Decay-Accelerating Factor Creates an Organ-Protective Phenotype after Hemorrhage in Conscious Rats.

Preclinical and clinical studies have shown that traumatic hemorrhage (TH) induces early complement cascade activation, leading to inflammation-associated multiple-organ dysfunction syndrome (MODS). Several previous studies have demonstrated the beneficial effects of complement inhibition in anesthetized (unconscious) animal models of hemorrhage. Anesthetic agents profoundly affect the immune response, microcirculation response, and coagulation patterns and thereby may confound the TH research data acquired. However, no studies have addressed the effect of complement inhibition on inflammation-driven MODS in a conscious model of hemorrhage. This study investigated whether early administration of decay-accelerating factor (CD55/DAF, a complement C3/C5 inhibitor) alleviates hemorrhage-induced organ damage and how DAF modulates hemorrhage-induced organ damage. DAF was administered to unanesthetized male Sprague Dawley rats subjected to pressure-controlled hemorrhage followed by a prolonged (4 h) hypotensive resuscitation with or without lactated Ringer's (LR). We assessed DAF effects on organ protection, tissue levels of complement synthesis and activation, T lymphocyte infiltration, fluid resuscitation requirements, and metabolic acidosis. Hemorrhage with (HR) or without (H) LR resuscitation resulted in significantly increased C3, C5a, and C5b-9 deposition in the lung and intestinal tissues. HR rats had significantly higher tissue levels of complement activation/deposition (particularly C5a and C5b-9 in the lung tissues), a higher but not significant amount of C3 and C5b-9 pulmonary microvascular deposition, and relatively severe injury in the lung and intestinal tissues compared to H rats. DAF treatment significantly reduced tissue C5b-9 formation and C3 deposition in the H or HR rats and decreased tissue levels of C5a and C3 mRNA in the HR rats. This treatment prevented the injury of these organs, improved metabolic acidosis, reduced fluid resuscitation requirements, and decreased T-cell infiltration in lung tissues. These findings suggest that DAF has the potential as an organ-protective adjuvant treatment for TH during prolonged damage control resuscitation.

Management of Hemorrhagic Shock: Physiology Approach, Timing and Strategies.

Hemorrhagic shock (HS) management is based on a timely, rapid, definitive source control of bleeding/s and on blood loss replacement. Stopping the hemorrhage from progressing from any named and visible vessel is the main stem fundamental praxis of efficacy and effectiveness and an essential, obligatory, life-saving step. Blood loss replacement serves the purpose of preventing ischemia/reperfusion toxemia and optimizing tissue oxygenation and microcirculation dynamics. The "physiological classification of HS" dictates the timely management and suits the 'titrated hypotensive resuscitation' tactics and the 'damage control surgery' strategy. In any hypotensive but not yet critical shock, the body's response to a fluid load test determines the cut-off point between compensation and progression between the time for adopting conservative treatment and preparing for surgery or rushing to the theater for rapid bleeding source control. Up to 20% of the total blood volume is given to refill the unstressed venous return volume. In any critical level of shock where, ab initio, the patient manifests signs indicating critical physiology and impending cardiac arrest or cardiovascular accident, the balance between the life-saving reflexes stretched to the maximum and the insufficient distal perfusion (blood, oxygen, and substrates) remains in a liable and delicate equilibrium, susceptible to any minimal change or interfering variable. In a cardiac arrest by exsanguination, the core of the physiological issue remains the rapid restoration of a sufficient venous return, allowing the heart to pump it back into systemic circulation either by open massage via sternotomy or anterolateral thoracotomy or spontaneously after aorta clamping in the chest or in the abdomen at the epigastrium under extracorporeal resuscitation and induced hypothermia. This is the only way to prevent ischemic damage to the brain and the heart. This is accomplishable rapidly and efficiently only by a direct approach, which is a crush laparotomy if the bleeding is coming from an abdominal +/- lower limb site or rapid sternotomy/anterolateral thoracotomy if the bleeding is coming from a chest +/- upper limbs site. Without first stopping the bleeding and refilling the heart, any further exercise is doomed to failure. Direct source control via laparotomy/thoracotomy, with the concomitant or soon following venous refilling, are the two essential, initial life-saving steps.

