Eur J Cardiothorac Surg 2004;25:605-609
© 2004 Elsevier Science NL
Mechanical versus medical bridge to transplantation in children. What is the best timing for mechanical bridge?
Shekar L.C. Reddy*,
Asif Hasan,
Leslie R.J. Hamilton,
John Dark,
Stephan W. Schueler,
David T. Bolton,
Simon R. Haynes,
Jon H. Smith
Department of Cardiac Surgery, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK
Received 16 November 2003;
received in revised form 20 January 2004;
accepted 21 January 2004.
* Corresponding author. Address: 40 Langham Close, North Baddesely, Southampton, Hampshire, SO52 9NT United Kingdom. Tel.: +44-2380-731674; fax: +44-2380-731674
e-mail: reddylcs{at}aol.com
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Abstract
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Objective: Precise timing of mechanical circulatory support as a bridge to transplantation is crucial for successful outcome. In our practice, increasing metabolic injury resulting from third organ (renal/gut) dysfunction is an indication for mechanical circulatory support. It is not known how metabolic injury would influence the outcomes in these patients. In this study we compared biochemical and clinical parameters between children who received mechanical circulatory support and those who were treated with medical management alone as a bridge to transplantation. Methods: Data from 24 patients were retrospectively analysed from their records. There were 11 patients in the mechanical group. In this group, five patients received biventricular assist device, five received veno arterial extra corporeal membrane oxygenation and one received left ventricular assist device. In the medical group, there were 13 patients who received various levels of inotropic support before transplantation. Five clinical and three biochemical parameters were identified and compared between the mechanical and medical groups. Mortality prior to transplantation was also compared between the two groups. Transplantation was the end point of the study. Results: Serum creatinine and serum lactate levels were significantly higher in the mechanical group (P=0.006 and 0.001, respectively), reflecting advanced metabolic injury in these patients. Mean fractional shortening in the mechanical group was 8.4%, compared to 14.5% in the medical group which was statistically significant (P=0.02). All of the 11 patients in the mechanical group were ventilated compared to 7 of the 13 (53.8%) in the medical group. Need for renal support was higher in the mechanical group (83.3%) in comparison to none in the medical group (P=0.023). Mortality in both groups was comparable with two patients in each group. 11 patients in the medical group (84.6%) and 9 in the mechanical group (81.8%) reached transplantation. Conclusion: This study confirmed that patients in the mechanical group were considerably worse in metabolic terms when compared to the medical group. Final outcome of bridging them to transplantation was comparable. This study seem to support the justification of reserving the mechanical circulatory support to those who are metabolically more injured without adversely affecting their outcomes.
Key Words: Mechanical circulatory support • Timing for mechanical support • Children • Metabolic injury • Biventricular assist device • Left ventricular assist device • Veno arterial extra corporeal membrane oxygenation
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1. Introduction
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Mechanical circulatory support in children as a concept of bridge to transplantation is well established. Experience with such devices in children is growing as evident from the reports in the literature [1–9]. However, this experience is limited to a few exclusive centres in the world. Precise timing of establishing mechanical circulatory support is crucial to a successful outcome in these children. This decision making is largely based on the clinical condition of the patient but is also influenced by the past experience of the institution. While each institution has its own agreed criteria for instituting mechanical circulatory support, there are no universally agreed criteria for the timing of such intervention. In our institution, evidence of third organ dysfunction, mostly renal and rarely gut, reflected in increasing metabolic injury remains the criteria for making a collective decision to institute mechanical circulatory support. Yet we do not know if this policy has been correct in determining the timing of such devices. In this study we aimed to review our data in relation to the precise timing of mechanical circulatory support.
