• Anemia
• Intensive care unit
• Mortality
• Organ failure
• Red blood cell
• Transfusion
• Ultra restrictive

• Humans
• Critical Illness/therapy
• Blood Transfusion/methods
• Blood Transfusion/standards
• Hemoglobins/analysis
• Hemoglobins/metabolism
• Adult
• Anemia/therapy
• Anemia/blood
• Transfusion Reaction

• gastric cancer
• long-term survival
• perioperative blood transfusion
• transfusion trend
• transfusion trigger

• Humans
• Stomach Neoplasms/surgery
• Stomach Neoplasms/mortality
• Male
• Female
• Middle Aged
• Blood Transfusion/statistics & numerical data
• Gastrectomy
• Hemoglobins/analysis
• Hemoglobins/metabolism
• Aged
• Retrospective Studies
• China/epidemiology
• Adult

• anemia
• non-bleeding critical patients
• red blood cell transfusion
• sepsis
• skin blood flow
• skin laser doppler
• tissue perfusion

Fluid selection and administration during shock is typically guided by consideration of macrovascular abnormalities and resuscitative targets (perfusion parameters, heart rate, blood pressure, cardiac output). However, the microcirculatory unit (comprised of arterioles, true capillaries, and venules) is vital for the effective delivery of oxygen and nutrients to cells and removal of waste products from the tissue beds. Given that the microcirculation is subject to both systemic and local control, there is potential for functional changes and impacts on tissue perfusion that are not reflected by macrocirculatory parameters. This chapter will present an overview of the structure, function and regulation of the microcirculation and endothelial surface layer in health and shock states such as trauma, hemorrhage and sepsis. This will set the stage for consideration of how these microcirculatory characteristics, and the potential disconnect between micro- and macrovascular perfusion, may affect decisions related to acute fluid therapy (fluid type, amount, and rate) and monitoring of resuscitative efforts. Available evidence for the impact of various fluids and resuscitative strategies on the microcirculation will also be reviewed.

• glycocalyx
• hemorrhage
• macrocirculation
• microcirculation
• sepsis
• shock

• cardiogenic shock
• critical care
• extracorporeal membrane oxygenation
• hemodynamics
• microcirculation

• critically ill
• leukoreduced
• red blood cell transfusion
• scoping review
• sublingual microcirculation

• Critical Illness
• Erythrocyte Transfusion
• Erythrocytes
• Humans
• Microcirculation
• Mouth Floor

• Blood bank
• Dielectric spectroscopy
• Interfacial polarization
• Red blood cells

The main concern in shock and resuscitation is whether the microcirculation can carry adequate oxygen to the tissues and remove waste. Identification of an intact coherence between macro- and microcirculation during states of shock and resuscitation shows a functioning regulatory mechanism. However, loss of hemodynamic coherence between the macro and microcirculation can be encountered frequently in sepsis, cardiogenic shock, or any hemodynamically compromised patient. This loss of hemodynamic coherence results in an improvement in macrohemodynamic parameters following resuscitation without a parallel improvement in microcirculation resulting in tissue hypoxia and tissue compromise. Hand-held vital microscopes (HVMs) can visualize the microcirculation and help to diagnose the nature of microcirculatory shock. Although treatment with the sole aim of recruiting the microcirculation is as yet not realized, interventions can be tailored to the needs of the patient while monitoring sublingual microcirculation. With the help of the newly introduced software, called MicroTools, we believe sublingual microcirculation monitoring and diagnosis will be an essential point-of-care tool in managing shock patients.

• Crit Care
• coherence
• microcirculation
• sepsis
• shock

Hemoglobin (Hb) transfusion thresholds are established in intensive care units. A restrictive transfusion threshold (Hb 70–75 g/l) is recommended in septic patients, and a liberal transfusion threshold (Hb 90 g/l) for cardiogenic shock. It is unclear whether these historically adopted transfusion thresholds meet the challenges of individual patients.

We evaluated microvascular flow index (MFI) and proportion of perfused vessels (PPV) in the sublingual microcirculation with CytoCam-IDF microscopy and near-infrared spectroscopy (NIRS). A study team-independent, treating intensivist assigned a total of 64 patients to 1 of 2 two transfusion thresholds, 43 patients to the Hb 75 g/l threshold and 21 patients to the Hb 90 g/l threshold, at a surgical intensive care unit. We performed microcirculatory measurements 1 h before and 1 h after transfusion of 1 unit of red blood cells.

