Long-term effects of muscle paralysing drugs on newborns needing mechanical ventilation are as yet unclear.
When newborn infants develop breathing difficulties, they need mechanical ventilation to help them breathe. Sometimes they do not breathe in rhythm with the ventilator but 'fight' the ventilator, causing bleeding in the brain or serious lung injuries. Treating distress or pain caused by the ventilator and adjusting the ventilator to the infant's own breathing pattern can help. Paralysing newborn infants with muscle relaxing drugs such as pancuronium also stops them fighting the ventilator. However, the review of trials found that, although there seems to be some advantage regarding bleeding in the brain, long term effects of this method are not clear. More research is needed.
For ventilated preterm infants with evidence of asynchronous respiratory effort, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular haemorrhage and possibly on pneumothorax. However, uncertainty remains regarding the long-term pulmonary and neurologic effects and the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomised trials on the effects of neuromuscular blocking agents other than pancuronium. The routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.
Ventilated newborn infants breathing in asynchrony with the ventilator are potentially exposed to more severe barotrauma and are at risk for complications such as pneumothorax or intraventricular haemorrhage. Neuromuscular paralysis, which eliminates the spontaneous breathing efforts of the infant, creates complete synchronization with the ventilator and may minimize these risks. However, complications have been reported with prolonged neuromuscular paralysis in newborn infants.
To determine whether routine neuromuscular paralysis compared with no routine paralysis results in clinically important benefits or harms in newborn infants receiving mechanical ventilation.
The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2009), MEDLINE (from 1966 to January 2009), EMBASE (from 1988 to January 2009) and Cinahl (from 2005 - January 2009) were searched. References of review articles were hand searched.
All trials using random or quasi-random patient allocation in which the use of neuromuscular blocking agents during mechanical ventilation were compared to no paralysis or selective paralysis in newborn infants.
Data were abstracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with independent evaluation of trial quality and abstraction and synthesis of data by both review authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference.
Ten possibly eligible trials were identified, of which six were included in the review. All the included trials studied preterm infants ventilated for respiratory distress syndrome and used pancuronium as the neuromuscular blocking agent. In the analysis of the results of all trials, no significant difference was found in mortality, air leak or chronic lung disease. There was a significant reduction in intraventricular haemorrhage and a trend towards less severe intraventricular haemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory effort, a significant reduction in intraventricular haemorrhage (any grade and severe IVH) was found, and a trend towards less air leak. In the subgroup analysis of trials studying an unselected population of ventilated infants, no significant differences were found for any of the outcomes.