Article

Ondansetron Compared With Metoclopramide for Hyperemesis Gravidarum

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Abstract

Objective: To compare ondansetron with metoclopramide in the treatment of hyperemesis gravidarum. Methods: We enrolled 160 women with hyperemesis gravidarum in a double-blind randomized trial. Participants were randomized to intravenous 4 mg ondansetron or 10 mg metoclopramide every 8 hours for 24 hours. Participants kept an emesis diary for 24 hours; at 24 hours, they expressed their well-being using a 10-point visual numeric rating scale and answered an adverse effects questionnaire. Nausea intensity was evaluated using a 10-point visual numeric rating scale at enrollment and at 8, 16, and 24 hours. Primary analysis was on an intention-to-treat basis. Results: Eighty women each were randomized to ondansetron or metoclopramide. Median well-being visual numeric rating scale scores were 9 (range, 5-10) compared with 9 (range, 4-10) (P=.33) and vomiting episodes in the first 24 hours were 1 (range, 0-9) compared with 2 (range, 0-23) (P=.38) for ondansetron compared with metoclopramide, respectively. Repeat-measures analysis of variance of nausea visual numeric rating scale showed no difference between study drugs (P=.22). Reported rates of drowsiness (12.5% compared with 30%; P=.01; number needed to treat to benefit, 6), xerostomia (10.0% compared with 23.8%; P<.01; number needed to treat to benefit, 8), and persistent ketonuria at 24 hours (12.5% compared with 30%; P=.01; number needed to treat to benefit, 6) were less frequent with ondansetron. Length of hospital stay was similar. Conclusion: Ondansetron and metoclopramide demonstrated similar antiemetic and antinauseant effects in hyperemesis gravidarum. However, the overall profile, particularly regarding adverse effects, was better with ondansetron. In our setting, metoclopramide was significantly less expensive than ondansetron and remained a reasonable antiemetic choice. Clinical trial registration: ISRCN Register, www.isrctn.org, ISRCTN00592566. Level of evidence: I.

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... Metoclopramide (a dopamine antagonist) and ondansetron (a serotonin receptor antagonist) are two common antiemetics used to manage HG (4) . Multiple randomized controlled trials (RCTs) compared the superiority of metoclopramide or ondansetron in treating pregnant women with HG (5)(6)(7)(8)(9) . But, small sample sizes and conflicting findings are a few limitations. ...
... Overall, five studies (comprising 695 patients, ondansetron=355 and metoclopramide=340) met the inclusion criteria ( Figure 1) (5)(6)(7)(8)(9) . Table 1 and Table 2 show the summary of the meta-analyzed RCTs and baseline characteristics of the patients, respectively. ...
... An overall "low" risk of bias was found in four out of the five included RCTs (Figure 2) (5)(6)(7)9) . Shaheen et al. (8) did not provide satisfactory information about randomization; therefore, a grading of "some concerns" was assigned to the randomization bias domain. ...
Article
This investigation examined the efficacy of ondansetron (intervention) versus metoclopramide (control) in managing parturient females with hyperemesis gravidarum (HG), by pooling data from randomized controlled trials (RCTs) using a meta-analysis approach. From inception until January 2022, five information sources were screened: Cochrane Central Register of Controlled Trials, Google Scholar, Scopus, PubMed and Web of Science. Quality assessment was done through the Cochrane Risk of Bias (version 2) assessment tool. The mean difference (MD) with 95% confidence interval (CI) was used to summarize the continuous data in a fixed-or random-effects model, depending on the extent of between-study heterogeneity. Five RCTs were included, comprising a total of 695 patients (355 and 340 females were assigned to ondansetron and metoclopramide, respectively). Four RCTs had an overall "low" risk of bias, whereas one RCT had an overall "some concerns" due to lack of sufficient information about randomization. There was no significant difference between both groups regarding the pregnancy-unique quantification of emesis and nausea score [MD=0.23, 95% CI (-0.42, 0.88), p=0.49], length of hospital stay [MD=-0.17 days, 95% CI (-0.35, 0.02), p=0.08], the number of doses of drug received [MD=0.45, 95% CI (-0.08, 0.98), p=0.10], and duration of intravenous fluids [MD=-1.73 hours, 95% CI (-5.79, 2.33), p=0.40]. Among parturient females with HG, there was no substantial difference in efficacy between both agents. Nevertheless, ondansetron is favored over metoclopramide in view of its trending therapeutic efficacy and better safety profile.
... A sífilis congênita (SC) resulta de uma infecção produzida pela espiroqueta 15 -19 4 (10,8) 8 (21,6) 5 (13,5) 12 (32,5) 8 (21,6) 37 (21) 20-34 15 (12,1) 22 (17,7) 26 (21) 29 (23,3) 32 (25,9) 124 ( arthropods to solving crimes and legal disputes. The aim of this work was to assess the entomological succession of diptera obtained from a pork burned with and without alcohol. ...
... Another large study showed brazilian blood donors prevalence of HTLV-1 on the order of one per 1,000 with regional differences probably due to the ethnic origin of the underlying population with indeed a higher prevalence in donors with black skin color (2.14/1,000) versus mixed (1.58/1,000) or white (0.79/1,000) Urinary manifestations may represent neurological commitment, with the occurrence of nocturia, urge urinary incontinence and dysuria being more frequent in its initial phase, which may progress to stress voiding, incomplete emptying and incontinence 11 . Hyperactivity of the detrusor muscle is the most frequent finding 1,3,4,14 . Urinary disorders are nowadays considered biological markers of an early onset of HAM/TSP and urinary incontinence is also seen as an oligosymptomatic form of this disease (CASTRO, 2002;TANAJURA, 2012;LIMA, 2016). ...
... Colite ulcerativa 81, 89 D Diagnóstico 6,10,15,25,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,43,45,58,62,74,77,79,81,84,85,89,105,107,126,139,140,141,142,143,145 Diarreia aguda 1,2,3,5,7,8,9,10 Disfunção motora 64 Hepatite B 11,13,14 Histopatologia 21,22 HTLV 63,64,65,66,67,69,70,71,72,73,145,146,147,148,149,150,151,152,153 I Idosa 74 ...
... Ondansetron, a serotonin receptor antagonist, and metoclopramide, a dopamine receptor antagonist, are widely used in the ED for the management of this condition. Differences in the onset of actions, effective dosages, and side effects make it difficult to choose the best antiemetic drug in patients with various causes of nausea and different clinical conditions (1,(8)(9)(10)(11)(12). Past studies mostly compared the antiemetic effects of ondansetron and metoclopramide in preventing or treating nausea related to chemotherapy and gastroenteritis and post-operative nausea (1,8,(13)(14)(15)(16)(17)(18). ...
... One study compared the effects of dexamethasone, in combination with metoclopramide or ondansetron, on preventing nausea after laparoscopic surgery and showed no significant difference between the two treatment arms (16). Abas et al. compared the efficacy of ondansetron and metoclopramide in the treatment of hyperemesis gravidarum, and the results showed no significant difference between the two drugs (9). In contrast to our findings, some studies have shown significant differences in the antiemetic effects of ondansetron and metoclopramide. ...
... Khatereh et al. showed that the required rescue dose was more frequent in metoclopramide (20%) compared to ondansetron (0%) (15). Abas reported that the frequency of headache, diarrhea, palpitation, and sleep issues showed no significant difference in those treated with ondansetron and metoclopramide but dry mouth mostly occurred in the metoclopramide arm (9). The difference between the results of these studies and the present study might be related to differences in the study population, dosage and way of administration of the drugs, time of side effects evaluation, mechanism and cause of nausea, and supportive treatments provided. ...
Article
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Objective: As nausea is one of the most common annoying symptoms in isolated head trauma (IHT) and needs timely management to prevent further adverse outcomes, this study was performed to compare ondansetron and metoclopramide as therapeutic agents in nauseous IHT. Methods: This study was a double-blind clinical trial. Participants were patients visiting the ED with the chief complaint of nauseous IHT event. Group A received 10mg/2ml of metoclopramide and group B 4mg/2ml of ondansetron through slow intravenous (IV) injection. The primary outcome was the severity of nausea 20 minutes after the intervention based on the visual analogue scale (VAS) score. Results: A total of 130 patients participated in the study (65 in each group). The mean age was 30.5±20.5 years, and 73.1% of the participants were male. The decrease in the mean nausea severity scores was statistically significant in both group A (78.3±9.7 before vs. 29.8±16.8 mm after the intervention; P < 0.001) and group B (78.5±11.1 vs. 27.8±13.9 mm; P < 0.001). There was no significant difference between the mean nausea severity scores of groups A and B before the intervention (P = 0.93) or after it (P = 0.65). The decrease in the severity score of nausea was 48.5 mm in group A and 50.6 mm in group B, with no significant difference between the two groups (P = 0.63). Conclusion: Both Ondansetron and metoclopramide significantly reduced the severity of nausea in patients with mild IHT visiting ED but no treatment arm was superior. Both drugs showed good safety profiles.
... Previous studies of ondansetron and metoclopramide have consistently documented improvements in mean symptom scores over 24-48 hours but none has reported the need for additional antiemetic treatment during the study period. [16][17][18]27,28 Abas et al. 18 reported that 14% of women randomised to ondansetron and 18% randomised to metoclopramide required open-label antiemetics after 24 hours of trial drug, although the duration of follow-up was not stated. The rates of TOP for NVP in the absence of fetal anomaly are poorly reported, and the factors associated with the decision are complex. ...
... Previous studies of ondansetron and metoclopramide have consistently documented improvements in mean symptom scores over 24-48 hours but none has reported the need for additional antiemetic treatment during the study period. [16][17][18]27,28 Abas et al. 18 reported that 14% of women randomised to ondansetron and 18% randomised to metoclopramide required open-label antiemetics after 24 hours of trial drug, although the duration of follow-up was not stated. The rates of TOP for NVP in the absence of fetal anomaly are poorly reported, and the factors associated with the decision are complex. ...
... ,18 Kashifard et al.17 compared ondansetron [4 mg per os (p.o.) three times per day] with metoclopramide (10 mg p.o. three times per day) in 83 women. Over the 14 days of the trial, the ondansetron group had lower vomiting scores than the metoclopramide group, but there was no difference in nausea scores. ...
Article
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Background: Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. Objectives: To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. Design: This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Participants: Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. Interventions: Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. Main outcome measures: The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Results: Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. Limitations: The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. Conclusions: The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. Trial registration: Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.
... 47,48 Compared with the serotonin 5-HT 3 receptor antagonist ondansetron, metoclopramide had similar antiemetic/ antinauseant effects and the length of stay in the hospital was the same. 50 As expected, metoclopramide caused more drowsiness and dry mouth. 50 In a clinical trial of 83 pregnant women randomly assigned to ondansetron or metoclopramide, ondansetron treatment resulted in significantly lower vomiting (P ¼ 0.042) but not nausea scores compared with metoclopramide. ...
... 50 As expected, metoclopramide caused more drowsiness and dry mouth. 50 In a clinical trial of 83 pregnant women randomly assigned to ondansetron or metoclopramide, ondansetron treatment resulted in significantly lower vomiting (P ¼ 0.042) but not nausea scores compared with metoclopramide. 51 In addition, an observational study using home subcutaneous therapy for HG suggested that metoclopramide is effective, safe, and economical. ...
... 51 When compared with metoclopramide, ondansetron had similar antiemetic/antinauseant effects and hospital length of stay and metoclopramide was associated with drowsiness and dry mouth. 50 In one study that compared the use of ondansetron with other antiemetic agents (metoclopramide, promethazine, prochlorperazine) for treatment of NVP in the emergency department, there was no difference in time from drug administration to disposition or administration of additional antiemetics among the agents. 62 There have been 4 published case reports of bowel obstruction with the use of ondansetron in pregnancy. ...
