Neonatal congenital diaphragmatic hernia and extracorporeal membrane oxygenation Neil N. Finer, MD; Anne J. Tierney, MB; Robert Hallgren, MD; Allen Hayashi, MD; Abraham Peliowski, MD; Philip C. Etches, MB Objective: To describe the outcome of infants with congenital diaphragmatic hernia (CDH) presenting early who were referred for possible extracorporeal membrane oxygenation (ECMO). Design: Retrospective descriptive study. Setting: Neonatal Intensive Care Unit of the Royal Alexandra Hospital, Edmonton. Patients: Fifteen infants referred to our program since its introduction, in February 1989; 13 received ECMO. The criterion for ECMO was the presence of an oxygen index of more than 40 on three occasions within 2 hours. Intervention: ECMO was performed by means of cannulation of the right carotid artery and jugular vein for 1 1 1.0 hours on average. Results: In 5 of the 13 infants who underwent ECMO the procedure was performed after surgical repair; all were successfully weaned off ECMO, and the cannula was removed without incident. In the remaining eight ECMO was started before surgical repair; of the six who received it during repair four ultimately survived. None of the previously described predictors of outcome for CDH, including diagnosis before 25 weeks' gestation (in six cases), were useful in determining the survival of the patients. Bleeding was the most common complication and cause of death. Conclusion: ECMO is associated with survival in infants with CDH who fail to respond to conventional therapy and who have a poor prognosis according to previously established criteria.
Objectif: Decrire l'issue chez des nouveau-nes atteints d'une hernie diaphragmatique congenitale (HDC) d'evolution precoce diriges pour une possibilite d'oxygenation extracorporelle (ECMO). Conception: Etude retrospective et descriptive. Contexte: Unite neonatale des soins intensifs de l'h6pital Royal Alexandra de Edmonton. Patients: Quinze nouveau-nes orientes vers notre programme depuis sa fondation en fevrier 1989; on a administre l'ECMO a 13 nouveau-nes. Le critere pour l'ECMO etait la presence d'un indice d'oxygene de plus de 40 a trois reprises en 2 heures. Intervention: L'ECMO a ete pratiquee au moyen d'une canulation de l'artere carotide et de la veine jugulaire droites pendant 111,0 heures en moyenne. Resultats: Chez 5 des 13 nouveau-nes qui ont subi l'ECMO, on a pratique l'intervention apres une refection chirurgicale; on a reussi a sevrer tous les nouveau-nes de l'ECMO, et on a enleve la canule sans incident. Chez les huit autres nouveau-nes, l'ECMO a debute avant la refection chirurgicale; des six nouveau-nes a qui l'on a administre l'ECMO pendant la refection, quatre ont survecu par la suite. Aucune des variables predictives de l'issue de la HDC decrites precedemment, y compris le diagnostic avant 25 semaines de gestation (dans six cas), n'a ete utile pour determiner la survie des patients. L'hemorragie etait la complication et la cause de deces la plus frequente. Conclusion: L'ECMO est reliee a la survie chez les nouveau-nes atteints de HDC qui ne reagissent pas au traitement classique et dont le pronostic est mauvais selon les criteres etablis precedemment. From the Department of Newborn Medicine, Royal Alexandra Hospital, Edmonton, Alta.
Reprint requests to: Dr. Neil N. Finer, Department ofNewborn Medicine, RoyalAlexandra Hospital, 10240 Kingsway Ave. NW, Edmonton, AB T5H 3V9 -
For prescribing information see page 629
CAN MED ASSOC J 1992; 146 (4)
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ongenital diaphragmatic hernia (CDH) ocin between 1 in 2000 and 1 in 5000 deliveries, about one-third of these ending in stillbirth.' Newborns who present with a posterolateral defect and respiratory distress within hours after birth have been found to have a death rate of 50% or greater.2 Early surgical repair has been associated with decreased lung compliance,3 and a number of centres have now reported encouraging results after the use of delayed surgery.4-6 Others have demonstrated that despite delayed surgery the death rate remains high.7 Bohn and associates2,8 developed indices to predict the outcome of infants presenting with CDH: the preoperative or postoperative partial pressure of carbon dioxide in arterial blood (Paco2) and the ventilatory index, which is the multiple of the mean airway pressure (MAP) and the respiratory rate. They claimed that infants with a preoperative or postoperative Paco2 of more than 40 mm Hg and a ventilatory index of more than 1000 had a death rate of 100%. Others have defined infants with CDH as responders or nonresponders to treatment on the basis of their ability to achieve a partial pressure of oxygen of more than 100 mm Hg in arterial blood obtained from a site distal to the ductus arteriosus, nonresponders reportedly having a death rate of 92%.9 Given the high rate of death among infants with CDH who present with early symptoms, extracorporeal membrane oxygenation (ECMO) has been used in an attempt to save such babies before or after surgery.'0 A previous review of the experience recorded in the ECMO Registry, Ann Arbor, Mich., revealed a survival rate of 58% among infants who met ECMO criteria after surgical repair of the hernia.1" More recent studies have reported even higher survival rates among infants who did not respond to conventional ventilation and were treated with ECMO.'2-"4 The first reported use of ECMO to treat CDH before surgical repair was by Weber and collaborators.'4 More recently, this group described two of three infants in whom ECMO was successful before surgery'5 and four of six infants who survived surgery while receiving ECMO.'6 These authors demonstrated that the previously described predictive indices and the presence or absence of a "honeymoon" period (a period lasting usually 12 hours or more after surgery, during which the infant remains stable with adequate gas exchange) were unreliable indicators of outcome. Given the previous suggestions that ECMO is associated with improved survival in near-term infants with severe hypoxemia unresponsive to conventional therapy'7"8 as well as the improved outcome of infants with CDH who have received ECMO" -16 we began the first neonatal ECMO proC
curs
502
CAN MED ASSOC J 1992; 146 (4)
gram
in Canada in February 1989. In this article
we
report our experience in treating 16 cases of severe
early-onset CDH since the introduction of the
pro-
gram.
Methods Before providing a clinical ECMO service we indicated to the level III neonatal intensive care units (NICUs) of Alberta, Saskatchewan and Manitoba that we would be developing an ECMO program and provided these units with ECMO eligibility criteria (Table 1). For infants with CDH we recommended that surgery be delayed until the infant's condition was stable and there was evidence of adequate oxygenation and ventilation and that telephone communication with our centre be considered for those who became hypoxemic (Pao2 of less than 50 mm Hg). All NICUs indicated that they would cooperate and consider referral when appropriate.
Infants were thought to be candidates for ECMO if they had intractable hypoxemia during comprehensive conventional management, which included the use of a fractional inspired oxygen concentration of 1 with an MAP of 18 cm H20 or more, resulting in a partial pressure of oxygen of less than 50 mm Hg. In a retrospective review of cases of persistent fetal circulation, meconium aspiration, CDH and other diagnoses in infants of 35 weeks' gestational age or more in our region, we determined that an oxygen index (MAP X 100 . Pao2)2' of 40 or more on three occasions, at least 30 minutes apart over a 2-hour interval, predicted a death rate of at least 70%. In addition, we found that all infants with CDH who had an oxygen index of more than 40 died. These infants usually also had a ventilatory index of more than 1200,2,8 which was associated with a predicted death rate of at least 90%. For each infant attempts were made to optimize mechanical ventilation (including trials of high-frequency oscillation), to improve the systemic blood pressure with the use of volume infusion and vasopressors, and to improve oxygenation and avoid the
Table 1: Eligibility criteria for extracorporeal membrane oxygenation (ECMO) in infants whih congenital diaphag ic hernia (CDH) Birth weight of more than 2O0(.g e of 35w.*isordo v Nom app r of head on ultrasonography image (inrvn a hemgrhp below ade 1I)1' No congental hear disease or oth leta anomaly Unresponse to comr iv nmedical treatment No evidence of severe brain iniu (i.e., stge 11l hypoxic ischenic e -halopathy meets oxygen irndex criteria Parental consent given LE 15 FEVRIER 1992
need for ECMO through the provision of adequate sedation and muscle relaxation. In addition, after the infant's condition was stabilized through adequate oxygenation, surgery to correct the CDH was delayed for as long as the infant's condition continued to improve and for at least 18 hours.3-6 For our first six infants who qualified for ECMO before repair, surgery was considered 24 to 48 hours after stabilization with the use of ECMO. In our two most recent cases (nos. 10 and 1 1) surgery was delayed until improvements in the infant's condition allowed us to wean the infant from ECMO (to an ECMO flow of less than 30 mL/kg per minute), at which time the diaphragmatic hernia was repaired and the cannula subsequently removed.
