Services on Demand
Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.58 no.2 Campinas Mar./Apr. 2008
Efectos del bloqueo pudendo, peridural y subaracnoideo sobre la coagulación sanguínea de embarazadas
Alberto Vasconcelos, TSAI; Lígia Andrade da Silva Telles Mathias, TSAII
Doutor, HC-FMUSP, Pro Matre Paulista
IIProfessora Adjunta de Anestesiologia; Responsável pelo CET/SBA, ISCMSP
OBJECTIVES: The significant reduction in postoperative thromboembolic complications
has been attributed to the use of regional block, probably due to attenuation
of the neuroendocrine-metabolic response. Pregnant women, who demonstrate important
hypercoagulability, can in theory benefit from this effect during labor. The
objective of this study was to determine the effects of regional block on coagulation
of pregnant women.
METHODS: Thirty patients in the 3rd trimester were enrolled; ten patients underwent epidural block for cesarean section with 150 mg of 0.5% bupivacaine without epinephrine and 2 mg of morphine (PD group); ten underwent subarachnoid block for cesarean section with 15 mg of 0.5% hyperbaric bupivacaine and 0,2 mg of morphine (SA group); and ten, pudendal block for vaginal delivery with up to 100 mg of 0.5% bupivacaine without epinephrine (BP group). Coagulation tests (prothrombin time, thrombin time, activated partial thromboplastin time) and thromboelastography (r-time, k-time, r+k-time, a-angle, maximum amplitude) were performed in the following moments: before and after the blockade, after delivery, and 24 hours after the blockade in PD and SA groups. In the BP group, the evaluation was done before the blockade, after delivery, and 24 hours after the blockade.
RESULTS: The results indicate that the anesthetic technique did not influence coagulation of pregnant women. They also demonstrate that coagulation is activated during labor, which is responsible for the changes seen in all the study groups.
CONCLUSIONS: In the conditions of the present study, the sympathetic blockade and the local anesthetic did not have any influence on the coagulation of pregnant women at term undergoing epidural, subarachnoid, or pudendal nerve block.
Key Words: ANESTHESIA, Obstetric; ANESTHETICS, Local: bupivacaine; ANESTHETIC TECHNIQUE, Regional: pudendal nerve block, epidural block, subarachnoid block; BLOOD: coagulation; MEASUREMENT TECHNIQUE: thromboelastography.
Y OBJETIVOS: La ha sido atribuida a la anestesia regional la disminución
significativa de las complicaciones trombo embolicas en el postoperatorio, probablemente
por su acción atenuante sobre la respuesta neuroendocrina-metabólica.
Las embarazadas, que presentan aumento importante de la coagulabilidad sanguínea,
pueden teóricamente, beneficiarse con ese efecto en ocasión del
parto. El objetivo de este estudio fue verificar el efecto de la anestesia regional
sobre la coagulación sanguínea en embarazadas.
MÉTODO: Se estudiaron 30 pacientes en el 3° trimestre de embarazo, siendo diez sometidas a la anestesia peridural para cesárea, con 150 mg de bupivacaína a 0,5% sin epinefrina y 2 mg de morfina (grupo PD); diez a la anestesia subaracnoidea para cesárea con 15 mg de bupivacaína hiperbárica a 0,5% y 0,2 mg de morfina (grupo SA); y diez a Bloqueo de pudendo para parto vaginal, con dosis de hasta 100 mg de bupivacaína a 0,5% sin epinefrina (grupo BP). La coagulación sanguínea se evaluó a través del coagulograma (tiempo de protrombina, tiempo de trombina, tiempo de tromboplastina parcial activada) y del tromboelastograma (tiempo r, tiempo k, tiempo r+k, ángulo alfa y amplitud máxima) en los siguientes momentos: antes y después de la anestesia, después del nacimiento del feto y 24 horas después de la anestesia en los grupos PD y SA. En el grupo BP la evaluación fue realizada antes de la anestesia, después del nacimiento del feto y 24 horas después de la anestesia.
RESULTADOS: Los resultados mostraron que ninguna de las técnicas anestésicas utilizadas tuvo influencia en la coagulación sanguínea de las embarazadas. También quedó demostrado que durante el trabajo de parto se inicia un proceso de activación de la coagulación, que es responsable por las alteraciones encontradas en los tres grupos estudiados.
