A Slow-Exchange Interstitial Fluid Compartment in Volunteers and Anesthetized Patients: Kinetic Analysis and Physiology.

BACKGROUND: Physiological studies suggest that the interstitial space contains 2 fluid compartments, but no analysis has been performed to quantify their sizes and turnover rates. METHODS: Retrospective data were retrieved from 270 experiments where Ringer's solution of between 238 and 2750 mL (mean, 1487 mL) had been administered by intravenous infusion to awake and anesthetized humans (mean age 39 years, 47% females). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed-models software. RESULTS: The kinetic analysis successfully separated 2 interstitial fluid compartments. One equilibrated rapidly with the plasma and the other equilibrated slowly. General anesthesia doubled the rate constants for fluid entering these 2 compartments (from 0.072 to 0.155 and from 0.026 to 0.080 min -1 , respectively). The return flows to the plasma were impeded by intensive fluid therapy; the rate constant for the fast-exchange compartment decreased from 0.251 to 0.050 when the infusion time increased from 15 to 60 minutes, and the rate constant for the slow-exchange compartment decreased from 0.019 to 0.005 when the infused volume increased from 500 to 1500 mL. The slow-exchange compartment became disproportionately expanded when larger fluid volumes were infused and even attained an unphysiologically large size when general anesthesia was added, suggesting that the flow of fluid was restrained and not solely determined by hydrostatic and oncotic forces. The dependence of the slow-exchange compartment on general anesthesia, crystalloid infusion rate, and infusion volume all suggest a causal physiological process. CONCLUSIONS: Kinetic analysis supported that Ringer's solution distributes in 2 interstitial compartments with different turnover times. The slow compartment became dominant when large amounts of fluid were infused and during general anesthesia. These findings may explain why fluid accumulates in peripheral tissues during surgery and why infused fluid can remain in the body for several days after general anesthesia.

Balanced Crystalloids Versus Normal Saline in Kidney Transplant Patients: An Updated Systematic Review, Meta-analysis, and Trial Sequential Analysis.

BACKGROUND: The use of balanced crystalloids over normal saline for perioperative fluid management during kidney transplantation and its benefits on acid-base and electrolyte balance along with its influence on postoperative clinical outcomes remains a topic of controversy. Therefore, we conducted this review to assess the impact of balanced solutions compared to normal saline on outcomes for kidney transplant patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing balanced lower-chloride solutions to normal saline in renal transplant patients. Our main outcome of interest was delayed graft function (DGF). Additionally, we examined acid-base and electrolyte measurements, along with postoperative renal function. We computed relative risk (RR) using the Mantel-Haenszel test for binary outcomes, and mean difference (MD) for continuous data, and applied DerSimonian and Laird random-effects models to address heterogeneity. Furthermore, we performed a trial sequential analysis (TSA) for all outcomes. RESULTS: Twelve RCTs comprising a total of 1668 patients were included; 832 (49.9%) were assigned to receive balanced solutions. Balanced crystalloids reduced the occurrence of DGF compared to normal saline, with RR of 0.82 (95% confidence interval [CI], 0.71-0.94), P = .005; I² = 0%. The occurrence was 25% (194 of 787) in the balanced crystalloids group and 34% (240 of 701) in the normal saline group. Moreover, our TSA supported the primary outcome result and suggests that the sample size was sufficient for our conclusion. End-of-surgery chloride (MD, -8.80 mEq·L -1 ; 95% CI, -13.98 to -3.63 mEq.L -1 ; P < .001), bicarbonate (MD, 2.12 mEq·L -1 ; 95% CI, 1.02-3.21 mEq·L -1 ; P < .001), pH (MD, 0.06; 95% CI, 0.04-0.07; P < .001), and base excess (BE) (MD, 2.41 mEq·L -1 ; 95% CI, 0.88-3.95 mEq·L -1 ; P = .002) significantly favored the balanced crystalloids groups and the end of surgery potassium (MD, -0.17 mEq·L -1 ; 95% CI, -0.36 to 0.02 mEq·L -1 ; P = .07) did not differ between groups. However, creatinine did not differ in the first (MD, -0.06 mg·dL -1 ; 95% CI, -0.38 to 0.26 mg·dL -1 ; P = .71) and seventh (MD, -0.06 mg·dL -1 ; 95% CI, -0.18 to 0.06 mg·dL -1 ; P = .30) postoperative days nor urine output in the first (MD, -1.12 L; 95% CI, -3.67 to 1.43 L; P = .39) and seventh (MD, -0.01 L; 95% CI, -0.45 to 0.42 L; P = .95) postoperative days. CONCLUSIONS: Balanced lower-chloride solutions significantly reduce the occurrence of DGF and provide an improved acid-base and electrolyte control in patients undergoing kidney transplantation.