Adenosine, Lidocaine, and Magnesium Support a High Flow, Hypotensive, Vasodilatory State With Improved Oxygen Delivery and Cerebral Protection in a Pig Model of Noncompressible Hemorrhage.

BACKGROUND: Noncompressible hemorrhage is the leading cause of preventable death in military and civilian trauma. Our aim was to examine the effect of adenosine, lidocaine, and magnesium (Mg2+; ALM) on cardiovascular and cerebral function in a porcine hepatic hemorrhage model. MATERIALS AND METHODS: Pigs (59.1 ± 0.34 kg) were anesthetized, instrumented, and randomly assigned into sham (n = 6), saline controls (n = 10) or ALM (n = 10) groups before laparoscopic liver resection. After 30 min, groups received 4 mL/kg 3% NaCl ± ALM bolus (Phase 1) followed 60 min later with 3 mL/kg/h 0.9% NaCl ± ALM drip (4 h; Phase 2), then transfusion. Hemodynamics, carotid artery flow, and intracranial pressure were measured continuously. Microdialysis samples were analyzed for metabolites. RESULTS: Saline controls had 20% mortality (mean survival time: 307 ± 38 min) with no ALM deaths over 6 h. Bolus administration increased mean arterial pressure (MAP) in both groups, and drip led to further increases to 62 ± 10 mmHg in controls compared with a steady fall to 47 ± 8 mmHg in ALM group at 240 min. The lower MAP was associated with a dramatic fall in systemic vascular resistance and improved oxygen delivery. ALM drip significantly increased cardiac output and stroke volume with lower dP/dtMin, indicating a less stiff heart. ALM drip also significantly decreased cerebral perfusion pressure, reduced cerebral oxygen consumption (28%), and reduced brain glycerol (60%), lactate (47%), and relative expression of hypoxia-inducible factor (38%) compared with saline controls. CONCLUSIONS: ALM therapy improved cardiac function and oxygen delivery by lowering systemic vascular resistance after noncompressible hemorrhage. ALM also appeared to protect the brain at hypotensive MAPs with significantly lower cerebral perfusion pressure, lower O2 consumption, and significantly lower cortical lactate and glycerol levels compared to saline controls.

Anesthesia for Patients with Extensive Trauma.

Trauma anesthesiology is a unique and growing subspecialty. With the growing number of adult and pediatric trauma centers in the United States, a thorough understanding of the early management of severely injured patients with trauma is an important aspect of anesthesia. Trauma anesthesiology requires the ability to adapt to different work environments, including the trauma bay, the operating room, and even the intensive care unit, where a patient room may require conversion to an operating suite for emergencies. This article provides a review of the anesthetic management for patients with extensive trauma, focusing on physiology, pharmacology, and bedside management.

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

BACKGROUND: Damage 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. OBJECTIVES: To 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. METHODS: PubMed, 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. RESULTS: Of 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. CONCLUSIONS: This 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.

Permissive hypotensive resuscitation in adult patients with traumatic haemorrhagic shock: a systematic review.

BACKGROUND: Permissive hypotensive resuscitation (PHR) is an advancing concept aiming towards deliberative balanced resuscitation whilst treating severely injured patients, and its effectiveness on the survival rate remains unexplored. This detailed systematic review aims to critically evaluate the available literature that investigates the effects of PHR on survival rate. METHODS: A systematic review design searched for comparative and non-comparative studies using EMBASE, MEDLINE, PubMed, Web-of-Science and CENTRAL. Full-text articles on adult trauma patients with low blood pressure were considered for inclusion. The risk of bias and a critical appraisal of the identified articles were performed to assess the quality of the selected studies. Included studies were sorted into comparative and non-comparative studies to ease the process of analysis. Mortality rates of PHR were calculated for both groups of studies. RESULTS: From the 869 articles that were initially identified, ten studies were selected for review, including randomised control trials (RCTs) and cohort studies. By applying the risk of bias assessment and critique tools, the methodologies of the selected articles ranged from moderate to high quality. The mortality rates among patients resuscitated with low volume and large volume in the selected RCTs were 21.5% (123/570) and 28.6% (168/587) respectively, whilst the total mortality rate of the patients enrolled in three non-comparative studies was 9.97% (279/2797). CONCLUSIONS: The death rate amongst post-trauma patients managed with conservative resuscitation was lower than standard aggressive resuscitation, which indicates that PHR can create better survival rate among traumatised patients. Therefore, PHR is a feasible and safely practiced fluid resuscitative strategy to manage haemorrhagic shock in pre-hospital and in-hospital settings. Further trials on PHR are required to assess its effectiveness on the survival rate. LEVEL OF EVIDENCE: Systematic review, level III.

