Permissive Hypotension and Desmopressin Enhance Clot Formation

Rezende-Neto, João; Rizoli, Sandro; Andrade, Marcus V.; Ribeiro, Daniel Dias; Lisboa, Thiago Assis; Camargos, Elizabeth Ribeiro da Silva; Martins, Paula; Cunha-Melo, José Renan

doi:10.1097/ta.0b013e3181c66393

Cited by 25 publications

(11 citation statements)

References 31 publications

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“…An aortic tear model in rabbits showed that both permissive hypotension and desmopressin augments clot formation; however, the desmopressin was then administered 1 hour before hypovolemic shock was induced. 45 In the cut tail model of the rat, neither tranexamic acid nor desmopressin had such an effect when given approximately 5 min before hemorrhage was induced. 46 In addition, desmopressin did not alleviate hemorrhage in the femoral artery model of hypothermic rats; here, the drug was injected 5 min after hypovolemic hypotension had been induced.…”

Section: Hemostatic Dressings and Drugsmentioning

confidence: 99%

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Hahn

2012

Acta Anaesthesiol Scand

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Intravenous fluid is life-saving in hypovolemic shock, but fluid sometimes aggravates the bleeding. During the past 25 years, animal models have helped our understanding of the mechanisms involved in this unexpected effect. A key issue is that vasoconstriction is insufficient to arrest the bleeding when damage is made to a major blood vessel. ‘Uncontrolled hemorrhage’ is rather stopped by a blood clot formed at the outside surface of the vessel, and the immature clot is sensitive to mechanical and chemical interactions. The mortality increases if rebleeding occurs. In the aortic tear model in swine, hemorrhage volume and the mortality increase from effective restoration of the arterial pressure. The mortality vs. amount of fluid curve is U-shaped with higher mortality at either end. Without any fluid at all, irreversible shock causes death provided the hemorrhage is sufficiently large. Crystalloid fluid administered in a 3 : 1 proportion to the amount of lost blood initiates serious rebleeding. Hypertonic saline 7.5% in 6% dextran 70 (HSD) also provokes rebleeding resulting in higher mortality in the recommended dosage of 4 ml/kg. Uncontrolled hemorrhage models in rats, except for the ‘cut-tail’ model, confirm the results from swine. To avoid rebleeding, fluid programs should not aim to fully restore the arterial pressure, blood flow rates, or blood volume. For a hemorrhage of 1000 ml, computer simulations show that deliberate hypovolemia (−300 ml) would be achieved by infusing 600–750 ml crystalloid fluid over 20–30 min or 100 ml of HSD over 10–20 min in an adult male

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Section: Hemostatic Dressings and Drugsmentioning

confidence: 99%

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Hahn

2012

Acta Anaesthesiol Scand

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“…Aggressive fluid resuscitation was the initial fluid therapy recommended for many decades. However, this approach may contribute to increased blood loss and higher mortality [23]. The warning concerning the massive administration of fluid was already reported about 100 years ago by Captain Cannon [24].…”

Section: Balanced Resuscitationmentioning

confidence: 99%

Damage control resuscitation: a practical approach for severely hemorrhagic patients and its effects on trauma surgery

Mizobata

2017

j intensive care

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Coagulopathy observed in trauma patients was thought to be a resuscitation-associated phenomenon. The replacement of lost and consumed coagulation factors was the mainstay in the resuscitation of hemorrhagic shock for many decades. Twenty years ago, damage control surgery (DCS) was implemented to challenge the coagulopathy of trauma. It consists of three steps: abbreviated surgery to control the hemorrhage and contamination, resuscitation in the intensive care unit (ICU), and planned re-operation with definitive surgery. The resuscitation strategy of DCS focused on the rapid reversal of acidosis and prevention of hypothermia through the first two steps. However, direct treatment of coagulopathy was not emphasized in DCS. Recently, better understanding of the pathophysiology of coagulopathy in trauma patients has led to the logical opinion that we should directly address this coagulopathy during major trauma resuscitation. Damage control resuscitation (DCR), the strategic approach to the trauma patient who presents in extremis, consists of balanced resuscitation, hemostatic resuscitation, and prevention of acidosis, hypothermia, and hypocalcemia. In balanced resuscitation, fluid administration is restricted and hypotension is allowed until definitive hemostatic measures begin. The administration of blood products consisting of fresh frozen plasma, packed red blood cells, and platelets, the ratio of which resembles whole blood, is recommended early in the resuscitation. DCR strategy is now the most beneficial measure available to address trauma-induced coagulopathy, and it can change the treatment strategy of trauma patients. DCS is now incorporated as a component of DCR. DCR as a structured intervention begins immediately after rapid initial assessment in the emergency room and progresses through the operating theater into the ICU in combination with DCS. By starting from ground zero with the performance of DCS, DCR allows the trauma surgeon to correct the coagulopathy of trauma. The effect of the reversal of coagulopathy in massively hemorrhagic patients may change the operative strategy with DCS.

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“…All animals were placed on a heating pad to maintain rectal temperature above 35 o C during the experiment as previously described 17 . In brief, MAP was continuously …”

Section: Hemorrhage Proceduresmentioning

confidence: 99%

Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

et al. 2015

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PURPOSE:To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding. METHODS:Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3:FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7:FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed. RESULTS:Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM. CONCLUSIONS:Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents.

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Permissive Hypotension and Desmopressin Enhance Clot Formation

Abstract: PH reduced bleeding and improved hemostasis compared with normotensive resuscitation. DDAVP given preshock exerted similar effects with normotensive resuscitation.

Cited by 25 publications

References 31 publications

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Damage control resuscitation: a practical approach for severely hemorrhagic patients and its effects on trauma surgery

Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

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