Fluids and body composition during anesthesia in children and adolescents: A pilot study.

The purpose of this study is to evaluate the intracellular and extracellular volume before and after anesthesia in order to ascertain their variations and determine the potential utility of this information in optimizing intraoperative fluid administration practices. A bioimpedance spectroscopy device (body composition monitor, BCM) was used to measure total body fluid volume, extracellular volume, and intracellular volume. BCM measurements were performed before and after general anesthesia in unselected healthy children and adolescents visiting the Pediatric Institute of Southern Switzerland for low-risk surgical procedures hydrated with an isotonic solution. In 100 children and adolescents aged 7.0 (4.8-11) years (median and interquartile range), the average total body water increased perioperatively with a delta value of 182 (0-383) mL/m2 from pre- to postoperatively, as well as the extracellular water content, which had a similar increase with a delta value of 169 (19-307) mL/m2. The changes in total body water and extracellular water content significantly correlated with the amount of fluids administered. The intracellular water content did not significantly change.   Conclusion: Intraoperative administration of isotonic solutions results in a significant fluid accumulation in low-risk schoolchildren during general anesthesia. The results suggest that children without major health problems undergoing short procedures do not need any perioperative intravenous fluid therapy, because they are allowed to take clear fluids up to 1 h prior anesthesia. In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy. What is Known: • Most children who undergo common surgical interventions or investigations requiring anesthesia are nowadays hydrated at a rate of 1700 mL/m2/day with an isotonic solution. • The use bioimpedance spectroscopy for the assessment of fluid status in healthy children has already been successfully validated. • The bioimpedance spectroscopy is already currently widely used in various nephrological settings to calculate fluid overload and determine patient's optimal fluid status. What is New: • Routine intraoperative fluid administration results in a significant fluid accumulation during general anesthesia in low-risk surgical procedures. • This observation might be relevant for children and adolescents with conditions predisposing to fluid retention. • In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy.

How to follow the guidelines, when the appropriate fluid is missing?

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution.

Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Impact of the utilization of 500 mL IV bags on crystalloid resuscitation volumes administered to trauma patients.

INTRODUCTION: Administering large volumes of crystalloids to trauma patients has been shown to exacerbate metabolic complications of hemorrhage including dilutional coagulopathy and worsening acidosis The aim of this study was to evaluate crystalloid administration volumes in trauma patients after replacing 1 L IV containers with 500 mL IV containers in the emergency department trauma resuscitation bay. MATERIALS AND METHODS: This was a single-center, IRB-approved, retrospective cohort evaluation of adult trauma patients conducted at an 864-bed community tertiary referral center located in the southeastern United States. Patterns of crystalloid administration were examined before and after the trauma resuscitation bay began to exclusively stock 500 mL IV containers. The primary outcome was mean total crystalloid volume infused from time of injury to hospital admission. Secondary outcomes included mean total crystalloid volume infused prior to administration of blood products, proportion of patients who received less than 2 L total of crystalloids, time to initiation of blood products, and mortality in both the emergency department and in-hospital. RESULTS: Patient characteristics were largely similar between both groups including age, mechanism of injury, and Injury Severity Score. For the primary outcome, the mean total crystalloid volume infused from time of injury to hospital administration, patients in the 500 mL IV fluid container group were administered 555 mL less crystalloid when compared to the 1 L IV fluid container group, 1048 mL vs 1603 mL (p < 0.01; 95% CI 406 mL - 704 mL), respectively. After conversion to the 500 mL IV container bags, there was a 27.5% increase in the proportion of patients receiving less than 2 L of crystalloid, 90.5% vs 63.0% in the 500 mL IV fluid container and 1 L IV fluid container groups, respectively (p < 0.01). CONCLUSIONS: Due to reduced mortality, expanding literature and guidelines clearly support minimizing IV crystalloid resuscitation. Institutions must now work to minimize use of IV crystalloids to hemorrhaging trauma patients and a simple solution of using smaller IV fluid bags was shown to improve adherence to this practice.

Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Clinical Trial.

Importance: In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. Objective: To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. Design, Setting, and Participants: A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). Interventions: The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. Main Outcomes and Measures: The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. Results: Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). Conclusions and Relevance: Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02560519.

Carbohydrate ingestion attenuates cognitive dysfunction following long-duration exercise in the heat in humans.

INTRODUCTION: To determine if electrolyte or carbohydrate supplementation vs. water would limit the magnitude of dehydration and decline in cognitive function in humans following long-duration hyperthermic-exercise. METHODS: 24 subjects performed 3 visits of 2 h walking (3mph/7% grade) in an environmental chamber (33 °C/10% relative humidity). In random order, subjects consumed water (W), electrolytes (Gatorade Zero; E), or electrolytes+carbohydrates (Gatorade; E+C). Throughout exercise (EX), subjects carried a 23 kg pack and drank ad-libitum. Pre-and post-EX, body mass (BM) and plasma osmolality (pOsm) were measured. Physiological Strain Index (PSI) and core temperature (TC) were recorded every 15 min. Plasma glucose (GLU) was measured every 30 min. Cognitive processing (SCWT) was measured post-EX and compared to baseline (BL). A subset of 8 subjects performed a normothermic (N) protocol (21 °C/ambient humidity) to ascertain how the exercise stimulus influenced hydration status and cognition without heat. RESULTS: There were no significant differences between fluid conditions (W, E, E+C) for BM loss (Δ2.5 ± 0.2, 2.5 ± 0.2, 2.3 ± 0.2 kg), fluid consumption (1.9 ± 0.2, 1.9 ± 0.2, 1.8 ± 0.2L), pOsm (Δ1.5 ± 2.7, 2.2 ± 2.4, 2.0 ± 1.5 mmol/L), peak-PSI (7.5 ± 0.4, 7.0 ± 0.6, 7.9 ± 0.5), and peak-TC (38.7 ± 0.1, 38.6 ± 0.2, 38.8 ± 0.2 °C). GLU decreased significantly in W and E, whereas it increased above BL in E+C at 60, 90, and 120 min (P < 0.05). Compared to BL values (43.6 ± 26 ms), SCWT performance significantly decreased in all conditions (463 ± 93, 422 ± 83, 140 ± 52 ms, P < 0.05). Importantly, compared to W and E, the impairment in SCWT was significantly attenuated in E+C (P < 0.05). As expected, when compared to the heat-stress protocol (W, E, E+C), N resulted in lower BM loss, fluid consumption, and peak-PSI (1.1 ± 0.1 kg, 1.2 ± 0.7L, 4.8, respectively), and improved SCWT performance. CONCLUSIONS: These data are the first to suggest that, independent of supplementation variety, cognitive processing significantly decreases immediately following long-duration exercise in the heat in healthy humans. Compared to water and fluids supplemented with only electrolytes, fluids supplemented with carbohydrates significantly blunts this decrease in cognitive function.

Noninvasive analysis and identification of an intramuscular fluid collection by postmortem 1H-MRS in a case of a fatal motor vehicle accident.

In a case of a fatal traffic accident, a suspicious finding was identified in the muscular tissue of the left thigh by whole-body postmortem computed tomography. To better interpret the finding, the lower extremities were investigated by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). MRI revealed the presence of an evenly distributed intramuscular fluid and 1H-MRS of a volume within the fluid detected concentrations of acetate and lactate. The fluid was assumed to be an extravasation of an intraosseous infusion, erroneously administered to the intermediate vastus of the left thigh during resuscitation, which was later confirmed when access to resuscitation protocols was granted. Further ex situ 1H-MRS investigations of five different infusion fluids showed the possible discrimination of the fluids and further indicated the unknown fluid to be a Ringer's acetate solution. This paper presents the case-based application of postmortem intramuscular 1H-MRS and introduces the possibility of its use to differentiate exo- and endogenic fluids for forensic interpretation. Further research for this method regarding problems in forensic pathology is needed.

