Jennifer Marie Watters

Standard liquid red blood cells (SLRBCs) are approved for use up to 42 days. During this period, a known storage lesion occurs resulting in increased complications and death. We have previously shown that transfusion of cryopreserved deglycerolized RBCs (CDRBCs), which can be stored for 10 years, results in increased tissue oxygenation compared to SLRBCs. This study was performed to compare the biochemical properties and effects of CDRBCs to SLRBCs. Our hypothesis is that CDRBCs would have a similar profile with respect to the storage lesion compared to SLRBCs. Fifty-seven stable trauma patients who required one or two units of blood were randomized to receive SLRBCs or CDRBCs. Laboratory assays were performed on the donated blood and the patients prior to transfusion and on the patients 12 hours after transfusion. The median age of blood was 14 days in the SLRBC group and 21 months in the CDRBC group (p0.01). Hematocrit increased similarly in both groups and remained similar throughout hospitalization. 2,3 diphosphoglycerate (2,3 DPG) was increased in patients who received CDRBCs and D-dimer levels increased in patients who received SLRBCs (p0.05). Pro- and anti-inflammatory cytokines did not differ between groups after transfusion. Alpha-2 macroglobin, haptoglobin, C-reactive protein, and serum amyloid P were all higher in donated SLRBCs compared to CDRBCs (p0.01). In conclusion, CDRBCs have superior characteristics with respect to the storage lesion compared to SLRBCs. Increases in 2,3 DPG are consistent with our prior findings of increased oxygenation in patients who receive CDRBCs.

Advanced hemostatic dressings perform superior to standard gauze (SG) in animal hemorrhage models but require 2 minutes to 5 minutes application time, which is not feasible on the battlefield. Twenty-four swine received a femoral artery injury, 30 seconds uncontrolled hemorrhage and randomization to packing with SG, Combat Gauze (CG), or Celox Gauze (XG) without external pressure. Animals were resuscitated to baseline mean arterial pressures with lactated Ringers and monitored for 120 minutes. Physiologic and coagulation parameters were collected throughout. Dressing failure was defined as overt bleeding outside the wound cavity. Tissues were collected for histologic and ultrastructural studies. All animals survived to study end. There were no differences in baseline physiologic or coagulation parameters or in dressing success rate (SG: 8/8, CG: 4/8, XG: 6/8) or blood loss between groups (SG: 260 mL, CG: 374 mL, XG: 204 mL; p > 0.3). SG (40 seconds ± 0.9 seconds) packed significantly faster than either the CG (52 ± 2.0) or XG (59 ± 1.9). At 120 minutes, all groups had a significantly shorter time to clot formation compared with baseline (p < 0.01). At 30 minutes, the XG animals had shorter time to clot compared with SG and CG animals (p < 0.05). All histology sections had mild intimal and medial edema. No inflammation, necrosis, or deposition of dressing particles in vessel walls was observed. No histologic or ultrastructural differences were found between the study dressings. Advanced hemostatic dressings do not perform better than conventional gauze in an injury and application model similar to a care under fire scenario.

Introduction: Pulmonary oedema and impairment of oxygenation are reported as common consequences of haemorrhagic shock and resuscitation (HSR). Surprisingly, there is little information in the literature examining differences in crystalloid type during the early phase of HSR regarding the development of pulmonary oedema, the impact on oxygenation and the haemodynamic response. These experiments were designed to determine if differences exist because of crystalloid fluid type in the development of oedema, the impact on oxygenation and the haemodynamic response to fluid administration in early HSR. Methods: Twenty anaesthetised swine underwent a grade V liver injury and bled without resuscitation for 30 minutes. The animals were randomised to receive, in a blinded fashion, either normal saline (NS; n = 10) or lactated Ringer's solution (LR; n = 10). They were then resuscitated with study fluid to, and maintained at, the preinjury mean arterial pressure (MAP) for 90 minutes. Results: Extravascular lung water index (EVLWI) began to increase immediately with resuscitation with both fluid types, increasing earlier and to a greater degree with NS. A 1 ml/kg increase in EVLWI from baseline occurred after administartion of (mean ± standard error of the mean) 68.6 ± 5.2 ml/kg of normal saline and 81.3 ± 8.7 ml/kg of LR (P = 0.027). After 150 ml/kg of fluid, EVLWI increased from 9.5 ± 0.3 ml/kg to 11.4 ± 0.3 ml/kg NS and from 9.3 ± 0.2 ml/kg to 10.8 ± 0.3 ml/kg LR (P = 0.035). Despite this, oxygenation was not significantly impacted (Delta partial pressure of arterial oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ≤ 100) until approximately 250 ml/kg of either fluid had been administered. Animals resuscitated with NS were more acidaemic (with lower lactates), pH 7.17 ± 0.03 NS vs. 7.41 ± 0.02 LR (P < 0.001). Conclusions: This study suggests that early resuscitation of haemorrhagic shock with NS or LR has little impact on oxygenation when resuscitation volume is less than 250 ml/kg. LR has more favourable effects than NS on EVLWI, pH and blood pressure but not on oxygenation.

