Diagnosis and Treatment of Chemotherapy-associated Hyponatremia

doi:10.12114/j.issn.1007-9572.2018.33.020

Abstract

Abstract: Objective　To determine the etiology of hyponatremia induced by chemotherapy，and to establish effective prevention as well as treatment measures.Methods　We analyzed the clinical data of adverse drug reactions following chemotherapy in patients treated with doxorubicin combined with cyclophosphamide.We also assessed the relationship between etiology，diagnosis，treatment，adverse reactions，and proposed treatment recommendations.Results　Cyclophosphamide was the main pathogenic factor in acute severe hypoosmotic hyponatremia following chemotherapy with doxorubicin combined with cyclophosphamide.Hypoosmotic hyponatremia may be related to the mechanism of abnormal antidiuretic hormone secretion.Severe acute hypotonic hyponatraemia can be induced by cyclophosphamide following chemotherapy with AC.The mechanism of cyclophosphamide-induced hyponatremia was related to inappropriate antidiuretic hormone secretion.Conclusion　Chemotherapeutic drugs can lead to hyponatremia with high clinical risk，is occult during early onset and involves different mechanisms，which require further investigation for early diagnosis and timely efficient treatments.

Key words: Consciousness disorders；Hyponatremia；Drug therapy, combination；Inappropriate ADH syndrome

摘要： 目的　探讨化疗药物导致低钠血症的病因，建立有效防治措施。方法　分析1例使用多柔比星联合环磷酰胺方案化疗患者化疗后出现药物不良反应的临床资料，探讨病因、诊治及不良反应的关系，提出治疗建议。结果　环磷酰胺是多柔比星联合环磷酰胺方案化疗后出现急性严重低渗性低钠血症的主要致病因素，低渗性低钠血症的发生可能与抗利尿激素分泌异常综合征相关。结论　化疗药物可导致低钠血症的临床风险高，发病初期隐匿性强，发生机制不尽相同，需遵循科学有效的判断，及时有效地处理。

关键词: 意识障碍, 低钠血症, 药物疗法, 联合, ADH分泌不当综合征

WANG Huaichong,SONG Xiaokun. Diagnosis and Treatment of Chemotherapy-associated Hyponatremia[J]. Chinese General Practice, 2018, 21(33): 4138-4143. DOI: 10.12114/j.issn.1007-9572.2018.33.020.
王怀冲,宋晓坤. 化疗相关性低钠血症病因分析与治疗[J]. 中国全科医学, 2018, 21(33): 4138-4143. DOI: 10.12114/j.issn.1007-9572.2018.33.020.

