Index
A
ABCs. See Airway-breathing-circulation format
Actin, testing for caspase-specific degradation fragments from, 43
Acute hemorrhagic shock, pathophysiology of, 4, 19-44
''Acute respiratory distress syndrome,''15
Acute respiratory failure, 50
Adenosine, 74
Adenosine diphosphate (ADP)
phosphorylation of, 26
release of, 52
Adenosine triphosphate (ATP)
depletion during ischemia, 26, 55
Adhesion molecules, intracellular, 58
Adrenergic downregulation, 37
Advanced Trauma Life Support® (ATLS® course, 100, 102
Aeromedical evacuation, prompt, 106
Airway
and breathing, 104-106
obstruction of, 10
Airway-breathing-circulation format, 103
Albumin-containing solutions
advantages of, 60
as a resuscitation fluid, 39, 51, 60
Altered physiologic states, 93
American College of Emergency Physicians (ACEP), 102
American College of Surgeons, 102, 118-119
Committee on Trauma, 39
Analgesia, administering, 101
Anemia, 51
Anesthesia
cardiovascular effects of, 114
depressant effects of, 114-115
inhalant, 114
intravenous, 114
role in hemorrhagic shock, 110, 114-115
rodent, 110-112
standardizing. 3
value of, 112
Antibiotics, administering. 101
Antibodies, monoclonal, 89
Antioxidant strategies, 86-87
endogenous, 54
APACHE scoring system, 118
Apoptotic signals, originating from cellular organelles, 35
complexity of system for, 36
cytoplasmic, 30
defined, 29-30
developmental, 30
plasmalemma receptor-induced, 30
Aptotic internucleosomal DNA fragmentation, 35
Arachidonate, oxidative metabolism of, 27
ARDS. See Acute respiratory distress syndrome
Arginine administration, 57
Ascorbic acid, 87
Assessment methodologies, 118
Asymmetric battlefields, 10
ATLS®. See Advanced Trauma Life Support® course
Auto-tyrosine phosphorylation, 36
B
Bacterial diseases, transmitted by transfusions, 41
Basic tactical casualty management plan, for Special Operations forces, 101
Basic Trauma Life Support (BTLS) course, 102
Battlefield
bulk of solutions that must be transported onto, 51
expected condition of combatants on, 98
ideal solution for fluid resuscitation on, 98
resuscitation needs on, 98-99
salvageable casualties on, 9, 98
Battlefield injuries
compared with inner city, 15
modeling, 113
Bleeding. See Blood loss
Blood, citrate-preserved, 38
Blood banking, 38
Blood hemoglobin concentration. acute isovolemic reduction of, 80-81
handling on battlefield, 2
molecular and cellular responses to, 4
rates of, 113
Blood plasma, 14
drawbacks of, 60
Blood pressure, 113
Blood substitutes, 41-42.
See also Oxygen therapeutics
Blood transfusions, 38
alternatives to, 41-42
risks of, 41
"Boutique fluids," 79
Brain injury, 10
compression, 29
Brain ischemia, 33
free fatty acids released during. 27
reducing, 85
salvaging vulnerable neurons after, 34
Breathing and airway, 101, 104-106
C
Calpain-specific degradation fragments of spectrin, testing for, 43
Cancer and Leukemia Group B, 121
Cannon, Walter, 13-14
Capillary leak syndrome, 15
Cardiac myocytes, ischemic death of, 30
Cardiogenic shock, defined, 20-21
Cardiopulmonary resuscitation, 101
Cardiovascular collapse, 114
Carolina Rinse solution, 73-74
Caspases
mediating degradation of eIF4G, 33
prototypic, 32
receptor-mediated activation of, 30
Caspase-specific degradation fragments from actin, testing for, 43
Catecholamines, 111-112
CD 18 cells, altering, 111
Cell hypoxia, 20
Cellular derangements, accompanying traumatic shock, 4
Cellular organelles, apoptic signals originating from, 35
Cellular responses to shock, 25-28
altered energy metabolism, 25-26
ion compartmentalization, 26-27
lipid metabolism, 27
radical production and metabolism, 27-28
Cellular responsiveness to growth factors, alterations in, 36-38
