**1. Introduction**

Hemorrhagic shock develops as a result of intravascular volume loss due to bleeding out of the body or into the anatomical spaces inside, causing insufficient oxygen delivery to the cells. Hemorrhagic shock is a type of hypovolemic shock. If the bleeding does not stop, inadequate oxygen supply may lead to death. Hemorrhagic shock in trauma patients is a predictor of worse outcomes and contributes to early mortality [1]. Intracellular synthesis of anaerobic metabolites impairs hemostasis, resulting in cell death, apoptosis, or necroptosis. Shock may develop due to several reasons including trauma, maternal hemorrhage, gastrointestinal hemorrhage, perioperative hemorrhage, or ruptured aneurysms [2]. Mortality due to bleeding is substantial on a global scale. Annually, 60,000 people in the US and 1.9 million people in the world lose their lives due to hemorrhage and its consequences. Out of them, 1.5 million people die of physical trauma around the world each year [3]. Unexpectedly, trauma affects young people; 1.5 million deaths per year cause an approximate loss of 75 million life year. In addition, functional outcomes are poor, and the long-term mortality rates are high in the hemorrhage survivors [4, 5].

Hemorrhage and hemorrhagic shock treatment is quite difficult and complex procedure as mentioned above. Although our knowledge related to hemorrhagic shock physiopathology has increased, our success in the treatment is limited by failure in injuries and still has high mortality rates. Control of bleeding should be the first priority, but resuscitation should be conducted through crystalloid fluids in the way that it will not form coagulopathy in order to protect hypoxia at the cellular level and so tissues and organs in case where the control cannot be assumed. Crystalloid solutions do not have superiority over each other, and there is not any type of treatment which is absolutely recommended apart from that they are kept limited.

### **1.1 Brief history**

As proposed by the historians, the first written definition of shock is made by Celsus (AD 20) after a penetrating heart injury as "The pulse fades away, the color is extremely pallid, cold and malodorous sweats break out the body as if the body has been wetted by dew, the extremities become cold and death quickly follows" [6]. LeDran, a military surgeon, derived a word from shock as "The bullet thrown from the gunpowder acquires such rapid force that the whole animal participates in the jarring (shock and agitation)" in his article in 1743 [7].

The emergence of biochemistry at the beginning of the twentieth century started serious scientific studies on the pathogenesis of circulatory shock. A number of physiologists agreed on the existence of a toxin released in response to injury, and it was identified to be histamine by Walter Cannon in the US and by Sir Henry Dale in England [8, 9]. However, neither histamine nor other identified vasoactive amines could successively mimic the picture of shock. In the late 1920s and 1930s, Blalock suggested an alternative hypothesis for shock and defined it as direct fluid loss from blood circulation culminating in peripheral vascular failure, a persistence of poor peripheral perfusion. After the proposal of this hypothesis, fluid replacement has become the principal therapy for circulatory shock.

Compilation of Artz and Fitts on that blood and fluids with salt are needed for closing the volume gap occurring after hemorrhage was not commonly appreciated [10]. This concept was supported by highlighting that saline solution should be given in ongoing hemorrhage later [11]. Kinney and Wells criticized the current immediate therapeutic attention to the many problems associated with trauma without regard to the patient's ventilation. Their article established a new objective: therapy in all injured patients should look beyond blood pressure so as to ensure provision and maintenance of effective gas exchange of tissues [12]. While Lansing et al. defended the need for vasoactive medicines for perfusion of vital organs, Nickerson and Gourzis defended the disadvantages of vasoconstriction [13, 14].

The term "golden hour" is widely attributed to R. Adams Cowley, founder of Baltimore's renowned Shock Trauma Institute, who in a 1975 article stated, "the first hour after injury will largely determine a critically injured person's chances for survival"—this was in an era characterized by a lack of an organized trauma system and inadequate prehospital care. The validity of this concept remains controversial. An analogous concept, the "platinum 10 minutes" places a time constraint on the prehospital care of seriously injured patients: no patient should have more than 10 min of scene-time stabilization by the prehospital team prior to transport to definitive care at a trauma center [15].
