Quantification of Budesonide Retained in the Sinonasal Cavity After High-Volume Saline Irrigation in Post-Operative Chronic Rhinosinusitis.

BACKGROUND: Budesonide high-volume saline irrigations (HVSIs) are routinely used to treat chronic rhinosinusitis (CRS) due to improved sinonasal delivery and efficacy compared to intranasal corticosteroid sprays. The off-label use of budesonide is assumed to be safe, with several studies suggesting the systemically absorbed dose of budesonide HVSI is low. However, the actual budesonide dose retained in the sinonasal cavity following HVSI is unknown. The objective of this study was to quantify the retained dose of budesonide after HVSI. METHODS: Adult patients diagnosed with CRS who had undergone endoscopic sinus surgery (ESS) and were prescribed budesonide HVSI were enrolled into a prospective, observational cohort study. Patients performed budesonide HVSI (0.5 mg dose) under supervision in an outpatient clinic, and irrigation effluent was collected. High-performance liquid chromatography was employed to determine the dose of budesonide retained after HVSI. RESULTS: Twenty-four patients met inclusion criteria. The average corrected retained dose of budesonide across the cohort was 0.171 ± 0.087 mg (37.9% of administered budesonide). Increased time from ESS significantly impacted the measured retained dose, with those 3 months post-ESS retaining 27.4% of administered budesonide (P = .0004). CONCLUSION: The retained dose of budesonide in patients with CRS after HVSI was found to be significantly higher than previously estimated and decreased with time post-ESS. Given that budesonide HVSI is a cornerstone of care in CRS, defining the retained dose and the potential systemic implications is critical to understanding the safety of budesonide HVSI.

ACETATE RINGER'S SOLUTION VERSUS NORMAL SALINE SOLUTION IN SEPSIS: A RANDOMIZED, CONTROLLED TRIAL.

ABSTRACT: Background: Normal saline solution (NSS) and Ringer's acetate solution (RAS) are commonly given to critically ill patients as a fundamental fluid therapy. However, the effect of RAS and NSS on sepsis patient outcomes remains unknown. Methods: We conducted a single-center prospective open-label parallel controlled trial to enroll adult patients (>18 years old) diagnosed with sepsis. Participants received either RAS or NSS for intravenous infusion for 5 days. The primary outcome was the incidence of major adverse kidney events within 28 days (MAKE28). Secondary outcomes included 30-/90-day mortality, acute kidney injury, and hyperchloremia. The patients were then reclassified as NSS-only, RAS-only, and RAS + NSS groups according to the type of fluid they had received before enrollment. Thereafter, a secondary post hoc analysis was performed. Results: Two hundred fifty-five septic patients were screened, and 143 patients (51.0% in RAS group and 49.0% in NSS group) were enrolled in the study. Each group received a median of 2 L of fluid administration during five interventional days. Of the patients, 39.3% had received 500 mL (500-1,000 mL) of balanced salt solutions (BSSs) before intensive care unit (ICU) admission. There was no statistical difference among the RAS and NSS group on the primary outcome MAKE28 in the initial analysis (23.3% vs. 20.0%; OR, 1.2 [0.6 to 2.2]; P = 0.69). MAKE28 was observed in 23.3% of RAS-only versus 27.3% of NSS-only group patients (0.82 [0.35-1.94], P = 0.65) in the secondary post hoc analysis. The patients in the NSS-only group had a longer invasive mechanical ventilation days and a trend toward the accumulation of serum chloride. Conclusion: This study observed no statistically significant difference on MAKE28 and secondary outcomes among sepsis patients receiving RAS and NSS. However, it is unclear whether the large amount of fluid resuscitation before ICU admission and carrier NSS narrowed the difference between BSSs and NSSs.

Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Protective Effects of Sesamol on Renal Ischemia-Reperfusion Injury Via Regulation of Nuclear Factor Erythroid 2-Related Factor 2 Pathway.

