允许性高碳酸血症在预防呼吸机相关性肺损伤中的作用_West China Medical Journal

Authors：

岳建明 ,  刘斌

四川大学华西医院麻醉手术中心（成都 610041）;

Corresponding author：

刘斌, Email: liubinhx@foxmail.com

Keywords：

机械通气; 呼吸机相关性肺损伤; 保护性肺通气策略; 允许性高碳酸血症

DOI：

10.7507/1002-0179.201511168

Video：

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机械通气（mechanical ventilation，MV）作为全身麻醉和生命支持的必要手段，在手术和危重患者的呼吸治疗中占有重要地位；然而，使用不当可能给患者带来潜在的损害，可诱发或加重肺部病变，如呼吸机相关性肺损伤（ventilator-induced lung injury，VILI），保护性肺通气是一种新的MV模式，能在一定程度上减轻肺损伤的程度。既往已有研究发现高碳酸血症的治疗性生理效应，且近年提出在保护性通气模式下允许一定程度的高碳酸血症，即允许性高碳酸血症（permissive hypercapnia，PHC），有望改善患者的转归。目前，PHC 在围术期及重症患者的 MV 治疗中逐渐增加，其有效性已被证实，但保护机制、适应证及禁忌证仍不完全明确，二氧化碳的允许范围、安全界限等方面仍缺乏共识。该文将近年来关于机械通气导致 VILI 的相关机制和 PHC 的研究结果作一综述。

Citation： 岳建明, 刘斌. 允许性高碳酸血症在预防呼吸机相关性肺损伤中的作用. West China Medical Journal, 2017, 32(6): 940-944. doi: 10.7507/1002-0179.201511168 Copy

