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Preparation for regional anaesthesia induces changes in thrombelastography
British Journal of Anaesthesia 84 (3): 403–4 (2000)
Preparation for regional anaesthesia induces changes in thrombelastography H. Gorton1, G. Lyons1 and P. Manraj2 1Obstetric
Anaesthesia, Level 5 Gledhow Wing, St James’ University Hospital, Leeds LS9 7TF, UK. 2Department of Anaesthetics, Hull Royal Infirmary, Hull HU3 2JZ, UK
The effects of crystalloid and colloid infusions on coagulation measured by thrombelastography (TEG) present a confused picture. The influence of environmental factors may explain the disparity between previous studies. We studied two groups of 20 women presenting at term for elective Caesarean section. In the first group, TEG analysis was performed before and after infusion of Gelofusine 500 ml over 15 min. The second group was treated in the same way except that subjects did not receive fluid. We found significant changes in r and k values in both groups, suggesting enhanced coagulation. As hypercoagulable changes were also seen in the group that did not receive fluid preload, the hypothesis that moderate haemodilution causes hypercoagulability must be questioned. The influence of environmental factors can explain differences reported between in vivo and in vitro studies. Br J Anaesth 2000; 84: 403–4 Keywords: measurement techniques, thrombelastography; blood, coagulation; anaesthetic techniques, regional; anaesthesia, obstetric Accepted for publication: September 13, 1999
Reports of the effects of crystalloid and colloid infusions on coagulation measured by thrombelastgraphy (TEG) are ambiguous. Two in vitro studies found that coagulation was enhanced1 2 and two found the reverse.3 4 In vivo studies showed either no change5 or changes attributed to hypercoagulability.6 Similar changes are seen in pregnancy, where a hypercoagulable state develops. This is secondary to increased concentrations of procoagulants, especially fibrinogen, and factors II, VII, VIII, X and XI, and decreased concentrations of natural anticoagulants such as protein S. The associated TEG changes are reduced r and k values, and increased α angle and maximum amplitude (MA).6 The influence of environmental factors may be one explanation for the disparity between in vivo and in vitro studies. In this observational study, we have assessed the effect of environmental factors with and without gelatine preload on coagulation measured by TEG, before spinal anaesthesia for Caesarean section.
Methods and results After obtaining approval from the Ethics Committee and informed consent, we studied two groups of 20 ASA I or II patients, presenting with uncomplicated pregnancies at 36–40 weeks’ gestation for elective Caesarean section with regional anaesthesia. Patients with pre-existing hypertension or gestational hypertension (diastolic pressure ⬎90 mm Hg), pre-existing haematological disorders, history of aspirin,
warfarin, heparin or magnesium treatment, or diabetes mellitus were excluded. In all women a 16-gauge cannula was inserted into a forearm vein and an initial blood sample was obtained for TEG analysis. The first 2 ml of each blood sample was discarded to avoid contamination by tissue thromboplastin, before using 0.36 ml for analysis. Each sample was analysed within 4 min of venepuncture. The samples were native whole blood, and were analysed using disposable cups and pins. Subsequently, subjects were studied sequentially in two groups. In group 1 (n⫽20), colloid (Gelofusine) 500 ml was given over 15 min. A second sample was obtained from the contralateral arm via a 22-gauge cannula after infusion. The only intervention between the two blood samples was administration of fluid. In group 2 (n⫽20), the same procedure was performed except that no fluid was given between the two samples. All women were prepared for double space combined epidural–spinal anaesthesia. This was performed in a standard manner according to established practice. To detect a 30% difference in r values with a power of 0.9 and 0.05 significance level, we calculated that 20 patients would be needed in each group. TEG variables were compared before and after preload using paired t tests with SPSS 7.1 for windows. Unpaired t tests were used to compare changes in TEG variables between groups. P⬍0.05 was considered significant.
© The Board of Management and Trustees of the British Journal of Anaesthesia 2000
Gorton et al.
