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Medicine Dec 2018In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets...
OBJECTIVE
In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT).
METHOD
A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were "Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets," and "poisoning," or "toxicity," in Chinese and in English.
RESULT
Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients.
CONCLUSION
The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.
Topics: Bronchodilator Agents; China; Drug Combinations; Ephedrine; Humans; Phenytoin; Tablets; Theophylline
PubMed: 30572493
DOI: 10.1097/MD.0000000000013689 -
Heart Failure Reviews May 2019Some randomized controlled trials (RCTs) have tested the efficacy of beta-blockers as prophylactic agents on cancer therapy-induced cardiotoxicity; however, the quality... (Meta-Analysis)
Meta-Analysis
Some randomized controlled trials (RCTs) have tested the efficacy of beta-blockers as prophylactic agents on cancer therapy-induced cardiotoxicity; however, the quality of this evidence remains undetermined. This systematic review and meta-analysis study aims to evaluate the prophylactic effects of beta-blockers, especially carvedilol, on chemotherapy-induced cardiotoxicity. RCTs were identified by searching the MEDLINE (PubMed), Embase (OvidSP), Cochrane CENTRAL (OvidSP), etc., until December 2017. Inclusion criteria were randomized clinical trial and adult cancer patients started beta-blockers before chemotherapy. We evaluated the mean differences (MD) by fixed- or random-effects model and the odds ratio by Peto's method. Primary outcome was the left ventricular ejection fraction (LVEF) of patients after chemotherapy, and secondary outcomes were all-cause mortality, clinically overt cardiotoxicity, and other echocardiographic measurements. In total, we included six RCTs that used carvedilol as a prophylactic agent in patients receiving chemotherapy. The LVEF was not significantly distinct between those using carvedilol and placebo after chemotherapy (MD, 1.74; 95% confidence interval (CI), - 0.18 to 3.66; P = 0.08). The incidence of clinically overt cardiotoxicity was lower in the carvedilol group compared with the control group (Peto OR, 0.42; 95% CI, 0.20-0.89; P = 0.02). Furthermore, after chemotherapy, the LV end-diastolic diameter did not increase in the carvedilol group compared with the placebo group (MD, - 1.41; 95% CI, - 2.32 to - 0.50; P = 0.002). The prophylactic use of carvedilol exerted no impact on the early asymptomatic LVEF decrease but seemed to attenuate the frequency of clinically overt cardiotoxicity and prevent ventricular remodeling.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Antineoplastic Agents; Cardiotoxicity; Carvedilol; Echocardiography; Female; Humans; Incidence; Male; Middle Aged; Protective Agents; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling; Young Adult
PubMed: 30523513
DOI: 10.1007/s10741-018-9755-3 -
International Journal of Surgery... Dec 2018In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with pre-eclampsia. A meta-analysis of the abovementioned trials is needed.
METHODS
Several databases (PubMed, Embase, Web of Science and Cochrane Library) were searched from inception to April 2018 for trials comparing phenylephrine with ephedrine in cesarean delivery. The primary outcome is the incidence of maternal hypotension.
RESULTS
Thirty-six trials (2439 patients) with elective cesarean delivery, three trials (400 patients) with emergency cesarean delivery and three trials (192 patients) with parturients with pre-eclampsia were included and analyzed. The incidence of hypotension did not differ in the elective surgery group (relative risk 0.83, 95% CI 0.66 to 1.05), emergency surgery group (relative risk 1.02, 95% CI 0.87 to 1.19) and pre-eclamptic parturients group (relative risk 0.93, 95% CI 0.63 to 1.37). The phenylephrine group had a higher incidence of bradycardia and lower incidences of tachycardia and nausea or vomiting in all three patient groups. The phenylephrine group also had lower fetal acidosis rate, higher umbilical artery and vein pH values and less base excess in the elective surgery. The abovementioned outcomes were similar in the emergency surgery group and the pre-eclampsia group. Publication bias for hypotension was detected. However, the trim and fill method demonstrated that the publication bias had little impact on hypotension. Trial sequential analysis of hypotension in elective surgery showed that this meta-analysis lacked a sufficient cumulative sample size and that further studies should be included.
