Resuscitation Of Hemorrhagic Shock Research Articles

Effectiveness and safety of hypotensive resuscitation in traumatic hemorrhagic shock: A protocol for meta-analysis.

Background:Hypotensive resuscitation is an old study. But its benefits and losses are still controversial. In clinic, the method of fluid resuscitation needs more reliable experimental evidence. This study's objective is to systematically evaluate the efficacy of hypotensive resuscitation in patients with traumatic hemorrhagic shock.Methods and analysis:Through October 2019, Web of Science, PubMed, the Cochrane Library, EMBASE, and Clinical Trials will be systematically searched to identify randomized controlled trials exploring the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock. Strict screening and quality evaluation will be independently performed on the obtained literature by 2 researchers; outcome indexes will be extracted, and a meta-analysis will be performed on the data using Revman 5.3 software.Ethics and dissemination:The stronger evidence about the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock will be provided for clinicians.Trial registration number:PROSPERO CRD42019133169.Strengths of this study:This study is not only a simple combination of data, but also to verify and discuss the reliability of the results, and provide more convincing evidence for clinicians.Limitations of this study:Firstly, according to the previous literature researching, it is found that the number of relevant randomized controlled trials is small and the quality level of the literature is uneven. Secondly, the efficacy of hypotensive resuscitation is discussed for a long time, different trials may take place at different times. Comparability between different trials is reduced.

Effect of tranexamic acid administration on acute traumatic coagulopathy in rats with polytrauma and hemorrhage.

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA’s various sites and modes of action may further improve patient outcomes.

Ultrasonographic Assessment of Caudal Vena Cava to Aorta Ratio as a Novel Endpoint in Hemorrhagic Shock Resuscitation in Dogs

Objective- The aim of this study was to assess ultrasonography-derived caudal vena cava to aorta ratio (CVC/Ao) as a novel endpoint in the resuscitation of experimental hemorrhagic shock in dogs. Design- Experimental study. Animals- Ten adult mongrel healthy dogs. Procedures- After induction of anesthesia (control assessments), hemorrhagic shock was induced by blood withdrawal to a mean arterial pressure of 40 to 50 mmHg within 30 minutes and then maintained in a hypovolemic situation for an additional 30 minutes (second and third stages of assessments). Afterward, the dogs were randomly assigned to two groups which received 20 ml/kg lactated Ringer's solution or 5 ml/kg Hydroxyethyl starch, in four consecutive 15 minutes intervals (fourth stage of assessments). One hour after the last resuscitation step, final ultrasonographic assessments were performed. Results- Hemorrhagic shock caused a significant decrease in the CVC and Ao diameters as well as the CVC/Ao (2.14 ± 0.28 cm, 0.85 ± 0.07 cm and 0.4 ± 0.06, respectively) (p<0.05). Following the fluid resuscitation, CVC/Ao increased and returned to pre-shock values in both groups. Conclusion and clinical relevance- Findings indicated that serial ultrasonographic assessment of the CVC/Ao can be a useful endpoint in the resuscitation of dogs with hemorrhagic shock.

Vasopressin as an Early Adjunct to Resuscitation in Hemorrhagic Shock: Crisis AVERTed?

Vasopressin as an Early Adjunct to Resuscitation in Hemorrhagic Shock: Crisis AVERTed?

Hydroxyethyl starches in equine medicine.

To review and discuss the use of hydroxyethyl starches (HES) in equine veterinary medicine, and to provide recommendations for its use. Veterinary and human peer-reviewed medical literature including scientific reviews, meta-analyses, and original research articles. Increasing evidences on adverse effects after HES use and decreasing support for beneficial effects with regards to volume expansion and colloid osmotic pressure (COP) support in critically ill subjects have led to a recent guideline to limit the use of HES in critically ill people. The rationale for HES use in horses is mainly extrapolated from human medicine, and very limited studies in horses are available. There is limited evidence suggesting a superiority of volume expansion effects of HES over crystalloids. The potential for HES to increase and maintain COP is well supported, but there is no evidence that maintaining or increasing plasma COP influences outcome, tissue edema formation, or rates of complications that potentially relate to edema formation. HES induce dose-dependent changes in coagulopathic parameters, but there is no evidence that HES causes clinical coagulopathies. Insufficient data are available on other adverse effects such as acute kidney injury, or mortality in horses. The use of HES should be restricted in septic patients, but may still have some use in cases of hemorrhagic shock resuscitation, hypoalbuminemia, or perioperative fluid replacement. The evidence supporting the use of HES in horses is weak due to lack of species-specific investigations. Acknowledging species differences, the use of HES should be judicious, yet with some recognition of its benefits in particular cases. More research is necessary to improve knowledge on use of HES in horses and to establish better future recommendations.

Effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats

Objective To evaluate the effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury (ALI) induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats. Methods Forty-five SPF healthy male Sprague-Dawley rats, weighing 200-220 g, were divided into 3 groups (n=15 each) using a random number table method: sham operation group (Sham group), ALI group and dexmedetomidine group (Dex group). A rat model of ALI was established by blunt chest trauma and hemorrhagic shock-resuscitation.Dexmedetomidine 5 μg·kg-1·h-1 was infused into the femoral vein after blunt chest trauma in Dex group.Blood samples were collected from the femoral artery at 6 h after blunt chest trauma for measurement of arterial oxygen partial pressure and concentrations of pro-inflammatory cytokines interleukin-1beta (IL-1β) and IL-18 in serum (by enzyme-linked immunosorbent assay). The oxygenation index was calculated.The rats were sacrificed and lungs were removed for examination of the pathological changes which were scored and for determination of the expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD (ASC) in lung tissues (by Western blot) and activities of lactic dehydrogenase (LDH) and myeloperoxidase (MPO) in lung tissues (by colorimetry). Results Compared with Sham group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was up-regulated, the activities of LDH and MPO were increased, and the concentrations of IL-1β and IL-18 in serum were increased in ALI group (P<0.05). Compared with ALI group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was down-regulated, the activities of LDH and MPO were decreased, and the concentrations of IL-1β and IL-18 in serum were decreased in ALI group (P<0.05). Conclusion Dexmedetomidine can alleviate blunt chest trauma and hemorrhagic shock-resuscitation induced ALI in rats, and the mechanism is related to inhibition of NLRP3 inflammasome activation and reduction of inflammatory response. Key words: Dexmedetomidine; Acute lung injury; NLR family, pyrin domain-containing 3 protein

Trigeminal Nerve Stimulation: A Novel Method of Resuscitation for Hemorrhagic Shock.

To determine if trigeminal nerve stimulation can ameliorate the consequences of acute blood loss and improve survival after severe hemorrhagic shock. Animal study. University research laboratory. Male Sprague-Dawley rats. Severe hemorrhagic shock was induced in rats by withdrawing blood until the mean arterial blood pressure reached 27 ± 1 mm Hg for the first 5 minutes and then maintained at 27 ± 2 mm Hg for 30 minutes. The rats were randomly assigned to either control, vehicle, or trigeminal nerve stimulation treatment groups. The effects of trigeminal nerve stimulation on survival rate, autonomic nervous system activity, hemodynamics, brain perfusion, catecholamine release, and systemic inflammation after severe hemorrhagic shock in the absence of fluid resuscitation were analyzed. Trigeminal nerve stimulation significantly increased the short-term survival of rats following severe hemorrhagic shock in the absence of fluid resuscitation. The survival rate at 60 minutes was 90% in trigeminal nerve stimulation treatment group whereas 0% in control group (p < 0.001). Trigeminal nerve stimulation elicited strong synergistic coactivation of the sympathetic and parasympathetic nervous system as measured by heart rate variability. Without volume expansion with fluid resuscitation, trigeminal nerve stimulation significantly attenuated sympathetic hyperactivity paralleled by increase in parasympathetic tone, delayed hemodynamic decompensation, and improved brain perfusion following severe hemorrhagic shock. Furthermore, trigeminal nerve stimulation generated sympathetically mediated low-frequency oscillatory patterns of systemic blood pressure associated with an increased tolerance to central hypovolemia and increased levels of circulating norepinephrine levels. Trigeminal nerve stimulation also decreased systemic inflammation compared with the vehicle. Trigeminal nerve stimulation was explored as a novel resuscitation strategy in an animal model of hemorrhagic shock. The results of this study showed that the stimulation of trigeminal nerve modulates both sympathetic and parasympathetic nervous system activity to activate an endogenous pressor response, improve cerebral perfusion, and decrease inflammation, thereby improving survival.

