NaCl Infusion Research Articles

Symptoms, causes, management and outcomes of hyponatraemia: a single centre study among hospitalised adult patients in Malaysia

Background Hyponatraemia is a common electrolyte abnormality seen in medical admissions. To date, there is no hospital-wide local study on hyponatraemia across the young, middle and older age groups. We evaluated the clinical features, aetiology, and outcomes of patients admitted in a tertiary hospital when hyponatraemia was noted as part of initial investigations. We also reviewed the documented management, aiming to promote local guideline development for hyponatraemia. Methods A retrospective study based in Hospital Sultan Ismail (HSI) Johor Bahru was undertaken between January 2020 to December 2022 on adults admitted with a serum sodium (Na) level of <135mmol/L. Patients were identified through the electronic database. Results 165 patients (mean age 64.4 ± 12.9, 52.6% females, 42.4% males) were diagnosed with mostly moderate or severe hyponatraemia. Severe hyponatraemia was significantly more prevalent among elderly patients (p= 0.002). Loss of appetite, generalised weakness and vomiting were the common presentations. 27.9% of patients were identified based on laboratory results without symptoms of hyponatraemia. The main causes of hyponatraemia were poor oral intake (20.6%), multifactorial (18.8%) and diarrhoea and vomiting (14.5%). Majority received 0.9% sodium chloride (NaCl) infusion. 18 patients (10.9%) have ≥10 mmol/L Na increment over the first day without complication. The overall mortality rate was 4.85% over 3 years. Conclusions Hyponatraemia may present with non-specific symptoms in hospitalised patients. Early recognition and management are required to avoid complications. Larger prospective studies to further explore the clinical profile of hyponatraemia among local patients will aid in protocol development to optimise patient outcome.

In-Use Physicochemical Stability of Sandoz Rituximab Biosimilar in 0.9% Sodium Chloride Solution After Prolonged Storage at Room Temperature Conditions.

Often, stability studies do not cover all facets of ensuring patient safety for biologics, unless the impact of the in-use and out-of-fridge conditions is also assessed. This study investigated the physicochemical and biological stability of Sandoz rituximab biosimilar (SDZ-RTX). In a worst-case setting, two SDZ-RTX batches in vials were exposed to long-term conditions (5 ± 3°C) for at least the shelf-life period (36 months). These batches were exposed to out-of-fridge conditions of up to 25 ± 2°C/60 ± 5% relative humidity in total for 14days, and subsequently to 30±2°C/75 ± 5% relative humidity for 7 days. Thereafter, these batches were diluted to 1mg/mL in 0.9% NaCl in 250-mL polyethylene infusion bags and stored at either 25 ± 2°C/60 ± 5% relative humidity for 30 days or 30 ± 2°C/75±5% relative humidity for 14 days, representing in-use conditions. The stability of SDZ-RTX was assessed using a variety of analytical methods, including size-exclusion chromatography, cation exchange chromatography, non-reducing capillary electrophoresis sodium dodecyl sulfate, complement-dependent cytotoxicity-bioactivity, and subvisible particle count by light obscuration. Results for all assessments were within the stringent shelf-life acceptance criteria for SDZ-RTX for both batches under both in-use conditions. These data show that the physicochemical and biological quality of SDZ-RTX diluted in 0.9% NaCl infusion bags is assured, even after prolonged worst-case (out-of-fridge and in-use) storage at elevated temperatures up to 30°C, if the medication is prepared under aseptic conditions according to the Summary of Product Characteristics.

Syndrome of inappropriate antidiuresis/hyponatremia in COVID-19.

