Pancuronium during mechanical ventilation speeds recovery of lungs of infants with hyaline membrane disease. Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome. Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome. Effect of morphine and pancuronium on the stress response in ventilated preterm infants.
Spontaneous breathing during mechanical ventilation in newborn infants may damage the lung. To find out whether the prevalence of lesions which might be due to trauma was reduced by muscle relaxation, fifty infants who required mechanical ventilation of hyaline membrane disease were randomly assigned to treated and control groups. The treated infants were kept muscle relaxed with pancuronium bromide until they needed a FiO2 of 0.40 or less during ventilation. The mean birthweight, gestational age, age at entry to the trial, duration of intubation and ventilation, FiO2 during the acute phase of the illness, and ventilator pressures were closely comparable in the two groups. Two of twenty-six treated infants and one of twenty-four controls died. Four treated and five control infants acquired pneumothoraces and/or interstitial emphysema. The length of time that the treated infants required added oxygen was significantly less than in the control infants. All treated infants were breathing room air spontaneously by one month of age whereas seven control infants were still dependent on added oxygen, needing an average FiO2 of 0.35 to achieve a mean PaO2 of 6.5 kPa (49 mm Hg). These seven infants required added oxygen until they were 5-18 (mean 10) weeks old. Muscle relaxation during mechanical ventilation for hyaline membrane disease speeds recovery of the lungs, probably owing to a reduction in traumatic damage. The strategy of non-selective neuromuscular paralysis was compared with that of synchronised (fast rate) ventilation and selective paralysis in infants receiving mechanical ventilation for respiratory distress syndrome with chronic lung disease as the primary outcome measure. One hundred and ninety three infants weighing under 2000 g were randomly allocated to receive either pancuronium during mechanical ventilation in the acute phase of respiratory distress syndrome (non-selective group) or synchronised ventilation (initial ventilatory rate at or above that of the infant's) (selective group). Infants in the selective group received pancuronium if they were consistently expiring during the inspiratory phase of the ventilator cycle. There was no significant difference between the groups with respect to birth weight, gestation, and sex distribution. There was no significant difference between the group with respect to death (selective 19%, non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks' postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of ventilated infants has potential complications that may be avoided by using synchronised ventilation. As the latter is not associated with an increased incidence of long term respiratory complications, it is concluded that it is the optimum strategy of the two for ventilating infants with respiratory distress syndrome. In a previous study of preterm infants requiring mechanical ventilation for the respiratory distress syndrome, we demonstrated a striking association of fluctuating cerebral blood-flow velocity in the first day of life with the subsequent occurrence of intraventricular hemorrhage. Because this fluctuating pattern could be eliminated by muscle paralysis, we conducted a prospective study of preterm infants receiving mechanical ventilation for the respiratory distress syndrome in which we evaluated the effect of paralysis and this flow-velocity pattern on the incidence and severity of intraventricular hemorrhage. Twenty-four infants with the fluctuating pattern in the first hours of life were identified and randomly selected to serve as controls (10) or to be subjected to muscle paralysis (14). Intraventricular hemorrhage developed in all 10 control infants but in only 5 of the 14 infants subjected to muscle paralysis. Moreover, in 4 of the 5 paralyzed infants in whom hemorrhage developed, it did so after cessation of the paralysis. Seven of the 10 control infants had Grade III hemorrhage, the most severe variety of intraventricular hemorrhage, whereas none of the paralyzed infants had Grade III hemorrhage. We conclude that elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome markedly reduces the incidence and severity of intraventricular hemorrhage. Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.
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.