CONCLUSION
Phenylephrine and ephedrine were both effective in maintaining hemodynamic balance. Newborns benefited more from phenylephrine in elective cesarean delivery, but not in emergency cesarean delivery or in parturients with pre-eclampsia. More trials should be included to achieve more conclusive results.
Topics: Adult; Anesthesia, Spinal; Cesarean Section; Ephedrine; Female; Humans; Hypotension; Incidence; Infant, Newborn; Phenylephrine; Pregnancy; Vasoconstrictor Agents
PubMed: 30389535
DOI: 10.1016/j.ijsu.2018.10.039 -
The Cochrane Database of Systematic... Oct 2018Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a non-selective beta-blocker with additional intrinsic alpha-blocking effects, which may be superior to traditional, non-selective beta-blockers in reducing portal pressure and, therefore, in reducing the risk of upper gastrointestinal bleeding.
OBJECTIVES
To assess the beneficial and harmful effects of carvedilol compared with traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.
SEARCH METHODS
We combined searches in the Cochrane Hepato-Biliary's Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 08 May 2018.
SELECTION CRITERIA
We included randomised clinical trials comparing carvedilol versus traditional, non-selective beta-blockers, irrespective of publication status, blinding, or language. We included trials evaluating both primary and secondary prevention of upper gastrointestinal bleeding in adults with cirrhosis and verified gastroesophageal varices.
DATA COLLECTION AND ANALYSIS
Three review authors (AZ, RJ and LH), independently extracted data. The primary outcome measures were mortality, upper gastrointestinal bleeding and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the quality of the evidence with GRADE.
MAIN RESULTS
Eleven trials fulfilled our inclusion criteria. One trial did not report clinical outcomes. We included the remaining 10 randomised clinical trials, involving 810 participants with cirrhosis and oesophageal varices, in our analyses. The intervention comparisons were carvedilol versus propranolol (nine trials), or nadolol (one trial). Six trials were of short duration (mean 6 (range 1 to 12) weeks), while four were of longer duration (13.5 (6 to 30) months). Three trials evaluated primary prevention; three evaluated secondary prevention; while four evaluated both primary and secondary prevention. We classified all trials as at 'high risk of bias'. We gathered mortality data from seven trials involving 507 participants; no events occurred in four of these. Sixteen of 254 participants receiving carvedilol and 19 of 253 participants receiving propranolol or nadolol died (RR 0.86, 95% CI 0.48 to 1.53; I = 0%, low-quality evidence). There appeared to be no differences between carvedilol versus traditional, non-selective beta-blockers and the risks of upper gastrointestinal bleeding (RR 0.77, 95% CI 0.43 to 1.37; 810 participants; 10 trials; I = 45%, very low-quality evidence) and serious adverse events (RR 0.97, 95% CI 0.67 to 1.42; 810 participants; 10 trials; I = 14%, low-quality evidence). Significantly more deaths, episodes of upper gastrointestinal bleeding and serious adverse events occurred in the long-term trials but there was not enough information to determine whether there were differences between carvedilol and traditional, non-selective beta-blockers, by trial duration. There was also insufficient information to detect differences in the effects of these interventions in trials evaluating primary or secondary prevention. There appeared to be no differences in the risk of non-serious adverse events between carvedilol versus its comparators (RR 0.55, 95% CI 0.23 to 1.29; 596 participants; 6 trials; I = 88%; very low-quality evidence). Use of carvedilol was associated with a greater reduction in hepatic venous pressure gradient than traditional, non-selective beta-blockers both in absolute (MD -1.75 mmHg, 95% CI -2.60 to -0.89; 368 participants; 6 trials; I = 0%; low-quality evidence) and percentage terms (MD -8.02%, 95% CI -11.49% to -4.55%; 368 participants; 6 trials; I = 0%; low-quality evidence). However, we did not observe a concomitant reduction in the number of participants who failed to achieve a sufficient haemodynamic response (RR 0.76, 95% CI 0.57 to 1.02; 368 participants; 6 trials; I = 42%; very low-quality evidence) or in clinical outcomes.
