Unformatted text preview: THE MANAGEMENT OF
NAUSEA AND VOMITING
Dr .Ashraf Fouda
Damietta General Hospital
[email protected] :Recommendations
Dietary and lifestyle changes should be liberally encouraged, and women should be counselled to eat whatever appeals to them. (IIIC) :Recommendations Alternative therapies, such as
1. ginger supplementation, 2. acupuncture, and 3. acupressure, may be beneficial. (IA) :Recommendations
A doxylamine /pyridoxine combination should be the standard of care, since it has the greatest evidence to support its efficacy and safety. (IA) :Recommendations
H1 receptor antagonists should be considered in the management of acute or breakthrough episodes of NVP. (IA) :Recommendations
Pyridoxine monotherapy supplementation may be considered as an adjuvant measure. (IA) :Recommendations
Phenothiazines are safe and effective for severe NVP. (IA) :Recommendations
Metoclopramide is safe to be Metoclopramide is safe to be used for management of NVP, although evidence for efficacy is more limited. (II2D) :Recommendations
Corticosteroids should be avoided during the first trimester because of possible increased risk of oral clefting and should be restricted to refractory cases. (IB) :Recommendations
When NVP is refractory to initial pharmacotherapy, investigation of other potential causes should be undertaken. (IIIA) INTRODUCTION
INTRODUCTION Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting 50%–90% of women.
The most severe form of NVP is commonly referred to as hyperemesis gravidarum (HG). INTRODUCTION
HG, defined as persistent vomiting that leads to weight loss greater than 5% of prepregnancy weight, with associated electrolyte imbalance and ketonuria, occurs in about 1% of pregnancies.
Although NVP may be classified as mild, moderate, or severe, the severity of nausea or vomiting may not adequately reflect the distress it causes. INTRODUCTION
The physical and emotional impact of NVP often results in feelings of anxiety and worry about the effect of the symptoms on the fetus. INTRODUCTION
It has a negative impact on family relationships and has major consequences on women’s working abilities; 47% of working women with NVP feel job efficiency is reduced, 35% lose work time (mean loss of 62 working hours per woman), and 25% lose time from housework (mean loss of 32 hours per woman). INTRODUCTION
NVP is also cited as a reason for elective termination of pregnancy.
This is not surprising when it is recognized that nausea experienced by pregnant women with NVP (excluding HG patients) is comparable in severity to the nausea experienced by patients undergoing cancer chemotherapy. INTRODUCTION 1..
2 Each year, a significant number of women have
one or more hospital admissions for NVP
(as many as 14
hospitalizations/ 1000 births).
Therefore, early recognition and management of
NVP could have:
A profound effect on women’s health and quality
of life during pregnancy, as well as
A financial impact on the health care system. INTRODUCTION The pathogenesis of NVP is poorly understood and the etiology is likely to be multifactorial. Other causes of nausea and vomiting must be ruled out, including:
1. Gastrointestinal, 2. Genitourinary, 3. Central nervous system, and 4. Toxic/metabolic problems. INTRODUCTION
Idiopathic NVP must be distinguished from NVP of known etiology, such as hydatidiform mole or multiple gestation. INTRODUCTION
In the aftermath of thalidomide ,the pharmacological antiemetic therapy is still used with great caution by some patients and health care providers to treat NVP, and is erroneously considered to be contraindicated in pregnancy. INTRODUCTION
Care providers play a major role in counselling and reassuring patients on safe and effective treatments available for NVP. INTRODUCTION
Early treatment with counselling is preferable, after appropriate history
taking and physical examinations have been done. INTRODUCTION 1.
2. Recognizing and treating NVP in a timely fashion will:
Prevent the progression of NVP to HG and maternal complications, and Reduce the risk of parenteral therapy and HG
related costs. This should eventually result in:
Improved maternal health and quality of life, as well as Better family relationships. DIETARY AND LIFESTYLE DIETARY AND LIFESTYLE CHANGES
There has been no evidence to prove the effectiveness of dietary changes on relieving NVP symptoms. Advice for women suffering from NVP has traditionally revolved around dietary changes. DIETARY AND LIFESTYLE CHANGES 1.