Use of intrathoracic pressure regulation therapy in breathing patients for the treatment of hypotension secondary to trauma.

BACKGROUND: Intrathoracic pressure regulation (IPR) therapy has been shown to increase blood pressure in hypotensive patients. The potential value of this therapy in patients with hypotension secondary to trauma with bleeding is not well understood. We hypothesized that IPR would non-invasively and safely enhance blood pressure in spontaneously breathing patients with trauma-induced hypotension. METHODS: This prospective observational cohort study assessed vital signs from hypotensive patients with a systolic blood pressure (SBP) ≤90 mmHg secondary to trauma treated with IPR (ResQGARD™, ZOLL Medical) by pre-hospital emergency medical personnel in three large US metropolitan areas. Upon determination of hypotension, facemask-based IPR was initiated as long as bleeding was controlled. Vital signs were recorded before, during, and after IPR. An increased SBP with IPR use was the primary study endpoint. Device tolerance and ease of use were also reported. RESULTS: A total of 54 patients with hypotension secondary to trauma were treated from 2009 to 2016. The mean ± SD SBP increased from 80.9 ± 12.2 mmHg to 106.6 ± 19.2 mmHg with IPR (p < 0.001) and mean arterial pressures (MAP) increased from 62.2 ± 10.5 mmHg to 81.9 ± 16.6 mmHg (p < 0.001). There were no significant changes in mean heart rate or oxygen saturation. Approximately 75% of patients reported moderate to easy tolerance of the device. There were no safety concerns or reported adverse events. CONCLUSIONS: These findings support the use of IPR to treat trauma-induced hypotension as long as bleeding has been controlled.

Fluid Resuscitation in Tactical Combat Casualty Care: Yesterday and Today.

The prevailing wisdom for the prehospital fluid resuscitation of trauma victims in hemorrhagic shock in 1992 was to administer 2 L of crystalloid solution as rapidly as possible. A review of the fluid resuscitation literature found that this recommendation was not well supported by the evidence at the time. Prehospital fluid resuscitation strategies were reevaluated in the 1993-1996 Tactical Combat Casualty Care (TCCC) research program. This article reviews the advances in prehospital fluid resuscitation as recommended by the original TCCC Guidelines and modified over the following 2 decades. These advances include hypotensive resuscitation, use of prehospital whole blood or blood components when feasible, and use of Hextend or selected crystalloids when logistical considerations make blood or blood component use not feasible.

Permissive hypotension/hypotensive resuscitation and restricted/controlled resuscitation in patients with severe trauma.

Achieving a balance between organ perfusion and hemostasis is critical for optimal fluid resuscitation in patients with severe trauma. The concept of "permissive hypotension" refers to managing trauma patients by restricting the amount of resuscitation fluid and maintaining blood pressure in the lower than normal range if there is continuing bleeding during the acute period of injury. This treatment approach may avoid the adverse effects of early, high-dose fluid resuscitation, such as dilutional coagulopathy and acceleration of hemorrhage, but does carry the potential risk of tissue hypoperfusion. Current clinical guidelines recommend the use of permissive hypotension and controlled resuscitation. However, it is not mentioned which subjects would receive most benefit from this approach, when considering factors such as age, injury mechanism, setting, or the presence or absence of hypotension. Recently, two randomized clinical trials examined the efficacy of titrating blood pressure in younger patients with shock secondary to either penetrating or blunt injury; in both trials, overall mortality was not improved. Another two major clinical trials suggest that controlled resuscitation may be safe in patients with blunt injury in the pre-hospital setting and possibly lead to improved outcomes, especially in patients with pre-hospital hypotension. Some animal studies suggest that hypotensive resuscitation may improve outcomes in subjects with penetrating injury where bleeding occurs from only one site. On the other hand, hypotensive resuscitation in blunt trauma may worsen outcomes due to tissue hypoperfusion. The influence of these approaches on coagulation has not been sufficiently examined, even in animal studies. The effectiveness of permissive hypotension/hypotensive resuscitation and restricted/controlled resuscitation is still inconclusive, even when examining systematic reviews and meta-analyses. Further investigation is needed to elucidate the effectiveness of these approaches, so as to develop improved treatment strategies which take into account coagulopathy in the pathophysiology of trauma.