Article
Objectives: To review the evidence-based management of nausea and vomiting of pregnancy and hyperemesis gravidarum. Evidence: MEDLINE and Cochrane database searches were performed using the medical subject headings of treatment, nausea, vomiting, pregnancy, and hyperemesis gravidarum. The quality of evidence reported in these guidelines has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on Preventative Health Care. Benefits: Nausea and vomiting of pregnancy has a profound effect on women's health and quality of life during pregnancy as well as a financial impact on the health care system, and its early recognition and management is recommended. COST: Costs, including hospitalizations, additional office visits, and time lost from work, may be reduced if nausea and vomiting in pregnancy is treated early. Recommendations:
... 12 This condition can be affected because the antiemetic strength of HG between these two drugs may not be too different. A study conducted by Abas et al. (2014) showed that ODN effectively reduced symptoms better than MCP but did not show a significant difference in the frequency of vomiting. 16 As a relatively new drug used to treat HG, ODN has a higher price than MCP. ...
... A study conducted by Abas et al. (2014) showed that ODN effectively reduced symptoms better than MCP but did not show a significant difference in the frequency of vomiting. 16 As a relatively new drug used to treat HG, ODN has a higher price than MCP. 11 This price difference occurs in oral and parenteral preparations. ...
... The total cost of HG treatment with ODN is slightly more expensive than MCP. These results align with the study conducted by Abas et al. (2014), which also showed that the cost of treatment with MCP was cheaper than ODN. However, the total cost of treatment in the two groups was not statistically different. ...
Article
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Background: Hyperemesis Gravidarum (HG) is nausea and vomiting which interfere pregnant women's daily activities. Ondansetron (ODN) is often used off label for the treatment of hyperemesis gravidarum. This study aimed to analyze the efficacy and cost of ondansetron versus metoclopramide (MCP), a drug that has been used in the standard regimen for the treatment of HG. patients in the largest hospital in Jakarta during year 2012 to 2016. Method: The research was conducted with a cross-sectional study design on respondents with criteria, namely pregnant patients hospitalized with HG at Dr. Cipto Mangunkusumo Hospital from 2012-2016. Assessment of clinical effectiveness was carried out by looking at the day's duration until the symptoms of nausea and vomiting stopped. Furthermore, a cost analysis was carried out by calculating the average direct medical costs associated with the HG's condition. Result: The effectiveness of both antiemetics was not statistically significant (p = 0.370). The average cost per patient with ondansetron compared to metoclopramide was not significantly different (p = 0,966). Conclusion: There was no difference in the effectiveness and cost of ODN versus MCP for the treatment of hyperemesis gravidarum.
... Three small randomised studies [44][45][46] have shown ondansetron to be superior to doxylamine and pyridoxine in reducing nausea and vomiting, 44 equally effective but with fewer adverse effects than metoclopramide 45 and more effective at reducing severe vomiting than metoclopramide. 46 Suggested antiemetics for UK use are given in Appendix III. ...
... Three small randomised studies [44][45][46] have shown ondansetron to be superior to doxylamine and pyridoxine in reducing nausea and vomiting, 44 equally effective but with fewer adverse effects than metoclopramide 45 and more effective at reducing severe vomiting than metoclopramide. 46 Suggested antiemetics for UK use are given in Appendix III. ...
Research
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Royal College of Obstetricians and Gynaecologists Green Top Guideline number 69 on the Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum
... The NVP-specific and validated Pregnancy-Unique Quantification of Emesis (PUQE) score was collected daily; however, the a priori primary effectiveness endpoint was determined to be the change in NVP symptoms as measured by the PUQE score from baseline to Day 15. This period of study drug dosing for two weeks is substantially longer than other therapeutic studies in NVP which rarely continue beyond five days [17][18][19]. For ethical reasons, denying women suffering from NVP a safe and effective treatment, and randomizing them to placebo should be for as limited duration as possible. ...
... In this study, a secondary analysis was conducted on Diclegis® efficacy as compared to placebo after three, four or five days of study drug dosing, as compared to the original study that conducted data analysis to assess efficacy after 14 dosing days. Most studies conducted todate on efficacy of antiemetics for NVP were much shorter, typically three to five days long but no standardized duration of measurement is in place [17][18][19]. A standardized duration of measurement would also allow for a more accurate comparison of results across studies. ...
Article
Full-text available
Background Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin® in Canada and Diclegis® in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment. Methods Women suffering from NVP were randomized to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from two to four tablets a day, based on a pre-specified titration protocol. The primary efficacy endpoint was the change in the validated Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15 between Diclegis®-treated and placebo-treated women. For the present study, the change in PUQE score between baseline and Day 15 (end of the study) was compared to the changes observed for Days 3, 4, and 5. Results The use of delayed-release doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy until the end of the trial. Conclusion A four day study drug dosing trial with Diclegis® is sufficient to document efficacy, as the results are similar to those achieved after 14 study drug dosing days. The benefit seen at the earlier time validates drug efficacy and minimizes the natural course of improvement. Trial registration CTR No. NCT006 14445 2007.
... When metoclopramide was compared to ondansetron, they were comparable in reducing nausea, although ondansetron had a greater effect on reducing vomiting (Kashifard et al. 2013). Both medications resulted in similar improvement in N/V, although metoclopramide was associated with sedation, dry mouth, and dystonias (Abas et al. 2014;Pasricha et al. 2006). Cohort studies have shown that metoclopramide does not increase the risk of fetal malformations (Matok et al. 2009;Pasternak et al. 2014). ...
... Many women do not experience resolution of their symptoms with existing treatments. Studies demonstrating the efficacy of ondansetron, for example, show that most women continue to have at least one episode of vomiting per day even after initiating therapy (Abas et al. 2014). The impairment associated with HG is demonstrated by women who pursue elective abortion due to the severity of their symptoms in otherwise desired pregnancies (Maltepe and Koren 2013a;Mazzota et al. 1997). ...
Article
Full-text available
Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3-2% of pregnancies and is defined by dehydration, ketonuria, and more than 5% body weight loss. Initial pharmacologic treatment for HG includes a combination of doxylamine and pyridoxine. Additional interventions include ondansetron or dopamine antagonists such as metoclopramide or promethazine. The options are limited for women who are not adequately treated with these medications. We suggest that mirtazapine is a useful drug in this context and its efficacy has been described in case studies. Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antidepressant, anxiolytic, antiemetic, sedative, and appetite-stimulating effects. Mirtazapine is not associated with an independent increased risk of birth defects. Further investigation of mirtazapine as a treatment for HG holds promise to expand treatment options for women suffering from HG.
... If we look at the findings before and after the likely distorted period of reports related to a pending legal action (see below), we see metoclopramide being consistently implicated in cases of tardive dyskinesia and accounting for 5-10% of the annual submissions reporting this complication. Going beyond tardive dyskinesia, we need to see these findings in the context of published trial data demonstrating a high incidence of other adverse effects in patients receiving metoclopramide [36,37]. ...
... Trials comparing metoclopramide with other antiemetics, primarily various 5HT 3 receptor antagonists, demonstrated inferiority of metoclopramide in chemotherapy-induced vomiting [66] and nausea and vomiting for other reasons [67], including postoperative problems [68]. Similarly, ondansetron was comparable or better and clearly safer in the management of hyperemesis gravidarum [37,69]. Refractory gastroesophageal reflux disease is the second of the two FDA-approved indications for metoclopramide. ...
Article
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Introduction: Medical management of gastroparesis and functional dyspepsia remains difficult with several recent trials showing limited or no benefit. If treatment comes with only marginal improvements, concerns about adverse events become more relevant. We therefore examined the type and outcomes of side effects submitted to a public repository. Methods: We searched the Federal Adverse Event Reporting System for reports associated with the treatment of dyspepsia or gastroparesis. Demographic data, medications used and implicated, side effects, and outcomes were abstracted for the years 2004-2015. Results: Acid-suppressive agents and prokinetics were the most commonly listed medications with a stronger emphasis on prokinetics in gastroparesis. Submissions related to metoclopramide by far exceeded reports about other agents and mostly described tardive dyskinesia or other neurological concerns. They peaked around 2012, driven by submissions through legal workers. Most reports about metoclopramide described short-term use to prevent or treat nausea and vomiting. Concerns about acid-suppressive medications increased over time and spanned a wide spectrum of potential problems, including osteoporosis, worsening renal function, or cardiac events. Conclusion: Despite biasing factors, such as pending legal action, the voluntary repository of adverse events provides insight into current medical practice and its associated risk. Knowing about common and uncommon, but potentially serious risks may enable patients and providers to decide on effective and safe management strategies.
... Ten percent of women need medication [7]. Various pharmacologic treatments and therapeutic approaches have been suggested for this purpose such as vitamin B6 [8,9], antihistamines [7,9] herbal medications and ginger [10,11], a combination of vitamin B6 and other agents [12,13], metoclopramide [7,14,15], ondansetron [15,16], methyl prednisolone for refractory cases [7], and alternative medicine [7]. Ginger and vitamin B6 have been proposed as effective and safe medications for NVP [17,18]. ...
... Ten percent of women need medication [7]. Various pharmacologic treatments and therapeutic approaches have been suggested for this purpose such as vitamin B6 [8,9], antihistamines [7,9] herbal medications and ginger [10,11], a combination of vitamin B6 and other agents [12,13], metoclopramide [7,14,15], ondansetron [15,16], methyl prednisolone for refractory cases [7], and alternative medicine [7]. Ginger and vitamin B6 have been proposed as effective and safe medications for NVP [17,18]. ...
Article
Introduction: Nausea and vomiting of pregnancy (NVP) are one of the most common complains of the early pregnancy period and are bothersome for pregnant women. Some prefer to use herbal medicine instead of chemical agents. Objective: The purpose of the present study was to compare the effects of ginger, pyridoxine (vitamin B6) and placebo for the treatment of NVP. Method: The study was performed as a triple blind clinical trial on pregnant women suffering mild to moderate NVP between 6–16 weeks of pregnancy. In these women ginger, 500 mg twice daily, vitamin B6 40 mg twice daily and placebo twice daily were administered for 4 days. Rhodes questionnaire was used for evaluation of the severity of symptoms. The severity of NVP was evaluated 24 hours before entering the study and up to 4 days after using medications and results were compared between the 3 groups. Results: Seventy-seven women finished the study (28 in Ginger group, 26 in B6 group and 23 in placebo group). The women of the three groups did not have significant differences according to age, gestational age, parity, and severity of each symptom before treatment and educational status. Total score of Rhodes questionnaire for nausea was decreased significantly in three groups after treatment. (p<0.001, p=0.012, and p=0.03 for ginger, vitamin B6 and placebo respectively.) Also total score of Rhodes questionnaire for vomiting was decreased in three groups (p=0.03 for ginger, p=0.02 for B6 and p=0.04 for placebo). Ginger and vitamin B6 could reduce the severity of all items of Rhodes questionnaire significantly; however, placebo was significantly effective only on the frequency of nausea, intensity of vomiting and frequency of retching. Ginger and vitamin B6 were more effective than placebo (p=0.039 and p=0.007 respectively), however, total score of Rhodes did not show significant difference between ginger and vitamin B6 (p=0.128). Ginger was more effective for nausea (intensity and distress) and distress of vomit. Conclusion: Ginger is more effective than placebo for the treatment of mild to moderate NVP and is comparable with vitamin B6. Trial registration number and registry website: IRCT2015020320923N1
... 5 The mainstays of our hospital's initial inpatient management for HG are intravenous rehydration, anti-emetics and thiamine supplementation. 6 In our experience, women with HG at hospitalisation are severely nauseated and averse to, and often vomit in response to, oral intake. Patients often ask about the inpatient start of oral feeding. ...
... All participants received our standard inpatient care for HG, which comprised intravenous rehydration with normal saline solution (with potassium chloride added if required for hypokalaemia), intravenous anti-emetic drug (first-line 10 mg metoclopramide 8-hourly 6,8 ) and supplementation with oral thiamine 1 mg daily. ...
