Hemorrhagic Shock Patients Research Articles

Endothelial oxidative stress induced by serum from patients with severe trauma hemorrhage

Shock induces oxidative stress by ischemia-reperfusion phenomenon. Endothelial cells are involved in the inflammatory response and oxidative stress responsible for microcirculation impairment and organ failure. We examined the potential of serum from patients to induce in vitro reactive oxygen species production by cultured human umbilical vein endothelial cells (HUVECs). Three groups were compared: hemorrhagic shock trauma patients, isolated brain injured patients, and healthy volunteers. In the hemorrhagic shock group we sought a correlation between reactive oxygen species production and severity of shock. Serum was separated and perfused in an in vitro model of perfused HUVECs. Ex vivo reactive oxygen species production was assessed by fluorescence microscopy using dichlorodihydrofluorescein, an intracellular dye oxidized by H2O2. Results are expressed in proportional change from baseline and normalized by protidemia to control for variation related to hemodilution. Reactive oxygen species production by endothelial cells exposed to serum from hemorrhagic shock patients (46.2+/-24.9%) was significantly greater than in those with brain injury (3.9+/-35.1%) and in healthy volunteers (-6.8+/-5.8%). In the hemorrhagic shock group dichlorodihydrofluorescein fluorescence was strongly correlated positively to Simplified Acute Physiology Score II and lactatemia and negatively to [HCO3-]. Serum from trauma patients with hemorrhagic shock induces reactive oxygen species formation in naive endothelial cells which is correlated to shock severity.

Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock

Resuscitation of patients in hemorrhagic shock remains one of the most challenging aspects of trauma care. We showed in experimental studies that vasopressin, but not fluid resuscitation, enabled short-term and long-term survival in a porcine model of uncontrolled hemorrhagic shock after penetrating liver trauma. In this case report, we present two cases with temporarily successful cardiopulmonary resuscitation (CPR) using vasopressin and catecholamines in uncontrolled hemorrhagic shock with subsequent cardiac arrest that was refractory to catecholamines and fluid replacement. In a third patient, an infusion of vasopressin was started before cardiac arrest occurred; in this case, we were able to stabilize blood pressure thus allowing further therapy. The patient underwent multiple surgical procedures, developed multi-organ failure, but was finally discharged from the critical care unit without neurological damage.

Direct Quantitation of Poly(ADP‐Ribose) Polymerase (PARP) Activity as a Means to Distinguish Necrotic and Apoptotic Death in Cell and Tissue Samples

The ability to regulate cell death is essential to the life of a multicellular organism, and two extremes on the cell-death spectrum are apoptosis and necrosis. Apoptosis is an energydependent cell-death program that enables the elimination of unwanted cells at distinct times and through defined mechanisms. Because apoptosis occurs without spillage of cellular contents into the extracellular environment, this death does not lead to inflammation. In contrast, necrosis arises from blunt traumatic injury, oxygen depravation, or other gross cellular insult, and the rupture of the cellular membrane during necrotic death provokes an inflammatory response. Both forms of cell death are observed in diseased tissue. For instance, much of the neurodegeneration observed in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS) probably arises from premature apoptosis, while damage seen in hemorrhagic shock and stroke patients can be due to massive necrotic death. Although apoptosis and necrosis represent two fundamentally different forms of death, they can be quite difficult to distinguish experimentally. Typically, several hallmarks must be observed before it can be conclusively stated that apoptotic death has occurred. These involve time-, labor-, and cost-intensive procedures such as immunoblotting, flow cytometry, and microscopy. The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) is differentially processed in apoptosis and necrosis, and therefore its activity can potentially be used as a means of distinguishing these two forms of cell death (Scheme 1A). In response to mild DNA damage, PARP-1 catalyzes the formation of ADP-ribose polymers (from NAD) onto protein acceptors; this response is part of the machinery that allows the DNA to be repaired and the cell to be saved. In contrast, during more severe DNA damage, the cell activates the apoptotic cascade, and PARP-1 is cleaved by caspases into 89 and 24 kDa sub-

Decision-making of hemorrhagic shock patients with intraperitoneal bleeding (IPB) by ultrasonography (US): the importance of early detection of an increase of IPB

Decision-making of hemorrhagic shock patients with intraperitoneal bleeding (IPB) by ultrasonography (US): the importance of early detection of an increase of IPB

