SUBJECT REVIEW
Past and Current Trends in Intravenous Therapy for Hemorrhagic Shock Captain Stewart A. Stancil, MD
Abstract One issue that has generated controversy in the area of trauma care is the administration of isotonic intravenous crystalloid volume for patients suffering from traumatic hemorrhagic shock. This practice, once accepted as the standard for good medical care, has become regarded over the past decade as substandard. This article looks at the scientific basis for fluid resuscitation and evidence for declining use of this therapy. Finally, there is recent evidence that some level of intravenous fluid therapy is, in fact, beneficial.
Over the past century, there has been some controversy regarding the use of intravenous (IV) fluids in the early resuscitation of trauma patients. Until the past decade, it was common teaching and practice to bolus infuse trauma victims with large volumes of high-volume crystalloids such as normal saline or lactated Ringer’s solution (LR). The practice was endorsed in well-accepted texts and courses such as Advanced Trauma Life Support (ATLS), in which volume resuscitation of 1-2 L is initially recommended in a 3:1 fashion. This means that for every liter of blood lost, 3 L crystalloid was recommended.1 In recent years, the practice of prehospital IV crystalloid fluid therapy for hemorrhagic shock patients has been discredited. However, it should be understood that the protocol for this treatment for hemorrhagic shock patients is not without scientific and experiential justification. Indeed, there was a robust body of research conducted in the 20th century supporting the doctrine of IV resuscitation as a therapy for hemorrhagic shock. Doctors Wiggers and Ingraham published a study in 1946 that examined factors contributing to “irreversible shock.” This was defined as over 40% blood loss
Darnall Army Medical Center, Fort Hood, TX, USA Address for correspondence: Captain Stewart A. Stancil, MD, Darnall Army Medical Center Emergency Department, Fort Hood, TX, [email protected] 1067-9991X/$36.00 Copyright 2014 by Air Medical Journal Associates http://dx.doi.org/10.1016/j.amj.2014.04.004 172
without subsequent recovery, a definition that is still used in current literature. They identified blood loss under 40% as a “hemorrhagic-hypotensive state” because the dogs used in the study were able to recover without intervention. In contrast, “hemorrhagic shock,” which was further divided into “impending shock” or “irreversible shock,” was defined as blood loss over 40%, and in this case, 27 of 39 dogs died despite blood infusions matching the amount lost. For the experiment, a mean arterial pressure (MAP) of less than 40 mm Hg was induced in all the animals. In all cases, there was a temporary rise in pressure after transfusion. It was noted in the dogs that recovered that there was a specific point in time during the blood loss when the dog began a process of “plasma dilution,” which was measured by blood specific gravity. It was postulated that animals that can maintain the hemodilution for the entire period of hypotension can remain in the “impending shock” state and avoid the “irreversible shock” state. The dogs that died either did not begin this maintenance process or the process was arrested. Wiggers and Ingraham found that the dogs that died usually had a bloody diarrhea, and this observation almost universally identified the survivors from nonsurvivors. It was noted in the study that in dogs that were bled and replenished with whole blood in the exact amount that was lost, the dogs that died from hemorrhage had recurrent hemoconcentration even after blood was replenished, whereas the surviving animals did not develop hemoconcentration. They called this recurrent hemoconcentration “irreversibility” and found that either reperfusion with saline or surgical removal of the intestinal tract protected against this. The time of “irreversible shock” was found to invariably occur after a 60-minute period of hypotension below 40 mm Hg MAP and was characterized as a state of hemoconcentration and persistent blood pressure decline. Before this 60-minute time frame, the patient persisted in “impending shock”; the patient should recover with whole blood resuscitation. This may have been the original research basis for the concept of “the golden hour” of trauma.2 What was the cause of the irreversible shock that was characterized by hemoconcentration? In the 2 decades after the research of Wiggers and Ingraham, subsequent studies attempted at answering this question. In 1947, Gibson et al3 showed that the presence of “red cell trapping” in the small vessels during hemorrhagic shock prevented adequate flow rates from allowing recovery even after whole blood was administered. Air Medical Journal 33:4
