Eva Klijn

The Heterogeneity of the Microcirculation in Critical Illness

Microcirculation, a complex and specialized facet of organ architecture, has characteristics that vary according to the function of the tissue it supplies. Bedside technology that can directly observe microcirculation in patients, such as orthogonal polarization spectral imaging and sidestream dark field imaging, has opened the way to investigating this network and its components, especially in critical illness and surgery. These investigations have underscored the central role of microcirculation in perioperative disease states. They have also highlighted variations in the nature of microcirculation, both among organ systems and within specific organs. Supported by experimental studies, current investigations are better defining the nature of microcirculatory alterations in critical illness and how these alterations respond to therapy. This review focuses on studies conducted to date on the microcirculatory beds of critically ill patients. The functional anatomy of microcirculation networks and the role of these networks in the pathogenesis of critical illness are discussed. The morphology of microvascular beds that have been visualized during surgery and intensive care at the bedside are also described, including those of the brain, sublingual region, skin, intestine, and eyes.

Assessment of tissue oxygen saturation during a vascular occlusion test using near-infrared spectroscopy: the role of probe spacing and measurement site studied in healthy volunteers

IntroductionTo assess potential metabolic and microcirculatory alterations in critically ill patients, near-infrared spectroscopy (NIRS) has been used, in combination with a vascular occlusion test (VOT), for the non-invasive measurement of tissue oxygen saturation (StO2), oxygen consumption, and microvascular reperfusion and reactivity. The methodologies for assessing StO2 during a VOT, however, are very inconsistent in the literature and, consequently, results vary from study to study, making data comparison difficult and potentially inadequate. Two major aspects concerning the inconsistent methodology are measurement site and probe spacing. To address these issues, we investigated the effects of probe spacing and measurement site using 15 mm and 25 mm probe spacings on the thenar and the forearm in healthy volunteers and quantified baseline, ischemic, reperfusion, and hyperemic VOT-derived StO2 variables.MethodsStO2 was non-invasively measured in the forearm and thenar in eight healthy volunteers during 3-minute VOTs using two InSpectra tissue spectrometers equipped with a 15 mm probe or a 25 mm probe. VOT-derived StO2 traces were analyzed for base-line, ischemic, reperfusion, and hyperemic parameters. Data were categorized into four groups: 15 mm probe on the forearm (F15 mm), 25 mm probe on the forearm (F25 mm), 15 mm probe on the thenar (T15 mm), and 25 mm probe on the thenar (T25 mm).ResultsAlthough not apparent at baseline, probe spacing and measurement site significantly influenced VOT-derived StO2 variables. For F15 mm, F25 mm, T15 mm, and T25 mm, StO2 ownslope was -6.4 ± 1.7%/minute, -10.0 ± 3.2%/minute, -12.5 ± 3.0%/minute, and -36.7 ± 4.6%/minute, respectively. StO2 upslope was 105 ± 34%/minute, 158 ± 55%/minute, 226 ± 41%/minute, and 713 ± 101%/minute, and the area under the hyperemic curve was 7.4 ± 3.8%·minute, 10.1 ± 4.9%·minute, 12.6 ± 4.4%·minute, and 21.2 ± 2.7%·minute in these groups, respectively. Furthermore, the StO2 parameters of the hyperemic phase of the VOT, such as the area under the curve, significantly correlated to the minimum StO2 during ischemia.ConclusionsNIRS measurements in combination with a VOT are measurement site-dependent and probe-dependent. Whether this dependence is anatomy-, physiology-, or perhaps technology-related remains to be elucidated. Our study also indicated that reactive hyperemia depends on the extent of ischemic insult.

Real-time assessment of renal cortical microvascular perfusion heterogeneities using near-infrared laser speckle imaging

Laser speckle imaging (LSI) is able to provide full-field perfusion maps of the renal cortex and allows quantification of the average LSI perfusion within an arbitrarily set region of interest and the recovery of LSI perfusion histograms within this region. The aim of the present study was to evaluate the use of LSI for mapping renal cortical microvascular perfusion and to demonstrate the capability of LSI to assess renal perfusion heterogeneities. The main findings were that: 1) full-field LSI measurements of renal microvascular perfusion were highly correlated to single-point LDV measurements; 2) LSI is able to detect differences in reperfusion dynamics following different durations of ischemia; and 3) renal microvascular perfusion heterogeneities can be quantitatively assessed by recovering LSI perfusion histograms.

