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Annals of Thoracic and Cardiovascular... Apr 2022To examine N-acetylcysteine's (NAC's) renoprotective effect in adult cardiac surgeryMethods: PubMed, Ovid Medline, and Embase were searched for randomized controlled... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine N-acetylcysteine's (NAC's) renoprotective effect in adult cardiac surgeryMethods: PubMed, Ovid Medline, and Embase were searched for randomized controlled trials published between January 1990 and May 2021 that investigated the effect of NAC in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery. The inclusion criterion was studies that assessed the effect of NAC in comparison to placebo by measuring the incidence of AKI.
RESULTS
Overall meta-analytic estimates of all 10 included trials showed that NAC did not have a significant effect (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.64-1.10) on AKI. Further subgroup analysis did not show a significant benefit of NAC in preventing AKI.
CONCLUSION
This meta-analysis suggests that NAC does not have a significant effect in reducing the incidence of AKI. However, there is notable heterogeneity among the included studies that could possibly account for the non-significant effect observed. It is worth noting that only one trial administered NAC high dosages perioperatively, and it is the only included trial to show a significant benefit in reducing the incidence of AKI (OR: 0.30, 95% CI: 0.11-0.81). Further studies on this dosage and duration of administration should be conducted to best elucidate the effect of administering NAC.
Topics: Acetylcysteine; Acute Kidney Injury; Adult; Cardiac Surgical Procedures; Female; Humans; Male; Odds Ratio; Treatment Outcome
PubMed: 34732600
DOI: 10.5761/atcs.oa.21-00132 -
Cureus May 2022Contrast media administration to patients during cardiac events increases the risk of developing contrast-induced nephropathy (CIN). CIN is among some complications... (Review)
Review
Evaluating the Effectiveness of Pretreatment With Intravenous Fluid in Reducing the Risk of Developing Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis.
Contrast media administration to patients during cardiac events increases the risk of developing contrast-induced nephropathy (CIN). CIN is among some complications usually associated with the percutaneous coronary intervention and may result in acute renal failure. Several risk factors are associated with CIN. These risk factors include; age (elderly patients), pre-existing renal impairment, diabetes mellitus, and the use of high osmolar contrast media. Studies have shown that several measures such as using low osmolar contrast media, N-acetylcysteine, intravenous sodium bicarbonate, and hydration through oral or intravenous fluid administration play a significant role in CIN incidence reduction. Hydration using intravenous fluid, especially saline solution, has been critical in preventing CIN. Prehydration using the intravenous fluid before contrast media administration is vital. A systematic literature search with meta-analysis for relevant and original articles was carried out from 2000 to 2022 on databases such as PubMed, Cochrane Library, Google Scholar, ScienceDirect, Web of Science, and Embase. The search on the databases was based on various keywords related to intravenous fluid and CIN. The studies that met the inclusion criteria were critically analyzed, and data such as study design, interventions, participants, and outcomes of the research were retrieved. Out of the 784 results yielded during the initial search, ten articles met the eligibility criteria and were included in the study. The data analysis obtained from the included studies showed that pretreatment using intravenous fluid has conflicting results. Some studies showed that hydrating patients using intravenous fluid before contrast media administration significantly reduces the risk of CIN. In contrast, others claimed that intravenous fluid has minimal impact on preventing CIN. Despite the different investigations conducted on CIN, it remains insufficiently understood. From the analysis, most of the studies support that intravenous fluid administration decreases the occurrence of CIN in patients that receive contrast media. The analysis also has established that oral hydration is similar to intravenous fluid administration in reducing CIN incidence.
PubMed: 35693368
DOI: 10.7759/cureus.24825 -
Drug Safety Nov 2022Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is...
INTRODUCTION
Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.
OBJECTIVE
We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population.
METHODS
We included original articles conducted in a paediatric population (< 18 years) in which a therapeutic intervention was described to manage APAP or idiosyncratic DILI. Findings were summarized based on age groups (preterm newborn neonates, term and post-term neonates, infants, children and adolescents).
