Uncontrolled Hemorrhagic Shock Research Articles

Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage.

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

Pilot study of frozen platelet extracellular vesicles as a therapeutic agent in hemorrhagic shock in rats.

Hemorrhage accounts for the most preventable deaths after trauma. Resuscitation is guided by studies that demonstrate improved outcomes in patients receiving whole blood or balanced administration of blood products. Platelets present a logistical challenge due to short shelf life and need for refrigeration. Platelet-derived extracellular vesicles (PEVs) are a possible platelet alternative. Platelet-derived extracellular vesicles are secreted from platelets, have hemostatic effects and mitigate inflammation and vascular injury, similar to platelets. This pilot study aimed to elucidate the therapeutic effects of PEVs in a rat model of uncontrolled hemorrhage. Male rats were anesthetized and femoral vessels cannulated. Vital signs (MAP, HR, and RR) were monitored. Electrolytes, lactate and ABG were obtained at baseline, 1-hour and 3-hours post injury. Laparotomy was performed, 50% of the middle hepatic lobe excised and the abdomen packed with gauze. Rats received 2 mL PEVs or lactated Ringers (LR) over 6 minutes immediately after injury. Peritoneal blood loss was quantified using preweighed gauze at 5 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes. Laparotomy was closed 1-hour postinjury. Animals were monitored for 3 hours postinjury then euthanized. Generalized Linear Mixed Effects models were performed to assess effects of treatment and time on lactate and MAP. Twenty-one rats were included (11 LR, 10 PEV). Overall blood loss was between 6 mL and 10 mL and not significantly different between groups. There was a 36% mortality rate in the LR group and 0% mortality in the PEV group ( p = 0.03). The LR group had significantly higher lactates at 1 hour ( p = 0.025). At 15 minutes, 45 minutes, 60 minutes, and 180 minutes, the MAP of the PEV group was significantly higher than the LR group. Early studies are encouraging regarding the potential use of PEVs in uncontrolled hemorrhagic shock based on improved survival and hemodynamics.

Abstract 200: A Newly Drug Delivery System Combined With the Resuscitative Endovascular Balloon Occlusion of the Aorta in a Pig With Hemorrhagic Shock Model

Background: The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for hemorrhagic shock (HS) has grown in popularity. However, REBOA has a risk of complications related to blocking the blood flow downstream to the visceral organs. Several drugs have been reported so far to mitigate ischemia, including hydrogen gas (H 2 ); however, they could not reach the downstream of REBOA as they are distributed through the bloodstream. This study aimed to develop a system to deliver drugs to the ischemic organs where REBOA blocks the bloodstream. Methods: Herein, a female 40-kg swine volume-regulated HS model was used. In addition to the REBOA in zone 1, a catheter was inserted for drug delivery retrograde into the right femoral artery. The top tip of the catheter was positioned distal to the REBOA balloon. After HS induction (20% of the total blood volume), drug delivery capability was evaluated in three REBOA use patterns, such as controlled HS in normal time of full inflation , uncontrolled HS with liver injury in extended time of full inflation, and partial inflation. Simultaneously with the REBOA inflation, the intra-aortic irrigation of a drug-containing solution, H 2 -dissolved saline, was initiated. Results: The occlusion by the REBOA was achieved in all cases after shock induction (approximately 40 mmHg). In all patterns, the concentration of H 2 in the portal vein, which represents the concentration of outflow from the intestine and inflow to the liver, increased immediately after the irrigation. A full inflation setting required 30 mL/min of irrigation speed to obtain the minimum effective concentration of H 2 (1%), whereas a partial inflation setting required 2 mL/min. Conclusion: A drug delivery system combined with the REBOA was developed, which enabled the drugs to be administered downstream of REBOA. The newly developed system can potentially overcome the major limitations of REBOA.

[Resuscitative Endovascular Balloon Occlusion of the Aorta: Implementation and Nursing Care].

