OBJECTIVE: To assess the long-term cost-effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure.
METHODS: A prospective economic evaluation was conducted alongside a pragmatic randomized, controlled trial in which 185 infants were randomly allocated to ECMO (n = 93) or conventional management (n = 92) and then followed up to 7 years of age. Information about their use of health services during the follow-up period was combined with unit costs (pound sterling, 2002-2003 prices) to obtain a net cost per child. The cost-effectiveness of neonatal ECMO was expressed in terms of incremental cost per additional life year gained and incremental cost per additional disability-free life year gained. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics at alternative willingness-to-pay thresholds held by decision-makers for an additional life year and for an additional disability-free life year.
RESULTS: Over 7 years, neonatal ECMO was effective at reducing known death or severe disability. Mean health service costs during the first 7 years of life were 30,270 pound sterling in the ECMO group and 10,229 pound sterling in the conventional management group, generating a mean cost difference of 20,041 pound sterling that was statistically significant. The incremental cost per life year gained was estimated at 13,385 pound sterling. The incremental cost per disability-free life year gained was estimated at 23,566 pound sterling. At the notional willingness-to-pay threshold of 30,000 pound sterling for an additional life year, the probability that neonatal ECMO is cost-effective at 7 years was estimated at 0.98. This translated into a mean net benefit of 24,362 pound sterling for each adoption of neonatal ECMO rather than conventional management.
CONCLUSIONS: This study provides rigorous evidence of the cost-effectiveness of neonatal ECMO during childhood.
OBJECTIVE: The UK Collaborative ECMO trial provided an opportunity to describe mortality and morbidity associated with a neonatal ECMO policy compared with conventional management. The improved survival in the ECMO group was not offset by an increase in disability at 4 years, but the children were too young to assess educational and other longer-term impacts. The objective of this study was to assess the longer-term impact of these policies at age 7 years.
METHODS: A psychologist assessed 90 of the 100 children available for follow-up without prior knowledge of treatment allocation. The assessments took place at the children's schools within 3 months of their 7th birthdays.
RESULTS: Sixty-eight of 89 (76%) children recorded a cognitive level within the normal range. Learning problems were similar in the 2 groups, and there were notable difficulties with spatial and processing tasks. A higher respiratory morbidity and increased risk of behavioral problems among children treated conventionally persisted. Progressive sensorineural hearing loss was found in both groups.
CONCLUSIONS: The underlying disease processes appear to be the major influence on morbidity at 7 years. The beneficial influence of an ECMO policy is still present at 7 years.
OBJECTIVE: Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes. METHODS: Neonates who were born at > or =34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) > or =15 and <25 on any 2 measurements in a 12-hour interval. Infants were randomized to early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. RESULTS: The trial enrollment was halted after 75% of target sample size was reached because of decreasing availability of eligible patients. The 150 infants who were given early iNO and 149 control infants had similar baseline characteristics. Arterial oxygen tension increased by >20 mm Hg in 73% of early iNO and 37% of control infants after study gas initiation. Control infants received standard iNO and deteriorated to OI >40 more often than infants who were given early iNO. The incidence of death (early iNO, 6.7% vs control, 9.4%), ECMO (10.7% vs 12.1%), and their combined incidence (16.7% vs 19.5%) were similar in both groups. CONCLUSION: iNO improves oxygenation but does not reduce the incidence of ECMO/mortality when initiated at an OI of 15 to 25 compared with initiation at >25 in term and near-term neonates with respiratory failure.
BACKGROUND: Congenital diaphragmatic hernia (CDH) with liver herniation and a lung area to head circumference ratio (LHR) < 1 [corrected] is associated with a high rate of neonatal death due to pulmonary hypoplasia.
METHODS: We report the development of a minimally invasive and reversible fetoscopic tracheal occlusion (FETO) with a balloon, carried out in 21 consecutive fetuses with severe CDH.
