Intraoperative Management Of Haemostasis

Adequate intravenous access is imperative for proper intra-operative management of bleeding during OLT. In addition to large bore intravenous catheters (9 and 8.5 French) for volume and blood product transfusion, an 18-French percutaneous veno-venous bypass (PVVB) cannula is often inserted in the right internal jugular vein.6 This PVVB cannula can also be used for blood product transfusions. A device that will allow rapid infusion of large volume of warmed fluids and blood products, is indispensable. The FMS 2000® (Belmont Instrument Corporation, Billerica, MA, USA) is such a device that can be used in the transplant procedure. It warms fluid and blood to body temperature, as they are administered to the patient. Rapid infusion (up to 500 ml/minute) of fluids and blood, safely to the patient, is assured with the incorporation of air detectors in the device. It is compact and quiet, and if blood loss is extremely rapid two devices can be utilised simultaneously, in parallel, to enable up to 1000 ml/minute infusion rate. Finally, a blood salvaging system, such as, the Brat 2® (COBE Cardiovascular, Inc., Arvada, CO, USA) cell saver will decrease the requirement for blood bank products.

After an OLT is scheduled, the hospital blood bank must receive a sample of the recipient patient's blood for type and cross matching. A minimal of 10 units of packed red blood cells (RBC), 10 units of fresh frozen plasma (FFP), and a 10-pool unit of PLT should be available before the patient is brought into the operating room.

The transplant procedure itself is divided into three stages. Stage I is the pre-anhepatic or dissection stage; Stage II is the anhepatic stage; and Stage III is the neo-hepatic stage. Stage I extends from the abdominal incision to vascular isolation and removal of the native or diseased liver. Stage II begins when the native liver is effectively removed from the patient's circulation by complete vascular isolation, until perfusion of the donor graft. Stage III begins with reperfusion of the donor graft and ends with closure.

In Stage I, the predominant factors influencing the haemostatic system include pre-existing coagulopathy, clotting factors' dilution, and thrombocytopenia. During Stage II, there is increased fibrinolysis due to absence of the liver. As a result, tPA is not cleared and there are decreased levels of plasminogen activator inhibitor-1 (PAI-1).1 The onset of Stage III is marked by the development of mild to moderate fibrinolysis. This is noted in approximately 80% of all transplant patients, but severe fibrinolysis with evidence of diffuse bleeding occurs in about 20% of the cases, and this must be treated.7

Treatment of coagulopathy requires careful monitoring of the clotting system through TEG or traditional clotting studies, at specific periods during the OLT procedure. The recommended intervals are shown in Table 1. Depending on the duration of the various stages, some of the intervals may overlap (e.g., II + 45 and III — 15) and would require only one study. If TEG is used, additives, such

Table 1. Recommended Clotting Study Intervals During OLT

Interval

Description

TEG Channels

B

Baseline

N

I + 60

Incision + 60 min

N

II - 30

30 min before Stage II

N

II + 10

Stage II + 10 min

N

II + 45

Stage II + 45 min

N + A

III - 15

15 min before Stage III

N

III + 5

Stage III + 5 min

N + A + P

III + 30

Stage III + 30 min

N + P

III + 90

Stage III + 90 min

N

Q2

Every 2 hrs

N

End

Closure

N

N = Natural, A = epsilon aminocaproic acid, P = protamine.

N = Natural, A = epsilon aminocaproic acid, P = protamine.

as, epsilon aminocaproic acid or protamine sulphate to the patient's native or natural blood, may be used to aid in the diagnosis and treatment of coagulopathies.

Use of FFP to replace clotting factor deficiencies is usually indicated and administered when necessary throughout Stages II and I. If significant haemorrhage exists during the procedure, then replacement of blood products with a rapid infusion system will be necessary. Typically, two units of packed RBC, two units of FFP, and 500 ml of normal saline are combined to the transfusion device reservoir to provide the patient with satisfactory levels of clotting factors (> 30%) and haematocrit (26 to 28%).

If fibrinolysis is detected, then small doses of anti-fibrinolytics, such as, tranexamic acid, aminocaproic acid (125 to 250 mg), or aprotinin must be carefully considered.7-10 If fibrinolysis is significant and fibrinogen levels are depleted, then the use of cryoprecipitate may be indicated. Occasionally, protamine sulfate may be required in Stage III, if the TEG detects a significant heparin effect. This hep-arin effect is usually self-limiting and resolves by 30 minutes after donor organ reperfusion, in a well-functioning graft.11

The optimal regime for aprotinin administration during OLT is still a point of debate. The prophylactic use of aprotinin in a large dose (1,000,000-2,000,000 KIU initial dose followed by 500,000KIU/h infusion), small dose (500,000KIU initial dose followed by 150,000KIU/h infusion), or lower dose (200,000KIU/h continuous infusion from the beginning of the case without a loading dose) has been recommended by various liver transplant centres in order to control fibrinolysis and reduce blood product transfusions.12,13 The European Multicentre Study on the use of Aprotinin in Liver Transplantation (EMSALT) showed significant reduction in blood loss and transfusion requirements by 50% and 30%, respectively.14 These results are a dose-dependent strong anti-fibrinolytic effect and a weaker anti-coagulant effect.15 Aprotinin is a non-specific serine protease inhibitor with anti-fibrinolytic activity. At low dose it also inhibits plasmin, while at higher doses it inhibits the effects of kallikrein- and leukocyte-derived proteases, such as, elastase.

Other pharmacological agents that have been used in liver transplantation with various levels of success include DDAVP, conjugated estrogens, recombinant Factor Vila (Novo Seven®), and Factor VIII/von Willebrand Factor combinations (Humate-P®).16--18

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