Uncontrolled hemorrhagic shock is the main cause of death in patients with traumatic injuries. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a rapidly performed and less-invasive treatment to stop bleeding. The REBOA balloon may be placed at the location of bleeding to achieve hemostasis. Prior to balloon placement, the indications for placement must be evaluated, including non-thoracic aortic trauma and non-traumatic patients with postpartum hemorrhage, and the appropriate sheath size (from 5 to 8 French) must be selected based on the bleeding site. As vascular injury of aortic dissection, rupture, or perforation may occur during the procedure, changes in hemodynamic parameters should be monitored. After balloon placement, ischemic complications due to blood flow occlusion such as lower extremity ischemia and acute renal failure should be tracked. After balloon removal, reperfusion injuries may occur, which can result in multiple organ failure, and should be observed closely. When caring for patients receiving REBOA, physicians should explain the procedure to their families to obtain informed consent. Also, nurses should prepare supplies and closely monitor changes in critical life signs to minimize the risks of hypotension, arrhythmia, and changes in consciousness during the procedure. After placement, the neurovascular and peripheral limbs "5P" (pain, pallor, paresthesia, pulselessness and paralysis) condition should be evaluated and recorded in detail. This treatment approach requires further study and research to assess the long-term impacts of placement and improve quality of care in these patients.

Effects of Mdivi-1 on Extending the Golden Treatment Time following Hemorrhagic Shock in Hot Environment in Rats.

It is found that a hot environment aggravates hemorrhagic shock-induced internal environment and organ dysfunction. Meanwhile mitochondria show over-fission. Whether inhibition of mitochondrial fission benefits from the early treatment of hemorrhagic shock under a hot environment is unclear. An uncontrolled hemorrhagic shock model in rats is used, and the effects of mitochondrial fission inhibitor mdivi-1 on mitochondrial function, organ function, and survival rate of rats are measured. The results show that 0.1-3 mg/kg mdivi-1 antagonizes hemorrhagic shock-induced mitochondrial fragment. In addition, mdivi-1 improves mitochondrial function, and alleviates hemorrhagic shock-induced oxidative stress and inflammation under a hot environment. Further studies show that 0.1-3 mg/kg Mdivi-1 reduces blood loss, and maintains a mean artery pressure (MAP) of 50-60 mmHg before bleeding-stops after hemorrhagic shock, compared with single Lactate Ringer's (LR) resuscitation. Notably, 1 mg/kg of Mdivi-1 extends the time of hypotensive resuscitation to 2-3 h. During 1 or 2 h of ligation, Mdivi-1 prolongs survival time and protects vital organ function by rescuing mitochondrial morphology and improving mitochondrial function. These results suggest Mdivi-1 is suitable for the early treatment of hemorrhagic shock under a hot environment and can extend the golden treatment time to 2-3 hour for hemorrhagic shock under a hot environment.

Emergent Subtotal Colectomies Have Higher Leak Rates in Subsequent J-Pouch Stages

PurposeThe most common surgery for ulcerative colitis (UC) is the staged restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). On occasion, an emergent first-stage subtotal colectomy must be performed. The purpose of this study was to compare rates of postoperative complications in three-stage IPAA patients who underwent emergent vs non-emergent first-stage subtotal colectomies in the subsequent staged procedures. MethodsThis was a retrospective chart review conducted at a single tertiary care inflammatory bowel disease (IBD) center. All UC or IBD-Unspecified patients who underwent a three-stage IPAA between 2008 and 2017 were identified. Emergent surgery was defined as that performed on an inpatient who had perforation, toxic megacolon, uncontrolled hemorrhage, or septic shock. The primary outcomes were the presence of anastomotic leak, obstruction, bleeding, and the need for reoperation for each within a 6-month postoperative period of the second (RPC with IPAA and DLI) and third surgical stages (ileostomy reversal). ResultsA total of 342 patients underwent a three-stage IPAA, of which 30 (9.4%) had emergent first-stage operations. Patients who underwent an emergent STC were more likely to have a post-operative anastomotic leak and need an additional procedure following the subsequent second and third-staged operations on both univariate and multivariate analysis (p < 0.05). No difference was found for obstruction, wound infection, intra-abdominal abscess, or bleeding (p > 0.05). ConclusionThree-stage IPAA patients with emergent first-stage subtotal colectomies were more likely to have a post-operative anastomotic leak and need an additional procedure for a leak following the subsequent second- and third-stage operations.

