The Influence of Noradrenaline Infusion on Coagulation and Fibrinolysis in Patients With Isolated Severe Brain Injury

STUDY DESIGN AND METHODS The research shall be carried out at the Department of Anaesthetics and Surgical Intensive Care/Intensive Care Unit (ICU) at the University Medical Centre Ljubljana and will begin once it is approved by the Slovenian National Medical Ethics Committee. Patients will be included in the research once the informed consent form is signed by their relatives or their legal guardian.

Patients and the course of the study The research study will focus on 60 consecutive patients with severe traumatic brain injury (TBI) hospitalised at the emergency unit's ICU, who will be treated according to the Advanced Trauma Life Support guidelines, will undergo a computerized tomography (CT) scan of the head, and will have been implanted with an electrode for monitoring intracranial pressure (ICP). Both female and male patients, age 18 to 80, with Glasgow Coma Scale (GCS) ≤ 8 and Head Abbreviated Injury Scale (AIS) ≥ 3 shall be included in the study. Patients with any kind of extracranial injury, patients receiving anticoagulation or anti aggregation therapy, patients with a known neurological, haematological, malign or liver disease, patients with an infection and after a cardiac arrest, after craniotomy, patients that have received transfusion of concentrated erythrocytes (> 1 bag) and/or fresh frozen plasma, thrombocyte plasma, patients with a body temperature of < 35°C and pregnant women will all be excluded from the study, as will be those cases where it will be impossible to perform targeted tests in the expected time frame.

At the ICU, patients will receive treatment according to the guidelines for the treatment of severe traumatic brain injury. All patients will be sedated with midazolam, they will receive analgesia with fentanyl, and when required considering the level of ICP, will also receive a 2% propofol infusion. They will all be mechanically ventilated. A non-heparinized central venous catheter and an artery catheter will both be routinely inserted in all cases. Blood samples for the study will be taken from the internal jugular vein with a singular puncture.

Systemic blood pressure, heart rate, central body temperature, peripheral blood oxygen saturation (SpO2), ICP, cerebral perfusion pressure (CPP) and bispectral index (BIS) of the depth of anaesthesia will be monitored at all times. Pupillary response and depth of sedation using the Richmond Agitation-Sedation Scale (RASS) will be performed once per hour. Hydration will be estimated with stroke volume variation (SVV) one or twice per day. Patients whose CPP will not meet the desired value (70 mmHg) will receive systemic intravenous infusion of NA solution (0.16 mg/ml) in the dosage required to meet the target CPP. Another CT scan will be performed 12 to 24 hours after injury and after sudden deterioration in health condition, if necessary.

Blood samples will be taken daily from the artery catheter to determine the values of electrolytes, glucose, number of leukocytes and haemogram, number of thrombocytes all of which are routinely performed on a daily basis.