N cesarean delivery fluid management[1] by Sanespi

REVIEW URRENT C OPINION

Cesarean delivery fluid management Fre´de´ric J. Mercier

Purpose of review To guide the optimal fluid management during cesarean delivery. The article focuses on fluid management to prevent hypotension during cesarean delivery performed under spinal anesthesia and excludes obstetric hemorrhage. Recent findings The literature underlines that crystalloid preloading is ineffective or poorly effective to prevent spinal hypotension during cesarean delivery. Crystalloid coloading is better but the effectiveness reported is variable and may depend on the volume used and the speed of administration at onset of sympathetic blockade. Hydroxyethyl starch (HES) preloading is more consistently effective in reducing the incidence and severity of hypotension. HES coloading appears as effective as HES preloading. Because none of these fluid-loading methods is completely effective at preventing hypotension, some sort of prophylactic vasopressor regimen should always be added. Routine fluid loading is no longer advocated prior to spinal anesthesia for cesarean delivery in preeclampsia and should be used with caution in women with multiple gestations. Summary Current evidence suggests that combining a prophylactic vasopressor regimen with HES preloading, HES coloading or crystalloid coloading is the best method of preventing maternal hypotension after the initiation of spinal anesthesia. Crystalloid preloading is clinically ineffective and thus should no longer be used. Keywords cesarean delivery/section, coload/coloading, fluid, multiple gestation, preeclampsia, preload/preloading, spinal anesthesia

INTRODUCTION

incidence of hypotension and most importantly, the potential severity of the hypotension [2 ,3 ]. Maternal consequences of spinal hypotension are well known and are usually limited to nausea–vomiting and/or dyspnea. However, hypotension can sometimes cause severe effects, including alteration of consciousness, inhalation of gastric content and/ or cardiovascular complications [3 ]. Fetal–neonatal consequences of decreased utero-placental perfusion resulting from maternal hypotension are debated. A retrospective review of 919 elective cesarean deliveries performed under neuraxial anesthesia (81% spinal anesthesia) &&

The purpose of this article is to review the most recent literature on fluid management during spinal anesthesia for cesarean delivery. As obstetric hemorrhage is a particular situation that we have recently reviewed [1], the present article will not address it. Rather, the current review will focus on the main indication of fluid loading during cesarean delivery, that is prevention of hypotension induced by spinal anesthesia, and will also address two specific obstetrical situations that are associated with fluid overload, that is preeclampsia and multiple gestation pregnancy.

USE OF SPINAL ANESTHESIA FOR CESAREAN DELIVERY AND HEMODYNAMIC CONSEQUENCES Single-shot spinal anesthesia is currently the technique of choice for routine scheduled cesarean delivery because it is a simple, fast, reliable and cost-effective technique. The most significant concern with the use of spinal anesthesia is the high www.co-anesthesiology.com

AP-HP, Hoˆpital Antoine Bećle`re, De´partement d’Anesthe´sie-Reánimation & Universite´ Paris-Sud, Clamart, France Correspondence to Fre´de´ric J. Mercier, MD, PhD, De´partement d’Anesthe´sie-Reánimation, Universite´ Paris-Sud, Hoˆpital Antoine Bećle`re, 157 rue de la Porte de Trivaux, 92141 Clamart Cedex BP 405, France. Tel: +33 1 45 37 42 73; fax: +33 1 45 37 49 85; e-mail: frederic. mercier@abc.aphp.fr Curr Opin Anesthesiol 2012, 25:286–291 DOI:10.1097/ACO.0b013e3283530dab Volume 25 Number 3 June 2012

Cesarean delivery fluid management Mercier

KEY POINTS

reduces the rate of fluid distribution (outside of the vascular bed), at least for crystalloids [9 ]. Thus, the intravascular volume increase provided by crystalloid infusion should be ‘administration timedependent’; the volume remaining in the vascular space should be smaller prior to spinal anesthesia (preloading) than just after induction of spinal anesthesia (coloading). Additionally, colloidal fluids are expected to reside longer in the intravascular space than crystalloid fluids. Therefore, multiple investigators have manipulated the combination of timing of fluid administration and type of fluid during cesarean delivery under spinal anesthesia in an attempt to reduce the incidence of hypotension (Fig. 1). &

