Extracorporeal membrane oxygenation in infants with meconium aspiration syndrome: a decade of experience with venovenous ECMO

Background

Despite the emergence of new therapies for respiratory failure of the newborn with meconium aspiration syndrome (MAS), extracorporeal membrane oxygenation (ECMO) has a significant role as a rescue modality in these infants. Our objective was to compare the use of venovenous (VV) vs venoarterial (VA) ECMO in newborns with MAS who need ECMO and to ascertain the impact of new therapies in these infants during the last decade. We also evaluated how disease severity or time of ECMO initiation affected mortality and morbidity.

Methods

A report of 12 years experience (1990-2002) of a single center, comparing VV and VA ECMO, is given. Venovenous ECMO was the preferred rescue modality for respiratory failure unresponsive to maximal medical therapy. Venoarterial ECMO was used only when the placement of a VV ECMO 14-F catheter was not possible; 128 patients met ECMO criteria, 114 were treated with VV ECMO, and 12 with VA ECMO. Two patients were converted from VV to VA ECMO.

Results

Venovenous and VA ECMO patients had comparable birth weight (mean ± SEM, 3.48 ± 0.05 vs 3.35 ± 0.15 kg) and gestational age (40.3 ± 0.1 vs 40.7 ± 0.3 weeks). Before ECMO, there was no difference between VV and VA ECMO patients in oxygenation index (60 ± 3 vs 63 ± 8), mean airway pressure (19.5 ± 0.4 vs 20.8 ± 1.5 cm H₂O), alveolar-arterial O₂ gradient (630 ± 2 vs 632 ± 4 torr), ECMO cannulation age (median [25th-75th percentiles], 23 [14-47] vs 26 [14-123] hours), or in the % of patients who needed vasopressors/inotropes (98% vs 100%). From November 1994, inhaled nitric oxide (NO) was available. Before VV ECMO, 67% of the patients received NO, 24% received surfactant, and 48% were treated with high-frequency ventilation (HFV). There was no significant difference between VV and VA ECMO patients in survival rate (94% vs 92%), ECMO duration (88 [64-116] vs 94 [55-130] hours), time of extubation (9 [7-11] vs 14 [9-15] days), age at discharge (23 [18-30] vs 27 [15-41] days), or incidence of short-term intracranial complications (5.3% vs 16.7%). For the total cohort of 126 infants, indices of disease severity (oxygenation index, alveolar-arterial O₂ gradient, mean airway pressure) did not correlate with outcome measures. Delay in ECMO initiation (>96 hours) was associated with prolonged mechanical ventilation and hospitalization (P < .01). New therapies (NO, HFV, surfactant) in the second part of the decade were associated with a longer ECMO duration (98 [80-131] vs 87 [60-116] hours; P < .05), no delay in ECMO initiation time (23 [10-40] vs 24 [14-52] hours), and no significant change in survival (97% vs 92.5%). No patient was treated with VA ECMO after 1994.

Conclusions

Venovenous ECMO is as reliable as VA ECMO in newborns with MAS in severe respiratory failure who need ECMO. Delay in ECMO initiation may result in prolonged mechanical ventilation and increased length of hospital stay. The emergence of new conventional therapies (NO, HFV, surfactant) and particularly increased experience enable sole use of VV ECMO with no significant change in survival in infants with MAS.     

Predictability model of the need for extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome treated with inhaled nitric oxide

Background

As the use of inhaled nitric oxide (iNO) resulted in a decline in the need for extracorporeal membrane oxygenation (ECMO) in neonates with hypoxic respiratory failure, iNO has become an accepted treatment modality even in non-ECMO centers. However, because not all neonates respond to iNO, the timely identification and transfer of nonresponders to an ECMO center are important.

Objectives

The objective of this study was to identify the risk factors predictive of the need of ECMO in neonates with hypoxic respiratory failure after the first 6 hours of iNO treatment in an ECMO center.

Methods and Patient Population

Forty-nine patients with hypoxic respiratory failure transferred for iNO therapy and potential ECMO during a 2-year period were identified in this retrospective study. None of the patients had received iNO before admission. Strict clinical guidelines were used to standardize lung inflation, cardiovascular support, and iNO administration and weaning and to define treatment failure. The relationship between treatment failure (ie, the need for ECMO) and a set of suspected risk factors after 6 hours of iNO administration was examined by logistic regression analysis.

Results

Twenty-two neonates responded to iNO (non-ECMO group) whereas 27 neonates failed and met ECMO criteria (ECMO group). There was no difference between the 2 groups in demographic data, ventilatory support, air leak syndrome at 6 hours of iNO treatment, and survival to discharge. However, the dose and duration of iNO therapy were predictive of the need for ECMO with an adjusted odds ratio of 1.12 (95% CI, 1.01-1.25; P = .04) and 0.45 (95% CI, 0.27-0.65; P = .0002), respectively.