Hyponatremia is the most frequent electrolyte alteration among hospitalized patients and it has been reported in 20-40% of patients with SARS-CoV-2 (COVID-19) infection. Multiple causes of hyponatremia have been hypothesized in these patients. The syndrome of inappropriate antidiuresis (SIAD) has been considered one of the main reasons leading to hyponatremia in this condition. SIAD can be secondary to cytokines release, in particular IL-6. Positive pressure ventilation can be another cause of hyponatremia due to SIAD. Other possible etiologies of hyponatremia in COVID-19 patients can be related to secondary hypocortisolism, nausea, vomiting, heart and kidney damage. Similar to many other clinical conditions, there is strong evidence that hyponatremia is associated with a worse prognosis also in patients with COVID-19 infection. In particular, hyponatremia has been identified as an independent risk of ICU transfer, need of non-invasive ventilation and death. Hyponatremia in COVID-19 patients is in principle acute and symptomatic and should be treated as such, according to the published guidelines. Therefore, patients should be initially treated with i.v. hypertonic saline (3% NaCl) infusion and serum [Na+] should be frequently monitored, in order to remain within a safe rate of correction. There is evidence showing that serum [Na+] correction is associated with a better outcome in different pathologies, including COVID-19 infection.

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-β on reno-renal reflexes in anaesthetised rats.

Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1β modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves. In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1β (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin. The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1β infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1β, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1β, by almost 80% below vehicle, again without effect on either MAP or HR. The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1β. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.

POLYCYSTIC OVARY SYNDROME (PCOS) AND ITS TREATMENT AS CAUSE OF SECONDARY ALDOSTERONISM: A DOG CHASING ITS TAIL

Objective: Polycystic Ovary Syndrome (PCOS) is a complex endocrine-metabolic disorder affecting about 7% of childbearing women. PCOS is characterized by anovulation, hyperandrogenism, insulin resistance and it is associated with an increased cardiovascular risk. PCOS patients may exhibit high blood pressure and signs of hydro-saline retention. Therefore, clinicians would be interested in performing hormonal screening for secondary hypertension. Design and method: We perform the aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism (PA). The test was proceed after serum potassium correction and previous a wash-out period of interfering medications. The recumbent saline suppression test was performed with infusion of 2L NaCl 0.9% in 4 hours under standardized salt intake (9gr/24h). Aldosterone and direct renin were determined by chemiluminescent immunoassay technology (DiaSorin®). Results: A 33yrs old woman attended our renal outpatient clinic because of recurrent episodes of generalized swelling, diuresis contraction and fluid retention. The patient, known for PCOS, was treated with combined oral contraceptives and loop diuretics. She had no history of hypertension, but she repeatedly displayed very high aldosterone values. Clinical examination was unremarkable, in-office and home blood pressure values were normal. Laboratory data showed normal renal function and the absence of acid-base disorders; serum potassium was at lower limit of normal. A CT-scan showed normal adrenal glands. We performed a recumbent saline suppression test, previous a wash-out period of oral contraceptives (> 6 weeks) and loop diuretics (> 2 weeks). The results listed below are consistent with a baseline hyperaldosteronism with normal aldosterone adrenal response to volume expansion, excluding PA. Several years before, the same results were presented, without suspension of the oral contraceptives. Conclusions: In patients with PCOS the increased adrenal production of aldosterone is usually secondary and independent from the renin-aldosterone axis (direct stimulation of adrenal zona glomerulosa via testosterone). Other iatrogenic factors may affect the renin-aldosterone values, such us the use of oral contraceptives and diuretics. Therefore, a confirmatory test performed under standardized conditions is often required, in order to exclude primary versus secondary forms of hyperaldosteronism.

The Contribution of Na+ or Cl− to Central NaCl−induced Cardiovascular Responses in Rodents

