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The Cochrane Database of Systematic... Jan 2020Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004.
OBJECTIVES
To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries.
SELECTION CRITERIA
We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older).
DATA COLLECTION AND ANALYSIS
We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables.
MAIN RESULTS
We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported.
SECONDARY OUTCOMES
use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE.
AUTHORS' CONCLUSIONS
We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential.
Topics: Adult; Antipsychotic Agents; Chlorpromazine; Delirium; Haloperidol; Humans; Lorazepam; Randomized Controlled Trials as Topic; Terminally Ill
PubMed: 31960954
DOI: 10.1002/14651858.CD004770.pub3 -
Psychological Medicine Nov 2020Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.
METHODS
Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).
RESULTS
Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a 'good' response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36-3.41; I2 = 48.9) and 'any' response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35-3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on 'any' response (74.7% v. 65%; RR 1.15; 95% CI 0.82-1.62).
CONCLUSIONS
Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.
Topics: Antipsychotic Agents; Barbiturates; Benzodiazepines; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 31625485
DOI: 10.1017/S003329171900285X -
AANA Journal Dec 2018The term vasoplegia describes hypotension refractory to vasopressor therapy, a common finding related to cardiac surgery requiring cardiopulmonary bypass. High doses of...
The term vasoplegia describes hypotension refractory to vasopressor therapy, a common finding related to cardiac surgery requiring cardiopulmonary bypass. High doses of vasoactive agents are associated with adverse effects such as peripheral and mesenteric ischemia. Databases were systematically searched for literature on methylene blue as an adjunct therapy to treat vasoplegia. Fifteen articles were selected. The quality of the studies was evaluated using the US Preventive Services Task Force (USPSTF) grading tool, and a chart was created to present the components of each study. Preoperative, intraoperative, and postoperative administration of methylene blue has been shown to increase systemic vascular resistance and mean arterial pressure, with the period after surgery being the most common time for use of this therapy. Decreased vasopressor requirements have also been consistently demonstrated after methylene blue administration. This catecholamine-sparing effect prevents vasopressor-related injury. Its favorable safety profile as well as hemodynamic effects have made methylene blue a valuable adjunct in the setting of vasoplegia. Methylene blue is an effective treatment of refractory hypotension related to cardiac surgery requiring cardiopulmonary bypass. Larger, randomized controlled trials are needed to strengthen the state of the evidence and to define specific doses.
Topics: Anesthesia; Coronary Artery Bypass; Humans; Intraoperative Complications; Methylene Blue; Nurse Anesthetists; Randomized Controlled Trials as Topic; Vasoplegia
PubMed: 31584419
DOI: No ID Found -
The Journal of Pediatrics Nov 2019To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the...
OBJECTIVES
To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the acute care setting.
STUDY DESIGN
Using keywords, 799 studies published up from December 1954 to February 2018 were extracted from MEDLINE via Pubmed, Embase via OVID, CINAHL via EBSCO, and Cochrane Controlled Trials Registry. Studies were evaluated for inclusion and exclusion by 2 independent reviewers using predetermined inclusion and exclusion criteria.
RESULTS
The search yielded 84 studies for full review, of which 54 were included in the systematic review. Studies were subsequently separated into 1 group of 6 case series studies containing quantitative data on sumatriptan, ondansetron, phenothiazines, prokinetic agents, carbohydrate, isometheptene, and aprepitant; 1 one group consisting only of qualitative studies containing expert recommendations.
CONCLUSIONS
Ondansetron has the most quantitative and qualitative evidence to support its inclusion in pediatric emergency department protocols as a rescue therapy. Sumatriptan and aprepitant are potential candidates for inclusion as abortive therapies. Qualitative data from retrospective studies and case reports are not applicable to a larger patient population. This report informs a need for controlled, prospective cohort studies and randomized, controlled trials to optimize current management protocols and to develop new medical interventions.
Topics: Child; Critical Care; Disease Management; Humans; Vomiting
PubMed: 31540764
DOI: 10.1016/j.jpeds.2019.06.057 -
International Journal of Molecular... Jul 2019The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.
Topics: Bacteroidaceae Infections; Biofilms; Candida; Candidiasis; Curcumin; Dental Caries; Humans; Methylene Blue; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Rosaniline Dyes; Streptococcal Infections; Streptococcus; Tolonium Chloride; Treatment Outcome
PubMed: 31340425
DOI: 10.3390/ijms20143585 -
European Journal of Obstetrics,... Jul 2019Methylene blue is commonly used as a tracer in sentinel lymph node mapping for many malignant diseases or chromopertubation during gynecologic laparoscopy. In contrast...
