TABLE 1.

Premedication for neonatal endotracheal intubation – published studies

Drug	Advantages	Disadvantages	Evidence
			Type of study	n	Subjects	Findings
Vagal blockade
Atropine	Dose requirements known	Potential for CNS complications in overdose	RCT; atropine vs no therapy (12)	30	Term and preterm newborns	Prevention of bradycardia compared with no therapy
Glycopyrrolate	Does not cross the blood-brain barrier	Uncertain dose requirements in the very preterm infant	RCT; given to both groups (16)	20	Term and preterm newborns	No bradycardia
Analgesia/anesthesia
Fentanyl	Potent opiate; PK data available (43) Good analgesic effect	Dose requirements for intubation unknown in the newborn, rare occurrence of chest wall rigidity (44), unpredictable sedative effect (45)	Cohort study (40) Used in both arms of numerous small RCTs	253	Term and preterm newborns	Showed safety of a protocol including fentanyl and succinylcholine
Alfentanil	Potent opiate	Dose requirements and kinetics unknown	RCT; in combination with succinylcholine vs meperidine without muscle relaxant (20)	20	Term and preterm newborns	Shorter intubation and reduced duration of hypoxia with alfentanil/succinylcholine
Morphine	Opiate; PK data available Sedative effect	Dose requirements unknown for this purpose, delayed onset of action limits efficacy for this purpose	RCT; morphine vs no premedication (21)	60	Term and preterm newborns	No effect on severity of physiological disturbance during intubation
			RCT; in combination with succinylcholine and atropine (17) vs nothing	20	Term and preterm newborns	Reduced time to intubate, (60 s vs 590 s), fewer attempts and less bradycardia
Meperidine	Opiate with sedative effect	Causes nausea in older patients	RCT; meperidine vs alfentanil and succinylcholine (16)	20	Term and preterm newborns	More hypoxia than comparison group
Remifentanil	Potent opiate Rapid acting, very rapid clearance and short duration of action, provides good levels of anesthesia	May cause chest wall rigidity, hemodynamic effects uncertain in the newborn, limited PK data in the newborn	RCT; remifentanil vs morphine (48)	20	Preterm newborns	Improved intubating conditions with remifentanil
			Cohort study (49)	21	Preterm newborns 29 to 32 wks’ gestation	Good intubation conditions, rapid extubation
			RCT; remifentanil vs fentanyl plus succinylcholine (23)	30	Term and preterm newborns	Similar intubation conditions and complications, longer intubations and more chest wall rigidity with remifentanil alone, not statistically significant
Methohexital	Barbiturate analogue Rapid acting, provides good levels of sedation	Unfamiliar to many neonatologists, no PK data	Cohort study (27)	18	Newborns >32 wks’ gestation	Good sedation and intubating conditions
Propofol	Very rapid acting, provides good levels of anesthesia	May cause hypotension, toxicity unknown in the newborn, little data on PK but reduced clearance in the newborn	Cohort study (50)	100	Newborns and infants 2.1 kg to 9.2 kg under halothane anesthesia	Short intubation time, excellent intubating conditions
			RCT; propofol vs morphine, succinylcholine and atropine (28)	63	Term and preterm newborns	Shorter intubation and less hypoxia with propofol
Thiopental	Rapid-acting anesthetic agent	Causes hypotension in older children, prolonged and extremely variable clearance	RCT (25); thiopental vs no therapy	30	Newborn infants >2 kg	Blunts hypertensive response
Muscle relaxation
Pancuronium	Nondepolarizing agent, few side effects	Prolonged duration	RCT; atropine alone vs atropine plus pancuronium vs no therapy (12)	30	Term and preterm newborns	Smaller increase in intracranial pressure and less hypoxia during intubation
Succinylcholine	Rapid acting, short duration of action	Depolarizing agent, rare serious complications, malignant hyperthermia, hyperkalemia, rhabdomyolysis	4 RCTs (1 only partly randomized) (13,16–18)	81	Term and preterm newborns	Reduces intracranial pressure increase, shortens duration of the procedure, reduces number of attempts, reduces trauma
Mivacurium	Nondepolarizing agent, few side effects, brief duration of action		Cohort study of use in combination with fentanyl and atropine (51)	34	Term and preterm newborns	Rapid onset (1–3 min), brief duration of action (5–15 min), very stable intubation conditions
			RCT; mivacurium vs no mivacurium (all infants received fentanyl and atropine) (19)	41	Term and preterm newborns	Much shorter intubations and less hypoxemia with mivacurium
Rocuronium	Nondepolarizing agent with rapid onset	Prolonged and variable duration (up to 1 h)	RCT; rocuronium vs no relaxant (all infants received fentanyl and atropine) (48)	44	Preterm newborns	Much more likely to be intubated on first attempt compared with controls

CNS Central nervous system; PK Pharmacokinetic; RCT Randomized controlled trial; vs Versus; wks Weeks