Vascular Calcification Is Accelerated by Hyponatremia and Low Osmolality.

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt (protein kinase B) pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

Evaluation and Management of Hyponatremia in Heart Failure.

PURPOSE OF REVIEW: To provide a contemporary overview of the pathophysiology, evaluation, and treatment of hyponatremia in heart failure (HF). RECENT FINDINGS: Potassium and magnesium losses due to poor nutritional intake and treatment with diuretics cause an intracellular sodium shift in HF that may contribute to hyponatremia. Impaired renal blood flow leading to a lower glomerular filtration rate and increased proximal tubular reabsorption lead to an impaired tubular flux through diluting distal segments of the nephron, compromising electrolyte-free water excretion. Hyponatremia in HF is typically a condition of impaired water excretion by the kidneys on a background of potassium and magnesium depletion. While those cations can and should be easily repleted, further treatment should mainly focus on improving the underlying HF and hemodynamics, while addressing congestion. For decongestive treatment, proximally acting diuretics such as sodium-glucose co-transporter-2 inhibitors, acetazolamide, and loop diuretics are the preferred options.

Plasma hyperosmolality during cardiopulmonary bypass is a risk factor for postoperative acute kidney injury: Results from double blind randomised controlled trial.

INTRODUCTION: The study objective was to investigate whether a Ringer's acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). METHODS: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer's acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer's acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. RESULTS: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). CONCLUSIONS: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Management of severe inaugural diabetic ketoacidosis in paediatric intensive care: retrospective comparison of two protocols.

The best protocol for severe inaugural diabetic ketoacidosis (DKA) in children remains unclear. We compared two protocols by assessing effects during the first 24 h on osmolality, serum sodium, and glucose variations, which are associated with the risk of cerebral oedema, the most dreaded complication of DKA. We also recorded complications. We retrospectively included children aged 28 days to 18 years and admitted for severe DKA to either of two paediatric intensive care units (PICUs) in Paris (France). The two protocols differed regarding hydration volume, glucose intake, and sodium intake. From 17 June 2010 to 17 June 2015, 93 patients were included, 29 at one PICU, and 64 at the other. We compared severe glycaemic drops (> 5.5 mmol/L/h), mean glycaemia variations, serum sodium, serum osmolality, and the occurrence of cerebral oedema (CE) during the first 24 h after PICU admission. Severe glycaemic drops occurred in 70% of patients, with no between-group difference. Blood glucose, serum sodium, and serum osmolality variations were comparable. Seven (7.5%) patients were treated for suspected CE, (4 [10.3%)] and 3 [6.3%]) in each PICU; none had major residual impairments. CONCLUSION:  The two paediatric DKA-management protocols differing in terms of fluid-volume, glucose, and sodium intakes had comparable effects on clinical and laboratory-test changes within 24 h. Major drops in glycaemia and osmolality were common with both protocols. No patients had residual neurological impairments. WHAT IS KNOWN: • Cerebral oedema is the most severe complication of diabteic ketoacidosis in children.The risk of cerebral oedema is dependant on both patient related and treatment-related factors. • The optimal protocol for managing severe inaugural diabetic ketoacidosis in children remains unclear, and few studies have targeted this specific population. WHAT IS NEW: • Two management protocols that complied with ISPAD guidelines but differed regarding the amounts of fluids, glucose, and sodium administered produced similar outcomes in children with severe inaugural diabetic ketoacidosis. • Cerebral oedema was rare with both protocols and caused no lasting impairments.

Postoperative Copeptin as a Biomarker for Development of Diabetes Insipidus Following Hypothalamic-Pituitary Surgery.