A high salt diet elevates plasma and cerebrospinal fluid NaCl concentrations in salt-sensitive hypertensive humans and animals. Acute or chronic intracerebroventricular (ICV) infusion of hypertonic NaCl elevates sympathetic nerve activity and blood pressure. However, it is unclear which ion, Na+ or Cl−, contributes to this response. The purpose of the present study was to investigate the extent to which acute increases in cerebrospinal fluid Na+ and Cl− increase ABP and HR in rodents. Male Sprague Dawley rats (n=6; body weight: 270-350 g) were anesthetized with isoflurane (2-3% in 100% O2) and instrumented with a lateral ventricle cannula for ICV infusions. Additionally, arterial and venous catheters were implanted to record BP and administer drugs, respectively. At least 4 days after recovery, ABP and HR were measured in response to ICV infusion (10uL over 10 min) of the following solutions: artificial cerebrospinal fluid (aCSF); 0.3 M and 0.6 M NaCl; 0.15 M and 0.3 M Na2SO4, and 0.3 M and 0.6 M NH4Cl. Each animal received one ICV infusion of each solution every other day. Data are presented as mean ± SE. Baseline ABP and HR did not differ across each ICV infusion (ABP: from 98 ± 6 mmHg to 106 ± 6 mmHg; and HR: from 337 ± 17 bpm to 363 ± 12 bpm). As expected, ICV infusion of 0.3 M and 0.6 M NaCl produced concentration-dependent increases in ABP (Δpeak ABP 0.3 M NaCl: 17 ± 2 mmHg; 0.6 M NaCl: 26 ± 3 mmHg). While ICV infusions of Na2SO4 at both concentrations also increased ABP, the magnitudes were reduced compared to NaCl (Δpeak ABP 0.15 M Na2SO4: 11 ± 2 mmHg; 0.3 M Na2SO4: 17 ± 3 mmHg). On the other hand, infusion of NH4Cl produced a modest increase in ABP (Δpeak ABP 0.3 M NH4Cl: 8 ± 2 mmHg and 0.6 M NH4Cl: 9 ± 3 mmHg). However, it did not differ from aCSF (Δpeak ABP aCSF: 6 ± 2 mmHg). HR responses induced by NaCl varied greatly (Δpeak HR 0.3 M NaCl: 15 ± 22 bpm; 0.6 M NaCl: 19 ± 17 bpm). In contrast, both concentrations of Na2SO4 consistently increased HR (Δpeak HR 0.15 M Na2SO4: 64±10 bpm; 0.3 M Na2SO4: 60±10 bpm). Additionally, ICV infusions of NH4Cl also tended to enhance HR (Δpeak HR 0.3 M NH4Cl: 38 ± 13 bpm and 0.6 M NH4Cl: 41 ± 23 bpm). To end, ICV infusion of aCSF increased HR by 18 ± 3 bpm. These results suggest that the NaCl−induced pressor response is largely attributed to Na+. However, Na+ alone cannot fully account for the NaCl−induced pressor response. NIH R01 HL163906, HL152680, HL145875. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of a Dexmedetomidine Intravenous Infusion in Septic Dogs: Preliminary Study.

The purpose of this study was to determine if a continuous rate infusion (CRI) of dexmedetomidine decreases vasopressor requirements in septic dogs undergoing surgery. Vital parameters, sequential organ failure assessment (SOFA) score, vasopressor requirement, and 28-day mortality were recorded. Dogs were randomly divided into two groups: a dexmedetomidine (DEX) (1 mcg/kg/h) group and a control group (NaCl), which received an equivalent CRI of NaCl. Dogs were premedicated with fentanyl 5 mcg/kg IV, induced with propofol, and maintained with sevoflurane and a variable rate fentanyl infusion. DEX or NaCl infusions were started 10 min prior to induction. Fluid-responsive hypotensive patients received repeated Ringer's lactate boluses (2 mL/kg) until stable or they were no longer fluid-responsive. Patients that remained hypotensive following fluid boluses received norepinephrine at a starting dose of 0.05 mcg/kg/min, with increases of 0.05 mcg/kg/min. Rescue adrenaline boluses were administered (0.001 mg/kg) if normotension was not achieved within 30 min of starting norepinephrine. The NaCl group received a significantly higher dose of norepinephrine (0.8, 0.4-2 mcg/kg/min) than the DEX group (0.12, 0-0.86 mcg/kg/min). Mortality was statistically lower in the DEX group (1/10) vs. the NaCl group (5/6). Results of this study suggest that a 1 mcg/kg/h CRI of dexmedetomidine decreases the demand for intraoperative vasopressors and may improve survival in septic dogs.

