Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis

doi:10.5847/wjem.j.1920-8642.2023.093

Abstract

Abstract:

BACKGROUND: Emergency patients with sepsis or septic shock are at high risk of death. Despite increasing attention to microhemodynamics, the clinical use of advanced microcirculatory assessment is limited due to its shortcomings. Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption, it may serve as a surrogate for microcirculation monitoring in septic treatment.

METHODS: We performed a search using PubMed, Web of Science, and Google scholar. The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included.

RESULTS: Based on the pathophysiology of oxygen metabolism, the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care. Notwithstanding flaws, several parameters are linked to changes in the microcirculation. A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients.

CONCLUSION: Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments. A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock.

Key words: Sepsis, Microcirculation, Blood gas analysis, Emergency service

Jingyi Wang, Li Weng, Jun Xu, Bin Du. Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis[J]. World Journal of Emergency Medicine, 2023, 14(6): 421-427.

Figures/Tables 3

References 59

1	Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021; 47(11): 1181-247. doi: 10.1007/s00134-021-06506-y pmid: 34599691
2	Trzeciak S, McCoy JV, Phillip Dellinger R, Arnold RC, Rizzuto M, Abate NL, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med. 2008; 34(12): 2210-7. doi: 10.1007/s00134-008-1193-6
3	De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, et al. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med. 2013; 41(3): 791-9. doi: 10.1097/CCM.0b013e3182742e8b pmid: 23318492
4	De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007; 11(5): R101.
5	De Backer D. Is microcirculatory assessment ready for regular use in clinical practice? Curr Opin Crit Care. 2019; 25(3): 280-4. doi: 10.1097/MCC.0000000000000605 pmid: 31022089
6	Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014; 40(12): 1795-815.
7	Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007; 49(1): 88-98, 98.e1-2. pmid: 17095120
8	Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004; 32(9): 1825-31. doi: 10.1097/01.ccm.0000138558.16257.3f pmid: 15343008
9	De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002; 166(1): 98-104. doi: 10.1164/rccm.200109-016OC
10	Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015; 19(Suppl 3): S8. doi: 10.1186/cc14726
11	Yajnik V, Maarouf R. Sepsis and the microcirculation: the impact on outcomes. Curr Opin Anaesthesiol. 2022; 35(2): 230-5. doi: 10.1097/ACO.0000000000001098 pmid: 35081058
12	Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol. 2021; 34(2): 77-84. doi: 10.1097/ACO.0000000000000963 pmid: 33652454
13	Mallat J, Lemyze M, Meddour M, Pepy F, Gasan G, Barrailler S, et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. Ann Intensive Care. 2016; 6(1): 10. doi: 10.1186/s13613-016-0110-3 pmid: 26842697
14	Lee CP, Bora V. Anesthesia monitoring of mixed venous saturation. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022.