Central nervous system
inhibiting insulin transport into, 37
injuries to, 9-10
protecting, 85
Circulatory support, 99
Citrate-preserved blood, 38, 40
Civilian data
applicability of, 121
Civilian trauma centers, 121-122
Clinically significant function, defined, 116
Clinical practice guidelines, 61
Clinical trauma. See Trauma
Clinical trials
applicability of civilian data, 121
defined, 116
endpoints and indications of, 116-120
heterogeneous subject populations, 120
of hypertonic saline-dextran (HSD), 71-73
informed consent, 120
role in developing therapies, 115-116
in trauma centers, 121-122
unique problems of, 3, 120-121
Clotting, 51
Clotting factors, alterations in amount of, 40
Coagulation
disseminated intravascular, 42-43
effects of fluid resuscitation on, 51-53
Colloid-deferoxamine conjugates, 88
Colloid resuscitation, 47-51
complications of, 60-62
polydisperse, 62
studies of, 12
vs. crystalloid, 51
Colocalization, of inhibited protein synthesis, 37
Combat environment, 97-101
defined, 11
Combat trauma, no "golden hour" in, 9
Combatants
expected condition of, 98
in future battles, 11
injury to, 113-114
limits of care on battlefield, 98-99
mortality rate in battle, 1, 9
resuscitation needs of, 99
tension pneumothorax in, 104-105
Compartmentalization, ion, 26-27
Compensatory mechanisms, 80
Complement activation, 84
"Congestive atelectasis," 15
Consent. See Informed consent
Continuing medical education (CME), 122
Controlled hemorrhage, vs. uncontrolled, 112-113, 123
Cortisol, 112
Crocetin, 84
Crystalloid overresuscitation, 68
Crystalloid resuscitation, 15, 39, 47-51
aggressive, 67
complications of, 62-73
effects on immune function, 62-67
overall cautions concerning, 75
studies of, 12
for treating hypovolemia, 1
vs. colloid, 51
Cyclosporin, 85
effects of crystalloid resuscitation on, 67-68
effects of hypertonic saline-dextran on, 71
D
"Danang lung," 15
"Death domain," 30
Decompensation, 24-25
Deferoxamine (DFO) conjugates, 88
Delphi method, 61
Desferal, 88
DFO. See Deferoxamine conjugates
Diagnostic instrumentation, for intervening in shock, 92
Diaspirin-cross-linked hemoglobin, 82
DIC. See Disseminated intravascular coagulation
Dilutional thrombocytopenia, 40
Disseminated intravascular coagulation (DIC), 41-43
laboratory abnormalities in, 43
thrombosis accompanying, 42
D-lactate, 69-70
removing from lactated Ringer's solution, 3, 76
E
Eastern Cooperative Oncology Group, 121
eIF2α, phosphorylated, 43
eIF4G
caspase-mediated degradation of, 33
proteolytic degradation of, 33
Electrolyte characteristics, of selected resuscitation fluids, 49
Electron paramagnetic resonance (EPR) spectroscopy, 54
Endothelial cell function, resuscitation-related changes in, 53
Endothelin production, 52
Endotoxin shock, 28
Endpoints of clinical trials, 117-118
surrogate, 117
Energy depletion, 22
Energy metabolism, altered, 25-26
EPR. See Electron paramagnetic resonance spectroscopy
Equipment, size and weight limits on, 99
Erythrocytes, 82
Estradiol, 92
Estrogenic effects, potential therapeutic effects of compounds with, 92
Evacuation
limited on battlefield, 98
prompt aeromedical, 106
recommendation concerning, 106
Evaluating resuscitation protocols, 118-120
Exsanguination. See Blood loss
Extraction reserve, 109
F
FDA. See U.S. Food and Drug Administration
First responders.
See also "Trained responders"
needs of, 2
training, 102
treatment protocol for, 105
FK506, 85
Fluid overload, 68
Fluid redistribution, after major trauma, 48
Fluid resuscitation, 101
on battlefield, 99
defined, 11
experience with and complications of, 5, 47-76
history of, 12-15
immediate vs. delayed, 99
research on, 3
Fluids.