Goal-Directed Fluid Therapy Does Not Improve Early Glomerular Filtration Rate in a Porcine Renal Transplantation Model.

BACKGROUND: Insufficient fluid administration intra- and postoperatively may lead to delayed renal graft function (DGF), while fluid overload increases the risk of heart failure, infection, and obstipation. Several different fluid protocols have been suggested to ensure optimal fluid state. However, there is a lack of evidence of the clinical impact of these regimens. This study aimed to determine whether individualized goal-directed fluid therapy (IGDT) positively affects the initial renal function compared to a high-volume fluid therapy (HVFT) and to examine the effects on renal endothelial glycocalyx, inflammatory and oxidative stress markers, and medullary tissue oxygenation. The hypothesis was that IGDT improves early glomerular filtration rate (GFR) in pigs subjected to renal transplantation. METHODS: This was an experimental randomized study. Using a porcine renal transplantation model, animals were randomly assigned to receive IGDT or HVFT during and until 1 hour after transplantation from brain-dead donors. The kidneys were exposed to 18 hours of cold ischemia. The recipients were observed until 10 hours after reperfusion, which included GFR measured as clearance of chrom-51-ethylendiamintetraacetat (Cr-EDTA), animal weight, and renal tissue oxygenation by fiber optic probes. The renal expression of inflammatory and oxidative stress markers as well as glomerular endothelial glycocalyx were analyzed in the graft using polymerase chain reaction (PCR) technique and immunofluorescence. RESULTS: Twenty-eight recipient pigs were included for analysis. We found no evidence that IGDT improved early GFR compared to HVFT (P = .45), while animal weight increased more in the HVFT group (a mean difference of 3.4 kg [1.96-4.90]; P < .0001). A better, however nonsignificant, preservation of glomerular glycocalyx (P = .098) and significantly lower levels of the inflammatory marker cyclooxygenase 2 (COX-2) was observed in the IGDT group when compared to HVFT. COX-2 was 1.94 (1.50-2.39; P = .012) times greater in the HVFT group when compared to the IGDT group. No differences were observed in outer medullary tissue oxygenation or oxidative stress markers. CONCLUSIONS: IGDT did not improve early GFR; however, it may reduce tissue inflammation and could possibly lead to preservation of the glycocalyx compared to HVFT.

Preventive Inhalation of Hypertonic Saline in Infants with Cystic Fibrosis (PRESIS). A Randomized, Double-Blind, Controlled Study.

Rationale: Cystic fibrosis (CF) lung disease starts in early infancy, suggesting that preventive treatment may be most beneficial. Lung clearance index (LCI) and chest magnetic resonance imaging (MRI) have emerged as promising endpoints of early CF lung disease; however, randomized controlled trials testing the safety and efficacy of preventive therapies in infants with CF are lacking. Objectives: To determine the feasibility, safety, and efficacy of preventive inhalation with hypertonic saline (HS) compared with isotonic saline (IS) in infants with CF, including LCI and MRI as outcome measures. Methods: In this randomized, double-blind, controlled trial, 42 infants with CF less than 4 months of age were randomized across five sites to twice-daily inhalation of 6% HS (n = 21) or 0.9% IS (n = 21) for 52 weeks. Measurements and Main Results: Inhalation of HS and IS was generally well tolerated by infants with CF, and the number of adverse events did not differ between groups (P = 0.49). The change in LCI from baseline to Week 52 was larger in infants with CF treated with HS (-0.6) than in those treated with IS (-0.1; P < 0.05). In addition, weight gain was improved in infants with CF treated with HS (P < 0.05), whereas pulmonary exacerbations and chest MRI scores did not differ in the HS group versus the IS group. Conclusions: Preventive inhalation with HS initiated in the first months of life was safe and well tolerated and resulted in improvements in LCI and weight gain in infants with CF. Our results support the feasibility of LCI as an endpoint in randomized controlled trials in infants with CF. Clinical trial registered with www.clinicaltrials.gov (NCT01619657).

Effectiveness of micronized nasal irrigations with hyaluronic acid/isotonic saline solution in non-polipoid chronic rhinosinusitis: A prospective, randomized, double-blind, controlled study.