Article
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Objective: To evaluate fasting for 12-hours compared to expedited oral feeding in hospitalised hyperemesis gravidarum (HG) DESIGN: Randomised trial SETTING: University Hospital, Malaysia: April 2016-April 2017 POPULATION: 160 women hospitalised for hyperemesis gravidarum (HG) METHOD: Women were randomised upon admission to fasting for 12-hours or expedited oral feeding. Standard HG care was instituted. Main outcome measure: Primary outcome was satisfaction score with overall treatment at 24 hours (0-10 Visual Numerical Rating Scale VNRS), vomiting episodes within 24 hours and nausea VNRS score at enrollment, 8, 16 and 24 hours. Results: Satisfaction score, median [interquartile range] 8 [5-9] vs. 8 [7-9] P=0.08 and 24-hour vomiting episodes were 1[0-4] vs. 1[0-5] P = 0.24 for 12-hours fasting vs. expedited feeding respectively. Repeated measures analysis of variance of nausea scores over 24-hours showed no difference (P=0.11) between trial arms. Participants randomised to 12-hours fasting compared to expedited feeding were less likely to prefer their feeding regimen in future hospitalisation 41% vs 65% P=0.001, to recommend to a friend 65% vs 84% P=0.01 (RR 0.8 95% CI 0.6-0.9) and to adhere to protocol 85% vs 95% P=0.04 (RR 0.9 95% CI 0.8-1.0). Symptoms profile, ketonuria status at 24 hours and length of hospital stay were not different. Conclusion: Advisory of 12-hours fasting compared to immediate oral feeding resulted in a non-significant difference in satisfaction score but adherence to protocol, fidelity to and recommendation of immediate oral feeding to a friend were lower. 24-hour nausea scores and vomiting episodes were similar.
... Similarly, conflicting results comparing two serotonin receptor antagonist are also reported. Abas et al. (2014) showed that ondansetron and metoclopramide (dopamine and serotonin receptor antagonist) demonstrated similar antiemetic and antinauseant effects in patients with HG. While another randomized trial reported that patients with HG treated with ondansetron had significantly lower vomiting scores versus the patients treated with metoclopramide (Kashifard et al., 2013). ...
... Similarly, ondansetron is reported to be superior to the combination of pyridoxine and doxylamine in the treatment of NVP (Oliveira et al., 2014). On the contrary, other studies in HG patients demonstrated no benefit of ondansetron over promethazine (Sullivan et al., 1996) and similar antiemetic and antinauseant effects of ondansetron and metoclopramide (Abas et al., 2014). Considering the equal effectiveness of ondansetron compared with promethazine, and no sedative effect (Sullivan et al., 1996), ondansetron has been suggested to be the preferred medication in women who have responded to antiemetics but experience significant sedation (Sanu and Lamont, 2011). ...
Article
Nausea and vomiting of pregnancy (NVP) is one of the most common disorders of pregnancy. The symptoms occur predominantly during the first trimester, although in a subgroup of patients they can continue throughout the entire pregnancy and can affect the woman's quality of life. A small percentage of women develop a severe form of NVP called hyperemesis gravidarum (HG) that if left untreated may lead to significant maternal morbidity and adverse birth outcomes. Overall, the morbidity in pregnant women with NVP is significant, although it tends to be underestimated. The pathogenesis of NVP remains unclear, but there is consensus that the disorder is multifactorial and that various genetic, endocrine and infectious factors may be involved. The treatment of NVP can be challenging as the optimal targets for therapy are not known. Currently, the therapy used depends on the severity of the disorder and it is focused on improving the symptoms while minimizing risks to mother and fetus. Therapies range from dietary changes, pharmacologic treatment or hospitalization with intravenous fluid replacement and nutrition therapy. The aims of this review are 1) to provide an overview of NVP, 2) to present possible links between the most important factors associated with the pathogenesis of NVP and 3) to discuss the effectiveness and safety of the pharmacologic and non-pharmacologic options available to treat this disorder.
... GBK tedavisinde antiemetiklerin kaşılaştırıldığı bir çalışmada ondansetron tedavisinin piridoksin + doksilamin kombinasyonundan üstün olduğu, fakat yan etki açısından (kabızlık ve sedasyon) fark olmadığı tesbit edilmiştir 113 . Yine HG tedavisinde ondansetron ve metoklopramidin karşlaştırıldığı bir çalışmada ikisininde benzer antiemetik etki gösterdiği, fakat ondansetronunun yan etki bakımından daha iyi olduğu, fiyat acısından da metoklopramidin daha ucuz olduğu vurgulanmıştır 114 . Başka bir çalışmada ise ağır HG tedavisinde transdermal klonidinin kullanılmasının, hastalığın septomları ve diğer destekleyici müdahale ve tedavi gereksiniminlerini önemli ölçüde azaldığı göserilmiştir 115 . ...
... Similarly, based on the study of Kashifard et al., the incidence of NVP was significantly lower in an ondansetron group than metoclopramide group (pregnant women = 83, and gestational age 8.7 weeks) (131). Additionally, ondansetron was demonstrated to have antiemetic and antinauseant effects in HG; moreover, it had less adverse effects and was less expensive than metoclopramide (131,132). Meanwhile, the safety of ondansetron during pregnancy was reported in a Danish study of 1970 exposed infants, who did not show an increased risk of fetal malformations or adverse pregnancy outcomes. ...
Article
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Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP, which is reported in 0.3–10.8% of pregnant women. NVP has a relatively benign course, but HG can be linked with some poor maternal, fetal, and offspring outcomes. The exact causes of NVP and HG are unknown, but various factors have been hypothesized to be associated with pathogenesis. With the advance of precision medicine and molecular biology, some genetic factors such as growth/differentiation factor 15 (GDF15) have become therapeutic targets. In our review, we summarize the historical hypotheses of the pathogenesis of NVP and HG including hormonal factors, Helicobacter pylori , gastrointestinal dysmotility, placenta-related factors, psychosocial factors, and new factors identified by genetics. We also highlight some approaches to the management of NVP and HG, including pharmacological treatment, complementary treatment, and some supporting treatments. Looking to the future, progress in understanding NVP and HG may reduce the adverse outcomes and improve the maternal quality of life during pregnancy.
... Patients were recruited from the gynaecology ward where patients HG in our hospital were exclusively admitted to and were initially assessed for eligibility by scrutinising their medical records. Inclusion criteria were admission for HG (defined as presence of nausea and intractable vomiting sufficient to cause dehydration and metabolic disturbance of a severity to require hospitalisation, occurrence early in pregnancy), 10 confirmed clinical pregnancy (at least a positive pregnancy test if an intrauterine gestational sac is not yet visible on ultrasound), gestation of less than 16 weeks, age 18 years old or older, and patient was within 24 hours of first admission for HG in their current pregnancy. Exclusion criteria included inability to participate or consume the food due to extreme symptoms, confirmed non-viable pregnancy, known taste or swallowing disorder and any allergies to foods tested. ...
Article
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Objective To evaluate four foods in women with hyperemesis gravidarum (HG) on their agreeability and tolerability. Design Prospective, randomised, within-subject cross-over trial. Setting Single-centre, tertiary, university hospital in Malaysia. Participants 72 women within 24-hour of first admission for HG who were 18 years or above, with confirmed clinical pregnancy of less than 16 weeks’ gestation were recruited and analysed. Women unable to consume food due to extreme symptoms, known taste or swallowing disorder were excluded. Interventions Each participant chewed and swallowed a small piece of apple, watermelon, cream cracker and white bread in random order and was observed for 10 min after each tasting followed by a 2 min washout for mouth rinsing and data collection. Outcome measures Primary outcome was food agreeability scored after 10 min using an 11-point 0–10 Visual Numerical Rating Scale (VNRS). Nausea was scored at baseline (prior to tasting) and 2 and 10 min using an 11-point VNRS. Intolerant responses of gagging, heaving and vomiting were recorded. Results On agreeability scoring, apple (mean±SD 7.2±2.4) ranked highest followed by watermelon (7.0±2.7) and crackers (6.5±2.6), with white bread ranked lowest (6.0±2.7); Kruskal-Wallis H test, p=0.019. Apple had the lowest mean nausea score and mean rank score, while white bread had the highest at both 2 and 10 min; the Kruskal-Wallis H test showed a significant difference only at 10 min (p=0.019) but not at 2 min (p=0.29) in the ranking analyses. The intolerant (gagged, heaved or vomited) response rates within the 10 min study period were apple 3/72 (4%), watermelon 7/72 (10%), crackers 8/72 (11%) and white bread 12/72 (17%): χ ² test for trend p=0.02. Conclusion Sweet apple had the highest agreeability score, the lowest nausea severity and intolerance–emesis response rate when tasted by women with HG. White bread consistently performed worst.
... 1 Early treatment of nausea and vomiting during pregnancy is recommended to provide symptom relief and prevent progression to hyperemesis gravidarum. 1 Although not formally approved for the treatment of nausea and vomiting during pregnancy, ondansetron, a 5-HT 3 receptor antagonist, has rapidly become the most frequently prescribed drug for nausea and vomiting during pregnancy in the United States because of its perceived superior antiemetic effects and improved adverseeffect profile compared with treatment alternatives. [2][3][4][5] In 2014, an estimated 22% of pregnant women used ondansetron in the United States. 6 Nausea and vomiting during pregnancy typically occurs during the first trimester, the most sensitive time for exposure to teratogens because of organogenesis. ...
Article
Importance Evidence for the fetal safety of ondansetron, a 5-HT3 receptor antagonist that is commonly prescribed for nausea and vomiting during pregnancy, is limited and conflicting. Objective To evaluate the association between ondansetron exposure during pregnancy and risk of congenital malformations. Design, Setting, and Participants A retrospective cohort study nested in the 2000-2013 nationwide Medicaid Analytic eXtract. The cohort consisted of 1 816 414 pregnancies contributed by 1 502 895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or longer after delivery; infants were enrolled in Medicaid for at least 3 months after birth. The final date of follow-up was December 31, 2013. Analyses were conducted between November 1, 2017, and June 30, 2018. Propensity score stratification was used to control for treatment indication and other confounders. Exposures Ondansetron dispensing during the first trimester, the period of organogenesis. Main Outcomes and Measures Primary outcomes were cardiac malformations and oral clefts diagnosed during the first 90 days after delivery. Secondary outcomes included congenital malformations overall and subgroups of cardiac malformations and oral clefts. Results Among 1 816 414 pregnancies (mean age of mothers, 24.3 [5.8] years), 88 467 (4.9%) were exposed to ondansetron during the first trimester. Overall, 14 577 of 1 727 947 unexposed and 835 of 88 467 exposed infants were diagnosed with a cardiac malformation, for an absolute risk of 84.4 (95% CI, 83.0 to 85.7) and 94.4 (95% CI, 88.0 to 100.8) per 10 000 births respectively. The absolute risk of oral clefts was 11.1 per 10 000 births (95% CI, 10.6 to 11.6; 1921 unexposed infants) and was 14.0 per 10 000 births (95% CI, 11.6 to 16.5; 124 exposed infants). The risk of any congenital malformation was 313.5 per 10 000 births (95% CI, 310.9 to 316.1; 54 174 unexposed infants) and was 370.4 (95% CI, 358.0 to 382.9; 3277 exposed infants). The adjusted relative risk (RR) for cardiac malformations was 0.99 (95% CI, 0.93 to 1.06) and the adjusted risk difference (RD) was −0.8 (95% CI, −7.3 to 5.7 per 10 000 births). For oral clefts, the adjusted RR was 1.24 (95% CI, 1.03 to 1.48) and the RD was 2.7 (95% CI, 0.2 to 5.2 per 10 000 births). The adjusted estimate for congenital malformations overall was an RR of 1.01 (95% CI, 0.98 to 1.05) and an RD of 5.4 (95% CI, −7.3 to 18.2 per 10 000 births). Conclusions and Relevance Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.
... administration may be beneficial. However, it is reported that prolongation of QT segment may be observed during ECG monitoring [20][21][22][23]. ...
