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Use of hypotonic intravenous fluid to maintain hydration in children in hospital has been associated with hyponatraemia, leading to neurological morbidity and mortality. We aimed to assess whether use of fluid solutions with a higher sodium concentration reduced the risk of hyponatraemia compared with use of hypotonic solutions. We did a randomised controlled double-blind trial of children admitted to The Royal Children's Hospital (Melbourne, VIC, Australia) who needed intravenous maintenance hydration for 6 h or longer. With an online randomisation system that used unequal block sizes, we randomly assigned patients (1:1) to receive either isotonic intravenous fluid containing 140 mmol/L of sodium (Na140) or hypotonic fluid containing 77 mmol/L of sodium (Na77) for 72 h or until their intravenous fluid rate decreased to lower than 50% of the standard maintenance rate. We stratified assignment by baseline sodium concentrations. Study investigators, treating clinicians, nurses, and patients were masked to treatment assignment. The primary outcome was occurrence of hyponatraemia (serum sodium concentration <135 mmol/L with a decrease of at least 3 mmol/L from baseline) during the treatment period, analysed by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN1260900924257. Between Feb 2, 2010, and Jan 29, 2013, we randomly assigned 690 patients. Of these patients, primary outcome data were available for 319 who received Na140 and 322 who received Na77. Fewer patients given Na140 than those given Na77 developed hyponatraemia (12 patients [4%] vs 35 [11%]; odds ratio [OR] 0·31, 95% CI 0·16–0·61; p=0·001). No clinically apparent cerebral oedema occurred in either group. Eight patients in the Na140 group (two potentially related to intravenous fluid) and four in the Na77 group (none related to intravenous fluid) developed serious adverse events during the treatment period. One patient in the Na140 had seizures during the treatment period compared with seven who received Na77. Use of isotonic intravenous fluid with a sodium concentration of 140 mmol/L had a lower risk of hyponatraemia without an increase in adverse effects than did fluid containing 77 mmol/L of sodium. An isotonic fluid should be used as intravenous fluid for maintenance hydration in children. National Health and Medical Research Council, Murdoch Childrens Research Institute, The Royal Children's Hospital, and the Australian and New Zealand College of Anaesthetists.

The authors investigated whether tolvaptan, an orally active vasopressin V 2 -receptor antagonist that promotes electrolyte-free water loss, might improve hyponatremia. Serum sodium concentrations in patients with euvolemic or hypervolemic hyponatremia and mild or marked hyponatremia improved with therapy at day 4 and day 30. Tolvaptan holds promise for treating patients with hyponatremic states. Serum sodium concentrations in patients with euvolemic or hypervolemic hyponatremia and mild or marked hyponatremia improved with tolvaptan therapy. Tolvaptan holds promise for treating patients with hyponatremic states. Hyponatremia, the most common electrolyte derangement occurring in hospitalized patients, 1 , 2 is usually classified as hypovolemic, euvolemic, or hypervolemic. The secretion of arginine vasopressin appears to be of central importance in the decline of serum sodium concentrations in all these conditions. 1 , 2 Hyponatremia is reported to be associated with increased morbidity and mortality among patients with heart, liver, or neurologic disease. 3 – 8 Even mild chronic hyponatremia has been associated with subtle neurologic defects, manifested as impairments in balance and attention that can increase the incidence of falls. 9 These deficits may be reversed with the correction of the hyponatremia. Tolvaptan, a . . .

Abstract Context Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. Design A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. Interventions and Outcome A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. Results Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126–129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. Conclusion FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.

The purpose of this study is to compare the effects of two different ways of stopping incubator humidification on episodes of hypothermia, hyperthermia, hyponatraemia, hypernatraemia, or skin injury. The design is a single site, two-armed, parallel, randomised, clinical trial conducted between April 2019 and March 2022. The setting was a quaternary referral and teaching hospital in Queensland, Australia. There were 140 extremely preterm infants, born < 28 weeks gestational age (GA). Intervention groups were (1) cease humidity: incubator humidification turned from 80% to off at 00.01am on day 8 of life ( n  = 70); or (2) gradually reduce humidity: incubator humidification reduced by 5% at 00:01 of each day from day 8 until ceased on day 14 ( n  = 70). The primary outcome was episodes of temperature instability: defined as either hypothermia < 36.5 °C or hyperthermia > 37.5 °C. Secondary outcomes included episodes of hyponatraemia: hypernatraemia or skin injury. One hundred forty infants were enrolled, 70 in each group. No statistically significant differences for any outcomes. Hyperthermia: 77% ( n  = 54) in the cease group and 73% ( n  = 51) in the gradual reduction group ( P  = 0.70). Hypothermia: 53% ( n  = 37) in the cease group and 37% ( n  = 26) in the gradual reduction group ( P  = 0.09). The number of hyponatraemic events was similar for both groups ( P  = 0.73), as for hypernatraemic events ( P  = 0.3). Skin injury in week 2 of life: 63% in the cease group and 67% in the gradual reduction group ( P  = 0.72). Conclusions : Ceasing or gradually reducing incubator humidification after day 7 of life had no effect on the number of episodes of hypothermia or hyperthermia in this cohort of extremely preterm infants (EPTI). There was also no effect on the number of episodes of hyponatraemia or hypernatraemia. Trial registration : ANZCTR.org.au (Australia New Zealand Clinical Trials Registry). ACTRN 1261 9000 266167 Registered 21/2/2019. What is Known: • Incubator humidification is a widely accepted and routine practice in the management of EPTI as it influences transepidermal water loss (TEWL) and supports thermoregulation. However, weaning practices remain varied and inconsistent across the globe. • There remains a paucity of data to inform specific evidenced-based humidification practices. What is New: • Ceasing or gradually reducing incubator humidification after 7 days had no effect on temperature stability, serum sodium levels, or frequency of skin injury in this cohort of EPTI between day 8 and day 14. • There is no apparent benefit in prolonging incubator humidity beyond day 7 of life in these EPTI.

