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The Premature Neonate

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The Premature Neonate Claude Abdallah, MD, MSc * * * * Thermoregulatory thresholds in unanesthetized and anesthetized humans. The slanted lines represent different ... – PowerPoint PPT presentation

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Title: The Premature Neonate


1
The Premature Neonate
  • Claude Abdallah, MD, MSc

2
Preterm Neonates
  • Morbidity and mortality in this population has
    decreased over the past 25 years.
  • In extremely low birth weight premature
    neonate(lt1000 g) mortality lt 50 (80 in 1980).
  • Contributing Factors
  • - Use of surfactant shortly after birth,
  • - Specialization of neonatal care units, and
  • - Changes in mechanical ventilator therapy.
  • However, physiological challenges persist and
    affect the anesthesia management.

3
Airway and Work of Breathing

Spaeth JP, O'Hara IB, Kurth CD Anesthesia for
the micropremie. Semin Perinatol 1998 22390-401.
4
Airway and Work of Breathing
  • Small airways predispositon to obstruction and
    difficulty with ventilation.
  • Insertion of an ETT increases resistance and
    work of breathing far greater for the premie (2.5
    or 3 mm inside diameter ID) (Resistance to
    airflow is inversely proportional to the fifth
    power for large airways and to the fourth power
    of the radius for small airways. )
  • Additional partial occlusion from loss of muscle
    tone during anesthesia.

5
Pediatr Crit Care Med. 200910(1)1-11.
6
Effect of airway pathology
  • Subglottic stenosis,
  • Tracheal stenosis,
  • and Tracheobronchomalacia
  • occur commonly in the micropremie ?increase
    further resistance to airflow and work of
    breathing.
  • Also, may necessitate the placement of even a
    smaller ETTgtgt airway resistance from the stenosis
    distal to the endotracheal tube

7
POSTNATAL DEVELOPMENT OF THE LUNGS AND THORAX
  • The respiratory system is not fully developed at
    birth.
  • The morphologic and physiologic development of
    the lungs continues throughout the first years of
    life.
  • Alveolar formation begins only about the 36th
    week of gestation.
  • Thick-walled saccular spaces ? decrease lung
    compliance.

8
Production of Surfactant
  • -Begins between 23 to 24 weeks of gestation,
  • -Remain inadequate until 36 weeks of gestation?
    lung volumes and compliance are decreased?
    increase intrapulmonary shunt and
    ventilation/perfusion mismatch and increase the
    risk of hypoxia.
  • -Anesthesia further decreases V/Q mismatch.
    Ventilation with continuous PEEP during
    anesthesia required but limited
  • Susceptibility to O2 toxicity, barotrauma, and
    development of bronchopulmonary dysplasia.

9
RAPID DESATURATION IN PREMIES?WHY?
  • -Lung volume disproportionately small
  • -Higher metabolic rates in infants The neonatal
    oxygen consumption is approximately 6 ml/kg/min
    versus 3 ml/kg/min in the adult
  • Even under normal circumstances the immature
    cardiac and respiratory systems must function
    near maximum to support this metabolic demand.
  • -Elastic recoil pressure of the lung and thorax
    are low
  • Poorly developed thoracic muscle mass
  • Increasing respiratory rate rather than tidal
    volume
  • The diaphragm is the primary respiratory muscle
    has fewer high-oxidative muscle fibers and is
    less resistant to fatigue than the adult
    diaphragm.
  • Mechanical challenge Ribs Raised ?small
    increase in thoracic cavity volume with
    contraction of the diaphragm.
  • ,

10
Respiratory Control and Prematurity
  • Response to hypoxia
  • Biphasic Ventilatory Response
  • - Initially, ventilation increases during
    hypoxia, but after several minutes,
  • - Ventilation decreases and apnea may ensue.
  • Anesthetic drugs
  • - depress the ventilatory responses to both
    hypoxia and hypercapnia.

11
Anesthesiology
Editorial 59495-498, 1983
  • Life-threatening Perioperative Apnea in the
    Ex-premie
  • George A. Gregory and David Steward

12
Post anesthetic Care Discharge of Neonates
  • Full Term Infant (Born at PCA 37 weeks) and
    otherwise healthy
  • If 45 weeks PCA Overnight stay in hospital in
    monitored bed.
  • Must have at least 12 hours of apnea-free period
    prior to discharge.
  • Preterm Infant (Born at PCA lt37 weeks) and
    otherwise healthy
  • If 55 weeks PCA Overnight stay in hospital in
    monitored bed.
  • Must have at least 12 hours of apnea-free period
    prior to discharge.
  • ?Ex-premature infants should not undergo
    anesthesia for elective surgery until they are at
    least 56 weeks of PCA and Hct gt 30.
  • A minimal stay of 2 hours of apnea free period
    in PACU is required for all these patients. If
    needed, they should be transported with
    monitoring and accompanied by a registered nurse.

