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Purpose: Accelerated trans-epithelial cross-linking (ATE-CXL), a therapy to halt keratoconus progression, has the merit of widening the indications for thinner corneas (<380 μm). Since a hypotonic solution affects the swollen cornea, corneas of <380 μm thickness at preoperative measurement can be an indication for ATE-CXL. The aim of this retrospective study was to compare the efficacy and safety of ATE-CXL for keratoconus between corneas with thicknesses <380 μm and ≥380 μm., Materials and Methods: Thirty-four eyes of 27 patients who underwent ATE-CXL (30 mW/cm 2 ; 3 minutes) with completion of a 24-month follow-up, were enrolled and divided into two groups: Group 1, thinnest corneal thickness (TCT), <380 μm (n = 10) and Group 2, TCT, ≥380 μm (n = 24). A hypotonic solution was administered to Group 1 until the corneal thickness increased by >380 μm before UV-A irradiation. We measured uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), maximum and average keratometric values (Kmax and AveK), central corneal thickness (CCT), TCT by anterior segment optical coherence tomography, and corneal endothelial cell density (ECD) using specular microscopy. The changes from baseline to 24 months postoperatively between the two groups were compared accordingly., Results: The changes in Kmax and AveK from baseline to 24 months in Group 1 (ΔKmax: -7.8 ± 7.7 D, ΔAveK: -4.3 ± 6.1 D) showed significant decreases compared to those in Group 2 (ΔKmax: 0.2 ± 3.0 D, ΔAveK: 0.6 ± 2.7 D) ( p = .004 and p = .001), and there were no significant changes from baseline to 24 months postoperatively in UCVA, BCVA, CCT, TCT, and ECD in both groups., Conclusion: ATE-CXL is effective and safe for keratoconic corneas in both groups. The effect of reducing keratometric values was greater in the group with thinner corneas.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Background : To prevent the risk of iatrogenic hyponatraemia in hospitalised children, isotonic fluid has been recommended as maintenance intravenous fluid (IVF). There are few studies which compare half normal saline with normal saline as maintenance IVF in general paediatric wards. Aim : To compare the safety and efficacy of half normal saline with normal saline as maintenance IVF in general paediatric wards. Methods : Children aged between 3 months and 5 years with an anticipated requirement for IVF for 24 h were randomised to receive either half normal saline (0.45% saline in 5% dextrose) or normal saline (0.9% saline in 5% dextrose). The primary objective was to compare the incidence of hyponatraemia (serum sodium <135 mmol/L with a decrease from baseline of at least 4 mmol/L) at 24 h in children receiving half normal saline with those receiving normal saline. Secondary objectives were to compare the incidence of moderate (sodium <130 mmol/L), severe (sodium <125 mmol/L) and symptomatic hyponatraemia, change in serum sodium level from baseline and the incidence of hypernatraemia. Results : A total of 168 children were randomised to receive either normal saline ( n = 84) or half normal saline ( n = 84). More than two-thirds of the children were suffering from respiratory diseases (pneumonia and bronchiolitis) and diseases of the nervous system (meningoencephalitis, febrile seizures and epilepsy). The incidence of hyponatraemia at 12 h in children receiving half normal saline was similar to that in those receiving normal saline (6 vs 4.8%; Relative risk (RR) 1.2; 95% CI 0.3.0-4.8; p = 0.73). Although the incidence of hyponatraemia at 24 h in children receiving half normal saline was higher than in those receiving normal saline, the difference was not statistically significant (14.3 vs 6%; RR 2.6; 95% CI 0.9-7.8; p = 0.07). One child in the isotonic group and one in the hypotonic group developed moderate and severe hyponatraemia, respectively. There was no significant difference in the incidence of hypernatraemia between two groups (RR 0.7; 95% CI 0.16-3.3). Conclusion : Half-normal saline as maintenance IVF does not result in a significantly increased risk of hyponatraemia in general paediatric ward patients under 5 years of age.

Hailey-Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, characterized by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. Mutation of the Golgi Ca 2+ -ATPase ATP2C1 has been identified as having a causative role in Hailey-Hailey disease. HHD-derived keratinocytes have increased oxidative-stress that is associated with impaired proliferation and differentiation. Additionally, HHD is characterized by skin lesions that do not heal and by recurrent skin infections, indicating that HHD keratinocytes might not respond well to challenges such as wounding or infection. Hypochlorous acid has been demonstrated in vitro and in vivo to possess properties that rescue both oxidative stress and altered wound repair process. Thus, we investigated the potential effects of a stabilized form of hypochlorous acid (APR-TD012) in an in vitro model of HHD. We found that treatment of ATP2C1-defective keratinocytes with APR-TD012 contributed to upregulation of Nrf2 (nuclear factor (erythroid-derived 2)-like 2). Additionally, APR TD012-treatment restored the defective proliferative capability of siATP2C1-treated keratinocytes. We also found that the APR-TD012 treatment might support wound healing process, due to its ability to modulate the expression of wound healing associated cytokines. These observations suggested that the APR-TD012 might be a potential therapeutic agent for HHD-lesions.

