Widely used in NICUs, some decades ago. The usual dose infusion is 10–60 μg/kg/hour. In very preterm infants a high incidence of hypotension and intraventricular hemorrhage have been reported and contraindicate its use [67]. Nowadays, however, data are insufficient to promote the use of intravenous midazolam infusion as a sedative for newborn infants undergoing intensive care [72]. Recently midazolam exposure was associated with structural alterations in hippocampal development and poorer outcomes consistent with hippocampal dysmaturation [73]. Data show that further research on the effectiveness and safety of midazolam in neonates is needed before its use routinely in NICUs.
Morphine
Has been used in low-dose infusion (10 μg/kg/h) to control stress in mechanically ventilated infants. Opioids prolong mechanical ventilation due to the suppression of the respiratory drive [67]. However, due to the lack of available alternative drugs, they are used in clinical practice in neonatology with marked variability among NICUs [74]. Although much is known about morphine in newborns, there is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, by clinical judgment and evaluation of pain. If sedation is required, morphine is safer than midazolam [75, 76].
Fentanyl
Infusion is usually of 1.5 μg/kg/h. It can induce chest wall rigidity and laryngospasm in both term and preterm newborns. There is a significant accumulation due to prolonged half-life in preterm neonates, even with low doses. So, continuous infusion of fentanyl should be avoided in preterm infants [67].
Remifentanil
Doses of 1–4 μg/kg showed to be as effective as the morphine-midazolam regimen for endotracheal intubation. The rapid administration of remifentanil provides insufficient sedation and is associated, like fentanyl, with a chest wall rigidity in preterm neonates [77].
