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Hydrochlorothiazide is a diuretic agent commonly used to treat hypertension, chronic edema from congestive heart failure or cirrhosis, and nephrogenic diabetes insipidus. Diuretics work by increasing urine output and are classified based on the specific renal segments they act on. As with all medications, they are not without their side effects. The most significant and serious include hypovolemia and electrolyte disturbances. Other more rare adverse effects include dermatitis and hypersensitivity reactions. We discuss an 86-year-old male who presented to the emergency room with complaints of lightheadedness and progressive exfoliating rash that began shortly after starting hydrochlorothiazide in an outpatient setting.
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AIMS: To help establish optimized treatment strategies for congestion in patients with acute heart failure, this study aimed to provide a detailed summary of real-world diuretic use in hospitalized patients with heart failure requiring urgent therapy in Japan. METHODS AND RESULTS: This observational study used a Japanese medical records database to extract data of patients admitted to hospital with a heart failure diagnosis and an intravenous diuretic prescription from the day before admission to 2 days after. Time from hospital visit to first dose, second dose, and maximum dose of intravenous diuretics were determined. Patients were grouped according to whether they received diuretic modification, defined as an intravenous diuretic dose increase or concomitant use of other diuretics. RESULTS: Overall, 1577 patients were included in the study (without diuretic modification, n = 1140 [72.3%]; with diuretic modification, n = 437 [27.7%]). The study population was 49.5% female (n = 780) and the mean age ± standard deviation was 80.1 ± 12.7 years. Intravenous diuretic treatment was received within 1 h of their hospital visit in 43.5% of patients (686/1577) and ≤2 h in 16.4% of patients (258/1577). Among 437 patients with an inadequate response following their first dose, 42.1% received an intravenous dose titration, 56.5% received combination diuretics, and 1.4% received both. Over half of the patients (59.0% [258/437]) with diuretic modification received it after the first 24 h of the hospital visit. The median time from hospital visit to first dose titration was similar to time to first combination diuretic use (18.6 h and 17.0 h, respectively). The mean ± standard deviation duration of intravenous diuretic use was significantly longer for patients with versus without diuretic modification (6.3 ± 5.2 vs. 3.7 ± 3.2 days), and a significantly greater proportion of patients (44.6% [195/437] vs. 35.0% [399/1140]) received repeated intravenous diuretic administration. Other characteristics/outcomes of intravenous diuretic use were similar with versus without diuretic modification, including in-hospital death (15.6% [68/437] vs. 13.9% [159/1140]) and mean ± standard deviation length of hospitalization (21.9 ± 14.7 days vs. 22.1 ± 21.2 days). CONCLUSIONS: In Japan, real-world patterns of intravenous diuretic administration for patients with heart failure remains far from the time-sensitive approach recommended in Japanese, European, and United States guidelines.
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BACKGROUND/AIMS: Congestion is prognostically relevant in cardiac transthyretin amyloidosis (ATTR-CA), but whether congestion has an incremental prognostic value beyond the well-established, congestion-sensitive NT-proBNP is unknown. Therefore, we aimed to comparatively evaluate the prognostic utility of several congestion surrogates over NT-proBNP. METHODS: We estimated hazard ratios by Cox proportional hazards regressions with time-varying covariates from a panel data set of the local amyloidosis cohort study AmyKoS. Different models were compared by using chi(χ)2-statistics measuring overall model significance. RESULTS/CONCLUSION: 131 ATTR-CA patients (wild-type 84.0%, hereditary 6.9%, without genetic testing 9.2%; median age 78.7 (quartiles 73.3, 82.1) years; 85.5% male) with 566 observations across a median follow-up of 38.2 (30.6; 48.2) months were analyzed. 83.2% received disease-modifying treatment; 20.6% participated concurrently in placebo-controlled gene silencer trials. Information on congestion improved biomarker-driven risk stratification and identified patients at the highest risk. Echocardiographic congestion markers performed better than clinical findings and daily diuretic use/dosage. Relevant adjusters were daily diuretic dosage, disease-modifying treatment, eGFR, and right atrial volume. NT-proBNP and the tricuspid regurgitation peak velocity (tr-vmax) provided an easy-to-use stratification with overall model performance similar to NAC and Mayo staging systems. Further analyses are necessary for validation and to identify the optimal cut points of the congestion markers.
