Evolving concepts in tumour lysis syndrome management

We have read with great interest the recently published guidelines for the management of tumour lysis syndrome (TLS) (Jones et al, 2015). The authors emphasized very well the fundamental points in taking preventive and curative care in the era of the use of rasburicase. However, we believe that these recommendations generate some comments. The first concerns the role of intensivists in the management of this pathology. This was mentioned only in the management of established TLS (Jones et al, 2015). It has been demonstrated that this approach to high-risk haematological patients is certainly too late, especially when acute kidney injury (AKI) is already established (Darmon et al, 2010; Canet et al, 2013). Many studies show that chemotherapy can be safely administered in the intensive care unit (ICU) and that the admission of haematological patients at high risk of complications, including TLS, is best done before the onset of organ failure (Benoit et al, 2006; Lengline et al, 2012; Algrin et al, 2015). We believe that a ‘preventive’ admission of these patients to the ICU will enable better management of overhydration (mainly with isotonic saline and, as highlighted by Jones et al (2015), without adding potassium, even in symptomatic hypokalaemia rather than with balanced solutions that all contain potassium), the response in terms of diuresis and correction of electrolyte abnormalities. As such, the study reported by Montesinos et al (2008) should be cited: in a retrospective study of 772 adult patients with acute myeloid leukaemia that received induction chemotherapy between 1980 and 2002, they demonstrated that only the development of clinical TLS had an impact on higher mortality rate from induction therapy. This policy of early ICU admission, however, requires, as very well written, close cooperation between haematologists and intensivists. The second concern is related to the management of hyperuricaemia. Although this recommendation cannot be classified as following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, the use of urinary alkalinization should not be recommended and, we believe, should be prohibited, both in the preventive and therapeutic care of TLS. Former experimental work showed that neutral diuresis caused by the induction of experimental diabetes insipidus led to a better clearance of uric acid than alkaline diuresis induced by an infusion of bicarbonates and acetazolamide (Conger & Falk, 1977). In the era of the use of recombinant urate oxidase, intra-renal precipitation of uric acid is no longer a problem (Darmon et al, 2013). However, the utilization of urinary alkalinization exposes the patient to a significantly increased risk of calcium phosphate precipitation in the renal parenchyma, which is currently the leading cause of AKI in patients with TLS. For the same reason, calcium should only be used with extreme caution due to the risk of increasing the dangerous phosphocalcic product. Although it is quite commonly used by paediatricians, the use of calcium should be reserved for adults with very symptomatic forms. In the presence of an associated hyperphosphataemia not controlled by medical treatment, the use of renal replacement therapy (RRT) is probably the safest way to correct the condition. This indication is likely to be part of the recommendations on the use of RRT in the therapeutic management of established TLS. Moreover, we do not believe that RRT has any role in the management of hyperuricaemia, as suggested by Jones et al (2015). We think that, as revealed by a recent study, coldtemperature handling to measure uric acid in cases of recombinant urate oxidase use is very questionable and should not be quoted as Grade 1B evidence (Lindeman et al, 2013). Cold handling (pre-chilled tubes, iced transportation, 4°C centrifugation) was equivalent to room temperature (RT) for immediate measurement in uric acid in a total of 65 pairs of blood samples collected from 34 patients, 12–24 h after receiving rasburicase. An additional 1-h delay at RT led to a 20% decrease in uric acid. The cold handling measures required by the manufacturer are probably not necessary if testing is performed without delay. Finally, concerning RRT, many questions remain unanswered: At what point did the phosphate start? After what medical treatment failure did this happen (despite expert reports to the contrary, chelating phosphorus probably has no indication in this situation)? What is the best technique to be used (the recommendation of continuous technical utilization in haemodynamically unstable patients is not based on any hard evidence)? The only certainty is that, as stated in the text, there is no room for the use of peritoneal dialysis. This is a reminder that, as we have emphasized, there is a need for interventional studies in order to decrease early TLS-related deaths in this setting (Darmon et al, 2013).