Outcome of cardiac surgery in low birth weight and premature infants q

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1 European Journal of Cardio-thoracic Surgery 26 (2004) Outcome of cardiac surgery in low birth weight and premature infants q Guido Oppido a, *, Carlo Pace Napoleone a, Roberto Formigari b, Davide Gabbieri a, Davide Pacini a, Guido Frascaroli c, Gaetano Gargiulo a a Department of Pediatric Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Via Massarenti, No. 9, Bologna, Italy b Department of Cardiology, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Bologna, Italy c Department of Anesthesiology, S. Orsola-Malpighi Hospital, University of Bologna Medical School, Bologna, Italy Received 31 August 2003; received in revised form 10 March 2004; accepted 6 April 2004; Available online 18 May 2004 Abstract Objective: Low birth weight or premature infants may require early surgical treatment of congenital cardiac lesions because of their poor clinical status. Even thought early repair or palliation is carried out with incremental risk factor for morbidity and mortality, it has been demonstrated to be preferable to medical management and delayed surgery. This retrospective study was undertaken to evaluate early and mid-term results in infants, weighing less than 2500 g, who underwent surgery other than patent ductus arteriosus closure. Methods: Since January 1993 to August 2002, 60 consecutive patients underwent early surgical treatment of congenital heart malformations at our institution. 27 patients were premature (born before 37 weeks of gestation). Ninety percent were severely symptomatic. Mean age at operation was 15.5 days (range 4 68 days). Mean weight was 2120 g (range g). Indications for surgery were: coarctation complex 11, transposition of great arteries 9, interrupted or severely hypoplastic aortic arch 9, hypoplastic left heart syndrome 7, truncus arteriosus 5, other 19. Thirtyfive patients were operated on CPB, Deep Hypothermia with Circulatory Arrest was used in 9. Complete repair was achieved in 32 patients. Aortic arch reconstruction was required in 32 cases. Results: There were nine early deaths (15%): heart failure (5), multiorgan failure (3), sepsis (1). Age, weight, prematurity, type of surgery and use of cardio pulmonary by-pass did not influence early mortality. Mean intensive care unit stay and duration of mechanical ventilation were 5.8 days and 75.5 h, respectively. Postoperative neurological complications did not occur in any patient. At follow-up (mean 48 months) there were nine late deaths. Kaplan Meier survival at 60 months was 70%. Conclusions: Surgery for congenital heart disease can be performed in low weight critically ill infants with reduced, but still acceptable early and mid-term survival. q 2004 Elsevier B.V. All rights reserved. Keywords: Congenital heart disease; Low birth weight; Cardio pulmonary by-pass; Cerebral protection 1. Introduction The incidence of low birth weight, defined as a body weight at birth less than 2500 g, in newborns affected by congenital heart disease, has been reported by many authors to be significantly higher when compared with normal newborns population. Incidence of low birth weight in congenital heart disease patients ranges between 8 and 18% compared with 6% of the normal population, whereas no q Presented at the joint 17th Annual Meeting of the European Association for Cardio-thoracic Thoracic Surgeons, Vienna, Austria, October 12 15, * Corresponding author. Tel.: þ ; fax: þ address: guidooppido@yahoo.com (G. Oppido). significant differences have been found between the two populations in terms of prematurity [1 5]. Continuous improvements in the management of premature or small for gestational age newborns, in the neonatology intensive care units, have considerably reduced the postnatal mortality of those babies; consequently, the request for surgical treatment of congenital heart lesions early in life in low weight babies, is expected to increase in the up-coming future. However, although the outcome of neonatal cardiac surgery, has dramatically enhanced in the last two decades, low body weight itself still constitutes an important risk factor for morbidity and mortality [6 9]. Intensive medical therapy and continuous prostaglandin infusion for prolonged time, in those neonates who benefit ductus patency, may guarantee clinical stability with /$ - see front matter q 2004 Elsevier B.V. All rights reserved. doi: /j.ejcts

