Patients Receiving Diuretic Therapy Research Articles

Abdominal Congestion as a Predictor of Worsening Renal Function in Patients With Acute Decompensated Heart Failure.

Worsening renal function is a frequent finding in patients with acute decompensated heart failure (ADHF) and is a powerful independent prognostic factor for adverse outcomes. The link between abdominal congestion and worsening renal function in such patients is not yet fully addressed. To evaluate the role of abdominal congestion in the early prediction of worsening renal function in hospitalized patients with acute decompensated heart failure. This was a prospective study that enrolled 100 patients with a diagnosis of ADHF and received intravenous diuretic therapy. Intra-abdominal pressure (IAP), splenic Doppler impedance indices and serum prouroguanylin were measured on admission, 24 h after admission and on discharge. Patients were then divided into 2 groups: those who developed WRF (WRF group), and those who did not (non-WRF group). Worsening renal function was defined as an increase in serum creatinine level ≥0.3 mg/dL above baseline admission value. Intrabdominal pressure was measured transvesically using standard Foley catheter. Splenic Doppler impedance indices (resistivity and pulsatility indices) were measured using splenic Doppler ultrasound. Among recruited patients (age: 54.73 ± 13.1 years, 72% are male), there was a significant decline in IAP (6.67 mmHg vs 8.36 mmHg, p = 0.001) and significant rise in splenic resistivity index (0.69 vs 0.67, p = 0.002) before discharge compared to admission values. The median level of serum prouroguanylin before discharge showed significant decline compared to admission level (29.2 vs 34.6 ng/l, p = 0.006). WRF developed in 37 (37%) patients. Independent predictors of WRF during hospitalization were high splenic arterial resistivity index 24 h after admission, high intra-abdominal pressure (≥8 mmHg) 24 h after admission, and low LVEF on admission. In ADHF patients receiving diuretic therapy, transvesical measurement of intra-abdominal pressure and splenic resistivity index by splenic Doppler early after admission can help to identify patients at increased risk of WRF near discharge.

Prevalence of Thiamine Deficiency in Chronic Heart Failure Patients: Ramathibodi Cardiology Clinic Experience

Objective: Thiamine deficiency is still a public health concern in developing countries including Thailand. Heart failure is associated with thiamine deficiency especially in patients receiving diuretic therapy. Therefore, we sought to find the prevalence of thiamine deficiency in chronic heart failure outpatients. Materials and Methods: A cross-sectional descriptive epidemiological study in 50 heart failure patients scheduled for regular follow-up visits at Ramathibodi Cardiology Clinic, Mahidol University, Bangkok, Thailand. Thiamine pyrophosphate effect was used to identify thiamine deficiency. Review of electrical medical records were made in order to collect variable clinical and demographic data. Results: The mean age was 60±2.1 years, 54% were male. The mean left ventricular ejection fraction was 37±2.5%. The prevalence of thiamine deficiency in a chronic heart failure outpatient was 6% (n=3). Thiamine status was negatively associated with left ventricular ejection fraction (r=-0.283, p=0.047) and thiamine status was positively associated with left ventricular dimension (r=0.462, p=0.001). However, there was no association between the dose of diuretic and thiamine status (r=0.024, p=0.882), duration of heart failure and thiamine status (r=-0.012, p=0.945). In patients with severe thiamine deficiency, there were subsequent serious adverse cardiovascular outcomes (one had cardiac arrest and underwent left ventricular assist device). Conclusion: We found that the prevalence of thiamine deficiency in chronic heart failure outpatients is low in an urban outpatient setting. Keywords: Thiamine deficiency; Heart failure; Prevalence

New renal haemodynamic indices can predict worsening of renal function in acute decompensated heart failure.