Methylene blue is commonly used as a tracer in sentinel lymph node mapping for many malignant diseases or chromopertubation during gynecologic laparoscopy. In contrast with other blue dyes such as patent blue V or isosulfan blue, methylene blue rarely causes an allergy-like reaction in patients undergoing sentinel lymph node mapping. However, in chromopertubation, some cases of allergy-like reaction to methylene blue have been reported; these comprise two types: an allergic reaction and methemoglobinemia. In this study, a systematic literature review of allergy-like reactions caused by methylene blue dye following laparoscopic chromopertubation was conducted. A search was conducted in PUBMED, Web of Science, and Scopus from inception until June 2018, using the terms: "methylene blue", "complication", "allergic", "hypersensitive", "lung/pulmonary edema"," methemoglobinemia", "anaphylactic shock", "chromopertubation", "pertubation", "laparoscopic", and "laparoscopy". Ultimately, the eligibility criteria were fulfilled by only 12 case reports. Among 13 cases including our case of severe anaphylactic shock after chromopertubation, allergic reactions were diagnosed in four cases, methemoglobinemia in six, and there was no confirmed diagnosis in three cases; the clinical course consisted of skin changes, blue discoloration of body fluids, respiratory failure, and hemodynamic failure, regardless of the underlying diagnoses. Regarding diagnosis, methemoglobinemia was confirmed with co-oximetry (spectrophotometry). First-line therapy included supportive care for both cases of allergic reactions and methemoglobinemia.
Topics: Adult; Anaphylaxis; Enzyme Inhibitors; Female; Humans; Laparoscopy; Methylene Blue
PubMed: 31112852
DOI: 10.1016/j.ejogrb.2019.03.019 -
Techniques in Coloproctology Apr 2019Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional...
BACKGROUND
Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness.
METHODS
This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles.
RESULTS
The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified.
CONCLUSIONS
Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined.
Topics: Fluorescence; Fluorescent Dyes; Fluoroscopy; Humans; Indocyanine Green; Laparoscopy; Methylene Blue; Spectroscopy, Near-Infrared; Ureter
PubMed: 31030340
DOI: 10.1007/s10151-019-01973-4 -
Epilepsy & Behavior : E&B Jun 2019The objective of the study was to characterize the electroencephalogram (EEG) changes associated with different antipsychotic medications based on the evidence from the...
OBJECTIVES
The objective of the study was to characterize the electroencephalogram (EEG) changes associated with different antipsychotic medications based on the evidence from the literature.
METHODS
A systematic search of the databases Medline, PsycINFO, and PubMed was conducted. The Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the construction of this systematic review. Primary research articles that reported descriptive EEG results, included comparisons of subjects with and without antipsychotic therapy, and excluded patients with epilepsy were included in the analysis. The outcome was the presence of epileptiform discharges or slowing on EEG. We analyzed pooled data, where possible, from studies with a similar intervention and methodology.
RESULTS
Fourteen articles reporting on a total of 665 patients were reviewed. Among the publications, clozapine was the drug most consistently accompanied by EEG slowing and epileptiform discharges, with an odds ratio of 16.9 (95% confidence intervals (CI): 5.4 to 53.2) and 6.2 (95% CI: 3.4 to 11.3), respectively in the analysis of pooled data. Only one study reported a significant increase in epileptiform discharges with phenothiazine antipsychotic therapy as a group, but the impact of individual drugs was not analyzed separately.
CONCLUSIONS
This systematic review suggests that, among antipsychotics, clozapine most frequently induces EEG slowing and epileptiform discharges. There remains limited data with respect to other individual antipsychotic agents and covariates including drug dose, plasma levels, dose adjustments, and treatment duration that influence EEG changes.
Topics: Antipsychotic Agents; Brain Waves; Diagnosis, Differential; Electroencephalography; Epilepsy; Humans; Psychotic Disorders
PubMed: 30999157
DOI: 10.1016/j.yebeh.2019.02.005 -
Headache May 2019The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED).
METHODS
Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia.
RESULTS
From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27).
CONCLUSIONS
For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.
Topics: Acute Disease; Akathisia, Drug-Induced; Dopamine Antagonists; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Hypotension, Orthostatic; Migraine Disorders; Prochlorperazine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30990883
DOI: 10.1111/head.13527 -
European Psychiatry : the Journal of... Apr 2019Non-pharmacological interventions preferably precede pharmacological interventions in acute agitation. Reviews of pharmacological interventions remain descriptive or... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Non-pharmacological interventions preferably precede pharmacological interventions in acute agitation. Reviews of pharmacological interventions remain descriptive or compare only one compound with several other compounds. The goal of this study is to compute a systematic review and meta-analysis of the effect on restoring calmness after a pharmacological intervention, so a more precise recommendation is possible.
METHOD
A search in Pubmed and Embase was done to isolate RCT's considering pharmacological interventions in acute agitation. The outcome is reaching calmness within maximum of 2 h, assessed by the psychometric scales of PANSS-EC, CGI or ACES. Also the percentages of adverse effects was assessed.
RESULTS
Fifty-three papers were included for a systematic review and meta-analysis. Most frequent studied drug is olanzapine. Changes on PANNS-EC and ACES at 2 h showed the strongest changes for haloperidol plus promethazine, risperidon, olanzapine, droperidol and aripiprazole. However, incomplete data showed that the effect of risperidon is overestimated. Adverse effects are most prominent for haloperidol and haloperidol plus lorazepam.
CONCLUSION
Olanzapine, haloperidol plus promethazine or droperidol are most effective and safe for use as rapid tranquilisation. Midazolam sedates most quickly. But due to increased saturation problems, midazolam is restricted to use within an emergency department of a general hospital.
Topics: Aggression; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Hypnotics and Sedatives; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome
PubMed: 30721802
DOI: 10.1016/j.eurpsy.2019.01.014