2 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) the rationale of delaying surgery letting babies gain weight. Nevertheless, this strategy seems not to be associated with a better outcome and furthermore it is not always practicable because of failure to thrive or permanent unstable hemodynamic conditions. Chang and colleagues [10] reported on a series of low birth weight and premature infants who were managed according to three different protocols: hospital survival rate was 82% in the complete repair group, 78% in the palliated group and 77% in the delayed surgery group, with an additional 10% mortality rate at the time of surgery for the latter. Aim of the present study was to report on the outcome of the entire population of neonates and infants weighing less than 2500 g who underwent surgery other than ductus arteriosus closure at our institution in the last decade, with the intent of giving our contribution to the determination of the ideal treatment strategy in this challenging subgroup of babies. 2. Material and methods Preoperative and operative data were retrospectively collected by reviewing the hospital records and the computerised database of the Department of Pediatric Cardiac Surgery of the S. Orsola-Malpighi Hospital, Bologna, Italy. Follow-up data were obtained from our institution outpatient records and from our Catheterization Laboratory database. Each patient underwent clinical examination, chest X-ray and echocardiogram at 6 12 month regular intervals. Study period was 10 years: from January 1993 to August Inclusion criterion was: body weight less then 2500 g at the time of surgery. Patients who underwent ductus arteriosus closure alone, as well as low birth weight or premature babies, who reached a body weight of more than 2500 g at the time of surgery, were not included in the study. End-point was in-hospital mortality (within 30 days after the operation) Statistical analysis Data are presented as mean ^ SD and range, unless otherwise specified. Statistical significance in the research of risk factors for mortality, was determined with X 2 test or Fisher s Exact analysis in the comparison of categorical variables and Student s t-test in the comparison of continuous variables. All variables that achieved P, 0:2 in the univariate analysis were included in a multivariate model and examined by stepwise logistic regression. Significance was defined as P, 0:05: Survival curves were obtained by Kaplan Meier product limit method and compared with log rank test. Software used for statistical analysis was SPSS (Chicago, IL, USA) for Windows version 8.0. Table 1 Patient demographics 2.2. Patient population A total of 60 consecutive patients (33 females and 27 males), either neonates or infants, met the inclusion criteria in the study time period (Table 1). Twenty-seven (45%) were born prematurely: 1 before the 28th week of gestation, 7 between the 29th and 32nd, 19 between the 33rd and 36th. Thirty-three (55%) were full term low birth weight newborns (less than 2500 g at birth). Mean weight at birth was 2190 ^ 310 g Preoperative clinical conditions All patients were preoperatively hospitalized either in the neonatal intensive care unit or in our cardiac intensive care unit: 54 (90%) were severely symptomatic because of their underlying hemodynamic disorder: low output in left heart obstructive lesions was the more recurrent clinical presentation, severe cyanosis for right to left shunt or transposition and congestive heart failure for unrestricted left to right shunt were observed in the remaining. Prenatal cardiac diagnosis was available in 21 patients. Thirty-seven patients were ductus dependent and were receiving prostaglandins, 10 were receiving high dose catecholamines infusion, five were permanently ventilated, three exhibited pulmonary complications in relation to prematurity, three developed metabolic acidosis requiring bicarbonates. None of the patients had intraventricular hemorrhage, necrotizing enterocolitis or sepsis. Mean age at operation was 15.5 ^ 13.4 days (range 4 68 days) and mean weight was 2120 ^ 370 g (range g) Diagnoses No. (%) Patients 60 Gender Male 33 (55) Female 27 (45) Gestational age # 28 weeks 1 (1.7) weeks 7 (11.7) weeks 19 (31.7) $ 37 weeks 33 (55) Mean ^ SD Range Weight at operation 2120 ^ 370 g g Weight at birth 2190 ^ 310 g g Age at operation 15.5 ^ 13.4 days 4 68 days Cardiac diagnoses included: coarctation complex (11 pts), transposition of great arteries (9 pts), interrupted or severely hypoplastic aortic arch 9, hypoplastic left heart