and included the use of an intra-arterial catheter for continuous monitoring of the blood pressure and heart rate, intermittent monitoring of the blood gas values (of the circuit and the baby) and continuous pulse oximetry. A no. 8 to 10 French thin-walled cannula was used for the artery and a no. 10 to 14 French cannula for the vein (Elecath, Eledro Catheter Corp., Rahway, NJ). The ECMO flow was begun at 50 mL and was gradually increased by 10 mL/min until it reached 100 to 120 mL/kg per minute. As with the cannulation, the surgical repair was performed on the infant's overhead warmer in the NICU with the use of electrocautery. Just before the hernia was repaired in infants receiving ECMO, the activated clotting time was lowered to 190 to 210 seconds by reducing the heparin infusion rate, and the platelet ECMO count was kept at more than 120 x 1 09/L. A general anesthetic was given intravenously in The mixed venous oxygen level (Pvo2) was the NICU with the infant lying on an overhead maintained at a saturation rate of 68% to 75%. The radiant warmer. A cannula was inserted into the infants were weaned from ECMO when their PvO2 right internal jugular vein and carotid artery. The increased. When the ECMO flow was reduced to 30 procedures for circuit preparation and cannulation mL/kg per minute a trial off ECMO was performed, were similar to those previously described.22 during which heparin was infused into the infant at The venous oxygen tension was continuously 40% of the previous rate and the arterial blood gas measured in the venous line proximal to the venous levels were monitored every 5 to 15 minutes. If the reservoir. All infants had an arterial line in either the infant tolerated at least 1 hour off ECMO and had umbilical artery or a peripheral artery during adequate blood gas values the cannulas were reECMO. Most of the intravenous infusions and all of moved. For our first four surviving infants the jugular the pressor infusions and heparin were administered vein and the carotid artery were permanently ligated through the ECMO circuit. Heparin was given just before cannulation; the at decannulation. However, given early reports indiactivated clotting time was maintained between 210 cating that surgical repair of the carotid artery was and 230 seconds with the use of continuous heparin feasible23'24 and associated with adequate carotid and infusion and the administration of boluses as re- cerebral blood flow24 we began to repair the vein and quired. The platelet count was maintained at more artery when possible after decannulation. In most than 100 X 109/L by means of platelet transfusions, infants the portion of the artery between the proxiand the plasma fibrinogen level was maintained at mal and distal ligatures, including the site of the more than 1.7 g/L by means of cryoprecipitate original arteriotomy, was excised and an end-to-end vascular anastomosis performed; in the remaining transfusions. The priming fluid for the circuit was about 400 infants the arteriotomy site was repaired. The infant mL of type 0, Rh-negative, cytomegalovirus-nega- was kept paralysed for the next 24 hours, and the tive irradiated blood, when available. Pall filters heparin infusion was tapered off over the next 6 (Pall Biomedical Inc., East Hills, NY) were used to hours. remove leukocytes and to reduce the risk of cytomegalovirus transmission when the blood products Results were being administered. We treated 13 infants who were referred to our The cannulation procedure was always performed on the infant's overhead warmer in the unit from established level III NICUs and 3 (cases 2, NICU. All nursing was done with the infants on a 3 and 15) who were born in our institution (Table 2). continuous weighing scale (model 4004, Scale-Tron- The latter three infants all had an antenatal diagnoic, Wheaton, Ill.). This scale is adapted for obtaining sis of CDH, and the mother had been referred to our roentgenograms so that the infant does not have to hospital for ongoing obstetric and perinatal care. All of the 13 infants who were born outside our be moved. The infants were anesthetized with fentafor used hospital were referred because of hypoxemia that nyl (initial dose 20 gg/kg); pancuronium was would not respond to mechanical ventilation and was muscle relaxation. Intraoperative monitoring ECMO other supportive therapy. As can be seen from Table identical to the routine monitoring during FEBRUARY 15, 1992
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2 these infants were markedly hypoxemic, and in- None of the infants had a significant wound infecdeed their condition usually deteriorated during tion. No infant was moved after being placed on the transportation. overhead radiant warmer for cannulation. The duration of ECMO was 111.0 hours on All surviving infants were discharged home average. Five infants (cases 4, 5, 6, 7 and 14) had from hospital. Those who were followed up between surgical repair of their hernia before ECMO. Of the 6 months and 2 years later were found to be remaining eight cases in which ECMO was started developmentally normal and to have no problems before surgical repair the repair was done during apart from mild hypotonia. Only one child was ECMO in six; four of these infants survived. Four of assessed at 2 years' follow-up; the Bayley score the infants in whom ECMO was started before (which indicates infant development)25 was normal, surgical repair died; one was born in our hospital and there was no evidence of handicap. (case 15) and the cannula inserted at 26 hours of age. During the time covered by this report we were In three cases (cases 1, 2 and 3) the infant's aware of four other infants with CDH and intractacondition was stabilized and surgery performed at 18 ble hypoxemia who met the ECMO criteria. One to 48 hours after admission; all survived without the infant died without a request for transfer, one died need for ECMO. before completion of transfer, and the third was Six infants had their CDH diagnosed before 25 judged not to be a candidate because of birth before weeks' gestation: in case 4 at 20 weeks' gestation, in term (at 34 weeks' gestation); this infant died within cases 1, 2 and 13 at 17 weeks, in case 15 at 15 weeks 12 hours after the request for transfer to our unit. and in case 16 at about 14 weeks. None of the six The fourth infant had an unrepaired CDH on the left pregnancies was noted to be complicated by poly- side and met all of our ECMO criteria. However, we hydramnios before 24 weeks' gestation, although in were unable to accept this referral because two other two cases there was evidence of increased fluid in the infants were already receiving ECMO at the time; we later stages of pregnancy. Three of the six infants arranged for this infant to receive ECMO in the survived, two without the need for ECMO (cases 2 United States. The CDH was repaired after the and 3). infant's condition was stabilized; however, the conNo difficulty was noted in performing the cor- dition subsequently deteriorated, and ECMO was rective surgery in the NICU. The most common required for 9 days, after which the cannula was cause of a fall in the Pvo2 during surgery was related successfully removed. to traction or pressure in the abdomen; the resultant To our knowledge in the NICUs that agreed to impaired venous return caused the pump to inter- consider transporting eligible infants with CDH to mittently stop. The release of such traction was our institution there have been no survivors among required occasionally, and in all cases the PvO2 those who met all our criteria, including the oxygen saturation could be maintained at more than 75%. indices, and did not receive ECMO.
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Deaths One child (case 12) underwent surgical repair uneventfully while receiving ECMO, and the cannula was removed after a well-tolerated trial off ECMO. The infant remained dependent on mechanical ventilation in 40% oxygen for the next 4 days; the condition progressively deteriorated, hypoxemia unresponsive to conventional and high-frequency ventilation developed, and the infant died. Recannulation was not attempted. In case 13 the infant was the most immature (born at 35 weeks' gestation); CDH had been diagnosed at 17 weeks' gestation. Cannulation was required 8 hours after birth; signs of an obstructed superior vena cava and poor ECMO flow developed. A smaller catheter was inserted, and on day 3 there was evidence of a right temporoparietal echodense lesion, which on day 5 was diagnosed as an expanding intracranial hematoma with a midline shift. The infant was rapidly weaned off ECMO and required support with the use of a high-frequency oscillator. The cannula was removed after 152 hours of ECMO. Surgical repair of the hernia during ECMO was not attempted because there had been no evidence of weaning. The infant died of intractable hypoxemia about 36 hours after decannulation. Autopsy findings confirmed a right-sided subdural and intracranial hematoma as well as lung hypoplasia. There was only one death among the infants treated with ECMO after surgical repair (case 14). This infant had undergone echocardiography in the referring NICU, and the findings were interpreted as being normal. She required massive inotropic support for hypotension after the repair; this included the administration of dopamine (20 ,g/kg per minute) and epinephrine (up to 60 ,g/kg per minute) to maintain a mean arterial blood pressure of more than 40 mm Hg before cannulation. Echocardiography repeated daily during ECMO was felt to yield normal results until day 3, when the ECMO flows were reduced: the right side of the heart was found to be smaller than normal. The diagnosis of pulmonary atresia and hypoplasia of the right ventricle, tricuspid valve and pulmonary artery was confirmed; the infant was weaned and the cannula removed after 157 hours of bypass without the need for vasopressor support. After further evaluation it was determined that there was no acceptable surgical option, and the infant died after withdrawal of life support, 9 days after decannulation. In case 15 an infant had CDH on the left side diagnosed at 15 weeks' gestation. He was delivered in our institution after spontaneous labour at more than 38 weeks' gestation. Mechanical ventilation with 100% oxygen was started immediately in the case room, and the infant was sedated and paralysed. FEBRUARY 15, 1992
Echocardiography and ultrasonography of the head gave normal findings, and ECMO was started at 26 hours of age. Immediately after cannulation ultrasonography of the head showed a grade II intraventricular hemorrhage. We therefore elected to repair the infant's diaphragm early, at 51 hours of age, with a large synthetic patch. Postoperatively there was excessive bleeding (100 to 150 mL/h) from a drain in the left side of the chest. Exploratory thoracotomy revealed that an intercostal artery had been lacerated by one of the sutures used to place the patch. Ultrasonography showed an extension of the intraventricular hemorrhage.. Shortly thereafter the infant suddenly became hypotensive because of arterial decannulation when the catheter eroded through the carotid artery; he died despite vigorous resuscitation attempts. Permission for autopsy was
denied. In case 16 the infant was transferred almost immediately after birth and the cannula inserted at about 51/2 hours of age. There was evidence of coagulopathy with pulmonary hemorrhage and a right pneumothorax. Myocardial contractility was poor; bleeding from the chest drain continued, as did the coagulopathy. After 5 days of ECMO there was evidence of progressive thrombocytopenia and failure to wean; sepsis was suspected. Vancomycin and cefotaxime were substituted for amikacin and ampicillin. A course of dexamethasone was tried later, but after 8 days the infant's condition had not improved. On day 9 there was a sudden loss of arterial circulation to the left arm and head. An ultrasound image confirmed lack of pulsation to the brain, and acute aortic thrombosis or aortic dissection was suspected. The cannulas were removed after 215 hours of ECMO, and the infant died soon afterward despite aggressive support. Postmortem findings included an absent left diaphragm, severe pulmonary hypoplasia and an aortic thrombus near the site of the carotid catheter tip. Fungal elements were detected in the clot; however, there was no cultural confirmation of the type of fungus.
