Physiology of Neonatal Resuscitation

Physiology of asphyxia in the neonate:

 

Following an asphyxial insult, the body is deprived of oxygen.  Breathing initially becomes deeper and more rapid, but within 2-3 minutes breathing ceases as the higher centres responsible for controlling normal rhythmic respiration are put out of action.  The body has a number of automatic reflex responses.   Energy is conserved by shutting down the circulation to the kidneys, gut and the skin, while preserving circulation to the vital organs i.e. the heart and the brain.  After a latent period of primary apnoea, automatic reflex gasping activity appears, triggered by the spinal centres.  These deep reflex gasps are easily distinguishable from normal breaths as they have a frequency of only 6-12 times per minute and involve all the accessory muscles of respiration in a maximal inspiratory effort. The gasping effort may be enough to reverse the hypoxia. However, if the hypoxia continues, this gasping activity will eventually cease as the spinal centres also get depressed. In the human infant, the time to reach this secondary or terminal apnoea is probably around 20 minutes. This sequence can start prior to delivery.

In the term baby, the circulation does not fail before all reflex respiratory activity has ceased, usually about 20 minutes after the onset of the asphyxia.  This is largely due to the reserves of glycogen in the heart.  Such reserves are not present in the more vulnerable preterm baby and are not present later in life. Resuscitation is, therefore, easy and straight-forward if it is begun before the baby becomes so anoxic that all reflex activity has ceased.  As long as oxygen reaches the lungs it will then be carried to the heart and brain by the circulation and revival will be rapid, automatic and almost always complete within minutes.

If resuscitation is not commenced, even after all spontaneous gasping has ceased, systemic blood pressure will eventually fall to the point where the circulation ceases and the heart-rate falls to zero. Even at this point resuscitation may still be effective, if commenced promptly. The chances of recovery will depend on the length of the secondary apnoea.  In practice it is very difficult to tell whether a baby is in primary or secondary apnoea and this is why resuscitation must be commenced effectively in all such infants.  In hindsight, it is possible to tell if a baby was in secondary apnoea as the first respiratory activity to recover will be reflex anoxic gasping.

Clearance of lung fluid:

During vaginal birth most fetal lung fluid is absorbed into the circulation by physiological mechanisms.  Approximately a third is removed during vaginal delivery by chest compression.  If the baby breathes spontaneously at birth, the remainder will clear fairly rapidly (within 1-2 breaths) by reabsorption into the blood stream and lymphatic system. Normally it is not necessary to suction the airways to remove this fluid. Attempting to do so may lead to inappropriate vagal stimulation causing bradycardia. Occasionally, suction will be required if there is thick particulate meconium obstructing the airway in a depressed infant. (See later).

Expansion of the lungs

Following lung expansion, there is a drop in pulmonary resistance and consequently the pulmonary blood flow increases.   Hypoxia, acidosis and hypothermia may lead to arrest of this process leading to persistent pulmonary hypertension (PPHN).  In PPHN, pulmonary vasoconstriction persists and the right sided pressures may be higher than the left causing cyanosis due to right to left shunting of blood through a patent foramen ovale and across the ductus arteriosus. Hypoxia, acidosis and hypothermia should therefore be avoided

Air or Oxygen?

In term infants receiving resuscitation with intermittent positive-pressure ventilation, 100% oxygen conferred no advantage over air in the short term and resulted in increased time to first breath or cry or both. Meta-analyses of these studies showed a decrease in mortality with the group for whom resuscitation was initiated with air. (Relative risk 0.71 [CI 0.54 – 0.94], Risk difference -0.05, NNT 20).

There are several good human RCTs in term babies that have showed quicker recovery during resuscitation in air resuscitated group when compared to 100% oxygen. The levels of oxidative stress markers were markedly elevated for prolonged periods in those resuscitated in 100% oxygen. The incidence of BPD was reduced by half in those resuscitated in 30% oxygen as compared 90% oxygen in a randomised trial of preterm babies 24-28 weeks gestation.

The best human study examining long term outcome suggest a odds ratio of 3.85 of serious adverse outcome (death / cerebral palsy) in babies with HIE exposed to  hyperoxia.

There is a plethora of evidence in newborn animal models of asphyxia that exposure to high concentrations of oxygen at resuscitation does not confer any clinical advantage and is potentially harmful at the cellular level due to generation of free oxygen radicals at the time of reperfusion.

In preterm infants at <32 weeks’ gestation, initial use of air or 100% oxygen is more likely to result in hypoxaemia or hyperoxaemia, respectively, than initiation of resuscitation with 30% or 90% oxygen and titration to oxygen saturation. There is insufficient evidence in babies born at 32–37 weeks’ gestation to define the appropriate oxygen administration strategy. Therefore the resuscitation council is recommending pragmatically starting resuscitation in preterm infants in 21-30% oxygen, more mature babies starting in air.