자궁외임신의 보존적 치료제로 Methotrexate의치료에 관한 임상 지침
Clinical Guidelines for Methotrexate in Conservative Treatment for Ectopic Pregnancy
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목적: MTX를 이용한 자궁외임신 치료 방법에 관하여, 환자 선택 기준과 실제적으로 필요한 치료 용량, 치료 예후 등 임상의가 보다 효과적으로 치료를 시도할 수 있는 지침을 마련하고자 함이다. 연구 방법: 2000년 1월부터 2004년 12월까지 본원에서 자궁외임신 진단 하에 전신적 MTX 요법으로 치료받은 환자 54명의 진료 기록을 후향적으로 분석하였다. MTX 1.0 mg/kg과 leucovorin 0.1 mg/kg을 1회에서 4회까지 번갈아 근주하였고 치료 시작 3일과 7일째, 이후 1주 간격으로 혈청 β-hCG의 변화를 추적 관찰하였다. 결과: 50명 (92.6%)에서 치료에 성공하였고, 4명 (7.4%)은 MTX 치료에 실패하여 수술적 중재가 필요하였는데, 실패군은 성공군에 비해 자궁내막 두께가 유의하게 증가되어 있었고 (14.3±4.0 mm vs 7.0±2.8 mm, p=0.0001), 혈색소치의 유의한 감소 변화를 보였다 (2.1±0.9 g/dL vs 1.0±0.8 g/dL, p=0.044). 정확한 진단을 위해 2일 간격으로 연속적인 혈청 β-hCG의 정량 측정을 시행한 환자에서 β-hCG 증가군에 비해 감소군은 혈청 β-hCG 치가 정상으로 회복되는데 경과된 시간이 유의하게 짧았다 (27.6±14.0 vs 17.7±8.6, p=0.016). MTX 치료 시작 3일에 측정한 β-hCG 농도가 오히려 증가한 8명 (15.1%) 모두 7일에는 β-hCG의 급격한 감소를 보여 성공적으로 치료가 종결되었다. 성공적인 치료에 필요했던 MTX의 용량을 근주 횟수별로 분류하였을 때, 치료 시작시의 β-hCG 농도가 높을수록 근주 횟수와 투여량이 유의하게 증가하였다 (p=0.021). 부작용은 12%에서 나타났으나 경미하여 곧 회복되었다. 치료 후 정상 임신에 성공하였거나 자궁난관조영술에 의해 난관의 소통을 확인한 예는 70%였다. 결론: 임상적으로 안정되어 있는 자궁외임신 환자에서 전신적 MTX 요법은 안전하고 효과적인 치료이며 투여 용량과 근주 횟수는 초기 혈청 β-hCG 농도에 따라 정해져야 한다.
Abstract
Objective: To provide more useful guidelines for methotrexate (MTX) treatment in ectopic pregnancy, including patient selection, therapeutic dose, and reproductive outcome. Methods: Retrospectively, records of 54 patients treated for ectopic pregnancy with systemic MTX were reviewed. MTX was administered 1.0 mg/kg intramuscularly, alternatively with leucovorin 0.1 mg/kg intramuscularly for up to four daily doses of each drug. Samples for β-hCG detection were obtained on days +3, +7 after beginning of the therapy and then weekly until values were undetectable. Results: 50 patients (92.6%) were treated successfully. 4 patients (7.4%) for whom MTX therapy failed, were treated surgically. The endometrial thickness significantly increased in the failed group, compared to the successful group (14.3±4.0 mm vs 7.0±2.8 mm, P=0.0001). The serum hemoglobin levels significantly changed in the failed group, compared to the successful group (2.1±0.9 g/dL vs 1.0±0.8 g/dL, P=0.044). Patients were divided into increasing group and decreasing group according to β-hCG levels on day 0, that were higher or lower than day -2 level. The resolution time of β-hCG between increasing group and decreasing group was significantly different (27.6±14.0 days vs 17.7±8.6 days, p=0.016). In 8 patients (15.1%), an immediate rise of β-hCG was recorded on day 3 after MTX treatment, but on day 7, a rapid decrease was recorded. Women were treated with significantly different therapeutic dose of MTX according to initial level of serum β-hCG (p=0.021). There were mild complications (12%). MTX treatment preserved the fallopian tube and thus preserved fertility (70%). Conclusion: Systemic MTX use with the dose according to initial level of serum β-hCG is a safe and highly effective treatment in clinically stable ectopic pregnancy.
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