The standard practice in paediatric departments in Danish hospitals is to prescribe hypotonic maintenance fluids (sodium content 20-40 mmol/l) for children, who are fasting or have a reduced enteral intake. The past decades have provided strong evidence, that this can lead to hypo-natraemia and subsequent neurologic damage or death. We recommend, that prefabricated isotonic solutions containing 140-154 mmol/l of sodium and 5% glucose, with or without an additional 20 mmol/l of potassium, are available as standard maintenance fluid for children in all Danish hospitals.

Electrolyte disturbances are frequently encountered in critically ill oncology patients. Hyponatremia and hypernatremia as well as hypocalcemia and hypercalcemia are among the most commonly encountered electrolyte abnormalities. In the intensive care unit, management of critical electrolyte disturbances is focused on initial evaluation and immediate treatment plan to prevent severe complications. A PubMed search was performed to identify best available evidence for evaluation and management of dysnatremias, hypocalcemia, and hypercalcemia. Current literature was reviewed regarding the management of electrolyte disturbances. The role of new therapeutic options, for example, vaptans for hyponatremia, teriparatide for hypocalcemia, and denosumab for hypercalcemia, is discussed. Early diagnosis and appropriate management are expected to reduce adverse outcomes.

We describe the first case of severe hypernatremia associated to laparoscopic surgery for hydatid cyst in an adult patient after the use of hypertonic saline solution with complete resolution. Severe hypernatremia is an unusual fact at the immediate postoperative period but may have fatal consequences for the patient and need immediate action. The patient reached a serum sodium concentration of 179 mmol/L without adverse effects after 6 days of treatment. Laparoscopy could play a crucial role in Na + absorption due to high intraabdominal pressure caused by the pneumoperitoneum and its limitations to avoid peritoneal absorption of hypertonic saline solution. The relation between this surgical technique and the severe complication is discussed. More experience is needed in terms of safety for the patient., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the early term topographic and aberration results of accelerated (9 mW/cm) corneal cross-linking (CXL) treatment in keratoconic thin corneas., Methods: Forty-nine eyes from 43 patients (mean age of 21.2 ± 7.1) with progressive keratoconic thin corneas (<400 μm without epithelium) who had accelerated corneal CXL with hypoosmolar riboflavin solution throughout the procedure were enrolled. We measured the uncorrected and corrected distance visual acuity, refraction, slit-lamp examination, topographic values, and corneal higher-order aberrations (Pentacam HR, Oculus Optikgeräte GmbH) preoperatively and 1, 3, and 6 months after surgery., Results: Before surgery, the corneal thickness was 404 ± 18 μm, and the thickness was reduced to 360 ± 24 μm after removing the epithelium. After the application of hypoosmolar riboflavin solution, the thickness increased to 432 ± 44 μm. At month 6, there was a significant increase in uncorrected distance visual acuity (P = 0.043) and corrected distance visual acuity (P = 0.024), a decrease in spherical refraction (P = 0.041), maximum keratometry (Kmax, P = 0.003), anterior elevation values (P = 0.008), corneal thickness (P < 0.001), coma (P = 0.022), spherical aberration (P = 0.001), higher-order root mean square (P = 0.004), and total root mean square (P < 0.001), whereas the cylindrical refraction (P = 0.627), anterior (P = 0.665) and posterior astigmatism (P = 0.165) of the cornea, posterior elevation (P = 0.198), and trefoil (P = 0.141) remained unchanged. No patients showed any complications or scar formation during follow-up., Conclusions: Accelerated corneal CXL with hypoosmolar riboflavin solution throughout the procedure is effective in thin corneas.