Transurethral resection of the prostate (TURP) is the gold standard surgical treatment for benign prostatic hyperplasia (BPH). Despite its widespread use, monopolar TURP carries a risk of significant complications, particularly transurethral resection (TUR) syndrome leading to hyponatremia and fluid overload. The study evaluates whether prophylactic furosemide prevents hyponatremia and TUR syndrome in monopolar TURP. This study was a triple-blind randomized clinical trial conducted in Al-Zahra and Khorshid educational hospitals of Isfahan, Iran, in 2022-2023. Patients undergoing monopolar TURP, were divided into two groups: those receiving preoperative furosemide and a control group. The primary outcomes were changes in serum sodium levels and the incidence of hyponatremia. Secondary outcomes included fluid balance, complication rates, and recovery times. Continuous data were analyzed using test/Mann-Whitney U, categorical data with Fisher's exact test, and time-based changes with repeated measures ANOVA. Normality was checked via Kolmogorov-Smirnov, and power analysis determined sample size. The furosemide group demonstrated a significantly lower incidence of hyponatremia than the control group (P=0.008). Additionally, serum sodium levels were significantly higher in the furosemide group after surgery (P=0.011), while potassium levels were lower (P=0.003). Mild hypokalemia was observed as a manageable side effect, primarily in patients with baseline potassium levels below 4.1 mmol/L. Preoperative administration of furosemide effectively reduces the risk of TUR syndrome during monopolar TURP. Furosemide effectively reduces hyponatremia but may increase hypokalemia in some cases, limiting its clinical utility during monopolar TURP. Patient-specific assessment and further research are needed to ensure its safe and effective use. IRCT20211208053328N2.

Hyponatremia in acute decompensated heart failure (HF) is indicative of a poor prognosis and predicts morbidity and mortality. We explored the predictive utility of hyponatremia at the time of hospital discharge among HF patients with normal admission sodium (Na). Characteristics and outcomes of HF patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial, who had normal Na on admission, were compared between those who were hyponatremic (Na <135 meq/L) or normonatremic on discharge. Three hundred six patients with normal admission Na had either hyponatremia (n = 86) or normal Na (n = 220) on discharge. Compared with patients with normal Na on discharge, hyponatremic patients were younger (p = 0.004), with lower discharge systolic (p <0.001) and diastolic (p = 0.004) blood pressure, higher discharge blood urea nitrogen (p = 0.011) despite similar creatinine (p = 0.566), lower ejection fraction (p = 0.007), and higher left ventricular end-diastolic (p = 0.028) and end-systolic (p = 0.007) dimensions. Despite comparable congestion on hospital admission, patients with discharge hyponatremia had a higher degree of decongestion throughout hospitalization evident in the significantly greater admission to discharge weight loss (p = 0.044) and admission to discharge reduction in inferior vena cava diameter (p = 0.014). Despite longer initial hospitalization (p = 0.004), total duration in hospital at 30 days (p = 0.004) and 6 months (p = 0.045), there were no significant differences between patients with discharge hyponatremia versus normal Na on discharge regarding rehospitalization (p = 0.386), all-cause mortality (p = 0.440), and composite of death, cardiac rehospitalization, and cardiac transplant (p = 0.799), all up to 6-month following randomization. Restricted cubic spline analysis also showed no significant relationships between discharge Na and the aforementioned 3 outcomes. Cox proportional hazards regressions showed that discharge hyponatremia did not significantly predict any of the 3 outcomes after adjustment for imbalances at baseline. Among patients with discharge hyponatremia, a poor outcome was more likely if they were also hyponatremic on admission: the composite end point occurred in 69.2% of those also hyponatremic on admission versus 51.2% of those with normal Na on admission but decreased Na on discharge (p = 0.045). Because the median discharge Na level in the discharge hyponatremia group was 132 meq/L, our findings suggest a benign nature of mild discharge hyponatremia in HF patients with normal admission Na.