Maxillofacial Injuries and Life-Threatening Hemorrhage

There are many reasons for hypotension in trauma patients with multiple injuries; one uncommon source is facial fractures. The treatment algorithm is volume replacement and local control of the bleeding. A retrospective study was undertaken to evaluate the treatment of patients with life-threatening hemorrhage secondary to facial fractures, and to develop a treatment algorithm. A retrospective chart review was undertaken to determine the incidence of hemorrhagic shock in patients with facial fractures exclusive of others sources, and the use of transcatheter arterial embolization to control the bleeding was evaluated. Over a 4-year period, 7562 patients were treated at Palmetto Richland Memorial Hospital, a Level I trauma center. There were 912 patients with facial injuries, with 11 of these patients presenting with life-threatening hemorrhage secondary to facial fractures. The incidence of life-threatening hemorrhage from facial fracture was 1.2%. The mechanism of injury was blunt in 10 patients and penetrating in 1. The blunt injuries resulted from six motor vehicles crashes, three motorcycle crashes, and one plane crash. The one penetrating injury was a shotgun blast. There were six patients with Le Fort III fractures, two patients with Le Fort II fractures, and three patients with a combination of Le Fort II and III fractures bilaterally. The average volume infused before the embolization was 7 L; this included blood and crystalloid. There were four complications: two minor groin hematomas, one partial necrosis of the tongue, and one facial nerve palsy. There were two deaths, both secondary to concomitant intracranial injury as a result of blunt trauma. The incidence of severe hemorrhage secondary to facial fractures is rare; however, it can be life threatening. When common modalities of treatment such as pressure, packing, and correction of coagulopathy fail to control the hemorrhage, transcatheter arterial embolization offers a safe alternative to surgical control.

M.T. Pepper Jenkins introduces Ringer's lactate to treat shock

M.T. Pepper Jenkins was one of the team that introduced balanced salt solutions (in those days, Ringer's Lactate) to the resuscitation of traumatic shock. The revolutionary proposal is one of the most important innovations in the modern care of the surgical patient. Before 1950, surgeons and physiologists felt that salt solutions were contraindicated in surgical patients because they did not excrete a sodium load. Anesthetized patients were given small amounts of D5W, and if blood loss was excessive, they were given transfusions of whole blood. The turning point came in 1950 when Jenkins reported a series of critical patients in hemorrhagic shock, who received D5W and whole blood for resuscitation. They developed high hematocrits, stiff lungs and pulmonary failure, called “congestive atelectasis.” Jenkins theorized that congestive atelectasis could be prevented if Ringer's Lactate was given with the blood. Over the next 30 years, Shires demonstrated the deficit of extracellular fluid, which occurs in hemorrhagic shock in dogs and humans, and the acute sequestered edema space that results from trauma. This work established the efficacy for the use of balanced salt solutions in shock. Salt solutions were not contraindicated, rather they are indicated and, in fact, life saving. Salt solutions are now used all over the world for the treatment of shock and have saved millions of lives. Our understanding of surgical fluid therapy has changed forever; and Jenkins could be compared to Copernicus who suggested that the earth and other planets rotate around the sun, changing the way we think about the universe.

International Trauma Anesthesia and Critical Care Society (ITACCS).

International Trauma Anesthesia and Critical Care Society (ITACCS).

Deferoxamine and hespan complex as a resuscitative adjuvant in hemorrhagic shock rat model.

The optimal type and amount of fluid for resuscitation of injured patients in hemorrhagic hypovolemic shock remains controversial. Use of deferoxamine, an iron chelator and oxygen-free radical scavenger, and hespan (hydroxyethyl starch), a colloid plasma expander, was evaluated in a rat hemorrhagic shock model. Eighty Sprague-Dawley male rats were utilized in four experiments. In these rats, bi-femoral cutdowns were performed for blood withdrawal, resuscitation, blood sampling, and continuous blood pressure monitoring. All rats, except control (with bilateral cutdown only), were bled and maintained at 40 mmHg for 90 min. The shed blood was returned and animals were resuscitated. One hour later, 2 mg/kg lidocaine was injected and blood samples were taken at 10, 15, 30, and 60 min for evaluation of lidocaine derivative monoethylglycinexylidide (MEGX) by fluorescent polarization immunoassay. In experiment 1 (n = 31), resuscitation with different volumes of Ringer's lactate (7.5 mL, 15.0 mL, and 30.0 mL/kg) was compared and 7.5 mL/kg LR was most beneficial. In experiment 2 (n = 22), resuscitation with three doses of Hespan (3.75 mL, 7.5 mL, and 15 mL/kg) was compared. A dose of 15 mL/kg significantly improved the liver function. In experiment 3 (n = 15), resuscitations with two doses of deferoxamine (30 mg and 100 mg/kg) were compared. A dose of 100 mg/kg significantly improved the liver function. In experiment 4 (n = 12), a combination of deferoxamine (100 mg/kg) and Hespan (3.75 and 7.5 mL) was used. Deferoxamine (100 mg/kg) complexed with 7.5 mL of Hespan was found the most beneficial resuscitation. This conjugate could be a choice as a resuscitative adjuvant in hypovolemic shock without any side effects.

