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289 Intravenous Labetalol versus Oral Nifedipine in the Treatment of Severe Hypertension ... December 2012 Table 2: Effects of drugs on blood pressure Table 3: Average time for control of blood pressure in minutes Group A (Labetalol) n = 25 Group B (Nifedipine) n = 25 Group Number of Patients who got BP controlled Mean (minutes) Blood Pressure Control Adequate Not adequate Doses required to get the therapeutic blood pressure goal 1 st dose 2 nd dose 3 rd dose 4 th dose 5 th dose Successful treatment with first dose Amount of drug required (mg) Fall in blood pressure in first 20 minutes Systolic BP (mmHg) Diastolic BP (mmHg) 24/25 1/25 nulliparous in the group A and 45% of patients were para 1 in the group B. Most of the patients in both the groups were unbooked. Nineteen patients (76%) of group A and 17 patients (68%) of group B were pre-eclamptic patients (Table 1). The blood pressure control was achieved in both the groups fairly well. In nifedipine group, the control of blood pressure was achieved in all the patients. In labetalol group, blood pressure was controlled in 24 out of 25 patients, one patient who was not controlled with full dose, received nitroglycerin for control of hypertension. However, the number of patients controlled with the first dose of the drug was lower in labetalol group as compared to nifedipine group (10 / 25 Vs 20 / 25, p = 0.03). Mean doses requirement of labetalol and nifedipine were 113.4 ± 20 mg and 20.5 ± 10 mg respectively. Mean SBP reduction of labetalol and nifedipine at first 20 minutes were 14.4 ± 6 mmHg and 18.3 ± 5 mmHg respectively and there was no significant difference (p = 0.257) in SBP reduction in both the groups. There was significant difference (p = 0.03) in reduction of DBP in first 20 minutes between nifedipine (15.1 ± 6 mmHg) and labetalol (8.3 ± 2 mmHg) groups (Table 2). The average time required for control of blood pressure was 44.2 ± 26.31 and 24 ± 8.2 minutes in labetalol and nifedipine groups respectively and there was significant difference in between the two groups (p = 0.006) (Table 3). DISCUSSION Hypertension is one of the most common problems arising during the pregnancy complicating up to 15% of all pregnancies, and within this disorder, approximately one in four patients will experience an episode of severe hypertension [12] . Treatment of 10 5 4 3 3 10 113.4 ± 20 14.4 ± 6 8.3 ± 2 25/25 0 20 5 0 0 0 20 (p = 0.03) 20.5 ± 10 (p = 0.0007) 18.3 ± 5 (p = 0.257) 15.1 ± 6 (p = 0.03) Group A (Labetalol) n = 25 Group B (Nifedipine) n =25 severe hypertension in pregnancy is mandatory as it decreases the incidence of maternal intracranial hemorrhage, hypertensive encephalopathy, abruptio placentae and maternal mortality. The maternal mortality from hypertensive disease has been studied for its attributing factors [13] . There is general agreement that rapid lowering of high blood pressure can reduce the maternal risk [14-16] . Labetalol and nifedipine, both are found to be safe drugs for the treatment of severe hypertension in pregnancy from the previous studies [17-20] . Previous reports [21,22] have indicated that there was apprehension in nifedipine use as the sublingual variety caused more sudden decrease in blood pressure, resulting thereby in overshoot hypotension and ischemia there upon. The oral variety does not seem to have this [23] effect as found in our study. There were minimal side effects in our patients with the use of either drug. No patient had sudden hypotension below 100 mmHg systolic during the initial two hours of treatment. Nifedipine achieved adequate control of blood pressure with only one dose in 20 / 25 patients whereas in the labetalol group only 10 / 25 patients achieved the control of blood pressure with one dose, and this difference was statistically significant (p = 0.03). Both drugs lowered the SBP in the first 20 minutes by 14.4 ± 6 mmHg and18.3 ± 5 mmHg in labetalol and nifedipine group respectively and there was no statistically significant difference between the two groups. However, there was significant fall in the blood pressure particularly diastolic with nifedipine as compared to labetalol in the first 20 minutes. This is substantiated in other studies by Vermillion et al [20] and by Raheem et al [24] ; these authors found that the use of nifedipine was associated with increase in urine output in addition to rapid control over blood pressure as compared to labetalol. Whether rapid fall in blood pressure is beneficial or not is unclear, particularly if it is not causing cerebral hypoperfusion or overshoot hypotension or any other adverse effects on the fetus or the mother. Nevertheless, the importance of close monitoring of blood pressure every 20 minutes or earlier as need arises has to be emphasized as the patient can have hypotension if the drugs are not adequately titrated. If the trends of blood pressure over two hours are carefully observed, it is evident that both drugs achieved fair control of blood pressure in our study. 24 25 44.21 ± 26.3 24 ± 8.2 (p = 0.006)
