Exhaled methane as an early non-invasive perfusion marker: relation with perioperative blood loss during elective large joint replacement surgery
Abstract
In surgical procedures associated with major blood loss, early recognition of perfusion insufficiency is essential, as hypovolemic shock resulting from hemorrhage is one of the most common yet preventable causes of death. Currently used hemodynamic parameters, such as blood pressure and heart rate, have limited predictive value. Measurement of exhaled methane (CH₄) concentration represents a novel approach for monitoring mesenteric perfusion, since the primary physiological response to blood loss is a reduction in blood flow within the superior mesenteric artery (SMA). The intestinal segments supplied by the SMA harbor the microbiota that constitute the primary source of exhaled methane. The aim of this study was to investigate changes in exhaled CH₄ concentration in patients undergoing major joint endoprosthesis implantation. A prospective study was conducted between September 1 and October 31, 2024, at the Department of Traumatology and Orthopedics, University of Szeged. Exhaled CH₄ concentrations were measured preoperatively and postoperatively in patients undergoing major joint endoprosthesis implantation. Measurements were performed using a photoacoustic spectroscopy (PAS) device. In addition, intraoperative blood loss, administered fluids, and vital parameters were recorded based on anesthesiology documentation. A total of 25 patients were included (56% male, 44% female; mean age: 66.12 ± 9.72 years). Thirty-two percent of the patients were methane producers. Mean intraoperative blood loss was 262 ± 159.61 mL. The administered crystalloid volume was 747.83 ± 307.29 mL, while the colloid volume was 521.42 ± 80.18 mL. A moderate positive correlation was observed between changes in exhaled CH₄ concentration and the extent of blood loss (r = 0.57); however, this association did not reach statistical significance (p = 0.1386). Our results are limited by the low level of surgical blood loss and the small sample size. If larger studies confirm these results, real-time monitoring of CH₄ could be useful in the early detection of blood loss and could improve the quality of emergency and surgical care.
References
Bársony A, Vida N, Gajda Á, Rutai A, Mohácsi Á, Szabó A, Boros M, Varga G, Érces D. Methane exhalation can monitor the microcirculatory changes of the intestinal mucosa in a large animal model of hemorrhage and fluid resuscitation. Front Med (Lausanne). 2020. Oct 22. 7: 567260. https://doi.org/10.3389/fmed.2020.567260
Cannon JW, Khan MA, Raja AS, Cohen MJ, Como JJ, Cotton BA, Dubose JJ, Fox EE, Inaba K, Rodriguez CJ, Holcomb JB, Duchesne JC. Damage control resuscitation in patients with severe traumatic hemorrhage. J Trauma Acute Care Surg. 2017 82(3): 605-617. https://doi.org/10.1097/TA.0000000000001333
Collins AS. Gastrointestinal complications in shock. Crit Care Nurs Clin North Am. 1990. 2(2): 269-277. https://doi.org/10.1016/S0899-5885(18)30827-X
Dawson B, Drewer J, Roberts T, Levy P, Heal M, Cowan N. Measurements of methane and nitrous oxide in human breath and the development of UK scale emissions. PLoS One. 2023. 18(12): e0295157. https://doi.org/10.1371/journal.pone.0295157
Di Stefano M, Corazza GR. Role of hydrogen and methane breath testing in gastrointestinal diseases. Digestive and Liver Disease Supplements, 2009. 3(2): 40-43. https://doi.org/10.1016/S1594-5804(09)60018-8
Dridi B, Henry M, El Khéchine A, Raoult D, Drancourt M. High prevalence of methanobrevibacter smithii and methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol. PLoS One. 2009. 4(9): e7063. https://doi.org/10.1371/journal.pone.0007063
Gottlieb K, Le C, Wacher V, Sliman J, Cruz C, Porter T, Carter S. Selection of a cut-off for high- and low-methane producers using a spot-methane breath test: results from a large north American dataset of hydrogen, methane and carbon dioxide measurements in breath. Gastroenterol Rep (Oxf). 2017. 5(3): 193-199. https://doi.org/10.1093/gastro/gow048
Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the intestinal mucosa during sepsis. Front Immunol. 2019. Apr 30; 10: 891. https://doi.org/10.3389/fimmu.2019.00891
Jávor P., Donka T, Horváth T, Sándor L, Török L, Szabó A, Hartmann P. Impairment of mesenteric perfusion as a marker of major bleeding in trauma patients. J Clin Med. 2023. 12(10): 3571. https://doi.org/10.3390/jcm12103571
Jávor P, Donka T, Solli HS, Sándor L, Baráth B, Perényi D, Mohácsi Á, Török L, Hartmann P. Could exhaled methane be used as a possible indicator for hemodynamic changes in trauma induced hemorrhagic shock? Scientific basis supported by a case study. Injury. 2024. 55. Suppl 3: 111456. https://doi.org/10.1016/j.injury.2024.111456
Jávor P, Rárosi F, Horváth T, Török L, Varga E, Hartmann P. Detection of exhaled methane levels for monitoring trauma-related haemorrhage following blunt trauma: study protocol for a prospective observational study. BMJ Open, 2022. 12(7): e057872. https://doi.org/10.1136/bmjopen-2021-057872
Levitt MD, Furne JK, Kuskowski M, Ruddy J. Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements. Clin Gastroenterol Hepatol. 2006. 4(2): 123-129. https://doi.org/10.1016/j.cgh.2005.11.006
Mutschler M, Paffrath T, Wölfl C, Probst C, Nienaber U, Schipper IB, Bouillon B, Maegele M. The ATLS® classification of hypovolaemic shock: A well established teaching tool on the edge? 2014. 45. Suppl 3: S35-38. https://doi.org/10.1016/j.injury.2014.08.015
Smith JB, Pittet J-F, Pierce A. Hypotensive resuscitation. Curr Anesthesiol Rep. 2014. 4(3): 209-215. https://doi.org/10.1007/s40140-014-0064-7
Szabó A, Unterkofler K, Mochalski P, Jandacka M, Ruzsanyi V, Szabó G, Mohácsi Á, Teschl S, Teschl G, King J. Modeling of breath methane concentration profiles during exercise on an ergometer. J Breath Res. 2016. 10(1): 017105. https://doi.org/10.1088/1752-7155/10/1/017105
Szűcs S, Bari G, Ugocsai M, Lashkarivand RA, Lajkó N, Mohácsi Á, Szabó A, Kaszaki J, Boros M, Érces D, Varga G. Detection of intestinal tissue perfusion by real-time breath methane analysis in rat and pig models of mesenteric circulatory distress. Crit Care Med. 2019. 47(5): e403-e411. https://doi.org/10.1097/CCM.0000000000003659
Tenhunen JJ, Uusaro A, Kärjä V, Oksala N, Jakob SM, Ruokonen E. Apparent heterogeneity of regional blood flow and metabolic changes within splanchnic tissues during experimental endotoxin shock. Anesth Analg. 2003. 97(2): 555-563. https://doi.org/10.1213/01.ANE.0000072703.37396.93
Tuboly E, Szabó A, Erős G, Mohácsi Á, Szabó G, Tengölics R, Rákhely G, Boros M. Determination of endogenous methane formation by photoacoustic spectroscopy. J Breath Res. 2013. 7(4): 046004. https://doi.org/10.1088/1752-7155/7/4/046004
Van Winkle B, DiBrito SR, Amini N, Levy MJ, Haut ER. A survey of hospitalized trauma patients in hemorrhage control education: are trauma victims willing to stop the bleed? J Surg Res. 2021. Aug 264: 469-473. https://doi.org/10.1016/j.jss.2021.03.015