Microcirculatory flow variables correlated negatively with pre-transfusion flow variables (ΔMFI: ρ = − 0.821, p <  0.001; ΔPPV: ρ = − 0.778, p <  0.001). Patients with good initial microcirculation (cutoffs: MFI > 2.84, PPV > 88%) showed a deteriorated microcirculation after red blood cell transfusion. An impaired microcirculation improved after transfusion. At both transfusion thresholds, approximately one third of the patients showed an initially impaired microcirculation. In contrast, one third in every group had good microcirculation above the cutoff variables and did not profit from the transfusion.

The data suggest that the established transfusion thresholds and other hemodynamic variables do not reflect microcirculatory perfusion of patients. Blood transfusion at both thresholds 75 g/l and 90 g/l hemoglobin can either improve or harm the microcirculatory blood flow, questioning the concept of arbitrary transfusion thresholds.

• Capillary density
• Critical illness
• Intensive care unit
• Sublingual microcirculation
• Transfusion
• Vessel perfusion

• Endothelium
• Microparticles
• Red blood cells
• Transfusion
• Vascular reactivity

• Aged
• Aged, 80 and over
• Area Under Curve
• Erythrocyte Transfusion/adverse effects
• Erythrocyte Transfusion/methods
• Erythrocyte Transfusion/standards
• Female
• Humans
• Intensive Care Units/organization & administration
• Intensive Care Units/statistics & numerical data
• Male
• Microvessels/drug effects
• Microvessels/physiopathology
• Middle Aged
• Prospective Studies
• ROC Curve
• Simplified Acute Physiology Score

Cardiac surgery, especially in the presence of cardiopulmonary bypass (CPB), is associated with an inflammatory reaction that may promote microcirculatory alterations, in addition to the general impact on system hemodynamics. Anemia and transfusion make patients more susceptible to the deleterious effects of CPB. In this study, it was aimed to evaluate the effect of dilutional anemia, which is caused by CPB and can be treated with 1–2 units of red blood cell (RBC) transfusion, on global tissue oxygenation parameters in cardiac surgery patients.

This prospective observational study comprised 127 patients who had a relatively stable operation period without any major anesthetic or surgical complications (e.g., operation duration >5 h, bleeding or hemodilution requiring more than 1–2 units of RBCs, or unstable hemodynamics, requiring inotropic support of more than 5 µg/kg/min dopamine). Patients were observationally divided into two groups: minimally transfused (Group Tr) and nontransfused (Group NTr). Global tissue oxygenation parameters were evaluated after anesthesia induction (T1) and at the end of the operation (T3) and compared between the groups.

Group Tr consisted of patients who had significantly lower preoperative hemoglobin values than Group NTr patients. The dilutional anemia of all Group Tr patients could be corrected with 1 unit of RBCs. The lactate levels at T3, increment rates of lactate, and venoarterial carbon dioxide pressure difference (ΔpCO2) levels [(T3 – T1) : T1] in Group Tr were significantly higher than those in Group NTr.

Dilutional anemia as a result of CPB mostly occurs in patients with borderline preoperative hemoglobin concentrations and its correction with RBC transfusion does not normalize the degree of microcirculatory and oxygenation problems, which the patients are already prone to because of the nature of CPB. Preventing dilutional anemia and transfusion, especially in patients with preoperative borderline hemoglobin levels, may therefore reduce the burden of impaired microcirculation-associated organ failure in on-pump cardiac surgery.

• Cardiac surgical procedures
• blood transfusion
• microcirculation
• lactate
• arteriovenous carbon dioxide difference

• children
• congenital heart disease
• cyanosis
• microcirculation
• sidestream dark field imaging

• cardiac surgery
• congenital heart disease
• microcirculation
• paediatric intensive care units

• Adult
• Animals
• Erythrocyte Transfusion/adverse effects
• Erythrocyte Transfusion/methods
• Erythrocytes/metabolism
• Female
• HMGB1 Protein/analysis
• Hemopexin/analysis
• Hemorrhage/etiology
• Hemorrhage/therapy
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Pneumonia/blood
• Pneumonia/etiology
• Pneumonia/mortality
• Pseudomonas Infections/blood
• Pseudomonas Infections/etiology
• Pseudomonas Infections/mortality
• Rats
• Shock, Hemorrhagic/complications
• Signal Transduction
• Survival Analysis
• Toll-Like Receptor 4/analysis
• Toll-Like Receptor 4/antagonists & inhibitors
• Transfusion Reaction/diagnosis
• Transfusion Reaction/metabolism
• Transfusion Reaction/mortality
• Wounds and Injuries/complications