RESULTS
Overall, 25 publications (fifteen case reports, six case series and four retrospective cohort studies) were included, including a total of 140 paediatric DILI cases, from preterm newborn neonates to adolescents. N-acetylcysteine was used to treat 19 APAP cases. N-acetylcysteine (n = 14), ursodeoxycholic acid (n = 3), corticosteroids (n = 31), carnitine (n = 16) and the combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine and S-adenosylmethionine (n = 31) were the therapeutic options for treating idiosyncratic DILI. The molecular adsorbent recirculating system was used in the management of either APAP (n = 4) or idiosyncratic DILI (n = 2), while 20 paediatric ALF cases received continuous renal replacement therapy.
CONCLUSIONS
This systematic review identified DILI in the paediatric population who have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need for high-quality studies to test the efficacy of known and novel therapies to treat DILI specifically addressed to the paediatric population. PROSPERO registration number CRD42021214702.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Adrenal Cortex Hormones; Adult; Carnitine; Chemical and Drug Induced Liver Injury; Child; Drug-Related Side Effects and Adverse Reactions; Glutathione; Glycyrrhizic Acid; Humans; Infant, Newborn; Liver; Liver Failure, Acute; Retrospective Studies; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 36006605
DOI: 10.1007/s40264-022-01224-w -
Otology & Neurotology : Official... Jan 2021This study aims to explore and determine the effectiveness of current pharmacologic agents for the prevention of noise-induced hearing loss (NIHL) via a systematic...
OBJECTIVE
This study aims to explore and determine the effectiveness of current pharmacologic agents for the prevention of noise-induced hearing loss (NIHL) via a systematic review.
DATABASES REVIEWED
The PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library databases were searched from inception through February 6, 2020.
METHODS
Full-text, English-language articles detailing prospective randomized and nonrandomized clinical trials with pharmacological interventions administered to prevent NIHL were included in accordance with PRISMA guidelines. The detailed search terms are included in the Appendix, http://links.lww.com/MAO/B67.
RESULTS
Eleven articles were included in this review with 701 patients receiving a pharmacologic prevention for various noise exposures. Various regimens included administration of alpha-lipoic acid, ambient oxygen, beta-carotene, carbogen, ebselen, Mg-aspartate, N-acetylcysteine, and vitamins C, E, and B12. A number of studies demonstrated statistically significant amelioration of NIHL with pharmacologic intervention. Two studies demonstrated significantly better hearing outcomes for pharmacological prophylaxis with carbogen or ebselen as compared with placebo for the 4 kHz frequency, where the noise-notch is most likely to be encountered. Given the considerable heterogeneity in agents and methodologies, however, it was not possible to conduct a meta-analysis.
CONCLUSIONS
While several heterogenous articles demonstrated promising results for Mg-aspartate, carbogen, vitamin B12, and alpha-lipoic acid, the clinical significance of these pharmaceuticals remains unclear. Initial data from this study alongside future clinical trials might potentially contribute to the generation of clinical practice guidelines to prevent NIHL.
LEVEL OF EVIDENCE
2.
Topics: Hearing; Hearing Loss, Noise-Induced; Humans; Noise; Prospective Studies
PubMed: 33229875
DOI: 10.1097/MAO.0000000000002858 -
JAMA Network Open Jul 2022The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI) have had contradictory results with recent trials confirming a lack of benefit.
OBJECTIVE
To systematically review the literature on NAC for the prevention of CI-AKI, and to explore the heterogeneity, publication bias, and small-study effect to determine the most suitable analytic method in a setting where the literature is contradictory.
DATA SOURCES
Medline, Embase, and Cochrane Central Register of Controlled Trials databases were used to find randomized clinical trials (RCTs) comparing NAC with any other prophylactic agent or placebo in adults.
STUDY SELECTION
The search included studies published in English from database inception to January 2020. Two independent reviewers screened the studies, extracted data, and performed the risk of bias assessment.
DATA EXTRACTION AND SYNTHESIS
A meta-analysis was conducted about the effect of NAC on CI-AKI, the need for dialysis, and mortality. Fixed and random effects analyses were also performed. Funnel plots and the trim and fill method were used for assessment of publication bias. Metaregression was performed to explore the heterogeneity and subgroup analysis to examine the association between NAC and CI-AKI when studies were categorized according to sample size and number of events.
