Colonization of Skilled‐Care Facility Residents with Antimicrobial‐Resistant Pathogens

To the Editor: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by an incapacity of excessive body water to inhibit antidiuretic hormone secretion (ADH). Water retention and an expanded extracellular fluid volume cause a dilution of plasma sodium. Age-related changes in the homeostasis of water and electrolytes increase the likelihood that older people will develop SIADH. Factors such as drugs, respiratory infections, tumors, stroke, and stress can precipitate SIADH. We describe SIADH associated with cilazapril, an angiotensin converting enzyme (ACE) inhibitor. An 85-year-old woman with hypertension, ischemic heart disease, and gastroesophageal reflux was admitted to the hospital on May 11, 1999, having experienced progressive weakness and mental deterioration for 1 week. She was taking aspirin (100 mg once a day), cilazapril (2.5 mg once a day, initiated April 4, 1999), and famotidine (20 mg twice a day). Examinations did not reveal any evidence of fluid overload, volume depletion, or peripheral edema. Heart rate was 68 beats/minute, blood pressure was 140 ⁄80 mmHg, with no postural changes, and body temperature was normal. Heart sounds were regular. Lungs were clear to auscultation. Neurological examinations were symmetrical. She was somnolent. Her replies to questions were slow and not clear. Laboratory results revealed plasma concentration of sodium 115 mmol/L, potassium 3.9 mmol/L, blood urea nitrogen 3.7 mmol/L, creatinine 0.5 mg/dL, glucose 6.7 mmol/L, total protein 72 g/L, triglycerides 1.94 mmol/L, and total cholesterol 4.73 mmol/L. The patient’s serum osmolality was 248 mOsm/kg, with a concurrent urine osmolality of 397 mOsm/kg, and a urine sodium of 68 mmol/L. Her adrenal and thyroid function tests were normal. Her electrocardiogram, chest x-ray, chest computed tomography (CT), and abdominal CT were also normal. Brain CT revealed mild brain atrophy. Cilazapril was discontinued. Drinking of free water was restricted. After two days, her physical state improved drastically and plasma sodium concentration increased to 127 mmol/L. On the sixth day of hospitalization, the day of discharge, plasma sodium concentration was 134 mmol/L. No occurrence of hyponatremia was observed during a follow-up period of 6 months. ACE inhibitor–induced SIADH is an increasingly recognized phenomenon. There are several possible mechanisms of ACE inhibitor–induced SIADH. Low doses of ACE inhibitors may stimulate drinking by causing an increase of renin in the peripheral tissue and hence angiotensin. 1,2 In the brain, the angiotensin-I is converted to angiotensin-II, which may stimulate thirst and the release of ADH. 1–3 In addition, ACE inhibitors delay the degradation of bradykinin, which causes stimulation of ADH secretion. 4 On the basis of our literature search (Medline 1966– 2000), we found 14 published cases with ACE inhibitor– induced SIADH, the majority in patients age 70 and older. In our case, like the other published cases of ACE inhibitor– induced SIADH, hyponatremia resolved with discontinuation of the drug. Therefore, we recommend monitoring sodium levels when ACE inhibitor treatment is initiated in older people, especially during the first few months of treatment.