今日の臨床サポート

SIADH(小児科)

著者: 神田祥一郎 東京大学医学部附属病院 小児科

監修: 五十嵐隆 国立成育医療研究センター

著者校正済:2020/09/10
現在監修レビュー中
参考ガイドライン:
  1. 一般社団法人日本間脳下垂体腫瘍学会バゾプレシン分泌過剰症(SIADH)の診断の手引き(平成22年度改訂)
  1. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant (2014) 29 (Suppl. 2)
  1. Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations. Am J Med (2013) 126(Suppl 1)
患者向け説明資料

概要・推奨   

  1. 原疾患の治療を行う(推奨度1)
  1. 中等度または重度の低ナトリウム血症では、水分摂取を制限することを提案する(推奨度1)。
  1. 急性、症候性の体液正常型低Na血症に対する治療において、高張食塩水投与が有効である(推奨度1)。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
神田祥一郎 : 未申告[2021年]
監修:五十嵐隆 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、参考ガイドラインと概要・推奨について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 抗利尿ホルモン(antidiuretic hormone、ADH、またはarginine vasopressin、AVP)は、体内水分量の恒常性を保つための重要な働きを担うホルモンである。
  1. ADHは、血漿浸透圧の増加(浸透圧刺激)によって浸透圧受容器を介して下垂体後葉より分泌され、腎集合管に作用し水の再吸収を行う。
  1. ADHはまた、血圧低下・循環血液量の減少(非浸透圧刺激)によっても浸透圧受容器を介し分泌される。
  1. 抗利尿ホルモン不適切分泌症候群(syndrome of inappropriate secretion of ADH、SIADH)とは、ADHが恒常性を逸脱して分泌される状態のことである。
  1. ADHの作用亢進状態により水分が体内に貯留し、低浸透圧血症および希釈性低Na血症を来す。さらに循環血液量の増加による糸球体濾過の増加、レニン-アルドステロン系の抑制、心房性Na利尿ペプチドの分泌増加のため尿中Na排泄が促進され、低Na血症が進行する[1][2][3]
  1. SIADHは体液量正常型低Na血症の代表である[4]
  1. SIADHは、何らかの原因疾患(中枢神経系疾患、呼吸器系疾患、悪性腫瘍)や薬剤に由来して発症する[2][3][5][6]<図表>
  1. 小児においては中枢神経系疾患、呼吸器系疾患が問題となるだけでなく、敗血症、発熱、ストレス、疼痛、嘔吐などの血圧・有効循環血液量の低下を引き起こす病態が非浸透圧刺激となり、ADHを分泌させる(nonosmotic ADH stimuli)。これらの状態にある患児に、漫然と低張輸液を行うことによりSIADHを発症、あるいは増悪させる可能性がある(hospital-acquired hyponatremia)[7][8]
  1. 症状は、低Na血症の重症度、急性か慢性かに依存し、治療も希釈性低Na血症に対するものが柱となる。
 
  1. 小児における低張性維持輸液によるhospital-acquired hyponatremiaについて(推奨度1CS)
  1. まとめ:小児において、入院となり輸液を要する多くの疾患(肺炎、細気管支炎、喘息、中枢神経感染症、嘔吐、疼痛、ストレス、低酸素等)は、nonosmotic ADH stimuliによりSIADHの要因となりやすい。これらの患児に低張性維持輸液を行うことでhospital-acquired hyponatremiaを引き起こし、神経学的な予後不良の転帰となる報告が多くなされている[7][9][10]
  1. 代表事例の説明:これらに対し、小児入院患児の維持輸液を等張性輸液にすることでhospital-acquired hyponatremiaを予防すべきと提唱した。その後、維持輸液に等張性輸液を使用した数多くのランダム化試験や後方視的検討の報告がなされ、その有用性が示されている[9][11]
  1. 結論:Moritzらは、維持輸液に等張性輸液を使用することを提唱している[9][11]
  1. コメント:Moritzらは、以前より小児入院患児への低張性維持輸液によるhospital-acquired hyponatremiaを指摘し続けている。(医原性)SIADH(と脳障害)への進展の予防を考慮した輸液を行うことは、小児科臨床医にとって重要なことである。
問診・診察のポイント  
  1. ADHの分泌亢進が予測される病態や、脳症、髄膜炎の治療中に低Na血症を呈したときは、SIADHの可能性を念頭に置く。

