Effectiveness of hypertonic saline infusion in management of traumatic brain injury: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to find out the efficacy of using Hypertonic saline solution (HSS) over mannitol in the management of TBI by comparing their performance in improving different outcomes. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the impact of HSS vs. mannitol on ICP in patients who suffered TBI. Outcomes of interest were mortality, neurologic functional outcomes, risk ratio (RR) of successful ICP treatment, reduction in ICP after 30-60 and 90-120 min, improvement in cerebral perfusion pressure (CPP) at 30-60 and 90-120 min, and also treatment failure. Evaluations were reported as RR or mean difference (MD) with 95% confidence intervals (CIs) using weighted random-effects models. RESULTS: The analysis included 624 patients from 15 RCTs. HSS infusion had a significant impact on the improvement of CPP at 30-60 min [MD = 5.54, 95% CI (3.04, 8.03),p < 0.001] compared to mannitol. However, results yielded no significant difference between HSS and mannitol in terms of mortality, neurologic functional outcomes, successful ICP treatment, reduction in ICP after 30-60 min and 90-120 min, improvement in CPP at 90-120 min, and treatment failure. CONCLUSION: HSS and mannitol are both effective treatments for elevated ICP due to TBI. However, further research is required to derive a better comparison.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

AIMS: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. METHODS AND RESULTS: 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). RESULTS: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114). CONCLUSIONS: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

The added value of hypertonic saline solution to furosemide monotherapy in patients with acute decompensated heart failure: A meta-analysis and trial sequential analysis.

We assessed the effects of hypertonic saline solution (HSS) plus furosemide versus furosemide alone in patients with acute decompensated heart failure (ADHF). We searched four electronic databases for randomized controlled trials (RCTs) until June 30, 2022. The quality of evidence (QoE) was assessed using the GRADE approach. All meta-analyses were performed using a random-effects model. A trial sequential analysis (TSA) was also conducted for intermediate and biomarker outcomes. Ten RCTs involving 3013 patients were included. HSS plus furosemide significantly reduced the length of hospital stay (mean difference [MD]: -3.60 days; 95% confidence interval [CI]: -4.56 to -2.64; QoE: moderate), weight (MD: -2.34 kg; 95% CI: -3.15 to -1.53; QoE: moderate), serum creatinine (MD: -0.41 mg/dL; 95% CI: -0.49 to -0.33; QoE: low), and type-B natriuretic peptide (MD: -124.26 pg/mL; 95% CI: -207.97 to -40.54; QoE: low) compared to furosemide alone. HSS plus furosemide significantly increased urine output (MD: 528.57 mL/24 h; 95% CI: 431.90 to 625.23; QoE: moderate), serum Na+ (MD: 6.80 mmol/L; 95% CI: 4.92 to 8.69; QoE: low), and urine Na+ (MD: 54.85 mmol/24 h; 95% CI: 46.31 to 63.38; QoE: moderate) compared to furosemide alone. TSA confirmed the benefit of HSS plus furosemide. Due to the heterogeneity in mortality and heart failure readmission, meta-analysis was not performed. Our study shows that HSS plus furosemide, compared to furosemide alone, improved surrogated outcomes in ADHF patients with low or intermediate QoE. Adequately powered RCTs are still needed to assess the benefit on heart failure readmission and mortality.

Effect of continuous infusion of hypertonic saline solution on survival of patients with brain injury: a systematic review and meta-analysis.