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INTRODUCTION: During Neonatal Intensive Care Unit hospitalization, children born preterm with bronchopulmonary dysplasia (BPD) are frequently prescribed diuretics for chronic respiratory symptoms. However, less is known about diuretic use and weaning in an outpatient setting. The study sought to characterize clinical features associated with outpatient diuretic use and timing of diuretic weaning in children with BPD. METHODS: Data was obtained by chart review from 1224 registry participants born <32 weeks gestation, discharged between 2008 and 2023 and recruited from outpatient BPD clinics at Johns Hopkins Children's Center and the Children's Hospital of Philadelphia (97.4% diagnosed with BPD). Data was analyzed using Chi-square tests, t-tests, and ANOVA tests. RESULTS: Children on diuretics at their first pulmonary visit (n = 737) were more likely to have lower birth weights, earlier gestational age, and severe BPD compared to those not on diuretics (n = 487). Of those prescribed diuretics, most children were on a thiazide alone (46.4%) or a thiazide and a potassium sparing agent (44.8%) with a minority prescribed loop diuretics alone (3.3%) or loop diuretic combinations (4.7%). Most children weaned off diuretics by 2 years of age. Public insurance, early gestational age, technology dependence, home supplemental oxygen use and loop diuretics were associated with slower diuretic weaning. CONCLUSION: Outpatient diuretic use is common in children with BPD, however variations in diuretic use and diuretic combinations exist across centers. Time to wean off home supplemental oxygen is similar between children on one diuretic compared to none. Timing of outpatient diuretic weaning is influenced by diuretic class, respiratory support, and co-morbidities.
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OBJECTIVES: The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3-5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3-5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). METHODS: Using data from the National Health Insurance Research Database (January 2008 to December 2019), we focused on individuals with stage 3-5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. RESULTS: The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (p-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all p-value <0.001). CONCLUSION: Among stage 3-5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal function. These findings highlight the need for randomized controlled trials to assess the safety of loop diuretics in this population, urging caution in their prescription without a clear clinical indication.
Fluid overload is common in patients with advanced chronic kidney disease (CKD) due to their decreased ability to excrete water. Diuretic therapy is often used to manage this condition. However, prolonged use of diuretics may activate harmful bodily systems, including the renin-angiotensin-aldosterone system and the sympathetic nervous system. Our study, focusing on Taiwanese patients with stage 35 CKD and hypertension, found that loop diuretics, such as furosemide, were linked to higher risks of hospitalization, mortality, and serious heart and kidney complications. Thiazide diuretics did not show these adverse effects, suggesting they may be safer for these patients. More research is needed to clarify the long-term impact of diuretics on this population.
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In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.
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AIMS: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload. METHODS AND RESULTS: Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6-h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6-h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output <50 mmol in the 6 h following diuretic administration). The NRPE was compared with urine sodium and measured urine output which are the methods currently recommended by international guidelines to assess diuretic response. Eighty-seven diuretic administrations from 49 patients were analysed. Mean age of patients was 57 ± 17 years and 67% were male. Mean estimated glomerular filtration rate was 65 ± 28 mL/min/1.73 m2, and ejection fraction was 35 ± 15%. Median dose of intravenous furosemide equivalents administered the day of the study was 80 mg (IQR 40 - 160). Poor natriuretic response occurred in 39% of the visits. The AUC of the NRPE to predict poor natriuretic response during the 6-h urine collection was 0.91 (95% CI 0.85-0.98). Compared with the NRPE, spot urine sodium concentration (AUC 0.75) and urine output during the corresponding nursing shift (AUC 0.74) showed lower discrimination capacity. CONCLUSIONS: In this cohort of patients with ADHF, the NRPE outperformed spot urine sodium concentration and all other metrics related to diuretic response to predict poor natriuretic response. Our findings support the use of this equation at other settings to allow rapid and accurate prediction of natriuretic response.
