Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury

doi:10.5847/wjem.j.1920-8642.2021.04.009

Abstract

Abstract:

BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury.
METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint.
RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group.
CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

Key words: Cardiac arrest, Swine, Alveolar surface-active protein, Oxidative stress injury, Pulmonary edema

Ji-yang Ling, Chun-sheng Li, Yun Zhang, Xiao-li Yuan, Bo Liu, Yong Liang, Qiang Zhang. Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury[J]. World Journal of Emergency Medicine, 2021, 12(4): 303-308.

Figures/Tables 3

References 33

1	Lin MH, Peng LN, Chen LK, Chen TJ, Hwang SJ. Cardiopulmonary resuscitation for hospital inpatients in Taiwan: an 8-year nationwide survey. Resuscitation. 2012; 83(3):343-6. doi: 10.1016/j.resuscitation.2011.09.006
2	Nehme Z, Andrew E, Bernard S, Smith K. Impact of cardiopulmonary resuscitation duration on survival from paramedic witnessed out-of-hospital cardiac arrests: an observational study. Resuscitation. 2016; 100:25-31. doi: 10.1016/j.resuscitation.2015.12.011
3	Chen YS, Chao A, Yu HY, Ko WJ, Wu IH, Chen RJC, et al. Analysis and results of prolonged resuscitation in cardiac arrest patients rescued by extracorporeal membrane oxygenation. J Am Coll Cardiol. 2003; 41(2):197-203.
4	Chen YS, Lin JW, Yu HY, Ko WJ, Jerng JS, Chang WT, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008; 372(9638):554-61. doi: 10.1016/S0140-6736(08)60958-7
5	Ortega-Deballon I, Hornby L, Shemie SD, Bhanji F, Guadagno E. Extracorporeal resuscitation for refractory out-of-hospital cardiac arrest in adults: a systematic review of international practices and outcomes. Resuscitation. 2016; 101:12-20. doi: 10.1016/j.resuscitation.2016.01.018 pmid: 26836946
6	Kim SJ, Kim HJ, Lee HY, Ahn HS, Lee SW. Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: a meta-analysis. Resuscitation. 2016; 103:106-16. doi: 10.1016/j.resuscitation.2016.01.019
7	Thiagarajan RR, Laussen PC, Rycus PT, Bartlett RH, Bratton SL. Extracorporeal membrane oxygenation to aid cardiopulmonary resuscitation in infants and children. Circulation. 2007; 116(15):1693-700. pmid: 17893278
8	Ding CQ, Zhang YP, Wang YW, Yang MF, Wang S, Cui NQ, et al. Death and do-not-resuscitate order in the emergency department: A single-center three-year retrospective study in the Chinese mainland. World J Emerg Med. 2020; 11(4):231-7. doi: 10.5847/wjem.j.1920-8642.2020.04.005
9	Menegazzi JJ, Salcido DD, Housler GJ, Logue ES. Feasibility of initiating extracorporeal life support during mechanical chest compression CPR: a porcine pilot study. Resuscitation. 2012; 83(1):130-3. doi: 10.1016/j.resuscitation.2011.07.030 pmid: 21835144
10	Stub D, Bernard S, Pellegrino V, Smith K, Walker T, Sheldrake J, et al. Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial). Resuscitation. 2015; 86:88-94. doi: 10.1016/j.resuscitation.2014.09.010
11	Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, et al. Part 7: adult advanced cardiovascular life support 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015; 132(18 Suppl 2):S444-64.
12	Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, et al. Part 8: post-cardiac arrest care 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015; 132(18 Suppl 2):S465-82.
13	Giannoni E, Sawa T, Allen L, Wiener-Kronish J, Hawgood S. Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2006; 34(6):704-10. doi: 10.1165/rcmb.2005-0461OC
14	Bridges JP, Davis HW, Damodarasamy M, Kuroki Y, Howles G, Hui DY, et al. Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid peroxidation and oxidative cellular injury. J Biol Chem. 2000; 275(49):38848-55. pmid: 10969075
15	Goto H, Ledford JG, Mukherjee S, Noble PW, Williams KL, Wright JR. The role of surfactant protein A in bleomycin-induced acute lung injury. Am J Respir Crit Care Med. 2010; 181(12):1336-44. doi: 10.1164/rccm.200907-1002OC