See "Boutique fluids";
Resuscitation fluids;
individual fluids
Fractures, immobilizing, 99, 101
Free fatty acids, release during brain ischemia, 27
Free radical, damage by, 27-28
Free radicals
confirming production of, 90
neutrophil-derived, 58
oxygen-derived, 55-56
preventing generation of, 85
reperfusion-mediated damage by, 54, 86-91
Free-radical scavengers, 53, 55
adding to lactated Ringer's solution, 3, 76
Future directions, in treating hemorrhagic shock, 6-7, 109-124
G
Gardenia jaminoides Ellis, 84
Gastrointestinal consequences of shock, 22
Genes. See Human genes
Glasgow Coma Score, 118-119
Global ischemia, development of tolerance to, 4, 93
Glucocorticoids, 37
Glucose-containing solutions
drawbacks off 60
as a resuscitation fluid, 60
Glutathione, 56
adding to lactated Ringer's solution, 3
"Golden hour," 9
Granulocyte colony-stimulating factor (GCSF), altering, 111
Growth factors, alterations in secretion of and cellular responsiveness to, 36-38
H
Hematocrit
decrease in, 52
restoring, 59
Hematologic abnormalities associated with shock, 38-43
disseminated intravascular coagulation, 42-43
transfusion-related, 39-42
Hematologic changes, 23
Hemoconcentration, 13
Hemodilution, 51-52
interoperative, 83
Hemodynamic measurements, 113
Hemoglobin.
See also Stroma-free hemoglobin
diaspirin-cross-linked, 82
polyoxyethlene, 82
recombinant, 82
Hemorrhage
autoregulatory mechanisms involved in, 23-24
consequences triggered by, 4
controlled vs. uncontrolled, 112-113, 123
control of massive, 99
major cause of salvageable battlefield casualty, 10
physiologic responses to, 23-25
regulatory mechanisms involved in, 23
studies of effects of rates of, 110-111
studies of injury with, 111
treating on the battlefield, 103-105
Hemorrhagic gastritis, 22
Hemorrhagic shock
animal models of, 109-112
associated with lactic acidosis, 28-29
definitions of, 19-23
future directions in treating. 6-7, 109-124
organ involvement in, 21-23
oxygen-derived free-radical-mediated injury in, 55-56
pathophysiology of acute, 19-44, 80
pure, 3
roles of induced nitric oxide in, 58
technical models of, 112-114
Hemostasis, achieving adequate, 29
Hemothorax, detection and treatment of, 99
Heparin therapy, 43
"Hibernation," pharmacologically induced, 93
Homeostasis, hypotheses involving. 110
Hormonal influences, intervening in shock, 92
HSD. See Hypertonic saline-dextran
Human genes. encoding CED-9-related proteins, 32
Human immunodeficiency virus (HIV), transmitted through transfusion, 53
Human subjects, protection of, 120
Hydroxyethyl starch, 61
Hyperglycemia, in patients with shock, 38
Hypernatremia, 48
Hypertonic saline-dextran (HSD). 71-73
clinical trials of, 71-73
limits of, 72-73
Hypertonic saline solutions
not causing neutrophil activation. 64
repeat administration of, 104
safety and efficacy of, 71-73
using minimum volumes of, 61
Hyponatremia, 48
Hypoperfusion, 25
Hypotension, studies of effects of, 110-111
Hypovolemia, crystalloid resuscitation for treating, 1
Hypovolemic shock
Hypoxanthine, 55
Hypoxia, reducing vulnerability to, 4, 93
I
Immune function
effects of crystalloid resuscitation on, 62-67
effects of hypotension and hemorrhage on, 110-111
Immunochemical assays, 43
Immunological impairment, 22-23, 65-66
Indexing systems, of trauma research findings, 3, 123
Inducible isoform of nitric oxide synthase (iNOS), 89-90
Informed consent, 120
Injury.