In 1955, Dr Fox attributed the hemoconcentration phenomenon to the interstitial compartment when he said, “If the vascular compartment were an inflexible system of rigid pipes, and if three liters of blood were lost in such a system containing seven liters, three liters of blood would presumably refill the system and achieve complete restoration of vital functions. The vascular compartment, however, is quite different: it is a flexible system of vessels which constrict and dilate: the walls of these vessels are semipermeable and are suspended in the interstitial fluid which surrounds the tissue cells.”4 In 1956, it was discovered by Dr Lellehei that 2 things could prevent irreversible shock in dogs: 1) removal of the intestines before hemorrhage and 2) reperfusion of the superior mesenteric artery. These findings confirmed and advanced the work of Wiggers and Ingraham that irreversible shock was accompanied by fluid loss into the bowel and bowel wall and was associated with liquid, bloody stools.5 Drs Tom Shires and James Carrico pioneered work on fluid resuscitation using both the animal and human model. In the 1960s, they conducted extensive research delineating the physiology and treatment for the hemorrhagic shock state. Of note, Dr Shires was chief of surgery and Dr Carrico was a surgical resident working in the emergency department (ED) at Parkland Memorial Hospital in Dallas, TX, on November 22, 1963. Dr Carrico initiated care and was involved in the emergency room treatment of President John F. Kennedy, Texas Governor John Connally, and gunman Lee Harvey Oswald. Dr Shires is credited with initiating and directing one of the first paramedic systems in the United States in Dallas, TX. They were coinvestigators in the landmark 1964 article titled “The Role of the Extracellular Fluid in Shock” along with Dr Dale Coln. Their article focused on the impact of trauma on extracellular fluid; they also summarized the work done over the past 2 decades leading to their current fund of knowledge. Drs Shires, Carrico, and Coln used radioisotope-tagged sodium sulfate as a marker for extracellular fluid measurement, tritium-tagged albumin as a plasma volume marker, and chromium as a marker for red blood cell mass. Using these surrogates, they were able to determine the volumes of the intravascular and nonvascular extracellular compartments. They then determined the amount of fluid lost from each compartment during an acute hemorrhage. The study was started on dogs and then was completed with 18 live human patients undergoing hemorrhagic shock. They found that the extravascular extracellular fluid became disproportionately reduced during hemorrhagic shock by a factor of about 4 over the amount of intravascular blood lost. After the bleeding was controlled, replacement of the extracellular fluid with LR at 5% body weight (roughly 3.5 L) resulted in a marked decrease in mortality. The return of the amount of shed blood with whole blood resuscitation resulted in only half the correction of extracellular fluid volume. Likewise, the use of norepinephrine to increase blood pressure did not increase extracellular fluid volume. July-August 2014
The work of Shires, Carrico, and Coln confirmed previous study findings that had reported recovery from severe shock by the administration of isotonic fluid.6,7 Thus, they concluded that hemorrhagic shock should first be treated by 1-2 L LR before blood administration to stabilize the extracellular fluid and then replace the vascular volume with whole blood. Furthermore, Carrico and Shires proposed a protocol based on their evidence obtained and previous studies that hemorrhagic shock should first be treated with 1-2 L LR to first alleviate the reduction of extracellular fluid. The patient should be type and crossed for a blood transfusion during this time. Some will be responders to the isotonic therapy. Those who only temporarily respond can be given matched whole blood.8 Building on the research by Shires, Carrico, Coln, and others, DePalma, Holden, and Robinson conducted a study assessing not only survival but also the microscopic cellular changes that occur during both hemorrhagic shock as well as resuscitation. They compared normal saline (NS), transfused whole blood, LR, and 5% dextrose. The whole blood had the highest survival rate in the murine model but only by 7% (90% survival for whole blood replacement compared with 80% survival for LR and 83% survival for NS. LR and NS were infused at a volume of 3 times the amount of blood lost from hemorrhage). The hepatocytes of the surviving mice were then examined under a microscope. The researchers found that LR provided the cells with an architectural appearance most similar to the prehemorrhage state. This, they hypothesized, may