Conducting fresh whole blood transfusion training.

Fresh whole blood is the optimal resuscitation fluid for casualties in hemorrhagic shock according to the Committee on Tactical Combat Casualty Care and has demonstrated to improve outcomes in severely wounded patients. Like all medical interventions, fresh whole blood transfusions are not without risks, but similarly can be mitigated through increased training to develop provider knowledge and proficiency. To date, no literature has been published regarding the proper technique to conduct fresh whole blood transfusion training. This article provides a structured foundation to establish a standardized fresh whole blood transfusion training program to increase skill and preparedness for fresh whole blood protocol implementation. Using these techniques in a training environment, providers will be able to provide optimal resuscitation in hemorrhagic shock in austere environments.

Prehospital whole blood resuscitation prevents coagulopathy and improves acid–base status at hospital arrival in a nonhuman primate hemorrhagic shock model

Hemorrhage remains the primary cause of preventable death in civilian and military trauma. The Committee on Tactical Combat Casualty Care recommends prehospital (PH) resuscitation with whole blood (WB). However, 6% hetastarch in lactated electrolyte (HEX) and crystalloids are more commonly available and used for PH resuscitation in military and civilian environments, respectively. The mechanistic benefits of PH WB resuscitation have not been well studied and remain to be elucidated. The aim of this study was to evaluate the differences in simulated PH WB and HEX resuscitation, specifically with regards to coagulation, physiologic, and metabolic outcomes to better elucidate the mechanistic benefits of WB. In a randomized study, the physiologic, coagulation, and metabolic responses to simulated PH WB (n = 12) or HEX (n = 12) were evaluated in a nonhuman primate model of severe polytraumatic hemorrhagic shock. Notable findings included 1) equivalence of shock reversal between simulated PH WB and HEX treatment groups as determined by hemodynamics and base deficit and 2) prevention of coagulopathy at simulated hospital arrival with initial WB resuscitation as determined by viscoelastic and plasmatic coagulation assays. The major benefit of WB, as compared to HEX, in simulated PH resuscitation appears to be prevention of coagulopathy at hospital arrival. Both fluids effectively reversed shock in this model, implying that efficacious provision preload (cardiac output support and hence oxygen delivery) and coagulation proteins (prevention of coagulopathy) are mechanisms underlying WB's effectiveness in early resuscitation of hemorrhagic shock.

Artificial oxygen carriers and red blood cell substitutes: A historic overview and recent developments toward military and clinical relevance.

Packed red blood cells are a critical component in the resuscitation of hemorrhagic shock. The availability of donor-derived blood products, however, suffers from issues of supply, immunogenicity, and pathogenic contamination. Deployment in remote or austere environments, such as the battlefield, is further hindered by the inherent perishability of blood products. To address the significant limitations of allogenic packed red blood cells and the urgent medical need for better resuscitative therapies for both combat casualties and civilians, there has been significant research invested in developing safe, effective, and field deployable artificial oxygen carriers. This article provides a comprehensive review of the most important technologies in the field of artificial oxygen carriers including cell-free and encapsulated hemoglobin-based oxygen carriers, perfluorocarbon emulsions, natural hemoglobin alternatives, as well as other novel technologies. Their development status, clinical, and military relevance are discussed. LEVEL OF EVIDENCE: Systematic review.

Caspase-(8/3) activation and organ inflammation in a rat model of resuscitated hemorrhagic shock: A role for uric acid.

