The Safety and Efficacy of Hypertonic Saline in Achieving Primary Fascial Closure Following Damage Control Laparotomy: A Systematic Review and Meta-Analysis.

Effective fluid management is critical in patients undergoing damage control laparotomy (DCL) for trauma and sepsis. Hypertonic saline (HTS) has been proposed as an alternative to isotonic fluids to enhance primary fascial closure rates and optimize fluid balance. This systematic review and meta-analysis aims to evaluate the efficacy and safety of HTS compared to isotonic fluids in patients undergoing DCL. A comprehensive literature search was conducted across multiple databases up to the 14th of June 2024, identifying studies that compared HTS to isotonic fluids in adult patients undergoing DCL for trauma or sepsis. Eligible studies included randomized controlled trials and observational studies reporting outcomes such as early primary fascial closure (EPFC) rates, time to fascial closure, fluid requirements, electrolyte imbalances, renal function, and mortality. Data extraction and quality assessment were performed independently by two reviewers, and pooled analyses were conducted using fixed-effect models where appropriate. Four studies encompassing 375 patients met the inclusion criteria, with 100 patients receiving HTS and 275 receiving isotonic fluids. HTS administration was associated with a significantly higher EPFC rate compared to isotonic fluids (odds ratio (OR): 0.314; 95% confidence interval (CI): 0.142-0.696; p=0.004). The mean time to fascial closure was also significantly reduced in the HTS group by approximately eight hours (mean difference (MD): 8.007 hours; 95% CI: 5.558-10.596; p<0.001). Patients receiving HTS required significantly less total fluid over 48 hours (MD: 1.055 liters; 95% CI: 0.713-1.398; p<0.001). While HTS use led to higher peak sodium levels (MD: -4.318 mEq/L; 95% CI: -4.702 to -3.934; p<0.001), there were no significant differences in peak creatinine levels, need for inpatient renal replacement therapy, or 28-day mortality between the groups. HTS appears to be effective in improving EPFC rates and reducing both time to closure and overall fluid requirements in patients undergoing DCL for trauma and sepsis. Although associated with higher serum sodium levels, HTS did not increase the risk of renal dysfunction or mortality. These findings suggest that HTS is a safe and efficacious alternative to isotonic fluids in the management of critically ill patients requiring DCL. Further large-scale, randomized controlled trials are warranted to confirm these results and inform clinical guidelines.

Exercise-Associated Hyponatremic Encephalopathy, Rhabdomyolysis, and Acute Kidney Injury While Hiking in the Grand Canyon.

We present an unusual case of concomitant exercise-associated hyponatremic encephalopathy (EAHE), exertional rhabdomyolysis (ER), and acute kidney injury (AKI) in a Grand Canyon hiker. Our case patient, an adult 41-year-old male, consumed an excessive amount of water during his descent into the Canyon during hot weather. The next day, he was unable to hike out due to severe leg pain and disorientation, and ultimately evacuated by helicopter, having a grand mal seizure in flight. Despite having no serum sodium level, medics administered an intravenous (IV) bolus of 3% hypertonic saline (HTS) before transporting him to the hospital. There, he was diagnosed with EAHE (serum sodium, 114 mmol⋅L-1), ER, bilateral compartment syndromes, and mild AKI. The life-threatening EAHE was immediately corrected with more IV HTS, the limb-threatening compartment syndromes by surgical fasciotomies, and eventually, the AKI by oral and IV fluids. This case demonstrates the seriousness of overconsumption of water, as well as the potential complications of muscle damage when a deconditioned person does prolonged, strenuous exercise. Furthermore, it also illustrates the importance of considering EAHE within the differential diagnosis for acute alterations in level of consciousness. Lastly, it shows the importance to prioritize patient treatments for conditions that are an immediate threat to life or limb.

Targeting Sodium in Heart Failure.