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2. Materials and methods
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During a period of 6 years (1996–2001), 24 children were admitted with acutely failing circulation. Data of these 24 patients were retrospectively analysed in this study. These children were treated with an intention to offer cardiac transplant at the earliest opportunity. Mechanical circulatory support was necessary in 11 of these patients to bridge them to transplantation. These 11 patients form the mechanical group. Timing of this intervention was made collectively, based on the clinical need and urgency in each patient. All these patients were on maximum medical therapy and with respiratory support. Evidence of failing third organ resulting in evidence of increasing metabolic injury was the main criteria. While renal impairment was the main issue in most of these patients, gut dysfunction formed a minor criterion. Intravenous feeding was given to those who could be supported for a reasonable length of time before a decision for mechanical circulatory support. Two patients in the medical group were supported with intravenous feeding avoiding immediate intervention. The remaining 13 patients were treated with medical therapy and form the medical group. The aim of this study was to investigate the appropriateness of timing of mechanical support in these patients. End point of the study was transplantation. Mortality in both groups before the end point of the study was compared. To compare the clinical severity of the patients various parameters were identified. These include: ventilatory status, fractional shortening of myocardium, right atrial venous saturation, renal support and need for intravenous feeding. Three biochemical parameters included were: serum creatinine, serum lactate and serum bilirubin levels. Data from the mechanical group at the time of decision to institute mechanical circulatory support were compared with the data in the medical group at the time of transplantation. Due to the small number of patients involved in this study, Fisher's exact test with two-tailed P value was used to compare the categorical variables. 2-Sample t-test was performed on continuous variable. P value of <0.05 was considered significant.
Of the 11 patients in the mechanical group, 5 received biventricular assist device (BiVAD) with Medos (Helmholtz Institut Aachen) device and one patient received left ventricular assist device (LVAD) with Haemopump (Johnson and Johnson). Five patients in this group received veno arterial extra corporeal membrane oxygenation (VA ECMO) with standard membrane oxygenator and non-heparinised circuit. In the medical group, first line inotropic support was a combination of milrinone (0.3–0.75 µg/kg per min-1) and dobutamine (5–20 µg/kg per min-1). Adrenaline was used as a second line inotropic support (0.01–0.10 µg/kg per min-1). Starting at their lowest dose, incremental increases were made tailoring to the response of each patient. After load optimisation was achieved with Ace inhibitors or vasoconstrictors such as noradrenaline and ephedrine to achieve optimum tissue perfusion. Pre-load optimisation was through judicious management of fluid intake and diuretics. All the patients in this study received medical treatment initially. Mechanical circulatory support was instituted for those patients who had reached maximum stipulated dosage of milrinione, dobutamine and adrenaline (as cited earlier) and had evidence of increasing metabolic injury. BiVAD was preferred when fully functional lungs and vascular anatomy were favourable for VAD cannulation. Four patients received VA ECMO because of the pulmonary artery or aortic vascular anomalies. In our earlier experience with VADs, arbitrary decision was made to treat children under 10 kg of weight with VA ECMO for the ease of cannulation and lack of appropriate sized paediatric VAD ventricles. One patient in the ECMO group qualified under these criteria. With availability of paediatric sized VAD ventricles and accumulated experience this policy has now been revised. One patient in the mechanical group received LVAD which was our first attempt of mechanical support. This patient received Haemopump (Johnson and Johnson) but succumbed to a total loss of vasomotor tone despite all extreme attempts to achieve vasoconstriction. Since then five patients have received Medos BiVAD.
Development of major complications such as neurological injury, sepsis, bleeding and thromboembolism which preclude transplantation were avoided by strict adherence to the protocols. Anticoagulation was managed by a loading dose of heparin (0.2 mg/kg) prior to cannulation or VAD insertion, followed by heparin infusion to keep the ACT between 150 and 180 s. Post-cardiotomy patients did not receive any form of anticoagulation for the first 24 h but a close watch was kept on the ACT results. ECMO circuits and VAD devices were closely inspected to detect thrombus formation. The artero-venous bridge link in the ECMO circuit was regularly released to avoid stasis and clot formation. Similarly, VAD ventricles and joints between the ventricle and cannulae were inspected on an hourly basis. Daily cultures were taken from the ECMO circuit and it was changed at the slightest suspicion of sepsis. A single dose of flucloxacillin was given at the time of ECMO cannulation or VAD insertion. Daily cultures were taken from all potential sources of infections including ECMO circuit, central venous lines and entry points of the VAD cannulae. Daily prophylactic antibiotics were avoided but a strict screening process and early treatment with appropriate antibiotic was adopted.
