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Intubation - premedication for intubation in neonate

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Indications

Most intubations occur at the time of delivery in the process of resuscitation, or semi-electively in infants with either poor respiratory effort or with severe immediate respiratory distress in the immediate newborn period. Intubation medications are therefore not usually given. However, once the infant is in the NICU environment and IV access is obtained, the use of intubation agents for elective or semi-elective intubations should be considered, particularly in large vigorous infants.

Contraindications and precautions

  1. Intubation drugs should not be used if there is a known allergy to any of the agents
  2. Suxamethonium should not be used if there is a family history of malignant hyperthermia, if there is a suspicion of muscular dystrophy, or if there is significant hyperkalaemia
  3. Suxamethonium should be used with caution if there is concern that the infant has abnormal upper airway anatomy (for example, severe micrognathia) and that intubation may be technically extremely difficult. In this situation, a consultant (and potentially an ENT surgeon) should also be present.

Preparation and equipment

  1. Consider intubation drug use in all elective or semi-elective intubations where IV access is available or can easily be obtained.
  2. Premedication should be strongly considered for all vigorous term infants.
  3. Equipment must be ready, especially the bag-mask circuit and laryngoscope. The infant will have no spontaneous respiratory effort once muscle relaxing agents (or Fentanyl) have been given.
  4. Suxamethonium should not be given if there is significant hyperkalaemia.
  5. If Fentanyl is given, Suxamethonium should be ready to be given if chest-wall rigidity occurs.
  6. Medications should be administered in the order below (see also intubation quick reference guide):
    1.   Anticholinergic  Atropine 20mcg/kg IV  (if given)  
    2.   Sedation Fentanyl 4mcg/kg IV Give slowly (30 seconds) to avoid muscle rigidity
    Allow at least 30 seconds for sedation
    3.   Muscle relaxation Suxamethonium 2mg/kg IV  (if given)  
    If Morphine is used instead of Fentanyl, drugs should be administered in the order of:
                                                      Morphine, then Atropine, then Suxamethonium
  7. The infant should have bag-mask ventilation during the administration of Fentanyl and Suxamethonium, or prior to this if respiratory effort is poor.
  8. Laryngoscopy should commence once spontaneous respiratory movements have ceased.
  9. Muscle fasciculation from Suxamethonium administration does not occur in neonates and should not be relied upon as a sign of successful neuromuscular blockade.
  10. If bradycardia occurs in the presence of hypoxaemia, a second dose of Atropine should not be given. The bradycardia is due to inadequate oxygenation and/or ventilation.
  11. If the intubation is unsuccessful, Suxamethonium can be re-administered but Atropine and Fentanyl should not be repeated.

Intubation premedication quick reference guide

Medication  Concentration
Weight (g)
Atropine  (600micrograms/ml)
20micrograms/kg IV
Fentanyl  (100micrograms/2ml)
4micrograms/kg IV
Suxamethonium  (100mg/2ml)
2mg/kg IV
500  0.02ml 0.04ml 0.02ml
750   0.03ml 0.06ml 0.03ml
1000  0.03ml 0.08ml 0.04ml
1250  0.04ml 0.10ml 0.05ml
1500  0.05ml 0.12ml  0.06ml
1750  0.06ml 0.14ml  0.07ml
2000  0.07ml 0.16ml  0.08ml
 2500  0.08ml 0.20ml  0.10ml
 3000  0.10ml 0.24ml  0.12ml
 3500  0.12ml 0.28ml  0.14ml
 4000  0.13ml 0.32ml  0.16ml
 4500  0.15ml  0.36ml  0.18ml
 5000  0.17ml  0.40ml  0.20ml

Notes

  1. Appropriate dose must be charted on Drug Prescription Chart. Please chart the concentration of the medication, as well as the volume.
  2. Choose the weight most appropriate for the baby (above).
  3. Suxamethonium should not be given in the presence of significant hyperkalaemia.
  4. Drugs should be given in the order of:
      1. Atropine (wait for a rise in HR of >20bpm)
      2. Fentanyl (wait at least 30 seconds for onset of action)
      3.Suxamethonium
  5. In the event of an unsuccessful intubation attempt, Suxamethonium can be administered again.
    Atropine and Fentanyl doses should not be repeated.
  6. Fentanyl should be given as a slow push (rapid pushes may cause chest wall rigidity). The onset of action is rapid.
  7. Dosage range for Suxamethonium 1 to 3 mg/kg IV

Rationale behind premedication for intubation

Physiological Effects of Intubation without Medications

Intubation without premedication is associated with vagal bradycardia due to instrumentation of the oropharynx, bradycardia due to hypoxaemia (in struggling infants), raised intracranial pressure (ICP)1,2,3, and systemic hypertension3. Elevated ICP and BP raise concerns that intubation could contribute to intraventricular haemorrhage. No studies have examined this.