... In recent years, Zofran is again becoming the most prescribed medication for primary treatment of patients with hyperemesis gravidarum [52] . A recent RCT did not show any differences in efficacy between metoclopramide or Zofran when therapy was randomly assigned to 160 patients with hyperemesis gravidarum [53] . In addition, meta-analysis of studies assessing intravenous pump infusions of metoclopramide and Zofran showed no benefit for continued use and in fact, showed an increased risk of side effects of this treatment modality, including extra-pyramedial symptoms and worsening of nausea/ vomiting [54] . ...
Article
Background: In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown. Although cases of mortality are rare, hyperemesis gravidarum has been associated with both maternal and fetal morbidity. The current mainstay of treatment relies heavily on supportive measures until improvement of symptoms as part of the natural course of hyperemesis gravidarum, which occurs with progression of gestational age. However, studies have reported that severe, refractory disease manifestations have led to serious adverse outcomes and to termination of pregnancies. Summary: Despite extensive research in the field, the pathogenesis of hyperemesis gravidarum remains unknown. Recent literature points to a genetic predisposition in addition to previously studied factors such as infectious, psychiatric, and hormonal contributions. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. The effect of hyperemesis gravidarum on neonatal health is still debated in literature with conflicting results regarding outcomes of birth weight and prematurity. Available therapy options remain largely unchanged in the past several decades and focus on parenteral antiemetic medications, electrolyte repletion, and nutritional support. Most studies of therapeutic options do not consist of randomized control studies and cross-study analysis is difficult due to considerable variation of diagnostic criteria. Key Messages: Hyperemesis gravidarum carries a significant burden on maternal health and US health care. Most published research on pathogenesis is observational and suggests multifactorial associations with hyperemesis gravidarum. Precise, strictly defined criteria for clinical diagnosis are likely to benefit meta-analyses of further research studies regarding pathogenesis as well as therapeutic options.
... Although the majority of published treatment studies are from the USA and Europe and very few are from less resourced settings such as African and Asian countries, the medical treatment of HG follows the same principles across continents: antiemetics, intravenous rehydration and electrolyte substitution 178,179 . Settings with a general lack of access to specialist or hospital care will affect the availability of infusion therapy and the use of relevant antiemetics may be hampered by a lack of medications in stock or their high cost (for example, ondansetron 180 ). In line with cultural differences in food habits, differ ent herbal remedies are promoted to alleviate NVP in different countries 181,182 . ...
Article
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Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.
... In another study conducted with pregnant women diagnosed with hyperemesis gravidarum; Patients who were administered ondansetron stated that their nausea disappeared more rapidly within 24 hours compared to patients who were administered metoclopramide. Thus, the duration of hospitalization has decreased 11 . ...
Article
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Objective: The complaint of nausea and vomiting can be a symptom or result of many diseases. It may impair the comfort and even the general condition of the patient. Therefore, patients admitted to the emergency room expect to correct these complaints as quickly as possible. The most commonly used drugs for this are metoclopramide and ondansetron. Materials and Methods: In our study; a one-month period, 99 patients who presented to our emergency department with complaints of nausea, vomiting, and diarrhea due to any disease were included (excluding trauma and cancer patients). It was noted how quickly the symptoms decreased when metoclopramide 10 mg or ondansetron 8 mg were administered intravenously. Results and Conclusion: After antiemetic application in the emergency room; We observed that the complaints disappeared more rapidly in patients treated with ondansetron than in patients treated with metoclopramide (mean 16/ minute, p<0,005).
... In the present study, there were significant improvements of patients with nausea and vomiting that treated with ondansetron when compared with patient treated with pyridoxine [75 women [96.2%] in group I versus 41 [52.6%] in group II. These results agreed with Abas et al. [24] , Kashifard et al. [25] and Oliveira et al. [9] , that shown ondansetron is better than doxylamine plus pyridoxine in improvement of nausea and vomiting during pregnancy, both had fewer adverse effects than metoclopramide and both more effective for reduction of severe vomiting than metoclopramide. The meta-analysis by Tramer et al. [26] reported that 8 mg dose of ondansetron was used to prevent nausea and vomiting during pregnancy. ...
Article
Background: Nausea and vomiting affects up to 80% of the pregnant women population and are the third leading causes of maternal hospitalization during pregnancy. Many pregnant females, and even some healthcare professionals, dread using antiemetic drugs due to a false beliefof their teratogenicrisk. Aim of the work:This study aimed to evaluate ondansetron to a combination of doxylamine and pyridoxine in controlling pregnancy-related nausea and vomiting. Patients and Methods:This randomized controlled trial included 156 pregnant women, at 16 weeks of gestation, with mild-to-moderate nausea and vomiting. Meanwhile, women with severe symptoms indicating admission, those already on anti-emetics, and those who wouldn’t be able to show up for follow-up visits were excluded. Seventy-eight patients received intravenous injection of ondansetron [Zofran] at a dose of 8 mg once daily for 5 days, whereas the other 78 patients received oral pyridoxine at a dose of 25 mg plus doxylamine at a dose of 12.5 mg [Diclegis] twice daily for 5 days. Each patient was subjected to full history taking, complete clinical examination and investigations. Results: Women on Ondansetron reported better alleviation of nausea compared to those receiving pyridoxine and doxylamine [96.2% vs. 52.6%, P
... Summarizing, metoclopramide should be avoided in patients with stress or neuropsychiatric disorders. This is in accordance with the results of a trial comparing ondansetron and metoclopramide for hyperemesis gravidarum which showed that the ondansetron group has fewer adverse events and that metoclopramide is associated with central adverse events like dizziness and drowsiness and with palpitations [20]. ...
Article
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Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.
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Abstract Background Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP – hyperemesis gravidarum (HG) – affects 0.3–1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. Objectives This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. Data sources MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. Review methods A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. Results Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. Limitations The main limitations were the quantity and quality of the data available. Conclusion There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. Study registration This study is registered as PROSPERO CRD42013006642. Funding The National Institute for Health Research Health Technology Assessment programme.
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Importance Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae. Objective To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum. Evidence Review Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings. Findings Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited. Conclusions and Relevance For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.
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Women with type 1 diabetes (T1DM) have unique needs during the preconception, pregnancy, and postpartum periods. Preconception counseling is essential for women with T1DM to minimize pregnancy risks. The goals of preconception care should be tight glycemic control with a hemoglobin A1c (A1C) < 7 % and as close to 6 % as possible, without significant hypoglycemia. This will lower risks of congenital malformations, preeclampsia, and perinatal mortality. The safety of medications should be assessed prior to conception. Optimal control of retinopathy, hypertension, and nephropathy should be achieved. During pregnancy, the goal A1C is near-normal at <6 %, without excessive hypoglycemia. There is no clear evidence that continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) is superior in achieving the desired tight glycemic control of T1DM during pregnancy. Data regarding continuous glucose monitoring (CGM) in pregnant women with T1DM is conflicting regarding improved glycemic control. However, a recent CGM study does provide some distinct patterns of glucose levels associated with large for gestational age infants. Frequent eye exams during pregnancy are essential due to risk of progression of retinopathy during pregnancy. Chronic hypertension treatment goals are systolic blood pressure 110–129 mmHg and diastolic blood pressure 65–79 mmHg. Labor and delivery target plasma glucose levels are 80–110 mg/dl, and an insulin drip is recommended to achieve these targets during active labor. Postpartum, insulin doses must be reduced and glucoses closely monitored in women with T1DM because of the enhanced insulin sensitivity after delivery. Breastfeeding is recommended and should be highly encouraged due to maternal benefits including increased insulin sensitivity and weight loss and infant and childhood benefits including reduced prevalence of overweight. In this article, we discuss the care of pregnant patients with T1DM.
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Background Nausea and vomiting of pregnancy affects up to 80% of pregnant women, it typically occurs during the first trimester which is the most sensitive time for environmental exposures given organogenesis. Metoclopramide is an antiemetic drug used widely during NVP, but the findings of studies evaluating its safety of use in pregnancy is inconsistent. Therefore, we conducted a systematic review and meta-analysis to assess whether metoclopramide use during first trimester of pregnancy is associated with the risk of major congenital malformations. Methods The systematic search using database included Pubmed, Embase, Web of science, and Cochrane library. Studies written in English, comprising with an exposed group and a control group, reporting major congenital malformation as an outcome were included. Results Six studies assessing a total number of 33374 metoclopramide-exposed and 373498 controls infants were included in this meta-analysis. No significant increase in the rate of major congenital malformation was detected following metoclopramide use during first trimester (OR, 1.14; 95% CI, 0.93–1.38). Conclusions Metoclopramide use during first trimester of pregnancy was not associated with the risk of major congenital malformations.
Article
Introduction: While nausea and vomiting in early pregnancy are very common, affecting approximately 80% of pregnancies, hyperemesis gravidarum is a severe form affecting 0.3–1.0% of pregnancies. Although hyperemesis gravidarum is rarely a source of mortality, it is a significant source of morbidity. It is one of the most common indications for hospitalization in pregnancy. Beyond the maternal and fetal consequences of malnutrition, the severity of hyperemesis symptoms causes a major psychosocial burden leading to depression, anxiety, and even pregnancy termination. The aim of this meta-analysis was to examine all randomized controlled trials of interventions specifically for hyperemesis gravidarum and evaluate them based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs. Material and methods: Randomized controlled trials were identified by searching electronic databases. We included all randomized controlled trials for the treatment of hyperemesis gravidarum. The primary outcome was intervention efficacy as defined by severity, reduction, or cessation in nausea/vomiting; number of episodes of emesis; and days of hospital admission. Secondary outcomes included other measures of intervention efficacy, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs. Results: Twenty-five trials (2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. Selected comparisons reported below: No primary outcome data were available when acupuncture was compared with placebo. There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (risk ratio (RR) 1.40, 95% CI 0.79–2.49 and RR 1.51, 95% CI 0.92–2.48, respectively). Midwife-led outpatient care was associated with fewer hours of hospital admission than routine inpatient admission (mean difference (MD) −33.20, 95% CI −46.91 to −19.49) with no difference in pregnancy-unique quantification of emesis and nausea (PUQE) score, decision to terminate the pregnancy, miscarriage, small-for-gestational age infants, or time off work when compared with routine care. Women taking vitamin B6 had a slightly longer hospital stay compared with placebo (MD 0.80 days, 95% CI 0.08–1.52). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI −0.40–1.40) or side effects. A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI −0.15–3.55, and MD −0.10, 95% CI −1.63–1.43; one study, 83 women, respectively). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23–4.69, and RR 2.38, 95% CI 1.10–5.11, respectively). There were no clear differences between groups for other side effects. In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (risk ratio (RR) 0.70, 95% CI 0.56–0.87, RR 0.48, 95% CI 0.34–0.69, and RR 0.31, 95% CI 0.11–0.90, respectively) There were no clear differences between groups for other important outcomes including quality of life and other side effects.
Article
Background The effects of ondansetron, used off‐label to treat nausea and vomiting during pregnancy, on common pregnancy complications are understudied. Modest effects of a commonly used drug could result in adverse events for large numbers of pregnant women. Therefore, our objective was to compare the risk of stillbirth, preterm birth, gestational hypertensive disorders, small for gestational age, and differences in birth weight between women prescribed ondansetron and women prescribed alternative antiemetics in early pregnancy. Methods A cohort of pregnant women receiving a prescription for ondansetron or comparator antiemetics (metoclopramide or promethazine) during the first 20 weeks of pregnancy was identified using electronic health record data from a health care system in North Carolina, USA. Confounding by multiple covariates was controlled using stabilized inverse probability of treatment weights. Weighted hazard ratios (HR) and 95% confidence intervals (CI) accounted for competing events. Results We identified 2677 eligible pregnancies with antiemetic orders, 66% for ondansetron. The small number of stillbirths (n = 15) resulted in an imprecise estimate of the association with ondansetron (HR = 1.60; 95%CI 0.51, 4.97). No association was observed for preterm birth (HR = 0.90; 95%CI 0.67, 1.20) or gestational hypertensive disorders (HR = 0.87; 95%CI 0.68, 1.12). We observed an association with small for gestational age (HR = 1.37; 95%CI 0.98, 1.90), however mean birth weight among term births was similar between groups. Conclusions Our results do not suggest that ondansetron increases the risk of preterm birth or gestational hypertensive disorders. The weak association observed between ondansetron use and small for gestational age warrants further investigation.
