Neonatal Physiology for the Anesthesiologist€¦ · Neonatal Physiology for the Anesthesiologist Linda J. Mason, M.D. Professor of Anesthesiology and Pediatrics Loma Linda University

Intensive Review of Pediatric Anesthesia 2015

Neonatal Physiology for the Anesthesiologist

Linda J. Mason, M.D. Professor of Anesthesiology and Pediatrics

Loma Linda University


Outline

• Renal Development – Basic physiology and the nephron – Fluids, electrolytes, and glucose

• Thermoregulation • Pulmonary Development • Respiratory Physiology • CV Development and Basic Physiology


Neonatal Renal Physiology Basics of the Nephron, Fluids,

Electrolytes, and Glucose


Percent of Body Weight as Water

60%

75%

4


Body Composition (%)

5


Body Water Distribution • ICF – 67% • ECF – 33% (50% at birth)

– Interstitial Fluid – 15% – Plasma - 10% of TBW (Similar except lower protein

content in interstitial fluid) – Trans-cellular 1-3% TBW

Age Group EBV (mL/kg)

Premie 100 Neonate 90

Infant 80 Child 75 Adult 70

6

ECF expanded at birth * Fluid reserve? •Hydrops Fetalis – excessive ECF •Placental insufficiency, maternal diuretics – reduced ECF


Glomerulus Proximal Tubule

Distal Tubule

Loop of Henle

1 2 5

3 4

Neonatal Renal Physiology 1. Low GFR

Low Systolic blood pressure High renal artery resistance

2. Immaturity – Responsiveness to change Na+ transport incomplete

3. Medullary hypotonicity 4. Shorter loops 5. Hormones ¯Response (levels) ¯ Ability to concentrate ¯ Ability to excrete K+

7


Glomerular Filtration Rate mL/min/1.73m2

8


Maximal Urine Concentration mOsm/kg

9


Neonatal Nephrology

• Decreased clearance

• Limited ability to conserve & excrete water

• Susceptible to hypo & hypernatremia

• Susceptible to hyperkalemia

• Susceptible to acidosis

10


Neonatal Fluid Requirements

• Day 1 Minimal – U/O is low

• Day 2-3 High – U/O is high, (ECF mobilization)

• Total Volume – 40-60 ml/kg/day

• Day 4-5 Formulaic – U/O @ Input

11


Neonatal Solute Requirements

• Day 1 – Glucose (D10W)

• Day 2 – Glucose and Na+ (2-3 mEq/dl NaCl)

• U/O – Glucose, Na+, and K+ (1-2 mEq/dl KCl)

12


Premie Fluid Requirements

Weight (grams) Age

(days) 750 - 1000

1000-1250

1250-1500

1500-2000

1 85 75 70 60 2-3 105 95 80 75 4-7 130 120 105 95

mL/kg/ day

13

IWL (ml/kg/day) 64 56 38 23-20


Calcium Homeostasis

• Renal – only unbound Ca++ filtered at glomerulus – 70 % reabsorbed - proximal tubule – 20% reabsorbed - ascending loop thick portion

• PTH Serum Ca++ – Distal tubule, collecting ducts, osteoclasts – Calcitriol intestine absorption

• Hypocalcemia common in the premature infant – Determined by measuring ionized Ca++

14


Premie Solute Requirements

• Day 1 – Glucose (D10W or higher)

• Day 2 – Na+ (3-5 mEq/dl NaCl)

• U/O – K+ (1-2 mEq/dl KCl)

• As needed Bicarb (1-2 mmol/kg/day)

• Calcium gluconate 100-200 mg/kg/day

15


Neonatal Intraoperative Requirements • Isotonic solutions

– Replacement of blood and other bodily fluids – Avoid hyponatremia

• Rule of 4-2-1 for maintenance (but not for infants) • Replacement of deficit and 3rd space (?) increased

proportion of extra-vascular fluid • Vasodilatation under GA • Hyperalimentation – ¯ to ⅓ -½ of maintenance rate

16


Electrolyte Imbalances • Hypernatremia

– More common in infants – High risk for mortality or permanent neurologic sequelae, seizures – Colloid or NS – Correct no faster than 1-2 mOsm/L/hr

• Excessively fast correction can result in cerebral edema – Check for (associated) hypoglycemia

• H2O deficit (L) = (observed [Na+] x TBW/desired [Na+]) –TBW – (TBW = ~75% x body weight)

– Acute/symptomatic - furosemide and D5W u/o replacement – Chronic/stable - ¼ NaCl with D2W at 1 mOsmol/kg/hr

17


Electrolyte Imbalances • Hyponatremia

– Common in children; common after surgery • Cerebral salt wasting • SIADH • Symptomatic if acute

– (older chidlren) nausea, anotrexia; – Can progress to altered mental status, irritability, seizures, respiratory arrest

• Na+ deficit (mmol) = (desired[Na]-observed[Na]) x TBW – TBW = ~75% x body weight

