Low-dose prazosin in patients with muscle cramps during hemodialysis.

Sympathetic nervous system response to volume stress is more marked in patients with frequent hemodialysis-associated skeletal muscle cramps than in most patients who cramp infrequently. Accordingly, we conducted a double-blind, randomized, and balanced trial in which five patients with frequent hemodialysis-associated cramps were given either placebo or a prazosin dose (ranging from 0.25 to 1.0 mg) at the start of 16 dialysis sessions. These low doses of prazosin appeared to reduce cramp frequency in four of the five patients, and patient-stratified multiple logistic regression analysis indicated an aggregate 58% reduction in cramp frequency (p = 0.030). On the other hand, prazosin therapy was associated with an increased incidence of hypotension that required therapeutic intervention both during (p = 0.033) and after (p = 0.010) hemodialysis. Our findings support the hypothesis that sympathetic activation plays a pathogenetic role in hemodialysis-associated skeletal muscle cramps and suggest that pharmacologic attenuation of this response may be of therapeutic benefit.

Hyponatremia in acute spinal cord injury.

OBJECTIVE: To define the occurrence rate, time course, and potential etiologic factors of hyponatremia in patients with acute spinal cord injury. DESIGN: Analysis of data obtained from a retrospective review of medical records and from a systematized, prospective database pertaining to patients with spinal cord injury. SETTING: A university hospital with a federally funded regional spinal cord injury center and a dedicated spinal cord injury intensive care unit. PATIENTS: Two hundred eighty-two patients admitted between January 1, 1988 and December 31, 1989 with acute (< 24-hr duration) spinal cord or vertebral column injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean age of patients was 36.7 +/- 17.6 (SD) yrs; 225 (80%) of the patients were male and 57 (20%) were female. Hyponatremia, when it occurred, developed at a mean time of 6.4 +/- 6.7 days postadmission, reached its nadir at 8.7 +/- 8.8 days, and occurred in 28% of those patients with cervical injuries, 34% with thoracic injuries, and 27% with lumbar injuries (p = NS). Logistic regression analysis demonstrated that the type of spinal cord injury (Frankel class: range is A = complete neurologic lesion to E = no neurologic lesion) was the strongest predictor of hyponatremia. The occurrence rate of hyponatremia was as follows: Frankel class-A 62%; Frankel class-B 48%; Frankel class-C 41%; Frankel class-D 23%; Frankel class-E 16% (p < .0001). CONCLUSIONS: The prevalence of hyponatremia in acute spinal cord injury is much higher than in the general medical or surgical patient population. This abnormality usually occurs within the first week postinjury. The most significant predictor of hyponatremia is the type rather than the level of spinal cord injury. The potential etiological factors are many and these factors are probably interrelated. The pathophysiological mechanisms that result in hyponatremia must be explored so that this occurrence and its consequences can be prevented.

Failure of deferoxamine to improve iron overload in chronic hemodialysis patients.

We prospectively studied the in vivo dialytic clearance of iron after deferoxamine (DFO) administration in four stable iron-overloaded chronic hemodialysis patients by quantifying iron concentration in blood entering and leaving the dialyzer and in dialysate after infusions of DFO. No significant arteriovenous iron differences were demonstrated. The mean ratio of venous to arterial iron approached identity at 1.005. All dialysate concentrates used contained large amounts of iron (300-610 micrograms/dl). No changes in efferent versus afferent dialysate iron concentration could be demonstrated. We conclude (a) iron removal during dialysis with DFO was not demonstrated; (b) the dialysate concentrate tested contained large amounts of iron; (c) in view of potentially significant toxicity, and lack of demonstrable therapeutic benefit, caution in prescribing DFO chelation therapy for iron overload is recommended.

Plasma estrogens, androgens, and von Willebrand factor in men on chronic hemodialysis.

The role of sex hormones in atherogenesis has not been well defined. Since hemodialysis patients show signs of feminization and an increased propensity for atherosclerosis they are particularly suited to probe the relationship between estrogen, testosterone, and atherosclerosis. Therefore, we measured plasma total, free, and protein-bound estradiol (E2), testosterone (Te), and prolactin in 28 hemodialysis patients and in 30 age-matched controls. Von Willebrand factor (vWF) levels were also assayed. Total and free E2 as well as Te were significantly decreased in the patients (p less than 0.001). However, the E2/Te ratio was elevated in the patients (p = 0.05), as was vWF (p less than 0.01). No correlations were found between hormone levels and vWF, gynecomastia or vascular disease, but vWF and vascular disease were highly correlated. We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis.

