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Eur J Cardiothorac Surg 1998;13:520-525
© 1998 Elsevier Science NL

When is extracorporeal life support worthwhile following repair of congenital heart disease in children?

Wessex Cardiothoracic Centre, Southampton, UK

Received 18 November 1997; received in revised form 9 February 1998; accepted 16 February 1998.

Corresponding author. Department of Perfusion, E Level Theatres, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Tel.: +44 1703 796930; fax: +44 01703 796614.

	Abstract

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
Background: Although the use of extracorporeal life support (ECLS) following repair of congenital heart defects in children is increasing, the criteria for ECLS usage in these patients is not well defined. The overall survival of such patients is disappointingly low and may depend on both the indication for support and the time at which ECLS is commenced. Methods: Between January 1993 and December 1996, 727 children underwent surgery for congenital heart defects at our institution with an overall hospital mortality of 5.8% (42 children). Nine of these children were treated with ECLS postoperatively. There were seven males and two females with a mean age of 7.2 months (range 2 weeks–3 years). Seven children could not be weaned from cardiopulmonary bypass (CPB) in the operating theatre. A further two were treated with ECLS later on during the postoperative period (commenced at 14 and 48 h). Full veno-arterial extra corporeal membrane oxygenation (ECMO) support was used in all children except one in whom a left ventricular assist device (LVAD) was used. Results: The median duration of support was 121 h (range 15–648 h). Four children (44%) were weaned from support and two of these are long-term survivors. Of the seven children in whom ECLS was instituted because of failure to wean from CPB, there was one long term survivor (LVAD support). Of the two patients in whom ECLS was instituted during the post-operative period there is one long-term survivor. Conclusions: Weaning form ECLS and decannulation in 44% of our patients is comparable to other series of post-cardiotomy patients requiring ECLS. However, full veno-arterial ECMO instituted because of a failure to wean from CPB during corrective surgery is associated with an extremely poor outcome (zero long-term survivors in six patients).

Key Words: Congenital heart disease • Extra corporeal membrane oxygenation • Life support

	Introduction

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
The use of extracorporeal life support (ECLS) following repair of congenital heart disease has increased since its' first use in 1973 [1]. In the 1980s the rate of increase was almost exponential [2]. The use of extracorporeal membrane oxygenation (ECMO) for respiratory failure in non-cardiac paediatric patients is well established and has an overall survival of 50% (81% in neonates) [3]. Overall survival for paediatric patients receiving ECLS for cardiac support is reported as 44% by the Extracorporeal Life Support Organisation in 1994 [3]. The term survival, however, equates to weaning from support and does not necessarily reflect the number of patients who leave hospital or those who are alive at one year following support for example. Furthermore, although `survival' data is given according to preoperative diagnosis, no indication is given to the precise indication for ECLS. This is clearly important as results vary widely according to indication for support.

Although criteria for ECMO usage in respiratory failure are clearly defined, this is not the case with patients undergoing cardiac support. In congenital heart surgery, the use of ECLS may have a number of indications including; preoperative support [4], failure to wean from cardiopulmonary bypass (CPB) [4] [5] [6] [7], pulmonary hypertension [8], cardiac arrest post-operatively [9], or as a bridge to cardiac transplantation [10]. These are all distinct groups and reported results vary not only between these groups but also within these groups, when different series are compared.

This paper summarises our experience with ECLS in paediatric patients with myocardial dysfunction unresponsive to conventional medical management following repair of congenital heart disease.

	Materials and methods

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
Between January 1993 and December 1996, 727 children underwent surgery for congenital heart disease using cardiopulmonary bypass at the Wessex Cardiothoracic Centre. The overall 30 day mortality was 5.8% (42 children). Nine children (1.2%) were commenced on ECLS post-operatively. There were seven males and two females with a mean age of 7.2 months (range 2 weeks–3 years) and mean weight of 6.6 kg (range 3.0–16.0 kg). The preoperative diagnosis and support details are summarised in Table 1.

Two patients were commenced on ECLS post-operatively having been successfully weaned from CPB in the operating theatre. One patient developed profound myocardial failure 14 h post-operatively and the other had a cardiac arrest secondary to pericardial tamponade 48 h post-operatively. These two patients both underwent full venoarterial ECMO.

