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財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 EBM Educational Prescription (教育處方)報告大綱 Learner: 曾 繁 聞 Department: 內科部 Date: 950223 * 臨床個案摘要:(個案病歷號:9x1x7xx1 ) 96 Y/O bedridden female resident of nursing home, with Hx of dementia, presented to ER with SOB of 1 day’s duration. Con’s: stupor, Vital signs: Temp 36.7C, PR 79 bpm, RR38/min, BP 221/85 mmHg, SaO2 89-92%, PE: pupil: +/2, OU, Chest:diffuse wheezing, Heart:RHB, no S3S4, a pressure sore 4*7 cm on L’t sole. Na=115, Hb=8.0. CxR: infiltration over RLL and L’t hilum. 詢問可以回答的處置問題(PICO) I) Patient and/or problem: Hypertensive urgency Intervention/ or exposure::sublingual short acting Nifedipine Comparison intervention (若有的話):No intervention or other anti-hypertensives Outcomes: complication, CVA, ischemia, infarction * One Question Sentence:Do patients receving sublingual short-acting Nifedipine have higher risks of developing complications(ex. Decreasd cerebral perfusion, CVA, or cardiac ischemia ) * Type of Question: (eg. Therapy or Diagnosis) Harm * Ideal Study type: (eg. RCT, cohort study) SR of RCTs * Feasible Study type :RCT, cohort study 找尋最有用的證據 II) * Search Strategy Design(事先搜尋策略設計) Database 的種類:(Non-prefiltered) PubMed Key words and search tactics: (("hypertensive urgencies" or "hypertensive urgency" or "severe asymptomatic hypertension" or "hypertensive crisis" or "DBP>120" or "DBP>130") ) AND ("nifedipine" or "adalat" or "calcium channel blocker" or 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -1- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 "CCB") * Actual Search Process and Results(實際搜尋過程與結果) Search process: 首先進入PubMed中clinical queries,選擇”THERAPY”輸入(("hypertensive urgencies" or "hypertensive urgency" or "severe asymptomatic hypertension" or "hypertensive crisis" or "DBP>120" or "DBP>130") ) AND ("nifedipine" or "adalat" or "calcium channel blocker" or "CCB") 共20筆資料 PubMed中clinical queries的分類是大略的,非專家之評判,因此不一定準,更何況有時 一篇文章的outcomes包含了therapy, harm and prognosis. 等。因此建議於「臨床實務」搜尋 的過程遵循「4S原則」最好。 Results 1: Gemici K, Baran I, Bakar M, Demircan C, Ozdemir B, Cordan J. Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis. Blood Press. 2003;12(1):46-8. PMID: 12699135 [PubMed - indexed for MEDLINE] 2: Aali BS, Nejad SS. Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia. Acta Obstet Gynecol Scand. 2002 Jan;81(1):25-30. PMID: 11942883 [PubMed - indexed for MEDLINE] 3: Sanchez M, Sobrino J, Ribera L, Adrian MJ, Torres M, Coca A. Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase. J Cardiovasc Pharmacol. 1999 Mar;33(3):479-84. PMID: 10069685 [PubMed - indexed for MEDLINE] 4: Risler T, Bohm R, Wetzchewald D, Nast HP, Koch HH, Stein G, Erley CM. A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine. Eur J Clin Pharmacol. 1998 Jun;54(4):295-8. PMID: 9696952 [PubMed - indexed for MEDLINE] 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -2- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 5: Damasceno A, Sevene E, Patel S, Polonia J. Nifedipine-retard versus nifedipine-capsules for the therapy of hypertensive crisis in black patients. J Cardiovasc Pharmacol. 1998 Jan;31(1):165-9. PMID: 9456291 [PubMed - indexed for MEDLINE] 6: Lopez NC, Corral JL, Perozo M, Garcia P, Bustillo N, Arreaza MR, Arocha I. [Nifedipine in the treatment of moderate and severe arterial hypertension. Long-term effect on arterial pressure and on the left ventricle] Rev Esp Cardiol. 1997 Aug;50(8):567-72. Spanish. PMID: 9340698 [PubMed - indexed for MEDLINE] 7: Damasceno A, Ferreira B, Patel S, Sevene E, Polonia J. Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis. J Hum Hypertens. 1997 Aug;11(8):471-6. PMID: 9322826 [PubMed - indexed for MEDLINE] 8: McDonald AJ, Yealy DM, Jacobson S. Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED. Am J Emerg Med. 1993 Sep;11(5):460-3. PMID: 8363681 [PubMed - indexed for MEDLINE] 9: Misra A, Jain P, Reddy RB. Sublingual captopril in hypertensive urgencies. Postgrad Med J. 1993 Jun;69(812):498-9. No abstract available. PMID: 8208656 [PubMed - indexed for MEDLINE] 10: Dadkar VN, Karnik ND, Izar M, Sharma SR, Gandhi YP, Narawane NM, Vyawahare SS, Sudhakar S, Gore AG, Kapadia NM, et al. Sublingual nifedipine and captopril in hypertensive urgencies and emergencies. Indian Heart J. 1993 May-Jun;45(3):185-7. PMID: 8314271 [PubMed - indexed for MEDLINE] 11: Bussmann WD, Kenedi P, von Mengden HJ, Nast HP, Rachor M. [Nitroglycerin in comparison with nifedipine in patients with hypertensive crisis] Z Kardiol. 1993 Jan;82(1):33-7. German. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -3- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 PMID: 8470417 [PubMed - indexed for MEDLINE] 12: Bussmann WD, Kenedi P, von Mengden HJ, Nast HP, Rachor N. Comparison of nitroglycerin with nifedipine in patients with hypertensive crisis or severe hypertension. Clin Investig. 1992 Dec;70(12):1085-8. PMID: 1467634 [PubMed - indexed for MEDLINE] 13: Mansur Ade P, Ramires JA, Avakian SD, de Paula RS, Pileggi F. [Comparison of the effects of diazepam, nifedipine, propranolol and a combination of nifedipine and propranolol, by sublingual administration, in patients with hypertensive crisis] Arq Bras Cardiol. 1991 Oct;57(4):313-7. Portuguese. PMID: 1824527 [PubMed - indexed for MEDLINE] 14: Schneider E, Jennings AA, Opie LH. Captopril, nifedipine and their combination for therapy of hypertensive urgencies. S Afr Med J. 1991 Sep 21;80(6):265-70. Erratum in: S Afr Med J 1991 Oct 19;80(8):411. PMID: 1925820 [PubMed - indexed for MEDLINE] 15: Komsuoglu B, Sengun B, Bayram A, Komsuoglu SS. Treatment of hypertensive urgencies with oral nifedipine, nicardipine, and captopril. Angiology. 1991 Jun;42(6):447-54. PMID: 2042792 [PubMed - indexed for MEDLINE] 16: Cristodorescu R, Bartha P, Dragan S, Nicolin M. [The treatment of hypertensive crisis with nifedipine as the basis] Rev Med Interna Neurol Psihiatr Neurochir Dermatovenerol Med Interna. 1989 Nov-Dec;41(6):529-38. Romanian. PMID: 2577015 [PubMed - indexed for MEDLINE] 17: von Arnim T, Erath A. Nitrates and calcium antagonists for silent myocardial ischemia. Am J Cardiol. 