This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia. Embase, PubMed and Web of Science databases were searched from their inception to February 2024 (INPLASY:202430023). Data on the animal species, stroke model, drug dose, time of treatment, method of administration, study quality, and outcomes were extracted and pooled in a meta-analysis. The combined standardized mean difference (SMD) or mean difference (MD) estimates and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Thirteen eligible studies involving >200 animals fulfilled the inclusion criteria and were included in this meta-analysis. Meta-analyses demonstrated that bumetanide treatment significantly reduced cerebral infarct volume (SMD: -0.42; 95% CI: -0.75, -0.09; p < 0.01; n = 186 animals) and consistently relieved brain edema (SMD: -1.39; 95% CI: -2.06, -0.72; p < 0.01; n = 64 animals). Subgroup analyses demonstrated that bumetanide treatment reduced infarct volume in transient but not permanent cerebral ischemia models. When administered after the stroke, it was more effective than treatment initiation before the stroke. Eight studies assessed the effect of bumetanide on behavioral function and the results showed that bumetanide treatment significantly improved neurobehavioral deficits (SMD: -2.35; 95% CI: -2.72, -1.97; p < 0.01; n = 250 animals). We conclude that bumetanide appears to be effective in reducing infarct volume and brain edema and improving behavioral recovery in animal models of cerebral ischemia. This mechanism needs to be confirmed through further investigation.

UNASSIGNED: Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials.
UNASSIGNED: To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure.
UNASSIGNED: PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide.
UNASSIGNED: Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded.
UNASSIGNED: Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient\'s home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunctive diuretic such as thiazide or acetazolamide should be added. If decongestion targets are not met, continuous infusion of furosemide may be considered.
UNASSIGNED: Heart failure with congestion can be managed with careful administration of high-dose loop diuretics, supported by thiazides and acetazolamide when necessary. Clinical trials are underway to further evaluate this strategy.
UNASSIGNED: L’insuffisance cardiaque est une maladie courante entraînant des coûts, une morbidité et une mortalité considérables. Les patients se présentent souvent à l’hôpital avec une dyspnée et un oedème. Une décongestion inadéquate des patients hospitalisés contribue largement aux taux élevés de réadmission. Il existe peu de données probantes concernant la diurèse pour guider les cliniciens dans la prise en charge des patients atteints d’insuffisance cardiaque aiguë décompensée. Les stratégies diurétiques contemporaines ont été définies par l’opinion d’experts et des essais cliniques de référence plus anciens.
UNASSIGNED: Présenter une revue narrative des recommandations contemporaines, ainsi que leurs données probantes sous-jacentes et leur justification pharmacologique, pour les stratégies diurétiques chez les patients hospitalisés souffrant d’insuffisance cardiaque aiguë décompensée.
UNASSIGNED: Les bases de données PubMed, OVID et Embase ont été consultées depuis leur création jusqu’au 22 décembre 2022, avec les termes de recherche suivants: insuffisance cardiaque, insuffisance cardiaque aiguë, insuffisance cardiaque décompensée, furosémide, bumétanide, acide éthacrynique, hydrochlorothiazide, indapamide, métolazone, chlorthalidone, spironolactone, éplérénone et acétazolamide.
UNASSIGNED: Les essais contrôlés randomisés et les revues systématiques portant sur au moins 100 patients adultes (plus de 18 ans) ont été inclus. Les essais impliquant le torsémide, le chlorothiazide et le tolvaptan ont été exclus.
UNASSIGNED: L’administration précoce et agressive d’un diurétique de l’anse a été associée à une résolution accélérée des symptômes, à une durée de séjour plus courte et éventuellement à une mortalité réduite. Les lignes directrices font des recommandations sur la dose et la fréquence, mais ne recommandent pas un diurétique de l’anse particulier plutôt qu’un autre; cependant, le furosémide est le plus couramment utilisé. Les lignes directrices recommandent que la dose initiale de furosémide à l’admission soit de 2 à 2,5 fois la dose à domicile du patient. Une réponse diurétique satisfaisante peut être définie comme une teneur ponctuelle en sodium dans l’urine supérieure à 50 à 70 mmol/L après 2 heures; débit urinaire supérieur à 100 à 150 mL/h au cours des 6 premières heures ou à 3 à 5 L en 24 heures; ou un changement de poids de 0,5 à 1,5 kg en 24 heures. Si la congestion persiste après la maximisation du traitement par diurétique de l’anse au cours des premières 24 à 48 heures, un diurétique d’appoint tel que le thiazidique ou l’acétazolamide doivent être ajoutés. Si les objectifs de décongestion ne sont pas atteints, une perfusion continue de furosémide peut être envisagée.
UNASSIGNED: L’insuffisance cardiaque accompagnée de congestion peut être gérée par l’administration prudente de diurétiques de l’anse à haute dose, appuyés par des thiazidiques et de l’acétazolamide si nécessaire. Des essais cliniques sont en cours pour évaluer davantage cette stratégie.