December 2012 KUWAIT MEDICAL JOURNAL 290 Therefore, either drug can be used successfully in the control of hypertension in pregnancy. The use of nifedipine for control of severe hypertension in pregnancy had been proven in earlier studies [25-30] as well. However, labetalol may be advantageous in delirious patient because of its intravenous route. CONCLUSION Both drugs effectively controlled the blood pressure in severe hypertension in pregnancy. However, nifedipine faired better than labetalol in time taken, reduction of DBP and number of patients responding with first dose (i.e, in 20 minutes). REFERENCES 1. Van Schie DL, De Jeu RM, Steyn DW, Odendaal HJ, Geijn HPV. The optimal dosage of ketanserin for patients with severe hypertension in pregnancy. Eur J Obstet Gynecol Rprod Biol 2002; 102:161-166 . 2. Bolte AC, Geijn HPV, Dekker GA. Pharmacological treatment of severe hypertension in pregnancy and the role of serotonin -2 receptor blockers. Eur J Obstet Gynecol Rprod Biol 2001; 95:22-36. 3. Redman CWG. Drugs, hypertension and pregnancy. In: Studd J, editor. Progress in Obstetrics and Gynaecology. Vol. 9. Edinburgh: Churchill Livingstone; 1991. p. 83- 97. 4. Bolte AC, Geijn HPV, Dekker GA. Management and monitoring of severe preeclampsia. Eur J Obstet Gynecol Reprod Biol 2001; 96:8-20. 5. Johansen PL. Pharmacology of combined alpha-beta blockade.II. Hemodynamic effects of labetalol. Drugs 1984; 28:35-50. 6. Mabie WC, Gonzalez AR, Sibai BM, Amon E. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987; 70:328-333. 7. Mahmoud TZ, Bjornsson S, Calder AA. Labetalol therapy in pregnancy induced hypertension: the effects on fetoplacental circulation and fetal outcome. Eur J Obstet Gynecol Reprod Biol 1993; 50:109-113. 8. Greer IA, Walker JJ, Mc Laren M, Calder AA, Forbes CD. A comparative study of the effects of adrenoreceptor antagonists on platelet aggregation and thromboxane generation. Thromb Haemost 1985; 54:480-484. 9. Michael CA. Early fetal lung maturation associated with labetalol therapy. Singapore J Obstet Gynaecol 1980; 11:2-5. 10. Management of preeclampsia, ACOG Technical Bulletin No.219, February, 1996. The American College of Obstetricians and Gynecologists, Washington, DC. 11. Ales K. Magnesium plus nifedipine. Am J Obstet Gynecol 1990; 162:288. 12. Brown MA, Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features. Med J Aust 1996; 165:360-365. 13. Lewis G, Drife J. Why Mothers Die 1997-1999: The fifth report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. London: RCOG Press, 2001. 14. Rey E, Lelorier J, Burgess E, Lange IR, Leduce L. Report of the Canadian Hypertension Society Consensus Conference: Pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ 1997; 157:1245-1254. 15. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000; 183:S1- S22. 16. Brown MA, Hague WM, Higgins J, et al. Australian Society for the Study of Hypertension in Pregnancy. The detection, investigation and management of hypertension in pregnancy: executive summary. Aust NZ J Obstet Gynecol 2000; 40:133-138. 17. Michael CA. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. Aust NZ J Obstet Gynecol 1986; 26:26-29. 18. Michael CA. Use of labetalol in the treatment of severe hypertension during pregnancy. Br. J Clin Pharmacol 1979; 8:211S-215S. 19. Aali BS, Nijad SS. Nifedipine or hydralazine as a first line agent to control hypertension in severe preeclampsia. Acta Obstet Gynecol Scand 2002; 81:25 -30. 20. Vermillion ST, Scardo JA, Newsman RB, Chauhan SP. A randomized, double blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. Am J Obstet Gynecol 1999; 181:858-861. 21. Wachter RM. Symptomatic hypotension induced by nifedipine in the acute treatment of severe hypertension. Arch Intern Med 1987; 147:556-558. 22. O’ Malia JJ, Sander GE, Giles TD. Nifedipine associated myocardial ischemia or infarction in the treatment of severe hypertension. Arch Intern Med 1987; 147:556- 558. 23. Scardo JA, Vermillion ST, Newman RB, Chauhan SP, Hogg BB. A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in pre-eclamptic hypertensive emergencies. Am J Obstet Gynecol 1999; 181:862-866. 24. Raheem IA, Saaid R, Omar SZ, Tan PC. Oral nifedipine versus intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy: a randomized trial. Br J Obstet Gynecol 2012; 119:78-85. 25. Papatsonis DN, Lok CA, Bos JM, Geijn HP, Dekker GA. Calcium channel blockers in the management of preterm labor and hypertension in pregnancy. Eur J Obstet Gynecol Reprod Biol 2001; 97:122-140. 26. Borgi C, Esposti DD, Cassani A, Immordino V, Bovicelli L, Ambrosioni E. The treatment of hypertension in pregnancy. J Hypertens Suppl 2002; 20:S52-56. 27. Magee LA, Miremadi S, Li J, et al. Therapy with both magnesium sulphate and nifedipine does not increase the risk of serious magnesium related maternal side effects in women with preeclampsia. Am Obstet Gynecol 2005; 193:153-163. 28. Magee LA, von Dadelszen P. The management of severe hypertension. Semin Perinatol 2009; 33:138-142. 29. Podymow T, August P. Hypertension in pregnancy. Adv Chronic Kidney Dis 2007; 14:178-190. 30. Podymow T, August P. Antihypertensive drugs in pregnancy. Semin Nephrol 2011; 31:70-85.
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