CONCLUSIONES: En las condiciones del presente estudio el Bloqueo simpático y el anestésico local no influenciaron en la coagulación en embarazadas sometidas a la anestesia peridural, subaracnoidea o Bloqueo pudendo.
Normal pregnancy causes changes in coagulation that lead to a hypercoagulable state. Those changes protect pregnant women from uncontrollable hemorrhage during labor, but at the same time they are responsible for a three- to four-fold increase in the risk of thromboembolism during the puerperium when compared with the remaining of the pregnancy 1-9.
Anesthesia and surgical intervention also affect coagulation. Several authors observed the inhibitory action of local anesthetics on coagulation and the inhibitory action of epidural anesthesia on platelet aggregation 10-11. In patients undergoing general anesthesia, it was observed a tendency to develop a hypercoagulable state, reduction in fibrinolysis, inhibition of platelet aggregation caused by inhalational agents and an increase in the total number of platelets 12-17.
Studies comparing general anesthesia to epidural block demonstrated the presence of a postoperative hypercoagulable state in patients undergoing general anesthesia, with a greater incidence of thromboembolic events 18-21.
There are no definitive studies in the literature on the influence of regional block on the coagulability of pregnant women.
The objectives of this study were to establish the coagulation profile and evaluate the influence of regional block on said profile in pregnant women in labor and in those undergoing cesarean section, using thromboelastography and routine tests (coagulation tests, fibrinogen. and platelets).
Thirty patients in the third trimester, with a single fetus, admitted to the Clínica Obstétrica of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, participated in this prospective study. The study protocol was approved by the Ethics Commission and all patients signed an informed consent.
Patients ASA II, according to the classification of the American Society of Anesthesiologists, were enrolled. Exclusion criteria included: a) use of aspirin or non-hormonal anti-inflammatory drugs up to two weeks before delivery; b) hemoglobin below 10 g.dL-1; c) failure of the regional block; d) 30 or 60 minutes after anesthesia, according to the group, if delivery had not occurred (M2).
Pre-anesthetic medication was not administered. In the operating room, venipuncture was performed and D5W was administered at approximately 100 mL.h-1.
Patients were divided in three groups:
- BP Group (n= 10) vaginal delivery with bilateral pudendal nerve block with 100 mg of 0.5% bupivacaine without epinephrine.
- PD Group (n= 10) cesarean section under epidural anesthesia; patients in the sitting position, epidural puncture at L2-L3 or L3-L4 and administration of 150 mg of 0.5% bupivacaine without epinephrine and 2 mg of morphine.
- SA Group (n= 10) cesarean section under subarachnoid block: patients in the sitting position, subarachnoid puncture at L2-L3 or L3-L4, with the administration of 15 mg of 0.5% hyperbaric bupivacaine and 0.2 mg of morphine at 0.05 mL.s-1.
Coagulation was assessed, in all three groups, through the following tests:
- Platelet count, hemoglobin, and hematocrit (Hb/Ht);
- Protrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen;
- Thromboelastography (TEG): reaction time (r), time to form the clot (k), and r+k time (r+k), expressed in minutes; alpha angle (a), expressed in degrees; maximum amplitude (MA), expressed in mm.
Parameters were analyzed in the following moments:
- BP Group: M0 immediately before bilateral pudendal nerve block; M2 and M3 30 min and 24 h after the blockade.
- PD Group: M0 immediately before the epidural block; M11, M2, and M3 15 and 60 minutes and 24 hours after the epidural block.
- SA Group: M0 immediately before the subarachnoid block; M1, M2, and M3 15 and 60 minutes and 24 h after the subarachnoid block.
The parameters were analyzed descriptively and Analysis of Variance (ANOVA) was used to evaluate the homogeneity of all three groups in M0.
Profile Analysis was used to determine the behavior of each group (BP, PD, and SA) at each moment (M0, M2, and M3). It was considered a critical level of significance of 5% (p < 0.05). The SAS system Statistical Analysis System was used for the calculations.
There were no differences among the three groups regarding: age, weight, height, gestational age, a regarding the parameters evaluated at the beginning of the study: PT, TT, aPTT, Hb, Ht, number of platelets, fibrinogen, and thromboelastography (k-time, r-time, and k+r-time, alpha angle, and maximum amplitude), which can be considered similar (Tables I and II).