• If symptomatic (e.g. seizing) – rapid correction (~20-30 mins) – Target raising [Na+] by 3-6mEq/L, with hypertonic saline, or until seizures stop – Further correction should be slow, target [Na+]= 120mEq/L

• If asymptomatic, slow correction (1-2 days), 0.9% NaCl – No faster than 0.5 mEq/L/hr

• If excessively fast, risk of pontine myelinolysis

18


Other Electrolyte Imbalances • Hypokalemia

– Associated with vomiting, diarrhea; hypertrophic pyloric stenosis; diabetes, renal disease, diuretics, steroids, beta-agonists

– Weakness, ECG changes (prolonged QT, loss of T, U waves) – K+ deficit – serum measurements unreliable for total K+ since serum

potassium represent small proportion of total body potassium – Generally replace at [K+] = 2 – 2.5 mEq/L – Acute/symptomatic – 0.5 mEq/kg over 30 min (don’t

exceed 1 mEq/kg/hr); but first correct hypochloremia (if present) with NS.

– Chronic/stable - Dietary: 3-5 mEq/day PO

19


Electrolyte Imbalances

• Hyperkalemia ECG changes – Calcium Gluconate 30-100 mg/kg – Glucose (D25 2-4mL/kg + insulin 0.1-0.3 units/kg – Bicarbonate 1 mEq/kg – Albuterol 1.25 – 2.5 mg/dose (1-2 puffs Q 6 hours) – Kayexalate (Na/K exchanger, PO, rectally; rarely used in

neonates) – Hemodialysis (last resort)

20


Electrolyte Imbalances • Hypocalcemia

• Distinguish between calcium salts • CaCl

• ~3x more potent than Ca Gluconate • Concerning as vesicant • 270mg elemental calcium per 1000mg CaCl salt

• Calcium Gluconate • 90mg elemental calcium per 1000mg CaGluconate salt

• Therapy − Acute/symptomatic – elem-Ca++ 2-4 mg/kg over 5-10 min. − Chronic/stable – elem-Ca++ 15 mg/kg over 4-6 hrs.

− Caveats − Avoid Calcium and ceftriaxone − ECG monitoring − Caution with high phosphate − Consider hypomagnesemia if hypocalcemia is refractory

− If hypomagnesemia – elem-Mg++ 6mg/kg over 1 hr. 21


Thermoregulation (for the Neonate and Beyond)


Thermoregulation Basics

• Central (Core) vs Peripheral vs Skin • Core (heart, brain, liver)

– Tightly regulated around 37 degrees (+/- 0.2 C)

• Muscle compartment is a buffer; Skin is outer shell

• Anesthesia can defeat normal temperature-homeostatic mechanisms

23


Temperature Monitoring • Thermocouple

– Seebeck effect: current produced at interface of 2 different metals; voltage related to temperature

• Thermistor – Measures resistance in a metal – Increases exponentially with increasing temperature

• Infrared Thermometers – Convenient – Accuracy depends on appropriate use

• LCD Skin monitors – Convenient – Imprecise

24


Temperature Monitoring • Core Sites

– Skin • No simple relationship with skin temperature (skin

temperature highly variable) • Single site skin temperatures may not capture mild

hypothermia (and are poor at capturing MH hyperthermia early in course)

– Tympanic Membrane – would require tight fitting probe; risk of perforation

25



– Nasopharyngeal monitoring • Should be place close to soft palate • Easy • May underestimate core temperature if significant airflow (e.g.

ETT with a large leak) • Can cause adenoidal bleeding

– Esophageal • In small children, airway gas temperature (transmitted from

trachea) may result in underestimation of core temperature • Best if in distal esophagus (probes with stethoscopes are useful

because can advance probe until cardiac sounds are loudest) • Generally requires an ETT • More reliable than rectal temperature

26



– Axillary • Very convenient • Operator Dependent

– If placed over axillary artery with arm close to body, similar temperature to other measurement sites

– Mal-positioning à underestimation of core temperature – Rectal

• Avoid in neutropenia, bowel disease, risk for GI bleeding • May be inaccurate because of

– Insulation by feces – Abdominal procedure with irrigation; bowel or bladder irrigation – Cool peripheral blood returning from lower extremities

27



– Bladder Catheter • Accurate if increased urine output

– Pulmonary Artery Catheter Thermistor • Gold standard but invasive

28


Temperature Monitoring • General Practice

– General Surgery • Axillary, Esophagus (if intubated), Rectum (not

recommended in general by AAP)

– Cardiac Surgery • Two or more sites

– Blood, Rectal, Esophagus, NP

29


Neonatal Heat Loss • Greater Surface Area to Body Mass Ratio

– 1:1 @ Infant (FT) 0.4 @ Adult (IBW) – Large head – thin skull, +/- hair – Radiation and convective loss – Head is well perfused

• Cold air to face à 23% increased oxygen consumption for term baby; 36% increase for pre-term

• Less Subcutaneous Fat (especially preemies) – Conductive loss

• Less Epidermal Keratin (especially preemies) – Evaporative loss

30


Neonatal Heat Loss in a Thermoneutral Environment

Process Energy Transfer Loss (%) Conduction Direct Contact 3 Convection Air or Liquid Movement 34 Evaporation Liquid to Gas 24 Radiation Distant Object 39

In non-thermal neutral environments, different processes can play various roles; for instance, in room temperature OR, radiation may account for up to 70% of heat loss.