Crystalloid preloading for cesarean delivery under spinal anesthesia is clinically ineffective, and therefore should be abandoned. Hydroxyethyl starch (HES) preloading reliably decreases the incidence and severity of hypotension, and may also decrease vasopressor requirements. HES coloading appears equally effective as preloading if it is rapidly infused after initiation of anesthesia. Crystalloid coloading is a cheaper alternative to colloid but its efficacy appears less reliable, at least when a substantial volume cannot be infused rapidly during onset of spinal sympathetic blockade. Fluid loading should be used cautiously in preeclampsia and multiple gestations.

reported that nearly one-half of the mothers underwent a decrease in their mean arterial blood pressure (BP) of more than 30% of the preoperative BP value; 8% had a decrease of more than 50%. However, none of these hypotension thresholds was predictive of any perinatal complications. Of note, only women with term singleton pregnancies were included in this study [4 ]. Conversely, in a secondary analysis of a large population-based study, spinal anesthesia was found to be associated with an increased risk of neonatal mortality in very preterm infants (27 to 32 weeks’ gestation) compared with general or epidural anesthesia. This association was independent of gestational age or other characteristics of the pregnancy, delivery and neonate (adjusted odds ratio, 1.7; 95% confidence interval 1.1 to 2.6), thus, it suggested a possible causal relationship. Information on fluid loading and vasopressor therapy was not recorded in this 1997 database, but it is likely that marked improvements have been made in routine spinal anesthesia protocols since this time. Nonetheless, this study suggests that inadequate hemodynamic control in the mother may result in severe consequences in high-risk fetuses [5]. Recent literature stresses that the use of vasopressors is the most important strategy to provide hemodynamic control during spinal anesthesia for cesarean delivery [2 ,6,7]. However, fluid loading remains frequently used in current clinical practice, either alone (44%) or in combination with vasopressors (53%) [8]. Many variables can be manipulated with regard to fluid loading, namely: volume, rate of administration, timing of administration and type of fluid. Volume kinetics predicts that a drop in the arterial pressure during induction of anesthesia &

CRYSTALLOID PRELOADING Crystalloid preloading is currently considered minimally effective or not effective in preventing hypotension during spinal anesthesia for cesarean delivery [2 ,3 ]. Faydaci and Gunaydin [10] assigned 90 parturients to receive 10, 15 or 20 ml/kg of Ringer’s Lactate preloading combined with an ephedrine infusion at 3 mg per min initiated immediately after induction of spinal anesthesia and continued until umbilical cord clamping. They reported a significantly reduced incidence of hypotension, nausea–vomiting and total ephedrine requirements in women preloaded with 20 ml/kg versus 10 ml/kg. This unexpected benefit is difficult to explain given the numerous negative studies on crystalloid preloading published in the past 20 years. For example, Muzlifah and Choy [11] recently confirmed that infusing 20 or 10 ml/kg of Ringer’s Lactate before spinal anesthesia gave very similar &&

Crystalloid preloading

Type II

Type I

Crystalloid coloading

Type IV

Colloid preloading

Type III

Colloid coloading

FIGURE 1. Diagram representing the four methods of intravascular fluid loading investigated during cesarean delivery under single-shot spinal anesthesia. The arrows indicate the comparisons between methods, labeled chronologically types I to IV, based roughly on the timing of their appearance in the literature. The dash arrow represents a further comparison that remains to be studied. Reproduced with permission from [3 ].

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incidence of hypotension and nausea–vomiting (12/40 and 5/40 versus 11/40 and 6/40, respectively). Ouerghi et al. [12] using low-dose spinal anesthesia also reported no difference in incidence of hypotension and ephedrine requirements in patients receiving 20 ml/kg of Ringer’s Lactate preloading (n ¼ 30) versus no fluid (n ¼ 30).