AUTHORS' CONCLUSIONS
We found no clear beneficial or harmful effects of carvedilol versus traditional, non-selective beta-blockers on mortality, upper gastrointestinal bleeding, serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient. However, the evidence was of low or very low quality, and hence the findings are uncertain. Additional evidence is required from adequately powered, long-term, double-blind, randomised clinical trials, which evaluate both clinical and haemodynamic outcomes.
Topics: Adrenergic beta-Antagonists; Adult; Carvedilol; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Nadolol; Primary Prevention; Propranolol; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 30372514
DOI: 10.1002/14651858.CD011510.pub2 -
Annals of Medicine Feb 2019Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be... (Comparative Study)
Comparative Study Meta-Analysis
Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of esmolol for perioperative cardiac protection. We searched PubMed, Ovid Medline and Cochrane Central Register for Controlled trials. Eligible randomized controlled studies (RCTs) reported a perioperative esmolol intervention with at least one of the primary (major cardiac or renal complications during the first 30 postoperative days) or secondary (postoperative adverse effects and all-cause mortality) outcomes. We included 196 adult patients from three RCTs. Esmolol significantly reduced postoperative myocardial ischaemia, RR =0.43 [95% confidence interval, CI: 0.21-0.88], p = .02. No association with clinically significant bradycardia and hypotension compared to patients receiving control treatment could be confirmed (RR =7.4 [95% CI: 0.29-139.81], p = .18 and RR =2.21 [95% CI: 0.34-14.36], p = .41, respectively). No differences regarding other outcomes were observed. No study reported postoperative renal outcomes. Esmolol seems promising for the prevention of perioperative myocardial ischaemia. However, the association with bradycardia and hypotension remains unclear. Randomized trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted. Key messages Short-acting cardioselective esmolol seems efficient in the prevention of perioperative myocardial ischaemia. The possibly increased risk of bradycardia and hypotension with short-acting intravenous beta blockade could not be confirmed or refuted by available data. Future adequately powered trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.
Topics: Acute Kidney Injury; Administration, Intravenous; Adrenergic beta-1 Receptor Antagonists; Bradycardia; Female; Heart; Heart Diseases; Hemodynamics; Humans; Hypotension; Male; Myocardial Infarction; Myocardial Ischemia; Perioperative Care; Postoperative Complications; Propanolamines; Protective Agents; Randomized Controlled Trials as Topic; Safety
PubMed: 30346213
DOI: 10.1080/07853890.2018.1538565 -
British Journal of Clinical Pharmacology Dec 2018Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI)...
AIM
Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI.
METHOD
Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087).
RESULTS
We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol-related side effects. In a case-control study, the DDI was not significantly associated with bradycardia.
CONCLUSION
Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta-blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol-related side effects is necessary.
Topics: Cytochrome P-450 CYP2D6; Drug Interactions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Metoprolol; Middle Aged; Paroxetine
PubMed: 30248178
DOI: 10.1111/bcp.13741 -
Emergency Medicine Journal : EMJ Sep 2018Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of β-blocker versus no β-blocker use among patients with CACP.
METHODS
We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used β-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating β-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between β-blocker versus no β-blocker usage in patients with CACP. Studies without a comparison between β-blocker and no β-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and Istatistics.
RESULTS
A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on β-blocker versus no β-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on β-blocker versus no β-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43).
CONCLUSIONS
In patients presenting with acute chest pain and underlying cocaine, β-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.
Topics: Humans; Acute Coronary Syndrome; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Carvedilol; Cocaine; Metoprolol; Propanolamines; Propranolol
PubMed: 29921621
DOI: 10.1136/emermed-2017-207065 -
The Cochrane Database of Systematic... Apr 2018Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular tumours are usually uncomplicated and tend to regress spontaneously. However, when haemangiomas occur in high-risk areas, such as near the eyes, throat, or nose, impairing their function, or when complications develop, intervention may be necessary. This is an update of a Cochrane Review first published in 2011.
OBJECTIVES
To assess the effects of interventions for the management of infantile haemangiomas in children.
