Volume 166 Issue 12

Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia". Abstract - Introduction - Methods - Data source - Study design - Analysis by demographic characteristics - Results - Discussion - Acknowledgements - References - Authors' details Abstract Objective: To examine patterns of surgical management of breast cancer among Australian women. Design: Retrospective survey of Medicare records (a national dataset of all services rendered on a "fee-for-service" basis for which a Medicare benefit has been paid). Patients: All Australian women (4683) who underwent surgery consistent with being for breast cancer in 1993 and for which Medicare benefits were paid. Main outcome measures: Proportions of women undergoing different forms of mastectomy, breast-conserving surgery and axillary surgery by patient age and State and region (urban or rural) of residence. Results: Modified radical mastectomy was the most common surgery, performed in 2097 of the 4683 women (44.8%), while 1868 (39.9%) had breast-conserving surgery. Frequency of breast conservation decreased significantly with age and varied significantly between States and region of residence. It ranged from 34% in Western Australia to 49% in South Australia and the Northern Territory, and from 34% among rural women to 42% among urban women. Axillary surgery was recorded for 83% of all women studied. Conclusions: There was substantial geographical variation in patterns of surgical management for breast cancer. The tendency for rural women to undergo mastectomy rather than breast-conserving surgery may reflect the relative lack of access to postoperative radiotherapy. We are unable to explain the variation between States. MJA 1997; 166: 626-629 Introduction Breast cancer is the commonest malignancy among Australian women after non-melanocytic skin cancer and is the commonest cause of cancer deaths in women.1 Until recently, the optimal management of breast cancer that is limited to the primary site (with or without axillary nodal involvement) was unclear, with some advocating routine mastectomy and others advocating a breast-conserving approach for selected patients. After randomised controlled clinical trials, a consensus has emerged that most patients with Stage I and II carcinoma of the breast (comprising about 80% of patients presenting with breast cancer) can be managed with a breast-conserving approach, with rates of local and regional control and survival equivalent to those obtained with mastectomy.2-6 Breast-conserving treatment also seems less disturbing to perceived body image and sexuality than mastectomy.7 Surgical management of breast cancer has been found to vary significantly between different population groups in the United States.8,9 We investigated surgical management of Australian women treated for breast cancer by analysing Medicare records, and assessing variations in management by patient age and State and region (urban or rural) of residence. Methods Data source Medicare statistics were obtained from the Commonwealth Department of Health and Family Services. They contain details of services rendered on a "fee-for-service" basis for which Medicare benefits were paid. They exclude services to public patients in hospitals and to Veterans' Affairs patients, and services for injuries that are eligible for compensation, unless an interim Medicare benefit is paid. Study design All women who received at least one Medicare benefit for surgical items on the Medicare Benefits Schedule (MBS) consistent with breast cancer surgery during the 1993 calendar year were included. These items comprised mastectomy -- simple, partial, extended simple, subcutaneous, modified radical an d radical -- and excision of a breast lump if followed by axillary dissection and/or radiotherapy. Medicare records for the first two quarters of 1994 were also examined to ensure that all subsequent episodes of breast surgery or radiotherapy were captured. It was assumed that very few patients would receive these treatments for non-malignant breast disease. Women who had had only excision of a breast lump but no radiotherapy or axillary dissection were excluded. Data recorded in addition to surgical procedure(s) were the date of service, and patient's personal identification number (PIN), date of birth, sex and postcode of residence. The identity of each person in the study was protected by a PIN which could not be decoded by the investigators. Analysis by demographic characteristics Patient age in 1993 was determined from year of birth, and State and region of residence from postcode. Postcodes were classified into regional zones according to the Rural, remote and metropolitan areas classification 1991 census edition.10 When a postcode extended into two regions, a factor based on population density was used to determine in which region it would be placed. To provide sufficient numbers for analysis in each State group, data were combined for the Australian Capital Territory (ACT) and New South Wales (NSW) and for the Northern Territory (NT) and South Australia (SA). Proportions were compared with the chi-squared test. Logistic regression analysis was performed with SPSS version 6.1.11 Results We identified 4683 women who received at least one Medicare benefit for surgical items consistent with breast cancer surgery in 1993. These represented 58% of the 8100 expected incident cases of female breast cancer in Australia in this year.1 Surgical procedures performed are summarised in Box 1 (below). Some form of total mastectomy was performed in 2815 women (60.1%), while surgery consistent with breast conservation was performed in 1868 (39.9%). The most frequently identified definitive surgical procedure was radical or modified radical mastectomy, with 2097 services recorded. It was the only surgical therapy in 1265 women, but was accompanied by other surgical items in 832. Patterns of surgery in different patient age groups are summarised in Box 2 (below). Breast-conserving surgery was most frequent in women aged less than 60 years, with the frequency falling to 32% in women aged 70 to 79 years. Variation in type of surgery by age was highly significant (chi-squared for trend = 16.3; P < 0.001). Frequency of breast-conserving surgery was significantly higher among women resident in urban regions than among those resident in rural regions (comprising large rural towns, rural areas and remote areas). Breast conservation was undertaken in 1462 of 3483 urban women (41.9%), but in only 397 of 1170 rural women (33.9%) (chi-squared = 23.3; P < 0.001). The frequency did not differ between women resident in large rural towns, in rural areas and in remote areas. The residential area of 30 women could not be classified. Patterns of surgery also varied significantly between States (Box 3), with breast-conserving surgery performed in 49.2% of those resident in SA and the NT, but in only 33.8% of those resident in Western Australia (WA). Multivariate analysis showed that this variation was not caused by State differences in population distribution between urban and rural areas. The axilla was treated surgically, either as part of a mastectomy or under specific axillary dissection MBS items, in 3889 women (83.0%). Frequency of axillary surgery was similar in most age groups, except those aged 80 years or older (Box 2). In this group, only 62.8% of women underwent axillary dissection versus 84.1% of women aged less than 80 years (chi-squared = 70.0; P < 0.001). Frequency of axillary surgery varied slightly between States, with WA having the highest rate and Tasmania the lowest (Box 2), but did not differ between urban and rural residents (2892 of 3483 [83.0%] urban residents and 970 of 1170 [82.9%] rural residents). Discussion We found that breast-conserving surgery was performed in almost 40% of Australian women undergoing breast cancer surgery reimbursed by Medicare in 1993. However, the proportion who underwent breast-conserving surgery tended to decrease with patient age and varied significantly beween States and between rural and urban women. Our results are similar to those of other studies of surgical care for breast cancer in Australia. In WA, Byrne et al. found that breast-conserving surgery was used in 29.4% of all women treated for breast cancer in 1989, and in 31.3% of those with "potentially eligible" tumours,12 compared with a figure of 33.7% for WA in our study. In NSW in 1988-1991, breast-conserving surgery was used to treat 40% of a series of 105 mammographically detected tumours,13 while a six-month survey of Victorian surgeons in 1990 found that breast conserving surgery was performed in 42% of cases of operable breast cancer.14 We found significant geographical variation in the proportion of women receiving breast-conserving surgery reimbursed by Medicare. Women living in rural or remote locations were more likely to undergo mastectomy. Breast conservation usually necessitates postoperative radiotherapy, and, as radiotherapy services are often not conveniently located for rural populations, this treatment can involve considerable social and financial costs to patients, which may influence the decision to undergo mastectomy. The proportion of women undergoing breast-conserving surgery also varied between States. This variation was not explained by differences between populations, such as proportions of women living in rural and urban regions. The reasons for this are unclear, but preference for mastectomy versus breast-conserving surgery among surgeons and women may vary between States, explaining the observed differences. Older women were less likely to have breast-conserving treatment. Similar patterns have been observed in surveys of breast cancer management.7 Some older women might reasonably prefer to avoid radiotherapy and be relatively less concerned about mastectomy. Alternatively, as the study could not detect women with breast cancer who had had only excision of the primary tumour but neither axillary dissection nor radiotherapy, if this treatment was more common in older patients, then the frequency