See also Combatants;
Combat trauma
inflammatory and organ dysfunction responses to, 50
penetrating vs. blunt, 15, 98, 113
protocols for care at the site of, 97-107
soft-tissue, 113
system for categorizing, 4
types of, 9-10
Injury severity score (ISS), 118-119
Inner city, casualties in, 15, 99
Insulin
high doses needed during postischemic reperfusion, 37
neuron-sparing effects of, 36-37
Insulin resistance, in patients with shock, 38
"Internal armor" concept, 92
Intervening in shock, 84-92
diagnostic instrumentation, 92
hormonal influences, 92
targets for, 84-86
therapies for reperfusion-mediated free-radical damage, 86-91
Intraosseous administration, 2, 103-104
Intravascular coagulation, disseminated, 42-43
Intravenous therapy, 101
Intubating laryngeal mask airway (LMA), 104
Ion compartmentalization, 26-27
Iron chelators, 88-89
adding to lactated Ringer's solution, 3
Ischemia.
See also Brain ischemia;
Global ischemia;
Myocardial ischemia
consequences triggered by, 4
enzymatic consequences of, 26-27
neuron-sparing effects in, 36
prolonged, 24
relationship to oxygen reperfusion, 87
transient forebrain, 37
Ischemia-reperfusion research, 4, 82
Isobaric models, 109
Isotonic solutions, 39
large volume use of, 47
Israeli Defense Forces, 10
ISS. See Injury severity score
K
Ketones, adding to lactated Ringer's solution as an energy source, 3, 76
Krebs cycle, failure of, 22
Kupffer cells, 28
L
Lactated Ringer's solution
adverse effects, 39, 67, 69-70
increasing neutrophil activation, 62
need for modifying, 2-3, 12-13, 76
safety of current regimens of, 70
upregulation of intracellular adhesion molecules by, 58
Lactic acidosis, hemorrhagic shock associated with, 28-29
Large volume use
of crystalloid resuscitation, 15, 68-69
of isotonic salt solutions, 47-48
Laryngeal mask airway (LMA), intubating, 104
"Lazarus solutions," 81
Lethal dose, 123
Leukocytosis, 84
Lipid metabolism, 27
Lipid peroxidation products and proteins, testing for, 43
Liposomes, for preventing shock, 83-84
L-lactate, reducing total load of in lactated Ringer's solution, 3, 76
LMA. See Laryngeal mask airway
Longer-term survival, 3
Lysis of clots, 29
M
Macrophage function, alterations in, 28-29
Major trauma, fluid redistribution following, 48
Massive transfusions, 40-41
defined, 40
Medical litter, monitoring, 106-107
Melatonin therapy, 91
Mercaptoethylguanidine (MEG), 85-86
Metabolic derangements, accompanying traumatic shock, 4
Metabolism
of lipids, 27
of radicals, 27-28
Methionine, 32
Military Trauma Life Support course, 102
Mitochondrial aerobic metabolism, 26
Models of hemorrhagic shock.
See Animal models;
Technical models
Monitoring
cardiac output, 106-107
passive, 106
of vital signs, 106
Monitoring equipment, miniaturizing. 106-107
Monitoring medical litter, 106-107
Monoclonal antibodies. 89
Mortality rate
reducing, 1-2
Myocardial contraction, decreased, 20
Myocardial ischemia, 30
N
N-acetylcysteine, 86-87
NADPH. See Nicotinamide adenine dinucleotide phosphate
National approach, needed in trauma research, 3-4
National Cancer Institute, 121
National Institutes of Health, 3, 124
National Research Council, 13, 15
Naval Blood Research Laboratory, 52
Naval operations, injuries in, 15
Nervous system. See Central nervous system
Neurogenic shock, defined, 20-21
Neutrophils
activated in reperfusion-mediated injury, 58-59, 62
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, 53
Nitric oxide (NO)
mediating cell injury, 57
mediating platelet dysfunction, 52
in reperfusion-mediated injury, 56-58
Nitric oxide (NO) synthase
inducible isoform of (iNOS), 89-90
phosphorylation of, 27
Nitrones, 90-91
Nitroxides, developing, 91
Nonlinear battlefields, 10
Nonthoracic trauma, 15
Normochloremic carbonate/carbon dioxide, 3
Novel approaches to treating shock, 4, 6, 75, 79-94
NOX, 90
