1 Department of Anaesthesia and 2 Department of Haematology, University of Cape Town, Medical School, Observatory, Cape 7925, South Africa*Corresponding author
Declaration of interest: Fresenius AG contributed to the costs of the investigation.
Accepted for publication: April 4, 2002
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Abstract |
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Methods. Patients were randomly allocated to receive either crystalloid or colloid intravenous fluid. An epidural was administered. Samples of venous blood were taken before fluid administration, after completion of the epidural and initial fluid load, during surgery before heparin, and after 24 h. Thrombelastograph® analysis was performed, and full blood count, international normalised ratio, activated partial thromboplastin time, D-dimers and thrombinantithrombin complex were measured.
Results. In the crystalloid group, enhanced coagulation compared with baseline was demonstrated after initial fluid load (mean (SD) r-time 10.1 (4.9) min; P<0.033; k-time 3.5 (1.7) min; P<0.01; -angle 54.9 (13.9) degrees; P<0.01) and before heparin administration (r-time 8.8 (3.9) min; P<0.01;
-angle 54.9 (12.6) degrees; P<0.02). There was no enhancement of coagulation in the colloid group. There were no changes from baseline after 24 h.
Conclusions. This study confirms that the enhanced perioperative coagulation mechanism is related to dilution, rather than surgery, and is triggered by rapid crystalloid haemodilution. Consideration should be given to the use of colloid rather than crystalloid solutions for rapid fluid loading in vasculopathic patients undergoing surgery.
Br J Anaesth 2002; 89: 22630
Keywords: blood, coagulation; blood, haemodilution; equipment, Thrombelastograph®
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Introduction |
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While haemodilution-related coagulation enhancement is of great interest, it has not yet been demonstrated whether it is relevant in a clinical setting and whether the effect occurs on the basis of a stress response or on the basis of the haemodilution-induced enhancement of coagulation. We have therefore performed a controlled in vivo study investigating the now established and well-described effects of intravenous fluid on coagulation in peripheral vascular surgery under regional anaesthesia. Furthermore, we investigated whether haemodilution-induced enhancement of coagulation is demonstrable after fluid administration, before surgical stimulus, or only after the surgery has begun; and whether the nature (crystalloid or colloid) of the fluid used has an influence on the effect.
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Methods |
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All subjects received premedication of oral temazepam 10 or 20 mg 1 h before surgery. When the patient arrived in the operating theatre, an intravenous cannula was inserted into a suitable forearm vein. A 20G cannula was inserted into a suitable vein on the opposite forearm for blood sampling. An intravenous infusion of either crystalloid (Plasmalyte B® or modified Ringers lactate) 1000 ml or hydroxyethyl starch (Haes-steril®) 500 ml was commenced. The choice of crystalloid was made on the basis of the diabetic state of the patient, Plasmalyte B being used in diabetic patients and modified Ringers lactate (from which calcium is excluded) in the remainder. All patients received an epidural anaesthetic consisting of 0.5% bupivacaine administered through an epidural catheter inserted at a suitable lumbar intervertebral space. No additional sedative agents were administered, and if the regional analgesic technique was inadequate, the patient was excluded from the study. The volume of bupivacaine used initially was 1012 ml, with subsequent top-up doses administered as necessary to achieve and maintain a sensory level at T10 or above. Approximately half the volume of the fluid load was administered before commencement of the regional block, and the remainder of fluid infused during the performance of the epidural. Hypotension requiring the administration of vasopressor agents was also a post-hoc exclusion criterion. Once a satisfactory block was established, the patient was transferred to the operating room and surgery was commenced. During surgery, patients received only crystalloid or colloid depending on their group, but the volume of fluid infused was judged against clinical criteria of fluid requirement. Blood samples were taken before the administration of any intravenous fluid (Sample 1; baseline), after completion of both the regional anaesthetic and the initial fluid load (Sample 2), during surgery immediately before heparin administration and arterial clamping (Sample 3) and 24 h after the administration of the regional block (Sample 4). Thrombelastograph® analysis and the following tests were performed: full blood count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and thrombinantithrombin (TAT) complexes.
