Traumatic Hemorrhagic Shock Research Articles

Use of Vasopressor Increases the Risk of Mortality in Traumatic Hemorrhagic Shock: A Nationwide Cohort Study in Japan.

To evaluate the possible association of vasopressor use with mortality in traumatic hemorrhagic shock patients. Retrospective cohort study. Traumatic hemorrhagic shock patients at 260 emergency hospitals in Japan between 2004 and 2015. Three-thousand five-hundred fifty-one traumatic hemorrhagic shock patients who had systolic hypotension (< 90 mm Hg) on arrival at the emergency department and a blood transfusion received within the first 24 hours. The use of vasopressor for traumatic hemorrhagic shock within the first 24 hours. Among 236,698 trauma patients, 3,551 were included in the study. Overall, 198 of 459 patients (43%) in the vasopressor+ group expired compared with 481 of 3,092 patients (16%) in the vasopressor- group. Use of vasopressor had an odds ratio of 2.172 (95% CI, 1.666-2.833) for in-hospital mortality adjusted for age, gender, year of onset, cause of injury, mechanism of injury, vital signs at the emergency department, Injury Severity Score, use of prehospital IV fluid, and volume of blood transfusion within the first 24 hours. In the propensity score-matched cohort and two subgroup analyses (massive transfusion and survivable injury models), use of vasopressor was associated with higher mortality (odds ratio, 2.168; 95% C, 1.442-3.320), (odds ratio, 2.029; 95% CI, 1.414-2.911; massive transfusion model), and (odds ratio, 1.959; 95% CI, 1.364-2.814; survivable injury model). Use of vasopressor for traumatic hemorrhagic shock was associated with mortality after controlling for biases (trauma severity; volume of fluid resuscitation).

Risks and benefits of hypotensive resuscitation in patients with traumatic hemorrhagic shock: a meta-analysis

BackgroundDamage control strategies play an important role in trauma patient management. One such strategy, hypotensive resuscitation, is being increasingly employed. Although several randomized controlled trials have reported its benefits, the mortality benefit of hypotensive resuscitation has not yet been systematically reviewed.ObjectivesTo conduct a meta-analysis of the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock patients relative to mortality as the primary outcome, with acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and multiple organ dysfunction as the secondary outcomes.MethodsPubMed, Medline-Ovid, Scopus, Science Direct, EMBASE, and CNKI database searches were conducted. An additional search of relevant primary literature and review articles was also performed. Randomized controlled trials and cohort studies reporting the mortality rate associated with hypotensive resuscitation or limited fluid resuscitation were selected. The random-effects model was used to estimate mortality and onset of other complications.ResultsOf 2114 studies, 30 were selected for this meta-analysis. A statistically significant decrease in mortality was observed in the hypotensive resuscitation group (risk ratio [RR]: 0.50; 95% confidence interval [CI]: 0.40–0.61). Heterogeneity was observed in the included literature (I2: 27%; degrees of freedom: 23; p = 0.11). Less usage of packed red cell transfusions and fluid resuscitations was also demonstrated. No significant difference between groups was observed for AKI; however, a protective effect was observed relative to both multiple organ dysfunction and ARDS.ConclusionsThis meta-analysis revealed significant benefits of hypotensive resuscitation relative to mortality in traumatic hemorrhagic shock patients. It not only reduced the need for blood transfusions and the incidences of ARDS and multiple organ dysfunction, but it caused a non-significant AKI incidence.

Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats.

Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact to their brain and pressure-controlled HS. Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96 hours postinjury. Hemoadsorption improved survival from 47% in sham-treated rats to 86% in HA-treated rats. There were no treatment-related changes in histologic appearance. Hemoadsorption affected biomarker concentrations both during the treatment and over the ensuing 4 days after injury. Distinct changes in biomarker concentrations were also measured in survivor and nonsurvivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. Blood purification by nonselective HA is an effective intervention to prevent death in a combined TBI/HS rat model. Hemoadsorption changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. Hemoadsorption has been safely implemented in human patients with sepsis and may be a treatment option after injury.

