The Preterm Neonate Phm 456 Michael Heffer BSc.Phm.MHSc.

What does it mean to be preterm? n Gestational age: – age in weeks dated from the first day of the mother’s last menstrual period. n Full term: weeks n Preterm: <37weeks n Viability: weeks ( g)

Resuscitation n Suction: lungs n Intubation n CPR: –Epinephrine: ETT n Establish IV access –IV (intravenous) –UVC (umbilical venous catheter) –UAC (umbilical arterial catheter).

Respiratory Distress Syndrome (RDS) n Primary cause: surfactant deficiency n Clinical picture: –atelectasis (deflated balloons) hypoxemia, poor lung compliance, alveolar epithelial damage, pulmonary edema. –Progresses to fibrous membranes and development of chronic lung disease. –Requires high ventilation support: risk of broncho-pulmonary dysplasia.

RDS Surfactant production n Endogenous cortisol stimulates synthesis at weeks in-utero. n Normal lung function (34-36wks) n Clinical test: amniocentesis –Lamellar Body Count: LBC –surfactant containing particles in amniotic fluid –reflection of lung maturity

RDS Surfactant production n Surfactant: –synthesized in Type II cells in alveolus. –composed of 80-90% lipid DPPC (dipalmitoyl phosphatidylcholine) –10-20% Proteins (spreading action) –lowers surface tension in alveolus –-stability on expiration.

RDS Prevention and Treatment n Risk of preterm delivery? –Betamethasone 6mg x2 dose q24h –stimulates surfactant production in the fetus –significant reduction in incidence of RDS n Multiple courses? –MACS study

RDS Prevention and Treatment n Exogenous surfactant replacement: n Synthetic: –Exosurf: contains DPPC and spreading agents. No proteins. n Natural source: –Survanta: minced bovine lung product contains proteins. –BLES: bovine lung exogenous lipid extract- Investigational Lung lavage. Contains proteins.

Apnea of Prematurity n Apnea –cessation of breathing for seconds. –complicated by cyanosis, pallor, hypotonia, bradycardia n Nursing scale –severity grade 1-4 depending on bradycardia and oxygen required. –amount of stimulation required gentle (G) vs vigorous (V) ie. 3G apnea

Apnea of Prematurity n Primary cause: immature systems: –decreased sensitivity of chemoreceptors to CO2. –diaphragm muscle fatigue n Secondary causes: (Rule out) –infection –low hemoglobin –medications (morphine) –ventilator related: blocked tube/positioning of infant

Apnea of Prematurity: Treatment n Methylxanthines: Caffeine / Theophylline n Doxapram infusion(off market-Mar 2001) n Mechanism: –increased sensitivity of medullary respiratory centre to CO2 –stimulates central respiratory drive –increases diaphragmatic contractility

Apnea of Prematurity: Treatment n Caffeine: –longer 1/2 life: hrs –once daily dosing n Side Effects: –tachycardia, jitteriness –rarely seen –caffeine levels if symptomatic ( micromoles/L) n CAP study: long term effects

Neonatal Sepsis n Congenital vs Nosocomial n Congenital source: –Vaginal flora –transplacental (viral infections) n Nosocomial ( > 7 days) –Environment –Instrumentation

Neonatal Risk Factors n Low birth weight /preterm n Instrumentation: – IV lines, intubation changes n Immune defense n Skin integrity

Maternal Risk Factors n Prolonged rupture of membranes >24hr n Intrapartum fever n Peripartum infection: – Chorioamnionitis, UTI n Group B Strep positive (carrier)

Neonatal Sepsis n Signs: non-specific –lethargy, temperature instability –poor feeding, poor colour and tone –apneas, increased ventilation requirements, increased blood glucose.

Neonatal Sepsis n Full Septic work up –Cultures: blood, urine, ETT, swab, LP –WBC (white blood cell count) and differential n Cultures: –Gram stain –bacteria: 48hours –ureaplasma: 4-5 days

Neonatal Sepsis n WBC (8-34 x10 9 /Litre) –trends –relative increase n Differential: left shift= immature neutrophils > 0.20(20%) total neutrophils immature neutr: bands, metamyelocytes,

Neonatal Sepsis n Treatment: always mg/kg –Congenital infection: –Prophylaxis: gram +ve and -ve coverage. –Ampicillin plus aminoglycoside –Nosocomial infection: –Prophylaxis: Cloxacillin and aminoglyc. –Methicillin (Beta lactamase) resistant? Switch to vancomycin and aminoglyc.

Neonatal Sepsis n Pharmacist follow up: DRP’s –Gram stain,cultures, sensitivities: –Coagulase negative staph. Staph. epidermidis: contaminant? –LP positive? 3 weeks treatment –consider better penetration: Cefotaxime –Therapeutic drug monitoring: –gentamicin, vancomycin

Patent Ductus Arteriosus (PDA) n Ductus arteriosus (DA) connects the pulmonary artery and the descending aorta n In utero: –Output of the right ventricle bypasses the unexpanded lungs by way of the DA and subsequently travels to the placenta for oxygenation n Patency of the DA in utero: –Maintained through high levels of circulating prostaglandins

Patent Ductus Arteriosus

Pathophysiology n At birth changes occur in the neonate’s circulation –umbilical cord is clamped resulting in an increase in systemic vascular resistance –lungs expand and pulmonary vascular resistance drops –results in switch from right-to-left shunting across the PDA during fetal life to a left-to- right shunt.

Risk with untreated PDA n Increased pulmonary blood volume –reduced lung compliance –pulmonary hemorrhage –chronic lung disease n Reduced systemic circulation –hypotension/ poor systemic perfusion –gut: Necrotizing enterocolitis –kidneys: renal failure –cerebral ishemia: Intra ventricular hemorrhage

Clinical Presentation n Increased heart rate/tachycardia n widened pulse pressure n bounding pulses n hyperactive precordium n continuous murmur n Echocardiographic diagnosis –diastolic turbulence on Doppler in the pulmonary artery

Risk Factors for PDA n Premature infants with: –Respiratory Distress Syndrome (RDS) –Hypoxia –Acidosis –Fluid Overload n incidence of PDA inversely related to the gestational age n spontaneous closure occurs more frequently in larger and healthier babies than smaller and sicker babies

PDA Treatment n Supportive Measures: –fluid restriction (80% of TFI requirements) –diuretics to control pulmonary edema if fluid restriction isn’t adequate –correction of anemia with transfusions –treatment of hypoxia and acidosis

PDA treatment: Indomethacin n Short course: –most commonly used –0.2mg/kg Q12H x 3 doses –>20% reopening rates:repeat courses n Long course: –0.1mg/kg Q24H x 5-7 doses n Best approach not yet determined.

Indomethacin: Side Effects n  Renal Function (urine output, creatinine, urea) –decreased renal blood flow n Necrotizing Enterocolitis (NEC) –decreased mesenteric blood flow n Hyponatremia –water retention n  platelet aggregation –COX inhibition n  bilirubin levels –displacement from binding site

Questions?