1988 Mar 25;61(9):15E-18E. PMID: 3279743 [PubMed - indexed for MEDLINE] 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -4- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 18: von Arnim T, Erath A, Reuschel-Janetschek E. Isosorbide-5-mononitrate and nifedipine can reduce ischaemic ST-segment changes during Holter monitoring in patients with spontaneous angina pectoris. Eur Heart J. 1988 Jan;9 Suppl A:113-8. PMID: 3409907 [PubMed - indexed for MEDLINE] 19: Spah F, Grosser KD. Treatment of hypertensive urgencies and emergencies with nitrendipine, nifedipine, and clonidine: effect on blood pressure and heart rate. J Cardiovasc Pharmacol. 1988;12 Suppl 4:S154-6. PMID: 2468862 [PubMed - indexed for MEDLINE] 20: Nieto M, Riambau E, Roma J, Samon R. [Hypertensive crisis in hemodialysis treated with nifedipine] Med Clin (Barc). 1987 May 2;88(17):697. Spanish. No abstract available. PMID: 3613703 [PubMed - indexed for MEDLINE] 再次進入 clinical queries,選擇 PROGNOSIS,鍵入相同關鍵字(("hypertensive urgencies" or "hypertensive urgency" or "severe asymptomatic hypertension" or "hypertensive crisis" or "DBP>120" or "DBP>130") ) AND ("nifedipine" or "adalat" or "calcium channel blocker" or "CCB")1 筆資料: Results: 1: Cherney D, Straus S. Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature. J Gen Intern Med. 2002 Dec;17(12):937-45. Review. PMID: 12472930 [PubMed - indexed for MEDLINE] 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -5- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 * 描述自己如何從上述搜尋結果中,選出與問題相關之一些文獻,並將這些文 獻分出「初步證據等級」(請附上摘要),進而從中選一篇做為期刊閱讀的主要 文獻加以評判: Clinical queriesTREATMENT中的文獻:建議嘗試分「證據等級」 其中 title 與主題相似的有: 1:Randomized controlled study;指出 PO Nifedipine 對 MCA 的 PI 值有不好影響,但未有實際病例診斷。 Blood Press. 2003;12(1):46-8. Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis. Gemici K, Baran I, Bakar M, Demircan C, Ozdemir B, Cordan J. Uludag University, School of Medicine, Department of Cardiology, Bursa, Turkey. [email protected] OBJECTIVE: This study was designed to show the effects of sublingually administered nifedipine and captopril on middle cerebral arterial blood flow during hypertensive crisis in the emergency department. METHODS AND RESULTS: Transcranial Doppler ultrasonography (TCD) was performed on the patients fulfilling the criteria (15 patients given captopril, 13 patients given nifedipine, mean (SD) age 56 11 and 54 10 years, respectively). Then, patients were randomized into sublingually administered captopril or nifedipine groups and after the drug administration, TCD was repeated. Initial systolic and diastolic blood pressures were 200 and 199 17/ 123 21/125 21 mmHg in the captopril group 20 mmHg in the nifedipine group. There was no significant difference between antihypertensive effects of the drugs after initiation of treatment. Before the treatment with captopril, middle cerebral artery (MCA) flow velocities (Vm) and pulsatility index (PI) were 76.74 cm/s and 1.18 6.38 0.09, respectively. The values after the treatment with captopril were 78.21 5.24cm/s (p < 0.05) and 0.92 0.08 (p < 0.001), respectively. Before the treatment with nifedipine, Vm and PIs were 64.73 5.11 cm/s and 1.14 Vm was 60.04 0.18, respectively. After the treatment with nifedipine, 5.36 cm/s (p < 0.01) and PI was 1.21 0.09 (p < 0.01). CONCLUSION: After treatment with captopril, PIs were decreased to normal limits but in the group treated with nifedipine, PIs increased to more pathological values. These results showed that we should reconsider the use of nifedipine in the emergency departments as an antihypertensive agent in hypertensive attack treatment. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -6- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 Publication Types: Clinical Trial Randomized Controlled Trial PMID: 12699135 [PubMed - indexed for MEDLINE] 2: Randomized controlled study;僅模糊指出短效 Nifedipine 的急劇降血壓效果可能’ 有害’ ,且病人全為非 裔人種 J Cardiovasc Pharmacol. 1998 Jan;31(1):165-9. Nifedipine-retard versus nifedipine-capsules for the therapy of hypertensive crisis in black patients. Damasceno A, Sevene E, Patel S, Polonia J. Faculdade Medicina Universidade Eduardo Mondlane, Maputo, Mozambique. In a randomized parallel-group placebo-controlled study, we compared the short-term hypotensive efficacy and the safety of a single administration of nifedipine-retard (20-mg tablets) with that of two administrations 6 h apart of nifedipine capsules (10 mg) in 10 and 11 black patients, respectively, with acute severe hypertension. Both groups had similar pretreatment blood-pressure (BP) values. Blood pressure was recorded at 10-min intervals for 12 h by using an automated device. In the first 3 h of treatment, nifedipine capsules induced a faster and greater hypotensive effect than nifedipine retard, which was associated with an increase in heart rate. At 2 h after treatment, nifedipine capsules decreased BP to levels (159 5/105 3 mm Hg) that were significantly lower than those reached by nifedipine-retard (175 4/118 4 mm Hg; p < 0.05). Both preparations induced a similar maximal BP decrease of approximately 30% of the placebo values, but the peak decrease of BP occurred significantly later with nifedipine-retard (283 than with nifedipine capsules (100 31 min after administration) 14 min; p < 0.01). Four hours after administration, the hypotensive effect of nifedipine capsules was blunted, and a second administration was necessary, whereas nifedipine-retard reduced BP slowly and continuously for < or =12 h and more smoothly. Flush and headache were more frequently found with nifedipine capsules. We conclude that in black patients with hypertensive crisis, nifedipine capsules produce an abrupt decrease in BP that may be potentially harmful. Thus for patients suitable for treatment with nifedipine, nifedipine-retard is preferable because it effectively reduces BP for > or =12 h while achieving a rapid enough effect without critical short-term decreases in BP. Publication Types: Clinical Trial 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -7- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 Randomized Controlled Trial PMID: 9456291 [PubMed - indexed for MEDLINE] 3: Randomized controlled study;探討對於高血壓的長期治療,並非針對 hypertensive urgency Rev Esp Cardiol. 