Andrea Carsetti

Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

IntroductionMicrovascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2) delivery but rarely improves tissue O2 uptake in patients with sepsis. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis.MethodsIn a prospective randomized trial, 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2 saturation (StO2) and tissue hemoglobin index (THI) were determined with near-infrared spectroscopy, and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage, and glycocalyx compounds (syndecan-1, hyaluronan, and heparan sulfate) were measured in the serum.ResultsNo differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When within-group changes were examined, microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01), and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2 upslope increased in both groups. StO2 and StO2 downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03).ConclusionsThis study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis, although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings.Trial registrationClinicalTrials.gov, NCT01584999

Plasma free hemoglobin and microcirculatory response to fresh or old blood transfusions in sepsis.

Background Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected. Methods This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed. Results Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003). Conclusions Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density. Trial Registration ClinicalTrials.gov NCT01584999

Fluid bolus therapy: monitoring and predicting fluid responsiveness.

Purpose of reviewWhen a condition of hypoperfusion has been identified, clinicians must decide whether fluids may increase blood flow or whether other therapeutic approaches are needed. For this purpose, several tests and parameters have been introduced in clinical practice to predict fluid responsiveness and guide therapy. Recent findingsFluid challenge is the gold standard test to assess the preload dependence of the patients. Moreover, several parameters and tests avoiding fluid administration are now available. Pulse pressure variation and stroke volume variation are based on heart–lung interaction and can be used to assess fluid responsiveness. These parameters have several limitations and can really be used in a limited number of critically ill patients. End-expiratory occlusion test and passive leg raising have been proposed to overcome these limitations. The aim of resuscitation is to increase blood flow and perfusion pressure. Dynamic arterial elastance has been recently proposed to predict the pressure response after fluid challenge in preload-dependent patients. Finally, the effects of volume expansion of hemodynamic parameters do not necessarily reach the microcirculation, which should also be assessed. SummaryNowadays, several parameters are available to assess fluid responsiveness. Clinicians need to know all of them, with their limitations, without forgetting that the final aim of all therapies is to improve the microcirculation.

Thermodilution vs pressure recording analytical method in hemodynamic stabilized patients

PURPOSE Many mini-invasive devices to monitor cardiac output (CO) have been introduced and, among them, the pressure recording analytical method (PRAM). The aim of this study was to assess the agreement of PRAM with the intermittent transpulmonary thermodilution and continuous pulmonary thermodilution in measuring CO in hemodynamically stabilized patients. MATERIALS AND METHODS This is a prospective clinical study in a mixed medical-surgical intensive care unit (ICU) and in a postcardiac surgical ICU. Forty-eight patients were enrolled: 32 patients to the medical-surgical ICU monitored with PiCCO (Pulsion Medical System AG, Munich, Germany) and 16 were cardiac patients monitored with Vigilance (Edwards Lifesciences, Irvine, CA). RESULTS A total of 112 measurements were made. Ninety-six comparisons of paired CO measurements were made in patients hospitalized in medical-surgical ICU; 16, in cardiac surgical patients. The mean Vigilance-CO was 4.49 ± 0.99 L/min (range, 2.80-5.90 L/min), and the mean PRAM-CO was 4.27 ± 0.88 L/min (range, 2.85-6.19 L/min). The correlation coefficient between Vigilance-CO and PRAM-CO was 0.83 (95% confidence interval, 0.57-0.94; P < .001). The bias was 0.22 ± 0.55 L/min with limits of agreement between 0.87 and 1.30 L/min. The percentage error was 25%. Mean TP-CO was 6.78 ± 2.04 L/min (range, 4.12-11.27 L/min), and the mean PRAM-CO was 6.11 ± 2.18 L/min (range, 2.82-10.90 L/min). The correlation coefficient between PiCCO-CO and PRAM-CO was 0.91 (95% confidence interval, 0.83-0.96; P < .0001). The bias was 0.67 ± 0.89 L/min with limits of agreement -1.07 and 2.41 L/min. The coefficient of variation for PiCCO was 4% ± 2%, and the coefficient of variation for PRAM was 10% ± 8%. The percentage error was 28%. CONCLUSIONS The PRAM system showed good agreement with pulmonary artery catheter and PiCCO in hemodynamically stabilized patients.

The role of cardiac dysfunction in multiorgan dysfunction

Purpose of review The aim of this review was to examine the main determinants of cardiac dysfunction in critically ill patients, as well as how a reduction in cardiac performance influences other organ function. Recent findings Cardiac dysfunction is a frequent complication in critically ill patients and contributes to organ hypoperfusion and poor outcome. Pathophysiological determinants may include a primary ischaemia/reperfusion injury of the heart, effects of systemic inflammatory and adrenergic responses of the body to a variety of acute insults, as well as cardiovascular effects of commonly applied intensive respiratory or haemodynamic treatments. A strict connection exists between cardiac and other organ function, mediated by haemodynamic, humoral, and immune mechanisms. Heart, lungs, kidneys, and other splanchnic organs such as gut and liver influence each other function in a bidirectional way: this organ crosstalk must be regarded as a key aspect in multiorgan dysfunction. Summary The heart should never be regarded as an isolated organ. When dealing with cardiac dysfunction, clinicians must consider the underlying pathophysiology, potential myocardial depressant effects of intensive treatments, and the complex interaction with other organ function.