Fresh Frozen Plasma Increases Hemorrhage in Blunt Traumatic Brain Injury and Uncontrolled Hemorrhagic Shock

Blunt traumatic brain injury (bTBI) and uncontrolled hemorrhagic shock (UCHS) are common causes of mortality in polytrauma. We studied the influence of fresh frozen plasma (FFP) resuscitation in a rat model with both bTBI and UCHS before achieving hemorrhage control. The bTBI was induced by an external weight drop (200 g) onto the bare skull of anesthetized male Lewis (Lew/SdNHsd) rats; UCHS was induced by resection of two-thirds of the rats' tails. Fifteen minutes following trauma, bTBI+UCHS rats underwent resuscitation with FFP or lactated Ringer's solution (LR). Eight groups were evaluated: (1) Sham; (2) bTBI; (3) UCHS; (4) UCHS+FFP; (5) UCHS+LR; (6) bTBI+UCHS; (7) bTBI+UCHS+FFP; and (8) bTBI+UCHS+LR. Bleeding volume, hematocrit, lactate, mean arterial pressure (MAP), heart rate, and mortality were measured. The study included 97 rats that survived the immediate trauma. Mean blood loss up to the start of resuscitation was similar among UCHS only and bTBI+UCHS rats (P=0.361). Following resuscitation, bleeding was more extensive in bTBI+UCHS+FFP rats (5.2 mL, 95% confidence interval [CI] 3.7, 6.6) than in bTBI+UCHS+LR rats (2.5 mL, 95% CI 1.2, 3.8) and bTBI+UCHS rats (1.9 mL, 95% CI 0, 3.9) (P=0.005). Overall mortality increased if bleeding was above 4.5 mL (92.3% versus 8%; P<0.001). Mortality was 83.3% (10/12) in bTBI+UCHS+FFP rats, 41.7% (5/12) in bTBI+UCHS+LR rats, and 64.3% (9/14) in bTBI+UCHS rats. The bTBI did not exacerbate bleeding in rats undergoing UCHS. Compared to LR, FFP resuscitation was associated with a significantly increased blood loss in bTBI+UCHS rats.

Low-dose norepinephrine in combination with hypotensive resuscitation may prolong the golden window for uncontrolled hemorrhagic shock in rats.

Hypotension resuscitation is an important principle for the treatment after trauma. Current hypotensive resuscitation strategies cannot obtain an ideal outcome for remote regions. With the uncontrolled hemorrhagic shock (UHS) model in rats, the effects of norepinephrine (NE) on the tolerance time of hypotensive resuscitation, blood loss, vital organ functions, and animal survival were observed. Before bleeding was controlled, only the LR infusion could effectively maintain the MAP to 50–60 mmHg for 1 h, while the MAP gradually decreased with prolonging time, even with increasing infusion volume. Low-dose NE during hypotensive resuscitation prolonged the hypotensive tolerance time to 2–3 h, and the effect of 0.3 μg/kg/min NE was the best. Further studies showed that 0.3 μg/kg/min NE during hypotensive resuscitation significantly lightened the damage of organ function induced by UHS via protecting mitochondrial function, while the LR infusion did not. At the same time, NE administration improved Hb content, DO2, and VO2, and restored liver and kidney blood flow. The survival results showed that low-dose NE administration increased the survival rate and prolonged the survival time. Together, low-dose NE during hypotensive resuscitation was suitable for the early treatment of UHS, which can strive for the golden window of emergency treatment for serious trauma patients by reducing blood loss and protecting vital organ functions.