3 46 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) Table 2 Cardiac diagnoses and associated malformations or syndromes Cardiac anomaly No. Syndromes No. Coarctation complex 11 Charge 1 Coarctation 10 Down s. 1 Coarctation, VSD 1 DiGeorge s. 1 IAA/aortic arch hypoplasia 9 Eterotaxia s. 2 IAA 5 Rubistain-taybi s. 1 IAA, A-P window 1 Arch hypoplasia, VSD 2 Malformations No. Arch hypoplasia, VSDs 1 Gastro-enteric 3 Transposition of great arteries 9 Oesophageal atresia 2 TGA/IVS 6 Anal atresia 1 TGA/VSD 1 Genito-urinary 4 TGA/VSD arch hypoplasia 1 Cryptorchism 1 TGA/VSDs arch hypoplasia 1 Multicystic kidney 1 Hypoplasic left heart syndrome 7 Vescico-ureteral reflux 1 Truncus arteriosus 5 Unilateral renal agenesis 1 Truncus type I A II A 3 Sensory organs 1 Truncus type IV A (with IAA) 2 Atresia auris 1 Double outlet right ventricle 4 Muscle-skeletal 2 DORV 3 Craniosynostosis 1 DORV, asplenia s. 1 Duchenne muscular dystrophy 1 Tetralogy of fallot 3 Central nervous system 3 ToF/PS 2 Corpus callosum agenesis 1 ToF/PA 1 Hydrocephalus 2 Pulmonary atresia intact V. septum 4 Double inlet left ventricle 3 DILV 1 DILV aortic arch hypoplasia 1 DILV, asplenia 1 VSD 2 VSD 1 VSDs 1 Tricuspid atresia, pulmonary atresia 1 Complete atrio-ven septal defect 1 Anomalous origin right pulmonary artery 1 VSD, ventricular septal defect; VSDs, multiple ventricular septal defects; IAA, interrupted aortic arch; A-P window, aortico-pulmonary window; TGA/IVS, transposition of the great arteries with intact ventricular septum; TGA/VSD, transposition of the great arteries with intact ventricular septum; DORV, double outlet right ventricle; ToF/PS, tetralogy of fallot; ToF/PA, tetralogy of fallot with pulmonary atresia; DILV, double inlet left ventricle. syndrome 7, truncus arteriosus 5, double outlet right ventricle 4, tetralogy of Fallot 3, pulmonary atresia intact ventricular septum 4, double inlet left ventricle 3, ventricular septal defect 1, tricuspid atresia 1, multiple ventricular septal defects 1, complete atrio-ventricular septal defect 1, anomalous origin of the right pulmonary artery 1 (Table 2). Associated non-cardiac malformations or syndromes were present in 19 patients (32%) and are summarized in Table Surgery Anesthetic protocols did not differ from those used in neonates with a body weight exceeding 2500 g and entailed: Fentanil 1 2 mg/kg/dose, Vecuronium mg/kg/dose, Midazolam mg/kg/dose and Sevofluorane. Extracorporeal neonatal circuits sized 3/16 1/4 and were primed with irradiated and deleucocytised red blood cells and fresh frozen plasma, bicarbonates and heparin, achieving a hematocrit value of 30%. Aortic cannulation was performed with number 20 Teflon straight cannula (Sofracob s.a., Reventin Vaugris, France) which corresponds to a 1.5 mm internal diameter tip. Bicaval venous cannulation was performed entering the right atrium with two 12 F curve cannulas (Baxter International, Inc. San Diego, CA, USA); a single 20 F atrial venous cannula (Baxter International, Inc. San Diego, CA, USA) was preferred in all Norwood stage I operations. Oxygenators utilized from 1993 to 2000 were hollow fibers Masterflow D 701 (Dideco Modena, Italy) and from 2000 to date hollow fibers Lilliput D 901 (Dideco Modena, Italy). Intermittent blood cold cardioplegia was administered antegradely into the aortic root or coronary ostia. During cardio-pulmonary bypass, blood gas analysis was achieved using alpha-stat

4 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) strategy. Pump flow was adjusted to maintain a blood pressure not above 40 mmhg and a mixed venous blood oxygen saturation, monitored continuously, never below 60 65%. Continuos ultrafiltration was carried out during cardio-pulmonary by-pass in each patient. Forty-six patients underwent median sternotomy and 14 underwent left postero-lateral thoracotomy in the third or fourth intercostals space. Thirty-five (58%) patients were operated on cardio-pulmonary by-pass and 25 (42%) underwent off-pump procedures. Cardio-pulmonary by-pass and X-clamp mean times were 178 ^ 87 min and 74 ^ 53 min, respectively. Deep hypothermia (, 18 8C) with circulatory arrest was avoided in all patients but 9, all of them operated on before In the anterior aortic arch surgery, cerebral selective perfusion technique, at a body temperature of C, was always preferred during the last 6 years. Aortic arch surgery alone or as part of more complex procedures, was required in 32 cases (53%): anterior or entire arch reconstruction in 21, isthmus and posterior arch in 11. Anterior or entire arch reconstruction was part of more complex procedures in 13 cases: Norwood stage I operation 7, arterial switch