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Eur J Cardiothorac Surg 2000;18:328-333
© 2000 Elsevier Science NL
a Department of Thoracic Surgery, A. Calmette Hospital, Centre Hospitalier Régional et Universitaire de Lille, Bd. du Professeur Leclercq, 59037 Lille cedex, France
b Department of Neonatology, J. de Flandre Hospital, Lille, France
Received 22 December 1999; received in revised form 10 May 2000; accepted 6 June 2000.
Corresponding author
e-mail: sjaillard{at}chru-lille.fr
| Abstract |
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Key Words: Extracorporeal membrane oxygenation Congenital diaphragmatic hernia Neonatal respiratory failure Venovenous bypass Venoarterial bypass
| 1. Introduction |
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| 2. Population and methods |
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Our ECMO entry criteria were: (1) gestational age (GA) over 34 weeks; (2) birth weight (BW) above 1800 g; (3) respiratory failure with oxygenation index (OI) calculated as:
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Both venovenous (VV) or venoarterial (VA) ECMO were used. VV ECMO was performed using a single lumen cannula surgically inserted through the right jugular vein with the tip in the mid portion of the right atrium. This type of VV ECMO uses alternative inflow and outflow. VA ECMO was performed with both surgical cannulation of the right common carotid artery (with a short cannula (tip<1.5 cm) inserted through the artery) and of the right jugular vein (in the same position as VV ECMO). VA ECMO allows continuous flow within the circuit: the vein was used for venous drainage and the artery was used for reinfusion of oxygenated blood (Fig. 1) . Systemic anticoagulation (heparin infusion in the venous line of the ECMO circuit) was set to maintain the Hemocron time between 160 and 180 s. During the course of ECMO, infants were systematically sedated (Fentanyl) and received diuretics (Lasilix). No prophylactic antibiotics were infused.
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All of the children were enrolled into a follow-up study with neurodevelopmental, respiratory and digestive examination. Neurologic evaluation consisted of clinical examination (1/6 months), electroencephalography (EEG) (at 6 months, 1 year and 2 years), cranial ultrasonography (at 1 month and 6 months) and computed tomography (CT) scan (at 1 year if cranial ultrasonography was abnormal). Neurological outcome was defined as normal neurologic development, developmental delay, or cerebral palsy according to Hagberg [4]. Neurosensorial evaluation was systematically performed including ocular and fundus oculi examination, and hearing evaluation by Boël-test and brainstem auditory-evoked potential (BAEP). Respiratory evaluation was performed: bronchopulmonary dysplasia was defined as oxygen dependency after 28 days of life, and persistence of oxygen dependency was recorded with the need of tracheostomy. Digestive evaluation consisted of the search for symptomatic gastroesophageal reflux. Growth, including weight, length and head circumference, was systematically recorded, and growth retardation was defined as weight<5th percentile. Rate of feeding gastrostomy was noted. Doppler ultrasonography was performed to check the blood flow of the repaired carotid artery.
Statistical analysis was performed using
2 or Fisher's exact test for difference of proportions, and the MannWhitney test for the comparison of groups of patients. Results are mean±standard deviation (SD). P-values of less than 0.05 were considered significant.
| 3. Results |
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The clinical characteristics of the population are summarized in Table 1. Two groups were compared according to the initial diagnosis: CDH (n=23) and other diagnosis (n=34). No difference between the two groups could be found for gestational age, birth weight, Apgar score, oxygenation index and age at ECMO initiation. However, ECMO duration was significantly longer in the CDH group (P=0.0053).
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Survival at 2 years (Table 2) was 40/57 (70%): it was highly related to initial diagnosis: CDH=12/23 (52%), NS=11/14 (79%), MAS=12/12 (100%) and others=5/8 (62%). Ten neonates died during extracorporeal circulation (early death): eight were on VV ECMO, two on VA ECMO. Five technical complications occurred during VV ECMO: pump malfunction (n=2), air in circuit (n=1), hemorrhagic complication (n=1) and heat exchanger malfunction (n=1). Five infants died due to medical complications: one intracranial hemorrhage, one cerebral ischemia, one multisystem organ failure and two persistent respiratory insufficiency. Seven infants (all CDH) died after ECMO support was discontinued: one total superior and inferior vena cava obstruction (1 month old), one sudden death (5 months old), one of gastric inhalation (7 months old), one secondary to general anesthesia for jejunostomy (1 year old), one bronchopulmonary dysplasia (18 months old) and one hemorrhage following insertion of a central venous line (2 years old).
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Anomalies of cranial ultrasonography was recorded in 16 neonates before decannulation. Anomalies ranged from moderate (intraventricular hemorrhage grade I of Papile, or transient intraparenchymal hyperechogenicity) (n=10/16), to severe (grade II or III and cerebral atrophia) (n=6/26). Persistent cerebral atrophia imaging was found in six infants. CT scan at 1 year was performed on 23 infants and showed nine abnormalities without lateralization (six cerebral atrophia and three minor abnormalities).
Study of electroencephalography shows that poor neurological outcome was related to ictal discharges lasting more than 1 day and associated with severe background abnormalities.
Beyond the neonatal period (among the 2-year survivors), respiratory and nutritional sequelae were recorded. Respiratory problems were frequent: 18/40 (45%) patients remained oxygen-dependent at 28 days (CDH=10/12 (83%), others=8/28 (29%); P=0.0021); two patients (CDH) remained oxygen-dependent at 2 years. Diagnosis of bronchopulmonary dysplasia was performed for 13 infants: all CDH, with the need of a tracheostomy for four infants. Nutritional and digestive problems were growth retardation (n=12), ten of whom were CDH; gastroesophageal reflux (n=11), all CDH, four of whom required surgical treatment and needed a feeding gastrostomy These respiratory and digestive sequelae were more frequent in the CDH group (P<0.01).