Abstract 190: Hybrid Strategy of Damage Control IR (DCIR) and REBOA Would be Feasible for Traumatic Hemorrhagic Shock Patients Suffering From Severe Pelvic Injuries

Introduction: Massive hemorrhage with pelvic injury is sometimes lethal. So, success or failure of hemostatic intervention in the hyperacute phase leads to survival of patients directly. Recently, a hybrid strategy with Operative Management (OM) and Interventional Radiology (IR) and/or Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for torso or pelvic severe trauma has been recognized world-widely. But, awareness of Damage control IR (DCIR) which is conscious of time and coagulopathy as Damage control surgery (DCS) is still not enough. So, we studied the possibility of the hybrid strategy with DCIR and REBOA for traumatic hemorrhagic shock patients with pelvic fracture. Methods: This study included patients who underwent traditional IR or DCIR with REBOA, if it were needed, for a traumatic shock state mainly due to pelvic fracture, at our emergency and trauma center. They were sorted into traditional IR group (group IR) and DCIR group (group DCIR). The primary endpoint was a survival rate in the first 30 days after injured. Secondary endpoints were fluid factors such as total amount of crystalloid infusion and blood transfusion within the first 24 hours, and for the duration of the recovery from shock state. Results: 64 trauma shock patients were sorted into group IR (n=38) and group DCIR (n=26). All REBOA patients (n=18) were in group DCIR. Initial systolic BP (group IR vs DCIR; 75mmHg vs. 54), RTS (5.66 vs. 4.12) and Ps (0.61 vs. 0.39) were significantly lower in group DCIR. ISS (32.8 vs. 41.5) and initial Shock Index (1.9 vs. 2.4) were higher in group DCIR significantly. There were no significant differences in the amount of total crystalloid infusion (7353+/-3152ml vs. 7140+/-5342ml) and blood transfusion (4183+/-3485ml vs. 3972+/-3188ml), and the survival rate (30/38 (79%) vs. 16/28 (62%)). But the required time to recovery from shock state was significantly shorter in group DCIR (65min vs. 43min). Conclusion: The hybrid strategy with DCIR and REBOA did not increase any amount of blood transfusion or crystalloid infusion or the mortality rate. But it could shorten the duration of shock state compared with traditional IR treatment. Thus, this hybrid strategy would be feasible for hemorrhage shock patients suffering from pelvic severe trauma.

Variability of the f-cell ratio after treatment of traumatic hemorrhagic shock

PurposeMeasuring total blood volume (TBV) in critically ill patients, using isotope techniques to determine red cell volume (RBCV) and plasma volume (PV) is laborious. Recently, PV measurement using a single bolus dose of tracers has been validated, thus, allowing TBV calculation using large venous hematocrit (LVHCT). However, this technique relies on using a correlation factor, the f-cell ratio, to adjust for differences in LVHCT and total body hematocrit (TBHCT). The normal f-cell ratio is 0.9 but has never been studied in patients recovering from hemorrhagic shock (HS). This study assesses the f-cell ratio at different phases after HS to determine accuracy in calculating TBV.Methods114 injured patients requiring immediate operation for HS were studied. All patients had measurements of PV and RBCV via isotope dilution enabling measurements of TBHCT. Correlation of LVHCT and TBHCT were used to calculate the f-cell ratio in the fluid sequestration (n = 81) and in the fluid mobilization period (n = 108).ResultsThe f-cell ratio (mean ± SD) averaged 0.89 ± 0.15 and 0.90 ± 0.01 in the first and second halves of the fluid sequestration period versus 0.90 ± 0.2 and 0.80 ± 0.07 in the first and second 48 h of the fluid mobilization period. The f-cell ratio was significantly lower (p=<0.001) in the mobilization period.ConclusionsThese data show for the first time that using PV and LVHCT to calculate TBV after HS is unreliable. The mechanisms causing this variation in f-cell ratio is unknown but likely related to capillary/interstitial dynamics and needs further scientific study.

