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Prevention of maternal hypotension after regional anaesthesiafor caesarean sectionWarwick D. Ngan KeeDepartment of Anaesthesia and Intensive Care,The Chinese University of Hong Kong, Prince of WalesHospital, Shatin, Hong Kong, China

Correspondence to Warwick D. Ngan Kee, Departmentof Anaesthesia and Intensive Care, The ChineseUniversity of Hong Kong, Prince of Wales Hospital,Shatin, Hong Kong, ChinaTel: +852 2632 2735; fax: +852 2637 2422;e-mail: warwick@cuhk.edu.hk

Current Opinion in Anaesthesiology 2010,23:304309

Purpose of reviewHypotension during regional anaesthesia for caesarean section remains a common

clinical problem, particularly for spinal anaesthesia. The purpose of this review is to

evaluate recent research in this area with a focus on English language papers from the

past 12 years.

Recent findings

Risk factors for hypotension include increased sympathetic tone, increasing age,

obesity, higher blocks and higher birthweight, but not multiple gestation. Methods aimed

at countering effects of aortocaval compression do not reliably prevent hypotension.

Intravenous crystalloid prehydration has poor efficacy, and focus has changed toward

cohydration and use of colloids. Phenylephrine is established as a first-line vasopressor,

although there are limited data from high-risk patients. Initial phenylephrine bolus dose

requirement may be surprisingly large. Phenylephrine infusions can be conveniently

titrated to maintain blood pressure and prevent maternal symptoms. Ephedrine crosses

the placenta more than phenylephrine and direct fetal effects of ephedrine may explain

associated depression of fetal pH and base excess.

Conclusion

Recent research supports decreased use of crystalloid prehydration and ephedrine and

increased use of cohydration, colloids, smaller spinal doses and phenylephrine. Further

research is required to investigate these techniques in high-risk patients and to evaluate

novel monitoring techniques.

Keywords

caesarean section, hypotension, spinal anaesthesia

Curr Opin Anaesthesiol 23:304309 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907IntroductionDespite having been a focus of research and controversyfor decades, hypotension during regional anaesthesia forcaesarean section remains a common clinical problem.The purpose of this review is to evaluate the most recentresearch in this area, focusing on spinal anaesthesia andEnglish language papers from the past 12 years.

MechanismsHypotension during regional anaesthesia is more commonand severe in pregnant patients. Factors contributing tothis include increased sensitivity to local anaesthetics,aortocaval compression and increased susceptibility tothe effects of sympathetic block. The last is associatedwith reduced sensitivity to endogenous vasoconstrictorscoupled with increased synthesis of endothelium-derivedvasodilators.

Sharwood-Smith and Drummond [1] provided interest-ing insight into the relevant mechanisms in an editorial.opyright Lippincott Williams & Wilkins. Unautho

0952-7907 2010 Wolters Kluwer Health | Lippincott Williams & WilkinsThey emphasized that strategies designed to counter theeffects of aortocaval compression are not reliably effec-tive and postulated that the main mechanism relates toincreased dependence on sympathetic vascular tone.This is supported by consideration of the pathophysiol-ogy of preeclampsia in which persistent vasoconstrictionsecondary to the effect of placenta-derived mediatorsleads to relative resistance to sudden decreases in sym-pathetic vascular tone and thus less hypotension duringspinal anaesthesia. This explanation supports the currenttrend toward the use of potent vasoconstrictors such asphenylephrine as the mainstay for maintaining bloodpressure (BP) and helps explain the relative ineffective-ness of techniques such as intravenous hydration anduterine displacement manoeuvres.

Pregnant patients develop more extensive spinalblocks than nonpregnant patients. This is related toincreased sensitivity to local anaesthetics as well asthe mechanical effects of epidural vein engorgement.However, this effect appears to diminish soon afterrized reproduction of this article is prohibited.

DOI:10.1097/ACO.0b013e328337ffc6

mailto:warwick@cuhk.edu.hkhttp://dx.doi.org/10.1097/ACO.0b013e328337ffc6

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Prevention of maternal hypotension Ngan Kee 305pregnancy. Teoh et al. [2] compared spinal anaesthesiausing identical doses in patients undergoing postpartumtubal ligation or caesarean section and found that, within48 h after delivery, maximal cephalic sensory block andintraoperative hypotension and related symptoms arereduced.Risk factorsSusceptibility to hypotension varies among patients.Recent studies [3,4] used multivariable analysis toidentify the following factors that increase risk: age(35 years), obesity (BMI >2935 kg/m2) and higherblock (>T4T6). Maayan-Metzger et al. [5] retrospec-tively reviewed 919 elective caesarean deliveries andfound that nearly half had a decrease in mean arterialpressure by at least 30%. The risk factors for hypotensionincluded preoperative hypertension, older age, type ofspinal anaesthesia and higher infant birthweight. Impor-tantly, despite the high prevalence of hypotension, noadverse effects on the fetus were found.