mean that some improvement in cellular function is obtained from the use of crystalloid and that further studies would need to quantify that.9 Thus, by the end of the 1960s, the scientific precedent had been established documenting the benefit of crystalloid therapy for the trauma patient and advocating its practice as standard medical care. However, in 1994, another landmark study once again heralded a swing of the pendulum away from this treatment standard. Bickell et al10 studied 589 patients with penetrating torso injuries. The 589 patients were blindly placed in either an immediate crystalloid resuscitation group (averaging 2,478 mL crystalloid given by emergency medical services and the emergency department) or in a delayed resuscitation group (averaging only 375 mL crystalloid given). The overall rate of survival was significantly higher in the delayed resuscitation group (70% vs. 62%, P ⫽ .04). This explanation of this finding was identified by the coagulation factor dilutional effect observed by the crystalloid as well as the disruption of the formed clot by increased hydrostatic pressure. Despite the study by Bickell et al,10 the model for initial crystalloid volume resuscitation continued well into the 21st century. Paramedic training programs continued to emphasize that blood volume lost must be repleted by a crystalloid volume of 3 times that amount. The surgery text, Sabiston Essentials of Surgery (2nd ed) gave the following insight into the contemporary ideal resuscitation strategy: 173
Volume loss must be corrected immediately once the diagnosis has been made. Intravenous fluid should be administered simultaneously as preparations are made to control the bleeding. Intravenous fluids are best given through large-bore catheters (16 gauge or larger). . .To replicate blood loss, crystalloid solutions should be given in a ratio of 3:1 or 4:1 with packed cells because they quickly equilibrate within the interstitial an intravascular spaces. . .Two to 3 liters of fluid given over 5 to 15 minutes resuscitates patients with arrested hemorrhage, and the need for administration of more fluid indicates continuing bleeding. . .If the patient is to be taken to the operating room soon, administration of blood should be withheld if possible until just before the induction of anesthesia. A young person can tolerate hematocrits as low as 15, as long as the blood volume is kept normal by the administration of fluid.11 As a result of the study of Bickell et al,10 a trend toward disavowment of the high-volume isotonic fluid infusion dogma eventually began. The 2008 edition of ATLS did include the 3-for-1 rule; however, it also made note of the importance of an approach of maintaining organ perfusion. Organ perfusion quality was measured by mental status, peripheral perfusion, and urine output balanced against the risk of rebleeding from voluminous IV fluid therapy.1 Despite the findings by Bickell et al,10 early prehospital and ED intravenous fluid volume administration remained the standard of care for many trauma systems until around 2008. In that year, 2008, the United States Office of the Surgeon General published the text War Surgery in Afghanistan and Iraq: A Series of Cases, 2003-2007. In this book, the established concepts of damage control resuscitation were further propagated and advanced. Some of the principles of damage control resuscitation are permissive hypotension below 90 mm Hg systolic, the use of thawed plasma as the primary resuscitation fluid in a 1:1 ratio with packed red blood cells and platelets, and the use of crystalloid mainly limited to merely keeping lines patent between administrations of blood product. The cornerstone of therapy is early diagnosis and treatment of the lethal triad (hypothermia, acidosis, and coagulopathy). The denial of crystalloid volume was shown in actual combat injury patients to help prevent the descent toward the lethal triad.12 In 2011, Haut et al13 published a retrospective chart review of 776,734 patients registered in the National Trauma Data Bank. They found that those patients in whom IV access was obtained and to whom IV fluids were administered had an overall higher death rate (4.8% vs. 4.5%, P ⬍ .001). To refute the criticism that patients needing a prehospital IV tend to be more hemodynamically unstable, they stratified the study to match similar patients. The interesting finding was that in severely injured patients (hypotensive patients, patients with severe mechanism, and patients with head injury), the trend toward mortality with those receiving prehospital IV therapy became even larger.13 Based on these studies and others, the trend toward reduction of large-volume prehospital and ED IV fluid therapy 174
