgA which has a high concentration of 2,3-DPG & so insures efficient oxygen off-loading at the tissues The gradual decrease in O2 carrying capacity in the first few months of life is thus well tolerated by normal, healthy infants There is no consensus about the lowest tolerable Hgb concentration for an infant The lowest limit will depend on factors such as duration of anemia, the acuity of blood loss, the intravascular volume & more important the impact of other conditions that might interfere with O2 transport

84. Oxygen Transport

85. Key Points Respiratory control mechanisms are not fully developed until 42-44 weeks postconception Most alveolar formation & elastogenesis occurs during the first year of life The thoracic structure is insufficient to support the negative pleural pressure during the respiratory cycle until the infant develops muscle strength from upright posture around 1 year old

86. Key Points Weakness of the thoracic structure is partly compensated for by contractions of the intercostal & accessory muscles Anesthesia abolishes this compensatory mechanism & the end expiratory lung volume (FRC) decreases to the point of airway closure & alveolar collapse Infants are prone to upper airway obstruction Due to anatomic & physiologic differences Anesthesia depresses pharyngeal & other neck muscles which resist the collapsing forces in the pharynx

87. Key Points HgF has high oxygen affinity & limits oxygen unloading at the tissue level This decreases O2 delivery to the tissues that have high oxygen demand Infants & young children are prone to perioperative hypoxemia & tissue hypoxia

88. Airway Management The technique of endotracheal intubation in the neonate & small infant differs from that in the adult because of the baby’s anatomical features The large head & short neck may necessitate the need for a shoulder roll The angle of the jaw is about 140 ° (adult is 120°) The epiglottis is more “U” shaped, usually resembling the Greek letter omega The epiglottis also protrudes over the larynx at a 45 ° angle The larynx of an infant is high & has an anterior inclination Straight (Miller or Phillips) blade is usually the best choice The view can be markedly improved by applying cricoid pressure

89. Airway Management Selection of Endotracheal Tube Size Diameter Greater than 2 years old In millimeters=Age+16 ÷4 In french=Age+18 12-24 months=4.0 6-12 months=3.5-4.0 Newborn-6 months=3.0-3.5 Premie=2.0-3.0 Cuffed tubes After 8 years old add 2 Fr. sizes to diameter

90. Airway Management Distance or Depth to Tape Tube If older than 2 years Age ÷2+12 If younger than 2 years 1-2-3-4 kg then it is taped at 7-8-9-10cm respectively Newborn to 6 months = 10cm 6 to 12 months = 11cm 1 to 2 years = 12cm

91. Renal Differences Body Fluid Compartments Full term infants have a large % of TBW & ECF TBW decreases with age mainly as a result of loss of water in extracellular fluid

92. Renal Differences Significance for Anesthesia Provider Higher dose of water soluble drug is needed due to the greater volume of distribution However, due to the immaturity of clearance & metabolism the dose given is equal to the dose used in adults In the fetus the placenta is the excretory organ However, it still produces a large volume of hypotonic urine & helps amniotic fluid volume It is only after birth that the kidney begins to maintain metabolic function

93. Renal Differences The healthy newborn has a complete set of nephrons at birth The glomeruli are smaller than adults The filtration surface related to body weight is similar The tubules are not fully grown at birth & may not pass into the medulla

94. Renal Differences Glomerular Filtration Rate (GFR) At birth is ~30% of the adult It increases quickly during the first two weeks, but then is relatively slow to approach the adult level by the end of the first year Low GFR in the full term infant affects the baby’s ability to excrete saline & water loads as well as drugs Full term infants can conserve Na+, as GFR increases so does the filtered load of Na+ increase & the ability of the proximal tubule to reabsorb the ion In premature infants a glomerulotubular imbalance is present which may result in Na+ wastage & hyponatremia

95. Renal Differences Factors that contribute to the increase in GFR Increase in CO Changes in renovascular resistance Altered regional blood flow Changes in the glomeruli Maturation of the glomerular function is complete at 5-6 months of age

96. Renal Differences Tubular Function & Permeability Not fully mature in the term neonate & even less in the premature infant The neonate can excrete dilute urine (50mOsm/L) However, the rate of excretion of H2O is less & it cannot concentrate to more than 700mOsm/L (adult, 1200mOsm/L) This is due, in part, to the lack of urea-forming solids in the diet, but mostly due to the hypotonicity of the renal medulla Maturation of the tubules is behind that of the glomeruli Peak renal capacity is reached at 2-3 years after which it decreases at a rate of 2.5% per year

97. Renal Differences The kidney does show some response to antidiuretic hormone (ADH), but is less sensitive to ADH than the cells of mature nephrons Diluting Capacity Matures by 3-5 weeks postnatal age The ability to handle a water load is reduced & the neonate may be unable to increase water excretion to compensate for excessive water intake They are very sensitive to over hydration In infants & children, hyponatremia occurs more frequently than hypernatremia