Higher blocks cause more extensive block of preganglio-nic sympathetic fibres, and decreasing spinal dosedecreases the incidence and severity of hypotension[68]. However, use of smaller doses decreases theduration of anaesthesia and may necessitate the use ofa combined spinalepidural (CSE) technique [9].Although it has previously been proposed that theCSE technique itself may be associated with higherblocks versus single-shot spinal anaesthesia using equiv-alent doses, this finding was not reproduced in two recentstudies [10,11].

Baricity of spinal injectate is known to affect hypo-tension, as evidenced by studies comparing plain andhyperbaric solutions. Cesur et al. [12] described a noveltechnique of sequential injection of 5 mg plain bupiva-caine followed by 5 mg hyperbaric bupivacaine, injectedover 10 s in the sitting position. Compared with 10 mghyperbaric bupivacaine, hypotension and related symp-toms were less (13.9 versus 66.7%) despite similarmaximum height of block. The authors postulatedthat the initial plain bupivacaine provided dense blockbelow T10 for surgical anaesthesia, whereas the hyper-baric bupivacaine provided less dense block to upperdermatomes. This unique method deserves furtherconfirmation.

Patients in labour are less susceptible to hypotension thannonlabouring patients. This was confirmed prospectivelyby Clark [13]. Clark showed that ruptured membranes(which might reduce vena caval compression fromreduced uterine volume) was not a significant factor,suggesting that autotransfusion during uterine contrac-tions remains the likely explanation.opyright Lippincott Williams & Wilkins. UnauthMonitoringIntermittent noninvasive measurement of BP and con-tinuous measurement of heart rate (HR) remain the mostcommon haemodynamic monitors in clinical practice.However, several recent studies have described themeasurement of cardiac output (CO) using minimallyinvasive or noninvasive techniques. It has been suggestedthat CO may be a better indicator of uteroplacental bloodflow [14].

Dyer et al. [15] reported the use of continuous COmonitoring via arterial pulse wave analysis using the LiD-COplus device (LiDCO, London, UK) to describe hae-modynamic changes during spinal anaesthesia in patientswith severe preeclampsia. Langester et al. [16] reportedthe use of invasive BP monitoring together with COmonitoring (also using the LiDCO device) in parturientshaving CSE anaesthesia. In the latter study, patients wererandomized to one of four groups to receive intrathecalbupivacaine 7 mg and sufentanil or bupivacaine 10 mg andsufentanil, with or without a low-dose phenylephrineinfusion. Haemodynamic control among the groups wasbest with low-dose bupivacaine and phenylephrine infu-sion. CO initially increased and BP and systemic vascularresistance decreased in all groups (Fig. 1). Tamilselvanet al. [17], using suprasternal Doppler ultrasound, foundthat prehydration increased CO, especially when a largevolume of colloid was given. However, hypotension andnausea still occurred.

New CO monitors provide the ability to monitor flow aswell as pressure. However, available devices give anestimate of total CO only, which does not necessarilyreflect regional blood flow in the uterus and placenta(which is considered to be pressure-dependent), andhypotension and maternal symptoms can still occurdespite elevated CO [17]. Further work is required todetermine the place of CO monitoring in clinical practice.

Aortocaval compressionAortocaval compression has long been considered funda-mentally important, and application of lateral uterinedisplacement using a wedge or table tilt is usually con-sidered mandatory even though this does not reliablyprevent hypotension [1]. The optimal degree of tilt isunknown and anaesthesiologists often overestimate theamount they apply. Zhou et al. [18] reported that a wedgeunder the right lumbar region was more effective atpreventing hypotension than a wedge under the rightpelvis (47 versus 77%). In an accompanying editorial,Paech [19] commented that, whenever maternal or fetalcompromise occurs and is suspected to be related toaortocaval compression, uterine displacement shouldbe increased or the patient should be placed in the fullleft lateral position if feasible.orized reproduction of this article is prohibited.