Background: Dysnatremias are common and prognostically serious in neurocritical care. We studied whether a standardized sodium protocol would improve our neurocritical care of dysnatremias., Methods: A 5-year prospective study of a standardized sodium protocol for 1,560 patients admitted with various brain diseases in an adult neurologic-neurosurgical intensive care unit (NNICU) was compared with a 5-year retrospective analysis of 1,440 patients without the sodium protocol. Hyponatremia was defined as serum sodium (SNa(+)) < 135 mmol/L and hypernatremia SNa(+ )> 150 mmol/L. The sodium protocol involved measuring SNa(+), serum, and urine osmolality, measured and calculated renal function parameters, fluid intake 40 mL/kg weight/day without hypotonic saline, thiazide, and desmopressin acetate in all normonatremic NNICU patients., Results: In the protocol study, hyponatremia occurred slightly less often (15.7 versus 16.3% of patients; p = 0.684), hypernatremia was significantly higher (respectively 8.5% versus 5.2% of patients; p < 0.001), and no differences were noted in hypo/hypernatremia (p = 0.483). There were no differences in the incidence of hypo-osmolal hyponatremia (respectively 3.5% versus 3.5% of patients; p = 0.987), cerebral salt wasting (CSW; respectively 1.7% versus 1.7% of patients; p = 0.883), syndrome of inappropriate secretion of antidiuretic hormone (SIADH; respectively 0.1% versus 0.3% of patients; p = 0.152), central diabetes insipidus (CDI; respectively 1.0% versus 0.6% of patients; p = 0.149). In hyponatremia there were no differences in the Glasgow Coma Scale (GCS) score upon onset of hyponatremia (p = 0.294), NNICU mortality (respectively 1.0% versus 0.4% patients; p = 0.074), and bad outcome upon discharge from NNICU (respectively 5.1% versus 6.5% of patients; p = 0.101), but in hypernatremia GCS score upon onset (p < 0.001), mortality (respectively 2.8% versus 1.0%; p < 0.001), and bad outcome from NNICU (respectively 6.7% versus 2.7% patients; p < 0.001) were significantly higher. Multivariate logistic regression analysis showed that hypernatremia, compared with hyponatremia, was a significant predictor of mortality during NNICU stay (respectively odds ratio [OR]: 1.14; p = 0.003 versus OR; 5.3; p = 0.002)., Conclusions: The standard sodium protocol lowered the frequency of SIADH, which was encountered in only one patient over 5 years. However, it did not significantly reduce the incidence and improve the outcome of hyponatremia. Hypernatremia occurred more often and had a higher mortality and worse outcome than hyponatremia, but these patients were neurologically worse upon its onset. The prospective study confirmed that CSW, SIADH, and CDI were not common in our neurocritical care., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The administration of hypotonic saline solution for maintenance intravenous fluid (IVF) therapy has been the standard of care, but recent evidence has shown this treatment to be associated with hyponatremia-related complications. The aim of this systematic review was to determine which IVF, i.e., a hypotonic or an isotonic saline solution, poses less risk for the development of hyponatremia among hospitalized children who require maintenance IVF therapy., Methods: Medline, Cochrane Library, LILACS, Current Controlled Trials, reference lists, and abstract proceedings were searched for randomized controlled trials (RCTs) comparing hypotonic and isotonic saline solutions for maintenance IVF therapy in hospitalized children. Two reviewers independently assessed all potentially relevant studies and subsequently extracted data and evaluated the methodological quality of the RCTs. Studies were then combined and analyzed using a random effects model., Results: Eleven RCTs met the inclusion criteria. Our analysis of these 11 RCTs showed that among hospitalized children receiving maintenance IVF therapy, isotonic solutions significantly decreased the risk of developing hyponatremia [relative risk (RR) 0.50, 95% confidence interval (CI) 0.40-0.62] without significantly increasing the risk for hypernatremia (RR 0.83, 95% CI 0.41-1.67)., Conclusions: Current evidence does not support the standard practice of prescribing a hypotonic saline solution as maintenance IVF therapy to hospitalized children. Although there is no single IVF composition ideal for all children, an isotonic saline solution does appear to be the safer choice when maintenance IVF therapy is used in the general pediatric population.

Purpose: Little is known about how the osmolarity of ophthalmic formulations affects the ocular surface. Because hyperosmolar eye drops could be therapeutic for treating corneal edema, this article presents an ex vivo model of corneal edema for testing ophthalmic drugs based on their osmolarity. The respective osmolarity of common eye drops found in the German market is also analyzed here., Methods: For modeling corneal edema, an Ex Vivo Eye Irritation Test was used to simulate an ocular anterior chamber with a physiological corneal barrier. To induce corneal edema, the anterior chamber was supplied with a hypoosmolar medium (148 mOsm/L) for 24 hours. Preserved and preservative-free 5% sodium chloride (hyperosmolar Omnisorb and Ocusalin 5% UD) were used for 1 hour, on 5 corneas each, to test their efficiency to reduce corneal edema in this model. Corneal thickness was determined by optical coherence tomography. Osmolarity of 87 common eye drops was measured by freezing point osmometry., Results: Ex vivo, the tested hypoosmolar condition induced corneal edema from 450 μm (±50 μm) at baseline to 851 μm (±94 μm, P < 0.0001). Omnisorb and Ocusalin 5% UD significantly reduced the corneal thickness by 279 μm (±28 μm, P < 0.001) for Omnisorb and 258 μm (±29 μm, P < 0.001) for Ocusalin 5% UD. Forty-three (49%) of the tested products had an osmolarity below and 44 (51%) above the physiological tear osmolarity of 289 mOsm/L. Osmolarity values of less than 200 mOsm/L were found in lubricant drops. The highest osmolarity was detected in Omnisorb (1955 mOsm/L)., Conclusions: The Ex Vivo Eye Irritation Test has proven to be a reliable novel model of corneal edema for evaluating osmotic eye drops. Osmolarity measurements revealed a wide range from hypotonic to hypertonic formulations for commonly marketed ophthalmic drugs.