RESULTS: Endotracheal placement of the balloon was successfully performed in all 21 cases and the mean duration of the operation was 20 (range, 5-54) min. The median gestation at FETO was 26 (range, 25-33) weeks. There were no maternal complications such as hemorrhage, placental abruption or pulmonary edema. In 11 (52.4%) patients there was postoperative prelabor amniorrhexis, which occurred within 2 weeks in five patients and after 2 weeks in six patients. Ultrasound scans after FETO demonstrated an increase in the echogenicity of the lungs within 48 h and improvement in the LHR from a median 0.7 (range, 0.4-0.9) before FETO to 1.8 (range, 1.1-2.9) within 2 weeks following surgery. The median gestation at delivery was 34 (range, 27-38) weeks and in 17 (77.3%) patients delivery occurred after 32 weeks. Nine babies died in the neonatal period due to complications from pulmonary hypoplasia. Surgical repair of the diaphragmatic hernia was carried out in 12 babies and in all but one the defect was extensive and required the insertion of a patch. Ten of these babies survived, and at the time of writing were aged 6-25 (median, 18) months and were developing normally. Survival was 30% in the first group of 10 fetuses and 63.6% in the second group of 11 fetuses. The total number of cases was too small for definite conclusions to be drawn as to the causes of this apparent improvement in survival. Nevertheless, improved survival coincided with a shift in the timing of FETO from the third to the second trimester, the administration of epidural rather than general anesthesia, reduced incidence of postoperative amniorrhexis and a change in the policy on the timing of removal of the balloon from the intrapartum to the prenatal period. During the same period of study there were 17 cases examined in the participating centers that met the criteria for FETO but which declined prenatal therapy. In all cases there was isolated left-sided CDH with liver in the thorax and LHR of 0.4-0.9 (mean, 0.7). In five cases the parents elected to terminate the pregnancy. In the 12 cases with expectant management all babies were liveborn but 11 died in the neonatal period due to pulmonary hypoplasia and only one (8.3%) survived.
CONCLUSION: Severe CDH can be successfully treated with FETO, which is minimally invasive and may improve postnatal survival.
OBJECTIVES: To determine the impact of surfactant replacement on survival, need for extracorporeal membrane oxygenation (ECMO), and chronic lung disease in term infants with prenatally diagnosed congenital diaphragmatic hernia (CDH).
STUDY DESIGN: Prenatally diagnosed infants born at > or =37 weeks' gestation with immediate distress at delivery and no other major congenital anomalies, who were enrolled in the CDH Registry, were analyzed. For univariate analysis, chi 2 tests were used for categoric variables and unpaired t tests for nominal variables. Multiple logistic regression was used to calculate adjusted odds ratios.
RESULTS: Eligible infants (n = 522) were identified. Demographic variables were similar between the surfactant-treated (n = 192) and nonsurfactant-treated (n = 330) groups, with the exception of race (white, 88.0% vs 71.2%; P =.0007). The use of ECMO and incidence of chronic lung disease were higher (59.8 vs 50.6, P =.04; 59.9 vs 47.6, P =.0066) and survival lower in the surfactant-treated cohort (57.3 vs 70.0, P =.0033). Adjusted logistic regression for use of ECMO, survival, and chronic lung disease resulted in odds ratios inconsistent with an improved outcome associated with surfactant use.
CONCLUSIONS: This analysis shows no benefit associated with surfactant therapy for term infants with a prenatal diagnosis of isolated CDH.
OBJECTIVE: To assess the cost effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure over a four year time span.
DESIGN: Cost effectiveness analysis based on a randomised controlled trial in which infants were individually allocated to ECMO (intervention) or conventional management (control) and then followed up to 4 years of age.
SETTING: Infants were recruited from 55 approved recruiting hospitals throughout the United Kingdom. Infants allocated to ECMO were transferred to one of five specialist regional centres. Follow up of surviving infants was performed in the community.
SUBJECTS: A total of 185 mature (gestational age at birth >or= 35 weeks, birth weight >or= 2000 g) newborn infants with severe respiratory failure (oxygenation index >or= 40).
MAIN OUTCOME MEASURES: Incremental cost per additional life year gained; incremental cost per additional disability-free life year gained.
RESULTS: Over four years, the policy of neonatal ECMO was effective at reducing known death or severe disability (relative risk = 0.64; 95% confidence interval 0.47 to 0.86; p = 0.004). After adjustment for censoring and discounting at 6%, the mean additional health service cost of neonatal ECMO was pound 17367 (95% confidence interval pound 12072 to pound 22224) per infant ( pound UK, 2001 prices). Over four years, the incremental cost of neonatal ECMO was pound 16707 ( pound 9828 to pound 37924) per life year gained and pound 24775 ( pound 13106 to pound 69690) per disability-free life year gained. These results remained robust after variations in the values of key variables performed as part of a sensitivity analysis.
CONCLUSIONS: The study provides rigorous evidence of the cost effectiveness of ECMO at four years for mature infants with severe respiratory failure.
BACKGROUND: There is considerable debate regarding the optimal management of congenital diaphragmatic hernia (CDH) in high-risk infants (those cases presenting with respiratory distress within 2 hours of birth or those diagnosed prenatally). The aim of this study was to analyze patient outcomes using a new treatment protocol for CDH in a tertiary care non-extracorporeal membrane oxygenation (ECMO) neonatal unit.