31


Humidified Environments for Nursery Care

• Radiant warmer - Tables may be an adequate environment for nursery care, But – Humidification may decrease insensible losses

and aid with electrolyte homeostasis. – However, high humidity may increase risk for

infection • New systems reduce this risk by chilling reservoir

water and creating sterile water vapor via boiling.

32


Neutral Thermal Environment • Temperature range in

incubator at which thermal homeostasis is maintained with minimal metabolic demand.

• Within this range of temperatures, alterations of vasomotor tone are sufficient for temperature regulation.

• Outside of this range, metabolic energy (and therefore increased oxygen consumption) is required to maintain body temperature.

(Adapted from Hey EN, Katz G: The optimum thermal environment for naked babies, Arch Dis Child 45:328-334, 1970.)Gleason, Christine A.; Devaskar, Sherin (2011-08-12). Avery's Diseases of the Newborn (Kindle Locations 24648-24649). Elsevier Health. Kindle Edition

For unclothed adult, neutral thermal environment at 28 degrees C. 33


Neutral Thermal Environment

• External heat – radiant warmer, incubation, plus metabolic heat production must balance losses for homeostasis.

• For radiant warmers with servo system, minimum metabolic demand is achieved at set point of ~36.5 C.

34


Thermoregulation • In GA and neuraxial anesthesia

– loss of peripheral afferents – central temperature sensing -- slower

• Inter-threshold Range – range of mean body temperature in which no temperature efferent

activity occurs – outside of this range, aggregate temperature afferent input induces

hypothalamic-directed efferent activity to raise or lower temperature • Central control present in term newborns, but less efficient than

adults. – Also reduced heat generation potential vs. children and adults

• Affected by medications, electrolyte concentrations, thyroid hormone, circadian rhythms, other physiologic factors

35


Non-Shivering Thermogenesis • Brown Fat

– 26-30 weeks of gestation – 2-6% of body weight – Scapulae (b/t) , axillae, mediastinum, and

@mammary arteries, adrenal glands, and kidneys – Mitochondria

• uncoupled oxidative phosphorylation – produce heat instead of ATP

• Mediated by UCP (Uncoupling Protein 1), thermogenin – C.O. (up to 25%) diverted to brown fat deposits

• More efficient warming of blood – Attenuated by GA (volatile and intravenous)

36


Thermoregulation and Heat Loss Prevention

After Birth and During Neonatal Intensive-Care

Unit Stabilization of Extremely

Low-Birthweight Infants

Journal of Obstetric, Gynecologic, & Neonatal Nursing Volume 36, Issue 3, pages 280-287, 2 MAY 2007 DOI: 10.1111/j.1552-6909.2007.00149.x http://onlinelibrary.wiley.com/doi/10.1111/j.1552-6909.2007.00149.x/full#f1

37

http://onlinelibrary.wiley.com/doi/10.1111/jogn.2007.36.issue-3/issuetoc

http://onlinelibrary.wiley.com/doi/10.1111/j.1552-6909.2007.00149.x/full





Shivering Thermogenesis • Last line of defense • More important for children and adults • Deleterious in anesthesia

– Although produces modest increase in metabolic heat production, there is cost in terms of oxygen consumption

– May increase ICP • May be unrelated to temperature in

anesthesia/surgery – Responds to meperidine

38


Oxygen Consumption and Temperature

• Key Point – – Oxygen consumption is NOT

proportional to core temperature

• Core temperature may be reflect very active metabolic response to significant on-going thermal losses

– Skin <-> environment temperature gradient more indicative of amount of metabolic work needed to maintain core temperature.

39


Oxygen Consumption and Temperature

• Key Point – – With cold stress, neonates

may double metabolic heat production via non-shivering thermogenesis

40


Hypothermia Prevention • Pre-Warming OR/Delivery Room

– If room cooled after patient covered, warmed, re-warm at end of case

• “sweaty” baby can rapidly loose heat (sweating more effective than autonomic warming response; wet baby in cold room can chill rapidly)

• Incubators (difficult for transport; resus; surg) – Hybrid

• Radiant Warmers (difficult for transport; surg) – Increased insensible fluid losses – Risk of overheating if servo system malfunctions

• Thermistor detachment is a risk • Alarms and close monitoring required • Ensure adequate distance from heating element to patient

41


Hypothermia Prevention • Warming Mattresses

– Maintain body temperature for smaller babies – Set to 40 degrees – Sheets between mattress and patient – Not effective for larger children and adults

• Forced Air Warmer – Very effective and convenient – Caution with vasoconstriction (risk of burns)

• Warming of – IV fluids, blood, irrigation fluid – Instruments – Table (chemical warmer) – (and humidification) Anesthetic Circuit

