Symposium on Shock
Hypovolemic Shock A. Wendell Nelson, D.V.M., Ph.D*
By definition, hypovolemic shock is a pathologic decrease in capillary perfusion resulting from a decrease in circulating blood volume. Hypovolemic shock generally results from blunt or sharp trauma, burns, and/or sepis. In addition, terminal phases may be complicated by myocardial failure.
CAUSES OF HYPOVOLEMIA Shock attributed to hypovolemia may be initiated by several clinical diseases. The least complicated form of hypovolemia is that resulting from pure hemorrhage which is usually the result of low velocity tears of large vessels. Loss of blood from the body usually results from lacerations or tears in the vessels supplying the head and limbs. This is usually the result of partial severence of large arteries which enables the laceration to stay open. Thus, a large volume of blood can be lost before a significant drop in blood pressure allows a clot to be established at the opening. This is in contrast to a completely severed artery that constricts and retracts into the surrounding tissue. The narrowed orifice and presence of surrounding tissue allow a clot to establish itself more rapidly. External hemorrhage can be fatal when the loss reaches 35 per cent of the initial circulating blood volume and the animal does not obtain treatment. The mortality rate for this condition reaches approximately 100 per cent after 50 per cent of the initial circulating blood volume is lost. Loss of blood into th,e thoracic and abdominal areas is usually due to penetration by sharp objects (i.e., knives, ice picks, low velocity bullets). Hemorrhage into the thoracic cavity is probably the most lethal Professor of Clinical Sciences. Surgical Laboratorv, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado
~.\ssociate
r,terinary Clinics ofNorth America- VoL 6, No.2, May 1976
187
188
A.
WENDELL NELSON
because of its compounding effects on decreasing heart and lung function as a result of organ volume displacement by the free blood. The large pressure difference between the intravascular blood and the thoracic cavity promotes hemorrhage. Soft tissue ischemia and trauma initiated by prolonged tourniquet application, blunt force, or high velocity, missile-mediated injury are associated with edema, or hemorrhage, or both. The damaged tissue will accumulate intracellular fluid resulting from impaired cellular function and extracellular edema and hemorrhage resulting from increased capillary permeability and lymphatic stasis. Shifts of fluid and other blood elements into large areas of damaged tissue may result in a significant loss of the circulating blood volume. In addition to the loss of fluid to the tissues, there is a shift of intracellular potassium, metabolites, and breakdown products into the extracellular environment. These are mobilized as the circulation to the damaged tissue is improved. In addition, bacteria from the intestinal tract have been shown to gain access to the peripheral circulation during shock and to localize in the damaged tissue where they can find a favorable media in which to grow. The combined effect of tissue debris, bacteria, and bacterial by-products can be toxic to the entire cardiovascular system. ~ Second and third degree burns of relatively large areas of the body surface will result in the loss of fluid owing to evaporation from and edema of the damaged tissue. This loss and sequestration of fluid will decrease the extracellular fluid volume resulting in hypovolemia and interstitial dehydration. In addition to the fluid loss, gram-negative bacteria (i.e., E. coli, Proteus sp., Pseudomonas sp.) can proliferate in the burn wound producing toxemia and septicemia. Hypovolemia can develop from primary septic disease because of the shifts of blood or plasma into the areas of bacterial proliferation. Infection involving peritoneal and pleural spaces, urogenital tract, and peripheral tissues result in the shift of plasma into these areas. Bacterial proliferation, liberation of bacterial toxins, and tissue breakdown products complicate the fluid loss (see section on septic shock). Gastroenteritis may result in electrolyte and fluid loss from diarrhea, or vomiting, or both. A less common cause of hypovolemic shock in animals is dehydration. Prolonged thirsting, polyuria, and insufficient fluid therapy can result in a decrease in circulating blood volume sufficient to bring about a hypovolemic shock state.