Augmentation of ventricular preload during treatment of cardiovascular collapse and cardiac arrest.

Despite aggressive measures for the treatment of cardiovascular collapse and cardiac arrest, the hypotension associated with these malignant processes usually leads to profound vital-organ ischemia and death. A fundamental therapeutic challenge of such life-threatening processes is the restoration of adequate blood flow to the heart and the brain. However, to maintain adequate forward blood flow out of the heart, venous blood return must be drawn back into the heart. With the exception of administration of exogenous fluid replacement, there are limited ways to enhance blood flow back to the heart during prolonged hypotension. This article describes the potential value of a new impedance threshold valve for the treatment of cardiac arrest and hypotension. The valve was designed to create a vacuum within the thorax during the decompression phase of cardiopulmonary resuscitation or during inhalation. By transiently blocking inspiratory gas exchange during the decompression phase of cardiopulmonary resuscitation, after phrenic nerve-stimulated gasping, or during spontaneous ventilation, the impedance-valve concept may have clinical value in the treatment of patients in cardiac arrest, hemorrhagic shock, and cardiovascular collapse secondary to a number of life-threatening clinical processes.

Hemoglobin Solution Not of Benefit in Traumatic Shock

A variety of hemoglobin-based oxygen carrier solutions have been developed for use in severely injured hemorrhagic shock patients. Diaspirin

What Determines Anesthetic Induction Dose? It’s the Front-End Kinetics, Doctor!

What Determines Anesthetic Induction Dose? It’s the Front-End Kinetics, Doctor!

Massive transfusion in trauma.

The critically injured trauma patient in severe hemorrhagic shock presents a complex and arduous challenge to even the most experienced trauma staff. Lives are at stake as trauma teams feverishly pour massive amounts of blood into severely injured patients attempting to replace entire blood volumes several times over. Prompt identification of patients at risk for hemorrhage and establishment of massive transfusion protocols can provide guidance in managing the transfusion needs of the exsanguinating patient. These state-of-the-art protocols address component therapy, endpoints to transfusion and complications related to massive transfusions. Other treatments, such as autotransfusion and blood substitutes, are promising adjunctive therapies that may in the near future help to improve outcomes in patients who require massive blood transfusions. This article reviews the current standard of care for the trauma patient requiring massive transfusion.

The effect of hemorrhagic shock on IL-10

IL-10 is an anti-inflammatory cytokine. Its blood concentration is said to rise in response to various invasive stimuli together with inflammatory cytokines. Studies on the effects of hemorrhagic shock on cytokine production are few, and they refer mainly to inflammatory cytokines. In this study, IL-10 was measured in patients with hemorrhagic shock. Its transition over time and its relation to inflammatory cytokines was investigated. The subjects were four patients in hemorrhagic shock due to non-trauma and 17 patients in hemorrhagic shock due to trauma. Their average age was 40.1 years. The APACHE-II score for the trauma subjects was 18.6 and 25.8 for non-trauma, with an average of 20.0 for all subjects. The average ISS of the trauma subjects was 26.1. A positive correlation was found between IL-10 and IL-6 (r = 0.777). IL-6 is generally regarded as reflecting the severity of a patient's condition, and as a consequence of our findings, IL-10 should also be useful as a marker of patient severity. Changes in cytokine levels were assessed in relation to the cause of hemorrhage. IL-6 and IL-10 levels were high in hemorrhagic shock due to trauma but did not rise remarkably in shock due to non-trauma, indicating that tissue injury is an important factor in causing high cytokine levels.

Resuscitation and the limited utility of the present generation of blood substitutes

T IS A MEASURE of medical progress that the term blood substitutes, which 50 years ago was used to refer to plasma expanders such as plasma itself or to gelatin and gum acacia, now refers to oxygen carriers intended for use as red blood cell (RBC) substitutes. ~ The term evolved with the realization that plasma expanders were not adequate replacements for blood in the treatment of hemorrhagic shock. It has become widely used in the last 2 decades to describe materials that could sustain life in exchange-transfused mammals. Blood substitutes are being developed to overcome the following clinical problems of conventional red blood cell transfusion: the transmission of disease, the storage limitations of liquid RBCs, and the requirement for cross-matching. Two types of these blood substitutes are now in human clinical trials: solutions of modified cell-free hemoglobin and perfluorocarbon (PFC) emulsions. Both types of blood substitutes were developed with the expectation that they would have wide clinical utility, including the ability to substitute for whole blood or packed red blood cells in the resuscitation of hemorrhagic shock patients. The resuscitation of hemorrhagic shock patients is normally accomplished with intravenous fluids that restore intravascular volume and hemodynamics and with RBCs to restore oxygen-carrying capacity. A candidate blood substitute may improve the outcome in shock purely on the basis of its fluid volume, but to be active as a RBC substitute, it must participate in and improve the delivery of oxygen to the tissues. Effective oxygen delivery is dependent on the ability to load oxygen in the