Table 1 Differences between the first and second samples of four TEG variables (mean (95% confidence intervals (CI) of the difference)) in the preload and control groups Mean difference 0–15 min
95% CI of difference
P
Preload group (n⫽20) r (mm) 7.7 k (mm) 2.57 α angle (°) –4.35 MA (mm) –0.45
3.22, 12.3 1.3, 3.9 –9.2, 0.5 –4.7, 3.84
0.002 0.001 0.076 0.83
Control group (n⫽20) r (mm) 9.8 k (mm) 1.8 α angle (°) –3.8 MA (mm) –2.9
4.4, –1.5, –7.7, –5.6,
0.001 0.05 0.05 0.038
15.3 3.6 0.13 –0.18
Patient characteristics in group 1 were: mean age 29.4 (range 19–38) yr, height 158.15 (SD 8.06) cm, weight 71.25 (12.44) kg and median gestation 38 [range 37–41] weeks; six had singleton pregnancies and two had twins. Characteristics in group 2 were: age 30.5 (20–39) yr, height 163.9 (6.03) cm, weight 78.25 (15.12) kg and gestation 38 [37–39] weeks; three had singleton pregnancies and one had twins. There were no clinically important differences between groups. Differences in TEG variables with and without preload are shown in Table 1; r and k values were significantly shortened (P⬍0.05) in the preload group. In the control group, r and k were significantly reduced and MA was increased (P⬍0.05). There were no significant differences in the magnitude of the changes between groups.
tion. Some of the changes may have been a result of increased circulating catecholamines, which cause platelet degranulation and enhanced platelet aggregation.7 Changes in platelet function have been shown to correlate only with changes in MA8 and because we also reported changes in r and k values, this cannot be regarded as a complete explanation. Although it is known that large volumes of Gelofusine inhibit platelet function, our data did not provide evidence for this. Previous in vivo studies were performed using varying degrees of haemodilution and fluid types, either in volunteers or in patients suffering blood loss during surgery. None independently assessed incidental factors. Changes after preload which indicate hypercoagulation have been attributed to haemodilution which is believed to alter the balance of the activities of thrombin and antithrombin III so that thrombin becomes the more active.1 This hypothesis must be questioned. We propose that changes in in vivo studies6 may be attributed to environmental influences acting on coagulation.
References
Comment We have shown that TEG variables (r and k) were reduced significantly over a 15-min period in women awaiting spinal anaesthesia for elective Caesarean section, whether or not an i.v. infusion was given. It was not possible to attribute changes in coagulation to the effects of preload alone. TEG changes were in keeping with those attributed previously to enhanced coagulation.6 The magnitude of the changes was not clinically significant. We hypothesize that siting an i.v. cannula, attachment of monitoring devices and a 15-min waiting period adjacent to our operating theatre were sufficient to influence coagula-
404
1 Ruttmann TG, James MFM, Viljoen JF. Haemodilution induces a hypercoagulable state. Br J Anaesth 1996; 76: 412–14 2 Ruttmann TG, James MFM, Wells KF. Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation. Br J Anaesth 1999; 82: 110–11 3 Egli GA, Zollinger A, Seifert B, Popovic D, Pasch T, Spahn DK. Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation. Br J Anaesth 1997; 78: 684–9 4 Mardel SN, Saunders FM, Allen H, et al. Reduced quality of clot formation with gelatin-based plasma substitutes. Br J Anaesth 1998; 80: 204–7 5 Karoutsos S, Nathan N, Lahrimi A, Grouille D, Feiss P, Cox DJA. Thrombelastography reveals hypercoagulability after administration of gelatin solution. Br J Anaesth 1999; 82: 175–7 6 Ruttmann TG, James MFM, Aronson I. In-vivo investigation into the effects of haemodilution with hydroxyethyl starch and normal saline on coagulation. Br J Anaesth 1998; 80: 612–16 7 Sharma SK, Philip J. The effect of anaesthetic techniques on blood coagulability in parturients as measured by thromboelastography. Anaesth Analg 1997; 85: 82–6 8 Orlikowski CEP, Rocke DA, Murrar WB, et al. Thrombelastographic changes in preeclampsia and eclampsia. Br J Anaesth 1996; 77: 157–61