42


Response to Excess Heat

• Centrally controlled response to temperatures above the “set point” – Sweating – Increased skin blood flow (vasodilation of skin

capillaries) – Most heat loss by evaporation – Hyperthermia (> 7 degrees above normal) not

tolerated

43


Hypothermia Prevention

• Polyethylene blankets and hats (excellent for transport) – Reduce convection, evaporative losses – Risk of skin injury, airway obstruction

• Tegaderm/Opsite – Semipermeable dressings – Applied to torso of ELBW infants

• may improve heat loss and electrolyte stability – Further study needed

44


Anesthesia and Thermoregulation

• Hypothermia under anesthesia is common – Anesthesia suppression of CNS thermoregulatory

centers -> lowered temperature at which compensatory mechanisms for cold are triggered and higher temperature at which those for heat are triggered (wider temperature threshold range by factor of 10)

– Decreased heat production – Increased environmental exposure (usually) – Heat redistribution

45


Anesthetics and Temperature Regulation

• Opioids, propofol – Linear decrease of lower temperature threshold at

which shivering and vasoconstriction occur

• Inhaled agents – Non linear relationship – at higher concentrations

of anesthetic get significantly higher suppression of thermoregulation

– N2O – less pronounced effect vs potent inhalational agents

46


Anesthesia and Hypothermia

• Phase I: Internal Redistribution of Heat – Major factor early in anesthetic

• May lose 0.5 – 1.5 degrees Celsius in first hour

– Central compartment heat à Peripheral Compartment (effectively, central compartment expands; peripheral compartment contracts)

• Core gets colder • Periphery (e.g. extremities) get warmer

– Limit: vasoconstrictors 47



• Phase II: Thermal Imbalance – Decreased production of heat (metabolic rate

decreased, no use of skeletal muscles – including muscles of respiration if PPV)

– Increased loss of heat to environment (radiation, evaporation, convection, conduction)

• As patient cools, rate of heat loss decreases

– 0.5-1 degree C / hour – Limit: warming measures

48



• Phase III: Thermal Equilibrium (steady state) – Heat Production = Heat Loss

• Major regulatory factor is vasoconstriction – “shrinks” central compartment, so heat produced is

distributed over small volume (so increased core temperature)

– 34.5 – 35.5 degrees Celsius – In neonates –

• Vasoconstriction effective enough that Phase III is actually a “re-warming” phase; core temperatures increase.

49


Cold Stress can Exacerbate PPHN

• SNS mediated vasoconstriction • Increased pulmonary vascular resistance • (vasoconstriction, hypoxia) Metabolic Acidosis • Increased pulmonary vascular resistance &

increased pulmonary arterial pressure • R -> Left Shunting • Hypoxia • Increased pulmonary vascular resistance

50


Pulmonary Development and

Respiratory Physiology


Lung Prenatal Development

52


Respiratory System Development

• AIRWAYS – Bronchial tree down to the terminal bronchioles by 16 wks

of gestation – Distal structures throughout the remainder of gestation

• ALVEOLI – After birth until 8 years

• PULMONARY VESSELS – Accompanying bronchial tree by 16 weeks – Distal vessels follow development of alveoli – Arterial smooth muscle not complete until teens

53


Perinatal Adaptation

• Resp. activity – in utero • Umbilical cord clamping – rhythmic breathing • Elevated PaO2 à augments/maintains SV • 1st breaths: 40-80 cmH2O à overcome surface

forces and air into fluid filled lungs • Breathing independent of PaCO2

• HYPOxia depresses breathing

54


Postnatal Development

• At birth infant has 1/10th of terminal air sacs

• Alveoli develop from birth-18 months

• Morphologic/physiologic development – 10yrs

• Static recoil pressure lungs/thorax increases 55


Lung Mechanics - Neonate

• High lung compliance – Elastic fibers develop post-natal – Static elastic recoil pressure is low

• High chest wall compliance – Cartilaginous ribs – Limited thoracic muscle mass

• Prone to atelectasis and resp. insufficiency

56


Lung Mechanics – Infancy/Childhood

• Static recoil pressures steadily increase • Compliance decreases

– Normalized for size

• Prone to obstruction of upper/lower airways • Absolute airway diameter small

– Inflammation, edema or secretions à é obst

57


Respiratory Mechanics Chest Wall and Respiratory Muscles

• Accessory muscles of inspiration ineffective due to the more horizontal ribs

• Inspiration àresult of diaphragm decent • Prone to respiratory fatigue

– Diaphragm type I fibers: slow twitch, high oxidative capacity

58


Respiratory Mechanics Elastic Properties

• Recoil of lungs and thorax à counteract inspiratory forces à reduced lung volume

• Elastic properties lung/thorax à Lung Compliance

• Compliance constant for normal TV • Infants high compliance àlow elastic recoil

59



• Static Pressure-Volume Relationship – Changing volume and elastic properties of lung

• Volume: main determinent of lung compliance – Increases throughout childhood

• Specific lung compliance remains constant • Specific compliance of the chest wall declines

60


Mechanics of Breathing Elastic Properties

• Infants OUTWARD recoil low à horizontal/cartilaginous rib cage & poorly developed resp. muscles