Aim: This study aimed to analyze the effect of isotonic versus hypotonic solution as intravenous maintenance fluid on level of plasma sodium in hospitalized children., Methods: A fully recursive literature search in May 2013 was conducted in PubMed and EMBASE to identify potentially relevant randomized controlled trials. Jadad score and allocation concealment were adopted to evaluate the methodological quality of each trial. RevMan5.2 was used for statistical analysis., Results: Eight randomized controlled trials with 752 patients were included. Combined analysis showed a significant lower risk of hyponatremia with isotonic solution (odds ratio, 0.36; 95% confidence interval, 0.26-0.51). The isotonic intravenous maintenance did not increase the possibility of hypernatremia (odds ratio, 0.86; 95% confidence interval, 0.36-2.06)., Conclusions: The meta-analysis revealed that there was potential risk of hyponatremia for routine infusion of hypotonic maintenance fluid. The use of isotonic solution was warranted in hospitalized pediatric patients.

Aim: To investigate the influence of hypotonic parenteral hydration on serum and urinary sodium and osmolality in infants with moderate bronchiolitis., Methods: We studied 36 infants (mean age 3.7 ± 2.3 months), with a diagnosis of moderate bronchiolitis admitted to a paediatric emergency unit in São Paulo, Brazil. Patients received a standard parenteral hypotonic solution, according to Holliday and Segar, during the first 24 h, due to respiratory distress. The disease was monitored by a respiratory severity score (RDAI-Respiratory Distress Assessment Instrument), respiratory rate and oxygen saturation. Serum and urinary sodium and osmolality were monitored at admission, 24 and 48 h after admission., Results: All respiratory parameters improved during hospitalisation. Serum sodium and osmolality dropped after 24 h (136.8 ± 2.8 and 135.8 ± 2.6 mEq/L, p = 0.031; 283.4 ± 4.1 and 281.6 ± 3.9 mOsm/kg, p = 0.004 respectively) as well as urinary osmolality (486.8 ± 243.4 mOsm/kg and 355.7 ± 205.0 mOsm/kg, p < 0.001) when compared to admission., Conclusion: This study reinforces the occurrence of hyponatraemia in bronchiolitis even in patients with moderate disease and highlights the risk of serum sodium drop caused by hypotonic parenteral hydration., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: To report the 12-month outcomes of corneal collagen cross-linking (CXL) with a hypoosmolar riboflavin and ultraviolet-A (UVA) irradiation in thin corneas., Methods: Eight eyes underwent CXL using a hypoosmolar riboflavin solution after epithelial removal. The corrected distance visual acuity (CDVA), manifest refraction, the mean thinnest corneal thickness (MTCT), and the endothelial cell density (ECD) were evaluated before and 6 and 12 months after CXL., Results: The MTCT was 413.9 ± 12.4 μm before treatment and reduced to 381.1 ± 7.3 μm after the removal of the epithelium. After CXL, the thickness decreased to 410.3 ± 14.5 μm at the last follow-up. Before treatment, the mean K-value of the apex of the keratoconus corneas was 58.7 ± 3.5 diopters and slightly decreased (57.7 ± 4.9 diopters) at 12 months. The mean CDVA was 0.54 ± 0.23 logarithm of the minimal angle of resolution before treatment and increased to 0.51 ± 0.21 logarithm at the last follow-up. The ECD was 2731.4 ± 191.8 cells/mm(2) before treatment and was 2733.4 ± 222.6 cells/mm(2) at 12 months after treatment., Conclusions: CXL with a hypoosmolar riboflavin in thin corneas seems to be a promising method for keratoconic eyes with the mean thinnest corneal thickness less than 400 μm without epithelium.

Intravenous maintenance fluid therapy aims to replace daily urinary and insensible losses for ill children in whom adequate enteric administration of fluids is contraindicated or infeasible. The traditional determination of fluid volumes and composition dates back to Holliday and Segar's seminal article from 1957, which describes the relationship between weight, energy expenditure, and physiologic losses in healthy children. Combined with estimates of daily electrolyte requirements, this information supports the use of the hypotonic maintenance fluids that were widely used in pediatric medicine. However, using hypotonic intravenous fluids in a contemporary hospitalized patient who may have complex physiologic derangements, less caloric expenditure, decreased urinary output, and elevated antidiuretic hormone levels is often not optimal; evidence over the last 2 decades shows that it may lead to an increased incidence of hyponatremia. In this review, we present the evidence for using isotonic rather than hypotonic fluids as intravenous maintenance fluid.