16	Belhaj A, Boven C, Dewachter L, Ruiz Patino M, Sokolow Y, Rondelet B. Influence of donor lung surfactant-A and -B protein expression on the development of primary graft dysfunction after lung transplantation: a pilot study. Ann Transplant. 2017; 22:361-9. doi: 10.12659/AOT.903313
17	Fan YW, Jiang SW, Chen JM, Wang HQ, Liu D, Pan SM, et al. A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function. World J Emerg Med. 2020; 11(1):18-26. doi: 10.5847/wjem.j.1920-8642.2020.01.003
18	Sato A, Whitsett JA, Scheule RK, Ikegami M. Surfactant protein D inhibits lung inflammation caused by ventilation in premature newborn lambs. Am J Respir Crit Care Med. 2010; 181(10):1098-105. doi: 10.1164/rccm.200912-1818OC
19	Thacker S, Moran AN, Lionakis M, Mastrangelo MAA, Halder T, Huby MDP, et al. Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock. J Infect. 2014; 68(3):231-41. doi: 10.1016/j.jinf.2013.11.010
20	Duda I, Grzybowska K, Jędrzejowska-Szypułka H, Lewin-Kowalik J. The sitting position during neurosurgical procedures does not influence serum biomarkers of pulmonary parenchymal injury. BMC Surg. 2012; 12:24. doi: 10.1186/1471-2482-12-24
21	Kurt A, Turut H, Acipayam A, Kirbas A, Yuce S, Cumhur Cure M, et al. Investigation of surfactant protein-D and interleukin-6 levels in patients with blunt chest trauma with multiple rib fractures and pulmonary contusions: a cross-sectional study in Black Sea Region of Turkey. BMJ Open. 2016; 6(10):e011797. doi: 10.1136/bmjopen-2016-011797
22	Ware LB, Koyama T, Billheimer DD, Wu W, Bernard GR, Thompson BT, et al. Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. Chest. 2010; 137(2):288-96. doi: 10.1378/chest.09-1484
23	Wen MN, Zhao G, Zhang JY, Zhao YH. Clinical study on the changes of lung-specific proteins: CC16 after lung contusion. Exp Ther Med. 2017; 14(3):2733-6. doi: 10.3892/etm.2017.4842
24	Wutzler S, Lehnert T, Laurer H, Lehnert M, Becker M, Henrich D, et al. Circulating levels of Clara cell protein 16 but not surfactant protein D identify and quantify lung damage in patients with multiple injuries. J Trauma. 2011; 71(2):E31-6.
25	Determann RM, Millo JL, Waddy S, Lutter R, Garrard CS, Schultz MJ. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study. BMC Pulm Med. 2009; 9(1):1-9. doi: 10.1186/1471-2466-9-1
26	Marikovsky M, Ziv V, Nevo N, Harris-Cerruti C, Mahler O. Cu/Zn superoxide dismutase plays important role in immune response. J Immunol. 2003; 170(6):2993-3001. pmid: 12626552
27	Jung O, Marklund SL, Geiger H, Pedrazzini T, Busse R, Brandes RP. Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice. Circ Res. 2003; 93(7):622-9. doi: 10.1161/01.RES.0000092140.81594.A8
28	Karaiskos T, Tomos P, Asouhidou I, Nikiteas N, Kontakiotis T, Papalois A. Oxidative and pre-inflammatory stress in wedge resection of pulmonary parenchyma using the radiofrequency ablation technique in a swine model. J Cardiothorac Surg. 2012; 7:7. doi: 10.1186/1749-8090-7-7
29	Meng L, Li LY, Lu S, Li K, Su ZB, Wang YY, et al. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways. Mol Immunol. 2018; 94:7-17. doi: S0161-5890(17)30601-6 pmid: 29241031
30	Şener G, Paskaloǧlu K, Toklu H, Kapucu C, Ayanoglu-Dulger G, Kacmaz A, et al. Melatonin ameliorates chronic renal failure-induced oxidative organ damage in rats. J Pineal Res. 2004; 36(4):232-41. doi: 10.1111/jpi.2004.36.issue-4
31	Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005; 77(5):598-625. doi: 10.1189/jlb.1204697
32	El Kebir D, József L, Pan WL, Wang LL, Petasis NA, Serhan CN, et al. 15-epi-lipoxin A4Inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. Am J Respir Crit Care Med. 2009; 180(4):311-9. doi: 10.1164/rccm.200810-1601OC
33	Lv H, Liu QM, Wen ZM, Feng HH, Deng XM, Ci XX. Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol. 2017; 12:311-24. doi: 10.1016/j.redox.2017.03.001

Variables	Baseline	ROSC6h	P-value
EVLW (mL/kg)
CCPR group	9.61±1.37	21.85±3.92	<0.001
ECPR group	9.39±1.70	11.78±1.82^*	0.017
PVPI
CCPR group	2.24±0.50	5.97±1.39	0.001
ECPR group	2.15±0.43	2.06±0.91^*	0.812