Study of the Degradation Rate of Polymeric Biodegradable Composites PLA (Powder) – PCL Produced by Solvent Casting in 0.3% NaCl Medium

The treatment of long-standing fractures is influenced by trauma, resorption, and bone pathology. Additional issues arise with the use of non-biodegradable metal implants, requiring additional procedures for removal, increasing the risk of infection, complications, and prolonging recovery time. The solution being studied is the use of biodegradable materials such as Polylactic Acid (PLA) - Polycaprolactone (PCL) polymers for bone repair and fixation, which can reduce the risk of complications and infection while accelerating healing. This research aims to analyze the effect of PLA powder percentage on the degradation rate of PCL mixtures using the solvent casting method. The specimen preparation process in this study utilizes the solvent casting method by mixing PLA and PCL using acetone as a solvent. The PLAPCL compositions used are 10 PLA: 90 PCL, 30 PLA: 70 PCL, and 50 PLA: 50 PCL. The specimens are then characterized through density and degradation testing by immersing them in a 0.9% NaCl infusion solution. The density testing results indicate that the 50 PLA: 50 PCL composition has the highest density, at 0.97 g/cm³. In degradation testing, the 10 PLA: 90 PCL composition exhibits the highest degradation rate, with a weight loss percentage of 22.01% in the fourth week and a degradation rate of 0.0128 mmpy in the first week.

Abstract 11373: Suppression of Plasma Angiotensin II by GLP-1 in Humans is Independent of Changes in Plasma Angiotensinogen

Introduction: In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is independent of changes in renal blood flow, renin, ANP, and aldosterone but is accompanied by suppression of angiotensin II (ANGII). The mechanism by which GLP-1 reduces ANGII independently of changes in renin is not clarified. Hypothesis: It was hypothesized that GLP-1 suppresses renin substrate, angiotensinogen, in plasma. Methods: To test this proposal, we measured arterial angiotensinogen concentration in biobanked plasma samples from healthy males during a 3-hour GLP-1 infusion that induced natriuresis (1). Samples were from a study with fixed sodium intake where eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg -1 min -1 ) or vehicle together with an intravenous infusion of 0.9% NaCl (750 mL/hour). Arterial plasma angiotensinogen was measured in plasma by dilution (1:200) and addition of excess exogenous human renin (Inst. Of Biological Standards UK). After prolonged incubation, ANGI was quantified by radioimmunoassay. Intraassay variation was 9-12%. Results: Arterial plasma angiotensinogen and renin levels decreased similarly and modestly (~15 and ~30%, respectively) after NaCl infusion during both studies whereas ANGII levels decreased significantly (~25%) only during GLP-1 infusion. Conclusions: Suppression of plasma angiotensinogen is less likely to account for GLP-1-mediated ANGII suppression in healthy young males. In perspective, GLP-1 could enhance pathways of ANGII degradation rather than inhibit its formation. 1. Asmar A et al. Extracellular fluid volume expansion uncovers a natriuretic action of GLP-1: a functional GLP-1-renal axis in man. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519.

1652-P: Suppression of Plasma Angiotensin II by GLP-1 in Humans Is Independent of Changes in Plasma Angiotensinogen

In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is independent of changes in renal blood flow, renin, ANP, and aldosterone but is accompanied by suppression of angiotensin II (ANGII). The mechanism by which GLP-1 reduces ANGII independently of changes in renin is not clarified. It was hypothesized that GLP-1 suppresses renin substrate, angiotensinogen, in plasma. To test this proposal, we measured arterial angiotensinogen concentration in biobanked plasma samples from healthy males during a 3-hour GLP-1 infusion that induced natriuresis (1). Samples were from a study with fixed sodium intake where eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg-1 min-1) or vehicle together with an intravenous infusion of 0.9% NaCl (750 mL/hour). Arterial plasma angiotensinogen was measured in plasma by dilution (1:200) and addition of excess exogenous human renin (Inst. of Biological Standards UK). After prolonged incubation, ANGI was quantified by radioimmunoassay. Intraassay variation was 9-12%. Arterial plasma angiotensinogen and renin levels decreased similarly and modestly (~15 and ~30%, respectively) after NaCl infusion during both studies whereas ANGII levels decreased significantly (~25%) only during GLP-1 infusion. Suppression of plasma angiotensinogen is less likely to account for GLP-1-mediated ANGII suppression in healthy young males. In perspective, GLP-1 could enhance pathways of ANGII degradation rather than inhibit its formation. 1. Asmar A et al. Extracellular fluid volume expansion uncovers a natriuretic action of GLP-1: a functional GLP-1-renal axis in man. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519. Disclosure B.L.Jensen: None. A.Asmar: Research Support; Novo Nordisk A/S.