Discussion Hemorrhagic complications related to ECMO have been reported by virtually all ECMO centres and can be successfully managed with heightened awareness and a rapid response."' The extensive use of cautery and tissue glue markedly reduces bleeding, and none of our infants with CDH has had to undergo re-exploration of the neck wound because of hemorrhage. Patient 13 was our most gestationally immature infant and the only one who had significant intracranial hemorrhage. Patient 14 would not have been CAN MED ASSOC J 1992; 146 (4)
S0S
an ECMO candidate had the correct diagnosis been made before referral. However, it is striking that this infant, who required intensive support before ECMO, was able to be weaned and supported after decannulation and had an adequate blood pressure without the need for inotropic agents. We have now treated eight infants whose condition deteriorated with severe hypoxemia before surgical repair; six subsequently underwent surgical repair during ECMO, four surviving. In addition, we have treated infants whose condition deteriorated postoperatively and others who have never had a partial pressure of oxygen of more than 100 mm Hg in arterial blood obtained distal to the ductus arteriosus, the so-called nonresponders of Vacanti and colleagues.9 Some centres provide ECMO support only to infants who have already had operative repair, most having had at least one Pao2 reading of 100 mm Hg.9"1"13'26,27 Bohn and associates2 have developed criteria to predict outcome in cases of early-onset CDH on the basis of the ventilatory index and the Paco2 2 hours before or after repair. The data for all 13 of our infants treated with ECMO predicted a death rate of 90% with the use of these criteria.2 Our results are in agreement with those of Van Meurs and coworkers,28 who showed a survival rate of 67% among infants with CDH who were in the "poor-prognosis" group.2 However, they excluded infants whose condition had to be stabilized with ECMO before surgical repair, a group that accounted for four of our five deaths. Our experience is similar to that reported by Bailey and associates,'" who demonstrated that indices to predict outcome in the absence of ECMO (e.g., blood gas values, the presence or absence of a "honeymoon" period and the presence of a Pao2 of more than 100 mm Hg) were unreliable in predicting the response to ECMO and concluded that no infant should be excluded from repair or ECMO support on the basis of these criteria. Our results are almost identical to those reported more recently by this group.29 Adzick and Harrison and their colleagues30-32 suggested that the early detection of a diaphragmatic hernia by means of ultrasonography may be associated with a poor prognosis. However, intrauterine repair appears to be an option for selected cases of prenatally diagnosed CDH.33 Our observations extend the conclusions of Bailey and associates"5 in that we had three survivors among the six infants whose CDH was diagnosed at or before 20 weeks in utero. In addition, one of these infants, whose CDH was diagnosed at 17 weeks, tolerated a primary repair without a patch; this suggests that early intrauterine diagnosis is not always associated with a severe defect. Further information is obviously required on the outcome of CDH diagnosed in early 506
CAN MED ASSOC J 1992; 146 (4)
pregnancy before fetal surgery is recommended. An increasing number of reports have described long-term survival (up to 10 years) in infants receiving ECMO; this suggests that about 60% of such infants develop normally. An additional 15% to 20% have been found to have some possible neurologic abnormality or a severe abnormality.34-38 The most recent report, by Adolph and coworkers,39 revealed that all but 1 of 57 infants had normal findings on neurologic examination, 75% showing normal development. In such a group of infants it is difficult to attribute handicap exclusively to ECMO given their unstable condition before cannulation. All of our surviving infants who have been assessed to date have shown normal neurodevelopment, and only 2 of the other 40 survivors who received ECMO for other conditions had evidence of a severe neurologic abnormality. We repaired the carotid artery and jugular vein when possible in our last 15 survivors, and in Doppler flow studies before discharge we have demonstrated excellent prograde flow in all of the repaired arteries. The veins that were repaired have usually not remained patent. We have re-evaluated the anastomotic site in three of our survivors at 6 months of age and found excellent flow, with no evidence of stenosis in the carotid artery. The absence of acute complications associated with such repair is consistent with the experience reported by others.40-42 We believe that repair of the carotid artery will re-establish normal intracranial flow patterns and reduce the long-term risks associated with ECMO. We feel that the best management of infants with CDH lies in early prenatal diagnosis and transfer so that delivery can occur at a tertiary care centre. Infants with severe CDH diagnosed very early in pregnancy can survive without ECMO; this suggests that appropriate resuscitation and stabilization prevent the ensuing pulmonary hypertension and associated hypoxemia. Since our program was begun, to our knowledge there have been no surviving infants in our catchment area who met all the ECMO criteria but did not receive this therapy. In addition, 12 of our 13 infants who received ECMO were initially managed in well-established academic tertiary care NICUs, and the decision to transfer was made by their attending neonatologist. None was able to be managed without ECMO. This indicates either our failure to provide optimal care or, more likely, the presence of intractable pulmonary hypertension and right-to-left shunting (as detected in all of our infants), despite comprehensive conventional treatment. ECMO is a technique that, like many other advances, was introduced and widely accepted into practice before adequately controlled randomized LE 15 FEVRIER 1992
trials could be performed to demonstrate unequivocally its efficacy. Subsequently, two controlled trials have shown the superiority of ECMO over conventional therapy,'7"'8 but these studies were criticized for their methods and the small control sample. Other investigators43 have challenged the validity of indices predictive of death, but even they have subsequently transferred infants with CDH to receive ECMO.44 Given the high rate of death among infants with CDH unresponsive to conventional therapy it is unlikely that any ECMO centre would agree to a trial in which such infants would be allowed to die without ECMO. In the absence of further definitive clinical trials ECMO still appears to offer the best hope of survival to infants with CDH and intractable hypoxemia despite maximum conventional therapy. Although imperfect, criteria established to predict death in infants with CDH have been widely adopted,2'8'9 and the use of ECMO has produced survivors who had been predicted to die according to these criteria. One way to assess the role of ECMO in CDH might be to randomly assign infants in a non-ECMO centre who meet ECMO criteria either to receive continued conventional therapy or to be transferred to an ECMO centre. Although not blinded, such a study would be biased against ECMO, because infants randomly assigned to receive ECMO would have to be transferred while critically ill. We thank our nurses, respiratory therapists, Wendy Ainsworth (ECMO coordinator), ECMO specialists, Drs. Raf Ocejo, Doug Davey, Rick Johnston, Gordon Lees and Keith Barrington, and the departments of Diagnostic Imaging and Pathology for their contribution to the care of the infants described in this article. We also thank Liz Borgel-Kish for preparing the manuscript.
8.
9.
10.
11.
12. 13. 14. 15.
16. 17.
18.
19.
20. 21.