AimsWorsening of renal function (WRF) is a common complication in patients with acute decompensated heart failure (ADHF). We aimed to evaluate the role of intrarenal Doppler ultrasound (IRD) in the early prediction of WRF in this patient group.Methods and resultsAmong 90 patients (age: 57.5 ± 11.1 years; 62% male) hospitalized with ADHF, resistivity index (RI), acceleration time (AT), and pulsatility index (PI) were measured on admission and at 24 and 72 h. WRF was defined as increased serum creatinine ≥0.3 mg/dL from baseline. Adverse clinical outcomes were defined as the composite of death, use of vasopressors, and need for ultrafiltration for refractory oedema. WRF developed in 40% of patients. Mean values of renal AT, RI, and PI on admission were 59.7 ± 15, 0.717 ± 0.08, and 1.5 ± 0.48 ms, respectively. At 24 h, there was significant decrease in AT (to 56.7 ± 10 ms, P = 0.02) and renal RI (to 0.732 ± 0.07; P < 0.001); these changes were maintained up to 72 h. Renal PI showed no significant changes. Independent predictors of WRF were renal AT at 24 h and admission values of renal RI, left ventricular ejection fraction, and plasma cystatin C. Renal AT at 24 h ≥ 57.8 ms had 89% sensitivity and 70% specificity for the prediction of WRF. Independent predictors for adverse clinical outcomes were left ventricular end systolic dimension and WRF.ConclusionsAmong ADHF patients receiving diuretic therapy, measurement of renal AT and RI by IRD can help identify patients at increased risk for WRF.

Abdominal Obesity Is Associated With Potassium Depletion and Changes in Glucose Homeostasis During Diuretic Therapy

The activation of the renin-angiotensin system (RAS) is an important mechanism that contributes to hypertension in obese individuals. Thiazide diuretics also activate the RAS in response to volume contraction and can lead to a decrease in serum potassium values and glucose metabolism abnormalities. To evaluate the impact of abdominal obesity on potassium depletion and glucose homeostasis in hypertensive patients receiving thiazide therapy, the authors studied 329 hypertensive patients without known diabetes or impaired renal function. Patients were stratified into 2 major groups according to whether they used thiazide diuretic therapy, and each group was further divided in 2 subgroups according to the presence of abdominal obesity. The authors demonstrated that obese patients receiving diuretic therapy had lower plasma potassium levels and higher glucose values compared with nonobese patients receiving diuretic therapy. In conclusion, abdominal obesity predisposes to potassium depletion during diuretic therapy in association with effects on glucose homeostasis.

Is it Meaningful to use Biochemical Parameters to Discriminate Between Transudative and Exudative Pleural Effusions?

The usefulness of biochemical criteria to separate pleural transudates from exudates is controversial, and the limitations of Light's criteria in patients receiving diuretic therapy is of general concern. We evaluated the added value of biochemical criteria to clinical judgment for separating transudates from exudates. A community teaching hospital. A prospective, observational study for the evaluation of diagnostic tests. In 249 consecutive patients referred for diagnostic thoracentesis, two physicians classified the pleural effusion as transudate or exudate based on all available information just before performing the thoracentesis. The sensitivity, specificity, and accuracy of the clinical presumption were compared with those of Light's criteria, and serum-pleural fluid albumin and protein gradients. The combined accuracy of biochemical and clinical criteria was also assessed. The accuracy of Light's criteria (93%) was significantly higher than that showed by the initial clinical presumption (84%; p < 0.01) and that of the alternative biochemical criteria: serum-pleural fluid albumin gradient (87%; p < 0.03) and serum-pleural fluid protein gradient (86%; p < 0.01). In patients receiving diuretic therapy, the accuracy of Light's criteria was 83% (60 of 72 cases), neither different to that of the albumin gradient (88%; 63 of 72 cases) nor to that of the protein gradient (86%; 62 of 72 cases). When these alternative biochemical criteria were applied exclusively to patients receiving diuretics who were thought to have a transudative effusion by clinical criteria, but having fluid identified as exudative by Light's criteria, the results did not improve significantly. Using a multiparametric model for the population receiving diuretics, the accuracy was greater (93%; 67 of 72 cases) than that of Light's criteria but without reaching statistical significance (p = 0.12). Light's criteria are significantly superior to the clinical presumption to separate pleural transudates from exudates. In patients receiving diuretics, Light's criteria lose accuracy, which is similar to that showed by the use of alternative biochemical criteria alone or combined with clinical judgment.

The automatic lung parameter estimator (ALPE) system: non-invasive estimation of pulmonary gas exchange parameters in 10-15 minutes.