1.	Do-Umehara HC, Chen C, Urich D, et al. Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. Nat Immunol, 2013, 14(5): 461-469.
2.	Needham DM, Colantuoni E, Mendez-Tellez PA, et al. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study. BMJ, 2012, 344: e2124.
3.	Protti A, Cressoni M, Santini A, et al. Lung stress and strain during mechanical ventilation: any safe threshold? Am J Respir Crit Care Med, 2011, 183(10): 1354-1362.
4.	Gattinoni L, Protti A, Caironi P, et al. Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med, 2010, 38(10 Suppl): S539-S548.
5.	Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med, 2013, 369(22): 2126-2136.
6.	Wu H, Kobayashi T, Wan Q, et al. Effects of surfactant replacement on alveolar overdistension and plasma cytokines in ventilator-induced lung injury. Acta Anaesthesiol Scand, 2010, 54(3): 354-361.
7.	Carrasco Loza R, Villamizar Rodríguez G, Medel Fernández N. Ventilator-Induced lung injury (VILI) in acute respiratory distress syndrome (ARDS): volutrauma and molecular effects. Open Respir Med J, 2015, 9: 112-119.
8.	Kneyber MC, Zhang H, Slutsky AS. Ventilator-induced lung injury. Similarity and differences between children and adults. Am J Respir Crit Care Med, 2014, 190(3): 258-265.
9.	Liu YY, Chiang CH, Chuang CH, et al. Spillover of cytokines and reactive Oxygen species in ventilator-induced lung injury associated with inflammation and apoptosis in distal organs. Respir Care, 2014, 59(9): 1422-1432.
10.	Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med, 2008, 178(4): 346-355.
11.	Han B, Lodyga M, Liu M. Ventilator-induced lung injury: role of protein-protein interaction in mechanosensation. Proc Am Thorac Soc, 2005, 2(3): 181-187.
12.	De Prost N, Dreyfuss D, Saumon G. Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation. J Appl Physiol (1985), 2007, 102(2): 794-802.
13.	Albert RK. The role of ventilation-induced surfactant dysfunction and atelectasis in causing acute respiratory distress syndrome. Am J Respir Crit Care Med, 2012, 185(7): 702-708.
14.	Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol, 1970, 28(5): 596-608.
15.	dos Santos CC, Slutsky AS. The contribution of biophysical lung injury to the development of biotrauma. Annu Rev Physiol, 2006, 68: 585-618.
16.	Liu D, Yan Z, Minshall RD, et al. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol, 2012, 302(4): L370-L379.
17.	戴惠军, 潘灵辉, 林飞, 等. 肺泡巨噬细胞 Toll 样受体 9-髓样分化因子 88 信号通路在呼吸机相关性肺损伤中的作用机制研究. 中华危重病急救医学, 2014, 26(5): 289-293.
18.	BENDIXEN HH, HEDLEY-WHYTE J, LAVER MB. Impaired oxygenation in surgical patients during general anesthesia controlled ventilation. A concept of atelectasis. N Engl J Med, 1963, 269: 991-996.
19.	Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med, 2004, 32(9): 1817-1824.
20.	Gajic O, Frutos-Vivar F, Esteban A, et al. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med, 2005, 31(7): 922-926.
21.	Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med, 1990, 16(6): 372-377.
22.	Peng G, Ivanovska J, Kantores C, et al. Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats. Am J Physiol Heart Circ Physiol, 2012, 302(12): H2599-H2611.
23.	Dunlop K, Gosal K, Kantores C, et al. Therapeutic hypercapnia prevents inhaled nitric oxide-induced right-ventricular systolic dysfunction in juvenile rats. Free Radic Biol Med, 2014, 69: 35-49.
24.	Emery MJ, Eveland RL, Min JH, et al. CO₂ relaxation of the rat lung parenchymal strip. Respir Physiol Neurobiol, 2013, 186(1): 33-39.
25.	Taghavi S, Jayarajan SN, Ferrer LM, et al. "Permissive hypoventilation" in a swine model of hemorrhagic shock. J Trauma Acute Care Surg, 2014, 77(1): 14-19.
26.	Nnorom CC, Davis C, Fedinec AL, et al. Contributions of KATP and KCa channels to cerebral arteriolar dilation to hypercapnia in neonatal brain. Physiol Rep, 2014, 2(8). pii: e12127.
27.	Peltekova V, Engelberts D, Otulakowski G, et al. Hypercapnic acidosis in ventilator-induced lung injury. Intensive Care Med, 2010, 36(5): 869-878.
28.	Contreras M, Ansari B, Curley G, et al. Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism. Crit Care Med, 2012, 40(9): 2622-2630.
29.	Yang WC, Song CY, Wang N, et al. Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury. Lab Invest, 2013, 93(12): 1339-1349.
30.	Otulakowski G, Engelberts D, Gusarova GA, et al. Hypercapnia attenuates ventilator-induced lung injury via a disintegrin and metalloprotease-17. J Physiol, 2014, 592(20): 4507-4521.
31.	Schellekens WJ, Van Hees HW, Kox M, et al. Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction. Crit Care, 2014, 18(1): R28.
32.	Gao W, Liu DD, Li D, et al. Effects of hypercapnia on T cells in lung ischemia/reperfusion injury after lung transplantation. Exp Biol Med, 2014, 239(12): 1597-1605.
33.	Cheng DS, Han W, Chen SM, et al. Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway. J Immunol, 2007, 178(10): 6504-6513.
34.	Ijland MM, Heunks LM, Van Der Hoeven JG. Bench-to-bedside review: hypercapnic acidosis in lung injury--from 'permissive' to 'therapeutic'. Crit Care, 2010, 14(6): 237.
35.	Hickling KG, Walsh J, Henderson S, et al. Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med, 1994, 22(10): 1568-1578.
36.	Davidson AC, Banham S, Elliott M, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax, 2016, 71(Suppl 2): ii1-i35.
37.	Nayak S, Jindal A. Permissive hypercapnia: Is there any upper limit? Indian J Crit Care Med, 2015, 19(1): 56-57.
38.	Urwin L, Murphy R, Robertson C, et al. A case of extreme hypercapnia: implications for the prehospital and accident and emergency department management of acutely dyspnoeic patients. Emerg Med J, 2004, 21(1): 119-120.
39.	Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med, 2000, 342(18): 1301-1308.
40.	Curley GF, Laffey JG, Kavanagh BP. CrossTalk proposal: there is added benefit to providing permissive hypercapnia in the treatment of ARDS. J Physiol, 2013, 591(11): 2763-2765.
41.	Guidry CA, Hranjec T, Rodgers BM, et al. Permissive hypercapnia in the management of congenital diaphragmatic hernia: our institutional experience. J Am Coll Surg, 2012, 214(4): 640-645, 647.e1; discussion 646-7.
42.	Curley G, Contreras MM, Nichol AD, et al. Hypercapnia and acidosis in sepsis: a double-edged sword? Anesthesiology, 2010, 112(2): 462-472.
43.	Maclntyre N, Huang YC. Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2008, 5(4): 530-535.
44.	Peters JI, Stupka JE, Singh H, et al. Status asthmaticus in the medical intensive care unit: a 30-year experience. Respir Med, 2012, 106(3): 344-348.
45.	Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med, 2015, 3(7): 534-543.
46.	O'toole D, Hassett P, Contreras M, et al. Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-kappaB dependent mechanism. Thorax, 2009, 64(11): 976-982.
47.	Helenius IT, Krupinski T, Turnbull DW, et al. Elevated CO₂ suppresses specific Drosophila innate immune responses and resistance to bacterial infection. Proc Natl Acad Sci U S A, 2009, 106(44): 18710-18715.
48.	Kilpatrick B, Slinger P. Lung protective strategies in anaesthesia. Br J Anaesth, 2010, 105(Suppl 1): i108-i116.