13
Kurth et al, 1987
  • Prospective study using pneumography
  • 47 premature infants
  • 37 incidence of postop. prolonged apnea in
    infants 32 - 55 wks. PCA
  • Initial episode may occur as late as 12 hrs.
    postop.
  • All types of surgical procedures, including NEC
    and VP shunts

14
How about caffeine?
15
Incidence of Perioperative Apnea and PB Caffeine
5mg/kg
  • Caffeine
    Controls
  • Postop. prolonged apnea none
    8(73)
  • with bradycardia
  • Postop. PB none
    2(18)
  • Postop. apnea lt 15 sec 8(89)
    1(9)
  • Postop. caffeine level 5-8.6
    zero
  • mg/L (range)
  • Periodic Breathing
  • Three or more periods of apnea 3-15 secs.
    separated by lt 20 secs. of normal respiration

16
Incidence of Postoperative Apnea, PB and
Desaturation Caffeine 10mg/kg
  • Caffeine
    Controls
  • Postop. prolonged apnea none
    13(8)
  • Postop. PB gt1 none
    4(25)
  • Postop. desat.lt 90 none
    8(50)
  • Postop. caffeine level 15-19
    zero
  • mg/L (range)

17
  • Caffeine concentrations as low as 3-5 mg/L can
    decrease apneic spells in neonates, Brief apnea
    persisted
  • Plasma concentrations of 8-20 mg/L are required
    for optimal response
  • No toxicity(????) with concentrations as high as
    50 mg/L

18
Survival without disability to age 5 years after
neonatal caffeine therapy for apnea of
prematurity. JAMA. 2012 Jan 18307(3)275-82.
  • Five-year follow-up in academic hospitals.
    Randomized, placebo-controlled. Caffeine for
    Apnea of Prematurity Study. A total of 1640
    children with birth weights of 500 to 1250 g.
  • The combined outcome of death or disability was
    not significantly different for the 833 children
    assigned to caffeine from that for the 807
    children assigned to placebo.

19
Postoperative Apnea in Former Preterm Infants
  • Spinal vs General Anesthesia

20
Incidence of Postoperative Apnea and PB
  • General
    Spinal Spinal
  • Anesthesia
    Anesthesia Ketamine
  • Prolonged Apnea 5(31) 0
    8(89)
  • with bradycardia
  • PB gt 1 1
    0 2
  • Intubation or 0
    0 0
  • ventilation

21
Is Preoperative Transfusion Necessary?
22
Postoperative Complications
  • Hct gt 30 Hct lt
    30
  • Brief Apnea 0
    0
  • PB gt 1 0
    20
  • Prolonged Apnea 21 80
  • Bradycardia 0
    20

23
Summary
  • Anemia in preterm infants increased
    incidence of postop. apnea
  • Anemic infants had high HbF and low 2,3 DPG
  • Defer elective surgery
  • Close postoperative monitoring

24
Anesthesiology 82809-822, 1995
  • Postoperative Apnea in Former Preterm Infants
    after Inguinal Herniorrhaphy
  • Metanalysis of previous studies
  • Limitations
  • Small number of patients
  • Significant variation of incidence of apnea
    between different institutions
  • Considerable variation in the duration and type
    of monitoring and definitions of apnea

25
  • Predicted probability of apnea after leaving
    recovery room by weeks postconceptual age (weeks)
    for infants who did not have apnea in recovery
    room or anemia . Bottom marks indicate the number
    of data points by postconceptual age. The risk
    does not fall below 1 with 95 statistical
    confidence until 56 weeks postconceptual age.

Anesthesiology. 82(4)809-822, April 1995.
26
Fisher D Anesthesiology 82807-808,1995
  • .....Establishing policy regarding the postop.
    management of ex-premature infants undergoing
    inguinal hernia repair requires a decision
    regarding acceptable risk

27
Pediatric Anesthesia 22 (2012) 1139-1141
28
Thermoregulation Premature Neonate
  • Small size and
  • Increased surface-area-to-volume ratio.
  • Increased thermal conductance .
  • Limited range of the neutral thermal environment
    Range of ambient temp. at which metabolic rate is
    minimal.
  • Normal body temp. range for a neonate is 36.5 to
    37.7 C.
  • Temp. below 36 C are considered hypothermic.
  • Predisposition to APNEA, BRADYCARDIA, and/or
    METABOLIC ACIDOSIS.
  • Maximum ventilatory response to PCO2 decreases.
  • Extubation and Transfer Criteria