usage continued so that by 2011 prehospital trauma life support teaching added to traumatic shock resuscitation management the guiding principle that fluid resuscitation should preferentially be treated with blood products and included the caveat that blood pressure normalization should not be a guideline of management. The Tactical Combat Casualty Course was originally developed in 1993 for the Naval Special Warfare Command and then adopted by the US Special Operations Command in recognition of the unique treatment challenges inherent with battlefield trauma with a focus on training warriors how to deliver optimal prehospital care. Care guidelines recommend no IV fluids for nonshock trauma, and in cases of hemorrhagic shock, the recommendation is to give two 500-mL boluses of Hextend (Hospira, Inc., Lake Forest, IL, a type of synthetic 6% hetastarch solution thought to have no adverse effect on coagulopathy) with a maximum administration volume of 1 L.14,15 The concept of no prehospital IV fluids for trauma patients seemed irrefutable by this time, but a new shift in the understanding of optimal resuscitation has just last year been identified. In a 2013 study assessing the efficacy of prehospital IV fluids, data were prospectively collected from 10 level 1 trauma centers and EMS agencies in the United States. Of 1,245 trauma patients, 1,009 received a median prehospital volume of 700 mL, whereas the comparison group received none. The IV fluid group was associated with increased survival. It is notable that this 700 mL is only about 28% of the volume amount given in the original 1994 Bickers study that found worse outcome from prehospital IV therapy. Because the patients receiving IV fluids had a lower blood pressure, the authors of the study concluded that IV fluids were associated with improved outcomes as long as a low MAP was maintained.16 This is a new finding because previous studies had linked poor outcomes with the IV fluid itself. The cumulative body of research tends to lead toward the conclusion that in traumatic shock the ideal resuscitation is one that maintains permissive hypotension while at the same time adding the judicious use of IV fluids to maintain organ perfusion prior to administration of blood products and damage control surgery. It will be interesting as research further delineates optimal protocol parameters.
References 1. American College of Surgeons Committee on Trauma. ATLS. 8th ed. Chicago, IL: American College of Surgeons; 2008:63-64. 2. Wiggers HC, Ingraham RC. Hemorrhagic shock: definition and criteria for its diagnosis. J Clin Invest. 1946;25:30-36. 3. Gibson JG, Seligman AM, Peacock WC, Fine J, Aub JC, Evans RD. The circulating red cell and plasma volume and the distribution of blood in large and minute vessels in experimental shock in dogs, measured by radioactive isotopes of iron and iodine. J Clin Invest. 1947;26:126. 4. Fox CL, Lasker SE. Fluid therapy in surgical emergencies. Surg Clin North Am. 1955;35:335. 5. Lillehei RC. The prevention of irreversible hemorrhagic shock in dogs by controlled cross perfusion of the superior mesenteric artery. Surg Forum. 1956;7:6. 6. Reynolds M. Cardiovascular effects of large volumes of isotonic saline infused intravenously into dogs following severe hemorrhage. Am J Physiol. 1949;158:418-428.
Air Medical Journal 33:4
7. Rosenthal SM, Tabor H. Electrolyte changes and chemotherapy in experimental burn and traumatic shock and hemorrhage. Arch Surg. 1945;51:244-252. 8. Shires GT, Carrico CJ, Coln D. The role of the extracellular fluid in shock. Int Anesthesiol Clin. 1964;2:435-454. 9. DePalma RG, Holden WD, Robinson AV. Fluid therapy in experimental hemorrhagic shock: ultrastructural effects in liver and muscle. Ann Surg. 1972;175:539-551. 10. Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994;331:11051109. 11. Sabiston DC, Lyerly HK. Sabiston Essentials of Surgery. 2nd ed. WB Saunders Company; 1994:26. 12. Nessen SC, Lounsbury DE, Hetz SP. War Surgery in Afghanistan and Iraq: A Series of Cases 2003-2007. Washington, DC: Office of the Surgeon General; 2011:33-50. 13. Haut ER, Kalish BT, Cotton BA, et al. Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis. Ann Surg. 2011;253:371-377. 14. Prehospital Trauma Life Support Committee of the National Association of Medical Technicians in Cooperation with The Committee on Trauma of the American College of Surgeons. PHTLS. 7th ed. Burlingon, Massachusetts: Jones and Bartlett; 2011:188. 15. Lenhart M, Savitsky E, Eastridge B. Combat Casualty Care: Lessons Learned from OEF and OIF. Washington, DC: Office of the Surgeon General Department of the Army; 2012:96-97. 16. Hampton DA, Fabricant LJ, Differding J, et al. Prehospital intravenous fluid is associated with increased survival in trauma patients. J Trauma Acute Care Surg. 2013;75 (suppl 1):S9-15.
