Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant.

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology-driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC-C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi-disciplinary family-directed decision-making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

Fluid and electrolyte management in the neonate and what can go wrong.

PURPOSE OF REVIEW: This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload and acute kidney injury contributing to poor clinical outcomes. Particular attention is given towards the care of extremely preterm infants. RECENT FINDINGS: Emerging data demonstrate (i) disproportionally large transepidermal water loss in the extremely preterm population, (ii) the relationship between postnatal weight loss (negative fluid balance) and improved outcomes, (iii) the frequency and negative effects of dysnatremias early in life, (iv) the role of sodium homeostasis in optimizing postnatal growth, and (v) the deleterious effects of fluid overload and acute kidney injury. SUMMARY: As clinicians care for an increasing number of preterm infants, understanding progress in approaches to fluid and electrolyte management and avoidance of fluid overload states will improve the care and outcomes of this vulnerable population. Further translational and clinical studies are needed to address remaining knowledge gaps and improve current approaches to fluid and electrolyte management.

Dysnatremia and subsequent sodium level changes following various intravenous treatments in infants with acute gastroenteritis.

Acute gastroenteritis is one of the main causes of electrolyte imbalance in infants. We aimed to determine the frequency of and factors associated with dysnatremia at presentation and establish the ideal intravenous treatment scheme. The records of hospitalized infants aged 1-12 months with community-acquired acute gastroenteritis between January 2017 and March 2021 were retrospectively reviewed. Factors associated with dysnatremia at presentation were analyzed by multivariable logistic regression analysis. Subsequent sodium levels 4-24 h after intravenous fluid treatments, which were categorized into 2 groups, were determined in the subgroup of infants with normal sodium levels at presentation. A total of 347 infants with a median age of 8.0 (5.0-10.0) months were included. The frequency of dysnatremia at presentation was 14% (hyponatremia 12% and hypernatremia 2.0%). Severe dehydration was associated with dysnatremia at presentation (p = 0.048). Among 68 infants with normal sodium levels at presentation, the median sodium change was highest in the 5% dextrose in saline group, with changes of + 3 (0.5-5) and + 1 (- 2 to 2) mmol/L in infants who received 5% dextrose in saline and 5% dextrose in 1/3-1/2 saline, respectively (p = 0.001). Four out of 47 infants (8.5%) developed hyponatremia while receiving 5% dextrose in 1/3-1/2 saline. None of those who received 5% dextrose in saline developed subsequent dysnatremia.   Conclusion: The frequency of dysnatremia at presentation among infants with acute gastroenteritis was 14%. Severe dehydration was associated with dysnatremia at presentation, so electrolyte levels need to be assessed in these patients. The use of isotonic solution did not promote acquired dysnatremia. This study supports once more that current guidelines recommending isotonic solution for children, and, especially, infant rehydration, are important also for infants in Thailand. What is Known: • There were a wide variation in the incidence of dysnatremia at presentation in children with acute gastroenteritis in previous pediatric series. • The AAP guidelines recommend using isotonic solution in children with acute illness from 28 days to 18 years of age to prevent acquired hyponatremia. What is New: • The incidence of dysnatremia at presentation in infants with acute gastroenteritis was 14% (hyponatremia 12% and hypernatremia 2.0%). • The use of isotonic solution did not promote acquired dysnatremia in infants with acute gastroenteritis.

Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal insufficiency.

CONTEXT: Fludrocortisone (FC) is the mineralocorticoid (MC) replacement treatment for patients with primary adrenal insufficiency (PAI). OBJECTIVE: To explore the dose of FC treatment and its relationship with glucocorticoid therapy, sodium, potassium, renin and clinical parameters. SETTING: Monocentric cohort. PATIENTS: Data of 193 patients with PAI (130 autoimmune) were collected during baseline (T0), intermediate (T1) and last follow-up visit (T2, respectively, after a mean of 38 and 72 months). MAIN OUTCOME MEASURE: Utility of endocrine and clinical parameters to titrate FC dose. RESULTS: FC dose (50-75 µg/daily) was stable in the follow-up in half patients. The MC activity of FC was dose-dependent: we observed a reduced but significant positive linear correlation between FC dose and sodium (r = 0.132) and negative linear correlation between FC and potassium (r = - 0.162) or renin (r = - 0.131, all p < 0.01). An overall reduction in the FC dose was observed at T2 in the group with longer follow-up (> 60 months, p < 0.05). Higher doses of FC were observed in patients with low-normal renin, especially in autoimmune PAI (86 vs 65 µg/daily, p < 0.05). On the contrary, reduced sodium and increased potassium levels were observed in patients with high renin at T2. The number of cardiovascular events (15 in the whole cohort) was similar in patients sorted by renin levels or FC dose. CONCLUSIONS: Renin and electrolytes can indicate the MC activity of FC treatment: they should be routinely evaluated and used to titrate its dose that can be reduced in the long-term follow-up.

