PREHOSPITAL TRAUMA CARE 3 PREHOSPITAL FLUID RESUSCITATION: WHAT TYPE, HOW MUCH AND CONTROVERSIES Fluid resuscitation is a vital

l treatment in the care of hypotensive trauma patients. Restoration of effective circulating blood volume improves oxygen delivery, thereby diminishing the untoward effects of shock at the cellular and organ level. However, fluid resuscitation, in and of itself, is not a panacea. Whereas restoration of effective circulating blood volume is essential, the method of supplying fluid is more controversial and complicated by several confounding factors. The inability to deliver definitive care in the field, the heterogeneity of patient populations, the variability in mechanism of injury, and the level of infield hemorrhage control make precise study of the topic challenging. Therefore, the debate persists concerning the type, the amount, and the timing of fluid administration. The purpose of this discussion is to provide insight in the use of fluid resuscitation of trauma patients in the prehospital setting. EPIDEMIOLOGY If trauma is the leading cause of civilian death in Americans aged less than 45 years and the fourth leading cause of death in the United States for all ages, hemorrhagic shock is the primary physiologic defect leading to death. Volume deficits develop not only as a result of blood loss, but also due to diffuse capillary-endothelial leak and fluid shifts from intravascular to the interstitial space. These deficits, and the attendant hypoperfusion, potentially lead to multiple organ dysfunction, failure, and death. Aggressive fluid administration has been mainstay therapy in trauma patients for over 40 years. Estimates of the numbers of trauma patients in the United Kingdom given prehospital intravenous fluid range from 8.6 to 65 patients per 100,000 population per year. However, for the last 15 years, this practice, especially in the setting of uncontrolled hemorrhage, has been questioned. CAUSES OF SIGNIFICANT HEMORRHAGE The causes of hemorrhage vary depending on the mechanism of injury. In blunt trauma, bleeding usually emanates from solid organs such as the spleen and liver, mesenteric blood vessel tears, pelvic and femur fractures, thoracic bleeding from lung lacerations or intercostal vessel bleeding from rib fractures or external causes such as scalp lacerations. Uncontained bleeding from aortic transection and cardiac rupture usually leads to exsanguination at the scene. When the wounding mechanism is secondary to penetrating trauma, uncontrolled major vascular injury usually is the source of the hemorrhage. DIAGNOSIS/ASSESSMENT In the prehospital setting, emergency medical technicians perform an immediate assessment of the trauma victim in the form of a primary and secondary survey. This assessment includes an evaluation of the patient for life-threatening conditions that need to be promptly addressed. The patency of the airway is initially evaluated. This is followed by auscultation of breath sounds assessing for pneumothoraces or hemothoraces. Attention is then turned to the circulation. Central and peripheral pulses are assessed. Obvious sources of external bleeding are controlled. The patients blood pressure is measured. Because definitive care cannot be rendered at the scene, a scoop and run rather than stay and stabilize philosophy should be evoked. Attempts at intravascular cannulation should not delay transfer to the trauma center. ACCESS WWW.MEDICALVILLAGE.BLOGSPOT.COM FOR MORE NOTES TO COME

 PREHOSPITAL TRAUMA CARE 3 CLASSES OF HEMORRHAGIC SHOCK Hemorrhage is the most common cause of shock in the injured patient. Shock is defined as the presence of inadequate oxygen for normal aerobic metabolism; aerobic metabolism occurs leading to lactic acidosis. If this process continues, cellular membranes lose their integrity leading to cellular swelling, progressive cellular damage, and ultimately, cellular death. Hemorrhage, an acute loss of circulating blood volume, is classified based on the percentage of blood volume loss. Specific hemodynamic, respiratory, central nervous system, urinary, and integumentary changes occur given the degree of shock (Table I). Whereas class I hemorrhage is associated with minimal clinical symptoms and requires little, if any, volume replacement, class IV hemorrhage is immediately life-threatening, necessitates blood transfusion, and usually calls for surgical intervention to halt on going bleeding.

MANAGEMENT Access The basic management principles to follow in hemorrhagic shock are to stop the bleeding and replace the volume loss. Establishing a patent airway with adequate ventilator exchange and oxygenation is the first priority. Supplemental oxygen is supplied while external bleeding is controlled. Two large-caliber (minimum of 16-gauge) peripheral intravenous catheters are inserted, preferably in the antecubital veins. Intravenous access should not delay transport of the patient to the trauma center. Types of Fluid Crystalloids A crystalloid is a solution of small non-ionic or ionic particles. They are freely permeable to the vascular membrane and are distributed mainly in the interstitial space. As such, only one-third of the volume of crystalloid infused expands the intravascular space. This accounts for the need to provide at least three times more volume of crystalloid than the volume of blood lost. Because of decreased colloid osmotic pressure secondary to decreased serum protein concentration from hemorrhage, capillary leaks, and crystalloid replacement, this ratio of volume of crystalloid infused to blood volume lost may even approach 7-10:1. Depletion of both the interstitial fluid volume and the intravascular space following severe injury may be a reason to use crystalloids for fluid resuscitation, which restore volume to both spaces. Animal and human studies demonstrating improved survival from shock when utilizing isotonic fluid ACCESS WWW.MEDICALVILLAGE.BLOGSPOT.COM FOR MORE NOTES TO COME

