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.

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.

Aporte de fluidos en el pacientes pediátricos hospitalizados / Fluid intake in hospitalized pediatric patients

El aporte de fluidos constituye un elemento central en la atención del paciente pediátrico hospitalizado, existiendo aún controversias acerca de cuál es la composición óptima, la dosis adecuada y la mejor estrategia para administrar los mismos. El propósito de este artículo de actualización es brindar al médico que se desempeña en las diferentes áreas de la internación pediátrica, conceptos y enfoques terapéuticos que lo ayuden en la asistencia de los pacientes que por diversos motivos requieren la administración de fluidos endovenosos. La recomendación de utilizar cristaloides en la reanimación es casi uniforme. Se observa una clara tendencia al uso de soluciones isotónicas balanceadas para la reposición del déficit previo y el aporte de fluidos de mantenimiento. En relación a la dosis y a la estrategia, es generalizada la recomendación de un enfoque más restrictivo en el aporte de volumen, aún en los pacientes con shock, donde es necesario lograr un balance entre una resucitación efectiva y el riesgo de sobrecarga de fluidos. Respecto a la administración de albúmina al 20% en el paciente crítico con hipoalbuminemia, la evidencia existente es escasa y no permite formular recomendaciones. Sin embargo, es frecuente su uso en la práctica asistencial

Intravenous fluids administration is a central element in the care of hospitalized pediatric patients, and there are still controversies about what is the optimal composition, the appropriate dose, and the best strategy for their administration. The purpose of this narrative review is to provide the physicians who works in the different areas of pediatric hospitalization, concepts and therapeutic approaches that help them in the care of patients who for diverse reasons require administration of intravenous fluids. The recommendation to use crystalloids in resuscitation is almost uniform. There is a clear trend towards the use of balanced isotonic solutions to replace the previous deficit and the supply of maintenance fluids. In relation to the dose and strategy, the recommendation of a more restrictive approach in volume administration is generalized, even in patients with shock, where it is necessary to strike a balance between effective resuscitation and the risk of fluid overload. Regarding the administration of 20% albumin in critically ill patients with hypoalbuminemia, the existing evidence is scarce and does not allow recommendations to be formulated. However, it is frequently used in healthcare 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.

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.

A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects.

BACKGROUND: Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms. METHODS: We grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial. RESULTS: Optate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (P < .001). Mechanistically, Optate inhibited expression of major endosomal trafficking genes and raised NHAE intracellular pH. Optate had no effect on NHAE cell viability at any time point. Inhaled Optate was well tolerated in 10 normal subjects, with no change in lung function, vital signs, or oxygenation. CONCLUSIONS: Inhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection.

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.

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.

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.

Comparative ultrasound study of gastric emptying between an isotonic solution and a nutritional supplement / Estudo comparativo do esvaziamento gástrico entre uma solução isotônica e um suplemento nutricional por meio da ultrassonografia

Abstract Background and objectives: Preoperative fasting may lead to undesirable effects in the surgical patient in whom there is a stimulus to ingesting clear liquids until 2 hours before anesthesia. The aim of this study was to evaluate the gastric emptying of two different solutions using ultrasound. Methods: In a prospective, randomized, blind study, 34 healthy volunteers ingested 200 mL of two solutions without residues in two steps: an isotonic solution with carbohydrates, electrolytes, osmolarity of 292 mOsm.L-1, and 36 kcal; and other nutritional supplementation with carbohydrates, proteins, electrolytes, osmolarity of 680 mO.L-1, and 300 kcal. After 2 hours, a gastric ultrasound was performed to assess the antrum area and gastric volume, and the relation of gastric volume to weight (vol.w-1), whose value above 1.5 mL.kg-1 was considered a risk for bronchoaspiration. A p-value <0.05 was considered statistically significant. Results: There was a significant difference between all parameters evaluated 2 hours after the ingestion of nutritional supplementation compared to fasting. The same occurred when the parameters between isotonic solution and nutritional supplementation were compared 2 hours after ingestion. Only one patient had vol.w-1 <1.5 mL.kg-1 2 hours after ingestion of nutritional supplementation; and only one had vol.w-1 >1.5 mL.kg-1 after ingestion of isotonic solution. Conclusion: This study demonstrated that gastric emptying of equal volumes of different solutions depends on their constitution. Those with high caloric and high osmolarity, and with proteins present, 2 hours after ingestion, increased the gastric volumes, which is compatible with the risk of gastric aspiration.