1. Do-Umehara HC, Chen C, Urich D, et al. Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ. Nat Immunol, 2013, 14(5): 461-469.
2. Needham DM, Colantuoni E, Mendez-Tellez PA, et al. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study. BMJ, 2012, 344: e2124.
3. Protti A, Cressoni M, Santini A, et al. Lung stress and strain during mechanical ventilation: any safe threshold? Am J Respir Crit Care Med, 2011, 183(10): 1354-1362.
4. Gattinoni L, Protti A, Caironi P, et al. Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med, 2010, 38(10 Suppl): S539-S548.
5. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med, 2013, 369(22): 2126-2136.
6. Wu H, Kobayashi T, Wan Q, et al. Effects of surfactant replacement on alveolar overdistension and plasma cytokines in ventilator-induced lung injury. Acta Anaesthesiol Scand, 2010, 54(3): 354-361.
7. Carrasco Loza R, Villamizar Rodríguez G, Medel Fernández N. Ventilator-Induced lung injury (VILI) in acute respiratory distress syndrome (ARDS): volutrauma and molecular effects. Open Respir Med J, 2015, 9: 112-119.
8. Kneyber MC, Zhang H, Slutsky AS. Ventilator-induced lung injury. Similarity and differences between children and adults. Am J Respir Crit Care Med, 2014, 190(3): 258-265.
9. Liu YY, Chiang CH, Chuang CH, et al. Spillover of cytokines and reactive Oxygen species in ventilator-induced lung injury associated with inflammation and apoptosis in distal organs. Respir Care, 2014, 59(9): 1422-1432.
10. Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med, 2008, 178(4): 346-355.
11. Han B, Lodyga M, Liu M. Ventilator-induced lung injury: role of protein-protein interaction in mechanosensation. Proc Am Thorac Soc, 2005, 2(3): 181-187.
12. De Prost N, Dreyfuss D, Saumon G. Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation. J Appl Physiol (1985), 2007, 102(2): 794-802.
13. Albert RK. The role of ventilation-induced surfactant dysfunction and atelectasis in causing acute respiratory distress syndrome. Am J Respir Crit Care Med, 2012, 185(7): 702-708.
14. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol, 1970, 28(5): 596-608.
15. dos Santos CC, Slutsky AS. The contribution of biophysical lung injury to the development of biotrauma. Annu Rev Physiol, 2006, 68: 585-618.
16. Liu D, Yan Z, Minshall RD, et al. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol, 2012, 302(4): L370-L379.
17. 戴惠军, 潘灵辉, 林飞, 等. 肺泡巨噬细胞 Toll 样受体 9-髓样分化因子 88 信号通路在呼吸机相关性肺损伤中的作用机制研究. 中华危重病急救医学, 2014, 26(5): 289-293.
18. BENDIXEN HH, HEDLEY-WHYTE J, LAVER MB. Impaired oxygenation in surgical patients during general anesthesia controlled ventilation. A concept of atelectasis. N Engl J Med, 1963, 269: 991-996.
19. Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med, 2004, 32(9): 1817-1824.
20. Gajic O, Frutos-Vivar F, Esteban A, et al. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med, 2005, 31(7): 922-926.
21. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med, 1990, 16(6): 372-377.
22. Peng G, Ivanovska J, Kantores C, et al. Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats. Am J Physiol Heart Circ Physiol, 2012, 302(12): H2599-H2611.
23. Dunlop K, Gosal K, Kantores C, et al. Therapeutic hypercapnia prevents inhaled nitric oxide-induced right-ventricular systolic dysfunction in juvenile rats. Free Radic Biol Med, 2014, 69: 35-49.
24. Emery MJ, Eveland RL, Min JH, et al. CO₂ relaxation of the rat lung parenchymal strip. Respir Physiol Neurobiol, 2013, 186(1): 33-39.
25. Taghavi S, Jayarajan SN, Ferrer LM, et al. "Permissive hypoventilation" in a swine model of hemorrhagic shock. J Trauma Acute Care Surg, 2014, 77(1): 14-19.
