Obstetrician's perspective—therapeutic trial and error?
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《英国医生杂志》
1 University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER I.A.Greer@clinmed.gla.ac.uk
About 70% of pregnant women experience nausea and vomiting. This troublesome condition has been recognised in medical literature since the days of Hippocrates, who noted that it began soon after conception and continued until the end of the fourth month. Despite the longevity of our knowledge of this association, our understanding of the mechanism of this condition and its possible physiological protective role has advanced little. Indeed, sickness in pregnancy, like pre-eclampsia, remains a "disease of theories." Many hypotheses have been advanced, ranging from psychological disturbance to nutritional deficiencies, disturbed thyroid function, and excessively high concentrations of chorionic gonadotropin.
Our ability to treat nausea and vomiting in pregnancy is hampered by our lack of knowledge, and treatment has been empirical, focusing on the symptoms rather than the cause and compounded by concerns for teratogenicity and a placebo effect. But perhaps there is no single cause. Could nausea and vomiting in pregnancy be a generic physical response to a variety of functional and physiological disturbances invoked by pregnancy? If so, it is not surprising that we have failed to identify reliably effective treatments. Perhaps this is the ideal condition for an n of 1 trial, as it is the individual's response to a range of possible treatments that is important.
Diet and lifestyle modifications are generally the first line treatments. Iron supplements should be avoided since they can cause nausea and vomiting. The woman will require reassurance and support from family, friends, and health professionals. Antihistamines and phenothiazines are safe to use and usually give some improvement in symptoms,1 2 but the size of improvement can be variable. Newer drugs such as ondansetron may be effective, but safety data are limited.1 Pyridoxine seems to be safe and is effective in reducing nausea, but there is no consistent effect on vomiting.3 There is also some evidence of benefit from alternative and natural remedies such as acupressure and ginger root extract.2 When sickness progresses to hyperemesis treatment focuses on rehydration, thiamine supplementation (to prevent Wernicke's encephalopathy), antiemetic therapy, thromboprophylaxis, and increasingly corticosteroids.4
What of Mrs Reynolds, the subject of the case report? Her case is not entirely typical since her sickness started later in pregnancy than is usual at 8 weeks and because she had not had this problem in previous pregnancies. Her history suggests that social or psychological factors were absent. She did not benefit from prochlorperazine, but it is important that antiemetics are taken regularly rather than on an as required basis and this should be clarified with her. It is also important to consider whether she was vomiting up the drugs. In this situation suppositories can be helpful.
Her condition seems to have progressed and was affecting her ability to function. However, she had no evidence of dehydration (absence of postural hypotension) and no ketonuria, features present when vomiting has progressed to hyperemesis. As sickness in pregnancy and hyperemesis are diagnoses of exclusion, it is essential to consider alternatives before embarking on further treatment. In particular, thyrotoxicosis (although transient gestational thyrotoxicosis, which is self limiting, often accompanies hyperemesis), urinary tract infection, and a twin or molar pregnancy (as there is an association with hyperplacentation) should be excluded. Thus, before proceeding, it would be useful to check thyroid function, urea and electrolytes, and liver function tests, pelvic ultrasound, and urine culture and sensitivity.
If other problems are excluded then an n of 1 trial of the conventional and alternative treatments is justified. In the context of nausea and vomiting in pregnancy, however, this trial and error approach will perhaps tell us more about what doesn't work than what does
Competing interests: None declared.
References
Magee LA, Mazzotta P, Koren G. Evidence based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol 2002;186: S256-61.
Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy: when should it be treated and with what? Drug Safety 1998;19(2): 155-64.
Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2003;(4): CD000145 .
Nelson-Piercy C, Fayers P, de Swiet M. Randomized, placebo-controlled trial of corticosteroids for hyperemesis gravidarum. BJOG 2001;108: 9-15.(Ian A Greer, regius profe)
About 70% of pregnant women experience nausea and vomiting. This troublesome condition has been recognised in medical literature since the days of Hippocrates, who noted that it began soon after conception and continued until the end of the fourth month. Despite the longevity of our knowledge of this association, our understanding of the mechanism of this condition and its possible physiological protective role has advanced little. Indeed, sickness in pregnancy, like pre-eclampsia, remains a "disease of theories." Many hypotheses have been advanced, ranging from psychological disturbance to nutritional deficiencies, disturbed thyroid function, and excessively high concentrations of chorionic gonadotropin.
Our ability to treat nausea and vomiting in pregnancy is hampered by our lack of knowledge, and treatment has been empirical, focusing on the symptoms rather than the cause and compounded by concerns for teratogenicity and a placebo effect. But perhaps there is no single cause. Could nausea and vomiting in pregnancy be a generic physical response to a variety of functional and physiological disturbances invoked by pregnancy? If so, it is not surprising that we have failed to identify reliably effective treatments. Perhaps this is the ideal condition for an n of 1 trial, as it is the individual's response to a range of possible treatments that is important.
Diet and lifestyle modifications are generally the first line treatments. Iron supplements should be avoided since they can cause nausea and vomiting. The woman will require reassurance and support from family, friends, and health professionals. Antihistamines and phenothiazines are safe to use and usually give some improvement in symptoms,1 2 but the size of improvement can be variable. Newer drugs such as ondansetron may be effective, but safety data are limited.1 Pyridoxine seems to be safe and is effective in reducing nausea, but there is no consistent effect on vomiting.3 There is also some evidence of benefit from alternative and natural remedies such as acupressure and ginger root extract.2 When sickness progresses to hyperemesis treatment focuses on rehydration, thiamine supplementation (to prevent Wernicke's encephalopathy), antiemetic therapy, thromboprophylaxis, and increasingly corticosteroids.4
What of Mrs Reynolds, the subject of the case report? Her case is not entirely typical since her sickness started later in pregnancy than is usual at 8 weeks and because she had not had this problem in previous pregnancies. Her history suggests that social or psychological factors were absent. She did not benefit from prochlorperazine, but it is important that antiemetics are taken regularly rather than on an as required basis and this should be clarified with her. It is also important to consider whether she was vomiting up the drugs. In this situation suppositories can be helpful.
Her condition seems to have progressed and was affecting her ability to function. However, she had no evidence of dehydration (absence of postural hypotension) and no ketonuria, features present when vomiting has progressed to hyperemesis. As sickness in pregnancy and hyperemesis are diagnoses of exclusion, it is essential to consider alternatives before embarking on further treatment. In particular, thyrotoxicosis (although transient gestational thyrotoxicosis, which is self limiting, often accompanies hyperemesis), urinary tract infection, and a twin or molar pregnancy (as there is an association with hyperplacentation) should be excluded. Thus, before proceeding, it would be useful to check thyroid function, urea and electrolytes, and liver function tests, pelvic ultrasound, and urine culture and sensitivity.
If other problems are excluded then an n of 1 trial of the conventional and alternative treatments is justified. In the context of nausea and vomiting in pregnancy, however, this trial and error approach will perhaps tell us more about what doesn't work than what does
Competing interests: None declared.
References
Magee LA, Mazzotta P, Koren G. Evidence based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol 2002;186: S256-61.
Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy: when should it be treated and with what? Drug Safety 1998;19(2): 155-64.
Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2003;(4): CD000145 .
Nelson-Piercy C, Fayers P, de Swiet M. Randomized, placebo-controlled trial of corticosteroids for hyperemesis gravidarum. BJOG 2001;108: 9-15.(Ian A Greer, regius profe)