July-August 2014
175
Past and Current Trends in Intravenous Therapy for Hemorrhagic Shock Captain Stewart A. Stancil, MD
Abstract One issue that has generated controversy in the area of trauma care is the administration of isotonic intravenous crystalloid volume for patients suffering from traumatic hemorrhagic shock. This practice, once accepted as the standard for good medical care, has become regarded over the past decade as substandard. This article looks at the scientific basis for fluid resuscitation and evidence for declining use of this therapy. Finally, there is recent evidence that some level of intravenous fluid therapy is, in fact, beneficial.
Over the past century, there has been some controversy regarding the use of intravenous (IV) fluids in the early resuscitation of trauma patients. Until the past decade, it was common teaching and practice to bolus infuse trauma victims with large volumes of high-volume crystalloids such as normal saline or lactated Ringer’s solution (LR). The practice was endorsed in well-accepted texts and courses such as Advanced Trauma Life Support (ATLS), in which volume resuscitation of 1-2 L is initially recommended in a 3:1 fashion. This means that for every liter of blood lost, 3 L crystalloid was recommended.1 In recent years, the practice of prehospital IV crystalloid fluid therapy for hemorrhagic shock patients has been discredited. However, it should be understood that the protocol for this treatment for hemorrhagic shock patients is not without scientific and experiential justification. Indeed, there was a robust body of research conducted in the 20th century supporting the doctrine of IV resuscitation as a therapy for hemorrhagic shock. Doctors Wiggers and Ingraham published a study in 1946 that examined factors contributing to “irreversible shock.” This was defined as over 40% blood loss
Darnall Army Medical Center, Fort Hood, TX, USA Address for correspondence: Captain Stewart A. Stancil, MD, Darnall Army Medical Center Emergency Department, Fort Hood, TX, [email protected] 1067-9991X/$36.00 Copyright 2014 by Air Medical Journal Associates http://dx.doi.org/10.1016/j.amj.2014.04.004 172
without subsequent recovery, a definition that is still used in current literature. They identified blood loss under 40% as a “hemorrhagic-hypotensive state” because the dogs used in the study were able to recover without intervention. In contrast, “hemorrhagic shock,” which was further divided into “impending shock” or “irreversible shock,” was defined as blood loss over 40%, and in this case, 27 of 39 dogs died despite blood infusions matching the amount lost. For the experiment, a mean arterial pressure (MAP) of less than 40 mm Hg was induced in all the animals. In all cases, there was a temporary rise in pressure after transfusion. It was noted in the dogs that recovered that there was a specific point in time during the blood loss when the dog began a process of “plasma dilution,” which was measured by blood specific gravity. It was postulated that animals that can maintain the hemodilution for the entire period of hypotension can remain in the “impending shock” state and avoid the “irreversible shock” state. The dogs that died either did not begin this maintenance process or the process was arrested. Wiggers and Ingraham found that the dogs that died usually had a bloody diarrhea, and this observation almost universally identified the survivors from nonsurvivors. It was noted in the study that in dogs that were bled and replenished with whole blood in the exact amount that was lost, the dogs that died from hemorrhage had recurrent hemoconcentration even after blood was replenished, whereas the surviving animals did not develop hemoconcentration. They called this recurrent hemoconcentration “irreversibility” and found that either reperfusion with saline or surgical removal of the intestinal tract protected against this. The time of “irreversible shock” was found to invariably occur after a 60-minute period of hypotension below 40 mm Hg MAP and was characterized as a state of hemoconcentration and persistent blood pressure decline. Before this 60-minute time frame, the patient persisted in “impending shock”; the patient should recover with whole blood resuscitation. This may have been the original research basis for the concept of “the golden hour” of trauma.2 What was the cause of the irreversible shock that was characterized by hemoconcentration? In the 2 decades after the research of Wiggers and Ingraham, subsequent studies attempted at answering this question. In 1947, Gibson et al3 showed that the presence of “red cell trapping” in the small vessels during hemorrhagic shock prevented adequate flow rates from allowing recovery even after whole blood was administered. Air Medical Journal 33:4