Multiple organ failure can develop after hemorrhagic shock (HS). Uric acid (UA) is released from dying cells and can be proinflammatory. We hypothesized that UA could be an alternative mediator of organ apoptosis and inflammation after HS. Ventilated male Wistar rats were used for the HS model. Two durations of shock (5 minutes vs. 60 minutes) were compared, and shams were instrumented only; animals were resuscitated and observed for 24 hours/72 hours. Caspases-(8/3), myeloperoxidase (MPO), TNF-α were measured in lungs and kidneys. Plasma UA and cytokine (IL-1β, IL-18, TNF-α) were measured. A second set of animals were randomized to vehicle versus Rasburicase intraperitoneal intervention (to degrade UA) during resuscitation. Another group received exogenous UA intraperitoneally without HS. Measures mentioned above, in addition to organs UA, were performed at 24 hours. In vitro, caspases-(8/3) activity was tested in epithelial cells exposed to UA. Hemorrhagic shock increased organ (kidney and lung) TNF-α, MPO, and caspases activity in various patterns while caspase-8 remained elevated over time. Hemorrhagic shock led to increased plasma UA at 2 hours, which remained high until 72 hours; TNF-α and IL-18 were elevated at 24 hours. The exogenous UA administration in sham animals reproduced the activation of caspase-8 and MPO in organs, and TNF-α in the lung. The increased plasma and organ UA levels, plasma and lung TNF-α, as well as organ caspase-(8/3) and MPO, observed at 24 hours after HS, were prevented by the administration of Rasburicase during resuscitation. In vitro, soluble UA induced caspases-(3/8) activity in epithelial cells. Uric acid is persistently high after HS and leads to the activation of caspases-8 and organ inflammation; these can be prevented by an intervention to degrade UA. Therefore, UA is an important biomarker and mediator that could be considered a therapeutic target during HS resuscitation in human.

Pharmacokinetics of Tranexamic Acid via Intravenous, Intraosseous, and Intramuscular Routes in a Porcine (Sus scrofa) Hemorrhagic Shock Model

Intravenous (IV) tranexamic acid (TXA) is an adjunct for resuscitation in hemorrhagic shock; however, IV access in these patients may be difficult or impossible. Intraosseous (IO) or intramuscular (IM) administration could be quickly performed with minimal training. We investigated the pharmacokinetics of TXA via IV, IO, and IM routes in a swine model of controlled hemorrhagic shock.Fifteen swine were anesthetized and bled of 35% of their blood volume before randomization to a single 1g/10mL dose of IV, IO, or IM TXA. Serial serum samples were obtained after TXA administration. These were analyzed with high-pressure liquid chromatography-mass spectrometry to determine drug concentration at each time point and define the pharmacokinetics of each route.There were no significant differences in baseline hemodynamics or blood loss between the groups. Peak concentration (Cmax) was significantly higher in IV and IO routes compared with IM (p = .005); however, the half-life of TXA was similar across all routes (p = .275).TXA administration via IO and IM routes during hemorrhagic shock achieves serum concentrations necessary for inhibition of fibrinolysis and may be practical alternatives when IV access is not available.

Abstract 186: Remote Limb Ischemic Preconditioning Improves Short and Long Term Survival and Maintains Intravascular Blood Volume During Resuscitation of Hemorrhagic Shock

Background: We further examined the protective effects of experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Methods: Sprague Dawley rats (both genders) were randomized into RIPC (n= 26) or control group (n= 27), and anesthetized with intraperitoneal ketamine/xylazine. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats remained anesthetized for another 30 min before recovery; endpoints were survival at 72 hours and 6 weeks. Results: The % of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in the RIPC group (41.7 ± 1.0 %) and control group (41.9 ± 1.0 %). Recovery of blood pressure during the early resuscitation phase was significantly improved in the RIPC group. The diastolic internal dimension of the left ventricle (echocardiogram), which indicates circulating intravascular blood volume, was significantly larger in the RIPC group at 1 hour after initiation of shed blood reinfusion (5.8 ± 0.1 mm) compared to 5.4 ± 0.1mm in the control group (p=0.04). Left ventricular fractional shortening was comparable between RIPC (50.9 ± 1.9 %) and control group (49.6 ± 1.8 %; p=0.64) at 1 hour after initiation of resuscitation. At 48 hours after shock, BUN was within normal range in the RIPC group (17.3 ± 1.2 mg/dl); but elevated in the control group (22.0 ± 1.7 mg/dl). At 72 hours after hemorrhagic shock injury, 6 of 27 (22.2 %) rats in the control group and 13 of 26 (50 %, p = 0.047) rats in the RIPC group survived. At 6 weeks, 5 of 27 (18.5 %) rats in the control group and 13 of 26 (50 %; p = 0.021) rats in the RIPC group survived. RIPC significantly increased survival rate at both 72 hours and 6 weeks. Conclusions: RIPC improved recovery of blood pressure and maintained more circulating intravascular blood volume in the early phase of resuscitation, improved BUN, and markedly and significantly improved short and long term survival in rats subjected to hemorrhagic shock.

