Comparison of weaning by patient triggered ventilation or synchronous intermittent mandatory ventilation in preterm infants. Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants. Flow-synchronized ventilation of preterm infants with respiratory distress syndrome. Multicentre randomised controlled trial of high against low frequency positive pressure ventilation. Oxford Region Controlled Trial of Artificial Ventilation OCTAVE Study Group. Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates. Comparison of synchronized and conventional intermittent mandatory ventilation in neonates. Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial. Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome. International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome. Prospective clinical comparison of two methods for mechanical ventilation of neonates: rapid rate and short inspiratory time versus slow rate and long inspiratory time. Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants.
Forty preterm infants were entered into a randomized controlled trial to compare the efficacy and duration of weaning by patient triggered ventilation (PTV) to that of synchronous intermittent mandatory ventilation (SIMV). Infants were randomized during recovery from respiratory distress once ventilator rate had been reduced to 40 breaths per minute; weaning during PTV was by reduction in ventilator pressure only, whereas infants randomized to SIMV were weaned by reduction in rate only. Weaning failed in 12 infants, 6 from each group, the 12 infants were more immature than those in whom weaning succeeded (p < 0.01). Overall, the duration of weaning did not differ significantly between the PTV and SIMV groups. Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning.
                The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure.
                Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death.
                There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency.
                The results of this study suggest that the addition of pressure support as a supplement to synchronized intermittent mandatory ventilation during the first 28 days may play a role in reducing the duration of mechanical ventilation in extremely low birth-weight infants, and it may lead to a reduced oxygen dependency in the 700- to 1000-g birth weight strata. Asynchrony of delivered and spontaneous breaths in mechanically ventilated infants may impair gas exchange and prolong the need for assisted ventilation. We conducted a randomized, controlled trial of a patient-triggered, flow-synchronized ventilator on 30 preterm infants with respiratory distress syndrome who weighed between 1100 and 1500 gm at birth. Entry criteria included radiographic evidence of respiratory distress syndrome and the need for mechanical ventilation and surfactant replacement therapy. Patients were assigned to either conventional time-cycled, pressure-limited ventilation or patient-triggered, flow-synchronized ventilation in an assist/control mode. Otherwise clinical management was identical. Time to extubation was the primary outcome measure. Patients treated with flow-synchronized ventilation were weaned more rapidly and had a significantly shorter mean time to extubation than those treated with time-cycled, pressure-limited ventilation, 119 versus 271 hours, p = 0.0152. In addition, there was no difference in the rate of complications between the two groups. There were, however, considerable reductions in patient charges of $4344 per patient in the flow-synchronized ventilation group. A total of 346 infants aged less than 72 hours were randomly allocated to be treated either by high frequency positive pressure ventilation (HFPPV; rate fixed at 60/minute throughout treatment and initial inspiratory:expiratory (I:E) ratio 1:2, increased to 1:1 if necessary) or by low frequency positive pressure ventilation (LFPPV; rate less than or equal to 40/minute and initial I:E ratio usually 1:1, both decreasing during weaning). The main hypotheses were that HFPPV reduces pneumothorax, chronic lung disease and death before discharge in all infants, as well as those with hyaline membrane disease, and that it reduces the incidence of later neurodevelopmental complications in infants of less than 33 weeks' gestation. Among all the infants the rate of pneumothorax was 19% in the HFPPV group and 26% in the LFPPV group (p = 0.13; odds ratio 0.7, 95% confidence intervals (CI) 0.4 to 1.1); there was no difference in mortality or the incidence of chronic lung disease. In infants of less than 33 weeks' gestation there were no differences in adverse neurodevelopmental outcomes. Among the subgroup of 237 infants with hyaline membrane disease, median fractional inspired oxygen at the time of entry to the trial was 0.6 in the HFPPV group and 0.7 in the LFPPV group, indicating that many had moderately severe disease. In patients with hyaline membrane disease HFPPV was associated with a lower rate of pneumothorax (18% in the HFPPV group compared with 33% in the LFPPV group, p = 0.013, odds ratio 0.5, 95% CI 0.3 to 0.8, with no differences in mortality, or in duration of intubation or supplementary oxygen in survivors. As used in this study, HFPPV was the preferred ventilator regimen for infants with hyaline membrane disease. To compare synchronized intermittent mandatory ventilation (SIMV) and conventional intermittent mandatory ventilation (IMV) in neonates.