BACKGROUND: Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
METHODS: A systematic review of animal and human studies was conducted to evaluate the efficacy and safety of bumetanide for neonatal seizures. PubMed, Embase, CINAHL and Cochrane databases were searched in March 2023.
RESULTS: 26 animal (rat or mice) studies describing 38 experiments (28 in-vivo and ten in-vitro) and two human studies (one RCT and one open-label dose-finding) were included. The study designs, methods to induce seizures, bumetanide dose, and outcome measures were heterogeneous, with only 4/38 experiments being in animal hypoxia/ischaemia models. Among 38 animal experiments, bumetanide was reported to have antiseizure effects in 21, pro-seizure in six and ineffective in 11. The two human studies (n = 57) did not show the benefits of bumetanide as an add-on agent to phenobarbital in their primary analyses, but one study reported benefit on post-hoc analysis. Overall, hearing impairment was detected in 5/37 surviving infants in the bumetanide group vs. 0/13 in controls. Four of the five infants with hearing impairment had received aminoglycosides concurrently. Other adverse effects reported were diuresis, mild-to-moderate dehydration, hypotension, and electrolyte disturbances. The studies did not report on long-term neurodevelopment. The certainty of the evidence was very low.
CONCLUSIONS: Animal data suggest that bumetanide has inconsistent effects as an antiseizure medication in neonates. Data from human studies are scarce and raise some concerns regarding ototoxicity when given with aminoglycosides. Well conducted studies in animal models of hypoxic-ischaemic encephalopathy are urgently needed. Future RCTs, if conducted in human neonates, should have an adequate sample size, assess neurodevelopment, minimize using aminoglycosides, be transparent about the potential ototoxicity in the parent information sheet, conduct early hearing tests and have trial-stopping rules that include hearing impairment as an outcome.

Neonatal stroke is the second cause of acute symptomatic neonatal seizures after hypoxic-ischemic encephalopathy. The aim of this systematic review is to determine which drug among those available represents the best therapeutic choice for treatment of secondary seizures due to neonatal stroke.
We performed a systematic review searching on PubMed the keywords \"Neonatal\", \"Stroke\", \"Seizures\" and \"Treatment\". Search was limited only to English language with no time limit. Last literature search was done on May 30, 2022.
We selected 5 articles involving a total of 52 full-term neonates. In 96.1% the first line treatment was phenobarbital and in 3.9% was used phenobarbital associated with midazolam from the seizure onset but in all of these cases it was necessary to introduce further medications for controlling the seizures. As second line treatment was used lidocaine (response rate of 53.3%), midazolam (response rate of 15.38%) bumetanide (response rate of 100%), and fosphenytoin (no response). As third line treatment was used lidocaine (response rate of 87.5%), Midazolam (response rate of 60%), levetiracetam and clonazepam (response rate of 100%).
Our review shows that the use of ASMs that act throughout a gabaergic mechanism are inadequate in controlling seizures secondary to neonatal stroke in full-term newborns. Very effective seems to be lidocaine and levetiracetam with an apparent safer profile in short and long term. Bumetanide shows promising results, but they need to be confirmed by phase 3 studies.