 PREHOSPITAL TRAUMA CARE 3 and blood versus blood transfusion alone support this view. Other advantages of crystalloid use in prehospital fluid resuscitation include its negligible cost in comparison to other resuscitative fluids, immediate availability, and long-term storage capacity. Given the predilection of crystalloid to primarily fill the interstitial space, tissue edema is common and may have deleterious effects. In head-injured patients, increased brain edema may adversely affect outcome. Gas exchange may be impaired secondary to pulmonary edema. Endothelial and red cell edema impair microcirculation and tissue oxygen exchange, potentially contributing to multiple organ dysfunction. According to Advanced Trauma Life Support (ATLS) guidelines, fluid resuscitation of the trauma patient begins with a 2-L bolus of crystalloid, usually lactated Ringers (LR) solution. LR is an isotonic fluid that contains L-lactate and D-lactate in a 50:50 mixture. The L-lactate is metabolized in the liver to bicarbonate, thereby providing additional buffer. Although the D-lactate isomer is thought to be a cause of acidosis, studies have shown that resuscitation with LR does not lead to increased lactic acid levels. However, normal saline (NS), another isotonic crystalloid, can induce a hyperchloremic acidosis when given in large volumes because of its concentration of chloride ions (154 mEq/L). Healey et al., suggest, in their animal model of massive hemorrhage, increased survival rate in animals resuscitated with LR and blood relative to those animals that received NS and blood. This difference was thought to be secondary to the profound acidosis occurring in the NS/blood group. Because LR has a lower osmolality than plasma (273 mOsm/l vs. 285-295 mOsm/l), large volumes of LR can reduce serum osmolality and contribute to cerebral edema. For this reason, NS may be the preferred resuscitative fluid in head-injured patients. Hypertonic sodium chloride (HS) in concentrations ranging from 3% to 7.5% has been used for the treatment of hypovolemic shock. Because of its elevated osmolality, (2400 mOsm/l in 7.5%), HS produces an increase in intravascular volume that far exceeds the improved myocardial contractility, decreased systemic and pulmonary vascular resistance, mobilization of tissue edema into the blood compartment, and reduction in venous capacitance. These effects are transient, however, so HS has been mixed with colloids (dextran or hydroxyethyl starch) to prolong its efficacy, especially when used for small volume resuscitation. HS decreases intracranial pressure (ICP), primarily in areas of the brain with an intact blood-brain barrier. Cooper et al., in a double-blind, randomized controlled trial of hypotensive patients with severe traumatic brain injury, studied the effects of prehospital resuscitation with hypertonic saline versus Ringers lactate on neurological outcome. These investigators did not find a significant difference in 3- or 6-month extended Glasgow Outcome Scores between the two groups.

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 PREHOSPITAL TRAUMA CARE 3 Immunomodulatory effects of HS, either immonostimulatory or immunosuppressive depending on the concentration, have been described. HS affects nuclear activation, protein synthesis and proliferation, polymorphonuclear leukocyte function, and cytoskeleton polymerization. In animal model of hemorrhage, these effects have been associated with reduced organ dysfunction and improved survival. Despite its benefits, a meta-analysis evaluating the effect of HS compared to isotonic crystalloid on 30-day outcome in trauma patients failed to show a survival advantage. As such, the role of HS in prehospital fluid resuscitation has been defined. Colloid Nonbiologically active Colloids seemingly have many advantages as resuscitative fluids over crystalloids. Their ability to effectively expand plasma volume exceeds that of crystalloids. Endpoints of resuscitation are met using smaller volumes of colloid, which in turn reduce tissue edema. However, some investigators suggest that colloids potentiate tissue edema. The capillary-endothelial cell leak that develop after sever injury may allow the colloid to pass into the interstitium and exacerbate swelling. Albumin, a natural colloid, is synthesized in the liver and is responsible for 80% of the oncotic pressure of the plasma. The molecular weight of albumin is approximately 69 kD. Infusion of the 25% solution expands plasma volume four to five times the volume infused (see Table 2). Derived from pooled human plasma, its risk of transmitting infectious diseases is low because of stringent heating and sterilization. Aside from its volume replacing properties, albumin also possesses a transport Table 2: Effect on Plasma Volume Expansion of Various Solutions Volume Infused (ml) 1000 1000 250 500 100 500 Fluid Infused D5W Lactated Ringers 7.5% hypertonic saline 5% albumin 25% albumin 6% hetastarch Plasma Volume Expansion (ml) 100 250 1000 375 450 750 function drugs for and

endogenous substances and may have

beneficial effect on membrane permeability secondary to

free radical scavenging. These theoretical effects have not been proven clinically. Disadvantages of albumin include its cost, short supply, and potential disease transmission. Additionally, albumins use for the resuscitation of critically ill patients has demonstrated either a ACCESS WWW.MEDICALVILLAGE.BLOGSPOT.COM FOR MORE NOTES TO COME