Chapter
A stepwise approach can be utilized for the assessment and treatment of nausea and vomiting in pregnancy and its most severe form, hyperemesis gravidarum. Prompt treatment is important to prevent further progression of symptoms. Diagnostic testing should focus on evaluation for signs of dehydration and electrolyte disturbance. In addition to volume and vitamin repletion, the use of antiemetic medications pyridoxine with doxylamine as first-line therapy is recommended for mild symptoms. Management of persistent/severe symptoms may include use of diphenhydramine, metoclopramide, ondansetron, and promethazine as second-line agents. Hospital admission is reserved for cases of refractory vomiting requiring continued intravenous antiemetics, failed outpatient management of symptoms, and severe fluid or electrolyte imbalance.
Article
Background Ondansetron is commonly used to treat nausea and vomiting in pregnancy despite inconclusive evidence of its safety. Previous studies have reported no increase in risk of miscarriage but relied on methods that failed to account for gestational weeks at risk and non‐user comparators, which may increase the potential for unmeasured confounding. Our objective was to estimate the risk of miscarriage among women prescribed ondansetron vs alternative antiemetics during the first 20 weeks of pregnancy. Methods A pregnancy cohort was created using electronic health record data from a health care system in North Carolina. Women were classified as exposed to either ondansetron or comparator antiemetics (metoclopramide or promethazine) based on the first antiemetic prescription received in the first 20 weeks of gestation. Cumulative incidence of miscarriage at 20 weeks was estimated in each antiemetic group. Hazard ratios (HR) were estimated with 95% confidence intervals and measured confounding was controlled using inverse probability of treatment weights. Sensitivity analyses assessed the potential impact of exposure misclassification, latency period, and selection bias. Results We identified 2620 eligible pregnancies with antiemetic orders; 65% had a first ondansetron order and 35% had a first comparator antiemetic order. In total, 95 women had a miscarriage. After adjustment, there was no difference in risk of miscarriage (HR 1.21, 95% CI 0.77, 1.90). Results from the per‐protocol and other sensitivity analyses were similar to the main analysis. Conclusions We did not observe an increase in the risk of miscarriage for pregnancies exposed to ondansetron vs comparator antiemetics.
Article
Background: Hyperemesis gravidarum (HG) is a common cause of hospital admission in early pregnancy. There is no international consensus on the definition of HG, or on outcomes that should be reported in trials. Consistency in definition and outcome reporting is important for the interpretation and synthesis of data in meta-analyses. Objective: To identify which HG definitions and outcomes are currently in use in trials. Search strategy: We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase and (3) Medline for published trials and the WHO-ICTRP database for ongoing trials (27 October 2017). Selection criteria: All randomised clinical trials reporting on any intervention for HG were eligible. Data collection and analysis: Two reviewers independently assessed trial eligibility and extracted data on HG definition and outcomes. Main results: We included 31 published trials reporting data from 2511 women and three ongoing trials with a planned sample size of 360 participants. We identified 11 definition items. Most commonly used definition items were vomiting (34 trials) and nausea (30 trials). We identified 34 distinct outcomes. Most commonly reported outcomes were vomiting (29 trials), nausea (26 trials), need for hospital treatment (14 trials) and duration of hospital (re)admission(s) (14 trials). Conclusion: There is substantial variation of HG definition and outcome reporting in trials. This hampers meaningful aggregation of trial results in meta-analysis and implementation of evidence in guidelines. To overcome this, international consensus on a definition and a core outcome set for HG trials should be developed. Tweetable abstract: There is a wide variation of definitions and outcomes reported in trials on hyperemesis gravidarum.
Article
Background: Several interventions were explored in clinical trials for treating hyperemesis gravidarum (HG). The present study is a network meta-analysis of such interventions. Methods: Electronic databases were searched for appropriate randomized clinical trials comparing interventions for treatment of patients with HG. Control of HG symptoms was the primary outcome and emetic episodes, hospital stay, nausea scores, patients requiring rescue antiemetics, hospital readmission, adverse events and adverse pregnancy outcomes were the secondary outcome measures. Random-effects model was used and odds ratio (OR) [95% confidence interval (CI)] was the effect estimate for categorical outcomes and weighted mean difference (WMD) [95% confidence interval] for numerical outcomes. Results: Twenty studies were included in the systematic review and 18 in the meta-analysis. Acupuncture (OR: 18.9; 95% CI: 2.1, 168), acupressure (OR: 26.7; 95% CI: 2.5, 283.1) and methylprednisolone (OR: 6.7; 95% CI: 1.1, 38.8) were associated with better control of HG symptoms than standard of care. Acupressure decreases the requirement of rescue antiemetics (OR: 0.06; 95% CI: 0.01, 0.44); ondansetron with reduced hospital stay (WMD: −0.2; 95% CI: −0.31, −0.01) and diazepam with reduced risk of hospital admission (OR: 0.11; 95% CI: 0.01, 0.95). The quality of evidence is very low. Conclusion: Acupuncture, acupressure and methylprednisolone were observed with better therapeutic benefits than other interventions for treating HG. However, the pooled estimates may change with the advent of results from future head-to-head clinical trials.
Article
Nausea and vomiting of pregnancy affect the majority of pregnancies, while the most severe version, hyperemesis gravidarum (HG), affects a much smaller subset of women. Despite the prevalence of nausea and vomiting of pregnancy and the severe consequences of HG, the pathophysiology of these conditions is not fully understood. Currently, it is thought that a combination of hormonal factors accounts for their development. Multiple treatments have been described for nausea and vomiting of pregnancy and HG with varying levels of success. In this paper we describe the epidemiology of nausea and vomiting of pregnancy and HG, the recommended workup, their proposed etiologic factors, treatments, and their potential impact on mother and baby.
Chapter
This chapter deals with the case of a 25‐year old primigravida at 10 weeks gestation, complaining of dizziness and decreased urination and having been treated for severe nausea and emesis earlier in the pregnancy. It discusses the incidence, etiology, effects of HG, differential diagnoses, laboratory evaluation, and treatment options of hyperemesis gravidarum (HG). While fetal growth restriction can result as a consequence of HG, having HG during pregnancy was found to be associated with an increased risk of preterm delivery in a large meta‐analysis. The most detrimental side effect of HG on the mother is Wernicke's encephalopathy. Non‐pharmacologic treatment includes avoiding foods that trigger their nausea and intake of ginger as an herbal option to battle nausea and vomiting of pregnancy. Studies have suggested that taking a multivitamin starting at time of conception may decrease the risk for nausea and vomiting of pregnancy, which will decrease the rare risk for progression to HG.
Article
Background Hyperemesis gravidarum is a disabling disease of nausea, vomiting, and undernutrition in early pregnancy for which there are no effective outpatient therapies. Poor weight gain in hyperemesis gravidarum is associated with several adverse fetal outcomes including preterm delivery, low birthweight, small for gestational age, low 5-minute Apgar scores, and neurodevelopmental delay. Gabapentin is most commonly used clinically for treating neuropathic pain but also substantially reduces chemotherapy-induced and postoperative nausea and vomiting. Pregnancy registry data have shown maternal first-trimester gabapentin monotherapy to be associated with a 1.2% rate of major congenital malformations among 659 infants, which compares favorably with the 1.6% to 2.2% major congenital malformation rate in the general population. Open-label gabapentin treatment in hyperemesis gravidarum was associated with reduced nausea and vomiting and improved oral nutrition. Objective This study aimed to determine whether gabapentin is more effective than standard-of-care therapy for treating hyperemesis gravidarum. Study Design A double-blind, randomized, multicenter trial was conducted among patients with medically refractory hyperemesis gravidarum requiring intravenous hydration. Patients were randomized (1:1) to either oral gabapentin (1800–2400 mg/d) or an active comparator of either oral ondansetron (24–32 mg/d) or oral metoclopramide (45–60 mg/d) for 7 days. Differences in Motherisk–pregnancy-unique quantification of nausea and emesis total scores between treatment groups averaged over days 5 to 7, using intention-to-treat principle employing a linear mixed-effects model adjusted for baseline Motherisk–pregnancy-unique quantification of nausea and emesis scores, which served as the primary endpoint. Secondary outcomes included Motherisk–pregnancy-unique quantification of nausea and emesis nausea and vomit and retch subscores, oral nutrition, global satisfaction of treatment, relief, desire to continue therapy, Nausea and Vomiting of Pregnancy Quality of Life, and Hyperemesis Gravidarum Pregnancy Termination Consideration. Adjustments for multiple comparisons were made employing the false discovery rate. Results A total of 31 patients with hyperemesis gravidarum were enrolled from October 2014 to May 2019. Among the 21 patients providing primary outcome data (12 assigned to gabapentin and 9 to the active comparator arm), 18 were enrolled as outpatients and all 21 were outpatients from days 5 to 7. The study groups’ baseline characteristics were well matched. Gabapentin treatment provided a 52% greater reduction in days 5 to 7 baseline adjusted Motherisk–pregnancy-unique quantification of nausea and emesis total scores than treatment with active comparator (95% confidence interval, 16–88; P=.01). Most secondary outcomes also favored gabapentin over active comparator treatment including 46% and 49% decreases in baseline adjusted Motherisk–pregnancy-unique quantification of nausea and emesis nausea (95% confidence interval, 19–72; P=.005) and vomit and retch subscores (95% confidence interval, 21–77; P=.005), respectively; a 96% increase in baseline adjusted oral nutrition scores (95% confidence interval, 27–165; P=.01); and a 254% difference in global satisfaction of treatment (95% confidence interval, 48–459; P=.03). Relief (P=.06) and desire to continue therapy (P=.06) both showed trends favoring gabapentin treatment but Nausea and Vomiting of Pregnancy Quality of Life (P=.68) and Hyperemesis Gravidarum Pregnancy Termination Consideration (P=.58) did not. Adverse events were roughly equivalent between the groups. There were no serious adverse events. Conclusion In this small trial, gabapentin was more effective than standard-of-care therapy for reducing nausea and vomiting and increasing oral nutrition and global satisfaction in outpatients with hyperemesis gravidarum. These data build on previous findings in other patient populations supporting gabapentin as a novel antinausea and antiemetic therapy and support further research on gabapentin for this challenging complication of pregnancy.
Article
Importance: Nausea and vomiting of pregnancy (NVP) affects a high proportion of the pregnant population. Objective: The aim of this study was to compare and synthesize recommendations from national guidelines regarding the management of NVP. Evidence acquisition: A descriptive review of 3 recently published national guidelines on NVP was conducted: Royal College of Obstetricians and Gynaecologists on "The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum," American College of Obstetricians and Gynecologists on "Nausea and Vomiting of Pregnancy," and Society of Obstetricians and Gynaecologists of Canada on "The Management of Nausea and Vomiting of Pregnancy." These guidelines were summarized and compared in terms of the recommended management of pregnant women. The quality of evidence was also reviewed based on the method of reporting. Results: Several differences were identified on the different guidelines regarding the management of NVP. Frequent small meals and avoidance of iron supplements are recommended for prevention. The consumption of ginger, acustimulations, antihistamines, phenothiazines, dopamine, and serotonin 5-hydroxytryptamine type 3 receptor antagonists is routinely recommended for use in the community as treatment. Conclusions: Evidence-based medicine may lead to the adoption of an international guideline for the management of NVP, which may lead to a more effective management of that entity.