There was no evidence of adverse effects observed during decannulation according to the carotid reconstruction: no hemodynamic instability or change in pulmonary vasomotor tone were observed during surgery. No short-term complications such as air emboli, thromboembolic episode, or major bleeding from the site of reconstruction were recorded. Patency and flow of repaired carotid artery (n=27; two deaths during the 29 VA ECMO performed) was assessed in 20 infants at 1 year of age using Doppler ultrasonography. Out of 20 carotid reconstructions, 19 were considered technically successful: ten children had patent carotid arteries with normal cephalad flow across the anastomotic site and nine infants had an inferior to 50% stenosis. One carotid reconstruction failure was recorded with a more than 50% carotid stenosis.
| 4. Discussion |
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Although a few authors reported series with a high level of OI [7,10], in our study OI was indeed higher (61±8) than the OI calculated in the majority of the other studies (calculated means from 36 to 49) [4,11,12]. These data underline the seriousness of our treated group. Similar survival rates were found in the ELSO experience (1997) [3] concerning more than 12 000 neonates treated by ECMO with a survival rate of 81% (including both VA and VV ECMO): VA ECMO mortality rates for MAS were 94%, mortality rates for sepsis were 77%, mortality rates for others (excluding CDH) were 81%, whereas mortality rates for CDH were 58%; regarding ECMO VV only, mortality rates were 90%. Experience reported in 1996 by the UK Collaborative Randomized Trial of Neonatal ECMO [7] compared two similar groups of newborn infants with severe respiratory failure. Infants were randomized to conventional management or to ECMO treatment, and were followed up to 1 year. Death rates differed between the two groups; 30 of 93 infants (32%) allocated ECMO died compared with 54 of 92 (59%) which were allocated to conventional care (relative risk=0.55, (P=0.0005)). These data showed a clear advantage with ECMO leading to an early halt to recruitment to the trial, and confirmed the significant beneficial effect of ECMO for the management of severe respiratory failure. However, the mortality rate of the CDH patients in this trial was 17/17 deaths (100%) with conventional management and 14/18 deaths (77%) with ECMO (P=0.10, Fisher's exact test). This high mortality rate emphasizes the severity of the respiratory failure in the CDH group.
Our ECMO experience began in October 1991 using VV ECMO with a single cannula with alternating inflow and outflow. The VV ECMO technique prevents carotid artery cannulation. However, in our experience alternative flow led to technical complications (all the technical complications (n=5) were observed during VV ECMO). Furthermore, whereas VV ECMO improves oxygenation, it does not support hemodynamic failure. Currently, the use of exogenous surfactant, inhaled nitric oxide (iNO), and high-frequency oscillatory ventilation (HFOV) in the management of respiratory hypoxemia decreases the indication of ECMO. Failure of this management with persistent hypoxemia leads to the selection of severe respiratory insufficiency associated with hemodynamic instability, mainly right ventricular failure. Introduction of VA ECMO, in our experience (from November 1993 onwards) allows us to manage right ventricular failure and to provide left ventricular support. This quality of VA ECMO appeared as especially interesting in the CDH group associated with impaired cardiac function.
Usually at the time of decannulation, carotids were ligated [13]. Different reports have demonstrated that the anatomical and physiological mechanisms that control cerebral circulation appeared to be sufficient to compensate for loss of a major inflow vessel to the brain [1416]. However, permanent ligation of the common carotid artery may have short- and long-term consequences and remains a major objection to the use of VA ECMO [17,18]. Long-term effects of definitive carotid ligation on the incidence and pattern of occlusive vascular disease in later life are unknown [16]. In each case of VA ECMO, we decided to perform carotid reconstruction. In order to accomplish reconstruction, the cannulation procedure had to be minimally traumatic. Excision of the edges of the arteriotomy site is recommended at the time of arterial repair [16]. Our follow-up demonstrates successful carotid reconstruction in 19 patients either with normal flow or with <50% stenosis. Nine infants had <50% stenosis. Desai [19] speculates that carotid reconstruction may have augmented the cerebral circulation during the first 5 years of life after neonatal ECMO. He demonstrates that stenosis after reconstruction may improve over time, but long-term risks and benefits remain unknown. In order to avoid cerebral emboli, and with a lack of any proven data, we chose to keep all the babies on aspirin with antiaggregant dosage (5 mg/kg per day).
In this prospective study, comparison of VV ECMO with VA ECMO is not appropriate, because of the historical composition of the two groups: two different management policies were successively introduced in our experience with an improvement of the technique and the improvement in conventional management. Comparison of the data concerning the CDH group with the other infants allows us to distinguish a population with a different short-term and long-term prognosis. These prospective studies expose the difficulty of long-term follow-up (only 36 infants of the 40 survivors had a complete and available follow-up at 2 years). Our experience began in 1991, with the introduction of VA ECMO (with systematic arterial reconstruction) by the end of 1993. We still have an insufficient retrospective in order to conclude neurological development delay for the milestones of long-term development of arterial reconstruction. Is it necessary to prescribe aspirin for infants and if so, for what duration? Current thinking suggests that a small dosage leads to a small incidence of morbidity.
ECMO improves survival of newborn infants with refractory hypoxemia. Higher survival rates and lower mortality were found in neonatal sepsis and meconium aspiration syndrome than in congenital diaphragmatic hernia. Current indication of ECMO treatment is rare with the development of conventional management including early admittance and associated techniques such as exogenous surfactant, inhaled nitric oxide, and high-frequency ventilation. However, ECMO still remains indicated for patients with failure of the maximal conventional treatment.
| Footnotes |
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| References |
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