Experience with uncrossmatched blood refrigerator in emergency department

BackgroundUncrossmatched packed red blood cell (PRBC) transfusion is fundamental in resuscitation of hemorrhagic shock. Ready availability of uncrossmatched blood can be achieved by storing uncrossmatched blood in a blood bank...

Intravenous Hydroxocobalamin Versus Hextend Versus Control for Class III Hemorrhage Resuscitation in a Prehospital Swine Model.

Hydroxyethyl starch (Hextend) has been used for hemorrhagic shock resuscitation, however, hydroxyethyl starch may be associated with adverse outcomes. To compare systolic blood pressure (sBP) in animals that had 30% of their blood volume removed and treated with intravenous hydroxocobalamin, hydroxyethyl starch, or no fluid. Twenty-eight swine (45-55 kg) were anesthetized and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged 20 mL/kg over 20 minutes and then administered 150 mg/kg IV hydroxocobalamin in 180 mL saline, 500 mL hydroxyethyl starch, or no fluid and monitored for 60 minutes. Data were modeled using repeated measures multivariate analysis of variance. There were no significant differences before treatment. At 20 minutes after hemorrhage, there was no significant difference in mean sBP between treated groups, however, control animals displayed significantly lower mean sBP (p < 0.001). Mean arterial pressure and heart rate improved in the treated groups but not in the control group (p < 0.02). Prothrombin time was longer and platelet counts were lower in the Hextend group (p < 0.05). Moreover, thromboelastography analysis showed longer clotting (K) times (p < 0.05) for the hydroxyethyl starch-treated group. Hydroxocobalamin restored blood pressure more effectively than no treatment and as effectively as hydroxyethyl starch but did not adversely affect coagulation.

7 Performance of Single Versus Double Site Intraosseous Blood Transfusion Strategies in a Swine [Sus Scrofa] Model of Hemorrhagic Shock

1. Discuss and clarify the utility of intraosseous blood transfusions for treating hypovolemic battlefield injuries in military out-of-hospital settings 2. Compare the advantages and complications of humeral versus sternal intraosseous access for resuscitation of hemorrhagic shock. 3. Identify flow rates, degree of intravascular hemolysis, and occurrence of coagulopathy in single versus double site intraosseous blood transfusion. The American College of Surgeons Advance Trauma Life Support (ATLS) endorses the use of intraosseous devices for the adult trauma patient in extremis. Intraosseous access is frequently used by military physicians administering fluids, blood, and medications for victims of severe battlefield trauma. The optimal intraosseous blood transfusion strategy appears to involve pressure bag transfusion through either the sternum or proximal humerus. Double anatomic site IO catheter placement has the potential to augment resuscitation in cases where vascular access is challenging. We sought to compare flow rates and complications among 4 single and double anatomic site transfusion strategies in a swine model of hemorrhagic shock. 48 Yorkshire swine were placed under general anesthesia during the study protocol. Data from 12 animals completed to date is presented below. Following intra-arterial catheter placement, 30-40% of the animal’s estimated blood volume was removed using the flow of gravity. Subsequently, 15-20% of the animals estimated blood volume was autologously infused via pressure bag through 1 of 4 randomly assigned treatment arms: 1) Proximal Humerus (n=12), 2) Sternum (n=12), 3) Proximal Humerus + Sternum (n=12), 4) Double Proximal Humerus (n=12). Flow rates, intravascular hemolysis, and coagulopathy were recorded. Presence of pulmonary arterial fat embolism was evaluated for by a pathologist blinded to treatment arm. The average weight of swine was 77.8 kg. Average bone density on DEXA scan of the proximal humerus and sternum was 1.001 cm/gm2 and 0.242 cm/gm2, respectively. Average transfusion pressures were 360 mmHg. Infusion rates were as follows: Single Humerus 58.8 ml/min; Sternum 54 ml/min; Sternum + Single Humerus 126 ml/min and Double Humerus 120.3 ml/min. Plasma free hemoglobin levels (baseline, post transfusion) were: Single Humerus 9, 13.2 μg/ml; Sternum 10.5, 18.4 μg/ml; Double Humerus 11.4, 17.8 μg/ml and Sternum + Single Humerus 8.8, 13.9 μg/ml. No significant differences in post transfusion coagulopathy were observed. Blinded pathologist review of pulmonary tissue for edema, inflammation and presence of pulmonary fat emboli between treatment arms is underway. In an animal model of hemorrhagic shock, double site IO transfusion under a pressure bag appears to confer a significant advantage in flow rates. Proximal humerus and sternal IO transfusions achieved similar flow rates in a model that closely resembles the bone density of an adult male. No significant differences between strategies were noted in regard to intravascular hemolysis or coagulopathy. In cases of severe trauma with challenging vascular access, double site access in either bilateral proximal humerus or sternum and proximal humerus may confer a clinical advantage in speed of transfusion without significant complications.

