Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BACKGROUND: Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. OBJECTIVES: To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. DATA COLLECTION AND ANALYSIS: Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. MAIN RESULTS: We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33). CONCLUSIONS: Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.

OS032. Pharmacotherapy for pre-eclampsia in low and middle income countries: An analysis of essential medicines lists (EMLS).

INTRODUCTION: Pre-eclampsia is the second leading cause of maternal mortality in low and middle income countries (LMIC). Pharmacological management of pre-eclampsia has five major components including antihypertensive therapy for severe and non-severe hypertension, magnesium sulphate for prevention or treatment of eclampsia, treatment of pre-eclampsia-related end-organ complications, antenatal corticosteroids for acceleration of fetal pulmonary maturity given iatrogenic preterm delivery for maternal and/or fetal indications, and labour induction for such indicated deliveries. Essential medicines are defined by the World Health Organization (WHO) as "drugs that satisfy the health care needs of the majority of the population". Essential Medicines Lists (EMLs) detail these essential medicines within an individual country and support the argument that the medication should be routinely available. OBJECTIVES: To determine how many drugs required for comprehensive pre-eclampsia management are listed in national EMLs of LMIC. METHODS: We conducted a descriptive analysis of relevant drug prevalence on identified EMLs. We searched for the national EMLs of the 144 LMIC identified by the World Bank. EMLs were collected by broad based internet searches and in collaboration with the WHO. The EMLs were surveyed for therapies for the different aspects of pre-eclampsia management: hypertension (non-severe and severe with oral or parenteral agents), eclampsia, pre-eclampsia complications (e.g., pulmonary oedema, thrombosis), preterm birth, and labour induction. RESULTS: EMLs were located and reviewed for 58(40.3%) of LMIC. One or more parenteral antihypertensive agents were listed in 51(87.9%) EMLs. The most common agents were: hydralazine (67.2%), verapamil (58.6%), propranolol (39.7%) and sodium nitroprusside (37.9%); parenteral labetalol was listed by only 19.0% of EMLs. The most prevalent oral antihypertensive therapies listed were: nifedipine (96.6%, usually 10 or 20mg intermediate-acting tablets), methyldopa (94.8%), propranolol (89.7%), and atenolol (87.9%). Captopril, enalapril, hydrochlorothiazide and spironolactone were commonly listed. Magnesium sulphate for prevention and management of eclampsia was present in 86.2% of EMLs (and its antidote, calcium gluconate in 82.8%). To manage complications of pre-eclampsia, oral frusemide was listed in 94.8% of EMLs and parenteral heparin in 91.4%. Most EMLs listed parenteral dexamethasone (91.4%) for acceleration of fetal pulmonary maturity and oxytocin (98.3%) or a prostanoid (usually misoprostol, 39.7%) for labour induction. CONCLUSION: EMLs of LMIC provide comprehensive coverage of all aspects of recommended pre-eclampsia pharmacotherapy. These EMLs may be used as advocacy tools to ensure the availability of these therapies within each country.

PP088. Oral antihypertensive therapy for severe hypertension in pregnancy.

INTRODUCTION: The hypertensive disorders of pregnancy are among the leading causes of maternal mortality and morbidity. The vast majority occurs in low and middle income countries. It is widely accepted that women with severe hypertension are at increased risk of stroke and benefit from blood pressure (BP) reduction. Although traditionally, parenteral antihypertensive agents have been studied for treatment of severe hypertension in pregnancy, oral agents would be ideal for use in the community and in under-resourced settings. OBJECTIVES: To review the published evidence for the effectiveness of oral antihypertensive therapy for severe hypertension in pregnancy. METHODS: The following databases were searched (to May/11) for randomised controlled trials (RCT) of oral antihypertensive therapy for severe hypertension in pregnancy: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews. Inclusion criteria were: severe hypertension [an inclusion criterion or average enrollment BP of: systolic BP ⩾160mmHg and/or diastolic BP ⩾110mmHg), use of oral or sublingual antihypertensive therapy in at least one of the treatment arms, and at least one relevant measure of maternal or perinatal outcome within a week of administration. Data were abstracted independently by two reviewers and discrepancies resolved by consensus. The Cochrane Revman 5.1 software was used for statistical analysis according to standardised methodology. RESULTS: We identified 14 eligible trials (796 women). Most compared oral/sublingual (SL) nifedipine 5-10mg (10 trials, 606 women, 8/10 trials specified capsule preparation), with either: intravenous (iv) hydralazine 5-20mg (6 trials, 282 women), oral nifedipine 10mg PA tablets (1 trial), oral prazosin 1mg (1 trial), iv labetalol (1 trial), or iv/intramuscular (im) chlorpromazine 12.5 (1 trial). Three trials (154 women) compared oral methyldopa (250-500mg initially) with either oral labetalol (100mg), atenolol (50-200mg) or kentanserin (80-120mg) (1 trial each). One trial (36 women) compared SL isosorbide 1.25mg with iv magnesium sulphate (4g iv then 1g/hr). No trials were identified that compared oral labetalol with either parenteral hydralazine or oral nifedipine. Nifedipine compared favourably with parenteral hydralazine with no differences seen in BP control or maternal or perinatal outcomes. Heterogeneity between trial results was seen within the oral/SL nifedipine vs. iv hydralazine subgroup in which one trial evaluated treatment success and side effects over 20min, and found that nifedipine was associated with relatively lower success and fewer side effects. The incidence of maternal hypotension in the nifedipine capsule arms of these trials was low (1/102, 3 trials), but hypotension was common in both arms of a trial of nifedipine 10mg capsule vs. 10mg PA tablet trial (i.e., 11/31 vs. 3/33, risk difference 26%, 95% CI7% to 46%). CONCLUSION: Given the available RCT data on which to base oral antihypertensive treatment of severe hypertension in pregnancy, the choice of antihypertensive agent may need to be driven by the availability of the drug, setting in which it is to be administered, and by whom. For facility use, the evidence supports oral nifedipine capsules.