METHODS: The records of 78 consecutive neonates with CDH presenting to Bambino Gesù Children's Hospital from 1996 to 2001 were analyzed retrospectively. Of these infants, 70 high-risk patients were identified (prenatal diagnosis or respiratory distress requiring intubation and assisted ventilation within 2 hours after birth), regardless of associated anomalies, medical condition on presentation, or degree of pulmonary hypoplasia. A prenatal diagnosis was made in 46 of 70 (66%) patients. Associated lethal malformations were present in 6 of the children (8.5%). The patients were placed in 3 historical groups: group 1, 19 patients from 1996 to 1997, group 2, 22 patients from 1998 to 1999, and group 3, 29 patients from 2000 to 2001. In the first 2 groups, a new protocol was introduced using inhaled nitric oxide (iNO) and high-frequency oxygen ventilation (HFOV). In the third group, gentle ventilation and permissive hypercarbia were also used routinely. Mortality and severe morbidity--defined as O2 requirement at discharge, need for a tracheostomy, neurologic impairment, or bilateral hearing loss-were evaluated when the patients were at 6 months old. Univariate analysis was performed.
RESULTS: The 3 groups were comparable with respect to predictive risk factors such as side of hernia, prenatal diagnosis, polyhydramnios, stomach and liver in the thorax, associated lethal malformations, and patch. Overall survival rate significantly increased from 47% (9 of 19) in group 1 and 50% (11 of 22) in group 2 to 90% (26 of 29) in group 3 (P =.02). None of the 19 patients in group 1 had severe morbidity compared with 2 of 22 (9%) patients in group 2 and 2 of 29 (7%) patients in group 3. Hearing loss was observed in 4 patients. Mortality rate and preoperative pneumothorax significantly decreased in group 3 compared with groups 1 and 2 (P =.03 and P =.00, respectively).
CONCLUSIONS: (1) The application of new treatment protocol for CDH, using gentle ventilation and permissive hypercarbia, produced a significant increase in survival with concomitant decrease in morbidity. (2) The rate of pneumothorax was significantly decreased by the introduction of permissive hypercarbia and gentle ventilation. (3) As more infants survive CDH without the use of ECMO, severe long-term sequelae of CDH can be recognized in these children.
BACKGROUND/PURPOSE: Initial laboratory and clinical data suggest that partial liquid ventilation (PLV) can enhance pulmonary function and that lung growth can be induced via distension of the newborn lung using perfluorocarbon in patients with congenital diaphragmatic hernia (CDH). The authors, therefore, performed a prospective, randomized pilot study evaluating PLV and perfluorocarbon-induced lung growth (PILG) in newborns with CDH on extracorporeal life support (ECLS) at 6 medical centers.
METHODS: Patients were selected randomly using a permuted block design to PLV/PILG (n = 8) or conventional mechanical ventilation (CMV/control, n = 5). Patients in the PILG group received daily doses which filled the lungs with perflubron for up to 7 days and were placed on continuous positive airway pressure of 5 to 8 cm H2O. CMV patients were treated with standard mechanical ventilation while on extracorporeal membrane oxygenation (ECMO).
RESULTS: A total of 13 patients were evaluated in this study. All 3 patients enrolled without being on ECLS rapidly transitioned to ECLS. The study, therefore, effectively evaluated PILG (n = 8) versus standard ventilation (control, n = 5) on ECLS. Mean (+/- SE) gestational age was 37 +/- 1 weeks and weight was 3.1 +/- 0.1 kg. Time on ECMO was 9.8 +/- 2.3 days in the PILG and 14.5 +/- 3.5 days (P =.58) in the control group. Survival rate in the PILG group was 6 of 8 (75%), whereas survival rate was 2 of 5 (40%) in the control group (P =.50). The number of days free from the ventilator in the first 28 days (VFD) was 6.3 +/- 3.3 days with PILG and 4.6 +/- 4.6 days with control (P =.9). Causes of death in the PILG group included sepsis and renal failure in one patient and pulmonary hypertension in the other. There were no safety issues, and the deaths in the PILG group did not appear to be related to the administration of perflubron.
CONCLUSIONS: These data show that PILG can be performed safely. The survival rate, VFD, and time on ECMO data, although not conclusive, are encouraging and indicate the need for a definitive trial of this novel intervention in these neonates with high mortality.
OBJECTIVE: Inhaled nitric oxide (iNO) improves oxygenation and reduces the need for extracorporeal membrane oxygenation in infants with severe persistent pulmonary hypertension of the newborn (PPHN). The effectiveness of iNO in the treatment of moderate PPHN has not been adequately defined. We therefore conducted a randomized, prospective multicenter study to assess whether iNO in patients with moderate PPHN would improve arterial p(a)O(2), prevent progression to severe PPHN, and improve outcomes.