Resumo Justificativa e objetivos: O jejum pré-operatório pode levar a efeitos indesejáveis no paciente cirúrgico, em que há um estimulo à ingestão de líquidos sem resíduos até 2 horas antes da anestesia. O objetivo deste estudo foi avaliar o esvaziamento gástrico de duas soluções diferentes por meio da ultrassonografia. Métodos: Em um estudo prospectivo, randomizado, cego, 34 voluntários saudáveis ingeriram 200 mL de duas soluções sem resíduos, em duas etapas: uma solução isotônica com carboidratos, eletrólitos, osmolaridade de 292 mOsm.L-1 e 36 kcal; e outra suplementação nutricional, com carboidratos, proteínas, eletrólitos, osmolaridade de 680 mOs.L-1 e 300 kcal. Após 2 horas, fez-se ultrassonografia gástrica com avaliação da área do antro e volume gástrico e relação do volume gástrico sobre o peso (vol.p-1), cujo valor acima de 1,5 mL.kg-1 foi considerado risco para broncoaspiração. Considerou-se p< 0,05 como estatisticamente significativo. Resultados: Houve diferença significativa entre todos os parâmetros avaliados 2 horas após a ingestão de suplementação nutricional em relação ao jejum. O mesmo ocorreu quando foram comparados os parâmetros entre solução isotônica e suplementação nutricional 2 horas após a ingestão. Apenas um paciente apresentou vol.p-1< 1,5 mL.kg-1 2 horas após a ingestão de suplementação nutricional; e apenas um apresentou vol.p-1 > 1,5 mL.kg-1, após a ingestão de solução isotônica. Conclusão: Este estudo demonstrou que o esvaziamento gástrico de volumes iguais de diferentes soluções depende de sua constituição. Aqueles com alto valor calórico e alta osmolaridade, e com proteínas presentes, 2 horas após a ingestão, aumentaram os volumes gástricos, compatíveis com o risco de aspiração gástrica.

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.

The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study.

PURPOSE: To assess the impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients, we conducted retrospective before-after study in a tertiary teaching hospital. METHODS: We examined all adult patients admitted ICU after an elective operation for head and neck cancer, or esophageal cancer from February 2014 to January 2017. From February 2014 to July 2015, patients were administered hypotonic fluid (sodium; 35 mmol/L) as the National Institute for Health and Care Excellence (NICE) have recommended. From August 2015 to January 2017, patients were administered isotonic fluid (sodium; 140 mmol/L). We defined the incidence of delirium as the primary outcome. The delirium was defined as the Intensive Care Delirium Screening Checklist during the ICU stay ≥ 4. A propensity score-matched model was used to adjust confounders. RESULTS: As postoperative intravenous maintenance fluid, hypotonic fluid was administered to 119 patients and isotonic fluid was administered to 92 patients. Among those total cohorts, the incidence of postoperative delirium in the hypotonic group was 21.8%, which was significantly higher than that (9.8%) in the isotonic group (p = 0.019). After propensity score matching, we selected 77 patients in each group. The incidence of delirium during the ICU stay in the hypotonic group was 26.0%, which was significantly higher than the incidence of 11.7% in the isotonic group (p = 0.023). CONCLUSIONS: In this study, the use of postoperative hypotonic maintenance fluid was associated with a higher risk of postoperative delirium than that when isotonic maintenance fluid was used.

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).

Clinical Practice Guideline: Maintenance Intravenous Fluids in Children.