Secretome Conveys the Protective Effects of ASCs: Therapeutic Potential Following Hemorrhagic Shock?

We tested whether resuscitation supplemented with rat adipose-derived stem cells (ASCs) or secretome (conditioned media) of ASCs can ameliorate inflammation, cell/organ injury, and/or improve outcome after hemorrhagic traumatic shock (HTS). Rats were subjected to HTS and a resuscitation protocol that mimics prehospital restrictive reperfusion followed by an adequate reperfusion phase. Twenty minutes into the restrictive reperfusion, animals received an intravenous bolus of 2 × 10 cells (ASC group) or the secretome produced by 2 × 10 ASCs/24 h (ASC-Secretome group). Controls received the vehicle (Vehicle group). All rats were observed for 28-day survival. HTS-induced inflammation represented by IL-6 was inhibited in the ASC (80%, P < 0.001) and in ASC-Secretome (59%, P < 0.01) group at 48 h compared with Vehicle group. At 24 h, HTS-induced liver injury reflected in plasma alanine aminotransferase was ameliorated by 36% (P < 0.001) in both the ASC and ASC-Secretome groups when compared with the Vehicle. There was no effect on kidney function and/or general cell injury markers. HTS induced a moderate 28-day mortality (18%) that was prevented (P = 0.08) in the ASC but not in the ASC-Secretome group (12%). Our data suggest that the ASC-secretome supplemented resuscitation following HTS, in the absence of the stem cells, exerts anti-inflammatory and liver protective effects. Given its ease of preparation, storage, availability, and application (in contrast to the stem cells) we believe that the cell-free secretome has a better therapeutic potential in the early phase of an acute hemorrhagic shock scenario.

Valproic Acid Treatment Attenuates Degenerative Brain Lesions, Neuroinflammation, and Apoptosis in Long-Term Survival Model of Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma in Swine

Valproic Acid Treatment Attenuates Degenerative Brain Lesions, Neuroinflammation, and Apoptosis in Long-Term Survival Model of Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma in Swine

Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study.

To assess the relationship between microcirculatory perfusion and multiple organ dysfunction syndrome in patients following traumatic hemorrhagic shock. Multicenter prospective longitudinal observational study. Three U.K. major trauma centers. Fifty-eight intubated and ventilated patients with traumatic hemorrhagic shock. Sublingual incident dark field microscopy was performed within 12 hours of ICU admission (D0) and repeated 24 and 48 hours later. Cardiac output was assessed using oesophageal Doppler. Multiple organ dysfunction syndrome was defined as Serial Organ Failure Assessment score greater than or equal to 6 at day 7 post injury. Data from 58 patients were analyzed. Patients had a mean age of 43 ± 19 years, Injury Severity Score of 29 ± 14, and initial lactate of 7.3 ± 6.1 mmol/L and received 6 U (interquartile range, 4-11 U) of packed RBCs during initial resuscitation. Compared with patients without multiple organ dysfunction syndrome at day 7, patients with multiple organ dysfunction syndrome had lower D0 perfused vessel density (11.2 ± 1.8 and 8.6 ± 1.8 mm/mm; p < 0.01) and microcirculatory flow index (2.8 [2.6-2.9] and 2.6 [2.2-2.8]; p < 0.01) but similar cardiac index (2.5 [± 0.6] and 2.1 [± 0.7] L/min//m; p = 0.11). Perfused vessel density demonstrated the best discrimination for predicting subsequent multiple organ dysfunction syndrome (area under curve 0.87 [0.76-0.99]) compared with highest recorded lactate (area under curve 0.69 [0.53-0.84]), cardiac index (area under curve 0.66 [0.49-0.83]) and lowest recorded systolic blood pressure (area under curve 0.54 [0.39-0.70]). Microcirculatory hypoperfusion immediately following traumatic hemorrhagic shock and resuscitation is associated with increased multiple organ dysfunction syndrome. Microcirculatory variables are better prognostic indicators for the development of multiple organ dysfunction syndrome than more traditional indices. Microcirculatory perfusion is a potential endpoint of resuscitation following traumatic hemorrhagic shock.

Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats

Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. Materials and methods: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer’s solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Results: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 ± 420 vs. 724 ± 75 AU) and in liver (474 ± 57 vs. 261 ± 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p < 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 ± 2 vs. 14 ± 0.5 RLU). Conclusion: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions.

Role of metabolic changes of mucosal layer in the intestinal barrier dysfunction following trauma/hemorrhagic shock

BackgroundThe mucosal layer plays an important role in regulating the intestinal barrier function. However, the underlying mechanisms of intestinal barrier dysfunction caused by trauma-hemorrhagic shock (THS) are still unknown. MethodsIn this study, we examined the barrier damages, inflammatory responses as well as the metabolic changes of the mucosal layer of the colon in a THS rat model. ResultsThe results showed that compared to the rats treated with trauma only, THS induced marked failure of intestinal barrier characterized by increased intestinal permeability, inflammatory cell infiltration and decreased expression of genes involved in epithelial integrity. Moreover, decreased colonic mucus content and goblet cell numbers indicated that the mucosal layer was also impaired in response to THS. This was companied by the anomalous inflammatory responses in the tissue. Finally, microdialysis catheter examination showed that metabolites including glycerol, glucose, lactate and pyruvate, glutamate and glutamine were also altered by THS. ConclusionOur results provide evidence that mucus layer-associated metabolic changes may contribute to the THS-induced intestinal barrier dysfunction.

Transfusion Therapy

Exsanguination occurs rapidly after trauma (median 2 to 3 hours after admission) and is the leading cause of preventable trauma deaths. The modern treatment for traumatic hemorrhagic shock is simultaneous mechanical hemorrhage control and damage control resuscitation (DCR), which emphasizes using plasma as the primary means for volume expansion. Other core DCR principles include minimization of crystalloid, permissive hypotension, and goal-directed resuscitation. The treatment of traumatic hemorrhage is complicated by trauma-induced coagulopathy (TIC); DCR is thought to address TIC directly despite incomplete understanding of the underlying mechanisms. Recent data point to a 1:1:1 ratio of plasma and platelets to red blood cells as the optimal blood product ratio for acute traumatic hemorrhage. However, this paradigm may soon be supplanted by a transition back to whole blood. Although it is intuitive to apply these same protocols and algorithms to patients with nontraumatic hemorrhage, the scientific evidence is lacking. Key words: endotheliopathy, hemorrhage, massive transfusion, trauma-induced coagulopathy

Transfusion Therapy

Exsanguination occurs rapidly after trauma (median 2 to 3 hours after admission) and is the leading cause of preventable trauma deaths. The modern treatment for traumatic hemorrhagic shock is simultaneous mechanical hemorrhage control and damage control resuscitation (DCR), which emphasizes using plasma as the primary means for volume expansion. Other core DCR principles include minimization of crystalloid, permissive hypotension, and goal-directed resuscitation. The treatment of traumatic hemorrhage is complicated by trauma-induced coagulopathy (TIC); DCR is thought to address TIC directly despite incomplete understanding of the underlying mechanisms. Recent data point to a 1:1:1 ratio of plasma and platelets to red blood cells as the optimal blood product ratio for acute traumatic hemorrhage. However, this paradigm may soon be supplanted by a transition back to whole blood. Although it is intuitive to apply these same protocols and algorithms to patients with nontraumatic hemorrhage, the scientific evidence is lacking. Key words: endotheliopathy, hemorrhage, massive transfusion, trauma-induced coagulopathy

Selective Brain Cooling Reduces Motor Deficits Induced by Combined Traumatic Brain Injury, Hypoxemia and Hemorrhagic Shock.

