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Topical nitroglycerin to detect reversible microcirculatory dysfunction in patients with circulatory shock after cardiovascular surgery: an observational study.

ABSTRACT: Persistent abnormalities in microcirculatory function are associated with poor clinical outcomes in patients with circulatory shock. We sought to identify patients with acutely reversible microcirculatory dysfunction using a low-dose topical nitroglycerin solution and handheld videomicroscopy during circulatory shock after cardiac surgery. Forty subjects were enrolled for the study, including 20 preoperative control and 20 post-operative patients with shock. To test whether microcirculatory dysfunction is acutely reversible during shock, the sublingual microcirculation was imaged with incident dark field microscopy before and after the application of 0.1 mL of a 1% nitroglycerin solution (1 mg/mL). Compared to the control group, patients with shock had a higher microcirculation heterogeneity index (MHI 0.33 vs. 0.12, p < 0.001) and a lower microvascular flow index (MFI 2.57 vs. 2.91, p < 0.001), total vessel density (TVD 22.47 vs. 25.90 mm/mm², p = 0.005), proportion of perfused vessels (PPV 90.76 vs. 95.89%, p < 0.001) and perfused vessel density (PVD 20.44 vs. 24.81 mm/mm², p < 0.001). After the nitroglycerin challenge, patients with shock had an increase in MFI (2.57 vs. 2.97, p < 0.001), TVD (22.47 vs. 27.51 mm/mm², p < 0.009), PPV (90.76 vs. 95.91%, p < 0.001), PVD (20.44 vs. 26.41 mm/mm², p < 0.001), venular RBC velocity (402.2 vs. 693.9 µm/s, p < 0.0004), and a decrease in MHI (0.33 vs. 0.04, p < 0.001. Thirteen of 20 patients showed a pharmacodynamic response, defined as an increase in PVD > 1.8 SD from shock baseline. Hemodynamics and vasoactive doses did not change during the 30-min study period. Our findings suggest a topical nitroglycerin challenge with handheld videomicroscopy can safely assess for localized recruitment of the microcirculatory blood flow in patients with circulatory shock and may be a useful test to identify nitroglycerin responsiveness.

SUBMITTER: Greenwood JC

PROVIDER: S-EPMC9464203 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Topical nitroglycerin to detect reversible microcirculatory dysfunction in patients with circulatory shock after cardiovascular surgery: an observational study.

Greenwood John C JC Talebi Fatima M FM Jang David H DH Spelde Audrey E AE Tonna Joseph E JE Gutsche Jacob T JT Horak Jiri J Acker Michael A MA Kilbaugh Todd J TJ Shofer Frances S FS Augoustides John G T JGT Bakker Jan J Brenner Jacob S JS Muzykantov Vladimir R VR Abella Benjamin S BS

Scientific reports 20220910 1

Persistent abnormalities in microcirculatory function are associated with poor clinical outcomes in patients with circulatory shock. We sought to identify patients with acutely reversible microcirculatory dysfunction using a low-dose topical nitroglycerin solution and handheld videomicroscopy during circulatory shock after cardiac surgery. Forty subjects were enrolled for the study, including 20 preoperative control and 20 post-operative patients with shock. To test whether microcirculatory dysf ...[more]

PMID: 36088474

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Project description:BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

Project description:BackgroundDespite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25-40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRESUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes.Methods and analysisThis will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be quantified with sublingual incident dark field videomicroscopy. Mitochondrial respiration will be measured by performing a substrate-uncoupler-inhibitor titration protocol with high resolution respirometry on peripheral blood mononuclear cells at baseline and serial timepoints during resuscitation and at recovery as a possible liquid biomarker. Plasma samples will be preserved for future analysis to examine endothelial injury and other mechanisms of microcirculatory dysfunction. Thirty-day ventilator and vasopressor-free days (VVFDs) will be measured as a primary outcome, along with sequential organ failure assessment scores, and other clinical parameters to determine if changes in microcirculation and mitochondrial respiration are more strongly associated with clinical outcomes compared to traditional resuscitation targets.DiscussionThis will be the first prospective study to examine both microcirculatory and mitochondrial function in human patients with circulatory shock undergoing cardiac bypass and address a key mechanistic knowledge gap in the cardiovascular literature. The results of this study will direct future research efforts and therapeutic development for patients with shock.

