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Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).

In a randomized, placebo-controlled trial, patients with acute decompensated heart failure and volume overload who received intravenous acetazolamide plus a loop diuretic had a higher incidence of decongestion.

Balanced fluid replacement solutions can possibly reduce the risks for electrolyte imbalances, for acid-base imbalances, and thus for renal failure. To assess the intraoperative change of base excess (BE) and chloride in serum after treatment with either a balanced gelatine/electrolyte solution or a non-balanced gelatine/electrolyte solution, a prospective, controlled, randomized, double-blind, dual centre phase III study was conducted in two tertiary care university hospitals in Germany. 40 patients of both sexes, aged 18 to 90 years, who were scheduled to undergo elective abdominal surgery with assumed intraoperative volume requirement of at least 15 mL/kg body weight gelatine solution were included. Administration of study drug was performed intravenously according to patients need. The trigger for volume replacement was a central venous pressure (CVP) minus positive end-expiratory pressure (PEEP) <10 mmHg (CVP <10 mmHg). The crystalloid:colloid ratio was 1:1 intra- and postoperatively. The targets for volume replacement were a CVP between 10 and 14 mmHg minus PEEP after treatment with vasoactive agent and mean arterial pressure (MAP) > 65 mmHg. The primary endpoints, intraoperative changes of base excess -2.59 ± 2.25 (median: -2.65) mmol/L (balanced group) and -4.79 ± 2.38 (median: -4.70) mmol/L (non-balanced group)) or serum chloride 2.4 ± 1.9 (median: 3.0) mmol/L and 5.2 ± 3.1 (median: 5.0) mmol/L were significantly different (p = 0.0117 and p = 0.0045, respectively). In both groups (each n = 20) the investigational product administration in terms of volume and infusion rate was comparable throughout the course of the study, i.e. before, during and after surgery. Balanced gelatine solution 4% combined with a balanced electrolyte solution demonstrated significant smaller impact on blood gas analytic parameters in the primary endpoints BE and serum chloride when compared to a non-balanced gelatine solution 4% combined with NaCl 0.9%. No marked treatment differences were observed with respect to haemodynamics, coagulation and renal function. ClinicalTrials.gov (NCT01515397) and clinicaltrialsregister.eu, EudraCT number 2010-018524-58.

Although electrolyte imbalances (EIs) are common in the emergency department (ED), few studies have examined the occurrence of such conditions in an unselected population. To investigate the frequency of EI among adult patients who present to the ED, with regards to type and severity, and the association with age and sex of the patient, hospital length of stay (LOS), readmission, and mortality. A retrospective cohort study. All patients ≥18 years referred for any reason to the ED between January 1, 2010, and December 31, 2015, who had measured blood electrolytes were included. In total, 62 991 visits involving 31 966 patients were registered. EIs were mostly mild, and the most common EI was hyponatremia (glucose-corrected) (24.6%). Patients with increasing severity of EI had longer LOS compared with patients with normal electrolyte measurements. Among all admitted patients, there were 12928 (20.5%) readmissions within 30 days from discharge during the study period. Hyponatremia (glucose-corrected) was associated with readmission, with an adjusted odds ratio (OR) of 1.25 (95% CI, 1.18-1.32). Hypomagnesemia and hypocalcemia (albumin-corrected) were also associated with readmission, with ORs of 1.25 (95% CI, 1.07-1.45) and 1.22 (95% CI, 1.02-1.46), respectively. Dysnatremia, dyskalemia, hypercalcemia, hypermagnesemia, and hyperphosphatemia were associated with increased in-hospital mortality, whereas all EIs except hypophosphatemia were associated with increased 30-day and 1-year mortality. EIs were common and increasing severity of EIs was associated with longer LOS and increased in-hospital, 30-days and 1-year mortality. EI monitoring is crucial for newly admitted patients, and up-to-date training in EI diagnosis and treatment is essential for ED physicians.

PurposeTo determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders.MethodsWe performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints.FindingsWe randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601–2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI − 0.2–30.4%, p = 0.05).ConclusionsIn adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.

