Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study

Abstract

BackgroundThe conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain.MethodsIn a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273.ResultsEleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4–2.9] vs. 3.0 [2.9–3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6–2.9] vs. 3.0 [2.9–3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6–14.8] vs. 18.0 [18.0–25.4] mm/mm2, p = 0.001 and 5.0 [3.5–7.3] vs. 10.9 [10.9–13.5] 1/mm, p = 0.001), but not in sublingual mucosa.ConclusionIn comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Contradictory responses of the microcirculation to changes in extracorporeal membrane oxygenation pump flow in patients on venoarterial extracorporeal membrane oxygenation: a prospective observational study

“…Moreover, brain rSO 2 correlated well with global cerebral perfusion [25]. Tamosuitis et al found that MFI scores were significantly lower for brain and sublingual mucosa of brain-dead patients compared with those of healthy controls [26].…”

Inter-visit variability of conjunctival microvascular hemodynamic measurements in healthy and diabetic retinopathy subjects

“…Furthermore, conjunctival microcirculation can provide insight into pathophysiology of conditions that can alter systemic circulation (Ohtani, 1996; Schaser et al, 2003; Tamosuitis et al, 2016; Yin et al, 2016). Establishing measurement variability is essential for discriminating between true hemodynamic alterations and random fluctuations.…”

“…Application of these imaging modalities has shown conjunctival microvasculopathy and hemodynamic alterations due to systemic diseases such as Alzheimer's disease (Smith et al, 2009), hypertension (To et al, 2013), hypotension (Gaynes et al, 2012), diabetes (Khansari et al, 2017; Cheung et al, 2009; Cheung et al, 2001; Owen et al, 2008; To et al, 2011), and sickle cell disease (Cheung et al, 2002a; Kord Valeshabad et al, 2015; Paton, 1962; Wanek et al, 2013). Furthermore, a recent study showed a significant decrease in conjunctival blood flow, vessel density and non-perfused areas in brain dead subjects as compared to normal controls (Tamosuitis et al, 2016). Moreover, abnormal conjunctival hemodynamics was reported during internal carotid artery surgery (Schaser et al, 2003).…”

University of Wisconsin vs normal saline solutions for preservation of blood vessels of brain dead donors: A histopathological study

“…Initially, the endothelial dysfunction occurs and inflammatory cytokines are secreted from the endothelial cells resulting in ultimate endothelial detachment. Finally, thrombosis of the vessels occurs . However, knowledge of vascular changes in brain dead patients is very primitive and data accordingly are scarce.…”