 PREHOSPITAL TRAUMA CARE 3 trend toward or a significant increase in mortality. Therefore, the use of albumin can not be recommended as a resuscitative fluid for hypotensive trauma patients. Synthetic colloids include dextran, hydroxyethyl starch (HES), and mixtures of dextran and HES with hypertonic saline solutions. Dextran is a glucose polymer available as 6% dextran 70 (70 kD) and 10% dextran 40 (40 kD) solutions. Increase of plasma volume after infusion of 1000 ml of dextran 70 ranges from 600 to 800 ml. dextran reduces blood viscosity, reduces platelet adhesiveness, and enhances fibrinolysis, resulting in increased bleeding tendency. Severe, life-threatening anaphylactic reactions are also well described. The use of dextran as an exclusive fluid resuscitant is limited by these side effects. As mentioned previously, dextran has been added to hypertonic saline (HSD) to extend its intravascular presence. Its use as a resuscitative fluid was compared with isotonic crystalloid and analysed via a meta-analysis of several randomized controlled trials of hypotensive trauma patients. Although HSD was safe, demonstrated higher increases in blood pressure, and decreased early fluid and blood requirements, no statistically significant survival benefit was attributed to its use. Conversely, in a study by Wade et al., survival to discharge was significantly improved in patients resuscitated with 250 ml of HSD that sustained penetrating torso trauma requiring surgical intervention. This suggests a subset of trauma patients may benefit from HSD in the prehospital setting. HES solutions are modified natural polymers of amylopectin. The pharmacokinetic properties of each formulation are determined by its molecular weight, the pattern of hydroxyethylation, and the ratio of C2:c6 hydroxyethylation. These properties influence the plasma expansion, degradation, and side effect profile of HES. Side effects associated with HES include pruritis and increased bleeding due to reduction of factor VIII and von Willebrand factor. However, most recent studies using modern HES preparations demonstrated no impairment of hemostasis or increased bleeding propensity. Still, despite the apparent advantages of colloids, meta-analyses suggest a trend toward increased mortality when they are used for the resuscitation of trauma patients. Although the methodology of these studies can be questioned, until better designed clinical trials provide irrefutable evidence suggesting improved outcome with the use of colloids for fluid resuscitation, these agents cannot be recommended.

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 PREHOSPITAL TRAUMA CARE 3 Biologically active When considering an ideal resuscitative fluid in hemorrhagic shock, its properties would include volume expansion, oxygen-carrying capacity, universal compatibility, immediate availability, longterm storage capacity, and the absence of vasoactive properties and disease transmission. Although blood transfusion effectively improves volume deficits and provides oxygen delivery, its use in the prehospital setting is limited by expense, short shelf-life, short supply, risk of disease transmission, and need for cross-matching. Allogenic red blood cells (RBCs) may have adverse

immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Hemoglobin-based oxygen carriers (HBOC) are attractive in the prehospital setting, then, for several reasons. Because HBOC can be treated, their risk of disease transmission is low. They have a shelflife of up to 3 years and have oxygen-carrying, as well as volume-expansion properties. They are universally compatible, thus eliminating the need for cross-matching. Phase II clinical trials, as well as in vitro and vivo work, suggest that resuscitation with a HBOCin lieu of stored RBCsattenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Clinical trials with HBOC have shown mixed results. When diaspirin cross-linked hemoglobin (DCLHb) was studied against normal saline in a U.S. multicenter trial for the treatment of severe traumatic hemorrhagic shock, the 28-day mortality was 46% for DCLHb compared to 17% for NS. An increase in systemic and pulmonary vascular resistance leading to decreased cardiac output was felt to be responsible for the higher mortality rate. However, polymerized hemoglobin solutions have shown more promise. In a prospective, randomized trial comparing the therapeutic benefits of Poly-Heme with that of allogenic RBCs in the treatment of acute blood loss, the Poly-Heme group demonstrated similar total hemoglobin concentration after infusion as the RBC group with less RBC transfusion required through the first day of treatment and without serious or unexpected adverse consequences resulting from Poly-Heme. In time, it is possible that one or more HBOC may be routinely used in the resuscitation of hemorrhagic shock. Resuscitation Targets Delayed Studies have begun to scrutinize the potential detrimental effects of raising the blood pressure during uncontrolled hemorrhage. Whereas early work utilizing controlled hemorrhage models was used to support the use of fluid resuscitation of post-traumatic hemorrhage, these models of resuscitation do not mimic the actual life situation of uncontrolled bleeding and concurrent treatment. In the setting of uncontrolled hemorrhage, fluid administration may disrupt thrombus ACCESS WWW.MEDICALVILLAGE.BLOGSPOT.COM FOR MORE NOTES TO COME