98. Renal Differences Creatinine Normal value is lower in infants than in adults This is due to the anabolic state of the newborn & the small muscle mass relative to body weight (0.4mg/dl vs. 1mg/dl in the adult) Bicarbonate (NaHCO3) Renal tubular threshold is also lower in the newborn (20mmol/L vs. 25mmol/L in the adult) Therefore, the infant has a lower pH, of about 7.34 BUN The infants urea production is reduced as a result of growth & so the “immature” kidney is able to maintain a normal BUN

99. Hepatic Differences Glucose from the mother is the main source of energy for the fetus Stored as fat & glycogen with storage occurring mostly in last trimester At 28 weeks gestation the fetus has practically no fat stored, but by term 16% of the body is fat & 35gms of glycogen is stored In utero liver function is essential for fetal survival Maintains glucose regulation, protein / lipid synthesis & drug metabolism The excretory products go across the placenta & are excreted by the maternal liver Liver volume represents 4% of the total body weight in the neonate (2% in adult) However, the enzyme concentration & activity are lower in the neonatal liver

100. Hepatic Differences Glucose is the infants main source of energy In the 1 st few hours following delivery there is a rapid drop in plasma glucose levels Hepatic & glycogen stores are rapidly depleted with fat becoming the principle source of energy The newborn should not be kept for a long period of time from enteral or IV nutrition The lower limit of normal for glucose is 30mg/dl in the term infant Infants do not usually show neurological signs & symptoms, but may develop sweating pallor or tachycardia A glucose level < 20mg/dl usually precipitates neurological signs such as apnea or convulsions Premature infants may have a tendency for hypoglycemia for weeks

101. Hepatic Differences Increased hepatic metabolic activity Occurs at about 3 months of age Reaches a peak at 2-3 years by which time the enzymes are fully mature, then they start to decline reaching adult values at puberty Renin, angiotensin, aldosterone, cortisol & thyroxine levels are high in the newborn & decrease in the first few weeks of life

102. Hepatic Differences Physiologic Jaundice Increased concentrations of bilirubin occur in the first few days of life This is excessive bilirubin from the breakdown of red blood cells & deficient hepatic conjugation due to immature liver function Treatment is phototherapy & occasionally exchange transfusions If left untreated it can lead to encephalopathy (kernicterus)

103. Hepatic Differences Coagulation At birth, Vit K dependent factors (II, VII, IX & X) are at a level of 20-60% of the adult volume This results in prolonged prothrombin times Synthesis of Vit K dependent factors occurs in the liver which being immature leads to relatively lower levels of these factors even with the administration of Vit K It takes several weeks for the levels of coagulation factors to reach adult values Administration of Vit K immediately after birth is important to prevent hemorrhagic disease

104. CNS Differences The brain of the neonate is relatively large 1/10 of the weight as compared to 1/50 of adult The brain grows rapidly Doubles in weight by 6 months Triples in weight by 1 year At birth ~25% of the neonatal cells are present By one year the development of cells in the cortex & brain stem is complete

105. CNS Differences Myelination & Elaboration of Dendritic Processes Continue into the third year of life Incomplete myelinization is associated with primitive reflexes such as motor and grasp Spinal Cord At birth the spinal cord extends to L-3 By one year old the infant spinal cord has assumed its permanent position at L-1

106. CNS Differences Structure & Function of the Neuromuscular System Incomplete at birth There are immature myoneural junctions & larger amount of extrajunctional receptors Throughout Infancy: Contractile properties change The amount of muscle increases The neuromuscular junction & acetylcholine receptors mature

107. CNS Differences Junctions & Receptors The presence of immature myoneural junctions might cause a predisposition to sensitivity A large number of extrajunctional receptors might result in resistance Within a short interval, (< 1 month) this variation diminishes & the myoneural junction of the infant behaves almost like that of an adult

108. Temperature Regulation Body Temperature Is a result of the balance between the factors leading to heat loss & gain and the distribution of heat within the body The potential exists for unstable conditions to progress to a positive feedback cycle The decrease in body temperature will lead to a decrease in the metabolic rate, leading to further heat loss & diminished metabolic rate The body normally safeguards against this unstable state by increasing BMR during the initial exposure to cold or by reducing heat loss through vasoconstriction

109. Temperature Regulation

110. Temperature Regulation Central Temperature Control Mechanism This is intact in the newborn It is limited, however, by autonomic & physiologic factors Is only able to maintain a constant body temperature within a narrow range of environmental conditions O2 consumption is at a minimum when the environmental temp is within 3-5% (1-2 °C) of body temp (an abdominal skin temp of 36°C) This is known as the neutral thermal environment (NTE) A deviation in either direction from the NTE will increase O2 consumption An adult can sustain body temperature in an environment as cold as 0°C where as a full term infant starts developing hypothermia at about 22°C

111. Temperature Regulation Generation of Heat Depends mostly on body mass Heat loss to the environment is mainly due to surface area Neonates have a ratio of surface area to mass about 3X’s higher than that of adults Therefore they have difficulty regulating body temperature in a cold environment