Hemorrhagic shock

A great deal has been learned about the pathophysiologic condition of hemorrhagic shock. The response of the hormonal and inflammatory mediator systems in patients in hemorrhagic shock appears to represent a distinct set of responses different from those of other forms of shock. The classic neuroendocrine response to hemorrhage attempts to maintain perfusion to the heart and brain, often at the expense of other organ systems. This intense vasoconstriction occurs via central mechanisms. The response of the peripheral microcirculation is driven by local tissue hypoperfusion that results in vasodilation in the ischemic tissue bed. Activation of the systemic inflammatory response by hemorrhage and tissue injury is an important component of the pathophysiologic condition of hemorrhagic shock. Activators of this systemic inflammatory response include ischemia/reperfusion injury and neutrophil activation. Capillary "no-flow" with prolonged ischemia and "no-reflow" with reperfusion may initiate neutrophil activation in patients in hemorrhagic shock. The mechanisms that lead to decompensated and irreversible hemorrhagic shock include (1) "arteriolar hyposensitivity" as manifested by progressive arteriolar vasodilation and decreased responsiveness of the microcirculation to alpha-agonists, and (2) cellular injury and activation of both proinflammatory and counterinflammatory mechanisms. These changes represent a failure of the microcirculation. Redistribution of cardiac output and persistent gut ischemia after adequate resuscitation may also contribute to the development of irreversible hemorrhagic shock. Treatment of hemorrhagic shock includes rapid operative resuscitation to limit activation of the mediator systems and abort the microcirculatory changes that result from hemorrhagic shock. Volume resuscitation and control of hemorrhage, should occur simultaneously. The end point in volume resuscitation of hemorrhagic shock must be maintenance of organ system and cellular function. Whether we use adequate urine output, correction of lactic acidemia, optimization of oxygen delivery, or oxygen consumption as our specific goal, the general objective is to provide adequate crystalloid solution and packed red blood cells to achieve and maintain normal organ and cellular perfusion and function.

Haemoglobin-based red cell substitutes: current status.

Chemically modified haemoglobin solutions represent a potential alternative to the transfusion of donor blood. The theoretical advantages of these products include an oxygen delivery potential greater than that of conventional plasma expanders, prolonged shelf-life, universal compatibility and the absence of pathogenic viruses. Principal concerns have been safety issues including renal toxicity, coagulopathy and vasoactivity. The proposed indications for these solutions are primarily resuscitation of patients in haemorrhagic shock and perioperative haemodilution during elective surgery. Three products have now undergone phase I safety trials in human subjects and phase II safety and efficacy trials are planned in the near future.

Hypertension-induced dysfunction of circulation in hemorrhagic shock

Arterial blood pressure and plasma concentration of Na+, K+, glucose, and urea were studied in patients with essential hypertension during hemorrhagic shock. All 15 patients had established essential hypertension, and all had massive hemorrhage and shock. The control group included 37 normotensive patients in hemorrhagic shock. There were no differences in blood volume loss and age between the hypertensive and normotensive groups. A significant reduction (P < .001) of systolic and diastolic blood pressure as well as plasma concentration of Na+ and K+ were observed in hypertensive patients with hemorrhagic shock as compared with normotensive patients in hemorrhagic shock. Hypertensive patients in shock were found to have significantly elevated (P < .001) plasma glucose, urea, and heart rate compared with normotensive patients in shock. The hypertensive group mortality was significantly (P < .001) higher (80%) than the normotensive group in shock (24.3%). These data suggest that essential hypertension induces alterations in regulation and modulation of peripheral resistance, Na+/K+ membrane exchange, and the metabolism of glucose and urea during hemorrhagic shock. This heterogeneity of dysfunction induced by essential hypertension during hemorrhagic shock is probably caused by a change in the mechanism (diminish) of oxygen consumption at the cellular level, which results in an increase in nitric oxide production (which is O2 dependent), and may play an important role in hypertension and hemorrhagic shock.