Conclusions

By the end of the first 6 hours of iNO treatment and under the specific conditions established by the use of the clinical guidelines, the dose and the duration of iNO administration were predictive of the probability for the need of ECMO in this patient population. Thus, one can establish a center-specific predictability model for the need of ECMO in neonates with hypoxic respiratory failure treated with iNO if strict clinical guidelines for iNO administration and weaning and respiratory and cardiovascular support are used in the given center.     

Histopathological features of open lung biopsies in children treated with extracorporeal membrane oxygenation (ECMO)

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established treatment for severe respiratory distress in a range of pediatric conditions. This study describes the histopathological features in a series of 22 children receiving ECMO therapy in whom open lung biopsy was carried out. AIMS: To describe the histopathological features of open lung biopsies in children receiving ECMO therapy. STUDY DESIGN: Retrospective review of clinical material. SUBJECTS: Children receiving ECMO therapy in whom open lung biopsy was carried out. RESULTS: In those investigated in infancy, open lung biopsy allowed a definite diagnosis to be made of the underlying condition in more than 90% of cases. In older children, the histopathological changes were more non-specific and, although providing useful clinical information, a definitive diagnosis could often not be made. In about a quarter of cases, there are additional pathological features, which may be related to ECMO treatment, such as significant intra-alveolar haemorrhage, but ECMO does not in itself impair the diagnostic usefulness of open lung biopsy in these selected patients. CONCLUSION: Open lung biopsy provides clinically useful information in infants receiving ECMO therapy. The histopathological changes may be complex and represent both the effects of ECMO and progression of the underlying disease.     

Dexamethasone therapy in neonates treated with extracorporeal membrane oxygenation

OBJECTIVE: To test the hypothesis that infants who received dexamethasone would have a shorter length of time on extracorporeal membrane oxygenation (ECMO).Study design Infants placed on ECMO for respiratory failure were randomly assigned to receive either dexamethasone for 3 days or placebo. Chest radiographs were scored through the use of a validated standard scoring system to assess lung injury. RESULTS: Thirty infants received dexamethasone and 29 received placebo. The median (25th%, 75th%) duration of time on ECMO was 143.5 (100, 313) hours in the dexamethasone group and 160 (111, 303) hours in the placebo group (not significant). Survival was 80% in the dexamethasone group and 83% in the placebo group. Radiographic lung injury scores (mean+/-SEM) were significantly improved in the dexamethasone group (10.5+/-0.6) versus placebo (12.3+/-0.5) on day 3 of ECMO (P=.013). Hypertension developed in 27 of the 30 infants receiving dexamethasone and 13 of the 29 infants in the placebo group during ECMO (P<.01). CONCLUSIONS: Dexamethasone given during the first 3 days of ECMO results in significant improvement in lung injury scores by day 3 of ECMO but does not significantly decrease the duration of ECMO or improve survival. The preponderance of evidence would not support the use of dexamethasone in this setting.     

A pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO)

OBJECTIVE: To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured. RESULTS: No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions. CONCLUSIONS: Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.     

Is surfactant therapy beneficial in the treatment of the term newborn infant with congenital diaphragmatic hernia?

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.     

Development of silicone rubber hollow fiber membrane oxygenator for ECMO

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.     

Mechanical Ventilation and Extracorporeal Membrane Oxygenation as a Bridging Strategy to Lung Transplantation: Significant Gains in Survival

Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are increasingly used to bridge patients to lung transplantation. We investigated the impact of using MV, with or without ECMO, before lung transplantation on survival after transplantation by performing a retrospective analysis of 826 patients who underwent transplantation at our high‐volume center. Recipient characteristics and posttransplant outcomes were analyzed. Most lung transplant recipients (729 patients) did not require bridging; 194 of these patients were propensity matched with patients who were bridged using MV alone (48 patients) or MV and ECMO (49 patients). There was no difference in overall survival between the MV and MV+ECMO groups (p = 0.07). The MV+ECMO group had significantly higher survival conditioned on surviving to 1 year (median 1,811 days ([MV] vs. not reached ([MV+ECMO], p = 0.01). Recipients in the MV+ECMO group, however, were more likely to require ECMO after lung transplantation (16.7% MV vs. 57.1% MV+ECMO, p < 0.001). There were no differences in duration of postoperative MV, hospital stay, graft survival, or the incidence of acute rejection, renal failure, bleeding requiring reoperation, or airway complications. In this contemporary series, the combination of MV and ECMO was a viable bridging strategy to lung transplantation that led to acceptable patient outcomes.