operation 3, truncus arteriosus repair 2, aortico-pulmonary window 1. In eight cases anterior arch reconstruction was associated to: ventricular septal defect closure 4, left ventricular outflow tract obstruction release 2 pulmonary artery banding 2. Each one of the 11 coarctation complex patients received repair of the coarctation and contemporarily enlargement of the posterior arch. 3. Results Single stage complete repair was achieved in 32 patients; staged univentricular palliation (18), or palliation in patients with anatomy amenable to biventricular repair (10), were undertaken in the remaining 28 (Table 3). Postoperative mechanical ventilation mean time was 75.4 ^ 106 h (range h) and postoperative intensive care unit stay was 5.8 ^ 6.6 days (range days) Early Mortality Nine patients died in the early postoperative period, accounting for a hospital mortality of 15%. Causes of death included: heart failure in five patients, multiorgan failure in three, sepsis in one. At the univariate analysis (Table 4), weight at surgery ðp ¼ 0:368Þ; age ðp ¼ 0:626Þ; gestational age ðp ¼ 0:144Þ; type of surgery (correction or palliation) ðp ¼ 1Þ; use of cardiopulmonary by-pass ðp ¼ 0:281Þ; cerebral selective perfusion ðp ¼ 0:38Þ; associated noncardiac malformations or syndromes ðp ¼ 0:096Þ did not result to be risk factors for early mortality. The more frequent cardiac pathologies: coarctation complex ðp ¼ 0:189Þ; transposition of great arteries ðp ¼ 0:1Þ; interrupted or severely hypoplastic aortic arch Table 3 Surgical procedures Procedure No. CPB Type of surgery Coarctation repair 11 End to end extended 9 Off Correction End to end extended PAB 1 Off Palliation Patch aortoplasty 1 Off Correction Arch reconstruction 9 Arch reconstruction VSD closure 4 On Correction Arch reconstruction PAB 2 On Palliation Arch reconstruction LVOTO 2 On Correction release Arch reconstruction APW repair 1 On Correction Truncus repair 5 Truncus repair 3 On Correction Truncus repair aortic arch rec 2 On Correction Arterial switch operation 10 ASO 6 On Correction ASO VSD closure 1 On Correction ASO VSD closure arch rec 1 On Correction ASO PAB arch rec 1 On Palliation Palliative* ASO arch rec 1 On Staged Norwood I stage 7 On Staged BT Shunt 12 BT Shunt 11 Off Pall(3)/stag(8) (10)/on (1) BT Shunt pulm valvuloplasty 1 On Staged Pulmonary artery banding 4 Off Pall(3)/stag(1) VSD closure 1 On Correction Pulmonary artery reimplantation 1 On Correction Stag. or Staged, univentricular staged repair; Pall., palliated; CPB, cardio pulmonary bypass; (on: operation performed on cardiopulmonary bypass; off: operation performed without cardiopulmonary bypass); PAB, pulmonary artery banding; VSD, ventricular septal defect; APW, aorticopulmonary window; LVOTO, left ventricular outflow tract obstruction; Arch Rec, arch reconstruction; ASO, arterial switch operation; BT shunt, Blalok Taussig shunt; Pulm valvuloplasty, Pulmonary valvuloplasty; (*) Palliative arterial switch operation performed in a patient with {SDD} double inlet left ventricle with transposition of the great artery, aortic arch hypoplasia and subaortic stenosis. ðp ¼ 0:125Þ; hypoplastic left heart syndrome ðp ¼ 0:281Þ and truncus arteriosus ðp ¼ 0:57Þ; were included in the analysis and did not reach statistical significance as well. Among all the variables investigated as risk factors for early mortality, use of deep hypothermia with circulatory arrest ðp ¼ 0:007Þ and longer cardiopulmonary bypass ðp ¼ 0:002Þ and cross-clamping ðp ¼ 0:006Þ times, were the only variables which reached statistical significance. Among patients amenable for complete biventricular repair, there was no difference between those who underwent single-stage correction vs. those who underwent palliation (15.6 vs. 20.0%, P ¼ 0:66). Multivariate analysis by stepwise logistic regression (Table 4) indicated, as the only significant independent risk factor for early mortality, the use of deep hypothermia with circulatory arrest (P ¼ 0:002; CI ; odds ratio ½ORŠ ¼9:4), while a body weight less than 1500 g (when analyzed as a dichotomic variable) reached P value ¼ 0:06 (CI ), with an odds ratio ½ORŠ ¼3:5:

