Drugs

1.8.4. Drugs

Bradycardia in newborns is usually caused by hypoxia and inadequate ventilation. Therefore establishing  effective ventilation takes priority over the administration of drugs to improve heart rate in the first instance.

Before considering drug administration, the resuscitation team should perform the following actions:

Ensure that effective positive pressure ventilation is being provided

• Check for mask leak or airway obstruction
• Ensure adequate peak inspiratory pressure to move the chest wall

If effective ventilation fails to correct bradycardia and the heart rate falls below 60 bpm:

• Increase the oxygen concentration to 100%
• Commence external chest compressions with positive pressure ventilation at a ratio of 3:1
• Reassess the heart rate after 30 seconds of ECC with PPV at 3:1

Consider intubating the infant and providing positive pressure ventilation via the endotracheal tube.

Consider as soon as possible umbilical venous catheterisation (as this is the ideal route of drug and fluid administration)

Administration of adrenaline is recommended if the heart rate remains below 60 bpm despite the above measures.

Volume expanders are indicated when hypovolaemia secondary to fetal blood loss or septic shock is suspected (see “Volume Expanders” below).

Other drugs (such as sodium bicarbonate and naloxone) are no longer routine and are rarely indicated during resuscitation of a newborn infant in the delivery room (See “Other Drugs” below)

Click here to access the Neonatal Worksheet, which will assist you to calculate emergency drug doses for a given gestational age and birth weight.

Adrenaline: 1:10,000

Indication:

• Despite effective positive pressure ventilation and external chest compressions for at least 30 seconds in 100% oxygen, the newborn infant remains asystolic or the heart rate remains below 60 bpm

Action:

• Sympathomimetic agent acting on alpha and beta adrenergic receptors

Effects:

• Increased heart rate & myocardial contractility
• Increased blood flow to skeletal muscle, brain, liver and the myocardium
• Increased cardiac conduction velocity
• Decreased renal blood flow

Presentation:

• 1:10,000 ampoule or mini-jet (0.1mg/mL)
• N.B. The 1:1,000 ampoule is only used for a continuous adrenaline infusion. This ampoule should not be kept in the resuscitaire with the 1:10,000 ampoule due to the risk of inadvertent overdose

Dilution:

• Not required

Route:

• Intravenous route recommended (umbilical vein or peripheral intravenous cannula)
• Given as a rapid push followed by a 0.5 mL flush of 0.9% sodium chloride

• Can be given via the tracheal route if IV access cannot be obtained as some infants may have an endotracheal tube inserted prior to intravenous access being established
• Up to ten times the intravenous dose can be administered via the endotracheal tube
• Given as a quick bolus into the endotracheal tube (ETT) followed by positive pressure inflations via the ETT
• N.B. Evidence for the endotracheal route is lacking. The safety and efficacy of the endotracheal dose has not been studied in human neonates.

Dose: For resuscitation/cardiac arrest

Special Notes:

• ILCOR state:Despite the widespread use of adrenaline (epinephrine) during resuscitation, no placebo controlled studies have evaluated either the tracheal or intravenous administration of adrenaline at any stage during cardiac arrest in human neonates. ILCOR, (2005), p. III-94

• Avoid the use of higher doses of intravenous adrenaline (greater than 2mL/kg IV). Animal studies using higher doses of intravenous adrenaline demonstrate adverse effects on cerebral blood flow and an increased risk of myocardial damage, intracranial haemorrhage, and post-resuscitation mortality (Hornchen, Lussi, & Schuttler, 1993; Berg, 2006; Gedeborg, 2000).

Volume Expanders

Indication:

• “Intravascular fluids should be considered when there is suspected blood loss and/or the infant appears to be in shock (pale, poorly perfused and with weak pulses) and has not responded adequately to other resuscitative measures”.
  (ANZCOR, 2016, Guideline 13.7)

Choice of volume expander:

• O negative, uncross-matched red blood cells are indicated for hypovolvaemia/ shock secondary to suspected fetal blood loss
• 0.9% sodium chloride is indicated for the treatment of hypotension secondary to other causes of shock

Action:

• Replacement of circulating blood volume

Effects:

• Improved heart rate
• Improved blood pressure
• Improved perfusion
• Correction of metabolic acidosis

Dilution:

• Not required

Route:

• Intravenous (umbilical vein preferably)
• Intra-osseous needle (IO)

Dose: For suspected hypovolaemia and/or hypotension

Special Notes:

• In the absence of O negative red blood cells (or whilst awaiting blood) 0.9% sodium chloride can be used as an initial volume expander as correction of hypovolaemia is critical to survival. The risk of only using sodium chloride is that the circulating blood volume becomes even further diluted.

• A standard 170 to 200microgram filter should be used whenever red blood cells are transfused. (Australian Red Cross, 2009)

• Infants who have suffered a significant blood loss may require a further 20 to 40 mL/kg (in separate boluses of 20 mL/kg) to restore their circulating blood volume and improve their heart rate.

Other drugs

Sodium Bicarbonate (NaHCO₃)

• The role of sodium bicarbonate in the resuscitation of human newborns remains controversial

• Level 1 evidence from two human RCT’s failed to demonstrate a beneficial impact on survival, neurologic outcome or acid-base balance in asphyxiated human infants (Lokesh, 2004; Murki, 2004).

• The known and potential side effects of sodium bicarbonate administration include:
  • Depressed myocardial function
  • Exacerbation of intracellular hypercarbia
  • Paradoxical intracellular acidosis
  • No benefit in terms of acid-base balance in the first 24 hours of life (LOE 1)
  • Reduced cerebral blood flow
  • Increased risk of intraventricular haemorrhage in preterm infants

• In 2010, ILCOR stated: “The use of sodium bicarbonate infusion should be discouraged during brief CPR but may be of some benefit in an infant with prolonged CPR unresponsive to other therapy including adequate ventilation.”

Naloxone

• There are concerns about both short and long term effects of naloxone administration. These include:
  • Myocardial depression
  • Cardiac arrhythmias, hypertension and non-cardiogenic pulmonary oedema
  • Exacerbation of long term neuro-histologic injury of cerebral white matter in asphyxiated animals
  • Seizures secondary to acute withdrawal in infants of narcotic dependant mothers (LOE 5)

• Several studies of human newborns describe no difference in pH, PCO₂, Apgar scores and neurologic outcomes in newborns who receive a placebo compared with newborns who receive naloxone

• There are concerns that the preparation and administration of naloxone may delay commencement of appropriate interventions for the apnoeic infant (i.e. the provision of effective positive pressure ventilation until the infant has a heart rate over 100 bpm and has established spontaneous breathing)

• In 2010, ILCOR stated: “There is no evidence of benefit and substantial evidence of risk. Consequently, naloxone should not be recommended during delivery room resuscitation”.

Drugs and fluids are rarely indicated during the resuscitation of newborn infants.

The vast majority of newborn infants requiring resuscitation have healthy hearts that are depressed by hypoxaemia, causing bradycardia.

Effective positive pressure ventilation is the key to correcting bradycardia and should be the priority. The administration of drugs is a secondary consideration.

Effective positive pressure ventilation and chest compressions should not be compromised by stopping to draw up or administer drugs.