Apnea of Prematurity & Neonatal Respiratory Distress Syndrome

What are the three different types of respiratory neonatal diseases ?

1. respiratory distress syndrome (RDS) — NOT SAME AS ARDS

2. Bronchipulmonary Disease / Chonic Lung Disease

3. Apnea of Prematurity

Risk Factors of Respiratory Distress Syndrome (Hyaline Membrane Disease):

• prematurity: 50% of patients were born before ___ weeks or less GA

• are females or males more likely to carry?

• are white people more or less likely to get disease?

• perinatal ______ or _________

• mother that is _____________

• unclosed ________ _______ ________ (typically closed when born)

• ___________ _________ syndrome (ingestion of first intestinal discharge/poop GETS INTO LUNG)

• pulmonary hyper/hypotension

• 30 weeks or less

• males

• WHITE MORE LIKELY

• diabetic 

• patet ducctus arteriosis (PDA)  

• meconium aspiration syndrome

• hypERtension

Pathophysiology of RDS (respiratory distress syndrome):

• deficiency of type ______ ________ and pulmonary ___________

• _____ protein deficiencies and mutation 

leading to 

• _________ surfactant and ___________ surface tension

• decreased type 2 pnsumocytes and surfractant 

• surfactant

• decreased surfactant = increased surface tension

alveoli expands for gas exchange- what happens in a patient with RDS? 

alveoli collapse because the gas from the smaller alveoli with higher pressure will move dramatically to the larger alveoli with less pressure leaving the smaller alveoli collapsed 

The following are symptoms you would see in which pediatric respiratory diseases?

• tachypnia

• nasal flaring

• chest rettractions

• cyanosis

• grunting

in SEVERE cases

• pulmonary edema

• apnea

• oliguria

• respiratory failure

Belly breathing (belly taking in a lot of air) — chest in, abdomen out is a sign of which pediatric respiratory disease?

RDS - respiratory distress syndrome

Respiratory Distress PREVENTION:

_______ agents prevent premature birth which is a risk factor 

which medication is commonly used?

• tocolytic 

• IV magnesium sulfate (relaxes smooth muscle PREVENTING uterine contractions) 

Respiratory Distress PREVENTION:

Antenatal steroids are to be taken by the mother to reach the fetus for preterm delivery between ____-____ weeks GA 

what are the advantages of this therapy? 

• decreased mortality in preterm neonates

• decreased RDS AND ________Lung Disease 

• decreased periventricular  __________ (decreased white matter in the brain or softening/death of brain tissue),_________. and intraventricular ___________

24-34 

• decreased chronic lung disease 

•  leukomalacia, ventriculomegaly, and hemorrhage

COMMON antenatal steroids to prevent RDS::

_______________ IM once a day for 2 doses (GIVEN WITHIN 24 hours BEFORE DELIVERY) — how long do these effects last in the baby if given during this time? 

• Why are antenatal steroids the best treatment for RDS?

• Are single or multiple courses preffered?

• Would you see any changes in growth or neonatal sepsis as adverse effects?

betamethasone 

7 days 

they can cross the placenta easily without changing electrolytes

multiple is preferred 

NO

what are the treatment options for Respiratory Distress Disorder (RDS)?

1. fluid restrict

2. continuous positive airway pressure (CPAP)- LESS INVASIVE

3. conventional and high frequency mechanical ventilation

_________ ___________are all used for the TREATMENT in premature infants

but for it to be used as a PREVENTATIVE measure it must be taken within the first ___-____ minutes of birth

________ treatment of it must be given ASAP when we find out the patient has RDS

• established RDS

• early versus late/delayed rescue

exogenous surfactant

• must be taken within first 10-30 minutes to be used as preventative measure

rescue

Mechanism of Action for Exogenous Surfactants: 

exogenous surfactant —> 

act on alveoli —>

decreased surface tension, work of breathing, need for oxygenation

the advantages of EXOGENOUS SURFRACTANTS IN RDS are more seen in patients experiencing __________ because it will

• improve ____________

and decrease

• __________ requirements

• pulmonary interstitial ______________

• _________ (collapsed lung)

• death

• prophylaxis

• improve oxygenation

decrease

• ventilatory

• emphysema

• pneumothorax

what are the three exogenous surfactants that are currently being used in practice? where are each of them derived from?