BACKGROUND: The objective was to determine the effects of continuous infusion of hypertonic saline solutions on outcomes of patients with brain injury. METHODS: Preferred Reported Items for Systemic Reviews and Meta-Analysis guidelines were followed. We searched the MEDLINE and COCHRANE clinical trials register (through December 2021) and reference lists of articles. We included all clinical trials conducted in brain-injured patients hospitalized in intensive care units evaluating continuous infusion of hypertonic saline solution (osmolarity above 308 mOsm/L). Two reviewers extracted data that were checked by two others. The primary outcome was the in-hospital mortality rate. The main secondary outcomes were the rates of intracranial hypertension, an unfavorable neurological outcome at day 90, and adverse events. RESULTS: We identified 23 clinical trials reporting the use of continuous infusion of hypertonic saline solution in brain-injured patients. The primary outcome was available in 10 studies (n = 1883 patients). The odds ratio (OR) for in-hospital death with the intervention was 0.68 (95% confidence interval (CI), 0.54-0.85, I2 = 0%). In the subgroup of studies including only traumatic brain-injured patients (7 studies, n = 1521 patients), the OR for the primary outcome was 0.74 (95%CI 0.57-0.95) with the intervention. The OR for intracranial hypertension and unfavorable neurological outcome at day 90 were 0.66 (95%CI 0.49-0.88, I2 = 42%, n = 787 patients) and 0.61 (95%CI 0.46-0.81, I2 = 15%, n = 956 patients), respectively. Regarding safety, the OR of acute kidney injury and severe hypernatremia were 0.82 (95%CI 0.47-1.44, I2 = 0%) and 3.38 (95%CI 2.16-5.27, I2 = 24%). CONCLUSIONS: Continuous hypertonic saline solution infusion reduced in-hospital mortality without increasing the risk of unfavorable neurological outcome at day 90 in brain-injured patients hospitalized in intensive care units. Given the inclusion of observational and heterogeneous studies, further randomized studies are needed before developing recommendations for implementation at the bedside. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021221367. Registered 13 May 2021.

Safety and Tolerability of 23.4% Hypertonic Saline Administered Over 2 to 5 Minutes for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.

BACKGROUND: Hyperosmolar therapy is the cornerstone of medical management of sustained elevated intracranial pressure from cerebral edema. Acute intracranial hypertension and herniation is a medical emergency that requires rapid treatment and stabilization to prevent secondary brain injury or death. Intravenous hypertonic sodium chloride (NaCl) 23.4% is an effective treatment modality commonly used in this setting. Because of its high osmolarity, use has historically been limited primarily to central venous line administration as an intermittent infusion due to concerns about thrombophlebitis, injection site pain, and tissue necrosis or injury with extravasation. The objective of this analysis was to prospectively evaluate the safety of administration of 23.4% NaCl as a rapid intravenous push over 2-5 min. METHODS: A prospective analysis of patients admitted between April 2021 and December 2021 who received 23.4% NaCl intravenous push over 2-5 min in a central or peripheral line was performed. Safety end points included incidence of new onset hypotension [defined as systolic blood pressure (SBP) < 90 mm Hg or SBP decrease of at least 20 mm Hg], bradycardia (defined as heart rate < 50 beats per minute), and infusion site reactions documented within 1 h of administration. For secondary safety outcomes, highest and lowest SBP and lowest heart rates documented within 1 h before 23.4% NaCl administration were compared with values collected within 1 h post administration and evaluated by mixed-design analysis of variance test with adjustment for peripheral versus central line administration. RESULTS: We identified 32 patients who received 79 administrations of 23.4% NaCl through a central line or peripheral line during the study period. An SBP decrease of at least 20 mm Hg was observed in 13% of patients, an SBP < 90 mm Hg occurred in 16% of patients, and bradycardia occurred in 3% of patients who received 23.4% NaCl. Injection site pain was reported by one patient without documented thrombophlebitis, cellulitis, or tissue damage. Pain was not reported during two subsequent administrations in the same patient. There was no documented occurrence of soft tissue injury or necrosis in any patient. Compared with baseline vital signs before 23.4% NaCl administration, no difference in vital signs post administration was observed. CONCLUSIONS: Central and peripheral administration of 23.4% NaCl over 2-5 min was well tolerated, and incidence of hypotension, bradycardia, or infusion site-related adverse events was rare.

A Comparative Study in the Management of Chronic Rhinosinusitis by Nasal Douching with Hypertonic Saline vs Isotonic Saline.

Chronic rhinosinusitis is one of the most commonly diagnosed medical conditions affecting all age groups. Hypertonic saline solution and isotonic saline solution are used in management of chronic rhinosinusitis. In this study we compare the effectiveness of isotonic saline and hypertonic saline in alleviation of symptoms and clinical outcome of patients with chronic rhinosinusitis. In our study 60 patients diagnosed with chronic rhinosinusitis are divided into two groups; Group A treated with isotonic saline and Group B with 3.5% hypertonic saline for a period of 6 weeks. The symptoms were evaluated using SNOT-20 score before and after treatment. It was found that hypertonic saline solution is more efficacious than isotonic saline solution in the treatment of patients with chronic rhinosinusitis.

Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial.

Background: COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods: We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results: During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions: Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

Impact of the updating of clinical guidelines for RSV bronchiolitis on the use of diagnostic testing and medications in tertiary hospitals in Colombia.

Introduction: the incidence of Respiratory Syncytial Virus (RSV) infection and their variability in the clinical management, make this disease a candidate for monitoring adequate use of resources. The objective of this study was to evaluate the impact of the updating of clinical guidelines for RSV bronchiolitis on the use of diagnostic testing and medications in tertiary hospitals in Colombia. Methods: we performed a cross-sectional study, evaluating the frequencies of drug prescription and medical tests, before (January-December 2016) and after (January to December 2019) of updating and dissemination of a new protocol for the treatment of RSV bronchiolitis in two tertiary hospitals in Colombia. Results: a total of 108 patients with RSV bronchiolitis were included. The demographic characteristics and clinical manifestations were similar in both groups. The length of hospital stays was similar in both groups. We did not find statistically significant differences in the frequency of medical tests. There was a decrease in the use of salbutamol (67.3% pre-protocol vs 51.8% post-protocol; P < .01). There were also significant reductions in the use of nebulized hypertonic saline solution (91.6% vs 82.6% P = 0.004). Conclusion: our results demonstrate that the updating of clinical guidelines for RSV bronchiolitis was effective, as it achieved decreases in the use of bronchodilators and nebulized hypertonic saline solution. It is necessary to continue developing new strategies targeted to increase adherence to guidelines and evaluate the impact on the use of resources.

Uso de solución salina hipertónica al 3 por ciento en niños con bronquiolitis aguda / Usage of 3 percent Hypertonic Saline Solution in Children with Acute Bronchitis

Introducción: La bronquiolitis aguda es la infección del tracto respiratorio inferior más frecuente en el lactante. Tiene una incidencia anual del 10 por ciento en los lactantes y una tasa de ingreso de entre el 2 y el 5 por ciento con un incremento importante en los últimos años. Objetivo: Determinar la efectividad del uso de solución salina hipertónica al 3 por ciento nebulizada en pacientes con bronquiolitis aguda. Métodos: Se realizó un estudio analítico longitudinal prospectivo de tipo casos y controles. El universo estuvo constituido por 132 pacientes distribuidos en 66 casos y 66 controles. Resultados: La edad media fue de 3,6 ± 2,5 meses. Los sibilantes se hallaron en 129 pacientes, lo que representó el 97,7 por ciento. Se encontró una estadía hospitalaria media de 3,19 ± 1,41 días en los casos, mientras que en los controles se encontró una media de 4,97 ± 1,77 días, diferencia que resultó altamente significativa (p < 0,001). Conclusiones: Aunque los pacientes tratados con solución salina hipertónica al 3 por ciento necesitaron más días con oxigenoterapia, el tratamiento resultó ser efectivo al mostrar una menor estadía hospitalaria y un menor número de complicaciones en pacientes con bronquiolitis aguda(AU)

Introduction: Acute bronchiolitis is the most frequent lower respiratory tract infection in the infant. It has a yearly incidence of 10 percent in infants and an admission rate of 2 percent to 5 percent, with a significant increase in recent years. Objective: To determine the effectiveness of nebulized 3 percent hypertonic saline solution treatment in patients with acute bronchiolitis. Methods: A prospective, longitudinal and analytical study of case-control design was carried out. The universe consisted of 132 patients distributed into 66 cases and 66 controls. Results: The mean age was 3.6±2.5 months. Wheezing was found in 129 patients, accounting for 97.7 percent. A mean hospital stays of 3.19±1.41 days was found in cases, while a mean of 4.97±1.77 days was found in controls, a difference that was highly significant (P<0.001). Conclusions: Although patients treated with 3 percent hypertonic saline solution required more days with oxygen therapy, the treatment proved to be effective by showing a shorter hospital stay and a lower number of complications in patients with acute bronchiolitis(AU)

The new therapeutic option for female stress and stress-predominant mixed urinary incontinence: Periurethral hypertonic saline (10%) injection.