The effects of hydroxyethyl starch and gelatine on lung tissue and coagulation during the resuscitation of rats with traumatic haemorrhagic shock.

This study was constructed to compare the effects of resuscitation with gelatine and hydroxyethyl starch (HES) on coagulopathy, haemodynamics, and tissue damage during an uncontrolled haemorrhagic shock model in rats. Twenty 6-month-old Sprague-Dawley rats were included in the study and divided into 4 groups. There was no haemorrhage in the sham group. The others were randomised into haemorrhage without volume replacement (control group), haemorrhage and gelatine (group G), and haemorrhage and HES (group V). Blood samples for thromboelastogram and annexin 5 values were obtained before bleeding and after resuscitation. In the control group, R (16.18 ± 2.74) and K (5.8 ± 1.1) were significantly higher than in all other groups ( P = 0.001), and the TEG alpha angle was 39.54 ± 5.94°, which was found to be significantly lower than in the sham group ( P = 0.001). In group V, the TEG MA value was found to be significantly lower at 30.54 ± 8.89 ( P = 0.001). The annexin A5 value was significantly higher in the control group, group V, and group G than in the sham group and was highest in the control group ( P = 0.001). Lung damage score measurement was 0.60 ± 0.19 in the control group, higher than in the gelatine and HES groups ( P = 0.001). Lung tissue damage and coagulation were positively affected by HES or gelatine resuscitation. A reduction in clot formation in the HES group might be observed due to the possible negative effect on platelets. Therefore, we concluded that the use of gelatine might be advantageous until blood transfusion is initiated in traumatic haemorrhagic shock.

A Novel Cross-Linked Hemoglobin-Based Oxygen Carrier, YQ23, Extended the Golden Hour for Uncontrolled Hemorrhagic Shock in Rats and Miniature Pigs.

Background: Hypotensive resuscitation is widely applied for trauma and war injury to reduce bleeding during damage-control resuscitation, but the treatment time window is limited in order to avoid hypoxia-associated organ injury. Whether a novel hemoglobin-based oxygen carrier (HBOC), YQ23 in this study, could protect organ function, and extend the Golden Hour for treatment is unclear. Method: Uncontrolled hemorrhagic shock rats and miniature pigs were infused with 0.5, 2, and 5% YQ23 before bleeding was controlled, while Lactate Ringer’s solution (LR) and fresh whole blood plus LR (WB + LR) were set as controls. During hypotensive resuscitation the mean blood pressure was maintained at 50–60 mmHg for 60 min. Hemodynamics, oxygen delivery and utilization, blood loss, fluid demand, organ function, animal survival as well as side effects were observed. Besides, in order to observe whether YQ23 could extend the Golden Hour, the hypotensive resuscitation duration was extended to 180 min and animal survival was observed. Results: Compared with LR, infusion of YQ23 in the 60 min pre-hospital hypotensive resuscitation significantly reduced blood loss and the fluid demand in both rats and pigs. Besides, YQ23 could effectively stabilize hemodynamics, and increase tissue oxygen consumption, increase the cardiac output, reduce liver and kidney injury, which helped to reduce the early death and improve animal survival. In addition, the hypotensive resuscitation duration could be extended to 180 min using YQ23. Side effects such as vasoconstriction and renal injury were not observed. The beneficial effects of 5% YQ23 are equivalent to similar volume of WB + LR. Conclusion: HBOC, such as YQ23, played vital roles in damage-control resuscitation for emergency care and benefited the uncontrolled hemorrhagic shock in the pre-hospital treatment by increasing oxygen delivery, reducing organ injury. Besides, HBOC could benefit the injured and trauma patients by extending the Golden Hour.