SEARCH METHODS
We updated our searches of the following databases to February 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, LILACS, and CINAHL. We also searched five trials registries and checked the reference lists of included studies for further references to relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of all types of interventions, versus placebo, active monitoring, or other interventions, in any child with single or multiple infantile haemangiomas (IHs) located on the skin.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcome measures were clearance, a subjective measure of improvement, and adverse events. Secondary outcomes were other measures of resolution; proportion of parents or children who consider there is still a problem; aesthetic appearance; and requirement for surgical correction. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included 28 RCTs, with a total of 1728 participants, assessing 12 different interventions, including lasers, beta blockers (e.g. propranolol, timolol maleate), radiation therapy, and steroids. Comparators included placebo, an active monitoring approach, sham radiation, and interventions given alone or in combination.Studies were conducted in a number of countries, including China, Egypt, France, and Australia. Participant age ranged from 12 weeks to 13.4 years. Most studies (23/28) included a majority of females and different types of IHs. Duration of follow-up ranged from 7 days to 72 months.We considered most of the trials as at low risk of random sequence generation, attrition bias, and selective reporting bias. Domains such as allocation concealment and blinding were not clearly reported in general. We downgraded evidence for issues related to risk of bias and imprecision.We report results for the three most important comparisons, which we chose on the basis of current use. Outcome measurement of these comparisons was at 24 weeks' follow-up.Oral propranolol versus placeboCompared with placebo, oral propranolol 3 mg/kg/day probably improves clinician-assessed clearance (risk ratio (RR) 16.61, 95% confidence interval (CI) 4.22 to 65.34; 1 study; 156 children; moderate-quality evidence) and probably leads to a clinician-assessed reduction in mean haemangioma volume of 45.9% (95% CI 11.60 to 80.20; 1 study; 40 children; moderate-quality evidence). We found no evidence of a difference in terms of short- or long-term serious adverse events (RR 1.05, 95% CI 0.33 to 3.39; 3 studies; 509 children; low-quality evidence), nor in terms of bronchospasm, hypoglycaemia, or serious cardiovascular adverse events. The results relating to clearance and resolution for this comparison were based on one industry-sponsored study.Topical timolol maleate versus placeboThe chance of reduction of redness, as a measure of clinician-assessed resolution, may be improved with topical timolol maleate 0.5% gel applied twice daily when compared with placebo (RR 8.11, 95% CI 1.09 to 60.09; 1 study; 41 children;low-quality evidence). Regarding short- or long-term serious cardiovascular events, we found no instances of bradycardia (slower than normal heart rate) or hypotension in either group (1 study; 41 children; low-quality evidence). No other safety data were assessed, and clearance was not measured.Oral propranolol versus topical timolol maleateWhen topical timolol maleate (0.5% eye drops applied twice daily) was compared with oral propranolol (via a tablet taken once per day, at a 1.0 mg/kg dose), there was no evidence of a difference in haemangioma size (as a measure of resolution) when measured by the proportion of patients with a clinician-assessed reduction of 50% or greater (RR 1.13, 95% CI 0.64 to 1.97; 1 study; 26 participants; low-quality evidence). Although there were more short- or long-term general adverse effects (such as severe diarrhoea, lethargy, and loss of appetite) in the oral propranolol group, there was no evidence of a difference between groups (RR 7.00, 95% CI 0.40 to 123.35; 1 study; 26 participants; very low-quality evidence). This comparison did not measure clearance.None of our key comparisons evaluated, at any follow-up, a subjective measure of improvement assessed by the parent or child; proportion of parents or children who consider there is still a problem; or physician-, child-, or parent-assessed aesthetic appearance.
AUTHORS' CONCLUSIONS
We found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs.Our key results indicate that in the management of IH in children, oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harms. We found no evidence of a difference between oral propranolol and topical timolol maleate with regard to reducing haemangioma size, but we are uncertain if there is a difference in safety. Oral propranolol is currently the standard treatment for this condition, and our review has not found evidence to challenge this. However, these results are based on moderate- to very low-quality evidence.The included studies were limited by small sample sizes and risk of bias in some domains. Future trials should blind personnel and participants; describe trials thoroughly in publications; and recruit a sufficient number of children to deduce meaningful results. Future trials should assess patient-reported outcomes, as well as objective outcomes of benefit, and should report adverse events comprehensively. Propranolol and timolol maleate require further assessment in RCTs of all types of IH, including those considered problematic, as do other lesser-used interventions and new interventions. All treatments should be compared against propranolol and timolol maleate, as beta blockers are approved as standard care.
Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Antineoplastic Agents; Bleomycin; Child, Preschool; Hemangioma, Capillary; Humans; Infant; Lasers, Dye; Methylprednisolone; Photochemotherapy; Prednisolone; Propranolol; Radiotherapy; Randomized Controlled Trials as Topic; Remission Induction; Skin Neoplasms; Timolol
PubMed: 29667726
DOI: 10.1002/14651858.CD006545.pub3 -
The Cochrane Database of Systematic... Mar 2018Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as an addition to the available treatment strategies. This review was originally published in 2012 and updated in 2017.
OBJECTIVES
The main objective was to establish the efficacy and safety of aromatherapy comparable to standard pharmacological treatments for PONV in adults and children.
SEARCH METHODS
We searched CENTRAL; MEDLINE; Embase; CINAHL; CAM on PubMed; Informit; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles up to March 2017. The original search was performed in August 2011.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat PONV. Interventions were all types of aromatherapy compared to placebo or with standard antiemetics. Primary outcomes were severity and duration of PONV. Secondary outcomes were adverse reactions, use of rescue antiemetics and patient satisfaction.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias in the included studies and extracted data. For dichotomous outcome variables, we used a random-effects model and calculated risk ratio (RR) with associated 95% confidence interval (95% CI). For continuous outcome variables, we used a random-effects model and calculated standardized mean difference (SMD) with associated 95% CI. We used the GRADE software to compile 'Summary of findings' tables.
MAIN RESULTS
We included seven new studies with 663 participants in the 2017 update; five RCTs and two CCTs. These were added to the nine previously included studies (six RCTs and three CCTs with a total of 373 participants) for a total of 16 included studies and 1036 participants in this updated review. The mean age and range data for all participants were not reported for all studies. We identified two registered trials that met the inclusion criteria for this review; however there are no results for these studies yet.Overall, the GRADE assessment of evidence quality ranged from moderate to very low. The method of randomization in 11 of the 12 included RCTs was explicitly stated and adequate. Incomplete or methodologically diverse reporting of data affected the completeness of the analysis. Data on additional aromatherapies were added in the 2017 update (blended aromatherapy products, and peppermint products). Heterogeneity of outcome measures and time points between studies affected the completeness of the analysis.In the summary of the findings of six studies, we did not find aromatherapy to be effective in reducing nausea severity in comparison to placebo (SMD -0.22, 95% CI -0.63 to 0.18, P value = 0.28, 241 participants, level of evidence: low). Those participants receiving aromatherapy were no more likely to be free of nausea at the end of the treatment period than those receiving placebo (RR 3.25, 95% CI 0.31 to 34.33, P value = 0.33, 4 trials, 193 participants, evidence level: very low), however they were less likely to require rescue antiemetics (RR 0.60, 95% CI 0.37 to 0.97, P value = 0.04, 7 trials, 609 participants, evidence level: low). There were no data reported on adverse events or patient satisfaction for this comparison.A specific comparison of peppermint aromatherapy to placebo did not show evidence of an effect on nausea severity at five minutes post-treatment in the pooled results (SMD -0.18, 95% CI -0.86 to 0.49, P value = 0.59, 4 trials, 115 participants, evidence level: low). There were no data reported on nausea duration, use of rescue antiemetics, adverse events or patient satisfaction for this comparison.When we pooled studies comparing isopropyl alcohol to standard antiemetic treatment in a GRADE summary of findings, in terms of nausea duration, there was a significant effect on the time in minutes to a 50% reduction in nausea scores (SMD -1.10, 95% CI -1.43 to -0.78, P value < 0.00001, 3 trials, 176 participants, evidence level: moderate). Fewer participants who received isopropyl alcohol required rescue antiemetics (RR 0.67, 95% CI 0.46 to 0.98, P value = 0.04, 215 participants, 4 trials, evidence level: moderate). Two studies with 172 participants measured patient satisfaction; there were high levels of satisfaction across both aromatherapy and standard treatment groups and no differences found (evidence level: low). There were no data reported on nausea severity or adverse events for this comparison.There was no difference in effectiveness between isopropyl alcohol vapour inhalation and placebo for reducing the proportion of participants requiring rescue antiemetics (RR 0.39, 95% CI 0.12 to 1.24, P value = 0.11, 291 participants, 4 trials, evidence level: very low). There were no data reported on nausea severity, nausea duration, adverse events or patient satisfaction for this comparison.