of breast conservation may have been underestimated. The rates of axillary surgery were generally high and relatively uniform across age groups and between States and regions. Treatment of the axilla is not recommended for in-situ disease15 and may reasonably be withheld for a small invasive cancer, particularly in older women, possibly explaining the omission of axillary dissection for a proportion of study patients.16 Our study, using data collected routinely for administrative purposes, has several advantages over special purpose surveys. These include timeliness, economy, objectivity and standardisation of data recording. In addition, such a study offers the possibility of examining trends in service delivery over time by means of repeated reviews. Special purpose surveys usually rely on healthcare providers to donate their own, or staff, time to complete the survey instrument, which can be a problem for both researchers and healthcare providers. However, a review based on administrative datasets has some limitations. It can provide only descriptive information and does not give insight into the reasons for disease management decisions. As subjects were identified by interpreting MBS items from Medicare records, the presence of an underlying diagnosis of breast cancer was inferred and not independently verified -- for example, by data matching. Therefore, no information was available about clinical or pathological features of the tumours (e.g., stage and size of primary tumour), which would have influenced the choice of surgical management. In addition, some women who underwent surgery for a breast neoplasm other than carcinoma, or for benign disease, may have been included as subjects. We believe that these instances would be rare, and that the vast majority of cases represented women with primary carcinoma of the breast or carcinoma-in-situ. It was also assumed that patients who had one procedure performed on a private "fee-for-service" basis would have subsequent related services provided on the same basis. However, if substantial numbers of women with breast cancer moved to the public hospital system for part of their surgical management, then this study would have underestimated the frequency of subsequent, more extensive, surgery. This might have led to underestimation of the frequency of mastectomy and axillary dissection, and could have had a variable effect between regions because of differences in private health insurance rates. Guidelines for the treatment of early breast cancer have been published recently and are expected to improve standards of care and treatment,6 and to reduce variability in clinical practice. However, the optimal ratio of mastectomies to breast conserving-surgery in Australia remains unknown. Ultimately, the choice of treatment is a decision taken by each individual, informed by advice from her surgeon and information from other sources. Secondary analyses of data collected for reimbursement purposes, such as in our study, can shed no light on such decisions. Detailed surveys of patterns of care should be undertaken and deserve the support of the medical community. Acknowledgements We wish to thank the Medicare Statistics Section of the Department of Health and Family Services for the data supplied within this report. Special thanks to David Wong for his assistance in supplying data. References Jelfs P, Coates M, Giles G, et al. Cancer in Australia 1989-1990 (with projections to 1995). Canberra: Australian Institute of Health and Welfare, 1996: 7-16. Cancer Series No. 5. Jamrozik K, Byrne MJ, Fitzgerald CJ, et al. Breast cancer in Western Australia in 1989. I. Presentation. Aust N Z J Surg 1993; 63: 617-623. Fisher B, Bauer M, Margolese R, et al. Five year results of a randomised clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985, 312: 665-673. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 1993; 328: 1587-1591. Blichert-Toft M. A Danish randomised trial comparing breast conservation with mastectomy in mammary carcinoma. Br J Cancer 1990; 62 Suppl 12: S15. National Health and Medical Research Council. Clinical practice guidelines. The management of early breast cancer. Canberra: AGPS, 1995: 46-50; 133-162. Kiebert GM, de Haes JCJM, van de Velde CJH. The impact of breast-conserving treatment and mastectomy on the quality of life of early-stage breast cancer patients: a review. J Clin Oncol 1991; 9: 1059-1070. Samet JM, Hunt WC, Farrow DC. Determinants of receiving breast-conserving surgery. The surveillance, epidemiology and end results program 1983-1986. Cancer 1994; 73: 2344-2351. Nattinger AB, Goottlieb MS, Veum J, et al. Geographic variation in the use of breast-conserving treatment for breast cancer. N Engl J Med 1992; 326: 1102-1107. Department of Primary Industries and Energy and Department of Human Services and Health Rural, remote and metropolitan areas classification 1991 census edition. Canberra: the Departments, 1994. SPSS Inc. Statistical package for the social sciences [computer program]. Version 6.1. Chicago, III: SPSS Inc, 1994. Byrne MJ, Jamrozik K, Parsons RW, et al. Breast cancer in Western Australia in 1989. II. Diagnosis and primary management. Aust N Z J Surg 1993; 63: 624-629. Harrison RI, Glenn DC, Niesche FW, et al. Surgical management of breast cancer. Experience of the Central Sydney Health Service Breast X-ray Programme, 1988-1991. Med J Aust 1994; 160: 617-620. Hill DJ, White VM, Giles GG, et al. Changes in the investigation and management of primary operable breast cancer in Victoria. Med J Aust 1994; 161: 110-122. Balch CM, Singletary E, Bland KI. Clinical decision-making in early breast cancer. Ann Surg 1993; 217: 207-255. Silverstein MJ, Gierson ED, Waisman JR, et al. Axillary lymph node dissection for T1a breast c arcinoma. Cancer 1994; 73: 664-669.(Received 6 Sep 1996, accepted 3 Mar 1997) Authors' details Medical Oncology Unit, Canberra Hospital, Canberra, ACT. Paul S Craft, MPH, FRACP, Director. Commonwealth Department of Health and Family Services, Woden, ACT. John G Primrose, FRACR, Senior Medical Advisor; Julie A Lindner, Computer Analyst, Drug Utilization Sub-Committee Secretariat; Peter R McManus, BPharm, MMedSc, Secretary, Drug Utilization Sub-Committee of the Pharmaceutical Benefits Advisory Committee. No reprints will be available. Correspondence: Dr P S Craft, Medical Oncology Unit, Canberra Hospital, Canberra, ACT 2607. E-mail: PAUL_CRAFT@dpa.act.gov.au

Paul S Craft · John G Primrose · Julie A Lindner · Peter R McManus

Withdrawal of nifedipine capsules: jeopardising the treatment of acute severe hypertension in pregnancy? Mark A Brown, Lesley M E McCowan, Robyn A North, Barry N Walters (for the Council of the Australasian Society for the Study of Hypertension in Pregnancy) Short-acting oral nifedipine has been withdrawn from the Australian market because of reports of its adverse effects after long-term treatment in non-pregnant patients with heart disease. This will have a major impact on the treatment of acutely hypertensive pregnant women, in whom the drug has proven to be safe, effective and easy to administer. Should pregnant women be forced to use less suitable agents, thus threatening their own and their babies' health? (MJA 1997; 166: 640-643) Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Introduction - Antihypertensive medications in pregnancy - Adverse effects of nifedipine - Risk-benefit analysis of nifedipine in pregnancy - Withdrawal of nifedipine from the Australian market - Conclusions - Acknowledgement - References - Authors' details Make a comment - - ©MJA1997 Introduction Pre-eclampsia is the development of hypertension after 20 weeks' gestation in a woman with no known history of hypertension or renal disease, whose blood pressure was normal in the first half of the pregnancy and returns to normal after delivery.1 Despite advances in maternal and neonatal care, it remains an important cause of maternal morbidity (and sometimes mortality) and of fetal prematurity, growth retardation and perinatal death. The dangers of cerebral haemorrhage in pre-eclampsia and of convulsions (eclampsia) have led to the belief that severe hypertension (systolic blood pressure 170 mmHg and/or diastolic blood pressure 110 mmHg) should be treated promptly in pre-eclamptic women. However, the ability to treat acute hypertensive crises in pregnancy is about to be retarded considerably because of recommendations by the Australian Drug Evaluation Committee (ADEC) to withdraw short-acting nifedipine capsules,2 one of the most common drugs for treating acute severe hypertension in pregnancy, effective from 1 May 1997. Antihypertensive medications in pregnancy There are only a few options for the treatment of acute severe hypertension in pregnancy. Nifedipine (given orally or sublingually) and hydralazine (given intravenously or, sometimes, intramuscularly) are the most commonly used agents. They have both been endorsed for use for severe hypertension in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) on the basis of clinical studies and extensive clinical experience by members of the ASSHP and other societies.1 Intravenous diazoxide was one of the earliest drugs to be used.3 It is effective but can cause sudden maternal hypotension, maternal hyperglycaemia and fetal hypoglycaemia, uterine atony and fetal distress. It is best given as incremental small-dose boluses to avoid a sudden drop in blood pressure. Intravenous labetalol has been used less widely but is at least as effective as intravenous diazoxide.3 Its safety in preterm infants has been questioned,4 with higher perinatal mortality than in subjects given hydralazine in one study. Intravenous glyceryl trinitrate is a potential candidate for treating severe hypertension in pregnancy.5 It has not yet been used widely and there is a risk that its predominant venodilator effect could reduce preload and compromise an already threatened cardiac output.6 Intravenous sodium nitroprusside is an excellent drug for acute severe hypertension, but its use in pregnancy is precluded by the risk of fetal