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5th Annual Meeting of ISOA ISRA and Pain Medicine Jakarta

Controversies in Cesarean Delivery Anesthesia

Cynthia A. Wong, MD Northwestern University Feinberg School of Medicine, Chicago, IL 60611 February 15, 2008

Objective: By the end of this lecture, participants should be able to Explain the reasoning behind choice of vasopressors (ephedrine and phenylephrine) for the treatment of neuraxial-anesthesia induced hypotension during cesarean delivery. Understand the benefits and limits of crystalloid and colloid administration for the prevention of hypotension during spinal anesthesia for cesarean delivery. Understand the risks and benefits of spinal versus epidural anesthesia for cesarean delivery in women with severe preeclampsia.

Ephedrine vs. phenylephrine for treatment of neuraxial anesthesia induced hypotension Ephedrine was the drug of choice for the treatment of hypotension during neuraxial anesthesia for cesarean delivery for many years. Studies in pregnant ewes suggested that ephedrine better maintained uterine blood flow compared to direct acting alpha-adrenergic agonists.1 Recent evidence, however, no longer supports this practice. A number of human studies in the last 15 years have demonstrated that phenylephrine is equally effective for treating maternal hypotension. More importantly, in studies of spinal anesthesia for elective cesarean delivery, fetal acid-base status is actually improved with phenylephrine compared to ephedrine.2-5 A metaanalysis found no differences in maternal blood pressure, although bradycardia was more likely after phenylephrine treatment. Umbilical artery pH was higher after treatment with phenylephrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04), however there was no difference in the number of neonates with umbilical artery pH < 7.2 (RR 0.78; 95% CI, 0.163.92) or Apgar score < 7 at 1 and 5 min.6 Cooper et al compared phenylephrine, ephedrine, and phenylephrine combined with ephedrine for the treatment of hypotension after spinal anesthesia.7 The incidence of fetal acidosis (pH < 7.2) was higher in the ephedrine group (22%) compared to the combined

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phenylephrine/ephedrine group (2%); however, the incidence of nausea or vomiting was higher in the two groups that received ephedrine compared to phenylephrine alone. Traditionally, anesthesiologists have maintained maternal blood pressure within 20% of baseline pressure. However, Ngan Kee and colleagues demonstrated that umbilical artery pH is higher, and the incidence of nausea and vomiting is lower, if maternal blood pressure is maintained at 100% baseline compared to 80% baseline.8 Large amounts of phenylephrine are required to maintain blood pressure at baseline: (median (IQR) infusion dose before delivery 1260 g (10101640 g)).9 The adverse effect of ephedrine compared to phenylephrine on fetal pH is likely a direct effect of ephedrine on the fetus (increased fetal metabolic activity).10 It is unlikely that this has any adverse effect on the healthy fetus. It is unclear whether there is an adverse effect on fetuses with decreased reserve. It is clear that maintaining maternal blood pressure close to baseline decreases the incidence of fetal acidosis and maternal nausea and vomiting. Ephedrine has a longer duration of action than phenylephrine, and a chronotropic effect; whereas the short duration of action of phenylephrine makes it more practical to administer as an infusion. Many anesthesiologists are currently using a combination of phenylephrine and ephedrine in order to reduce the dose of both drugs, thus decreasing the likelihood of both fetal acidosis and maternal bradycardia. Crystalloid and colloid administration to prevent hypotension during spinal anesthesia Factors associated with an increased risk for hypotension after spinal anesthesia include dose of local anesthesia (and maximum cephalad extent of blockade), low baseline blood pressure, high interspinous level of dural puncture, lack of labor (e.g., elective procedure), and increased sympathetic tone as assessed by heart rate variability indices.11 Traditional preloading with crystalloid prior to the induction of spinal or epidural anesthesia does not significantly decrease the incidence of hypotension.12 A crystalloid preload may be ineffective because of rapid redistribution from the intravascular to interstitial space.13 Several groups of investigators have compared crystalloid preload to colloid (starch) preload and found that the incidence of hypotension after induction of spinal anesthesia is lower after colloid preload.14-16 In 1993, Rout observed that women who received crystalloid 20 mL/kg 10 min before induction of spinal anesthesia had a lower incidence of hypotension compared to those who received the preload 20 min before the procedure.17 Dyer and colleagues took this a step further and found that crystalloid administered simultaneously with induction of anesthesia (co-load) had a lower incidence of hypotension and need for ephedrine compared to a preload 20 min prior to induction.18 Ngan Kee demonstrated that the combination of crystalloid coload with a prophylactic phenylephrine infusion decreased the incidence of hypotension to 1.9% (95% CI

