Noninvasive Monitoring of Peripheral Perfusion in Critically Ill Patients

The evolution of medical knowledge over history happened more recently than advances in the art, industry and other sciences. The industrial revolution through the 18th and 19th centuries was bringing innovations and transforming life in America and Europe whereas it was widely accepted that diseases were the result of an imbalance in humours, and one of the conventional treatments to bring back the good healthy was draining blood through a phlebotomy (bloodletting) (1). Bloodletting was a common ‘cure for everything’ from ancient times until the nineteenth century. The practice gained wide acceptance in America in the eighteenth century with Dr. Benjamin Rush, who treated George Washington for acute laryngitis by draining one liter (nine pounds) of blood in less than 24 hours (2). George Washington died soon afterward. In that time, there was no knowledge of the association between loss of blood and circulatory shock. In fact, shock was still an abstract concept, usually described as ‘sudden vital depression’, ‘great nervous depression’, or ‘final sinking of vitality’. The history of hemodynamic monitoring overlaps with the history of shock and much of the history of shock relates to the history of traumatic shock. The term shock only came into clinical use with Edwin A. Morri, who began to popularize the term using it in his 1867 Civil War text, ‘A Practical Treatise on Shock After Operations and Injuries’ (3). Since then, the word shock started to be linked with the concept of cardiovascular collapse. In the same year, a British Surgeon named Jordan Furneaux wrote what it is known to be one of the first elaborate descriptions of abnormalities in peripheral perfusion during shock conditions (4). In his description, he emphasized the cold, clammy and mottle skin associated with high heart rate (Figure 1). The belief held by notable physicians of that time was that those alterations in peripheral perfusion during shock were the result of a disorder of the nervous system, known as ‘nervous collapse’. Despite these results, the final studies about neural regulation of cardiovascular function in shock did not occur until 1950s

Vasodilators in Septic Shock Resuscitation: A Clinical Perspective

ABSTRACT: Microcirculatory abnormalities have been shown to be frequent in patients with septic shock despite “normalization” of systemic hemodynamics. Several studies have explored the impact of vasodilator therapy (prostacyclin, inhaled nitric oxide, topic acetylcholine and nitroglycerin) on microcirculation and tissue perfusion, with contradictory findings.In this narrative review, we briefly present the pathophysiological aspects of microcirculatory dysfunction, and depict the evidence supporting the use of vasodilators and other therapeutic interventions (fluid administration, blood transfusion, vasopressors and dobutamine) aiming to improve the microcirculatory flow in septic shock patients

Postural change in volunteers: sympathetic tone determines microvascular response to cardiac preload and output increases

Purpose: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. Methods: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30° passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). Results: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. Conclusion: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best pa

Tissue perfusion and oxygenation to monitor fluid responsiveness in critically ill, septic patients after initial resuscitation: a prospective observational study

Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a ≥5 or 10 % increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock

Introduction: Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients.Methods: This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error).Results: Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P <0.05), from 3.3°C (0.7°C) to 0.7°C (0.6°C) (P <0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P <0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P <0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P <0.05), respectively. The magnitude of changes in StO2 was more prono

Clinical assessment of peripheral perfusion to predict postoperative complications after major abdominal surgery early: A prospective observational study in adults

Introduction: Altered peripheral perfusion is strongly associated with poor outcome in critically ill patients. We wanted to determine whether repeated assessments of peripheral perfusion during the days following surgery could help to early identify patients that are more likely to develop postoperative complications.Methods: Haemodynamic measurements and peripheral perfusion parameters were collected one day prior to surgery, directly after surgery (D0) and on the first (D1), second (D2) and third (D3) postoperative days. Peripheral perfusion assessment consisted of capillary refill time (CRT), peripheral perfusion index (PPI) and forearm-to-fingertip skin temperature gradient (Tskin-diff). Generalized linear mixed models were used to predict severe complications within ten days after surgery based on Clavien-Dindo classification.Results: We prospectively followed 137 consecutive patients, from among whom 111 were included in the analysis. Severe complications were observed in 19 patients (17.0%). Postoperatively, peripheral perfusion parameters were significantly altered in patients who subsequently developed severe complications compared to those who did not, and these parameters persisted over time. CRT was altered at D0, and PPI and Tskin-diff were altered on D1 and D2, respectively. Among the different peripheral perfusion parameters, the diagnostic accuracy in predicting severe postoperative complications was highest for CRT on D2 (area under the receiver operating characteristic curve = 0.91 (95% confidence interval (CI) = 0.83 to 0.92)) with a sensitivity of 0.79 (95% CI = 0.54 to 0.94) and a specificity of 0.93 (95% CI = 0.86 to 0.97). Generalized mixed-model analysis demonstrated that abnormal peripheral perfusion on D2 and D3 was an independent predictor of severe postoperative complications (D2 odds ratio (OR) = 8.4, 95% CI = 2.7 to 25.9; D2 OR = 6.4, 95% CI = 2.1 to 19.6).Conclusions: In a group of patients assessed following major abdominal surgery, peripheral perfusion alterations were associated with the development of severe complications independently of systemic haemodynamics. Further research is needed to confirm these findings and to explore in more detail the effects of peripheral perfusion-targeted resuscitation following major abdominal surgery

Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and in Vivo Evaluation

Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is largely unknown, while shell properties have been shown to be an important factor for their performance. The aim of our study was to produce UCAs in-house for hfCEUS. Twelve different UCA formulations A-L were made by either sonication or mechanical agitation. The gas core consisted of C4F10 and the main coating lipid was either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC; A-F formulation) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; G-L formulation). Mechanical agitation r

Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. Methods: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline

Clinical monitoring of peripheral perfusion: There is more to learn

Irrespective of initiating factors, the peripheral circulation shows two general phases during the development and treatment of shock. Most published reports support earlier knowledge that the peripheral circulation is among the first to deteriorate and the last to be restored. With the advent of new and old techniques that allow us to continuously monitor peripheral perfusion, we may further shift our focus from pressure-based to flow-based resuscitation. The persisting challenge is the validation (effect on outcome parameters) of peripheral perfusion monitoring tools that can be simple and readily available worldwide