Preclinical safety evaluation of ET-26 hydrochloride, a novel intravenous anesthetic agent, in beagle dogs.

ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue, approved for clinical trials, which has an effective sedative-hypnotic effect, a stable myocardial performance, and milder adrenocortical suppression than etomidate in rats and beagle dogs. Additionally, ET-26HCl showed similar hemodynamic stability as etomidate in the rat uncontrolled hemorrhagic shock model. Furthermore, ET-26HCl, in the rat lipopolysaccharide-induced sepsis model, was found to have a higher survival rate, a lower inflammatory reaction, and less organ injury. In the present study, we measured the potential adverse effects of ET-26HCl in beagle dogs in accordance with the Guidance on single- and repeated-dose toxicity published by the China Food and Drug Administration. In toxicity studies, single and repeated (14 days) intravenous doses of up to 16 mg/kg were well tolerated, with only pharmacologically related clinical signs seen in both studies. Thus, the no-observed-adverse-effect level (NOAEL) of ET-26HCl was found at 16 mg/kg/day. Toxicokinetic examination demonstrated that ET-26HCl showed a dose-dependent increase to exposure, no gender difference, and no evidence of accumulation. These results provide useful information for guiding a phase I clinical trial of ET-26HCl in healthy volunteers.

Impact of high-dose norepinephrine during intra-hospital damage control resuscitation of traumatic haemorrhagic shock: A propensity-score analysis

IntroductionThe use of norepinephrine (NE) during uncontrolled haemorrhagic shock (HS) has mostly been investigated in experimental studies. Clinical data including norepinephrine dose and its impact on fluid resuscitation and organ function are scarce. We hypothesized that there is great variability in NE use and that high doses of NE could lead to increased organ dysfunction as measured by the sequential organ failure assessment (SOFA). MethodWe included patients with HS (systolic blood pressure < 90 mmHg in severely injured patients) who required haemostasis surgery and a transfusion of more than 4 packed red blood cells (PRBC) in the first 6 h of admission and the used of norepinephrine infusion to maintain the blood pressure goal, between admission and the end of haemostasis surgery in a prospective trauma database. A ROC curve determined that, using Youden's criterion, a dose of NE ≥ 0.6 µg/kg/min was the optimal threshold associated with intrahospital mortality. Patients were compared according to this threshold in a propensity score (PS) model. In a generalized linear mixed model, we searched for independent factors associated with a SOFA ≥ 9 at 24 h ResultsA total of 89 patients were analysed. Fluid infusion rate ranged from 1.43 to 57.9 mL/kg/h and norepinephrine infusion rate from 0.1 to 2.8 µg/kg/min. The HDNE group received significantly less fluid than the LDNE group. This dose is associated with a higher SOFA score at 24h: 9 (7–10) vs. 7 (6–9) (p = 0.003). Factors independently associated with a SOFA score ≥ 9 at 24 h were maximal norepinephrine rate ≥ 0.6 µg/kg/min (OR 6.69, 95% CI 1.82 – 25.54; p = 0.004), non-blood resuscitation volume < 9 mL/kg/h (OR 3.98, 95% CI 1.14 – 13.95; p = 0.031) and lactate at admission ≥ 5 mmol/L (OR 5.27, 95% CI 1.48 – 18.77; p = 0.010) ConclusionHigh dose of norepinephrine infusion is associated with deleterious effects as attested by a higher SOFA score at 24 h and likely hypovolemia as measured by reduced non-blood resuscitation volume. We did not find any significant difference in mortality over the long term.