5 48 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) Table 4 Univariate and multivariate analysis for early mortality Dicotomic variables Patients Death Univariate Multivariate No. % No. % P value Odds ratio 95% Confidence interval P value Associated malformations or syndromes Yes No Type of surgery 1.00 Correction Palliation (mono- and biventricular) Complete biventricular repair 0.66 One-stage Palliation (biventricular) Use of cardio pulmonary by-pass Yes No Cerebral selective perfusion 0.38 Yes No Deep hypothermia with circulatory arrest Yes No Very low body weight (,1500 g) Yes No Coarctation Yes No Hypoplastic left heart syndrome Yes No Interrupted or hypoplastic aortic arch Yes No Truncus arteriosus 0.57 Yes No Transposition of the great arteries 1.00 Yes No Continuous variables Alive Death P value No. Mean No. Mean Weight at surgery Age at surgery Gestational age Cardio pulmonary by-pass time X-clamp time Complications Among 46 interventions carried out via median sternotomy, sternum was left open in 15 patients; mostly just to prevent hemodynamic problems during the early postoperative period for the more complex surgical reconstructions. The following complications occurred in 18 of the 51 early survivors: two patients were successfully resuscitated from cardiac arrest occurred in the day of surgery, nine developed low cardiac output requiring prolonged high dose inotropic support (dopamine and/or dobutamine. 10 mg/kg/min, and/or adrenaline.0.1 mg/kg/min) and two of them needed a systemic-to-pulmonary shunt resizing few hours after the operation, six developed acute renal insufficiency, two had pulmonary hypertensive crisis requiring inhaled nitric oxide therapy and two had severe systemic postcoarctectomy hypertension, four acquired sepsis and were found positive

6 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) to blood colture and successfully treated with selective antibiotic therapy, three patients required reintubation and prolonged mechanical ventilation for non-cardiac-related reasons: one had transitory phrenic nerve palsy, one disclosed tracheomalacia and one developed bilateral atelettasia. All the patients were pre- and postoperatively routinely screened with cerebral echography by an experienced neonatologist in order to exclude the occurrence of brain damage at any time. Postoperative neurological complications were not observed in any patient Late mortality Follow-up mean time was 48 ^ 33 months (range months) and was 100% complete. Of the 51 early survivors nine patients died during the follow-up (late mortality 17.5%), three of them within six months from the operation. The following causes of death could be detected in all nine patients: one heart failure and one shunt thrombosis (both occurred within the sixth month after the operation, in patients waiting for Norwood stage II procedure), two severe pulmonary hypertension (one in a patient who received valve replacement for mitral valve stenosis and one in a patient who underwent pulmonary artery banding with a reabsorbable band), one pneumonia, one ab ingestis, one Duchenne muscular dystrophy, one patient died during cardiac reoperation in another hospital and one during esophageal reoperation. Kaplan Meier overall actuarial survival rate at 60 months was 70.0% (Fig. 1). There was no significant difference ðp ¼ 0:88Þ in survival between term and preterm patients (Fig. 2) (65.4 vs. 74.0%, respectively) or between babies who underwent repair in respect to those who had palliative procedures (Fig. 3) (74.7 vs. 64.6%, P ¼ 0:7) Reinterventions After a mean follow-up time of 48 ^ 33 months (range months), 29 out of 51 survivors needed 47 procedures (Table 5), either as catheter intervention (20 procedures in 16 patients), or as surgical procedure (27 operations in 21 patients). The major interventions in the catheterization laboratory were balloon angioplasty for recurrent coarctation in five cases (after interrupted aortic arch repair in two and coarctation repair in three), balloon pulmonary angioplasty for peripheral pulmonary stenosis in five (two in one patient after aortico-pulmonary window and interrupted aortic arch repair, one after truncus and interrupted aortic arch repair, one after BT-shunt and one after Norwood stage II procedure) and balloon angioplasty/ valvuloplasty of a narrowed homograft/heterograft in three. Four patients (8%) needed six reoperations for residual defects: subaortic stenosis resection two (both after interrupted aortic arch repair), mitral valve replacement two, mitral valve plasty one and residual ventricular septal defect closure one. Two patients had homograft/heterograft replacement due to somatic overgrowth. The remaining 19 operations were part of staged univentricular repair (13) or delayed correction after palliation (6) and are reported in Table 5. Fig. 1. Overall actuarial survival (Kaplan Meier). Survival rate at 60 months was 70.0%. Patients at risk at any time are indicated in parentheses.

