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1.
BMC Anesthesiol ; 24(1): 152, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649834

ABSTRACT

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.


Subject(s)
Hepatectomy , Isotonic Solutions , Laparoscopy , Ringer's Lactate , Humans , Male , Female , Laparoscopy/methods , Hepatectomy/methods , Ringer's Lactate/administration & dosage , Middle Aged , Isotonic Solutions/administration & dosage , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Adult , Ringer's Solution , Lactic Acid/blood , Bicarbonates , Treatment Outcome
2.
Eur J Pediatr ; 183(5): 2251-2256, 2024 May.
Article in English | MEDLINE | ID: mdl-38407589

ABSTRACT

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.


Subject(s)
Anesthesia, General , Body Composition , Fluid Therapy , Humans , Child , Pilot Projects , Male , Female , Anesthesia, General/methods , Adolescent , Child, Preschool , Fluid Therapy/methods , Dielectric Spectroscopy/methods , Body Water , Isotonic Solutions/administration & dosage , Electric Impedance , Switzerland
3.
JAMA ; 330(21): 2096-2105, 2023 12 05.
Article in English | MEDLINE | ID: mdl-38051327

ABSTRACT

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.


Subject(s)
Fetal Therapies , Isotonic Solutions , Kidney Diseases , Lung Diseases , Oligohydramnios , Female , Humans , Infant , Infant, Newborn , Pregnancy , Fetal Therapies/methods , Gestational Age , Kidney/diagnostic imaging , Kidney Diseases/complications , Kidney Diseases/congenital , Kidney Diseases/mortality , Kidney Diseases/therapy , Prospective Studies , Infusions, Parenteral/methods , Oligohydramnios/etiology , Oligohydramnios/mortality , Oligohydramnios/therapy , Fetal Diseases/etiology , Fetal Diseases/mortality , Fetal Diseases/therapy , Lung Diseases/congenital , Lung Diseases/etiology , Lung Diseases/mortality , Lung Diseases/therapy , Isotonic Solutions/administration & dosage , Isotonic Solutions/therapeutic use , Ultrasonography, Interventional , Pregnancy Outcome , Treatment Outcome , Premature Birth/etiology , Premature Birth/mortality
6.
Ludovica Pediatr ; 25(2): 41-58, dic.2022.
Article in Spanish | LILACS | ID: biblio-1414378

ABSTRACT

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


Subject(s)
Humans , Child , Critical Care , Fluid Therapy , Shock/therapy , Electrolytes/administration & dosage , Hypotonic Solutions/administration & dosage , Isotonic Solutions/administration & dosage
7.
JAMA ; 328(3): 251-258, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35852528

ABSTRACT

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.


Subject(s)
Albumins , Cardiac Surgical Procedures , Cardiopulmonary Bypass , Fluid Therapy , Heart Diseases , Isotonic Solutions , Aged , Albumins/administration & dosage , Albumins/adverse effects , Albumins/therapeutic use , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/methods , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Double-Blind Method , Female , Fluid Therapy/adverse effects , Fluid Therapy/methods , Heart Diseases/surgery , Heart Diseases/therapy , Humans , Isotonic Solutions/administration & dosage , Isotonic Solutions/adverse effects , Isotonic Solutions/therapeutic use , Male , Middle Aged , Solutions/administration & dosage , Solutions/adverse effects , Solutions/therapeutic use
8.
Am J Emerg Med ; 51: 214-217, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34775194

ABSTRACT

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.


Subject(s)
Isotonic Solutions/administration & dosage , Wounds and Injuries/therapy , Administration, Intravenous , Adolescent , Adult , Aged , Aged, 80 and over , Crystalloid Solutions , Emergency Service, Hospital , Female , Florida , Humans , Injury Severity Score , Isotonic Solutions/therapeutic use , Male , Middle Aged , Resuscitation , Retrospective Studies , Tertiary Care Centers , Treatment Outcome , Wounds and Injuries/mortality , Young Adult
9.
J Therm Biol ; 100: 103026, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34503773

ABSTRACT

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.


Subject(s)
Cognition/drug effects , Exercise , Glucose/pharmacology , Heat Stress Disorders/prevention & control , Isotonic Solutions/pharmacology , Adult , Dietary Supplements , Female , Fluid Therapy , Glucose/administration & dosage , Glucose/therapeutic use , Heat Stress Disorders/drug therapy , Hot Temperature , Humans , Isotonic Solutions/administration & dosage , Isotonic Solutions/therapeutic use , Male , Random Allocation
10.
Mayo Clin Proc ; 96(9): 2464-2473, 2021 09.
Article in English | MEDLINE | ID: mdl-34366137

ABSTRACT

Administration of fluid is a cornerstone of supportive care for sepsis. Current guidelines suggest a protocolized approach to fluid resuscitation in sepsis despite a lack of strong physiological or clinical evidence to support it. Both initial and ongoing fluid resuscitation requires careful consideration, as fluid overload has been shown to be associated with increased risk for mortality. Initial fluid resuscitation should favor balanced crystalloids over isotonic saline, as the former is associated with decreased risk of renal dysfunction. Traditionally selected resuscitation targets, such as lactate elevation, are fraught with limitations. For developing or established septic shock, a focused hemodynamic assessment is needed to determine if fluid is likely to be beneficial. When initial fluid therapy is unable to achieve the blood pressure goal, initiation of early vasopressors and admission to intensive care should be favored over repetitive administration of fluid.