Descriptive data such as sex distribution, age, weight, diagnosis and duration of support in the total study group and in the medical and mechanical groups are summarised in Table 1. Values for age, weight, duration of support and duration of post-transplant ITU stay are given as mean, median and range. In view of the small numbers involved in this study, emphasis is placed on the median and range values.
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3. Results
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Mean serum lactate levels in the mechanical group was 6.9 mmol/l compared to 3.3 mmol/l in the medical group (P=0.001). Serum creatinine was also significantly elevated in the mechanical group, 166 mmol/l against 79 mmol/l in the medical group (P=0.006). Both these reflect a significant metabolic injury of patients in the mechanical group. Fractional shortening percentage in the mechanical group was 8.4 compared to 14.5 in the medical group (P=0.02). This reflected the advanced state of myocardial dysfunction in the mechanical group. Renal support with haemofiltration was incorporated in the ECMO circuit of all the patients in the ECMO group (5). None in the medical or VAD group was given renal support. All the patients in the mechanical group (11) were ventilated compared to 7 (53.8%) in the medical group (P=0.013). Mean venous saturation of right atrial blood in the mechanical group was 35% compared to 49% in the medical group (P=0.007). Serum bilirubin levels was slightly higher in the medical group but failed to reach statistical significance. Intravenous feeding was given to four patients in the mechanical group compared to two in the medical group which was not a significant difference.
Comparative data between both groups are summarised in Table 2. Continuous data are given as mean, median and standard deviations.
There were two mortalities in both mechanical and medical groups. The patient who received haemopump LVAD in the mechanical group died 12 h after the procedure. This was our first attempt of mechanical support and this patient suffered a complete lack of vascular tone. Our first Medos BiVAD patient was found to have displaced the left atrial cannula on the 3rd post-procedure day. In an attempt to re-position the cannula, opening the chest resulted in massive air embolism and death. Trans mitral cannulation through left atrial approach proved difficult with earlier cannulae. Following this experience, we changed to left ventricular apical cannulation which proved technically superior because of improved sewing cuff. In the medical group, two patients succumbed to sepsis precluding transplantation. The second patient in this group had a failed cardiac transplant with high antibody titres against minor blood group antigens and finding a suitable donor organ proved difficult. Offering mechanical support to this patient posed an ethical dilemma before the onset of sepsis. Of the nine patients in the mechanical group who reached transplantation, eight survived and one from the ECMO group suffered a significant neurological injury. In the medical group of 11 patients, 10 survived and one succumbed to acute rejection.
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4. Discussion
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Instituting mechanical circulatory support is one of the most important clinical decisions any medical team is faced with making. Failing circulation and deteriorating tissue perfusion will determine the urgency for such an intervention. Other factors such as availability of appropriate device and experience in using them will also influence such a decision. Delay in supporting circulation will lead to continued metabolic injury which may prove irreversible, while an early decision may commit a patient to a mechanical device with all its attending complications along with a considerable commitment of monetary and manpower resources. Unpredictability of donor organs availability adds a dimension of gamble to this situation. The level of metabolic injury acceptable in a patient is a difficult entity to define, hence, the importance of accurate timing of mechanical devices to achieve a favourable outcome. It is unethical and impractical to conduct case control prospective studies in such areas of clinical practice. Sharing information with other institutions offers a means of addressing some of the issues.