7 50 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) Fig. 2. Term vs. premature patients actuarial survival. Comparison of premature patients (solid line) vs. term patients (dashed line) actuarial survival curves. Survival rates at 60 months were 74.0 and 65.4%, respectively. Statistically significant difference was not found between the two curves (Log Rank test: P ¼ 0:88). Patients at risk at any time are indicated in parentheses. 4. Discussion Low birth weight and prematurity are well acknowledged risk factors for mortality in infants with congenital heart disease [11]. Early repair of congenital heart disease offers the theoretical benefits of avoiding the negative hemodynamic effects of congenital heart disease physiology on the heart itself and other organs, which in low weight babies might be less tolerated, thus avoiding progressively more severe and sometime irreversible secondary organ damages. However, if compared with normal weight newborns undergoing cardiac surgery, low weight babies show an increased mortality [9,12]. On the other hand, deferring Fig. 3. Corrected vs. palliated patients actuarial survival. Comparison of corrected patients (solid line) vs. palliated patients (dashed line) actuarial survival curves. Survival rates at 60 months were 74.7 and 64.6%, respectively. Statistically significant difference was not found between the two curves (Log rank test: P ¼ 0:7). Patients at risk at any time are indicated in parentheses.

8 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) Table 5 Re-interventions Catheter Intervention (number of patients) 16 Balloon aortic isthmus angioplasty 5 Balloon aortic valvuloplasty 1 Balloon pulmonary valvuloplasty 2 Balloon pulmonary angioplasty 5 Balloon HG/EG dilatation 3 Balloon ascending aorta angioplasty 1 Balloon common carotid artery angioplasty 1 Hemiazigos coil embolization 1 MAPCA coil embolization 1 Surgery (number of patients) 21 BCPA 6 BCPA pulmonary arteries plasty 3 BCPA RV outflow patch 1 Fontan 3 HG/EG replacement 2 Subaortic stenosis resection 2 Residual VSD closure 1 Mitral valve replacement 2 Mitral valve plasty 1 De-banding PA plasty VSDs closure 1 De-banding PA plasty VSD closure 1 De-banding PA plasty CAVC repair 1 De-banding PA plasty DORV repair 1 Take down BT shunt ToF repair 2 Cath, catheterization; HG, homograft; EG, heterograft; MAPCA, main aortico-pulmonary collateral; BPCA, bidirectional cavo-pulmonary anastomosis; VSD, ventricular septal defect; VSDs, multiple ventricular septal defects; PA, pulmonary artery; CAVC, complete atrio-ventricular canal; DORV, double outlet right ventricle; BT Shunt, Blalok Taussig shunt; ToF, tetralogy of fallot. surgical treatment in order to achieve an increase in body size does not necessarily warrant an increase in survival [10]. Indeed, non-cardiac factors may be associated with low birth weight, and may jeopardize the outcome of surgery, thus requiring careful evaluation [9,12,13,14]. Our study population is composed by patients for whom, due to severely symptomatic cardiac lesions, a conservative approach by intensive medical treatment only, has been judge to be at higher risk in respect to a prompt surgical resolution. The overall 15% in-hospital mortality, comprising palliative and corrective procedures as well as complex cardiac malformations, shows that: an early surgical strategy may be highly rewarding in the treatment of this difficult group of patients. However, in our opinion this does not necessarily mean that every low-weight neonate should be aggressively treated by early surgery, unless intensive medical treatment is required because of severely symptomatic cardiac lesions. Cardio-pulmonary bypass time, aortic cross-clamp time and the use of deep hypothermia with circulatory arrest were the only risk factors found at univariate analysis; whereas No. only the latter resulted as an independent variable associated with early mortality. Prolonged by-pass and aortic cross-clamp time may not constitute risk factors themselves but could simply reflect the more complex type of surgical procedure. Probably, a type II error should be taken into account for what concerns potentially important variables like: type of cardiac malformation, type of surgery (palliation vs. repair), use of cerebral selective perfusion, off-pump vs. on-pump procedures, prematurity or presence of associated noncardiac malformations. Indeed, the 28% mortality of Norwood stage I procedures in our group was fairly higher in respect to the 0% of the patients who underwent repair of aortic coarctation. For the same reason, we have no statistical evidence of complete repair surgery to be at higher risk in respect to palliation, due to the limited number of