Maintenance intravenous fluids (IVFs) are used to provide critical supportive care for children who are acutely ill. IVFs are required if sufficient fluids cannot be provided by using enteral administration for reasons such as gastrointestinal illness, respiratory compromise, neurologic impairment, a perioperative state, or being moribund from an acute or chronic illness. Despite the common use of maintenance IVFs, there is high variability in fluid prescribing practices and a lack of guidelines for fluid composition administration and electrolyte monitoring. The administration of hypotonic IVFs has been the standard in pediatrics. Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVFs could prevent the development of hyponatremia. Our goal in this guideline is to provide an evidence-based approach for choosing the tonicity of maintenance IVFs in most patients from 28 days to 18 years of age who require maintenance IVFs. This guideline applies to children in surgical (postoperative) and medical acute-care settings, including critical care and the general inpatient ward. Patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, or severe burns; neonates who are younger than 28 days old or in the NICU; and adolescents older than 18 years old are excluded. We specifically address the tonicity of maintenance IVFs in children.The Key Action Statement of the subcommittee is as follows:1A: The American Academy of Pediatrics recommends that patients 28 days to 18 years of age requiring maintenance IVFs should receive isotonic solutions with appropriate potassium chloride and dextrose because they significantly decrease the risk of developing hyponatremia (evidence quality: A; recommendation strength: strong).

Goal-directed hemodynamic management in patients undergoing primary debulking gynaecological surgery: A matched-controlled precision medicine study.

BACKGROUND: Usefulness of intraoperative goal-directed hemodynamic management (GDHM) for patients without comorbidities is debated. After clinical implementation of a pulse contour analysis-guided GDHM protocol, which foresees early vasopressor use for recruiting unstressed volume, we conducted a matched-controlled analysis to explore its impact on the amount of fluids intraoperatively administered to patients without comorbidities who underwent extended abdominal surgery for ovarian cancer. METHODS: After 1:1 matching accounting for body mass index, oncologic disease severity and intraoperative blood losses, 22 patients treated according to this GDHM protocol were compared to a control group of 22 patients who had been managed according to the clinical decision of attending physicians, taken without advanced monitoring. Results are displayed as median[interquartile range]. RESULTS: All analyzed patients underwent radical hysterectomy, bilateral adnexectomy, bowel resection, peritonectomy and extended pelvic/periaortic lymphadenectomy; median length of surgery was 517[480-605] min in patients receiving GDHM and 507[480-600] min in control group. Intraoperatively, patients undergoing GDHM received less fluids (crystalloids 2950[2700-3300] vs. 5150[4700-6000] mL, p < 0.001; colloids 100[50-200] vs. 750[500-1000] mL, p < 0.001) and showed a trend to more frequent vasopressor administration (32 vs 9%, p = 0.13). Greater intraoperative diuresis (540[480-620] mL vs. 450[400-500] mL, p = 0.007), lower blood lactates at surgery end (1.5[1.1-2] vs. 4.1[3.3-5] mmol/L, p < 0.001), shorter time to bowel function recovery (1 [1, 2] vs. 4 [3-5] days, p < 0.001) and hospital discharge (7 [6-8] vs 12 [9-16] days, p < 0.0001) were detected in patients receiving GDHM. CONCLUSIONS: In high-tumor load gynaecological patients without comorbidities who receive radical and prolonged surgery, intraoperative use of this novel GDHM protocol helped limit fluids administration with safety.

Myocardial protection in on-pump coronary artery bypass grafting surgery: analysis of the effectiveness of the use of retrograde Celsior®.

BACKGROUND: We analyzed the adequacy of the myocardial protection achieved with a single dose of retrograde crystalloid Celsior®, compared with an accepted standard (microplegia), in on-pump coronary artery bypass grafting surgery (CABG). METHODS: This was a retrospective comparative clinical study conducted in a single institution that included all the patients operated on who had elective isolated on-pump CABG, from March 2006 to June 2014. We evaluated maximum postoperative troponin T (TnT) as a marker of myocardial damage, adjusted for possible confounders using propensity score matching. We also analyzed markers of recovery of myocardial function, and the safety of the intravenous use of Celsior®. RESULTS: During the study period, 261 patients were included, divided in two groups: (a) continuous retrograde blood-based microplegia (114 patients); (b) retrograde single-dose crystalloid Celsior® (147 patients). The propensity score adjusted maximum TnT was significantly lower in the Celsior group [average treatment effect = -0.55 ng/dl; 95% confidence interval (CI) -1.10 to -0.1 ng/dl; p = 0.048]. There were no differences in the postoperative use of intra-aortic balloon of counterpulsation or in the requirements of high-dose inotropic medications. In-hospital mortality was equivalent in both study groups ( p = 0.73); surgical re-exploration because of bleeding was equivalent ( p = 0.37). There were no differences in prolonged mechanical ventilation ( p = 0.65) and intensive care unit length of stay ( p = 0.87). CONCLUSION: An isolated single dose of retrograde Celsior® may be an effective and safe myocardial protection strategy in on-pump CABG.