A dominant event determining the course of heart failure (HF) includes the disruption of the delicate sodium (Na+) and water balance leading to (Na+) and water retention and edema formation. Although incomplete decongestion adversely affects outcomes, it is unknown whether interventions directly targeting (Na+), such as strict dietary (Na+) restriction, intravenous hypertonic saline, and diuretics, reverse this effect. As a result, it is imperative to implement (Na+)-targeting interventions in selected HF patients with established congestion on top of quadruple therapy with angiotensin receptor neprilysin inhibitor, ß-adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor, which dramatically improves outcomes. The limited effectiveness of (Na+)-targeting treatments may be partly due to the fact that the current metrics of HF severity have a limited capacity of foreseeing and averting episodes of congestion and guiding (Na+)-targeting treatments, which often leads to dysnatremias, adversely affecting outcomes. Recent evidence suggests that spot urinary sodium measurements may be used as a guide to monitor (Na+)-targeting interventions both in chronic and acute HF. Further, the classical (2)-compartment model of (Na+) storage has been displaced by the (3)-compartment model emphasizing the non-osmotic accumulation of (Na+), chiefly in the skin. 23(Na+) magnetic resonance imaging (MRI) enables the accurate and reliable quantification of tissue (Na+). Another promising approach enabling tissue (Na+) monitoring is based on wearable devices employing ion-selective electrodes for electrolyte detection, including (Na+) and (Cl-). Undoubtably, further studies using 23(Na+)-MRI technology and wearable sensors are required to learn more about the clinical significance of tissue (Na+) storage and (Na+)-related mechanisms of morbidity and mortality in HF.

Hypertonic Saline Induces Host Protective Immune Responses against Brucella abortus Infection in Mice.

Hypertonic saline (HTS) resuscitation can enhance immune responses against various pathogens, however, the effect of HTS on brucellosis is yet to be defined. In this study, we found that HTS inhibited Brucella infection in mice by augmenting Th1 immunity. HTS treatment enhanced the serum cytokines production and the expression of nitric oxide synthase (NOS2) and nuclear factor kappa B (NF-ĸB) p50 and p65, crucial anti-Brucella effectors in splenocytes. In addition, HTS treatment also inhibited the phosphorylation of MAPK signaling, accompanied by the down-regulation of the autophagy marker LC3B-II. Due to directing an appropriate immune response, HTS treatment substantially decreased bacterial burden in spleen and liver tissues. In summary, corroborating previous studies showing the antimicrobial effects of HTS, our findings indicate that HTS treatment triggers a protective immune response against Brucella infection. Additionally, these results provide promising evidence of the immunomodulatory role of HTS in controlling bacterial infections.

Hypertonic saline achieves superior brain relaxation in tumor craniotomy: An updated systematic-network meta-analysis.

Background: Brain tumor craniotomy requires relaxation of the brain through decreasing the intracranial pressure (ICP). Osmo-hyperosmolar therapy can be used to lower the ICP. Objectives: This study was aimed at updating previous studies to determine the effects and safety of using hypertonic saline (HTS) and mannitol to decrease ICP in adult patients with brain tumors undergoing craniotomy. Methods: To identify randomized controlled trials (RCTs) comparing HTS vs mannitol, we performed a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, by examining records from 2013 to December of 2023 in five databases. The primary outcome was brain relaxation, and the secondary outcomes were cerebral perfusion pressure (CPP), urine output (UO), fluid input, mean arterial pressure (MAP), and plasma sodium. Conventional meta-analysis, Bayesian meta-insight analysis, trial-sequential analysis, and trial quality assessment were conducted. Results: Eleven RCTs involving 593 participants were included in the meta-analysis. Use of HTS, compared with mannitol, was associated with significantly greater brain relaxation, and significantly lower UO and fluid input. HTS was also significantly associated with elevated MAP. Plasma sodium was significantly higher in the HTS group than the mannitol group. No significant difference in CPP was observed between groups. Trial sequential analysis indicated true significance for the brain relaxation outcomes. Bayesian analysis demonstrated the superiority of 3% HTS at 5 ml/kg in achieving brain relaxation, followed by 3% HTS at 5.3 ml/kg and 20% mannitol at 5 ml/kg. Conclusions: HTS is superior to mannitol in achieving optimal brain relaxation, maintaining stable blood flow, and minimizing diuretic effects. However, use of HTS during tumor craniotomy procedures can increase plasma sodium levels. The optimal dose for achieving brain relaxation appears to be 3% HTS at 5 ml/kg body weight.

Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

Comparison of 4.54% hypertonic saline and 20% mannitol for brain relaxation during auditory brainstem implantation in pediatric patients: a single-center retrospective observational cohort study.

