-
The Cochrane Database of Systematic... Oct 2020Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
OBJECTIVES
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded.
DATA COLLECTION AND ANALYSIS
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
MAIN RESULTS
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
AUTHORS' CONCLUSIONS
We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).
Topics: Adult; Anesthesia, General; Antiemetics; Drug Therapy, Combination; Female; Humans; Male; Network Meta-Analysis; Placebos; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33075160
DOI: 10.1002/14651858.CD012859.pub2 -
RSC Advances Oct 2020The British Pharmacopeia (BP) reported that the carcinogenic and hepatotoxic, benzophenone (BZP) is a dimenhydrinate (DMH) impurity. On the other hand, cinnarizine (CIN)...
The British Pharmacopeia (BP) reported that the carcinogenic and hepatotoxic, benzophenone (BZP) is a dimenhydrinate (DMH) impurity. On the other hand, cinnarizine (CIN) is reported to have five impurities (A-E). The toxicity profile of CIN impurities was studied and the data revealed that impurity A [1-(diphenylmethyl)piperazine] (DPP) was the most toxic CIN impurity, and hence it was selected during this work. TLC-densitometric method was developed for separation and simultaneous quantitation of DMH, CIN and their toxic impurities. In the proposed method hexane : ethanol : acetone : glacial acetic acid (7 : 3 : 0.7 : 0.5, by volume) with UV scanning at 225 nm were used. Method validation was carried out according to ICH guidelines and linearity was achieved in the range 0.2-4, 0.5-5, 0.1-2.0, and 0.05-2.2 μg per band for DMH, CIN, BZP and DPP, respectively. On the application of the method to pharmaceutical formulation, no interference from additives was observed. The greenness of the method was evaluated using the analytical eco-scale and the results revealed the low negative environmental impact of the developed method.
PubMed: 35521250
DOI: 10.1039/d0ra06147f -
Toxicology Reports 2020has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific...
has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific evidence of the plant extract as antiemetic. Therefore, this study was intended to assess the antiemetic activity of Juice (JCR), aqueous (CRAE) and methanolic extract (CRME) of in pigeons. Emesis was induced through GIT irritants like ampicillin (300 mg/kg, IM), copper sulphate (100 mg/kg, PO), conc. sodium chloride solution (1600 mg/kg, PO) and cisplatin (5-HT receptor stimulator) (6 mg/kg, IM). Dimenhydrinate acted as a positive control (2 mg/kg; IM). JCR [(1 ml/kg (1 %) and 1 ml/kg (2 %)], CRAE, and CRME were administered intramuscularly at different doses (50, 100 and 200 mg/kg) to each pigeon ( = 6). In each group, calculation of total number of jerks & vomiting episodes, and vomiting-weight was carried out to evaluate its antiemetic activity. The JCR exhibited a significant ( < 0.05) antiemetic impact on both the frequency and onset of emesis at 1 ml/kg (2 %) against various emesis mediator, except sodium chloride. Similarly, CRAE and CRME elicited marked dose dependent inhibition both on onset and frequency of emesis with highly significant ( < 0.001) effect at 200 mg/kg. The study reflects that juice, aqueous and methanolic extract of have significant antiemetic potential and possess pharmacological active constituent(s) that interfered with the emetic mediators by acting through GIT irritation and 5-HT receptor stimulations. Results of this study provide a scientific background to its traditional antiemetic uses.
PubMed: 33024704
DOI: 10.1016/j.toxrep.2020.09.009 -
ORL; Journal For Oto-rhino-laryngology... 2021Vertigo appears as a result of a sudden neural activity imbalance of the vestibular system. The vertigo prevalence is higher in patients over 60 years of age compared to...
INTRODUCTION
Vertigo appears as a result of a sudden neural activity imbalance of the vestibular system. The vertigo prevalence is higher in patients over 60 years of age compared to patients under 40 years of age.