1660-P: Lactate Inhibits Lipolysis in Healthy Males—A Randomized Crossover Trial

Background: The intermediary metabolite lactate has signaling capacities through the lactate specific receptor GPR81/HCA1. Ex-vivo, lactate inhibits lipolysis through GPR81, but in-vivo human data are scarce. Lactate-mediated inhibition of lipolysis could improve insulin sensitivity. The aim of the study was to investigate if hyperlactatemia at physiological concentrations inhibits palmitate lipolysis and affects glucose metabolism in healthy males. Methods: In a randomized cross-over design, eight healthy men were studied after an overnight fast on two occasions 1) during a sodium-lactate infusion (LAC) and 2) during a NaCl infusion (CTL). Both study days comprised a 3-hour basal period followed by a 3-hour hyperinsulinemic euglycemic clamp (HEC) period. Lipolysis rate and endogenous glucose production (EGP) were evaluated using [9,10-3H]-palmitate and [3H]-glucose tracers. Average glucose infusion rate (mg/kg/min) during the last 30 min of the HEC (M-value) was used as a measure of insulin sensitivity. Data are mean±SD Results: Plasma lactate increased to 2.6 ±0.6 mmol/L during LAC vs. 0.8 ±0.3 mmol/L during CTL (p<0.001). At the end of the basal period, palmitate flux was 30% lower during LAC compared with CTL (84 ±32 μmol/min vs. 120 ±35 μmol/min, p=0.003). At the end of the HEC, palmitate flux was similarly suppressed during both interventions (p=0.7). Plasma FFA were lower during LAC compared with CTL (0.2 ±0.1 mmol/L vs. 0.3 ±0.1 mmol/L, p=0.03) at the end of the basal period and equally suppressed during both interventions at the end of the HEC (p=0.7). EGP was unaffected by LAC compared with CTL at the end of the basal period (p=1.0) and suppressed at the end of the HEC during both interventions (p=1.0). M-value was unaffected by LAC compared with CTL (p=0.8). Conclusion: Lactate inhibits palmitate lipolysis by 30 %, an effect which per se may improve insulin sensitivity. Hyperlactatemia did not affect EGP or insulin sensitivity, possibly because lactate intrinsically may induce insulin resistance. Disclosure M.G.B.Pedersen: None. N.Rittig: Research Support; ARLA. E.Søndergaard: None. L.C.Gormsen: None. N.Møller: Other Relationship; Aarhus University/Ketlace.

RENAL8: Hypertonic Bicarbonate during Continuous Renal Replacement Therapy in Acute Liver Failure