In 1955, Dr Fox attributed the hemoconcentration phenomenon to the interstitial compartment when he said, “If the vascular compartment were an inflexible system of rigid pipes, and if three liters of blood were lost in such a system containing seven liters, three liters of blood would presumably refill the system and achieve complete restoration of vital functions. The vascular compartment, however, is quite different: it is a flexible system of vessels which constrict and dilate: the walls of these vessels are semipermeable and are suspended in the interstitial fluid which surrounds the tissue cells.”4 In 1956, it was discovered by Dr Lellehei that 2 things could prevent irreversible shock in dogs: 1) removal of the intestines before hemorrhage and 2) reperfusion of the superior mesenteric artery. These findings confirmed and advanced the work of Wiggers and Ingraham that irreversible shock was accompanied by fluid loss into the bowel and bowel wall and was associated with liquid, bloody stools.5 Drs Tom Shires and James Carrico pioneered work on fluid resuscitation using both the animal and human model. In the 1960s, they conducted extensive research delineating the physiology and treatment for the hemorrhagic shock state. Of note, Dr Shires was chief of surgery and Dr Carrico was a surgical resident working in the emergency department (ED) at Parkland Memorial Hospital in Dallas, TX, on November 22, 1963. Dr Carrico initiated care and was involved in the emergency room treatment of President John F. Kennedy, Texas Governor John Connally, and gunman Lee Harvey Oswald. Dr Shires is credited with initiating and directing one of the first paramedic systems in the United States in Dallas, TX. They were coinvestigators in the landmark 1964 article titled “The Role of the Extracellular Fluid in Shock” along with Dr Dale Coln. Their article focused on the impact of trauma on extracellular fluid; they also summarized the work done over the past 2 decades leading to their current fund of knowledge. Drs Shires, Carrico, and Coln used radioisotope-tagged sodium sulfate as a marker for extracellular fluid measurement, tritium-tagged albumin as a plasma volume marker, and chromium as a marker for red blood cell mass. Using these surrogates, they were able to determine the volumes of the intravascular and nonvascular extracellular compartments. They then determined the amount of fluid lost from each compartment during an acute hemorrhage. The study was started on dogs and then was completed with 18 live human patients undergoing hemorrhagic shock. They found that the extravascular extracellular fluid became disproportionately reduced during hemorrhagic shock by a factor of about 4 over the amount of intravascular blood lost. After the bleeding was controlled, replacement of the extracellular fluid with LR at 5% body weight (roughly 3.5 L) resulted in a marked decrease in mortality. The return of the amount of shed blood with whole blood resuscitation resulted in only half the correction of extracellular fluid volume. Likewise, the use of norepinephrine to increase blood pressure did not increase extracellular fluid volume. July-August 2014
The work of Shires, Carrico, and Coln confirmed previous study findings that had reported recovery from severe shock by the administration of isotonic fluid.6,7 Thus, they concluded that hemorrhagic shock should first be treated by 1-2 L LR before blood administration to stabilize the extracellular fluid and then replace the vascular volume with whole blood. Furthermore, Carrico and Shires proposed a protocol based on their evidence obtained and previous studies that hemorrhagic shock should first be treated with 1-2 L LR to first alleviate the reduction of extracellular fluid. The patient should be type and crossed for a blood transfusion during this time. Some will be responders to the isotonic therapy. Those who only temporarily respond can be given matched whole blood.8 Building on the research by Shires, Carrico, Coln, and others, DePalma, Holden, and Robinson conducted a study assessing not only survival but also the microscopic cellular changes that occur during both hemorrhagic shock as well as resuscitation. They compared normal saline (NS), transfused whole blood, LR, and 5% dextrose. The whole blood had the highest survival rate in the murine model but only by 7% (90% survival for whole blood replacement compared with 80% survival for LR and 83% survival for NS. LR and NS were infused at a volume of 3 times the amount of blood lost from hemorrhage). The hepatocytes of the surviving mice were then examined under a microscope. The researchers found that LR provided the cells with an architectural appearance most similar to the prehemorrhage state. This, they hypothesized, may mean that