BACKGROUND: Mannitol is frequently utilized to achieve intracranial brain relaxation during the retrosigmoid approach for auditory brainstem implantation (ABI). Hypertonic saline (HS) is an alternative for reducing intracranial pressure; however, its application during ABI surgery remains under-investigated. We aimed to compare the efficacy and safety between HS and mannitol for maintaining brain relaxation. METHODS: This single-center retrospective cohort study included pediatric patients undergoing ABI surgery from September 2020 to January 2022 who received only 4.54% HS or 20% mannitol for brain relaxation. The analysis involved initial doses, subsequent doses, and dosing intervals of the two hyperosmolar solutions, as well as the time elapsed from meningeal opening to the first ABI electrode placement attempt. Additionally, the analysis encompassed electrolyte testing, hemodynamic variables, urine output, blood transfusion, second surgeries, adverse events, intensive care unit length of stay, and 30-day mortality. RESULTS: We analyzed 68 consecutive pediatric patients; 26 and 42 in the HS and mannitol groups, respectively. The HS group exhibited a reduced rate of supplementary use (7.7% vs. 31%) and lower total urine volume. Perioperative outcomes, mortality, and length of intensive care unit stay did not exhibit significant between-group differences, despite transient increases in blood sodium and chloride observed within 2 h after HS infusion. CONCLUSIONS: In pediatric ABI surgery, as an osmotherapy for cerebral relaxation, 4.54% HS demonstrated a lower likelihood of necessitating additional supplementation than 20% mannitol. Furthermore, the diuretic effect of HS was weak and the increase in electrolyte levels during surgery was temporary and slight.

Volume Calibration with Cardiac MRI vs Hypertonic Saline for Right Ventricular Pressure-Volume Loops with Exercise: Impact on ventricular function and ventricular-vascular coupling.

Right ventricular (RV) pressure-volume (PV) loops require post-acquisition volume calibration by cardiac MRI (CMR) or hypertonic saline (HS). We defined the impact of these two volume calibration methods on rest-to-exercise ventricular contractility (end-systolic elastance: Ees), arterial afterload (Ea) and coupling (Ees/Ea). In a prospective study, 82 RV PV-loop datapoints (rest, exercise stages-every 25watts and recovery) and CMR were acquired in 19 participants. In comparison to CMR, HS-based calibration over-estimated RV end-systolic volume at rest, mean (SD) by +38 mL (48) and end-diastolic volume by +46 mL (68), resulting in underestimated RVEF by -8%. However, Ees and Ea were similar at rest (r2=0.76 and 0.71 respectively, p<0.001 for both) and Ees:Ea was identical (r2=1.00, p<0.001). Exercise metrics also remained similar: RV reserve (ΔEes) and change in coupling (ΔEes/Ea). In comparison to CMR (gold-standard), HS-based calibration under-estimates RVEF at rest, however it is a robust approach for measuring coupling and RV reserve.

No Benefit of 3% Hypertonic Saline Following Experimental Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a stroke subtype with a high mortality rate (~ 40%). After ICH, the mass effect of the hematoma and edema contribute to raised intracranial pressure (ICP) and poor outcome. Endogenous compensatory mechanisms that blunt ICP elevations include redirection of venous blood and cerebrospinal fluid, along with brain tissue compliance (e.g., decreased cell volume, increased cell density); however, these limited reserves can be exhausted after severe stroke, resulting in decompensated ICP that requires careful clinical management. Management strategies can include administration of hypertonic saline (HTS), an osmotic agent that putatively attenuates edema, and thereby ICP elevations. Evidence regarding the efficacy of HTS treatment following ICH remains limited. In this study, adult male rats were given a collagenase-induced striatal ICH and a bolus of either 3% HTS or 0.9% saline vehicle at 2- and 14-hours post-stroke onset. Neurological deficits, edema, ipsilateral cell volume and density (in areas S1 and CA1), and contralateral CA1 ultrastructural morphology were assessed 24 h post-ICH. Animals had large bleeds (median 108.2 µL), extensive edema (median 83.9% brain water content in ipsilateral striatum), and evident behavioural deficits (median 5.4 neurological deficit scale score). However, HTS did not affect edema (p ≥ 0.4797), behaviour (p = 0.6479), cell volume (p ≥ 0.1079), or cell density (p ≥ 0.0983). Qualitative ultrastructural assessment of contralateral area CA1 suggested that HTS administration was associated with paradoxical cellular swelling in ICH animals. Overall, there was no benefit with administering 3% HTS after ICH.

Effectiveness of hypertonic saline with or without hyaluronic acid among patients with cystic fibrosis: a systematic review and meta-analysis.

