**4.2 Treatment**

*Clinical Management of Shock - The Science and Art of Physiological Restoration*

gen ion concentrations to normal levels [80].

after HES infusion [82].

half [85].

intermediate approach rather than 100 mmHg as it is in the conventional standard methods. The results did not demonstrate any significant benefit in mortality [78]. In regard to damage control resuscitation (DCR), Holcomb suggested an exchange of plasma with limited amounts of volume and crystalloids and proposed an early use of plasma with limited support for systolic blood pressure [79]. Plasma helps prevent coagulopathy due to acidosis and hypothermia. In the daily clinical practice, the patients treated with conventional methods were compared with the patients to whom DCR was applied, resulting in findings favoring DCR. Increasing the blood volume may prevent the development of both acidosis and hypothermia. Plasma contains coagulation factors activated by temperature and brings the hydro-

There is not any proof on that fluids are superior over each other in patients with trauma in the literature. Due to the fact that colloidal fluids quickly increase oncotic pressure, they are much faster than the plasma expansion colloidal fluids. Although crystalloids are cheap, benefits of colloid applications on survival could not be proved in the studies [81]. In a review of clinical studies dating back to 2002 with safety data documented in ICU patients who received hydroxyethyl starch (HES), gelatin, dextran, or albumin, Groeneveld et al. showed that impaired coagulation, clinical bleeding, and acute kidney injury were frequently reported

Although blood to plasma ratios have not been definitely established yet, their increase from 1:8 to 1:1.4 provided a decrease in the mortality rates from 64 to 9% in injured patients with approximately the same severity [83]. Kashuk et al. reported that blood-plasma ratios of 1:2 improved the mortality rates and that fluid replacements with lactated ringer solution resulted in increased international normalized ratios [84]. A multi-center study reported that the daily clinical use of plasma-red blood cell ratios at 1:1 or more in civilians reduced the 24-hour mortality rates by

In the treatment of hemorrhagic shock, Velasco et al. brought resuscitation with hypertonic saline solution (HTS) to the forefront. Their studies were conducted both on animals and on the patients in hemorrhagic or septic shock using either HTS alone or HTS and 6% dextrane combination [86]. Vassar et al. reported the efficacy of the latter combination in injured patients in their country [87]. The purpose of this combination lied on the fact that HTS moved the intracellular fluid to the extracellular space, while dextrane kept a significant amount of that fluid in the vascular bed. The relative efficacy of 7.5% NaCl did not cause a significant change in the survival rates regardless of its use either alone or in combination with dextrane; however, it has been demonstrated that this mode of treatment increased the costs [88]. The Resuscitation Outcomes Consortium found out that neither HTS nor hypertonic dextrane solution provided benefits compared to the fluid resuscitation with normal saline solution during the prehospitalization period in a mixed population of patients with either penetrating or blunt injuries [89]. Similarly, albumin did not provide any benefits over crystalloid solutions [90]. A recent retrospective analysis of a cohort, where trauma patients in the war were compared, demonstrated that a prehospital transfusion of an erythrocyte suspension or plasma or a combination of both, all provided significant benefits on survival. However, a number of studies being conducted currently have reported that they do not provide benefits in the daily practice [91]. Current practice shows that the radial pulse should be maintained in the patients with serious hemorrhage in the prehospital interventions, and crystalloid solutions should be used in relatively smaller quantities to keep the

**50**

patients conscious [92].

A successful resuscitation requires to stop the hemorrhage at all sources and to replace the intravascular volume immediately. These allow for preventing the mounting oxygen debt and replacing it [51]. In the trauma patients, a combination of damage-control surgery and damage-control resuscitation helps to achieve these objectives. In several hemorrhage cases except trauma, the patients similarly benefit from controlling the bleeding upon identifying the hemorrhage source and from resuscitation with blood and blood products [93–95].