RESULTS
A total of 101 trials were included in this meta-analysis. The median sample size was 112 (range, 20 to 4993). Twenty-nine trials had a sample size of 200 or more, and only 3 trials had a sample size of 500 or more. Forty-five trials reported the need for kidney replacement therapy, and 41 trials reported mortality as an outcome. NAC seemed to show a benefit, with a pooled OR of 0.72 (95% CI, 0.63-0.82) using random effects model and a pooled OR of 0.82 (95% CI 0.76-0.90) using a fixed effects model. However, there was significant heterogeneity (I2 = 37.6; P < .001) and significant publication bias, which was reduced only when restricting to large RCTs (N ≥ 500). The clinical outcomes (ie, the need for kidney replacement therapy and mortality) revealed little heterogeneity and no publication bias, and each provided a robust neutral summary result.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, NAC was associated with a benefit in the prevention of CI-AKI. However, because of substantial publication bias and other biases, standard meta-analytic techniques resulted in significant heterogeneity and a spurious, or factitious, association, even when using a random effects model. When the analysis was restricted to RCTs with a large sample size to account for publication bias or restricted to trials with clinical outcomes, this issue was reduced and resulted in more robust and neutral effect sizes.
Topics: Acetylcysteine; Acute Kidney Injury; Humans; Publication Bias; Renal Dialysis; Renal Replacement Therapy
PubMed: 35788669
DOI: 10.1001/jamanetworkopen.2022.20671 -
Neuroscience and Biobehavioral Reviews Feb 2024Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural... (Review)
Review
BACKGROUND
Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments.
METHODS
PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles.
RESULTS
High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes.
CONCLUSIONS
Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.
Topics: Humans; Animals; Cognitive Dysfunction; Cancer Survivors
PubMed: 38135266
DOI: 10.1016/j.neubiorev.2023.105514 -
BMJ Open Oct 2020Several studies evaluating the preventive effect of N-acetylcysteine (NAC) on contrast-associated acute kidney injury (CA-AKI) among patients with ST segment elevation... (Meta-Analysis)
Meta-Analysis
Effect of N-acetylcysteine on prevention of contrast-associated acute kidney injury in patients with STEMI undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
Several studies evaluating the preventive effect of N-acetylcysteine (NAC) on contrast-associated acute kidney injury (CA-AKI) among patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) have suggested inconsistent results and that a systematic review and meta-analysis should be performed.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, MEDLINE, EMBASE, ClinicalTrials.gov and the Cochrane Central databases were searched from inception to 15 November 2019.
ELIGIBILITY CRITERIA
Randomised controlled trials assessing use of NAC compared with non-use of NAC (eg, placebo) in preventing CA-AKI in patients with STEMI following PPCI were included.
DATA SYNTHESIS
Relative risks with 95% CIs were pooled using a random-effects model. Evidence level of conclusions was assessed by Cochrane GRADE measure.
RESULTS
Seven trials including 1710 patients were identified. Compared with non-use of NAC, use of NAC significantly reduced the incidence of CA-AKI by 49% (risk ratio (RR) 0.51, 95% CI 0.31 to 0.82, p<0.01) and all-cause in-hospital mortality by 63% (RR 0.37, 95% CI 0.17 to 0.79, p=0.01). The estimated effects on the requirement for dialysis (RR 0.61, 95% CI 0.11 to 3.38, p=0.24) were not statistically significant. Trial sequential analysis confirmed the true positive of NAC in reducing risk of CA-AKI. Subgroup analyses suggested that the administration of NAC had greater benefits in patients with renal dysfunction and in those receiving oral administration and higher dosage of NAC.
CONCLUSIONS
NAC intake reduces the risk of CA-AKI and all-cause in-hospital mortality in patients with STEMI undergoing PPCI. The estimated potential benefit of NAC in preventing dialysis was ambiguous, and further high-quality studies are needed.