1997 Aug;50(8):567-72. [Nifedipine in the treatment of moderate and severe arterial hypertension. Long-term effect on arterial pressure and on the left ventricle] [Article in Spanish] Lopez NC, Corral JL, Perozo M, Garcia P, Bustillo N, Arreaza MR, Arocha I. Unidad de Hipertension Arterial, Hospital Central de Maracay, Estado Aragua, Venezuela. [email protected] INTRODUCTION AND OBJECTIVES: Moderate-to-severe hypertension is less prevalent than mild hypertension, but it is responsible for more incidences of complications. Its complex treatment requires several drugs, and is often inadequate. This study assessed the efficacy and safety of nifedipine GITS (oral release osmotic system) as monotherapy, in addition to the effects on left ventricular hypertrophy, after a long term follow-up (one year). PATIENTS AND METHODS: Thirty patients with diastolic blood pressure above 105 mmHg were studied after a short placebo phase. They received nifedipine GITS as monotherapy in a single daily dose of 30 mg; dose titration was made the first three months according to response and until they reached figures equal to or below 95 mmHg. By M-Mode echocardiogram, left ventricular mass index and systolic function were calculated at the end of the placebo phase and at 3, 6, 9 and 12 months. Hematological parameters, lipid profile, electrolytes and liver enzymes were assessed at the same periods. RESULTS: In 70% of the patients the blood pressure reached values of 140-90 mmHg. In 16 patients with adequate M-mode recordings, a 12% reduction in left ventricular mass was observed without modification in systolic function. Five patients were retired: two due to adverse events and three due to different reasons (drop out, evidence for secondary hypertension). There were no changes of clinical significance in the hematological or biochemical parameters and no hypertensive crisis occurred. CONCLUSION: The monotherapy with nifedipine GITS was effective in reducing high blood pressure, induced regression in ventricular hypertrophy and showed good tolerance in one year follow-up. Publication Types: Clinical Trial Clinical Trial, Phase II Randomized Controlled Trial 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -8- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 PMID: 9340698 [PubMed - indexed for MEDLINE] 4: Randomized controlled study;僅 20 名研究對象,並未觀察到立即的治療不良反應 Am J Emerg Med. 1993 Sep;11(5):460-3. Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED. McDonald AJ, Yealy DM, Jacobson S. Department of Emergency Medicine, Jersey Shore Medical Center, Neptune, NJ 07753. Therapy in hypertensive urgencies is debated and complicated by the side effects of available agents. In a prospective, randomized, open labeled study, the use of oral labetalol, an alpha- and beta-adrenergic blocker, with oral nifedipine in hypertensive urgencies in the emergency department was compared. Patients with diastolic blood pressures (DBP) of more than 120 mm Hg without criteria for a hypertensive emergency were eligible. The drugs were given in a loading manner with doses and timing based on their respective pharmacokinetics until a DBP of 110 mm Hg or lower was obtained or 4 hours had passed. Either an initial labetalol dose of 200 mg and a repeat dose of 100 to 200 mg at 2 hours, depending on the DBP or nifedipine, 10-mg bite and swallow every hour up to a total dose of 20 mg were given. Ten patients were enrolled into each study group. A 100% response rate was defined as a DBP of 110 mm Hg or less was observed for nifedipine and an 80% response rate for labetalol (P > .2) was observed. The mean time to control was 67.5 minutes for labetalol and 60.0 minutes for nifedipine (P > .2). The pretreatment pressure for labetalol was 195/127 mm Hg and for nifedipine was 198/128 mm Hg (P > .2), which decreased to a posttreatment pressure for labetalol of 154/100 mm Hg and for nifedipine of 163/100 mm Hg (P > .2). The mean decrease in systolic (SBP)/DBP was 42.6/26.5 mm Hg with labetalol and 34.9/28.4 mm Hg for nifedipine (P > .2). No significant side effects occurred with either drug.(ABSTRACT TRUNCATED AT 250 WORDS) Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8363681 [PubMed - indexed for MEDLINE] 5: Randomized controlled study;52 名病人,比較 nifedipine, captopril 的效果,均未發現重大不良反應 Indian Heart J. 1993 May-Jun;45(3):185-7. Sublingual nifedipine and captopril in hypertensive urgencies and emergencies. Dadkar VN, Karnik ND, Izar M, Sharma SR, Gandhi YP, Narawane NM, Vyawahare SS, Sudhakar S, Gore AG, Kapadia NM, et al. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC -9- 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 Department of Medicine and Pharmacology, L.T.M. Medical College and Hospital, Sion, Bombay. Fifty two patients of severe hypertension, diastolic blood pressure > or = 115 mmHg, with or without acute complications, were treated with sublingual nifedipine 10 mg or sublingual captopril 25 mg in a randomized prospective in patient study with careful clinical monitoring. Both the drugs were safe and effective in rapidly lowering blood pressure. Nifedipine appeared to be superior to captopril with earlier onset of action, greater magnitude of response and longer duration of action. No significant side effects were observed in either of the two groups. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 8314271 [PubMed - indexed for MEDLINE] 6: Randomized controlled study;合併 nifedipine-captopril 治療效果較佳,未提及不良反應 S Afr Med J. 1991 Sep 21;80(6):265-70. Erratum in: S Afr Med J 1991 Oct 19;80(8):411. Captopril, nifedipine and their combination for therapy of hypertensive urgencies. Schneider E, Jennings AA, Opie LH. Department of Medicine, University of Cape Town. Twenty patients with acute severe hypertension were randomised to therapy with either nifedipine capsules (10 mg) or captopril tablets (25 mg) given sublingually and the blood pressure recorded for 240 minutes. Oral monotherapy with either agent followed for 3 weeks, then the agents were combined for a further 2 weeks and in the final 6 weeks of the trial a beta-blocker and diuretic were added, if needed. Thirteen patients completed the trial. The major results were: (i) nifedipine decreased blood pressure more rapidly than captopril 60 minutes after first ingestion but at 240 minutes equal degrees of fall in blood pressure had been obtained; (ii) neither agent given as sustained monotherapy was able to reduce blood pressure adequately, although nifedipine was better than captopril; and (iii) combination therapy with both agents was conspicuously successful in achieving reduction in blood pressure. It is suggested that combination nifedipine-captopril therapy be subject to a formal trial for early therapy in acute severe hypertension. Publication Types: 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 10 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 Clinical Trial Randomized Controlled Trial PMID: 1925820 [PubMed - indexed for MEDLINE] 7: Randomized controlled study;nifedipine-furosemide 可作為緊急降壓藥物,未發現不良反應 Rev Med Interna Neurol Psihiatr Neurochir Dermatovenerol Med Interna. 