                Prospective, multicenter, randomized clinical trial.
                Level III neonatal intensive care units at six university or children's hospitals.
                Three hundred twenty-seven infants receiving conventional IMV for respiratory distress syndrome, pneumonia, or meconium aspiration pneumonitis were randomly assigned a 7.5 +/- 6 hours of age to either continue with IMV or change to SIMV. Infants assigned to each mode of ventilation had similar birth weight (BW), gestational age, and Apgar scores at birth, and similar oxygenation indexes at randomization. They received similar surfactant therapy and had similar incidence of sepsis, seizures, secondary pneumonia, and necrotizing enterocolitis. In the infants with BW less than 1000 gm, more infants receiving IMV had surgical ligation of their patent ductus arteriosus than did those receiving SIMV (27 vs. 7 %; p = 0.02).
                Data was analyzed overall for all infants and also separately within three BW groups: less than 1000 gm, 1000 to 2000 gm, and more than 2000 gm. The 1000 to 2000 gm BW group was further analyzed in subgroups weighing 1000 to 1499 gm and 1500 to 2000 gm.
                In all infants, at 1 hour after randomization, the infants receiving SIMV had a lower mean airway pressure than those receiving IMV (8.08 +/- 2.15 vs. 8.63 +/- 2.59; p<0.05), with similar fractions of inspired oxygen and oxygenation indexes. Infants whose BW was 1000 to 2000 gm at 0.5 hour required a lower fraction of inspired oxygen with SIMV than with IMV (0.52 +/- 0.20 vs. 0.62 +/- 0.27; p<0.05) and had better oxygenation at 1 hour, as shown by lower oxygenation indexes with SIMV than with IMV (6.14 +/- 4.17 vs. 9.42 +/- 8.41; p = 0.01). Infants whose BW was 1000 to 2000 gm received a lower number of unit doses of sedative/analgesic drugs per infant during the first 4 days of SIMV than did infants receiving IMV (3.8 +/- 3.4 vs 6.3 +/- 5.5 unit doses; p = 0.02). Infants whose BW was more than 2000 gm had a shorter duration of mechanical ventilation with SIMV than with IMV (median, 72 vs 93 hours; p = 0.02). Three of the forty-six infants receiving IMV but none of the 47 infants receiving SIMV required extracorporeal membrane oxygenation. In the infants with BW less than 1000 gm, fewer infants treated with SIMV required supplemental oxygen at 36 weeks of postconceptional age than did those treated with IMV (47 vs 72%; p<0.05). In 83 infants whose lungs were mechanically ventilated for 14 days or longer, all with BW less than 2000 gm, those treated with SIMV regained their BW earlier than those treated with IMV (median, 21.5 vs 29 days; p<0.01). There were no differences in the rates of death, intraventricular hemorrhage (grades III and IV), air leak, need for pharmacologic paralysis, or need for supplemental oxygen at 28 days.
                We found that SIMV was at least as efficacious as conventional IMV, and may have improved certain outcomes in BW-specific groups. Between October 1993 and April 1995, a total of 77 neonates requiring mechanical ventilation were enrolled in this study and were randomly divided into two groups. Group A consisted of 31 premature infants (mean birthweight 1.36 +/- 0.29 kg) with respiratory distress syndrome (RDS) and seven neonates (mean birthweight 3.2 +/- 0.5 kg) with meconium aspiration syndrome (MAS). Group B consisted of 31 premature infants (mean birthweight 1.31 +/- 0.3 kg) with RDS and eight neonates (mean birthweight 3.3 +/- 0.5 kg) with MAS. Infants in group A received synchronized intermittent mandatory ventilation (SIMV) and infants in group B received conventional intermittent mandatory ventilation (CIMV) therapy. In premature infants with RDS, our data showed: (i) the duration of ventilation was significantly shorter (P < 0.05) in the synchronized group (156 +/- 122 h) compared to the conventional group (242 +/- 175 h); (ii) significantly fewer (P < 0.05) patients required reintubation in the synchronized group than in the conventional group (three vs 11 patients); (iii) incidence of severe intraventricular hemorrhage (grades 3 and 4) was significantly lower (P < 0.05) in the synchronized group compared to the conventional group (one vs seven patients); (iv) incidence of bronchopulmonary dysplasia was significantly lower (P < 0.05) in the synchronized group than in the control group (one vs seven patients). In neonates with MAS, our data showed no significant difference (P < 0.05) on duration of ventilation, incidence of reintubation, incidence of pneumothorax or mortality rate between synchronized and control groups. To test the hypothesis that pressure-regulated volume control (PRVC), an assist/control mode of ventilation, would increase the proportion of very low-birth-weight infants who were alive and extubated at 14 days of age as compared with synchronized intermittent mandatory ventilation (SIMV).
