Downloaded from dtb.bmj.com on August 15, 2014 - Published by group.bmj.com
DTB | Management of hyperemesis gravidarum
DTB CME/CPD* BNF 4.6
Management of hyperemesis gravidarum Nausea and vomiting in pregnancy are common complaints and vary considerably in duration and severity. Hyperemesis gravidarum represents the extreme end of the spectrum associated with dehydration and weight loss. As embryonic organogenesis occurs during the first trimester, pharmacological intervention for any condition during this period poses a significant clinical dilemma requiring careful assessment of risks and benefits. In the UK, there are no formal national guidelines for the management of hyperemesis gravidarum. In addition, no high-quality evidence exists for i.v. fluid and electrolyte replacement in hyperemesis gravidarum, and a Cochrane review on interventions for the treatment of nausea and vomiting in pregnancy specifically excluded studies on hyperemesis gravidarum.1 In this article, we review the evidence for the efficacy and safety of different management options for hyperemesis gravidarum.
About hyperemesis gravidarum Although nausea and vomiting in pregnancy (NVP) is common, affecting 50–75% of pregnant women, hyperemesis gravidarum affects less than 1%.2 The pathophysiology is likely to be multifactorial with hormonal, genetic, and gastrointestinal factors contributing. 3 Hyperemesis gravidarum is typically associated with higher levels of human chorionic gonadotrophin, and its onset and severity mirrors the peak levels of this hormone. Helicobacter pylori infection is also associated with an increased risk of hyperemesis gravidarum.4
Diagnosis Distinguishing hyperemesis gravidarum from NVP is not always easy. Most differentiating criteria relate to the severity and duration of symptoms. Hyperemesis gravidarum is characterised by persistent, intractable nausea and vomiting beginning in the first trimester and associated with a weight loss >5% of pre-pregnancy weight, dehydration, electrolyte imbalance and ketosis. 5,6 Diagnosis is by exclusion and other causes of severe nausea and vomiting such as gastrointestinal conditions (e.g. appendicitis, cholecystitis, small bowel obstruction, pancreatitis), neurological causes (e.g. migraine, pseudotumour cerebri, vestibular lesions, tumours of the central nervous system), metabolic and endocrine disorders (e.g. thyrotoxicosis, hyperparathyroidism, diabetic ketoacidosis, Addison’s disease), urinary tract infection, pyelonephritis, antibiotic use or iron supplements must be excluded. 5,6
Potential Complications Hyperemesis gravidarum, particularly if severe, has been associated with fetal growth restriction, pre-term delivery, Wernicke’s encephalopathy due to thiamine (vitamin B1) deficiency, central pontine myelinolysis due to hyponatraemia, increased risk of venous thromboembolism (VTE) and rarely maternal death.7–11 There is an increased risk of recurrence in subsequent pregnancies; 15% in a woman with a previous episode of hyperemesis gravidarum compared with 0.7% in a woman with no prior episode.12
Management principles There are no published studies comparing outcomes associated with inpatient or outpatient management of hyperemesis gravidarum. Outpatient management may have potential benefits in terms of healthcare costs and maintaining the woman within her family environment. Suggested criteria for referral to secondary care services include continued nausea and vomiting associated with an inability to keep down oral antiemetics, ketonuria or weight loss (>5% body weight) despite oral antiemetics, or comorbidity. 5
126
It should be noted that none of the drugs discussed in this article are licensed for the management of hyperemesis gravidarum. Detailed prescribing information is available in the British National Formulary (http://www.bnf.org) and in the summary of product characteristics for each drug (http://medicines.org.uk/emc).
Fluid and electrolyte replacement The most important intervention is fluid and electrolyte replacement. Current management is based on evidence from other conditions associated with dehydration and electrolyte imbalance. A randomised controlled trial comparing the use of 5% dextrose and 0.9% sodium chloride with 0.9% sodium chloride in women with hyperemesis gravidarum showed no difference after 24 hours in persistent ketonuria, wellbeing, nausea visual numerical rating scales, vomiting or resolution of electrolyte abnormalities.13 However, glucose containing solutions can precipitate Wernicke’s encephalopathy in thiamine deficient states,14 and 0.9% sodium chloride is therefore thought to be preferable. Potassium supplementation is often necessary and should be tailored to the serum potassium concentration. 3
Thiamine (vitamin B1) supplementation Thiamine requirements increase during pregnancy to 1.5mg/day.14 Thiamine supplementation should be given to all pregnant women who have been vomiting for more than 3 weeks.14 Oral thiamine can be prescribed at a dose of 100mg daily as thiamine hydrochloride.14 For those unable to tolerate oral tablets, thiamine can be administered intravenously.