	ECLS technique

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
In all patients treated with ECMO, access was by the venoarterial route through the operative median sternotomy. Venous drainage was achieved via the right atrium using a single DLP (DLP, Grand Rapids, MI, USA) straight wire reinforced cannula. The oxygenated blood was returned into the ascending aorta through a DLP wire reinforced arterial cannula. In patients unable to be weaned from conventional CPB the cannulae were already in place and patients were transferred from CPB to ECMO by merely switching the cannulae connections to the ECMO circuit.

In all patients the ECMO circuit ( Fig. 1 ) consisted of a hard shell venous cardiotomy reservoir and a Biomedicus (Biomedicus, Minneapolis, MN, USA) centrifugal pump. In three of the patients a Dideco (Dideco, 41037 Mirandola (Mo) Italy) D701 hollow fibre membrane oxygenator was used and in all other patients a Jostra (Jostra Medizintechnik. Hirrlingen. Germany) M8 or M16 diffusion membrane oxygenator used; both types have an integral heat exchanger which was used to maintain a core temperature of 35°C. The Dideco oxygenator was routinely changed every 48 h in order to prevent plasma leakage through the hollow fibres. The Jostra silicone plate oxygenators were not changed. Blood gas analysis was carried out hourly. The sweep gas was oxygen enriched air with the gas flow rate adjusted to maintain a PaCo₂ of 4.5 to 5.5 kPa and the FiO₂ adjusted to keep the PaO₂ between 20 and 30 kPa.

View larger version (24K): [in this window] [in a new window]   Fig. 1. ECLS circuit.

Anticoagulation was achieved by continuous heparin infusion maintaining an activated clotting time of 180–200 s. The haematocrit was maintained at 30–35% and the platelet count greater than 100 000/mm³. Transfusions of packed cells or platelet concentrate were given as required.

ECMO flow was maintained between 100 to 200 ml/kg per min throughout the period of support. Our standard flow during routine CPB in this age group is 100–120 ml/kg per min. The higher flows on ECLS theoretically increase capillary velocity therefore improving tissue perfusion. Higher flow rates were determined by measurement of the anion gap. At full flow, lung ventilation was reduced. Patients were ventilated, on air, at low frequency (10 breaths/min) with a tidal volume of 10 ml/kg and low pressure (20 cm H₂O) with positive end expiratory pressure (PEEP) of 4–10 cm H₂O.

The mean arterial pressure was maintained over 50 mmHg. Renal dopamine (2–3 µg/kg per min) and dobutamine (5 µgkg per min) were continued to help maintain myocardial contractility with the hope of consequently reducing myocardial oedema. The absence of acidosis, evidence of good or improving ventricular function assessed daily by echocardiography, satisfactory visual inspection of the heart in cases where the chest was open and improving haemodynamics are our usual criteria for weaning. When appropriate, flow was reduced by 10% per hour to maintain haemodynamic stability.

Broad spectrum prophylactic antibiotic therapy was avoided. Blood and urine cultures and bronchial aspirates were performed daily. Antibiotic therapy was tailored due to specific infections. Nutrition was commenced 24–48 h after institution of ECLS. The enteral route was used preferentially unless the feed was poorly absorbed when parenteral nutrition was commenced instead. When urine output fell below 3ml/kg per h either frusemide or mannitol were given to promote diuresis. Patients who were persistently oliguric or anuric received peritoneal dialysis (PD) or underwent ultrafiltration. In the PD group where more vigorous fluid removal was required a haemoconcentrator was also used. During ECLS patients were paralysed and sedated using morphine and midazolam at 20–100 µg/kg per h.

	Results

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
The median duration of support was 121 h (range 15–648 h). Inability to wean from ECLS resulted in death in five of the nine patients. Recovery of cardiac function sufficient to allow decannulation from ECLS was seen in four patients. Of these four only two are long term survivors. Patient 4 died 2 months following weaning, from bronchopneumonia on a background of severe myocardial dysfunction. Patient 9 had a rapid deterioration in myocardial function just 2 h after deccanulation following 123 h of support. ECLS was not reinstituted as recovery from the myocardial dysfunction, even with further support, was considered by all attending surgeons and physicians to be beyond reasonable hope. The two remaining patients who were successfully weaned from ECLS were discharged from hospital and are currently alive and without symptoms 16 and 29 months later. One of these (patient 7) failed to wean from CPB and spent 89 h on LVAD, the other was treated with full venoarterial ECMO following cardiac arrest postoperatively. Both long term survivors are girls. All six patients commenced on full venoarterial ECMO because of failure to wean from CPB have died. The cause of death of each patient was established at post mortem, These were myocardial failure in four patients, one died from irreversible pulmonary hypertension and the other from bronchopneumonia. Patient 1 was treated early in our series. He died of bilateral pulmonary haemorrhage, after just 15 h of support.

