[Newborn infants supported by extracorporeal membrane oxygenation: survival and clinical outcome]. / Survie et devenir clinique des nouveau-nés mis en assistance respiratoire extracorporelle.

OBJECTIVES: To assess the prognosis of newborn infants with refractory hypoxemia who required extracorporeal membrane oxygenation (ECMO). METHODS: Eighty-nine newborn infants treated by ECMO during more than 24 hours over a 8-year period (1996-2003) were included in this observational cohort study with a 9-month and 24-month evaluation. RESULTS: Respiratory failure mainly resulted from meconium aspiration syndrome (MAS, 43%), congenital diaphragmatic hernia (CDH, 15%) and sepsis (15%). Overall survival at hospital discharge was 67%. Infants with MAS had the best survival rate (82%) and those with CDH had the worst (46%). Of the remaining 60 survivors, 53% remained oxygen dependent at 28 days and 33% at 45 days. At the age of 2 years, only 1 infant remained oxygen dependent (but did not required oxygen at 3 years) and only 3 infants had significant neurodevelopmental problems. CDH group was associated with a prolonged duration in supplementary oxygen (P<0.001) and a prolonged duration for tube feeding (P=0.01) as compared with other diagnoses. Regarding neurologic outcome, CDH infants had the poorer neurological acquisition rate at 9 months but a very good evolution by the time of the 24-month evaluation. CONCLUSIONS: Morbidity in ECMO survivors is low considering the severity of illness in the newborn period, mainly related to pulmonary and feeding dysfunctions during the first months, in particular for the CDH group. Outcome at the age of 2 years of CDH infants is most often favourable regarding growth and neurodevelopmental evolution.

[Meconium aspiration syndrome requiring mechanical ventilation: incidence and respiratory management in France (2000-2001)]. / Inhalations méconiales nécessitant une ventilation mécanique: indicence et prise en charge respiratoire en France (2000-2001).

OBJECTIVES: To precise the number of term neonates with a meconium aspiration syndrome requiring mechanical ventilation in 2000 and 2001 in continental France and the related mortality. To study the different respiratory management. METHOD: A written questionnaire was sent to all intensive care units of continental France. RESULTS: Thirty-nine units were contacted and 31 answered (80%). On 30 answering centers, 265 cases are reported in 2000 and 249 in 2001. Extrapolation to the 39 centers led to a number of 347 cases in 2000 and 324 in 2001. Mortality rate was 6.4% for 2 years. Causes of death were: neurological 61%, respiratory 18% and others 21%. Twenty-six on 29 units used exogenous surfactant and/or high frequency oscillatory ventilation (HFOV) and/or inhaled nitric oxide (iNO). The sequence of use and the indication criteria of these therapies were quite variable with a majority of units using HFOV in the first place. CONCLUSIONS: Meconium aspiration syndrome is still a frequent neonatal condition despite a codified prevention strategy. Respiratory management in intensive care units remains very variable.

[Evolution of extracorporeal membrane oxygenation (ECMO) in neonatal acute respiratory failure, fifteen years of experience]. / Evolution sur 15 ans de l'assistance respiratoire extra-corporelle dans la prise en charge des détresses respiratoires néonatales sévères.

UNLABELLED: Over the last decade, several new therapies including exogenous surfactant therapy, inhaled nitric oxide and high-frequency ventilation have become available for the treatment of neonatal pulmonary failure. The aim of this retrospective study was to evaluate to what extent these modalities have impacted the use of neonatal extracorporeal membrane oxygenation at our institution and to discuss the role of ECMO in 2003 in the management of newborn infants with refractory hypoxemia. POPULATION AND METHODS: Two hundred and twenty six newborn infants treated by ECMO before 15 days of life and during more than 24 h in our intensive care unit were retrospectively included from two time periods (group 1: 1988-1993 and group 2: 1996-2003). RESULTS: As compared with the first group, the number of newborns supported by ECMO in the second group has clearly diminished and their severity has increased. Overall survival rate was 80% in the first group and 69% in the second group. Meconium aspiration syndrome remains the major indication for ECMO (44%). Pulmonary sequelae, assessed by bronchopulmonary dysplasia rate (41%) are more frequent that neurologic sequelae (4.8%). CONCLUSION: ECMO remains an useful technique in the management of newborn infants with refractory hypoxemia, with a consideration to institute ECMO early in order to increase survival rate.