BACKGROUND: Sesamol is a natural antioxidant known for its potent antioxidant and free radical scavenging properties. This study aimed to explore the therapeutic effects and underlying mechanisms of sesamol in the development of renal ischemia-reperfusion injury (IRI) in mice. METHODS: C57BL/6J wild-type mice were divided into 3 groups: IR group, treated with normal saline after undergoing the IRI procedure; Sesamol + IR group, treated with 30 mg/kg/d of sesamol after the IRI procedure; and Sham group, treated with normal saline but not subjected to the IRI process. Renal IRI was induced by performing a right kidney nephrectomy and subjecting the left kidney to 30-minute ischemia, followed by 24-hour reperfusion. Kidney tissues and serum were collected 24 hours post-IRI to assess the impact of sesamol on renal function after IRI. Serum creatinine and blood urea nitrogen levels were assessed, and renal cell apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. The levels of interleukin 1ß and interleukin 18 in kidney tissues, as well as indicators of oxidative stress, were also measured. Furthermore, Nrf2-deficient mice were used to examine the protective function of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by sesamol, as determined by western blot assay. RESULTS: Sesamol demonstrated significant improvement in renal function, along with reductions in renal tubular injury, cell necrosis, and apoptosis in mice. It also effectively lowered key inflammatory mediator levels. Sesamol exhibited antioxidant properties by reducing malondialdehyde levels and enhancing superoxide dismutase activities 24 hours after IRI. Western blot assay revealed increased Nrf2, HO-1, and NQO-1 protein levels with sesamol treatment. Notably, Nrf2-deficient mice did not exhibit the beneficial effects of sesamol. CONCLUSIONS: This study demonstrates that sesamol effectively alleviates renal IRI by enhancing antioxidant defenses and reducing inflammation potentially through the Nrf2/HO-1 and NQO1 signaling pathways.

Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C-reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

A CONSORT-guided, randomized controlled clinical trial of nebulized administration of dexamethasone and saline on lower airway cytokine mRNA expression in horses with moderate asthma.

BACKGROUND: Nebulized administration of dexamethasone on cytokine regulation in horses with moderate asthma has not been investigated. OBJECTIVE: To investigate the changes in expression of inflammatory cytokine mRNA after nebulized administration of dexamethasone treatment of horses with moderate asthma. ANIMALS: Horses with naturally occurring moderate asthma (n = 16) and healthy control horses (n = 4). All horses were kept in a dusty environment during the study. METHODS: Prospective, parallel, randomized, controlled, blinded clinical trial. Blood endogenous cortisol, tracheal mucus, and bronchoalveolar lavage (BAL) were sampled before and after 13 days treatment with either nebulized administration of dexamethasone (15 mg once daily) or 0.9% saline (3 mL). Treatment groups were randomly allocated via randomization function (Microsoft Excel). Amplification of target mRNA in BAL fluid (IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23, IFN-γ, Eotaxin-2, and TNF-α) was achieved by qPCR, and the relative expression software tool was used to analyze BAL inflammatory cytokine mRNA. RESULTS: Horses treated with nebulized administration of dexamethasone had increased relative expression of IL-5 (1.70-fold), IL-6 (1.71-fold), IL-17 (3.25-fold), IL-12 (1.66-fold), and TNF-α (1.94-fold), and decreased relative expression of IL-23 (1.76-fold; P = .04) in samples collected on Day 14, in comparison to samples collected on Day 0 (all P < .05). Horses treated with nebulized administration of saline had no significant difference in the relative expression of any gene (all P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Nebulized administration of dexamethasone was associated with increased expression of inflammatory cytokine mRNA. There was no improvement in inflammatory airway cytology associated with either dexamethasone or saline treatment.

Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size. METHODS: This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment-elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up. RESULTS: A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8-423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0-66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%; P<0.001) and Thrombolysis in Myocardial Infarction flow grade 3 (51.0% versus 18.0%; P<0.001) and had smaller infarct size (21.91±10.84% versus 26.85±12.37%; P=0.016). There was no increase in major bleeding (r-SAK, 1.0% versus control, 3.0%; P=0.616). CONCLUSIONS: A single bolus r-SAK before primary PCI for ST-segment-elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05023681.

Normal saline for children with bronchiolitis: study protocol for a randomised controlled non-inferiority trial.