O
Office of Naval Research, 1, 16
Oligosaccharides, 59
Oncotic proteins, 51
Operation Desert Storm, 106
Opsonic proteins, 51
Organelles. See Cellular organelles
Overhydration, 15
Oxygen delivery
consequences of impaired, 4
enhancing, 4
supraphysiologic concentrations of, 53-54
Oxygen-derived free radicals, in reperfusion-mediated injury, 55-56
Oxygen reperfusion, relationship to ischemia, 87
Oxygen therapeutics, for preventing shock, 80-82
Oxygen toxicity, associated with resuscitation, 53-54
Oxyglobin (veterinary use), 81
P
Parameters, of fluid therapy fluids, 2
Parenteral saline, 3
normochloremic carbonate, 75
PARS. See Poly(ADP ribose) synthetase
Pathophysiology of acute hemorrhagic shock, 19-44
Penetrating injury, 113-114
Perfluorocarbons, as blood substitutes, 42
Perfluorochemicals, for preventing shock, 83
Peroxynitrite, 57-58
scavenging, 89
Pharmaceutical industry, 121
Phosphoprotein phosphatase1, 33
Phosphorylated eIF2α, testing for, 43
Phosphorylation
auto-tyrosine, 36
tyrosine, 37
Physiologic responses to hemorrhage, 23-25
PKR. See Protein kinase
Plasma. See Blood plasma; Reduced plasma
Plasma catecholamines, 111
Plasmalemma receptor-activated caspase response, 31, 35
Platelet aggregation, 52
Platelet dysfunction, nitric oxide-mediated, 52
Pneumothorax, detection and treatment of, 99
Poly(ADP ribose) synthetase (PARS), 57
Polyhemoglobin, 86
Polymorphonuclear neutrophil adherence, inhibiting, 89
Polynitroxylation, of biomacromolecules, 82-83
Polyoxyethlene hemoglobin, 82
Polypharmaceutical treatment approaches, 44
Postischemic reperfusion, high doses of insulin needed during, 37
Prehospital Trauma Life Support (PHTLS) course, 102
Preventing shock, 80-84
first- to third-generation therapeutics, 82-83
liposomes, 83-84
oxygen therapeutics, 80-82
perfluorochemicals, 83
Private sector, 3
Professional organizations, 3
Prolactin release, 92
Protective equipment, need for research into, 92
Protein kinase (PKR), function of, 34
Protein synthesis
colocalization of inhibited, 37
suppression of, 34
Proteolytic degradation, of eIF4G, 33
evaluating efficacy of, 3
need to change, 2
Protocols of resuscitation, 118-120
Pulmonary edema, 69
contributing factors, 50
Pulmonary infection, following hemorrhagic shock, 28
Purines, oxidation by, 54
Pyruvate, pathway producing, 26
R
Radicals.
See also Free radicals
production and metabolism of, 27-28
Recombinant hemoglobin, 82
Recombinant technology, 61
Recommendations, 2-7
Red blood cell
complement-mediated destruction of, 41
substitutes for, 40-41
Reduced plasma, 51
Renal failure, 21-22
Reperfusion
neuron-sparing effects in, 36
postischemic, 37
Reperfusion-mediated injury, 54-59
activated neutrophils, 58-59
nitric oxide, 56-58
oxygen-derived free radicals, 55-56
therapies for intervening in, 86-91
treating, 4
Research, defined, 115-116
Respiratory failure. See Acute respiratory failure
Responders. See First responders
Resuscitation
alternative approaches to, 73-74
complications of, 51-73
disadvantages to current solutions for, 2
evaluating protocols of, 118-120
hematologic abnormalities associated with, 38-43
immediate vs. delayed, 99
initial, 2
late, 59
oxygen toxicity associated with, 53-54
using colloids and crystalloids, 47-51
Resuscitation fluids
developing new, 2
electrolyte characteristics of selected, 49
ideal, 79
for military use, 81
Resuscitation protocols, evaluating, 118-120
Revised Trauma Score (RTS), 118-119
Ringer's solution. See Lactated Ringer's solution
Risks, of blood transfusion, 41
RTS. See Revised Trauma Score
S
Saline solutions.
See also Hypertonic saline solutions
controversy over, 47
Scavenging strategies, 86-87
Scoring systems, 118
Secondary shock, 13
Secretion of growth factors, alterations in, 36-38
Septic shock, 113
defined, 20-21
Shear stress, 52
Shock.