• Infants INWARD recoil minimally lower than adult

• Static balance of outward/inward recoil àLow FRC

61



• Awake infants maintain FRC actively – “premature” stop of expiration – Fast breathing – Glottic closure during expiratory phase (laryngeal

braking) – Diaphragmatic “braking” – Tonic contractions of diaphragm/intercostals (higher

tone) à stiffens chest wall à maintain higher end expir. Volume

• All lost by GA à reduced FRC/airway closure/atelectasis

62


Ventilation - Neonates

• Periodic breathing à apnea < 10 sec – Without cyanosis or brady – During quiet sleep – 80% of term neonates – 100% of preterm – 30% of infants up to 1 yo

63


Ventilation Central Apnea

• Apnea > 15 seconds • Apnea associated with HR< 100, cyanosis or

pallor • Rare in full term • Majority of premature

64


Lung Volumes and Mechanics

65

May be only 15% of TLC in young infants under GA + muscle relaxant

= 50% of TLC

= 60 ml/kg infant after18 mo increases to adult 90 ml/kg by age 5


Lung Volumes

66


Lung Volumes

• Total Lung Capacity smaller in infants vs adults by mass: 63 vs 82 ml/kg

• (dynamic) Functional Residual Capacity similar/KG across ages à different mechanics – Adults: volume when elastic forces of passive

recoil of the chest is balanced by recoil of lung – Infants: premature stop of expiration (with

laryngeal braking, initiation of next breath)

67


Lung Volumes Closing Capacity

• With exhalation small airways in dependent regions can collapse leading to atelectasis, V/Q mismatch and desaturation

• Closely related to age – Infants high closing capacity: tidal breathing

occurs at similar volumes to closing capacity – Childhood/teens: decreasing closing capacity – Adult: Increasing closing capacity

68



• Larynx • Limited space in oropharynx • Preferential nasal air exchange

• ⬆ Laryngeal-Tracheal-Bronchial Compliance

• Airway Resistance in small airways accounts for work of breathing

69



• Chest Wall: Floppy, Ribs horizontal

• Diaphragm: ⇩ Type I muscles/fatigue-resistant – 10-25%

• ⇩ Lung Elastic Recoil • Minute Ventilation : FRC = 5:1 • FRC (30 ml/kg) maintained dynamically • Closing Capacity > FRC

70


Respiratory Control

• ⬇CO2 Response: Slope function of gestational age, postnatal age & pO2

• ⬇ O2: ⬆ Ventilation ➜ ⬇ Ventilation • Anemia, Hypoglycemia, Hypocalcemia &

Hypothermia ➜ ⬇ Ventilatory Drive • Hering Breuer Reflex: Lung Inflation ➜ Apnea • Vagus-mediated airway reflexes ➜ Apnea

71


CO2 response curve

Respiratory Control

72


Oxygen Transport

• Functional Components of O2 Transport – Pulmonary ventilation – Cardiac Output – Hemoglobin concentration

• Majority of O2 carried by hemoglobin • Small amount dissolved in plasma àlow solub

73


O2 Transport – Increased Demand

• Acute – Increased CO – Increased alveolar vent à maintain alveolar PO2 and

PCO2 • Chronic

– Increased erythropoietin – Increased plasma volume to maintain viscosity

74


Oxygen-Hemoglobin Dissociation

• Reflects affinity of hemoglobin for oxygen • P50 – the PaO2 where hemoglobin is 50%

saturated • P50 normal adult is 27 • Alkalosis (êH+, CO2) êTo

– Increases affinity/curve to left à Bohr effect

• Acidosis (éH+, CO2) éTo

– Decrease affinity/curve to right 75


Oxygen transport

(Bohr effect)

= 27, normal adult (19, fetus/newborn)

O2 Dissociation Curve - Blood O2 Affinity Factors

76


O2 Transport – Newborn O2 Dissociation Curve

• Organic Phosphates – 2,3-DPG, ATP –é P50

– Curve shifts to right • 2,3 DPG increases with chronic hypoxia • Newborn 2,3-DPG is low àlow P50 (18 mmHg)

– That is, fetal hemoglobin reaches 50% saturation at lower PaO2 than adult hemoglobin.

• Fetal Hb reacts poorly with 2,3-DPG • O2 affinity is high à tissue delivery low

77


Oxygen transport

6 months 66 4

Neonatal, Infant, Adult O2-Hb Dissociation Curves

If SpO2 = 91% then PaO2 = Neonate 40 Adult 60 Infant 65

78


Surfactant

• Lungs lined with surface-active materials • Reduce alveolar surface tension

– Prevent atelectasis – Decrease Pulmonary compliance

• Produced by type II pneumocytes • First detected – 23 weeks gestation • Mature levels – 34 weeks gestation • Insufficient surfactant à Respiratory Distress