29
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30
Non Shivering Thermogenesis
-Principally metabolism of brown fat (2-6 of
TBW). -Brown fat differentiates at the 26 to 30
weeks gestational period. -Multinucleated cells,
numerous mitochondria. -Abundant vascular supply
and innervation. -COST increases in
norepinephrine (3X), glucocorticoids and
thyroxine production. Prevention of hypothermia
is extremely important
31
Thermoregulatory Thresholds
The intersection of line with the temp scale
threshold. Interthreshold range Core
temperatures not triggering autonomic
thermoregulatory responses 0.2-0.4 deg.
C ASessler DI Temperature monitoring. In Miller
RD (ed) Anesthesia, 4th ed. New York, Churchill
Livingstone, 1994, p 1363.
32
Effects of Mild Hypothermia
  • - Stress response V-C (incr. SVR, CVP).
  • - Decreased RBF and GF. Cold diuresis, impaired
    sodium reabsorption hypovolemia.
  • Impaired coagulation Defect in platelet fction
    clotting factors.
  • Leftward shift of oxy-Hb dissociation curve
    ?BMR deleterious effect.
  • Increased wound infections (immune function
    v-c). ?Duration of hosp. by 20.
  • Shivering Increase in wound pain and in
    intraocular and intracranial pressures.

33
Effects of Anesthesia Medications on
Thermoregulation
  • Volatile anesthetics Hypothalamus direct
    vasodilatory effect. Inhibit brown fat
    thermogenesis. Dose-dependent.
  • Opioids reduce vasoconstriction.
  • Barbiturates peripheral vasodilation.
  • Ketamine less thermoregulatory effect.
  • Muscle relaxants prevent shivering thermogenesis
    by effect on muscle tone.

34
Pharmacological Effects of Hypothermia
  • Decreased hepatic renal blood flow metabolism
    Prolongation of drug effects.
  • Protein binding increases as body temperature
    decreases.
  • The MAC of inhalational agents is ?5-7 per ?1C?
    in core temp, but no change in speed of
    inhalational induction.
  • Prolong the duration of neuromuscular blocking
    agents.
  • Delays discharge from PACU and may prolong the
    need for mechanical ventilation.

35
Cycle resulting from cooling in the neonate.
(From Klaus M and Fanaroff A Care of the
high-risk neonate, ed. 3, Philadelphia, WB
Saunders Co.)
36
Covering the infants head with plastic wrap can
greatly reduce the evaporative heat loss.
37
During maxillofacial surgery, rectal temp.
increased in infants given forced-air but
remained nearly constant in patients warmed with
circulating-water. (From Kurz et al. Anesth Analg
7789, 93).
38
Anesthetics and the Immature Brain
  • Of particular concern are the reports in
    immature rats showing that prolonged exposure to
    isoflurane, ketamine, or midazolam precipitates
    apoptosis in many regions of the brain.
  • Attributed to the neurotransmitters glutamate and
    ?-aminobutyric acid, which act as trophic factors
    in the developing brain
  • Based on the life cycle of the rat compared with
    the human, the 4-day, 7-day, 10-day, and 14-day
    postnatal age rat corresponds to 28-week
    gestation, 32-week gestation, 40-week gestation,
    and 55-week postconceptual age human.
  • Prolonged exposure at very high concentrations.
  • Potential for neurotoxicity from inhaled
    anesthetics, midazolam, and ketamine.. may be
    greater in preterm infants than full-term
    infants, although there is no evidence that
    similar neurotoxicity occurs in humans at any age
    exposed to any anesthetics.

39
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40
Arguments- Drug Dose
  • Anesthetic requirements for injectable agents
    much higher in small animals
  • Propofol 100x
  • Ketamine 10x
  • Higher doses led to much higher blood levels

41
Prematurity Cardiovascular System
  • Greater risk of cardiovascular collapse during
    anesthesia
  • Structural More connective tissue, less
    organized contractile elements
  • Increased dependence on extracellular calcium
    concentration.
  • Less compliant fetal heart has a flatter
    Frank-Starling curve
  • Less sensitive to catecholamines because of
    near-maximal baseline ß-adrenergic stimulation.
  • Cardiac output depends more on heart rate in the
    premature than the full term neonate.
  • The high resting heart rate in the premature
    does not permit cardiac output to increase to the
    same extent as full term.