The arrival of a patient with hemorrhage at the hospital first requires restoration of the intravascular volume with fluid replacement and hemorrhage control. The strategies in replacing the intravascular volume include the conventional fluid resuscitation with plasma, platelet, red blood cells, or whole blood. Massive blood transfusion can be performed with universal blood products including packed red cells, plasma, platelets, and cryoprecipitate in predetermined volumes accompanied with the administration of several pharmaceutical agents like calcium and tranexamic acid at the patient bedside. These treatment protocols provide benefits for patients with acute hemorrhage in regard to survival [95]. Multiple scoring systems guide the therapeutic teams in identifying the need for massive blood transfusion. Any delays in actualizing the treatment protocols increase the mortality rates [96].

A panel moderated by Sheldon et al. announced a warning stating that blood is the most dangerous drug we have ever used [97]. Potentially, the best alternative to replace the blood is the crystalloid solutions without colloid; its use should be followed by type-specific blood according to the specific need of a patient. The required multiple component therapy is provided by transfusing a single unit of whole blood. Increasing the hematocrit levels over 30% provides no benefits in injuries [98]. In a review evaluating the use of whole blood and blood expanders during the Vietnam war, Sheldon et al. suggested the use of type-specific fresh whole blood preferably [99]. Although the experts in the area agree that blood is the best fluid replacement therapy in hemorrhagic patients, blood transfusion is not free of risks. Therefore, the use of "blood substitutes" or administration of a blood component therapy or acellular oxygen carriers should be considered [98]. Gervin and Fischer have reported type-specific noncross-matched blood as a safer alternative option to the use of cross-matched blood [100].

Red blood cell, plasma, and platelet ratios provide clinical values; however, the ratios have not been definitely established yet. A systemic review and two prospective studies reported that plasma, platelet, and red blood cell ratios around 1:1:1 were safe and decreased the mortality rates in trauma-associated hemorrhages. The general use is to administer six units of plasma and one unit of platelets processed by apheresis for each six units of red blood cells, which constitute an equivalent to six units of pooled thrombocytes [95, 101, 102]. A platelet to red blood cell ratio of over 1:2 has been demonstrated to reduce the mortality in the first 48 hours; however, plasma use at these ratios has not provided any benefits [103]. Barry et al. a total of 17 studies were included in this meta-analysis and including total of 10,610 patients. High fresh frozen plasma (FFP) to packed red blood cell ratios result low posthemorrhage mortality; however, the need for further optimization is highlighted as evidenced by reported increase in post-damage control resuscitation (DCR) sepsis, MOF, and hospital lengths of stay among survivors [104].

All of these blood products contain citrate as an anticoagulant, which is metabolized rapidly by a healthy human liver. However, the use of high volumes of blood products may reach toxic doses in the patients in hemorrhagic shock and may lead to the development of life-threatening hypoglycemia and progressive coagulopathy [68, 105]. Empirically, 1 gram of calcium chloride infusion can be administered following four units of blood product infusion, and the electrolyte levels should be monitored at frequent intervals.

Resuscitation with isotonic crystalloids has been in use for decades since the historical treatments for hemorrhage. However, isotonic crystalloids provide no intrinsic benefits other than increasing the intravascular volume temporarily. Complication rates are increased after high-volume infusions of isotonic crystalloids. The potential complications may include respiratory failure, compartment syndromes in the abdomen or in the extremities, and coagulopathy. In acute hemorrhagic trauma patients, it is recommended to administer crystalloid infusions in the first 6 hours of admission to the hospital, but the volume of infusion should not exceed 3 l [106]. Blood products are not included in this limit. No benefits of prehospital resuscitation with colloid, dextran, and hypertonic saline infusions have been demonstrated as discussed previously.

Pruit et al. found out that fluid resuscitation with normal saline was sufficient to replace both the blood loss and the sequestrated extravascular fluid in males with a moderate level of hemorrhage [107]. Lactated ringer's solution has found to be superior probably because it does not contain acetate or magnesium, and its chlorine content is low [108]. Recent studies stress that infusion of normal saline may lead to hyperchloremic acidosis. In addition, caution is advised against uncontrolled use of crystalloids [109, 110]. The experiences during the times of war showed that administration of blood in combination with protein-free fluids did not cause edema and did not lower the serum albumin levels in severely injured persons [111].