• Mentored Research Training Grant from the Foundation for Anesthesia Education and Research
• School of Medicine, University of Alabama at Birmingham

The primary goal of red blood cell (RBC) transfusion is to supply oxygen to tissues and organs. However, due to a growing number of studies that have reported negative transfusion outcomes, including reduced blood perfusion, there is rising concern about the risks in blood transfusion. RBC are characterized by unique flow-affecting properties, specifically adherence to blood vessel wall endothelium, cell deformability, and self-aggregability, which define their hemodynamic functionality (HF), namely their potential to affect blood circulation. The role of the HF of RBC in blood circulation, particularly the microcirculation, has been documented in numerous studies with animal models. These studies indicate that the HF of transfused RBC (TRBC) plays an important role in the transfusion outcome. However, studies with animal models must be interpreted with reservations, as animal physiology may not reflect human physiology. To test this concept in humans, we have directly examined the effect of the HF of TRBC, as expressed by their deformability and adherence to vascular endothelium, on the transfusion-induced effect on the skin blood flow and hemoglobin increment in β-thalassemia major patients. The results demonstrated, for the first time in humans, that the TRBC HF is a potent effector of the transfusion outcome, expressed by the transfusion-induced increase in the recipients' hemoglobin level, and the change in the skin blood flow, indicating a link between the microcirculation and the survival of TRBC in the recipients' vascular system. The implication of these findings for blood transfusion practice and to vascular function in blood recipients is discussed.

• RBC adhesion
• RBC deformability
• RBC hemodynamic functionality
• blood transfusion
• microcirculation
• red blood cells

• Intensive care unit
• Microcirculation
• Red blood cell transfusion
• Systematic review
• Tissue oxygenation

The microvascular reperfusion injury after retransfusion has not been completely characterized. Specifically, the question of heterogeneity among different microvascular beds needs to be addressed. In addition, the identification of anaerobic metabolism is elusive. The venoarterial PCO₂ to arteriovenous oxygen content difference ratio (P_v-aCO₂/C_a-vO₂) might be a surrogate for respiratory quotient, but this has not been validated. Therefore, our goal was to characterize sublingual and intestinal (mucosal and serosal) microvascular injury after blood resuscitation in hemorrhagic shock and its relation with O₂ and CO₂ metabolism.

Anesthetized and mechanically ventilated sheep were assigned to stepwise bleeding and blood retransfusion (n = 10) and sham (n = 7) groups. We performed analysis of expired gases, arterial and mixed venous blood gases, and intestinal and sublingual videomicroscopy.

In the bleeding group during the last step of hemorrhage, and compared to the sham group, there were decreases in oxygen consumption (3.7 [2.8–4.6] vs. 6.8 [5.8–8.0] mL min⁻¹ kg⁻¹, P < 0.001) and increases in respiratory quotient (0.96 [0.91–1.06] vs. 0.72 [0.69–0.77], P < 0.001). Retransfusion normalized these variables. The P_v-aCO₂/C_a-vO₂ increased in the last step of bleeding (2.4 [2.0–2.8] vs. 1.1 [1.0–1.3], P < 0.001) and remained elevated after retransfusion, compared to the sham group (1.8 [1.5–2.0] vs. 1.1 [0.9–1.3], P < 0.001). P_v-aCO₂/C_a-vO₂ had a weak correlation with respiratory quotient (Spearman R = 0.42, P < 0.001). All the intestinal and sublingual microcirculatory variables were affected during hemorrhage and improved after retransfusion. The recovery was only complete for intestinal red blood cell velocity and sublingual total and perfused vascular densities.

Although there were some minor differences, intestinal and sublingual microcirculation behaved similarly. Therefore, sublingual mucosa might be an adequate window to track intestinal microvascular reperfusion injury. Additionally, P_v-aCO₂/C_a-vO₂ was poorly correlated with respiratory quotient, and its physiologic behavior was different. Thus, it might be a misleading surrogate for anaerobic metabolism.