Introduction: Hypotonic fluids have been associated with the development of iatrogenic hyponatremia., Objectives: To assess variations in serum sodium (sNa) following the intravenous administration of isotonic maintenance fluids (0.9% NaCl/5% dextrose) compared to hypotonic maintenance fluids (0.45% NaCl/5% dextrose)., Material and Methods: Randomized, controlled, double-blind clinical trial. Pediatric patients with an expected length of stay in the intensive care unit of more than 24 hours were enrolled, with normal serum Na, and IV fluids >80% of total maintenance fluids. Serum Na level was measured before administering maintenance fluids and when reducing the administration to <80% of total fluids., Results: The study included 63 patients who were randomly assigned to receive hypotonic (n= 32) or isotonic (n= 31) maintenance fluids. Baseline characteristics were similar in both groups. There were no differences in terms of volume of fluid administered (hypotonic group: 865 ± 853 mL; isotonic group: 778 ± 649 mL; p= 0.654) or infusion duration (hypotonic group: 24 ± 10.8 hours; isotonic group: 27.6 ± 12.8 hours; p= 0.231). A difference was found in the serum Na following the administration of maintenance fluids (hypotonic group: 137.8 ± 4.3 mmol/L; isotonic group: 140.0 ± 4.1 mmol/L, p= 0.04). None of these two maintenance fluids increased the risk of hyponatremia (Na 145 mmol/L)., Conclusions: Neither hypotonic nor isotonic maintenance fluids increased the risk of developing iatrogenic hyponatremia with the 24 hour infusion.

Purpose: To monitor corneal thickness during the corneal collagen cross-linking procedure in corneal ectatic diseases, by using isoosmolar riboflavin solution with 20% dextran and hypoosmolar riboflavin solution without dextran., Methods: The corneal thickness measurements were obtained at 5 different time points: after epithelial removal, after isotonic riboflavin solution application for 30 minutes, after hypotonic riboflavin solution application for 10 minutes, and after 10 and 30 minutes of isotonic riboflavin solution application., Results: A total of 9 eyes of 9 patients with progressive keratoconus (n = 8) and pellucid marginal degeneration (n = 1) were included in this study. After epithelial debridement, the thinnest pachymetric readings were between 331 and 399 μm (average, 376.11 ± 19.88 μm). The thinnest pachymetric measurements decreased significantly after the application of isoosmolar riboflavin solution for 30 minutes (by 55.22 ± 13.40 μm) and increased significantly after hypoosmolar riboflavin application for 10 minutes (by 59.56 ± 29.71 μm) (P < 0.01 for both). This artificial swelling effect was transient, and the thinnest pachymetric readings decreased significantly after 10 and 30 minutes of isoosmolar riboflavin application compared with thickness at the end of hypoosmolar riboflavin application (by 50.22 ± 29.68 μm and 65.11 ± 27.94 μm, respectively) (P < 0.01 for both)., Conclusions: The iatrogenic swelling effect of the hypoosmolar riboflavin solution might be short acting and not durable throughout the UVA application in collagen cross-linking procedure.

Purpose: We report a case of failure of corneal collagen cross-linking (CXL) for progressive keratoconus after preoperative stromal swelling with hypoosmolar riboflavin solution in an extremely thin cornea., Methods: CXL was performed using the protocol established for the treatment of thin corneas. Preoperative minimal thickness after abrasion was 268 μm and increased to 406 μm after swelling with hypoosmolar riboflavin solution., Results: Despite CXL, a distinct progression of up to 1.9 diopters was observed at 3 months after the procedure on the anterior corneal surface. At 6 months after CXL, progression had increased to 2.3 diopters. Although swelling with hypoosmolar riboflavin solution was effective and led to a preoperative thickness of more than 400 μm, the increase in biomechanical resistance was not sufficient to arrest the progression of the disease., Conclusions: Little is known about the minimal stromal thickness required for effective CXL to occur. Although swelling with hypoosmolar riboflavin solution over 400 μm and safety of the procedure can be achieved in even thinner corneas, the outcome of this case suggests that a minimal preoperative stromal thickness of 330 μm needs to be respected for a successful CXL procedure.

Objective: To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children., Study Design: We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours., Results: A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups., Conclusion: The addition of zinc and prebiotics to ORS limits diarrhea duration in children., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The recommendations for intraoperative fluid therapy in children have been adapted from hypotonic to isotonic electrolyte solutions with lower glucose concentrations (1-2.5% instead of 5%) to avoid hyponatremia and hyperglycemia., Objective: The objective of this prospective multicentre observational post-authorization safety study was to evaluate the intraoperative use of a novel isotonic-balanced electrolyte solution with 1% glucose (BS-G1) with a particular focus on changes in acid-base status, electrolyte and glucose concentrations., Methods: Following local ethics committee approval, pediatric patients aged up to 4 years with an ASA risk score of I-III undergoing intraoperative administration of BS-G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid-base status, electrolyte and glucose concentrations., Results: In 107 patients (ASA I-III; age 16.2 ± 15.4, range day of birth to 47.7 months; body weight 8.8 ± 4.8, range 1.6-18.8 kg), the mean volume infused was 20 ± 12.6 (range 3.6-83.3) ml·kg(-1) BS-G1. During the infusion, hemoglobin, hematocrit, anion gap, strong ion difference, and calcium decreased and chloride and glucose increased significantly within the physiologic range. All other measured parameters including sodium, bicarbonate, base excess, and lactate remained stable. Neither hypoglycemia (glucose <2.5 mmol·l(-1) ) nor hyperglycemia (glucose >10 mmol·l(-1) ) was documented after BS-G1 infusion. No adverse drug reactions were reported., Conclusion: The studied isotonic-balanced electrolyte solution with 1% glucose helps to avoid perioperative acid-base imbalance, hyponatremia, hyperglycemia, and ketoacidosis in infants and toddlers and may therefore enhance patient safety., (© 2010 Blackwell Publishing Ltd.)