Introduction: Acute liver failure (ALF) is particularly alarming when presenting with vasodilated shock and multi-organ system failure. Standard manufactured hemofiltration fluid (sodium [Na+] = 140 mEq/L) would result in hyponatremia in vivo. We present a case study of hypertonic NaHCO3 infusion to address simultaneous serum Na+ target and correction of acidemia during continuous therapy. Case Presentation: A 42-year-old female with a history of seizures, and heavy alcohol use presented from outside the hospital for evaluation of stroke-like symptoms and subsequent mechanical fall. Urgent head CT was non-contributory. She was found to be in acute liver failure with total bilirubin 4.7, AST: 15,525 ALT: 5,727, ammonia 267 umol/L [reference range: 18-72], acetaminophen level 29 mcg/mL [reference range 10-30], Na+ 128 mEq/L, lactate >20 mmol/L, PT INR 8.1, PH 7.0 on blood gas and a negative ethanol level/salicylate/urine drug screen. After emergent intubation for encephalopathy and multiorgan system failure, she required multiple vasopressors (epinephrine, vasopressin, and norepinephrine), and received N-acetylcysteine protocol, with intravenous bicarbonate infusion and broad-spectrum antibiotic. High dose continuous veno-venous hemodiafiltration (CVVHDF) was initiated via Baxter PrisMax platform and global effluent dosing of 58mL/kg/hr with post-filter 3% NaCl at a rate of 100 mL/hr to reach goal serum sodium of 140 mEq/dL. [3% NaCl infusion rate calculation: (target infused Na – 140 mEq/L)/ (513 mEq/L – 140 mEq/L) x hemofiltration rate (mL/h)]. She also received Therapeutic Plasma Exchange for ALF for 5 daily sessions using fresh frozen plasma. She continued to have ongoing acidosis with a lactate of 11.7 mmol/L, and serum bicarbonate of 17 mEq/L. On Hospital Day 6, 3% NaCl was changed to hypertonic NaHCO3 drip [4.2% NaHCO3 solution (500 mEq/L in 1L of D5W) at a rate of 100 mL/hr, replacing 3% NaCl on a 1:1 ratio mL/mL]. After 24 hours she had improvement in metabolic acidosis with improvement in serum bicarbonate from 17 to 24 mEq/L, pH of 7.34 to 7.40; pCO2 32 to 42, HCO3 17 to 25 mmHg and serum Na 133 to 140 mEq/L. Unfortunately, on hospital day 8 developed worsening shock requiring vasopressors; a repeat abdominal imaging noted high-grade small bowel obstruction with ischemic bowel and pneumatosis intestinalis and was transitioned to comfort care. Discussion: While CVVHDF can address elevated ammonia in ALF, infused standard therapy fluid (Na+ = 140 mEq/L) would equilibrate serum Na+ to 133 - 135 mEq/L, in the presence of plasma proteins. Post-filter hypertonic saline infusion during CVVHDF would enable simultaneous clamping of serum Na+ to the appropriate target level. Due to heavier molecular size, 4.2% NaHCo3 results in identical Na+ delivery of 3% saline along with the added benefit of improving acidosis. Clinical studies are desirable to define optimal serum Na+ concentrations during CVVDF in various clinical settings.

Tissue Glue-Based Sealing Patch for the in vivo Prevention of Iatrogenic Prelabor Preterm Rupture of Fetal Membranes

Introduction: One of the main concerns for all fetal surgeries is the risk of preterm delivery due to the preterm prelabor rupture of the fetal membranes (iPPROM). Clinical approaches to seal fetal membrane (FM) defects are missing due to the lack of appropriate strategies to apply sealing biomaterials at the defect site. Methods: Here, we test the performance of a previously developed strategy to seal FM defects with cyanoacrylate-based sealing patches in an ovine model up to 24 days after application. Results: Patches sealed tightly the fetoscopy-induced FM defects and remained firmly attached to the defect over 10 days. At 10 days after treatment, 100% (13/13) of the patches were attached to the FMs, and 24 days after treatment 25% (1/4) of the patches placed in CO₂ insufflation, and 33% (1/3) in NaCl infusion remained. However, all successfully applied patches (20/24) led to a watertight sealing at 10 or 24 days after treatment. Histological analysis indicated that cyanoacrylates induced a moderate immune response and disrupted the FM epithelium. Conclusion: Together, these data show the feasibility of minimally invasive sealing of FM defects by locally gathering tissue adhesive. Further development to combine this technology with refined tissue glues or healing-inducing materials holds great promise for future clinical translation.

Effect of esketamine on opioid consumption and postoperative pain in thyroidectomy: A randomized controlled trial.