Syndrome 79


Surfactant

• Lethicin:Sphingomyelin Ratio > 2.0 low risk of RDS • Type II Pneumocytes

– Progenitors of type 1 pneumocytes – Specialized lamellar bodies released via merocrine

secretion – Recycle degraded surfactant

• 90% lipids (phopholipifd and phosphatidylcholines), 10% protein; some carbohydrates

80


Surfactant – Laplace’s law P = 2g/r (assumes alveolus is a sphere) – P = intraalveolar pressure (“collapse pressure”) Pressure needed to counteract contracting molecular forces

produced at air-fluid interface – r = radius of alveolus – g = surface tension Small radius alveolae require more pressure to stay open

81


Surfactant

• Inadequate surfactant production – Prematurity (< 32 weeks)

• Treat with maternal steroids; exogenous surfactant administered via ETT

– Infant of diabetic mother – Inactivation of surfacant

• Meconium aspiration

82


Ciliary Activity

• Removal of mucoid secretions, foreign particles, cell debris

• Defense mechanism • Function influenced by mucus layer • 50% humidity maintains normal activity • 3 hours dry air à complete cessation • 100% O2, PPV, Inhalationals ê ciliary function

83


Ventilation/Perfusion

• Both components affected by position/gravity • Gravity é effect with ê BP and ê volume • Upright: V/Q > 1 apex and < 1 bases • Supine: V/Q > 1 anterior and < 1 posterior • Infants/children PA pressures relatively high

– Pulm. Blood flow more uniform throughout à gravity less of effect

84


V/Q Disease States

• Uneven vent and/or perfusion à changes V/Q • CHD with é pulm blood flow à ê V/Q

– Left-to-right shunt

• CHD with ê pulm blood flow à é V/Q

85


V/Q Regulation

• Limited intrinsic regulatory mechanism • Areas of high V/Q with low PCO2 à

airway const/pulm vessels dilate • Areas of low V/Q with high PCO2, low PO2 à

airway dilate/pulm vessels const • Lung units with low V/Q breathing é FiO2 will

tend to collapse and atelectasis occurs

86


Hypoxic Pulmonary Vasoconstriction

• HPV à ê regional blood flow to éV/Q • Inhaled agents depress HPV in vitro • Drugs depress HPV

– Isoproterenol, NTG, theophylline and SNP

87


Respiratory Physiology – Key Points

• Postnatal adaptation: especially respiratory control until 44 wks PCA

• Post GA apnea common in premature and/or anemic infants

• Alveoli formation until 18 months • Elastic/collagen fiber development continues

until 10 years

88


Respiratory Physiology – Key Points

• Infant chest wall VERY Compliant à difficulty sustaining FRC against lung elastic recoil – Worsen by GA and/or relaxation – Leads to airway closure/progressive atalectasis – PEEP helps

• Hb O2 affinity changes during first months – HbF – low P50

– P50 increases and peaks in later infancy 89


Cardiovascular Physiology of the Newborn: the Basics


Cardiac Physiology

91

www.pted.org/pics/fetal2a.gif medicineworld.org/images/


Fetal Circulation

• Low resistance placenta and low SVR • Circulation is parallel • Ducts and bypasses allow for the maximal

amount of oxygenated blood to reach brain, heart and body

• High resistance (PVR) in lungs forces most of RV output across ductus arteriosus

92


Fetal Circulation • Blood from placenta goes to umbilical vein → • Liver (40%) and ductus venosus (60%) →IVC • IVC also gets blood from R and L hepatic veins– 2

streams – Fast and more oxygenated-from ductus venosus and L

hepatic vein – Slow-from liver and R hepatic vein and abdominal IVC

• At R atrium fast flow goes across foramen ovale to L atrium

• Slow Flow goes to RV→Pulmonary artery → ductus arteriosus

93


Fetal circulation

94

http://www.embryology.ch/images/pimgcardio/09umstellung/p9a_KreislaufvorA.gif


95


Hemodynamic Changes at Birth Right Ventricle Left Ventricle

Decreased afterload: Increased afterload: Decreased pulmonary vascular resistance Placenta eliminated

Ductal closure Ductal closure

Decreased volume load: Increased volume load:

Eliminated umbilical vein return Increased pulmonary venous return

Output diminished 25% Output increased almost 50%

Transient left-to-right shunt at ductus

96

Schure and Dinardo from A Practice of Anesthesia for Infants and Children. Fig 16.4, Edited by Cote, Lermann Anderson, 2013


Normal Circulation at Birth

• Change from Parallel circulation to Series • Lose placenta → ↑ SVR

• Lungs go from being fluid filled to air-filled • Closure of ducts that allowed for parallel

circulation • Lung inflation and increased O2 tension → ↓

PVR → ↑pulmonary flow

97


Transitional Circulation

• Increased LA pressure closes foramen ovale • Lack of flow though ductus venosus leads to

involution of that structure • Ductus arteriosus (DA) normally will

vasoconstrict and close, although closure is reversible until fibrosis occurs several weeks after birth. Hypoxemia, acidosis can keep DA open longer

98


99

http://www.rci.rutgers.edu


Pulmonary Vascular Resistance

• PVR decreases in last trimester due to growth of pulmonary vasculature

• At birth, lung inflation, endogenous mediators and interstitial fluid and pressure changes cause a rapid decrease in the PVR to half that of SVR.