26. Nnorom CC, Davis C, Fedinec AL, et al. Contributions of KATP and KCa channels to cerebral arteriolar dilation to hypercapnia in neonatal brain. Physiol Rep, 2014, 2(8). pii: e12127.
27. Peltekova V, Engelberts D, Otulakowski G, et al. Hypercapnic acidosis in ventilator-induced lung injury. Intensive Care Med, 2010, 36(5): 869-878.
28. Contreras M, Ansari B, Curley G, et al. Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism. Crit Care Med, 2012, 40(9): 2622-2630.
29. Yang WC, Song CY, Wang N, et al. Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury. Lab Invest, 2013, 93(12): 1339-1349.
30. Otulakowski G, Engelberts D, Gusarova GA, et al. Hypercapnia attenuates ventilator-induced lung injury via a disintegrin and metalloprotease-17. J Physiol, 2014, 592(20): 4507-4521.
31. Schellekens WJ, Van Hees HW, Kox M, et al. Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction. Crit Care, 2014, 18(1): R28.
32. Gao W, Liu DD, Li D, et al. Effects of hypercapnia on T cells in lung ischemia/reperfusion injury after lung transplantation. Exp Biol Med, 2014, 239(12): 1597-1605.
33. Cheng DS, Han W, Chen SM, et al. Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway. J Immunol, 2007, 178(10): 6504-6513.
34. Ijland MM, Heunks LM, Van Der Hoeven JG. Bench-to-bedside review: hypercapnic acidosis in lung injury--from 'permissive' to 'therapeutic'. Crit Care, 2010, 14(6): 237.
35. Hickling KG, Walsh J, Henderson S, et al. Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med, 1994, 22(10): 1568-1578.
36. Davidson AC, Banham S, Elliott M, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax, 2016, 71(Suppl 2): ii1-i35.
37. Nayak S, Jindal A. Permissive hypercapnia: Is there any upper limit? Indian J Crit Care Med, 2015, 19(1): 56-57.
38. Urwin L, Murphy R, Robertson C, et al. A case of extreme hypercapnia: implications for the prehospital and accident and emergency department management of acutely dyspnoeic patients. Emerg Med J, 2004, 21(1): 119-120.
39. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med, 2000, 342(18): 1301-1308.
40. Curley GF, Laffey JG, Kavanagh BP. CrossTalk proposal: there is added benefit to providing permissive hypercapnia in the treatment of ARDS. J Physiol, 2013, 591(11): 2763-2765.
41. Guidry CA, Hranjec T, Rodgers BM, et al. Permissive hypercapnia in the management of congenital diaphragmatic hernia: our institutional experience. J Am Coll Surg, 2012, 214(4): 640-645, 647.e1; discussion 646-7.
42. Curley G, Contreras MM, Nichol AD, et al. Hypercapnia and acidosis in sepsis: a double-edged sword? Anesthesiology, 2010, 112(2): 462-472.
43. Maclntyre N, Huang YC. Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2008, 5(4): 530-535.
44. Peters JI, Stupka JE, Singh H, et al. Status asthmaticus in the medical intensive care unit: a 30-year experience. Respir Med, 2012, 106(3): 344-348.
45. Thome UH, Genzel-Boroviczeny O, Bohnhorst B, et al. Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. Lancet Respir Med, 2015, 3(7): 534-543.
46. O'toole D, Hassett P, Contreras M, et al. Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-kappaB dependent mechanism. Thorax, 2009, 64(11): 976-982.
47. Helenius IT, Krupinski T, Turnbull DW, et al. Elevated CO₂ suppresses specific Drosophila innate immune responses and resistance to bacterial infection. Proc Natl Acad Sci U S A, 2009, 106(44): 18710-18715.
48. Kilpatrick B, Slinger P. Lung protective strategies in anaesthesia. Br J Anaesth, 2010, 105(Suppl 1): i108-i116.

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允许性高碳酸血症在预防呼吸机相关性肺损伤中的作用

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