                Ventilated infants with birth weight of 500 to 1249 g were randomized at less than 6 hours of age either to pressure-limited SIMV or to PRVC on the Servo 300 ventilator (Siemens Electromedical Group, Danvers, Mass). Infants received their assigned mode of ventilation until extubation, death, or meeting predetermined failure criteria.
                Mean +/- SD birth weights were similar in the SIMV (888 +/- 199 g, n = 108) and PRVC (884 +/- 203 g, n = 104) groups. No differences were detected between SIMV and PRVC groups in the proportion of infants alive and extubated at 14 days (41% vs 37%, respectively), length of mechanical ventilation in survivors (median, 24 days vs 33 days, respectively), or the proportion of infants alive without a supplemental oxygen requirement at 36 weeks' postmenstrual age (57% vs 63%, respectively). More infants receiving SIMV (33%) failed their assigned ventilator mode than did infants receiving PRVC (20%). Including failure as an adverse outcome did not alter the overall outcome (39% of infants in the SIMV group vs 35% of infants in the PRVC group were alive, extubated, and had not failed at 14 days).
                In mechanically ventilated infants with birth weights of 500 to 1249 g, using PRVC ventilation from birth did not alter time to extubation. To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure.
                Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator.
                There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups.
                Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident. To compare the effects of patient triggered ventilation (PTV) with conventional ventilation (IMV) in preterm infants ventilated for respiratory distress syndrome (RDS).
                Nine hundred and twenty four babies from 22 neonatal intensive care units were assessed. They were under 32 weeks of gestation and had been ventilated for respiratory distress syndrome (RDS) for less than 6 hours within 72 hours of birth. The infants were randomly allocated to receive either PTV or IMV. Analysis was on an "intention to treat" basis. Death before discharge home or oxygen therapy at 36 weeks of gestation; pneumothorax while ventilated; cerebral ultrasound abnormality nearest to 6 weeks; and duration of ventilation in survivors were the main outcome measures.
                There was no significant difference in outcome between the two groups. Unadjusted rates for death or oxygen dependency at 36 weeks of gestation were 47.4% and 48.7%, for PTV and IMV, respectively; for pneumothorax these were 13.4% and 10.3%; and for cerebral ultrasound abnormality nearest to 6 weeks these were 35.4% and 36.9%. Median duration of ventilation for survivors in both groups was 6 days. Overall, 79% of babies received only their assigned ventilation. PTV babies were more likely to depart from their intended ventilation (27% vs 15%). The trend towards higher pneumothorax rates with PTV occurred only in infants below 28 weeks of gestation (18.8% vs 11.8%).
                There was no observed benefit from the use of PTV, with a trend towards a higher rate of pneumothorax under 28 weeks of gestation. Although PTV has a similar outcome to IMV for treatment of RDS in infants of 28 weeks or more gestation, within 72 hours of birth, it was abandoned more often. It cannot be recommended for infants of less than 28 weeks' gestation with the ventilators used in this study. A prospective comparison was made of the clinical courses of two groups of neonates ventilated according to different protocols: one group at rates of 20 to 40/minute with a one-second IT, and the other at a rate of 60/minute and 0.5 second IT. Other ventilator settings were adjusted within protocol limits to maintain desired blood gas values. Mean starting and highest PIP were lower in the rapid rate group. The results showed no difference in mortality, failure to remain within protocol limits, time requiring respiratory treatment or FiO2 more than 0.6, and incidence of PDA or chronic lung disease. There was a difference (P = 0.011) in number of infants developing pneumothoraces (14% in the rapid group vs 35% in the slow group). Rapid rate ventilation can be used to decrease the incidence of pneumothorax, reserving long IT and higher PIP for infants who cannot be oxygenated or ventilated without them. Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.
Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential newer forms of triggered ventilation are tested in adequately powered randomised trials with long-term outcomes before they are incorporated into routine clinical practice.