Studies Evaluating Drug Use

Most studies have evaluated short-term, physiological effects on small numbers of infants requiring elective intubation. Some studies have evaluated clinical outcomes (time to intubation). One large cohort study4 demonstrated relative safety, even in very small infants. It is difficult to determine the specific effects of each agent, as studies have used different agents in varying combinations. However,

  • Atropine use has been associated with tachycardia3, systemic hypertension5, systemic hypotension6, and less bradycardia7.
  • Sedation moderates the rise in ICP3. Some authors advocate sedation on humane and ethical grounds.
  • Muscle relaxation is associated with quicker intubations7,8,9, raised ICP, no rise in ICP3,8, bradycardia, and tachycardia.

Choice of agents

Sedative agents

Fentanyl has been studied in sedative doses of 3-4mcg/kg. Anaesthetic doses are higher (5-50mcg/kg)10. It has a short onset (30-60 seconds) and short duration of action. Chest wall rigidity impairing ventilation may occur with rapid IV administration (but can be overcome with muscle relaxation).

Morphine may be used, particularly if an infusion is already being given. It has a longer onset (minutes) and duration of action (hours) than Fentanyl. It may cause significant hypotension in some infants.

Anticholinergic agents

Atropine reduces vagally-mediated bradycardia. Duration of action is long (6 hours). There are concerns that administration of Atropine may mask bradycardia secondary to hypoxaemia. Prolonged desaturation, in the absence of bradycardia, indicates inadequate oxygenation and/or ventilation.

Muscle relaxants

Suxamethonium has a short onset (<30 seconds) and duration of action (usually <5 minutes at 2mg/kg). It is a depolarising agent which results in neuromuscular blockade by its agonistic effect at the cholinergic receptor of the neuromuscular junction. Adverse effects include transient hyperkalaemia (↑K+>0.5mml/l), bradycardia (agonist effect at autonomic cholinergic receptors), raised intra-abdominal pressure, and raised intra-ocular pressure. There are also concerns of raised ICP.

  • Blockade is enhanced by alkalosis, hypothermia and hypokalaemia. 
  • Blockade is impaired by acidosis and reduced cardiac output. 

There have been occasional reports of malignant hyperthermia (MH) in association with use of Suxamethonium (and inhalational anaesthetics) in infants with family histories of MH or muscular dystrophy. If MH is suspected (hyperthermia, tachycardia, dysrhythmias, rigidity, cyanosis, mottling), give Dantrolene (Dantrium) 1mg/kg IV (available in Operating Theatres). Repeat as necessary to a maximum cumulative dose of 10mg/kg. Seek help.

Pancuronium (a non-depolarising agent) has a longer onset (2-3 minutes) and longer duration of action (1-4 hours). It should be used with extreme caution as an intubation agent.

Other non-depolarising agents (e.g. Vecuronium, Atracurium) may be used by some anaesthetists to induce muscle relaxation. They are not available for use in NICU.

References

  1. Raju TN, Vidyasagar D, Torres C, Grundy D, Bennett EJ. Intracranial pressure during intubation and anesthesia in infants. J Pediatr 1980 May;96(5):860-2. 
  2. Stow PJ, McLeod ME, Burrows FA, Creighton RE. Anterior fontanelle pressure responses to tracheal intubation in the awake and anaesthetized infant. Br J Anaesth. 1988 Feb;60(2):167-70. 
  3. Millar C, Bissonnette B. Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants. Can J Anaesth. 1994 Apr;41(4):281-7. 
  4. Barrington KJ, Byrne PJ. Premedication for neonatal intubation. Am J Perinatol. 1998 Apr;15(4):213-6. 
  5. Kelly MA, Finer NN. Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium. J Pediatr. 1984 Aug;105(2):303-9. 
  6. Hinkle AJ. Awake neonatal laryngoscopy: pre-oxygenation alone versus continuous oxygenation. Anesthesiology. 1983 Sep; 59(3): A437 
  7. Oei J, Bhuta T, Hari R, Lui K. Suxamethonium, atropine and morphine as induction for neonatal nasotracheal intubation: a randomised controlled trial. PSANZ 4th Annual Congress, Brisbane 2000:A77.
  8. Barrington KJ, Finer NN, Etches PC. Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. Crit Care Med. 1989 Dec;17(12):1293-6. 
  9. Pokela ML, Koivisto M. Physiological changes, plasma beta-endorphin and cortisol responses to tracheal intubation in neonates. Acta Paediatr. 1994 Feb;83(2):151-6. 
  10. 10 Young TE, Mangum OB. Neofax ®: A manual of drugs used in neonatal care, ed 10. Raleigh, North Carolina: Acorn Publishing, USA, 1997, p.162

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Document Control

  • Date last published: 30 June 2015
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years