Mechanical support as a bridge to myocardial recovery is reported. Hetzer et al. [9] in their series reported that two of the five patients with myocarditis recovered enough to withdraw mechanical support. Duncan et al. [6] in their large series reported 67% (45/67) in the ECMO group and 66% (19/29) in the VAD group, achieved myocardial recovery facilitating withdrawal of mechanical support. In another series by Duncal et al. [7] they reported a recovery rate of 60% (9/15) in patients with fulminant myocarditis treated with mechanical support. In our small series, we do not have cases that recovered adequately to withdraw mechanical support. This, we feel, may partly reflect on our patient selection criteria. There were three patients with proven viral myocarditis and two were supported with BiVAD for 8 and 29 days. The third patient was medically treated for 33 days. All three patients reached transplantation. Myocardial biopsy to diagnose viral myocarditis is not a routine practice in our institution and it is possible that some of the cases may have been mislabelled. If an earlier institution of mechanical support in some of these patients would have resulted in recovery, remains a difficult point to address. Hetzer et al. [9] suggested that an earlier utilization of these devices is now justifiable. To date, there are no data to support the view that such a practice would either hasten cardiac recovery or reduce the need for transplantation. In our small series of patients, our cautious approach seem to have resulted in comparable outcomes with other published results. Duncan et al. [6] showed an overall survival of 40% in their mechanical group. Failure of metabolic recovery after 24 h was associated with increased mortality in their study. Hetzer et al. showed a 57% survival in their BiVAD group. Both these studies are their early results.
Inability to wean cardiopulmonary bypass and cardiac failure following cardiac surgery pose a difficult choice for mechanical support. Hetzer et al. [9] argued that post-cardiotomy patients had poor results and offering mechanical support to these patients may not be appropriate. In our series four patients with post-surgical cardiac failure were treated with ECMO for periods ranging 1–16 days and all reached transplantation. Pedro J. del Nido et al. [5] reported five survivors out of seven who were treated with mechanical support for cardiac failure following surgery for anomalous origin of left coronary artery from pulmonary artery (ALCAPA). This view is also partly supported by Duncan et al. [6] who reported a survival of 26.3% (10/38) in this group of patients. Our experience supports this view and we feel that with appropriate patient selection, children with post-surgical cardiac failure should be offered mechanical support with a view to recovery or transplantation.
Results in our series confirm our belief that moderate metabolic injury before instituting mechanical circulatory support will not adversely influence the outcome in these patients. However, defining moderate metabolic injury is difficult and is partly based on the intuitive feelings of the medical team. With accumulating experience in using such mechanical devices, a choice to utilise these earlier may become apparent. Some institutions may already be facing that choice. To some extent, this may be influenced by the economic climate under which they function. So far our data have supported our practice and helped us avoid making that leap to earlier usage of these devices.
4.1. Limitations of the study
This study is based on a small number of patients. The statistical power to be drawn from such small numbers is limited. This resulted in an element of observational connotation in the conclusions stated. This study also fails to answer the question posed in its title directly. Inference is drawn from a perceived similarity in the survival of both the groups of patients, thus justifying our practice. We hope to make this study relevant in generating discussion between the two notions of earlier or delayed usage and to enquire about the need to change one's practice without convincing evidence to do so.
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5. Conclusions
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The data from this study confirm that the patients in the mechanical group were considerably worse in metabolic terms when compared to the medical group. Outcome in both groups is comparable with two mortalities in each group. In the mechanical group, our initial lack of experience contributed to the mortality. Data from this small cohort of patients concludes that the outcomes in the mechanical group are not affected in the presence of metabolic injury. The post-transplant recovery periods (ITU stay) in both groups were comparable (P=0.32). These data seem to support the justification of reserving the mechanical circulatory support to those who are metabolically more injured. This review of our practice confirms the appropriateness of our timing of mechanical circulatory support.
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Acknowledgments
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We wish to acknowledge the contributions made by Dr J.C. Scarth, Dr J.V. Cassidy and Dr F.K. Gould, in this project.
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Footnotes
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Presented at the Joint 17th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 11th Annual Meeting of the European Society of Thoracic Surgeons, Vienna, Austria, October 12–15, 2003.
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References
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Top
Abstract
1. Introduction
