deamino-arginine-vasopressin and Hypothermia

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

Hypothermia has been demonstrated to induce pancytopenia in animals, but whether this association exists in humans is unknown. The authors report the case of an 8-year-old girl in whom hypothermia (temperature 33 degrees C-35 degrees C) is the cause of pancytopenia. The patient developed thermoregulatory dysfunction subsequent to surgical resection of a craniopharyngioma. Her recurrent cytopenias could not be explained by any etiology except chronic hypothermia. The pancytopenia improved upon rewarming the patient to a temperature of 36 degrees C. This association between hypothermia and pancytopenia has rarely been reported in humans and may be underdiagnosed especially in cases of transient or milder presentations. The authors recommend careful hematologic monitoring of patients with thermoregulatory dysfunction.

Topics: Adrenal Insufficiency; Blood Cell Count; Cerebral Infarction; Child; Chronic Disease; Consciousness Disorders; Craniopharyngioma; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Female; Frontal Lobe; Humans; Hyponatremia; Hypophysectomy; Hypopituitarism; Hypothalamus; Hypothermia; Hypothyroidism; Pancreatitis; Pancytopenia; Pituitary Neoplasms; Postoperative Complications; Seizures; Sleep Stages

Mild hypothermia (34-35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers.. Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively.. Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34-39.74 %, p = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5-20.85 %, p < 0.001) and 8.0 % (95 %CI 6.38-10.04 %, p = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32-36.49 %, p = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C (p = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram (p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only (p = 0.011).. It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period.. ClinicalTrials.gov: NCT01382134.

Topics: Adenosine Diphosphate; Aspirin; Collagen; Deamino Arginine Vasopressin; Double-Blind Method; Epinephrine; Female; Follow-Up Studies; Hemostasis; Hemostatics; Humans; Hypothermia; Male; Platelet Function Tests

Mild hypothermia (34-35 °C) increases peri-operative blood loss. We have previously demonstrated the beneficial effect of in vitro desmopressin on impairment of primary haemostasis associated with hypothermia. This study evaluated subcutaneous desmopressin in 52 healthy volunteers, randomly assigned to receive either normal saline or desmopressin 1.5, 5 or 15 μg (with 13 in each group). Blood samples were collected before and 2 h after drug administration and incubated at 32 and 37 °C. Platelet function analyser PFA-100(®) closure times were measured. Hypothermia at 32 °C prolonged mean (95% CI) closure times (for adenosine diphosphate/collagen by 11.3% (7.5-15.2%) and for adrenaline/collagen by 16.2% (11.3-21.2%); these changes were reversed by desmopressin. A very small dose was found to be effective (1.5 μg); this dose did not significantly change closure times at 37 °C, but fully prevented its prolongation at 32 °C. Subcutaneous desmopressin prevents the development of hypothermia-induced impairment of primary haemostasis.

Topics: Adult; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Hemostasis; Humans; Hypothermia; Male

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 aim of the present study was to examine whether minimizing plasma volume loss due to cold-induced diuresis can increase the survival time of rats maintained in long-term stable hypothermia (~24 h at a body temperature of 19 degrees C). Infusion of desmopressin (0.5-2.0 microg), a potent antidiuretic agent, during the cooling period enhanced survival over saline controls in a dose-related manner. The enhanced survival was accompanied by a significant delay in the expected increase of hematocrit and decrease of plasma volume as compared with those seen in saline controls. In contrast, treating the rats with the same dose range of another vasopressin analog, [beta-mercapto-beta,beta-cyclopentamethyl enepropionyl]-vasopressin, which has no antidiuretic action, failed to enhance survival over saline control. Further, treating the rats with the optimal dose of desmopressin (1 microg) at the later stage of hypothermia failed to elicit any beneficial effect. Our results indicate that by using desmopressin early during the cooling phase of the hypothermia, plasma volume and rheological parameters important for sustaining microcirculation can be better maintained than those seen in saline controls. These improvements may have contributed to the observed longer survival time in hypothermia.

Topics: Animals; Deamino Arginine Vasopressin; Diuresis; Hematocrit; Hypothermia; Infusions, Intravenous; Male; Microcirculation; Plasma Volume; Rats; Rats, Sprague-Dawley; Renal Agents; Rheology; Survival Rate; Time Factors; Vasopressins

The aim of this study was to investigate whether the increased diuresis in consequence of hypothermia is due to a depression of the hypothalamic release of antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and the effect of intravenous (i.v.) administration of 65 ng kg-1 desmopressin (selective V2-receptor agonist) were determined in the anaesthetized rat. In spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P < 0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma antidiuretic hormone decreased from 7.5 +/- 1.1 to 3.8 +/- 0.4 pg mL-1 (P = 0.01). After injection of desmopressin urine flow was completely restored, whereas urine osmolality and sodium excretion were only partially normalized. Since tubular conservation of water and fractional water reabsorption decreased during hypothermia, the diuresis must have resulted from an augmented loss of water. This is further supported by the fact that osmolal excretion was not influenced either by hypothermia or by desmopressin. It is concluded that the diuresis in consequence to hypothermia is due both to a decrease in the release of ADH and to a reduction of renal medullary hypertonicity.

Topics: Anesthesia; Animals; Blood Pressure; Cold Temperature; Deamino Arginine Vasopressin; Diuresis; Glomerular Filtration Rate; Hypothermia; Injections, Intraperitoneal; Kidney; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Vasopressins