PROSPERO REGISTRATION NUMBER
CRD42020155265.
Topics: Acetylcysteine; Acute Kidney Injury; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Renal Dialysis; ST Elevation Myocardial Infarction
PubMed: 33067289
DOI: 10.1136/bmjopen-2020-039009 -
Frontiers in Pharmacology 2022Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute...
Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute liver failure (ALF), for which there is no effective therapy. N-acetylcysteine (NAC) has been occasionally tested for the treatment of non-acetaminophen drug-induced ALF. However, limited evidence for its efficacy and safety is currently available. Our aim was to elucidate the benefit and safety of NAC in DILI and evaluate its hepatoprotective effect. We conducted a systematic review to evaluate the management and prevention focused on NAC in idiosyncratic DILI. The main outcomes included mortality due to DILI, time to normalization of liver biochemistry, transplant-free survival, and adverse events. We included clinical trials and observational studies, either prospective or retrospective. A total of 11 studies were included after literature screening. All studies had different methodologies, and some of them had important risk of bias that may lead to interpreting their findings with caution. The majority of the studies proved NAC efficacy in a cohort of patients with ALF due to different etiologies, where DILI represented a subgroup. NAC seemed to improve transplant-free survival; however, its benefit was inconclusive in terms of overall survival. With regard to safety, NAC showed an adequate safety profile. In prevention studies, NAC showed a possible hepatoprotective effect; however, this finding is limited by the lack of studies and presence of bias. NAC treatment seems to have some benefit in non-acetaminophen drug-induced liver failure patients with acceptable safety; however, due to the lack of evidence and limitations detected across studies, its benefit must be corroborated in clinical trials with adequate methodology.
PubMed: 35656297
DOI: 10.3389/fphar.2022.876868 -
European Journal of Radiology Aug 2022Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to establish the efficacy of prophylaxis interventions used in adult patients prior to intravenous exposure to iodinated contrast to reduce the risk of CIN.
METHODS
An electronic search for published peer-reviewed articles was performed, supplemented with manual review of references from previous systematic reviews and the National Institute for Health and Care Excellence guidelines. Risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Random-effect meta-analyses were used to assess CIN incidence, need for kidney replacement therapy (KRT), mortality, fluid overload and persistent kidney dysfunction.
RESULTS
22 studies assessing a range of interventions were included in the qualitative analysis. The incidence of CIN was reduced by the use of N-acetylcysteine compared to a control group of saline (risk difference = -0.07, 95% CI -0.13 to -0.01) but not by sodium bicarbonate compared to control group of saline (risk difference = -0.02, 95% CI -0.04 to 0.01). Published studies give no indication that prophylactic interventions have significant impact on the need for KRT, mortality or persistent renal impairment.
CONCLUSION
Evidence for prophylaxis against CIN in patients receiving intravenous iodinated contrast is limited. There was an association with the use of NAC with reduced incidence of CIN following intravenous contrast but there was no impact on other clinical outcomes assessed. The clinical significance of these findings remains unclear and further research focusing on these clinical outcomes is required.
Topics: Acetylcysteine; Adult; Contrast Media; Humans; Kidney Diseases; Renal Insufficiency; Sodium Bicarbonate
PubMed: 35636024
DOI: 10.1016/j.ejrad.2022.110368 -
The Cochrane Database of Systematic... Oct 2021Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate... (Review)
Review
BACKGROUND
Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate receptor modulators for depression in bipolar disorder.
OBJECTIVES
1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder. 2. To review the acceptability of ketamine and other glutamate receptor modulators in people with bipolar disorder who are experiencing depressive symptoms.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020. We did not apply any restrictions to date, language or publication status.
SELECTION CRITERIA
RCTs comparing ketamine or other glutamate receptor modulators with other active psychotropic drugs or saline placebo in adults with bipolar depression.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. Primary outcomes were response rate and adverse events. Secondary outcomes included remission rate, depression severity change scores, suicidality, cognition, quality of life, and dropout rate. The GRADE framework was used to assess the certainty of the evidence.