INTRODUCTION: Bronchiolitis is one of the most common reasons for hospital admissions in early childhood. As supportive treatment, some treatment guidelines suggest using nasal irrigation with normal saline (NS) to facilitate clearance of mucus from the airways. In addition, most paediatric departments in Denmark use nebulised NS for the same purpose, which can mainly be administered as inpatient care. However, no studies have ever directly tested the effect of saline in children with bronchiolitis. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, randomised, controlled non-inferiority trial and will be performed at six paediatric departments in eastern Denmark. We plan to include 300 children aged 0-12 months admitted to hospital with bronchiolitis. Participating children are randomised 1:1:1 to nebulised NS, nasal irrigation with NS or no saline therapy. All other treatment will be given according to standard guidelines.The primary outcome is duration of hospitalisation, analysed according to intention-to-treat analysis using linear regression and Cox regression analysis. By including at least 249 children, we can prove non-inferiority with a limit of 12 hours admission, alpha 2.5% and a power of 80%. Secondary outcomes are need for respiratory support with nasal continuous positive airway pressure or high-flow oxygen therapy and requirement of fluid supplements (either by nasogastric tube or intravenous). ETHICS AND DISSEMINATION: This study may inform current practice for supportive treatment of children with bronchiolitis. First, if NS is found to be helpful, it may be implemented into global guidelines. If no effect of NS is found, we can stop spending resources on an ineffective treatment. Second, if NS is effective, but nasal irrigation is non-inferior to nebulisation, it may reduce the workload of nurses, and possible duration of hospitalisation because the treatment can be delivered by the parents at home. TRIAL REGISTRATION NUMBER: NCT05902702.

Dexmedetomidine and magnesium sulfate in preventing junctional ectopic tachycardia after pediatric cardiac surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) is a serious tachyarrhythmia following pediatric cardiac surgery. It isn't easy to treat and better to be prevented. This study aimed to examine the prophylactic effects of dexmedetomidine, MgSO4, or their combination in reducing JET following pediatric open cardiac surgery. METHODS: Hundred and twenty children under 5 years, weighing more than 5 kg, who were scheduled for corrective acyanotic cardiac surgeries were randomized into three groups. Group MD (Dexmedetomidine-MgSO4 group): received dexmedetomidine 0.5 µg/kg IV over 20 min after induction, then infusion 0.5 µg/kg/h for 72 h, and 50 mg/kg bolus of MgSO4 with aortic cross-clamp release, then continued administration for 72 h postoperatively at a dose of 30 mg/kg/day. Group D (the dexmedetomidine group) received the same dexmedetomidine as the MD group in addition to normal saline instead of MgSO4. Group C (control group): received normal saline instead of dexmedetomidine and MgSO4. The primary outcome was the detection of JET incidence; the secondary outcomes were hemodynamic parameters, ionized Mg, vasoactive-inotropic score, extubation time, PCCU and hospital stay, and perioperative complications. RESULTS: The incidence of JET was significantly reduced in Group MD and Group D (p = .007) compared to Group C. Ionized Mg was significantly higher in Group MD than in Groups D and C during rewarming and in the ICU (p < .001). Better hemodynamic profile in Group MD compared to Group D and Group C throughout surgery and in the ICU, the predictive indexes were significantly better in Group MD than in Groups D and C (p < .001). Including the extubation time, PCCU, and hospital stay. CONCLUSION: Dexmedetomidine alone or combined with MgSO4 had a therapeutic role in the prevention of JET in children after congenital heart surgery.

A randomized, blinded, placebo-controlled, prospective clinical study to evaluate the effectiveness of a diluted liposomal-encapsulated bupivacaine suspension in dogs undergoing a ventral midline celiotomy.