Preparation for regional anaesthesia induces changes in thrombelastography H. Gorton1, G. Lyons1 and P. Manraj2 1Obstetric
Anaesthesia, Level 5 Gledhow Wing, St James’ University Hospital, Leeds LS9 7TF, UK. 2Department of Anaesthetics, Hull Royal Infirmary, Hull HU3 2JZ, UK
The effects of crystalloid and colloid infusions on coagulation measured by thrombelastography (TEG) present a confused picture. The influence of environmental factors may explain the disparity between previous studies. We studied two groups of 20 women presenting at term for elective Caesarean section. In the first group, TEG analysis was performed before and after infusion of Gelofusine 500 ml over 15 min. The second group was treated in the same way except that subjects did not receive fluid. We found significant changes in r and k values in both groups, suggesting enhanced coagulation. As hypercoagulable changes were also seen in the group that did not receive fluid preload, the hypothesis that moderate haemodilution causes hypercoagulability must be questioned. The influence of environmental factors can explain differences reported between in vivo and in vitro studies. Br J Anaesth 2000; 84: 403–4 Keywords: measurement techniques, thrombelastography; blood, coagulation; anaesthetic techniques, regional; anaesthesia, obstetric Accepted for publication: September 13, 1999
Reports of the effects of crystalloid and colloid infusions on coagulation measured by thrombelastgraphy (TEG) are ambiguous. Two in vitro studies found that coagulation was enhanced1 2 and two found the reverse.3 4 In vivo studies showed either no change5 or changes attributed to hypercoagulability.6 Similar changes are seen in pregnancy, where a hypercoagulable state develops. This is secondary to increased concentrations of procoagulants, especially fibrinogen, and factors II, VII, VIII, X and XI, and decreased concentrations of natural anticoagulants such as protein S. The associated TEG changes are reduced r and k values, and increased α angle and maximum amplitude (MA).6 The influence of environmental factors may be one explanation for the disparity between in vivo and in vitro studies. In this observational study, we have assessed the effect of environmental factors with and without gelatine preload on coagulation measured by TEG, before spinal anaesthesia for Caesarean section.
Methods and results After obtaining approval from the Ethics Committee and informed consent, we studied two groups of 20 ASA I or II patients, presenting with uncomplicated pregnancies at 36–40 weeks’ gestation for elective Caesarean section with regional anaesthesia. Patients with pre-existing hypertension or gestational hypertension (diastolic pressure ⬎90 mm Hg), pre-existing haematological disorders, history of aspirin,
warfarin, heparin or magnesium treatment, or diabetes mellitus were excluded. In all women a 16-gauge cannula was inserted into a forearm vein and an initial blood sample was obtained for TEG analysis. The first 2 ml of each blood sample was discarded to avoid contamination by tissue thromboplastin, before using 0.36 ml for analysis. Each sample was analysed within 4 min of venepuncture. The samples were native whole blood, and were analysed using disposable cups and pins. Subsequently, subjects were studied sequentially in two groups. In group 1 (n⫽20), colloid (Gelofusine) 500 ml was given over 15 min. A second sample was obtained from the contralateral arm via a 22-gauge cannula after infusion. The only intervention between the two blood samples was administration of fluid. In group 2 (n⫽20), the same procedure was performed except that no fluid was given between the two samples. All women were prepared for double space combined epidural–spinal anaesthesia. This was performed in a standard manner according to established practice. To detect a 30% difference in r values with a power of 0.9 and 0.05 significance level, we calculated that 20 patients would be needed in each group. TEG variables were compared before and after preload using paired t tests with SPSS 7.1 for windows. Unpaired t tests were used to compare changes in TEG variables between groups. P⬍0.05 was considered significant.
© The Board of Management and Trustees of the British Journal of Anaesthesia 2000
Gorton et al.