OBJECTIVE: Copeptin is a surrogate marker of arginine vasopressin release with better stability and simplicity of measurement. Postoperative copeptin levels may guide clinicians in stratifying patients who need close monitoring of fluid balance. The objective is to determine whether copeptin is a predictive marker of postoperative diabetes insipidus (DI). METHODS: This is a prospective diagnostic study. Patients who underwent neurosurgical intervention of the sellar-suprasellar regions were recruited. Serum copeptin levels were measured before and after surgery, within 24 hours. Logistic regression analysis and diagnostic performance measures were calculated to determine the relationship between postoperative copeptin levels and DI. RESULTS: Of 82 patients, 26 (31.7%) developed postoperative DI, with 7 patients (8.5%) having permanent DI. The samples for copeptin measurement were taken at 13 ± 2.1 hours postoperatively. From the receiver operating characteristic analysis, low postoperative copeptin levels (<2.5 pmol/L) demonstrated an acceptable ability to predict DI (area under the curve, 0.72; 95% CI, 0.60-0.84). Discriminative power was stronger in the permanent DI group (area under the curve, 0.82; 95% CI, 0.64-1.00). Postoperative copeptin levels <2.5 pmol/L were associated with DI (specificity > 91%). However, postoperative copeptin levels >20 pmol/L were rarely associated with DI, with a negative predictive value of 100%. CONCLUSIONS: In patients undergoing sellar-suprasellar interventions, low postoperative copeptin levels within the first postoperative day predict postoperative DI, whereas high levels exclude it. Copeptin measurement should be applied in the clinical practice of postoperative care in patients following hypothalamic-pituitary surgery. This study may expand the potential use of copeptin, including in the Asian population.

Neuronal Swelling: A Non-osmotic Consequence of Spreading Depolarization.

An acute reduction in plasma osmolality causes rapid uptake of water by astrocytes but not by neurons, whereas both cell types swell as a consequence of lost blood flow (ischemia). Either hypoosmolality or ischemia can displace the brain downwards, potentially causing death. However, these disorders are fundamentally different at the cellular level. Astrocytes osmotically swell or shrink because they express functional water channels (aquaporins), whereas neurons lack functional aquaporins and thus maintain their volume. Yet both neurons and astrocytes immediately swell when blood flow to the brain is compromised (cytotoxic edema) as following stroke onset, sudden cardiac arrest, or traumatic brain injury. In each situation, neuronal swelling is the direct result of spreading depolarization (SD) generated when the ATP-dependent sodium/potassium ATPase (the Na+/K+ pump) is compromised. The simple, and incorrect, textbook explanation for neuronal swelling is that increased Na+ influx passively draws Cl- into the cell, with water following by osmosis via some unknown conduit. We first review the strong evidence that mammalian neurons resist volume change during acute osmotic stress. We then contrast this with their dramatic swelling during ischemia. Counter-intuitively, recent research argues that ischemic swelling of neurons is non-osmotic, involving ion/water cotransporters as well as at least one known amino acid water pump. While incompletely understood, these mechanisms argue against the dogma that neuronal swelling involves water uptake driven by an osmotic gradient with aquaporins as the conduit. Promoting clinical recovery from neuronal cytotoxic edema evoked by spreading depolarizations requires a far better understanding of molecular water pumps and ion/water cotransporters that act to rebalance water shifts during brain ischemia.

Thirst-guided participant-controlled intravenous fluid rehydration: a single blind, randomised crossover study.

BACKGROUND: Dehydration is common in hospitals and is associated with increased mortality and morbidity. Clinical assessment and diagnostic measures of dehydration are unreliable. We sought to investigate the novel concept that individuals might control their own intravenous rehydration, guided by thirst. METHODS: We performed a single-blind, counterbalanced, randomised cross-over trial. Ten healthy male volunteers of mean age 26 (standard deviation [sd] 10.5) yr were dehydrated by 3-5% of their baseline body mass via exercising in the heat (35°C, 60% humidity). This was followed by a 4 h participant-controlled intravenous rehydration: individuals triggered up to six fluid boluses (4% dextrose in 0.18% sodium chloride) per hour in response to thirst. Participants undertook two blinded rehydration protocols which differed only by bolus volume: 50 ml (low volume [LV]) or 200 ml (high volume [HV]). Each hour during the rehydration phase, plasma osmolality (pOsm) was measured and thirst score recorded. Nude body mass was measured at baseline, after dehydration, and after the rehydration phase. RESULTS: In both conditions, the mean dehydration-related body mass loss was 3.9%. Thirst score was strongly associated with pOsm (within-subject r=0.74) and demand for fluid decreased as pOsm corrected. In the HV condition, participants rapidly rehydrated themselves (mean fluid delivered 3060 vs 981 ml in the LV condition) to body mass and pOsm no different to their euhydrated state. CONCLUSION: Healthy individuals appear able to rely on thirst to manage intravenous fluid intake. Future work must now focus on whether patient-controlled intravenous fluids could represent a paradigm shift in the management of hydration in the clinical setting. CLINICAL TRIAL REGISTRATION: NCT03932890.