BACKGROUND: Sodium hyaluronate has been proposed as a treatment for improving the symptoms of chronic rhinosinusitis. The present study evaluated the effect of the intranasal administration of hyaluronic acid in a group of patients affected by chronic rhinosinusitis without nasal polyps (CRSsNP). MATERIALS AND METHODS: Thirty subjects aged 18-65 years affected by CRSsNP were enrolled. The subjects were randomly administered hyaluronic acid or isotonic saline solution by nasal nebulizer twice per day for 30 days. They were evaluated before (T0) and after the treatment (T1) with Sino-Nasal Outcome Test-22, visual analogue scale for rhinorrhea, nasal obstruction, facial pain and hyposmia/hypogeusia, nasal endoscopy, active anterior rhinomanometry, peak nasal inspiratory flow and nasal cytology. RESULTS: Comparing the study and the control group, at T1 no significant differences were observed in both objective and subjective parameters. Being included in the study group rather than in the control group did not have a significant effect on the variation of the considered parameters between T0 and T1. Considering the effects of the micronized douches independently from the type of solution used (either hyaluronic acid or isotonic saline solution), although no difference emerged between study and control group for any of the objective parameters, there was an improvement of Sino-Nasal Outcome Test-22 scores (p = .0005), visual analogue scale for nasal obstruction (p = .0006) and for hyposmia/hypogeusia (p = .04). CONCLUSIONS: The treatment with micronized nasal douches can improve the sino-nasal symptoms of CRSsNP, in particular nasal obstruction and olfactory ability. No advantage of the use of hyaluronic acid over isotonic saline solution emerged.

Efficacy of buffered hypertonic seawater in different phenotypes of chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery: a randomized double-blind study.

PURPOSE: Nasal douching is commonly used as a postoperative management strategy for chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies to date have compared the effectiveness of nasal douching in CRSwNP phenotypes after endoscopic sinus surgery (ESS). We evaluated the efficacy of seawater types in eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (nonECRSwNP) after ESS. METHODS: Patients with bilateral CRSwNP who had undergone ESS were blindly randomized to receive buffered hypertonic seawater (BHS) (n = 48) or physiological seawater (PS) (n = 45). CRSwNP patients were stratified by phenotypes (ECRSwNP and nonECRSwNP) retrospectively according to whether tissue eosinophils exceeded 10%. Follow-up evaluations were conducted at 2, 8, 16, and 24 weeks after surgery. Evaluations included the 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale (VAS), Lund-Kennedy endoscopic score (LKES), saccharine clearance time (SCT), and adverse events. RESULTS: All of the patients experienced significant improvements in SNOT-22 scores, VAS scores, and LKES over time. BHS resulted in better improvement of LEKS and SCT relative to PS at 8 weeks postoperatively. Mucosal edema formation was significantly reduced with less crusting among HBS recipients at 8 weeks. After stratification, only patients in the nonECRSwNP + BHS subgroup showed a significant improvement in LEKS and SCT at 8 weeks postoperatively. Side effect profiles were not significantly different among the groups. CONCLUSIONS: BHS has a better inhibitory effect on mucosal edema and crusting during the early postoperative care period of CRSwNP. Among all of the patients, nonECRSwNP patients showed a significant improvement in LEKS and SCT at 8 weeks.

Fluid management in the critically ill.

Fluid therapy, which is provided to restore and maintain tissue perfusion, is part of routine management for almost all critically ill patients. However, because either too much or too little fluid can have a negative impact on patient outcomes, fluid administration must be titrated carefully for each patient. The "salvage, optimization, stabilization, de-escalation" (SOSD) mnemonic should be used as a general guide to fluid resuscitation, and fluid administration should be adapted according to the course of the disease. In the initial salvage phase, lifesaving fluid should be administered generously. Once hemodynamic monitoring is available, fluid administration should be optimized by determining the patient's fluid status and the need for further fluid. This determination can be difficult, however; clinical indicators of hypovolemia, such as heart rate, blood pressure, and urine output, may not detect early hypovolemia, and edema is a late sign of fluid overload. Dynamic tests of fluid responsiveness such as pulse pressure or stroke volume variation can be used in only a small percentage of critically ill patients, and thus a fluid challenge technique is most frequently used to assess ongoing fluid requirements. Once a patient has been stabilized, efforts should start to concentrate on removing excess fluid. Which fluid should be used remains a matter of some debate. Crystalloid solutions are cheaper than colloid solutions, but colloid solutions remain in the intravascular space for a longer period, making edema less likely. Thus crystalloids and colloids should be used together, especially in patients likely to require large fluid volumes. Human albumin is a natural colloid and may have beneficial effects in patients with sepsis in addition to its volume effects. Fluids should be prescribed as are other medications, taking into account individual patient factors, disease processes, and other treatments.