BODY RESPONSE TO HYPOVOLEMIA Hypovolemia leads to a decreased venous return, cardiac output, and arterial blood pressure. The early decrease in arterial blood pres-
HYPOVOLEMIC SHOCK
189
sure is sensed by the baroreceptors and the decrease is reversed by sympathetic nervous system-mediated vasoconstriction, and increased rate and strength of myocardial contraction. A sustained decrease in blood pressure leads to a lowered capillary pressure which allows an influx of interstitial fluid into the vascular system to augment the circulating plasma volume. The expanded plasma has a low total protein because interstitial fluid is lower in protein than plasma. In addition, sympathetic stimulation of the spleen. results in contraction with extrusion of erythrocytes into the circulating blood volume. These erythrocytes plus the interstitial fluid augment the blood volume in a proportion that does not change the normal packed cell volume. This response can replace up to 20 per cent of the circulating blood volume in the dog. · Hypovolemia caused by plasma volume loss alone results in hemoconcentration and the splenic reaction will initially decrease the hemoconcentration (added blood has a normal packed cell volume). This response is short-lived and further fluid loss will again increase the hemoconcentration. Peripheral vasoconstriction appears to affect the terminal arterioles and precapillary sphincters and venules to bring about tissue ischemia. Arteriole and venule constriction persists longer than constriction of the sphincters. Sphincter control by the sympathetic system is over-ridden by local metabolic (pC02 ) and vasodilating agents (kinins, histamine, serotonin). The net result is some degree of sphincter-regulated capillary circulation with a relatively normal capillary pressure although total flow is diminished. This state exists until local hypoxia destroys sphincter function, then all capillaries remain filled and blood flow is sluggish or static. In the relatively "healthy" hypotensive vascular system (after acute hemorrhage), there is still some ability to react to vasopresser drugs if the blood pressure is above 35 to 40 mmHg. An increase in pressure owing to exogenous vasopresser drugs can be elicited; however, this does not result in a significant improvement in tissue perfusion and reflects only an increase in heart rate and peripheral resistance. The more that the blood pressure has recovered from severe hypotension, the greater will be the response to vasopresser, vasodilator, and cardiotropic agents. Therefore, an animal which has compensated for hypoYolemia by fluid and erythrocyte shift is extremely susceptible to anything that could affect the cardiovascular system (i.e., anesthesia, alphalytic agents, vasodilators). Tissue ischemia during hypovolemia is accentuated by shunting of blood. This occurs through precapillary arteriovenous connections which may provide the path of least resistance during periods of increased peripheral vascular resistance. Blood traveling by this pathway is not available for nutrient exchange with tissue.
190
A.
WENDELL NELSON
Effects of Hypovolemia and Cardiovascular Response Tissue hypoxia, resulting from ischemia, reduces the oxygen available for hydrogen ion reception. Thus, oxidative phosphorylation is reduced or blocked and glucose metabolism stops at pyruvic and lactic acid. The net result is a decrease in cell energy production (adenosine triphosphate- A TP) and an increase in intracellular hydrogen ion concentration. Decreased cellular A TP reduces cell membrane function which allows a change in permeability. Potassium loss and sodium, water, and hydrogen ion loading of the cell result in swelling of the cell and cell organelles, intracellular acidosis, and cessation of cell function. A similar change in the lysosome membrane causes swelling and rupture of these organelles liberating hydrolases into the cytoplasm. Cell autolysis and death follow. As the tissue hypoxia and decreased cell function become significant, all organ systems begin to demonstrate reduced metabolic activity and function. Glucagon and catecholamines are secreted and activate cyclic adenosine monophosphate (AMP) which results in glycogenolysis with hyperglycemia. Insulin is secreted although its glucose transport activity is antagonized by catecholamines and cortisol. Glucose metabolism results in lactic and pyruvic acid production instead of carbon dioxide and water. Thus, rapidly progressing intracellular acidosis develops which in itself limits some enzyme function. The accumulating acids permeate the cell membrane and result in acidemia. Liver and kidney function depression is indicated