Comparison of measured and calculated osmolality levels.

BACKGROUND: Serum osmolality levels are measured to determine acid-base and electrolyte imbalance in serum. In cases where measurement is not possible, the serum osmolality value can be calculated by various calculation methods. In this study, we compared the Worthley osmolality calculation method which is used most frequently mentioned in literature and the measurements made with vapor pressure osmometer used in our laboratory. We compared whether there was a difference between the results obtained by measurement and calculation method in different age groups. METHODS: 221 serum samples of patients who were admitted to the Eskisehir Osmangazi University Hospital Biochemistry Laboratory between December 2016 and May 2018 were included in this study. Glucose, blood urea nitrogen and sodium values were recorded to determine the calculated osmolality values of the patients. RESULTS: There was a statistically significant difference between the measured osmolality values and the calculated osmolality values of the patients (p < 0.001). When compared according to age groups, there was a significant difference between calculated osmolality values (p = 0.006), but there was no difference in measured osmolality values (p = 0.787) in different age groups. It has been observed that this difference in the calculated osmolality values between the age groups is derived from the adult group (18-65, p < 0.001). CONCLUSION: Our results showed that it is not reliable to calculate serum osmolality values, especially in the adult age group. According to our results the calculated osmolality values are higher than our measured osmolality values.

Reference values for osmolal gap in healthy subjects and in medical inpatients.

Methanol and ethylene glycol poisonings are associated with high morbidity and mortality rates if treatment is not initiated early. Since few hospitals measure these toxic alcohols on a 24/7 basis, calculation of the osmolal gap (OG) is an important diagnostic tool. The reference value for the OG lacks consensus. We, therefore, wanted to update the reference value for OG in presumed healthy subjects and study OG values in internal medicine patients. The OG was calculated in 285 patients at the Medical Clinic at Oslo University Hospital, and in 118 healthy blood donors at Vestfold Hospital Trust. OG was calculated by the formula: OG = Measured osmolality - calculated osmolality ((1.86 × s-sodium + s-glucose + s-urea)/0.93) mOsm/kg H2O. In the patients, median OG was 0 mOsm/kg H2O (interquartile range -3 to 3 mOsm/kg H2O, range -16 to103 mOsm/kg H2O). When corrected for one outlier, the central 95% interval for OG was -10 to 20. The healthy blood donors had a median OG of -1 mOsm/kg H2O (interquartile range -3 to1 mOsm/kg H2O, range -13 to 8 mOsm/kg H2O). When corrected for outliers, the reference range was -6 to 5 mOsm/kg H2O. Based on results from a healthy population, we suggest a reference value for the OG of ≤5 mOsm/kg H2O, but also recommend, based on our results from medical inpatients, to keep today's practice for suspecting poisoning with toxic alcohols at an elevated OG of ≥20 mOsm/kg H2O.

[About salt and immunity-a story of Mr. Hyde : The influence of hyperosmolar microenvironment on immune response]. / Über Salz und Immunität ­ Eine Geschichte von Mr. Hyde : Oder wie hyperosmolares Mikromilieu die Immunabwehr beeinflussen kann.

Hyperosmolar micromilieu has been observed in physiologic (kidney medulla, lymphatic tissue) and pathologic (renal allorejection, solid tumors) conditions. Hyperosmolarity can modulate gene expression and alter the stimulatory profile of macrophages and dendritic cells. We have reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Moreover, we showed that a hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells. Using ovalbumin as a model antigen, we showed that exposure of dendritic cells to hyperosmolarity strongly inhibits activation of antigen-specific T cells despite enhancement of antigen uptake, processing, and presentation; it can reduce dendritic cell-T cell contact time. We have identified TRIF as key mediator of this phenomenon. Moreover, we detected a hyperosmolarity-triggered, TRIF-dependent clustering of MHC class I­antigen complexes, but not of unloaded MHCI molecules, providing a possible explanation for a reduced T cell activation. Our findings identify dendritic cells as important players in hyperosmolarity-triggered immune imbalance and suggest that targeting local hyperosmolarity in tumor micromilieu may contribute to an enhanced specific anti-tumor immune response.

Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations.

PURPOSE: Some patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, although this action has never been proved. MATERIALS AND METHODS: We conducted a double-blind, randomized, placebo controlled, crossover study of 21 calcium urinary stone formers stratified into majority calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was collected at the end of weeks 1 and 3. RESULTS: Tolvaptan vs placebo decreased urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of urinary solute excretion rates, including sodium and calcium, did not change significantly, although oxalate secretion increased slightly (from mean ± SD 15 ± 8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p = 0.04) all dramatically decreased. Effects did not differ between the calcium oxalate and calcium phosphate groups (p >0.05 for all interactions). CONCLUSIONS: Tolvaptan increases urine volume and decreases urinary supersaturation in calcium stone formers. Further study is needed to determine if long-term use of V2 receptor antagonists results in fewer stone events.

Renal Safety of Iodinated Contrast Media Depending on Their Osmolarity - Current Outlooks.

Iodinated contrast media (ICM) are commonly administered pharmaceutical agents. Most often they are used intravenously and intraarterially. Although iodinated contrast agents are relatively safe and widely used, adverse events occur and questions remain about their use, safety, and interactions. The most important adverse effects of contrast media include hypersensitivity reactions, thyroid dysfunction, and contrast-induced nephropathy. Radiologists must be aware of the risk factors for reactions to contrast media. Nonionic iodinated contrast agents can be divided into monomeric, low-osmolar, and dimeric, iso-osmolar classes. The osmotic characteristics of contrast media have been a significant focus in many investigations of contrast-induced nephropathy.

Fluid retention index predicts the 30-day mortality in geriatric care.

The incidence and medical consequences of dehydration and fluid retention in senior citizens are unclear. The present study used urine sampling to detect renal conservation of water, which is an early sign of dehydration, and assessed its relationship to mortality in elderly patients admitted for acute hospital care. A urine sample was collected from 256 patients (mean age 82 years) and analyzed for color, specific gravity and osmolality. These markers were used to calculate a composite index of fluid retention, which was indicated by urine color ≥ 4, specific gravity ≥ 1.020 and osmolality ≥ 600 mOsmol/kg as suggested from eight previous studies of exercise-induced dehydration, of which one extends to age 69. Concentrated urine consistent with dehydration was present in 39 (16%) of the patients. This finding was relatively more common among those with confusion and/or dementia, but less common in patients with medical disease, and in those taking diuretics daily. Patients with such fluid retention had a higher 30-day mortality when compared to those who were euhydrated (21% versus 8%; p < 0.03). A difference of 10% remained at three months and one year after the admission to hospital. Concentrated urine consistent with fluid retention was found in 16% of the geriatric patients admitted to hospital for acute care. In these patients the mortality within 30 days was almost tripled compared to those who were euhydrated.

The prevalence, risk factors and clinical implications of dehydration in older patients: a cross-sectional study.

OBJECTIVES: Adequate hydration is essential for the maintenance of physiological functions. Older adults may not be able to maintain adequate hydration, which is often not recognized. Our aim was to investigate the prevalence, risk factors and clinical implications of dehydration in older adults. METHODS: This cross-sectional study included 964 older adults in one geriatric outpatient clinic in Turkey. Dehydration was defined as a calculated [1,86 × (Na+K)+1,15×glucose+urea +14] plasma osmolarity of ≥ 295 mOsm/L. Clinical characteristics and measures of comprehensive geriatric assessments of patients with dehydration and normohydration were compared. Predictors of dehydration were assessed using logistic regression analysis. RESULTS: Mean age was 79.9 ± 7.7 years, (71.7% female). The prevalence of dehydration was 31%. Female patients, diabetes mellitus (DM), chronic renal failure (CKD), a higher risk of falling (based on Timed Up and Go test), probable sarcopenia, dependence based on basic and instrumental daily living activities (BADL and IADL) were more common in the dehydrated group (p < 0.05). After adjusting for age and gender, dependency on BADL and IADL, the risk of falling were still higher in the dehydrated group (p < 0.05). There were significant relationships between dehydration and risk of falling (OR 1.38, 95% CI 1.00-1.90; p < 0.05), after adjustment for age, gender, DM, CKD. CONCLUSION: Dehydration is common among older adults and is associated with a dependency, probable sarcopenia, and an increased risk of falling. Screening for dehydration and taking preventive measures may be beneficial in avoiding the negative consequences associated with dehydration.