 PREHOSPITAL TRAUMA CARE 3 formation, induce coagulopathy by diluting clotting factors, and lead to increased bleeding. In 1918, Cannon observed increased bleeding induced by rapid fluid infusion prior to hemorrhage control. More recently, in a study of penetrating torso trauma, hypotensive patients were randomized to immediate versus delayed fluid resuscitation with isotonic crystalloid. Prehospital fluid resuscitation group had the higher mortality and higher rates of postoperative complications. Although the results of this study have been argued, the study rekindled interest and stimulated thought concerning approaches of management for the treatment of uncontrolled hemorrhage. Hypotensive This strategy of resuscitation attempts to maintain adequate vital organ perfusion while minimizing further bleeding. A mean arterial pressure (MAP) of 60 mm Hg has been used as a resuscitation target. It is regarded as the lowest safe level because it is lowest MAP of active autoregulation of cerebral blood flow. No lower limit of hypotensive resuscitation, however, has been firmly established. Using blood pressure as a guideline stimulates prehospital scenarios in which this variable is one of the only hemodynamic parameters available. Dutton et al., randomized hypotensive blunt and penetrating trauma patients to a systolic blood pressure (SBP) of 70 mm Hg (hypotensive) or more than 100 mm Hg (normotensive). Crystalloid or blood products were administered to maintain the intended SBP for each group. There was no difference in survival between the two cohorts. This was partly attributed to the difficulty in maintaining the targeted blood pressure. The averages SBP for the hypotensive and normotensive groups were 100 mm Hg and 114 mm Hg, respectively. This response suggests spontaneous reduction of bleeding due to inherent hemostatic mechanisms and may validate use of this resuscitation strategy in certain scenarios of uncontrolled hemorrhage. Normotensive The traditional approach to the resuscitation of trauma patients in hemorrhagic shock has been to normalize blood pressure by administering large volumes of crystalloid followed by transfusion of blood products. This method of resuscitation developed from animal models of controlled hemorrhage. Restoration of vital organ perfusion improved survival, whereas untreated animals developed organ dysfunction and succumbed. In situations of uncontrolled hemorrhage, animal studies revealed decreased splanchnic perfusion and greater blood loss. In situations in which bleeding has spontaneously resolved, the standard approach ton resuscitation is reasonable. It is difficult to predict, however, whether bleeding has spontaneously ceased to predict or may be exacerbated by aggressive resuscitation. ACCESS WWW.MEDICALVILLAGE.BLOGSPOT.COM FOR MORE NOTES TO COME

 PREHOSPITAL TRAUMA CARE 3 MORBIDITY AND COMPLICATIONS Prehospital fluid resuscitation is not without its own complications. Exacerbated bleeding, dilution of clotting factors, and dislodgement of thrombi, among other problems, have already been mentioned, and may act to decrease survival of hemorrhagic shock. Additionally, a balance needs to be achieved between under-resuscitation and over-resuscitation, as both of these concerns contribute to increased morbidity and mortality. Whereas the goal of prehospital fluid resuscitation is to preserve blood flow to vital organs (brain, heart) without incurring significant, irreversible damage to other organs systems (renal, splanchnic), excess crystalloids resuscitation may contribute to the development of the abdominal compartment syndrome. Hypothermia develops commonly after traumatic shock and is exacerbated with the administration of cold fluids. Adverse consequences of hypothermia include impaired coagulation function, reduction of oxygen delivery, and increased rate of infection. The importance of administering warm fluids to avoid the untoward effects of hypothermia cannot be overstated. SUMMARY The clinical study of massive hemorrhage and resuscitation is complicated by small numbers, urgency of care, varying goals and end-points, and patient heterogeneity with respect of age, comorbidity, mechanism of injury, prehospital time and therapy. And complications of resuscitation, some definite conclusions can be drawn from the vast literature. The rapid transport of the trauma patient to a center where definitive care can be rendered is paramount. Second, the importance of hemorrhage control prior to aggressive fluid resuscitation cannot be overstated. Despite the number of options of resuscitation strategies and fluids, no single choice is perfectly applicable in every trauma scenario. Until human studies can be performed utilizing particular strategies for particular injuries with proven improved outcomes, ATLS guidelines should continue to be practiced.

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