Table III shows the mean values of the parameters evaluated in all three groups throughout the study.
Prothrombin time and thrombin time: no differences were observed among the groups, but there was a statistical variation throughout the study (p = 0.0356 for PT, and p = 0.0053 for TT). Comparing the different moments, an increase in TT and PT from M0 to M2was observed, followed by a reduction and return to baseline values. The isolated analysis of PD and AS groups demonstrated the same pattern of change (Tables IV and V).
Activated partial thromboplastin time: differed among the groups throughout the study (0.0461). BP and SA groups showed no significant variation at the different moments (p = 0.2038 and p = 0.4012, respectively), contrary to the PD group (p = 0.0185), whose analysis demonstrated and increase in aPTT after the blockade (M1), which was sustained after labor (M2), returning to baseline values after 24 hours (M3) (Tables IV and V).
Fibrinogen: all three groups behaved similarly, with a significant variation throughout the study (p = 0.0026); reduction up to M2, followed by an increase, with higher levels at the final moment. Analysis of PD and SA groups also demonstrated the same pattern of change (Tables IV and V).
Platelet Numbers: similar behavior in all three groups (p = 0.8796), with no statistically significant differences among the different groups and throughout the study (Table IV).
Hemoglobin and hematocrit: showed statistically significant differences in the BP group, with similar levels before the blockade and after labor, decreasing 24 h after labor. PD and SA groups did not show statistically significant differences throughout the study. Analysis of the Ht showed similar results (Tables IV and V).
Thromboelastography: r-time, k-time, r+k- time all three groups showed statistically significant variation throughout the study (r: p = 0.0163; k: p = 0.0502; r+k: p = 0.0268), with a reduction up to M2, which was maintained during the first 24 hours. When only the PD and SA groups were analyzed, no statistically significant differences were observed at the different moments (Tables IV and V).
Alpha angle and maximum amplitude: all three groups showed statistically significant differences (alpha angle: p = 0.0409; maximum amplitude: p = 0.0250), with an increase from M2 to 24 hours after labor. Analysis of PD and SA groups demonstrated no statistically significant differences (Table IV and V).
In non-obstetric populations, surgeries performed under spinal block have a lower incidence of thromboembolic events 12,18,19,22.
It is not known whether the spinal block affects coagulation through the sympathetic blockade it induces or through the plasma levels of the local anesthetic 23. Besides, routine laboratorial tests do not contribute to elucidate this question, since they do not report the level of activity of coagulation factors, only their plasma levels.
This study evaluated, in all three groups, which of the two factors affected coagulation.
Blood samples were scheduled to be drawn during the period of maximal intensity of the sympathetic blockade and during the peak plasma level of the local anesthetic 23,24.
Hemoglobin and hematocrit levels were included in this study to rule out the influence of hemodilution on coagulation factors. It is known that reduced levels of those factors secondary to hemodilution can affect coagulation 25. The BP group demonstrated a significant reduction of those levels 24 hours after the blockade when compared with post-labor levels. There was a 14.9% reduction (12.43 to 10.58%) in hemoglobin and 14.8% in hematocrit. This data are not in accordance with other studies, which demonstrated little change or a slight increase in hemoglobin levels after labor, even after a 20 to 30% loss in blood volume 26. Therefore, it is possible that this group of patients experienced above average blood loss.
Prothrombin and thrombin times behaved similarly in all three groups, increasing after labor (M2). Although significant, those results have no clinical implications. The increase in prothrombin time usually reflects the presence of inhibitors of coagulation, such as heparin or fibrin split products. It is possible that, in the present study, the slight increase detected was an expression of the increased consumption of coagulation factors that begins after expulsion of the placenta, during hemostasis of the surface of the uterus 27.
We did not find in the literature any reports on the profile of aPTT in pregnant women during or after anesthesia. Although the three groups behaved differently, only the PD group demonstrated a slight increase in aPTT, which was not clinically significant.
Fibrinogen levels were similar in all three groups, with a significant reduction after labor (M2) and an increase after 24 hours, but those changes were not clinically significant.
The reduction in r- and k-times and, consequently, r+k-time, along with an increase in maximum amplitude and alpha-angle, observed in all three groups represent activation of coagulation 28-30.