Abstract 118: Resuscitative Transfusion With Hemoglobin Vesicles in the Management of Post-Partum Hemorrhage

Background: We developed a Hemoglobin vesicles (HbV), which are artificial substitute for Red blood cells (RBCs). Objective: To evaluate the efficacy of HbV for alternative treatment instead of RBCs transfusion in rabbits with hemorrhagic shock due to post-partum hemorrhage. Methods: New Zealand white rabbits at late gestation underwent uncontrolled hemorrhagic shock by transecting a right mid-artery in the myometrium, after cesarean section of right side uterus. Initially, in the simulated ordinal treatment of bleeding, rabbits received colloid fluids (Voluven®) through an femoral vein with equivalent volume of the bleeding every 5 minutes. Once blood loss achieved 100ml, animals subsequently faced on critical hemorrhagic situation, where mean arterial pressure (MAP) reduced to approximately 48mmHg. They were randomly divided into three isovolemic resuscitation regimens: continuing colloid fluid resuscitation (n=4); transfusion of autologous washed RBCs with plasma (n=4); HbV infusion combining 5% human serum albumin (n=4). After 60 minutes of bleeding, all animals underwent surgical control of bleeding and cesarean section of left side uterus. Results: At the point of critical hemorrhagic situation, Hb concentration reduced to 4.8 g/dl. At the end of resuscitation, HbV infusion regained MAP and restored Hb concentration as well as RBCs transfusion, besides colloid fluid resuscitation exaggerated the severe hemorrhagic shock as shown in the table. Conclusions: HbV treatment may be effective in the management of post-partum hemorrhagic shock.

Higher Concentration of Hypertonic Saline Shows Better Recovery Effects on Rabbits with Uncontrolled Hemorrhagic Shock.

BackgroundOur previous study found a novel fluid combination with better resuscitation effects under hypotensive condition at the early stage of uncontrolled hemorrhagic shock (UHS). However, the optimal recovery concentration of hypertonic saline in this fluid combination remains unknown. This experiment aimed to explore the optimal concentration.Material/MethodsNew Zealand white rabbits (n=40) were randomly divided into 5 groups, including a sham-operated group (SO), a shock non-treated group (SNT), a normal saline group (NS), and hypertonic saline groups (4.5% and 7.5%). We established an UHS model and administered various fluid combinations (dose-related sodium chloride solution+crystal-colloidal solution) to the groups followed by monitoring indexes of hemodynamic and renal function, measuring infusion volume and blood loss, and analyzing pathological morphology by hematoxylin and eosin staining.ResultsThe hypertonic saline groups showed more stable hemodynamic indexes, reduced blood loss, fewer required infusions, and milder decreases in renal function than those of control groups (SNT and NS groups), and exhibited fewer pathological changes in the heart, lung, kidney, and liver. All indexes in the 4.5% and 7.5% groups were better than those of the NS group, and the hemodynamic indexes in the 7.5% group were more stable than those of the 4.5% group (P<0.05), with reduced blood loss and infusion volume and a milder decrease in renal function.ConclusionsThe novel fluid combination with 7.5% hypertonic saline group had a better recovery effect at the early stage of UHS before hemostasis compared to that of the 4.5% hypertonic saline group. This result may provide guidance for clinical fluid resuscitation.

Adenosine, lidocaine, and Mg2+ fluid therapy leads to 72-hour survival after hemorrhagic shock: A model for studying differential gene expression and extending biological time.

Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 4 hours 0.9% NaCl/ALM "drip" in a rat model of uncontrolled hemorrhagic shock. Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at -80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1α, and sirt-1 genes were determined. Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared with controls, and PGC-1α was 75% lower. Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1, and mtCO3 to presumably "boost" mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.

[Beneficial effects of hemoglobin-based oxygen carriers on early resuscitation in rats with uncontrolled hemorrhagic shock].

To investigate the early resuscitation effect of hemoglobin-based oxygen carriers (HBOC) in rats with uncontrolled hemorrhagic shock. 170 Sprague-Dawley (SD) rats were randomly divided into five groups: lactate Ringer solution (LR) control group, whole blood control group, and 0.5%, 2.0%, 5.0% HBOC groups, with 34 rats in each group. The uncontrolled hemorrhagic shock model in SD rats was reproduced by cutting off the splenic artery branch, and induced mean arterial pressure (MAP) reducing to 40 mmHg (1 mmHg = 0.133 kPa). The corresponding solution was infused after model reproduction in each group, maintaining MAP at 50 mmHg for 1 hour, then completely ligating and hemostasis, and maintaining MAP at 70 mmHg for 1 hour and 80 mmHg for 1 hour respectively, after maintaining MAP 80 mmHg, all were supplemented with LR to 2 times blood loss volume. The survival rate and blood loss rate were observed in 16 rats in each group, hemodynamics parameters including MAP, left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (+dp/dt max) were determined in another 10 rats, and cardiac output (CO) and tissue oxygen supply (DO2) were observed in the rest 8 rats. (1) When resuscitation by LR alone, the blood loss rate of animals was as high as 60% to 70%. Compared with the LR control group, whole blood recovery could significantly reduce the blood loss rate before hemostasis in uncontrolled hemorrhagic shock rats [(46.6±4.5)% vs. (62.3±4.0)%, P < 0.01]; 0.5%, 2.0%, 5.0% HBOC could significantly decrease the blood loss rate, especially in 5.0% HBOC group with significant difference as compared with that in the LR control group [(45.6±4.1)% vs. (62.3±4.0)%, P < 0.01]. (2) When LR was used alone for resuscitation, the rats died quickly and survived for a short time. Only one rat survived for 12 hours, and no rat survived for more than 24 hours. Compared with the LR control group, whole blood resuscitation could improve the survival rate of uncontrolled hemorrhagic shock rats, and the survival time was significantly prolonged (hours: 20.4±4.6 vs. 3.5±1.1, P < 0.01); 0.5%, 2.0% and 5.0% HBOC also significantly prolonged the survival time of rats. The 5.0% HBOC group had the best effect, 4 rats survived in 24 hours, and the survival time was significantly longer than that of the LR control group (hours: 18.4±4.0 vs. 3.5±1.1, P < 0.01), and it was the same as the whole blood control group. (3) Compared with pre-shock, CO, DO2 and hemodynamic parameters of uncontrolled hemorrhagic shock rats were significantly decreased, and the above parameters were gradually increased with the prolongation of rehydration time. Compared with the LR control group, whole blood resuscitation could significantly increase CO and DO2, and improve hemodynamics in rats with uncontrolled hemorrhagic shock at different time points. Three concentrations of HBOC could also increase CO, DO2 and other hemodynamic parameters of rats at 1 hour of maintaining MAP of 80 mmHg after hemostasis and 1 hour and 2 hours after resuscitation. The effect of 5.0% HBOC group was more significant than that of the LR control group with statistically significant difference [CO (×10-3, L/min): 72.84±2.84 vs. 63.11±2.38 at 1 hour of maintaining MAP of 80 mmHg, 70.25±4.55 vs. 59.88±9.31 at 1 hour after resuscitation, 71.51±2.90 vs. 53.24±6.32 at 2 hours after resuscitation; DO2 (L×min-1×m-2): 271.9±13.5 vs. 159.1±25.4 at 1 hour of maintaining MAP of 80 mmHg, 261.0±15.0 vs. 145.7±20.1 at 1 hour after resuscitation, 249.6±12.0 vs. 107.4±18.2 at 2 hours after resuscitation; MAP (mmHg): 82.1±2.1 vs. 74.0±2.8 at 1 hour of maintaining MAP of 80 mmHg, 107.5±9.3 vs. 64.0±5.7 at 1 hour after resuscitation, 104.0±9.7 vs. 73.0±4.2 at 2 hours after resuscitation; LVSP (mmHg): 128.6±7.9 vs. 103.8±0.8 at 1 hour of maintaining MAP of 80 mmHg, 129.3±15.0 vs. 99.4±0.0 at 1 hour after resuscitation, 127.5±11.3 vs. 97.4±0.0 at 2 hours after resuscitation; +dp/dt max (mmHg/s): 6 534.2±787.6 vs. 5 074.0±71.7 at 1 hour of maintaining MAP of 80 mmHg, 5 961.5±545.4 vs. 4 934.5±510.2 at 1 hour after resuscitation, 5 897.4±350.5 vs. 4 534.7±489.2 at 2 hours after resuscitation, all P < 0.05]. HBOC infusion prolonged the survival time, increased survival rate, and improved hemodynamics, cardiac function and tissue oxygen supply in a dose-dependent manner in the early stage of uncontrolled hemorrhagic shock. The recovery effect of 5.0% HBOC was similar to that of the whole blood.