Chapter
Nausea and vomiting of pregnancy (NVP) is one of the most common GI disorders of pregnancy, affecting 70–80% of pregnant women [1]. It is characterized by nausea and vomiting which typically begin within 4 weeks of the last menstrual period, peaks between 10 and 16 weeks gestation, and resolves after 20 weeks gestation [2]. NVP is often erroneously referred to as “morning sickness” as NVP is limited to the morning in less than 2% of women and more commonly persists throughout the day [2]. Women with severe symptoms may have hyperemesis gravidarum (HG), a condition associated with fluid, electrolyte and acid-base imbalance, nutritional deficiency, and weight loss [3]. HG is much less common than NVP, affecting only 0.3–3.6% of all pregnancies worldwide [4]. While there are no strict criteria for HG, it is commonly defined as the occurrence of greater than three episodes of vomiting per day with accompanying ketones in the urine and weight loss of more than 3 kg or 5% of body weight [5].
Article
Importance: Hyperemesis gravidarum (HEG) affects 0.3% to 3% of pregnancies and requires additional therapies beyond those commonly used for less severe instances of nausea and vomiting of pregnancy (NVP). Differentiating between NVP and HEG is a vital yet challenging function for any obstetrician. The literature for management of HEG is lacking compared with that of NVP. Objective: Review etiology of NVP/HEG highlights key considerations in the workup of HEG as they compare to NVP and explore management options for recalcitrant HEG focusing principally on how they affect maternal and fetal outcomes and secondarily on where data are nonprescriptive. Evidence acquisition: This was a literature review primarily using PubMed and Google Scholar. Results: Short-course corticosteroids and treatment for Helicobacter pylori have the most favorable risk-reward profiles of the 4 pharmacologic therapies evaluated. Mirtazapine and diazepam may have a place in highly selected patients. If nutritional supplementation is required, enteral nutrition is strictly preferred to parenteral nutrition. Postpyloric feeding approaches are less likely to induce vomiting. Surgically placed feeding tubes are less likely to be dislodged and may be worth the invasive insertion procedure if nasogastric or nasojejunal tubes are not tolerated. Conclusions and relevance: Hyperemesis gravidarum is a diagnosis reserved for refractory cases of NVP and therefore by definition poses treatment challenges. Any clinical presentation that lent itself to prescriptive, algorithmic management would likely fall short of the diagnostic criteria for HEG. However, data can inform management on a patient-by-patient basis or at least help patient and provider understand risks and benefits of therapies reserved for refractory cases.
Chapter
Nausea and vomiting during pregnancy (NVP) occurs commonly with a prevalence of 50–80% for nausea and up to 50% for vomiting and retching. The pathophysiology of NVP is most likely multifactorial. Hypotheses include psychological factors, evolutionary adaptation, hormone alterations, genetic inheritance, infection, and gastrointestinal dysfunction. Differential diagnosis depends on the time of onset. Typically, NVP abates by 9–10 weeks’ gestation. NVP is a clinical diagnosis of exclusion after other gastrointestinal, medical, drug‐induced, or surgical conditions have been ruled out. Treatment begins with prevention which includes multivitamins and dietary and lifestyle changes. Acupressure at the Nei Guan acupoint has been proposed to alleviate symptoms of NVP. The combination of vitamin B6 (pyridoxine) and doxylamine is the recommended first‐line treatment for NVP. Persistent nausea and vomiting for three weeks or longer may result in a deficiency of vitamin B1 (thiamine) leading to Wernicke encephalopathy.
Thesis
Hintergrund und Ziele: Übelkeit und Erbrechen während der Schwangerschaft (NVP) sind bei über 50% der Schwangeren anzutreffen und sind doch in ihrer Pathogenese noch immer unverstanden. Eine genetische Prädisposition bei multifaktorieller Genese ist nach aktuellem Wissensstand naheliegend. Ziel der hier vorliegenden Studie war die Korrelation genetischer Variationen (SNPs) in den Genen des Serotoninrezeptors (5-HT3R), Ryanodin-Rezeptors (RyR2) und Glukokortikoidrezeptors (NR3C1) mit dem Auftreten von NVP. Methodik: Zur Bearbeitung der Fragestellung wurden 461 Datensätze der prospektiven PRIMA-Studie untersucht. An der PRIMA-Studie nahmen 688 schwangere Probandinnen im Zeitraum 2010 - 2015 an der Frauenklinik der Universität Erlangen-Nürnberg teil. Neben der anamnestischen Erfassung der Symptome Übelkeit und Erbrechen im vierwöchentlichen Rhythmus im Tagebuchformat erfolgte die Genotypisierung der Probandinnen. Mittels multivariablem logistischem Regressionsmodell wurden die Datensätze auf eine Assoziation der SNPs mit dem Auftreten von Übelkeit und Erbrechen getestet, adjustiert für potenzielle Störfaktoren, unterteilt in verschiedene Schweregrade. Ergebnisse und Beobachtungen: In unserem Studienkollektiv gaben 80,9 % der Schwangeren Übelkeit im 1. Schwangerschaftstrimenon an, 25,4% der Schwangeren benannten im gleichen Zeitraum mindestens einmaliges Erbrechen. Im weiteren Schwangerschaftsverlauf bis SSW 24 zeigten sich Schweregrad und Häufigkeit der Symptomatik regredient. In Bezug auf die ausgewählten SNPs in den Genen 5-HT3R, RyR2 und NR3C1 zeigte sich keine signifikante Assoziation mit dem Vorhandensein von Übelkeit und/oder Erbrechen in unserem Studienkollektiv. Der Risikofaktor „weibliches Geschlecht des Fetus“ wurde in unserer Untersuchung bestätigt (OR 1,95). Schlussfolgerung: Unsere Studienergebnisse legen nahe, dass die untersuchten SNPs nicht für Übelkeit und Erbrechen in der Schwangerschaft prädisponieren. Darüber hinaus kann kein Rückschluss auf eine Korrelation mit Hyperemesis gravidarum gemacht werden. Aufgrund der kleinen Anzahl untersuchter SNPs im Verhältnis zur Gesamtzahl von SNPs im menschlichen Genom lässt sich keine generelle Aussage über eine genetische Prädisposition aus unseren Ergebnissen ableiten. Weitere genotypische Untersuchungen bei Schwangeren mit NVP sowie mit Hyperemesis gravidarum sind in Zukunft nötig.
Article
Nausea and vomiting in pregnancy (NVP), or morning sickness, is the most common symptom experienced by pregnant women and affects 80% of pregnancies. NVP occurs across a spectrum, ranging from mild to severe, with hyperemesis gravidarum (HG) representing the most extreme form. HG is a complication of pregnancy affecting 1% of pregnancies, and if left untreated can cause maternal and fetal morbidity and mortality. Early treatment of NVP in primary care can prevent progression to HG. This article aims to help GP trainees understand the natural history of HG and provides a framework for its assessment and management.
Chapter
Hyperemesis gravidarum (HG) is characterized by unrelenting nausea and vomiting in pregnancy and may be accompanied by weight loss, electrolyte abnormalities, and dehydration. Prompt recognition and early efforts to control symptoms are essential to limiting progression of disease. Fluid and electrolyte repletion, as well as pharmacologic control of symptoms, is the mainstay of acute HG management. Pharmacologic therapy includes dopamine antagonists, selective serotonin inhibitors, and H1 antagonists. For patients with prolonged symptoms, treatment should include supplemental folate and thiamine. Admission is reserved for patients with significant electrolyte abnormalities or severe symptoms refractory to pharmacologic intervention.
Article
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Nausea and vomiting of pregnancy (NVP) are seen in 50-80% of pregnancies. However, in severe NVP, called hypermesis gravidarum (HG), medical therapy to reduce nausea and vomiting is inevitable and ondansetron (OND) as an effective drug has recently been proposed. This study evaluated the effectiveness of OND versus metoclopramide (MET) in the treatment of HG. In this clinical trial study, 83 pregnant women with HG were enrolled in 2011-2012 and randomly divided in two groups. The first group received oral administration of MET and the second group was treated with OND for two weeks. Severity of nausea and vomiting were evaluated according to visual analogue scale (VAS) criteria. Data analysis was done by chi2, Fisher exact test and Student's t-test. Comparison of the trend of change of vomiting in the two groups during the 14-day treatment showed the OND group had significantly lower vomiting scores versus the MET group (p = 0.042), while there was no significant difference in the trend of nausea. OND has a more favorable effect in controlling severe vomiting.
Article
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Ondansetron is frequently used to treat nausea and vomiting during pregnancy, but the safety of this drug for the fetus has not been well studied. We investigated the risk of adverse fetal outcomes associated with ondansetron administered during pregnancy. From a historical cohort of 608,385 pregnancies in Denmark, women who were exposed to ondansetron and those who were not exposed were included, in a 1:4 ratio, in propensity-score-matched analyses of spontaneous abortion (1849 exposed women vs. 7396 unexposed women), stillbirth (1915 vs. 7660), any major birth defect (1233 vs. 4932), preterm delivery (1792 vs. 7168), and birth of infants at low birth weight and small for gestational age (1784 vs. 7136). In addition, estimates were adjusted for hospitalization for nausea and vomiting during pregnancy (as a proxy for severity) and the use of other antiemetics. Receipt of ondansetron was not associated with a significantly increased risk of spontaneous abortion, which occurred in 1.1% of exposed women and 3.7% of unexposed women during gestational weeks 7 to 12 (hazard ratio, 0.49; 95% confidence interval [CI], 0.27 to 0.91) and in 1.0% and 2.1%, respectively, during weeks 13 to 22 (hazard ratio, 0.60; 95% CI, 0.29 to 1.21). Ondansetron also conferred no significantly increased risk of stillbirth (0.3% for exposed women and 0.4% for unexposed women; hazard ratio, 0.42; 95% CI, 0.10 to 1.73), any major birth defect (2.9% and 2.9%, respectively; prevalence odds ratio, 1.12; 95% CI, 0.69 to 1.82), preterm delivery (6.2% and 5.2%; prevalence odds ratio, 0.90; 95% CI, 0.66 to 1.25), delivery of a low-birth-weight infant (4.1% and 3.7%; prevalence odds ratio, 0.76; 95% CI, 0.51 to 1.13), or delivery of a small-for-gestational-age infant (10.4% and 9.2%; prevalence odds ratio, 1.13; 95% CI, 0.89 to 1.44). Ondansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. (Funded by the Danish Medical Research Council.).
Article
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We examined treatment outcomes in women with severe nausea and vomiting of pregnancy (NVP) receiving outpatient nursing support and either subcutaneous metoclopramide or subcutaneous ondansetron via a microinfusion pump. Among women receiving outpatient nursing services, we identified those diagnosed with severe NVP having a Pregnancy-Unique Quantification of Emesis (PUQE) score of greater than 12 at enrollment and prescribed either metoclopramide (N = 355) or ondansetron (N = 521) by their physician. Maternal characteristics, response to treatment, and start versus stop values were compared between the medication groups. Allocation to group was based on intention-to-treat protocol. Maternal characteristics were similar between the groups. Days to reduction in PUQE score levels were similar (median 2 days, metoclopramide; 3 days, ondansetron; P = 0.206). Alteration from metoclopramide to ondansetron (31.8%) was more frequent than alteration from ondansetron to metoclopramide (4.4%; P < 0.001). Improvement of NVP symptoms and reduced need for hospitalization was noted with both medications. Treatment with either metoclopramide or ondansetron resulted in significant improvement of NVP symptoms with half of women showing a reduction from severe symptoms to moderate or mild symptoms within 3 days of treatment initiation. Alteration in treatment was significantly greater in patients initially prescribed metoclopramide.
Article
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In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy. We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever. There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis. In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.