Selective brain cooling (SBC) can potentially maximize the neuroprotective benefits of hypothermia for traumatic brain injury (TBI) patients without the complications of whole body cooling. We have previously developed a method that involved extraluminal cooling of common carotid arteries, and demonstrated the feasibility, safety and efficacy for treating isolated TBI in rats. The present study evaluated the neuroprotective effects of 4-h SBC in a rat model of penetrating ballistic-like brain injury (PBBI) combined with hypoxemic and hypotensive insults (polytrauma). Rats were randomly assigned into two groups: PBBI+polytrauma without SBC (PHH) and PBBI+polytrauma with SBC treatment (PHH+SBC). All animals received unilateral PBBI, followed by 30-min hypoxemia (fraction of inspired oxygen = 0.1) and then 30-min hemorrhagic hypotension (mean arterial pressure = 40 mmHg). Fluid resuscitation was given immediately following hypotension. SBC was initiated 15 min after fluid resuscitation and brain temperature was maintained at 32–33°C (core temperature at ~36.5°C) for 4 h under isoflurane anesthesia. The PHH group received the same procedures minus the cooling. At 7, 10, and 21 days post-injury, motor function was assessed using the rotarod task. Cognitive function was assessed using the Morris water maze at 13–17 days post-injury. At 21 days post-injury, blood samples were collected and the animals were transcardially perfused for subsequent histological analyses. SBC transiently augmented cardiovascular function, as indicated by the increase in mean arterial pressure and heart rate during cooling. Significant improvement in motor functions were detected in SBC-treated polytrauma animals at 7, 10, and 21 days post-injury compared to the control group (p < 0.05). However, no significant beneficial effects were detected on cognitive measures following SBC treatment in the polytrauma animals. In addition, the blood serum and plasma levels of cytokines interleukin-1 and −10 were comparable between the two groups. Histological results also did not reveal any between-group differences in subacute neurodegeneration and astrocyte/ microglial activation. In summary, 4-h SBC delivered through extraluminal cooling of the common carotid arteries effectively ameliorated motor deficits induced by PBBI and polytrauma. Improving cognitive function or mitigating subacute neurodegeneration and neuroinflammation might require a different cooling regimen such as extended cooling, a slow rewarming period and a lower temperature.

Mesenchymal Stem Cell-Derived Exosomes Provide Neuroprotection and Improve Long-Term Neurologic Outcomes in a Swine Model of Traumatic Brain Injury and Hemorrhagic Shock.

Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remains a leading cause of preventable death worldwide. Mesenchymal stem cell-derived exosomes have demonstrated promise in small animal models of neurologic injury. To investigate the effects of exosome treatment in a clinically realistic large animal model, Yorkshire swine underwent TBI and HS. Animals were maintained in shock for 2 h before resuscitation with normal saline (NS). Animals were then resuscitated either with NS (3 × volume of shed blood) or with the same volume of NS with delayed exosome administration (1 × 1013 particles/4 mL) (n = 5/cohort). Exosomes were administered 9 h post-injury, and on post-injury days (PID) 1, 5, 9, and 13. Neurologic severity scores (NSS) were assessed for 30 days, and neurocognitive functions were objectively measured. Exosome-treated animals had significantly lower NSS (p < 0.05) during the first five days of recovery. Exosome-treated animals also had a significantly shorter time to complete neurologic recovery (NSS = 0) compared with animals given NS alone (days to recovery: NS = 16.8 ± 10.6; NS + exosomes = 5.6 ± 2.8; p = 0.03). Animals treated with exosomes initiated neurocognitive testing earlier (days to initiation: NS = 9.6 ± 0.5 vs. NS + exosomes = 4.2 ± 0.8; p = 0.008); however, no difference was seen in time to mastery of tasks. In conclusion, treatment with exosomes attenuates the severity of neurologic injury and allows for faster neurologic recovery in a clinically realistic large animal model of TBI and HS.

Red tides: Mass casualty and whole blood at sea.