• Ducts close permanently over time

100


22.1

The Normal Transition

Rudolph, A.M., Prenatal and postnatal pulmonary circulation, in Congenital diseases of the heart: Clinical-physiological considerations. 2009, Wiley-Blackwell: West Sussex, UK. p. 89.


Rudolph, A.M., Congenital cardiovascular malformations and the fetal circulation. Arch Dis Child Fetal Neonatal Ed, 2010. 95(2): p.

F132-6

23.1

Persistent Pulmonary Hypertension of the Newborn PPHN

In fetal lamb, as gestation increases, PVR becomes increasingly sensitive to hypoxia


1. Rudolph, A. M. and S. Yuan (1966). "Response of the pulmonary vasculature to hypoxia and H+ ion

concentration changes." J Clin Invest 45(3): 399-411.

23.2

Persistent Pulmonary Hypertension of the Newborn PPHN

Response of the newborn lamb to changes in oxygen saturation is markedly different depending on blood pH


Conditions Prolonging Transitional Circulation

• Prematurity • Sepsis • Hypoxemia, • Hypercarbia • Congenital Heart

Disease (CHD) • Pulmonary Disease

• Acidosis • High Altitude • Prolonged Stress • Hypothermia

Schure and Dinardo from A Practice of Anesthesia for Infants and Children. Fig 16.4, Edited by Cote, Lerman Anderson, 2013

104


Selected Factors that Modulate Pulmonary Vascular Resistance

Factors that modulate PVR

Decreases PVR Increases PVR

Endogenous mediators

Oxygen Nitric Oxide

Hypoxia,

Prostaglandins: PG12, E2, D2 Prostaglandin PGF2a Leukotrienes, thromboxanes

Alkalosis Acidosis

Vagal Nerve and β-Adrenergic stimulation

Α-adrenergic stimulation

Histamine, acetylcholine, Platelet activating factor

Adenosine, ATP, magnesium, Ca++ channel activation

Mechanical Lung Inflation Over or under inflation

Vascular Structural changes of cells Muscularization or remodeling

Interstitial Fluid Ventricular dysfunction, venous hypertension

Shear Stress Pulmonary hypoplasia, pulm thromboemboli, capillary dysplasia

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Persistent Neonatal Pulmonary Hypertension

Diagnosis Signs and Symptoms Treatment

Congenital Diaphragmatic Hernia

Respiratory distress Displaced cardiac signs No breath sounds over one hemithorax Scaphoid Abdomen

Intubation, adequate ventilation and oxygenation May require nitric oxide, HFOV, ECMO

Meconium Aspiration Syndrome

Fetal distress, Respiratory distress Meconium stained amniotic fluid, meconium in trachea and pharynx

Suction tracheo-bronchial tree Intubation, ventilation and oxygenation (see above)

Birth Asphyxia Fetal Distress, difficult delivery, Low Apgars, +/- CV compromise and respiratory distress, seizures, poor UOP,

Intubation, ventilation, CV support as needed, seizure control

Sepsis Hypo or hyperthermia Hypotonicity CV compromise, poor UOP +/- respiratory distress

Antibiotics Respiratory support CV support

106 Modified from: Lӧnnqvist. Management of the Neonate :Anesthetic Considerations. Chapter 86.Pediatric Anesthesia. Edited by Bissonette, PMPH-USA 2011; Tables 86.2 and 86.3


Myocardial Function Myocyte

• Less able to generate force – More non-contractile elements – Different organization of intra-celluar elements – Increased dependence on extracellular CA++

• Sarcoplasmic reticulum and T-tubule network are immature • More sensitive to calcium channel antagonists

• Less Compliant – Type 1: Type 3 collagen ratio higher in infants vs adults – Delayed diastolic relaxation – Decreased diastolic filling

107


Myocytes • Mitochondria

– Fewer – Less mature – Organization differs , function, organization, and

maturation of mitochondria – Less able to metabolize fatty acids – Dependent on carbohydrates and lactate

• More resistant to hypoxia • Fewer myocytes per muscle fiber

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Myocardial innervation

• Parasympathetic innervation more developed than sympathetic – Increased cholinergic receptors

• Variable time for anatomical and functional maturation of sympathetic nervous system

• High levels of catecholamines at birth – Maximal adrenergic stimulation of myocardium – Reduced functional reserve

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110 Left ventricular output in 37 stable newborn infants (closed circles) and 3 infants with patent ductus arteriosus (open circles). Figures A and B show absolute LVO (ml.min-1), figures C and D show weight corrected LVO (ml.kg-1.min-1).

http://www1.imperial.ac.uk/medicine/divisions/cs/imagesci/pedmr_0/cardiac_mri/


Cardiac Output

• Limited (but some) capacity to generate increased stroke volume in response to increased pre-load

• Poor tolerance to decreased pre-load • CO decreases with decreasing HR and HR

>180-190 • Decreased myocardial compliance ∴

decreased ability to compensate for increases in systemic vascular resistance

111


Frank-Starling Relationship in Fetal Lambs

112

Frank-Starling relationship in fetal lamb model (gestational age, 135 ± 5 days). A, The relationship between left ventricular end-diastolic pressure (LVEDP) and shortening in a chronically instrumented fetal lamb model. Although myocardial performance improves with increasing LVEDP, the effect achieves a plateau at 10 mm Hg. B, In the same model, the relationship between left ventricular end-diastolic diameter (LVEDD) and left ventricular shortening. Taken together, these experiments support the capacity, albeit blunted, of the fetal heart to change stroke volume on the basis of volume loading conditions. Each point and vertical bars represent mean ± standard error (SE).