Article
Importance: Metoclopramide, a drug frequently used for nausea and vomiting in pregnancy, is thought to be safe, but information on the risk of specific malformations and fetal death is lacking. Objective: To investigate the safety of metoclopramide use in pregnancy. Design, setting, and participants: Register-based cohort study in Denmark, 1997-2011. From a cohort of 1,222,503 pregnancies, metoclopramide-exposed and unexposed women were matched (1:4 ratio) on the basis of age, calendar year, and propensity scores. Main outcomes and measures: Primary outcomes were major congenital malformations overall, 20 individual malformation categories (selected according to power criteria), spontaneous abortion, and stillbirth. In matched analyses, logistic regression was used to estimate prevalence odds ratios of malformations and Cox regression to estimate hazard ratios (HRs) of spontaneous abortion. Results: Among 28,486 women exposed to metoclopramide in the first trimester, 721 had an infant with a major congenital malformation (25.3 [95% CI, 23.5-27.1] cases per 1000 births), compared with 3024 among 113,698 unexposed women (26.6 [95% CI, 25.7-27.5] per 1000 births). There were no significant associations between metoclopramide use and malformations overall (prevalence odds ratio, 0.93 [95% CI, 0.86-1.02]) or any of the 20 individual malformation categories, eg, neural tube defects, transposition of great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip, cleft palate, anorectal atresia/stenosis, and limb reduction (upper limit of 95% CI below 2.0 for 17 of 20 categories). Metoclopramide was not associated with increased risk of spontaneous abortion (757 cases [20.0 {95% CI, 18.5-21.4} per 1000] among 37,946 metoclopramide-exposed women and 9414 cases [62.1 {95% CI, 60.9-63.3} per 1000] among 151,661 unexposed women; HR, 0.35 [95% CI, 0.33-0.38]) and stillbirth (142 cases [3.5 {95% CI, 2.9-4.1} per 1000] among 40,306 metoclopramide-exposed women and 634 cases [3.9 {95% CI, 3.6-4.2} per 1000] among 161,098 unexposed women; HR, 0.90 [95% CI, 0.74-1.08]). Conclusions and relevance: Metoclopramide use in pregnancy was not associated with increased risk of major congenital malformations overall, any of the 20 individual malformation categories assessed, spontaneous abortion, or stillbirth. These safety data may help inform decision making when treatment with metoclopramide is considered in pregnancy.
Article
There is an impression of poor management of pregnancy sickness in Australia, specifically an apparent total reliance on metoclopramide, as a first-line choice. To determine what management options are commonly used in by distributing a survey to Fellows and Diplomates of RANZCOG. A web-based survey questionnaire distributed using an email list obtained from RANZCOG. A total of 495 responses were received (23%). For morning sickness, 89% of those replying give dietary advice frequently or always, and 70% prescribe metoclopramide frequently or always, whereas 59% advise pyridoxine and 10% prescribe doxylamine. For hyperemesis gravidarum, 86% prescribe metoclopramide and 75% ondansetron. Despite guidelines suggesting the use of antihistamines and dopamine agonists (phenothiazines), very few practitioners in this region make use of these in any numbers.
Article
Background/aims: The incidence of postoperative nausea and vomiting is truly high after laparoscopic cholecystectomy. Ondansetron and metoclopramide may be effective in preventing it. Our aim was to estimate the efficacy of ondansetron vs. metoclopramide in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy. Methodology: We searched MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Science Citation Index Expanded, EMBASE etc. to obtain relevant randomized controlled trials until October 2011. Two authors independently assessed the trials for inclusion and extracted the data. The odds ratio (OR) for dichotomous data was used with 95% confidence intervals (CI). Sensitivity and subgroup analysis were performed, if necessary. Results: The total incidence of postoperative nausea and vomiting within 24 hours after laparoscopic cholecystectomy was 31% (74 of 235) in the ondansetron group and 56% (127 of 225) in the metoclopramide group (OR=0.33, 95%CI=0.22-0.49, p<0.00001, 12=49%). The total incidences of nausea and vomiting were lower in the ondansetron group (OR=0.28, 95%CI=0.15-0.54, p=0.0002, I²=0%) and (OR=0.31, 95%CI=0.17-0.55, p<0.0001, I²=0%), respectively. Conclusions: Based on the evidence, ondansetron has a better effect than metoclopramide for preventing postoperative nausea and vomiting after laparoscopic cholecystectomy. If we ignore the price factor, ondansetron is recommended for adhibition.
Article
Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, but its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects. Using data from the National Birth Defects Prevention Study (NBDPS)-a multi-site, population-based, case-control study-we examined whether NVP or its treatment was associated with the most common noncardiac defects in the NBDPS (nonsyndromic cleft lip with or without cleft palate [CL/P], cleft palate alone [CP], neural tube defects, and hypospadias) compared with randomly selected nonmalformed live births. Among the 4524 cases and 5859 controls included in this study, 67.1% reported first-trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or neural tube defects, but modest risk reductions were observed for CL/P (adjusted odds ratio [aOR] = 0.87; 95% confidence interval [CI], 0.77-0.98) and hypospadias (aOR = 0.84; 95% CI, 0.72-0.98). Regarding treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR = 4.36; 95% CI, 1.21-15.81), steroids and hypospadias (aOR = 2.87; 95% CI, 1.03-7.97), and ondansetron and CP (aOR = 2.37; 95% CI, 1.18-4.76), whereas antacids were associated with a reduced risk for CL/P (aOR = 0.58; 95% CI, 0.38-0.89). NVP was not observed to be associated with an increased risk of birth defects; however, possible risks related to three treatments (i.e., proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation.
Article
The aim of this study was to evaluate urine microscopy, dipstick analysis and urinary symptoms in screening for urinary tract infection (UTI) in hyperemesis gravidarum (HG).   A prospective cross-sectional study was performed on women at first hospitalization for HG. A clean-catch mid-stream urine sample from each recruit was sent for microscopy (for bacteria, leucocytes and erythrocytes), dipstick analysis (for leukocyte esterase, nitrites, protein and hemoglobin) and microbiological culture. The presence of current urinary symptoms was elicited by questionnaire. UTI is defined as at least 10(5) colony-forming units/mL of a single uropathogen on culture. Screening test parameters were analyzed against UTI. UTI was diagnosed in 15/292 subjects (5.1%). Receiver-operator characteristic curve analysis of microscopic urine leucocytes revealed area under the curve=0.64, 95% confidence interval (CI) 0.5-0.79, P=0.063 and erythrocytes area under the curve=0.53, 95%CI 0.39-0.67, P=0.67 for UTI indicating the limited screening utility of these parameters. Microscopic bacteriuria (likelihood ratio [LR] 1.1, 95%CI 0.7-1.5) and urine dipstick leukocyte esterase (LR 1.4, 95%CI 1.1-1.8), nitrites (LR 2.3, 95%CI 0.3-17.2), protein (LR 1.0, 95%CI 0.7-1.6) and hemoglobin (LR 0.8, 95%CI 0.4-1.5) were not useful screening tests for UTI in HG. Elicited symptoms were also not predictive of UTI. Urine microscopy, dipstick analysis and urinary symptoms were not useful in screening for UTI in HG. UTI should be established by urine culture in HG before starting antibiotic treatment.
Article
Nausea and vomiting of pregnancy (NVP) affects 90% of pregnant women and its impact is often underappreciated. Hyperemesis gravidarum, the most severe end of the spectrum, affects 0.5-2% of pregnancies. The pathogenesis of this condition remains obscure and its management has largely been empirical. This review aims to provide an update on advances in pregnancy hyperemesis focusing on papers published within the past 2 years. The cause of hyperemesis is continuing to be elaborated. Recent data attest to the effectiveness of the oral doxylamine-pyridoxine in NVP. Follow-up data of children exposed in early pregnancy to doxylamine-pyridoxine for NVP are reassuring. Evidence is increasing for ginger as an effective herbal remedy for NVP. Metoclopramide is effective in NVP and hyperemesis gravidarum, with a good balance of efficacy and tolerability. A recent large-scale study on first trimester exposure to metoclopramide is reassuring of its safety. Evidence is emerging for the treatment of acid reflux to ameliorate NVP. The role of corticosteroids for hyperemesis gravidarum remains controversial. Transpyloric feeding may be warranted for persistent weight loss, despite optimal antiemetic therapy. Women with significant NVP should be identified so that they can be safely and effectively treated.
Article
A 25-year-old woman presents with persistent nausea and vomiting 8 weeks after her last menstrual period in her first pregnancy. Her primary care provider is reluctant to give her medications. She has lost 5 lb (2.3 kg) in 6 weeks. How should she be treated?
Article
To compare the effects of promethazine with those of metoclopramide for hyperemesis gravidarum. Women at their first hospitalization for hyperemesis gravidarum were approached when intravenous antiemetic therapy was needed. They were randomly assigned to receive 25 mg promethazine or 10 mg metoclopramide every 8 hours for 24 hours in a double-blind study. Primary outcomes were vomiting episodes by diary and well-being visual numerical rating scale score (10-point scale) in the 24-hour main study period. Participants also filled out an adverse-effects questionnaire at 24 hours and a nausea visual numerical rating scale score at recruitment and at 8, 16, and 24 hours. A total of 73 and 76 women, randomized to metoclopramide and promethazine, respectively, were analyzed. Median vomiting episodes were one (range 0-26) compared with two (range 0-26) (P=.81), and well-being visual numerical rating scale scores were 8 (range 1-10) compared with 7 (range 2-10) (P=.24) for metoclopramide and promethazine, respectively. Repeat-measures analysis of variance of the nausea visual numerical rating scale scores showed no significant difference between study drugs (F score=0.842, P=.47). Reported drowsiness (58.6% compared with 83.6%, P=.001, number needed to treat to benefit [NNTb] 5), dizziness (34.3% compared with 71.2%, P<.001, NNTb 3), dystonia (5.7% compared with 19.2%, P=.02, NNTb 8), and therapy curtailment owing to adverse events (0 of 73 [0%] compared with 7 of 76 [9.2%], P=.014) were encountered less frequently with metoclopramide. Promethazine and metoclopramide have similar therapeutic effects in patients who are hospitalized for hyperemesis gravidarum. The adverse effects profile was better with metoclopramide.
Article
Nausea and vomiting occur in up to 80% of normal pregnancies. Hyperemesis gravidarum, resulting in dehydration and ketonuria, is a more severe, disabling and potentially life threatening condition affecting up to 1.5% of pregnancies. Treatment is supportive with intravenous rehydration, antiemetics and correction of vitamin deficiency to minimize complications. There are good safety data to support the use of antihistamines, phenothiazines and metoclopromide in hyperemesis gravidarum, though trials of efficacy are lacking and there is little evidence on which to chose the optimum therapy. This review discusses the diagnosis and management of hyperemesis gravidarum and the prevention, recognition and treatment of the serious complications of Wernicke encephalopathy, osmotic demyelination syndrome and thromboembolism.
Article
To evaluate oral pyridoxine in conjunction with standard therapy in women hospitalized for hyperemesis gravidarum (HG). Patients with HG were randomized at hospitalization to 20 mg oral pyridoxine thrice daily or to placebo. Intravenous rehydration, metoclopramide and oral thiamine were also administered. Metoclopramide and thiamine were continued for 2 weeks after discharge. Rehospitalization for HG in the 2-week study period was ascertained, vomiting was recorded by diary, and nausea was evaluated with a 10-point visual analogue scale (VAS) at enrolment, after hospital discharge and on week 1 and 2 reviews. Ninety-two women were included in the analysis. The rehospitalization rate was 37.5 versus 21.1% (relative risk 1.8, 95% confidence interval 0.9-3.7, p = 0.14) for pyridoxine and placebo, respectively. Daily vomiting episodes after discharge were not different (mean +/- SD): 1.9 +/- 2.4 versus 1.4 +/- 1.1, p = 0.28 during week 1 and 1.4 +/- 1.3 versus 1.4 +/- 1.6, p = 0.98 during week 2. Repeated-measures analysis of variance showed no difference in the nausea visual analogue scale (p = 0.59). The use of oral pyridoxine in conjunction with metoclopramide during the inpatient stay and during the 2 weeks after hospital discharge for hyperemesis gravidarum did not improve the rehospitalization rate, the vomiting frequency or the nausea score. Larger studies need to be done.