The U.S. Navy's casualty-receiving ships provide remote damage control resuscitation platforms to treat injured combatants deployed afloat and ashore. We report a significant mass casualty incident aboard the USS Bataan, and the most warm fresh whole blood (WFWB) transfused at sea for traumatic hemorrhagic shock since the Vietnam War. Casualty-receiving ships have robust medical capabilities, including a frozen blood bank with packed red blood cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented with WFWB collected from a "walking blood bank." Following a helicopter crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1 had a pelvic fracture, was managed with a pelvic binder, and received 4 units of pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and fibula fracture, underwent lower extremity four-compartment fasciotomy, and received 4 units of WFWB. Patient 3 underwent several procedures, including left anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28 units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed nonoperatively. Patient 6, with open tibia and fibula fractures, underwent lower extremity four-compartment fasciotomy with tibia external fixation and received 1 unit of WFWB. All patients survived aeromedical evacuation to a role 4 medical facility and subsequent transfer to local hospitals. Maritime military mass casualty incidents are challenging, but the U.S. Navy's casualty-receiving ships are ready to perform remote damage control resuscitation at sea. Activation of the ship's walking blood bank to transfuse WFWB is essential for hemostatic resuscitations afloat. Study type: case series, level V.

Protective effect of calcium-sensing receptor inhibitor Calhex231 on traumatic hemorrhagic shock rats

Objective To observe the protective effects of calcium-sensing receptor (CaSR) inhibitor Calhex231 on traumatic hemorrhagic shock rats. Methods 144 SD rats were divided into six groups by random number table method: normal group, shock group, lactated Ringer's solution (LR) group, LR+ Calhex231 0.1 mg/kg group, LR+ Calhex231 1 mg/kg group, and LR+ Calhex231 5 mg/kg group, with 16 rats in each group for survival observation and 8 rats for hemodynamics test. 64 SD rats were divided into four groups: normal group, shock group, lactated Ringer's solution (LR) group, LR + Calhex231 1 mg/kg group, with 8 rats in each group for detecting organ blood flow and superior mesenteric artery vascular reactivity and the other 8 rats for mesenteric artery vascular reactivity. After the establishment of traumatic hemorrhagic shock model, the shock group did not receive resuscitation, and the LR group was resuscitated with LR equal to two times of the blood loss volume. The three LR+ Calhex231 groups with different dosages were firstly given LR of equal volume to that of blood loss, and then the Calhex231 was dissolved into LR ( equal to the blood loss volume) to resuscitate. The wound was ligated and sutured immediately after resuscitation. The effect of Calhex231 on animal's 24-hour survival since the beginning of resuscitation was observed. The hemodynamics including the mean arterial blood pressure(MAP), left intraventricular systolic pressure(LVSP), maximal rising, and declining rate of left intraventricular pressure (±dp/dtmax) were observed before shock, at the end of shock, 1 hour after resuscitation, and 2 hours after resuscitation. The effects of Calhex231 on vital organ blood flow and vascular reactivity were observed 2 hours after resuscitation. Results All the shock rats died within 9 hours after the shock model was established. The survival outcomes of LR group rats were slightly improved compared with the shock group rats(P<0.05) . The survival time and 24 hour survival rate of LR+ Calhex231 1 mg/kg group and LR + Calhex231 5 mg/kg group rats were significantly increased compared with the shock group rats (P<0.05). The hemodynamic indexes of LR+ Calhex231 groups were higher than those of the LR group. The best effect was observed in LR + Calhex231 1 mg/kg group rats (P<0.01). The MAP, LVSP and ±dp/dtmax were restored to normal level (64.9%, 82.4%, 89.8%, and 77.8%, respectively). Meanwhile, the blood flow in liver and kidney of LR+ Calhex231 1 mg/kg group rats were increased from 57.2% and 41% to 108.7% and 95.1%, respectively. The vascular reactivity including superior mesenteric artery and mesenteric artery of LR+ Calhex231 1 mg/kg group rats were also increased (P<0.01). Conclusions In rats with hemorrhagic shock, the calcium sensitive receptor inhibitor Calhex231 can improve the vascular reactivity, the hemodynamics, and the blood flow of important organs. It plays a role in protecting the cardiovascular function and reducing the mortality after traumatic hemorrhagic shock. Key words: Receptors, calcium-sensing; Shock, hemorrhagic; Calhex231

Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.

Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI) and is worsened by hypotension. Glibenclamide may reduce cerebral edema by inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema exacerbated by hypotension/resuscitation is unknown. We aimed to determine if glibenclamide improves pericontusional and/or diffuse edema in controlled cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min), and compare its effects in CCI alone. C57BL/6 mice were divided into five groups (n = 10/group): naïve, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and CCI+HS+glibenclamide. Intravenous glibenclamide (10 min post-injury) was followed by a subcutaneous infusion for 24 h. Brain edema in injured and contralateral hemispheres was subsequently quantified (wet-dry weight). This protocol brain water (BW) = 80.4% vehicle vs. 78.3% naïve, p < 0.01) but was not reduced by glibenclamide (I%BW = 80.4%). Ipsilateral edema also developed in CCI alone (I%BW = 80.2% vehicle vs. 78.3% naïve, p < 0.01); again unaffected by glibenclamide (I%BW = 80.5%). Contralateral (C) %BW in CCI+HS was increased in vehicle (78.6%) versus naive (78.3%, p = 0.02) but unchanged in CCI (78.3%). At 24 h, glibenclamide treatment in CCI+HS eliminated contralateral cerebral edema (C%BW = 78.3%) with no difference versus naïve. By 72 h, contralateral cerebral edema had resolved (C%BW = 78.5 ± 0.09% vehicle vs. 78.3 ± 0.05% naïve). Glibenclamide decreased 24 h contralateral cerebral edema in CCI+HS. This beneficial effect merits additional exploration in the important setting of TBI with polytrauma, shock, and resuscitation. Contralateral edema did not develop in CCI alone. Surprisingly, 24 h of glibenclamide treatment failed to decrease ipsilateral edema in either model. Interspecies dosing differences versus prior studies may play an important role in these findings. Mechanisms underlying brain edema may differ regionally, with pericontusional/osmolar swelling refractory to glibenclamide but diffuse edema (via Sur1) from combined injury and/or resuscitation responsive to this therapy. TBI phenotype may mandate precision medicine approaches to treat brain edema.

Activities of the THOR-AABB Working Party.

The AABB (formerly the American Association of Blood Banks) is an international authority on transfusion medicine and tissue banking. The Trauma, Hemostasis and Oxygenation Research (THOR) Network is an international multidisciplinary network of civilian and military providers ranging from first responders and medics to critical care physicians and from basic scientists to clinical trialists. The THOR Network's vision is to improve outcomes from traumatic hemorrhagic shock by optimizing the acute phase of resuscitation. Its mission is to develop and implement best practices for prehospital care through to the completion of the acute phase of hemorrhagic shock resuscitation. Thus, there is significant overlap between the missions of these two groups. To this end, the joint THOR-AABB Working Party (WP) was created in the summer of 2016 with a view to improving patient outcomes by the establishment of a formal collaboration between these two groups. The WP has been engaged in many different endeavors, from successfully changing the AABB's standards for the administration of whole blood, to writing commentaries on the safety of unncrossmatched red blood cells and antibody titer methods and thresholds in potentially incompatible plasma products, to hosting a daylong symposium on blood product resuscitation of massively bleeding patients in conjunction with the AABB annual meeting. This review details the activities of the WP and indicates some future activities.