Clinical measurements of pulmonary gas exchange abnormalities might help prevent hypoxaemia and be useful in monitoring the effects of therapy. In clinical practice single parameters are often used to describe the abnormality e.g., the "effective shunt." A single parameter description is often insufficient, lumping the effects of several abnormalities. A more detailed picture can be obtained from experiments where FiO2 is varied and two parameters estimated. These experiments have previously taken 30-40 minutes to complete, making them inappropriate for routine clinical use. However with automation of data collection and parameter estimation, the experimental time can be reduced to 10-15 minutes. A system has been built for non-invasive, Automatic, Lung Parameter Estimation (ALPE). This system consists of a ventilator, a gas analyser with pulse oximeter, and a computer. Computer programs control the experimental procedure, collect data from the ventilator and gas analyser, and estimate pulmonary gas exchange parameters. Use of the ALPE system, i.e. in estimating gas exchange parameters and reducing experimental time, has been tested on five normal subjects, two patients before and during diuretic therapy, and on 50 occasions in patients before and after surgical intervention. The ALPE system provides estimation of pulmonary gas exchange parameters from a simple, clinical, non-invasive procedure, automatically and quickly. For normal subjects and in patients receiving diuretic therapy, data collection by clinicians familiar with ALPE took (mean +/- SD) 13 min 40 sec +/- 1 min 23 sec. For studies on patients before and after surgery, data collection by an intensive care nurse took (mean +/- SD) 10 min 47 sec +/- 2 min 14 sec. Parameter estimates were: for normal subjects, shunt = 4.95% +/- 2.64% and fA2 = 0.89 +/- 0.01; for patients with heart failure prior to diuretic therapy, patient 1, shunt = 11.50% fA2 = 0.41, patient 2 shunt = 11.61% fA2 = 0.55; and during therapy: patient 1, shunt = 11.51% fA2 = 0.71, patient 2, shunt = 11.22% fA2 = 0.49. The ALPE system provides quick, non-invasive estimation of pulmonary gas exchange parameters and may have several clinical applications. These include, monitoring pulmonary gas exchange abnormalities in the ICU, assessing post-operative gas exchange abnormalities, and titrating diuretic therapy in patients with heart failure.

Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications

Although the prevalence of nephrotoxicity in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) is relatively low, the extensive use profile of these agents implies that many persons are at risk. At basal states of normal renal function, the role of renal prostaglandin production for maintenance of stable renal hemodynamic function is relatively limited. Nonetheless, in the clinical setting of reduced renal perfusion as seen in various forms of cardio-renal disease, dehydration, and the aging kidney, the adequacy of renal prostaglandin production mediated predominantly by cyclooxygenase-1 (COX-1) and, potentially, by COX-2 enzyme activity becomes of major significance in the activation of compensatory renal hemodynamics. Inhibition of renal prostaglandin production by the use of NSAIDs in these circumstances can potentially lead to the emergence of several distinct syndromes of disturbed renal function. These include fluid and electrolyte disorders, acute renal dysfunction, nephrotic syndrome/interstitial nephritis, and renal papillary necrosis. In addition, by blunting the homeostatic renal effects of prostaglandins, NSAIDs can adversely influence blood pressure control, particularly during the use of angiotensin-converting enzyme (ACE) inhibitors, diuretics, and β blockers. This is a matter of considerable public health concern, in that some 12 million US citizens are concurrently treated with NSAIDs and antihypertensive drugs. Finally, the risk of congestive heart failure is significantly increased when NSAIDs are given to patients receiving diuretic therapy who have cardiovascular risk factors. Physiologic factors, clinical presentations, diagnostic modalities, and clinical management strategies appropriate to these NSAID-induced renal syndromes are described.

