Factors Affecting Tissue Oxygenation in Erythrocyte Transfusions.

Red blood cell transfusions are used to increase the oxygen-carrying capacity of blood in anemic states. But, because of the changes during storage of blood components and the specifics of preparation, erythrocytes may have controversial effects on tissue oxygenation and microcirculation. Also, the patient situation may play a role in the differing responses in oxygenation and microcirculation. In this review, the studies concerning the effects of banked blood and patient characteristics on microcirculation and tissue oxygenation are summarized.

The effects of non-leukoreduced red blood cell transfusions on microcirculation in mixed surgical patients.

BACKGROUND: The impact of the storage process on oxygen-carrying properties of red blood cells and the efficacy of red blood cell (RBC) transfusions concerning tissue oxygenation remain an issue of debate in transfusion medicine. Storage time and leukocyte content probably interact since longer storage duration is thought to cause greater accumulation of leukocyte-derived cytokines and red blood cell injury. OBJECTIVES: The aim of this study was to investigate the effects of storage and the efficacy of fresh (stored for less than 1 week) versus aged (stored for more than 3 weeks) non-leukoreduced RBC transfusions on sublingual microvascular density and flow in mixed surgical patients. METHODS: Eighteen surgical patients were included in this study. Patients were randomly assigned into two groups receiving fresh (Group A) and aged (Group B) RBC transfusions. Sublingual microcirculatory functional capillary density (FCD) and microvascular flow index (MFI) were assessed using orthogonal polarization spectral (OPS) imaging. Measurements and collection of blood samples were performed after induction of general anesthesia, before RBC transfusion and 30 min after the RBC transfusion ended. RESULTS: In both groups RBC transfusions caused an increase in hemoglobin concentration (p<0.001). RBC transfusions increased FCD in Group A (p<0.001), while FCD remained unaffected in Group B. Changes in MFI following RBC transfusion in both groups remained unaltered. CONCLUSIONS: Fresh non-leukoreduced RBC transfusions but not RBCs stored for more than 3weeks, were effective in improving microciruculatory perfusion by elevating the number of perfused microvessels in mixed surgical patients.

Transfusion of banked red blood cells and the effects on hemorrheology and microvascular hemodynamics in anemic hematology outpatients.

BACKGROUND: The aim of this study was to investigate the effects of red blood cell (RBC) transfusion on the hemorrheologic properties and microcirculatory hemodynamics in anemic hematology outpatients receiving 2 to 4 RBC units of either "fresh" (leukoreduced storage for less than 1 week) or "aged" (leukoreduced storage for 3-4 weeks) RBCs. STUDY DESIGN AND METHODS: Measurements were performed before and 30 minutes after RBC transfusion in hematology outpatients. Leukoreduced RBC suspensions were stored in saline-adenine-glucose-mannitol (SAGM) additive solution. Whole blood viscosity was measured using Couette low-shear viscometry, RBC deformability and aggregability were measured using laser-assisted optical rotational cell analysis, and microcirculatory density and perfusion were assessed using sidestream dark field imaging. RESULTS: One group of patients (n = 10) received a median (interquartile range) of 3 (2-3) RBC bags that were stored for 7 (5-7) days (fresh) and the other group of patients (n = 10) received 3 (3-3) RBC bags that were stored for 23 (22-28) days (aged). After transfusion of fresh versus aged RBCs, hematocrit increased to 32 ± 3% versus 31 ± 2% (p < 0.363), whole blood viscosity increased to 4.2 ± 0.4 Pa/sec versus 4.2 ± 0.6 Pa/sec (p < 0.912), RBC deformability index remained unaffected, RBC aggregability index increased to 55 ± 10 versus 55 ± 13 (p = 0.967), microcirculatory flow remained unaffected, and microcirculatory density increased to 19.3 ± 2.5 mm/mm(2) versus 18.7 ± 1.9 mm/mm(2) (p = 0.595), respectively. CONCLUSION: Storing leukoreduced SAGM-suspended RBCs for 3 to 4 weeks did not affect their ability to improve hemorrheologic properties and microcirculatory hemodynamics in our small group of anemic hematology outpatients. Larger studies are needed to confirm this finding.

Why Rudolph's nose is red: observational study.

OBJECTIVE: To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus's sleigh, is due to the presence of a highly dense and rich nasal microcirculation. DESIGN: Observational study. SETTING: Tromsø, Norway (near the North Pole), and Amsterdam, the Netherlands. PARTICIPANTS: Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. MAIN OUTCOME MEASURES: Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. RESULTS: Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers' nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm(2). Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. CONCLUSIONS: The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph's legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer's brain, factors essential for flying reindeer pulling Santa Claus's sleigh under extreme temperatures.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery.

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm(2) (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm(2) before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system.

The acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock.

INTRODUCTION: Fluid resuscitation therapy is the initial step of treatment for hemorrhagic shock. In the present study we aimed to investigate the acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock. We hypothesized that acetate-balanced solutions would be superior in correcting impaired renal perfusion and oxygenation after severe hemorrhage compared to unbalanced solutions. METHODS: In anesthetized, mechanically ventilated rats, hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 30 mmHg. One hour later, animals were resuscitated with either hydroxyethyl starch (HES, 130/0.42 kDa) dissolved in saline (HES-NaCl; n=6) or a acetate-balanced Ringer's solution (HES-RA; n=6), as well as with acetated Ringer's solution (RA; n=6) or 0.9% NaCl alone (NaCl; n=6) until a target MAP of 80 mmHg was reached. Oxygen tension in the renal cortex (CµPO2), outer medulla (MµPO2), and renal vein were measured using phosphorimetry. RESULTS: Hemorrhagic shock (MAP=30 mmHg) significantly decreased renal oxygenation and oxygen consumption. Restoring the MAP to 80 mmHg required 24.8±1.7 ml of NaCl, 21.7±1.4 ml of RA, 5.9±0.5 ml of HES-NaCl (p<0.05 vs. NaCl and RA), and 6.0±0.4 ml of HES-RA (p<0.05 vs. NaCl and RA). NaCl, RA, and HES-NaCl resuscitation led to hyperchloremic acidosis, while HES-RA resuscitation did not. Only HES-RA resuscitation could restore renal blood flow back to ∼85% of baseline level (from 1.9±0.1 ml/min during shock to 5.1 ml±0.2 ml/min 60 min after HES-RA resuscitation) which was associated with an improved renal oxygenation (CµPO2 increased from 24±2 mmHg during shock to 50±2 mmHg 60 min after HES-RA resuscitation) albeit not to baseline level. At the end of the protocol, creatinine clearance was decreased in all groups with no differences between the different resuscitation groups. CONCLUSION: While resuscitation with the NaCl and RA (crystalloid solutions) and the HES-NaCl (unbalanced colloid solution) led to hyperchloremic acidosis, resuscitation with the HES-RA (acetate-balanced colloid solution) did not. The HES-RA was furthermore the only fluid restoring renal blood flow back to ∼85% of baseline level and most prominently improved renal microvascular oxygenation.

Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients.

BACKGROUND: There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin (Hb) and tissue oxygenation levels and that these conditions would be improved after RBC transfusions. STUDY DESIGN AND METHODS: Near-infrared spectroscopy (NIRS) was used to determine tissue oxygen saturation (StO(2)) and tissue Hb index (THI; an index of the amount of Hb in the NIRS measurement volume) in the thenar eminence and sublingual tissue before and 30 minutes after RBC transfusions in 20 chronically anemic hematology outpatients. Data are presented as median (25%-75%). RESULTS: The patients received three (two to three) bags of RBCs in saline-adenine-glucose-mannitol with an age of 21 (7-21) days, which was infused intravenously at the rate of 0.7 bag/hr. RBC transfusions significantly increased hematocrit level from 26% (24%-28%) to 32% (30%-34%; p < 0.0001), Hb level from 8.2 (7.6-8.9) g/dL to 11.0 (9.9-11.8) g/dL (p < 0.0001), whole blood viscosity from 3.4 (3.1-3.5) mPa/sec to 4.2 (4.0-4.5) mPa/sec (p < 0.0001), thenar StO(2) from 81% (80%-84%) to 86% (81%-89%; p = 0.002), thenar THI from 11.2 (9.3-13.3) AU to 13.7 (9.7-15.3) AU (p = 0.024), sublingual StO(2) from 86% (81%-89%) to 91% (86%-92%; p < 0.0001), and sublingual THI from 15.2 (13.0-17.4) AU to 17.2 (13.5-19.7) AU (p = 0.040). CONCLUSION: Although anemia in chronically anemic hematology outpatients was not associated with low StO(2) and THI levels, RBC transfusions were successful in improving these variables.

Blood transfusions recruit the microcirculation during cardiac surgery.

BACKGROUND: Perioperative red blood cell transfusions are commonly used in patients undergoing cardiac surgery to correct anemia caused by blood loss and hemodilution associated with cardiopulmonary bypass circulation. The aim of this investigation was to test the hypothesis that blood transfusion has beneficial effects on sublingual microcirculatory density, perfusion, and oxygenation. To this end, sidestream dark field (SDF) imaging and spectrophotometry were applied sublingually before and after blood transfusion during cardiac surgery. STUDY DESIGN AND METHODS: Twenty-four adult patients undergoing on-pump cardiac surgery, including coronary artery bypass grafting, cardiac-valve surgery, or a combination of these two procedures, were included consecutively in this prospective, observational study. Sublingual microcirculatory density and perfusion were assessed using SDF imaging in 12 patients (Group A). Sublingual reflectance spectrophotometry was applied in 12 patients (Group B) to monitor microcirculatory oxygenation and hemoglobin (Hb) concentration. RESULTS: Blood transfusion caused an increase in systemic Hb concentration (p < 0.01) and hematocrit (p < 0.01). At the microcirculatory level, blood transfusion resulted in increased microcirculatory density (from 10.5 ± 1.2 to 12.9 ± 1.2 mm capillary/mm(2) tissue, p < 0.01) as shown using SDF imaging. In concert with the SDF measurements, spectrophotometry showed that microcirculatory Hb content increased from 61.4 ± 5.9 to 70.0 ± 4.7 AU (p < 0.01) and that microcirculatory Hb oxygen saturation increased from 65.6 ± 8.3% to 68.6 ± 8.4% (p = 0.06). CONCLUSION: In this study we have shown that blood transfusion: 1) improves the systemic circulation and oxygen-carrying capacity, 2) improves sublingual microcirculatory density but not perfusion velocity, and 3) improves microcirculatory oxygen saturation.