1. Beractant (survanta) - bovine derived (calf) 4 mg/kg/dose

2. Calfactant (infasurf) - bovine derived (calf) 3 mg/kg/dose

3. Poractant Alfa (Curosurf) - porcine derived (pig) 2.5 then 1.5 ml/kg/dose

How could you tell from a chest xray if a patient has used an exogenous surfactant or not? 

before surfactant administration there is cloudiness, but after treatment the x-rays are clear

rank the exogenous surfactants based of least to most effective

Beractant (survanta) is the least effective since it is an older treatment

Colfactant (infasurf) and Poractant (Curosurf) have the same effectiveness

SO

beracatent < colfactant = poractant 

how are exogenous surfractants for RDS administered? 

• ______ tube administration followed by ____ tube ventilation 

• __ or __ aliquots (doses)

• is positioning necessary?

itratracheal tube followed by bag tube ventilation 

2 or 4 doses

positioning NOT neccesary

what happens if water goes down trachea instead of esophagus 

cough out 

what are adverse effects of exogenous surfactants that make it to the trachea?

• transient _________

• hypo/hyper tension

• oxygen _____________

• _________ tube blockage

• pulmonary air _______

• pulmonary _________

• bradycardia 

• hypOtension 

• desaturation 

• endotracheal

• leaks

• hemmorage

Combination CPAP and SRT

INtubation- SURfractant- Exubation (INSURE): 

• Why would this form of therapy be used for Respiratory Distress Disorder?

• How would administration go? 

• decreases the need for mechanical ventilation , improve mortality

• intubate short period on time—> administer surfractant —> immediately exubate and then have them on CPAP 

Less Invasive Surfactant Administration (LISA): 

• reduce the need for _______, __________ _______, and other complications

• reduce early _________ rates and ________ _______ disease compared to INSURE

• the surfactant is instilled DIRECTLY into trachea using ______ while receiving noninvasive respiratory support

CPAP, mechanical ventilation

intubation chronic lung

catheter

CHRONIC LUNG DISEASE (CLD) / BRONCHOPULMONARY DYSPLASIA (BPD):

CLD can be classified as 

• MILD- requires oxygen for ___ days STRIAGHT until they reach corrected age, ___ weeks post conceptional DONT REQUIRE any more oxygenation

• MODERATE- require oxygen for ____ days STRAIGHT but once they reach corrected age of ____ weeks they only need ____% of that initial oxygen 

• SEVERE- require oxygen for ____ days STRAIGHT but once they reach corrected  age of _____ weeks they’ll need to continue oxygenation by ____ %

• 28 36

• 28 36 less than 30%

• 28 36 more than 30%

risk factors of 

CHRONIC LUNG DISEASE (CLD) / BRONCHOPULMONARY DYSPLASIA (BPD):

• very low birth _________ less than _______ grrams— less than _____weeks

• ________(like RDS) 

• unclosed ____ 

• ________ infection

weight 1500grams 28 weeks

prematurity

PDA 

maternal

SEQ PATHOPHYSIOLOGY OF CLD and BPD

1. surfactants deficiency

2. RDS

3. immature lung and chest wall (from continuous oxygenation

4. CLD !

what are some potential adverse effects of treatments for chronic lung disease?

1. oxygen toxicity (babies are receiving oxygen through ventilation so there is always the risk of getting to higher levels and having interactions due to oxygens radical nature)

2. baroauma  (increased pressure) and volutrauma (increased volume) due to ventilation which delivers both

You would see the following in a premature baby with CHRONIC LUNG DISEASE/ BRONCHOPULMONARY DYSPLASIA

• __________ (fast breathing)

• _________ (wet sound)

• airway _____________

• poor ____ ___________

• wheezing

• broncho_________

tachypnea

rales

resistance

gas exchange

spasms

PREVENTION OF CHRONIC LUNG DISEASE/ BONCHOPULMONARY DYSPLASIA:

• prevent ________ birth using ___________

• exogenous ________ administration 

• _______!!! (best taken within 3 days of life) 

• prevent _____ _________ as much as you can to avoid barotrauma and volutrauma

• increase nutrition to ______-____ kcal/kg/day to outgrow disease

why are blood transfusions no longer used as preventative treatment?

