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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

ABSTRACT: Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for 1h. Volume restitution was performed by infusion of the equivalent of 2.5 units of packed cells, and the animals were followed for 90 min. Resuscitation study groups were non-oxygen functional fresh RBCs where the hemoglobin (Hb) was converted to methemoglobin (MetHb) [MetRBC], fully oxygen functional fresh RBCs [OxyRBC] and 10% hydroxyethyl starch [HES] as a volume control solution. Measurement of systemic variables, microvascular hemodynamics and capillary perfusion were performed during the hemorrhage, hypovolemic shock and resuscitation. Final blood viscosities after the entire protocol were 3.8 cP for transfusion of RBCs and 2.9 cP for resuscitation with HES (baseline: 4.2 cP). Volume restitution with RBCs with or without oxygen carrying capacity recovered higher mean arterial pressure (MAP) than HES. Functional capillary density (FCD) was substantially higher for transfusion versus HES, and the presence of MetHb in the fresh RBC did not change FCD or microvascular hemodynamics. Oxygen delivery and extraction were significantly lower for resuscitation with HES and MetRBC compared to OxyRBC. Incomplete re-establishment of perfusion after resuscitation with HES could also be a consequence of the inappropriate restoration of blood rheological properties which unbalance compensatory mechanisms, and appear to be independent of the reduction in oxygen carrying capacity.

SUBMITTER: Cabrales P

PROVIDER: S-EPMC3224809 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

Cabrales Pedro P Intaglietta Marcos M Tsai Amy G AG

Resuscitation 20070503 1

Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for 1h. Volume restitution was performed by infusion of th ...[more]

PMID: 17481796

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Project description:Background: Centhaquine (CQ) (Lyfaquin®) is in late stage clinical development as a safe and effective first-in-class resuscitative agent for hemorrhagic shock patients (NCT02408731, NCT04056065, and NCT04045327). Acute kidney injury (AKI) is known to be associated with hemorrhagic shock. Hence, effect of CQ on protection of kidneys from damage due to hemorrhagic shock was investigated. Methods: To assess effect of CQ on AKI in shock, we created a rat model with hemorrhagic shock and AKI. Renal arteries were clamped and de-clamped to induce AKI like ischemia/reperfusion model and hemorrhage was carried out by withdrawing blood for 30 min. Rats were resuscitated with CQ (0.02 mg/kg) for 10 min. MAP, heart rate (HR), and renal blood flow (RBF) were monitored for 120 min. Results: CQ produced a significant improvement in RBF compared to vehicle (p< 0.003) even though MAP and HR was similar in CQ and vehicle groups. Blood lactate level was lower (p = 0.0064) in CQ than vehicle at 120 min post-resuscitation. Histopathological analysis of tissues indicated greater renal damage in vehicle than CQ. Western blots showed higher HIF-1α (p = 0.0152) and lower NGAL (p = 0.01626) levels in CQ vs vehicle. Immunofluorescence in the kidney cortex and medulla showed significantly higher (p< 0.045) expression of HIF-1α and lower expression of Bax (p< 0.044) in CQ. Expression of PHD 3 (p< 0.0001) was higher, while the expression of Cytochrome C (p = 0.01429) was lower in the cortex of CQ than vehicle. Conclusion: Results show CQ (Lyfaquin®) increased renal blood flow, augmented hypoxia response, decreased tissue damage and apoptosis following hemorrhagic shock induced AKI, and may be explored to prevent/treat AKI. Translational Statement: Centhaquine (CQ) is safe for human use and currently in late stage clinical development as a first-in-class resuscitative agent to treat hemorrhagic shock. In the current study, we have explored a novel role of CQ in protection from hemorrhagic shock induced AKI, indicating its potential to treat/prevent AKI.

Project description:OBJECTIVES:To present the recommendations and supporting literature for RBC transfusions in critically ill children with bleeding developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN:Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children. METHODS:The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The bleeding subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS:Transfusion and Anemia Expertise Initiative Consensus Conference experts developed a total of six recommendations focused on transfusion in the critically ill child with acute bleeding. In critically ill children with nonlife-threatening bleeding, we recommend giving a RBC transfusion for a hemoglobin concentration less than 5?g/dL, and be considered for a hemoglobin concentration between 5 and 7?g/dL. In critically ill children with hemorrhagic shock, we suggest that RBCs, plasma and platelets transfusion ratio between 2:1:1 to 1:1:1 until the bleeding is no longer life-threatening. We recommend future studies to develop physiologic and laboratory measures to indicate the need for RBC transfusions, and to determine if goal directed hemostatic resuscitation improves survival. Finally, we recommend future studies to determine if low titer group O whole blood is more efficacious and safe compared with reconstituted whole blood in children with hemorrhagic shock. CONCLUSIONS:The Transfusion and Anemia Expertise Initiative Consensus Conference developed pediatric specific recommendations regarding RBC transfusion management in the critically ill child with acute bleeding, as well as recommendations to help guide future research priorities.