Hypertonic Saline Treatment of Uncontrolled Hemorrhagic Shock at Different Periods From Bleeding

Hypertonic saline has been recently recommended for treatment of patients in hemorrhagic shock. Infusion of hypertonic saline at different periods in cases of uncontrolled hemorrhagic shock was studied in rats. The animals were divided into six groups: in group 1 uncontrolled hemorrhagic shock was induced by tail resection and no hypertonic saline was administered; in group 2 hypertonic saline was administered 5 minutes after shock was induced; in group 3 hypertonic saline was administered 15 minutes after shock was induced; in group 4 hypertonic saline was administered 30 minutes after shock was induced; in group 5 hypertonic saline was administered 60 minutes after shock was induced; and in group 6 hypertonic saline was administered 120 minutes after shock was induced. Tail resection in rats in group 1 was followed by a mean +/- SEM bleeding of 2.7 +/- .03 mL in 5 minutes. Infusion of hypertonic saline after 5 and 15 minutes resulted in additional bleeding of 6.3 +/- 1.0 mL and 3.8 +/- 0.5 mL, respectively, and a drop in mean arterial pressure to 36 +/- 8 mm Hg and 56 +/- 9 mm Hg, respectively. Mortality was 80% in group 2 and 53% in group 3. Infusion of hypertonic saline 30 and 60 minutes after shock was induced did not alter bleeding, mean arterial pressure, or survival. Infusion of hypertonic saline within 15 minutes of hemorrhagic shock resulted in increased bleeding, hypotension, and early death. Infusion 30 minutes or later did not alter these variables. This potential danger of early hypertonic saline therapy should be considered in the treatment of patients in trauma.

Prehospital Hypertonic Saline/Dextran Infusion for Post-traumatic Hypotension The U.S.A. Multicenter Trial

The safety and efficacy of 7.5% sodium chloride in 6% dextran 70 (HSD) in posttraumatic hypotension was evaluated in Houston, Denver, and Milwaukee. Multicentered, blinded, prospective randomized studies were developed comparing 250 mL of HSD versus 250 mL of normal crystalloid solution administered before routine prehospital and emergency center resuscitation. During a 13-month period, 422 patients were enrolled, 211 of whom subsequently underwent operative procedures. Three hundred fifty-nine patients met criteria for efficacy analysis, 51% of whom were in the HSD group. Seventy-two per cent of all patients were victims of penetrating trauma. The mean injury severity score (19), Trauma Score plus Injury Severity Score (TRISS) probability of survival, revised trauma scores (5.9), age, ambulance times, preinfusion blood pressure, and etiology distribution were identical between groups. The total amount of fluid administered, white blood cell count, arterial blood gases, potassium, or bicarbonate also were identical between groups. The HSD group had an improved blood pressure (p = 0.024). Hematocrit, sodium chloride, and osmolality levels were significantly elevated in the Emergency Center. Although no difference in overall survival was demonstrated, the HSD group requiring surgery did have a better survival (p = 0.02), with some variance among centers. The HSD group had fewer complications that the standard treatment group (7 versus 24). A greater incidence of adult respiratory distress syndrome, renal failure, and coagulopathy occurred in the standard treatment group. No anaphylactoid nor Dextran-related coagulopathies occurred in the HSD group. Although this trial demonstrated trends supportive of HSD in hypotensive hemorrhagic shock patients requiring surgery, a larger sample size will be required to establish which subgroups of trauma patients might maximally benefit from the prehospital use of a small volume of hyperosmolar solution. This study demonstrates the safety of administering 250 mL 7.5% HDS to this group of patients.

Shock, Transfusion, and Pneumonectomy

To determine the physiologic cardiopulmonary abnormalities leading to death when pneumonectomy is required to stop bleeding in patients in hemorrhagic shock, we compared cardiopulmonary responses to resuscitation in pigs undergoing hemorrhagic shock alone, pneumonectomy alone, and hemorrhagic shock plus pneumonectomy. Four shock-plus-pneumonectomy pigs died acutely from right heart failure. When the five remaining shock-plus-pneumonectomy pigs were compared to the two control groups, pulmonary vascular resistance (PVR) increased to significantly higher levels than would be expected from the increase in PVR noted with resuscitation from shock alone and pneumonectomy alone. Right ventricular compensation maintained cardiac index in the hemorrhage-alone group and the pneumonectomy-alone group but could not maintain cardiac index in the shock-plus-pneumonectomy group, despite maximal increases in right ventricular systolic pressure, heart rate, and right ventricular end diastolic volume. These data indicated that resuscitation from shock plus pneumonectomy cannot be effectively accomplished because increased PVR leads to right ventricular failure, which limits left ventricular preload to levels that are insufficient to maintain cardiac index.