Fluid responsiveness in critically ill patients

The first therapeutic approach to patients affected by shock is fluids infusion. In particular, patients affected by sepsis usually require a great amount of fluids in the first phase of resuscitation. Fluids must be considered as other drugs with beneficial but also adverse effects especially in patients with a limited cardiac reserve. For this reason, it is helpful to know, if the patient will respond to fluids. Several studies have shown that hemodynamic parameters classically use to evaluate vascular volumes such as central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP), are not able to predict the response to fluids administration.[1] Volumetric parameters such as global end diastolic volume (GEDV) and left ventricular end diastolic volume (LVEDV), are better related to volume status but are not able to accurately predict fluid responsiveness.[2] Therefore, several dynamic parameters have been developed during the last years to assess fluid responsiveness. The easiest approach is a fluid challenge. It consists to give a small amount of fluid (250–500 ml of crystalloid in few minutes) and verify patient response in term of increase in cardiac output (CO).[3] However, also this small amount of fluid could be deleterious in patients with a limited cardiac reserve. In mechanically ventilated patients, the clinician can use cardiopulmonary interaction to predict patient response to the fluid.[4] Dynamic parameters such as pulse pressure variation, stroke volume variation, and systolic pressure variation are a better predictor of fluid responsiveness than static pressometric and volumetric parameters such as CVP, PAOP, GEDV, and LVEDV.[1] Furthermore, several mini-invasive monitoring systems are able to calculate CO and stroke volume continuously showing dynamic parameters.[5,6] However, these parameters have several limitations and cannot be used in every patient. In fact, a correct interpretation of dynamic parameters requires controlled ventilation with a tidal volume at least of 8 ml/kg, absence of arrhythmias, ventricular dysfunction, intra-abdominal hypertension, and a ratio between heart rate and respiratory rate 3 to 6. All these criteria are difficult to meet in the intensive care setting where we usually apply protective lung ventilation and patients are frequently in spontaneous ventilation. In these situations, an alternative approach could be the assessment of CO variation after a passive leg raising maneuver, responsible for a shift of small amount of blood from legs to the heart. Considering these approaches to hemodynamic evaluation, which could be the role for CVP? Do we still need to measure this parameter? The actual value of CVP is not related to volume status because it is determined by interaction between cardiac and pulmonary function. However, it is still very useful to determine if the patient has a problem in volume status and it has a greater significance, when a dynamic test is performed. With this perspective, the Guytons approach is needed to understand the importance of CVP.[7] If blood pressure is low, and CO is normal or elevated, low systemic vascular resistance is responsible for low blood pressure. If the CO is decreased, this can be due to a decrease in cardiac function or a decrease in the venous return. CVP helps to define whether a decrease in cardiac function or a decrease in return function is the primary problem. If the CVP is high, the problem is primarily decreased cardiac function. On the other hand, if the CVP is low, the primary problem is the venous return and providing more volume will probably solve the problem. CVP is also helpful to evaluate the effect of fluid challenge and to determine the amount of fluid need to perform this test. Sufficient fluid is given when the CVP will be raised by 2 mmHg or more. A concomitant increase in CO indicates that the patient is fluid responsive whereas an increase in CVP without an increase in CO shows that further fluids are not indicated. During spontaneous ventilation, CVP assessment during an inspiratory fall in pleural pressure is very helpful. According to Guytons approach, a decrease in pleural pressure makes the pressures in the heart more negative. When the heart functions on the ascending part of the cardiac function curve, this results in a fall in CVP and an increase in the gradient for venous return and, an increase in right heart output. Under this condition, a volume infusion should increase CO. However, when the heart is functioning on the flat part of the cardiac function curve, the fall in pleural pressure does not produce a change in CVP and therefore the gradient for venous return and consequently CO do not change. Finally, we know that response to fluids may be different if we consider macro-hemodynamic parameters or if we look at the micro-circulatory level. Macro- and micro-hemodynamic are not always coupled, and patients may improve hemodynamic parameters without a concomitant improvement of micro-vascular flow.[8,9] Because the capillary network is the site of oxygen delivery to tissue, every therapeutic intervention should aim to improve micro-vascular flow. The evaluation of sublingual micro-circulation is able to predict which patients are really fluid responsive.[10] In conclusion, the assessment of fluid responsiveness is very important in the management of critically ill patients. Dynamic parameters derived from heart-lungs interaction are very helpful in this setting, but the intensivist should not forget the important information that classical hemodynamic parameters such as CVP, can give us. The evaluation of sublingual micro-circulation may add useful information in decision making about the fluid administration. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A rare case of central venous catheter malpositioning in polytraumatic patient not recognized by chest x-ray