OBJECTIVES: We aimed to evaluate the safety and efficacy of periurethral hypertonic saline (10% NaCl) injection in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (S-MUI) in women. METHODS: This was a prospective study conducted between January 2014 and April 2018 with 64 women (44 SUI and 21 S-MUI). Patients with SUI and S-MUI were evaluated using the Urinary Distress Inventory 6. Quality of life was evaluated with the Incontinence Quality of Life Scale and lower urinary tract symptoms of the women were evaluated with the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules. Incontinence status and treatment success were assessed via the Stamey incontinence grade and pad test. RESULTS: The subjective success rate was 58.5%, and the objective success rate was 81.5%. The rate of reinjection was 21.5%, and the mean duration of reinjection was 8.92 months (3-19 months). Minor adverse effects were observed in 30.4% of the 79 injections. International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules and Incontinence Quality of Life Scale scores improved remarkably starting from the first month. Urinary Distress Inventory 6 scores in the S-MUI group also improved. CONCLUSIONS: The results indicate that hypertonic saline injection is an effective and safe method in the treatment of SUI and S-MUI. Since hypertonic saline is a much cheaper and more accessible substance compared to bulking agents, it seems to be a viable alternative for urinary incontinence treatment in women.

Adjunct Hypertonic Saline in Patients with Diffuse Edema Due to Heart Failure: A Randomized Double-Blinded Clinical Trial.

In patients with diuretic resistance due to heart failure, higher doses or continuous furosemide infusion and adding hypertonic saline solution (HSS) to diuretics could be effective. The goal of this study was to assess the effectiveness of hypertonic saline solution administration in weight loss of hospitalized patients with diuretic-resistant edema due to heart failure. In a randomized double-blinded clinical trial, adult patients with diffuse peripheral edema due to heart failure who were unresponsive to 80 mg of oral furosemide were enrolled. The patients were randomized into two groups. In the intervention and control groups, patients received 150 mL of HSS and normal saline, respectively. Subjects in both groups received 250 mg IV furosemide every 12 h for 48 h. The change in body weight, urine output, blood pressure, uric acid, urine osmolality, blood biochemistry, and urinary cystatin C levels were assessed. Based on defined inclusion and exclusion criteria, 28 patients, 14 in each group, were recruited. The groups were similar in demographic and baseline laboratory characteristics. A significant decrease in body weight was observed in the intervention group (P = 0.002). The change in other measured parameters, including urine output and urinary cystatin C levels, was not reached statistical significance. Our findings suggest that the administration of HSS as an adjunct to loop diuretics could provide a safe and effective treatment for increasing urine output and decreasing weight in patients with heart failure.

Bronchodilator response to albuterol nebulized with hypertonic saline in asthmatic children.

INTRODUCTION: Asthma is distinguished by bronchial obstruction reversible by bronchodilators. The first-line treatment for asthmatic exacerbations is the use of inhaled beta-agonists, by pressurized metered-dose inhalers or nebulized with normal saline solution (NSS). There are no reports of nebulized beta agonists' efficacy in asthmatic children when administered with hypertonic saline solution (HSS). OBJECTIVE: To evaluate bronchodilator responses (BDR) to albuterol nebulized with 3%-HSS in asthmatic children, compared to albuterol nebulized with NSS. POPULATION AND METHODS: In a prospective, experimental, double-blind, randomized clinical study, children with a confirmed diagnosis of asthma with mild or moderate bronchial obstruction (FEV1 40%-79% of predicted) were randomized to receive a nebulization with 2.5 mg of albuterol diluted in 3 cc of 3%-HSS or NSS (0.9%), by means of a jet nebulizer. After 30 min, the BDR was assessed. RESULTS: Fifty patients (mean age 12.0 ± 3 years, 29 males) were enrolled; 25 were randomized to the 3%-HSS group (FEV1 65.2% ± 10) and 25 to the NSS group (FEV1 69.1% ± 7.1). The BDR of FEV1 was 41.2% (SD: ±20.1; 95% confidence interval [CI]: 35.1-50.4) and 17.3% (SD: ±19.4; 95% CI: 9.7-24.9) (p < .0001) and of maximum mid-expiratory flow was 130% (SD: ±90.8; 95% CI: 94.6-166) and 69.8% (SD: ±72.5; 95% CI: 41.4-98.2) (p < .01), for the 3%-HSS and NSS groups, respectively. CONCLUSION: Albuterol produces a greater BDR when nebulized with 3%-HSS compared to NSS in asthmatic children with mild or moderate bronchial obstruction.

Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study.

BACKGROUND: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. METHODS: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed. RESULTS: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). CONCLUSION: There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.

BACKGROUND: Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. METHODS: We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. RESULTS: We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. CONCLUSIONS: Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.

Uso de Solución Hipertónica en pacientes con insuficiencia cardiaca aguda como terapia adyuvante a altas dosis de diuréticos / Use of Hypertonic Solution in patients with acute heart failure as adjunctive therapy to high-dose diuretics

Resumen La insuficiencia cardíaca aguda descompensada (ICAD) es una causa común de hospitalización, con repercusiones significativas en los sistemas de salud. El manejo agudo se basa en la reducción de la volemia con diuréticos de asa, sin embargo, un porcentaje de pacientes presenta resistencia o no logra la respuesta clínica esperada con este tratamiento. Una de las medidas que ha comprobado ser efectiva en este contexto, es el uso de solución salina hipertónica (SSH) en conjunto con dosis altas de diuréticos de asa, como medida terapéutica temida por sus posibles repercusiones sobre la función renal y posible sobrecarga de sodio. Objetivos: Determinar si el uso de solución salina hipertónica en pacientes con falla cardiaca aguda e hipervolemia genera un deterioro de la función renal. Determinar la respuesta del Pro-BNP ante el uso de la solución salina hipertónica en pacientes con falla cardiaca aguda como marcador de respuesta terapéutica. Determinar si el uso de solución salina hipertónica aumenta la diuresis sin generar cambios importantes en el sodio. Se muestran datos de pacientes con insuficiencia cardiaca aguda descompensada, que tras no presentar mejoría con altas dosis de diurético de asa en bolo, se les aplicó la solución hipertónica como adyuvante a este tratamiento. Se toma un total de 26 pacientes analizando datos generales clínicos y de laboratorio, se valoran curvas con la respuesta diurética y por parámetros de laboratorio a las 48 y 72 horas. El uso de solución salina hipertónica consigue un aumento de más de un 200% de la diuresis en 24 horas, con un descenso del Pro BNP de más de un 60% a las 48 horas, sin mostrar un cambio importante en los niveles de creatinina, nitrógeno ureico y sodio. Se requirió reposición de potasio en la totalidad de los pacientes. Se concluye que la infusión de furosemida más solución hipertónica es efectiva tanto en disminuir niveles de NT Pro-BNP en los pacientes, como en generar un aumento en el volumen de diuresis. La principal complicación fue la hipokalemia, sin cambios considerables en el valor de sodio, creatinina y nitrógeno ureico séricos.

Abstract Uso de Solución Hipertónica en pacientes con insuficiencia cardiaca aguda como terapia adyuvante a altas dosis de diuréticos Acute decompensated heart failure (AHF) is a common cause of hospitalization, with significant repercussions on health systems. Acute management is based on the reduction of blood volume with loop diuretics; however, a percentage of patients show resistance or do not achieve the expected clinical response with this treatment. One of the measures that has proven to be effective in this context is the use of hypertonic saline (HSS) in conjunction with high doses of loop diuretics, as a therapeutic measure feared due to its possible repercussions on kidney function and possible sodium overload. Objetives: To determine if the use of hypertonic saline in patients with acute heart failure and hypervolemia leads to a deterioration in renal function. To determine the response of Pro-BNP to the use of hypertonic saline in patients with acute heart failure as a marker of therapeutic response. Determine if the use of hypertonic saline increases urine output without causing significant changes in sodium. Data are shown from patients with acute decompensated heart failure, who after not presenting improvement with high doses of bolus loop diuretic, the hypertonic solution was applied as an adjunct to this treatment. A total of 26 patients are taken analyzing general clinical and laboratory data, curves with the diuretic response and by laboratory parameters are evaluated at 48 and 72 hours. The use of hypertonic saline solution achieves an increase of more than 200% in diuresis in 24 hours, with a decrease in Pro BNP of more than 60% at 48 hours, without showing a significant change in creatinine levels, urea nitrogen and sodium. Potassium replacement was required in all patients. It is concluded that the infusion of furosemide plus hypertonic solution is effective both in reducing levels of NT Pro-BNP in patients, and in generating an increase in the volume of diuresis. The main complication was hypokalemia, without significant changes in serum sodium, creatinine, and urea nitrogen.