Other considerations Women are typically advised to eat small frequent bland meals, although there is no evidence to support this recommendation. 3 Enteral or parenteral nutrition should only be considered if the woman cannot maintain her weight due to persistent vomiting and failure to respond to antiemetic therapy.15 Discontinuation of iron supplements may reduce symptoms of NVP.16 The Royal College of Obstetricians and Gynaecologists guideline on thromboprophylaxis in pregnancy suggests the use of low molecular weight heparin as the agent of choice for thromboprophylaxis in a pregnant woman * DTB CME/CPD A CME/CPD module based on this article is available for completion online via BMJ Learning (learning.bmj.com) by subscribers to the online version of DTB. If prompted, subscribers must sign into DTB with their username and password. All users must also complete a one-time registration on BMJ Learning and subsequently log in (with a BMJ Learning username and password) on every visit. The answers to the multiple choice questions will be freely available on dtb.bmj.com on publication of the next issue of DTB.
| DTB | Vol 51 | No 11 | November 2013dtb.bmj.com
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Downloaded from dtb.bmj.com on August 15, 2014 - Published by group.bmj.com
DTB | Management of hyperemesis gravidarum
with three or more current or persisting risk factors that include hyperemesis, immobility and dehydration.17 VTE prophylaxis should therefore be considered for women admitted with hyperemesis gravidarum. Women should be continually assessed for persistence of risk factors to determine the duration of VTE prophylaxis.
Treatment options Treatment options include antiemetics; herbal medications such as ginger; vitamins particularly pyridoxine (vitamin B6); alternative therapies such as acupressure, acupuncture, progressive muscle relaxation and hypnosis (trance induction); and corticosteroid therapy. However, for some options there is very limited published information available and many trials comparing such interventions are small and have methodological limitations.
Antiemetics Although antiemetics are the mainstay of therapy for NVP and hyperemesis gravidarum, there are few studies assessing their safety and efficacy in hyperemesis gravidarum. Antiemetics that have been used include antihistamines such as cyclizine, promethazine, doxylaminei and dimenhydrinatei; phenothiazines such as prochloperazine, chlorpromazine and pherphenazine; dopamine antagonists such as metoclopramide and domperidone; and more recently the 5HT3-receptor anatagonist ondansetron.18 A randomised controlled trial comparing i.v. metoclopramide (n=73) with i.v. promethazine (n=76) in women with hyperemesis gravidarum found similar reductions in nausea and vomiting, and improvements in wellbeing scores, but less drowsiness (59% vs. 84%, p=0.001), dizziness (34% vs. 71%, p
DTB | Management of hyperemesis gravidarum
DTB CME/CPD* BNF 4.6
Management of hyperemesis gravidarum Nausea and vomiting in pregnancy are common complaints and vary considerably in duration and severity. Hyperemesis gravidarum represents the extreme end of the spectrum associated with dehydration and weight loss. As embryonic organogenesis occurs during the first trimester, pharmacological intervention for any condition during this period poses a significant clinical dilemma requiring careful assessment of risks and benefits. In the UK, there are no formal national guidelines for the management of hyperemesis gravidarum. In addition, no high-quality evidence exists for i.v. fluid and electrolyte replacement in hyperemesis gravidarum, and a Cochrane review on interventions for the treatment of nausea and vomiting in pregnancy specifically excluded studies on hyperemesis gravidarum.1 In this article, we review the evidence for the efficacy and safety of different management options for hyperemesis gravidarum.
About hyperemesis gravidarum Although nausea and vomiting in pregnancy (NVP) is common, affecting 50–75% of pregnant women, hyperemesis gravidarum affects less than 1%.2 The pathophysiology is likely to be multifactorial with hormonal, genetic, and gastrointestinal factors contributing. 3 Hyperemesis gravidarum is typically associated with higher levels of human chorionic gonadotrophin, and its onset and severity mirrors the peak levels of this hormone. Helicobacter pylori infection is also associated with an increased risk of hyperemesis gravidarum.4
Diagnosis Distinguishing hyperemesis gravidarum from NVP is not always easy. Most differentiating criteria relate to the severity and duration of symptoms. Hyperemesis gravidarum is characterised by persistent, intractable nausea and vomiting beginning in the first trimester and associated with a weight loss >5% of pre-pregnancy weight, dehydration, electrolyte imbalance and ketosis. 5,6 Diagnosis is by exclusion and other causes of severe nausea and vomiting such as gastrointestinal conditions (e.g. appendicitis, cholecystitis, small bowel obstruction, pancreatitis), neurological causes (e.g. migraine, pseudotumour cerebri, vestibular lesions, tumours of the central nervous system), metabolic and endocrine disorders (e.g. thyrotoxicosis, hyperparathyroidism, diabetic ketoacidosis, Addison’s disease), urinary tract infection, pyelonephritis, antibiotic use or iron supplements must be excluded. 5,6
Potential Complications Hyperemesis gravidarum, particularly if severe, has been associated with fetal growth restriction, pre-term delivery, Wernicke’s encephalopathy due to thiamine (vitamin B1) deficiency, central pontine myelinolysis due to hyponatraemia, increased risk of venous thromboembolism (VTE) and rarely maternal death.7–11 There is an increased risk of recurrence in subsequent pregnancies; 15% in a woman with a previous episode of hyperemesis gravidarum compared with 0.7% in a woman with no prior episode.12
Management principles There are no published studies comparing outcomes associated with inpatient or outpatient management of hyperemesis gravidarum. Outpatient management may have potential benefits in terms of healthcare costs and maintaining the woman within her family environment. Suggested criteria for referral to secondary care services include continued nausea and vomiting associated with an inability to keep down oral antiemetics, ketonuria or weight loss (>5% body weight) despite oral antiemetics, or comorbidity. 5
126
It should be noted that none of the drugs discussed in this article are licensed for the management of hyperemesis gravidarum. Detailed prescribing information is available in the British National Formulary (http://www.bnf.org) and in the summary of product characteristics for each drug (http://medicines.org.uk/emc).
