Neonatal Disease & Pharmacotherapy Approach1

8/6/2019 Neonatal Disease & Pharmacotherapy Approach1

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Norliza Mat AriffinClinical PharmacistSelayang Hospital


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The Premature Infant : < 37 weeks gestation

Low birth weight :


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TERM : Respiratory distress syndrome

(pneumonia,TTN, meconium aspiration),

infant of diabetec mother, sepsis.

PRETERM : RDS, patent ductus arteriosus,

necrotizing of enterocolitis, sepsis


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RDS or HMD (hyaline membrane disease)

Incidence : 14-50% ( 24-34 weeks gestation)

Risk factor : premature, male, electiveceasarean & maternal diabetes


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Surfactant deficiency or dysfunction

Surfactant : dipamitoylphosphatidylcholine +

other phospholipids.

Indications of surfactant:

Early rescue therapy (treatment) confirmed byxray and requiring mechanical ventilation


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Benefits:

1. improves survival, reduced pneumothorax,

intraventricular haemorhage2. early (before 2 hours) : reduced mortality

& chronic lung disease


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Natural ( eg Survantae, Curosurf) vs synthetic(Exosurf)

Natural : greater early improvement, shorterventilatory support, less air leak

Dosing : Survantae (4ml/lg; 100mgphospholipids/kg)

Method : intra-intrachealAdministration : First dose on less than 2 hours of

life & 2nd dose if necessary 6 hours later frominitial dose, 4ml/kg


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It is a general term for long-

term respiratory problems inpremature babies. It is also

known as bronchopulmonary

dysplasia (BPD).


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CLD results from lung injury to

newborns who must use a

mechanical ventilator and extra

oxygen for breathing.


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Some of the causes of lung injury includethe following :-

1. prematurity - the lungs, especially the airsacs, are not fully developed

2. low amounts of surfactant (a substance inthe lungs that helps keep the tiny air sacs

open)3. oxygen use (high concentrations of

oxygen can damage the cells of the lungs)4. mechanical ventilation - the pressure of

air from breathing machines, suctioning ofthe airways, use of an endotracheal tube.


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Medication therapy

* Bronchodilators (to help open the airways)

* Steroids to help reduce inflammation

limiting fluids and giving a medication (diuretic) tohelp reduce excess fluid which can worsen breathingability

nutrition (to help the baby and the lungs grow)

immunization against lung infection by respiratory

syncytial virus (RSV) and influenza


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Ventilated preterm babies who are still

seriously oxygen dependent 7-10 days after

birth are at serious risk of developing vhroniclung disease.

Traditional regimen 250mcg/kgdexamethasone PO/IV bd for 7 days.

Durand trial regimen -100mcg/kgdexamethasone PO/IV for 3 days, 50mcg/kg

bd for 4 days (total 1mg/kg)


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Risk factors:

1. Prematurity ~ 45% in < 1750g, ~80% in


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Presentation : heart murmur, hyperactive

precordium, bounding pulses, hypotension,

respiratory deterioration Diagnosis : Chest Xray, echocardiography

Mx : Respiratory support, fluid restriction,treat anemia, diuretics,

indomethacin/ibuprofen, surgery (ligation)

Patent Ductus Arteriousus


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Constriction of ductus

Ductus closes within 72 hours1

At birth: declining prostagladin E2 (PGE2)1

Intrauterine life: ductus remains open, allows blood flow from the pulmonary artery to the aorta1

PDA: ductus arteriosus isunable to close after 72 hours1

Closure of ductus arteriosusmay be delayed in:2

Premature infants

Low-birth weight infants

1. Kumar,Vinay, NelsoFausto, and Abul Abbas. 2004.Robbins & Cotran PathologicBasis of Disease, Seventh Edition. 7thed. Saunders.

2. Cotton, R B et al. 1978. Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants. The Journal of Pediatrics93:647-651.


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Indomethacin: reduces the risk of intraventricular haemorrhage2

It therefore reduces the morbidity and complications among:2

Premature neonates between 28-30 weeks of gestational age, OR

With birth weight less than 1 kg

Closure of ductus arteriosus1

Eliminates the vasodilator effect of PGE series on ductus arteriosus1

Inhibits the production of prostaglandins1

Indomethacin: NSAID, blocks cyclo-oxgenase1

1. Widmaier, Eric P., Hershel Raff, and Kevin T. Strang. 2003. Vander, Sherman, Luciano's Human Physiology: The Mechanisms of Body Function. 9th ed.Mcgraw-Hill (Tx).

2. Fowlie, P W, and P G Davis. 2003. Prophylactic indomethacinfor preterm infants: a systematic review andmeta-analysis. Archives of Disease in Childhood.Fetaland Neonatal Edition 88:F464-466.


