Lund J N, Scholefield J H
Department of Surgery, University Hospital, Nottingham, UK.
Lancet. 1997 Jan 4;349(9044):11-4. doi: 10.1016/S0140-6736(96)06090-4.
Anal fissure is most commonly treated surgically by internal anal sphincterotomy. However, there is some concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate (GTN) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases. This study reports a prospective, randomised, double-blind, placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure.
80 consecutive patients were randomised to receive treatments with topical 0.2% GTN ointment or placebo. Maximum anal resting pressure (MARP) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment. Anodermal blood flow was measured during manometry by laser Doppler flowmetry. After initial treatments, patients were given a supply of ointment (either GTN or placebo) to be applied to the lower anal canal twice daily. Patients were reviewed 2-weekly. At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score. Endpoints were healing of the fissure or condition after 8 weeks of treatment.
After 8 weeks, healing was observed in 26/38 (68%) patients treated with GTN and in 3/39 (8%) patients treated with placebo (p < 0.0001, chi 2 test). Linear analogue pain score fell significantly in both groups after 2 weeks of treatment. This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo. MARP fell significantly from a mean of 115.9 (SD 31.6) to 75.9 (30.1) cm H2O (p < 0.001, Student's paired t-test) in patients treated with GTN but no change was seen in MARP after placebo. Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo.
Topical GTN provides rapid, sustained relief of pain in patients with anal fissure. Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing. Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN.
肛裂最常见的手术治疗方法是内括约肌切开术。然而，人们对该手术对控便功能的影响存在一些担忧。一氧化氮供体，如硝酸甘油（GTN），已被证明能在一小系列病例中引起可逆性化学性括约肌切开术，从而治愈肛裂。本研究报告了一项前瞻性、随机、双盲、安慰剂对照试验，以检验局部使用GTN是慢性肛裂最佳一线治疗方法这一假设。
80例连续患者被随机分为接受局部使用0.2% GTN软膏或安慰剂治疗。在首次涂抹试验软膏前后，使用持续灌注侧孔导管测量最大肛管静息压（MARP）。在测压过程中，通过激光多普勒血流仪测量肛管皮肤血流。初始治疗后，给予患者一批软膏（GTN或安慰剂），每天两次涂抹于肛管下段。每两周对患者进行复查。在初始和随访就诊时，要求患者在线性模拟疼痛评分上记录排便时的疼痛情况。终点指标是治疗8周后肛裂愈合或病情改善。
8周后，接受GTN治疗的38例患者中有26例（68%）愈合，接受安慰剂治疗的39例患者中有3例（8%）愈合（p<0.0001，卡方检验）。治疗2周后，两组的线性模拟疼痛评分均显著下降。接受GTN治疗的患者疼痛评分下降得以维持，但接受安慰剂治疗4周后，疼痛评分恢复到治疗前水平。接受GTN治疗的患者MARP从平均115.9（标准差31.6）显著降至75.9（30.1）cm H2O（p<0.001，配对t检验），而接受安慰剂治疗后MARP未见变化。应用GTN软膏后，通过激光多普勒血流仪测量的肛管皮肤血流显著增加，但不受安慰剂影响。
局部使用GTN能迅速、持续缓解肛裂患者的疼痛。以这种方式治疗的患者中有超过三分之二避免了原本愈合所需的手术。需要进行长期随访以评估接受GTN治疗患者肛裂复发的风险。