Background: The clinical effectiveness of hypertonic saline (HS) in individuals with cystic fibrosis (CF) can be compromised by adverse effects. The objective of this study was to examine the efficacy of hyaluronic acid (HA) in mitigating these negative occurrences. Methods: A comprehensive review of the literature was carried out using three electronic databases: Medline, Cochrane Central, and Embase. This systematic review and meta-analysis investigate the efficacy of hypertonic saline (HS) with and without hyaluronic acid (HA) in treating cystic fibrosis. Primary outcomes include the incidence of cough, throat irritation, unpleasant taste, and changes in FEV1. Our findings suggest that adding HA to HS significantly reduces adverse effects and enhances patient tolerability, marking a potential improvement in cystic fibrosis therapy. Risk ratios (RRs) and mean differences (MDs) with 95% CI were used to present evaluations. The quality of RCTs was evaluated using the Cochrane Risk of Bias Tool (CRBT). The quality of the observational study was evaluated using the Newcastle-Ottawa Scale. Results: From the 1960 articles retrieved from the initial search, five relevant studies (n=236 patients) were included in the final analysis. Compared with patients only on HS, patients with HS and HA were significantly less likely to experience cough (RR: 0.45; 95% CI, 0.28-0.72, P=0.001), throat irritation (RR: 0.43; 95% CI, 0.22-0.81, P=0.009), and unpleasant smell (RR: 0.43; 95% CI, 0.23-0.80, P=0.09). In addition, patients with HS with HA had significantly less forced expiratory volume (FEV1) (MD: -2.97; 95% CI, -3.79--2.15, P=0.52), compared to patients only on HS. Patients on HA + HS had significantly lower rates of cough (RR: 0.45; 95% CI, 0.28-0.72, P=0.001), throat irritation (RR: 0.43; 95% CI, 0.22-0.81, P=0.009), and bad smell (RR: 0.43; 95% CI, 0.23-0.80, P=0.09) when compared to patients on HS alone. Furthermore, compared to patients solely on HS, patients with HS plus HA exhibited a substantially lower forced expiratory volume (FEV1) (MD: -2.97; 95% CI, -3.79 to -2.15, P=0.52) as well. Conclusion: For CF patients who need ongoing HS therapy and have a history of poor therapy tolerance, adding HA is beneficial.

The Effect of Hypertonic Saline Nebulization on Arterial Blood Gas Parameters Among Patients on a Mechanical Ventilator.

Introduction Care of the airway is an essential part of the management of patients receiving mechanical ventilation. If the airway is not properly managed, an endotracheal airway can result in retained secretions, airway obstructions, and infections. These complications may prolong mechanical ventilation duration and length of hospital stay and may increase the cost of affordability. Hypertonic saline nebulized suctioning is a technique used to lessen the duration of mechanical air flow and enhance airway clearance, which helps patients on mechanical ventilation breathe easier. Aim The objective of the study is to assess the effectiveness of nebulization with hypertonic saline on arterial blood gas parameters among mechanically ventilated patients. Methods The quasi-experimental design adopted with thirty-five mechanically ventilated samples was chosen using a non-probability purposive sample technique. Following the pre-test in the endotracheal tube, nebulization was given with 2 ml of hypertonic saline over 15-20 mins, two times each day, to the mechanically ventilated patients. Post-test was carried out about 15-20 minutes after the procedure using arterial blood gas analysis results were obtained and interpreted. Results The study reveals that the p values corresponding to the arterial blood gas parameters PCo2, pO2, and HCo3 are less than 0.01 and are significant at a 1% level, and arterial blood gas (ABG) pH is less than 0.05 and is significant at a 5% level; hence there is a high significant difference between the pre-test and post-test mean scores of arterial blood gas parameters PCo2, pO2, HCo3, and ABG pH. Hence, the study concluded that nebulization with hypertonic saline for patients with mechanical ventilators is more effective in improving arterial blood gas parameters.

Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial.