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Indomethacin- Prostaglandin synthetase inhibitor

- Effectiveness limited to premature infants,decreases with post natal age (3-4 weeks)

Prophylaxis:0.1mg/kg Indocid IV at within 24 hours of life

(after FBC platelet >50x 109/L followed byday 2 until day 3.


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Indomethacin

Adverse effect:

1. Reduced GFR, urine output (stop if


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Indomethacin

Contraindications1. Serum creatinine >80umol/L2. Bleeding or coagulopathy3. Necrotizing enterocolitis (NEC)4. Sepsis


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An important cause of morbidity & mortality

May occur at pre term and term

Early onset (


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Prematurity

Neutropenia

Maternal carrrier GBS, PROM, PPROM, fever Damaged skin

Central lines

Overcrowding of nurseries

Inadequate hand washing


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Clinical subtle (worsening of apnea,

tolerance of feeds, temperature instability) or

dramatic (septic shock)

Lab: neutropenia, thrombocytopenia, CRP

Specific : blood, urine, CSF cultures, X rays


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Prevention:1. Intrapartum antibiotic prophylaxis (GBS

carrier, chorioamnionitis, maternal fever,

preterm labor)2. Hand washing3. Breast milk4. Prophylactic IVIG, GM-CSF/G-CSF


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Treatment

Antibiotic

Early onset : Benzylpenicillin plusgentamycin

Late onset : covers gram positive &negative organisms

IVIG adjuvant RxSupportive


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Aim :To provide nutritional requirement for

optimal growth & maturation of infant

Why is it necessary?1. Often need time to achieve full enteral feeds2. Catabolism retards growth, predisposes to

infections3. Sick newborns have higher caloric

requirement


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1. Premature


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Minimal requirement to prevent catabolism at

least 40kcal/kg/ay

For adequate growth, 100kcal/kg/day withprotein intake of 3g/kg/day for term and

3.5g/kg/day for pretermNutritional support should be initiated within 3

days and should include protein


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Through central lines preferably

Peripheral lines only if


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Guaranteed caloric intake

Complete absorption

Does not worsen gastrointestinal problemsHigh percentage of tolerance


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Risk of infection Line sepsis,

thrombophlebitis, extravasation into soft

tissue- necrosis High cost

Need for sophisticated infrastructure (nursingmedical, technical and laboratory)


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Solution A

Solution B

Intralipid


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Carbohydrate Begin at 4-6mg/kg/min using D10-12.5% Advance by 1-3mg/kg/min to max of

12mg/kg/min Dextrose yields 3.4kcal/g Potential complication

Hyperglycemia / hypoglycemia

Glycosuria and potential osmotic diuresis

Cholestasis from long term high concentrationinfusion


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Amino acids Synthetic crystaline amino acid solution

(vamin), start at 1gm/kg/day; advanced byday 3-4 age to 3gm/kg/day of protein (term)and 3.7-4.0gm/kg/day (extremely LBW)

Reduction in dosage may be needed in

critically ill, significant hypoxaemia,suspected or proven infection and high dosesteroids

Adverse effect : urea and ammonia high


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Intralipid

Essential components

Provides fatty acids and concentratedenergy source for growth and development

Intake of 0.25-0.5g/kg/day is required toprevent essential fatty acid deficiency

yields 10kcal/g

Start at 0.5g/kg/day and increase to

maximum of 3g/kg/day


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Do not allow lipid to exceed 60% of total

caloric intake

20% solution cleared efficiently fromcirculation

Continuous infusion over 24 hours

Protect from light

Complications : hyperlipidemia, increase riskof chronic lung disease, lipid overload

syndrome with liver failure and coagulopathy.


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Apnea of the Prematurity

Osteopenia of prematurity

Neonatal SeizureNeonatal Abstinence Syndrome


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Definition : Cessation of respiratory for >15 to

20 seconds with a fall in heart rate to 1.8 mmol/L

Osteopenia of prematurity


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The incidence of seizures in infants born at term is 13per 1000 live births; the incidence is even higher in

preterm infants, ranging from 113% of very low birthweight infants.

Seizures are the most frequent manifestation of

neonatal neurological diseases. It is important to recognize seizures, determine theiretiology and treat them because:1. The seizures may be related to significant diseasesand may require specific treatment2. The seizures may interfere with supportivemeasures e.g. feeding and assistedrespiration for associated disorders3. The seizures per se may be a cause of brain injury.


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Immature brain relative excess of excitatoryneurotransmitters and receptors.

Neonatal seizures are usually focal, often short lasting.

