Use of Surrogate Samples to Monitor pH During High dose Methotrexate Therapy.

Abstract

High dose methotrexate (Mtx) therapy is commonly used in hemato-oncological practice. Alkalization of urine is a part of high dose methotrexate therapy for preventing crystallization in urine to avert renal insufficiency. Alkalization is monitored by urine pH at regular intervals. Oral pH has occasionally been used as a surrogate for oral mucositis. To compare and correlate pH of various body secretions (venous blood, oral salivary, lacrimal and urine) among patients undergoing alkalization with intravenous sodium bicarbonate during high dose methotrexate therapy. A prospective single center study in patients with hematological malignancies receiving Mtx>1.5g/m2 over 4-24h. Patients were assessed for pH (from all 4 body fluids) at regular time intervals (q8h) starting 6h-prior and 48h-post initiation of Mtx therapy. Mean pH of urine/oral was compared to surrogate samples. The mean oral pH was 6.9 (SD 0.65), the mean urinary pH was 7.59 (SD 0.773) the mean pH by venous blood gas analysis (venous pH) was 7.388 (SD 0.059), the mean lacrimal pH was 7.4536 (SD 0.527). Repeated measures ANOVA suggests that pH of different body fluids differ and cannot be used interchangeably [F (2.417, 309.361)=54.89, p<0.0005]. There was no statistically significant correlation between any other pair of assessed body fluids. On paired t test only the means of venous pH and urinary pH did not differ statistically (p 0.056). Venous pH significantly correlated with urinary pH but the strength of correlation was weak (r 0.184; p 0.037). pH of different body fluids is statistically different even when sampled simultaneously thus the pH of one fluid cannot be substituted for other. Based on this study we cannot substitute urinary pH with any other body fluids presently in patients undergoing high dose methotrexate and alkalization except in rare circumstances when venous pH can be used as a poor surrogate for urinary pH in situations where urinary pH cannot be monitored due to any reason. There was no surrogate for oral pH among the studied body fluids.