Normal Saline Solution and Lactated Ringer's Solution Have a Similar Effect on Quality of Recovery: A Randomized Controlled Trial.

STUDY OBJECTIVE: The purpose of this study is to test the hypothesis that balanced crystalloids improve quality of recovery more than normal saline solution (0.9% sodium chloride) in stable emergency department (ED) patients. Secondary outcomes measured differences in health care use. METHODS: A single-site, participant- and evaluator-blinded, 2-arm parallel allocation (1:1), comparative effectiveness, randomized controlled trial allocated adults receiving intravenous fluids in the ED before discharge to receive 2 L of lactated Ringer's solution or normal saline solution. The primary outcome was symptom scores measured by the validated Quality of Recovery-40 instrument (scores 40 to 200) 24 hours after enrollment. Secondary outcomes included subsequent health care use and medication compliance. RESULTS: Participants (N=157) were enrolled and follow-up was analyzed for 94 (follow-up rate of 60%) with intention-to-treat methodology. There was no difference in postenrollment Quality of Recovery-40 scores between normal saline solution and lactated Ringer's solution groups (mean difference 2.4; 95% confidence interval [CI] -6.8 to 11.6). Although preenrollment scores were higher in the lactated Ringer's solution group (mean difference 10.5; 95% CI 1.9 to 19.0), adjusting for presurvey imbalances did not change the primary outcome (adjusted difference -3.9; 95% CI -12.9 to 5.2). There were no differences in return to ED (mean difference 7.5%; 95% CI -8.7% to 23.8%), prescriptions filled (mean difference 22.2%; 95% CI -3.3% to 47.6%), or seeking care from another provider (mean difference -2.0%; 95% CI -19.9% to 15.9%) at 7 days. CONCLUSION: Normal saline solution and lactated Ringer's solution were associated with similar 24-hour recovery scores and 7-day health care use in stable ED patients. These results supplement those of recent trials by informing fluid choice for stable ED patients.

Fluid Management Practices After Surgery for Congenital Heart Disease: A Worldwide Survey.

OBJECTIVES: To determine common practice for fluid management after cardiac surgery for congenital heart disease among pediatric cardiac intensivists. DESIGN: A survey consisting of 17 questions about fluid management practices after pediatric cardiac surgery. Distribution was done by email, social media, World Federation of Pediatric Intensive and Critical Care Societies website, and World Federation of Pediatric Intensive and Critical Care Societies newsletter using the electronic survey distribution and collection system Research Electronic Data Capture. SETTING: PICUs around the world. SUBJECTS: Pediatric intensivists managing children after surgery for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred eight responses from 18 countries and six continents were received. The most common prescribed fluids for IV maintenance are isotonic solutions, mainly NaCl 0.9% (42%); followed by hypotonic fluids (33%) and balanced crystalloids solutions (14%). The majority of the respondents limit total fluid intake to 50% during the first 24 hours after cardiac surgery. The most frequently used fluid as first choice for resuscitation is NaCl 0.9% (44%), the second most frequent choice are colloids (27%). Furthermore, 64% of respondents switch to a second fluid for ongoing resuscitation, 76% of these choose a colloid. Albumin 5% is the most commonly used colloid (61%). Almost all respondents (96%) agree there is a need for research on this topic. CONCLUSIONS: Our survey demonstrates great variation in fluid management practices, not only for maintenance fluids but also for volume resuscitation. Despite the lack of evidence, colloids are frequently administered. The results highlight the need for further research and evidence-based guidelines on this topic.

Effect of the retention ring-assisted continuous application of riboflavin in pulsed-light accelerated corneal collagen cross-linking on the progression of keratoconus.