Subject(s)
Crystalloid Solutions/administration & dosage , Fluid Therapy/methods , Shock, Septic/therapy , Fluid Therapy/adverse effects , Hemodynamics , Hospital Mortality , Hospitalists , Humans , Isotonic Solutions/administration & dosage , Isotonic Solutions/adverse effects
11.
Pediatrics ; 148(1)2021 07.
Article in English | MEDLINE | ID: mdl-34158314

ABSTRACT

BACKGROUND: Maintenance intravenous fluids (IVFs) are commonly used in the hospital setting. Hypotonic IVFs are commonly used in pediatrics despite concerns about high incidence of hyponatremia. We aimed to increase isotonic maintenance IVF use in children admitted from the emergency department (ED) from a baseline of 20% in 2018 to >80% by December 2019. METHODS: We included patients aged 28 days to 18 years receiving maintenance IVFs (rate >10 mL/hour) at the time of admission. Patients with active chronic medical problems were excluded. Interventions included institutional discussions on isotonic IVF based on literature review, education on isotonic IVF use per the American Academy of Pediatrics guideline (isotonic IVF use with appropriate potassium chloride and dextrose), electronic medical record changes to encourage isotonic IVF use, and group practice review with individual physician audit and feedback. Balancing measures were the frequency of serum electrolyte checks within 24 hours of ED admission and occurrence of hypernatremia. Data were analyzed by using statistical process control charts. RESULTS: Isotonic maintenance IVF use improved, with special cause observed twice; the 80% goal was met and sustained. No difference was noted in serum electrolyte checks within 24 hours of admission (P > .05). There was no increase in occurrence of hypernatremia among patients who received isotonic IVF compared with those who received hypotonic IVF (P > .05). CONCLUSIONS: The application of improvement methods resulted in improved isotonic IVF use in ED patients admitted to the inpatient setting. Institutional readiness for change at the time of the American Academy of Pediatrics guideline release and hardwiring of preferred fluids via electronic medical record changes were critical to success.


Subject(s)
Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/standards , Fluid Therapy/methods , Isotonic Solutions/administration & dosage , Adolescent , Child , Child, Preschool , Electronic Health Records , Fluid Therapy/adverse effects , Guideline Adherence , Humans , Hyponatremia/prevention & control , Infant , Infant, Newborn , Infusions, Intravenous , Isotonic Solutions/adverse effects , Medical Staff, Hospital/education , Patient Care Team , Practice Guidelines as Topic , Quality Improvement , Tertiary Care Centers/organization & administration , Tertiary Care Centers/standards , United States
12.
Trials ; 22(1): 89, 2021 Jan 25.
Article in English | MEDLINE | ID: mdl-33494795

ABSTRACT

BACKGROUND: Previous study drew different conclusions on significant differences between saline and balanced crystalloid solution infused in critical illness but both showed a statistical difference in the sepsis subgroup. Thus, we will specifically focus on septic patients in this study to compare the effects of saline and balanced solution. We hypothesize that effects of saline on renal outcomes are related to the underline acute kidney injury (AKI) severity and total volumes of infusion. METHODS/DESIGN: The investigators designed a pragmatic, multi-center parallel controlled trial recruiting 312 patients who are diagnosed with sepsis/septic shock in the intensive care unit (ICU) and will be assigned with either acetate Ringer's solution or saline in the corresponding month. Patients with an end-stage renal disease (ESRD) or who need renal replacement therapy (RRT) prior to or at the time of enrolment are excluded. Enrolled patients will be regarded as with mild, moderate, or severe sepsis on the basis of the severity of their illness and will be divided into subgroups according to their initial renal function and various intravenous infusion volumes when being analyzed. The primary outcome is major adverse kidney events within 28 days (MAKE28), including the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 28-day mortality, internal environment disturbance, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, duration of RRT, and ICU and hospital length of stay. RESULTS AND CONCLUSIONS: To our knowledge, this study will be the first to focus on septic patients and provide credible and evident data on the comparison of outcome between acetate Ringer's solution and saline for intravenous infusion in adult septic patients on the basis of baseline renal function and infusion volumes taken into consideration. TRIAL REGISTRATION: ClinicalTrials.gov NCT03685214 . Registered on August 15, 2018.