1989 Nov-Dec;41(6):529-38. [The treatment of hypertensive crisis with nifedipine as the basis] [Article in Romanian] Cristodorescu R, Bartha P, Dragan S, Nicolin M. In 48 patients (p) with hypertensive crisis (HC) the effect of nifedipine (N) sublingual 10-20 mg alone (group I, n = 19, mean control AH 15.3/132.5 SD 232 4.9 mmHg) or associated with furosemide and clonidine (group II, n = 29, AT 249 21/131.8 13.6 mmHg). In both groups the AT fell significantly starting five minutes after the administration of N (except diastolic AT in group II); the values measured at 45 min. being 177 13 mmHg in group I and 164.6 44.4/100.1 16.3 mmHg in group II (the mean proportional difference at 45 min. for systolic AT was 24.6 group I and 28.7 I, and 27 32/105.4 12.2% in group II; for diastolic AT 20.5 11.4% in 9.4% in group 12.2% for group II). The good clinical results consisted of lowering of the AT values below critical levels and clinical improvement in 42 p (87.5%). Tolerance to N was good, in a single case was hypotension associated with fainting, both being promptly treated by simple means. CONCLUSIONS. 1. N administered sublingual, 10-20 mg, alone or associated with furosemide has in most patients a rapid hypotensive effect, lowering AT below critical limits within 45 min; 2. the drug is readily administered and without the risk of side effects and can be used in the field in the emergency treatment of hypertension. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 2577015 [PubMed - indexed for MEDLINE] Clinical queriesPROGNOSIS中的文獻: 1: systematic reviews;探討 hypertensive emergency and urgency 的治療效果及預後,其搜尋資料庫為 medline from 1966 to 2001 及 Cochrane Library,對象包含 randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research。內容與搜尋 主題相符,且證據等及為以上文獻中最高,故選擇為期刊閱讀的主要文獻: J Gen Intern Med. 2002 Dec;17(12):937-45. (此篇文獻的證據等級 IIa) 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 11 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature. Cherney D, Straus S. Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. [email protected] BACKGROUND: Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined "safe" goal blood pressures (BPs), and to prevent adverse events. METHODS: medline was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. RESULTS: None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. CONCLUSIONS: Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 12 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit. Publication Types: Review PMID: 12472930 [PubMed - indexed for MEDLINE] III) 評判證據(critical appraisal) 請附上文獻全文,依據PICO問題的種類,選用適當之Users’ Guide,依照其設 計之問句,逐一回答,並標示出評判的重點處。以「Therapy」問題之文獻評論 為例: Management of Patients With Hypertensive Urgencies and Emergencies A Systematic Review of the Literature David Cherney, MD, Sharon Straus, MD, FRCPC BACKGROUND:Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined "safe" goal blood pressures (BPs), and to prevent adverse events. METHODS:MEDLINE was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. RESULTS:None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. CONCLUSIONS:Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit. Hypertensive urgencies and emergencies are common clinical occurrences that may account for as many as 27.5% of all medical emergencies presenting to the emergency department1 and 3% of all emergency room visits,2 and that may affect as many as 1% of hypertensive patients.3,4 However, clinical treatment practices for the management of hypertensive urgencies and emergencies vary considerably.1 This practice variability is in part because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies in terms of the agents' ability to reach a predetermined "safe" target blood pressure (BP) and to prevent adverse events. For this paper, we used the following definitions for hypertensive urgencies and emergencies, which were taken from the literature: in a hypertensive emergency, a patient has evidence of target end-organ damage, such as encephalopathy, unstable angina, stroke, or a dissecting aortic aneurysm. The absolute level of BP in this situation is not as important as 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 13 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 the evidence of end-organ damage.1 In hypertensive urgencies, the patient has elevated BP but has no evidence of end-organ damage. METHODS Go to: Choose Search Strategy We searched MEDLINE from 1966 to 2001 using the terms hypertensive urgency, hypertensive emergency, hypertensive crisis, uncontrolled hypertension, refractory hypertension, poorly responsive hypertension, poorly responsive blood pressure, and malignant hypertension. We also used search terms for finding systematic reviews.5 We then retrieved the references of all the articles and searched the bibliographies for additional relevant references. Experts in the field were contacted to identify any relevant studies. We also searched the Cochrane Library using the terms hypertension and malignant hypertension. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research, i.e., Level 1 or 2 evidence. We did not include any language restrictions in the literature search. Our study included all classes of antihypertensive agents. The agents could have been given via sublingual (SL), oral (PO), or parenteral (IV) routes, depending on the agent and the setting. The articles were appraised by 2 independent reviewers who assessed their level of evidence on the basis of the definitions that can be found in Table 1. Levels of evidence are useful in assessing the validity of evidence and in interpreting evidence. They have been designed to identify the specific methods that maximize the validity of a study's conclusions and structure them into a hierarchy of study types with the most valid at the forefront. 