4. Recommendations have included Separating solids and liquids; Eating small, frequent meals consisting of bland foods; Avoiding fatty foods such as potato chips; and Avoiding drinking cold, tart, or sweet beverages. DIETARY AND LIFESTYLE CHANGES
Other advice has been to avoid sensory stimuli, particularly strong odours. Women alter their dietary habits to eat small frequent meals, to tolerate the NVP.
This makes a randomized controlled trial (RCT) of these habits very difficult to perform. DIETARY AND LIFESTYLE CHANGES
There is no evidence that shortterm dietary deficiencies during the early weeks of pregnancy will have longterm consequences on pregnancy outcome. DIETARY AND LIFESTYLE CHANGES
The use of vitamin supplements (including Bcomplex) is encouraged during pregnancy, and even if the woman is unable to tolerate her prenatal vitamin, it is important to maintain folic acid supplementation until the embryo’s neural tube has closed. DIETARY AND LIFESTYLE CHANGES
Caution is warranted with diets containing suprapharmacological doses of individual vitamins, given the paucity of data regarding their safety for the fetus. DIETARY AND LIFESTYLE CHANGES
Sleep requirements increase in early pregnancy.
Because fatigue seems to exacerbate NVP, women should be encouraged to increase their rest, especially while they are symptomatic. DIETARY AND LIFESTYLE CHANGES
It would seem appropriate for health care providers to adopt a liberal attitude toward providing leavesofabsence from work. Such a policy should ultimately shorten the number of days lost from work. DIETARY AND LIFESTYLE CHANGES
Enlisting the support and understanding of close friends and family as well as supportive counselling may be of benefit to the woman suffering from NVP. RECOMMENDATION
Dietary and lifestyle changes should be liberally encouraged, and women should be counselled to eat whatever appeals to them. (IIIC) NON
PHARMACOLOGICAL THERAPIES GINGER
Ginger (Zingiber officinale) is present as a spice in foods and beverages. It can also be taken in the form of tea or tablet extracts. There is only one RCT examining the efficacy, but not the safety, of 1000 mg/day of ginger. GINGER
Ginger is a nonregulated food product and most preparations available are of uncertain purity and composition. No evidencebased studies have been published to exclude the possibility of teratogenicity, and at the present time, large quantities of ginger should not be recommended as a treatment for NVP. ACUPUNCTURE AND ACUPRESSURE
ACUPUNCTURE AND ACUPRESSURE
Stimulation of the P6 (Neiguan) point, located threefingers’ breadth proximal to the wrist, has been used for thousands of years by acupuncturists to treat nausea and vomiting from a variety of causes. ACUPUNCTURE AND ACUPRESSURE Though there are no theoretical concerns about the safety of acupressure in pregnancy, efficacy of P6 acupressure is difficult to prove because it is impossible to perform a true doubleblind trial compared with no intervention. Nonetheless, nonblinded RCTs have demonstrated a decrease in “persisting nausea” by at least 50%. Bands worn on the wrist to apply acupressure may also be helpful. RECOMMENDATION
RECOMMENDATION Alternative therapies, such as ginger supplementation, acupuncture, and acupressure, may be beneficial. (IA) PHARMACOLOGICAL THERAPIES
When conservative measures have not been effective, pharmacological intervention is warranted. Treatment should start as soon as possible after the diagnosis of NVP. ANTIHISTAMINES
Doxylamine is an H1 receptor antagonist that has been shown to be effective in the treatment of NVP. It is currently marketed in Canada as a fixed combination of 10 mg doxylamine with 10 mg of pyridoxine (vitamin B6), in a delayedrelease formulation (Diclectin®). DOXYLAMINE
The standard recommended dose is up to 4 tablets a day, but recent data suggest that additional daily tablets (between 5 to 8 or up to 2.0 mg/kg) may be beneficial to address larger body size or suboptimally controlled symptoms. RECOMMENDATION
RECOMMENDATION A doxylamine/pyridoxine combination should be the standard of care, since it has the greatest evidence to support its efficacy and safety. (IA) OTHER ANTIHISTAMINES