Fluid and electrolyte replacement The most important intervention is fluid and electrolyte replacement. Current management is based on evidence from other conditions associated with dehydration and electrolyte imbalance. A randomised controlled trial comparing the use of 5% dextrose and 0.9% sodium chloride with 0.9% sodium chloride in women with hyperemesis gravidarum showed no difference after 24 hours in persistent ketonuria, wellbeing, nausea visual numerical rating scales, vomiting or resolution of electrolyte abnormalities.13 However, glucose containing solutions can precipitate Wernicke’s encephalopathy in thiamine deficient states,14 and 0.9% sodium chloride is therefore thought to be preferable. Potassium supplementation is often necessary and should be tailored to the serum potassium concentration. 3
Thiamine (vitamin B1) supplementation Thiamine requirements increase during pregnancy to 1.5mg/day.14 Thiamine supplementation should be given to all pregnant women who have been vomiting for more than 3 weeks.14 Oral thiamine can be prescribed at a dose of 100mg daily as thiamine hydrochloride.14 For those unable to tolerate oral tablets, thiamine can be administered intravenously.
Other considerations Women are typically advised to eat small frequent bland meals, although there is no evidence to support this recommendation. 3 Enteral or parenteral nutrition should only be considered if the woman cannot maintain her weight due to persistent vomiting and failure to respond to antiemetic therapy.15 Discontinuation of iron supplements may reduce symptoms of NVP.16 The Royal College of Obstetricians and Gynaecologists guideline on thromboprophylaxis in pregnancy suggests the use of low molecular weight heparin as the agent of choice for thromboprophylaxis in a pregnant woman * DTB CME/CPD A CME/CPD module based on this article is available for completion online via BMJ Learning (learning.bmj.com) by subscribers to the online version of DTB. If prompted, subscribers must sign into DTB with their username and password. All users must also complete a one-time registration on BMJ Learning and subsequently log in (with a BMJ Learning username and password) on every visit. The answers to the multiple choice questions will be freely available on dtb.bmj.com on publication of the next issue of DTB.
| DTB | Vol 51 | No 11 | November 2013dtb.bmj.com
▶
Downloaded from dtb.bmj.com on August 15, 2014 - Published by group.bmj.com
DTB | Management of hyperemesis gravidarum
with three or more current or persisting risk factors that include hyperemesis, immobility and dehydration.17 VTE prophylaxis should therefore be considered for women admitted with hyperemesis gravidarum. Women should be continually assessed for persistence of risk factors to determine the duration of VTE prophylaxis.
Treatment options Treatment options include antiemetics; herbal medications such as ginger; vitamins particularly pyridoxine (vitamin B6); alternative therapies such as acupressure, acupuncture, progressive muscle relaxation and hypnosis (trance induction); and corticosteroid therapy. However, for some options there is very limited published information available and many trials comparing such interventions are small and have methodological limitations.
Antiemetics Although antiemetics are the mainstay of therapy for NVP and hyperemesis gravidarum, there are few studies assessing their safety and efficacy in hyperemesis gravidarum. Antiemetics that have been used include antihistamines such as cyclizine, promethazine, doxylaminei and dimenhydrinatei; phenothiazines such as prochloperazine, chlorpromazine and pherphenazine; dopamine antagonists such as metoclopramide and domperidone; and more recently the 5HT3-receptor anatagonist ondansetron.18 A randomised controlled trial comparing i.v. metoclopramide (n=73) with i.v. promethazine (n=76) in women with hyperemesis gravidarum found similar reductions in nausea and vomiting, and improvements in wellbeing scores, but less drowsiness (59% vs. 84%, p=0.001), dizziness (34% vs. 71%, p