cyanide toxicity.7 Adverse effects of nifedipine Unfortunately, some authors fail to discriminate between pregnant and non-pregnant subjects when providing recommendations about the continued use of nifedipine capsules. For example, Grossman et al. did a MEDLINE search of articles from 1966 to 1994 using the terms "side-effects" and "nifedipine" to document serious adverse effects with oral or sublingual nifedipine.8 They recommended that, given the seriousness of the reported adverse cardiac events and the lack of any clinical documentation attesting to a benefit, the use of nifedipine capsules for hypertensive emergencies and pseudoemergencies should be abandoned. Only one case of fetal distress was reported in this review9 (although we have noted three other cases), in a pregnant woman whose blood pressure fell from 150/115 mmHg to 90/55 mmHg, hardly a surprising event and one which could have occurred with any drug which lowered the blood pressure to this extent. A more disturbing report by Rehman et al. noted that 98% of hospitalised patients receiving nifedipine capsules failed to have a bedside evaluation and only half had had their blood pressure followed up within an hour of treatment.10 This is poor medical practice and a good reason to improve medical education, but not a reason to withdraw a drug from the market. Risk-benefit analysis of nifedipine in pregnancy Many small studies, comprising a total of about 150 pregnant women, have shown that nifedipine will acutely lower maternal blood pressure within 30 minutes of administration, without compromising the fetus.11-22 In studies involving approximately 200 pregnant women treated with nifedipine over a longer period, no adverse fetal effects were recorded.12,23-27 Three case reports (of four patients) have, at the same time, reported the potential risk of sudden hypotension following the use of nifedipine in severe pre-eclampsia, particularly when combined with magnesium sulfate (used parenterally as convulsion prophylaxis in pre-eclampsia).9,28,29 However, in a more recent prospective study, 10 women with severe pre-eclampsia already receiving intravenous magnesium sulfate were given between 10 mg and 40 mg nifedipine orally. Blood pressure was well controlled in each woman, none had significant hypotension and there was no fetal distress.30 Sudden hypotension has been reported with other antihypertensive drugs used to acutely lower blood pressure in pregnancy, including hydralazine.3,31 The risk of sudden hypotension with any form of acute antihypertensive therapy can be minimised by concomitant plasma volume expansion1,20,32 and avoidance of diuretics, as pre-eclampsia is a volume-contracted state compared with normal pregnancy.33 Several studies have found that nifedipine lowers maternal blood pressure without adversely affecting uteroplacental blood flow.13,14,17,23,34 Several studies have compared intravenous hydralazine with nifedipine in pre-eclampsia;12,19,20,35 all showed nifedipine to be of equal or greater efficacy and safety for both mother and fetus. Visser and Wallenburg observed similar maximum reductions in blood pressure during administration of each drug, but greater falls in pulmonary capillary wedge pressure as well as increased occurrence of fetal distress in women receiving hydralazine.20 In one randomised trial, there were fewer preterm infants and less acute fetal distress in the group of women given nifedipine than in the group of women given intravenous and then oral hydralazine.12 The most recent and largest studies showed that maternal and fetal outcomes were similar in pregnant women with severe hypertension (diastolic blood pressure > 120 mmHg) who received either sublingual nifedipine or intravenous hydralazine.36 The authors concluded that sublingual nifedipine may be advantageous "for use by midwives who work in rural areas where speed is essential in reducing acute hypertension . . ." Nifedipine also relaxes the myometrium, and therefore has a potentially important role in the treatment of preterm labour. In five separate randomised trials involving a total of 290 women, nifedipine was as effective as ritodrine for tocolysis and was associated with fewer serious maternal side effects.37-41 No adverse fetal effects were attributable to nifedipine in studies reporting on more than 350 women treated with the drug in preterm labour.42 Recent prospective data have provided further support for the safety of nifedipine, even when used in early pregnancy.43 Withdrawal of nifedipine from the Australian market The "position of comfort" -- that nifedipine can be used safely and easily in an emergency (before insertion of an intravenous cannula) -- has been lost. The plan to withdraw nifedipine capsules arose out of concern over the potential adverse effects (myocardial infarction, death) in non-pregnant patients with hypertension and ischaemic heart disease receiving long-term treatment with the drug.44-46 In New Zealand, the Ministry of Health has stated that nifedipine and some other calcium