42
Prematurity and Circulation
  • Small absolute blood volume?little blood loss
    during surgery can cause hypovolemia, and shock.
  • Autoregulation is not well developed in the
    premie, heart rate may not increase with
    hypovolemia ? blood flow and oxygen delivery to
    the brain and heart may decrease with little
    blood loss.
  • Anesthesia blunts baroreflexes in the
    micropremie, further limiting the ability to
    compensate for hypovolemia?predispose the
    micropremie to cardiovascular collapse during
    major surgery.

43
Circulating Blood Volume in Micropremature
Infants, Premature Infants, Full-Term Neonates,
Infants, and Children
  Blood Volume (mL/kg) Weight (kg) Total Blood Volume (mL) 25 mL Blood Loss Percentage Total Blood Volume ()
Micropremie 110 1 110 23
Premie 100 1.75 175 14
Full-term neonate 90 3 270 9
Infant 80 10 800 3
Child 70 20 1400 2

44
Neurologic Development
  • The impact of premature birth on the central
    nervous system (CNS) depends on gestational age
    at birth and the severity of cardiovascular,
    respiratory, and other postnatal stressors.
  • The area of the brain most susceptible to injury
    in the micropremie is the periventricular white
    matter.
  • The white matter consists of preoligodendrocytes,
    astrocytes, and neuronal axons.
  • Late in the second trimester (2427 weeks'
    gestation), preoligodendrocytes and astrocytes
    multiply tremendously and most cortical and
    subcortical structures begin to develop.
  • The periventricular white matter is a watershed
    region and sus-ceptible to poor perfusion and
    hypoxic-ischemic injury during conditions of
    hypotension, low cardiac output, hypoxemia, and
    hypocarbia.

45
Intraventricular Hemorrhage
Premature neonates are more likely to exhibit severe long-term neurocognitive sequelae, Risk factors include fetal distress, vaginal delivery, low APGAR scores, metabolic acidosis, hypercapnia, and the need for mechanical ventilation. Respiratory distress syndrome, seizures, pneumothoraces, hypoxemia, acidosis, severe hypocarbia, and the use of vasopressor infusions. Rapid fluctuations in cerebral blood flow, cerebral blood volume, and cerebral venous pressure appear to play a role in the development of IVH .Factors that may decrease the incidence and severity of IVH include administration of sedation with opioids, antenatal glucocorticoids, or indomethacin Grade 1 hemorrhage limited to the germinal matrix
Premature neonates are more likely to exhibit severe long-term neurocognitive sequelae, Risk factors include fetal distress, vaginal delivery, low APGAR scores, metabolic acidosis, hypercapnia, and the need for mechanical ventilation. Respiratory distress syndrome, seizures, pneumothoraces, hypoxemia, acidosis, severe hypocarbia, and the use of vasopressor infusions. Rapid fluctuations in cerebral blood flow, cerebral blood volume, and cerebral venous pressure appear to play a role in the development of IVH .Factors that may decrease the incidence and severity of IVH include administration of sedation with opioids, antenatal glucocorticoids, or indomethacin Grade 2 hemorrhage extending into the ventricular system
Premature neonates are more likely to exhibit severe long-term neurocognitive sequelae, Risk factors include fetal distress, vaginal delivery, low APGAR scores, metabolic acidosis, hypercapnia, and the need for mechanical ventilation. Respiratory distress syndrome, seizures, pneumothoraces, hypoxemia, acidosis, severe hypocarbia, and the use of vasopressor infusions. Rapid fluctuations in cerebral blood flow, cerebral blood volume, and cerebral venous pressure appear to play a role in the development of IVH .Factors that may decrease the incidence and severity of IVH include administration of sedation with opioids, antenatal glucocorticoids, or indomethacin Grade 3 hemorrhage into the ventricular system and with ventricular dilatation
Premature neonates are more likely to exhibit severe long-term neurocognitive sequelae, Risk factors include fetal distress, vaginal delivery, low APGAR scores, metabolic acidosis, hypercapnia, and the need for mechanical ventilation. Respiratory distress syndrome, seizures, pneumothoraces, hypoxemia, acidosis, severe hypocarbia, and the use of vasopressor infusions. Rapid fluctuations in cerebral blood flow, cerebral blood volume, and cerebral venous pressure appear to play a role in the development of IVH .Factors that may decrease the incidence and severity of IVH include administration of sedation with opioids, antenatal glucocorticoids, or indomethacin Grade 4 hemorrhage extending into brain parenchyma.
46
Retinopathy of Prematurity
  • Occurs in approximately 50 of extremely low
    birth weight infants, with the incidence being
    inversely proportional to birth weight and
    gestational age.
  • Variations in arterial oxygenation (hypoxia or
    hyperoxia) and exposure to bright light appear to
    play a role.
  • During anesthesia, we use the lowest inspired
    oxygen concentration that provides oxygen
    saturations between 92 and 96 and strive to
    avoid significant fluctuations in oxygen
    saturations.