BACKGROUND: Loop diuretics help to manage the patients with edema associated with congestive heart failure, liver cirrhosis, and renal disease and hypertension. The patients taking loop diuretics may receive other medications to treat comorbidities leading to drug interactions.
METHODS: The literature was searched in databases such as Medline/PMC/PubMed, Google Scholar, Cochrane Library, Science Direct, EMBASE, Web of science, Ebsco, Directory of open access journals (DOAJ) and reference lists were used to spot relevant articles using keywords Drug interactions, Pharmacodynamic interactions, Loop diuretics, Bumetanide, Ethacrynic acid, Furosemide, and Torsemide.
RESULTS: Loop diuretics are associated with hypokalemia, ototoxicity and other adverse effects. The drugs affected by hypokalemia and having the potential of inducing ototoxicity could interact with loop diuretics pharmacodynamically. Loop diuretics can interact with drugs such as amphotericin B, digoxin, angiotensin-converting enzyme inhibitors (ACE inhibitors), antidiabetic drugs, antifungal agents, dobutamine, gossypoland sotalol due to diuretic associated hypokalemia. In addition, the risk of ototoxicity could be enhanced by the concomitant use of loop diuretics and cisplatin, aminoglycoside antibiotics or phosphodiesterase 5 (PDE 5) inhibitors. Loop diuretics may also interact pharmacodynamically with drugs like cephalosporins, ceritinib, levothyroxine, pixantrone, probenecid, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonylureas and herbal drugs.
CONCLUSIONS: Clinicians, pharmacists and other health care providers should take responsibility for the safe use of medications. In addition, they are required to be aware of the drugs interacting with loop diuretics to prevent adverse drug interactions.

Background: The therapeutic effect of bumetanide on autism spectrum disorder (ASD) seems to be controversial. To obtain better evidence on the efficacy of bumetanide, a systematic review and meta-analysis were performed. Methods: Randomized, placebo-controlled trials (RCTs) of bumetanide treatment in children with ASD were identified through systematic review from database inception to January 17, 2021. Subsequently, a meta-analysis was carried out to examine the effect of bumetanide on the severity of symptoms of ASD as assessed by the Childhood Autism Rating Scale (CARS) and Social Responsive Scale (SRS); core symptoms according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 of the American Psychiatric Association [social affect (SA), restricted, repetitive patterns of behavior, interests, or activities (RRB) and sensory symptoms]; and the therapeutic effect as assessed by Clinical Global Impressions-Efficacy (CGI-E). Results: In total, six RCTs involving 496 participants with ASD were identified in our study. The results showed that bumetanide could significantly improve the severity of the ASD symptoms measured by CARS and SRS. There was also evidence that bumetanide had positive effect on the core symptoms of ASD such as the SA and RRB, but there was no statistically significant effect on sensory symptoms. A significant positive effect on CGI-E scores in ASD patients was also observed. Conclusion: Our meta-analysis provided some support that bumetanide could improve the symptoms of children with ASD. However, additional large-scale longitudinal studies that provide clearer information and better control for confounding factors are needed to confirm our findings.

The clinical use of continuous bumetanide infusion for acute heart failure and volume overload is common. However, there is not enough supporting evidence for the use of continuous bumetanide infusion. Thus, we conducted this systematic review and meta-analysis aiming to describe the treatment outcomes of continuous bumetanide infusion. We searched Ovid MEDLINE, EMBASE and the Cochrane Library for eligible publications. Inclusion criteria were patients age ≥18 years with bumetanide infusion for heart failure, acute kidney injury (AKI) or volume overload. From 1564 citations, three studies (n = 94 patients) were included in the systematic review and meta-analysis. The mean dose of bumetanide was 1.08 ± 0.43 mg/hour with a mean treatment duration of 45.09 ± 10.12 hours. Mean urine output in response to continuous bumetanide infusion was 1.88 mL/kg/hour (95% confidence interval [CI], 1.72-2.05). The incidence of AKI with continuous bumetanide infusion was 24.7% (95% CI, 8.2-54.6). By using Pearson\'s correlation coefficient, increasing doses of bumetanide were correlated with increased urine output (P = .026) and increased incidence of AKI (P < .01). There was no correlation between increasing urine output and the incidence of AKI (P = .739). In conclusion, with available evidence, continuous bumetanide infusion may be used in the treatment of acute heart failure or volume overload with close monitoring for new-onset or worsening AKI.