Diuretic Drug Utilization Study

Objective: To evaluate the present use of diuretics in our institution, and determine the appropriateness of that use and the incidence of adverse reactions and interactions. Design: This retrospective study describes the indications for use of an identified drug or combination of drugs. By the time the data were collected, some patients had been discharged or had died. Setting: The study was carried out in a referral center, the University Hospital “Virgen Macarena,” Seville, Spain. Patients: All patients receiving diuretic therapy. Those undergoing hemodialysis or receiving home care were excluded from the study. Intervention: A therapeutic audit was performed using specific standards of reference. Two models were used — one for each of the most frequent indications, ascites and congestive heart failure (CHF). Main Outcome Measures: A structured protocol gathered data on (1) demographic characteristics, (2) causes of admission and pathologic antecedents, (3) diuretic treatment, (4) basic controls (24-h diuresis and daily basal weight), (5) clinical evolution, and (6) concurrent complementary studies. The protocol included a checklist of the most frequent adverse drug reactions and interactions whose degree of causality was determined by applying the modified algorithm of Karch-Lasagna, used in the World Health Organization voluntary reporting system of adverse drug reactions. Results: One hundred twenty-six patients (16% of total admissions) received diuretic therapy. Of these, 71% were analyzed; information in the medical records was incomplete for the rest (29%). Fifty-one percent of the patients were more than 60 years old. The most frequent admission diagnoses were cardiovascular (51.5%), followed by digestive (16.7%) diseases. A total of 134 cardiac symptoms was seen in 50 patients. The most notable were acute pulmonary edema (26%), ischemic cardiopathy (12%), and cardiogenic shock (8%). Most patients receiving diuretic therapy (47.3%) were admitted to the internal medicine service. The most-prescribed diuretic was furosemide (59%), followed by spironolactone (27%). The combined use of furosemide and spironolactone occurred in all but 1 of the patients with hepatic ascites (92%), whereas in those with CHF the figure for the combined use of furosemide and spironolactone fell to 38% (p = 0.001). In 63% of the patients with ascites, the spironolactone dosage was changed in the first 48 hours of treatment. There was a high percentage of deaths (21%) in the study patients. Conclusions: Therapeutic strategy often does not follow the guidelines laid down in the standards of reference on diuretic use in serious CHF and/or ascites in this institution.

The Diurnal Rhythm of Plasma Potassium

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

The Value of Serum Magnesium Determination in Hypertensive Patients Receiving Diuretics

Some clinicians contend that hypomagnesemia is a common problem in patients receiving diuretic therapy and that routine serum magnesium determinations may be indicated in such patients. We determined serum magnesium (Mg++) levels in 354 patients with uncomplicated hypertension. No significant difference was observed in the mean Mg++ between the 245 diuretic-treated patients and the 109 patients not receiving diuretics, 0.965 vs 0.97 mmol/L (1.93 vs 1.94 mEq/L). When analyzed by type of diuretic, there were statistically significant differences in the mean serum Mg++ concentrations between those receiving thiazides, 0.94 mmol/L (1.87 mEq/L); those receiving no diuretics, 0.97 mmol/L (1.94 mEq/L); and those receiving triamterene-containing diuretics, 1.01 mmol/L (2.01 mEq/L). These absolute differences, however, were clinically quite small, and hypomagnesemia was uncommon. Neither patient age, the duration of diuretic use, nor the serum potassium level correlated with Mg++. With respect to dose, those receiving 100 mg/d of hydrochlorothiazide had the lowest Mg++ concentrations and the greatest prevalence of hypomagnesemia (12%), defined as Mg++ less than 0.75 mmol/L (1.5 mEq/L). Serum Mg++ need not routinely be determined in patients with uncomplicated hypertension who are receiving triamterene-containing diuretics or low-dose (50 mg/d or less) hydrochlorothiazide.

The Value of Serum Magnesium Determination in Hypertensive Patients Receiving Diuretics

Some clinicians contend that hypomagnesemia is a common problem in patients receiving diuretic therapy and that routine serum magnesium determinations may be indicated in such patients. We determined serum magnesium (Mg++) levels in 354 patients with uncomplicated hypertension. No significant difference was observed in the mean Mg++ between the 245 diuretic-treated patients and the 109 patients not receiving diuretics, 0.965 vs 0.97 mmol/L (1.93 vs 1.94 mEq/L). When analyzed by type of diuretic, there were statistically significant differences in the mean serum Mg++ concentrations between those receiving thiazides, 0.94 mmol/L (1.87 mEq/L); those receiving no diuretics, 0.97 mmol/L (1.94 mEq/L); and those receiving triamterene-containing diuretics, 1.01 mmol/L (2.01 mEq/L). These absolute differences, however, were clinically quite small, and hypomagnesemia was uncommon. Neither patient age, the duration of diuretic use, nor the serum potassium level correlated with Mg++. With respect to dose, those receiving 100 mg/d of hydrochlorothiazide had the lowest Mg++ concentrations and the greatest prevalence of hypomagnesemia (12%), defined as Mg++ less than 0.75 mmol/L (1.5 mEq/L). Serum Mg++ need not routinely be determined in patients with uncomplicated hypertension who are receiving triamterene-containing diuretics or low-dose (50 mg/d or less) hydrochlorothiazide.