Objective: To evaluate the effectiveness of a liposomal-encapsulated bupivacaine suspension (LEBS; Nocita), at a 1:5 dilution with 0.9% NaCl, for the reduction of postoperative pain scores and a related reduction in the need for postoperative opioids in dogs undergoing ventral midline celiotomy. Hypothesis: When infused at a 1:5 dilution, LEBS results in less postoperative pain (as indicated by pain scale scores), and a reduction in postoperative opioids, in dogs undergoing ventral midline celiotomy. The use of LEBS does not affect wound healing when compared to placebo. Study design: This was a randomized, blinded, prospective clinical trial. Animals: We studied 40 client-owned dogs undergoing abdominal surgery via a ventral midline celiotomy. Procedure: Dogs undergoing a ventral midline celiotomy were enrolled and randomly allocated to 1 of 2 groups: those receiving LEBS or a placebo injection protocol into tissue planes during closure. The Glasgow Composite Pain Scale-Short Form (GCPS-SF) was used by an observer blinded to the treatment group to assess patients at 0, 1, 2, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 h after extubation. Dogs with a score of ≥ 3 in any single category or ≥ 6 total were given a rescue analgesia. Data were analyzed to compare the number of rescue therapy doses administered between the 2 treatment groups. Results: Forty dogs completed the study. Dogs that received a diluted LEBS protocol were equally likely to require a rescue therapy as those that received the placebo (0.9% NaCl). There were no significant difference in the pain scores or the total number of opioid injections required between the 2 treatment groups. Conclusion and clinical relevance: In dogs undergoing ventral midline celiotomy, 1:5 diluted LEBS administration alone should not be considered the sole method of pain relief. Liposomal-encapsulated bupivacaine suspension should be used in conjunction with systemic opioids as part of a multimodal analgesic regime. This multimodal approach would allow a reduction in dose or frequency of opioids, therefore lessening the undesired side effects associated with opioids while also decreasing client costs.

Une étude clinique prospective, randomisée, en aveugle, contrôlée par placebo, visant à évaluer l'efficacité d'une suspension diluée de bupivacaïne encapsulée dans des liposomes chez des chiens subissant une cœliotomie via la ligne médiane ventrale. Objectif: Évaluer l'efficacité d'une suspension de bupivacaïne encapsulée dans des liposomes (LEBS; Nocita), à une dilution de 1:5 avec 0,9 % de NaCl, pour la réduction des scores de douleur postopératoire et une réduction connexe du besoin d'opioïdes postopératoires chez des chiens subissant une céliotomie via la ligne médiane ventrale. Hypothèse: Lorsqu'il est perfusé à une dilution de 1:5, LEBS entraîne moins de douleur postopératoire (comme l'indiquent les scores de l'échelle de douleur) et une réduction des opioïdes postopératoires chez les chiens subissant une cœliotomie via la ligne médiane ventrale. L'utilisation du LEBS n'affecte pas la cicatrisation des plaies par rapport au placebo. Design expérimental: Il s'agissait d'un essai clinique prospectif, randomisé et en aveugle. Animaux: Nous avons étudié 40 chiens appartenant à des clients subissant une chirurgie abdominale par cœliotomie via la ligne médiane ventrale. Procédure: Les chiens subissant une cœliotomie via la ligne médiane ventrale ont été recrutés et répartis au hasard dans 1 groupe sur 2 : ceux recevant du LEBS ou un protocole d'injection de placebo dans les plans tissulaires pendant la fermeture. Le Glasgow Composite Pain Scale-Short Form (GCPS-SF) a été utilisé par un observateur aveugle au groupe de traitement pour évaluer les patients à 0, 1, 2, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 et 72 h après l'extubation. Les chiens avec un score ≥ 3 dans n'importe quelle catégorie ou ≥ 6 au total ont reçu une analgésie de secours. Les données ont été analysées pour comparer le nombre de doses de thérapie de secours administrées entre les 2 groupes de traitement. Résultats: Quarante chiens ont complété l'étude. Les chiens ayant reçu un protocole LEBS dilué étaient tout aussi susceptibles de nécessiter une thérapie de secours que ceux ayant reçu le placebo (NaCl à 0,9 %). Il n'y avait aucune différence significative dans les scores de douleur ou le nombre total d'injections d'opioïdes nécessaires entre les 2 groupes de traitement. Conclusion et pertinence clinique: Chez les chiens subissant une cœliotomie via la ligne médiane ventrale, l'administration de LEBS dilué à 1:5 seule ne doit pas être considérée comme la seule méthode de soulagement de la douleur. La suspension de bupivacaïne encapsulée dans des liposomes doit être utilisée en association avec des opioïdes systémiques dans le cadre d'un régime analgésique multimodal. Cette approche multimodale permettrait de réduire la dose ou la fréquence des opioïdes, réduisant ainsi les effets secondaires indésirables associés aux opioïdes tout en diminuant également les coûts pour les clients.(Traduit par Dr Serge Messier).