The debate continues over type and quantity of fluid to administer for resuscitation after traumatic injury. This study aimed to examine effects of resuscitation with lactated Ringer’s (LR) and Hextend (HEX) on the inflammatory response after uncontrolled hemorrhagic shock (UHS). There were 38 swine randomized. Control swine were anesthetized and killed. Sham swine underwent laparotomy, splenectomy, and 2 hours of anesthesia. UHS swine received a grade V liver injury after laparotomy and splenectomy and were randomized to no fluid (NF) resuscitation or to blinded resuscitation 30 minutes after injury with LR or HEX. Fluids were infused as needed to maintain baseline blood pressure for 90 minutes. Lung tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor alpha (TNF-α) were determined. Lung sections were examined for neutrophils (PMNs) sequestered within alveolar walls. All UHS animals survived and initial blood loss was similar between groups. Mean arterial pressures (MAPs) were similar for all UHS animals until resuscitation was initiated. MAPs of resuscitated animals remained similar and were significantly higher than MAPs of the NF animals. Sequestered PMNs were equally elevated in all UHS animals. Cytokine analysis showed increased IL-6, G-CSF, and TNF-α gene transcription in resuscitated swine compared with NF swine. LR and HEX resuscitated swine tissue mRNA levels showed no differences. Fluid resuscitation after solid organ injury and uncontrolled hemorrhage results in greater proinflammatory gene transcription than no resuscitation. LR and HEX resuscitation have equivalent effects on indices of inflammation in the lungs.

The optimal fluid for early resuscitation of hemorrhagic shock would restore perfusion without increasing blood loss, hypothermia, acidosis, or coagulopathy. This study examined effects of a single bolus of hypertonic saline (HTS) with or without (±) dextran (D) after uncontrolled hemorrhage (UH) and determined optimal fluid composition. Fifty swine were anesthetized and underwent invasive line placement, celiotomy, splenectomy, suprapubic catheterization, and grade V liver injury. After 30 minutes of UH, blinded fluid resuscitation was initiated with a 250-mL bolus. Animals were randomized to five groups: normal saline (NS), 3% HTS (3%), 3% HTS/6% D (3% D), 7.5% HTS (7.5%), or 7.5% HTS/6% D (7.5% D). Mean arterial pressure (MAP) and tissue oxygen saturation (StO2) were recorded. Laboratory and thrombelastography (TEG) data were collected every 30 minutes. Animals were sacrificed 120 minutes after injury. Analysis of variance was used to compare groups. Significance was defined as p < 0.05. Baseline characteristics and laboratory values were similar in all groups. All groups achieved a similar degree of shock. Two NS and two 3% animals did not survive to 120 minutes. Fluids containing dextran produced a significantly greater increase in MAP (p < 0.02). Animals receiving 3% D maintained a higher MAP 90 minutes after fluid bolus. Also, 7.5% ± D produced a significantly greater initial increase in StO2 (p < 0.05). This effect declined after fluid bolus while 3% D continued to improve tissue oxygenation. Significant differences developed between groups in TEG values, hematocrit, fibrinogen, urine sodium, serum sodium, serum chloride, and urine output. A single bolus of 3% D after uncontrolled hemorrhagic shock produces an adequate and sustained rise in MAP and StO2 and attenuates hypercoagulability. Resuscitation with 7.5% ± D produces significantly increased urine output accompanied by a decline in MAP and StO2 over time. A single bolus of 7.5% D results in significant dilutional anemia and relative hypofibrinogenemia.