Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report. Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study. Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant.
A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS. The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later. The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg(-1) doxapram bolus, followed by an infusion at 1 mg kg(-1) h(-1), or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min(-1), if PCO2 < 55 mmHg, pH > 7.26, and FiO2 < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO2 > 55 mmHg), excessive oxygen requirement (FiO2 > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies.
The evidence does not support the routine use of doxapram to assist endotracheal extubation in preterm infants who are eligible for methylxanthine and/or CPAP. The results should be interpreted with caution because the small number of infants studied does not allow reliable assessment of the benefits and harms of doxapram. Further trials are required to evaluate the benefits and harms of doxapram compared with no treatment or with other treatments, such as methylxanthines or CPAP, to evaluate whether it is more effective in infants not responding to these other treatments, and to assess whether the drug is effective when given orally.