by increased levels of plasma ammonia and urea nitrogen. The plasma ammonia is a central nervous system toxin and will result in coma if allowed to accumulate. Decreased urine production, as a result of hypotension and vasoconstriction, progresses to complete shutdown as arterial blood pressure falls to 70 mmHg. In addition to the decreased urine production, renal hypotension stimulates renin secretion by the juxtaglomerular cells. Renin is converted to angiotension II, a powerful vasoconstrictor that enhances tissue ischemia. Angiotension II also stimulates aldosterone secretion which promotes sodium and water resorption and potassium and hydrogen ion excretion in the urine. Hypoxia of the intestine initially stimulates motility which may lead to multiple bowel movements and diarrhea. Severe vasoconstriction results in mucosal ischemia and early permeability and death of this tissue. Intestinal stasis occurs with later stages of hypoxia and this promotes bacterial proliferation. The combination of mucosal death and stasis with bacterial growth enhances absorption of bacteria, bacterial toxins, and metabolic products from the intestinal lumen. The absorbed bacteria and toxins are removed by the reticuloendothelial sys-
HYPOVOLEMIC SHOCK
191
tern until this system is exhausted and septicemia and toxemia are allowed to progress. Heart function is depressed by decreased myocardial perfusion secondary to hypotension (especially of diastolic pressure) and elevated heart rate. Since the majority of the blood flow through the myocardium occurs during diastole, a low diastolic pressure decreases coronary perfusion. An elevated heart rate decreases the time of diastole and thus the available time for perfusion. Therefore during periods of increased cardiac work in shock patients, there is less opportunity for adequate myocardial perfusion. The myocardium will begin to fail as the ratio of perfusion to work begins to decrease. Heart rates above 120 beats per minute are not efficient and do not produce increased cardiac output; in fact they can decrease cardiac output. The central nervous system is affected by hypovolemia in a manner similar to the myocardium. Local agents and not the sympathetic nervous system regulate the vessel tone (constriction), and blood flow to the central nervous system and heart is not restricted by this system as in other tissues. Oxygen, carbon dioxide, and hydrogen ion levels are the main regulatory agents and their alteration usually promotes vasodilation in shock patients. However, an increased respiratory rate in response to metabolic acidosis will result in lowering of the pC02 and maintenance of a normal p02 in arterial blood. This combination can cause vasoconstriction of the vasculature of the central nervous system during hypotension and decreased perfusion. This does not affect the myocardium as much because p02 and not pC02 is the local regulator. Decreased perfusion in the central nervous system results in anxiety and restlessness which progress to personality changes, depression, vocal outbursts, confusion, and coma. The responses outlined are aimed at short-term survival and if perpetuated are as lethal as the original hypovolemia. The vasoconstriction may provide the central nervous system and myocardium with an adequate blood flow, but it is at the expense of the remainder of the body. The only hope the animal has is to compensate for the hypovolemia by fluid reserve mobilization until it can obtain oral or intravenous fluid.
COMPENSATED HYPOVOLEMIA The degree and adequacy of compensation will depend on the se,-erity of hypovolemia and on the fluid reserves of the body. A 35 per cent loss in circulating blood volume can usually be compensated by moderate vasoconstriction and erythrocyte and fluid mobilization with little or no mortality. A 45 to 50 per cent loss in circulating blood volume may be partially compensated by maximal vasoconstriction and
192
A.
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blood augmentation yet will eventually result m a 50 to 100 per cent mortality rate without additional treatment. Thus an additional 10 to 15 per cent loss in circulating blood volume will change a nonlethal compensated hypovolemia to a highly lethal condition. This represents a blood volume loss or vascular volume gain of 160 to 240 ml in a 20 kg dog and will change a 35 per cent mortality rate to 50 per cent. General anesthesia and hemorrhage during surgery are the most common causes of such additional disparity in vascular space and blood volume. Thus, it is of clinical importance to identify early compensated shock states in animals in which surgery is contemplated.