PP164. Magnesium sulphate for prevention and treatment of eclampsia in low and middle income countries: Systematic review of tested regimens.

INTRODUCTION: Magnesium sulphate (MgSO4) is regarded as the most effective prophylactic and therapeutic agent for eclampsia. Although well studied and widely used in high income countries (HICs), MgSO4 is under utilized in low and middle income countries (LMICs) due to many factors including lack of adequately trained health care providers, supplies for administration, or the MgSO4 itself, in addition to fear of potential adverse effects. OBJECTIVES: To systematically review the dosing and effectiveness of MgSO4 regimens administered in LMICs to women with pre-eclampsia or eclampsia. METHODS: We searched Medline, EMBASE, IPA, CINAHL, CDSR and CENTRAL databases for English language randomized controlled trials (RCT) and observational studies of MgSO4 regimens administered in LMICs to women with pre-eclampsia or eclampsia. Two authors independently reviewed search results and extracted relevant data from eligible studies. No quality assessment was performed. RESULTS: Twenty two papers (7 RCT and 15 observational studies) from 12 LMIC met our inclusion criteria, of which 21 were conducted in hospital settings. Two studied MgSO4 for eclampsia prevention ,14 for eclampsia treatment and 6 studied MgSO4 for both. In 20 studies, both loading and maintenance MgSO4 dosing was administered, with intravenous (IV) or combined IV and intramuscular (IM) loading doses of 4-15g and IV or IM maintenance doses up to 2g/h. Five studies used only the IV route of administration, while the remainder coupled IV with IM administration. All studies were effective at preventing the initiation and/or recurrence of eclamptic seizures. One study of 265 women with eclampsia found that MgSO4 loading dose administration in the community (4g IV over 20min plus 3g IM in each buttock) before referral and administration of maintenance therapy in hospital was more effective in decreasing recurrent eclampsia compared with the standard practice of referral to hospital where the initial dose of MgSO4 was administered [RR of 0.23, 95% CI 0.11, 0.49]. The two studies of 4g IV plus 10g IM loading dose-only regimens did not show a significant reduction in eclamptic seizures compared with identical loading dose plus 5g/4h IM maintenance dose regimens [RR of 1.38, 95% CI of 0.23, 8.45]. However the combined sample size was small (N=180 women). CONCLUSION: In LMICs, most studies of MgSO4 for pre-eclampsia or eclampsia were conducted in high level health care facilities and administered MgSO4 by the IV route, at least in part. The one study of community administration of a MgSO4 loading dose showed this approach to be effective. There are limited data to support loading dose-only regimens.

Rumination in eating disorders: literature review.

Rumination is defined as regurgitation of partially digested food that is subsequently re-chewed and then swallowed or ejected by mouth. We report a case of rumination and a review of selected literature to emphasize: 1. Risk factors for rumination in eating disorders are unknown, 2. A history of rumination must be taken routinely because shame prevents patients from volunteering this history, 3. Rumination usually lessens with improvement of the eating disorder, but other methods including behavior modification, breathing techniques, and gum chewing have shown success in individual cases or small case series. There have been no controlled trials published of any treatment for rumination in eating disorders.