112. Temperature Regulation Premature Infants & Temperature Control Are more susceptible to environmental changes in temperature The preemie has skin only 2-3 cells thick & has a lack of keratin This allows for a marked increase in evaporative water loss (in extremes this can be in excess of heat production)

113. Temperature Regulation Important Mechanisms for Heat Production Metabolic activity Shivering Non-shivering thermogenesis Newborns usually do not shiver Heat is produced primarily by non-shivering thermogenesis Shivering does not occur until about 3 months of age

114. Temperature Regulation Non-shivering Thermogenesis Exposure to cold leads to production of Norepi This in turn increases the metabolic activity of brown fat Brown fat is highly specialized tissue with a great number of mitochondrial cytochromes (these are what provide the brown color) The cells have small vacuoles of fat & are rich in sympathetic nerve endings They are mostly in the nape & between the scapulae but some are found in the mediastinal (around the internal mammary arteries & the perirenal regions (around the kidneys & adrenals)

115. Temperature Regulation Once released Norepi acts on the alpha & beta adrenergic receptors on the brown adipocytes This stimulates the release of lipase, which in turn splits triglycerides into glycerol & fatty acids, thus increasing heat production The increase in brown fat metabolism raises the proportion of CO diverted through the brown fat (sometimes as much as 25%), which in turn facilitates the direct warming of blood The increased levels of Norepi also causes peripheral vasoconstriction & mottling of the skin

116. Temperature Regulation

117. Temperature Regulation Heat Loss The major source of heat loss in the infant is through the respiratory system A 3kg infant with a MV of 500ml spends 3.5cal/min to raise the temperature of inspired gases To saturate the gases with water vapor takes an additional 12cal/min The total represents about 10-20% of the total oxygen consumption of an infant

118. Temperature Regulation The sweating mechanism is present in the neonate, but is less effective than in adults Possibly because of the immaturity of the cholinergic receptors in the sweat glands Full term infants display structurally well developed sweat glands, but these do not function appropriately Sweating during the first day of life is actually confined mostly to the head

119. Temperature Regulation Heat Exchange Review 1. Conduction: The kinetic energy of the vibratory motion of the molecules at the surface of the skin or other exposed surfaces is transmitted to the molecules of the medium immediately adjacent to the skin Rate of transfer is related to temperature difference between the skin & this medium Use warm blankets, Bair huggers & warmed gel pads 2. Convection: Free movement of air over a surface Air is warmed by exposure to the surface of the body then rises & is replaced by cooler air from the environment Increase OR temp, radiant warmers, wrap in saran wrap, cover with blankets and/or OR drapes

120. Temperature Regulation 3. Radiation: Radiation emitted from the body is in the infrared region of the electromagnetic spectrum The quantity radiated is related to the temperature of the surrounding objects Radiation is the major mechanism of heat loss under normal conditions (same techniques to prevent as used in Convection) 4. Evaporation: Under normal conditions ~20% of the total body heat loss is due to evaporation This occurs both at the skin & lungs Since the infant’s skin is thinner & more permeable than the older child’s or adult’s evaporative heat loss from the skin is greater In the anesthetized infant the MV (relative to body weight) is high thus increasing evaporative heat loss through the respiratory system

121. Temperature Regulation Summary Decreased body temperature is initially compensated for by increased metabolism If this fails & temperature continues to decrease, regional blood flow shifts, causing a metabolic acidosis & eventually apnea

122. Pharmacological Differences with Inhalation Anesthetics Review Factors that determine uptake & distribution of inhaled agents Factors that determine the rate of delivery of gas to the lungs Inspired concentration Alveolar ventilation FRC Factors that determine the rate of uptake of the anesthetic from the lung CO Solubility of the agent Alveolar-to-venous partial pressure gradient

123. Pharmacological Differences with Inhalation Anesthetics In children there is a more rapid rise from inspired partial pressure to alveolar partial pressure than in adults This is due to 4 differences between children & adults 1. The ratio of alveolar ventilation to FRC This a measure of the rate of “wash-in” of the anesthetic into the alveoli In the neonate the ration is 5:1 compared to adults of 1.5:1

124. Pharmacological Differences with Inhalation Anesthetics 2. There is a higher proportion of CO distributed to the VRG in the child In adults an increase in CO slows the rate of rise in alveolar to inspired partial pressure, but in neonates it speeds the rate of induction because the CO is preferentially distributed to the VRG The VRG constitutes 18% of the body weight of the neonate as opposed to only 6% in adults Therefore, the partial pressure in the VRG (which includes the brain) equilibrates faster with the alveolar partial pressure

125. Pharmacological Differences with Inhalation Anesthetics 3. Neonates have a lower blood/gas solubility of inhaled anesthetics (the less soluble the greater the amount that remains in the alveolus This allows a more rapid rise in the alveolar to inspired partial pressure 4. Neonates have a lower tissue/blood solubility of inhaled anesthetics Less agent is removed from the blood therefore the partial pressure of the agent in the blood returning to the lungs increases

126. Pharmacological Differences with Inhalation Anesthetics There are age related differences in MAC of inhalation agents

127. Questions