antagonists are contraindicated in pregnancy.47 There is no basis for this pronouncement in studies of nifedipine use in human pregnancy. As nifedipine was never officially listed in the Australian Register of Therapeutic Goods for use in pregnancy, clinicians cannot argue to retain the drug for the treatment of hypertension in pregnancy. The simple solution could be to accept defeat and rely on parenteral hydralazine. However, the most recent preparation of this drug is not marketed for intramuscular use (presumably because of its variable absorption), so that treatment must be delayed until an intravenous cannula is inserted. This delay adds to the dangers of severe hypertension for the pregnant woman. Moreover, it has been speculated that parenteral hydralazine will also be withdrawn shortly as it has been superseded by better drugs with fewer side-effects in non-pregnant patients. We now face the following situation: nifedipine capsules have been withdrawn from sale, and it is possible that intravenous hydralazine and diazoxide will also be withdrawn from the Australian market. Intravenous labetalol is not available in Australia, and magnesium sulfate, while known to have some blood pressure lowering effects, is not a sufficiently powerful antihypertensive agent for treatment of severe hypertension in pre-eclampsia. Therefore, intravenous sodium nitroprusside and glyceryl trinitrate will be the only agents left for the treatment of acute severe hypertension in pregnancy. The former can induce fetal cyanide toxicity, while the latter has been subject to far fewer studies in pregnancy than nifedipine, hydralazine or diazoxide -- and both drugs require highly skilled dose titration. Why do pregnant women now face the very real prospect that we will no longer be able to treat their severe hypertension as efficiently as before? In part, this relates to the bureaucratic nature of administering such matters -- if a drug has not been officially listed for an approved indication in the Australian Register of Therapeutic Goods (and nifedipine was never listed for use in pregnancy), then, despite widespread clinical use for that purpose, it can be withdrawn from the market by the pharmaceutical regulatory authorities. To be fair, this is probably the safest approach overall. At the same time, however, this situation highlights deficiencies in clinical and scientific interaction among clinicians, pharmaceutical companies and government agencies. The pharmaceutical company concerned has long known that nifedipine was being used for treating severe hypertension in pregnancy. They, of course, could not endorse such an action, but could have worked with clinicians to study the clinical outcomes in a proper manner, leading to an application for approval of a new indication. They chose not to do so. We clinicians are as much at fault here for not taking such an initiative when the company failed to do so. ADEC tried to balance these issues in its most recent consideration of the problem, but had no option other than to withdraw nifedipine capsules from sale. In New Zealand, nifedipine capsules are now available only in hospitals, which limits the access of rural practitioners to this drug. Perhaps this situation should force us to reconsider the speed at which we need to lower blood pressure in pre-eclampsia. Pregnancy outcomes are very good when severe hypertension is treated rapidly (over 20-30 minutes) and cerebral haemorrhage and eclampsia are now relatively rare. This does not mean there is necessarily a causal relationship between such treatment and the low rates of intracerebral haemorrhage and eclampsia. However, it would be difficult to prove a causal relationship because of the rarity of these complications as well as the ethical problems involved in randomising severly hypertensive pregnant women to a trial comparing rapid reductions in blood pressure (e.g., using nifedepine) with slower reductions (e.g., using oral clonidine or methyldopa). Conclusions The "best case" scenario is that withdrawal from sale of nifedipine capsules and intramuscular hydralazine will leave Australian clinicians with only intravenous diazoxide and intravenous hydralazine to fill an essential therapeutic niche (with intravenous labetalol still available in New Zealand). None of these drugs can be given urgently in hospitals without resident medical staff, and even in the larger tertiary hospitals resident medical staff can be delayed in other wards or operating theatres. Such delays could result in serious complications for the pregnant woman and her baby. The "worst case" scenario is that none of these drugs (nifedipine, labetalol, hydralazine or diazoxide) will be available for the treatment of acute severe hypertension in pregnancy. Pregnant women will then suffer from inadequate treatment or be exposed to the side effects of the remaining antihypertensive drugs, which are currently not recommended for use in pregnancy. Is all this enough to justify continued availability of short-acting nifedipine