It is known that coagulation is activated after delivery of the fetus, and this is related with uterine contraction during expulsion, reaching maximal activation during the separation of the placenta, which was confirmed by coagulation tests and thromboelastography 29,31,32. Although we did not find any reports on thromboelastography levels in pregnant women during and after anesthesia, in the present study those changes were observed at the same moments in all three groups, leading to the conclusion that they are secondary to the activation of coagulation caused by labor itself, regardless of the anesthetic technique used.
It is interesting to note that, when the BP group was excluded from the statistical analysis, PD and SA groups did not demonstrate variation at the different moments. Labor was the fundamental difference between this group and the other two. This suggests that coagulation is activated at this moment, probably due to the degeneration of the placental bed that exposes collagen and activates the intrinsic pathway of coagulation 27.
Analysis of the three groups, subjected to different anesthetic techniques, demonstrated a variation in coagulation at different moments only in the BP group. This allowed us to conclude that once labor is initiated, it imposes subclinical changes in coagulation, detected by thromboelastography, lasting at least 24 hours after delivery. It should be noted that blood loss was greater in the BP group, as indicated by the concentration of hemoglobin and hematocrit, which might have influenced the results.
In the present study, the spinal block was not responsible for important changes in the coagulation profile.
Although it was not the objective of this study, the usefulness of thromboelastography on the dynamic evaluation of the coagulation profile, especially as a marker of coagulability in populations at risk, should be noted. In this study, it was more reliable than coagulation tests to detect changes in coagulation, even though it did not allow the characterization of the exact mechanism of those changes. This observation is in accordance with that of several authors who reported that thromboelastography is more sensitive and provides faster results in clinical and surgical settings that require repeated measurements to evaluate changes in coagulation dynamics 31-35.
01. Benzon HT, Wong CA, Wong HY et al. The effect of low-dose bupivacaine on postoperative epidural fentanyl analgesia and thrombelastography. Anesth Analg 1994;79:911-917. [ Links ]
02. Bigeleison PE, Kang YG Thrombelastography as an aid regional anesthesia: preliminary communication. Reg Anesth, 1991;16:59-61. [ Links ]
03. Bonnar J, McNicol GP, Douglas AS Coagulation and fibrinolytic mechanisms during and after normal childbirth. BMJ 1970;2: 200-203. [ Links ]
04. Borg T, Modig J Potential anti-thrombotic effects of local anesthetics due to their inhibition of platelet aggregation. Acta Anaesthesiol Scand, 1985;29:739-742. [ Links ]
05. Carvalho JCA, Mathias RS, Senra WG et al. Farmacocinética da bupivacaína em anestesia peridural para cesariana. II. Solução a 0,5% com e sem epinefrina. Rev Bras Anestesiol, 1986; 36:273-278. [ Links ]
06. Christopherson R, Beattie C, Frank SM et al. Perioperative morbidity in randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology, 1993;79:422-434. [ Links ]
07. Condie RG A serial study of coagulation factors Xll, Xl and X in plasma in normal pregnancy and in pregnancy complicated by pre-eclampsia. Br J Obstet Gynecol, 1976;83:636-639. [ Links ]
08. Corash L Laboratory Evaluation of Hemostasis, em: Russel KL Jr, ed. Blood Disorders in Pregnancy. Philadelphia, Lea & Febiger, 1986;125-149. [ Links ]
09. Simon L, Santi TM, Sacquin P et al. Pre-anesthetic assessment of coagulation abnormalities in obstetric patients: usefulness, timing and clinical implications. Br J Anaesth, 1997;78:678-683. [ Links ]
10. Corral FS, Rozas A, Rajo P Tromboelastografia en el embarazo, parto y puerperio. Rev Clin Inst Matern Lisboa, 1967;18: 205-211. [ Links ]