Table 1 Differences between the first and second samples of four TEG variables (mean (95% confidence intervals (CI) of the difference)) in the preload and control groups Mean difference 0–15 min
95% CI of difference
P
Preload group (n⫽20) r (mm) 7.7 k (mm) 2.57 α angle (°) –4.35 MA (mm) –0.45
3.22, 12.3 1.3, 3.9 –9.2, 0.5 –4.7, 3.84
0.002 0.001 0.076 0.83
Control group (n⫽20) r (mm) 9.8 k (mm) 1.8 α angle (°) –3.8 MA (mm) –2.9
4.4, –1.5, –7.7, –5.6,
0.001 0.05 0.05 0.038
15.3 3.6 0.13 –0.18
Patient characteristics in group 1 were: mean age 29.4 (range 19–38) yr, height 158.15 (SD 8.06) cm, weight 71.25 (12.44) kg and median gestation 38 [range 37–41] weeks; six had singleton pregnancies and two had twins. Characteristics in group 2 were: age 30.5 (20–39) yr, height 163.9 (6.03) cm, weight 78.25 (15.12) kg and gestation 38 [37–39] weeks; three had singleton pregnancies and one had twins. There were no clinically important differences between groups. Differences in TEG variables with and without preload are shown in Table 1; r and k values were significantly shortened (P⬍0.05) in the preload group. In the control group, r and k were significantly reduced and MA was increased (P⬍0.05). There were no significant differences in the magnitude of the changes between groups.
tion. Some of the changes may have been a result of increased circulating catecholamines, which cause platelet degranulation and enhanced platelet aggregation.7 Changes in platelet function have been shown to correlate only with changes in MA8 and because we also reported changes in r and k values, this cannot be regarded as a complete explanation. Although it is known that large volumes of Gelofusine inhibit platelet function, our data did not provide evidence for this. Previous in vivo studies were performed using varying degrees of haemodilution and fluid types, either in volunteers or in patients suffering blood loss during surgery. None independently assessed incidental factors. Changes after preload which indicate hypercoagulation have been attributed to haemodilution which is believed to alter the balance of the activities of thrombin and antithrombin III so that thrombin becomes the more active.1 This hypothesis must be questioned. We propose that changes in in vivo studies6 may be attributed to environmental influences acting on coagulation.
References
Comment We have shown that TEG variables (r and k) were reduced significantly over a 15-min period in women awaiting spinal anaesthesia for elective Caesarean section, whether or not an i.v. infusion was given. It was not possible to attribute changes in coagulation to the effects of preload alone. TEG changes were in keeping with those attributed previously to enhanced coagulation.6 The magnitude of the changes was not clinically significant. We hypothesize that siting an i.v. cannula, attachment of monitoring devices and a 15-min waiting period adjacent to our operating theatre were sufficient to influence coagula-
404
1 Ruttmann TG, James MFM, Viljoen JF. Haemodilution induces a hypercoagulable state. Br J Anaesth 1996; 76: 412–14 2 Ruttmann TG, James MFM, Wells KF. Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation. Br J Anaesth 1999; 82: 110–11 3 Egli GA, Zollinger A, Seifert B, Popovic D, Pasch T, Spahn DK. Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation. Br J Anaesth 1997; 78: 684–9 4 Mardel SN, Saunders FM, Allen H, et al. Reduced quality of clot formation with gelatin-based plasma substitutes. Br J Anaesth 1998; 80: 204–7 5 Karoutsos S, Nathan N, Lahrimi A, Grouille D, Feiss P, Cox DJA. Thrombelastography reveals hypercoagulability after administration of gelatin solution. Br J Anaesth 1999; 82: 175–7 6 Ruttmann TG, James MFM, Aronson I. In-vivo investigation into the effects of haemodilution with hydroxyethyl starch and normal saline on coagulation. Br J Anaesth 1998; 80: 612–16 7 Sharma SK, Philip J. The effect of anaesthetic techniques on blood coagulability in parturients as measured by thromboelastography. Anaesth Analg 1997; 85: 82–6 8 Orlikowski CEP, Rocke DA, Murrar WB, et al. Thrombelastographic changes in preeclampsia and eclampsia. Br J Anaesth 1996; 77: 157–61