Neuromuscular paralysis for newborn infants receiving mechanical ventilation.
BACKGROUND
Ventilated newborn infants breathing in asynchrony with the ventilator are at risk for complications during mechanical ventilation, such as pneumothorax or intraventricular hemorrhage, and are exposed to more severe barotrauma, which consequently could impair their clinical outcome. Neuromuscular paralysis, which eliminates spontaneous breathing efforts of the infant, has potential advantages in this respect. However, a number of complications have been reported with muscle relaxation in infants, so that concerns exist regarding the safety of prolonged neuromuscular paralysis in newborn infants.


OBJECTIVE
To determine whether routine neuromuscular paralysis of newborn infants receiving mechanical ventilation compared with no routine paralysis results in clinically important benefits or harms.


METHODS
MEDLINE (from 1966 to May 2000) and EMBASE (from 1988 to May 2000) were searched, as well as The Cochrane Controlled Trials Register (issue 2, 2000). References of review articles were hand searched. Language restriction was not imposed.


METHODS
All trials using random or quasi-random patient allocation, in which the routine use of neuromuscular blocking agents during mechanical ventilation was compared to no paralysis or selective paralysis in newborn infants. Methodological quality was assessed blindly and independently by the two authors.


METHODS
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 authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference.


RESULTS
Ten possibly eligible trials were identified, of which five 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 difference was found in mortality, air leak or chronic lung disease, but there was a significant reduction in intraventricular hemorrhage and a trend towards less severe intraventricular hemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory efforts, a significant reduction in intraventricular hemorrhage (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 differences were found for any of the outcomes.


CONCLUSIONS
For ventilated preterm infants with evidence of asynchronous respiratory efforts, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular hemorrhage and possibly on air leak. Uncertainty remains, however, regarding the long term pulmonary and neurologic effects, and regarding the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomized trials on the effects of neuromuscular blocking agents other than pancuronium. Therefore, the routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.
Cools
F
F
Pediatrics, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, Brussels, Belgium, 1090. Filip.Cools@az.vub.ac.be
Offringa
M
M
D002543:Cerebral Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D010197:Pancuronium / Q000627:therapeutic use; D011030:Pneumothorax / Q000209:etiology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial / Q000009:adverse effects*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy*
D003473:Neuromuscular Nondepolarizing Agents; D010197:Pancuronium