Three patients had an incomplete repair of the congenital defect. This is defined as a repair requiring a further corrective procedure on CPB at the time of the first operation or during a second operation [5]. In addition to TGA requiring a Switch procedure, patient 1 had unrecognised multiple VSDs which required a further repair at the time of the first operation. Patient 4 developed a regurgitant atrio-ventricular valve after AVSD closure requiring mitral valve replacement at a second operation. Patient 6 has a residual atrial septal defect after a Switch procedure requiring closure at a second operation.

Four patients required re-exploration of the mediastinum for bleeding. This includes patient 8 who had a cardiac arrest secondary to tamponade after displacement of the left atrial line. The three other patients re-explored for bleeding had a number of mediastinal bleeding points requiring diathermy. In no case was the bleeding related to the cannulation sites. Seven patients required dialysis because of renal impairment. Six of these were treated with peritoneal dialysis alone. This was instituted early, prior to biochemical evidence of renal failure, when there was evidence of a decline in the urine output (<2 ml/kg h) and always when the child had been anuric for more than two hours. One child was treated with haemofiltration. Three patients had a ventricular fibrillation arrest requiring defibrillation. Sepsis developed in five patients whilst on ECLS. This was defined as a patient with a raised white cell count in the presence of positive blood and/or sputum or urine cultures requiring specific antibiotic treatment.

In addition, clinical evidence of infection was also present in three patients who developed chest infections. No patients developed mediastinitis. Patient 4 developed pulmonary hypertension on ECLS and was successfully treated with nitric oxide. Pulmonary haemorrhage as evidenced by fresh blood in the endotracheal tube was confirmed bronchospically in one patient. Seizures were noted in one patient but there were no other neurological complications.

	Discussion

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 
In paediatric patients with myocardial dysfunction following cardiac surgery there are a number of management options. Our first line of treatment in these patients is induced hypothermia using a cooling blanket to achieve a core temperature of 32–33°C [11]. Those who fail to respond to maximal medical therapy and who cannot be weaned from CPB in the operating theatre present a particular problem. ECLS as a technique of cardiac rescue is invasive, expensive, has a high complication rate and a variable and often unpredictable outcome. If the myocardial dysfunction is considered reversible however, then ECLS may be the only option available to such patients.

The overall survival for paediatric patients receiving ECLS for cardiac support has been reported as 44% [3]. The distinction between postcardiotomy patients commenced on ECLS because of failure to wean from CPB or because of myocardial dysfunction at some point following successful weaning is important.

In most series, survival is greater when ECLS is instituted at some point after successful weaning from CPB [3] [4] [7] [12] [13] [14] [15] [16] (Table 2). Other series group all postcardiotomy patients together and survival is given for the whole group [5] [9] [17] [18] thus making comparison with other series more difficult. The best results in the larger of the series are reported by Ziomek et al. [7] who has 47% survival in patients who could not be weaned from CPB. Five of these patients underwent ECLS for pulmonary hypertension and furthermore the overall usage of ECLS in this series is 6.8% [7]. A relatively higher usage than in most series is reported by Raithel et al. [14] in which 8.4% of paediatric patients required ECLS following cardiac surgery [14]. This highlights the difficulties of direct comparison between series.

Ferrazzi et al. [6] however, reported six patients treated with ECLS. Two patients were commenced on support in the operating theatre because of failure to wean from CPB and both are survivors. The four other patients commenced on ECLS later, all died. They conclude that early institution of mechanical support is the key to survival with ECLS [6].

Our relatively low use of ECLS post cardiac surgery (1.2%), reflects our policy for induced hypothermia in the management of refractory low cardiac output states following cardiac surgery in infants and children [11].

Patients with an incomplete repair do very badly. Black reports 100% mortality in this group [5]. All three patients in our series who met this definition died. Complete surgical repair should be a prerequisite for instituting ECLS and intraoperative transoesophageal echocardiography should be performed in all cases before ECLS is contemplated.

Patients who suffer intractable cardiac arrest after cardiac surgery represent a somewhat different population than the more commonly seen patients with postcardiotomy low output failure. In our series, one patient suffered cardiac arrest and is a long term survivor. In a series of 11 patients, del Nido et al. [9] [10] reported early survival of 64% and long term survival of 55% following sudden cardiac arrest in the postoperative period [9]. Patients requiring ECLS following cardiac arrest would therefore appear to be in a somewhat better prognostic group.

