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Clinical Toxicology (Philadelphia, Pa.) Dec 2016Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local... (Review)
Review
BACKGROUND
Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.
METHODS
Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.
RESULTS
For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.
CONCLUSION
Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.
Topics: Administration, Intravenous; Anesthetics; Animals; Calcium Channel Blockers; Cocaine; Diphenhydramine; Disease Models, Animal; Evidence-Based Medicine; Fat Emulsions, Intravenous; Humans; Lamotrigine; Poisoning; Randomized Controlled Trials as Topic; Triazines
PubMed: 27608281
DOI: 10.1080/15563650.2016.1214275 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2016Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local... (Review)
Review
BACKGROUND
Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local anesthetics and various other drugs. The dosing regimen for the clinical toxicology indications differs significantly from those used for parenteral nutrition. The evidence on the efficacy of ILE to reverse acute toxicity of diverse substances consists mainly of case reports and animal experiments. Adverse events to ILE are important to consider when clinicians need to make a risk/benefit analysis for this therapy.
METHODS
Multiple publication databases were searched to identify reports of adverse effects associated with acute ILE administration for either treatment of acute poisoning or parenteral nutrition. Articles were selected based on pre-defined criteria to reflect acute use of ILE. Experimental studies and reports of adverse effects as a complication of long-term therapy exceeding 14 days were excluded.
RESULTS
The search identified 789 full-text articles, of which 114 met the study criteria. 27 were animal studies, and 87 were human studies. The adverse effects associated with acute ILE administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection.
CONCLUSION
The emerging use of ILE administration in clinical toxicology warrants careful attention to its potential adverse effects. The dosing regimen and context of administration leading to the adverse events documented in this review are not generalizable to all clinical toxicology scenarios. Adverse effects seem to be proportional to the rate of infusion as well as total dose received. Further safety studies in humans and reporting of adverse events associated with ILE administration at the doses advocated in current clinical toxicology literature are needed.
Topics: Acute Kidney Injury; Acute Lung Injury; Administration, Intravenous; Anesthetics, Local; Animals; Databases, Factual; Disease Models, Animal; Dose-Response Relationship, Drug; Embolism, Fat; Fat Emulsions, Intravenous; Heart Arrest; Humans; Hypersensitivity; Pancreatitis; Poisoning; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thromboembolism
PubMed: 27035513
DOI: 10.3109/15563650.2016.1151528 -
The Cochrane Database of Systematic... Sep 2012Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent.
OBJECTIVES
To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas Ophthalmologica Europaea from 2005 to July 2011.
SELECTION CRITERIA
We included randomised controlled trials only.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. Due to the small number of studies and the diversity of outcome measures, interventions and participants, we presented results narratively.
MAIN RESULTS
We found three RCTs with a total of 58 participants that were eligible for inclusion. There was significant variability between the trials in interventions, methodology and outcome measures and therefore we did not perform meta-analysis.One study reported on the use of 2% CsA in maize oil and two on the use of a commercial emulsion of 0.05% CsA. Of these three studies, one showed a beneficial effect of topical CsA in controlling signs and symptoms of AKC, one in controlling signs of AKC and one did not show evidence of an improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other did not show evidence of this improvement. No serious adverse events were reported in the trials.
AUTHORS' CONCLUSIONS
This systematic review highlights the relative scarcity of controlled clinical trials assessing the efficacy of topical CsA therapy in AKC and suggests that evidence on the efficacy and safety of topical CsA treatment in patients with CsA remains limited. However, the data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. No serious adverse events were reported. Reported adverse events in patients treated with topical CsA include intense stinging and eyelid skin maceration. One patient in the placebo group developed a severe allergic response to maize antigens. However, the total number of patients in the trials was too small to assess the safety of this treatment.Additional well-designed and powered RCTs of topical CsA in AKC are needed. Ideal study designs should include adequate randomisation and concealment of allocation; masking of participants, personnel and outcome assessors; adequate follow-up periods and minimisation of attrition bias; and comparison groups with similar clinical and epidemiologic characteristics. Samples should be large enough to provide sufficient statistical power to assess the safety of CsA and to detect clinically relevant treatment effect sizes of the primary outcomes. Analyses should be appropriate to the study's design and outcome measures. Moreover, standardisation of outcome measures and follow-up periods across studies would be beneficial to maximise study comparability.