15	Hartog C, Bloos F. Venous oxygen saturation. Best Pract Res Clin Anaesthesiol. 2014; 28(4): 419-28. doi: 10.1016/j.bpa.2014.09.006 pmid: 25480771
16	van Beest PA, van Ingen J, Boerma EC, Holman ND, Groen H, Koopmans M, et al. No agreement of mixed venous and central venous saturation in sepsis, independent of sepsis origin. Crit Care. 2010; 14(6): R219. doi: 10.1186/cc9348
17	Soussi MS, Jebali MA, Le Manach Y, Nasri M, Zouari B, Chenik S, et al. Central venous saturation is not an alternative to mixed venous saturation during cardiopulmonary bypass in coronary artery surgery patients. Perfusion. 2012; 27(4): 300-6. doi: 10.1177/0267659112442902 pmid: 22499058
18	Lorentzen AG, Lindskov C, Sloth E, Jakobsen CJ. Central venous oxygen saturation cannot replace mixed venous saturation in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2008; 22(6): 853-7. doi: 10.1053/j.jvca.2008.04.004
19	Kopterides P, Bonovas S, Mavrou I, Kostadima E, Zakynthinos E, Armaganidis A. Venous oxygen saturation and lactate gradient from superior vena cava to pulmonary artery in patients with septic shock. Shock. 2009; 31(6): 561-7. doi: 10.1097/SHK.0b013e31818bb8d8 pmid: 18838939
20	Reinhart K, Kuhn HJ, Hartog C, Bredle DL. Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intensive Care Med. 2004; 30(8): 1572-8.
21	He HW, Long Y, Zhou X, Wang XT, Zhang HM, Chai WZ, et al. Oxygen-flow-pressure targets for resuscitation in critical hemodynamic therapy. Shock. 2018; 49(1): 15-23. doi: 10.1097/SHK.0000000000000929 pmid: 28650929
22	Squara P. Central venous oxygenation: when physiology explains apparent discrepancies. Crit Care. 2014; 18(6): 579. doi: 10.1186/s13054-014-0579-9
23	Thooft A, Favory R, Salgado DR, Taccone FS, Donadello K, De Backer D, et al. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care. 2011; 15(5): R222. doi: 10.1186/cc10462
24	Arango-Granados MC, Umaña M, Sánchez ÁI, García AF, Granados M, Ospina-Tascón GA. Impact of red blood cell transfusion on oxygen transport and metabolism in patients with sepsis and septic shock: a systematic review and meta-analysis. Rev Bras Ter Intensiva. 2021;33(1): 154-66.
25	Textoris J, Fouché L, Wiramus S, Antonini F, Tho S, Martin C, et al. High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality. Crit Care. 2011; 15(4): R176. doi: 10.1186/cc10325
26	Perz S, Uhlig T, Kohl M, Bredle DL, Reinhart K, Bauer M, et al. Low and “supranormal” central venous oxygen saturation and markers of tissue hypoxia in cardiac surgery patients: a prospective observational study. Intensive Care Med. 2011; 37(1): 52-9. doi: 10.1007/s00134-010-1980-8
27	Wittayachamnankul B, Apaijai N, Sutham K, Chenthanakij B, Liwsrisakun C, Jaiwongkam T, et al. High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: a prospective observational study. J Cell Mol Med. 2020; 24(11): 6485-94. doi: 10.1111/jcmm.15299 pmid: 32352229
28	Huber W, Zanner R, Schneider G, Schmid R, Lahmer T. Assessment of regional perfusion and organ function: less and non-invasive techniques. Front Med (Lausanne). 2019; 6: 50.
29	Haase N, Perner A. Central venous oxygen saturation in septic shock—a marker of cardiac output, microvascular shunting and/or dysoxia? Crit Care. 2011; 15(4): 184. doi: 10.1186/cc10314