BACKGROUND: Highly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up. METHODS: We electronically surveyed SIMPLIFY participants every 4 weeks for 24 weeks after trial completion but before the main trial results were publicly disclosed. We asked them how often they used medications during the previous week. We estimated covariate-adjusted odds ratios (ORs) of DA or HS non-use by logistic regression with generalized estimating equations. RESULTS: After exclusions mostly due to lack of any surveys, 472 participants were included in the analysis population, 181 from the HS trial and 291 from the DA trial. Approximately half of the analysis population completed all six surveys. At every month of follow-up in both trials, the percentage of individuals reporting non-use of DA or HS during the previous week was greater among those randomized to discontinue therapy. Among participants with responses at 24 weeks, 30/122 (24.6 %) in the HS trial and 79/222 (35.6 %) in the DA trial reported non-use of the respective study medication. After adjusting for covariates, participants randomized to discontinue DA were 8.7-times (95 % CI: 4.3-17.7) more likely to not use DA during follow-up than those randomized to continue DA, and participants randomized to discontinue HS were 5.2-times (95 % CI: 2.1-12.8) more likely to not use HS during follow-up compared to those randomized to continue. CONCLUSIONS: In healthy pwCF on ETI, randomization to discontinue DA or HS during SIMPLIFY was associated with greater odds of not using each medication after the trial compared to randomization to continue. These findings suggest that participation in a treatment discontinuation trial can influence participants' post-trial treatment decisions. This possibility may be relevant during discussions about research participation and clinical care.

Efficacy of hypertonic saline in treatment of corneal edema: A randomized crossover trial.

Background: To determine the efficacy of sodium chloride (NaCl) 5% drops in comparison to 6% ointment and study tear Osmolarity as an objective measure correlating with clinical findings in the treatment of corneal edema. Methods: This is a prospective, randomized, interventional, open-label, crossover study of 40 eyes of 40 patients with corneal edema due to Bullous keratopathy and Fuchs endothelial dystrophy. Subjects were divided into 2 groups by simple randomization: group A received NaCl 5% drops and group B received NaCl 6% ointment. Both treatments were administered four times daily for seven days. Subsequently, after a 1-week wash-out period, switch over of treatment was done. Central corneal thickness (CCT) and tear osmolarity were primarily efficacy variables. Results: Baseline parameters were comparable. The median reduction in CCT from baseline (706.7 ± 58.41 µm), at 6 hours with NaCl 5% drops was 23 µm (-27, 74) and that with NaCl6% ointment was 37.5 µm (-7, 85). The reduction in CCT was more with 6% ointment (p = 0.013). The difference in reduction in CCT between two treatments at one week was not statistically significant, although there was a substantial reduction in thickness with each treatment individually. The change in tear osmolarity from the baseline at 2 Hours with both NaCl5% drops and 6% ointment was significant, and it remained so till 6 h. Side-effects such as stickiness, stinginess, blurring, and foreign body sensation were more with 6% eye ointment. Conclusion: Topical NaCl 6% eye ointment in QID dosage is more effective than NaCl 5% drops in the medical management of corneal edema. In patients symptomatically intolerant to ointment, NaCl 5% eye drops may be prescribed as an effective option.

Hypertonic saline and heart failure: "sodium-centric" or "chlorine-centric"?

Up to 50% of patients admitted for heart failure (HF) have congestion at discharge despite diagnostic and therapeutic advances. Both persistent congestion and diuretic resistance are associated with worse prognosis. The combination of hypertonic saline and loop diuretic has shown promising results in different studies. However, it has not yet achieved a standardized use, partly because of the great heterogeneity in the concentration of sodium chloride, the dose of diuretic or the amount of sodium in the diet. Classically, the movement of water from the intracellular space due to an increase in extracellular osmolarity has been postulated as the main mechanism involved. However, chloride deficit is postulated as the main up-regulator of plasma volume changes, and its correction may be the main mechanism involved. This "chloride centric" approach to heart failure opens the door to therapeutic strategies that would include diuretics to correct hypochloremia, as well as sodium free chloride supplementation.

Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis.

Background: Nontraumatic brain injury encompasses various pathological processes and medical conditions that result in brain dysfunction and neurological impairment without direct physical trauma. The study aimed to assess the efficacy of intravenous administration of 20% mannitol and 3% hypertonic saline to reduce intracranial pressure in nontraumatic brain injury. Materials and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed for study selection and data extraction. The search was conducted in the PubMed, Embase, and Scopus databases, including articles published in English from January 2003 to December 2023. Our study included randomized controlled trials, comparative studies, prospective analyses, and retrospective cohort studies. We extracted data on baseline characteristics of patients, intervention details, major outcomes, and complications. Quality assessment was performed using the Jadad scale and the Robvis assessment tool for risk of bias. Results: A total of 14 studies involving 1,536 patients were included in the analysis. Seven studies reported hypertonic saline as more effective in reducing intracranial pressure, while three studies found similar effectiveness for both interventions. Adverse events were reported in only three studies. The studies that reported complication rates ranged from 21 to 79%. A meta-analysis was conducted on five studies, showing varying rates of adverse events associated with mannitol and hypertonic saline. Conclusion: Both hypertonic saline solution and mannitol have been explored as treatment options for decreasing intracranial pressure in nontraumatic brain injuries. While some studies indicate the superiority of hypertonic saline, others report similar effectiveness between the two interventions. How to cite this article: Choudhury A, Ravikant, Bairwa M, Jithesh G, Kumar S, Kumar N. Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(7):686-695.