Performance of closed-loop resuscitation of haemorrhagic shock with fluid alone or in combination with norepinephrine: an experimental study

BackgroundClosed-loop resuscitation can improve personalization of care, decrease workload and bring expert knowledge in isolated areas. We have developed a new device to control the administration of fluid or simultaneous co-administration of fluid and norepinephrine using arterial pressure.MethodWe evaluated the performance of our prototype in a rodent model of haemorrhagic shock. After haemorrhagic shock, rats were randomized to five experimental groups: three were resuscitated with fluid and two with co-administration of fluid and norepinephrine. Among groups resuscitated with fluid, one was resuscitated by a physician and two were resuscitated according to two different closed-loop algorithms. Among groups resuscitated with fluid and norepinephrine, one was resuscitated by a physician and the other one by the closed-loop device. The precision of arterial pressure during the resuscitation period was assessed using rising time, time passed in the target area and performance error calculations.ResultsGroups resuscitated with fluid had similar performances and passed as much time in the target area of 80–90 mmHg as the manual group [manual: 76.8% (67.9–78.2), closed-loop: 64.6% (45.7–72.9) and 80.9% (59.1–85.3)]. Rats resuscitated with fluid and norepinephrine using closed-loop passed similar time in target area than manual group [closed-loop: 74.4% (58.4–84.5) vs. manual: 60.1% (46.1–72.4)] but had shorter rising time to reach target area [160 s (106–187) vs. 434 s (254–1081)] than those resuscitated by a physician. Rats resuscitated with co-administration of fluid and norepinephrine required less fluid and had less hemodilution than rats resuscitated with fluid alone. Lactate decrease was similar between groups resuscitated with fluid alone and fluid with norepinephrine.ConclusionsThis study assessed extensively the performances of several algorithms for closed-loop resuscitation of haemorrhagic shock with fluid alone and with co-administration of fluid and norepinephrine. The performance of the closed-loop algorithms tested was similar to physician-guided treatment with considerable saving of work for the caregiver. Arterial pressure closed-loop guided algorithms can be extended to combined administration of fluid and norepinephrine.

Sevoflurane postconditioning improves the spatial learning and memory impairments induced by hemorrhagic shock and resuscitation through suppressing IRE1α-caspase-12-mediated endoplasmic reticulum stress pathway

Severe hemorrhagic shock induces cognitive dysfunction by promoting cell death mediated by activating endoplasmic reticulum (ER) stress. Sevoflurane postconditioning prevents neuronal apoptosis against cerebral ischemia/reperfusion injury. It is unknown if this protective effect on hemorrhagic shock and resuscitation rats (HSR) is associated with ER stress attenuation. Male adult Sprague-Dawley rats were subjected HSR by removing 40% blood volume within 30 min, and 60 min later the animals were resuscitated with infusion of the removing blood in 30 min. Sevoflurane postconditioning was performed by inhaling sevoflurane at three different concentrations (0.5, 1.0, 1.5 MAC) at the onset of resuscitation for 30 min. Severe hypotension (mean arterial pressure 40–45 mmHg) occurred in the shock session for 60 min accompanying with significantly elevated lactate, decreased BE and pH values in arterial blood gas analysis. There were impaired spatial learning and memory following HSR indicated by persistently longer escape latency and lower correct rate, as well as less duration and crossing in the target quadrant by using Morris water maze and Y-maze tests. In the hippocampal CA1 region, there was significantly higher activity of caspase-3 induced by HSR. HSR also elevated the expression of inositol-requiring enzyme 1α (IRE1α) and caspase-12 in the hippocampus by western blot analysis. Sevoflurane postconditioning at 1.0 and 1.5 MAC significantly reversed these changes. These findings suggested that sevoflurane postconditioning could improve spatial learning and memory deficits induced by severe hemorrhagic shock and subsequent resuscitation. The suppression of endoplasmic reticulum stress provided critical contribution in neural apoptosis mediated by IRE1α-caspase-12 pathway.