See also Hemorrhagic shock;
Secondary shock
biochemical effects of, 22
cellular responses to, 4, 25-38
classifications of, 19-20
future directions in treating, 6-7, 109-124
gastrointestinal consequences of, 22
hematologic abnormalities associated with, 38-43
increasing tolerance toward, 92-93
insulin resistance and hyperglycemia in patients with, 38
irreversibility in severe, 25
molecular responses to, 4
novel approaches to treating, 4, 6, 79-94
organ involvement in, 21
prevention, 80-84
Shock decompensation, 24-25
Shock syndrome, treating complications of, 4
Signal transduction, 29
evolutionary development of mechanisms for, 35
Site of injury, protocols for care at, 6, 97-107
SOD. See Superoxide dismutase
Soft-tissue injury, 113
Southwest Oncology Group, 121
Special Operations forces, 98, 100
basic tactical casualty management plan for, 101
Spectrin, testing for calpain-specific degradation fragments of, 43
Starch-chelator conjugates, 88
Stress measurements, 113
Stroma-free hemoglobin, 42
Superoxide dismutase (SOD), 82, 86
Supplies and equipment, size and weight limits on, 99
Surgeon General's History of Surgery in World War II, 50
Surgical bleeding disorders, 29
Surrogate endpoints, 117
longer-term, 3
probability of, 119
Systemic inflammatory responses, 62-64
T
Tachycardia, 22
Technical models, of hemorrhagic shock, 112-114
in combat casualties, 104-105
detection and treatment of, 99
symptoms of, 105
Testosterone, adverse effects of, 92
Tetramers, 81
Therapeutic regimens, 97-107
"Third spacing," 48
Thoracostomy, 105
dilutional, 40
Thrombosis, accompanying disseminated intravascular coagulation (DIC), 42
Tirilazad mesylate, 88
Tissue macromolecules, radical-mediated damage to, 27
Tissue macrophages, activation of, 28
Tissue perfusion, decreased, 20, 25
T lymphocytes, 28
Torso, injuries to, 9
"Trained responders," 100
Training, for first responders, 102
Transcript formation, 34-35
Transcription and translation, fundamental alterations in, 29-36
Transfusions.
See also Blood transfusions
alternatives to, 41-42
massive, 40-41
of the patient in shock, 39-40
transmitting diseases, 41
Translation
fundamental alterations in, 29-36
initiation system for protein synthesis, 32
Trauma
classifying severity of clinical, 3
fluid redistribution following major, 48
Trauma and injury severity score (TRISS) assessment methodology, 118-119
Trauma centers
civilian, 121-122
clinical trials in, 3
Trauma research, 3
national approach needed in, 3-4
Traumatic shock.
See also Hemorrhagic shock
associated with tissue injury, 3
defined, 20
metabolic and cellular derangements accompanying, 4
"Traumatic wet lung," 15
Treatment approaches, 102-107
airway and breathing, 104-106
future directions in, 6-7, 109-124
for hemorrhage, 103-104
monitoring, 106-107
prompt aeromedical evacuation, 106
repeat administration of hypertonic saline solution, 104
TRISS. See Trauma and injury severity score
Trolox, 87
Tubular necrosis, 39
Tumor necrosis factor a, 28, 30
21st century battlefields, 10, 97
Tyrosine phosphorylation, 37
U
Uncontrolled hemorrhage, vs. controlled, 112-113, 123
U.S. Department of Defense, 3, 124
U.S. Department of Veterans Affairs, 3, 124
U.S. Food and Drug Administration (FDA), 116-117
U.S. Navy Seals, 103
Urban warfare, 97
Utstein system, 119
V
Vasoactivity, factors influencing, 82
Vasoconstriction, 52
Vasopressin, release of, 24
Vietnam conflict, 10, 15, 22, 39, 50, 100
Viral diseases, transmitted by transfusions, 41, 53, 60
Vital signs, monitoring, 106
Vitamins, 87
adding to lactated Ringer's solution, 3
Volume replacement therapy, 4, 14
goal of early, 24-25
W
Wars of the future, 10-11
Wounds
data on. 10
dressing, 101
X
Xanthine oxidase, 55
Y
Yom Kippur War, 22
