Kongragunta V R, Druz W S, Sharp J T
Department of Medicine, Hines VA Hospital.
Am Rev Respir Dis. 1988 Mar;137(3):662-7. doi: 10.1164/ajrccm/137.3.662.
This study sought answers to 2 questions: (1) Is severe dyspnea to the point of exhaustion regularly accompanied by diaphragmatic fatigue in patients with moderately severe chronic obstructive pulmonary disease (COPD)? (2) When diaphragmatic fatigue occurs in such patients, does theophylline prevent or delay its onset? Eight eucapnic patients with moderately severe COPD were subjected to 2 different stresses to the point of severe dyspnea requiring cessation of the stress. The stresses were cycle exercise and inspiratory resistive breathing, the latter requiring a tidal Pdi equal to 60% of Pdimax. Despite incapacitating dyspnea, objective evidence of diaphragmatic fatigue was not encountered during cycle exercise. During inspiratory resistive breathing, diaphragmatic fatigue was encountered in all patients as defined by consistent inability to attain a target Pdi during final moments of the resistance run. Patients were uniformly extremely dyspneic at this point. In neither stressful maneuver did oral sustained-release theophylline show a convincing or significant advantage over placebo when administered in a randomized double-blind crossover protocol. These results suggest that the diaphragmatic fatigue encountered in this sort of COPD patient may be of predominantly central rather than peripheral (myogenic) origin and that theophylline may not be effective in this type of fatigue.
（1）中重度慢性阻塞性肺疾病（COPD）患者出现严重呼吸困难至疲惫不堪时，是否经常伴有膈肌疲劳？（2）此类患者出现膈肌疲劳时，茶碱能否预防或延缓其发作？八名中度COPD的等碳酸血症患者承受两种不同的应激直至出现严重呼吸困难而需要停止应激。应激方式为循环运动和吸气阻力呼吸，后者要求潮气量时的跨膈压（Pdi）等于最大跨膈压（Pdimax）的60%。尽管出现了使人丧失能力的呼吸困难，但在循环运动期间未发现膈肌疲劳的客观证据。在吸气阻力呼吸期间，所有患者均出现了膈肌疲劳，定义为在阻力运动的最后时刻持续无法达到目标Pdi。此时患者均极度呼吸困难。在随机双盲交叉试验方案中，口服缓释茶碱在两种应激操作中均未显示出比安慰剂有令人信服的或显著的优势。这些结果表明，此类COPD患者出现的膈肌疲劳可能主要源于中枢而非外周（肌源性），并且茶碱可能对此类疲劳无效。