How many patients could benefit from REBOA in prehospital care? A retrospective study of patients rescued by the doctors of the Paris fire brigade

IntroductionResuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique to control haemorrhage by placing a retrograde catheter in an artery and inflating a balloon at its tip. This...

Acute high-altitude exposure shortens survival after uncontrolled hemorrhagic shock in rats

BackgroundUncontrolled hemorrhage (UH) remains the most common cause of death on the battlefield. This study examined the pathophysiological characteristics of UH in rats acutely exposed to high altitude. Material and methodsRats raised at sea level were randomly divided into two groups. Rats in the high-altitude group were exposed to hypobaric hypoxia in a hypobaric chamber (simulating 4000 m above sea level) for 2 d and then were performed a hemorrhagic shock protocol in the hypobaric chamber. Rats that underwent the same hemorrhage procedure at sea level were used as control. Anesthetized rats were bled to maintain their mean arterial pressure at 45 mmHg for 1 h. The distal quarter of the tail was amputated to allow free blood loss. After 1 h, the tail cut was ligated to induce hemostasis. mean arterial pressure, acid–base balance, blood loss, and survival were recorded. Rats were killed, and tissues were obtained for histological analysis. ResultsRats in the high-altitude group suffered less uncontrolled blood loss, more severe acidosis (lower pH and base excess), and inferior tissue oxygen supply (lower oxygen saturation and higher arterial lactate concentration) during the hemorrhage periods compared with the control group. Survival rates were significantly lower in the high-altitude group than those in the control group (P < 0.05), which was consistent with the results of pathological tissue injury. ConclusionsIn this rat model of hemorrhagic shock, acute high-altitude exposure resulted in decreased UH but more serious hemorrhagic shock injuries than that at sea level.

Vascular embolization for treatment of primary gastric lymphoma combined with acute upper gastrointestinal hemorrhage: report of two cases and review of literature

Objective To investigate the clinical features of primary gastric lymphoma (PGL) combined with acute upper gastrointestinal hemorrhage, and to improve the diagnosis and treatment level. Methods The clinical manifestations and treatment of 2 PGL cases combined with acute upper gastrointestinal hemorrhage were analyzed retrospectively, and the related literature was reviewed. Results Two patients suffered from venosity, abdominal pain and weight loss, which were diagnosed by gastroscopy mucosa biopsy with upper gastrointestinal hemorrhage and uncontrolled hemorrhagic shock. Vascular embolization was used to stop bleeding and systemic chemotherapy was followed to achieve further curative effect. Conclusion Embolization treatment is safe and effective for PGL combined with acute upper gastrointestinal hemorrhage without any influences on chemotherapy. Key words: Lymphoma, large B-cell, diffuse; Stomach; Burkitt lymphoma; Gastrointestinal hemorrhage; Embolization, therapeutic

355 A Trial of Terlipressin Compared to Small Volume Resuscitation in a Swine (Sus scrofa) Model of Uncontrolled Hemorrhage and Severe Hemorrhagic Shock

355 A Trial of Terlipressin Compared to Small Volume Resuscitation in a Swine (Sus scrofa) Model of Uncontrolled Hemorrhage and Severe Hemorrhagic Shock