Lack of efficacy of digoxin in treatment of compensated congestive heart failure with third heart sound and sinus rhythm in elderly patients receiving diuretic therapy

Use of digitalis for treatment of patients with congestive heart failure (CHF) and sinus rhythm is controversial. 1–4 Using a clinicoradiographic scoring system, Lee et al 2 found that the severity of CHF was reduced by digoxin therapy in 14 of 25 outpatients (56%) in sinus rhythm. They showed that the presence of a third heart sound was the strongest correlate of a beneficial response to digoxin therapy. We investigated the effect of digoxin on symptoms, clinical signs and chest x-ray evidence of CHF, cardiothoracic ratio on chest x-ray, echocardiographic left ventricular ejection fraction and treadmill exercise duration in 10 elderly patients with compensated CHF and a third heart sound. All patients were in sinus rhythm and were receiving digoxin and diuretic therapy.

Unexpected effects of treating hypertension in men with electrocardiographic abnormalities: a critical analysis.

The relationship between diuretic therapy and possible increased risk of coronary heart disease (CHD), especially sudden death, is controversial. The initial report from the Multiple Risk Factor Intervention Trial (MRFIT) raised the possibility that the increased CHD mortality observed in a subset of special intervention men with hypertension and certain electrocardiographic abnormalities on their baseline examination might be an unexpected adverse effect of diuretic therapy. Subsequent reports from the MRFIT have revealed a stronger association of CHD mortality to hydrochlorothiazide than to chlorthalidone. There was no consistent relationship of CHD mortality to the dose of either drug, to the most recent serum potassium level, or to the presence of ventricular premature beats. Unfavorable trends of the same magnitude were also seen among similar white men in the Hypertension Detection and Follow-up Program and in the Oslo hypertension trial, although the sample sizes in these two studies were too small to yield clearcut conclusions. Clinical studies have shown an increased risk of CHD death among hypertensive men with left ventricular hypertrophy. Such men are also noted to have a higher frequency of ventricular premature beats, even in the absence of diuretic therapy. Other studies have shown that diuretic-induced hypokalemia is accentuated in the presence of epinephrine and that low potassium levels decrease the threshold for ventricular fibrillation. Thus, although the evidence is still incomplete, it is possible that the excess CHD mortality among MRFIT special intervention men with electrocardiographic abnormalities may have been caused by a combination of increased left ventricular mass in the presence of coronary atherosclerosis, and hypokalemia caused by good compliance with diuretic therapy and accentuated by stress-induced increases in circulating catecholamines. Given the very large population of patients receiving diuretic therapy, further evaluation of this possibility is important.

Diuretics and potassium metabolism: A reassessment of the need, effectiveness and safety of potassium therapy

In the past decade approximately forty-eight billion milliequivalents of a single oral potassium chloride preparation have been produced and sold by a single pharmaceutical manufacturer (WETTER MS, Ciba Pharmaceutical Co., June, 1976, personal communication). Precise figures for the total quantity of potassium prescribed annually are not available, but an estimate of 20 to 30 billion milliequivalents is probably reasonably accurate. It is also a reasonable assumption that a substantial fraction of this electrolyte supplement is prescribed to prevent or to treat the hypokalemia and potassium deficiency generally thought to result from diuretic therapy. The conclusion seems inescapable, considering the enormous amounts of potassium prescribed, that the majority of physicians feel confident that routine treatment with an oral potassium preparation is warranted in patients receiving diuretic therapy. This opinion is maintained even though several recent studies have raised serious question about the need for such therapy and have also pointed out the potential risk of treatment [1–6]. Indeed, the casual approach to the administration of potassium contrasts sharply with the cautious approach to the use of a drug such as chloramphenicol, even though the ratio of risk to benefit is probably considerably higher for potassium salts as compared to the antibiotic. The purpose of this review is to discuss the magnitude of potassium deficiency in patients receiving diuretics, the influence of diuretic-induced acid-base derangements on potassium balance, the necessity and effectiveness of therapy with potassium salts and potassium conserving drugs and, finally, the benefits and costs of therapy.