Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

BACKGROUND Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration. METHODS This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry. RESULTS All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site. CONCLUSION This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would be time consuming. LEVEL OF EVIDENCE Prospective, randomized, therapeutic feasibility study in an animal model, level V.

[1]  H. Schöchl,et al.  Trauma Bleeding Management: The Concept of Goal-Directed Primary Care , 2014, Anesthesia and analgesia.

[2]  D. Fries,et al.  Fibrinogen concentrate in dilutional coagulopathy: a dose study in pigs , 2014, Transfusion.

[3]  R. Balog,et al.  What is the evidence of utility for intraosseous blood transfusion in damage-control resuscitation? , 2013, The journal of trauma and acute care surgery.

[4]  K. Inaba,et al.  Impact of fibrinogen concentrate alone or with prothrombin complex concentrate (+/− fresh frozen plasma) on plasma fibrinogen level and fibrin-based clot strength (FIBTEM) in major trauma: a retrospective study , 2013, Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine.

[5]  H. Redl,et al.  The effect of fibrinogen concentrate and factor XIII on thromboelastometry in 33% diluted blood with albumin, gelatine, hydroxyethyl starch or saline in vitro. , 2013, Blood transfusion = Trasfusione del sangue.

[6]  K. Brohi,et al.  Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy , 2013, Critical Care.

[7]  K. Inaba,et al.  Estimation of plasma fibrinogen levels based on hemoglobin, base excess and Injury Severity Score upon emergency room admission , 2013, Critical Care.

[8]  W. Voelckel,et al.  Practical application of point-of-care coagulation testing to guide treatment decisions in trauma , 2013, The journal of trauma and acute care surgery.

[9]  M. Donald,et al.  Intraosseous access in the prehospital setting-ideal first-line option or best bailout? , 2013, Resuscitation.

[10]  M. Pasquier,et al.  EZ-IO(®) intraosseous device implementation in a pre-hospital emergency service: A prospective study and review of the literature. , 2013, Resuscitation.

[11]  S. Stanworth,et al.  Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes , 2012, Journal of thrombosis and haemostasis : JTH.

[12]  B. Sørensen,et al.  Fibrinogen as a Hemostatic Agent , 2012, Seminars in Thrombosis & Hemostasis.

[13]  W. Voelckel,et al.  Early and individualized goal-directed therapy for trauma-induced coagulopathy , 2012, Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine.

[14]  Kenichi A. Tanaka,et al.  Fibrinogen and Hemostasis: A Primary Hemostatic Target for the Management of Acquired Bleeding , 2012, Anesthesia and analgesia.

[15]  U. Schweigkofler,et al.  Efficacy of the EZ-IO® needle driver for out-of-hospital intraosseous access - a preliminary, observational, multicenter study , 2011, Scandinavian journal of trauma, resuscitation and emergency medicine.

[16]  L. Chambers,et al.  Frequency and characteristics of coagulopathy in trauma patients treated with a low- or high-plasma-content massive transfusion protocol. , 2011, American journal of clinical pathology.

[17]  J. Heltne,et al.  Emergency intraosseous access in a helicopter emergency medical service: a retrospective study , 2010, Scandinavian journal of trauma, resuscitation and emergency medicine.

[18]  R. Rossaint,et al.  Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury , 2010, Critical care.

[19]  C. Solomon,et al.  Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery , 2010, British journal of anaesthesia.

[20]  R. Rossaint,et al.  A New Model for Blunt Liver Injuries in the Swine , 2009, European Surgical Research.

[21]  James M Burgert Intraosseous infusion of blood products and epinephrine in an adult patient in hemorrhagic shock. , 2009, AANA journal.

[22]  W. Chandler,et al.  TRANSFUSION PRACTICE: Thrombin generation in trauma patients , 2009, Transfusion.

[23]  Kenichi A. Tanaka,et al.  Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. , 2009, British journal of anaesthesia.

[24]  R. Christy,et al.  Evaluation of intraosseous delivery of factor VIIa during hemorraghic shock in the pig. , 2009, Military medicine.

[25]  C. P. Mahoney,et al.  Intra-Osseous Access (EZ-IO®) for Resuscitation: UK Military Combat Experience , 2007, Journal of the Royal Army Medical Corps.

[26]  E. Racht,et al.  Clinical evaluation of a novel intraosseous device for adults: prospective, 250-patient, multi-center trial. , 2005, JEMS : a journal of emergency medical services.

[27]  T. Haas,et al.  Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. , 2005, British journal of anaesthesia.

[28]  M. James,et al.  Haemodilution-Induced Enhancement of Coagulation is Attenuated in Vitro by Restoring Antithrombin III to Pre-Dilution Concentrations , 2001, Anaesthesia and intensive care.

[29]  B. Seifert,et al.  Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation. , 1997, British journal of anaesthesia.

[30]  M. Plewa,et al.  Hematologic safety of intraosseous blood transfusion in a swine model of pediatric hemorrhagic hypovolemia. , 1995, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[31]  E. Vahtera,et al.  Hemostatic Factors and Replacement of Major Blood Loss with Plasma-Poor Red Cell Concentrates , 1995, Anesthesia and analgesia.

[32]  W. Martini Fibrinogen Availability and Coagulation Function after Hemorrhage and Resuscitation in Pigs , 2011, Molecular medicine.