Electrolytes Play a Role in Detecting Cisplatin-Induced Kidney Complications and May Even Prevent Them-Retrospective Analysis.

Background and Objective: Cisplatin is a chemotherapy drug used to treat several types of malignancies. It is a platinum-based compound that interferes with cell division and DNA replication. Cisplatin has been associated with renal damage. This study evaluates the early detection of nephrotoxicity through routine laboratory tests. Materials and Methods: This is a retrospective chart review based on the Saudi Ministry of National Guard Hospital (MNGHA). We evaluated deferential laboratory tests for cancer patients treated with cisplatin between April 2015 and July 2019. The evaluation included age, sex, WBC, platelets, electrolytes, co-morbidities and interaction with radiology. Results: The review qualified 254 patients for evaluation. Around 29 patients (11.5%) had developed kidney function abnormality. These patients presented with abnormally low magnesium 9 (31%), potassium 6 (20.7%), sodium 19 (65.5%) and calcium 20 (69%). Interestingly, the whole sample size had abnormal electrolytes presenting magnesium 78 (30.8%), potassium 30 (11.9%), sodium 147 (58.1%) and calcium 106 (41.9%). Some pathological features were detected, such as hypomagnesemia, hypocalcemia and hypokalemia. In addition, infections that needed antibiotics were dominant in patients treated with cisplatin alone, representing 50% of this group. Conclusions: We report that an average of 15% of patients with electrolyte abnormalities develop renal toxicity and reduced function. Moreover, electrolytes may serve as an early indicator for renal damage as part of chemotherapy complication. This indication represents 15% of renal toxicity cases. Changes in electrolyte levels have been reported with cisplatin. Specifically, it has been linked to hypomagnesemia, hypocalcemia and hypokalemia. This study will help reduce the risk of dialysis or the need for kidney transplant. It is also important to manage any underlying conditions and control patients' intake of electrolytes.

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs.

BACKGROUND: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. METHODS: We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. RESULTS: Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. CONCLUSIONS: Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort.

BACKGROUND: Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. METHODS: Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. RESULTS: Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure. CONCLUSIONS: AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. CLINICAL TRIALS REGISTRATION: NCT02754765.

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial].

BACKGROUND & AIMS: The choice of resuscitation fluid in patients with cirrhosis and sepsis-induced hypotension is unclear. 5% albumin was superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties, to plasmalyte in reversing sepsis-induced hypotension. METHODS: Critically ill patients with cirrhosis underwent open-label randomization to receive either 20% albumin (0.5-1.0 g/kg over 3 hours; n = 50) or plasmalyte (30 ml/kg over 3 hours, n = 50). The primary endpoint of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at 3 hours. RESULTS: Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate (6.16±3.18 mmol/L vs. 6.38±4.77 mmol/L; p = 0.78), MAP (51.4±6.52 mmHg vs. 49.9±4.45 mmHg; p = 0.17) and SOFA score (10.8±2.96 vs. 11.1±4.2; p = 0.68), respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat analysis, albumin was superior to plasmalyte in achieving the primary endpoint (62% vs. 22%; p <0.001). A faster decline in arterial lactate (p = 0.03), a reduced need for dialysis (48% vs. 62%; p = 0.16), and a longer time to initiation of dialysis (in hours) (68.13±47.79 vs. 99.7± 63.4; p = 0.06) were seen with albumin. However, the 28-day mortality rate was not different (58% vs. 62%, p = 0.57) and treatment had to be discontinued in 11 (22%) patients in the albumin group due to adverse effects compared to no discontinuations in the plasmalyte group. CONCLUSION: In patients with cirrhosis and sepsis-induced hypotension, 20% albumin leads to a faster improvement in hemodynamics and lactate clearance than plasmalyte, while 28-day survival was similar. However, patients on 20% albumin need to be closely monitored as it was more often associated with pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT02721238. LAY SUMMARY: The current randomized-controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores arterial pressure more quickly but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in survival at 28 days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.

Hyponatremia in Patients with Heart Failure beyond the Neurohormonal Activation Associated with Reduced Cardiac Output: A Holistic Approach.