47
Renal and Metabolic Function
  • Glomeruli continue to form postnatally until
    approximately 40 days
  • Fewer nephrons and smaller glomerular size, low
    cardiac output, hypotension, and nephrotoxic
    drugs may inhibit glomerular growth and
    development. Baseline plasma creatinine levels
    are higher with increasing prematurity and remain
    elevated until 3 weeks of age.
  • Susceptibility to hyponatremia because of
    reduced proximal tubular reabsorption of sodium
    and water and reduced receptors for hormones that
    influence tubular sodium transport.
  • Plasma potassium concentration occurs in preterm
    infants and results from a shift in potassium
    from the intracellular to extracellular space.
    Greater with decreasing gestational age and birth
    weight.
  • Low cardiac output and urine output may further
    increase serum potassium concentrations and
    predispose to cardiac arrhythmias.

48
Glucose Regulation
  • The micropremie is at risk for hypoglycemia as
    well as hyperglycemia. Decreased glycogen and
    body fat predispose to fasting hypoglycemia,
    whereas decreased insulin production with
    infusion of dextrose predisposes to
    hyperglycemia.42,43 Glucose production is
    poorly regulated within a large range of glucose
    and insulin concentrations. The micropremie is
    also relatively insulin resistant and requires a
    higher insulin infusion rate to reach
    normoglycemia.44 The use of total parenteral
    nutrition and glucocorticoids places them at high
    risk for hyperglycemia.

49
Glucose and the Brain
  • Hyperglycemia in neonates appears to protect the
    brain from ischemic damage. Strikingly different
    outcome between neonates and adults.
  • Relatively mild hypoglycemia is known to cause
    brain damage in preterm infants Limited stores
    of glucose and consume glucose anaerobically.
  • Administration of dextrose-containing fluids and
    close monitoring of blood glucose levels is vital
    during anesthesia.
  • Mild or moderate hyperglycemia during surgery is
    best managed by reducing the rate of infusion of
    dextrose-containing solutions and not
    administering insulin.

50
Hepatic and Hematologic Function
  • Immature hepatic function
  • Reduced albumin synthesis enhancing the free
    concentration of anesthetic drugs .
  • Particular risk for spontaneous liver
    hemorrhage during laparotomy for necrotizing
    enterocolitis (NEC), is associated with large
    intravenous fluid resuscitation, and is difficult
    to control surgically.
  • The ideal hematocrit level controversial. Ht
    44 to 48.
  • Liberal vs restrictive transfusion group
    Restrictive transfusion group had a higher
    incidence of intraparenchymal brain hemorrhage,
    periventricular leukomalacia, and episodes of
    apnea.
  • The risks of blood transfusion should be weighed
    against the benefits of improved oxygen delivery
    and fewer medical complications.
  • Thrombocytopenia (lt150,000/mm3) occurs frequently
    (70 of micropremature infants.) (sepsis,
    disseminated intravascular coagulation, and NEC
    are common causes.) Preoperative evaluation
    include a recent platelet count for major
    procedures.

51
Inhaled Agents
MAC in the micropremie is considerably less than
in full-term infants
LeDez KM, Lerman J The minimum alveolar
concentration MAC of isoflurane in preterm
neonates. Anesthesiology 1987 67301-307.
52
Intravenous Agents
  • Half-life and clearance of fentanyl and morphine
    are increased. Thus, for a given dose of
    fentanyl, higher plasma fentanyl concentrations
    and a slower clearance of the drug will occur in
    the micropremie, which serves to prolong
    analgesia as well as prolong respiratory
    depression.
  • Thiopental is that it depresses cardiac output
    and causes venodilation and may precipitate
    cardiovascular collapse in the setting of
    hypovolemia it also has a very long half-life in
    preterm and term infants.
  • Recovery from propofol anesthesia is slower in
    micropremies compared with term infants because
    they have less fat and muscle tissue to
    redistribute the drug.
  • Benzodiazepines are eliminated by the liver and
    thus can last several hours in the micropremie
    with decreased liver function.

53
Arguments- Drug Dose
  • MAC of isoflurane in infant mice is 2.26
  • Jevtovic-Todorovic et al showed significant
    neurodegeneration with 0.75(0.33 MAC)

54
Arguments - Lifespan
  • Humans have a more prolonged synaptogenesis
    period
  • May require much longer exposure for significant
    apoptosis
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