OTHER ANTIHISTAMINES Other H1 receptor antagonists (e.g., dimenhydrinate [Gravol®], diphenhydramine [Ergocryl®], and hydroxyzine [Atarax®]) are considered safe in pregnancy, with no human teratogenic potential. Data have actually shown a slightly reduced incidence of major and minor malformations with first trimester exposure to various antihistamines. OTHER ANTIHISTAMINES Pooled data from seven controlled trials looking at the effectiveness of various antihistamines for NVP indicate that these drugs are effective. Availability in parenteral and suppository formulations makes these agents a good choice for treatment of acute or breakthrough episodes of NVP. Caution should be taken to avoid excessive dosing of H1 receptor antagonists by combining different antihistamines in therapy. RECOMMENDATION
RECOMMENDATION H1 receptor antagonists should be considered in the management of acute or breakthrough episodes of NVP. (IA) PYRIDOXINE VITAMINS
VITAMINS Pyridoxine, vitamin B6, has been proven to be nonteratogenic in combination with doxylamine. A retrospective cohort study also concluded that pyridoxine monotherapy had no increased risk for major malformations. The effectiveness of vitamin B6 monotherapy versus placebo has been shown in two RCTs (75 mg/day and 30 mg/day orally). RECOMMENDATION
Pyridoxine monotherapy supplementation may be considered as an adjuvant measure. (IA) DOPAMINE ANTAGONISTS
DOPAMINE ANTAGONISTS PHENOTHIAZINES Like antihistamines, Like antihistamines, phenothiazines (i.e., chlorpromazine, perphenazine, prochlorperazine, promethazine, trifluoperazine) have also been proven safe for use in pregnancy. PHENOTHIAZINES Prospective and retrospective cohort, case control, and recordlinkage studies of patients with exposure to various and multiple phenothiazines have failed to demonstrate an increased risk for major malformations. Significant therapeutic effect was demonstrated by three RCTs of various phenothiazines versus placebo for the treatment of severe NVP. RECOMMENDATION
RECOMMENDATION Phenothiazines are safe and effective for severe NVP. (IA) METOCLOPRAMIDE
METOCLOPRAMIDE Metoclopramide is an upper gastrointestinal motility stimulant.
Since NVP is associated with gastric dysrhythmia, the use of metoclopramide is common in clinical practice in many countries. METOCLOPRAMIDE
There are limited studies of its potential to cause teratogenesis,but information to date is reassuring; two recently published studies have confirmed that there is no association between the drug exposure during the first trimester and congenital malformations. METOCLOPRAMIDE
No RCTs have been published to support the effectiveness of metoclopramide in the treatment of NVP. An observational study using home subcutaneous therapy for HG suggested that metoclopramide is effective, safe, and economical. RECOMMENDATION
Metoclopramide is safe to be used for management of NVP, although evidence for efficacy is more limited.
(II2D) SEROTONIN 5HT3 ANTAGONISTS
SEROTONIN 5HT3 ANTAGONISTS
Limited data are available on 5HT3 antagonist safety. No malformations were reported in three case reports of exposure in pregnancy.
One RCT of 15 first trimester exposures demonstrated no increased risk of malformation. ONDANSETRON
ONDANSETRON Limited evidence is available on the effectiveness of ondansetron for NVP. Intravenous ondansetron did not demonstrate a therapeutic benefit over promethazine in one trial for the treatment of HG. ONDANSETRON
Ondansetron is also significantly more expensive per dose than promethazine.
In general, 5HT3 antagonists may be safe to use during the first trimester, but the data are scant. Because of their limited effectiveness, they should not be advocated for firstline use until agents with established safety and effectiveness have been tried and have failed. CORTICOSTEROIDS
Recent casecontrol studies revealed a small but significantly increased risk of oral clefting associated with first trimester exposure to corticosteroids.
However, the data on effectiveness are weak. CORTICOSTEROIDS
Although a few controlled studies showed some effectiveness, pooled results of those studies comparing corticotropin to placebo and methylprednisolone to promethazine in HG women failed to show a reduction in the number of subsequent re
admissions to hospital compared with controls. CORTICOSTEROIDS In addition, corticotropin was not found to be superior to placebo based on “severity” or “relief ” scores.