11. Davis FM, McDermott E, Hickton C et al. Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. Br J Anaesth 1987;59:561-571. [ Links ]
12. De Nicola P, Mazzetti GM Evaluation of thrombelastography. Am J Clin Pathol, 1955;25:447-451. [ Links ]
13. Feinstein MB, Fiekers J, Fraser C An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. J Pharmacol Exp Ther, 1976;197:215-228. [ Links ]
14. Gibbs NM, Crawford GPM, Michalopoulos N The effect of epidural blockade on postoperative hypercoagulability following abdominal aortic bypass surgery. Anaesth Intensive Care, 1992;.20:487-490. [ Links ]
15. Chamone DAF, Gomes OM, Langer B Alterações da Coagulação Sangüínea durante a Gravidez e Puerpério, em: Gomes OM, Langer B Coagulação e Cirurgia. São Paulo, Sarvier, 1974;17-22. [ Links ]
16. Greenburg AG Indications for Transfusion, em: Wilmore DW, Cheung LY, Harken AH et al. Emergency Care. New York, Scientific American Medicine, 1989;1-19. [ Links ]
17. Hellgren M, Blombäck M Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I Normal condition. Gynecol Obstet Invest, 1981;12:141-154. [ Links ]
18. Henny CP, Odoom JA, Cate HT et al. Effects of extradural bupivacaine on the haemostatic system. Br J Anaesth, 1986; 58:301-305. [ Links ]
19. Kang YG, Abouleish E Thrombelastography in obstetrics. Anesthesiology, 1981;55(Suppl 3A):A304. [ Links ]
20. Kang YG Monitoring and Treatment of Coagulation, em: Winter PM, kang YG Hepatic Transplantation. New York, Praeger Scientific, 1986;151-173. [ Links ]
21. Markarian M, Jackson J Comparison of the kinetics of clot formation, fibrinogen, fibrinolysis and hematocrit in pregnant women and adults. Am J Clin Obstet Gynecol, 1968;101:593-602. [ Links ]
22. Mathias LAST Efeitos da bupivacaína por via peridural sobre a coagulação sangüínea: estudo experimental no cão. São Paulo, 1992. Tese (Doutorado) Faculdade de Medicina, Universidade de São Paulo; 101p. [ Links ]
23. Modig J, Borg T, Karlström G et al. Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth Analg, 1983;62:174-180. [ Links ]
24. Modig J, Hjelmstedt A, Sahlstedt B et al. Comparative influences of epidural and general anaesthesia on deep venous thrombosis and pulmonary embolism after total hip replacement. Acta Chir Scand, 1981;147:125-130. [ Links ]
25. Modig J Thromboembolism and blood loss. Continuous epidural block versus general anesthesia with controlled ventilation. Reg Anesth, 1982;7:S84-88. [ Links ]
26. Montella KR Hypercoagulable States in Pregnancy, em: Lee RV, Barron WM, Cotton DB et al. Current Obstetric Medicine. Chigaco, Mosby, 1993;141-162. [ Links ]
27. Pechet L, Alexander B Increased clotting factors in pregnancy. N Engl J Med, 1961;265:1093-1096. [ Links ]
28. Rem J, Feddersen C, Brandt MR et al Postoperative changes in coagulation and fibrinolysis independent of neurogenic stimuli and adrenal hormones. Br J Surg, 1981;68:229-233. [ Links ]
29. Steer PL, Krantz H Thrombelastography and sonoclot analysis in the parturient, em: Society for Obstetric Anesthesia and Perinatology, 24, Charleston, 1992 Annual Meeting Poster exhibit abstracts; 57.6. [ Links ]
30. Stirling Y, Woolf L, North WRS et al. Haemostasis in normal pregnancy. Thromb Haemost 1984;52:176-182. [ Links ]
31. Tuman KJ, McCarthy RJ, March RJ et al. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg, 1991;73:696-704. [ Links ]
32. Tuman KJ, Spiess BD, Mccarthy RJ et al. Effects of progressive blood loss on coagulation as measured by thrombelastography. Anesth Analg, 1987;66:856-863. [ Links ]
33. Ueland K Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol, 1976;126:671-677. [ Links ]
34. Yeager MP, Glass DD, Neff RK et al. Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology, 1987;66:729-736. [ Links ]
35. Yoshimura T, Ito M, Nakamura T et al. The influence of labor on thrombotic and fibrinolytic systems. Eur J Obstet Gynecol Reprod Biol, 1992;44:195-199. [ Links ]
Dra. Lígia Andrade da Silva Telles Mathias
Alameda Campinas, 139/41
01404-000 São Paulo, SP
Submitted em 30
de setembro de 2006
Accepted para publicação em 18 de dezembro de 2007
* Received from Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP