R J Anderson, H M Chung, R Kluge, R W Schrier
Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin.
Ann Intern Med. 1985 Feb;102(2):164-8.
Abstract/Text
We prospectively evaluated the frequency, cause, and outcome of hyponatremia (plasma sodium concentration, less than 130 meq/L), as well as the hormonal response to this condition, in hospitalized patients. Daily incidence and prevalence of hyponatremia averaged 0.97% and 2.48%, respectively. Two thirds of all hyponatremia was hospital acquired. Normovolemic states (so-called syndrome of inappropriate secretion of antidiuretic hormone) were the most commonly seen clinical setting of hyponatremia. The fatality rate for hyponatremic patients was 60-fold that for patients without documented hyponatremia. Nonosmotic secretion of vasopressin was present in 97% of hyponatremic patients in whom it was sought. In edematous and hypovolemic patients, plasma hormonal responses (increases in plasma renin activity and aldosterone and norepinephrine levels) were compatible with baroreceptor-mediated release of vasopressin. Hyponatremia is a common hospital-acquired electrolyte disturbance that is an indicator of poor prognosis. Nonosmotic secretion of arginine vasopressin is a major pathogenetic factor in this electrolyte disturbance.
Robert C Hawkins
Age and gender as risk factors for hyponatremia and hypernatremia.
Clin Chim Acta. 2003 Nov;337(1-2):169-72.
Abstract/Text
BACKGROUND: This study assesses gender and age as independent risk factors for hypo- and hypernatremia and describes the prevalence of hypo- and hypernatremia in different population groups.
METHODS: Details of all serum Na results with accompanying patient demographics for 2 years were downloaded from the laboratory database into Microsoft Access for multiple logistic regression analysis using SPSS. Female gender and age <30 years were the reference groups.
RESULTS: Data from 303577 samples on 120137 patients were available for analysis. Prevalence at initial presentation to a health care provider of Na<136, <116, >145, and >165 mmol/l were for acute hospital care patients: 28.2%, 0.49%, 1.43%, and 0.06%; ambulatory hospital care: 21%, 0.17%, 0.53%, and 0.01%; community care: 7.2%, 0.03%, 0.72%, and <0.01%. Age odds ratios rose with increasing age to 1.89 and 8.70 (Na<136 and <116 mmol/l) and 7.09 and 24.39 (Na>145 and >165 mmol/l, respectively) for age >81 years. Male gender was a mild risk factor for Na<136 mmol/l and was otherwise unimportant.
CONCLUSIONS: Hyponatremia is a common but generally mild condition while hypernatremia is uncommon. Increasing age is a strong independent risk factor for both hypo- and hypernatremia. Gender is not an important risk factor for disturbances of serum Na concentration.
L H Beck
Hypouricemia in the syndrome of inappropriate secretion of antidiuretic hormone.
N Engl J Med. 1979 Sep 6;301(10):528-30. doi: 10.1056/NEJM197909063011005.
Abstract/Text
M A Katz
Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression.
N Engl J Med. 1973 Oct 18;289(16):843-4. doi: 10.1056/NEJM197310182891607.
Abstract/Text
T A Hillier, R D Abbott, E J Barrett
Hyponatremia: evaluating the correction factor for hyperglycemia.
Am J Med. 1999 Apr;106(4):399-403.
Abstract/Text
PURPOSE: There are no controlled experimental data that assess the accuracy of the commonly used correction factor of a 1.6 meq/L decrease in serum sodium concentration for every 100 mg/dL increase in plasma glucose concentration. The purpose of this study was to evaluate experimentally the hyponatremic response to acute hyperglycemia.
SUBJECTS AND METHODS: Somatostatin was infused to block endogenous insulin secretion in 6 healthy subjects. Plasma glucose concentrations were increased to >600 mg/dL within 1 hour by infusing 20% dextrose. The glucose infusion was then stopped and insulin given until the plasma glucose concentration decreased to 140 mg/dL. Plasma glucose and serum sodium concentrations were measured every 10 minutes.
RESULTS: Overall, the mean decrease in serum sodium concentration averaged 2.4 meq/L for every 100 mg/dL increase in glucose concentration. This value is significantly greater than the commonly used correction factor of 1.6 (P = 0.02). Moreover, the association between sodium and glucose concentrations was nonlinear. This was most apparent for glucose concentrations >400 mg/dL. Up to 400 mg/dL, the standard correction of 1.6 worked well, but if the glucose concentration was >400 mg/dL, a correction factor of 4.0 was better.
CONCLUSION: These data indicate that the physiologic decrease in sodium concentration is considerably greater than the standard correction factor of 1.6 (meq/L Na per 100 mg/dL glucose), especially when the glucose concentration is >400 mg/dL. Additionally, a correction factor of a 2.4 meq/L decrease in sodium concentration per 100 mg/dL increase in glucose concentration is a better overall estimate of this association than the usual correction factor of 1.6.
厚生労働科学研究費補助金難治性疾患等政策研究事業「間脳下垂体機能障害に関する調査研究」班編：間脳下垂体機能障害の診断と治療の手引き,2019；18-20. Available from: https://www.jstage.jst.go.jp/article/endocrine/95/S.May/95_1/_pdf/-char/ja
A I Arieff
Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women.
N Engl J Med. 1986 Jun 12;314(24):1529-35. doi: 10.1056/NEJM198606123142401.
Abstract/Text
Severe hyponatremia developed after elective surgery in 15 previously healthy women who subsequently either died or had permanent brain damage. The mean age was 41 years (range, 22 to 66), and the preoperative serum sodium level was 138 mmol per liter. All the patients recovered from anesthesia, but about 49 hours after surgery, when the average plasma sodium level was 108 mmol per liter, grand mal seizures, followed by respiratory arrest requiring intubation, developed in all 15. At that time, the urinary sodium level and the osmolality averaged 68 mmol per liter and 501 mOsm per kilogram, suggesting inappropriate secretion of antidiuretic hormone. In 10 of 15 patients, an acute cerebral vascular disorder was suspected, leading to a delay in treatment and multiple diagnostic studies, including CT scanning, cerebral angiography, and open-brain biopsies. The net postoperative fluid retention was 7.5 liters, and when correction of the serum sodium level was initiated, the rate of correction was less than 0.7 mmol per liter per hour. Histologic studies of the brain in five patients were not diagnostic, and no patient had any evidence of central pontine myelinolysis on the basis of autopsy, brain biopsy, or CT scanning. Seven patients recovered from coma after the serum sodium level was increased to 131 mmol per liter, but coma recurred two to six days later and ended in either death or a persistent vegetative state. Overall, 27 percent of the patients died, 13 percent had limb paralysis, and 60 percent were left in a persistent vegetative state.
J C Ayus, J M Wheeler, A I Arieff
Postoperative hyponatremic encephalopathy in menstruant women.
Ann Intern Med. 1992 Dec 1;117(11):891-7.
Abstract/Text
OBJECTIVES: To determine factors associated with the development of encephalopathy and with its clinical course in patients with postoperative hyponatremia.
SETTING: Consultation and referral services of two university medical centers and community hospitals.
DESIGN: Case-control study (risk factors for encephalopathy) and cohort study (clinical course among patients with encephalopathy).
PATIENTS: Case patients included 65 adults with postoperative hyponatremic encephalopathy; controls included 674 adult patients who had postoperative hyponatremia without encephalopathy and who were selected from 76,678 consecutive adult surgical inpatients.
MEASUREMENTS: Age, gender, menstrual status, neurologic symptoms, time to development and degree of hyponatremia, arterial blood gas determinations, serum chemistries, morbidity and mortality.
RESULTS: Case patients included 40 women (62%) and 25 men (38%) (P > 0.05); controls included 367 women (54%) and 307 men (46%) (P > 0.1). Of the 34 case patients who developed permanent brain damage or died, 33 (97%) were women (P < 0.001). Among the women with brain damage, 25 (76%) were menstruant (P < 0.001). The relative risk for death or permanent brain damage from hyponatremic encephalopathy in women compared with men was 28 (95% Cl, 5 to 141) and in menstruant women compared with postmenopausal women, 26 (Cl, 11 to 62). Arterial PO2 at diagnosis was significantly lower in female than in male case patients (34 +/- 5 compared with 91 +/- 3 mm Hg; P < 0.001). Further, of the 38 case patients who had respiratory arrest before the diagnosis of hyponatremic encephalopathy, 36 (95%) were women. Extent of or time to development of hyponatremia did not correlate with subsequent brain damage (P > 0.1).
CONCLUSIONS: Women and men are equally likely to develop hyponatremia and hyponatremic encephalopathy after surgery. However, when hyponatremic encephalopathy develops, menstruant women are about 25 times more likely to die or have permanent brain damage compared with either men or postmenopausal women.
A I Arieff, J C Ayus, C L Fraser
Hyponatraemia and death or permanent brain damage in healthy children.
BMJ. 1992 May 9;304(6836):1218-22.
Abstract/Text
OBJECTIVE: To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults.
DESIGN: Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre.
PATIENTS: 16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l).
MAIN OUTCOME MEASURES: Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies.
RESULTS: By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded.
CONCLUSIONS: Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment.
J Kelly, W Wassif, J Mitchard, W N Gardner
Severe hyponatraemia secondary to beer potomania complicated by central pontine myelinolysis.
Int J Clin Pract. 1998 Nov-Dec;52(8):585-7.
Abstract/Text
A case of severe hyponatraemia in a 56-year-old male alcohol misuser secondary to beer potomania is presented. In view of severe volume depletion and the patient's inability to drink, normal saline was cautiously infused. Despite initial improvement, he subsequently deteriorated neurologically. Magnetic resonance imaging demonstrated the classical lesion of central pontine myelinolysis (CPM). The rate of correction of plasma sodium was within limits normally considered safe. Beer potomania should be considered as a cause of hyponatraemia in alcohol misusers. Recognition is important as the electrolyte imbalance repairs simply with cessation of alcohol intake and institution of normal diet. Correction of chronic hyponatraemia by infusion of normal or hypertonic saline should not be attempted unless life-threatening neurological complications supervene. When the balance of risks favours correction, caution should be exercised, as CPM may occur. Although a rate of correction of plasma sodium of up to 10 mM per 24-hour period has been associated with a low risk of precipitating CPM, this case illustrates that a completely safe rate of correction probably cannot be defined.
R H Sterns, J E Riggs, S S Schochet
Osmotic demyelination syndrome following correction of hyponatremia.
N Engl J Med. 1986 Jun 12;314(24):1535-42. doi: 10.1056/NEJM198606123142402.
Abstract/Text
The treatment of hyponatremia is controversial: some authorities have cautioned that rapid correction causes central pontine myelinolysis, and others warn that severe hyponatremia has a high mortality rate unless it is corrected rapidly. Eight patients treated over a five-year period at our two institutions had a neurologic syndrome with clinical or pathological findings typical of central pontine myelinolysis, which developed after the patients presented with severe hyponatremia. Each patient's condition worsened after relatively rapid correction of hyponatremia (greater than 12 mmol of sodium per liter per day)--a phenomenon that we have called the osmotic demyelination syndrome. Five of the patients were treated at one hospital, and accounted for all the neurologic complications recorded among 60 patients with serum sodium concentrations below 116 mmol per liter; no patient in whom the sodium level was raised by less than 12 mmol per liter per day had any neurologic sequelae. Reviewing published reports on patients with very severe hyponatremia (serum sodium less than 106 mmol per liter) revealed that neurologic sequelae were associated with correction of hyponatremia by more than 12 mmol per liter per day; when correction proceeded more slowly, patients had uneventful recoveries. We suggest that the osmotic demyelination syndrome is a preventable complication of overly rapid correction of chronic hyponatremia.
Robert W Schrier, Peter Gross, Mihai Gheorghiade, Tomas Berl, Joseph G Verbalis, Frank S Czerwiec, Cesare Orlandi, SALT Investigators
Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.
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].).
Benaya Rozen-Zvi, Dafna Yahav, Mihai Gheorghiade, Asher Korzets, Leonard Leibovici, Uzi Gafter
Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis.
Am J Kidney Dis. 2010 Aug;56(2):325-37. doi: 10.1053/j.ajkd.2010.01.013. Epub 2010 Jun 9.
Abstract/Text
BACKGROUND: In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined.
STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs).
SETTING & POPULATION: In- and outpatients with euvolemic or hypervolemic hyponatremia.
SELECTION CRITERIA FOR STUDIES: We included all RCTs regardless of publication status or language.
INTERVENTION: Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction.
OUTCOMES: Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia.
RESULTS: 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome.
LIMITATIONS: Significant heterogeneity in the primary outcome.
CONCLUSIONS: Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia.
Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Hiroshi Arima, Koichi Goto, Tomohisa Motozawa, Makoto Mouri, Ryo Watanabe, Takahiro Hirano, San-E Ishikawa
Open-label, multicenter, dose-titration study to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone.
Endocr J. 2021 Jan 28;68(1):17-29. doi: 10.1507/endocrj.EJ20-0216. Epub 2020 Aug 29.
Abstract/Text
The purpose of this study was to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This multicenter, open-label, dose-escalation, phase III study enrolled Japanese patients (20-85 years old) with hyponatremia secondary to SIADH who were unresponsive to fluid restriction. Oral tolvaptan was administered for up to 30 days, initially at 7.5 mg/day, but escalated daily as necessary, based on the serum sodium concentration and safety, over the first 10 days until the optimal maintenance dose was determined for each patient (maximum 60 mg/day). The primary endpoint was the proportion of patients with normalized serum sodium concentration on the day after the final tolvaptan dose. Secondary endpoints included the mean change in serum sodium concentration from baseline on the day after the final dose. Sixteen patients (male, 81.3%; mean ± standard deviation age 71.9 ± 6.1 years) received tolvaptan treatment and 11 patients completed the study with one patient re-administered tolvaptan in the treatment period. Serum sodium concentrations normalized in 13 of 16 (81.3%) patients on the day after the final tolvaptan dose. The mean change in serum sodium concentration from baseline on the day after the final dose was 11.0 ± 4.3 mEq/L. Adverse events considered related to tolvaptan (10 [62.5%] patients) were generally of mild to moderate severity. Oral tolvaptan corrects hyponatremia in Japanese patients with SIADH with a similar efficacy and safety profile as that noted in non-Japanese patients.
Daisuke Hagiwara, Miyuki Matsukawa, Junko Tasaki, Yumiko Nakamura, Hiroshi Arima
A retrospective study on tolvaptan prescription in clinical practice in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) using the Japanese claims database.
Endocr J. 2023 Dec 28;70(12):1195-1205. doi: 10.1507/endocrj.EJ23-0256. Epub 2023 Oct 31.
Abstract/Text
We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.
A F List, J D Hainsworth, B W Davis, K R Hande, F A Greco, D H Johnson
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small-cell lung cancer.
J Clin Oncol. 1986 Aug;4(8):1191-8.
Abstract/Text
Review of clinical data from 350 patients with small-cell lung cancer (SCLC) revealed hyponatremia (sodium less than 130 mEq/L) attributable to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 40 patients (11%). Although hyponatremia was severe in most instances (median, sodium 117 mEq/L), symptoms attributable to water intoxication were identified in only 27% of hyponatremic episodes. Development of SIADH showed no correlation with clinical stage, distribution of metastatic sites, sex, or histologic subtype of small-cell carcinoma. SIADH occurred most often with initial presentation (33 of 40), and resolved promptly (less than 3 weeks) with initiation of combination chemotherapy in 80% of evaluable patients. The presence of SIADH did not influence response to chemotherapy or overall survival as an independent variable. However, in five patients profound hyponatremia developed immediately following primary cytotoxic therapy (range, one to five days). Despite initial control of SIADH, dilutional hyponatremia recurred in 70% of patients with tumor progression. Our findings suggest that development of clinically demonstrable SIADH in patients with SCLC is dependent on functional properties of the neoplastic cells, rather than tumor burden or metastatic site. The potential for development of clinically significant hyponatremia early in the course of cytotoxic therapy emphasizes the need to closely monitor patients, particularly those receiving chemotherapy regimens requiring substantial intravenous hydration.
L H Maurer, J F O'Donnell, S Kennedy, C S Faulkner, K Rist, W G North
Human neurophysins in carcinoma of the lung: relation to histology, disease stage, response rate, survival, and syndrome of inappropriate antidiuretic hormone secretion.
Cancer Treat Rep. 1983 Nov;67(11):971-6.
Abstract/Text
At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.
T J Wilkinson, E J Begg, A C Winter, R Sainsbury
Incidence and risk factors for hyponatraemia following treatment with fluoxetine or paroxetine in elderly people.
Br J Clin Pharmacol. 1999 Feb;47(2):211-7.
Abstract/Text
AIMS: To establish the incidence, time course and risk factors of hyponatraemia complicating treatment with fluoxetine or paroxetine in an elderly population.
METHODS: Retrospective descriptive and case control study in an inpatient/outpatient assessment and rehabilitation service for people aged 65 years and over. Fourteen elderly patients with hyponatraemia complicating treatment with fluoxetine or paroxetine, matched with 56 controls drawn from 845 patients treated with fluoxetine or paroxetine over 3.5 years. No other SSRI antidepressants were used over the study period.
RESULTS: The incidence of hyponatraemia was 4.7/1000 people treated/year (6.3/1000 for fluoxetine and 3.5/1000 for paroxetine). Hyponatraemia was detected at a median 13.5 (mean 18.6, range 4-64) days after commencing the drug. Mean (95% confidence intervals) body weights were lower in cases at 53.0 (95% CI 46.5-59.5) kg compared with controls at 64.5 (95% CI 60.1-68.4) kg (P<0.01). 71% of cases were women compared with 45% of controls (P=0.07) but the effect of gender was confounded by body weight. There were trends for cases to be older (odds ratio 1.10: 95% CI 0.99, 1.23) and lighter (odds ratio 0.92, 95% CI 0.86, 0.99).
CONCLUSIONS: Approximately 1 in 200 elderly people treated per year with fluoxetine or paroxetine developed complicating hyponatraemia. Low body weight was a particular risk factor. Most cases occurred within 3 weeks of treatment.