CRYSTALLOID COLOADING During this last decade, several pharmacokinetic and clinical studies during cesarean delivery have shown that delaying the administration of crystalloids until immediately after induction of spinal anesthesia (‘coloading technique’) improves efficacy, when compared with a conventional preloading technique used before spinal anesthesia [3 ]. In an important clinical study, Ngan Kee et al. [13] documented that a crystalloid coload of 2 liters (versus no fluid) improved the hypotension prophylaxis provided by a phenylephrine infusion alone. Unexpectedly, this benefit of using crystalloid coloading rather than preloading was not confirmed in a recent meta-analysis by Banerjee et al. [14 ]. Of note, the positive study by Ngan Kee et al. [13] was not included in this meta-analysis because they did not include a preload fluid control group. In addition, another study included in the metaanalysis used a small volume (10 ml/kg) of crystalloid and the volume might have been insufficient to detect a difference between the coloading and the preloading group [3 ]. Williamson et al. [15] compared the combination of crystalloid preload and coload (10 þ 10 ml/kg) to a full crystalloid preload (20 ml/kg) in 87 patients. The incidence of hypotension was not clearly provided and the medications used for treatment of hypotension (ephedrine, phenylephrine additional fluid boluses) were left to the discretion of anesthesia providers. Nonetheless, total intravenous fluid and additional fluid requirements were significantly lower in the preloading plus coloading group versus the conventional preloading group; vasopressor requirements tended also to be lower. In another study, Gunusen et al. [16 ] reported that a crystalloid coload (1 l) combined with a low-dose ephedrine infusion (1.25 mg per min) was more effective for preventing moderate and severe hypotension than a fluid preload with crystalloid alone (20 ml/kg) or colloid alone (0.5 l of 4% gelatin solution). Therefore, they advocated this technique in the absence of phenylephrine availability. Although this study does not permit one per se to draw any direct conclusion on the fluid regimens, it does again demonstrate the benefit of combining fluid loading with vasopressor prophylaxis. Overall, my view of the current &&

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literature is that crystalloid coloading is better than crystalloid preloading (which has minimal effectiveness, if any). However, crystalloid coloading does not appear consistently more efficacious than preloading, and this is likely to be related to volume and speed of administration, particularly during the first 5–10 min after induction of spinal anesthesia during which most of the sympathetic blockade takes effect.

COLLOID PRELOADING Studies during the last decade have consistently shown that colloid preloading is more effective than crystalloid preloading to reduce the incidence of hypotension. In addition, colloid preloading reduces the severity of hypotension and may also decrease the vasopressor requirements [2 ,3 ,17]. Tamilselvan et al. [18] used suprasternal Doppler flow technique for serial maternal cardiac output measurements at 5 min intervals in patients (n ¼ 20 3) who received 1.5 liters crystalloid, 0.5 liter of 6% hydroxyethyl starch (HES) or 1 liter of 6% HES preload. Spinal anesthesia was induced 30 min later and vasopressors were used only if hypotension occurred. The increase in cardiac output after preload was greater with HES and it remained significant after induction of spinal anesthesia only in the HES 1 liter group. No difference was detected in the incidence of hypotension (which remained high in all three groups) but the study was not powered for this outcome. The authors concluded that the cardiac output increases documented after these preload regimens cannot compensate for reductions in arterial BP produced by spinal anesthesia. In my opinion, the authors should add ‘unless vasopressor prophylaxis is added’. Indeed, we have just completed a large (n ¼ 167), multicenter, randomized, double-blind study comparing 500 ml of 6% HES (130/0.4) followed by 500 ml of Ringer’s Lactate (HES group) to 2 500 ml of Ringer’s Lactate (RL group) both given as preloading. In addition, we used prophylactic boluses of phenylephrine (50–150 mg) according to a predefined algorithm as soon as the 1 min systolic BP (SBP) recording was less than 95% of baseline. The incidence of hypotension was significantly lower in the HES group (37 versus 55%, P ¼ 0.02) with no difference in total phenylephrine requirements; the incidence of nausea–vomiting tended also to be lower (12 versus 22%, P ¼ 0.09). There was no detectable placental transfer of HES in umbilical cord blood of 11 patients tested, six of whom had received HES. The decrease in maternal hemoglobin value the day after surgery was small and very similar between the two groups &&