some improvement in cellular function is obtained from the use of crystalloid and that further studies would need to quantify that.9 Thus, by the end of the 1960s, the scientific precedent had been established documenting the benefit of crystalloid therapy for the trauma patient and advocating its practice as standard medical care. However, in 1994, another landmark study once again heralded a swing of the pendulum away from this treatment standard. Bickell et al10 studied 589 patients with penetrating torso injuries. The 589 patients were blindly placed in either an immediate crystalloid resuscitation group (averaging 2,478 mL crystalloid given by emergency medical services and the emergency department) or in a delayed resuscitation group (averaging only 375 mL crystalloid given). The overall rate of survival was significantly higher in the delayed resuscitation group (70% vs. 62%, P ⫽ .04). This explanation of this finding was identified by the coagulation factor dilutional effect observed by the crystalloid as well as the disruption of the formed clot by increased hydrostatic pressure. Despite the study by Bickell et al,10 the model for initial crystalloid volume resuscitation continued well into the 21st century. Paramedic training programs continued to emphasize that blood volume lost must be repleted by a crystalloid volume of 3 times that amount. The surgery text, Sabiston Essentials of Surgery (2nd ed) gave the following insight into the contemporary ideal resuscitation strategy: 173
Volume loss must be corrected immediately once the diagnosis has been made. Intravenous fluid should be administered simultaneously as preparations are made to control the bleeding. Intravenous fluids are best given through large-bore catheters (16 gauge or larger). . .To replicate blood loss, crystalloid solutions should be given in a ratio of 3:1 or 4:1 with packed cells because they quickly equilibrate within the interstitial an intravascular spaces. . .Two to 3 liters of fluid given over 5 to 15 minutes resuscitates patients with arrested hemorrhage, and the need for administration of more fluid indicates continuing bleeding. . .If the patient is to be taken to the operating room soon, administration of blood should be withheld if possible until just before the induction of anesthesia. A young person can tolerate hematocrits as low as 15, as long as the blood volume is kept normal by the administration of fluid.11 As a result of the study of Bickell et al,10 a trend toward disavowment of the high-volume isotonic fluid infusion dogma eventually began. The 2008 edition of ATLS did include the 3-for-1 rule; however, it also made note of the importance of an approach of maintaining organ perfusion. Organ perfusion quality was measured by mental status, peripheral perfusion, and urine output balanced against the risk of rebleeding from voluminous IV fluid therapy.1 Despite the findings by Bickell et al,10 early prehospital and ED intravenous fluid volume administration remained the standard of care for many trauma systems until around 2008. In that year, 2008, the United States Office of the Surgeon General published the text War Surgery in Afghanistan and Iraq: A Series of Cases, 2003-2007. In this book, the established concepts of damage control resuscitation were further propagated and advanced. Some of the principles of damage control resuscitation are permissive hypotension below 90 mm Hg systolic, the use of thawed plasma as the primary resuscitation fluid in a 1:1 ratio with packed red blood cells and platelets, and the use of crystalloid mainly limited to merely keeping lines patent between administrations of blood product. The cornerstone of therapy is early diagnosis and treatment of the lethal triad (hypothermia, acidosis, and coagulopathy). The denial of crystalloid volume was shown in actual combat injury patients to help prevent the descent toward the lethal triad.12 In 2011, Haut et al13 published a retrospective chart review of 776,734 patients registered in the National Trauma Data Bank. They found that those patients in whom IV access was obtained and to whom IV fluids were administered had an overall higher death rate (4.8% vs. 4.5%, P ⬍ .001). To refute the criticism that patients needing a prehospital IV tend to be more hemodynamically unstable, they stratified the study to match similar patients. The interesting finding was that in severely injured patients (hypotensive patients, patients with severe mechanism, and patients with head injury), the trend toward mortality with those receiving prehospital IV therapy became even larger.13 Based on these studies and others, the trend toward reduction of large-volume prehospital and ED IV fluid therapy 174