OBJECTIVES
The purpose of this study was to analyze the effect of craniosacral osteopathy on dizziness and balance in individuals who have peripheral vestibular pathology.
METHODS
A total of 30 individuals, aged 24-50 years, participated in this study. Twenty-four of the participants were female (80%) and 6 were male (20%). The participants were separated into 2 groups, with 15 patients included in the cranial osteopathy treatment group (study group) and 15 patients included in the group that used dimenhydrinate (control group). The individuals were evaluated in terms of dizziness and balance. A visual analog scale was used to evaluate dizziness. Balance was evaluated using the Berg balance scale and the Activities-Specific Balance Confidence scale. The craniosacral treatment program was applied once per week for 6 sessions. All of the individuals included in this study were evaluated 3 times, i.e., prior to treatment, on the third week of treatment, and on the sixth week of treatment.
RESULTS
Significant improvement was noted within each group in terms of dizziness and balance (p < 0.05). When the groups were compared with each other, it was observed that craniosacral osteopathy was more effective than dimenhydrinate treatment for dizziness and balance (p < 0.05).
CONCLUSION
Craniosacral osteopathy is an effective treatment choice in individuals who have chronic peripheral vestibular pathology. In individuals who have resistant and chronic vestibular pathology, craniosacral osteopathy should be evaluated among the treatment choices.
Topics: Adult; Aged; Dizziness; Female; Humans; Male; Middle Aged; Treatment Outcome; Vertigo; Vestibular Diseases; Vestibule, Labyrinth; Visual Analog Scale; Young Adult
PubMed: 32906128
DOI: 10.1159/000509486 -
International Journal of Clinical... Apr 2020Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the...
Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥ 3 for concurrent medications or a dose-standardized average daily score of ≥ 3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson's disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.
Topics: Age Factors; Aged; Aged, 80 and over; Cholinergic Antagonists; Comorbidity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Utilization; Female; Humans; Insurance Claim Review; Male; Polypharmacy; Republic of Korea; Risk Factors; Sex Factors; Socioeconomic Factors
PubMed: 32281075
DOI: 10.1007/s11096-020-01010-7 -
Pediatrics Apr 2020Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use. (Meta-Analysis)
Meta-Analysis
CONTEXT
Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use.
OBJECTIVE
To determine the effectiveness and safety of antiemetics for controlling vomiting in children with acute gastroenteritis.
DATA SOURCES
Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Latin America and the Caribbean Literature on Health Sciences, and gray literature, until December 2018.
STUDY SELECTION
We selected randomized clinical trials comparing metoclopramide, ondansetron, domperidone, dexamethasone, dimenhydrinate, and granisetron.
DATA EXTRACTION
Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model.
RESULTS
Twenty-four studies were included (3482 children). Ondansetron revealed the largest effect in comparison to placebo for cessation of vomiting (odds ratio = 0.28 [95% credible interval = 0.16 to 0.46]; quality of evidence: high) and for hospitalization (odds ratio = 2.93 [95% credible interval = 1.69 to 6.18]; quality of evidence: moderate). Ondansetron was the only intervention that reduced the need for intravenous rehydration and the number of vomiting episodes. When considering side effects, dimenhydrinate was the only intervention that was worse than placebo.
LIMITATIONS
Most treatment comparisons had low- or very low-quality evidence, because of risk of biases and imprecise estimates.
CONCLUSIONS
Ondansetron is the only intervention that revealed an effect on the cessation of vomiting, on preventing hospitalizations, and in reducing the need for intravenous rehydration. Ondansetron was also considered a safe intervention.
Topics: Acute Disease; Antiemetics; Child; Child, Preschool; Dexamethasone; Diarrhea; Dimenhydrinate; Domperidone; Fluid Therapy; Gastroenteritis; Granisetron; Hospitalization; Humans; Infant; Metoclopramide; Network Meta-Analysis; Ondansetron; Randomized Controlled Trials as Topic; Regression Analysis; Vomiting
PubMed: 32132152
DOI: 10.1542/peds.2019-3260 -
Turkish Archives of Otorhinolaryngology Dec 2019Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular system disease causing dizziness. It occurs more in the 5th decade of life and...