patients and the relatively high heterogeneity of our study group, which entails palliative operations both as part of a staged monoventricular procedure as well as a bridge before complete biventricular repair. Age at surgery has been reported by Reddy and coworkers (8) to be an important morbidity factor in lowweight infants. We did not find any correlation between age at surgery and surgical mortality ðp ¼ 0:63Þ: Nineteen patients (32%) had associated non-cardiac malformations, the literature reporting a prevalence between 27 and 45% (2,4,6,10 and 15) with an ominous surgical outcome (14). The reduced significance of this variable in our analysis may be due to the low impact on the early postoperative period exerted by the low degree of malignancy of the types of extra cardiac malformations or syndromes found in our study group. Indeed, three patients died late after surgery (one patient with respiratory failure due to Duchenne muscular dystrophy and two other during non-cardiac surgery). Interestingly, bronco-pulmonary dysplasia and tracheo-bronchomalacia were a rare occurrence in our patients, with only one neonate requiring postoperative reintubation and prolonged mechanical ventilation. Similarly, necrotizing enterocolitis and intraventricular hemorrhage [15 17] were not detected in our patient population. Respiratory prematurity-related issues, such as jaline membrane disease, were present in three patients and required preoperative mechanical ventilation. Routine preoperative and postoperative cerebral echographic evaluation allowed us to rule out major neurological complications, particularly intracranial bleeding. Selective cerebral perfusion is our technique of choice for brain protection since 1996, and is currently used in all patients undergoing surgery of the anterior aortic arch. While no definitive statement may be drawn from a limited experience in such a heterogeneous group of high risk patients, our study shows that primary complete repair may be achieved with an acceptable mortality (15.6% in our group), with no difference in respect to palliation in patients with anatomy potentially amenable

9 52 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) to biventricular repair (20.0% in our group). Similarly, the 11.1% mortality of surgery in single ventricle-physiology shows that a definitive monoventricular palliation may be undertaken even in the setting of high risk low-weight neonates. In conclusion, even thought the management of low birth weight and premature infants still represents a major challenge for all who take care of such patients, surgical treatment of their congenital malformations should be undertaken as soon as satisfactory hemodynamic stability and major organs recovery is achieved, with enhanced, but still acceptable early and mid-term morbidity and mortality Limits of our study Limits of our study are certainly represented by the relatively small number of patients, and the nature of any retrospective study. In order to achieve a fair number of patients to be included into univariate and multivariate analysis, a decision was made to unify patients who underwent surgery with and without cardiopulmonary bypass, thus leading to a difficult interpretation of the statistical results and potential underestimation of potentially important variables. However, our study group represents a difficult and relatively rare type of patient with congenital heart disease, which deserves a multicentric study collecting a large number of cases. References [1] Fyler D. Report of the New England regional infant cardiac program. Pediatrics 1980;65: [2] Kramer HH, Trampisch HJ, Rammos S, Giese A. Birth weight of children with congenital heart disease. Eur J Pediatr 1990;149: [3] Rosenthal GL, Wilson PD, Permutt T, Boughman JA, Ferencz C. Birth weight and cardiovascular malformations: a population-based study. Am J Epidemiol 1991;133: [4] Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neil CA, Perry LW, Hepner SI, Downing JW. Congenital heart disease: prevalence at live birth (the Baltimore Washington Infant Study). Am J Epidemiol 1885; 121:31 6. [5] Levy RJ, Rosenthal A, Fyler DC, Nada AS. Birth weight of infants with congenital heart disease. Am J Dis Child 1978;132: [6] Rossi AF, Seiden HS, Sadeghi AM, Nguyen KH, Quintana CS, Gross RP, Griepp RB. The outcome of cardiac operations in infants weighing two kilograms or less. J Thorac Cardiovasc Surg 1998;116: [7] Beyens T, Biarent D, Bouton JM, Demanet H, Viart P, Dessy H, Deville A, Lamote J, Deuvaert FE. Cardiac surgery with extracorporeal circulation in 23 infants weighing 2500 g or less: short and intermediate term outcome. Eur J Cardio-thorac Surg 1998;14(2): [8] Reddy VM, McElhinney