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文献 

著者: F C Bartter, W B Schwartz
雑誌名: Am J Med. 1967 May;42(5):790-806.
Abstract/Text
PMID 5337379  Am J Med. 1967 May;42(5):790-806.
著者: Joseph G Verbalis, Stephen R Goldsmith, Arthur Greenberg, Robert W Schrier, Richard H Sterns
雑誌名: Am J Med. 2007 Nov;120(11 Suppl 1):S1-21. doi: 10.1016/j.amjmed.2007.09.001.
Abstract/Text Although hyponatremia is a common, usually mild, and relatively asymptomatic disorder of electrolytes, acute severe hyponatremia can cause substantial morbidity and mortality, particularly in patients with concomitant disease. In addition, overly rapid correction of chronic hyponatremia can cause severe neurologic deficits and death, and optimal treatment strategies for such cases are not established. An expert panel assessed the potential contributions of aquaretic nonpeptide small-molecule arginine vasopressin receptor (AVPR) antagonists to hyponatremia therapies. This review presents their conclusions, including identification of appropriate treatment populations and possible future indications for aquaretic AVPR antagonists.

PMID 17981159  Am J Med. 2007 Nov;120(11 Suppl 1):S1-21. doi: 10.1016/・・・
著者: Michael L Moritz, Juan Carlos Ayus
雑誌名: Pediatrics. 2003 Feb;111(2):227-30.
Abstract/Text OBJECTIVE: The current standard of care in pediatrics is to administer hypotonic saline in maintenance parenteral fluids. The safety of this approach has never been evaluated.
METHODS: A review of the literature reveals that the administration of hypotonic fluids is potentially dangerous and may not be physiologic for the hospitalized child.
RESULTS: There have been >50 reported cases of neurologic morbidity and mortality, including 26 deaths, in the past 10 years resulting from hospital-acquired hyponatremia in children who were receiving hypotonic parenteral fluids. Common childhood conditions requiring parenteral fluids, such as pulmonary and central nervous system infections, dehydration, and the postoperative state, are associated with a nonosmotic stimulus for antidiuretic hormone production, which can lead to free water retention and hyponatremia. Children are at particularly high risk of developing symptomatic hyponatremia as they have a larger brain-to-skull size ratio.
CONCLUSIONS: The administration of isotonic saline in maintenance parenteral fluids is the most important prophylactic measure that can be taken to prevent the development of hyponatremia in children who receive parenteral fluids.

PMID 12563043  Pediatrics. 2003 Feb;111(2):227-30.
著者: Michael L Moritz, Juan Carlos Ayus
雑誌名: Pediatrics. 2011 Nov;128(5):980-3. doi: 10.1542/peds.2011-2015. Epub 2011 Oct 17.
Abstract/Text
PMID 22007008  Pediatrics. 2011 Nov;128(5):980-3. doi: 10.1542/peds.20・・・
著者: K Choong, M E Kho, K Menon, D Bohn
雑誌名: Arch Dis Child. 2006 Oct;91(10):828-35. doi: 10.1136/adc.2005.088690. Epub 2006 Jun 5.
Abstract/Text BACKGROUND: The traditional recommendations which suggest that hypotonic intravenous (i.v.) maintenance fluids are the solutions of choice in paediatric patients have not been rigorously tested in clinical trials, and may not be appropriate for all children.
AIMS: To systematically review the evidence from studies evaluating the safety of administering hypotonic versus isotonic i.v. maintenance fluids in hospitalised children.
METHODS: Data sources: Medline (1966-2006), Embase (1980-2006), the Cochrane Library, abstract proceedings, personal files, and reference lists. Studies that compared hypotonic to isotonic maintenance solutions in children were selected. Case reports and studies in neonates or patients with a pre-existing history of hyponatraemia were excluded.
RESULTS: Six studies met the selection criteria. A meta-analysis combining these studies showed that hypotonic solutions significantly increased the risk of developing acute hyponatraemia (OR 17.22; 95% CI 8.67 to 34.2), and resulted in greater patient morbidity.
CONCLUSIONS: The current practice of prescribing i.v. maintenance fluids in children is based on limited clinical experimental evidence from poorly and differently designed studies, where bias could possibly raise doubt about the results. They do not provide evidence for optimal fluid and electrolyte homoeostasis in hospitalised children. This systematic review indicates potential harm with hypotonic solutions in children, which can be anticipated and avoided with isotonic solutions. No single fluid rate or composition is ideal for all children. However, isotonic or near-isotonic solutions may be more physiological, and therefore a safer choice in the acute phase of illness and perioperative period.

PMID 16754657  Arch Dis Child. 2006 Oct;91(10):828-35. doi: 10.1136/ad・・・
著者: Guy Decaux, Alain Soupart, Gilbert Vassart
雑誌名: Lancet. 2008 May 10;371(9624):1624-32. doi: 10.1016/S0140-6736(08)60695-9.
Abstract/Text Arginine-vasopressin is a hormone that plays an important part in circulatory and water homoeostasis. The three arginine-vasopressin-receptor subtypes--V1a, V1b, and V2--all belong to the large rhodopsin-like G-protein-coupled receptor family. The vaptans are orally and intravenously active non-peptide vasopressin receptor antagonists that are in development. Relcovaptan is a selective V1a-receptor antagonist, which has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhoea, and tocolysis. SSR-149415 is a selective V1b-receptor antagonist, which could have beneficial effects in the treatment of psychiatric disorders. V2-receptor antagonists--mozavaptan, lixivaptan, satavaptan, and tolvaptan--induce a highly hypotonic diuresis without substantially affecting the excretion of electrolytes (by contrast with the effects of diuretics). These drugs are all effective in the treatment of euvolaemic and hypervolaemic hyponatraemia. Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia.

PMID 18468546  Lancet. 2008 May 10;371(9624):1624-32. doi: 10.1016/S01・・・
著者: R H Sterns, J D Cappuccio, S M Silver, E P Cohen
雑誌名: J Am Soc Nephrol. 1994 Feb;4(8):1522-30.
Abstract/Text Severe, symptomatic hyponatremia is often treated urgently to increase the serum sodium to 120 to 130 mmol/L. Recently, this approach has been challenged by evidence linking "rapid correction" (> 12 mmol/L per day) to demyelinating brain lesions. However, the relative risks of persistent, severe hyponatremia and iatrogenic injury have not been well quantified. Data were sought on patients with serum sodium levels < or = 105 mmol/L from the membership of the American Society of Nephrology. Respondents were given a report form asking specific questions regarding the cause of hyponatremia, presenting symptoms, rate of correction, and neurologic sequelae. Data on 56 patients were analyzed. Fourteen developed posttherapeutic complications (10 permanent, 4 transient) after correction to a serum sodium > 120 mmol/L. Eleven of these 14 patients (including 3 with documented central pontine myelinolysis) had a biphasic course in which neurologic findings initially improved and then worsened on the second to sixth day. Posttherapeutic complications were not explained by age, sex, alcoholism, presenting symptoms, or hypoxic episodes. Increased chronicity of hyponatremia and a high rate of correction in the first 48 h of treatment were significantly associated with complications. No neurologic complications were observed among patients corrected by < 12 mmol/L per 24 h or by < 18 mmol/L per 48 h or in whom the average rate of correction to a serum sodium of 120 mmol/L was < or = 0.55 mmol/L per hour. It was concluded that patients with severe chronic hyponatremia are most likely to avoid neurologic complications when their electrolyte disturbance is corrected slowly.

PMID 8025225  J Am Soc Nephrol. 1994 Feb;4(8):1522-30.
著者: Michael L Moritz, Juan Carlos Ayus
雑誌名: Pediatr Nephrol. 2010 Jul;25(7):1225-38. doi: 10.1007/s00467-009-1323-6. Epub 2009 Nov 6.
Abstract/Text Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP).

PMID 19894066  Pediatr Nephrol. 2010 Jul;25(7):1225-38. doi: 10.1007/s・・・
著者: J N Forrest, M Cox, C Hong, G Morrison, M Bia, I Singer
雑誌名: N Engl J Med. 1978 Jan 26;298(4):173-7. doi: 10.1056/NEJM197801262980401.
Abstract/Text We evaluated demeclocycline and lithium therapy in 10 patients with the syndrome of inappropriate secretion of antidiuretic hormone. Despite severe water restriction, all patients had hyponatremia (mean +/- S.E.M. serum sodium of 122 +/- 1.1 meq per liter) and elevated urine osmolality (744 +/- 59 mOsm per kilogram) before treatment. Demeclocycline (600 to 1200 mg daily) restored serum sodium concentration to 139 +/- 1.1 meq per liter within five to 14 days, permitting unrestricted water intake in all patients. In three patients given lithium carbonate (900 mg daily) the serum sodium concentration, urine osmolality and urine volume were unchanged; since two patients had adverse central-nervous-system symptoms during lithium therapy, further study of this agent was abandoned. A patient with an unusual 22-year history of the syndrome was unresponsive to lithium, whereas long-term treatment with demeclocyline was markedly effective. Demeclocycline is superior to lithium in the treatment of the syndrome and may obviate the need for severe water restriction.

PMID 413037  N Engl J Med. 1978 Jan 26;298(4):173-7. doi: 10.1056/NE・・・
著者: Robert W Schrier, Peter Gross, Mihai Gheorghiade, Tomas Berl, Joseph G Verbalis, Frank S Czerwiec, Cesare Orlandi, SALT Investigators
雑誌名: N Engl J Med. 2006 Nov 16;355(20):2099-112. doi: 10.1056/NEJMoa065181. Epub 2006 Nov 14.
Abstract/Text BACKGROUND: Hyponatremia (serum sodium concentration, <135 mmol per liter) is a predictor of death among patients with chronic heart failure and cirrhosis. At present, therapy for acute and chronic hyponatremia is often ineffective and poorly tolerated. We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free water--might be of benefit in hyponatremia.
METHODS: In two multicenter, randomized, double-blind, placebo-controlled trials, the efficacy of tolvaptan was evaluated in patients with euvolemic or hypervolemic hyponatremia. Patients were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15 mg daily. The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30.
RESULTS: Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of patients with mild or marked hyponatremia improved (P<0.001 for all comparisons). During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred. Side effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. A planned analysis that combined the two trials showed significant improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Component of the Medical Outcomes Study 12-item Short-Form General Health Survey.
CONCLUSIONS: In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30. (ClinicalTrials.gov numbers, NCT00072683 [ClinicalTrials.gov] [SALT-1] and NCT00201994 [ClinicalTrials.gov] [SALT-2].).

PMID 17105757  N Engl J Med. 2006 Nov 16;355(20):2099-112. doi: 10.105・・・
著者: Joseph G Verbalis, Suzanne Adler, Robert W Schrier, Tomas Berl, Qiong Zhao, Frank S Czerwiec, SALT Investigators
雑誌名: Eur J Endocrinol. 2011 May;164(5):725-32. doi: 10.1530/EJE-10-1078. Epub 2011 Feb 11.
Abstract/Text OBJECTIVE: Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies. This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) to evaluate the efficacy and safety of tolvaptan in this group.
DESIGN AND PATIENTS: Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators. Subjects were randomized to receive oral placebo (n=52) or tolvaptan 15 mg daily, with further titration to 30 and 60 mg daily, if necessary, based on the response of serum [Na(+)] (n=58).
RESULTS: In patients with SIADH, improvement in serum [Na(+)] was significantly greater (P<0.0001) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study, with minimal side effects of increased thirst, dry mouth, and urination. Only 5.9% of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines. After discontinuation of tolvaptan, serum [Na(+)] declined to values similar to placebo. A significant positive treatment effect favoring tolvaptan on the physical component, and a near-significant trend on the mental component, was found using the SF-12 Health Survey. Tolvaptan was associated with a significantly reduced incidence of fluid restriction.
CONCLUSIONS: Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group.

PMID 21317283  Eur J Endocrinol. 2011 May;164(5):725-32. doi: 10.1530/・・・
著者: Ectopic ADH Syndrome Therapeutic Research Group, Ken Yamaguchi, Noriharu Shijubo, Tetsuro Kodama, Kiyoshi Mori, Takahiko Sugiura, Takayuki Kuriyama, Masaaki Kawahara, Tetsu Shinkai, Haruo Iguchi, Masanori Sakurai
雑誌名: Jpn J Clin Oncol. 2011 Jan;41(1):148-52. doi: 10.1093/jjco/hyq170. Epub 2010 Nov 17.
Abstract/Text Ectopic antidiuretic hormone syndrome is a medical emergency characterized by dilutional hyponatremia. Clinical effectiveness of the vasopressin V2 receptor antagonist mozavaptan was evaluated in 16 patients. In short-term (7-day) treatment with the drug, serum sodium concentration (mean ± standard deviation) significantly (P = 0.002) increased from 122.8 ± 6.7 to 133.3 ± 8.3 mEq/l, and symptoms due to hyponatremia were improved. On the basis of these results, mozavaptan (Physuline(®)) was approved as an orphan drug for the treatment of the syndrome in 2006 in Japan. During the 43 months following its launch, 100 patients have been treated with the drug; overall clinical effects of the drug were found similar to those of this clinical trial. Clinically, mozavaptan may allow hyponatremic patients to be treated by aggressive cancer chemotherapy with platinum-containing drugs. Moreover, the drug may free patients from strict fluid-intake restrictions and thereby improve their quality of life.

PMID 21087977  Jpn J Clin Oncol. 2011 Jan;41(1):148-52. doi: 10.1093/j・・・
著者: David Zeltser, Steven Rosansky, Hannes van Rensburg, Joseph G Verbalis, Neila Smith, Conivaptan Study Group
雑誌名: Am J Nephrol. 2007;27(5):447-57. doi: 10.1159/000106456. Epub 2007 Jul 26.
Abstract/Text BACKGROUND: Most cases of hyponatremia--serum sodium concentration ([Na+]) < 135 mEq/l (< 135 mM)--are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V1A/V2-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia.
METHODS: Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na+] 115 to < 130 mEq/l) were randomly assigned to receive intravenous placebo or conivaptan administered as a 30-min, 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day. The primary efficacy measure was change in serum [Na+], measured by the baseline-adjusted area under the [Na+]-time curve. The secondary measures included time from first dose to a confirmed > or = 4 mEq/l serum [Na+] increase, total time patients had serum [Na+] > or = 4 mEq/l higher than baseline, change in serum [Na+] from baseline to the end of treatment, and number of patients with a confirmed > or = 6 mEq/l increase in serum [Na+] or normal [Na+] (> or = 135 mEq/l).
RESULTS: Both conivaptan doses increased area under the [Na+]-time curve during the 4-day treatment (p < 0.0001 vs. placebo). From baseline to the end of treatment, the least-squares mean +/- standard error serum [Na+] increase associated with placebo was 0.8 +/- 0.8 mEq/l; with conivaptan 40 mg/day, 6.3 +/- 0.7 mEq/l; and with conivaptan 80 mg/day, 9.4 +/- 0.8 mEq/l. Conivaptan significantly improved all secondary efficacy measures (p < 0.001 vs. placebo, both doses). Conivaptan was generally well tolerated, although infusion-site reactions led to the withdrawal of 1 (3%) and 4 (15%) of patients given conivaptan 40 and 80 mg/day, respectively.
CONCLUSION: Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.

2007 S. Karger AG, Basel
PMID 17664863  Am J Nephrol. 2007;27(5):447-57. doi: 10.1159/000106456・・・
著者: Eric A Huang, Brian J Feldman, I David Schwartz, David H Geller, Stephen M Rosenthal, Stephen E Gitelman
雑誌名: J Pediatr. 2006 Jan;148(1):128-31. doi: 10.1016/j.jpeds.2005.08.031.
Abstract/Text We report the successful use of oral urea in the management of children with chronic syndrome of inappropriate antidiuretic hormone secretion (SIAD). We performed a retrospective review of four children with chronic SIAD. After initial attempts at management with fluid restriction, each was started on a 30% to 50% oral urea solution, and the dose was titrated until normal serum sodium was achieved. Fluid intake was liberalized after serum sodium normalization. All four children normalized their serum sodium. No side effects or toxicities were experienced. Oral urea is a safe, effective treatment for chronic SIAD in children.

PMID 16423613  J Pediatr. 2006 Jan;148(1):128-31. doi: 10.1016/j.jpeds・・・
著者: Hassib Chehade, Luigi Rosato, Eric Girardin, Francois Cachat
雑誌名: Acta Paediatr. 2012 Jan;101(1):e39-42. doi: 10.1111/j.1651-2227.2011.02382.x. Epub 2011 Jun 29.
Abstract/Text UNLABELLED: Hyponatremia is the main complication of inappropriate antidiuretic hormone secretion (SIADH), sometimes fatal. Treatment strategy depends on the cause and the severity of the hyponatremia. Recent studies have shown the efficacy of urea in treating acute hyponatremia secondary to SIADH, by inducing an osmotic water drive. We describe an infant with chronic hyponatremia secondary to SIADH in which the long-term oral treatment with urea was successful and well tolerated. The aim of this paper is to highlight the potential benefits of urea treatment in case of chronic hyponatremia secondary to SIADH.
CONCLUSION: Chronic oral urea treatment in children with SIADH allows an easy and safe water and sodium control and may permit a decrease in fluid restriction in this situation.

© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.
PMID 21672011  Acta Paediatr. 2012 Jan;101(1):e39-42. doi: 10.1111/j.1・・・

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