Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation

Abstract

Background: Internal hemorrhage is a medical emergency, which requires immediate causal therapy, but the recognition may be difficult. The reactive changes of the mesenteric circulation may be part of the earliest hemodynamic responses to bleeding. Methane is present in the luminal atmosphere; thus, we hypothesized that it can track the intestinal circulatory changes, induced by hemorrhage, non-invasively. Our goal was to validate and compare the sensitivity of this method with an established technique using sublingual microcirculatory monitoring in a large animal model of controlled, graded hemorrhage and the early phase of following fluid resuscitation. Materials and Methods: The experiments were performed on anesthetized, ventilated Vietnamese minipigs (approval number: V/148/2013; n = 6). The animals were gradually bled seven times consecutively of 5% of their estimated blood volume (BV) each, followed by gradual fluid resuscitation with colloid (hydroxyethyl starch; 5% of the estimated BV/dose) until 80 mmHg mean arterial pressure was achieved. After each step, macrohemodynamic parameters were recorded, and exhaled methane level was monitored continuously with a custom-built photoacoustic laser-spectroscopy unit. The microcirculation of the sublingual area, ileal serosa, and mucosa was examined by intravital videomicroscopy (Cytocam-IDF, Braedius). Results: Mesenteric perfusion was significantly reduced by a 5% blood loss, whereas microperfusion in the oral cavity deteriorated after a 25% loss. A statistically significant correlation was found between exhaled methane levels, superior mesenteric artery flow (r = 0.93), or microcirculatory changes in the ileal serosa (ρ = 0.78) and mucosa (r = 0.77). After resuscitation, the ileal mucosal microcirculation increased rapidly [De Backer score (DBS): 2.36 ± 0.42 vs. 8.6 ± 2.1 mm −1 ], whereas serosal perfusion changed gradually and with a lower amplitude (DBS: 2.51 ± 0.48 vs. 5.73 ± 0.75). Sublingual perfusion correlated with mucosal (r = 0.74) and serosal (r = 0.66) mesenteric microperfusion during the hemorrhage phase but not during the resuscitation phase. Conclusion: Detection of exhaled methane levels is of diagnostic significance during experimental hemorrhage as it indicates blood loss earlier than sublingual microcirculatory changes and in the early phase of fluid resuscitation, the exhaled methane values change in association with the mesenteric perfusion and the microcirculation of the ileum.

Detection of exhaled methane levels for monitoring trauma-related haemorrhage following blunt trauma: study protocol for a prospective observational study

“…In contrast to global markers of hypoperfusion, regional indicators such as intestinal macroperfusion and microperfusion reflect on the early, compensatory phase of haemorrhage when blood flow becomes redistributed away from non-vital organs such as the gut and the skin to maintain adequate cerebral and coronary perfusion. 15 16 The reduction of mesenteric perfusion is among the first compensatory responses to blood loss, 17 thus being a potential revealer of occult haemorrhage and early predictor of HS. According to studies on large animal models, the superior mesenteric artery (SMA) flow displays a significant drop already at 5% loss of total blood volume and continues to diminish in parallel with ongoing haemorrhage.…”

“…According to studies on large animal models, the superior mesenteric artery (SMA) flow displays a significant drop already at 5% loss of total blood volume and continues to diminish in parallel with ongoing haemorrhage. 17 Unfortunately, methods for continuous monitoring of the SMA blood flow and downstream intestinal microcirculation have not been elaborated to date. Nevertheless, animal experiments suggest that exhaled methane (CH 4 ) levels correspond to the SMA blood flow, 18 making CH 4 a promising new clinical indicator of haemodynamic deterioration.…”

“…The gas sample passes through the photoacoustic cell generating a photoacoustic signal, which is detected by a microphone. 17 …”

“…Although there is evidence for a relation between the two regional microcirculatory systems, 28 32 reactions of the sublingual microperfusion to haemodynamic changes are considered to be significantly slower than the response of more distal gastrointestinal regions. 17 …”

“… 35 The HI describes perfusion heterogeneity by dividing the difference between the highest MFI and the lowest MFI by the mean MFI. 17 34 Through providing DBS, PVD, MFI and HI, the sublingual microcirculation of each patient will be described quantitatively. Disagreements between the two independent investigators will be resolved by consensus.…”