Osmolality in oral supplements drives ileostomy output: Defining the Goldilocks zone.

BACKGROUND: Patients with an ileostomy often have impaired quality of life, sodium depletion, secondary hyperaldosteronism, and other organ-specific pathologies. The osmolality of oral supplements influences ileostomy output and increases sodium loss. We hypothesized the existence of an osmolality range in which fluid absorption and secondary natriuresis are optimal. METHODS: This was a single-center, quasi-randomized crossover intervention study, including patients with an ileostomy and no home parenteral support. After an 8-h fasting period, each patient ingested 500 mL of 3-18 different oral supplements and a standardized meal during the various intervention periods, followed by a 6-h collection of ileostomy and urine outputs. The primary outcome was 6-h ileostomy output. RESULTS: A total of 14 ileostomy patients with a median age of 65 years (interquartile range 38-70 years) were included. The association between osmolalities (range 5-1352 mOsm/kg) and ileostomy output forecasted an S-curve. A linear association between osmolality of oral supplements (range 290-600 mOsm/kg) and ileostomy output was identified and assessed with a mixed-effects model. Ileostomy output increased by 57 g/6 h (95% confidence interval (CI) 21-94) when the oral supplement osmolality increased by 100 mOsm/kg (p = 0.005). CONCLUSION: Osmolality in oral supplements correlated with ileostomy output. Our results indicate that patients with an ileostomy may benefit from increased ingestion of oral supplements with osmolalities between 100 and 290 mOsm/kg. We define this range as the Goldilocks zone, equivalent to optimal fluid and electrolyte absorption.

Filling In the Gaps: Ethylene Glycol Poisoning Presenting With Isolated Lactate and Osmolar Gaps.

Ethylene glycol (EG) is an organic compound used in antifreeze. In 2020 alone, there were 5,277 EG exposures, with only 617 reported as intentional ingestions. Therefore, encountering EG toxicity is rare; however, it is essential to identify it promptly based on a focused history, exam, and rapid identification of commonly associated EG-induced metabolic derangements. If the diagnosis is not made within 12 hours of ingestion or exposure, severe morbidity and mortality can occur. Previous reports of EG poisoning have occurred in the setting of a lactate gap (LG) and osmolar gap (OG); however, they also had commonly associated findings of EG toxicity such as high anion gap acidosis (HAGMA), acute kidney injury (AKI), hypocalcemia, calcium oxalate stones, and suggestive histories of EG ingestion. We present a case of a 57-year-old male who presented from home for slurred speech and gait imbalance. He was intubated for airway protection due to obtundation. Labs only revealed the presence of both LG and OG, non-anion gap acidosis (NAGMA), and an EG level of 112 mg/dL three days after admission. Hemodialysis (HD) was initiated solely based on these findings within eight hours of admission, and he was subsequently able to be extubated without developing an acute or chronic cardio-pulmonary or renal injury. The patient's partner reported to the care team that they found multiple empty bottles of rum and whisky, an empty anti-freeze bottle, and a Sprite bottle with a light blue substance that was nearly empty in their basement. After extubation, the patient admitted to ingesting the antifreeze with the intention of self-harm. He recovered without complication and was transferred to the inpatient psychiatric unit to manage his depression and suicidality further. The early diagnosis and treatment of EG poisoning is critical to prevent severe morbidity and mortality occurring only 12 hours after ingestion. Therefore, reliance on prompt recognition of common laboratory findings, understanding of EG toxicity-specific signs and symptoms, and awareness of other rapid diagnostic tools for EG are essential in clinching the diagnosis. This case highlights the potential atypical presentations of EG toxicity, helpful diagnostic strategies, and the importance of avoiding anchoring bias when commonly associated disease processes are absent.

Optimizing Mannitol Use in Managing Increased Intracranial Pressure: A Comprehensive Review of Recent Research and Clinical Experiences.

