Oxygen therapy of very low birth weight neonates with pneumonia

Pneumonia deliberately account for approximately 15% death of children below 5 years of

age. It is the largest single cause of death in that group1. Specifically in neonates, pneumonia is

also a dangerous and a lethal disease. Pneumonia is accountable for 6-9% death of 750,000 to

1,200,000 infected neonates worldwide every year. The mortality rate of pneumonia of neonates

is emphatically based on the prematurity and onset of infection. The younger neonates and

infection which took place since antenatal period would bring the highest risk of death2. Besides,

it is known that prematurity, along side with premature rupture of membrane and mother urinary

tract infection are the major risk factor for neonatal pneumonia.

The signs of neonatal pneumonia are tachypnea (respiratory rate > 60/min), snorting,

flaring, withdrawals and cyanosis2. The premature infant already has the immature lung system as

in lack of canalicular and saccules will cause inadequate surfactant production and ultimately

insufficient oxygen diffusion through the alveolar membrane3. Weak immune defense and

presence of pathogen colony in the airway of premature neonates could cause severe lung

parenchyma infection that will further compromise the oxygen diffusion4. Pediatrician has been

dealing with pneumonia with precise and adequate antibiotic therapy, ventilatory support including

oxygen supplementation and chest therapy4. Antibiotic guidelines of neonatal pneumonia have

been evaluated and updated according to the responsible pathogen in any of specific case.

Streptococcus is the likeliest of being responsible for neonatal pneumonia that happen soon after

birth, thus the causal agents of late onset neonatal pneumonia there are respiratory viruses

(adenovirus, respiratory syncytial virus), gram-positive microbes, (group I, B, and G streptococci

or Staphylococcus aureus) and gram-negative enteric microscopic organisms most strikingly

neonatal pneumonia.

Currently, the approved first choice antibiotics in our national guideline for neonatal

infection are ampicillin and gentamycin5. They are applied in general infection (sepsis) or in

localized site infection such as pneumonia, urinary tract infection etc. The national guideline for

neonatal pneumonia is yet to be exist, but the perinatologist usually use the rule of empiric

antibiotic escalation that is similar in treating sepsis. The escalated antibiotics are more specific

targeting the gram-negative bacteria that might be the causative agent of further complicated and

life threatening infection4–6. According to the neonatal sepsis guideline in our hospital, antibiotic

regiment should be started within 1st hour after sepsis was highly suspicious. The tolerance of

starting antibiotics in neonate with sepsis is different in each case. It is dependent on the pregnancy

age, the process of delivery and maternal infection. Younger pregnancy with confirmed maternal

infection will have the lowest tolerance. Interestingly, neonatal pneumonia diagnosis in infants is

very tricky to be confirmed, as the respiratory symptoms of pneumonia might be also the

contribution of sepsis. Radiograph of the chest will be the difference between those two diagnosis,

as in neonatal pneumonia the image will have peri-bronchial infiltration and sub-segmental

atelectasis2. Establishing diagnosis of pneumonia in premature infant is even more difficult,

findings of neonatal pneumonia in plain chest x-ray could possibly overlapping with another

respiratory distress diseases such hyaline membrane disease and bronchopulmonary dysplasia7.

Despite the tricky and overlapping diagnosis of sepsis and pneumonia, the main treatment is the

same.

The perinatologist in Indonesia conclude in a consensus that antibiotic for neonatal

pneumonia should be given at least 7 days since the symptom and sign occurred. However a
research by Engle et.al (2000) conclude that in term and near term infant with pneumonia, 4 day

course of antibiotics with good clinical observation will have similar outcome with 7 day course

of antibiotics5. Sophistication of medicine ironically increase the life expectancy of infant with

pneumonia together with its iatrogenic infection. Ventilation support for sick infant is delivered

through tubes that could possibly transfer the pathogen colony to the lung’s parenchyma. These

days, there is no international consensus that define neonatal ventilator associated pneumonia

(VAP). The case definition is differed from one center to one another. However, it is well agreed

that radiological signs, clinical signs and use of ventilation device are all needed to suspect

neonatal VAP. Review study by Goerens et al (2018) found out that the suspected case of VAP

and use of concomitant antibiotics is much higher than for confirmed case of VAP. However the

inter-reability of chest-x ray to suspect VAP is low at 0.257,8.

Ventilatory support has main purpose to deliver oxygen to the alveoli and prevent its from

collapsing. High oxygen fraction is received and thus will increase its partial pressure in the blood.

High oxygen content could damage the retina of premature infants, promote the periventricular

leukocyte infiltration and ultimately damaged the lungs9,10. Oxygen therapy through ventilatory

support is also the mainstay treatment for neonatal pneumonia together with empirical antibiotics.

It’s dilemmatic that the improvement of health technology will increase the life expectancy of

neonate with pneumonia, especially preterm neonate; but in the other hand it could damage the

eyes, brains and lungs that could debilitate the future of the neonate. The current guideline of

oxygen therapy for neonate with respiratory distress is the restricted oxygen therapy, which we

start as low as 21% of inspired O2 fraction in term and near-term neonate and around 30-40% in

preterm and very preterm neonate. Liberal oxygen therapy is only given to neonates with persistent

pulmonary hypertension9. A meta-analysis by Askie et.al (2009) found out that early liberal
oxygen therapy in preterm infant with pneumonia will introduce significant risk to develop ROP

later in their life without reducing the mortality rate9. Earlier in 2001, Askie et al review RCTs

systematically to figure out that early weaning of oxygen or abrupt cessation is no difference in

mortality or ROPs. Abrupt cessation definition is stopping the O2 within 4 days and reduce the

inspired fraction as low as 21% once the neonate is stabilized and be able to support his own

ventilatory system10.

Our patient was born on 31st week of pregnancy with birth weight of 1481 grams. She had

respiratory distress soon after birth. Ventilatory support was given with nasal CPAP with PEEP of

8 and 40% of inspired fraction of oxygen, later support is escalated to non-invasive ventilation due

to respiratory distress. Peripheral oxygen saturation targeted approximately at 90-92%. Empirical

antibiotics was already administered. Other supportive treatment such as regulation of temperature

and humidity, fluid requirement and calorie intake were given according to the needs of preterm

neonates. The oxygen support was restrictive, started at 40% of FiO2 and will be weaned as soon

as possible when neonate has been stabilized and could support her own respiratory function.
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