deamino-arginine-vasopressin and Acidosis

Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality.. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality.. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

Topics: Acidosis; Antifibrinolytic Agents; Bandages; Blood Coagulation Disorders; Blood Transfusion; Cause of Death; Critical Care; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Fibrinogen; Hemorrhage; Hemostatics; Humans; Hyperkalemia; Hypocalcemia; Hypothermia; Military Medicine; Recombinant Proteins; Resuscitation; Risk Factors; Transfusion Reaction; United States; Wounds and Injuries; Zeolites

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma victims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.

Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Substitutes; Blood Transfusion; Deamino Arginine Vasopressin; Factor VIIa; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Hypothermia; Multiple Trauma; Plasma; Platelet Transfusion; Preoperative Care; Prothrombin

Desmopressin (DDAVP) and fibrinogen improve platelet function and clot stability. We investigated the influence of DDAVP and fibrinogen on whole blood coagulation in an in vitro model of hypothermia and acidosis.. After IRB approval and written consent blood samples were taken from 10 healthy volunteers. Samples were prepared with hydrochloric acid to maintain--beside normal pH--reduced pH (∼7.2) and severely reduced pH (∼7.0), and were assigned to four treatment groups: addition of either isotonic saline for compensation of dilutional effects (ISO), desmopressin (DDAVP+), fibrinogen (FIB+), or both substances (DDAVP+FIB+). Baseline was ISO at 37°C and normal pH. Remaining samples were incubated for 30 min and measured at 32°. Rotation thrombelastometry (ROTEM) after extrinsically activation and fibrin polymerization was tested. Repeated measures ANOVA were performed (p < 0.05).. Hypothermia and acidosis synergistically impaired whole blood coagulation. DDAVP+ normalized maximum clot firmness (MCF) at normal pH. Coagulation time (CT) was not affected. FIB+ normalized MCF at pH 7.35 and pH 7.2. CT was normalized independently of pH. DDAVP+FIB+ did not show additional effects to FIB+. Fibrin polymerization was increased by FIB+ and DDAVP+FIB+ independently of pH. DDAVP+ did not alter fibrin polymerization.. DDAVP and fibrinogen increased whole blood coagulation under hypothermia. Acidosis diminished this effect. Thus, acidosis should be corrected first and then both substances could be used for bridging until normothermia can be achieved. In combination, the effects of fibrinogen were overwhelming DDAVP effects. Thus, combined administration did not show any benefit compared to fibrinogen administration alone.

Topics: Acidosis; Adult; Blood Coagulation; Deamino Arginine Vasopressin; Female; Fibrin; Fibrinogen; Humans; Hypothermia; Male; Protein Multimerization; Thrombelastography; Whole Blood Coagulation Time

Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Topics: Acidosis; Adenosine Diphosphate; Adult; Blood Platelets; Cells, Cultured; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hydrogen-Ion Concentration; Hypothermia; Male; Platelet Activation; Platelet Aggregation; Young Adult

The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine.

Topics: Acidosis; Acute Disease; Ammonia; Animals; Chronic Disease; Deamino Arginine Vasopressin; Dogs; Glomerular Filtration Rate; Glutamine; Hypotonic Solutions; Kidney; Osmolar Concentration; Sodium; Sodium Chloride