Over the past two decades, our understanding of the impact of acute kidney injury, disorders of fluid balance, and their interplay have increased significantly. In recent years, the epidemiology and impact of fluid balance, including the pathologic state of fluid overload on outcomes has been studied extensively across multiple pediatric and neonatal populations. A detailed understating of fluid balance has become increasingly important as it is recognized as a target for intervention to continue to work to improve outcomes in these populations. In this review, we provide an update on the epidemiology and outcomes associated with fluid balance disorders and the development of fluid overload in children with acute kidney injury (AKI). This will include a detailed review of consensus definitions of fluid balance, fluid overload, and the methodologies to define them, impact of fluid balance on the diagnosis of AKI and the concept of fluid corrected serum creatinine. This review will also provide detailed descriptions of future directions and the changing paradigms around fluid balance and AKI in critical care nephrology, including the incorporation of the sequential utilization of risk stratification, novel biomarkers, and functional kidney tests (furosemide stress test) into research and ultimately clinical care. Finally, the review will conclude with novel methods currently under study to assess fluid balance and distribution (point of care ultrasound and bioimpedance).

BackgroundWe evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study.MethodsRetrospective analysis of infants <36 weeks’ gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. Outcome: Mechanical ventilation (MV) at postnatal day 7.ResultsOne hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: −2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10–1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07–1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06–1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12–0.35).ConclusionsPositive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

Overhydration is associated with increased morbidity and mortality in patients on peritoneal dialysis (PD). Early detection of overhydration is possible by monitoring hydration metrics, but the critical gap for treatment is obtaining timely and actionable data. This study compares the detection of overhydration and clinical outcomes in patients on PD using the Chronic Kidney Disease-Peritoneal Dialysis (CKD-PD) smartphone app with standard monitoring and management. An open-label randomized controlled trial was conducted at 3 hospitals in northeast Thailand. Enrolled participants from PD clinics were randomized into 2 equal groups: CKD-PD (App users) and usual management (No-App). Participants or their caregivers in the App group recorded hydration metrics in the CKD-PD app, which were uploaded to a central database monitored by nephrology staff. The No-App group used a handwritten logbook. Both groups had bimonthly clinic visits. The primary outcome was the incidence rate ratio (IRR) for clinical interventions for overhydration. Secondary outcomes included hospitalizations, technique failure, and death. A total of 208 participants were randomized into App (N=103) and No-App (N=105) groups with the median follow-up time of 11.2 months. Hydration metric upload compliance in the App group was 85.7% (IQR 71.4-95.6). The IRR of overall interventions for overhydration was 2.51 times higher in the App group (95% CI 2.18-2.89; P<.001). Types of clinical interventions for overhydration differed between groups with dietary change and prescription of antihypertensive drugs more frequent in App users and diuretics and change of dialysis prescription more frequent in the No-App group. Hospitalizations were significantly higher in the No-App group due to any cause (adjusted IRR 1.58) and volume overload (adjusted IRR 4.07). There was no significant difference in survival analysis and technique failure between the 2 groups. Use of the CKD-PD app improved early detection of overhydration and early treatment interventions, resulting in fewer all-cause and volume overload hospitalizations. ClinicalTrials.gov NCT04797195; https://clinicaltrials.gov/study/NCT04797195.

Electrolyte and acid–base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid–base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid–base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid–base spectrum. Because most electrolyte and acid–base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

Objective The aim of this review was to determine whether employees exposed to effort-reward imbalance (ERI) at work have a higher risk of depressive disorders than non-exposed employees. Methods We conducted a systematic review and meta-analysis of published prospective cohort studies examining the association of ERI at baseline with onset of depressive disorders at follow-up. The work was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a detailed study protocol was registered before literature search commenced (Registration number: CRD42016047581). We obtained a summary estimate for the association of ERI with risk of depressive disorders by pooling the study-specific estimates in a meta-analysis. We further conducted pre-defined sensitivity analyses. Results We identified eight eligible cohort studies, encompassing 84 963 employees and 2897 (3.4%) new cases of depressive disorders. Seven of the eight studies suggested an increased risk of depressive disorders among employees exposed to ERI. The pooled random-effects estimate was 1.49 [95% confidence interval (95% CI) 1.23-1.80, P＜0.001], indicating that ERI predicts risk of depressive disorders. The estimate was robust in sensitivity analyses stratified by study quality, type of ERI ascertainment and type depressive disorder ascertainment, respectively. Conclusions Employees exposed to ERI were at increased risk of depressive disorder. Future studies on ERI and depressive disorders should examine if this association is stronger or weaker when ERI is measured repeatedly during follow-up and with other methods than self-report or when depressive disorders are ascertained with clinical diagnostic interviews.