• preterm —antennal steroid 

• surfractant 

• CAFFEINES ! 

• mechanical ventilation 

• 120-180 

blood transfusions allowed for patients deficient in oxygen carrying hemoglobin to recieve hemoglobin from donors to increase delivery of oxygen through the body (no longer used BECUASE of side effects) 

TREATMENT OF chronic lung disease/ bronchopulmonary dysplasia

• oxygenation through _______ or _______ ___________

• _______ restriction to decrease __________ ________ and improve lung function

• ____________ (what are the three classes?)

• combination therapy of _______ and ________ is better than _________ alone to reduce _____+ wasting

• CPAP or mechanical ventilation

• restrict fluid to decrease interstitial edema

• diuretics (loop, thiazole, potassium sparing)

• chlorothiazide + spironolactone > furosemide alone to spare Ca2+

Corticosteroid prevention therapy for CLD/BPD must be taken before ____ days of age 

MOA: suppresses lung __________ and promotes ________ production

what are the three types of corticosteroids that are used and how are they administered?

• 7

• inflammation and surfactant

• dexamethasone (IV or inhaled), hydrocortisone (IV), and inhaled (budesonide, beclomethasone, fluticasone, flunisolide) 

Dexamethasone (Systemic)- Adverse Effects: 

• hyper/hypo glycemia 

• hyper/hypo tension 

• ____ bleeding/ preforation 

• ________ failure 

ALSO abnormla neurological examination and _________ ____________

hyperglycemia

hypertension 

GI 

growth 

cerebral palsy

Hydrocortisone (Systemic)- Adverse Effects:

• hyper/hypo glycemia

• hyper/hypo tension

• ____ bleeding/ preforation

• ________ failure

hyperglycemia 

hypertension 

GI 

growth 

Although Budesonide is inhaled and has less systemic adverse effects, its _______ is questionable

efficacy

Dexamethasone used as PREVENTION for CLD/BPD:

• must be taken ___ days BEFOE birth 

Benefit: successful ______ and decreased _______

Disadvantage: long term abnormal _______ exam and higher adverse effects bc of __________________

• 7

• extubation CLD 

• neurologic dexamethasone has ALOT of adverse reactions becuase it has a long half life, increased potency, and doesnt bind to mineralocorticoud recepotr leaving it out in the CNS for long periods of time leading to neuro apoptosis 

Dexamethasone used as TREATMENT for CLD/BPD:

• must be taken ____ days AFTER birth

• facilitates _________

• this pretreatment is the best for infants who cannot _____ while on mechanical ventilation

• minimize the dose and duration, avoiding a high doses of _____mg/kg or more

• 7

• extubation

• wean

• always give dose 0.5mg/kg OR LESS

Hydrocortisone used as PREVENTION for CLD/BPD: 

• must be taken ____ days before birth

• where does it bind to?

• does it act more like our endogenous corticosteroids?

Advantages: may prevent CLD or ____; for neonates who have had less than ______ grams exposed to___________ (bacteria entering fetal membranes) 

• 7

• binds to both glucocorticoid and mineralocorticoid receptor (more like our endogenous corticoids) 

• death

• 1000 chorioamnionitis 

Hydrocortisone used as TREATMENT for CLD/BPD:

• taken ___ days AFTER birth 

• Advantages: survival without ______ and abnormal ________ exam similar to placebo 

• 7 

• CLD neurological 

how can inhaled corticosteroids such as Budesonide, Beclomethasone, fluticasone, flunisolide, and dexamethasone PREVENT and/or TREAT CLD/BPD?

inhaled corticosteroids cant be used as PREVENTION OR TREATMENT for CLD/BPD

Recommendations of Corticosteroid use in CLD/BPD:

• stop taking if you don’t see any results after ____ hours

• should you take corticosteroids on a daily basis?