in pregnant women in Australia and New Zealand? Most clinicians would rapidly respond "yes" as they continue to practise medicine as both an art and a science. The "art" of using nifedipine successfully in pregnancy is well known to most of us, but, although the above review of the available literature shows that nifidepine capsules are as safe as any other drugs currently used to treat acute severe hypertension in pregnancy, we have failed to gather the science to a sufficient extent. We hope our patients will not suffer as a result of our combined shortfalls. Acknowledgement We thank Mrs Jodie Hendley for assistance in preparing this manuscript. References Brown MA, Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features. Med J Aust 1996; 165: 360-365. Australian Drug Evaluation Committee. Resolution No. 5857. Commonwealth of Australia Gazette No. GN 10, 25 October 1995. (See also Resolution No. 7129. 5-6 December 1996.) Michael CA. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. Aust N Z J Obstet Gynaecol 1986; 26: 26-29. Visser W, Wallenburg HCS. Should labetalol be used in severe early onset preeclampsia patients? Protagonist and presentations. Proceedings of the 8th World Congress on Hypertension in Pregnancy; 1992 Nov 8-12; Buenos Aires, Argentina. Abstract 104: 290. Ramsay B, de Belder A, Campbell S, et al. A nitric oxide donor improves uterine artery diastolic blood flow in normal early pregnancy and in women at high risk of pre-eclampsia. Eur J Clin Invest 1994; 24: 76-78. Visser W, Wallenburg HCS. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991; 17: 1072-1077. Baker A. Management of severe pregnancy induced hypertension, or gestosis, with sodium nitroprusside. Anaesth Intensive Care 1990; 18: 361-365. Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudo emergencies? JAMA 1996; 276: 1328-1331. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol 1993; 100: 959-961. Rehman F, Mansoor GA, White WB. Inappropriate physician habits in prescribing oral nifedipine capsules in hospitalised patients. Am J Hypertens 1996; 9: 1035-1039. Walters BNJ, Redman CWG. Treatment of severe pregnancy-associated hypertension with the calcium antagonist nifedipine. Br J Obstet Gynaecol 1984; 91: 330-336. Fenakel K, Fenakel G, Appelman Z, et al. Nifedipine in the treatment of severe preeclampsia. Obstet Gynecol 1991; 77: 331-337. Hanretty KP, Whittle MJ, Howie CA, Rubin PC. Effect of nifedipine on Doppler flow velocity waveforms in severe preeclampsia. BMJ 1989; 299: 1205-1206. Lindow SW, Davies N, Davey DA, Smith JA. The effect of sublingual nifedipine on uteroplacental blood flow in hypertensive pregnancy. Br J Obstet Gynaecol 1988; 95: 1276-1281. Duggan PM, McCowan LME, Stewart AW. Antihypertensive drug effects on placental flow velocity waveforms in pregnant women with severe hypertension. Aust N Z J Obstet Gynaecol 1992; 32: 335. Lurie S, Fenakel K, Friedman A. Effect of nifedipine on fetal heart rate in the treatment of severe pregnancy-induced hypertension. Am J Perinatal 1990; 7: 285-286. Pirhonen JP, Erkkola RU, Ekblad UU. Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. Obstet Gynecol 1990; 76: 37-41. Puzey MS, Ackovic KL, Lindow SW, Gonin R. The effect of nifedipine on fetal umbilical artery Doppler waveforms in pregnancies complicated by hypertension. S Afr Med J 1991; 79: 192-194. Seabe SJ, Moodley J, Becker P. Nifedipine in acute hypertensive emergencies in pregnancy. S Afr Med J 1989; 76: 248-250. Visser W, Wallenburg HCS. A comparison between the haemodynamic effects of oral nifedipine and intravenous dihydralazine in patients with severe preeclampsia. 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The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 275: 620-625. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction. A hypothesis formulated but not yet tested. JAMA 1995; 274: 654-645. Horton R. Spinning the risks and benefits of calcium antagonists. Lancet 1995; 346: 586-587. New Zealand Ministry of Health. Managing high blood pressure in pregnancy. Prescriber Update 1994; 7: 2-10. (Received 26 Aug 1996, accepted 28 Jan 1997) Authors' details Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW. Mark A Brown, FRACP, MD, Associate Professor of Medicine. Department of Obstetrics and Gynaecology, University of Auckland School of Medicine, National Women's Hospital, Auckland, NZ. Lesley M E McCowan, FRCOG, FRNZCOG, Senior Lecturer in Obstetrics and Gynaecology; Robyn A North, PhD, FRACP, Senior Lecturer in Obstetric Medicine. King Edward Memorial Hospital for Women, Perth, WA. Barry N Walters, FRACP, Physician in Obstetric Medicine. Council of the Australasian Society for the Study of Hypertension in Pregnancy, 145 Macquarie Street, Sydney, NSW 2000. No reprints will be available. Correspondence: Dr M A Brown, Departments of Medicine, Renal Medicine and Obstetrics, St George Hospital, Kogarah, NSW 2217. To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia. We appreciate your comments.

Mark A Brown · Robyn A North · Barry N Walters