Salpeter S, Ormiston T, Salpeter E
Department of Medicine, Santa Clara Valley Medicial Center, 2400 Moorpark Ave., Suite 118, San Jose, CA 95128, USA.
Cochrane Database Syst Rev. 2001;2002(2):CD002992. doi: 10.1002/14651858.CD002992.
Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.
To assess the effect of cardioselective beta-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component.
A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to February, 2000. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language.
Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta-agonist administration, or the presence of asthma as defined by the American Thoracic Society.
Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta-agonist given after the study drug.
Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta-agonist response compared to placebo, a response not seen with beta-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]).
REVIEWER'S CONCLUSIONS: Cardioselective beta-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be withheld from patients with mild-moderate reversible airway disease.
β受体阻滞剂治疗对高血压、心力衰竭和冠心病患者以及围手术期患者具有降低死亡率的益处。传统上,这些药物被认为是可逆性气道疾病患者的禁忌药。
评估心脏选择性β受体阻滞剂对可逆性气道疾病患者呼吸功能的影响。可逆性气道疾病定义为哮喘或具有可逆性阻塞成分的慢性阻塞性肺疾病。
使用Cochrane气道组注册库对EMBASE、MEDLINE和CINAHL进行全面检索,以识别1966年至2000年2月期间的随机双盲安慰剂对照试验。检索使用的术语为:哮喘*、支气管高反应性*、呼吸音*、哮鸣*、阻塞性肺疾病或阻塞性气道疾病,以及肾上腺素能拮抗剂*、抗交感神经药或肾上腺素能受体阻滞剂。我们没有基于语言排除试验。
研究心脏选择性β受体阻滞剂对可逆性气道疾病患者一秒用力呼气量(FEV1)、症状和短效吸入β受体激动剂使用情况影响的单剂量或更长疗程的随机、双盲、安慰剂对照试验。可逆性气道疾病通过对乙酰甲胆碱激发试验的反应、给予β受体激动剂后FEV1至少增加15%或根据美国胸科学会定义的哮喘的存在来记录。
两名独立的审阅者从选定的文章中提取数据,通过协商一致解决差异。心脏选择性β受体阻滞剂分为两组,即有或无内在拟交感活性(ISA)的药物。研究的两种干预措施是给予β受体阻滞剂,单次给药或更长疗程给药,以及在研究药物后使用β受体激动剂。
19项单剂量治疗研究和10项更长疗程治疗研究符合入选标准。患者有轻度至中度气道阻塞。作为一个整体的心脏选择性β受体阻滞剂,与安慰剂相比,单次给药导致FEV1降低7.98%(95%CI,6.19%至9.77%),但β受体激动剂反应增加13.16%(95%CI,10.76%至15.56%)。症状没有增加。在持续数天至数周的治疗后,与安慰剂相比,FEV1没有下降,症状或吸入器使用也没有增加。与安慰剂相比,定期使用无ISA的心脏选择性β受体阻滞剂使β受体激动剂反应增加13.13%(95%CI,5.97%至20.30%),而含ISA的β受体阻滞剂未见此反应(-0.60%[95%CI,-11.7%至+10.5%])。
给予轻度至中度可逆性气道疾病患者心脏选择性β受体阻滞剂,短期内不会产生具有临床意义的不良呼吸影响。对于病情更严重或可逆性更差的患者,以及它们对急性加重的频率或严重程度的影响,无法进行评论。鉴于它们在心力衰竭、冠心病和高血压等疾病中已证明的益处,不应拒绝给予轻度至中度可逆性气道疾病患者心脏选择性β受体阻滞剂。