Newer Advances to Curb Uncontrolled Trauma Bleeding

An analysis of data in cardiac patients from Liverpool indicates that in most haemorrhage cases (82 per cent), a surgical cause for the bleeding is readily identifiable

Dr. V Muralidhar

Massive uncontrolled bleeding is a major problem after major trauma or surgery. The patient is often rushed to a hospital where he is administered fluids (colloids and crystalloids) in large quantities followed by blood and blood components. Simultaneously, efforts are made to surgically control bleeding. If there is a specific surgical cause, then the bleeding is quickly controlled by plugging and tying the cause. But in some situations, there is a diffuse and non-specific bleeding which continues and quickly goes out of control because of limited supplies of blood and blood products. Medical plugging of the site is done by supplying various components of the coagulation cascade which are basically blood and blood products in the right proportions. However, in many cases, this proves unsuccessful which results in the death of the patient. To prevent or decrease mortality and morbidity, there is a search for a medical plug to decrease the need for blood and blood products and their complications. In this article, we will look at advances in managing such patients.

Assessment of Haemorrhage

In situations where patients are bleeding, the first question is to determine whether this is surgically correctable. Confirmation with specific factor levels can follow if necessary. No agent, however, should be seen as a 'plug' for the control of surgical bleeding, and where postoperative blood loss is excessive, early surgical re-exploration should be undertaken. An analysis of data in cardiac patients from Liverpool indicates that in most such cases (82 per cent), a surgical cause for the bleeding is readily identifiable. Delay in taking such patients back to theatre not only results in a waste of transfusion resources, but more importantly, also results in increased morbidity and mortality. Congenital bleeding and clotting disorders would have a significant history of repeated bleeds and transfusions and must be ruled out. Development of primary and secondary fibrinolysis may also complicate the bleeding and may need to be considered, diagnosed and treated accordingly. But, in this article, the focus is only on massive bleeding without being associated with any such syndromes.

Monitoring

A profusely bleeding patient needs basic and advanced monitoring. Basic monitoring includes noninvasive pulse oximetry (SpO2), continuous ECG for analysis of heart rate and rhythm, noninvasive blood pressure immediately followed by invasive blood pressure monitoring. A central venous pressure can guide fluid replacement. In some cases, this may be inadequate and may necessitate a Swan- Ganz pulmonary artery catheter for cardiac output measurement and pulmonary artery catheter wedge pressure measurement. A transoesophageal echocardiography (TEE) may help in diagnosis and continuous monitoring of cardiac and vascular injuries not diagnosed by the routine monitoring. Continuous temperature monitoring is vital as hypothermia occurs due to massive transfusion. Electrolyte and acid base monitoring is an absolute necessity and this is estimated by conducting a blood-gas analysis.

Blood Sampling, Grouping & Cross Matching

In case of uncontrolled bleeding, blood should be sent for blood count, grouping, cross matching and coagulation studies. The technique of blood sampling is important as these patients often have multiple cannulas and it is important that the sample is not taken through a line contaminated with heparin. The drug chart should be examined especially for anticoagulants, antifibrinolytics and antiplatelet drugs.

Testing for Clotting

Traditional measurement of coagulation relies on blood assays undertaken by a hospital laboratory. The traditional tests which are carried out are prothrombin time (PT) and activated partial thromboplastin time (APPT), combined with supplementary tests such as fibrinogen level, and thrombin time, usually give an indication as to the type of haemostatic defect. In addition, platelet counts are carried out.

Thromboelastography

Thromboelastography is a diagnostic technology that is used to identify coagulation problems such as those resulting from surgery or trauma with a view to preventing excessive blood loss. In comparison to traditional tests, this is usually carried out in the operating room. Through the measurement of multiple aspects of coagulation, including time to initial clotting, speed of clot strengthening, maximum clot strength (platelet and fibrin interaction) and fibrinolysis, thromboelastography can help diagnose the cause of bleeding or identify patients at high risk of excessive blood loss. It can be used as a replacement for laboratory assays or can be used alongside traditional assay testing. Thromboelastography is particularly well suited for use in surgical procedures which are associated with a high volume of blood loss including cardiac surgery, orthopaedic procedures, liver transplantation/resection, major vascular surgery, trauma surgery, obstetrics, and paediatric surgery.