Procoagulant hemostatic such as activated recombinant factor VII, tranexamic acid, prothrombin complex concentrate, and fibrinogen concentrate can be included in the treatment in patients with hemorrhage [112]. The use of procoagulant hemostatic is off-label in patients receiving warfarin and in patients with hemophilia except for the use of prothrombin complex concentrate in the former group of patients and the use of activated recombinant factor VII and tranexamic acid in the latter, respectively. Vasopressin, included in the treatment of patients in hemorrhagic shock, reduces the need for administering blood products and fluids [113].

Prolonged hemostasis in pelvic fractures or in patients with a ruptured aneurysm of aorta or with gastrointestinal bleeding causes an increased need for blood transfusion, elevates the risk levels for mortality, or it may cause both of them simultaneously [114–116]. The duration of emergency department stay should be less than 10 minutes to make a diagnosis and start the initial treatment for trauma patients with hemorrhage in the body in order to keep the mortality risk at a relatively lower level [116]. Patients bleeding out of their extremities, who were applied tourniquets, should be immediately operated to perform a vascular exploration. In a patient bleeding into more than one space in the body, vascular exploration should be performed in the space where most of the bleeding occurs in order to reduce mortality [117].

Regardless of the origin of bleeding, the patients with abdominal or pelvic hemorrhage may benefit from the endovascular occlusion of the aorta as a temporary measure. This approach is called as resuscitative endovascular balloon occlusion of aorta (REBOA). In severe bleeding, this approach reduces the perfusion pressure distal to the origin of bleeding, increases the afterload, and the remaining blood volume is redirected especially to the brain and heart. REBOA reduces intraoperative mortality in patients with a ruptured aneurysm of the abdominal aorta [118]. The method can also be used in gastrointestinal bleeding or in peripartum hemorrhages [119].

Aoki et al. reported that the use of vasopressor agents increases mortality in the traumatic hemorrhagic shock in the retrospective cohort study [120].

**53**

*Hemorrhagic Shock*

**5. Conclusion**

*DOI: http://dx.doi.org/10.5772/intechopen.82358*

The definite treatment of hemorrhage is to stop the bleeding in its source as soon as possible. However, almost all of these hemorrhages occur at locations away from the hospitals. The time from the start of the bleeding until the time of intervention and the ultimate treatment is critical in the management of hemorrhages occurring due to an illness or due to trauma. Then, the primary approach should aim to shorten this period. Critical time is considerably exceeded when the time required for fluid resuscitation is added to the time elapsed at the scene where hemorrhage occurred. Crystalloid solutions are always at our disposal, and they are cheap and available fluids for intravenous use. Physiological saline administration in high volumes is a cause for increased mortality. No kinds of crystalloid fluids are superior to the other. What can be their alternatives? Type-specific blood and blood products have limitations in their supply, storage, and transport to the event scene. If the supply of these products and their storage can be achieved especially in the absence of cold chain facilities, they can provide solutions to the existing issues; however, the near future is not promising at all in this respect. There is continuing research on the use of 0-type whole blood and the use of freeze-dried plasma in the manage-

Systems, preventing the blood loss mechanically, such as REBOA can be developed. Generally, the first people to arrive at the scene are paramedics and young doctors. The required time and feasibility of applying these systems to a patient with weakened or no peripheral pulses in the adverse conditions of the scene during

We may suggest that hemorrhage and hemorrhagic shock has been an issue since the initial existence of humanity. Initiated by a toxin hypothesis, the understanding in physiopathology of shock has already been advanced; however, our achievements in terms of creating solutions to the existing problems are still limited. Technology progresses at a faster pace in terms of creating a trauma, causing injuries, and kill-

ment of patients with trauma-associated hemorrhage [121, 122].

ing people compared to its advances in maintaining survival.

\*Address all correspondence to: sarperturker@gmail.com

the induced sense of panic should be reviewed and estimated in detail.

provided the original work is properly cited.

**Conflict of interest**

**Author details**

Elazığ, Turkey

Fevzi Sarper Türker

There is no conflict of interest

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Elazığ Town Hospital, Cardiovascular Surgery Clinic, University of Health Sciences,
