Emilia Lubart

Early and late effects of low-dose aspirin on renal function in elderly patients

BACKGROUND Although low-dose aspirin is used by many elderly patients, monitoring of renal function is currently not recommended. We recently reported transient retention of uric acid and creatinine caused by aspirin in doses of 75 to 325 mg/d. We therefore evaluated the renal effects of aspirin (100 mg/d), including post-treatment effects. METHODS We studied 83 stable geriatric patients in long-term care (aged 56 to 98 years) who were treated with low-dose aspirin (100 mg/d) for 2 weeks and 40 control patients. Other medications and diet were kept constant. Biochemical monitoring including blood samples and 24-hour urinary collections for creatinine and uric acid at baseline and weekly for a total of 5 weeks. RESULTS After 2 weeks on aspirin, urinary excretion of creatinine decreased in 60 (72%) and excretion of uric acid decreased in 54 (65%) of the 83 patients, and their mean clearances decreased; during the same period, serum blood urea nitrogen, creatinine, and uric acid levels increased (P <0.05 for all). Deterioration from baseline levels was significantly greater (and more prevalent) in the aspirin-treated group than in the 40 control patients (P = 0.001 to 0.09). After withdrawal of aspirin these parameters improved. However, 3 weeks after stopping aspirin, 48% (35 of the 73 in whom this measurement was available) had a persistent decline in creatinine clearance from baseline, as compared with only 8% (3/36) controls (P <0.001). CONCLUSION Short-term low-dose aspirin treatment may affect renal function in elderly patients. These effects persist 3 weeks after cessation of the drug in some of these patients.

Mortality after Nasogastric Tube Feeding Initiation in Long-Term Care Elderly with Oropharyngeal Dysphagia – The Contribution of Refeeding Syndrome

Background: The refeeding syndrome (RS) is an underappreciated but clinically important entity characterized by acute electrolyte abnormalities, mainly hypophosphatemia, fluid retention and dysfunction of various organs and systems, which can result in significant morbidity and occasionally death. Objective: To examine the incidence of death cases and death causes following nasogastric tube (NGT) feeding initiation in frail elderly with particular reference to RS. Methods: Forty patients with feeding problems for at least 72 h before restarting of alimentation by NGT were included. Excluded were those in any critical clinical situation. Clinical parameters and nutritional assessment were recorded before and after refeeding. Blood samples were taken before, daily for the first 3 days and 1 week after refeeding initiation. Results: During the 1st week of refeeding, 9 patients (22.5%) died and within 1 month 10 more, summing to 47.5%. Most deaths were due to infectious causes [15 out of 19, (79%)]; some were due to no obvious reason [4 out of 19, (21%)]. Significant electrolyte changes were observed in the 2–3 days following refeeding. Significant were the decreases in phosphorus and elevations in potassium and lymphocytes (day 7). We found no correlations between the severity of decreases in levels of phosphorus and mortality. Conclusions: Mortality after NGT feeding initiation was high, mainly due to infectious complications. However, in a considerable number of patients hypophosphatemia was noted, suggesting that RS could be a contributory factor of mortality. Since this is a treatable condition, more attention should be paid to detecting and coping with this problem.

Phenytoin Blood Concentrations in Hospitalized Geriatric Patients: Oral Versus Nasogastric Feeding Tube Administration