BACKGROUND: Heart failure (HF) is considered an epidemic disease with considerable morbidity, mortality, and immense healthcare costs. Electrolyte abnormalities are often encountered in patients with HF, posing a diagnostic and therapeutic challenge for clinicians. Hyponatremia affects up to one-third of HF patients and represents an unfavorable prognostic factor. SUMMARY: Low sodium levels in HF are mainly attributed to the neurohormonal activation secondary to decreased effective circulating volume. However, patients with HF often have several comorbidities which may cause or exacerbate the preexisting hyponatremia. Factors that provoke HF, such as alcohol overconsumption, may also be involved in hyponatremia development. Furthermore, drugs which are frequently prescribed to HF patients, especially diuretics, are potential culprits of hyponatremia and should always be addressed since their withdrawal may reverse hyponatremia. Despite the great prevalence and deleterious effects of hyponatremia in these patients, it is often overlooked and consequently undertreated. In this review, we present the mechanisms involved in the development of hyponatremia focusing on those besides neurohormonal activation. We also discuss the proper management of this electrolyte disorder which is frequently complex in patients with HF. KEY MESSAGES: Hyponatremia in patients with HF is not only the result of neurohormonal activation; several comorbidities and frequently used drugs should also be addressed. Hence, a holistic approach is required both for the diagnosis and optimal treatment.

Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study.

INTRODUCTION: Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery. AIMS: The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. METHODS: Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. RESULTS: 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kg-1 . The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change -1.1 ± 1.8 [95% CI: -1.2 to -0.9] g·dL-1 ). Acid-base parameters were more stable with bal-GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. CONCLUSION: Moderate doses up to 20 ml kg-1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid-base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Supraventricular tachycardia associated with severe diabetic ketoacidosis in a child with new-onset type 1 diabetes mellitus.

Diabetic ketoacidosis is one of the most serious and common complications of diabetes, with between 15 and 70% of new-onset type 1 diabetes mellitus worldwide presented with diabetic ketoacidosis. Supraventricular tachycardia, however, is an infrequent complication of diabetic ketoacidosis. We present the case of a child with a new-onset type 1 diabetes mellitus with supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis. The patient received intravenous fluid resuscitation, insulin, and potassium supplementation and subsequently developed stable supraventricular tachycardia initially, confirmed on a 12-lead electrocardiogram despite a structurally normal heart and normal electrolytes. Vagal manoeuvers failed to achieve sinus rhythm. The patient went into respiratory distress and was intubated, for mechanical ventilation. She received one dose of adenosine with successful conversion to sinus rhythm and a heart rate decreased from 200 to 140 beats per minutes. We conclude that supraventricular tachycardia can occur as a complication of diabetic ketoacidosis, including in new-onset type 1 diabetes mellitus. Furthermore, a combination of acidosis, potassium derangement, falling magnesium, and phosphate levels may have precipitated the event. Here, we report a case of supraventricular tachycardia as a complication of paediatric diabetic ketoacidosis.

[Clinical efficacy of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation: a prospective randomized controlled trial]. / 自适应式生物反馈疗法联合口服复方聚乙二醇4000ç”µè§£è´¨æ•£æ²»ç–—å„¿ç«¥å‡ºå£æ¢—é˜»åž‹ä¾¿ç§˜çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC). METHODS: A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment. RESULTS: There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05). CONCLUSIONS: Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.

Balanced Crystalloids versus Saline in Noncritically Ill Adults.

BACKGROUND: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS: We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first. RESULTS: A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01). CONCLUSIONS: Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT-ED ClinicalTrials.gov number, NCT02614040 .).

Balanced Crystalloids versus Saline in Critically Ill Adults.

BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first. RESULTS: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60). CONCLUSIONS: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).

Fluid and electrolyte therapy in childhood diabetic ketoacidosis management: A rationale for new national guideline.

Fluid and electrolyte therapy in childhood diabetic ketoacidosis (DKA) management has been controversial. Previous National Institute for Health and Care Excellence (NICE) 2015 guidance advocated a restricted fluid regimen while more recent guidelines have advocated a more liberal approach to fluid replacement in DKA. At the core of the debate is the need to avoid developing cerebral oedema as a complication. Although subtle asymptomatic cerebral oedema is common in children presenting in DKA, clinically apparent cerebral oedema is rare and has been reported in approximately 0.5%-1% of DKA cases in children. Recent research evidence has shown that there was no clear evidence of a difference in rates of clinically apparent cerebral injury in children in DKA managed with a range of fluid volumes and rates of rehydration. In view of this, NICE has updated its guideline. In this paper, we review literature evidence underpinning the current understanding of the pathophysiology of cerebral oedema in children and discuss the rationale for the new NICE guidance.

