Abstract
Background The recommended dose of rasburicase is quite expensive, thus limiting its use. Whether a lower dose of rasburicase would be equally effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown. Objective To explore the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies who are at high risk of tumour lysis syndrome. Setting A single-centre retrospective cohort study. Method Children with haematological malignancies who had a history of rasburicase exposure during an intensive care unit stay were enrolled. Patients were divided into two groups according to the initial dosage of rasburicase: the standard-dose group (> 0.1 mg/kg/day) and the low-dose group (≤ 0.1 mg/kg/day). The adverse events and short-term prognosis of the two groups were compared. Results Thirty-seven children were selected, 22 in the standard-dose group and 15 in the low-dose group. The most common tumour type was Burkitt’s lymphoma (81%), followed by acute lymphoblastic leukaemia (11%). All patients were at high risk of tumour lysis syndrome, and 73% of them had 3 or more tumour lysis syndrome risk factors. The uric acid levels of 90% of patients with hyperuricaemia returned to the normal range within 12 h (100% in the standard-dose group and 75% in the low-dose group, P = 0.083). Eighty-four percent of patients presented serious complications, including tumour lysis syndrome (73%), acute kidney injury (59%), renal replacement treatment (24%), respiratory failure (24%), disseminated intravascular coagulation (16%) and heart failure (11%). There was no significant difference in the incidence of serious complications between the two groups. The overall 7-day and 28-day survival rates after intensive care unit admission were 86% and 84%, respectively. The average length of stay in the intensive care unit was 9.92 ± 5.13 days. Neither the short-term mortality nor the length of stay in the intensive care unit were significantly different between the two groups. Conclusion Low-dose rasburicase is effective and may be an acceptable choice for critically ill children with haematological malignancies.
Highlights
Tumour lysis syndrome (TLS) is an important cause of early death as well as admission to the intensive care unit (ICU) in children with newly diagnosed haematologic malignancies [1]
International Journal of Clinical Pharmacy (2020) 42:1440–1446 quantities of cellular contents into the blood circulation and may result in hyperkalaemia, hypocalcaemia, hyperuricaemia, hyperphosphatemia and multiple organ dysfunction [2]. Both hyperuricaemia and hyperphosphatemia can cause the deposition of crystals in the renal tubular system. This deposition may result in acute kidney injury (AKI), a serious complication associated with a poor short-term prognosis in children [3]
Two uric-acid-lowering agents were applied according to different risk stratifications: rasburicase was given prophylactically before or within the first week of initial chemotherapy for children at high risk of TLS after Paediatric Intensive Care Unit (PICU) admission, while allopurinol was given for the others
Summary
Tumour lysis syndrome (TLS) is an important cause of early death as well as admission to the intensive care unit (ICU) in children with newly diagnosed haematologic malignancies [1]. International Journal of Clinical Pharmacy (2020) 42:1440–1446 quantities of cellular contents into the blood circulation and may result in hyperkalaemia, hypocalcaemia, hyperuricaemia, hyperphosphatemia and multiple organ dysfunction [2]. Both hyperuricaemia and hyperphosphatemia can cause the deposition of crystals in the renal tubular system. Children with haematologic malignancies have a high potential for cell lysis; they are considered to have a high risk of developing TLS, and combined treatment regimens, including close laboratory and clinical monitoring, increased hydration and uric acid control therapy, have been proposed. Whether a lower dose of rasburicase would be effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown
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