Many medications administered to frail geriatric patients are not in a liquid form, but are crushed and dissolved in water before their administration through a nasogastric tube (NGT). Some medications are enteric coated and others are extended release. Only sparse information is available on their pharmacokinetics when administered through NGT. The aim of our study was to evaluate the pharmacokinetics of phenytoin administered through an NGT and to compare these with the pharmacokinetics of a group of patients receiving the drug orally. Twenty patients were studied in a stable clinical condition, from the long-term care ward of the Geriatric Medical Center Shmuel Harofeh. They were consistently treated with phenytoin for the prevention of seizure disorders. Patients in group 1 (n = 12) had oropharyngeal dysphagia and received feeding and medications by NGT. Group 2 (n = 8), included age-matched orally fed patients from the same department, who received phenytoin orally. Blood samples for phenytoin concentration were taken at baseline, time 0, and at 1, 3, 4, 6, and 8 hours postdrug administration; phenytoin was measured using the AxSYM assay. The mean daily dose was not statistically different between the 2 groups: 291 ± 28 (200-300) mg/d and 300 ± 53 (200-400) mg/d, in the NGT, and the orally fed group, respectively, in one dose. Pharmacokinetic parameters of phenytoin were not significantly different between the 2 groups; trough concentrations, 1.9 ± 1.7 (0.5-4.9) versus 2.2 ± 1.8 (1.0-6.5) μg/mL; Cmax, 6.6 ± 3.4 (2.5-9.1) versus 7.3 ± 6.7 (2.7-8.4) μg/mL; tmax, 5.1 ± 3.1 (3.1-8.2) versus 4.6 ± 2.7 (2.3-8.4) hours; area under the curve, 52.2 ± 40.1 (41.1-61.2) versus 62.3 ± 84.7 (30.2-77.2) μg/h/mL, in the NGT fed versus the oral fed, respectively. Phenytoin pharmacokinetic parameters are not significantly different between patients receiving the drug through NGT as compared with those who received it orally, but the implication of the low concentrations measured should be evaluated carefully.

The Impact of Refeeding on Blood Fatty Acids and Amino Acid Profiles in Elderly Patients: A Metabolomic Analysis

BACKGROUND Refeeding of elderly frail patients after food deprivation is commonly associated with a high mortality rate. OBJECTIVE To evaluate the effect of refeeding on metabolite fluctuation of blood carnitine fatty acids (15 compounds) and free amino acids (14 compounds). METHODS Metabolite fluctuation was followed up in an exploratory, cohort, and noninterventional study in elderly and frail patients (84.5 ± 5 years) after a long period of food deprivation. Patients in the study group were refed by enteral nutrition (EN) and were followed up during 7 days for blood metabolites (n = 27). Patients in the control group (n = 26) had been fed by EN for more than 3 months. Refeeding was initiated with 10 kcal/kg/d and gradual increases of 200 kcal/d for 3 days afterwards. Blood metabolites were assayed in a sample of 25 µL. RESULTS On food deprivation, the concentrations of all even monocarboxylic carnitine fatty acids were much higher in the study group than in the EN control group (P < .01). Upon refeeding, a remarkable decrease in all carnitine fatty acids was observed. In addition, significant daily fluctuations were observed for most metabolites in the study group of the refed patients as compared with the EN control group (P < .01). The highest fluctuations were observed following refeeding in the 7 patients who later died. CONCLUSION A significant metabolic instability is observed on refeeding even with a slow refeeding schedule of 10 kcal/kg/d. Measurement of metabolomics parameters may be used for the evaluation of malnutrition, refeeding status, and optimization of the enteral formula.

The application of information theory for the estimation of old-age multimorbidity

Elderly patients are commonly characterized by the presence of several chronic aging-related diseases at once, or old-age “multimorbidity,” with critical implications for diagnosis and therapy. However, at the present there is no agreed or formal method to diagnose or even define “multimorbidity.” There is also no formal quantitative method to evaluate the effects of individual or combined diagnostic parameters and therapeutic interventions on multimorbidity. The present work outlines a methodology to provide such a measurement and definition, using information theoretical measure of normalized mutual information. A cohort of geriatric patients, suffering from several age-related diseases (multimorbidity), including ischemic heart disease, COPD, and dementia, were evaluated by a variety of diagnostic parameters, including static as well as dynamic biochemical, functional-behavioral, immunological, and hematological parameters. Multimorbidity was formally coded and measured as a composite of several chronic age-related diseases. The normalized mutual information allowed establishing the exact informative value of particular parameters and their combinations about the multimorbidity value. With the currently intensifying attempts to reduce aging-related multimorbidity by therapeutic interventions into its underlying aging processes, the proposed method may outline a valuable direction toward the formal indication and evidence-based evaluation of effectiveness of such interventions.