Central venous catheter (CVC) insertion is one of the most widely practiced procedures in the intensive care unit (ICU) and the most common complications of this procedure are pneumothorax, artery puncture and malposition. The location of malpositioned subclavian vein catheters may include the ipsilateral internal jugular vein, the controlateral brachiocephalic vein and loop formation. The cannulation of tributaries of the main intra-thoracic vein is a rare complication (1). A 40-year-old man was admitted to our ICU for polytrauma following an eight meter fall into a manhole left accidentally uncovered. He reported a thoracic trauma and pelvic fractures. The patient was sedated, intubated and mechanically ventilated and a CVC was inserted through the left subclavian vein without complications. No resistance was felt during insertion and venous blood was aspirated through the lumen without signs of obstruction. A chest x-ray was performed to verify the correct position of the central line and no complication was recognized (Fig. 1). A chest CT scan was then performed to control the lung contusion and this revealed that the CVC tip was controlaterally inserted into the right internal thoracic vein (Fig. 2). Thus, the catheter was removed and inserted into the right internal jugular vein. Most of the cases reported in literature associate this complication with left internal jugular vein cannulation with the catether tip into the ipsilateral internal thoracic vein. Other possibilities are azygos vein or pericardiophrenic vein cannulation. Finally, some congenital variant could be present such as the persistence of the left superior vena cava (2). The peculiarity of our case (the first of this kind) is left subclavian vein cannulation with the catheter tip into the controlateral internal thoracic vein. A predisposition of this complication in patients with portal hypertension has been reported because of engorgement of the venous system (3). Patients can be symptomatic or asymptomatic. Symptoms include chest pain, especially during hyperosmolar solution infusion (e.g., total parenteral nutrition) and during high flow infusion rate. Other complications may include venous thrombosis or thrombophlebitis, extravasation of infusate, pleural effusion, pulmonary edema and chest wall abscess (4). Central venous pressure (CVP) waveform analysis could help us suspect this rare complication, by showing flattened waves instead of the typical a, c, v, x, y waves (5). Conclusion: The chest x-ray cannot always demonstrate CVC malpositioning since the catheter can be projected into the vena cava profile (2). We must suspect this complication in case of difficult catheter insertion, typical DOI: 10.5301/jva.5000101

Accuracy of an automatic analysis software to detect microvascular density parameters

Analysis of microvascular density parameters is time consuming and operator-dependent.1 This is the main limitation to use microvascular monitoring in clinical practice as a “point-of-care” tool. Recently, an automatic analysis software has been developed and could allow us to obtain results quickly.

From cardiac output to blood flow auto-regulation in shock

Shock is defined as a state in which the circulation is unable to deliver sufficient oxygen to meet the demands of the tissues, resulting in cellular dysoxia and organ failure. In this process, the factors that govern the circulation at a haemodynamic level and oxygen delivery at a microcirculatory level play a major role. This manuscript aims to review the blood flow regulation from macro- and micro-haemodynamic point of view and to discuss new potential therapeutic approaches for cardiovascular instability in patients in cardiovascular shock. Despite the recent advances in haemodynamics, the mechanisms that control the vascular resistance and the venous return are not fully understood in critically ill patients. The physical properties of the vascular wall, as well as the role of the mean systemic filling pressure are topics that require further research. However, the haemodynamics do not totally explain the physiopathology of cellular dysoxia, and several factors such as inflammatory changes at the microcirculatory level can modify vascular resistance and tissue perfusion. Cellular vasoactive mediators and endothelial and glucocalix damage are also involved in microcirculatory impairment. All the levels of the circulatory system must be taken into account. Evaluation of microcirculation may help one to detect under-diagnosed shock, and together with classic haemodynamics, guide one towards the appropriate therapy. Restoration of classic haemodynamic parameters is essential but not sufficient to detect and treat patients in cardiovascular shock.

Haemodynamic coherence in perioperative setting

Over the last decade, there has been an increased interest in the use of goal-directed therapy (GDT) in patients undergoing high-risk surgery, and various haemodynamic monitoring tools have been developed to guide perioperative care. Both the complexity of the patient and surgical procedure need to be considered when deciding whether GDT will be beneficial. Ensuring optimum tissue perfusion is paramount in the perioperative period and relies on the coherence between both macrovascular and microvascular circulations. Although global haemodynamic parameters may be optimised with the use of GDT, microvascular impairment can still persist. This review will provide an overview of both haemodynamic optimisation and microvascular assessment in the perioperative period.