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Background: Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia. Methods: All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level ≥135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125-134 mmol/L). Results: A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively). Conclusion: Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.
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PURPOSE: This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet-cold pattern), from the viewpoint of cardiorenal syndrome. METHODS: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria-Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. RESULTS: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet-cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). CONCLUSION: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF.
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Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic-centred) paradigm of long-term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms.
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Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (Nâ¯= 2267, 1564 women, 703 men, mean age ± standard deviation 81.9⯱ 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1⯱ 7.3 years, pâ¯= 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (pâ¯= 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.
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BACKGROUND: The efficacy of dapagliflozin in patients with acute heart failure remains unclear. OBJECTIVE: To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure. METHODS: In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People's Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM). RESULTS: A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385-1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441-1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P<0.001), lower total loop diuretic dose during hospitalization (106.06 ± 31.23 mg vs. 144.50 ± 45.39 mg, P = 0.038) and a decreased number of diuretic types used (11.88% vs. 23.12%, P = 0.008). CONCLUSIONS: DAPA reduced the dose of intravenous loop diuretics. However, it did not improve all-cause readmission for 90 days or readmission for heart failure after discharge.
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Benzhydryl Compounds , Glucosides , Heart Failure , Patient Readmission , Propensity Score , Sodium Potassium Chloride Symporter Inhibitors , Humans , Heart Failure/drug therapy , Heart Failure/diagnosis , Heart Failure/physiopathology , Retrospective Studies , Male , Female , Aged , Middle Aged , Treatment Outcome , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Sodium Potassium Chloride Symporter Inhibitors/adverse effects , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Acute Disease , Glucosides/adverse effects , Glucosides/therapeutic use , Glucosides/administration & dosage , Time Factors , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/administration & dosage , Risk Factors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Drug Therapy, Combination , China/epidemiology , Aged, 80 and over , Risk AssessmentABSTRACT
Background: The use of diuretics in patients on haemodialysis (HD) is thought to maintain diuresis. However, this assumption and the optimal dose are based on little scientific evidence, and associations with clinical outcomes are unclear. Methods: We reported international variations in diuretic use and loop diuretic dose across 27 759 HD patients with dialysis vintage <1 year in the Dialysis Outcomes and Practice Patterns Study phases 2-5 (2002-2015), a prospective cohort study. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent doses. Adjusted Cox, logistic and linear regressions were used to investigate the association of diuretic use and dose with outcomes. Results: Diuretic utilization varied widely by country at vintage <3 months, ranging from >80% in Germany and Sweden to <35% in the USA, at a median dose ranging from 400-500 mg/day in Germany and Sweden to <100 mg/day in Japan and the USA. Neither diuretic use nor higher doses were associated with a lower risk of all-cause mortality, a higher risk of hospitalization for fracture or elevated parathyroid hormone levels, but the prescription of higher doses (>200 mg/day) was associated with a higher risk of all-cause hospitalization. Conclusions: Substantial international differences exist in diuretic prescriptions, with use and doses much higher in some European countries than the USA. The prescription and higher doses of loop diuretics was not associated with improved outcomes.
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Bidirectional ventricular tachycardia (BVT) is a rare form of malignant ventricular arrhythmia characterized by beat-to-beat alternation in the QRS axis. BVT is a hallmark of digitalis toxicity, but digoxin-induced BVT secondary to digoxin-diuretic interaction in cardiac surgery patients is not widely reported. We present the case of a 62-year-old woman undergoing mitral valve replacement with tricuspid annuloplasty who developed postoperative congestive heart failure and vasoplegic syndrome requiring norepinephrine, vasopressin, and loop diuretics. During postoperative care, she presented atrial fibrillation with rapid ventricular response, achieving rate control with digoxin, but later displayed hemodynamically stable BVT associated with digitalis toxicity. The case highlights the importance of physicians monitoring digoxin toxicity when prescribing digoxin to patients with a diuretic regimen, particularly loop diuretics. During digoxin-induced-BVT, supportive treatment, including discontinuing digitalis coupled with potassium and magnesium supplements, can be considered as long as digoxin-specific antibodies are unavailable, and the patient is hemodynamically stable.