Efficacy and safety of hypertonic saline therapy in ambulatory patients with heart failure: The SALT-HF trial.

AIMS: Combination of hypertonic saline solution (HSS) with intravenous loop diuretics has been suggested to improve diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this approach in the ambulatory setting remain unexplored. METHODS AND RESULTS: In this multicentre, double-blind, randomized study, we allocated ambulatory patients with worsening heart failure (WHF) to a 1-h infusion of intravenous furosemide (ivFurosemide)-HSS versus ivFurosemide. The primary endpoint was the volume of diuresis at 3 h. Secondary endpoints included 3-h natriuresis and weight variation, 7-day congestion data, kidney function and electrolytes, and 30-day clinical events. Overall, 167 participants (median age: 81 years, 30.5% female) were randomized across 13 sites between December 2020 and March 2023. There were no differences in 3-h diuresis between treatments (ivFurosemide-HSS: 1099 ml vs. ivFurosemide: 1103 ml, p = 0.963), 3-h natriuresis (∆ +2.642 mEq/L, p = 0.559), or 3-h weight (∆ +0.012 kg, p = 0.920). Patients in the ivFurosemide-HSS arm experienced significant weight decrease at 7 days (Δ -0.586 kg, p = 0.048). There were no between-treatment differences in clinical congestion score, biomarkers, inferior vena cava diameter, or the presence of lung ultrasound B-lines. At 30 days, 26.5% of the patients in the ivFurosemide-HSS group versus 33.3% in the ivFurosemide group experienced WHF (hazard ratio 0.76, p = 0.330). The incidence of death from any cause or HF hospitalization was 6% of patients in the ivFurosemide-HSS group and 8.3% of patients in the ivFurosemide group (hazard ratio 0.69, p = 0.521). The incidence of worsening kidney function or metabolic derangements was not significantly different in the two arms. CONCLUSIONS: A single infusion of ivFurosemide-HSS did not improve 3-h diuresis or congestion parameters in patients with ambulatory WHF. This therapy showed an appropriate safety profile.

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.

Use of hypertonic saline in severe symptomatic hyponatraemia; results from a national survey of endocrinologists in the United Kingdom.

BACKGROUND: Severe symptomatic hyponatraemia is potentially life-threatening and hypertonic saline (HTS) is effective at rapidly correcting serum sodium. Several clinical guidelines have aimed to standardise the administration of HTS. However, evidence supporting the guidelines is limited, and concerns have been raised regarding the potential for overcorrection. OBJECTIVE: To assess the practices and perceptions surrounding HTS use in severe symptomatic hyponatraemia among United Kingdom (UK) endocrinologists and trainees. METHODS: An anonymous online survey was disseminated to Society for Endocrinology (UK) clinical members between 24/10/2023 and 30/11/2023 using a web-based multiple-choice questionnaire. RESULTS: We received 133 responses with a survey response rate of 8.3% (60.1% consultants, 33.1% trainees, 6.8% others). 85% of respondents employed bolus treatment with HTS only, with 9.8% using both bolus and continuous infusions. Most (53.2%) preferred 150 mL boluses, followed by 100 mL boluses (19.8%), while 5.5% of respondents used weight-based dosage. Commonly used HTS strengths were 2.7% (45.1%), followed by 1.8% (31.6%), while the 3% HTS strength recommended in guidelines was used by 21.8%. Contrary to guidelines, 78.6% did not administer a second bolus without waiting for the sodium result after the first bolus. Moreover, 86% have experience using venous blood gas sodium readings for monitoring. Overcorrection targets defined by 10 and 8 mmol/24 h cut-offs were used by 48.9% and 39.9%, respectively. For definite or anticipated overcorrection, 75.9% preferred 5% dextrose, while 40.6% had experience with desmopressin. CONCLUSION: Significant variation exists in HTS use for severe symptomatic hyponatraemia in the UK. Most clinicians prefer a more cautious approach in administering HTS. These data offer insight into real-life care and call for future research.