Manifestations include:1. Ocular phenomena (staring, blinking, eye deviation, eye

opening)2. Oral phenomena (mouthing, chewing, sucking, smiling)3. Autonomic phenomena (change in blood pressure and/or

heart rate, pallor, increased salivation or secretions;central apnoea occurring rarely as the only seizuremanifestation)

4. Fragmentary body movements (limb posturing,swimming, pedalling).


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A


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A


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A constellation of signs and symptoms whichresult from the abrupt cessation of a drug to

which the fetus/neonate has becomephysiologically dependent


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OpiatesOpiates Heroin Methadone

Morphine Other

Oxycodone

NonNon--opiatesopiates Alcohol Barbiturates Benzodiazepines SSRIs Other (caffeine,

tricyclics, valproate,

antihistamines)


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Heroin addiction on the rise

0.1% pregnant women

Less expensive, purer, & more potent, even viaoral route

Prescription drugs

Available via the internet


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Eases symptoms of physical dependency Blocks euphoria

Longer duration than heroin (T

/2=24-36 hrs) Increases fetal safety Enables mother to attend to her health & nutrition

Stabilizes maternal metabolic processes/ ANS

Prevents fetal withdrawal

Optimal fetal growth


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Accelerated clearance from maternalAccelerated clearance from maternalcirculation in late pregnancy due tocirculation in late pregnancy due to

Larger blood volumeLarger blood volume

Increased metabolism (Increased metabolism (progestinsprogestins))

Higher fetal tissue concentrationHigher fetal tissue concentration

Pregnant women may need an increased/Pregnant women may need an increased/

split dose.split dose.


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CNSCNS = majority of signs especiallyIrritability & sleep disturbance

In preterms less frequent & milderNon specific

R/O other conditions sepsis, hypoglycemia,hyperthyroidism, hypocalcemia,

hypomagnesemia, asphyxia


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WW -- wakefulnesswakefulnessII -- irritabilityirritabilityTT --tremors, twitching,tremors, twitching, tachypneatachypnea

HH -- hyperventilation,hyperventilation, hypertoniahypertonia, hyperpyrexia,, hyperpyrexia,hyperaccusishyperaccusis, hiccups, hiccupsDD -- diarrhea, diaphoresis,diarrhea, diaphoresis,RR -- rub marksrub marksAA -- alkalosisalkalosis

WW -- weight lossweight lossAA -- apneaapneaLL -- lacrimationlacrimation,,SS -- seizures (seizures (myoclonicmyoclonic), sneezing, skin), sneezing, skin

mottlingmottling


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Disturbed sleep 53% Mottling 53% Excess sucking 45% Tremors 43% Tachypnea 43% Hypertonia 41% Fever 40% Seizures 2-11% (often later)


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Paregoric 0.2-0.5 ml/dose q 3-4 p.o. or 4-6

drops q 4-6h; may increase by 2drops until clinical improvement

Improves most of the withdrawalsymptoms especially diarrhea,taper dose by 10-20% per day over2-4 week after symptoms stable for3-5 days.

Neonatal Opium Dilution 0.4%solution (contains 0.4 mgmorphine equivalent per ml)guidelines:

0.8 ml/kg/day for NAS 8-10 1.2 ml/kg/day for NAS 11-13 1.6 ml/kg/day for NAS 14-16 2.0 ml/kg/day for NAS >16 Doses given orally every 3-4 h with

feeds ( not prn)

Phenobarbital 15-20 mg/kg/day loading

dose to achieve level of 20-40 mg/ml. Maintenance

dose =2-8 mg/kg/day. Taper dose by 10-20% perday after symptoms stablefor 3-5 days.Diazepam

0.3-0.5 mg/kg q 8 h; initialdose i.m then p.o

Allows rapid suppressionof symptoms, decreasedsuck, avoid in jaundice orpremature infants.


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Methadone 0.1-0.5 mg/kg/day

divided q 4 to 12 h Increase by

0.05mg/kg/dose untilsymptoms are wellcontrolled

Taper dose by 10-20%per day over 1 mo

T

reatment usuallylonger (5 days-4 mo) Long half-life (26 h )

Chlorpromazine 0.5-0.7 mg/kg/dose loading

then 2-2.8 mg/kg/day in

divided doses q 6 h Decrease dose over 2-3 wkClonidine 0.5-1 ug/kg single dose

then 3-5 ug/kg/day divided

dose q 4-6 h Increase by 0.5 ug/kg over1-2 days until maintenancedose is achieved


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Exaggerated crying curve in first 2 to 3

months

By 4 months: most infants have no s/ s ofwithdrawal

Severity of NAS does not affect prognosis.


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The EndThe End

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Neonatal Disease & Pharmacotherapy Approach1