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(mean SD: 1.2 1.0 versus 1.0 0.9 g/dl) [19 ]. Of note, physicochemical and pharmacokinetic differences exist between the generations of HES; therefore, as pointed out in a recent review, efficacy and safety results may not be extrapolated from one starch to another [20]. Encouragingly, a recent study demonstrated that thromboelastographic (TEG) parameters remained within or very close to the normal range after preloading with 500 ml 6% HES (130/0.4) [21 ], the starch that was used in our recent study [19 ]. &

COLLOID COLOADING Three randomized studies recently assessed colloid coloading, compared with colloid preloading. In each of them, the colloid used was a HES. The use of HES is recommended in obstetric anesthesia because of much lower risk in both the incidence and severity of allergic reactions compared with gelatins or dextrans [3 ]. Carvalho et al. [22] compared 500 ml 6% hetastarch (670/0.75) administered as a preload or coload and reported no differences in vasopressor prophylactic requirements or in any other important maternal hemodynamic or neonatal outcome values. They concluded that hetastarch coloading was as effective as preloading for the prevention of hypotension, and therefore that surgery should not be delayed to allow a predetermined preload to be administered before induction of spinal anesthesia. Teoh and Sia [23] reported a significant increase in maternal cardiac output for the first 5 min after spinal anesthesia when 15 ml/kg of 6% tetrastarch (130/0.4) was given quickly as a preload, but not as a coload, in combination with prophylactic phenylephrine boluses. However, there were no significant between-group differences in the incidence of hypotension and nausea–vomiting, or in the minimum SBP, predelivery phenylephrine requirements, or neonatal outcomes. Therefore, the authors advocated the use of a modest preload or coload (e.g., 500 ml) and support of SBP close to baseline with phenylephrine. SiddikSayyid et al. [24] performed a large (n ¼ 178), doubleblind study comparing 500 ml 6% HES (130/0.4) preloading with 500 ml 6% HES (130/0.4) coloading. There were no significant between-group differences in incidence of hypotension (68 versus 75%, respectively), severe hypotension defined as SBP less than 80 mmHg (16 versus 22%) and vasopressor requirements. The authors concluded that both modalities of HES loading were inefficient as single interventions. Banerjee et al. [14 ] performed a meta-analysis including these three studies and a previous one and concluded, as expected, that HES coloading was equally effective as HES preloading. More recently, &&

McDonald et al. [25 ] performed the first comparison between a 1 liter HES coloading and a 1 liter Hartmann (crystalloid) coloading both given very quickly within 5 min after spinal injection (n ¼ 30 2). In addition, phenylephrine infusion was started at the time of spinal injection (100 mg per min) and then titrated to maintain maternal baseline SBP. Maternal cardiac output was measured at 5 min intervals for 20 min after initiation of spinal anesthesia. This double-blind study showed very similar cardiac output values and no significant differences in phenylephrine requirements, which were very high in both groups (mean SD: 2210 900 versus 2590 1050 mg, respectively). The study was not powered to detect differences in incidence of hypotension (40 versus 60%, P ¼ 0.20) or in percentage of patients that experienced more than one episode of hypotension (7 versus 27%, P ¼ 0.08). The authors concluded that there was no advantage in using colloid over crystalloid coload, when used in combination with a phenylephrine infusion. Despite the high quality of the study, I do not share entirely this conclusion given the trend observed in the secondary hemodynamic outcomes detailed above.