Subject(s)
Acute Kidney Injury/diagnosis , Fluid Therapy/methods , Isotonic Solutions/administration & dosage , Saline Solution/administration & dosage , Sepsis/therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Fluid Therapy/statistics & numerical data , Hospital Mortality , Humans , Infusions, Intravenous , Male , Middle Aged , Multicenter Studies as Topic , Pragmatic Clinical Trials as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Sepsis/complications , Sepsis/mortality , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
13.
Respir Care ; 66(1): 113-119, 2021 01.
Article in English | MEDLINE | ID: mdl-32962996

ABSTRACT

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.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Epithelial Cells/drug effects , Glycine/pharmacology , Isotonic Solutions/pharmacology , Lung/drug effects , SARS-CoV-2 , Virus Replication/drug effects , Administration, Inhalation , Antiviral Agents/administration & dosage , Cells, Cultured/drug effects , Glycine/administration & dosage , Healthy Volunteers , Humans , Hydrogen-Ion Concentration/drug effects , Isotonic Solutions/administration & dosage
15.
JAMA Netw Open ; 3(11): e2024596, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33196806

ABSTRACT

Importance: Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. Objective: To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. Design, Setting, and Participants: This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. Interventions: Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule. Main Outcomes and Measures: The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. Results: Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03). Conclusions and Relevance: In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA. Trial Registration: ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.


Subject(s)
Crystalloid Solutions/therapeutic use , Diabetic Ketoacidosis/drug therapy , Fluid Therapy/statistics & numerical data , Saline Solution, Hypertonic/therapeutic use , Acidosis/chemically induced , Acidosis/prevention & control , Adult , Cluster Analysis , Cross-Over Studies , Crystalloid Solutions/adverse effects , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/diagnosis , Electrolytes/blood , Emergency Service, Hospital/statistics & numerical data , Female , Fluid Therapy/methods , Humans , Infusions, Intravenous/methods , Insulin/administration & dosage , Insulin/therapeutic use , Intensive Care Units/statistics & numerical data , Isotonic Solutions/administration & dosage , Isotonic Solutions/adverse effects , Male , Middle Aged , Outcome Assessment, Health Care , Saline Solution, Hypertonic/adverse effects , Time Factors
17.
Am J Otolaryngol ; 41(5): 102554, 2020.
Article in English | MEDLINE | ID: mdl-32521299

ABSTRACT

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.


Subject(s)
Ethmoid Sinus/surgery , Isotonic Solutions/administration & dosage , Nasal Polyps/surgery , Nasal Polyps/therapy , Postoperative Care/methods , Rhinitis/surgery , Rhinitis/therapy , Saline Solution, Hypertonic/administration & dosage , Sinusitis/surgery , Sinusitis/therapy , Therapeutic Irrigation/methods , Adult , Buffers , Chronic Disease , Double-Blind Method , Edema/prevention & control , Endoscopy/methods , Female , Humans , Male , Middle Aged , Nasal Mucosa , Nasal Polyps/complications , Otorhinolaryngologic Surgical Procedures/methods , Paranasal Sinus Diseases/prevention & control , Postoperative Complications/prevention & control , Rhinitis/complications , Sinusitis/complications , Treatment Outcome
18.
Am J Otolaryngol ; 41(4): 102502, 2020.
Article in English | MEDLINE | ID: mdl-32460989

ABSTRACT

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.


Subject(s)
Hyaluronic Acid/administration & dosage , Isotonic Solutions/administration & dosage , Nasal Lavage/methods , Saline Solution/administration & dosage , Sinusitis/therapy , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Prospective Studies
19.
Anesth Analg ; 130(3): 599-609, 2020 03.
Article in English | MEDLINE | ID: mdl-31609257

ABSTRACT

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.


Subject(s)
Fluid Therapy , Glomerular Filtration Rate , Isotonic Solutions/administration & dosage , Kidney Transplantation/adverse effects , Kidney/surgery , Postoperative Complications/prevention & control , Animals , Cyclooxygenase 2/metabolism , Endothelial Cells/metabolism , Female , Glycocalyx/metabolism , Inflammation Mediators/metabolism , Kidney/metabolism , Kidney/physiopathology , Models, Animal , Oxidative Stress , Postoperative Complications/metabolism , Postoperative Complications/physiopathology , Sus scrofa , Time Factors
20.
Int J Legal Med ; 134(3): 1167-1174, 2020 May.
Article in English | MEDLINE | ID: mdl-31713679

ABSTRACT

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.


Subject(s)
Accidents, Traffic , Infusions, Intraosseous , Isotonic Solutions/administration & dosage , Proton Magnetic Resonance Spectroscopy , Thigh/diagnostic imaging , Thigh/injuries , Autopsy , Child , Humans , Intramuscular Absorption , Magnetic Resonance Imaging , Tomography, X-Ray Computed
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