Single Instillation of Hypertonic Saline Immediately Following Transurethral Resection of Bladder Tumor for Recurrence Prevention -A Phase I Study.

BACKGROUND: Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. OBJECTIVE: To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. METHODS: In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12-24 hours after instillation. Adverse effects were documented and compared between the groups. RESULTS: In rats, average sodium levels were 140.0 mEq/L and 140.3 mEq/L before and following instillation, respectively. Necropsy revealed no signs of inflammation or blue discoloration. In humans the average plasma sodium levels were 138.6 mEq∖L, 138.8 mEq∖L and 137.7 mEq∖L before, 1 hour and 12-24 hours after instillation, respectively. During the postoperative follow-up there was one case of fever. A month after the surgery, dysuria was reported by 5 patients while urgency and hematuria were reported by one patient each. The most severe adverse events were grade 2 on the Clavien-Dindo scale. Adverse events were similar in the control group. CONCLUSIONS: Hypersal instillation is safe and tolerable immediately after TURBT.

Clinical application of 2.16% hypertonic saline solution to correct the blood sodium concentration in diarrheic calves with hyponatremia.

The aim of this study was to examine whether 2.16% hypertonic saline solution (HSS) is useful for the treatment of diarrheic calves with hyponatremia. Eleven of 13 female Holstein calves exhibiting moderate diarrhea and hyponatremia received 1,250 ml of 2.16% HSS over 15 min regardless of body weight. The remaining two calves that were unable to stand and had severe hyponatremia received 2,500 ml of 2.16% HSS intravenously over 30 min. As a result, hyponatremia in all diarrheic calves was significantly improved by the administration of 2.16% HSS from 122.2 ± 7.0 mEq/l at pre to 134.8 ± 3.7 mEq/l at post, which was above the threshold of 132 mEq/l for hyponatremia. Therefore, 2.16% HSS may be useful for hyponatremia in calves with diarrhea.

Safety and efficacy of hypertonic saline solution (5%) versus placebo in the treatment of postoperative corneal edema after uneventful phacoemulsification: a randomized double-blind study.

PURPOSE: To evaluate safety and efficacy of hypertonic saline solution administration after uneventful cataract surgery. DESIGN: Prospective double-blind randomized study METHODS: In total, 183 eyes of 183 patients undergoing phacoemulsification were randomly allocated into two equal groups. Treatment group (TG) subjects received single-dose hypertonic (NaCl 5%) solution 4 times daily for 14 days, while placebo group (PG) received single dose of normal saline solution (0.9%) at the same frequency in addition to ordinary postoperative treatment. All patients underwent assessment of central corneal thickness (CCT), endothelial cell density (ECD), best-corrected visual acuity (BCVA), clinical staging of postoperative corneal edema and questionnaire regarding the procedure success and impact on patient's life. Measurements were taken at baseline and 1, 4, 9 and 30 days following surgery. RESULTS: CCT increased by 134.67 ± 94.51 µm (25.1 ± 19.4%) on postoperative day 1, without any difference between study groups (p = 0.58). Corneal edema showed a significant recession in TG compared to PG on day 4, in terms of both pachymetry (10.73% vs 7.39%, p = 0.004), BCVA (BCVATG = 0.64 ± 0.24 [logMARTG = 0.25 ± 0.3], BCVAPG = 0.56 ± 0.23 [logMARPG = 0.33 ± 0.3], p = 0.04) and clinical staging (p = 0.02). Similar results were recorded on postoperative day 9 in subjects demonstrating marked corneal edema on the first postoperative day. Endothelial cell loss showed no statistically significant difference between study groups (p = 0.48). No adverse events were recorded in relation to treatment. More patients in the TG (92.4% vs 57.1% in the PG) reported a subjectively clear vision 1 week postoperatively (p = 0.04). CONCLUSION: The use of 5% hypertonic saline solution is found to be a safe and effective adjunct in the management of postoperative corneal edema after uneventful phacoemulsification, achieving rapid corneal clearance and expediting a good visual outcome, especially in cases with marked postoperative edema.