Topics: Administration, Topical; Cyclosporine; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Randomized Controlled Trials as Topic
PubMed: 22972132
DOI: 10.1002/14651858.CD009078.pub2 -
Nanotoxicology Apr 2024Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity... (Review)
Review
Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity should be considered in therapeutic applications. Nanotechnology has paved the way to improve drug delivery systems and reduce toxicity. The present study, for the first time, comprehensively reviews the studies from 2011 to 2023 on reducing the toxicity of AmB. The findings showed that loading AmB with micellar structures, nanostructured lipid carriers, liposomes, emulsions, poly lactide-co-glycolide acid, chitosan, dendrimers, and other polymeric nanoparticles increases the biocompatibility and efficacy of the drug and significantly reduces toxicity. In addition, modified carbon nanoparticles (including graphene, carbon nanotubes, and carbon dots) with positively charged amine groups, PEI, and other components showed favorable drug delivery properties. Uncoated and coated magnetic nanoparticles and silver NPs-AmB composites had less cytotoxicity and more antifungal activity than free AmB. Citrate-reduced GNPs and lipoic acid-functionalized GNPs were also effective nanocarriers to reduce AmB cytotoxicity and improve anti-leishmania efficacy. In addition, zinc oxide-NPs and PEGylated zinc oxide-NPs showed favorable antifungal activity and negligible toxicity. According to a review study, carbon-based nanoparticles, metal nanoparticles, and especially polymer nanoparticles caused some reduction in the toxicity and improved solubility of AmB in water. Overall, considering the discussed nanocarriers, further research on the application of nanotechnology as a cost-effective candidate to improve the efficiency and reduce the cytotoxicity of AmB is recommended.
PubMed: 38646931
DOI: 10.1080/17435390.2024.2340467 -
Lipid resuscitation in acute poisoning: after a decade of publications, what have we really learned?Current Opinion in Anaesthesiology Aug 2017The decision to provide intravenous lipid emulsion (ILE) therapy as a treatment modality for the reversal of various drug toxicity was discovered in the last decade.... (Review)
Review
PURPOSE OF REVIEW
The decision to provide intravenous lipid emulsion (ILE) therapy as a treatment modality for the reversal of various drug toxicity was discovered in the last decade. Numerous publications, in both humans and animals attest to its clinical use, but current supporting evidence is inconsistent.
RECENT FINDINGS
A recent systematic review reported evidence for benefit of ILE in bupivacaine toxicity. Human randomized trials, large observational studies as well as animal models of orogastric poisoning failed to report a clear benefit of ILE for nonlocal anesthetics poisoning.
SUMMARY
ILE can be used to resuscitate local anesthetics especially bupivacaine. The impact of ILE on oral overdoses is controversial and clear evidence on benefit is lacking. A thorough risk benefit assessment with consideration of alternative options is warranted to minimize the risk of adverse effects. Evidence supports using bolus doses of ILE, while infusion rates are still debatable.
Topics: Anesthesia, Local; Anesthetics, Local; Animals; Bupivacaine; Fat Emulsions, Intravenous; Humans; Resuscitation
PubMed: 28562387
DOI: 10.1097/ACO.0000000000000484 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2010To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients.
METHODS
We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects.
RESULTS
Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning.
CONCLUSION
The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.
Topics: Animals; Clinical Trials as Topic; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Fat Emulsions, Intravenous; Humans; Poisoning; Treatment Outcome
PubMed: 20095812
DOI: 10.3109/15563650903544124 -
Journal of the European Academy of... Mar 2023Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown.... (Meta-Analysis)
Meta-Analysis
Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown. We performed this network meta-analysis to compare different emollients in preventing infant AD. A systematic search was performed in PubMed, EMBASE and Cochrane library to identify relevant studies from their inception through 28 February, 2022. We evaluated the quality of eligible studies using the Cochrane risk of bias assessment tool. Data analysis was performed using STATA 14.0. Eleven studies were included for data analysis. Direct meta-analysis suggested that early application of emollients effectively prevented AD development in high-risk infants (risk ratio [RR], 0.64; 95% confidence interval [CI], 0.47 to 0.88). Network meta-analysis suggested that emollient emulsion might the better option for preventing infant AD development, with a surface under the cumulative ranking curve (SUCRA) of 82.6% for all populations, 78.0% for high-risk populations and 79.2% for populations with food sensitization. Moreover, subjects receiving emollients more frequently experienced adverse events. Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants and emollient emulsion may be the optimal type. Future study with well-designed and large scale are warranted to validate our findings.
Topics: Humans; Infant; Dermatitis, Atopic; Emollients; Emulsions; Network Meta-Analysis; Risk Factors
PubMed: 36415973
DOI: 10.1111/jdv.18688 -
American Journal of Therapeutics
Recurrence of Symptoms or Re-elevation of Drug Concentration After Termination of Lipid Emulsion Treatment for Drug Toxicity: Analysis of Case Reports and Systematic Review.