SELECTED READINGS 2. 3. 4. 5. 6. 7. 8. 9. 10.
Brantigan, J. W., Ziegler, E. C., Hynes, K. M., et al.: Tissue gases during hypovolemicshock.J. Appl. Physioi.,J7:117, 1974. Couves. C. M., King, E. G., and MacKenzie, W. C.: Shock syndromes: Intensive care and renal shutdown. In Wells, C., Kyle, J., and Dunphy, J. E. (eds.): Scientific Foundations of Surgery, Vol. 2. Edition 2. Philadelphia, W. B. Saunders Co., 1974. Holcroft, J. W., and Trunkey, D. D.: Extravascular lung water following hemorrhagic shock in the baboon. Ann. Surg., 180:408, 1974. Nelson, A. W., and Swan, H.: Blood volume. II. Precise long-term measurements using chromium-tagged erythrocytes. Ann. Surg., 173:496-503, 1971. Nelson, A. W., and Swan, H.: The effects of the canine spleen on red cell and blood volume determinations using 51 RBC. Surgery, 71 :215, 1972. Nelson, A. W., and Swan, H.: Hemorrhage: Responses determining survival. Circ. Shock, 1:273, 1974. Schumer, W., and Erve, P. R.: Cellular metabolism in shock. Circ. Shock, 2:109, 1975. Schumer, W., and Nyhus, L. M.: Treatment of Shock: Principles and Practice. Philadelphia, Lea & Febiger, 1974. Thai, A. P., Brown, E. B., Jr., Hermreck, A. S., et al.: Shock: A Physiologic Basis for Treatment. Chicago, Year Book Medical Publishers, 1971. Zweifach, B. W., and Fronek, A.: The interplay of central and peripheral factors in irreversible hemorrhagic shock. Prog. Cardiovasc. Dis., 18:147, 1975.
Surgical Laboratory College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado 80523
Hypovolemic Shock A. Wendell Nelson, D.V.M., Ph.D*
By definition, hypovolemic shock is a pathologic decrease in capillary perfusion resulting from a decrease in circulating blood volume. Hypovolemic shock generally results from blunt or sharp trauma, burns, and/or sepis. In addition, terminal phases may be complicated by myocardial failure.
CAUSES OF HYPOVOLEMIA Shock attributed to hypovolemia may be initiated by several clinical diseases. The least complicated form of hypovolemia is that resulting from pure hemorrhage which is usually the result of low velocity tears of large vessels. Loss of blood from the body usually results from lacerations or tears in the vessels supplying the head and limbs. This is usually the result of partial severence of large arteries which enables the laceration to stay open. Thus, a large volume of blood can be lost before a significant drop in blood pressure allows a clot to be established at the opening. This is in contrast to a completely severed artery that constricts and retracts into the surrounding tissue. The narrowed orifice and presence of surrounding tissue allow a clot to establish itself more rapidly. External hemorrhage can be fatal when the loss reaches 35 per cent of the initial circulating blood volume and the animal does not obtain treatment. The mortality rate for this condition reaches approximately 100 per cent after 50 per cent of the initial circulating blood volume is lost. Loss of blood into th,e thoracic and abdominal areas is usually due to penetration by sharp objects (i.e., knives, ice picks, low velocity bullets). Hemorrhage into the thoracic cavity is probably the most lethal Professor of Clinical Sciences. Surgical Laboratorv, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado
~.\ssociate
r,terinary Clinics ofNorth America- VoL 6, No.2, May 1976
187
188
A.
