Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Minerva Anestesiol. 2011 Jul;77(7):723-33.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）与气体交换受损、严重炎症和包括细胞死亡在内的肺泡损伤有关。ALI 或 ARDS 患者通常会出现呼吸衰竭，因此需要机械通气支持，而机械通气本身可能会加重肺损伤。该领域的最新进展揭示了几种可改善气体交换、提高生存率和最小化机械通气有害影响的治疗策略。其中的策略包括降低潮气量并允许通气期间发生高碳酸血症，或主动诱导高碳酸血症。在这里，我们概述了高碳酸血症和通常随之而来的高碳酸酸中毒，以及高碳酸血症和酸中毒在 ALI 的临床研究和实验模型中的治疗效果。具体而言，我们综述了高碳酸血症和酸中毒对肺炎症衰减、肺泡上皮细胞凋亡减少、脓毒症诱导的 ALI 改善以及对其他器官系统的治疗效果的影响，以及这些策略的潜在有害影响。高碳酸血症和高碳酸酸中毒的临床意义尚不完全清楚。然而，未来的研究应集中在介导 ALI 发展的细胞内信号通路，可能侧重于活性生物物质在 ALI 发病机制中的作用。未来的研究还可以阐明高碳酸血症和高碳酸酸中毒如何通过这些途径来减轻肺损伤。