Topics: Female; Humans; Male; Middle Aged; Fat Emulsions, Intravenous; Recurrence; Drug-Related Side Effects and Adverse Reactions
PubMed: 38219233
DOI: 10.1097/MJT.0000000000001687 -
Clinical Nuclear Medicine Oct 2015Intermittent unavailability of sincalide for determination of gallbladder ejection fraction (GBEF) prompted increased usage of fatty meal cholecystagogues (FMCs). The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Intermittent unavailability of sincalide for determination of gallbladder ejection fraction (GBEF) prompted increased usage of fatty meal cholecystagogues (FMCs). The aim of this systematic review was to identify the state of current FMC options in cholescintigraphy, focusing on the quality of corresponding normal GBEF values.
METHODS
We performed an extensive literature search of the MEDLINE, Cochrane, and CINAHL databases without date or language restrictions with a broad spectrum of search terms. Selection criteria required both that the study use a FMC as part of a stimulated GBEF examination to gather data on normal volunteers or patients without evidence of gastrointestinal disease and that the meal used be described sufficiently for emulation. A cumulative point system was used to grade the quality of normal GBEF values: 1 point for screening ultrasound, 1 point for detailed screening questionnaire, 1 point for 20 or greater number of participants in a study, 1 additional point for 60 or greater number of participants in a study, 0.5 points for cursory screening questions, and 0 points when no screening process was mentioned. The meal was expressed in grams of fat per volume, when available.
RESULTS
Twelve studies met inclusion criteria out of 15 studies claiming to report normal values. Two studies (17%) achieved a score of 3, 5 studies (42%) at 2 to 2.5, 3 studies (25%) at 1 to 1.5, and the remaining 2 studies (17%) at 0 to 0.5. Total number of participants examined ranged from 6 to 100. Meal composition varied widely. In 1 study, sham feeding was used. Most meals had components that could present problems to patients with relatively common dietary restrictions (ie, lactose intolerance, egg protein allergy, etc). Results for proposed normal values varied widely (from 16.3% to 85.6%). The commercial fatty meal products of Humana Infant Formula 1 and Ensure Plus offered the highest-quality normal values.
CONCLUSIONS
There is a need to establish high-quality normal GBEF range for a ubiquitous fatty meal (ie, a meal that would be widely available, easy to prepare, inexpensive, and free of sensitivity-provoking ingredients). A corn oil emulsion, has immense potential as an ideal FMC, limited currently only by its lack of established normal values. Currently, the highest-quality normal GBEF values available for FMC exist for 2 commercial products, Humana Infant Formula 1 and Ensure Plus. However, these products may not be readily available at some institutions, and neither one is free from dietary restrictions.
Topics: Dietary Fats; Female; Gallbladder; Gallbladder Emptying; Humans; Male; Meals; Middle Aged; Perfusion Imaging; Sincalide
PubMed: 26222535
DOI: 10.1097/RLU.0000000000000913 -
The British Journal of Dermatology Oct 2011Rosacea is a common chronic skin disease affecting the face. There are numerous treatment options, but it is unclear which are the most effective. The aim of this review... (Meta-Analysis)
Meta-Analysis Review
Rosacea is a common chronic skin disease affecting the face. There are numerous treatment options, but it is unclear which are the most effective. The aim of this review was to assess the evidence for the efficacy and safety of treatments for rosacea. Searches included the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and Ongoing Trials Registers (updated February 2011). Randomized controlled trials in people with moderate to severe rosacea were included. Fifty-eight trials, including 27 from the original review, comprising 6633 participants were included in this updated review. Interventions included topical metronidazole, oral antibiotics, topical azelaic cream or gel, topical benzoyl peroxide and/or combined with topical antibiotics, sulphacetamide/sulphur, and others. There was some evidence that topical metronidazole and azelaic acid were more effective than placebo. Two trials indicated that doxycycline 40mg was more effective than placebo. There was no statistically significant difference in effectiveness between doxycycline 40mg and 100mg but there were fewer adverse effects. One study reported that ciclosporin ophthalmic emulsion was significantly more effective than artificial tears for treating ocular rosacea. Although the majority of included studies were assessed as being at high or unclear risk of bias, there was some evidence to support the effectiveness of topical metronidazole, azelaic acid and doxycycline (40mg) in the treatment of moderate to severe rosacea, and ciclosporin 0·05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately powered randomized controlled trials are required.
Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Dermatologic Agents; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Rosacea; Selection Bias; Treatment Outcome
PubMed: 21692773
DOI: 10.1111/j.1365-2133.2011.10473.x