Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2015

Open Access 01-12-2015 | Research article

Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury

Authors: Wanchao Yang, Ziyong Yue, Xiaoguang Cui, Yueping Guo, Lili Zhang, Huacheng Zhou, Wenzhi Li

Published in: BMC Anesthesiology | Issue 1/2015

Login to get access

Abstract

Background

We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 “doses” (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis.

Methods

Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined.

Results

In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch–induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05).

Conclusions

Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.
Literature
1.
Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis. 1985;132(4):880–4.PubMed
2.
Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998;157(1):294–323.CrossRefPubMed
3.
Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338(6):347–54.CrossRefPubMed
4.
Maeda YFY, Uchiyama A, Matsuura N, Mashimo T, Nishimura M. Effects of peak inspiratory flow on development of ventilator-induced lung injury in rabbits. Anesthesiology. 2004;101(3):722–8.CrossRefPubMed
5.
Laffey JGTM, Engelberts D, Luo X, Yuan S, Keith Tanswell A, Post M, et al. Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. Am J Respir Crit Care Med. 2000;162(6):2287–94.CrossRefPubMed
6.
Shibata KCN, Engelberts D, Takeuchi A, Fedorko L, Kavanagh BP. Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1578–84.CrossRefPubMed
7.
Laffey JGHD, Hopkins N, Hyvelin JM, Boylan JF, McLoughlin P. Hypercapnic acidosis attenuates endotoxin-induced acute lung injury. Am J Respir Crit Care Med. 2004;169(1):46–56.CrossRefPubMed
8.
Nichol AD, O’Cronin DF, Naughton F, Hopkins N, Boylan J, McLoughlin P. Hypercapnic acidosis reduces oxidative reactions in endotoxin-induced lung injury. Anesthesiol. 2010;113(1):116–25.CrossRef
9.
Costello J, Higgins B, Contreras M, Chonghaile MN, Hassett P, O’Toole D, et al. Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis. Crit Care Med. 2009;37(8):2412–20.CrossRefPubMed
10.
Higgins BD, Costello J, Contreras M, Hassett P, O’Toole D, Laffey JG. Differential effects of buffered hypercapnia versus hypercapnic acidosis on shock and lung injury induced by systemic sepsis. Anesthesiol. 2009;111(6):1317–26.CrossRef
11.
Broccard AFHJ, Vannay C, Markert M, Sauty A, Feihl F, Schaller MD. Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med. 2001;164(5):802–6.CrossRefPubMed
12.
Contreras M, Ansari B, Curley G, Higgins BD, Hassett P, O’Toole D, et al. Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-kappaB-dependent mechanism. Crit Care Med. 2012;40(9):2622–30.CrossRefPubMed
13.
Sinclair SEKD, Lamm WJ, Starr IR, Chi EY, Hlastala MP. Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med. 2002;166(3):403–8.CrossRefPubMed
14.
Peltekova V, Engelberts D, Otulakowski G, Uematsu S, Post M, Kavanagh BP. Hypercapnic acidosis in ventilator-induced lung injury. Intensive Care Med. 2010;36(5):869–78.CrossRefPubMed
15.
Laffey JGED, Duggan M, Veldhuizen R, Lewis JF, Kavanagh BP. Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation. Crit Care Med. 2003;31(11):2634–40.CrossRefPubMed
16.
Kregenow DA, Swenson ER. The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia. Eur Respir J. 2002;20(1):6–11.CrossRefPubMed
17.
Blackwell TS, Christman JW. The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol. 1997;17(1):3–9.CrossRefPubMed
18.
Christman JW, Lancaster LH, Blackwell TS. Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 1998;24(11):1131–8.CrossRefPubMed
19.
Chen LW, Egan L, Li ZW, Greten FR, Kagnoff MF, Karin M. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003;9(5):575–81.CrossRefPubMed
20.
O’Toole D, Hassett P, Contreras M, Higgins BD, McKeown ST, McAuley DF, et al. Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-kappaB dependent mechanism. Thorax. 2009;64(11):976–82.CrossRefPubMed