Two patients developed the transurethral resection (TUR) syndrome after having absorbed mannitol 5% during TUR of the prostate. Both developed pulmonary edema and became severely hypoatremic (lowest serum sodium 99 and 97 mmol/l, respectively). Hypertonic saline was infused to raise the serum sodium level and plasma volume expansion used to combat hypotension. One patient also required positive-pressure ventilation and intravenous administration of norepinephrine. Both patients recovered completely.

Objective: To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT)., Study Design: Double-blinded, placebo-controlled, prospective, randomized study., Animals: Dogs (n=30) with spontaneous, cutaneous, solitary MCT., Methods: The wound bed of MCT, resected with margins <0.5 cm, was injected with either hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner., Results: Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods., Conclusion: No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT., Clinical Relevance: Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.

Objective: To evaluate the effects of different fluid resuscitation strategies on superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) activities in the lung tissue in pregnant rabbits with uncontrolled hemorrhagic shock., Methods: Thirty pregnant New Zealand rabbits were randomized into 5 equal groups, namely the sham shock.(SS) group, shock group without interventions (SH group), and hemorrhagic shock groups with conventional normal saline (NS) resuscitation, NS hypotensive resuscitation, and hypertonic hyperosmotic hypotensive resuscitation (NS, NH, HHH groups, respectively) 30 min after the shock. At the end of the experiment, the rabbits were sacrificed, and the lungs were taken for detection of MDA, MPO and SOD levels., Results: Ischemia-reperfusion injury of the lungs in uncontrolled hemorrhagic shock resulted in decreased SOD and increased MDA and MPO contents. The MDA and MPO contents in HHH group were significantly lower than those in NH group, and both the groups, MDA and MPO contents were significantly lower than those of NS group (P<0.05). SOD activity was significantly higher in HHH group than in NH group (P<0.05)., Conclusion: In pregnant rabbits with uncontrolled hemorrhagic shock, hypotensive resuscitation more effectively ameliorates ischemia-reperfusion injuries in the lungs than aggressive fluid resuscitation, and hyperosmotic crystalloid and hyperonoctic colloid resuscitation provide significant protective effects against such injuries.

A systematic review of studies comparing hypotonic versus isotonic intravenous maintenance fluids in hospitalized children was conducted to determine whether hypotonic solutions increase the risk of acute hyponatremia. Studies were identified from electronic databases and hand-searched reference lists. A total of 283 abstracts were reviewed, 55 full-text articles were retrieved, and 3 studies were included. All studies were observational and were overall inconclusive. All authors cautioned against the routine use of hypotonic maintenance fluids, but hypotonic fluid administration did not always explain the development of acute hyponatremia. Further evidence is required as to the appropriate maintenance solution for hospitalized children.

Hypernatraemia over 160 mmol/L is considered to be severe. This case reports a patient who developed extreme hypernatraemia with a serum sodium concentration of 196 mmol/L. The patient was known to have chronic renal impairment and was admitted with acute deterioration of renal function secondary to dehydration. This was considered to be secondary to poor oral fluid intake (related to depression) and lithium-induced nephrogenic diabetes insipidus with salt-losing nephropathy. The patient had a high urinary sodium excretion but was also in a pure water losing state as evidenced by an inappropriately low urine osmolality for the plasma osmolality and was successfully treated with hypotonic intravenous fluid and desmopressin.

Hospital-acquired hyponatremia can be lethal. There have been multiple reports of death or permanent neurological impairment in both children and adults. The main factor contributing to the development of hospital-acquired hyponatremia is routine use of hypotonic fluids in patients in whom the excretion of free water, which is retained in response to excess arginine vasopressin (AVP), might be impaired. The practice of administering hypotonic parental fluids was established over 50 years ago, before recognition of the fact that there are numerous potential stimuli for AVP production in most hospitalized patients. Virtually all neurological morbidity resulting from hospital-acquired hyponatremia has been associated with administration of hypotonic fluids. Multiple prospective studies have shown that 0.9% NaCl is effective prophylaxis against hyponatremia. There is not a single report in the literature of neurological complications resulting from the use of 0.9% NaCl in non-neurosurgical patients. Patients at greatest risk of developing hyponatremic encephalopathy following hypotonic fluid administration are children, premenopausal females, postoperative patients, and those with brain injury or infection, pulmonary disease or hypoxemia. When hyponatremic encephalopathy develops, immediate administration of 3% NaCl is essential. In this Review, we discuss the question of why administering hypotonic fluids is unphysiologic and potentially dangerous, the settings in which isotonic fluids should be administered to prevent hyponatremia, and the appropriate treatment of hyponatremic encephalopathy.