Mannitol, derived from mannose sugar, is crucial in treating patients with elevated intracranial pressure (ICP). Its dehydrating properties at the cellular and tissue levels increase plasma osmotic pressure, which is studied for its potential to reduce ICP through osmotic diuresis. While clinical guidelines support mannitol use in these cases, the best approach for its application continues to be debated. Important aspects needing further investigation include: 1) bolus administration versus continuous infusion, 2) ICP-based dosing versus scheduled bolus, 3) identifying the optimal infusion rate, 4) determining the appropriate dosage, 5) establishing fluid replacement plans for urinary loss, and 6) selecting monitoring techniques and thresholds to assess effectiveness and ensure safety. Due to the lack of adequate high-quality prospective research data, a comprehensive review of recent studies and clinical trials is crucial. This assessment aims to bridge the knowledge gap, improve understanding of effective mannitol use in elevated ICP patients, and provide insights for future research. In conclusion, this review aspires to contribute to the ongoing discourse on mannitol application. By integrating the latest findings, this review will offer valuable insights into the function of mannitol in decreasing ICP, thereby informing better therapeutic approaches and enhancing patient outcomes.

First-morning urine osmolality and nocturnal enuresis in children: A single-center prospective cohort study.

PURPOSE: To investigate the treatment outcome of nocturnal enuresis (NE) according to first-morning urine osmolality (Uosm) before treatment. MATERIALS AND METHODS: Ninety-nine children (mean age, 7.2±2.1 y) with NE were enrolled in this retrospective study and divided into two groups according to first-morning Uosm results, that is, into a low Uosm group (<800 mOsm/L; 38 cases, 38.4%) or a high Uosm group (≥800 mOsm/L; 61 cases, 61.6%). Baseline parameters were obtained from frequency volume charts of at least 2 days, uroflowmetry, post-void residual volume, and a questionnaire for the presence of frequency, urgency, and urinary incontinence. Standard urotherapy and pharmacological treatment were administered initially in all cases. Enuresis frequency and response rates were analyzed at around 1 month and 3 months after treatment initiation. RESULTS: The level of first-morning Uosm was 997.1±119.6 mOsm/L in high Uosm group and 600.9±155.9 mOsm/L in low Uosm group (p<0.001), and first-morning voided volume (p=0.021) and total voided volume (p=0.019) were significantly greater in the low Uosm group. Furthermore, a significantly higher percentage of children in the low Uosm group had a response rate of ≥50% (CR or PR) at 1 month (50.0% vs. 24.6%; p=0.010) and 3 months (63.2% vs. 36.1%; p=0.009). CONCLUSIONS: Treatment response rates are higher for children with NE with a lower first-morning Uosm.

The Contribution of Plasma Urea to Total Osmolality During Iatrogenic Fluid Reduction in Critically Ill Patients.

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR-1.9-18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P < .05 and P < .01, respectively), whereas urea's proportion increased (P < .001). The urea's proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea's proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea's proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals. ClinicalTrials.org Identifier: NCT03972475.

Identification of potentially irritating intravenous medications.

AIMS: To identify commonly used intravenous drugs that may produce endothelial damage. METHODS: An experimental research study was performed using a sample of 62 intravenous drugs commonly used in emergency care, pH and osmolarity were measured. Subsequently, based on these values, the theoretical capacity to cause irritation or endovascular damage was determined and classified as high, moderate, and low. RESULTS: Samples from 19 drugs for fluid therapy, 21 antibiotics and 22 drugs for intravenous use were studied. Glucose solutions, sodium bicarbonate 1M and mannitol 10% showed a high capacity to cause venous irritation. Vancomycin, ciprofloxacin, amiodarone, haloperidol, and labetalol solution presented a high capacity for irritation based on their acidic pH. The antibiotics, dexketoprofen, diazepam, digoxin, etomidate, phenytoin, levetiracetam and metamizole also showed high osmotic values in their reconstituted or undiluted presentations. Moreover, osmolarity of diazepam, digoxin and phenytoin remained high despite being diluted in 100 ml of saline. CONCLUSIONS: Knowing the pH and osmolarity of intravenous drugs allows their capacity to cause endothelial damage to be assessed. The use of comprehensive tables based on the chemical properties of the drugs can be a useful tool to help prevent chemically-induced phlebitis.