FLUID WARMING Two randomized studies recently investigated intraoperative fluid warming during cesarean delivery under neuraxial anesthesia. One study used 10 ml/kg crystalloid preloading prior to combinedspinal anesthesia and reported that prewarming the fluids mitigated the decrease in maternal temperature and increased thermal comfort [26]. Of note, there were no differences between groups with regard to incidence of shivering, hypotension, phenylephrine requirements, estimated blood loss or neonatal outcome values. In the second study, patients received 400 ml of 6% HES (70/0.55) before spinal anesthesia followed by 300 ml of the same fluid before delivery [27]. Maternal core temperature was significantly higher in the prewarmed fluid group at delivery (mean SD: 36.4 0.2 versus 35.5 0.38C) and decrease in hemoglobin value for the first 24 postoperative hours was significantly smaller (0.8 0.6 versus 1.6 1.1 g/dl). There were no differences in incidence or severity of maternal hypotension, nor in neonatal rectal temperature, but 1 min Apgar scores and umbilical arterial pH (7.33 0.045 versus 7.29 0.034) were significantly higher in the prewarmed fluid group. Although the differences observed may have only limited clinical meaning, these two studies suggest that prewarming the fluids is potentially beneficial for the mother and the baby [26,27].

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MONITORING

CONCLUSION

Prespinal anesthesia tests and/or noninvasive monitoring have been proposed to predict the risk of hemodynamic instability in an attempt to better individually tailor vasopressor and fluid prophylaxis. However, these tests are not convenient to use in daily practice or are not yet routinely available [2 ,3 ]. Skin conductance monitoring that aimed to provide information about skin sympathetic tone gave disappointing results recently as a means of predicting hypotension after spinal anesthesia for cesarean delivery [28 ].

Recent literature stresses that prevention of hypotension during spinal anesthesia for cesarean delivery relies mainly on the use of vasopressor prophylaxis. However, fluid administration remains useful to further decrease the incidence and severity of hypotension and/or the vasopressor requirements. The best method of fluid administration is still a matter of controversy. HES preloading is the more reliable and the best documented; HES coloading appears equally effective if infused rapidly after the initiation of anesthesia. Crystalloid coloading is a cheaper alternative but its efficacy may be less reliable, at least when a substantial volume cannot be rapidly infused during the 5–10 min after induction of spinal anesthesia when most of the sympathetic blockade takes effect. Crystalloid preloading is clinically ineffective, and therefore its use should be abandoned. Future areas of research should focus on tools that would help in predicting the risk of hemodynamic instability and/or guiding individual vasopressor and fluid prophylaxis. The benefit of combining HES preloading with crystalloid coloading should be also investigated [3 ].

PREECLAMPSIA In a recent review on preeclampsia, Gogarten [29] summarized evidence that the incidence of hypotension and the vasopressor requirements are greatly reduced during spinal anesthesia for cesarean delivery in preeclamptic compared with nonpreeclamptic patients. In addition, current evidence does not support vascular fluid loading in preeclamptic patients to improve maternal and/or fetal outcome, particularly given that the risk of pulmonary edema is markedly increased in the immediate postpartum period in preeclamptic parturients. Thus, routine fluid preloading should not be used before spinal anesthesia, because of potential harm and lack of demonstrated benefit on hemodynamic control. Whenever fluid loading is deemed necessary, it will be better postponed until after induction of spinal anesthesia (i.e. as coloading during onset of sympathetic blockade) to lessen the risk of fluid overload.

MULTIPLE GESTATION PREGNANCY There is no available literature on fluid management for parturients with multiple gestation pregnancy undergoing spinal anesthesia for cesarean delivery. Surprisingly, one study suggested that the risk of hypotension after induction of spinal anesthesia was not different in women with multiple gestation (36 twins and four triplets) compared with a singleton gestation control group (n ¼ 60) [30]. These data contrast with what is usually written in textbooks, that is the risk of hypotension should increase because of greater aortocaval compression and greater cephalad spread of neuraxial block. The physiological increase in total blood volume and cardiac output that exists in patients with multiple gestation pregnancy might be a sufficient compensatory mechanism, at least when a prophylactic vasopressor regimen is used. Thus, fluid loading should be used cautiously, because of lack of demonstrated benefit and likely increased risk of fluid overload [31]. 290