MAIN RESULTS
Ten studies (647 participants) were included in this review (an additional five studies compared to the 2015 review). There were no additional studies added to the comparisons identified in the 2015 Cochrane review on ketamine, memantine and cytidine versus placebo. However, three new comparisons were found: ketamine versus midazolam, N-acetylcysteine versus placebo, and riluzole versus placebo. The glutamate receptor modulators studied were ketamine (three trials), memantine (two), cytidine (one), N-acetylcysteine (three), and riluzole (one). Eight of these studies were placebo-controlled and two-armed. In seven trials the glutamate receptor modulators had been used as add-on drugs to mood stabilisers. Only one trial compared ketamine with an active comparator, midazolam. The treatment period ranged from a single intravenous administration (all ketamine studies), to repeated administration for riluzole, memantine, cytidine, and N-acetylcysteine (with a follow-up of eight weeks, 8 to 12 weeks, 12 weeks, and 16 to 20 weeks, respectively). Six of the studies included sites in the USA, one in Taiwan, one in Denmark, one in Australia, and in one study the location was unclear. All participants had a primary diagnosis of bipolar disorder and were experiencing an acute bipolar depressive episode, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (IV) or fourth edition text revision (IV-TR). Among all glutamate receptor modulators included in this review, only ketamine appeared to be more efficacious than placebo 24 hours after infusion for response rate (odds ratio (OR) 11.61, 95% confidence interval (CI) 1.25 to 107.74; P = 0.03; participants = 33; studies = 2; I² = 0%, low-certainty evidence). Ketamine seemed to be more effective in reducing depression rating scale scores (MD -11.81, 95% CI -20.01 to -3.61; P = 0.005; participants = 32; studies = 2; I = 0%, very low-certainty evidence). There was no evidence of ketamine's efficacy in producing remission over placebo at 24 hours (OR 5.16, 95% CI 0.51 to 52.30; P = 0.72; participants = 33; studies = 2; I = 0%, very low-certainty evidence). Evidence on response, remission or depression rating scale scores between ketamine and midazolam was uncertain at 24 hours due to very low-certainty evidence (OR 3.20, 95% CI 0.23 to 45.19). In the one trial assessing ketamine and midazolam, there were no dropouts due to adverse effects or for any reason (very low-certainty evidence). Placebo may have been more effective than N-acetylcysteine in reducing depression rating scale scores at three months, although this was based on very low-certainty evidence (MD 1.28, 95% CI 0.24 to 2.31; participants = 58; studies = 2). Very uncertain evidence found no difference in response at three months (OR 0.82, 95% CI 0.32 to 2.14; participants = 69; studies = 2; very low-certainty evidence). No data were available for remission or acceptability. Extremely limited data were available for riluzole vs placebo, finding only very-low certainty evidence of no difference in dropout rates (OR 2.00, 95% CI 0.31 to 12.84; P = 0.46; participants = 19; studies = 1; I = 0%).
AUTHORS' CONCLUSIONS
It is difficult to draw reliable conclusions from this review due to the certainty of the evidence being low to very low, and the relatively small amount of data usable for analysis in bipolar disorder, which is considerably less than the information available for unipolar depression. Nevertheless, we found uncertain evidence in favour of a single intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo in terms of response rate up to 24 hours, however ketamine did not show any better efficacy for remission in bipolar depression. Even though ketamine has the potential to have a rapid and transient antidepressant effect, the efficacy of a single intravenous dose may be limited. We did not find conclusive evidence on adverse events with ketamine, and there was insufficient evidence to draw meaningful conclusions for the remaining glutamate receptor modulators. However, ketamine's psychotomimetic effects (such as delusions or delirium) may have compromised study blinding in some studies, and so we cannot rule out the potential bias introduced by inadequate blinding procedures. To draw more robust conclusions, further methodologically sound RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine, and to study different methods of sustaining antidepressant response, such as repeated administrations.
Topics: Adult; Bipolar Disorder; Depression; Humans; Ketamine; Quality of Life; Receptors, Glutamate
PubMed: 34623633
DOI: 10.1002/14651858.CD011611.pub3