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.

Patients with chronic kidney disease (CKD) are at risk to develop acute renal failure (ARF) after open heart surgery. This complication is associated with high morbidity, mortality, and cost. Because the ability to concentrate urine is lost early in the progression of CKD, renal patients kept on fluid restriction prior to surgery may develop severe dehydration, a situation consistently found to be one of the most critical risk factors for postoperative ARF. Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD. This is a prospective study in a tertiary cardiac surgery center. Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD, as evidenced by a quantified glomerular filtration rate less than 45 mL/min, were assigned using a 2/1 randomization process, to either receive an intravenous infusion of half-isotonic saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29 men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in clinical and intraoperative variables associated with postoperative renal injury. ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of the 30 (30%) patients in the hydration group. Four patients in the control group (27%), but no one in the hydration group, required dialysis after the operation (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group. Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery.

Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis.

Aims: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline., Methods: A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T(0)) and 4 hours after (T(4)) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T(0)., Results: At T(0), mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124-142), with 37/102 (36%) hyponatraemic. At T(4), mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic., Conclusions: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.

The use of hypotonic intravenous solutions, especially 4% dextrose/0.18% saline, remains standard practice in many paediatric units in the UK. The practice of prescribing hypotonic intravenous fluids derives from the work of investigators in the 1950s, who produced arbitrarily-derived formulae for calculating the maintenance requirements for water and electrolytes in hospitalised patients. Combining these values led to the widespread acceptance of hypotonic solutions such as 4% dextrose/0.18% saline as 'standard maintenance' parenteral fluids. Unfortunately, these calculations do not account for the effects of antidiuretic hormone, the secretion of which is stimulated by many factors encountered during acute illness and especially in the perioperative period. In this setting, the administration of hypotonic intravenous fluids results in the retention of free water and the development of hyponatraemia. The routine administration of hypotonic intravenous fluids has been shown to be associated with severe morbidity and the deaths of many previously healthy children. The problem is compounded by the fact that 4% dextrose/0.18% saline is labelled as 'isotonic'. Whilst this solution is isosmolar compared to plasma, lack of osmotically-effective solutes means that it is hypotonic with reference to the cell membrane. There is no justification for the routine administration of hypotonic intravenous fluids.

Objective: To determine hypotonic liquid containing colloid on hemorrhagic dogs with celiac seawater immersion wound., Methods: Thirty-five dogs were randomly divided into five groups: control group (group A), 0.9% NaCl therapy group (group B) and 0.45% NaCl therapy group (group C), 5% glucose therapy group(group D) and hypotonic liquid containing colloid therapy group (group E). Changes of mean artery pressure (MAP), cardiac output (CO), urine volume, plasma osmotic pressure and pathologic changes of lung and brain were observed., Results: hypotonic liquid containing colloid could effectively ameliorate MAP and CO, improve urine volume, decrease plasma osmotic pressure and prevent occurrence of lung and brain edema., Conclusion: Hypotonic liquid containing colloid can exert satisfactory therapeutic effects on hemorrhagic dogs with celiac seawater immersion wound.

Hyponatraemia is the commonest electrolyte abnormality in hospitalized patients. If the plasma sodium concentration (P(Na)) declines to approximately 120 mM in <48 h, brain cell swelling might result in herniation, with devastating consequences. The volume and/or the composition of fluids used for intravenous therapy often contribute to the development of acute hyponatraemia. Our hypothesis is that the traditional calculation of the daily loss of insensible water overestimates this parameter, leading to an excessive daily recommended requirement for water. We offer suggestions to minimize the risk of iatrogenic hyponatraemia.