The response of the host microcirculation to bacterial sepsis: does the pathogen matter?

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte–endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis.

Microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock.

Objectives:To study regional perfusion during experimental endotoxemic and obstructive shock and compare the effect of initial cardiac output-targeted fluid resuscitation with optimal cardiac output-targeted resuscitation on different peripheral tissues. Design:Controlled experimental study. Setting:University-affiliated research laboratory. Subjects:Fourteen fasted anesthetized mechanically ventilated domestic pigs. Interventions:Domestic pigs were randomly assigned to the endotoxemic (n = 7) or obstructive shock (n = 7) model. Central and regional perfusion parameters were obtained at baseline, during greater than or equal to 50% reduction of cardiac output (T1), after initial resuscitation to baseline (T2), and after optimization of cardiac output (T3). Measurements and Main Results:Regional perfusion was assessed in the sublingual, intestinal, and muscle vascular beds at the different time points and included visualization of the microcirculation, measurement of tissue oxygenation, and indirect assessments of peripheral skin perfusion. Hypodynamic shock (T1) simultaneously decreased all regional perfusion variables in both models. In the obstructive model, these variables returned to baseline levels at T2 and remained in this range after T3, similar to cardiac output. In the endotoxemic model, however, the different regional perfusion variables were only normalized at T3 associated with the hyperdynamic state at this point. The magnitude of changes over time between the different vascular beds was similar in both models, but the endotoxemic model displayed greater heterogeneity between tissues. Conclusions:This study demonstrates that the relationship between the systemic and regional perfusion is dependent on the underlying cause of circulatory shock. Further research will have to demonstrate whether different microvascular perfusion variables can be used as additional resuscitation endpoints.

Laser speckle imaging identification of increases in cortical microcirculatory blood flow induced by motor activity during awake craniotomy

OBJECT The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In this study, the authors hypothesized that LSI can be useful as a noncontact method of functional brain mapping during awake craniotomy for tumor removal. Such a modality would be an advance in this type of neurosurgery since current practice involves the application of invasive intraoperative single-point electrocortical (electrode) stimulation and measurements. METHODS After opening the dura mater, patients were woken up, and LSI was set up to image the exposed brain area. Patients were instructed to follow a rest-activation-rest protocol in which activation consisted of the hand-clenching motor task. Subsequently, exposed brain areas were mapped for functional motor areas by using standard electrocortical stimulation (ECS). Changes in the LSI signal were analyzed offline and compared with the results of ECS. RESULTS In functional motor areas of the hand mapped with ECS, cortical blood flow measured using LSI significantly increased from 2052 ± 818 AU to 2471 ± 675 AU during hand clenching, whereas capillary blood flow did not change in the control regions (areas mapped using ECS with no functional activity). CONCLUSIONS The main finding of this study was that changes in laser speckle perfusion as a measure of cortical microvascular blood flow when performing a motor task with the hand relate well to the ECS map. The authors have shown the feasibility of using LSI for direct visualization of cortical microcirculatory blood flow changes during neurosurgery.

Serum C-reactive protein as a predictor of morbidity and mortality in intensive care unit patients after esophagectomy.

BACKGROUND Serum C-reactive protein (CRP) is an acute-phase protein, synthesized during any proinflammatory response in the body. Preoperative elevation of serum CRP has been reported to be a prognostic indicator in oncologic surgery. The aim of this study was to investigate the value of postoperative serum CRP elevation as a prognostic parameter in patients undergoing elective esophagectomy followed by routine admission to the intensive care unit (ICU). METHODS In a prospective follow-up cohort study, data were collected of 63 patients admitted to the ICU after elective esophagectomy surgery from October 2007 to December 2008. Postoperative serum CRP levels were determined at the moment of admission to the ICU, 24, 48, and 72 hours postoperatively, and the relation with the development of complications and the 1-year survival status was investigated. RESULTS In postoperative esophagectomy patients admitted to the ICU, CRP levels at T24 and T48 were significantly higher in the patients who developed postoperative complications, which in itself was associated with lower 1-year survival. CONCLUSIONS In patients undergoing esophagectomy with gastric tube reconstruction, increased CRP levels were associated with the occurrence of postoperative complications and higher 1-year mortality. Postoperative serum CRP levels can easily be monitored in the ICU in order to identify patients at risk for the development of postoperative complications; future research is needed to determine whether these complications can be prevented and improve outcome.