METHODS: Infants > or = 34 weeks gestation with moderate pulmonary hypertension (alveolar-arterial oxygen gradient (AaDO(2)) 500-599 Torr) were randomly assigned to continue standard medical therapy (control group) or standard medical therapy plus iNO (iNO group). For each patient in the iNO group, iNO concentration was increased in steps of 10-20 ppm every 30 minutes until there was no further improvement in arterial p(a)O(2). This concentration of iNO was then maintained while all other ventilatory support, including inspired oxygen concentration, was weaned according to a predefined protocol.
RESULTS: In all, 27 of 40 control patients (58%) compared to six of 40 infants (15%) in the iNO group failed assigned therapy and developed severe PPHN (p<0.0005). Arterial p(a)O(2) improved from 112+/-48 to 133+/-100 (p=0.132) in control infants compared to an increase from 101+/-29 to 208+/-118 (p<0.0005) in iNO-treated patients. For the first 36 hours after study, entry AaDO(2) levels and ventilatory support were significantly lower in iNO-treated infants compared to control patients.
CONCLUSION: In patients with moderate PPHN, treatment with iNO improves arterial p(a)O(2), reduces the amount of ventilatory support needed, and prevents progression to severe PPHN.
OBJECTIVE: As previously reported, high postnatal mortality seen in fetuses with congenital diaphragmatic hernia (CDH) with liver herniation and low lung-to-head ratio (LHR) appears to be improved in fetuses who undergo fetoscopic temporary tracheal occlusion (TO). To test whether further evolution of this technique produces results that justify a randomized controlled trial comparing prenatal intervention to postnatal care, the authors analyzed 11 additional cases and the cumulative experience with 19 cases.
METHODS: The authors analyzed retrospectively the outcome of 11 new and 8 previously reported cases of fetoscopic temporary tracheal occlusion. Various factors were studied including maternal morbidity, antenatal outcome, physiologic lung response, and neonatal course.
RESULTS: Temporary TO can be accomplished using 3 5-mm radially expanding uterine ports without hysterotomy. Obstetric morbidity included mild pulmonary edema in 6 cases, chorioamniotic separation and premature rupture of membranes in 12 patients, and preterm labor and delivery in all patients. Thirteen of 19 (68%) neonates survived for 90 days after delivery; one died in utero, and 5 died after birth. Late mortality included one death caused by sepsis and 2 by complications associated with tracheostomies. Morbidity from gastroesophageal reflux requiring Nissen fundoplication, tracheal injury requiring repair or tracheostomy, and recurrent hernias after diaphragmatic repair were characteristic in longterm survivors.
CONCLUSIONS: Fetoscopic temporary TO may improve outcome in poor-prognosis fetuses with CDH. However, complications related to tracheal dissection, premature delivery and late morbidity are significant. This experience has led to simpler techniques for fetoscopic tracheal occlusion and to an National Institutes of Health-sponsored randomized controlled trial comparing fetoscopic tracheal occlusion with optimal postnatal care.
To assess the long-term cost-effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure.
METHODS:
A prospective economic evaluation was conducted alongside a pragmatic randomized, controlled trial in which 185 infants were randomly allocated to ECMO (n = 93) or conventional management (n = 92) and then followed up to 7 years of age. Information about their use of health services during the follow-up period was combined with unit costs (pound sterling, 2002-2003 prices) to obtain a net cost per child. The cost-effectiveness of neonatal ECMO was expressed in terms of incremental cost per additional life year gained and incremental cost per additional disability-free life year gained. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics at alternative willingness-to-pay thresholds held by decision-makers for an additional life year and for an additional disability-free life year.
RESULTS:
Over 7 years, neonatal ECMO was effective at reducing known death or severe disability. Mean health service costs during the first 7 years of life were 30,270 pound sterling in the ECMO group and 10,229 pound sterling in the conventional management group, generating a mean cost difference of 20,041 pound sterling that was statistically significant. The incremental cost per life year gained was estimated at 13,385 pound sterling. The incremental cost per disability-free life year gained was estimated at 23,566 pound sterling. At the notional willingness-to-pay threshold of 30,000 pound sterling for an additional life year, the probability that neonatal ECMO is cost-effective at 7 years was estimated at 0.98. This translated into a mean net benefit of 24,362 pound sterling for each adoption of neonatal ECMO rather than conventional management.
CONCLUSIONS:
This study provides rigorous evidence of the cost-effectiveness of neonatal ECMO during childhood.