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Acknowledgements None. Conflicts of interest F.J.M. received honoraria for lectures and research funding from Kabi-Fresenius. No funding has been received for this work and Kabi-Fresenius has not been involved in the writing of the manuscript.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 391). 1. Mercier FJ, Bonnet MP. Use of clotting factors and other prohemostatic drugs for obstetric hemorrhage. Curr Opin Anaesthesiol 2010; 23:310– 316. 2. Ngan Kee WD. Prevention of maternal hypotension after regional anaes&& thesia for caesarean section. Curr Opin Anaesthesiol 2010; 23:304– 309. A nice review on prevention of hypotension after neuraxial anesthesia for cesarean delivery, including an interesting paragraph on intravenous fluid therapy. 3. Mercier FJ. Fluid loading for cesarean delivery under spinal anesthesia: Have && we studied all the options? Anesth Analg 2011; 113:677–680. An editorial summarizing current knowledge on fluid loading techniques to prevent hypotension during spinal anesthesia for cesarean delivery. 4. Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotension & during elective cesarean section and short-term neonatal outcome. Am J Obstet Gynecol 2010; 202:56e1–56e5. In this retrospective review of 919 elective cesarean deliveries largely performed under spinal anesthesia, moderate and severe hypotension did not predict perinatal complications.

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Cesarean delivery fluid management Mercier 5. Laudenbach V, Mercier FJ, Roze´ JC, et al. Anaesthesia mode for caesarean section and mortality in very preterm infants: An epidemiologic study in the EPIPAGE cohort. Int J Obstet Anesth 2009; 18:142–149. 6. Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from preeclampsia. Br J Anaesth 2009; 102:291– 294. 7. Dyer RA, Reed AR. Spinal hypotension during elective Cesarean delivery: closer to a solution. Anesth Analg 2010; 111:1093–1095. 8. Allen TK, Muir HA, George RB, Habib AS. A survey of the management of spinal-induced hypotension for scheduled cesarean delivery. Int J Obstet Anesth 2009; 18:356–361. 9. Hahn RG. Volume kinetics for infusion fluids. Anesthesiology 2010; & 113:470–481. A review article on volume kinetics, a method used for analyzing and simulating the distribution and elimination of infusion fluids. 10. Faydaci F, Gunaydin B. Different preloading protocols with constant ephedrine infusion in the prevention of hypotension for elective cesarean section under spinal anesthesia. Acta Anaesthesiol Belg 2011; 62:5–10. 11. Muzlifah KB, Choy YC. Comparison between preloading with 10 ml/kg and 20 ml/kg of Ringer’s lactate in preventing hypotension during spinal anaesthesia for caesarean section. Med J Malaysia 2009; 64:114–117. 12. Ouerghi S, Bougacha MA, Frikha N, et al. Combined use of crystalloid preload and low dose spinal anesthesia for preventing hypotension in spinal anesthesia for cesarean delivery: a randomized controlled trial. Middle East J Anesthesiol 2010; 20:667–672. 13. 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; 103:744–750. 14. Banerjee A, Stocche RM, Angle P, Halpern SH. Preload or coload for spinal & anesthesia for elective Cesarean delivery: a meta-analysis. Can J Anaesth 2010; 57:24–31. A meta-analysis of studies that compared preloading with coloading. The authors found that the incidence of hypotension was similar with these two loading techniques when colloids were used (as expected) but also when crystalloids were used (unexpected). 15. Williamson W, Burks D, Pipkin J, et al. Effect of timing of fluid bolus on reduction of spinal-induced hypotension in patients undergoing elective cesarean delivery. AANA J 2009; 77:130–136. 16. Gunusen I, Karaman S, Ertugrul V, Firat V. Effects of fluid preload (crystalloid & or colloid) compared with crystalloid co-load plus ephedrine infusion on hypotension and neonatal outcome during spinal anaesthesia for caesarean delivery. Anaesth Intensive Care 2010; 38:647–653. A crystalloid coload (1 l) combined with a low-dose ephedrine infusion (1.25 mg per min) was more effective to prevent hypotension than a fluid preload with crystalloid alone (20 ml/kg) or with colloid alone (0.5 l of 4% gelatin solution). 17. Cyna AM, Andrew M, Emmett RS, et al. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2006:CD002251. 18. Tamilselvan P, Fernando R, Bray J, et al. The effects of crystalloid and colloid preload on cardiac output in the parturient undergoing planned cesarean delivery under spinal anesthesia: a randomized trial. Anesth Analg 2009; 109:1916–1921.