La taquicardia ventricular bidireccional (TVB) es una arritmia rara caracterizada por alternancia latido a latido en el eje QRS. La TVB es característica de intoxicación digitálica; sin embargo, la TVB secundaria a interacción digoxina-diurético en pacientes posoperados de cirugía cardíaca no se ha reportado ampliamente. Presentamos el caso de una mujer de 62 años sometida a cirugía cardiaca que desarrolló falla cardiaca congestiva y síndrome vasopléjico en el posoperatorio por lo que requirió noradrenalina, vasopresina y diurético de asa. Durante la hospitalización presentó fibrilación auricular con respuesta ventricular rápida; se logró control con digoxina, pero posteriormente presentó TVB asociada a intoxicación digitálica. Este caso resalta la importancia de detectar intoxicación digitálica durante la prescripción de digoxina a pacientes con un régimen diurético, especialmente diuréticos de asa. Durante la TVB inducida por digoxina, el tratamiento de soporte se puede considerar cuando no haya disponible anticuerpos específicos para digoxina y el paciente este hemodinámicamente estable.
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Patients with acutely decompensated heart failure (ADHF) are usually admitted to hospital for management. There is growing interest in delivering intravenous (IV) diuretic therapy at home, in the community or at hospital day-care units; the safety and effectiveness of outpatient-based management (OPM) for ADHF has not been established. We conducted a systematic literature review and meta-analysis to investigate the short-term safety and effectiveness of OPM compared with inpatient management (IPM) of ADHF. Pre-specified endpoints were 30 day mortality and 30 day hospitalization. The meta-analysis was conducted using RevMan 5.4 software. Twenty-nine studies of OPM were identified, including 7683 patients. Only five studies directly compared OPM (n = 1303) with IPM (n = 2047), including three observational studies, and two randomized controlled trials (RCTs). The other 24 studies only stated OPM outcomes. For the five studies comparing IPM versus OPM, patients were generally aged >75 years and of similar age for each strategy, with a similar proportion of men (56%). In a study-level, aggregate analysis, 30 day all-cause mortality was 9.3% (121/1303) for OPM, compared with 15.6% (320/2047) for IPM [OR 0.29 (95% CI 0.09, 0.93) P = 0.04]. Four studies reported 30 day all-cause hospitalization; 22.0% for IPM versus 16.8% for OPM [OR 0.73 (95% CI 0.61, 0.89), P = 0.001]. In the two RCTs, we found no difference in 30 day mortality or hospitalization. In observational studies, OPM of ADHF is associated with lower 30 day hospitalization and lower 30 day mortality; such differences were not observed in two small, single-centre RCTs. A substantial, multicentre RCT is required to confirm the safety and effectiveness of OPM for ADHF.
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Hyponatremia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as 100 mL IV bolus or continuous infusion depends on the severity and persistence of the symptoms, and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatremia. In asymptomatic mild hyponatremia, an adequate solute intake with an initial fluid restriction (FR) of 500 mL/d adjusted according to the serum sodium levels is preferred. Almost half of the syndrome of inappropriate diuresis hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered as most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatremia is lacking. Oral urea is considered as very effective and safe treatment. Mild and asymptomatic hyponatremia is treated with adequate solute intake (salt and protein) and an initial FR with adjustments based on serum sodium levels. Specific treatment with vaptans may be considered in either euvolemic or hypervolemic patients with high ADH activity. In order to ensure optimal patient outcome, a close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in decision making process for specific treatment and eventual overcorrection consequences. According to the guidelines, a gradual correction and clinical evaluation is preferable over the rapid normalization of serum sodium towards the laboratory reference ranges.
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Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion, every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.