6 Only those articles with Level 1 or 2 evidence were included in this review. Number needed to treat (NNT) and relative risk (RR) calculations were performed using the Mount Sinai Hospital Center for Evidence Based Medicine statistics calculator7 and were included for comparative purposes. The NNT calculations were given, when possible, for the most effective agent in trials comparing more than 1 antihypertensive. The RR calculations were also performed, when possible, to give an estimate of the likelihood of the less-effective agent reaching the target BP. Study Participants Study participants were over the age of 18 years and had had a hypertensive emergency or urgency at the time of their enrollment in the study. Exclusion criteria were varied and included the very elderly (>80 years old), 8,9 pregnancy and lactation,8 19 history of organ transplantation,8,17 immunosuppression,17 19 acute8,9,17,18 or chronic renal failure,8,11,12,17,18,20 dialysis,17 19 valvular heart disease,11,12,14,21 recent stroke,11,12,14,21,22 acute myocardial infarction,9,11,12,14 16,21 coronary bypass surgery or congestive heart failure,11,12"bilateral stenosis"9 or arrhythmia,15 20 or a known secondary cause of hypertension such as pheochromocytoma.8,17 19 Other exclusion criteria included hypothyroidism,19 hepatic14,15,17 19 or hematological disease,14,17,18 asthma or chronic obstructive pulmonary disease,16 alcohol intoxication,12 parenteral analgesia,17,18 dopamine antagonists17 19 or "considerable pain."13 Patients with signs of end-organ involvement were excluded in the hypertensive urgency studies. Signs of end-organ involvement (acute myocardial infarction, aortic dissection, and focal neurological deficits) aside from hypertensive changes in the retina were exclusion criteria in 1 study of hypertensive emergencies. 10 RESULTS Go to: Choose Six hundred hypertensive urgency or hypertensive emergency abstracts were identified in the literature. Most of these studies were excluded because they were nonhuman studies, did not involve patients with high enough BP to qualify as an urgency or an emergency, were safety/tolerability studies, or were case-series or case reports. We were left with 39 studies after excluding all of the above. Ten studies were then excluded because they did not include a target BP and were therefore of limited usefulness to clinicians and could not be compared to other agents in terms of NNT or RR. Other studies were excluded because they were methodologically flawed in their randomization (5 studies) or because the target BP was arbitrarily described as an appropriate target BP according to the treating physician (1 study). Methodologically flawed RCTs were excluded because they were of a lower quality and level of evidence compared to some of the well-designed cohort studies that we evaluated. Other reasons for exclusion were that the study involved nonpharmacological interventions (e.g., coffee and cigarette smoking or concurrent hemodialysis)2 or that the study was a follow-up of patients who had already been treated for a hypertensive emergency or urgency1 or who had had a run-in period with other drugs (1 study), making the interpretation of the results very difficult in terms of the drug of interest. Nineteen trials met the criteria for Level 1 or 2 evidence. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. Eight of the 19 trials included in this review were open label or did not mention if the trial was blinded. 8 10,16,17,19,23,24 We included these studies because they met our review's inclusion of Evidence Level 1 or 2. In addition, the number of studies of this quality is limited and the further exclusion of studies would further limit the conclusions of this review. The definitions of hypertensive emergencies and urgencies did vary in the studies with respect to specific BP measurements, but emergencies always involved hypertension with target end-organ damage, and urgencies without such damage. Moreover, measures of outcome were not uniform between studies. Some studies used the diastolic blood pressure (DBP) as the endpoint to indicate success, and either used a specific blood pressure (usually 95 to 110 mm Hg),8 a percentage reduction in 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 14 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 blood pressure20 or a numeric (20 mm Hg)13,20 fall in the DBP. Fewer studies used the systolic blood pressure (SBP) as the goal. Many of the studies included in this review used adverse effects as outcome measures as well. None of the studies used immediate or long-term mortality endpoints. In addition, in the hypertensive emergency studies, resolution of end-organ dysfunction did not figure prominently as outcome measures in all the studies. Treatment for Hypertensive Emergencies We were unable to identify any prospective studies that addressed the questions of how quickly BP should be controlled in a hypertensive emergency or when maintenance therapy with antihypertensive medications should begin. We identified 3 small, level 2b trials and one level 1b trial that compared various therapies in patients with hypertensive emergencies (Table 2).8,10,21,23 Each of the 3 level 2b trials used different entry criteria. One study included patients with increased SBP and/or increased DBP and any evidence of target end-organ damage.8 They found that nitroprusside led to a faster response (49%) than did urapidil (20%) in the first 15 minutes of therapy (P< .001). However, due to the short half-life of nitroprusside, this difference was not seen at 4 hours.8 Nitroprusside was associated with more adverse side effects, including 2 episodes of hypotension, although none of them was associated with clinical sequelae (23% vs 11%; P< .04). In addition, nitroprusside requires invasive monitoring. Another study included patients with an elevated DBP and hypertensive retinopathy and found that nitroprusside achieved the target BP more slowly than did nifedipine, 10 while a third study included patients with DBP >120 mm Hg but did not provide explicit information about target organ damage. 