Thyroidectomy is frequently associated with substantial postoperative pain. Esketamine, an N-methyl-d-aspartate receptor antagonist, has been demonstrated to be effective in multiple analgesia scenarios. We hypothesized that intraoperative administration of esketamine may reduce perioperative opioid consumption and postoperative pain in patients undergoing thyroidectomy. Sixty patients undergoing thyroidectomy were randomly assigned to two groups. Patients in the esketamine group received a pre-incisional intravenous bolus of esketamine (0.5mg kg-1 ) followed by a continuous infusion of 0.24 mg kg-1 h-1 until the beginning of wound closure. Patients in the placebo group received 0.9% NaCl (bolus and infusion). The primary outcome was perioperative sufentanil consumption. The postoperative pain, sleep quality and adverse events during the first postoperative 24 h were also evaluated. Patients in the esketamine group consumed significantly less sufentanil than those in the saline group (24.6 ± 3.1μg vs. 33.7 ± 5.1μg, mean difference, 9.1; 95% confidence interval [CI], 6.9-11.3, P < .001). Postoperative pain scores were significantly lower in the esketamine group than those in the saline group during the first 24 h postoperatively (P < .05). Patients receiving esketamine experienced higher sleep quality than those in the saline group during surgical night (P = .043). There were no significant differences in adverse events between the two groups. Intraoperative administration of esketamine reduces perioperative sufentanil consumption and postoperative pain without increasing psychotomimetic side effects in patients undergoing thyroidectomy. The development of combined anaesthesia regimens, including esketamine, may foster strategies for pain management during thyroidectomy.

Altered Neuronal Discharge in the Organum Vasculosum of the Lamina Terminalis Contributes to Dahl Salt-Sensitive Hypertension.

Salt-sensitive hypertension in humans and experimental models is associated with higher plasma and cerebrospinal fluid sodium chloride (NaCl) concentrations. Changes in extracellular NaCl concentrations are sensed by specialized neurons in the organum vasculosum of the lamina terminalis (OVLT). Stimulation of OVLT neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP), whereas chronic activation produces hypertension. Therefore, the present study tested whether OVLT neuronal activity was elevated and contributed to SNA and ABP in salt-sensitive hypertension. Male Dahl salt-sensitive (Dahl S) and Dahl salt-resistant (Dahl R) rats were fed 0.1% or 4.0% NaCl diets for 3 to 4 weeks and used for single-unit recordings of OVLT neurons or simultaneous recording of multiple sympathetic nerves during pharmacological inhibition of the OVLT. Plasma and cerebrospinal fluid Na+ and Cl- concentrations were higher in Dahl S rats fed 4% versus 0.1% or Dahl R rats fed either diet. In vivo single-unit recordings revealed a significantly higher discharge of NaCl-responsive OVLT neurons in Dahl S rats fed 4% versus 0.1% or Dahl R rats. Interestingly, intracarotid infusion of hypertonic NaCl evoked greater increases in OVLT neuronal discharge of Dahl S versus Dahl R rats regardless of NaCl diet. The activity of non-NaCl-responsive OVLT neurons was not different across strain or diets. Finally, inhibition of OVLT neurons by local injection of the gamma-aminobutyric acid agonist muscimol produced a greater decrease in renal SNA, splanchnic SNA, and ABP of Dahl S rats fed 4% versus 0.1% or Dahl R rats. A high salt diet activates NaCl-responsive OVLT neurons to increase SNA and ABP in salt-sensitive hypertension.

GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading.

Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.

Optimization of infusion supply using the probabilistic economic order quantity (EOQ) method at Sanglah Center General Hospital

Inventory planning is important to avoid the advantages or lack of goods. Hospitals as health care providers also have a share in the stock of goods, one of which is infusion. This study aims to optimize infusion supply at Sanglah Central General Hospital using Economic Order Quantity (EOQ) method with (q, r) model. The forecasting method used in forecasting infusion requirements at Sanglah Hospital is an Autoregressive Integrated Moving Average (ARIMA) method. The results of this study indicate the amount of infusion of NaCl 0.9% 500 ml and 5% 500 ml glucose infusion which is expected to be ordered by Sanglah Hospital at the beginning of the booking period is 11,921 and 560 units. Sanglah Hospital need to re-order when the stock of infusion of NaCl 0.9% 500 ml touched the number 3,593 and 5% 500 ml glucose infusion stock touched 202 units. To anticipate the spike of demand, Sanglah Hospital is expected to provide infusion as a safety reserve of 190 units for infusion of NaCl type 0.9% 500 ml and 21 units for glucose type 5% 500 ml. The total inventory cost of the infusion to be issued by Sanglah Hospital in the planning of the infusion needs for 6 months is also obtained.