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0.3-9.9%) compared to a group who received minimal fluids with phenylephrine (28.3% (95% CI 18.0 to 41.6%)).19 These studies suggest that crystalloid be administered rapidly at the time of induction of spinal anesthesia, and the use of colloid should be considered in women considered at high risk of hypotension. Spinal versus epidural anesthesia for severe preeclampsia Traditionally, spinal anesthesia has been avoided in parturients with severe preeclampsia as it was thought that rapid onset of sympathectomy would increase the risk of hypotension in these volume-contracted women. However, in both an observational 20 and RCT,21 there was no difference in the incidence or degree of hypotension, or in neonatal outcome, in women who received epidural compared to spinal anesthesia. Aya and colleagues observed that women with severe preeclampsia actually had less hypotension after spinal anesthesia compared to healthy controls.22,23 The uterine artery pulsatility index did not change after the induction of spinal anesthesia.24 Finally, Dyer and colleagues demonstrated that general compared to spinal anesthesia for urgent cesarean delivery in severely preeclamptic parturients resulted in better hemodynamic stability and better 1-min Apgar scores.25 Therefore, given these data, it is appropriate to induce spinal anesthesia for urgent (or elective) cesarean delivery in women with severe preeclampsia.
References 1. Ralston DH, Shnider SM, DeLorimier AA. Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology 1974;40:354-70 2. Hall PA, Bennett A, Wilkes MP, Lewis M. Spinal anaesthesia for caesarean section: comparison of infusions of phenylephrine and ephedrine. Br J Anaesth 1994;73:471-4 3. LaPorta RF, Arthur GR, Datta S. Phenylephrine in treating maternal hypotension due to spinal anesthesia for caesarean delivery: Effects on neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaethesiol Scand 1995;39:901-5 4. Moran DH, Perillo M, LaPorta RF, Bader AM, Datta S. Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery. J Clin Anesth 1991;3:301-5 5. Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for Caesarean section. Br J Anaesth 1996;76:61-5 6. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesthesia & Analgesia 2002;94:920-6 7. Cooper DW, Carpenter M, Mowbray P, Desira WR, Ryall DM, Kokri MS. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology 2002;97:158290 8. Ngan Kee WD, Khaw KS, Ng FF. Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section. Br J Anaesth 2004;92:469-74 9. Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2004;98:815-21 10. Riley ET. Editorial I: Spinal anaesthesia for Caesarean delivery: keep the pressure up and don't spare the vasoconstrictors. Br J Anaesth 2004;92:459-61

4/4 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. Hanss R, Bein B, Francksen H, Scherkl W, Bauer M, Doerges V, Steinfath M, Scholz J, Tonner PH. Heart rate variability-guided prophylactic treatment of severe hypotension after subarachnoid block for elective cesarean delivery. Anesthesiology 2006;104:635-43 Hofmeyr G, Cyna A, Middleton P. Prophylactic intravenous preloading for regional analgesia in labour. Cochrane Database Syst Rev 2004:CD000175 Ueyama H, He YL, Tanigami H, Mashimo T, Yoshiya I. Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section. Anesthesiology 1999;91:1571-6 Ko JS, Kim CS, Cho HS, Choi DH. A randomized trial of crystalloid versus colloid solution for prevention of hypotension during spinal or low-dose combined spinal-epidural anesthesia for elective cesarean delivery. Int J Obstet Anesth 2007;16:8-12 Dahlgren G, Granath F, Wessel H, Irestedt L. Prediction of hypotension during spinal anesthesia for Cesarean section and its relation to the effect of crystalloid or colloid preload. Int J Obstet Anesth 2007;16:128-34 Siddik SM, Aouad MT, Kai GE, Sfeir MM, Baraka AS. Hydroxyethylstarch 10% is superior to Ringer's solution for preloading before spinal anesthesia for Cesarean section. Can J Anaesth 2000;47:616-21 Rout CC, Rocke DA, Levin J, Gouws E, Reddy D. A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology 1993;79:262-9 Dyer RA, Farina Z, Joubert IA, Du Toit P, Meyer M, Torr G, Wells K, James MF. Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section. Anaesth Intensive Care 2004;32:351-7 Ngan Kee WD, Khaw KS, Ng FF. Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration. Anesthesiology 2005;103:744-50 Hood DD, Curry R. Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: a retrospective survey. Anesthesiology 1999;90:1276-82 Wallace DH, Leveno KJ, Cunningham FG, Giesecke AH, Shearer VE, Sidawi JE. Randomized comparison of general and regional anesthesia for cesarean delivery in pregnancies complicated by severe preeclampsia. Obstetrics & Gynecology 1995;86:193-9 Aya AG, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg 2003;97:867-72 Aya AG, Vialles N, Tanoubi I, Mangin R, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Spinal anesthesia-induced hypotension: a risk comparison between patients with severe preeclampsia and healthy women undergoing preterm cesarean delivery. Anesth Analg 2005;101:869-75 Karinen J, Rasanen J, Alahuhta S, Jouppila R, Jouppila P. Maternal and uteroplacental haemodynamic state in pre-eclamptic patients during spinal anaesthesia for Caesarean section. Br J Anaesth 1996;76:616-20 Dyer RA, Els I, Farbas J, Torr GJ, Schoeman LK, James MF. Prospective, randomized trial comparing general with spinal anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace. Anesthesiology 2003;99:561-9