Project description:BackgroundIn patients with septic shock, the skin is often chosen for the evaluation of peripheral perfusion and oxygenation. Changes in skin microcirculatory vessel oxygen saturation and relative hemoglobin concentration can be described using a mottling score or captured with hyperspectral imaging. However, the effectiveness of the mottling score in assessing microcirculation remains to be shown. We hypothesize that the mottling score in patients with septic shock is related to skin microcirculatory perfusion indices quantified by hyperspectral imaging, biomarkers that reflect endothelium activation and damage, and clinical outcome.MethodsHyperspectral imaging of the knee area was performed in 95 intensive care patients with septic shock enrolled in a single-center observational study to obtain relative oxy/deoxyhemoglobin concentration values and construct anatomical maps of skin microcirculatory saturation. The blood was sampled to obtain concentrations of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-2, and syndecan-1. The spectrophotometrically obtained skin microvascular perfusion indices were compared to the mottling score and biomarker concentration. The association between mottling score, skin microcirculatory perfusion indices, and 28-day mortality was also analyzed.ResultsMicrocirculatory oxygen saturation was significantly lower and total hemoglobin concentration was significantly higher in patients with a mottling score of 2 compared to those with a score of 0 (p = 0.02), with no difference between other scores. We found an association between microcirculatory oxygen saturation and PAI-1 levels (rho = - 0.3; p = 0.007). Increased mottling score and decreased microcirculatory oxygen saturation were predictive of 28-day mortality (mottling score 2 vs 0: OR 15.31, 95% CI 4.12-68.11; microcirculatory oxygen saturation: OR 0.90, 95% CI 0.85-0.95). Endothelial biomarkers did not increase the predictive value of skin microcirculatory perfusion indices.ConclusionsHigher mottling scores are associated with lower microcirculatory oxygen saturation but with significant overlap between scores. Microcirculatory oxygen saturation is a quantitative measure of peripheral oxygenation and is more specific than the mottling score in predicting 28-day mortality.

Project description:BackgroundVentilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS.MethodsForty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after.ResultsPercentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001).ConclusionIncreased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.

Project description:Systemic administration of melatonin exerts tissue protective effects in the context of hemorrhagic shock. Intravenous application of melatonin prior to hemorrhage improves gastric microcirculatory perfusion and maintains intestinal barrier function in dogs. The aim of the present study was to analyze the effects of a topical mucosal melatonin application on gastric microcirculation during hemorrhagic shock in vivo and on mucosal barrier function in vitro. In a randomized cross-over study, six anesthetized female foxhounds received 3.3 mg melatonin or the vehicle as a bolus to the gastric and oral mucosa during physiological and hemorrhagic (-20% blood volume) conditions. Microcirculation was analyzed with reflectance spectrometry and laser doppler flowmetry. Systemic hemodynamic variables were measured with transpulmonary thermodilution. For analysis of intestinal mucosal barrier function in vitro Caco-2 monolayers were used. The transepithelial electrical resistance (TEER) and the passage of Lucifer Yellow (LY) from the apical to the basolateral compartment of Transwell chambers were measured. Potential barrier protective effects of melatonin against oxidative stress were investigated in the presence of the oxidant H2O2. During physiologic conditions topical application of melatonin had no effect on gastric and oral microcirculation in vivo. During hemorrhagic shock, gastric microcirculatory oxygenation (μHbO2) was decreased from 81 ± 8% to 50 ± 15%. Topical treatment with melatonin led to a significant increase in μHbO2 to 60 ± 13%. Topical melatonin treatment had no effect on gastric microcirculatory perfusion, oral microcirculation or systemic hemodynamics. Incubation of H2O2 stressed Caco-2 monolayers with melatonin did neither influence transepithelial electrical resistance nor LY translocation. Topical treatment of the gastric mucosa with melatonin attenuates the shock induced decrease in microcirculatory oxygenation. As no effects on local microcirculatory and systemic perfusion were recorded, the improved μHbO2 is most likely caused by a modulation of local oxygen consumption. In vitro melatonin treatment did not improve intestinal barrier integrity in the context of oxidative stress. These results extend the current knowledge on melatonin's protective effects during hemorrhage in vivo. Topical application of melatonin exerts differential effects on local microcirculation compared to systemic pretreatment and might be suitable as an adjunct for resuscitation of hemorrhagic shock.

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Topical nitroglycerin to detect reversible microcirculatory dysfunction in patients with circulatory shock after cardiovascular surgery: an observational study.

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Topical nitroglycerin to detect reversible microcirculatory dysfunction in patients with circulatory shock after cardiovascular surgery: an observational study.

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