21.
Yang WC, Song CY, Wang N, Zhang LL, Yue ZY, Cui XG, et al. Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury. Lab Invest. 2013;93(12):1339–49.CrossRefPubMed
22.
Laffey JGJR, Engelberts D, Tanswell AK, Post M, Lindsay T, Mullen JB, et al. Effects of therapeutic hypercapnia on mesenteric ischemia-reperfusion injury. Am J Respir Crit Care Med. 2003;168(11):1383–90.CrossRefPubMed
23.
Zhou Q, Cao B, Niu L, Cui X, Yu H, Liu J, et al. Effects of permissive hypercapnia on transient global cerebral ischemia-reperfusion injury in rats. Anesthesiol. 2010;112(2):288–97.CrossRef
24.
Imanaka H, Shimaoka M, Matsuura N, Nishimura M, Ohta N, Kiyono H. Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesth Analg. 2001;92(2):428–36.CrossRefPubMed
25.
Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis. 1987;136(3):730–6.CrossRefPubMed
26.
Sinclair SE, Kregenow DA, Starr I, Schimmel C, Lamm WJ, Hlastala MP, et al. Therapeutic hypercapnia and ventilation-perfusion matching in acute lung injury: low minute ventilation vs inspired CO2. Chest. 2006;130(1):85–92.CrossRefPubMed
27.
Brogan TV, Hedges RG, McKinney S, Robertson HT, Hlastala MP, Swenson ER. Pulmonary NO synthase inhibition and inspired CO2: effects on V’/Q’ and pulmonary blood flow distribution. Eur Respir J. 2000;16(2):288–95.CrossRefPubMed
28.
Akca O, Doufas AG, Morioka N, Iscoe S, Fisher J, Sessler DI. Hypercapnia improves tissue oxygenation. Anesthesiol. 2002;97(4):801–6.CrossRef
29.
Liu SF, Ye X, Malik AB. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes. Circ. 1999;100(12):1330–7.CrossRef
30.
Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB, et al. Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med. 1996;24(8):1285–92.CrossRefPubMed
31.
Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW. In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. J Immunol. 1996;157(4):1630–7.PubMed
32.
Cummins EP, Oliver KM, Lenihan CR, Fitzpatrick SF, Bruning U, Scholz CC, et al. NF-kappaB links CO2 sensing to innate immunity and inflammation in mammalian cells. J Immunol. 2010;185(7):4439–45.CrossRefPubMed
33.
Coakley RJ, Taggart C, Greene C, McElvaney NG, O’Neill SJ. Ambient pCO2 modulates intracellular pH, intracellular oxidant generation, and interleukin-8 secretion in human neutrophils. J Leukoc Biol. 2002;71(4):603–10.PubMed
34.
Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat. Pediatr. 1995;95(6):868–74.
35.
Vannucci RC, Towfighi J, Brucklacher RM, Vannucci SJ. Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat. Pediatr Res. 2001;49(6):799–803.CrossRefPubMed
36.
Marini JJ. Pressure-targeted, lung-protective ventilatory support in acute lung injury. Chest. 1994;105(3 Suppl):109S–15.CrossRefPubMed
Metadata
Title
Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury
Authors
Wanchao Yang
Ziyong Yue
Xiaoguang Cui
Yueping Guo
Lili Zhang
Huacheng Zhou
Wenzhi Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2015
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-015-0050-8

Other articles of this Issue 1/2015

BMC Anesthesiology 1/2015 Go to the issue

Research article

Drug concentrations in the serum and cerebrospinal fluid of patients treated with cefoperazone/sulbactam after craniotomy

Research article

Lithotomy versus jack-knife position on haemodynamic parameters assessed by impedance cardiography during anorectal surgery under low dose spinal anaesthesia: a randomized controlled trial

Research article

Pilot study comparing simulation-based and didactic lecture-based critical care teaching for final-year medical students

Erratum

Erratum to: Obesity – a risk factor for postoperative complications in general surgery?

Research article

Normal values for pancreatic stone protein in different age groups

Research article

Long-term treated intensive care patients outcomes: the one-year mortality rate, quality of life, health care use and long-term complications as reported by general practitioners