Serial Changes in Fibrinolysis during and Following Resuscitation of Severe Hemorrhagic Shock in Patients Requiring Immediate Operation

Serial Changes in Fibrinolysis during and Following Resuscitation of Severe Hemorrhagic Shock in Patients Requiring Immediate Operation

The effect of acetated ringer's solution on inflammatory mediators on lung tissue and their signaling pathways in rats with shock

Objective To study the effects of acetated ringer's solution resuscitation in hemorrhagic shock rats on inflammatory mediators on lung tissue and their JNK (c-Jun N-terminal kinase) signaling pathways. Methods Thirty-two SD rats were randomly(random number) divided into four groups: shock without resuscitation group (CR, n=8), saline group (NR, n=8), lactated ringer's solution group (LR, n=8) and acetated ringer's solution group (AR, n=8). The rats of NR group, LR group and AR group were prepared into shock models (mean arterial blood pressure maintained at 40-45 mmHg), The rats of NR group, LR group and AR group were in the shock for 60 min and then the corresponding kinds of liquid were administered for 30 min and observation was carried out for 4 hours. The rats of CR group without liquid resuscitation were observed for 4 hours after shock. After that, the lung tissues of rats were taken from NR group, LR group and AR group as well as from CR group 4 hours after shock (if the rats died, the lung tissues were immediately taken). The levels of TNF-α, IL-4 and IL-10 mRNA in lung were measured by real-time polymerase chain reaction (RT-PCR) , and Western blot was used to measure the levels of JNK phosphorylation and MKP-1 acetylation. The one-way ANOVA was used for comparison among groups . Between the two groups, the comparison was analyzed by using LSD-t test. Results The IL-4 mRNA expression of lung tissue in AR group was higher than that in CR group, NR group and LR group (CR group:0.42±0.34; NR group:2.60±0.66; LR group:6.24±2.95; AR group:11.08±4.24; P<0.05).The IL-10 mRNA expression of lung tissue in AR group was significantly higher than that in CR group, NR group and LR group (CR group:0.25±0.25; NR group:2.79±1.62; LR group:3.51±1.66; AR group:9.35±2.86; P<0.01).The TNF-α mRNA expression in AR group was significantly lower than that in CR group, NR group and LR group (CR group:4.98±1.26; NR group:2.50±0.76; LR group:3.87±3.00; AR group:0.19±0.09; P<0.01). The level of JNK phosphorylation in lung tissue of rats in AR group was significantly lower than that in CR group, NR group and LR group (CR group:0.52±0.12; NR group:0.42±0.08; LR group:0.30±0.08; AR group:0.17±0.06; P<0.01). The level of MKP-1 acetylation in lung tissue of rats in AR group was significantly higher than that in CR group, NR group and LR group (CR group:0.14±0.07; NR group:0.30±0.07; LR group:0.37±0.02; AR group:0.48±0.06; P<0.01). Compared with normal saline and lactated ringer's solution, acetated ringer's solution used in hemorrhagic shock rats could promote MKP-1 acetylation, inhibit the phosphorylation of JNK, significantly inhibit the lung tissue TNF-α released, promote the release of anti-inflammatory factors, IL-4 and IL-10. Conclusions The acetated ringer's solution for resuscitation of hemorrhagic shock in rats could reduce inflammation of lung tissue in a certain extent, probably by enhanced the acetylation of MKP-1 to inhibited JNK signaling pathway and reduced lung tissue inflammation. Key words: Acetated ringer's solution; Hemorrhagic shock; Rat; Fluid resuscitation; Inflammatory mediators; JNK signaling pathway; lung tissue; MAPK phosphatases-1