Two-pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling.

Two-pore channels (TPCs) constitute a small family of cation channels expressed in endo-lysosomal compartments. TPCs have been characterized as critical elements controlling Ca2+ -mediated vesicular membrane fusion and thereby regulating endo-lysosomal vesicle trafficking. Exo- and endocytotic trafficking and lysosomal degradation are major mechanisms of adaption of epithelial transport. A prime example of highly regulated epithelial transport is the tubular system of the kidney. We therefore studied the localization of TPC protein 1 (TPC1) in the kidney and its functional role in the dynamic regulation of tubular transport. Immunohistochemistry in combination with tubular markers were used to investigate TPC1 expression in proximal and distal tubules. The excretion of phosphate and ammonium, as well as urine volume and pH were studied in vivo, in response to dynamic challenges induced by bolus injection of parathyroid hormone or acid-base transitions via consecutive infusion of NaCl, Na2 CO3 , and NH4 Cl. In TPC1-deficient mice, the PTH-induced rise in phosphate excretion was prolonged and exaggerated, and its recovery delayed in comparison with wildtype littermates. In the acid-base transition experiment, TPC1-deficient mice showed an identical rise in phosphate excretion in response to Na2 CO3 compared with wildtypes, but a delayed NH4Cl-induced recovery. Ammonium-excretion decreased with Na2 CO3 , and increased with NH4 Cl, but without differences between genotypes. We conclude that TPC1 is expressed subapically in the proximal but not distal tubule and plays an important role in the dynamic adaptation of proximal tubular phosphate reabsorption towards enhanced, but not reduced absorption.

231-LB: GLP-1 Promotes Cortical and Medullary Perfusion in Human Kidney and Maintains Tissue Oxygenation during Na Loading

Purpose: GLP-1 receptor agonism has shown beneficial cardiovascular effects which could include the kidneys. In the human kidney, the high GLP-1 extraction and its natriuretic effect depend on the GLP-1 receptor and is accompanied by suppression of angiotensin II, independent of changes in renal plasma flow. Preclinical data showed that angiotensin II constricts the vasa recta and lowers medullary perfusion. The current randomized, controlled study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods: Healthy male participants (n=10, 27 ± 4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg/min) or placebo together with infusion of 0.9% NaCl (750 mL/h) . Interleaved measurements of renal artery flow, oxygenation (R2*) , and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. Results: GLP-1 infusion increased medullary perfusion (32 ± 7%, p&amp;lt;0.001) and cortical perfusion (13 ± 4%, p&amp;lt;0.001) compared to placebo. Here, NaCl infusion decreased medullary perfusion (-5 ± 2%, p=0.007) while cortical perfusion remained unchanged. R2* values increased by 3 ± 2% (p=0.025) in the medulla and 4 ± 1% (p=0.008) in the cortex during placebo, indicative of decreased oxygenation but remained unchanged during GLP-1. Renal arterial blood flow was not altered significantly by either intervention. Conclusions: GLP-1 increases predominantly medullary but also cortical perfusion in healthy human kidneys and maintains oxygenation during NaCl-loading. In perspective, GLP-1 may exert protective effects against renal hypoperfusion and ischemia. Disclosure B. Haddock: n/a. B. L. Jensen: None. A. Asmar: None.

In-use stability of diluted thiamazole (methimazole) infusion solutions in prefilled 0.9% sodium chloride infusion bags for continuous infusion

ObjectiveIn patients with severe hyperthyroidism unable to tolerate oral antithyroid therapy, diluted thiamazole infusion solutions (dose 120–240 mg) are administered by continuous infusion over 24 hours. Information about the type...