Project description:ImportanceBlood transfusion is a mainstay of therapy for trauma-induced coagulopathy, but the optimal modalities for plasma transfusion in the prehospital setting remain to be defined.ObjectiveTo determine whether lyophilized plasma transfusion can reduce the incidence of trauma-induced coagulopathy compared with standard care consisting of normal saline infusion.Design, setting, and participantsThis randomized clinical trial was performed at multiple centers in France involving prehospital medical teams. Participants included 150 adults with trauma who were at risk for hemorrhagic shock and associated coagulopathy between April 1, 2016, and September 30, 2019, with a 28-day follow-up. Data were analyzed from November 1, 2019, to July 1, 2020.InterventionPatients were randomized in a 1:1 ratio to receive either plasma or standard care with normal saline infusion (control).Main outcomes and measuresThe primary outcome was the international normalized ratio (INR) on arrival at the hospital. Secondary outcomes included the need for massive transfusion and 30-day survival. As a safety outcome, prespecified adverse events included thrombosis, transfusion-related acute lung injury, and transfusion-associated circulatory overload.ResultsAmong 150 randomized patients, 134 were included in the analysis (median age, 34 [IQR, 26-49] years; 110 men [82.1%]), with 68 in the plasma group and 66 in the control group. Median INR values were 1.21 (IQR, 1.12-1.49) in the plasma group and 1.20 (IQR, 1.10-1.39) in the control group (median difference, -0.01 [IQR, -0.09 to 0.08]; P = .88). The groups did not differ significantly in the need for massive transfusion (7 [10.3%] vs 4 [6.1%]; relative risk, 1.78 [95% CI, 0.42-8.68]; P = .37) or 30-day survival (hazard ratio for death, 1.07 [95% CI, 0.44-2.61]; P = .89). In the full intention-to-treat population (n = 150), the groups did not differ in the rates of any of the prespecified adverse events.Conclusions and relevanceIn this randomized clinical trial including severely injured patients at risk for hemorrhagic shock and associated coagulopathy, prehospital transfusion of lyophilized plasma was not associated with significant differences in INR values vs standard care with normal saline infusion. Nevertheless, these findings show that lyophilized plasma transfusion is a feasible and safe procedure for this patient population.Trial registrationClinicalTrials.gov Identifier: NCT02736812.

Project description:Acute kidney injury is a common complication of trauma and hemorrhagic shock. In a porcine model of hemorrhagic shock, resuscitative endovascular balloon aortic occlusion (REBOA) and hemodilution, we hypothesized that invasive kidney oxygen concentration measurements would correlate more strongly with noninvasive near infra-red spectroscopy (NIRS) oxygen saturation measurements when cutaneous sensors were placed over the kidney under ultrasound guidance compared to placement over the thigh muscle and subcutaneous tissue. Eight anesthetized swine underwent hemorrhagic shock 4 of which were resuscitated with intravenous fluids prior to the return of shed blood (Hemodilution protocol) and 4 of which underwent REBOA prior to resuscitation and return of shed blood (REBOA protocol). There was a moderate correlation between the NIRS and kidney tissue oxygen measurements (r = 0.61 p < 0.001; r = 0.67 p < 0.001; r = 0.66 p < 0.001for left kidney, right kidney, and thigh NIRS respectively). When the animals were separated by protocol, the Hemodilution group showed a weak or nonsignificant correlation between NIRS and kidney tissue oxygen measurements (r = 0.10 p < 0.001; r = 0.01 p = 0.1007; r = 0.28 p < 0.001 for left kidney, right kidney, and thigh NIRS respectively). This contrasts with the REBOA group, where left and right kidney as well as thigh NIRS were moderately correlated with kidney tissue oxygen (r = 0.71 p < 0.001; r = 0.74 p < 0.001; r = 0.70 p < 0.001; for left kidney, right kidney, and thigh NIRS respectively). There was a strong correlation between both kidney NIRS signals and thigh NIRS measurements (r = 0.85 p < 0.001; r = 0.88 p < 0.001;for left kidney vs thigh and right kidney vs thigh respectively). There was also a strong correlation between left and right kidney NIRS (r = 0.90 p < 0.001). These relationships were maintained regardless of the resuscitation protocol. These results suggest that kidney NIRS measurements were more closely related to thigh NIRS measurements than invasive kidney tissue oxygen concentration.

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

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