• preferentially a ____ dose and _____ duration

• 72

• NO

• low dose and low duration

does treatment for CLD/BPD reduce the risk or duration of the disease? 

what is the only medication that has been successful in treating CLD? 

NO can only treat symptoms but cant reverse damage 

CAFFEINES

BRONNCHODILATORS FOR CLD/BOD:

goal of bronchodilators is to

• improve airway _________

• increase lung _________

• _____ ______

• decrease airway _________

• resistance

• compliance

• gas exchange 

• hyperactivity 

Bronchodilators are used to manage _______ ___________ epsiodes for CLD/BPD

• what are some bronchodilators used for neonates? what are there dosage forms?

• what are some adverse effects? 

• acute bronchoconstriction

• ‘albuterol - MDI (connected to mechanical ventilation) or nebulizer 

• tachycardia, hypertension, cardiac arrythmia (if bind to B1)

methylxanthines (theophyliine AND CAFFEINE) have ________ and ________ effects and can be used for the treatment of CLD/BPD

bronchodilation and diuretic effects

Cromolyn Sodium for the treatment of CLD/BPD:

• The goal is to decrease _______________by inhibiting _________ and _______ release (______ ______ ________)

• Would treatment with cromolyn sodium be for acute episodes or prophylaxis?

• Requires __-__ weeks of therapy

• what are some adverse effects? 

**note this therapy is not common

• decrease inflamation by inhibiting HISTAMINE and LEUKOTRIENE release (mast cell stabilizer)

• used for PROPHYLAXIS

• 2-4

• airway irritation 

Vitamin A (Retinoic Acid) for CLD/ BPD PREVENTION:

Goal is to decrease ________ _________ requirement at 36 weeks postconceptual age in neonates that are less than 1000 grams (2 pounds)

What is the mechanism of action?

Why might its dosage from be an issue?

• aim to decrease supplemental oxygenation required

• MOA: counteract oxidant stress associated with CLD

• it has to be given three times a week INTRAMUSCULARLY (very painful for baby)

What are PREVENTIVE options for CLD/BPD?

What is the ONE drug that can be used as TREATMENT IF taken early enough

PREVENTION:

• Vitamin A (reduce need for oxygenation)

• Beta Adrenergic Agonists- bronchodilation (albuterol)

• mast cell stabilizers (cromylyn)

• Corticosteroids (Dexamethasone+ Hydrocortisone)

TREATMENT:

CAFFEINE (methyl-xanthine)- used as diuretic and bronchodilator !

Apnea of Prematurity:

• Breathing cessation for ____ seconds with or without bradycardia/cyanosis

• what does ABD stand for? If a patient had a low ABD would you continue their treatment or develop a new plan of action? 

• what increases a baby’s risk for developing apnea (unable to breath)?

• 20

• ABD= Apnea/ Bradycardia / Desaturation of oxygen

low ABD—> you have been able to control apnea, bradycardia, desaturation of oxygen with the current treatment so you may CONINUE with the treatment 

risk factors; 

• prematurity (the smaller you are the more likely too have a spout of being unable to breath) 

• metabolic or electrolyte disorder 

• seizures

Pathophysiology of APNEA OF PREMATURITY: 

Explain the differences between the three types of apneas: 

1. central/diaphragmatic

2. obstructive

3. mixed

which is the most common? 