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666-671 Sakai H, Tamura M, Hosokawa Y et al: Effect of surgical repair on respiratory mechanics in congenital diaphragmatic hernia. JPediatr 1987; 111: 432-438 Miyasaka K, Sankawa H, Nakajo T et al: Congenital diaphragmatic hernia: Is emergency radical surgery really necessary? Jpn JPediatr Surg 1984; 16: 1417-1422 Cartlidge PHT, Mann NP, Kapila L: Preoperative stabilisation in congenital diaphragmatic hernia. Arch Dis Child 1986; 61: 1226-1228 Tibboel D, Bos AP, Pattenier JW et al: Pre-operative stabilisation with delayed repair in congenital diaphragmatic hernia. Z Kinderchir 1989; 44: 139-143 Shanbhogue LKR, Tam PKH, Ninan G et al: Preoperative
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stabilisation in congenital diaphragmatic hernia. Arch Dis Child 1990; 65: 1043-1044 Bohn D, Tamura M, Perrin D et al: Ventilatory predictors of pulmonary hypoplasia in congenital diaphragmatic hernia, confirmed by morphologic assessment. J Pediatr 1987; 111: 423-431 Vacanti JP, O'Rourke P, Lillehei CR et al: The cardiopulmonary consequences of high-risk congenital diaphragmatic hernia. Pediatr Surg Int 1988; 3: 1-5 Hardesty RL, Griffith BP, Debski RF et al: Extracorporeal membrane oxygenation: successful treatment of persistent fetal circulation following repair of congenital diaphragmatic hernia. J Thorac Cardiovasc Surg 1981; 81: 556-563 Langham MR, Krummel TM, Bartlett RH et al: Mortality with extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernia in 93 infants. J Pediatr Surg 1987; 22: 1150-1154 Heiss K, Manning P, Oldham KT et al: Reversal of mortality for congenital diaphragmatic hernia with ECMO. Ann Surg 1989; 209: 225-230 Heaton JFG, Redmond CR, Graves ED et al: Congenital diaphragmatic hernia: improving survival with extracorporeal membrane oxygenation. Pediatr Surg Int 1988; 3: 6- 10 Weber TR, Connors RH, Pennington G et al: Neonatal diaphragmatic hernia: an improving outlook with extracorporeal membrane oxygenation. Arch Surg 1987; 122: 615-618 Bailey PV, Connors RH, Tracy TF Jr et al: A critical analysis of extracorporeal membrane oxygenation for congenital diaphragmatic hernia. Surgery 1989; 106: 611-616 Connors RH, Tracy T Jr, Bailey PV et al: Congenital diaphragmatic hernia repair on ECMO. J Pediatr Surg 1990; 25: 1043-1047 Bartlett RH, Roloff DW, Cornell RG et al: Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics 1985; 76: 479-487 O'Rourke PP, Crone RK, Vacanti JP et al: Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study. Pediatrics 1989; 84: 957-963 Papile LA, Burnstein J, Burnstein R et al: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 grams. JPediatr 1978; 92: 529-534 Robertson CM, Finer NN: Term infants with hypoxic ischemic encephalopathy: outcome at 3.5 years. Dev Med Child Neurol 1985; 27: 473-484 Bartlett RH, Toomasian J, Roloff D et al: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure: 100 cases. Ann Surg 1986; 204: 236-245 Short BL, Pearson GD: Neonatal extracorporeal membrane oxygenation: a review. Int Care Med 1986; 1: 47 Spector ML, Wiznitzer M, Walsh-Sukys MC et al: Carotid reconstruction following ECMO. Presented at the Extracorporeal Life Support Organization Charter Meeting, Oct 1-3, 1989, Ann Arbor, Mich Lewin JS, Masary TJ, Modic MT et al: Extracorporeal membrane oxygenation in infants: angiographic and parenchymal evaluation of the brain with MR imaging. Radiology 1989; 173: 361-365 Bayley N: Bayley Scales of Infant Development, Psychological Corp, New York, 1969 Langham MR, Krummel TM, Greenfield LJ et al: Extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernias. Ann Thorac Surg 1987; 44: 247-252 Stolar C, Dillon P, Reyes C: Selective use of extracorporeal membrane oxygenation in the management of congenital diaphragmatic hernia. J Pediatr Surg 1988; 23: 207-21 1 Van Meurs KP, Newman KD, Anderson KD et al: Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. J Pediatr 1990; 1 17: CAN MED ASSOC J 1992; 146 (4)
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954-960 29. Weber TR, Connors RH, Tracy TF Jr et al: Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns. Ann Thorac Surg 1990; 50: 720-723 30. Adzick NS, Harrison MR, Glick PL et al: Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases. J Pediatr Surg 1985; 20: 357-361 31. Adzick NS, Vacanti JP, Lillehei CW et al: Fetal diaphragmatic hernia: ultrasound diagnosis and clinical outcome in 38 cases. JPediatrSurg 1989; 24: 654-658 32. Harrison MR, Adzick NS, Longaker MT et al: Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax. N Engl J Med 1990; 322: 1582-1584 33. Harrison MR, Langer JC, Adzick NS et al: Correction of congenital diaphragmatic hernia in utero: 5. Initial clinical experience. J Pediatr Surg 1990; 25: 47-57 34. Andrews AF, Nixon CA, Cilley RE et al: One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation. Pediatrics 1986; 78: 125-131 35. Taylor GA, Glass P, Fitz CR et al: Neurologic status in infants treated with extracorporeal membrane oxygenation: correlation of imaging findings with developmental outcome. Radiology 1987; 165: 679-682 36. Taylor GA, Fitz CR, Glass P et al: CT of cerebrovascular
Conferences
continuedfrom page 462 June 10-13, 1992: ISPRAD VI - 6th International Symposium on the Planning of Radiological Departments (in conjunction with the International Meeting on Hospital Economy [IMHE]) Grieg Hall, Bergen, Norway Official language: English IMHE/ISPRAD VI, c/o Lilly Hausberg, PLUSreiser, PO Box 946, N-5001 Bergen, Norway; fax 011-47-5-47590-20-91 June 17-19, 1992: 6th Annual Forensic Conference - The Roots of Violence: Implications for Interventions with Adults (sponsored by the Mental Health Centre,
Penetanguishene) Highland Inn, Midland, Ont. Margaret Milligan, conference coordinator, Mental Health Centre, PO Box 5000, Penetanguishene, ON LOK 1 PO; (705) 549-3181, ext. 2204 June 17-20, 1992: Society for Scholarly Publishing Annual Meeting
Chicago Society for Scholarly Publishing, 304-10200 W 44th Ave., Wheat Ridge, CO 80033; (303) 422-3914 June 21-24, 1992: 4th Symposium on Violence and Aggression Saskatoon, Sask.
Registration Office, Extension Division, University of Saskatchewan, Saskatoon, SK S7N OWO; (306) 966-5560, fax (306) 966-5567 508
CAN MED ASSOC J 1992; 146 (4)
37.
38. 39.
40. 41. 42. 43. 44.