References

［1］VERBALIS J G，GOLDSMITH S P，GREENBERG A，et al．Hyponatremia treatment guidelines 2007：expert panel recommendations［J］．Am J Med，2007，120（11 Suppl）：S1-21．DOI：10.1016/j.amjmed.2007.09.001.
［2］GOH K P.Management of hyponatremia［J］．Am Fain Physician，2004，69（10）：2387-2394.
［3］BERARDI R，RINALDI S，CARAMANTI M，et al．Hyponatremia in cancer patients：time for a newapproach［J］．Crit Rev Oncol Hematol，2016，102：15-25．DOI：10.1016/j.critrevonc.2016.03.010.
［4］SPASOVSKI G，VANHOLDER R，ALLOLIO B，et al．Clinical practice guideline on diagnosis and treatment of hyponatraemia［J］．Eur J Endocrinol，2014，170（3）：G1-47．DOI：10.1530/EJE-13-1020.
［5］PALMER B F，GATES J R，LADER M.Causes and management of hyponatremia［J］．Ann Pharmacother，2003，37（11）：1694-1702．DOI：10.1345/aph.1D105.
［6］ELLISON D H，BERL T.Clinical practice.The syndrome of inappropriate antidiuresis［J］．N Engl J Med，2007，356（20）：2064-2072．DOI：10.1056/NEJMcp066837.
［7］FUJIOKA S，NAKAMURA H，MIWA K，et al．Syndrome of inappropriate secretion of antidiuretic hormone（SIADH） following carboplatin-paclitaxel administration in a patient with lung cancer［J］．Pharmazie，2011，66（9）：729-730.
［8］SUGIYAMA Y，NAIKI T，KONDO M，et al．Syndrome of inappropriate secretion of antidiuretic hormone caused by carboplatin after switching from cisplatin in a metastatic urethral cancer patient［J］．Urol Case Rep，2017，12：17-19．DOI：10.1016/j.eucr.2017.02.001.
［9］SCHWARTZ W B，BENNETT W，CURELOP S，et al．A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone.1957.［J］．J Am Soc Nephrol，2001，12（12）：2860-2870.
［10］HOORN E J，BOULOUX P M，BURST V.Perspectives on the management of hyponatraemia secondary to SIADH across Europe［J］．Best Practice Clin Endocrinol Metab，2012，26（suppl 1）：S27-32．DOI：10.1016/S1521-690X（12）70005-2.
［11］MORITZ M L，AYUS J C.Hyponatraemia：isotonic fluids prevent hospital-acquired hyponatraemia［J］．Nat Rev Nephrol，2015，11（4）：202-203．DOI：10.1038/nrneph.2014.253.
［12］JAYACHANDRAN N V，CHANDRASEKHARA P K，THOMAS J，et al．Cyclophosphamide-associated complications：we need to be aware of SIADH and central pontine myelinolysis［J］．Rheumatology （Oxford），2009，48（1）：89-90．DOI：10.1093/rheumatology/ken402.
［13］GENG C，TANG P，ZHANG Y，et al．Hyponatremia induced by low-dose cyclophosphamide in two patients with breast cancer［J］．Breast J，2014，20（4）：442-443．DOI：10.1111/tbj.12296.
［14］BAKER M，MARKMAN M，NIU J.Cyclophosphamide-induced severe acute hyponatremic encephalopathy in patients with breast cancer：report of two cases［J］．Case Rep Oncol，2014，7（2）：550-554．DOI：10.1159/000365832.
［15］BERGER A K，BELLOS F，SIEGMUND A，et al．Symptomatic hyponatraemia caused by cylophosphamide［J］．Onkologie，2009，32（5）：280-282．DOI：10.1159/000209292.
［16］ELAZZAZY S，MOHAMED A E，GULIED A.Cyclophosphamide-induced symptomatic hyponatremia，a rare but severe side effect：a case report［J］．Onco Targets Ther，2014，7：1641-1645．DOI：10.2147/OTT.S66350.
［17］GILBAR P J，RICHMOND J，WOOD J，et al．Syndrome of inappropriate antidiuretic hormone secretion induced by a single dose of oral cyclophosphamide［J］．Ann Pharmacother，2012，46（9）：e23．DOI：10.1345/aph.1R296.
［18］HWANG S B，LEE H Y，KIM H Y，et al．Life-threatening acute hyponatremia with generalized seizure induced by low-dose cyclophosphamide in a patient with breast cancer［J］．J Breast Cancer，2011，14（4）：345-348．DOI：10.4048/jbc.2011.14.4.345.
［19］WEBBERLEY M J，MURRAY J A.Life-threatening hyponatremia induced by low-dose cyclophosphamide and indomethacin［J］．Postgrad Med J，1989，65（770）：950-952.
［20］ADROGUE H J，MADIAS N E.Hyponatremia［J］．N Engl J Med，2000，342（21）：1581-1589．DOI：10.1056/NEJM200005253422107.
［21］VERBALIS J G，GOLDSMITH S R，GREENBERG A，et al．Diagnosis，evaluation，and treatment of hyponatremia：expert panel recommendations［J］．Am J Med，2013，126（10 Suppl 1）：S1-42．DOI：10.1016/j.amjmed.2013.07.006.
［22］《老年患者低钠血症的诊治中国专家建议》写作组.老年患者低钠血症的诊治中国专家建议［J］．中华老年医学杂志，2016，35（8）：795-803．DOI：10.3760/cma.j.issn.0254-9026.
2016.08.001.
［23］GROHE C，BERARDI R，BURST V.Hyponatraemia-SIADH in lung cancer diagnostic and treatment algorithms［J］．Crit Rev Oncol Hematol，2015，96（1）：1-8．DOI：10.1016/j.critrevonc.2015.04.005.
［24］CUESTA M，THOMPSON C J.The syndrome of inappropriate antidiuresis（SIAD）［J］．Best Pract Res Clin Endocrinol Metab，2016，30（2）：175-187．DOI：10.1016/j.beem.2016.02.009.