1. baby stops breathing for 20+ seconds because of tiredness of rapid breathing (60 breaths per minute)  and diaphragm movements 

2. baby stops breathing for 20+ seconds because of a blocked airway  

3. baby stops breathing for 20+ seconds because their airway is blocked AND they are tired of the effort it takes to breath

most common is mixed apnea, least common is obstructive

What are the 3 Non-pharmacologic treatment of Apnea:

1. tactile stimulation: press baby hard while they are asleep and unsuspecting, their natural reaction will be to activate respiration

2. positioning   

3. CPAP or mechanical ventilation if they really can still not breath on their own 

• chocalate

• tea

• coffee 

what do they all contain? 

methylxanthines (diuretic and bronchodilator) 

tea and coffee = caffeine 

chocolates = theobromine 

__________ are indicated for the treatment of apnea (loss of breath for 20 seconds) of premature neonates

what are two examples?

methylxanthines

• caffeine

• theophylline

what is the mechanism of action for Methylxanthine? (used for apnea and CLD/BPD):

where does it bind?

inhibits phosphodiesterase enzymes which turns cAMP—> AMP

giving you increased levels of cAMP and cGMP

• competitively binds at adenosine receptor (adenosine is respiratory suppressant)

• decreases Ca2+ influx

Difference between Theophylline and Caffeine (methylxanthines):

Explain the dynamic between theophylline and caffeine

Which is linear, which is nonlinear?

when theophyline is metabolized through methylation it becomes caffiene

in preterm babies, metabolism is not fully complete so you have 50% theophylline and 50% caffeine

in preterm babies have longer half life of theophyline as there is less metabolism (30 hours). Full term babies with higher metabolism have shorter halflife for theophyline

Theophyline is not linear. If you prescribe 20% more theophylin, your level may increase irregularly whereas if you increase caffein by 20% the effect will be greater by 20%

Caffeine undergoes metabolic ___________ 

why don’t we usually check caffeine levels? 

• demethylation

• because of their prolonged half-life they are usually at steady state, no need to constantly check on their levels 

Caffeine:

• Decreases duration of ________ _________

• facilitates mechanical ventilation extubating in very ____ ________

• failure of _________found in patients WITHOUT caffeine

• High dose vs standard dose

• mechanical ventilation

• low weights

• extubation ( hard to get patient off of ventilator without the push of them breathing on their own from caffeine)

CPD/BPD occurs due to PROLONGED USE OF ____________ from treatment of ____________ how can caffeine help wean off neonates from mechanical ventilation? 

prolonged oxygenation from RDS

since caffeine is a competitive adenosine receptor antagonist, it blocks respiratory suppresion, allowing babies to breath on their own as opposed to relying on the mechanical ventilation—→ will make the trasnition from ventilation to exudation and taking out the tube MUCH EASIIER 

High doses of caffeine (____ mg//kg/day followed by ___ mg/kg/day) may lead to whcih side effect?

initial 40/mg/kg/day then 20mg/kg/day follwoing

leads to tachcardia

When should premature apnea therapy be discontinued?

when baby is close to being full term (36 weeks+)

caffeine is no longer necessary

Why is caffeine preffered over theophylline as a methylxanthine? 

• theophylline has a narrow therapeutic range (6-14mcg/ml) compared to caffeine (8-20mcg/ml— don’t actually experience adverse effects until 40mcg) 

• caffiene has longer half life

• caffeine is unchanged in the urine whereas theophylline is methylated to caffeine

• theophyline has more CNS and cardiac effects 

What are the therapeutic effects of theophylline and caffeine? 

Indicate which drug causes a greater effect. 

1. CNS stimulation (caffeine) 

2. Skeletal Muscle Relaxation (caffeine) 

3. Cardiac Stimulation (theophyline) 

4. Smooth Muscle Relaxation (theophyline)

5. Diuresis (theophyline) 

theophyline is more prone to adverse effects!

what adverse effect is seen in theophylline that is not seen in caffeine citrate?

decreased cerebral blood flow

26 Year Old (gestational age) male (1.2kg) was born 

• patient is in respiratory failure and was intubated on a mechanical ventilator immediately after delivery 

• he is transferred to NICU 15 minutes after delivery for further evaluation 

• after stabilizing the baby he was diagnosed with Respiratory Distress Disorder (RDS)

what is your recommendation? 

exogenous surfactant: Colfactant or Poractant alfa (Beractant doesn’t work as well)

The baby boy with RDS then develops apneic spells which continue to worsen, what do you recommend?

caffeine citrate (theophyline no longer used as safe option)