BACKGROUND: To investigate the efficacy and safety of the retention ring-assisted continuous application of 0.1% riboflavin in pulsed-light accelerated corneal collagen cross-linking on the progression of keratoconus. METHODS: The medical records of 20 eyes of 18 patients with progressive keratoconus who received collagen cross-linking at Seoul National University Hospital were retrospectively reviewed. Isotonic 0.1% riboflavin was continuously applied for 10 min using an 8.0-mm retention ring before the irradiation and accelerated cross-linking was applied with 30-mW pulsed-ultraviolet light at a wavelength 365 nm for eight minutes (1 s on/1 s off; 30 mW/cm2, cumulative dose of 7 .2J/cm2) without further intermittent application of riboflavin. Visual acuity, refractive error, topographic index, corneal thickness, and endothelial cell density were evaluated before the operation and at 1, 3, 6, and 12 months. RESULTS: The best corrected visual acuity in logMAR improved from preoperative 0.43 to 0.17 in 12 months (p = 0.050). Maximum keratometry decreased from 51.8 D to 50.4 D at 6 months (p = 0.015) and 50.1 D at 12 months (p = 0.0003). Astigmatism decreased from preoperative 5.5 D to 4.1 D at 12 months (p < 0.0001). Thinnest corneal thickness decreased at three and 6 months but recovered in 12 months (p > 0.05). Endothelial cell density decreased at postoperative 1 month (p = 0.02) but gradually recovered in 12 months (p > 0.05). CONCLUSIONS: Retention ring-assisted continuous application of riboflavin for 10 minutes in pulsed-light accelerated cross-linking is a comparably safe and effective treatment for halting the progression of keratoconus in 12 months when compared to outcomes of the standard Dresden protocol shown in previous reports.

Optimal crystalloid volume ratio for blood replacement for maintaining hemodynamic stability and lung function: an experimental randomized controlled study.

BACKGROUND: Crystalloids are first line in fluid resuscitation therapy, however there is a lack of evidence-based recommendations on the volume to be administered. Therefore, we aimed at comparing the systemic hemodynamic and respiratory effects of volume replacement therapy with a 1:1 ratio to the historical 1:3 ratio. METHODS: Anesthetized, ventilated rats randomly included in 3 groups: blood withdrawal and replacement with crystalloid in 1:1 ratio (Group 1, n = 11), traditional 1:3 ratio (Group 3, n = 12) and a control group with no interventions (Group C, n = 9). Arterial blood of 5% of the total blood volume was withdrawn 7 times, and replaced stepwise with different volume rations of Ringer's acetate, according to group assignments. Airway resistance (Raw), respiratory tissue damping (G) and tissue elastance (H), mean arterial pressure (MAP) and heart rate (HR) were assessed following each step of fluid replacement with a crystalloid (CR1-CR6). Lung edema index was measured from histological samples. RESULTS: Raw decreased in Groups 1 and 3 following CR3 (p < 0.02) without differences between the groups. H elevated in all groups (p < 0.02), with significantly higher changes in Group 3 compared to Groups C and 1 (both p = 0.03). No differences in MAP or HR were present between Groups 1 and 3. Lung edema was noted in Group 3 (p < 0.05). CONCLUSIONS: Fluid resuscitation therapy by administering a 1:1 blood replacement ratio revealed adequate compensation capacity and physiological homeostasis similar with no lung stiffening and pulmonary edema. Therefore, considering this ratio promotes the restrictive fluid administration in the presence of continuous and occult bleeding.

Effect of Environmental Temperature on Serum Sodium Level in Hospitalized Non-critically Ill Children.

BACKGROUND: Intravenous hypotonic fluid administered in children is associated with an increased risk of developing hyponatremia. This finding has been reported from temperate countries where climate is relatively cold. But whether this risk also occurs in tropical countries has not been elucidated. OBJECTIVE: The objective of this study was to determine the relationship between environmental temperature and serum sodium in non-critically ill children. METHODS: A retrospective study. RESULTS: A total of 1061 hospitalized children were enrolled. Incidences of hyponatremia were not different between patients who received isotonic and hypotonic fluids (29% vs. 31%). Subgroup analysis showed a trend of higher incidence of hyponatremia in patients who received hypotonic fluid than isotonic fluid only in patients admitted to the air-conditioned wards (29% vs. 21%, p = 0.08). CONCLUSION: Children admitted to the air-conditioned wards who received hypotonic fluid seemed to carry a higher risk of developing hyponatremia than those admitted to the non-air-conditioned ward.