Article
Our objectives were to describe the presentation and course of hyperemesis gravidarum with respect to thyroid function and to test the hypothesis that patients with biochemical hyperthyroidism differ in clinical presentation from euthyroid hyperemesis patients. Sixty-seven patients seen at Los Angeles County Women's Hospital over a 10-month period with hyperemesis gravidarum were studied prospectively with respect to thyroid function. Forty-four patients (66%) had biochemical hyperthyroidism (increased free thyroxine index [n = 39] or suppressed thyroid-stimulating hormone [n = 40]) that was self-limited, resolving by 18 weeks' gestation. Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte levels (23/39 [59%] vs 6/28 [21%] and increased liver enzyme levels (23/59 [59%] vs 5/28 [18%], p less than 0.01). The severity of hyperemesis was found to vary directly with the degree of hyperthyroidism. Hyperthyroidism is a common, self-limited finding in hyperemesis. The cause of the hyperthyroidism may be linked to the cause of hyperemesis itself.
Article
A programme of pre-clinical safety evaluation of ondansetron has been undertaken which involved a series of studies - single dose studies, repeat dose studies, reproduction studies, genotoxicity studies, oncogenicity studies, local irritancy studies, and a hypersensitivity study. Ondansetron was found to have a very good safety profile, and the only toxicity identified was associated with central nervous system activity when near lethal doses were administered. It was not genotoxic and had no reproductive or oncogenic potential.
Article
During the period of 4 years between 1985 and 1988, 190 patients suffering from hyperemesis gravidarum (HG) were hospitalized at the Soroka Medical Center. From the 190 patients, 164 were followed up throughout their pregnancies and delivered at our Medical Center. The epidemiology of HG as well as the incidence of maternal complications and pregnancy outcome were analyzed and compared with 209 controls. The incidence of HG in our patient population was 6.3/1000 live births. The patients in the study group had fewer pregnancies and deliveries and more spontaneous abortions in the past than in the control population. Premature contractions and vaginal bleeding during the first trimester were more common among women with HG. Other complications of pregnancy were no more common than among controls. Women with HG in their current pregnancy had a lower incidence of spontaneous abortions (3.1%) as compared with previously reported rates in the general population (15%). Perinatal outcome was no different in women with HG than in the controls. Women with severe HG did not have statistically significant differences in the incidence of pregnancy complications and their pregnancy outcome was the same as in those without severe HG.
Article
We attempted to determine whether the antiemetic ondansetron would be more effective than promethazine in treating hyperemesis gravidarum. Patients with hyperemesis gravidarum who required hospital admission were randomized to receive either intravenous ondansetron (n = 15) or intravenous promethazine (n = 15) in a double-blind manner. Severity of disease was determined by electrolyte status, weight loss, ketonuria, and prior use of outpatient antiemetics. Outcome variables included degree of nausea, weight gain during treatment, days of hospitalization, and number of medication doses. In this preliminary investigation ondansetron offered no advantage when compared with promethazine in the relief of nausea, weight gain, days of hospitalization (4.5 +/- 2.3 vs 4.5 +/- 1.5), and total doses of medication per hospitalization (2.1 +/- 1.2 vs 1.9 +/- 1.3). This preliminary trial of ondansetron demonstrated no benefit over promethazine in patients hospitalized for hyperemesis gravidarum.
Article
To review the role of serotonin in chemotherapy-induced emesis and the mechanism by which 5-hydroxytryptamine3 (5-HT3)-receptor antagonists block the action of serotonin; to review the pharmacology and clinical efficacy of the 5-HT3-receptor antagonists in controlling nausea and vomiting induced by highly emetogenic chemotherapy regimens, including a comparison of agents in this class. Journal articles and proceedings of clinical oncology conferences. Prior to the availability of 5-HT3-receptor antagonists, metoclopramide was the therapy of choice for prevention of cisplatin-associated emesis. Several randomized, double-blind, comparative trials have established that a 5-HT3-receptor antagonist used alone is more effective than metoclopramide and equal to or better than the combination of metoclopramide and dexamethasone. 5-HT3-receptor antagonists contribute significantly to the current armamentarium of antiemetic agents. Clinical trials consistently have demonstrated a benefit with these agents that exceeds the previously established antiemetic standards. 5-HT3-receptor antagonists have had a profound impact on the clinical management of acute chemotherapy-induced nausea and vomiting. Based on their unique mechanism of action and low toxicity profile, the 5-HT3-receptor antagonists offer a relatively new approach to controlling nausea and vomiting associated with highly emetogenic chemotherapy.
Article
To assess the efficacy of ondansetron and the incidence of headache when used as prophylaxis for postoperative vomiting. Studies were identified using MEDLINE (January 1990 to July 1997) with the key words: "vomiting," "ondansetron," and "surgery" and/or "anesthesia." All prospectively randomized trials in which ondansetron and placebo had been administered for prevention of postoperative vomiting. Data on patient numbers, gender and ages, drug dosage, outcomes (incidence of vomiting and incidence of headache), time of outcome (up to 8 hrs or up to 48 hrs postoperatively), and baseline risk for vomiting according to type of surgical intervention were extracted. 48 trials involving 12,078 patients (10,390 adults and 1688 children) met the selection criteria. No evidence was found that the drug became more effective at doses larger than 4 mg. The dose of 8 mg was not statistically demonstrated to be superior (p = 0.558), while that of 1 mg was barely effective. The meta-analysis indicated that when the incidence of vomiting is elevated (e.g., the combined average of the placebo groups of 48%), on the statistical (i.e., hypothetical) grounds of six patients being treated with 4 mg of ondansetron, one will not vomit due to the treatment and, of the rest, two patients would have vomited despite the treatment and three patients would not have vomited anyway. The overall incidence of headache was 7.05% in ondansetron groups versus 6.16% in placebo groups. While ondansetron is an effective antiemetic with minimal adverse effects, the data obtained on the numbers needed to be treated calculation for prophylaxis of postoperative vomiting should be considered in future cost-effective strategies of postoperative management.
Article
5-HT3 receptor antagonists are used to treat radiation-induced sickness. The purpose of this study was to define anti-emetic efficacy and potential for harm of these drugs in radiotherapy. A systematic search, critical appraisal and quantitative analysis of relevant data using the number-needed-to-treat or harm (NNT/H) were conducted. Acute (0 to 24h) and delayed (beyond 24 h) anti-emetic efficacy were analysed separately. Data from 1,404 patients were found in 40 trials published in 36 reports. Data from 197 patients receiving ondansetron or granisetron in five randomised trials were regarded as valid according to preset criteria. One placebo-controlled trial had 10 patients per group and in this ondansetron was not significantly different from placebo. In a larger (n = 105) placebo-controlled trial, ondansetron was significantly more efficacious than metoclopramide for complete control of acute vomiting (NNT 2.2, 95% confidence interval (CI) 1.7-3.3) and acute nausea (NNT 3.6, 95% CI 2.2-10.2). Three trials reported delayed outcomes with ondansetron or granisetron: there was no evidence of any difference compared with placebo or other anti-emetics. Two trials reported no acute or delayed but a 'worst day' outcome; in these ondansetron's antivomiting effect was significantly better than placebo (NNT 4.4, 95% CI 2.5-23) or prochlorperazine (NNT 3.8, 95% CI 2.4-10.3), but not its antinausea effect. Constipation and headache were associated significantly with 5-HT3 receptor antagonists compared with other anti-emetics or placebo (NNH 6.4 and 17.1, respectively). Only 14% of published data enabled valid estimation of the anti-emetic efficacy of 5-HT3 receptor antagonists in radiotherapy. There was some evidence that these drugs prevent acute vomiting: 40% of treated patients will benefit (NNT approximately 2.5). The evidence for nausea was less clear. There was no evidence that these drugs are of any benefit beyond 24 h. There was evidence that they produce specific adverse effects.
Article
Unlabelled: Postoperative nausea and vomiting are important causes of morbidity after anesthesia and surgery. We performed a meta-analysis of published, randomized, controlled trials to determine the relative efficacy and safety of ondansetron, droperidol, and metoclopramide for the prevention of postoperative nausea and vomiting. We performed a literature search of English references using both the MEDLINE database and a manual search. Double-blinded, randomized, controlled trials comparing the efficiency of the prophylactic administration of ondansetron, droperidol, and/or metoclopramide therapy during general anesthesia were included. A total of 58 studies were identified, of which 4 were excluded for methodological concerns. For each comparison of drugs, a pooled odds ratio (OR) with a 95% CI was calculated using a random effects model. Ondansetron (pooled OR 0.43, 95% CI 0.31, 0.61; P < 0.001) and droperidol (pooled OR 0.68, 95% CI 0.54, 0.85; P < 0.001) were more effective than metoclopramide in preventing vomiting. Ondansetron was more effective than droperidol in preventing vomiting in children (pooled OR 0.49; P = 0.004), but they were equally effective in adults (pooled OR 0.87; P = 0.45). The overall risk of adverse effects was not different among drug combinations. We conclude that ondansetron and droperidol are more effective than metoclopramide in reducing postoperative vomiting. Implications: We performed a systematic review of published, randomized, controlled trials to determine the relative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting. Ondansetron and droperidol were more effective than metoclopramide in reducing postoperative vomiting. The overall risk of adverse effects did not differ.
Article
To compare the relative efficacy of prophylactic metoclopramide, ondansetron, and placebo in nonemergent cesarean section patients given epidural anesthesia intraoperatively and for the first 24-hour period after delivery. Randomized, double blind, placebo-controlled study. Inpatient obstetric unit at a university hospital center. 164 nonemergent cesarean section patients given epidural anesthesia. At time of umbilical cord clamp, patients received intravenously (IV) either 4 mg ondansetron (Group O) or 10 mg metoclopramide (Group M) or 10 mL normal saline (Group P). Episodes and severity of nausea and vomiting, rescue antiemetic requirement, patient satisfaction, and side effects were recorded. The frequency of intraoperative nausea were 24%, 43%, and 57% for Group O, Group M, and Group P, respectively (p < 0.03). The frequency of nausea for the 24-hour study period were 26%, 51% and 71% for Groups O, M, and P respectively (p < 0.03). The frequency of intraoperative and postoperative vomiting were similar between Group O and Group M, but significantly higher in Group P (p < 0.05). Overall patient satisfaction was highest in Group O compared with Groups P and M (p < 0.05). Maximum analog sedation score was higher in Group M compared to Groups O and P (p < 0.05). In cesarean section patients given epidural anesthesia, prophylactic ondansetron, 4 mg IV, is more efficacious and has a higher patient satisfaction than that with metoclopramide, 10 mg IV, or placebo in preventing nausea and achieving complete responses during intraoperative period and the first 24-hour postdelivery period. However, there is no difference between ondansetron and metoclopramide in reducing frequency of vomiting. Prophylactic ondansetron 4 mg IV is more effective in preventing nausea than vomiting.
Article
Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations. A prospective comparative observational study. Teratogen Information Services (TIS). Pregnant women. Our three groups included women who were exposed to ondansetron and women exposed to (1) other anti-emetics and (2) non-teratogen exposures. All of the women called either our NVP Helpline or TIS at The Motherisk Program in Toronto, Canada, or The Mothersafe Program in Sydney, Australia. Rates of major malformation. We have completed 176 pregnancy outcomes in each group. In the ondansetron cohort, there were 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations and the mean birthweight was 3362 g [SD 525]. There were no statistical differences in any of the study endpoints between the ondansetron and the comparison groups. This drug does not appear (although the sample size is limited) to be associated with an increased risk for major malformations above baseline.
Article
In a retrospective analysis of 192 cases of presumed hyperemesis gravidarum, there were no biochemical markers that predicted hospital readmission. There was, however, statistically significant negative predictive value in abnormal liver function tests. This could represent acute self-limited illness with a component of hepatitis as the cause for the clinical presentation, rather than hyperemesis. © 2006 The Authors Journal compilation © 2006 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.