Pre-operative fluid bolus for improved haemodynamic stability during minor surgery: A prospectively randomized clinical trial.

BACKGROUND: Haemodynamic instability during the induction of anaesthesia and surgery is common and may be related to hypovolaemia caused by pre-operative fasting or chronic diuretic therapy. The aim of our prospective, controlled, randomized study was to test the hypothesis that a predefined fluid bolus given prior to general anaesthesia for minor surgery would increase haemodynamic stability during anaesthetic induction. METHODS: Two hundred and nineteen fairly healthy adult patients requiring minor surgery were enrolled. All received standard treatment, including a pulse contour analysing device for non-invasive measurement of cardiac index. Infusion therapy was started in all patients at induction. The intervention group (106 patients) was randomized to receive an additional fluid bolus of 8 mL/kg Ringer's acetate solution before the induction of anaesthesia. The primary endpoint was the incidence of haemodynamic instability, defined as a significant reduction of blood pressure or cardiac index during induction of anaesthesia. RESULTS: The interventional group had a lesser incidence of haemodynamic instability during induction (41.5% vs 56.6%, P = .025). This group also had higher cardiac index, stroke volume index, systolic and mean blood pressure and a greater left ventricular end-diastolic area. CONCLUSIONS: A fluid bolus prior to anaesthesia reduced the incidence of haemodynamic instability during induction of general anaesthesia. The total fluid volume was slightly greater in the intervention group compared to the control group (1370 ± 439 mL vs 1219 ± 483 mL, P = .007). We conclude that a defined fluid bolus can help stabilizing haemodynamics in patients undergoing general anaesthesia.

Impact of resuscitation fluid bag size availability on volume of fluid administration in the intensive care unit.

BACKGROUND: Iatrogenic fluid overload is associated with increased mortality in the intensive care unit (ICU). Decisions on fluid therapy may, at times, be based on other factors than physiological endpoints. We hypothesized that because of psychological factors volume of available fluid bags would affect the amount of resuscitation fluid administered to ICU patients. METHODS: We performed a prospective intervention cross-over study at 3 Swedish ICUs by replacing the standard resuscitation fluid bag of Ringer's Acetate 1000 mL with 500 mL bags (intervention group) for 5 separate months and then compared it with the standard bag size for 5 months (control group). Primary endpoint was the amount of Ringer's Acetate per patient during ICU stay. Secondary endpoints were differences between the groups in cumulative fluid balance and change in body weight, hemoglobin and creatinine levels, urine output, acute kidney failure (measured as the need for renal replacement therapy, RRT) and 90-day mortality. RESULTS: Six hundred and thirty-five ICU patients were included (291 in the intervention group, 344 in the control group). There was no difference in the amount of resuscitation fluid per patient during the ICU stay (2200 mL [1000-4500 median IQR] vs 2245 mL [1000-5630 median IQR]), RRT rate (11 vs 9%), 90-day mortality (11 vs 10%) or total fluid balance between the groups. The daily amount of Ringer's acetate administered per day was lower in the intervention group (1040 (280-2000) vs 1520 (460-3000) mL; P = .03). CONCLUSIONS: The amount of resuscitation fluid administered to ICU patients was not affected by the size of the available fluid bags. However, altering fluid bag size could have influenced fluid prescription behavior.

Pyruvate as a novel carrier of hydroxyethyl starch 130/0.4 may protect kidney in rats subjected to severe burns.