injury after neonatal extracorporeal membrane oxygenation: implications for neurodevelopmental outcome. AJR 1989; 153: 121-126 Hofkosh D, Clouse H, Smith-Jones J et al: Ten years of ECMO: neurodevelopmental outcome among survivors [abstr]. Pediatr Res 1990; 27: 245A Lott IT, McPherson D, Towne B et al: Long-term neurophysiologic outcome after neonatal extracorporeal membrane oxygenation. J Pediatr 1990; 116: 343-349 Adolph V, Ekelund C, Smith C et al: Developmental outcome of neonates treated with extracorporeal membrane oxygenation. J Pediatr Surg 1990; 25: 43-46 Karl TR, Iyer KS, Sano S et al: Infant ECMO cannulation technique allowing preservation of carotid and jugular vessels. Ann Thorac Surg 1990; 50: 488-489 Adolph V, Bonis S, Falterman K et al: Carotid artery repair after pediatric extracorporeal membrane oxygenation. J Pediatr Surg 1990; 25: 867-870 Crombleholme TM, Adzick S, deLorimier AA et al: Carotid artery reconstruction following extracorporeal membrane oxygenation. Am JDis Child 1990; 144: 872-874 Dworetz AR, Moya FR, Sabo B et al: Survival of infants with persistent pulmonary hypertension without extracorporeal membrane oxygenation. Pediatrics 1989; 84: 1-6 Gross I: The extracorporeal membrane oxygenation debate [C]. Pediatrics 1990; 85: 383-384
June 21-25, 1992: Canadian Association of Radiologists 55th Annual Scientific Meeting Halifax World Trade and Convention Centre Roxanne Saumur, administrative secretary, Canadian Association of Radiologists, 510- 5101 Buchan St., Montreal, PQ H4P 2R9; (514) 738-3111, fax (514) 738-5199
Du 21 au 25 juin 1992: 55e Reunion scientifique annuelle de l'Association canadienne des radiologistes Halifax World Trade and Convention Centre Roxanne Saumur, secretaire administrative, l'Association canadienne des radiologistes, 510-5101, rue Buchan, Montreal, QC H4P 2R9; (514) 738-3111, fax (514) 738-5199 Les 22 et 23 juin 1992: 6e Reunion internationale de la Societe francophone de cancerologie - Le cancer de l'uterus (col et endometre) : experience et perspectives
nouvelles Universite de Montreal Departement d'obstetrique-gynecologie, Faculte de medecine, Universite de Montreal, CP 6128, Succ. A, Montreal, QC H3C 3J7; fax (514) 876-7468 June 25-28, 1992: 27th Meeting of the Canadian Congress of Neurological Sciences Winnipeg Convention Centre Permanent Secretariat, Canadian Congress of Neurological Sciences, Ste. 810, 906-12 Ave. SW, Calgary, AB T2R 1K7; (403) 229-9544, fax (403) 229-1661
continued on page 551 LE 15 FEVRIER 1992
Objectif: Decrire l'issue chez des nouveau-nes atteints d'une hernie diaphragmatique congenitale (HDC) d'evolution precoce diriges pour une possibilite d'oxygenation extracorporelle (ECMO). Conception: Etude retrospective et descriptive. Contexte: Unite neonatale des soins intensifs de l'h6pital Royal Alexandra de Edmonton. Patients: Quinze nouveau-nes orientes vers notre programme depuis sa fondation en fevrier 1989; on a administre l'ECMO a 13 nouveau-nes. Le critere pour l'ECMO etait la presence d'un indice d'oxygene de plus de 40 a trois reprises en 2 heures. Intervention: L'ECMO a ete pratiquee au moyen d'une canulation de l'artere carotide et de la veine jugulaire droites pendant 111,0 heures en moyenne. Resultats: Chez 5 des 13 nouveau-nes qui ont subi l'ECMO, on a pratique l'intervention apres une refection chirurgicale; on a reussi a sevrer tous les nouveau-nes de l'ECMO, et on a enleve la canule sans incident. Chez les huit autres nouveau-nes, l'ECMO a debute avant la refection chirurgicale; des six nouveau-nes a qui l'on a administre l'ECMO pendant la refection, quatre ont survecu par la suite. Aucune des variables predictives de l'issue de la HDC decrites precedemment, y compris le diagnostic avant 25 semaines de gestation (dans six cas), n'a ete utile pour determiner la survie des patients. L'hemorragie etait la complication et la cause de deces la plus frequente. Conclusion: L'ECMO est reliee a la survie chez les nouveau-nes atteints de HDC qui ne reagissent pas au traitement classique et dont le pronostic est mauvais selon les criteres etablis precedemment. From the Department of Newborn Medicine, Royal Alexandra Hospital, Edmonton, Alta.
Reprint requests to: Dr. Neil N. Finer, Department ofNewborn Medicine, RoyalAlexandra Hospital, 10240 Kingsway Ave. NW, Edmonton, AB T5H 3V9 -
For prescribing information see page 629
CAN MED ASSOC J 1992; 146 (4)
501
ongenital diaphragmatic hernia (CDH) ocin between 1 in 2000 and 1 in 5000 deliveries, about one-third of these ending in stillbirth.' Newborns who present with a posterolateral defect and respiratory distress within hours after birth have been found to have a death rate of 50% or greater.2 Early surgical repair has been associated with decreased lung compliance,3 and a number of centres have now reported encouraging results after the use of delayed surgery.4-6 Others have demonstrated that despite delayed surgery the death rate remains high.7 Bohn and associates2,8 developed indices to predict the outcome of infants presenting with CDH: the preoperative or postoperative partial pressure of carbon dioxide in arterial blood (Paco2) and the ventilatory index, which is the multiple of the mean airway pressure (MAP) and the respiratory rate. They claimed that infants with a preoperative or postoperative Paco2 of more than 40 mm Hg and a ventilatory index of more than 1000 had a death rate of 100%. Others have defined infants with CDH as responders or nonresponders to treatment on the basis of their ability to achieve a partial pressure of oxygen of more than 100 mm Hg in arterial blood obtained from a site distal to the ductus arteriosus, nonresponders reportedly having a death rate of 92%.9 Given the high rate of death among infants with CDH who present with early symptoms, extracorporeal membrane oxygenation (ECMO) has been used in an attempt to save such babies before or after surgery.'0 A previous review of the experience recorded in the ECMO Registry, Ann Arbor, Mich., revealed a survival rate of 58% among infants who met ECMO criteria after surgical repair of the hernia.1" More recent studies have reported even higher survival rates among infants who did not respond to conventional ventilation and were treated with ECMO.'2-"4 The first reported use of ECMO to treat CDH before surgical repair was by Weber and collaborators.'4 More recently, this group described two of three infants in whom ECMO was successful before surgery'5 and four of six infants who survived surgery while receiving ECMO.'6 These authors demonstrated that the previously described predictive indices and the presence or absence of a "honeymoon" period (a period lasting usually 12 hours or more after surgery, during which the infant remains stable with adequate gas exchange) were unreliable indicators of outcome. Given the previous suggestions that ECMO is associated with improved survival in near-term infants with severe hypoxemia unresponsive to conventional therapy'7"8 as well as the improved outcome of infants with CDH who have received ECMO" -16 we began the first neonatal ECMO proC
curs
502
CAN MED ASSOC J 1992; 146 (4)
gram
in Canada in February 1989. In this article
we
report our experience in treating 16 cases of severe
early-onset CDH since the introduction of the
pro-
gram.
Methods Before providing a clinical ECMO service we indicated to the level III neonatal intensive care units (NICUs) of Alberta, Saskatchewan and Manitoba that we would be developing an ECMO program and provided these units with ECMO eligibility criteria (Table 1). For infants with CDH we recommended that surgery be delayed until the infant's condition was stable and there was evidence of adequate oxygenation and ventilation and that telephone communication with our centre be considered for those who became hypoxemic (Pao2 of less than 50 mm Hg). All NICUs indicated that they would cooperate and consider referral when appropriate.
Infants were thought to be candidates for ECMO if they had intractable hypoxemia during comprehensive conventional management, which included the use of a fractional inspired oxygen concentration of 1 with an MAP of 18 cm H20 or more, resulting in a partial pressure of oxygen of less than 50 mm Hg. In a retrospective review of cases of persistent fetal circulation, meconium aspiration, CDH and other diagnoses in infants of 35 weeks' gestational age or more in our region, we determined that an oxygen index (MAP X 100 . Pao2)2' of 40 or more on three occasions, at least 30 minutes apart over a 2-hour interval, predicted a death rate of at least 70%. In addition, we found that all infants with CDH who had an oxygen index of more than 40 died. These infants usually also had a ventilatory index of more than 1200,2,8 which was associated with a predicted death rate of at least 90%. For each infant attempts were made to optimize mechanical ventilation (including trials of high-frequency oscillation), to improve the systemic blood pressure with the use of volume infusion and vasopressors, and to improve oxygenation and avoid the
Table 1: Eligibility criteria for extracorporeal membrane oxygenation (ECMO) in infants whih congenital diaphag ic hernia (CDH) Birth weight of more than 2O0(.g e of 35w.*isordo v Nom app r of head on ultrasonography image (inrvn a hemgrhp below ade 1I)1' No congental hear disease or oth leta anomaly Unresponse to comr iv nmedical treatment No evidence of severe brain iniu (i.e., stge 11l hypoxic ischenic e -halopathy meets oxygen irndex criteria Parental consent given LE 15 FEVRIER 1992
need for ECMO through the provision of adequate sedation and muscle relaxation. In addition, after the infant's condition was stabilized through adequate oxygenation, surgery to correct the CDH was delayed for as long as the infant's condition continued to improve and for at least 18 hours.3-6 For our first six infants who qualified for ECMO before repair, surgery was considered 24 to 48 hours after stabilization with the use of ECMO. In our two most recent cases (nos. 10 and 1 1) surgery was delayed until improvements in the infant's condition allowed us to wean the infant from ECMO (to an ECMO flow of less than 30 mL/kg per minute), at which time the diaphragmatic hernia was repaired and the cannula subsequently removed.