WENDELL NELSON
because of its compounding effects on decreasing heart and lung function as a result of organ volume displacement by the free blood. The large pressure difference between the intravascular blood and the thoracic cavity promotes hemorrhage. Soft tissue ischemia and trauma initiated by prolonged tourniquet application, blunt force, or high velocity, missile-mediated injury are associated with edema, or hemorrhage, or both. The damaged tissue will accumulate intracellular fluid resulting from impaired cellular function and extracellular edema and hemorrhage resulting from increased capillary permeability and lymphatic stasis. Shifts of fluid and other blood elements into large areas of damaged tissue may result in a significant loss of the circulating blood volume. In addition to the loss of fluid to the tissues, there is a shift of intracellular potassium, metabolites, and breakdown products into the extracellular environment. These are mobilized as the circulation to the damaged tissue is improved. In addition, bacteria from the intestinal tract have been shown to gain access to the peripheral circulation during shock and to localize in the damaged tissue where they can find a favorable media in which to grow. The combined effect of tissue debris, bacteria, and bacterial by-products can be toxic to the entire cardiovascular system. ~ Second and third degree burns of relatively large areas of the body surface will result in the loss of fluid owing to evaporation from and edema of the damaged tissue. This loss and sequestration of fluid will decrease the extracellular fluid volume resulting in hypovolemia and interstitial dehydration. In addition to the fluid loss, gram-negative bacteria (i.e., E. coli, Proteus sp., Pseudomonas sp.) can proliferate in the burn wound producing toxemia and septicemia. Hypovolemia can develop from primary septic disease because of the shifts of blood or plasma into the areas of bacterial proliferation. Infection involving peritoneal and pleural spaces, urogenital tract, and peripheral tissues result in the shift of plasma into these areas. Bacterial proliferation, liberation of bacterial toxins, and tissue breakdown products complicate the fluid loss (see section on septic shock). Gastroenteritis may result in electrolyte and fluid loss from diarrhea, or vomiting, or both. A less common cause of hypovolemic shock in animals is dehydration. Prolonged thirsting, polyuria, and insufficient fluid therapy can result in a decrease in circulating blood volume sufficient to bring about a hypovolemic shock state.
BODY RESPONSE TO HYPOVOLEMIA Hypovolemia leads to a decreased venous return, cardiac output, and arterial blood pressure. The early decrease in arterial blood pres-
HYPOVOLEMIC SHOCK
189
sure is sensed by the baroreceptors and the decrease is reversed by sympathetic nervous system-mediated vasoconstriction, and increased rate and strength of myocardial contraction. A sustained decrease in blood pressure leads to a lowered capillary pressure which allows an influx of interstitial fluid into the vascular system to augment the circulating plasma volume. The expanded plasma has a low total protein because interstitial fluid is lower in protein than plasma. In addition, sympathetic stimulation of the spleen. results in contraction with extrusion of erythrocytes into the circulating blood volume. These erythrocytes plus the interstitial fluid augment the blood volume in a proportion that does not change the normal packed cell volume. This response can replace up to 20 per cent of the circulating blood volume in the dog. · Hypovolemia caused by plasma volume loss alone results in hemoconcentration and the splenic reaction will initially decrease the hemoconcentration (added blood has a normal packed cell volume). This response is short-lived and further fluid loss will again increase the hemoconcentration. Peripheral vasoconstriction appears to affect the terminal arterioles and precapillary sphincters and venules to bring about tissue ischemia. Arteriole and venule constriction persists longer than constriction of the sphincters. Sphincter control by the sympathetic system is over-ridden by local metabolic (pC02 ) and vasodilating agents (kinins, histamine, serotonin). The net result is some degree of sphincter-regulated capillary circulation with a relatively normal capillary pressure although total flow is diminished. This state exists until local hypoxia destroys sphincter function, then all capillaries remain filled and blood flow is sluggish or static. In the relatively "healthy" hypotensive vascular system (after acute hemorrhage), there is still some ability to react to vasopresser drugs if the blood pressure is above 35 to 40 mmHg. An increase in pressure owing to exogenous vasopresser drugs can be elicited; however, this does not result in a significant improvement in tissue perfusion and reflects only an increase in heart rate and peripheral resistance. The more that the blood pressure has recovered from severe hypotension, the greater will be the response to vasopresser, vasodilator, and cardiotropic agents. Therefore, an animal which has compensated for hypoYolemia by fluid and erythrocyte shift is extremely susceptible to anything that could affect the cardiovascular system (i.e., anesthesia, alphalytic agents, vasodilators). Tissue ischemia during hypovolemia is accentuated by shunting of blood. This occurs through precapillary arteriovenous connections which may provide the path of least resistance during periods of increased peripheral vascular resistance. Blood traveling by this pathway is not available for nutrient exchange with tissue.