Background This study aimed to compare the effect of two methods of maintenance intravenous fluid therapy on hyponatremia in hospitalized infants with sepsis. Methods In a double-blinded randomized clinical trial, 60 term infants with sepsis were enrolled. Blood samples were taken to determine sodium, potassium, Creatinine, and BUN levels before the initiation of treatment. Urine samples were taken to assess specific gravity and urinary output. Infants in the intervention group received half saline in 10% dextrose and infants in the control group were assigned to receive the conventional solution as maintenance. The above indicators were re-evaluated 24 and 48 h after the initiation of treatment. Two groups were compared concerning the incidence of hyponatremia, and other criteria such as urinary output and urinary specific gravity, blood urea nitrogen (BUN), and creatinine levels. Results Hyponatremia was more common in the control group. Sodium levels were significantly higher in half saline recipients 24 h (137.83 ± 2.86 vs. 134.37 ± 1.91 mmol/L), and 48 h (138.10 ± 2.41 vs. 133.66 ± 1.98 mmol/L) after treatment ( P  < 0.001). Although BUN in the intervention group was significantly higher in comparison to the control group, the difference in urinary output, urine specific gravity, potassium, and Creatinine levels were not significant in the two groups. Conclusions The use of a half-saline solution as maintenance fluid reduces the risk of hyponatremia after 48 h when compared to 0.18%NaCl. Trial registration This has been registered at Iranian Registry of Clinical Trials (Retrospectively registered, Registration date: 2017-10-12, identifier: IRCT2017053034223N1, https://irct.behdasht.gov.ir/trial/26204 ).

Purpose Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and has a lower incidence of overly rapid correction of serum sodium. Methods Single TLV doses of 3.75, 7.5, and 15 mg were administered to 14 healthy adults in a crossover design and to 29 subjects ≥18 years with SIADH and serum sodium between 120 and 133 mmol/L in a parallel-group design. Pharmacodynamics and TLV plasma concentrations were assessed for 24 h post-dose. Results In SIADH subjects, corrections of serum sodium (Δ of ≥8 mmol/L in the first 8 h or ≥12 mmol/L in the first 24 h) were observed in one, one, and two subjects in the 3.75-, 7.5-, and 15-mg dose groups. Fluid balance (FB) for 0–6 h post-dose was correlated ( r 2  = 0.37) with maximum increases in serum sodium; subjects with large corrections had large (~1 L) negative FB. Compared to healthy adults, subjects with SIADH did not drink in response to their negative FB and had larger increases in serum sodium at 24 h. Median time of maximum increase in healthy adults was 6 h, with no rapid corrections, and FB was near 0 mL by 24 h. Conclusion Starting titration with 7.5 mg TLV will not eliminate the risk of rapid corrections in serum sodium. Monitoring FB may indicate that a subject is at risk for over correction.

Background Status, refractory status and super refractory status epilepticus are common neurologic emergencies. The objective of this study is to investigate the feasibility, safety and effectiveness of a ketogenic diet (KD) for refractory status epilepticus (RSE) in adults in the intensive care unit (ICU). Methods We performed a retrospective, single-center study of patients between ages 18 and 80 years with RSE treated with a KD treatment algorithm from November 2016 through April 2018. The primary outcome measure was urine ketone body production as a biomarker of feasibility. Secondary measures included resolution of RSE and KD-related side effects. Results There were 11 adults who were diagnosed with RSE that were treated with the KD. The mean age was 48 years, and 45% ( n  = 5) of the patients were women. The patients were prescribed a median of three anti-seizure medications before initiating the KD. The median duration of RSE before initiation of the KD was 1 day. Treatment delays were the result of Propofol administration. 90.9% ( n  = 10) of patients achieved ketosis within a median of 1 day. RSE resolved in 72.7% ( n  = 8) of patients; however, 27.3% ( n  = 3) developed super-refractory status epilepticus. Side effects included metabolic acidosis, hypoglycemia and hyponatremia. One patient (20%) died. Conclusions KD may be feasible, safe and effective for treatment of RSE in the ICU. A randomized controlled trial (RCT) may be indicated to further test the safety and efficacy of KD.

The aim of this study was to compare the effect of three different intravenous (i.v.) fluid regimes on the incidence of hyponatraemia in hospitalized children ranging in age from 3 months to 12 years. Children who required the administration of i.v. maintenance fluid for at least 24 h following hospitalization were eligible for inclusion. The children were randomized to three i.v. fluid groups: Group A, 0.9% saline in 5% dextrose at the standard maintenance rate; Group B, 0.18% saline in 5% dextrose at the standard maintenance rate; Group C, 0.18% saline in 5% dextrose at two-thirds of the standard maintenance rate. The primary outcome measure was incidence of hyponatraemia (plasma sodium < 130 mEq/L). Of the 167 patients enrolled, 58, 56 and 53 patients were randomized to Group A, B and C, respectively. We observed that 14.3% (8/56) of the children administered 0.18% saline in 5% dextrose at the standard maintenance rate (Group B) developed hyponatraemia compared with 1.72% of the children in Group A and 3.8% of those in Group C. Based on these results, we conclude that the administration of 0.9% saline in 5% dextrose as i.v. maintenance fluid helps in reducing the incidence of hospital-acquired hyponatraemia among children.