and included the use of an intra-arterial catheter for continuous monitoring of the blood pressure and heart rate, intermittent monitoring of the blood gas values (of the circuit and the baby) and continuous pulse oximetry. A no. 8 to 10 French thin-walled cannula was used for the artery and a no. 10 to 14 French cannula for the vein (Elecath, Eledro Catheter Corp., Rahway, NJ). The ECMO flow was begun at 50 mL and was gradually increased by 10 mL/min until it reached 100 to 120 mL/kg per minute. As with the cannulation, the surgical repair was performed on the infant's overhead warmer in the NICU with the use of electrocautery. Just before the hernia was repaired in infants receiving ECMO, the activated clotting time was lowered to 190 to 210 seconds by reducing the heparin infusion rate, and the platelet ECMO count was kept at more than 120 x 1 09/L. A general anesthetic was given intravenously in The mixed venous oxygen level (Pvo2) was the NICU with the infant lying on an overhead maintained at a saturation rate of 68% to 75%. The radiant warmer. A cannula was inserted into the infants were weaned from ECMO when their PvO2 right internal jugular vein and carotid artery. The increased. When the ECMO flow was reduced to 30 procedures for circuit preparation and cannulation mL/kg per minute a trial off ECMO was performed, were similar to those previously described.22 during which heparin was infused into the infant at The venous oxygen tension was continuously 40% of the previous rate and the arterial blood gas measured in the venous line proximal to the venous levels were monitored every 5 to 15 minutes. If the reservoir. All infants had an arterial line in either the infant tolerated at least 1 hour off ECMO and had umbilical artery or a peripheral artery during adequate blood gas values the cannulas were reECMO. Most of the intravenous infusions and all of moved. For our first four surviving infants the jugular the pressor infusions and heparin were administered vein and the carotid artery were permanently ligated through the ECMO circuit. Heparin was given just before cannulation; the at decannulation. However, given early reports indiactivated clotting time was maintained between 210 cating that surgical repair of the carotid artery was and 230 seconds with the use of continuous heparin feasible23'24 and associated with adequate carotid and infusion and the administration of boluses as re- cerebral blood flow24 we began to repair the vein and quired. The platelet count was maintained at more artery when possible after decannulation. In most than 100 X 109/L by means of platelet transfusions, infants the portion of the artery between the proxiand the plasma fibrinogen level was maintained at mal and distal ligatures, including the site of the more than 1.7 g/L by means of cryoprecipitate original arteriotomy, was excised and an end-to-end vascular anastomosis performed; in the remaining transfusions. The priming fluid for the circuit was about 400 infants the arteriotomy site was repaired. The infant mL of type 0, Rh-negative, cytomegalovirus-nega- was kept paralysed for the next 24 hours, and the tive irradiated blood, when available. Pall filters heparin infusion was tapered off over the next 6 (Pall Biomedical Inc., East Hills, NY) were used to hours. remove leukocytes and to reduce the risk of cytomegalovirus transmission when the blood products Results were being administered. We treated 13 infants who were referred to our The cannulation procedure was always performed on the infant's overhead warmer in the unit from established level III NICUs and 3 (cases 2, NICU. All nursing was done with the infants on a 3 and 15) who were born in our institution (Table 2). continuous weighing scale (model 4004, Scale-Tron- The latter three infants all had an antenatal diagnoic, Wheaton, Ill.). This scale is adapted for obtaining sis of CDH, and the mother had been referred to our roentgenograms so that the infant does not have to hospital for ongoing obstetric and perinatal care. All of the 13 infants who were born outside our be moved. The infants were anesthetized with fentafor used hospital were referred because of hypoxemia that nyl (initial dose 20 gg/kg); pancuronium was would not respond to mechanical ventilation and was muscle relaxation. Intraoperative monitoring ECMO other supportive therapy. As can be seen from Table identical to the routine monitoring during FEBRUARY 15, 1992
CAN MED ASSOC J 1992; 146 (4)
503
e
2 these infants were markedly hypoxemic, and in- None of the infants had a significant wound infecdeed their condition usually deteriorated during tion. No infant was moved after being placed on the transportation. overhead radiant warmer for cannulation. The duration of ECMO was 111.0 hours on All surviving infants were discharged home average. Five infants (cases 4, 5, 6, 7 and 14) had from hospital. Those who were followed up between surgical repair of their hernia before ECMO. Of the 6 months and 2 years later were found to be remaining eight cases in which ECMO was started developmentally normal and to have no problems before surgical repair the repair was done during apart from mild hypotonia. Only one child was ECMO in six; four of these infants survived. Four of assessed at 2 years' follow-up; the Bayley score the infants in whom ECMO was started before (which indicates infant development)25 was normal, surgical repair died; one was born in our hospital and there was no evidence of handicap. (case 15) and the cannula inserted at 26 hours of age. During the time covered by this report we were In three cases (cases 1, 2 and 3) the infant's aware of four other infants with CDH and intractacondition was stabilized and surgery performed at 18 ble hypoxemia who met the ECMO criteria. One to 48 hours after admission; all survived without the infant died without a request for transfer, one died need for ECMO. before completion of transfer, and the third was Six infants had their CDH diagnosed before 25 judged not to be a candidate because of birth before weeks' gestation: in case 4 at 20 weeks' gestation, in term (at 34 weeks' gestation); this infant died within cases 1, 2 and 13 at 17 weeks, in case 15 at 15 weeks 12 hours after the request for transfer to our unit. and in case 16 at about 14 weeks. None of the six The fourth infant had an unrepaired CDH on the left pregnancies was noted to be complicated by poly- side and met all of our ECMO criteria. However, we hydramnios before 24 weeks' gestation, although in were unable to accept this referral because two other two cases there was evidence of increased fluid in the infants were already receiving ECMO at the time; we later stages of pregnancy. Three of the six infants arranged for this infant to receive ECMO in the survived, two without the need for ECMO (cases 2 United States. The CDH was repaired after the and 3). infant's condition was stabilized; however, the conNo difficulty was noted in performing the cor- dition subsequently deteriorated, and ECMO was rective surgery in the NICU. The most common required for 9 days, after which the cannula was cause of a fall in the Pvo2 during surgery was related successfully removed. to traction or pressure in the abdomen; the resultant To our knowledge in the NICUs that agreed to impaired venous return caused the pump to inter- consider transporting eligible infants with CDH to mittently stop. The release of such traction was our institution there have been no survivors among required occasionally, and in all cases the PvO2 those who met all our criteria, including the oxygen saturation could be maintained at more than 75%. indices, and did not receive ECMO.
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Deaths One child (case 12) underwent surgical repair uneventfully while receiving ECMO, and the cannula was removed after a well-tolerated trial off ECMO. The infant remained dependent on mechanical ventilation in 40% oxygen for the next 4 days; the condition progressively deteriorated, hypoxemia unresponsive to conventional and high-frequency ventilation developed, and the infant died. Recannulation was not attempted. In case 13 the infant was the most immature (born at 35 weeks' gestation); CDH had been diagnosed at 17 weeks' gestation. Cannulation was required 8 hours after birth; signs of an obstructed superior vena cava and poor ECMO flow developed. A smaller catheter was inserted, and on day 3 there was evidence of a right temporoparietal echodense lesion, which on day 5 was diagnosed as an expanding intracranial hematoma with a midline shift. The infant was rapidly weaned off ECMO and required support with the use of a high-frequency oscillator. The cannula was removed after 152 hours of ECMO. Surgical repair of the hernia during ECMO was not attempted because there had been no evidence of weaning. The infant died of intractable hypoxemia about 36 hours after decannulation. Autopsy findings confirmed a right-sided subdural and intracranial hematoma as well as lung hypoplasia. There was only one death among the infants treated with ECMO after surgical repair (case 14). This infant had undergone echocardiography in the referring NICU, and the findings were interpreted as being normal. She required massive inotropic support for hypotension after the repair; this included the administration of dopamine (20 ,g/kg per minute) and epinephrine (up to 60 ,g/kg per minute) to maintain a mean arterial blood pressure of more than 40 mm Hg before cannulation. Echocardiography repeated daily during ECMO was felt to yield normal results until day 3, when the ECMO flows were reduced: the right side of the heart was found to be smaller than normal. The diagnosis of pulmonary atresia and hypoplasia of the right ventricle, tricuspid valve and pulmonary artery was confirmed; the infant was weaned and the cannula removed after 157 hours of bypass without the need for vasopressor support. After further evaluation it was determined that there was no acceptable surgical option, and the infant died after withdrawal of life support, 9 days after decannulation. In case 15 an infant had CDH on the left side diagnosed at 15 weeks' gestation. He was delivered in our institution after spontaneous labour at more than 38 weeks' gestation. Mechanical ventilation with 100% oxygen was started immediately in the case room, and the infant was sedated and paralysed. FEBRUARY 15, 1992
Echocardiography and ultrasonography of the head gave normal findings, and ECMO was started at 26 hours of age. Immediately after cannulation ultrasonography of the head showed a grade II intraventricular hemorrhage. We therefore elected to repair the infant's diaphragm early, at 51 hours of age, with a large synthetic patch. Postoperatively there was excessive bleeding (100 to 150 mL/h) from a drain in the left side of the chest. Exploratory thoracotomy revealed that an intercostal artery had been lacerated by one of the sutures used to place the patch. Ultrasonography showed an extension of the intraventricular hemorrhage.. Shortly thereafter the infant suddenly became hypotensive because of arterial decannulation when the catheter eroded through the carotid artery; he died despite vigorous resuscitation attempts. Permission for autopsy was
denied. In case 16 the infant was transferred almost immediately after birth and the cannula inserted at about 51/2 hours of age. There was evidence of coagulopathy with pulmonary hemorrhage and a right pneumothorax. Myocardial contractility was poor; bleeding from the chest drain continued, as did the coagulopathy. After 5 days of ECMO there was evidence of progressive thrombocytopenia and failure to wean; sepsis was suspected. Vancomycin and cefotaxime were substituted for amikacin and ampicillin. A course of dexamethasone was tried later, but after 8 days the infant's condition had not improved. On day 9 there was a sudden loss of arterial circulation to the left arm and head. An ultrasound image confirmed lack of pulsation to the brain, and acute aortic thrombosis or aortic dissection was suspected. The cannulas were removed after 215 hours of ECMO, and the infant died soon afterward despite aggressive support. Postmortem findings included an absent left diaphragm, severe pulmonary hypoplasia and an aortic thrombus near the site of the carotid catheter tip. Fungal elements were detected in the clot; however, there was no cultural confirmation of the type of fungus.