All samples were taken following a 5 ml blood flush to remove contaminants from the sampling site.
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Results |
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Discussion |
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The regional anaesthetic technique is highly effective at blocking the stress response to surgical stimulation that might normally have an effect on the enhancement of coagulation. Had the surgery produced a discernible effect on coagulation, some change in the Thrombelastograph® parameters would have been expected after the infusion of fluid and the administration of heparin (between Samples 2 and 3); however, this was not demonstrable. Indeed the colloid studied, hydroxyethyl starch 200/0.5, had almost no effect on coagulation either at the time of acute haemodilution, or during surgery. The Thrombelastograph® measures were only marginally changed by the time of heparin administration. Whilst it is possible that the colloid impaired a purely surgically induced enhancement of coagulation, this is unlikely, and it appears that the major part of the alteration in coagulation seen in the crystalloid group was attributable to the fluid administered, rather than the surgical stimulus. It is clear that enhanced coagulation in the crystalloid group occurred before commencement of surgery, and continued during the surgical stimulus. In the colloid group, the enhancement of coagulation may have been inhibited by the antiplatelet activation effect of the hydroxyethyl starches2 through its prevention of platelet clumping. This in turn may result in the findings of non-altered coagulation in the starch group compared with the crystalloid group.
We have recently shown that the probable cause for the hypercoagulability is an imbalance between the naturally occurring anticoagulants and activated procoagulants, with a reduction in antithrombin III probably being the most important. This effect lowers the threshold above which positive feedback into the intrinsic coagulation pathway occurs, thus leading to the enhanced coagulation.16 Of note is that this is not dependent on a mass effect, as even a relatively small decrease in anticoagulants (2030%) can result in this imbalance.17 18 We have been able to demonstrate that the enhanced coagulability is induced by the rapid infusion of fluid, which alters the balance between anticoagulants and the spontaneously activated fraction of procoagulants, which by definition results in an enhancement of clot formation. It is of interest that the INR was increased at Sample 3 in the colloid group. This is a test of the extrinsic coagulation pathway, which is not measured by the Thrombelastograph®. This may be the site of action of the colloids, thus offsetting the haemodilution-induced reduction in anticoagulant factors, which is similar with both crystalloid and colloid dilution.2
Janvrin and colleagues19 have previously shown an increase in coagulation and incidence of deep vein thrombosis in patients receiving crystalloid fluid during surgery. We have now taken this one step further, and have managed to define the onset of enhanced coagulation related to haemodilution per se. We have also demonstrated that this effect is independent of the response to surgery. It is noted that while the major part of the enhanced coagulation observed in this study was the result of the crystalloid fluid administered, we cannot totally exclude the possibility that surgical trauma resulted in the release of procoagulant factors into the systemic circulation. This in turn may have contributed to the enhanced coagulation seen in the crystalloid group. This effect appears to be modulated by the use of colloids, with no change in Thrombelastograph® values from normal after haemodilution, or surgery. This has also been previously demonstrated.2
While this study focuses on the intra-operative response of coagulation to fluids and surgery, it is of interest that enhanced coagulability was not demonstrated in either group 24 h after surgery. However, the lack of difference either within or between groups at 24 h (Sample 4) was not investigated, as this study was not designed, nor powered, to look at outcome variables in the postoperative period.
It is tempting to speculate that the increase in coagulation during the pre-heparin phase in the crystalloid group may lead to an increased risk of occlusive vascular events, but such a conclusion cannot be drawn on the basis of these results. However, this study does suggest that the mechanism of enhanced coagulation is related to dilution itself, and thus an imbalance between coagulants and anticoagulants, and that this is triggered by the rapid crystalloid haemodilution. Given that patients undergoing vascular surgery may be at an increased risk of coagulation, especially intra-arterial coagulation, consideration should be given to avoiding the use of crystalloids for rapid fluid loading in vasculopathic patients undergoing surgery.
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References |
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