23 This last study looked at 120 patients who were randomized to 1 of 4 treatment groups including: 10 mg nifedipine SL; 50 mg captopril SL; 0.15 mg clonidine IM; or 10 mg nifedipine SL and 40 mg furosemide IV. No significant blood pressure differences were found between the 4 groups after treatment. The last study, by Angeli et al., found that 7 of 10 patients treated with captopril or 5 of 10 treated with nifedipine were complete responders (not significant).21 This study also found that the duration of action for the 2 drugs was similar. Treatment for Hypertensive Urgencies We were unable to identify any high-quality studies that addressed what blood pressure defines a hypertensive urgency, how quickly blood pressure should be decreased in a hypertensive urgency, when maintenance therapy should be started, or whether patients with hypertensive urgencies should be treated in observed settings. We found 15 prospective trials representing levels 1b and 2b evidence that addressed therapy in patients with hypertensive urgencies (Table 3). Although many of these studies defined hypertensive urgencies differently, the most consistently used definition was a DBP of >120 mm Hg. Methodological problems in the trials included small sample size, 11,13,14,16,25 open label design,9,16,17,19,24 lack of follow-up in most of the studies, and contamination.14 In addition, few studies looked at outcomes more than 24 hours after randomization, and follow-up ranged from only 15 minutes to 1 week. Moreover, the trials used various definitions of "therapeutic response" and none looked at long-term blood pressure control or important cardiovascular endpoints. In one study comparing nicardipine to placebo, nicardipine therapy led to effective blood pressure control in 65% of patients compared to 22% of patients in the placebo group (P = .002).26 This is one of the few therapies that have been evaluated in a randomized control trial, and demonstrated statistical superiority over placebo. 26 In another study, nifedipine was more effective at lowering the SBP at 30 minutes when compared with captopril, clonidine, and furosemide (P< .02), but this difference was no longer seen after 30 minutes.11 Three dosage regimens of labetalol were compared in another study and differed only in their response at 2 hours, when the 200-mg dose was associated with significantly less tachycardia than either the 100-mg or 300-mg doses.20 In a study comparing long- and short-acting calcium channel blockers, long-acting lacidipine was more effective than nifedipine at keeping the blood pressure controlled at 24 hours (P = .001).25 In addition, 1 patient had a stroke syndrome 30 minutes after taking nifedipine (see Table 3). When compared with clonidine, nifedipine controlled blood pressure significantly more quickly.12 In a study by Rutledge et al., enalaprilat was significantly better at reducing blood pressure than placebo in the moderate hypertension group defined arbitrarily as a DBP of 100 to 114 mm Hg. 14 Interestingly, 58% of patients assigned to the placebo group responded to hospitalization and no active medications. When enalaprilat was compared with furosemide, the 2 agents did not differ in terms of efficacy. Hirschl et al. showed that urapidil had a significantly higher rate of response when compared with nifedipine after a single dose, (92% vs 70%; P< .04). This response was 100% and 50%, in the urapidil and nifedipine groups, respectively, after a second dose in those patients who did not respond to the first dose. 24 In addition, urapidil was associated with a shorter stay in the emergency room (83 vs 113 minutes; P< .05). The studies that compared oral nifedipine with oral labetalol, and oral nifedipine with oral nitrendipine found the agents to be of similar efficacy.15,16 In the 3 studies that examined fenoldopam in comparison to nitroprusside, the drugs were of comparable efficacy and all resulted in the achievement of the target BP in either the initial infusion phase or the maintenance phase (depending on the trial).17 19 The agents also had similar adverse event profiles. Nitroprusside was found to have an accumulation of thiocyanate metabolites, but did not result in clinical toxicity. 19 In the study by Hirschl et al.,9 urapidil was found to be almost uniformly successful when compared to the 70% to 72% response rates in the nifedipine or enalaprilat groups (NNT for urapidil of 4). In addition, the RR for nifedipine or enalaprilat to 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 15 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 reach the target BP compared to urapidil was significantly less than 1. One nifedipine patient in this study had a transient ischemic attack (TIA). In the study by Wallin et al., the second placebo-controlled trial involving nicardipine concluded that the drug is a more successful antihypertensive than placebo,22 but this study involved both hypertensive urgencies and emergencies, as opposed to the study by Habib et al., which involved only hypertensive urgencies. 26 DISCUSSION Go to: Choose After reviewing all of the available evidence, the best choice of hypertensive agent in urgencies and emergencies remains unclear. In emergencies, the most desirable NNT is for urapidil,8 although nitroprusside, captopril, and clonidine are likely acceptable choices as well. Comparing nitroprusside and urapidil with captopril and clonidine is difficult because no head-to-head studies have ever been done with these agents. Hypertensive urgencies can also be treated with a variety of agents, including nicardipine, 26 lacidipine,25 and urapidil,9 and nitroprusside or fenoldopam,17 19 which have the most favorable NNT profiles. Nifedipine can be used, but has rapid blood pressure–lowering properties that are not necessary in this nonemergent situation. This agent therefore shouldn't be used in the treatment of urgencies. In addition, nifedipine was associated with a TIA in 2 hypertensive urgency studies, 9,25 and has been implicated by others as a cause of cardiovascular morbidity and mortality. 27 No other antihypertensive agent in the studies we reviewed was associated with this complication. This association has been debated in medical literature and is still of uncertain significance.28,29 These recommendations must be viewed with caution and are meant to show what is known, and what is not known, about hypertensive urgencies and emergencies. The studies included in this review have many limitations. First, tremendous variation and inconsistency exists in the definitions and cutoffs for urgencies and emergencies and for target blood pressures. Second, long-term outcomes were not well studied, and important clinical outcomes were often not measured. Third, studies were often underpowered, leading to wide confidence intervals with respect to treatment efficacy. Further, as demonstrated in Tables 2 and 3, the confidence intervals were so wide that they gave both NNT and number of patients needed to harm (NNH) data, indicating that the various agents may have