Discussion Hemorrhagic complications related to ECMO have been reported by virtually all ECMO centres and can be successfully managed with heightened awareness and a rapid response."' The extensive use of cautery and tissue glue markedly reduces bleeding, and none of our infants with CDH has had to undergo re-exploration of the neck wound because of hemorrhage. Patient 13 was our most gestationally immature infant and the only one who had significant intracranial hemorrhage. Patient 14 would not have been CAN MED ASSOC J 1992; 146 (4)
S0S
an ECMO candidate had the correct diagnosis been made before referral. However, it is striking that this infant, who required intensive support before ECMO, was able to be weaned and supported after decannulation and had an adequate blood pressure without the need for inotropic agents. We have now treated eight infants whose condition deteriorated with severe hypoxemia before surgical repair; six subsequently underwent surgical repair during ECMO, four surviving. In addition, we have treated infants whose condition deteriorated postoperatively and others who have never had a partial pressure of oxygen of more than 100 mm Hg in arterial blood obtained distal to the ductus arteriosus, the so-called nonresponders of Vacanti and colleagues.9 Some centres provide ECMO support only to infants who have already had operative repair, most having had at least one Pao2 reading of 100 mm Hg.9"1"13'26,27 Bohn and associates2 have developed criteria to predict outcome in cases of early-onset CDH on the basis of the ventilatory index and the Paco2 2 hours before or after repair. The data for all 13 of our infants treated with ECMO predicted a death rate of 90% with the use of these criteria.2 Our results are in agreement with those of Van Meurs and coworkers,28 who showed a survival rate of 67% among infants with CDH who were in the "poor-prognosis" group.2 However, they excluded infants whose condition had to be stabilized with ECMO before surgical repair, a group that accounted for four of our five deaths. Our experience is similar to that reported by Bailey and associates,'" who demonstrated that indices to predict outcome in the absence of ECMO (e.g., blood gas values, the presence or absence of a "honeymoon" period and the presence of a Pao2 of more than 100 mm Hg) were unreliable in predicting the response to ECMO and concluded that no infant should be excluded from repair or ECMO support on the basis of these criteria. Our results are almost identical to those reported more recently by this group.29 Adzick and Harrison and their colleagues30-32 suggested that the early detection of a diaphragmatic hernia by means of ultrasonography may be associated with a poor prognosis. However, intrauterine repair appears to be an option for selected cases of prenatally diagnosed CDH.33 Our observations extend the conclusions of Bailey and associates"5 in that we had three survivors among the six infants whose CDH was diagnosed at or before 20 weeks in utero. In addition, one of these infants, whose CDH was diagnosed at 17 weeks, tolerated a primary repair without a patch; this suggests that early intrauterine diagnosis is not always associated with a severe defect. Further information is obviously required on the outcome of CDH diagnosed in early 506
CAN MED ASSOC J 1992; 146 (4)
pregnancy before fetal surgery is recommended. An increasing number of reports have described long-term survival (up to 10 years) in infants receiving ECMO; this suggests that about 60% of such infants develop normally. An additional 15% to 20% have been found to have some possible neurologic abnormality or a severe abnormality.34-38 The most recent report, by Adolph and coworkers,39 revealed that all but 1 of 57 infants had normal findings on neurologic examination, 75% showing normal development. In such a group of infants it is difficult to attribute handicap exclusively to ECMO given their unstable condition before cannulation. All of our surviving infants who have been assessed to date have shown normal neurodevelopment, and only 2 of the other 40 survivors who received ECMO for other conditions had evidence of a severe neurologic abnormality. We repaired the carotid artery and jugular vein when possible in our last 15 survivors, and in Doppler flow studies before discharge we have demonstrated excellent prograde flow in all of the repaired arteries. The veins that were repaired have usually not remained patent. We have re-evaluated the anastomotic site in three of our survivors at 6 months of age and found excellent flow, with no evidence of stenosis in the carotid artery. The absence of acute complications associated with such repair is consistent with the experience reported by others.40-42 We believe that repair of the carotid artery will re-establish normal intracranial flow patterns and reduce the long-term risks associated with ECMO. We feel that the best management of infants with CDH lies in early prenatal diagnosis and transfer so that delivery can occur at a tertiary care centre. Infants with severe CDH diagnosed very early in pregnancy can survive without ECMO; this suggests that appropriate resuscitation and stabilization prevent the ensuing pulmonary hypertension and associated hypoxemia. Since our program was begun, to our knowledge there have been no surviving infants in our catchment area who met all the ECMO criteria but did not receive this therapy. In addition, 12 of our 13 infants who received ECMO were initially managed in well-established academic tertiary care NICUs, and the decision to transfer was made by their attending neonatologist. None was able to be managed without ECMO. This indicates either our failure to provide optimal care or, more likely, the presence of intractable pulmonary hypertension and right-to-left shunting (as detected in all of our infants), despite comprehensive conventional treatment. ECMO is a technique that, like many other advances, was introduced and widely accepted into practice before adequately controlled randomized LE 15 FEVRIER 1992
trials could be performed to demonstrate unequivocally its efficacy. Subsequently, two controlled trials have shown the superiority of ECMO over conventional therapy,'7"'8 but these studies were criticized for their methods and the small control sample. Other investigators43 have challenged the validity of indices predictive of death, but even they have subsequently transferred infants with CDH to receive ECMO.44 Given the high rate of death among infants with CDH unresponsive to conventional therapy it is unlikely that any ECMO centre would agree to a trial in which such infants would be allowed to die without ECMO. In the absence of further definitive clinical trials ECMO still appears to offer the best hope of survival to infants with CDH and intractable hypoxemia despite maximum conventional therapy. Although imperfect, criteria established to predict death in infants with CDH have been widely adopted,2'8'9 and the use of ECMO has produced survivors who had been predicted to die according to these criteria. One way to assess the role of ECMO in CDH might be to randomly assign infants in a non-ECMO centre who meet ECMO criteria either to receive continued conventional therapy or to be transferred to an ECMO centre. Although not blinded, such a study would be biased against ECMO, because infants randomly assigned to receive ECMO would have to be transferred while critically ill. We thank our nurses, respiratory therapists, Wendy Ainsworth (ECMO coordinator), ECMO specialists, Drs. Raf Ocejo, Doug Davey, Rick Johnston, Gordon Lees and Keith Barrington, and the departments of Diagnostic Imaging and Pathology for their contribution to the care of the infants described in this article. We also thank Liz Borgel-Kish for preparing the manuscript.