Preparation of bacteriologically safe bicarbonate concentrate for hemodialysis.

To determine whether bacteriologic hazards associated with bicarbonate concentrate may be reduced or prevented, evaluation of a system consisting of a mixing tank supplied with R.O. water and two separate storage tanks was undertaken. Bicarbonate was mixed on a schedule specific to usage and dispensed to the storage tanks from which it was drawn off into 2.5 gallon jugs for each treatment. The mixing tank was disinfected with hypochlorite solution (200 ppm) before each use. Storage tanks and 2.5 gallon jugs were disinfected weekly and sampled immediately before scheduled disinfection and after the longest storage time. The mixing tank was sampled for corresponding batches. A 1 ml inoculum of concentrate was plated onto tryptic soy sheep blood agar, incubated for 48 hours at 35 degrees C and colony counts/ml recorded. A total of 225 batches on a 10% sampling schedule were monitored. All cultures have grown less than 50 cfu/ml, which is less than AAMI standards for maximum allowable level for water and dialysate. Bacteriologically safe bicarbonate concentrate can be reliably produced using R.O. water, controlled storage times, and rigid disinfection schedules.

Central nervous system and cardiac manifestations of hydrochlorothiazide overdosage; treatment with hemodialysis.

A patient with end-stage renal failure inadvertently received high-dose hydrochlorothiazide as treatment for hypertension, resulting in CNS and cardiac toxicity. These toxic manifestations were successfully treated with hemodialysis. A hydrochlorothiazide dialysance of 62.5 mL/min was demonstrated. The possibility of hydrochlorothiazide toxicity should be considered in any patient with renal insufficiency who exhibits unexplained arrhythmias or symptoms related to the CNS.

Severe anaphylactoid reactions to cuprammonium cellulose hemodialyzers.

Twenty-one severe reactions to hemodialysis occurred in approximately 260,000 dialysis treatments at three centers within a 10 1/2-year period. Reactions typically appeared within minutes of initiating dialysis, and were characterized by cardiopulmonary, mucocutaneous, and/or gastrointestinal tract symptoms highly suggestive of anaphylaxis. Four respiratory arrests and one death resulted. Analysis of dialyzer use patterns and of each patient's dialyzer exposure history strongly implicated hollow-fiber dialyzers made of cuprammonium cellulose (CC) as a cause of these reactions. No obvious factors could be found to identify predisposed patients. Less than optimal rinsing of the CC hollow-fiber dialyzers prior to use may have been responsible for some, but not all, of these reactions.

The renin-angiotensin-aldosterone system in primary and secondary hypertension.

Important advances have been made in understanding the role of the renin-angiotensin-aldosterone system in the pathogenesis and diagnosis of hypertensive disorders. Measurement of plasma renin activity (PRA) and aldosterone is very important in the assessment of secondary hypertension. Hypertensions with increased PRA include renovascular hypertension, some cases of unilateral and bilateral renal parenchymal disease, malignant hypertension, hypertension associated with oral contraceptive agents, and renin-secreting tumors. Hypertension with decreased PRA is observed in four recognized types of primary aldosteronism: adenoma, bilateral hyperplasia, indeterminate aldosteronism, and glucocorticoid-responsive aldosteronism. Other conditions with hypertension and depressed PRA include ACTH and DOC secreting tumors, primary hyperpituitarism, syndromes of 17-hydroxylase and 11-beta-hydroxylase deficiency. Liddle's syndrome, licorice abuse, exogenous administration of mineralocorticoids, and preeclampsia.

Role of the laboratory in management of acute and chronic renal failure.

The initial assessment and differential diagnosis of acute renal failure is greatly facilitated by laboratory procedures of varying sensitivity and specificity; these are reviewed in detail. Patients with chronic renal failure receiving maintenance dialysis exhibit many laboratory abnormalities which may differ significantly between patients treated with hemodialysis and those receiving peritoneal dialysis. These are also reviewed.