Effect of Del Nido cardioplegia on ventricular arrhythmias after cardiovascular surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients. METHODS: This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups. RESULTS: In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries. CONCLUSIONS: Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.

Short communication: Effects of different blood buffers administered in electrolyte solution to grain-fed veal calves experiencing diarrhea.

Calf diarrhea can commonly lead to dehydration and metabolic acidosis due to the loss of fluid and electrolytes. The objective of this randomized clinical trial was to examine differences between treating male dairy calves experiencing diarrhea with either a basic bicarbonate electrolyte powder (BBP) composed of sodium bicarbonate (50.7 mmol/L); a mixed buffer powder (MBP) including sodium bicarbonate (33.8 mmol/L), sodium citrate (8.4 mmol/L), sodium acetate (6.3 mmol/L), and potassium citrate (1.9 mmol/L); or a liquid electrolyte (HAL) composed of sodium acetate (50.1 mmol/L). All 3 electrolyte solutions were standardized to provide 50 mmol/L blood buffers and a similarly strong ion difference (74.4, 74.9, and 82.6 mEq/L for BBP, MBP, and HAL, respectively). Holstein male calves (n = 80) were sourced from auction barns or local farms and delivered in 1 batch to the research facility. Calves were housed in individual pens and fed a 24% crude protein and 17% fat calf milk replacer (CMR) twice daily. Starter grain and water were offered ad libitum. Calves were randomly enrolled in 1 of the 3 treatments when experiencing either 2 consecutive days of a fecal score of 2 (runny, spreads easily) or 1 d with a fecal score of 3 (liquid devoid of solid material). Calves were blocked by the different enrollment criteria. The respective electrolyte solution was administered via esophageal tube 1 h after feeding CMR until the fecal score returned to 0 (normal consistency) or 1 (semiformed or pasty). Blood gas measurements were taken at 1, 8, and 24 h post the initial electrolyte feeding, and weight was measured at 1, 2, 7, 14, and 28 d postenrollment. Mixed repeated measure linear regression models were built to assess the effect that the electrolyte solutions had on the blood gas measurements and body weight. A total of 45 calves were enrolled in the trial with 14, 16, and 15 calves randomly assigned to the MBP, HAL, and BBP groups, respectively. As compared with BBP, MBP increased blood CO2 at 8 and 24 h, increased bicarbonate at 24 h, increased base excess at 8 and 24 h, and increased anion gap at 24 h. Calves in the BBP and HAL groups noted more severe eye recession when compared with the MBP group. Average daily gain did not differ between treatments at any time point. Although a severe dehydration challenge was not present, which should be considered a limitation of the study, MBP improved the acid-base status of calves compared with BBP, whereas HAL performed similarly to MBP.

Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.

Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.

Efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric diabetic ketoacidosis and its effect on serum inflammatory factors.

Diabetic ketoacidosis (DKA) is a very serious disease that can occur in both types of diabetes (type 1 and 2). It is caused by a combination of high blood sugar and low insulin levels, which can cause the body to produce too much ketone. Ketones are toxic to human organs. This research aimed to investigate the clinical efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric DKA and its effect on serum inflammatory factors. For this purpose, a total of 122 children with DKA admitted to our hospital from April 2013 to May 2016 were selected as research objects. They were divided into group A with 60 cases and group B with 62 cases. Group B was treated with supplemental electrolytes, and group A was treated with low-dose insulin based on group B. The serum levels of TNF-α, IL-6, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment, and the blood sugar, sodium, and potassium levels were measured by an automatic biochemical analyzer. The time when blood sugar reached the standard level when acidosis was corrected and hospitalization time was compared between the two groups. The total effective rate of group A was significantly higher than that of group B (p< 0.05). There was no significant difference in blood glucose, sodium, potassium, TNF-α, IL-6, and IL-18 levels between the two groups before treatment. (all p > 0.05). But the blood glucose, sodium and potassium levels in group A were significantly better than those in group B (all p< 0.001). The levels of serum TNF-α, IL-6, and IL-18 in group A were significantly lower than those in group B after treatment (all p< 0.001). After treatment, the time when blood sugar reached the standard level when acidosis was corrected and hospitalization time in group A were significantly shorter than those in group B (all p< 0.001). Low-dose insulin combined with electrolyte supplementation is effective in the treatment of DKA in children, which can effectively control blood sugar, sodium, potassium level, and inflammatory factor concentration.