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stabilisation in congenital diaphragmatic hernia. Arch Dis Child 1990; 65: 1043-1044 Bohn D, Tamura M, Perrin D et al: Ventilatory predictors of pulmonary hypoplasia in congenital diaphragmatic hernia, confirmed by morphologic assessment. J Pediatr 1987; 111: 423-431 Vacanti JP, O'Rourke P, Lillehei CR et al: The cardiopulmonary consequences of high-risk congenital diaphragmatic hernia. Pediatr Surg Int 1988; 3: 1-5 Hardesty RL, Griffith BP, Debski RF et al: Extracorporeal membrane oxygenation: successful treatment of persistent fetal circulation following repair of congenital diaphragmatic hernia. J Thorac Cardiovasc Surg 1981; 81: 556-563 Langham MR, Krummel TM, Bartlett RH et al: Mortality with extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernia in 93 infants. J Pediatr Surg 1987; 22: 1150-1154 Heiss K, Manning P, Oldham KT et al: Reversal of mortality for congenital diaphragmatic hernia with ECMO. Ann Surg 1989; 209: 225-230 Heaton JFG, Redmond CR, Graves ED et al: Congenital diaphragmatic hernia: improving survival with extracorporeal membrane oxygenation. Pediatr Surg Int 1988; 3: 6- 10 Weber TR, Connors RH, Pennington G et al: Neonatal diaphragmatic hernia: an improving outlook with extracorporeal membrane oxygenation. Arch Surg 1987; 122: 615-618 Bailey PV, Connors RH, Tracy TF Jr et al: A critical analysis of extracorporeal membrane oxygenation for congenital diaphragmatic hernia. Surgery 1989; 106: 611-616 Connors RH, Tracy T Jr, Bailey PV et al: Congenital diaphragmatic hernia repair on ECMO. J Pediatr Surg 1990; 25: 1043-1047 Bartlett RH, Roloff DW, Cornell RG et al: Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics 1985; 76: 479-487 O'Rourke PP, Crone RK, Vacanti JP et al: Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study. Pediatrics 1989; 84: 957-963 Papile LA, Burnstein J, Burnstein R et al: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 grams. JPediatr 1978; 92: 529-534 Robertson CM, Finer NN: Term infants with hypoxic ischemic encephalopathy: outcome at 3.5 years. Dev Med Child Neurol 1985; 27: 473-484 Bartlett RH, Toomasian J, Roloff D et al: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure: 100 cases. Ann Surg 1986; 204: 236-245 Short BL, Pearson GD: Neonatal extracorporeal membrane oxygenation: a review. Int Care Med 1986; 1: 47 Spector ML, Wiznitzer M, Walsh-Sukys MC et al: Carotid reconstruction following ECMO. Presented at the Extracorporeal Life Support Organization Charter Meeting, Oct 1-3, 1989, Ann Arbor, Mich Lewin JS, Masary TJ, Modic MT et al: Extracorporeal membrane oxygenation in infants: angiographic and parenchymal evaluation of the brain with MR imaging. Radiology 1989; 173: 361-365 Bayley N: Bayley Scales of Infant Development, Psychological Corp, New York, 1969 Langham MR, Krummel TM, Greenfield LJ et al: Extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernias. Ann Thorac Surg 1987; 44: 247-252 Stolar C, Dillon P, Reyes C: Selective use of extracorporeal membrane oxygenation in the management of congenital diaphragmatic hernia. J Pediatr Surg 1988; 23: 207-21 1 Van Meurs KP, Newman KD, Anderson KD et al: Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. J Pediatr 1990; 1 17: CAN MED ASSOC J 1992; 146 (4)
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954-960 29. Weber TR, Connors RH, Tracy TF Jr et al: Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns. Ann Thorac Surg 1990; 50: 720-723 30. Adzick NS, Harrison MR, Glick PL et al: Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases. J Pediatr Surg 1985; 20: 357-361 31. Adzick NS, Vacanti JP, Lillehei CW et al: Fetal diaphragmatic hernia: ultrasound diagnosis and clinical outcome in 38 cases. JPediatrSurg 1989; 24: 654-658 32. Harrison MR, Adzick NS, Longaker MT et al: Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax. N Engl J Med 1990; 322: 1582-1584 33. Harrison MR, Langer JC, Adzick NS et al: Correction of congenital diaphragmatic hernia in utero: 5. Initial clinical experience. J Pediatr Surg 1990; 25: 47-57 34. Andrews AF, Nixon CA, Cilley RE et al: One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation. Pediatrics 1986; 78: 125-131 35. Taylor GA, Glass P, Fitz CR et al: Neurologic status in infants treated with extracorporeal membrane oxygenation: correlation of imaging findings with developmental outcome. Radiology 1987; 165: 679-682 36. Taylor GA, Fitz CR, Glass P et al: CT of cerebrovascular
Conferences
continuedfrom page 462 June 10-13, 1992: ISPRAD VI - 6th International Symposium on the Planning of Radiological Departments (in conjunction with the International Meeting on Hospital Economy [IMHE]) Grieg Hall, Bergen, Norway Official language: English IMHE/ISPRAD VI, c/o Lilly Hausberg, PLUSreiser, PO Box 946, N-5001 Bergen, Norway; fax 011-47-5-47590-20-91 June 17-19, 1992: 6th Annual Forensic Conference - The Roots of Violence: Implications for Interventions with Adults (sponsored by the Mental Health Centre,
Penetanguishene) Highland Inn, Midland, Ont. Margaret Milligan, conference coordinator, Mental Health Centre, PO Box 5000, Penetanguishene, ON LOK 1 PO; (705) 549-3181, ext. 2204 June 17-20, 1992: Society for Scholarly Publishing Annual Meeting
Chicago Society for Scholarly Publishing, 304-10200 W 44th Ave., Wheat Ridge, CO 80033; (303) 422-3914 June 21-24, 1992: 4th Symposium on Violence and Aggression Saskatoon, Sask.
Registration Office, Extension Division, University of Saskatchewan, Saskatoon, SK S7N OWO; (306) 966-5560, fax (306) 966-5567 508
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40. 41. 42. 43. 44.
injury after neonatal extracorporeal membrane oxygenation: implications for neurodevelopmental outcome. AJR 1989; 153: 121-126 Hofkosh D, Clouse H, Smith-Jones J et al: Ten years of ECMO: neurodevelopmental outcome among survivors [abstr]. Pediatr Res 1990; 27: 245A Lott IT, McPherson D, Towne B et al: Long-term neurophysiologic outcome after neonatal extracorporeal membrane oxygenation. J Pediatr 1990; 116: 343-349 Adolph V, Ekelund C, Smith C et al: Developmental outcome of neonates treated with extracorporeal membrane oxygenation. J Pediatr Surg 1990; 25: 43-46 Karl TR, Iyer KS, Sano S et al: Infant ECMO cannulation technique allowing preservation of carotid and jugular vessels. Ann Thorac Surg 1990; 50: 488-489 Adolph V, Bonis S, Falterman K et al: Carotid artery repair after pediatric extracorporeal membrane oxygenation. J Pediatr Surg 1990; 25: 867-870 Crombleholme TM, Adzick S, deLorimier AA et al: Carotid artery reconstruction following extracorporeal membrane oxygenation. Am JDis Child 1990; 144: 872-874 Dworetz AR, Moya FR, Sabo B et al: Survival of infants with persistent pulmonary hypertension without extracorporeal membrane oxygenation. Pediatrics 1989; 84: 1-6 Gross I: The extracorporeal membrane oxygenation debate [C]. Pediatrics 1990; 85: 383-384
June 21-25, 1992: Canadian Association of Radiologists 55th Annual Scientific Meeting Halifax World Trade and Convention Centre Roxanne Saumur, administrative secretary, Canadian Association of Radiologists, 510- 5101 Buchan St., Montreal, PQ H4P 2R9; (514) 738-3111, fax (514) 738-5199
Du 21 au 25 juin 1992: 55e Reunion scientifique annuelle de l'Association canadienne des radiologistes Halifax World Trade and Convention Centre Roxanne Saumur, secretaire administrative, l'Association canadienne des radiologistes, 510-5101, rue Buchan, Montreal, QC H4P 2R9; (514) 738-3111, fax (514) 738-5199 Les 22 et 23 juin 1992: 6e Reunion internationale de la Societe francophone de cancerologie - Le cancer de l'uterus (col et endometre) : experience et perspectives
nouvelles Universite de Montreal Departement d'obstetrique-gynecologie, Faculte de medecine, Universite de Montreal, CP 6128, Succ. A, Montreal, QC H3C 3J7; fax (514) 876-7468 June 25-28, 1992: 27th Meeting of the Canadian Congress of Neurological Sciences Winnipeg Convention Centre Permanent Secretariat, Canadian Congress of Neurological Sciences, Ste. 810, 906-12 Ave. SW, Calgary, AB T2R 1K7; (403) 229-9544, fax (403) 229-1661
continued on page 551 LE 15 FEVRIER 1992