Simultaneous multi-depth assessment of tissue oxygen saturation in thenar and forearm using near-infrared spectroscopy during a simple cardiovascular challenge

IntroductionHypovolemia and hypovolemic shock are life-threatening conditions that occur in numerous clinical scenarios. Near-infrared spectroscopy (NIRS) has been widely explored, successfully and unsuccessfully, in an attempt to use it as an early detector of hypovolemia by measuring tissue oxygen saturation (StO2). In order to investigate the measurement site dependence and probe dependence of NIRS in response to hemodynamic changes, such as hypovolemia, we applied a simple cardiovascular challenge: a posture change from supine to upright, causing a decrease in stroke volume (as in hypovolemia) and a heart rate increase in combination with peripheral vasoconstriction to maintain adequate blood pressure.MethodsMulti-depth NIRS was used in nine healthy volunteers to assess changes in StO2 in the thenar and forearm in response to the hemodynamic changes associated with a posture change from supine to upright.ResultsA posture change from supine to upright resulted in a significant increase (P < 0.001) in heart rate. Thenar StO2 did not respond to the hemodynamic changes following the posture change, whereas forearm StO2 did. Forearm StO2 was significantly lower (P < 0.001) in the upright position compared to supine for all probing depths.ConclusionsThe primary findings in this study were that forearm StO2 is a more sensitive parameter to hemodynamic changes than thenar StO2 and that the depth at which StO2 is measured is of minor influence. Our data support the use of forearm StO2 as a sensitive parameter for the detection of central hypovolemia and hypovolemic shock in (trauma) patients.

Postoperative sublingual microcirculatory derangement following esophagectomy is prevented with dobutamine.

INTRODUCTION Esophagectomy with gastric tube reconstruction is characterized by high postoperative morbidity rates. Recently it was shown that decreased sublingual microvascular blood flow (MBF) preoperatively was associated with increased rate of complications after abdominal surgery. Similar observations in severely septic patients could be treated with dobutamine, independent of cardiac output. Based on these considerations we hypothesized that sublingual MBF derangements are more likely to be found in patients undergoing high risk surgery such as esophagectomy, and if present, might be prevented with administration of low dose dobutamine. METHODS In this single-centre, prospective, double-blinded study, we randomized 20 patients admitted to the Intensive Care Unit following esophagectomy with gastric tube reconstruction into two groups. The intervention group (D) received a small dose of dobutamine (2.5 μg/kg/min) directly postoperative until two days postoperatively, whereas the placebo group (P) received a similar volume of saline. A subset of patients undergoing pancreaticoduodenectomy surgery was included as control group (C) for comparison with the study group. Sublingual MBF was determined one day prior to surgery until two days postoperatively. RESULTS At the first postoperative day, patients in the esophagectomy/placebo group (P), showed a significant lower microvascular flow index, perfused vessel density and proportion of perfused vessels compared to baseline (p < 0.001) and the pancreaticoduodenectomy group (C) (p < 0.001). Administration of dobutamine significantly prevented the overall decrease in microvascular blood flow the first postoperative day. CONCLUSION Postoperative sublingual MBF is markedly impaired in esophagectomy patients compared to patients who underwent a pancreaticoduodenectomy and could be prevented by early administration of a small dose dobutamine.

Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients.

Aim: Peripheral perfusion may predict harmful hypovolemic hypotension during fluid withdrawal by continuous veno-venous hemofiltration (CVVH) in critically ill patients with acute kidney injury. Methods: Twenty-three critically ill AKI patients were subjected to progressive fluid withdrawal. Systemic hemodynamics and peripheral perfusion index (PPI) by pulse oximetry, forearm-to-fingertip skin temperature gradient (Tskin-diff) and tissue oxygen saturation (StO2, near infra-red spectroscopy) were measured. Results: Most hemodynamic values decreased with fluid withdrawal, particularly in the hypotensive group, except for stroke volume (SV) and cardiac output, which decreased to a great extent in the non-hypotensive patients. Increases in systemic vascular resistance (SVR) were less in hypotension. Baseline pulse pressure and PPI were lower in hypotensive (n = 10) than non-hypotensive patients and subsequent PPI values paralleled SV decreases. A baseline PPI ≤0.82 AU predicted hypotension with a sensitivity of 70%, and a specificity of 92% (AUC 0.80 ± 0.11, p = 0.004). Conclusion: Progressive fluid withdrawal during CVVH is poorly tolerated in patients with less increases in SVR. The occurrence of hypotension can be predicted by low baseline PPI.