Extracorporeal life support in the acute management of tumour lysis syndrome

Abstract

A 16-month old boy presented with a severe tumour lysis syndrome (TLS) complicating induction therapy for acute myeloid leukaemia. This was further complicated by a respiratory syncytial virus infection. The failure of response to escalating treatment necessitated the use of extracorporeal life support (ECLS) during continuation of his induction chemotherapy. He was weaned from support after the resolution of the TLS and completed chemotherapy successfully. ECLS may have a role to play in the acute support of children with cardiorespiratory failure as a result of malignancy or the required treatment.

INTRODUCTION

Tumour lysis syndrome (TLS) is the most common disease-related emergency encountered during the treatment of haematological malignancies. The reported incidence varies from 0.9 to 26% of cases undergoing chemotherapy. It occurs most commonly with leukaemia and lymphoma, either spontaneously or in response to therapy, causing renal failure and multiorgan dysfunction syndrome (MODS), and can be notoriously aggressive [1]. Extracorporeal life support (ECLS) is proven to benefit children with severe respiratory or cardiac failure [2]. Its use in patients with malignancy has been subject to controversy due to the perceived risks of infection and tumour dissemination [3].

Herein, we report a case of a child with acute myeloid leukaemia (AML) who developed TLS and MODS following induction chemotherapy and was supported successfully with ECLS.

CASE REPORT

A 16-month old boy presented with recurrent viral infections and a history of Bell's palsy 2 weeks earlier. He was afebrile, with a heart rate of 150/min, blood pressure of 97/45 mmHg and respiratory rate of 30/min. His haemoglobin was 6.1 g/dl, platelet count 29 × 10³/µl and white cell count 2.01 × 10³/µl. The diagnosis of AML was made based on the presence of blasts, pronormocytes and abnormal mononocytes in the peripheral smear and bone marrow exam.

Induction chemotherapy was commenced with etoposide, daunorubicin and cytarabine. The day following admission, he developed respiratory failure (after general anaesthesia for bone marrow aspiration and intrathecal chemotherapy) in combination with worsening renal function. Pressure ventilation was commenced. A chest X-ray showed bilateral opacities suggestive of leukaemic infiltration, fluid overload and TLS, exacerbated by respiratory syncytial virus. The ventilatory requirements escalated with the onset of acute renal failure and acidosis, necessitating inotropic support. Despite conversion to high frequency oscillating ventilation (HFOV), he continued to deteriorate, with an arterial pH 7.01 and pCO₂ 80 mmHg. He was started on ECLS [veno-arterial extracorporeal membrane oxygenation (VA ECMO) via right jugulo-carotid cannulation]. His internal jugular vein (IJV) was too small to accept an adequately sized two-lumen cannula for veno-venous (VV) ECMO. The circuit consisted of 14 Fr DLP venous and 12 Fr Biomedicus arterial cannulae (Medtronic Inc., Minneapolis, MN, USA), Jostra Rotaflow pump head and Quadrox-D oxygenator (Macquet GmbH & Co. KG, Rastatt, Germany). The flow was maintained between 80 and 100 ml/kg to achieve HbSO₂ >85% and pCO₂ within the normal range with minimal ventilator settings.

Echocardiogram (on ECLS) showed a structurally normal heart with good contractility. The inotropes were changed to milrinone. Chemotherapy was continued on ECMO, as were antibiotics (piperacillin–tazobactam, teicoplanin). Feeding was maintained via a transpyloric tube. Blood products transfused included 33 units platelets, 19 units packed red cells and 16 units fresh frozen plasma. Complications encountered on ECLS included thrombocytopenia, pericardial effusion requiring percutaneous drainage, ECLS flow compromise requiring cannula repositioning, bleeding from vascular access site, renal failure requiring haemofiltration and ischaemic fingers and toes (managed conservatively). Surveillance cultures did not reveal infection while on ECLS.

He improved steadily and could be weaned from ECLS support on Day 16. The right carotid artery was repaired and a smaller dual-lumen VV ECLS cannula (Avalon Laboratories, LLC, CA, USA) was inserted into the right IJV and retained for 3 days to enable some level of VV ECMO support if needed and to provide access for haemofiltration. He was thereafter stabilized on HFOV and continuous veno-venous haemofiltration (CVVHF). He was weaned from the ventilator and CVVHF was discontinued on Day 20. He recovered well, completing induction chemotherapy successfully.

DISCUSSION

Childhood malignancies, both solid and haematological, comprise the most common causes of death in infants and children, due to direct effects of the malignancy and secondary effects on cardiorespiratory system. The evolution of treatment modalities with more targeted agents, radio-therapeutic techniques and stem cell and bone marrow transplant have all contributed to an improved prognosis [4].

TLS is a complication of malignancy itself or its treatment. It occurs as a result of lysis of tumour cells with the release of potassium, phosphorus and nucleic acids that are then metabolized to uric acid via the xanthine–hypoxanthine pathway. This leads to a number of metabolic insults. Hyperkalemia and hyperphosphatemia (via hypocalcemia) cause arrhythmia; uric acid and calcium phosphate precipitation cause renal injury; release of cytokines causes systemic inflammatory response and MODS [1]. The metabolic effects of TLS are potentially short-lived and correctable, making aggressive interim support with ECLS justifiable (we estimate <1% of all patients undergoing chemotherapy).

The use of ECLS in cardiac and respiratory failure has evolved over the past 35 years and results have improved dramatically [2]. The most important applications of non-cardiac ECLS have been in ARDS, paediatric respiratory failure, congenital diaphragmatic hernia, persistent pulmonary hypertension, meconium aspiration syndrome, hyaline membrane disease and poisoning. The potential complications of ECLS, including bleeding, infection, immune suppression, stroke and embolus have made its use less attractive in malignancies in the past. However, ECLS for respiratory or cardiac support in patients with malignancy has shown a survival to decannulation of 42% with 35% of patients surviving to discharge [3]. This must be weighed against the probable definite mortality in similar cases that are not supported.

ECLS can be instituted either as veno-venous or veno-arterial support, depending upon the degree of respiratory or cardiac instability. Renal failure can be managed with the addition of haemofiltration to the circuit. The potential risk of infection should be managed with antibiotic therapy as there are reports of good outcomes in spite of sustained bacteraemia in patients with leukaemia supported on ECLS [5].

It is difficult to state the indications or contraindications to ECLS in patients with TLS, as cases needing support are rare and clinical details vary enormously. However, one can assume that standard criteria (e.g. oxygenation index, hemodynamic instability, disease prognosis, etc.) would be useful. In any case, ECLS should not be denied to potential survivors solely because of the presence of malignancy. With further experience in managing these patients, the results should continue to improve.

CONCLUSION

Rescue of a critically ill patient with respiratory failure related to malignancy and TLS is feasible, and deserves consideration in cases for which 100% mortality would be expected with lower-level interventions.

Conflict of interest: none declared.