The main economic benefit of thromboelastography testing is that it can reduce the need for prophylactic or inappropriate transfusions, and the costs associated with them, and enables more rapid diagnosis and treatment of the cause of bleeding with a potential reduction in death, complications and length of ITU or hospital stay. Given the scarcity of blood products and critical care beds in hospitals, these are important outcomes. Although viral infections resulting from transfusions are relatively rare, transfusions in surgical patients are associated with increased mortality and morbidity Thromboelastometry, as used in the ROTEMSystems, is based on rotation thromboelastography (Calatzis et al, 1996) which is related, but in some aspects different from classical thromboelastography. In classical thromboelastography (Hartert 1948), a blood sample is placed into a cuvette (cup) which rotates gently back and forth with a cycle time of 6/min. The non-physiological surface of the cup (+/- added calcium ions) activates coagulation. A sensor (pin), connected with a torsion wire, is inserted into the sample. Clot formation generates a physical connection between the inner surface of the cup and the surface of the sensor. The change of elasticity is detected with an appropriate technology, today by a computer. Results obtained by classical thromboelastography are dependent on the activity of the plasmatic coagulation system, platelet function, fibrinolysis and many factors which influence these interactions, including several drugs. A practical limitation of many instruments, however, is the requirement for exact leveling and its susceptibility to mechanical shocks or vibrations. Many limitations of classical thromboelastography are overcome by the innovative rotation thromboelastometry (ROTEM). Data obtained with ROTEMSystems correlate well with the classical thromboelastography (Calatzis et. al, 1996).

In ROTEMSystems, the pin (sensor) is fixed on the tip of a rotating shaft which is guided by a high precision ball bearing system. The shaft rotates back and forth (+/- 4.75 °; cycle time 10/min). It is connected with a spring for the measurement of elasticity. The exact position of the axis is detected by the reflection of light by a small mirror which is attached to the shaft. The loss of the elasticity upon clotting of the sample leads to a change in the rotation of the shaft. This is detected by a CCD array and the data are analysed by a computer. This opto-mechanical detection method provides good protection against the impact of vibrations and mechanical shocks. Transportation and installation of the instrument has become very simple.

The other newer technologies include functional platelet function monitor which gives us an idea about the percentage of platelets which are normal and the percentage of platelets which have a qualitative defect. Sonoclot is another technology to determine clotting disorders.

Basic Requirements

Two basic requirements are rapid administration of fluids and blood and; salvage technologies for preserving blood. Rapid administration of blood and blood products need special large bore cannulas inserted into cental veins. There are a number of large bore cannulas which are 7-8.5 F arterial and venous sheaths. These are large enough to administer one-two liters of fluids and blood in a minute. A newer sheath which is now available and which deserves mention is the Advanced Venous Access device (9.5 F) which also has a port for placement of a Swan-Ganz pulmonary artery cardiac output catheter (Edwards).

To assist in rapid administration a number of devices are used - pressure bags, level-one rapid transfusers, rapid transfusers, combined rapid transfusers and blood salvage equipment.

Blood salvage is a technique to use the blood being lost from the patient (autologous transfusion). This is commonly called the cell saver. The blood is sucked into the blood salvage machine (cell saver) and the blood is centrifuged and washed with heparinised saline. The washed cells are then retransfused, which helps in saving bank blood and prevents the complications of receiving blood.

Recombinant Activated Factor VII (rFVIIa)

In recent years, there has been increasing interest in using factor VIIa in major haemorrhage in non-haemophilia patients. Recombinant activated factor VII (rFVIIa) has been approved by the US Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors.

Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. Other recently approved indications for rFVIIa was extended in Europe to include the treatment of bleeding episodes and prevention of bleeding in relation to surgery or invasive procedures in patients with congenital FVII deficiency and in patients with Glanzmann's thrombasthenia with antibodies to GP IIb-IIIa and/or human leukocyte antigen (HLA), and with past or present refractoriness to platelet transfusions.

Guidelines are still being developed for use of rFVIIa in massive bleeding and hold a lot of promise. The limitations are the inability to carry out randomised double blind studies in clinical situations. A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel to develop guidelines for use of rFVIIa use in uncontrolled bleeding.

Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomised, controlled trials allow for the introduction of more established evidence-based guidelines.

The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa.

Cessation of bleeding was achieved in 26 of 36 (72 per cent) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61 per cent (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30-57 per cent). As a result of the lack of controlled trials, these guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.

The writer is Senior Consultant Department of Anaesthesiology and Intensive care Indraprastha Apollo Hospitals New Delhi
Email: murali2v@gmail.com