190
A.
WENDELL NELSON
Effects of Hypovolemia and Cardiovascular Response Tissue hypoxia, resulting from ischemia, reduces the oxygen available for hydrogen ion reception. Thus, oxidative phosphorylation is reduced or blocked and glucose metabolism stops at pyruvic and lactic acid. The net result is a decrease in cell energy production (adenosine triphosphate- A TP) and an increase in intracellular hydrogen ion concentration. Decreased cellular A TP reduces cell membrane function which allows a change in permeability. Potassium loss and sodium, water, and hydrogen ion loading of the cell result in swelling of the cell and cell organelles, intracellular acidosis, and cessation of cell function. A similar change in the lysosome membrane causes swelling and rupture of these organelles liberating hydrolases into the cytoplasm. Cell autolysis and death follow. As the tissue hypoxia and decreased cell function become significant, all organ systems begin to demonstrate reduced metabolic activity and function. Glucagon and catecholamines are secreted and activate cyclic adenosine monophosphate (AMP) which results in glycogenolysis with hyperglycemia. Insulin is secreted although its glucose transport activity is antagonized by catecholamines and cortisol. Glucose metabolism results in lactic and pyruvic acid production instead of carbon dioxide and water. Thus, rapidly progressing intracellular acidosis develops which in itself limits some enzyme function. The accumulating acids permeate the cell membrane and result in acidemia. Liver and kidney function depression is indicated by increased levels of plasma ammonia and urea nitrogen. The plasma ammonia is a central nervous system toxin and will result in coma if allowed to accumulate. Decreased urine production, as a result of hypotension and vasoconstriction, progresses to complete shutdown as arterial blood pressure falls to 70 mmHg. In addition to the decreased urine production, renal hypotension stimulates renin secretion by the juxtaglomerular cells. Renin is converted to angiotension II, a powerful vasoconstrictor that enhances tissue ischemia. Angiotension II also stimulates aldosterone secretion which promotes sodium and water resorption and potassium and hydrogen ion excretion in the urine. Hypoxia of the intestine initially stimulates motility which may lead to multiple bowel movements and diarrhea. Severe vasoconstriction results in mucosal ischemia and early permeability and death of this tissue. Intestinal stasis occurs with later stages of hypoxia and this promotes bacterial proliferation. The combination of mucosal death and stasis with bacterial growth enhances absorption of bacteria, bacterial toxins, and metabolic products from the intestinal lumen. The absorbed bacteria and toxins are removed by the reticuloendothelial sys-
HYPOVOLEMIC SHOCK
191
tern until this system is exhausted and septicemia and toxemia are allowed to progress. Heart function is depressed by decreased myocardial perfusion secondary to hypotension (especially of diastolic pressure) and elevated heart rate. Since the majority of the blood flow through the myocardium occurs during diastole, a low diastolic pressure decreases coronary perfusion. An elevated heart rate decreases the time of diastole and thus the available time for perfusion. Therefore during periods of increased cardiac work in shock patients, there is less opportunity for adequate myocardial perfusion. The myocardium will begin to fail as the ratio of perfusion to work begins to decrease. Heart rates above 120 beats per minute are not efficient and do not produce increased cardiac output; in fact they can decrease cardiac output. The central nervous system is affected by hypovolemia in a manner similar to the myocardium. Local agents and not the sympathetic nervous system regulate the vessel tone (constriction), and blood flow to the central nervous system and heart is not restricted by this system as in other tissues. Oxygen, carbon dioxide, and hydrogen ion levels are the main regulatory agents and their alteration usually promotes vasodilation in shock patients. However, an increased respiratory rate in response to metabolic acidosis will result in lowering of the pC02 and maintenance of a normal p02 in arterial blood. This combination can cause vasoconstriction of the vasculature of the central nervous system during hypotension and decreased perfusion. This does not affect the myocardium as much because p02 and not pC02 is the local regulator. Decreased perfusion in the central nervous system results in anxiety and restlessness which progress to personality changes, depression, vocal outbursts, confusion, and coma. The responses outlined are aimed at short-term survival and if perpetuated are as lethal as the original hypovolemia. The vasoconstriction may provide the central nervous system and myocardium with an adequate blood flow, but it is at the expense of the remainder of the body. The only hope the animal has is to compensate for the hypovolemia by fluid reserve mobilization until it can obtain oral or intravenous fluid.