ECLS instituted to treat critical pulmonary hypertension has encouraging results with one series reporting five patients (three postcardiotomy) with 100% survival. The three surgical patients underwent ECMO support at a mean of 48 h (range 28–78) after coming off CPB [8].

The efficacy of inhaled nitric oxide in the treatment of severe pulmonary hypertension accompanying congenital heart disease is now well established [19] and has been used at the Wessex Cardiothoracic Centre for the past 4 years. It is now our first line of treatment in these patients.

The duration of ECLS has been shown to affect survival. Black showed that no patients survived when on support for over six days [5]. Our results also bear this out with the survivors being supported for 89 and 49 h. Longer periods of support are perhaps only really justified as a bridge to transplantation. Other series do have survivors when periods of support up to 10 days have been used [10] [18]. However, in his series of 54 children supported on ECMO for cardiac failure del Nido observes that the majority of children who eventually recover sufficient contractile function that they are weaned from mechanical support, do so within 48–72 h [10].

In our series, no patients had venting of the left ventricle. This is considered by some authors to be an important part of ECLS in order to ensure complete decompression of the left side of the heart. Not all agree however, including Ziomek et al. [7] whose overall results are better than any other series. Ventricular overdistension was minimised by maintaining a low central venous pressure, adequate venous outflow and high ECMO flow rates. Failure to completely decompress the left ventricle will result in elevation of the left ventricular end diastolic pressure particularly when left ventricular function is markedly decreased and forward pulsatile flow is minimal.

This may lead to a reduction in coronary perfusion to the subendocardial layers of the left ventricle and may provide inadequate rest and support for the left ventricle. The left ventricle, therefore, may not be optimally rested during ECLS. We believe that decompression of the left ventricle in cases of obvious biventricular failure is advisable and have modified our technique to this effect.

There were six complications, one fatal associated with bleeding in our series. Some series have reported almost 70% of patients having bleeding complications [15]. Meticulous haemostasis and close monitoring of the ACT and platelet count are essential in keeping these complications to a minimum. Some authors believe that heparin-coated surfaces circuit components would decrease dependence on systemic heparinisation thereby reducing bleeding complications [17]. Whilst the circuit is `anticoagulated' in this situation the patient is not and the risk of thrombus formation in the poorly contracting heart is not insignificant. We would therefore advocate systemic anticoagulation in all patients on ECLS. Heparin titration must be based on whole blood ACT rather than the activated partial thromboplastin ratio (a measurement in plasma) because of the effects of platelets on heparin response. When the platelet count is high more heparin is required to achieve the same degree of anticoagulation. If the APTR is used, too little heparin will be given initially and too much later when the platelet count drops. If fibrin degradation products increase, the clotting times are prolonged and heparin dosage must therefore be reduced.

It is more satisfactory and results in less bleeding from open surfaces, however, to infuse fresh frozen plasma to keep clotting factors at normal levels rather than reduce the heparin dose [20].

The use of ECLS in children with cardiac failure following cardiac surgery has had limited success in our series. This is largely due to residual anatomical defects and the irreversible nature of cardiac injury. Once the myocardial architecture is destroyed no amount or duration of support will enable tissue to regenerate and recover. Reversibility of heart dysfunction is a key determinant to the success of ECLS. We believe that increased experience with ECLS would improve our results, just as it has at other centres [14] [18]. We hope that as more experience with the use of ECLS in the postoperative period is gained, the relative indications and contraindications will become more defined.

In conclusion, we recommend induced hypothermia as the first line technique for the management of myocardial dysfunction in the postcardiotomy paediatric patient. If this is unsuccessful, then, having demonstrated echocardiographically that the surgical repair is complete, we would initiate ECLS. Despite the poor results in patient who could not be weaned from CPB we would currently advocate the use of ECLS for a period of up to 5 days providing improvement was realistically anticipated. If however, after this time there was no significant improvement in myocardial function we would not recommend its continued use.

	References

Top Abstract Introduction Materials and methods ECLS technique Results Discussion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Stephen M. Langley Stuart V. Sheppard Victor T. Tsang James L. Monro Robert K. Lamb Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langley, S. M. Articles by Lamb, R. K. Search for Related Content PubMed PubMed Citation Articles by Langley, S. M. Articles by Lamb, R. K.