[Extracorporeal oxygenation in newborn infant born to diabetic mother with severe hypertrophic myocardiopathy]. / Oxygénation extracorporelle chez un nouveau-né de mère diabétique avec une myocardiopathie hypertrophique sévère.

UNLABELLED: Hypertrophic cardiomyopathy is a common complication in infants born to diabetic mothers but it is rarely life threatening. CASE REPORT: A neonate born to a diabetic mother with a severe hypertrophic cardiomyopathy with life threatening respiratory and haemodynamic distress was successfully supported by extracorporeal membrane oxygenation. CONCLUSION: Extracorporeal membrane oxygenation can be an efficient transitory therapy for very severe hypertrophic cardiomyopathy in infants of diabetic mothers.

[Clinical and respiratory function follow-up of 39 infants treated with neonatal respiratory extracorporeal assistance]. / Suivi clinique et fonctionnel respiratoire de 39 nourrissons traités par assistance respiratoire extracorporelle néonatale.

UNLABELLED: The aim of this prospective study was to evaluate the consequences of neonatal treatment with a venovenous extracorporeal respiratory assistance. POPULATION AND METHODS: Thirty nine neonates (28 boys) with acute respiratory failure were included. Extracorporeal respiratory assistance consisted of an apnoeic oxygenation with low frequency positive pressure ventilation and extracorporeal membrane CO2 removal through a venous single canula perfusion circuit. The causes of respiratory distress were: 15 meconium aspiration syndrome, 12 respiratory distress syndrome, six hyaline membrane disease, three sepsis, two diaphragmatic hernia, and one post-surgery Mendelson syndrome. The mean duration of mechanical ventilation was 18 days, including 5 days of extracorporeal respiratory assistance. The prospective follow-up included physical examination, chest radiographs, scintigraphy and pulmonary function tests. These tests studied the following parameters: functional residual capacity by helium dilution technique, lung resistance and dynamic lung compliance by the esophageal balloon technique and blood gases with arterialized blood samples. RESULTS: The mean duration of the follow-up was 21.3 months (6 months to 5 years). Results showed in the first year 33% of children with chronic obstructive pulmonary disease and chest (X-ray abnormalities, such as bronchopulmonary dysplasia in 23% of children. Data of pulmonary function test at the end of the first year: lung resistance and functional residual capacity were within limits of predicted values for height, and dynamic lung compliance was slightly decreased; according to the analysis of the functional profile: 31% without abnormality, 41% of obstructive syndrome and 26% with restrictive pattern. Blood gases were normal in 37 children. At the end of the second year, we noticed normal functional residual capacity, an increase of lung resistance while lung compliance was normalized; functional profile was quite different: with a decrease of the number of patients without abnormality (22%) and increase of those with obstructive syndrome (56%). CONCLUSION: The percentage of abnormalities is high but these are moderate in most cases, especially if we compare with the initial seriousness of the pulmonary pathology. We suggest a regular follow-up to study the respective incidence of pulmonary disease and/or extracorporeal respiratory assistance over these abnormalities.

Induced cell trauma during in vitro perfusion: a comparison between two different perfusion systems.

The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.

Abolition of breathing rhythmicity in lambs by CO2 unloading in the first hours of life.

The mechanisms responsible for the maintenance of regular breathing after initiation of breathing at birth are still poorly understood. This study was designed to test the hypothesis that removing the chemical CO2 drive would abolish breathing rhythmicity in lambs in the first hours of life. A technique of graded CO2 removal through a veno-venous extracorporeal circuit was used in five unanesthetized lambs aged from 4 to 12 hours. In all lambs, CO2 unloading invariably resulted in sustained central apnea, after a decrease in Paco, of 6.9 +/- 5.7 Torr. We were unable to find a significant relationship between the decrease in PaCO2 and PaO2 (range 35-275 Torr) at onset of apnea. During apnea, the passage from behavioral quiet sleep to arousal or to active sleep was marked by transient and weak breathing movements. We conclude that the CO2 drive, but not the behavioral states, is a major factor for maintaining breathing rhythmicity in lambs in the first hours of life.

[Cytomegalovirus pneumopathies in pediatric intensive care units]. / Pneumopathies à cytomégalovirus en réanimation pédiatrique.