OBJECTIVE
Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular system disease causing dizziness. It occurs more in the 5th decade of life and affects the posterior canal in 90% of the patients. The most effective treatment method is canalith repositioning (CRP) maneuver. The aim of this study is to evaluate the effects of betahistine and dimenhydrinate therapies in addition to CRP maneuver on BPPV patients.
METHODS
The study included 64 patients who had complaints of dizziness and were diagnosed with BPPV by their history and provocation maneuvers. The patients were divided into two groups. In Group 1, only repositioning maneuver was performed. Group 2 was divided into two subgroups. In Group 2a, repositioning maneuver was performed and betahistine 24 mg twice daily was given for 10 days. In Group 2b, repositioning maneuver was performed and dimenhydrinate 50 mg once daily was given for five days. On the 10 day, all patients were reexamined, and provocation maneuver was performed. Dizziness handicap inventory (DHI) was completed and outcomes were reviewed for therapeutic efficacy.
RESULTS
Mean DHI scores in all patient groups statistically significantly decreased from a pre-treatment level of 52.16 (range, 20-100) to a post-treatment level of 17.84 (range, 0-78) (p<0.001). No statistically significant differences were found in terms of DHI scores between Group 1 (repositioning maneuver only) and Group 2 (repositioning maneuver plus betahistine or dimenhydrinate).
CONCLUSION
The most effective treatment method of BPPV is repositioning maneuver. Addition of betahistine or dimenhydrinate pharmacotherapy to repositioning maneuver did not show superiority to treatment with repositioning maneuvers alone.
PubMed: 32128517
DOI: 10.5152/tao.2019.4185 -
CMAJ : Canadian Medical Association... Feb 2020
Topics: Aged; Antiemetics; Benign Paroxysmal Positional Vertigo; Dimenhydrinate; Head Impulse Test; Hearing Tests; Humans; Male; Middle Aged; Neurologic Examination; Nystagmus, Pathologic; Patient Positioning; Vestibular Neuronitis
PubMed: 32094268
DOI: 10.1503/cmaj.190334 -
International Journal of Environmental... Feb 2020Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women...
Medication use during pregnancy is a common practice that has been increasing in recent years. The aim of this study is to describe medication use among pregnant women from the 2015 Pelotas (Brazil) Birth Cohort Study. This paper relies on a population-based cohort study including 4270 women. Participants completed a questionnaire about the antenatal period, including information about medication use. We performed descriptive analyses of the sample and the medications used and adjusted analyses for the use of medications and self-medication. The prevalence of medication use was 92.5% (95% CI 91.7-93.3), excluding iron salts, folic acid, vitamins, and other minerals. The prevalence of self-medication was 27.7% (95% CI 26.3-29.1). In the adjusted analysis, women who had three or more health problems during pregnancy demonstrated higher use of medicines. Self-medication was higher in lower income groups and among smokers and multiparous women (three pregnancies or more). Acetaminophen, scopolamine, and dimenhydrinate were the medications most commonly used. This study describes the pattern of drug use among pregnant women in a population-based cohort study, with a high prevalence of self-medication. Greater awareness of the risks of self-medication during pregnancy is required, focusing on groups more prone to this practice, as well as ensuring qualified multidisciplinary prenatal care.
Topics: Acetaminophen; Adult; Brazil; Cohort Studies; Dietary Supplements; Female; Folic Acid; Humans; Interviews as Topic; Pharmacoepidemiology; Pregnancy; Prenatal Care; Prevalence; Qualitative Research; Self Medication; Surveys and Questionnaires; Vitamins; Young Adult
PubMed: 32033282
DOI: 10.3390/ijerph17030989