ORCID Profile
0000-0003-3193-2559
Current Organisation
Australian Red Cross Blood Service New South Wales and Australian Capital Territory
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Publisher: Springer Science and Business Media LLC
Date: 04-04-2022
DOI: 10.1186/S40635-022-00439-6
Abstract: Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock. A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA. Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently ( p 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L ( p 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels ( p 0.0001). The novel crystalloid supported rapid peripheral vasodilation ( p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery ( p = 0.012) but delayed peripheral perfusion ( p = 0.034). Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.51893/2021.1.OA3
Abstract: BACKGROUND: Haemorrhage is a major cause of death in severe trauma. Fibrinogen plays a critical role in maintaining haemostasis in traumatic haemorrhage, and early replacement using fibrinogen concentrate (FC) or cryoprecipitate (Cryo) is recommended by several international trauma guidelines. Limited evidence supports one product over the other, with widespread geographic and institutional variation in practice. Two previous trials have investigated the feasibility of rapid FC administration in severely injured trauma patients, with conflicting results. OBJECTIVE: To compare the time to fibrinogen replacement using FC or Cryo in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia. DESIGN, SETTING, PATIENTS AND INTERVENTIONS: A multicentre controlled pilot trial in which adult trauma patients with haemorrhage were randomly assigned (1:1) to receive FC or Cryo for fibrinogen replacement, guided by FIBTEM A5 (functional fibrinogen assessment at 5 minutes after clot formation, using rotational thromboelastometry). MAIN OUTCOME MEASURES: The primary outcome was time to commencement of fibrinogen replacement. Secondary outcomes included effects of the intervention on plasma fibrinogen levels and clinical outcomes including transfusion requirements and mortality. RESULTS: Of the 100 randomly assigned patients, 62 were hypofibrinogenaemic and received the intervention (n = 37) or Cryo (n = 25). Median (interquartile range [IQR]) time to delivery of FC was 29 min (23–40 min) compared with 60 min (40–80 min) for Cryo (P = 0.0001). All 62 patients were hypofibrinogenaemic before receiving FC or Cryo (FC: median FIBTEM A5, 8 mm [IQR, 7–9 mm] Cryo: median FIBTEM A5, 9 mm [IQR, 5–10 mm]). In the FC arm patients received a median of 3 g FC (IQR, 2–4 g), and in the Cryo arm patients received a median of 8 units of Cryo (IQR, 8–14 units). Restoration of fibrinogen levels was achieved in both arms after the intervention. Blood product transfusion, fluid resuscitation and thromboembolic complications were similar in both arms. Overall mortality was 15.3%, with more deaths in the FC arm. CONCLUSION: Fibrinogen replacement in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia was achieved substantially faster using FC compared with Cryo. Fibrinogen levels increased appropriately using either product. The optimal method for replacing fibrinogen in traumatic haemorrhage is controversial. Our results will inform the design of a larger trial powered to assess patient-centred outcomes.
Location: Australia
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