Schure and Dinardo from A Practice of Anesthesia for Infants and Children. Fig 16.4, Edited by Cote, Lermann Anderson, 2013


Treatment of Low Cardiac Output

• Goal: Increase oxygen delivery to tissues – Optimize volume and hemoglobin – Catecholamine or catecholamine like substances

are the most useful – Dopamine and Dobutamine increase both HR and

contractility – Drugs that increase afterload only are NOT useful

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Commonly used inotropes and vasopressors in Agent Dose Comments

Dopamine 2-20 µg/kg/min β1 and β1 and dopaminergic receptor agonist Dose related effects α adrenergic effects at higher doses Endogenous catecholamine affects potential vasoconstriction at higher doses

Dobutamine 2-20 µg/kg/min

β1 stimulation, some β2, tachycardia and vasodilation at higher doses, less potent than dopamine in immature myocardium, no α effects,

Epinephrine 0.02-2.0 µg/kg/min

Primary β effects at doses < 0.10 µg/kg/min Higher doses → more α effects, and increased contractility and vasoconstriction

Vasopressin 0.0005-0.002 U/kg/min

V1a receptor agonist-vasoconstriction, V2 –increased renin and renal reabsorption of water. NOT proven useful in most neonate; may be helpful as rescue in pts with CHD

Phenylephrine 1-10 mcg/kg bolus, followed by 0.1-0.5 mcg/kg/min

Pure α, rarely useful in neonates

114


Other agents

115

Dose Comments

Calcium Chloride Calcium Gluconate

10-20 mg/kg 30-60mg/kg

Positive inotrope of iCa++ is low and/or ventricular function depressed by other agents Vasoconstriction

Amrinone and Milrinone

A: 2-4mg/kg LD followed by infusion 10 mcg/kg/min M: 50-75 mcg/kg LD followed by 0.5-1.0 mcg/kg/min

Phosphodiesterase inhibitors, increase cAMP → positive inotropy, lusitropy, and smooth muscle relaxation


Ventricular Pressure Volume Curve

116

From A Practice of Anesthesia for Infants and Children. Fig 16.3, Edited by Cote, Lerman Anderson, 2013


Anesthetic Effects on the Cardiovascular System

Volatile Agents: • MAC varies with age-higher in full term neonates, lower in premature infants • Volatile agents decrease intracellular Ca++ and ↓myocardial contractility • Halothane -Greater decreases of BP and HR • Sevoflurane and Isoflurane decrease SVR and myocardial contractility, but maintain HR

117


Anesthetic Effects on CV System

Volatile Agents • SBP can ↓ up to 30% with all agents • Halothane decreases conduction

– Reports of bradycardia, junctional rhythm and asystole

– Isoflurane and Desflurane may increase HR +/- BP due to sympathetic responses

118


Anesthetic Effects on CV System

Intravenous Agents • Propofol decreases HR and SBP • Clearance may be prolonged in neonates with

great inter-individual variability

119


Cardiac Physiology Key points

• Parallel fetal circulation with high pulmonary vascular resistance transitions to neonatal circulation with low pulmonary vascular resistance

• Myocyte has relatively fewer contractile elements and is more dependent on extracellular calcium

• Myocardium is less compliant and is generating near maximal force

120


Cardiac Physiology Key points

• Decreases in preload, increases in systemic vascular resistance and decreases in HR are poorly tolerated

• Goal of treating low cardiac output is to increase oxygen delivery to tissues

• MAC of volatile agents varies with age, but all decrease BP

121


References • Coté and Lerman’s A Practice of Anesthesia for Infants

and Children 5th Edition, Coté, Lerman and Anderson Editors. Elsevier Saunders 2013

• Smith’s Anesthesia for Infants and Children. Davis, Cladis and Motoyama editors, 8th Edition, Elsevier Mosby 2011 (kindle edition)

• Gregory ’ s Pediatric Anesthesia, Gregory and Andropoulos Editors, Wiley Blackwell 2012 (kindle edition)

• Pediatric Anesthesia-Basic Principles-State of the Art-Future, Bissonnette Editor, PMPH-USA, 2011

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Documents

Neonatal Physiology for the Anesthesiologist€¦ · Neonatal Physiology for the Anesthesiologist Linda J. Mason, M.D. Professor of Anesthesiology and Pediatrics Loma Linda University