Heparin vs Saline Infusion to Maintain Patency of Arterial Catheters in Children: A Randomized, Double-Blind, Noninferiority Trial.

OBJECTIVE: To determine whether normal saline flush solution is noninferior to heparinised saline for maintaining the patency of arterial intravascular catheters in children. METHODS: A single centre, double blind, parallel group, noninferiority, randomized control study was conducted in the Pediatric Intensive Care Unit of Kanchi Kamakoti CHILDS Trust hospital, a tertiary children's hospital, Chennai, India. 92 children requiring arterial catheters for more than 12 hours were randomized to receive either normal saline or heparinized saline (1 U/ml) flush solution. Primary outcome was a noninferiority comparison between normal saline and heparinised saline in maintaining the patency of arterial catheters using the proportion of occlusion of arterial catheters as primary endpoint. Secondary outcome was mean duration of patency of arterial catheters in each treatment group. RESULTS: Ninety-two children with a median (interquartile range, age of 84 (33.5-132) months and 52% males were enrolled. 15.2% of catheters in the heparin group and 17.4% of catheters in the normal saline group were occluded (P = 0.77). The 95% upper confidence interval for the difference in proportion was 0.148 (+14.8%), establishing noninferiority (< 15%). The median (IQR) duration of a patent arterial catheter was 47 (27.75 - 94.5) hours in the heparin group and 35.50 (24.50 - 62) hours in the normal saline group (P = 0.10). Comparison of duration of patency using Kaplan Meier survival analysis and log rank test showed no statistically significant difference. There were no serious adverse events noted in either group. CONCLUSIONS: Our data suggests that normal saline is noninferior to heparinized saline infusion in maintaining the patency of arterial lines in children. This may benefit clinicians worldwide as normal saline would be a safer and cost-effective option.

Balanced crystalloids versus saline for critically ill patients (BEST-Living): a systematic review and individual patient data meta-analysis.

BACKGROUND: The effect of balanced crystalloids compared with that of saline in critically ill patients overall and in specific subgroups is unclear. We aimed to assess whether use of balanced solutions, compared with 0·9% sodium chloride (saline), decreased in-hospital mortality in adult patients in intensive care units (ICUs). METHODS: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, and CENTRAL databases from inception until March 1, 2022 (updated Sept 1, 2023) for individually randomised and cluster-randomised trials comparing balanced solutions with saline for adult patients in the ICU. Eligible trials were those that allocated patients to receive balanced solutions or saline for fluid resuscitation and maintenance fluids, or for maintenance fluids only; and administered the allocated fluid throughout ICU admission or, for trials using landmark mortality as their primary outcome, until the timepoint at which mortality was assessed (if ≥28 days). Authors of eligible trials were contacted to request individual patient data. Data obtained from eligible trials were merged, checked for accuracy, and centrally analysed by use of Bayesian regression models. The primary outcome was in-hospital mortality. Prespecified subgroups included patients with traumatic brain injury. This study was registered with PROSPERO (CRD42022299282). FINDINGS: Our search identified 5219 records, yielding six eligible randomised controlled trials. Data obtained for 34 685 participants from the six trials, 17 407 assigned to receive balanced crystalloids and 17 278 to receive saline, were included in the analysis. The mean age of participants was 58·8 years (SD 17·5). Of 34 653 participants with available data, 14 579 (42·1%) were female and 20 074 (57·9%) were male. Among patients who provided consent to report in-hospital mortality, 2907 (16·8%) of 17 313 assigned balanced solutions and 2975 (17·3%) of 17 166 assigned saline died in hospital (odds ratio [OR] 0·962 [95% CrI 0·909 to 1·019], absolute difference -0·4 percentage points [-1·5 to 0·2]). The posterior probability that balanced solutions reduced mortality was 0·895. In patients with traumatic brain injury, 191 (19·1%) of 999 assigned balanced and 141 (14·7%) of 962 assigned saline died (OR 1·424 [1·100 to 1·818], absolute difference 3·2 percentage points [0·7 to 8·7]). The probability that balanced solutions increased mortality in patients with traumatic brain injury was 0·975. In an independent risk of bias assessment, two trials were deemed to be at low risk of bias and four at high risk of bias. INTERPRETATION: The probability that using balanced solutions in the ICU reduces in-hospital mortality is high, although the certainty of the evidence was moderate and the absolute risk reduction was small. In patients with traumatic brain injury, using balanced solutions was associated with increased in-hospital mortality. FUNDING: HCor (Brazil) and The George Institute for Global Health (Australia).

Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial.

PURPOSE: Fluid use could modulate the effect of balanced solutions (BS) on outcome of intensive care unit (ICU) patients. It is uncertain whether fluid use practices are driven more by patient features or local practices. It is also unclear whether a "dose-response" for the potential benefits of balanced solutions exists. METHODS: The secondary analysis of the Balanced Solution in Intensive Care Study (BaSICS) compared 0.9% saline versus Plasma-Lyte 148® (BS) for fluid therapy in the ICU. The relative contribution of patient features and enrolling site (the random effect) on the volume of fluid used up to day 3 after admission was assessed using different methods, including a Bayesian regression, a frequentist mixed model, and a random forest, all adjusted for relevant patient confounders. Subsequently, a variety of methods were used to assess whether volume of fluid used modulated the effect of BS on 90-day mortality, including a traditional subgroup analysis for patients that remained alive and in the ICU up to 3 days, a Bayesian network accounting for competing risks, and an analysis based on site practices. RESULTS: 10,505 patients were analyzed. Median fluid use in the BS arm and in the 0.9% saline arm were 2500 mL and 2488 mL, respectively. The random effect in the Bayesian regression explained 0.32 (95% credible intervals (CrI) 0.24-0.41) of all model variance (0.33, 95% credible intervals from 0.32-0.35). Frequentist and random forest models produced similar results. In the analysis including only patients alive and in the ICU at 3 days, there was a strong suggestion of interaction between fluid use and the effect of BS, driven mostly by a lower mortality with BS compared to 0.9% saline as fluid use increased for patients with sepsis. These results were consistent in the Bayesian network analysis and in an analysis based on site practices, where septic patients enrolled to BS at high fluid use sites had a lower mortality (absolute risk reduction of - 0.13 [95% credible interval - 0.27 to - 0.01]; 0.98 probability of benefit). CONCLUSION: Baseline patient characteristics collected in the BaSICS trial explain less of the variance of fluid use during the first 3 days than the enrolling site. Volume of fluid used and the effects of BS appear to interact, mostly in the sepsis subgroup where there was a strong association between fluid use after enrollment and the effect of BS on 90-day mortality.

Comparison of Fluid Resuscitation with Lactate Ringer's Versus Normal Saline in Acute Pancreatitis: An Updated Meta-Analysis.

BACKGROUND: Fluid resuscitation is one of the main therapies for acute pancreatitis (AP). There is still no consensus on the type of fluid resuscitation. This study investigated the differences between lactate Ringer's (LR) and normal saline (NS) in treating AP. METHODS: Two authors systematically searched Web of Science, Embase (via OVID), Cochrane Library, and PubMed to find all published research before July, 2023. The odds of moderately severe/severe AP and intensive care unit (ICU) admission are set as primary endpoints. RESULTS: This meta-analysis included 5 RCTs and 4 observational studies with 1424 AP patients in LR (n = 651) and NS (n = 773) groups. The results suggested that the odds of moderately severe/severe AP (OR 0.48; 95%Cl 0.34 to 0.67; P < 0.001) and ICU admission (OR 0.37; 95%Cl 0.16 to 0.87; P = 0.02) were lower in the LR group compared to NS group. In addition, the LR group had lower rates of local complications (OR 0.54; 95%Cl 0.32 to 0.92; P = 0.02), lower level of CRP, as well as a shorter hospital stay (WMD, - 1.09 days; 95%Cl - 1.72 to - 0.47 days; P < 0.001) than the NS group. Other outcomes, such as mortality, the rate of organ failure, SIRS, acute fluid collection, pancreatic necrosis, pseudocysts, and volume overload, did not differ significantly between two groups (P > 0.05). CONCLUSIONS: LR is preferred over NS as it decreases the odds of moderately severe/severe AP, the rate of ICU admission, local complication, and length of hospital stay. However, large-scale RCT are lacking to support these evidence.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

Ameliorative effect of nebivolol in doxorubicin-induced cardiotoxicity.