Nitroglycerin Patch in Traumatic Hemorrhagic Shock to Improve Signs of Poor Peripheral Perfusion

AbstractBackground: Microcirculatory function is the main pre-requisite for adequate tissue oxygenation and organ function. It transports oxygen and nutrients to tissue cells, ensure adequate immunological function and, in disease, delivers therapeutic drugs to target cells. Recruiting microcirculation, i.e., non-perfused or intermittently perfused capillaries might improve tissue perfusion, mitigating the progression to organ failure and death. Nitroglycerin has been used in different shock states particularly in sepsis. The effect is variable and debatable suggesting an improvement of microcirculation.Patients and Methods: 60 adult patients with hemorrhagic shock admitted to the Emergency Department within 6 hours of trauma event, resuscitation immediately started according to advanced trauma life support ATLS® protocol 2016 with control of the bleeding source. Nitroglycerine patch 5mg applied to patients after the first hour of resuscitation. The study period corresponded to the outcome of the first 48 hours of trauma unit or ICU resuscitation. Patients considered successfully resuscitated if they had normal lactate levels (£2mmol/L).Results: 60 patients enrolled in this study, 10 patients were excluded; 3 of them due to uncontrolled bleeding and 7 due to marked hypotension. 50 patients continued in the study (38 men, 12 women) with mean age was (29.1±10.8ys); of them 45 survived (90%) and 5 did not survive (10%). Patients received mean crystalloid volume (6100±1410.67ml), mean colloid volume (490±457.25ml), mean packed RBCs (4.34±1.33 units), mean fresh frozen plasma (3.08±1.65 units) and mean nor-adrenaline dose (7.94±10.55mg/kg/minute). Baseline perfusion index was (0.37±0.21), mean heart rate (128.46±18.18 beat/minute), systolic blood pressure (78.08± 7.47mmHg), diastolic blood pressure (40.20±7.39mmHg), mean arterial pressure (53.44±6.43mmHg), central venous pressure (–1 .46±2.77cmH2O) and baseline modified shock index was (2.45±0.56). Baseline serum lactate was (8.61±1.86 mmol/L), base deficit was (–12.59±5.57). Perfusion index showed statistically significant increase in survivors than non survivors at 12, 18, 24, 30, 36, 42, 48 hours (p<0.001). Serum lactate level was significantly higher in non survivors group than survivor group (p<0.001). Base deficit was significantly higher in non survivors than survivors (p<0.001). Conclusion: Use of nitroglycerin patch 5mg improved PI at 6 to 48 hours post resuscitation and reduce mortality rate (in this study was 10%) while in other previous studies with the same sample size of hemorrhagic shock patients without use of nitroglycerin it was higher (about 30%).This study is registered at www.clinicaltrials.gov under number NCT03235921.

The safety and efficacy of fluid resuscitation with hypertonic saline in traumatic hypovolemic shock: a meta-analysis

Objective To assess the safety and efficacy of hypertonic saline in traumatic hypovolemic shock with Meta-analysis. Methods Comprehensive electronic search strategies were developed using the following electronic databases: PubMed, EMBASE, Medline, Ovid、Clinical Trials, CNKI, Wan Fang, CBM and FMJS. The Literature published before August of 2017 was searched. The randomized controlled trials (RCTs) about hypertonic saline in traumatic hypovolemic shock were included. A data-extraction sheet was developed based on the preset standards. The data from eligible studies were pooled through Meta-analysis. Results 9 trials with a total of 1600 patients(741cases in observation group, 859 cases in control group ) met the inclusion criteria. The meta-analysis showed that the hypertonic saline group displayed remarkable increase in the systolic blood pressure and decrease in hemoglobin level, compared with the isotonic saline group [MD=6.43, 95% CI(1.16, 11.70), P 0.05]. Conclusions Available evidence shows that small volume hypertonic Sodium Chloride saline is safe and effective for resuscitation in patients with traumatic hemorrhagic shock. Since the quality of the inclued studes were not high, more high-quality, multicenter randomized controlled clinical studies need to provide better evidence for the above conclusion. Key words: Saline solution, hypertonic/TU; Shock, traumatic/DT; Resuscitation/MT; Meta-analysis