BACKGROUND: Cytomegalovirus (CMV) infection can result in major complications in immunocompromised infants and children. CMV pneumonia may be difficult to diagnose and the true pathogenic role of the virus in the disease is not always clear. This report describes a cohort of 20 children who suffered from CMV pneumonia. POPULATIONS AND METHODS: Twenty children aged 1 month to 11 years 10 months were admitted to our intensive care unit between 1981 and 1990 because of pneumonia with evidence of CMV infection. They were classified into three groups: group I (cases 1-10) with hemopathy or cancer, group II (cases 11-14) with AIDS, and group III (cases 15-20): non immunodeficient or immunosuppressed children. CMV infection was diagnosed after isolation of CMV from bronchoalveolar lavage (BAL) fluid (15 patients), lung biopsy revealing intranuclear inclusions or CMV antigens, or CMV-positive cultures (four patients), CMV-positive urine cultures (one patient). RESULTS: Clinical manifestations and X-rays findings were unspecific; interstitial pneumonia was found only in immunodeficient patients. CMV pneumonia was diagnosed only in two patients on post mortem examination. Concomitant pneumocystis carinii was found on BAL in two patients (group I) and two others (group II). Thirteen patients required ventilation. Eleven patients were given ganciclovir for 2 or 3 weeks; one of them was given a single dose. This treatment was well tolerated. Mortality was 90% in group I, 100% in group II and 33% in group III. CONCLUSION: Ganciclovir did not appear to benefit the immunocompromised patients with CMV pneumonia. Future treatment should include hyperimmune CMV immunoglobulins plus ganciclovir. Careful hand washing is important for all those caring for these patients to prevent contamination as is the use of CMV-negative blood products.

Venovenous single lumen cannula extracorporeal lung support in neonates. A five year experience.

The authors have developed a venovenous extracorporeal lung support technique with an original single lumen cannula to avoid the carotid ligation of venoarterial extracorporeal membrane oxygenation (ECMO). During a 5 year period, the authors have used the technique in 107 neonates (weight: 3.045 +/- 0.6 1 kg; gestational age: 38.1 +/- 2.2 weeks). All of the neonates had severe respiratory failure despite maximal conventional treatment and the same indications as those for ECMO. The venovenous technique associates extracorporeal CO2 removal and apneic oxygenation. The system includes a single lumen cannula, an alternating clamp that generates a tidal flow, and an original non-occlusive roller pump that avoids the use of a venous bladder. The PaCO2 was normal (34.6 +/- 3.9 mmHg) with a blood flow of 40-50% of the total cardiac output. Under apneic oxygenation, PaO2 improved rapidly, allowing a decrease in FiO2 and mean airway pressure, minimizing barotrauma. The mean duration of bypass was 117.8 +/- 83.9 hr, and 91 of the 107 (85%) neonates were weaned from AREC. The technical complications were less important than those associated with venoarterial ECMO. The authors conclude that AREC is as effective as venoarterial ECMO and is easier to use.

[Extracorporeal oxygenation and extracorporeal respiratory assistance in newborn infants]. / Oxygénation extracorporelle et assistance respiratoire extracorporelle chez le nouveau-né.

The authors present the principle and discusses the indications and contraindications of two technics of extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure, respectively veno-arterial and veno-venous. The two technics appear to give comparable results. They are indicated in neonates with refractory hypoxemia after failure of other methods such as surfactant, high frequency oscillatory ventilation and nitrous monoxyde.

Miliary tuberculosis with acute respiratory failure and histiocytic hemophagocytosis. Successful treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213.

A 14-year-old girl with high fever, dyspnea and bilateral miliary nodules on chest X-ray, developed a rapidly progressive respiratory failure associated with histiocytic hemophagocytosis. Histologic examination of bone marrow biopsy revealed tuberculous granulomas with caseating necrosis. We report a pediatric case in which treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213 was successful.

Partial and massive lung lavages in an infant with severe pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis is a rare disease of unknown etiology, characterized by progressive respiratory failure. Lung lavage has only been applied in a few children. A 6 month old boy suffering from severe pulmonary alveolar proteinosis was treated with three lung lavages. The first two were partial (or unilateral) lavages; a 3.5 mm flexible bronchoscope was introduced adjacent to a no. 3 cuffed endotracheal tube. This procedure allowed selective ventilation of one lung, and contralateral lung lavage. Respiratory improvement was observed during 1 week after the two procedures. At the third lavage we used partial veno-venous extracorporeal circulation because of severe respiratory failure. A significant improvement during the 5 following months was achieved. These results suggest that both partial and total lung lavage can be performed even in young infants and they may control the declining respiratory status in severe pulmonary alveolar proteinosis.