19. Mercier FJ, Diemunsch P, Ducloy-Bouthors A-S, et al. 6% HES (130/0.4) vs. Ringer’s Lactate to Prevent Hypotension during Spinal Anesthesia for C-section. Proceedings of the American Society of Anesthesiologists annual meeting; 17 October 2011; Chicago. p. A973. http://www.asaabstracts. com/strands/asaabstracts/abstract.htm; jsessionid¼0EBCAEBC720C023 FB2A0FEAE114A77E4?year¼2011&index¼13&absnum¼5096. A preliminary report of a multicenter, randomized, double-blind study showing the efficacy and the safety of a third generation starch preloading versus a crystalloid preloading, when combined with standardized intravenous phenylephrine prophylaxis. 20. Westphal M, James MF, Kozek-Langenecker S, et al. Hydroxyethyl starches: different products–different effects. Anesthesiology 2009; 111:187–202. 21. Turker G, Yilmazlar T, Mogol EB, et al. The effects of colloid preloading on & thromboelastography prior to caesarean delivery: hydroxyethyl starch 130/0.4 versus succinylated gelatine. J Int Med Res 2011; 39:143–149. Thromboelastographic (TEG) parameters remained within or very close to the normal range after preloading with either 500 ml 6% tetrastarch or 500 ml 4% gelatin. 22. Carvalho B, Mercier FJ, Riley ET, et al. Hetastarch co-loading is as effective as preloading for the prevention of hypotension following spinal anesthesia for Cesarean delivery. Int J Obstet Anesth 2009; 18:150–155. 23. Teoh WH, Sia AT. Colloid preload versus coload for spinal anesthesia for Cesarean delivery: the effects on maternal cardiac output. Anesth Analg 2009; 108:1592–1598. 24. Siddik-Sayyid SM, Nasr VG, Taha SK, et al. A randomized trial comparing colloid preload to coload during spinal anesthesia for elective Cesarean delivery. Anesth Analg 2009; 109:1219–1224. 25. McDonald S, Fernando R, Ashpole K, Columb M. Maternal cardiac output && changes after crystalloid or colloid coload following spinal anesthesia for elective delivery. Anesth Analg 2011; 113:803–810. This well designed double-blind study is the first to compare crystalloid coload versus colloid coload. In both groups, a phenylephrine prophylactic infusion was used in addition to the fluid coloading. The maternal cardiac output changes over a 20 min period after spinal anesthesia were very similar in the two groups. 26. Woolnough M, Allam J, Hemingway C, et al. Intra-operative fluid warming in elective caesarean section: a blinded randomised controlled trial. Int J Obstet Anesth 2009; 18:346–351. 27. Yokoyama K, Suzuki M, Shimada Y, et al. Effect of administration of prewarmed intravenous fluids on the frequency of hypothermia following spinal anesthesia for Cesarean delivery. J Clin Anesth 2009; 21:242–248. 28. Ledowski T, Paech MJ, Browning R, et al. An observational study of skin & conductance monitoring as a means of predicting hypotension from spinal anaesthesia for caesarean delivery. Int J Obstet Anesth 2010; 19:282–286. Skin conductance monitoring, that aims at providing information about skin sympathetic tone, did not predict hypotension after spinal anesthesia for cesarean delivery. 29. Gogarten W. Preeclampsia and anaesthesia. Curr Opin Anaesthesiol 2009; 22:347–351. 30. Ngan Kee WD, Khaw KS, Ng FF, et al. A prospective comparison of vasopressor requirement and hemodynamic changes during spinal anesthesia for cesarean delivery in patients with multiple gestation versus singleton pregnancy. Anesth Analg 2007; 104:407–411. 31. Poggi SH, Barr S, Cannum R, et al. Risk factors for pulmonary edema in triplet pregnancies. J Perinatol 2003; 23:462–465. &

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