UNASSIGNED: Autism Spectrum Disorder (ASD) is characterized by several impairments in communications and social interactions, as well as restricted interests or stereotyped behaviors. Interventions applied for this disorder are based on multi-modal approaches, including pharmacotherapy. No definitive cure or medication has been introduced so far; therefore, researchers still investigate potential drugs for treating ASD. One of the new medications introduced for this purpose is bumetanide. The present article aimed to review the efficacy of this drug on the core symptoms of ASD and its potential side effects.
UNASSIGNED: We searched all papers reported on pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of bumetanide on animal models and humans with ASD. The papers were extracted from the main databases of PubMed, Web of Science, and Scopus.
UNASSIGNED: The findings revealed that cortical neurons have high Chloride ion (Cl-)i and excitatory actions of gamma-aminobutyric acid in the valproic acid animal model with ASD and mice with fragile X syndrome. Bumetanide, which has been introduced as a diuretic, is also a high-affinity-specific Na+-K+-Cl- cotransporter (NKCC1) antagonist that can reduce Cl- level. The results also indicate that bumetanide can attenuate behavioral features of autism in both animal and human models. Moreover, the studies showed that such medication could activate fusiform face area in individuals with ASD while viewing emotional faces. Also, recent findings suggest that a dose of 1 mg/d of this drug, taken twice daily, might be the best compromise between safety and efficacy.
UNASSIGNED: Recent studies provided some evidence that bumetanide can be a novel pharmacological agent in treating core symptoms of ASD. Future studies are required to confirm the efficacy of this medication in individuals with ASD.

Stroke often leads to neuronal injury and neurological functional deficits. Whilst spontaneous neurogenesis and axon regeneration are induced by ischemic stroke, effective pharmacological treatments are also essential for the improvement of neuroplasticity and functional recovery after stroke. However, no pharmacological therapy has been demonstrated to be able to effectively improve the functional recovery after stroke. Bumetanide is a specific Na+-K+-Cl- co-transporter inhibitor which can maintain chloride homeostasis in neurons. Therefore, many studies have focused on this drug\'s effect in stroke recovery in recent years. Here, we first review the function of Na+-K+-Cl- co-transporter in neurons, then how bumetanide\'s role in reducing brain damage, promoting neuroplasticity, leading to functional recovery after stroke, is elucidated. Finally, we discuss current limitations of bumetanide\'s efficiency and their potential solutions. These results may provide new avenues for further exploring mechanisms of post-stroke functional recovery as well as promising therapeutic targets for functional disability rehabilitation after ischemic stroke.

To evaluate clinical trials using bumetanide in autism spectrum disorder (ASD) treatment.
PubMed and Ovid MEDLINE (1946 to October 2018) were searched using terms bumetanide and autism. Bibliographies were reviewed for other relevant trials.
English language, randomized, controlled, clinical trials in humans were evaluated. Three trials met all inclusion criteria.
Oral bumetanide was studied in 208 patients, 2 to 18 years old, with ASD. Trials evaluated bumetanide\'s impact on core behavioral features using several different autism assessment scales. All trials used the Childhood Autism Rating Scale to assess improvement at 90 days, with one trial finding statistical significance. The Clinical Global Impressions Scale identified statistically significant improvements in 2 of the 3 trials. The Autism Behavioral Checklist and Social Responsiveness Scales identified statistical benefit in the 2 trials utilizing those outcomes. Behaviors most improved by bumetanide included social communication, interactions, and restricted interest. No dose-effect correlation was identified in the dose-ranging trial. Adverse effects, including hypokalemia and polyuria, occurred more often with higher doses and resulted in withdrawal rates of 17% to 43%. Bumetanide 0.5 mg twice daily was the most studied and best tolerated dose. Limitations included unclear clinical success definitions and evaluation methodology variability. Relevance to Patient Care and Clinical Practice: No effective treatment options for core ASD symptoms have been approved. This review presents preliminary safety and efficacy data for bumetanide in ASD.
Low-dose oral bumetanide may be useful in patients with moderate to severe ASD when behavioral therapies are not available.