BACKGROUND: The carrier of hydroxyethyl starch (HES) may play a critical role in kidney injury in fluid resuscitation. This study aimed mainly to compare effects of pyruvate-enriched saline with normal saline (NS) and acetate Ringer's (AR) solution as a carrier in HES130/0.4 on kidney function in rats subjected to severe burns. METHODS: Using a lethal burn model, 140 rats were randomly allocated in seven groups (n = 20): sham group (group S); no fluid after burn (group N); burn resuscitated with NS (group NS); burn resuscitated with pyruvate saline (group PS); burn resuscitated with AR plus pyruvate-HES (group SP); burn resuscitated with AR plus acetate-HES (group SA), and burn resuscitated with AR plus NS-HES (group SN). A low volume (18.75 mL·kg-1 during 12 h) of HES130/0.4 was infused with the ratio of 1:1 to crystalloids. Renal surface blood flow, blood creatinine and blood urea nitrogen, early sensitive indicators of kidney function: alpha-1 microglobulin, cystatin-C, and neutrophil gelatinase-associated lipocalin in blood and urine, and kidney tissue water contents were determined. Renal histopathological alterations with Paller scores were also measured at 8 h and 24 h after burn (n = 10), respectively. RESULTS: The results showed in a comparable manner that group SP was the best in three HES groups and group PS was superior to group NS in renal preservation; group SP appeared significantly beneficial compared with group PS in renal surface blood flow, cystatin-C, neutrophil gelatinase-associated lipocalin, water contents, and Paller scores at 8-h or both time points after burn, respectively (all P < 0.05). CONCLUSIONS: The carrier of HES130/0.4 played a crucial role in kidney injury in fluid resuscitation of rats subjected to severe burns. Pyruvate-enriched HES130/0.4 was superior and HES130/0.4, per se, might be not renocytotoxic, but renoprotective. Further studies are warranted.

Balanced 10% hydroxyethyl starch compared with balanced 6% hydroxyethyl starch and balanced crystalloid using a goal-directed hemodynamic algorithm in pancreatic surgery: A randomized clinical trial.

BACKGROUND: While hydroxyethyl starch (HES) solutions are not recommended any longer in critically ill patients, data on efficacy and safety during surgery are still limited. METHODS: In a randomized controlled trial 63 patients were assigned to receive 10% HES (130/0.42), 6% HES (130/0.42), or crystalloid within a goal-directed hemodynamic algorithm during pancreatic surgery. The primary endpoints were intraoperative volume of HES and time until fully on oral diet. RESULTS: The trial was terminated early upon recommendation of an independent data monitoring committee due to futility for efficacy at a planned interim analysis. The intraoperative volume of HES was not different between 10% and 6% HES group (2000 [1500; 2250] vs 2250 [1750; 3000] mL, P=.059). However, considering an inhomogeneity of patient's body weight between HES groups, there was a significant difference in intraoperative volume of HES between 10% and 6% group after adjusting for patient's body weight (24.0 [21.6; 28.3] vs 33.3 [28.2; 46.2] mL kg BW, P = .002). Patients in the HES groups required less additional fluid after dose limit than those in the crystalloid group, resulting in lower intraoperative net balances. The time until fully on oral diet was not different between all study groups. Applying KDIGO oliguria criterion, patients receiving 10% HES had more AKI compared to patients receiving crystalloids (86.7 vs 45.0%, P = .010), whereas those receiving 6% HES and crystalloids did not differ (58.8 vs 45.0%, P = .253). Further explorative analyses using a gray-zone approach indicated that patients receiving 6% HES below 18.8 mL kg will not experience AKI with near certainty. CONCLUSIONS: After adjusting for patient's body weight, patients receiving 6% HES required more volume of HES than patients receiving 10% HES. The relation of 140% represents very well the volume effect of a hyperoncotic 10% HES solution. Nonetheless, both HES solutions were similarly effective in reducing intraoperative fluid administration compared with crystalloid, but this did not result into differences in gastrointestinal outcomes. Patients receiving 10% HES showed an increased rate of AKI, whereas those receiving 6% HES and crystalloid did not differ. However, 6% HES should not be applied beyond 18 mL kg during surgery.