DB, Sagrado T, Parr AJ, Teitel DF, Hanley FL. Results of 102 of complete repairs of congenital heart defects in patients weighing grams. J Thorac Cardiovasc Surg 1999; 117: [9] Pawade A, Waterson K, Laussen P, Karl TR, Mee RBB. Cardiopulmonary bypass in neonates weighing less than 2.5 kg: analysis of the risk factors for early and late mortality. J Card Surg 1993;8:1 8. [10] Chang AC, Hanley FL, Lock JE, Castaneda AR, Wessel DL. Management and outcome of low birth weight neonates with congenital heart disease. J Pediatr 1994;124: [11] Kecskes Z, Cartwright DW. Poor outcome of very low birthweight babies with serious congenital heart disease. Arch Dis Child Fetal Neonatal Ed 2002;87:F31 3. [12] Wernovsky G, Rubenstein SD, Spray TL. Cardiac surgery in the low birth weight neonate: new approaches. Clin Perinatol 2001;28(1): [13] Reddy VM, Hanley FL. Cardiac surgery in infants with very low birth weight. Semin Pediatr Surg. 2000;9(2):91 5. [14] Numa A, Butt W, Mee RB. Outcome of infants with birth weight or less who undergo major cardiac surgery. J Paediatr Child Health 1992; 28: [15] Dees E, Lin H, Cotton RB, Graham TP, Dodd DA. Outcome of preterm infants with congenital heart disease. J Pediatr 2000;137: [16] Leung MP, Chau KT, Hui PW, Tam AYC, Chang FL, Lai CY, Yeung CY. Necrotizing enterocolitis in neonates with symptomatic congenital heart disease. J Pediatr 1988;113: [17] Hebra A, Brown MR, Hirschl RB, McGeehin K, O Neill JA, Norwood WI, Ross AJ. Mesenterich ischemia in hypoplastic left heart syndrome. J Pediatr Surg 1993;28: Appendix A. Conference discussion Dr T. Ebels (Groningen, The Netherlands): This paper is on 60 patients. Are these all patients in the period from 1993 to 2002, or were there other patients not included in the study, that had deferred treatment of any sort? Dr Oppido: These are 60 consecutive surgical patients. We did not collect all the babies who died before the operation or who were not referred for surgery because of major non-cardiac clinical issues. Moreover, we excluded all the premature and low birth weight babies for whom urgent surgery was not indicated, or who reached a body weight superior to 2500 grams at the time of surgery. Therefore, our population is composed by 60 consecutive patients who needed urgent surgical treatment because of heart failure or some kind of ductus dependent congenital cardiac malformation. Dr M. Pozzi (Liverpool, UK): Would you be able to point out a cutoff point in terms of weight with regards to seeing a difference in postoperative complication, and in particular, neurological complication? Dr Oppido: All of our patients were routinely screened with brain ultrasound to rule out the presence of either preoperative or postoperative neurological complications, which were excluded in all cases. Dr T. Bottio (Padova, Italy): Did you support any one of these patients with ECMO? Dr Oppido: No, we did not. Dr B. Maruszewski (Warsaw, Poland): Maybe I haven t noticed, but was one of your variables the date of the operation? Did the date of the operation influence the outcome that you studied? Were patients operated earlier, for example, in your time span? Did they do better or worse? Was there any change depending on the date of the operation? Dr Oppido: We know from the literature that the earlier those patients are operated the less complications seem to occur in the postoperative period. We did not observe this in our patient population. We rather believe that a major effort in order to stabilize the patient before surgery is warranted, regardless the time needed.

10 G. Oppido et al. / European Journal of Cardio-thoracic Surgery 26 (2004) Dr Ebels: I don t think this is an answer to the question. The question is whether you performed better earlier in your experience or worse? Was there a learning curve? Dr Oppido: Yes, there was a learning curve in our experience. Dr Maruszewski: But was it one of the variables? Dr Oppido: No it was not. Dr R. Bartkowski (Poznan, Poland): Have you had any experience with hemofiltration or dialysis in this group of patients, renal failure or any problems? Dr Oppido: Acute renal failure occurred in 6 patients, but none of them underwent any sort of hemofiltration or dialysis. Dr F. Lacour-Gayet (Denver, CO, USA): I noticed in your analysis that deep circulatory arrest was a risk factor. My question to you is, do you avoid circulatory arrest and go to palliation or do you use full flow? Dr Oppido: Deep hypothermia with circulatory arrest has been only adopted before 1996 and for the treatment of hypoplastic left heart syndrome or interrupted aortic arch, as it was for the 9 reported patients. Whereas, cerebral selective perfusion is the current technique of choice since 1996.