Background: A decrease in plasma sodium (P(Na)) concentration is common after surgery and attributed to the secretion of antidiuretic hormone in response to such nonosmotic stimuli as pain or nausea. In this setting, acute hyponatremia may lead to seizures, coma, and permanent neurological damage. Sporadic case reports have described severe neurological symptoms caused by hyponatremia occurring within hours after cardiac catheterization. We evaluated the prevalence, contributing clinical circumstances, and course of hyponatremia in patients undergoing cardiac catheterization., Methods: We prospectively studied 309 consecutive patients scheduled for an elective cardiac catheterization. Plasma and urine electrolytes and urine osmolarity were measured at baseline and again 1 to 4 hours and 24 hours after the procedure., Results: P(Na) level was 139.4 +/- 2.3 mEq/L at baseline. At 1 to 4 hours, P(Na) level decreased to 134.2 +/- 3.6 mEq/L (P < 0.0001). Mild (> or =5 to 10 mEq/L), moderate (11 to 14 mEq/L), and severe (> or =15 mEq/L) reductions in P(Na) levels occurred in 50%, 5%, and 0.3% of patients, respectively. At the 24-hour point, P(Na) level increased to 137.3 +/- 2.4 mEq/L, but was significantly lower compared with baseline (P < 0.0001). In hyponatremic patients at the 1- to 4- and 24-hour points, mean urine osmolarity values were 428 +/- 139 and 420 +/- 204 mOsm/kg, respectively; almost every urine sample was inappropriately concentrated. Multivariate logistic regression identified the amount of electrolyte-free water administered to be a predictor for the development of hyponatremia (3.7-fold incremental risk for every 1 L administered to a 70-kg patient)., Conclusion: An acute reduction in P(Na) level commonly occurs shortly after cardiac catheterization. The cause of hyponatremia appears to be related to the administration of hypotonic fluids, together with impaired urinary dilutional capacity. Although symptomatic hyponatremia is rare, the diagnosis should be entertained when neurological symptoms develop in this setting., (Copyright 2002 by the National Kidney Foundation, Inc.)

The present review discusses the hemodynamic effects of hypertonic saline in experimental shock and in patients with sepsis. We comment on the mechanisms of action of hypertonic saline, calling upon data in hemorrhagic and septic shock. Specific actions of hypertonic saline in severe sepsis and septic shock are highlighted. Data are available that support potential benefits of hypertonic saline infusion in various aspects of the pathophysiology of sepsis, including tissue hypoperfusion, decreased oxygen consumption, endothelial dysfunction, cardiac depression, and the presence of a broad array of proinflammatory cytokines and various oxidant species. The goal of research in this field is to identify reliable therapies to prevent ischemia and inflammation, and to reduce mortality.

Background: Acute renal failure induced by contrast agents represents the third cause of acute nephropathy in hospitalized patients. Some mediators are potentially involved in this process: recent data underscored the role of oxidising agents and prophylactic administration of NAC showed a lower incidence of acute renal damage after using contrast agents., Methods: We analyzed 100 patients consecutively undergoing coronary angiography and/or transluminal angioplasty: the study group was given NAC orally at a dose of 600 mg twice daily, on the day before and on the day of administration of the contrast agent, together with hydration, while the control group was given only the hydration protocol with hypotonic saline., Results: Twenty patients had baseline serum creatinine concentrations > 1.2 mg/dL (mild renal insufficiency group). The mean dose of contrast agent (Iodixanol; Visipaque 320, Nycomed) was 203 mL/procedure, with no statistical difference between groups. Among the patients with normal renal function, 5.7% in the NAC group and 8.8% in the control group had baseline serum creatinine concentrations above 0.3 mg/dL after 48 hours (p=NS). In patients with mild renal failure, 16.6% in the NAC group and 0% in the control group had serum creatinine concentrations > 0.5 mg/dL at 48 h (p=NS). We found no significant differences in serum creatinine values at 48 hours vs. baseline in anyone (NAC group with normal renal function or mild renal insufficiency, control group with normal renal function or mild renal insufficiency). Similarly, serum creatinine values at either baseline or after 48 hours were not significantly different in patients with normal renal function (NAC vs. control group) and with mild renal failure., Conclusions: Our study showed no potential advantage in the prevention of acute nephropathy, induced by high volumes of contrast agent, through the administration of NAC in patients with normal renal function and mild renal failure. However, the NAC dose used in our study might not be sufficient in balancing the contrast agent volume employed in these procedures.

The most common enteric viruses responsible for diarrhoea are rotavirus, enteric adenoviruses, caliciviruses including the Norwalk agent and astrovirus. These infections are usually mild to moderate in severity, self-limiting and of short duration and thus, specific antiviral therapy is not recommended. The standard management of these infections is restoration of fluid and electrolyte balance and then maintenance of hydration until the infection resolves. WHO oral rehydration therapy (ORT) was introduced about 30 years ago and has saved the lives of many infants and young children. During the last 10 years it has become evident that the efficacy of ORT can be increased by reducing the osmolality of the WHO oral rehydration solution (ORS) to produce a relatively hypotonic solution. Hypotonic ORS appears to be safe and effective in all forms of acute diarrhoea in childhood. Complex substrate ORS, which is also usually hypotonic, has been shown to have increased efficacy in cholera but not in other bacterial or viral diarrhoeas. Nevertheless, the scientific rationale for using rice or resistant starch as substrate in ORS is of physiological interest. Other treatments such as hyperimmune bovine colostrum, probiotics and antiviral agents are largely experimental and have not been introduced into routine clinical practice. Cytomegalovirus (CMV) infection of the gastrointestinal tract occurs mainly in the immunocompromised although it has been reported in immunocompetent individuals. CMV infects both the oesophagus and colon to produce oesophagitis, often with discrete ulcers, and colitis, respectively. Both conditions can be treated with ganciclovir or foscarnet. Failure to respond to monotherapy is an indication to use both agents concurrently.