This study aimed to investigate the potential of nebivolol in preventing doxorubicin-induced cardiotoxicity by targeting the inflammatory, oxidative, and apoptotic pathways. Twenty-eight male rats were randomly divided into four groups, each consisting of seven rats. The control group received standard diets and unrestricted access to water. The rats in the normal saline (N/S) group were administered a 0.9% normal saline solution for two weeks. The doxorubicin group (the "induced group") received doxorubicin at a dosage of 2.5 mg/kg three times per week for two weeks. The nebivolol group received an oral dose of 4 mg/kg of nebivolol for the same duration. The cardiac tissues of rats treated with doxorubicin exhibited increased levels of tumor necrosis factor, interleukin-1, malondialdehyde, and caspase-3 compared to the normal saline control group (p<0.05), along with decreased levels of total antioxidant capacity and Bcl-2. These results show that doxorubicin is harmful to the heart. The administration of nebivolol significantly reduced the cardiotoxic effects induced by doxorubicin, as indicated by a statistically significant decrease in the levels of inflammatory markers, specifically tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) (p<0.05). The nebivolol group exhibited a significant decrease in malondialdehyde levels, which serves as a signal of oxidation, in cardiac tissue compared to the doxorubicin-only group (p<0.05). Additionally, the nebivolol group showed a significant increase in overall antioxidant capacity. Nebivolol dramatically attenuated doxorubicin-induced cardiotoxicity in rats, likely by interfering with oxidative stress, the inflammatory response, and the apoptotic pathway.

Revisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer.

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing.

Nebulised 3% hypertonic saline versus 0.9% saline for treating patients hospitalised with acute bronchiolitis: protocol for a randomised, double-blind, multicentre trial.

INTRODUCTION: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis. METHODS AND ANALYSIS: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation. ETHICS AND DISSEMINATION: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06069336).

Changes in respiratory mechanics in response to crystalloid infusions in extremely premature infants.

Extremely premature infants are at a higher risk of developing respiratory distress syndrome and circulatory impairments in the first few weeks of life. Administration of normal saline boluses to manage hypotension is a common practice in preterm infants. As a crystalloid, a substantial proportion might leak into the interstitium; most consequently the lungs in the preterm cohorts, putatively affecting ventilation. We downloaded and analyzed ventilator mechanics data in infants managed by conventional mechanical ventilation and administered normal saline bolus for clinical reasons. Data were downloaded for 30 min prebolus, 60 min during the bolus followed by 30 min postbolus. Sixteen infants (mean gestational age 25.2 ± 1 wk and birth weight 620 ± 60 g) were administered 10 mL/kg normal saline over 60 min. The most common clinical indication for saline was hypotension. No significant increase was noted in mean blood pressure after the saline bolus. A significant reduction in pulmonary compliance (mL/cmH2O/kg) was noted (0.43 ± 0.07 vs. 0.38 ± 0.07 vs. 0.33 ± 0.07, P = 0.003, ANOVA). This was accompanied by an elevation in the required peak inspiratory pressure to deliver set volume-guarantee (19 ± 2 vs. 22 ± 2 vs. 22 ± 3 mmHg, P < 0.0001, ANOVA), resulting in a higher respiratory severity score. Normal saline infusion therapy was associated with adverse pulmonary mechanics. Relevant pathophysiologic mechanisms might include translocation of fluid across pulmonary capillaries affected by low vascular tone and heightened permeability in extremes of prematurity, back-pressure effects from raised left atrial volume due to immature left-ventricular myocardium; complemented by the effect of cytokine release from positive pressure ventilation.NEW & NOTEWORTHY Administration of saline boluses is common in premature infants although hypovolemia is an uncommon underlying cause of hypotension. This crystalloid can redistribute into pulmonary interstitial space. In the presence of an immature myocardium and diastolic dysfunction, excess fluid can also be "edemagenic." This study on extremely premature infants (25 wk gestation) noted adverse influence on respiratory physiology after saline infusion. Clinicians need to choose judiciously and reconsider routine use of saline boluses in premature infants.