30	He HW, Liu DW, Long Y, Wang XT. Mind the influence of arterial oxygen tension on central venous oxygen saturation. Crit Care. 2014; 18(5): 569. doi: 10.1186/s13054-014-0569-y
31	Vincent JL, Theerawit P, Simion D. Basic principles of oxygen transport and calculations. Alternatives to Blood Transfusion in Transfusion Medicine. Oxford: Wiley-Blackwell, 2010: 203-9.
32	Nasser B, Tageldein M, AlMesned A, Kabbani M. Effects of blood transfusion on oxygen extraction ratio and central venous saturation in children after cardiac surgery. Ann Saudi Med. 2017; 37(1): 31-7. doi: 10.5144/0256-4947.2017.31 pmid: 28151454
33	An X, Zhang H, Sun YN, Ma XC. The microcirculatory failure could not weaken the increase of systematic oxygen extraction rate in septic shock: an observational study in canine models. Clin Hemorheol Microcirc. 2016; 63(3): 267-79. doi: 10.3233/CH-152022 pmid: 26639767
34	Ospina-Tascón GA, García Marin AF, Echeverri GJ, Bermudez WF, Madriñán-Navia H, Valencia JD, et al. Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O₂ extraction during septic shock. J Appl Physiol (1985). 2017;122(6): 1406-17.
35	Levy B. Lactate and shock state: the metabolic view. Curr Opin Crit Care. 2006; 12(4): 315-21. doi: 10.1097/01.ccx.0000235208.77450.15 pmid: 16810041
36	Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014; 371(24): 2309-19. doi: 10.1056/NEJMra1309483
37	Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states. Shock. 2008; 30(4): 417-21. doi: 10.1097/SHK.0b013e318167378f pmid: 18323749
38	Taylor DJ, Faragher EB, Evanson JM. Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro. Circ Shock. 1992; 37(2): 105-10.
39	Ospina-Tascon G, Neves AP, Occhipinti G, Donadello K, Büchele G, Simion D, et al. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med. 2010; 36(6): 949-55. doi: 10.1007/s00134-010-1843-3 pmid: 20221744
40	Filbin MR, Hou PC, Massey M, Barche A, Kao E, Bracey A, et al. The microcirculation is preserved in emergency department low-acuity sepsis patients without hypotension. Acad Emerg Med. 2014; 21(2): 154-62. doi: 10.1111/acem.12314 pmid: 24673671
41	Puskarich MA, Shapiro NI, Massey MJ, Kline JA, Jones AE. Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow. Acad Emerg Med. 2016; 23(6): 690-3. doi: 10.1111/acem.12928 pmid: 26825368
42	Patel H, Kerndt CC, Bhardwaj A. Physiology, respiratory quotient. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022.
43	Randall HM Jr, Cohen JJ. Anaerobic CO₂ production by dog kidney in vitro. Am J Physiol Leg Content. 1966; 211(2): 493-505.
44	da Rocha EE, Alves VG, da Fonseca RB. Indirect calorimetry: methodology, instruments and clinical application. Curr Opin Clin Nutr Metab Care. 2006; 9(3): 247-56. doi: 10.1097/01.mco.0000222107.15548.f5
45	De Waele E, Honore PM, Spapen HD. New generation indirect calorimeters for measuring energy expenditure in the critically ill: a rampant or reticent revolution? Crit Care. 2016; 20(1): 138. doi: 10.1186/s13054-016-1315-4
46	Ltaief Z, Schneider AG, Liaudet L. Pathophysiology and clinical implications of the veno-arterial PCO₂ gap. Crit Care. 2021; 25(1): 318. doi: 10.1186/s13054-021-03671-w