Preliminary report: extracorporeal lung support for neonatal acute respiratory failure.

A technique for ventilatory support of life-threatening neonatal acute respiratory failure by use of apnoeic oxygenation and low-frequency positive-pressure ventilation, with extracorporeal membrane CO2 removal through a single-cannula perfusion circuit, is described. 20 severely ill babies with respiratory failure were treated with this technique, 17 of whom survived with no clinical evidence of pulmonary handicap or neurological deficit at discharge from hospital. All 10 patients followed up at 6 months showed normal growth and development.

[Severe neonatal respiratory distress with linear inspiratory pressure-volume curve]. / Détresses respiratoires graves néonatales à courbe pression-volume inspiratoire linéaire.

Twenty-four newborns with severe respiratory distress, treated by mechanical ventilation, are investigated by inspiratory pressure-volume curve. The curves are obtained by slow continuous inflation technique. Two shapes are described: concave curve, ten newborns (group I), linear curve, fourteen newborns (group II). The gestational age is over 36 weeks in both groups. Determination of respiratory mechanics is indicated when mean AaDO2 is higher than 500 torr in both groups, and when there is a hypercapnia (PaCO2 = 53 +/- 11 torr, with p less than 0.05) in group II. Mechanical ventilation is conducted with individually adjusted PEEP in group I, and without PEEP in group II. Twelve hours after; mean AaDO2 in group I (260 +/- 101 torr) and in group II (420 +/- 188 torr) are significantly different (p less than 0.05). The variance analysis in group II shows that PaCO2 and pH are normalized (p less than 0.001). All the newborns in group I recovered. Three newborns in group II died. Group I can be assimilated to hyaline membrane disease in full-term neonates. Practically, the cases of neonatal respiratory distress in which PEEP is not indicated can be identified by the functional characteristics of group II.

Single-cannula venovenous bypass for respiratory membrane lung support.

Clinical use of a single cannula would make extracorporeal membrane oxygenation simpler and less aggressive. It would probably limit the occurrence of the complications of currently used techniques (double-cannula, venoarterial, or venovenous bypass). In this experimental study an original system is described that is composed of a single cannula, an alternating clamp, and a nonocclusive roller pump, the characteristics of which permit its use as a venous reservoir. To overcome the limitations of the oxygenation in any venovenous bypass, we used the method of "apneic oxygenation" through the natural lungs, which we previously proved efficient in infants and children. The optimal setting of the alternative clamp was first tested in vitro to obtain the maximal flow in the circuit and the minimal amount of recirculation. The single-cannula bypass then was compared with a two-cannula circuit regarding the efficiency of carbon dioxide removal and the hemodynamic consequences. At less than 50% of the maximal speed of the pump, flows were equivalent in both types of circuits. The efficiency of carbon dioxide removal was only slightly decreased by the use of a single cannula (30 +/- 2 ml/min versus 36 +/- 2 ml/min with two cannulas). This could easily be offset by increasing the gas flow/blood flow ratio in the oxygenator. Arterial carbon dioxide tension was maintained at normal levels in both types of circuits. Hemodynamic condition was only slightly affected by the alternative flow of the bypass. This system of single-cannula membrane lung support thus seems to be adequate for clinical use.

Use of total inspiratory pressure-volume curves for determination of appropriate positive end-expiratory pressure in newborns with hyaline membrane disease.

Thirty newborns with hyaline membrane disease were treated by mechanical ventilation with individualized appropriate positive end-expiratory pressure (APEEP) from inspiratory pressure-volume curves of the total respiratory system. APEEP was started before H24 in group 1 (19 patients), and after H24 in group 2 (11 patients). Until APEEP, the 2 groups had classical PEEP levels (lower than 0.8 kPa) either without or with incomplete improvement in arterial hypoxia. The mean APEEP of each group was greater than classical PEEP (p less than 0.001). In group 1 the time of exposure to FiO2 greater than 0.4 was shorter (23.8 +/- 13.7 h) than in group 2 (88.6 +/- 56.9 h) (p less than 0.001) and rapid improvement in blood gas exchanges was seen in group 1 compared to group 2 that was independent of the severity of the disease. Tolerance was excellent. APEEP ventilation started before H24 is of special interest in the management of newborns with severe alveolar injury.