COMPENSATED HYPOVOLEMIA The degree and adequacy of compensation will depend on the se,-erity of hypovolemia and on the fluid reserves of the body. A 35 per cent loss in circulating blood volume can usually be compensated by moderate vasoconstriction and erythrocyte and fluid mobilization with little or no mortality. A 45 to 50 per cent loss in circulating blood volume may be partially compensated by maximal vasoconstriction and
192
A.
WENDELL NELSON
blood augmentation yet will eventually result m a 50 to 100 per cent mortality rate without additional treatment. Thus an additional 10 to 15 per cent loss in circulating blood volume will change a nonlethal compensated hypovolemia to a highly lethal condition. This represents a blood volume loss or vascular volume gain of 160 to 240 ml in a 20 kg dog and will change a 35 per cent mortality rate to 50 per cent. General anesthesia and hemorrhage during surgery are the most common causes of such additional disparity in vascular space and blood volume. Thus, it is of clinical importance to identify early compensated shock states in animals in which surgery is contemplated.
SELECTED READINGS 2. 3. 4. 5. 6. 7. 8. 9. 10.
Brantigan, J. W., Ziegler, E. C., Hynes, K. M., et al.: Tissue gases during hypovolemicshock.J. Appl. Physioi.,J7:117, 1974. Couves. C. M., King, E. G., and MacKenzie, W. C.: Shock syndromes: Intensive care and renal shutdown. In Wells, C., Kyle, J., and Dunphy, J. E. (eds.): Scientific Foundations of Surgery, Vol. 2. Edition 2. Philadelphia, W. B. Saunders Co., 1974. Holcroft, J. W., and Trunkey, D. D.: Extravascular lung water following hemorrhagic shock in the baboon. Ann. Surg., 180:408, 1974. Nelson, A. W., and Swan, H.: Blood volume. II. Precise long-term measurements using chromium-tagged erythrocytes. Ann. Surg., 173:496-503, 1971. Nelson, A. W., and Swan, H.: The effects of the canine spleen on red cell and blood volume determinations using 51 RBC. Surgery, 71 :215, 1972. Nelson, A. W., and Swan, H.: Hemorrhage: Responses determining survival. Circ. Shock, 1:273, 1974. Schumer, W., and Erve, P. R.: Cellular metabolism in shock. Circ. Shock, 2:109, 1975. Schumer, W., and Nyhus, L. M.: Treatment of Shock: Principles and Practice. Philadelphia, Lea & Febiger, 1974. Thai, A. P., Brown, E. B., Jr., Hermreck, A. S., et al.: Shock: A Physiologic Basis for Treatment. Chicago, Year Book Medical Publishers, 1971. Zweifach, B. W., and Fronek, A.: The interplay of central and peripheral factors in irreversible hemorrhagic shock. Prog. Cardiovasc. Dis., 18:147, 1975.
Surgical Laboratory College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado 80523