47	Mekontso-Dessap A, Castelain V, Anguel N, Bahloul M, Schauvliege F, Richard C, et al. Combination of venoarterial PCO₂ difference with arteriovenous O₂ content difference to detect anaerobic metabolism in patients. Intensive Care Med. 2002; 28(3): 272-7. doi: 10.1007/s00134-002-1215-8
48	Mesquida J, Saludes P, Gruartmoner G, Espinal C, Torrents E, Baigorri F, et al. Central venous-to-arterial carbon dioxide difference combined with arterial-to-venous oxygen content difference is associated with lactate evolution in the hemodynamic resuscitation process in early septic shock. Crit Care. 2015; 19(1): 126. doi: 10.1186/s13054-015-0858-0
49	He H, Long Y, Liu D, Wang X, Tang B. The prognostic value of central venous-to-arterial CO₂ difference/arterial-central venous O₂ difference ratio in septic shock patients with central venous O₂ saturation ≥80. Shock. 2017;48(5): 551-7.
50	Ospina-Tascón GA, Umaña M, Bermúdez W, Bautista-Rincón DF, Hernandez G, Bruhn A, et al. Combination of arterial lactate levels and venous-arterial CO₂ to arterial-venous O₂ content difference ratio as markers of resuscitation in patients with septic shock. Intensive Care Med. 2015;41(5): 796-805.
51	Ospina-Tascón GA, Umaña M, Bermúdez WF, Bautista-Rincón DF, Valencia JD, Madriñán HJ, et al. Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock? Intensive Care Med. 2016;42(2): 211-21.
52	He HW, Liu DW, Long Y, Wang XT, Yu C, Yao B, et al. Using peripheral perfusion index and venous-to-arterial CO(2) difference/arterial-central venous O(2) difference ratio to assess lactate clearance in septic patients after resuscitation. Zhonghua Nei Ke Za Zhi. 2018;57(12): 917-21. [Article in Chinese]
53	Troskot R, Šimurina T, Žižak M, Majstorović K, Marinac I, Mrakovčić-Šutić I. Prognostic value of venoarterial carbon dioxide gradient in patients with severe sepsis and septic shock. Croat Med J. 2010;51(6): 501-8.
54	Mallat J, Pepy F, Lemyze M, Gasan G, Vangrunderbeeck N, Tronchon L, et al. Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: a prospective observational study. Eur J Anaesthesiol. 2014; 31(7): 371-80. doi: 10.1097/EJA.0000000000000064 pmid: 24625464
55	Guo ZQ, Yin M, Kong JC, Wang B, Dai KP, Zuo T, et al. Relationship analysis of central venous-to-arterial carbon dioxide difference and cardiac index for septic shock. Sci Rep. 2019; 9(1): 8822. doi: 10.1038/s41598-019-45252-6 pmid: 31217467
56	Dres M, Monnet X, Teboul JL. Hemodynamic management of cardiovascular failure by using PCO(2) venous-arterial difference. J Clin Monit Comput. 2012; 26(5): 367-74. doi: 10.1007/s10877-012-9381-x pmid: 22828858
57	Mallat J, Lemyze M, Tronchon L, Vallet B, Thevenin D. Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock. World J Crit Care Med. 2016; 5(1): 47-56. doi: 10.5492/wjccm.v5.i1.47 pmid: 26855893
58	Durkin R, Gergits MA, Reed JF 3rd, Fitzgibbons J. The relationship between the arteriovenous carbon dioxide gradient and cardiac index. J Crit Care. 1993; 8(4): 217-21. pmid: 8305959
59	Habicher M, von Heymann C, Spies CD, Wernecke KD, Sander M. Central venous-arterial pCO₂ difference identifies microcirculatory hypoperfusion in cardiac surgical patients with normal central venous oxygen saturation: a retrospective analysis. J Cardiothorac Vasc Anesth. 2015; 29(3): 646-55. doi: 10.1053/j.jvca.2014.09.006 pmid: 25575410