Hypotensive resuscitation for traumatic hemorrhagic shock: a systematic review / 中华急诊医学杂志

Objective To systematically review the efficacy of hypotensive resuscitation for traumatic-hemorrhagic shock.Methods Randomized controlled trails (RCTs) or quasi-Randomized controlled trails (qRCTs) were searched in Pubmed,Embase and the Corchrane Library from inception to August 2015.Two reviewers respectively picked out the useful data and performed quality evaluation.Metaanalysis was carried out with RevMan 5.3 software,risk ratio (RR) and its 95％ confidence interval (CI) were pooled to estimate the enumeration data,and GRADE 3.6.1 software was used to rate the level of evidence.Results The results of meta-analysis and GRADE rating system which included 4 studies showed that:compared with conventional resuscitation,hypotensive resuscitation was associated with lower total mortality [RR =0.77,95％ CI:0.62-0.95,P =0.01;n =984,GRADE rating:moderate],and 24-hour mortality [RR =0.47,95％ CI:0.24-0.91,P =0.03;n =281,GRADE rating:moderate],but the subgroup analysis of total mortality showed that there were no significant differences in mortality between the subgroup of blunt or penetrating trauma and the subgroup of penetrating trauma.Conclusions Hypotensive resuscitation reduced total mortality and 24-hour mortality,and the quality of the evidence was moderate.The future studies should do further research to explore the efficacy of hypotensive resuscitation for different types of trauma.

[Advanced methods of prehospital bleeding management based on the experience and standards of tactical medicine]. / Zaawansowane metody tamowania krwotoku w warunkach przedszpitalnych w oparciu o doswiadczenia i standardy medycyny taktycznej.

Hemostatic agents are currently used in the form of special granules or soaked gauze. Their use is particularly advantageous in difficult body location (e.g. on neck, armpit or groin), where other methods of bleeding control are impossible to use or fail. In a tactical environment tranexamic acid received first class recommendation for use in case of severe bleeding in the US Army. Its application should be considered in case of traumatic amputation, penetrating chest and abdominal trauma or hemorrhagic shock. The aim of the implementation of hypotensive resuscitation is to maintain perfusion of vital organs in patient with hypovolemia, without excessive fluid infusion. Modern method of bleeding control in combat condition are compression clamps. The purpose of these devices is to compress blood vessel by external pressure pads, especially in difficult to access arteries and large veins in the pelvis or in the distal abdominal aorta.

Hypotensive Resuscitation.

Hypotensive resuscitation is a component of damage control resuscitation, the evolving approach to resuscitation in severely injured trauma patients. Resuscitation strategies used in treating severely injured trauma patients have changed dramatically over the last 20 years. The purpose of this review is to examine the current literature pertaining to hypotensive resuscitation, explore its use in damage control resuscitation, and examine blood pressure management in the setting of severe trauma.

Non-operative management of blunt liver injury: a new protocol for selected hemodynamically unstable patients under hypotensive resuscitation.

BACKGROUND: The objective of this study was to evaluate our new protocol for performing non-operative management for selected unstable patients under hypotensive resuscitation using improved diagnostic imaging techniques. METHODS: This retrospective study included 77 consecutive patients with blunt liver injury. They were divided into two groups: those treated before and those treated after the revision. Under the new protocol, we attempted to manage the patients non-operatively, usually with angioembolization, including those whose shock improved with fluid resuscitation and continuous loading, permitting the maintenance of a target systolic blood pressure of 80 mmHg. The outcomes of the two groups were evaluated and compared. RESULTS: While comparing the groups, although there was no change in the liver-related morbidity and mortality rates, the urgent and overall laparotomy rates and transfusion requirements in 24 h significantly decreased after the protocol revision. While comparing the subgroups of high-grade injury (AAST Grades 3-5), the overall laparotomy rates and transfusion requirements in 24 h significantly decreased after the protocol revision. CONCLUSIONS: All the selected unstable patients were successfully managed non-operatively after the protocol revision. The decrease in laparotomy rates and transfusion requirements confirmed the feasibility of our new protocol for these selected patients.

Target blood pressure for hypotensive resuscitation.

BACKGROUND: Good outcomes have resulted from hypotensive resuscitation of hemorrhagic shock patients. We hypothesized that mean arterial pressure (MAP) 60mmHg is the target blood pressure for hypotensive resuscitation during uncontrolled hemorrhagic shock in trauma. METHODS: To determine the effective target MAP for hypotensive resuscitation during uncontrolled hemorrhagic shock, we randomly assigned 80 rats to one of 8 treatment groups (n=10 for each group). We then observed the effects of different target MAPs (control, 40, 50, 60, 70, 80, 90mmHg, and sham) on fluid resuscitation of uncontrolled hemorrhagic shock. Blood pressure, serum lactate, hematocrit, fluid therapy, blood loss, and plasma cytokine levels were measured at 0, 30, 90, 120, 180, 240, 300min after the start of the surgical procedure. RESULTS: A target MAP of 90, 80 and 70mmHg had increased blood loss and decreased hematocrit and IL-6 and TNF-α production. A target MAP of 60, 50 and 40mmHg had lower blood loss, good hematocrit, higher IL-6 and TNF-α production, and decreased animal survival. Only target MAPs of 40 and 50 had and decreased animal survival. The differences in blood loss, hematocrit, lactate, post-resuscitation MAP, survival, IL-6, IL-10, and TNF-α production between rats with a target MAP of 60mmHg and those with a target MAP of 70mmHg were not significant. The amount of fluid therapy in the BP 60 groups was less than in the BP 70 groups (P<0.001). CONCLUSION: A MAP of 60mmHg should be considered for evaluation in human studies as a target for hypotensive resuscitation.

The clinical effectiveness of permissive hypotension in blunt abdominal trauma with hemorrhagic shock but without head or spine injuries or burns: a systematic review.

BACKGROUND: Trauma is a major cause of death and disability. The current trend in trauma management is the rapid administration of fluid as per the Advanced Trauma Life Support guidelines, although there is no evidence to support this and even some to suggest it might be harmful. Some guidelines, protocols, and recommendations have been established for the use of permissive hypotension although there is reluctance concerning its application in blunt injuries. OBJECTIVES: The aim of this review is to determine whether there is evidence of the use of permissive hypotension in the management of hemorrhagic shock in blunt trauma patients. This review also aims to search for any reason for the reluctance to apply permissive hypotension in blunt injuries. METHODS: This systematic review has followed the steps recommended in the Cochrane Handbook for Systematic Reviews of Interventions. It is also being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement and checklist. Database searches of MEDLINE, EMBASE, the Centre for Reviews and Dissemination databases and the Cochrane Library were made for eligible studies as well as journal searches. Inclusion criteria included systematic reviews that have similar primary questions to this review and randomized controlled trials where patients with blunt torso injuries and hemorrhagic shock were not excluded. Rapid or early fluid administration was compared with controlled or delayed fluid resuscitation and a significant outcome was obtained. RESULTS: No systematic reviews attempting to answer similar questions were found. Two randomized controlled trials with mixed types of injuries in the included patients found no significant difference between the groups used in each study. Data concerning the question of this review was sought after these papers were appraised. CONCLUSION: The limited available data are not conclusive. However, the supportive theoretical concept and laboratory evidence do not show any reason for treating blunt injuries differently from other traumatic injuries. Moreover, permissive hypotension is being used for some nontraumatic causes of hemorrhagic shock and in theater. Therefore, this should encourage interested researchers to continue clinical work in this important field.