either harmed or benefited patients. In addition, the small numbers of patients in the studies limited their power to detect differences in mortality and morbidity, and may also account for some of the inconsistencies found in the results. Finally, the reporting of adverse effects was not consistent, making comparison of adverse effects difficult (Tables 2 and 3), and the small study sizes may also have limited the ability to detect important differences in adverse effect profiles. When faced with hypertensive urgencies and emergencies, the clinician has to not only select an appropriate antihypertensive agent but also assess how rapidly the blood pressure must be lowered. Unfortunately, the literature does not have data to support one timetable over another. Therefore, clinical judgement must be used in order to set a goal for the rate of decline of blood pressure, as well as for the target blood pressure. Clinical practice guidelines for the management of hypertensive emergencies suggest that the mean arterial blood pressure be reduced by ≤25% within 2 hours and to 160/100 mm Hg by 6 hours.30 32 In hypertensive urgencies, the goal blood pressure should be achieved over hours to days. Avoiding excessive reductions in blood pressure is advised because this can precipitate renal, cerebral, or coronary ischemia. 9,25 Frequent monitoring of blood pressure response to treatment (every 15 to 30 minutes) is also recommended. As some authors have pointed out,8 the rate of blood pressure lowering should be considered in the context of the patient's clinical condition, and does have clinical significance; patients with an aortic dissection, for example, require more rapid blood pressure control, 33 35 compared to a patient with a hypertensive emergency and cerebrovascular symptoms, where a sudden drop in blood pressure might be dangerous. Finally, many important questions remain unanswered. Future studies need to be consistent with respect to their operational definitions and cutoffs for urgencies and emergencies and for target blood pressures. This may serve as a better guide for clinicians. Second, studies need to follow patients over a period of time long enough to gather outcome data, such as cardiovascular morbidity and mortality, reduction in the number of hospitalizations, and length of stay information. The studies included in this review are of limited value because they use the surrogate endpoint of blood pressure control. Third, it remains unknown as to when patients with hypertensive crises should start maintenance therapy after initial blood pressure control is accomplished in the emergency room. Another issue that has not been explored is how quickly the blood pressure should be lowered in this context. Finally, none of the studies we reviewed evaluated which patients should be admitted to the hospital and for how long, and which patients should be managed as outpatients. In addition, it is unclear whether these patients can be triaged outside of the emergency department in such settings as physicians' offices or over the phone. We believe that there is more research to be done in this area, and hope that future collaborative, multicenter, randomized double-blind controlled trials will be performed to address these issues. REFERENCES 1. Go to: Choose Kitiyakara C, Guzman N. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol. 1998;9: 133–42. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 16 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 2. Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P. Hypertensive urgencies and emergencies. Prevalence and clinical presentation. Hypertension. 1996;27: 144–7. 3. Kincaid-Smith P, McMichael J, Murphy EA. The clinical course and pathology of hypertension with papilloedema (malignant hypertension). QJM. 1958;37: 117–53. 4. Bechgaard P, Kopp H, Neilson J. One thousand hypertensive patients followed from 16–22 years. Acta Med Scand. 1956;312(suppl): 175–83. 5. Haynes RB, Wilczynski C, McKibbon A, Walker C, Sinclair J. Developing optimal search strategies for detecting clinically sound studies in MEDLINE. J Am Med Inform Assoc. 1994;1: 447–58. 6. Sackett DL, Straus S, Richardson WS, Rosenberg W, Hagro RB. Evidence-Based Medicine. How to Practice and Teach Evidence-Based Medicine. 2nd ed. London: Churchill Livingston; 2000. 7. Mount Sinai Hospital-University Health Network. 2000. Centre for Evidence Based Medicine: NNT Tables. Available at: http://www.mtsinai.on.ca/masterframe.html. Accessed April 12, 2001. 8. Hirschl MM, Binder M, Bur A, et al. Safety and efficacy of urapidil and sodium nitroprusside in the treatment of hypertensive emergencies. Intensive Care Med. 1997;23: 885–8. 9. Hirschl MM, Seidler D, Zeiner A, et al. Intravenous urapidil versus sublingual nifedipine in the treatment of hypertensive urgencies. Am J Emerg Med. 1993;11: 653–6. 10. Franklin C, Nightengale S, Mambani B. A randomized comparison of nifedipine and sodium nitroprusside in severe hypertension. Chest. 1993;90: 500–3. 11. Komsuoglu B, Sengun B, Bayram A, Komsuoglu SS. Treatment of hypertensive urgencies with oral nifedipine, nicardipine, and captopril. Angiology. 1991;42: 447–54. 12. Jaker M, Atkin S, Soto M, Schmid G, Brosch F. Oral nifedipine vs. oral clonidine in the treatment of urgent hypertension. Arch Intern Med. 1989;149: 260–5. 13. Zeller KR, Kuhnert LV, Matthews C. Rapid reduction of severe asymptomatic hypertension: a prospective, controlled trial. Arch Intern Med. 1989;149: 2186–9. 14. Rutledge J, Ayers C, Davidson R, et al. Effect of intravenous enalaprilat in moderate and severe hypertension. Am J Cardiol. 1988;62: 1062–67. 15. Rohr G, Reimnitz P, Blanke P. Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules. Intensive Care Med. 1994;20: 268–71. 16. McDonald AJ, Yealy DM, Jacobson S. Oral labetalol vs. oral nifedipine in hypertensive emergencies in the emergency department. Am J Emerg Med. 1993;11: 460–3. 17. Panacek EA, Bednarczyk EM, Dunbar LM, Foulke GE, Holcslaw TL. Randomized, prospective trial of fenoldopam vs. sodium nitroprusside in the treatment of acute severe hypertension. Acad Emerg Med. 1995;2: 959–65. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 17 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 18. Pilmer BL, Green JA, Panacek EA, et al. Fenoldopam mesylate versus sodium nitroprusside in the acute management of severe systemic hypertension. J Clin Pharmacol. 