[1]	Hui Chen, Yuanhua Lu, Songjie Bai, Yang Li, Tao Wang, Long Cai, Xinyi Yang, Yang Fang, Jianguo Wan, Yaqun Tang, Wenqiang Tao, Meiling Huang, Wei Zhong, Fen Liu, Kejian Qian. Stress-hyperglycemia ratio and glycemic variability predict severity and mortality in sepsis-associated acute respiratory distress syndrome [J]. World Journal of Emergency Medicine, 2026, 17(3): 250-257.
[2]	Yi Yao, Wenjin Li, Dejiang Hong, Ze Chen, Kai Peng, Guangju Zhao. Prediction model for quality of life in sepsis survivors one year after discharge [J]. World Journal of Emergency Medicine, 2026, 17(2): 105-112.
[3]	Zengzheng Ge, Xin Lu, Shiyuan Yu, Mubing Qin, Chao Gong, Qun Xu, Yanxia Gao, Joseph Harold Walline, Huadong Zhu, Yi Li. Diagnostic value of mismatch-negativity and P3a event-related potentials for sepsis-associated encephalopathy in non-sedated patients: a pilot study [J]. World Journal of Emergency Medicine, 2026, 17(2): 172-178.
[4]	Jinlan Ma, Li Peng, Hongming Yu, Jianfeng Xie, Ying Tang, Shenglin Su, Libing Ma, Xiaojun Yang. Single-cell transcriptomics reveals pathogen-specific monocyte heterogeneity and potential biomarkers in gram-positive versus gram-negative bloodstream infections [J]. World Journal of Emergency Medicine, 2026, 17(2): 162-171.
[5]	Xin Lu, Mubing Qin, Zengrui Song, Ying Chen, Huadong Zhu, Yanxia Gao, Yi Li. Normal initial lactate level in sepsis patients: is lactate still useful for prognosis prediction? [J]. World Journal of Emergency Medicine, 2026, 17(1): 57-64.
[6]	Yuhui Pan, Yanyan Ma, Ke Wan, Yizhou Xu, Guoxing Wang, Miaorong Xie. Endothelial cell injury: a crucial link in microcirculatory dysfunction associated with sepsis [J]. World Journal of Emergency Medicine, 2026, 17(1): 28-35.
[7]	Wei Gu, Jie Zhong, Chuanzhu Lyu, Guoqiang Zhang, Miaorong Xie, Yuefeng Ma, Wei Guo. An approach for the emergency diagnosis and treatment of sepsis-associated encephalopathy in elderly individuals: a literature review [J]. World Journal of Emergency Medicine, 2025, 16(5): 415-422.
[8]	Zesheng Wu, Fanghui Chen, Chen Xiao, Xue Zhao, Yuansheng Xu, Jinyan Fang, Yinyan Shao. Long-term cardiovascular outcomes and risk factors in adult sepsis survivors: a systematic review and meta-analysis [J]. World Journal of Emergency Medicine, 2025, 16(5): 423-430.
[9]	Qiaosheng Wang, Qiong Luo, Zhiwei Su, Yan Xu, Liangshan Peng, Yin Wen, Hongke Zeng, Hongguang Ding. Activation of the α7 nicotinic acetylcholine receptor mitigates cognitive deficits in mice with sepsis-associated encephalopathy by inhibiting microglial pyroptosis [J]. World Journal of Emergency Medicine, 2025, 16(5): 438-446.
[10]	Sen Jiang, Xiandong Liu, Tong Liu, Yi Gu, Bo An, Chunxue Wang, Dongyang Zhao, Haitao Zhang, Lunxian Tang. Performance of a novel medical artificial intelligence large language model on supporting decision-making for emergency patients with suspected sepsis [J]. World Journal of Emergency Medicine, 2025, 16(5): 447-455.
[11]	Quan Li, Yun Qu, Jinfang Xue, Hai Kang, Chuanzhu Lyu. Exploring lipid-modifying therapies for sepsis through the modulation of circulating inflammatory cytokines: a Mendelian randomization study [J]. World Journal of Emergency Medicine, 2025, 16(3): 256-261.
[12]	Peili Chen, Yan Ge, Huiqiu Sheng, Wenwu Sun, Jiahui Wang, Li Ma, Enqiang Mao. The role of early changes in routine coagulation tests in predicting the occurrence and prognosis of sepsis [J]. World Journal of Emergency Medicine, 2025, 16(2): 136-143.
[13]	Chunxue Wang, Dianyin Yang, Yuxin Zhu, Qian Yang, Tong Liu, Xiandong Liu, Dongyang Zhao, Xiaowei Bao, Tiancao Dong, Li Shao, Lunxian Tang. Circulating circular RNAs act as potential novel biomarkers for sepsis secondary to pneumonia: a prospective cohort study [J]. World Journal of Emergency Medicine, 2025, 16(2): 144-152.
[14]	Azzah S Alharbi, Raghad Hassan Sanyi, Esam I Azhar. Bacteria and host: what does this mean for sepsis bottleneck? [J]. World Journal of Emergency Medicine, 2025, 16(1): 10-17.
[15]	Chao Gong, Shengyong Xu, Youlong Pan, Shigong Guo, Joseph Harold Walline, Xue Wang, Xin Lu, Shiyuan Yu, Mubing Qin, Huadong Zhu, Yanxia Gao, Yi Li. Effects of probiotic treatment on the prognosis of patients with sepsis: a systematic review [J]. World Journal of Emergency Medicine, 2025, 16(1): 18-27.