The online version of this article (doi:10.1186/s40635-017-0136-3) contains supplementary material, which is available to authorized users.

• Hemorrhage
• Hypoxia
• Microcirculation
• Shock
• Transfusion

To investigate the microvascular (skeletal muscle tissue oxygenation; SmO₂) response to transfusion in patients undergoing elective complex spine surgery.

After IRB approval and written informed consent, 20 patients aged 18 to 85 years of age undergoing > 3 level anterior and posterior spine fusion surgery were enrolled in the study. Patients were followed throughout the operative procedure, and for 12 h postoperatively. In addition to standard American Society of Anesthesiologists monitors, invasive measurements including central venous pressure, continual analysis of stroke volume (SV), cardiac output (CO), cardiac index (CI), and stroke volume variability (SVV) was performed. To measure skeletal muscle oxygen saturation (SmO₂) during the study period, a non-invasive adhesive skin sensor based on Near Infrared Spectroscopy was placed over the deltoid muscle for continuous recording of optical spectra. All administration of fluids and blood products followed standard procedures at the Hospital for Special Surgery, without deviation from usual standards of care at the discretion of the Attending Anesthesiologist based on individual patient comorbidities, hemodynamic status, and laboratory data. Time stamps were collected for administration of colloids and blood products, to allow for analysis of SmO₂ immediately before, during, and after administration of these fluids, and to allow for analysis of hemodynamic data around the same time points. Hemodynamic and oxygenation variables were collected continuously throughout the surgery, including heart rate, blood pressure, mean arterial pressure, SV, CO, CI, SVV, and SmO₂. Bivariate analyses were conducted to examine the potential associations between the outcome of interest, SmO₂, and each hemodynamic parameter measured using Pearson’s correlation coefficient, both for the overall cohort and within-patients individually. The association between receipt of packed red blood cells and SmO₂ was performed by running an interrupted time series model, with SmO₂ as our outcome, controlling for the amount of time spent in surgery before and after receipt of PRBC and for the inherent correlation between observations. Our model was fit using PROC AUTOREG in SAS version 9.2. All other analyses were also conducted in SAS version 9.2 (SAS Institute Inc., Cary, NC, United States).

Pearson correlation coefficients varied widely between SmO₂ and each hemodynamic parameter examined. The strongest positive correlations existed between ScvO₂ (P = 0.41) and SV (P = 0.31) and SmO₂; the strongest negative correlations were seen between albumin (P = -0.43) and cell saver (P = -0.37) and SmO₂. Correlations for other laboratory parameters studied were weak and only based on a few observations. In the final model we found a small, but significant increase in SmO₂ at the time of PRBC administration by 1.29 units (P = 0.0002). SmO₂ values did not change over time prior to PRBC administration (P = 0.6658) but following PRBC administration, SmO₂ values declined significantly by 0.015 units (P < 0.0001).

Intra-operative measurement of SmO₂ during large volume, yet controlled hemorrhage, does not show a statistically significant correlation with either invasive hemodynamic, or laboratory parameters in patients undergoing elective complex spine surgery.

• Transfusion
• Complex spine surgery
• Near infrared spectroscopy
• Microvascular blood flow
• Hemodynamic monitoring

• RBC storage
• microcirculation
• tissue oxygenation
• transfusion

• Aged
• Aged, 80 and over
• Blood Preservation/methods
• Cardiac Surgical Procedures
• Erythrocyte Transfusion/methods
• Erythrocytes/metabolism
• Female
• Follow-Up Studies
• Humans
• Male
• Microcirculation/physiology
• Middle Aged
• Oxygen/blood
• Prospective Studies
• Regional Blood Flow/physiology
• Spectroscopy, Near-Infrared
• Time Factors

• K12 HL109068 NHLBI NIH HHS
• R01 HL101382 NHLBI NIH HHS

• transfusion microcirculation

• Acute lung injury
• Heme
• Hemin
• Hemoglobin
• Nitric oxide
• Resuscitation
• Storage lesion

• Animals
• Erythrocytes/cytology
• Heme/antagonists & inhibitors
• Hemorrhage/therapy
• Humans
• Mice
• Mice, Inbred C57BL
• Nitrites/administration & dosage
• Wounds and Injuries/therapy

• R01 HL095468 NHLBI NIH HHS
• T32 HL007918 NHLBI NIH HHS
• HL095468 NHLBI NIH HHS