usage continued so that by 2011 prehospital trauma life support teaching added to traumatic shock resuscitation management the guiding principle that fluid resuscitation should preferentially be treated with blood products and included the caveat that blood pressure normalization should not be a guideline of management. The Tactical Combat Casualty Course was originally developed in 1993 for the Naval Special Warfare Command and then adopted by the US Special Operations Command in recognition of the unique treatment challenges inherent with battlefield trauma with a focus on training warriors how to deliver optimal prehospital care. Care guidelines recommend no IV fluids for nonshock trauma, and in cases of hemorrhagic shock, the recommendation is to give two 500-mL boluses of Hextend (Hospira, Inc., Lake Forest, IL, a type of synthetic 6% hetastarch solution thought to have no adverse effect on coagulopathy) with a maximum administration volume of 1 L.14,15 The concept of no prehospital IV fluids for trauma patients seemed irrefutable by this time, but a new shift in the understanding of optimal resuscitation has just last year been identified. In a 2013 study assessing the efficacy of prehospital IV fluids, data were prospectively collected from 10 level 1 trauma centers and EMS agencies in the United States. Of 1,245 trauma patients, 1,009 received a median prehospital volume of 700 mL, whereas the comparison group received none. The IV fluid group was associated with increased survival. It is notable that this 700 mL is only about 28% of the volume amount given in the original 1994 Bickers study that found worse outcome from prehospital IV therapy. Because the patients receiving IV fluids had a lower blood pressure, the authors of the study concluded that IV fluids were associated with improved outcomes as long as a low MAP was maintained.16 This is a new finding because previous studies had linked poor outcomes with the IV fluid itself. The cumulative body of research tends to lead toward the conclusion that in traumatic shock the ideal resuscitation is one that maintains permissive hypotension while at the same time adding the judicious use of IV fluids to maintain organ perfusion prior to administration of blood products and damage control surgery. It will be interesting as research further delineates optimal protocol parameters.
References 1. American College of Surgeons Committee on Trauma. ATLS. 8th ed. Chicago, IL: American College of Surgeons; 2008:63-64. 2. Wiggers HC, Ingraham RC. Hemorrhagic shock: definition and criteria for its diagnosis. J Clin Invest. 1946;25:30-36. 3. Gibson JG, Seligman AM, Peacock WC, Fine J, Aub JC, Evans RD. The circulating red cell and plasma volume and the distribution of blood in large and minute vessels in experimental shock in dogs, measured by radioactive isotopes of iron and iodine. J Clin Invest. 1947;26:126. 4. Fox CL, Lasker SE. Fluid therapy in surgical emergencies. Surg Clin North Am. 1955;35:335. 5. Lillehei RC. The prevention of irreversible hemorrhagic shock in dogs by controlled cross perfusion of the superior mesenteric artery. Surg Forum. 1956;7:6. 6. Reynolds M. Cardiovascular effects of large volumes of isotonic saline infused intravenously into dogs following severe hemorrhage. Am J Physiol. 1949;158:418-428.
Air Medical Journal 33:4
7. Rosenthal SM, Tabor H. Electrolyte changes and chemotherapy in experimental burn and traumatic shock and hemorrhage. Arch Surg. 1945;51:244-252. 8. Shires GT, Carrico CJ, Coln D. The role of the extracellular fluid in shock. Int Anesthesiol Clin. 1964;2:435-454. 9. DePalma RG, Holden WD, Robinson AV. Fluid therapy in experimental hemorrhagic shock: ultrastructural effects in liver and muscle. Ann Surg. 1972;175:539-551. 10. Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994;331:11051109. 11. Sabiston DC, Lyerly HK. Sabiston Essentials of Surgery. 2nd ed. WB Saunders Company; 1994:26. 12. Nessen SC, Lounsbury DE, Hetz SP. War Surgery in Afghanistan and Iraq: A Series of Cases 2003-2007. Washington, DC: Office of the Surgeon General; 2011:33-50. 13. Haut ER, Kalish BT, Cotton BA, et al. Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis. Ann Surg. 2011;253:371-377. 14. Prehospital Trauma Life Support Committee of the National Association of Medical Technicians in Cooperation with The Committee on Trauma of the American College of Surgeons. PHTLS. 7th ed. Burlingon, Massachusetts: Jones and Bartlett; 2011:188. 15. Lenhart M, Savitsky E, Eastridge B. Combat Casualty Care: Lessons Learned from OEF and OIF. Washington, DC: Office of the Surgeon General Department of the Army; 2012:96-97. 16. Hampton DA, Fabricant LJ, Differding J, et al. Prehospital intravenous fluid is associated with increased survival in trauma patients. J Trauma Acute Care Surg. 2013;75 (suppl 1):S9-15.
July-August 2014
175