1993;33: 549–53. 19. Reisin E, Huth M. Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension. Hypertension. 1990;15(suppl I):I59–I62. 20. Gonzalez ER, Peterson MA, Racht EM, Ornato JP, Due DL. Dose-response evaluation of oral labetalol in patients presenting to the emergency department with accelerated hypertension. Ann Emerg Med. 1991;20: 333–8. 21. Angeli P, Chiesa M, Caregaro L, et al. Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial. Arch Intern Med. 1991;151: 678–82. 22. Wallin JD, Fletcher E, Ram CV, et al. Intravenous nicardipine for the treatment of severe hypertension: a double-blind, placebo-controlled multicenter trial. Arch Intern Med. 1989;149: 2662–9. 23. Pascale C, Zampaglione B, Marchisio M. Management of hypertensive crisis: nifedipine in comparison with captopril, clonidine and furosemide. Curr Ther Res. 1992;51: 9–18. 24. Hirschl MM, Seidler D, Mullner M, et al. Efficacy of different antihypertensive drugs in the emergency department. J Human Hypertension. 1996;24: 1684–9. 25. Sanchez M, Sobrino J, Ribera L, Adrian AJ, Torres M, Coca A. Long-acting lacidipine versus short-acting nifedipine in the treatment of acute asymptomatic acute blood pressure increase. J Cardiovasc Pharmacol. 1999;33: 479–84. 26. Habib GB, Dunbar LM, Rodrigues R, Neale AC, Friday KJ. Evaluation of the efficacy and safety of oral nicardipine in the treatment of urgent hypertension: a multicenter, randomized, double-blind, parallel, placebo-controlled trial. Am Heart J. 1995;129: 917–23. 27. Psaty BM, Guralnik JM, Corti MC, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995;274: 620–5. 28. Epstein M. Calcium antagonists should continue to be first-line treatment of hypertension. Arch Intern Med. 1995;155: 2150–6. 29. Messerli FH. Case-control study, meta-analysis and bouillabaisse: putting the calcium antagonist scare into context. Ann Intern Med. 1995;123: 888–9. 30. Ramsay LE, Williams B, Johnston GD, et al. for the British Hypertension Society. Guidelines for the management of hypertension: report of the Third Working Party of the British Hypertension Society. J Hum Hypertens. 1999;13: 569–92. 31. Feldman RD, Campbell N, Larochelle P, et al. for the Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension. 1999 Canadian recommendations for the management of hypertension. CMAJ. 1999;161(suppl 12):1–17. 32. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension. Arch Intern Med. 1997;157: 2413–46. 33. DeSanctis RW, Doroghazi RM, Austen WG. Aortic dissection. N Engl J Med. 1987;317: 1060–7. 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 18 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 34. Crawford ES. The diagnosis and management of aortic dissection. JAMA. 1990;264: 2537–41. 35. Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22: 1642–81. CRITICAL REVIEW FORM FOR SYSTEMATIC REVIEW Citation: ____________________________________________________________________ GUIDE COMMENTS I. Are the Results Valid? 1. Did this review address a focused clinical question? 2. Were the criteria for article inclusion appropriate? 是的,本文章旨在探討 hypertensive emergency and hypertensive urgency 的治 療,是否有最合適的藥物及降壓目標,以及造成的副作用。 所收錄關於 hypertensive emergency and hypertensive urgency 的治療及 結果文章種類包括 systematic reviews of randomized control trials (RCTs), individual RCTs, all-or-none studies, systematic reviews of cohort studies,and individual cohort studies, and outcomes research,也就是 Level 1 or 2 evidence. 3. Is it unlikely that relevant studies were missed? 4. Was the validity of the included studies appraised? 所搜尋範圍是 MEDLINE from 1966 to 2001 關鍵字(hypertensive urgency, hypertensive emergency, hypertensive crisis, uncontrolled hypertension, refractory hypertension, poorly responsive hypertension, poorly responsive blood pressure, and malignant hypertension)還有 Cochrane Library 關鍵字(hypertension and malignant hypertension)。此外也從以上 所取得文章的 references 和 bibliographies 找尋可供參考文獻,並由相關 領域中的專家們提供相關的研究。搜尋過程中並未使用語言限制。各種類 的降血壓藥物不論是 sublingual (SL), oral (PO), or parenteral (IV) 使用的 都在包含範圍之內。所以對於此一主題的包含度應該是相當足夠。 所取得的文獻由兩位獨立的 reviewer 進行 critical appraisal,文獻種類與證 據等級的相關為: Level of Evidence Study Design 1a Systematic review of RCTs 1b Individual RCT 1c All or none6,* 2a Systematic review of cohort studies 2b Individual cohort study 2c Outcomes research6, 3a Systematic review of case control study 3b Individual case control study 4 Case series 5 Expert opinion, consensus meeting 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 19 - 財團法人彰化基督教醫院 PBL/EBM 臨床教學紀錄單 5. Was the assessments of 由兩位獨立的 reviewer 進行 critical appraisal 即是。 studies reproducible? 6. Were the results similar from study to study? 雖然所收錄文章均是探討 hypertensive emergency and urgency 的治療, 但由於各篇文章所比較的藥物不盡相同,因此難以比較。所使用藥物與 placebo 相比都呈現有意義的治療差異。個別藥物間的藥效,速度,持久在 文章間互不衝突的原因實是因為所比較藥物的組合不同所致。 II. What Are the Results? 1. What are the overall results of the review? 在 hypertensive emergencies 的治療方面,NNT 的表現最好的是 urapidil,但 nitroprusside, captopril, clonidine 也都是可接受的藥物。 而對於 Hypertensive urgencies 可使用的藥物包括 nicardipine,lacidipine, urapidil, nitroprusside, fenoldopam. 但 Nifedipine 降壓的速度過快,並不 適合使用在 hypertensiveurgency 這種不需如此快速降壓的情況下。 但最好的單一藥物,降壓速度,和降壓目標仍然是未知,此外長期 outcome 也因為追蹤時間過短,因此沒有有力的說法。 2. How precise are the results? 並未提供個別藥物的 confidence interval,因沒有做 metaanalysis III. Will the Results Help Me In My Patient Care? 1. Can the results be applied to my patients? 2. Were all clinically important outcomes considered? 3. Are the benefits worth the harms and costs? References: 研究對象為 18 歲以上的 hypertensive emergency or urgency 病人。 Exclusion criteria 包括 very elderly (>80 years old), pregnancy and lactation, history of organ transplantation, immunosuppression, acute or chronic renal failure, dialysis, valvular heart disease, recent stroke, acute myocardial infarction, coronary bypass surgery or congestive heart failure,bilateral stenosis or arrhythmia, or a secondary cause of hypertension 如 pheochromocytoma。雖然未 提及人種,但與病房所遇到病人情境相似,一般情況下可以套用。但我的這個病例 是 96 歲高齡女性,已經超過了研究的年齡限制,因此 grade of recommendation 需另做考量。 並不是所有的收錄文章都有提到。大部分的文章以舒張壓低於 120mmHg 或下降某個固定數值的血壓或某個百分比的血壓為治療成功的定義。但因 為追蹤時間只有 15 分鐘到一個禮拜,因此對於心血管系統的長期影響沒有 說明。 所用的治療藥物都能有意義的降低血壓,但如前所述因為追蹤時間的不 足,沒有長期 outcome 的統計,因此治療的建議停留在以往教科書的內容。 但使用 nifedipine 治療的病患有兩例發生腦缺血液外,對冠狀血流降低的威 脅都告訴我們 adalat 不該使用在這種情況之下。 JAMA 1994; 272: 1367-1371 彰化市南校街 135 號.彰化基督教醫院(http://www.cch.org.tw).TEL:886-4-7238595 135 Nan-Shaou strest, Changhua, Taiwan, ROC - 20 -