[1]	Sohyeon Chun, Gi Woon Kim, Han Bit Kim. Association between on-scene cardiopulmonary resuscitation duration and outcomes in out-of-hospital cardiac arrest patients [J]. World Journal of Emergency Medicine, 2026, 17(2): 137-145.
[2]	Ping Gong, Hong Zhao, Peijuan Li, Ling Wang, Jin Wang, Rui Yang, Zhangping Sun. Elevated serum osmolarity is associated with 28-day all-cause mortality in patients with cardiac arrest [J]. World Journal of Emergency Medicine, 2026, 17(1): 50-56.
[3]	Xing Luo, Jinzhao Zhang, Fanrong Lin, Siqi Liu, Zhengfei Yang. Beyond the chain of survival: a scoping review of artificial intelligence applications in cardiac arrest [J]. World Journal of Emergency Medicine, 2026, 17(1): 7-14.
[4]	Gannan Wang, Yi Zhu, Hao Zhou, Tao Ding, Yutong Shi, Xiaoquan Xu, Hai Xu, Wei Li, Xufeng Chen. Association between chest computed tomography features and prognosis in patients treated with extracorporeal cardiopulmonary resuscitation [J]. World Journal of Emergency Medicine, 2025, 16(6): 567-572.
[5]	Shin Ae Lee, Jongwon Ha, Ye Rim Chang. Defining optimal volume of inflation for partial resuscitative endovascular balloon occlusion of the aorta in swine hemorrhagic shock model [J]. World Journal of Emergency Medicine, 2025, 16(5): 431-437.
[6]	Young Min Kim, Hyun Seok Chai, Gwan Jin Park, Sang Chul Kim, Hoon Kim, Seok Woo Lee, Hyeon Jeong Park, Han Bit Kim, Hyo Been Lee, Ji Han Lee. Effect of bag valve ventilation versus mechanical ventilation after endotracheal intubation during cardiopulmonary resuscitation on outcomes following out-of-hospital cardiac arrest: a propensity score analysis [J]. World Journal of Emergency Medicine, 2025, 16(4): 313-320.
[7]	Rui Shao, Chenchen Hang, Xingsheng Wang, Luying Zhang, Fei Shao, Ziren Tang. The “SOOTEST-ICU” bundle for optimizing cerebral hypoxia and reperfusion to minimize brain injury after resuscitation from cardiac arrest [J]. World Journal of Emergency Medicine, 2025, 16(3): 206-211.
[8]	Jie Chen, Zhonghao Li, Xiaoyu Liu, Tianpeng Hu, Nan Gao, Weijian Zhang, Guoqiang Zhang. Potential common key genes associated with myocardial dysfunction and brain injury following cardiac arrest resuscitation in a rat model [J]. World Journal of Emergency Medicine, 2025, 16(3): 231-238.
[9]	Tingting Xu, Shaokun Wang, Liqiang Zhao, Jiawen Wang, Jihong Xing. A two-sample Mendelian randomization study on the relationship of body weight, body mass index, and waist circumference with cardiac arrest [J]. World Journal of Emergency Medicine, 2025, 16(2): 129-135.
[10]	Wachira Wongtanasarasin, Daniel K. Nishijima, Wanrudee Isaranuwatchai, Jeffrey S. Hoch. Real-world cost-effectiveness of targeted temperature management in out-of-hospital cardiac arrest survivors: results from an academic medical center [J]. World Journal of Emergency Medicine, 2025, 16(1): 28-34.
[11]	Subi Abudurexiti, Shihai Xu, Zhangping Sun, Yi Jiang, Ping Gong. Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest: a prospective single-center observational study [J]. World Journal of Emergency Medicine, 2024, 15(3): 197-203.
[12]	Rashed Alremeithi, Quincy K. Tran, Megan T. Quintana, Soroush Shahamatdar, Ali Pourmand. Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers [J]. World Journal of Emergency Medicine, 2024, 15(1): 3-9.
[13]	Jing Yang, Hanqi Tang, Shihuan Shao, Feng Xu, Yangyang Fu, Shengyong Xu, Chen Li, Yan Li, Yang Liu, Joseph Harold Walline, Huadong Zhu, Yuguo Chen, Xuezhong Yu, Jun Xu. A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study [J]. World Journal of Emergency Medicine, 2024, 15(1): 16-22.
[14]	Gannan Wang, Zhe Wang, Yi Zhu, Zhongman Zhang, Wei Li, Xufeng Chen, Yong Mei. The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation [J]. World Journal of Emergency Medicine, 2023, 14(5): 354-359.
[15]	Guang-qi Guo, Yan-nan Ma, Shuang Xu, Hong-rong Zhang, Peng Sun. Effect of post-rewarming fever after targeted temperature management in cardiac arrest patients: a systematic review and meta-analysis [J]. World Journal of Emergency Medicine, 2023, 14(3): 217-223.