Until more data are available, corticosteroids should be kept as the last line of therapy under ten weeks’ gestation, and only when maternal benefits outweigh fetal risk. RECOMMENDATION
Corticosteroids should be avoided during the first trimester because of possible increased risk of oral clefting and should be restricted to refractory cases. (IB) ADJUVANT THERAPIES
ADJUVANT THERAPIES ESOPHAGEAL REFLUX THERAPIES
ESOPHAGEAL REFLUX THERAPIES
The following adjuvant therapies are used primarily to reduce esophageal acid reflux associated with NVP. They have all been shown to bring symptomatic relief in the non
pregnant population and are presumed to be effective in pregnancy as well. ESOPHAGEAL REFLUX THERAPIES
Antacids usually contain salts of magnesium, calcium, or aluminum. A wide proportion of pregnant women already use this kind of medication. These are not considered human teratogens when used in recommended doses. ESOPHAGEAL REFLUX THERAPIES
H2 receptor antagonists include: cimetidine, ranitidine, and famotidine. Use of these medications has not been associated with an increased risk for major malformations following first trimester exposure. ESOPHAGEAL REFLUX THERAPIES
Proton pump inhibitors : such as omeprazole have been used in limited numbers during pregnancy. A recent study did not show an increased risk of congenital malformations. REHYDRATION
When dehydration is demonstrated at any time in the course of evaluation and treatment of NVP, intravenous rehydration may be warranted. Careful attention is paid to electrolyte imbalances present, and appropriate crystalloid therapy is instituted. REHYDRATION
Intravenous vitamin supplementation may be provided at the same time. In centres that have the ability to offer home parenteral therapy, NVP may be an appropriate condition to treat in this manner. OTHER CAUSES OF NVP
OTHER CAUSES OF NVP
When NVP is refractory to initial pharmacotherapy, it may be appropriate to investigate other potential causes or exacerbating factors associated with NVP. Electrolytes, TSH, renal function, liver function, drug levels, ultrasound, and Helicobacter pylori testing may be considered. RECOMMENDATION
RECOMMENDATION When NVP is refractory to initial pharmacotherapy, investigation of other potential causes should be undertaken.
(IIIA) MOOD DISORDERS
It is common for mood disorders to accompany NVP. Some of those disorders may require treatment with safe therapeutic agents, such as antidepressants. MOOD DISORDERS
Selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) are effective, not cardiotoxic, and are safe even if used in excess (with the exception of citalopram). They are not associated with an increased risk for major malformations when used in the first trimester. Tricyclic antidepressants
Tricyclic antidepressants Tricyclic antidepressants (TCAs) (amitriptyline, nortriptyline, and imipramine) have now been used for many years for several conditions. Although studies involving more than 1000 patients have shown TCAs are not teratogenic when used in the first trimester,their narrow therapeutic index, lifethreatening cardiotoxicity in overdose, and severe anticholinergic effects make them less appealing. HELICOBACTER PYLORI
An increased rate of seroposivity to Helicobacter pylori among patients with HG compared to asymptomatic, healthy pregnant controls has been recently reported. Several case reports have suggested a beneficial effect of Helicobacter pylori eradication. HELICOBACTER PYLORI
Gastric dysmotility has also been demonstrated among patients with HG. Several serendipitous cases have been reported in which erythromycin, administered for other indications, was effective in the resolution of otherwise intractable HG. HELICOBACTER PYLORI
It is possible that the benefit resulted from the motilin like action of erythromycin. This new field of evidence appears to be of significance in severe cases of NVP only and warrants further investigations before recommendations can be made. CONCLUSION
NVP can and should be managed safely and effectively. A doxylamine/ pyridoxine combination should be the standard of care since it has the greatest evidence to support its efficacy and safety (IA). CONCLUSION
Other drugs may also be used, primarily dimenhydrinate, in conjunction with the doxylamine/pyridoxine combination.
When these are not optimal in relieving NVP symptoms, consideration should be given to dopamine antagonists (phenothiazines and CONCLUSION
If possible, corticosteroid use should be avoided in the first 10 weeks of pregnancy, a critical period for oral cleft formation. Helicobacter pylori colonization diagnosis and treatment warrants further investigation. CONCLUSION
The choice of pharmacological treatment for NVP is as important as the choice of when to start using it. Because newer evidence suggests that the quality of life may be impaired before severe physical symptoms occur, even women with mild or moderate physical symptoms should be counselled early in their pregnancy on safe and effective treatments. ...
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- Fall '11
- 5-HT3 antagonist, NVP