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Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill--where do we stand?

ABSTRACT: A growing body of evidence exists associating depressed microcirculatory function and morbidity and mortality in a wide array of clinical scenarios. It has been suggested that volume replacement therapy using fluids and/or blood in combination with vasoactive agents to modulate macro- and microvascular perfusion might be essential for resuscitation of severely septic patients. Even after interventions effectively optimizing macrocirculatory hemodynamics, however, high mortality rates still persist in critically ill and especially in septic patients. Therefore, rather than limiting therapy to macrocirculatory targets alone, microcirculatory targets could be incorporated to potentially reduce mortality rates in these critically ill patients. In the present review we first provide a brief history of clinical imaging of the microcirculation and describe how microcirculatory imaging has been of prognostic value in intensive care patients. We then give an overview of therapies potentially improving the microcirculation in critically ill patients and propose a clinical trial aimed at demonstrating that therapy targeting improvement of the microcirculation results in improved organ function in patients with severe sepsis and septic shock. We end with some recent technological advances in clinical microcirculatory image acquisition and analysis.

SUBMITTER: Bezemer R

PROVIDER: S-EPMC3580600 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill--where do we stand?

Bezemer Rick R Bartels Sebastiaan A SA Bakker Jan J Ince Can C

Critical care (London, England) 20120619 3

A growing body of evidence exists associating depressed microcirculatory function and morbidity and mortality in a wide array of clinical scenarios. It has been suggested that volume replacement therapy using fluids and/or blood in combination with vasoactive agents to modulate macro- and microvascular perfusion might be essential for resuscitation of severely septic patients. Even after interventions effectively optimizing macrocirculatory hemodynamics, however, high mortality rates still persi ...[more]

PMID: 22713365

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Project description:BackgroundLittle is known about the microcirculatory alterations in patients with chronic mesenteric ischemia (CMI). We hypothesized that patients with CMI have an impaired microcirculatory function and show an oral microcirculatory response after caloric challenge compared to healthy controls.MethodsAll patients and controls received the standard workup for CMI. Sublingual micro-circulation was evaluated before (T0) and 20 minutes after (T1) feeding. The total vessel density (TVD; mm/mm2), perfused vessel density (PVD; mm/mm2), proportion of perfused vessels (PPV; %) and microvascular flow index (MFI; AU) were assessed.ResultsWe included 12 patients (63.2 years [IQR 48.8-70.4 years], 67% males) and 12 controls (32.7 years [IQR 27.7-38.1 years], 42% males). At baseline, patients with CMI had a decreased PPV of the sublingual small vessels (median 84.8% vs 95.7%, P=0.006), PPV of all vessels (PPV median 85.4% vs 95.3%, P=0.007) and microvascular flow index of all vessels (MFIa; median 3.00 vs 2.80, P=0.039) compared to healthy controls. After caloric challenge, PVD increased significantly in both small vessels (perfused vessel density of the small vessels [PVDs]) and all vessels (perfused vessel density of all vessels [PVDa]; PVDs [T0]) median 16.3 [IQR 13.3-22.1] vs [T1] median 19.9 [IQR 14.2-26.2], P=0.008; PVDa [T0] median 19.1 [IQR 16.2-23.6] vs [T1] median 22.2 [IQR 16.5-28.9], P=0.02; proportion of perfused vessels of the small vessels (PPVs; [T0] median 84.8% [IQR 75.3-90.4] vs [T1] median 91.0% [IQR 80.1-93.8], P=0.010). In contrast, no significant changes in microcirculatory parameters were observed after caloric challenge in healthy controls.ConclusionPatients with CMI have an impaired sublingual microcirculation at baseline and show a significant response in the sublingual microcirculation after caloric challenge, whereas healthy controls have a normal microcirculation at baseline and show no reactive response upon a caloric challenge as seen in CMI patients. Sublingual microcirculation visualization may offer a rapid noninvasive method to identify patients at risk for having CMI.

Project description:ObjectiveTo investigate the potential of employing sublingual microcirculation as an early noninvasive screening technique for diabetic nephropathy (DN).Research design and methodsWe recruited 89 patients with type 2 diabetes mellitus (T2DM) and 41 healthy subjects in this cross-sectional observational study. All participants underwent fluorescein fundus angiography, vibration perception testing, 10 g (Semmes-Weinstein) monofilament examination, nerve conduction velocity, and 24-h urine microalbumin determination. HbA1c, fasting plasma glucose, blood lipid, and estimated glomerular filtration rate(eGFR) were measured. Sublingual microcirculatory images were captured using side-stream dark-field (SDF) microcirculation microscopy, and total and perfused vascular density (TVD and PVD) were calculated.ResultsThe sublingual microcirculatory parameters denoting microvascular density and perfusion were negatively correlated with both fasting plasma glucose (TVD, r = - 0.316, P < 0.001; PVD, r = - 0.350, P < 0.001; PPV, r = - 0.279, P = 0.001) and HbA1c (TVD, r = - 0.367, P < 0.001; PVD, r = - 0.423, P < 0.001; PPV, r = - 0.399, P < 0.001). Diabetes patients already had a reduction in sublingual microcirculation compared with healthy control, and more severe reductions in TVD (7.07 ± 1.64 vs. 9.67 ± 1.94 mm/mm2, P < 0.001) and PVD (5.88 ± 1.82 vs. 8.64 ± 2.46 mm/mm2, P < 0.001) were found in those diabetes patients developed microvascular complications. Sublingual microcirculation impairment was accompanied with higher urinary albumin creatinine ratio (UACR). Receiver operating characteristic (ROC) analysis showed that TVD (area under the curve, AUC = 0.890 [0.836 0.944], P < 0.001) and PVD (AUC = 0.883 [0.826, 0.940], P < 0.001) could be indicators for DN screening. We derived a combined predictor index (CPI) considering both TVD and PVD for screening DN, and both the AUC (0.892, [0.838 0.945], P < 0.001) and cutoff point of 11.30 mm/mm2 showed great improvement (sensitivity: 95.5%, specificity: 67.4%).ConclusionsDiabetes patients experienced impaired sublingual microcirculation, which was closely correlated with UACR. Sublingual microcirculation monitoring could be used for the noninvasive early detection of DN.

Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyteÂ® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyteÂ® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyteÂ® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyteÂ® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyteÂ® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyteÂ® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator

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Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill--where do we stand?

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Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill--where do we stand?

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