AUTHORS' CONCLUSIONS
Overall, for nausea severity at the end of treatment, aromatherapy may have similar effectiveness to placebo and similar numbers of participants were nausea-free. However, this finding is based on low-quality evidence and therefore very uncertain. Low-quality evidence also suggests that participants who received aromatherapy may need fewer antiemetic medications, but again, this is uncertain. Participants receiving either aromatherapy or antiemetic medications may report similar levels of satisfaction with their treatment, according to low-quality evidence.
Topics: 2-Propanol; Administration, Inhalation; Antiemetics; Aromatherapy; Controlled Clinical Trials as Topic; Humans; Plant Oils; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 29523018
DOI: 10.1002/14651858.CD007598.pub3 -
The Cochrane Database of Systematic... Mar 2018Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP.
OBJECTIVES
To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP.
SEARCH METHODS
We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross-references and handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings.
SELECTION CRITERIA
We considered for inclusion randomised or quasi-randomised clinical trials that used beta-blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta-blockers in infants with established stage 2 or higher ROP with plus disease.In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti-VEGF or laser therapy; and arterial hypotension or bradycardia requiring inotropic support. Evidence was of moderate quality for the following outcomes: progression to stage 2 with plus disease; progression to stage 3 ROP; and progression to stage 4 or 5 ROP.Meta-analysis of three trials (N = 366) suggested beneficial effects of oral beta-blockers on the risk of requiring anti-VEGF agents (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.86; I² = 0%; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.01; I² = 75%; number needed to treat for an additional beneficial outcome (NNTB) 18, 95% CI 14 to 84) and laser therapy (typical RR 0.54, 95% CI 0.32 to 0.89; typical RD -0.09, 95% CI -0.16 to -0.02; I² = 31%; NNTB 12, 95% CI 8 to 47). Meta-analysis of two trials (N = 161) demonstrated a beneficial effect of oral beta-blockers on progression to stage 3 ROP (typical RR 0.60, 95% CI 0.37 to 0.96; I² = 0%; typical RD -0.15, 95% CI -0.28 to -0.02; I² = 73%; NNTB 7, 95% CI 5 to 67). There was no significant effect of oral beta-blockers on progression to stage 2 ROP with plus disease or to stage 4 or 5 ROP. Although meta-analysis did not indicate a significant effect of beta-blockers on arterial hypotension or bradycardia, propranolol dosage in one study was reduced by 50% in infants of less than 26 weeks' gestational age due to severe hypotension, bradycardia, and apnoea in several participants. Analyses did not indicate significant effects of beta-blockers on complications of prematurity or mortality. None of the trials reported on long-term visual impairment.
AUTHORS' CONCLUSIONS
Limited evidence of low-to-moderate quality suggests that prophylactic administration of oral beta-blockers might reduce progression towards stage 3 ROP and decrease the need for anti-VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long-term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta-blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long-term functional outcomes. We would encourage researchers to conduct large, well-designed trials to confirm or refute the role of beta-blockers for prevention and treatment of ROP in preterm infants. Trials should report on long-term visual impairment. Researchers should consider dose-finding studies of systemic beta-blockers and topical administration of beta-blockers, in order to optimise drug delivery and minimise adverse events.
Topics: Adrenergic beta-Antagonists; Angiogenesis Inhibitors; Cryotherapy; Disease Progression; Humans; Infant, Newborn; Infant, Premature; Laser Coagulation; Propranolol; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Salvage Therapy; Vascular Endothelial Growth Factor A
PubMed: 29499081
DOI: 10.1002/14651858.CD011893.pub2