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306 Obstetric and gynaecological anaesthesia

Figure 1 Mean differences in haemodynamic variables following spinal anaesthesia in patients who received phenylephrine infusionor placebo

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(a) Cardiac output. (b) SBP. (c) Heart rate. (d) Stoke volume. Baseline is marked on the y-axis. Error bars show standard error. Reproduced withpermission from [16].Intravenous fluid therapyAlthough current evidence has shown crystalloid prehy-dration (preload) not to be effective for preventing hypo-tension, a survey of practice shows that fluid therapyremains popular [20]. Recent research has focused ontype of fluid and timing of administration.

Recent studies have reconfirmed that colloids are moreeffective than crystalloids. Madi-Jebara et al. [21] com-pared prehydration with 1 l lactated Ringers solutionversus 500 ml hydroxyethyl starch (HES) 130/0.4solution. In the colloid group, the incidence of hypo-tension was smaller (63.9 versus 81.4%, P 0.033), theminimal recorded SBP was higher and the maximumrecorded HR was lower. Tamilselvan et al. [17] usedsuprasternal Doppler ultrasound to measure CO changesafter prehydration with either 1.5 l lactated Ringerssolution, or either 0.5 l or 1 l 6% HES solution. Theyopyright Lippincott Williams & Wilkins. Unauthoshowed that prehydration increased CO in all groups butthe effect was greater with colloid and more sustained inthe larger volume colloid group. There was no differencein the incidence of hypotension among groups, althoughthe study was not powered for this outcome.

Several recent studies have compared prehydration ver-sus cohydration with colloids and shown that haemody-namic changes and vasopressor requirement are similar.Teoh and Sia [22] compared prehydration with cohydra-tion using 15 ml/kg HES 130/0.4. BP changes and vaso-pressor requirement were similar between groups,although CO measured using suprasternal Dopplerultrasound was greater in the prehydration group inthe first 5 min after intrathecal injection. Carvalho et al.[23] compared prehydration with cohydration using500 ml 6% HES. BP changes and vasopressor require-ment were similar between groups. Siddik-Sayyid et al.[24] compared prehydration with cohydration usingrized reproduction of this article is prohibited.

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Prevention of maternal hypotension Ngan Kee 307500 ml HES 130/0.4. Consistent with the above studies,they also reported no difference in the incidence ofhypotension or vasopressor requirement between groups.Banerjee et al. [25] performed a meta-analysis (eightstudies, 518 patients) of studies that compared prehydra-tion with cohydration. They found the incidence ofhypotension to be similar [odds ratio 0.93, 95% confi-dence interval (CI) 0.541.6] for cohydration to thatfor prehydration.

What are the clinical implications of these studies? First,although colloids appear to be more effective than crys-talloids, the decision to use them will depend on indi-vidual assessment of benefits compared with potentialdisadvantages of colloids, the latter including cost, fluidoverload, allergy and pruritus. Second, regardless of thetype and timing of fluids, most studies have shown thatthe incidence of hypotension remains relatively high andthus one still needs to be prepared to administer avasopressor. Third, as prehydration has not been shownto be superior to cohydration, it should not be considerednecessary to delay surgery in order to administer a pre-determined volume of fluid before proceeding withspinal anaesthesia, particularly in urgent cases.Other nonpharmacological methodsArai et al. [26] found that transcutaneous electrical nervestimulation at the Neiguan (PC-6) and Jianshi (PC-5)acupoints resulted in less hypotension and vasopressorrequirement than control. The authors postulated thattheir findings might be related to augmented sym-pathetic tone from the electroacupuncture simulation.Bjrnestad et al. [27] compared wrapping the legs withtight elastic bandages with intravenous boluses ofphenylephrine 50mg given immediately and at 5 and10 min after epidural block. They found no differencebetween groups in the incidence of hypotension. Severalprevious studies have shown that leg wrapping is moder-ately effective in preventing hypotension, but this tech-nique does not appear to have found wide acceptance inclinical practice.VasopressorsA key recent advance in vasopressor use has been theincreased use and acceptance of alpha agonists such asphenylephrine. Their efficacy for maintaining vascularresistance means they can be effectively titrated tomaintain maternal BP and prevent maternal symptomssuch as nausea, vomiting and dizziness. Data fromelective cases have shown that phenylephrine doesnot appear to be harmful to the fetus when given inthe dose range required to prevent hypotension.Evidence for this comes from the observation thatphenylephrine has less propensity to depress fetal pHopyright Lippincott Williams & Wilkins. Unauthand base excess than ephedrine. However, a number ofcontroversies remain.

The optimal method of administration and dosing regi-men for phenylephrine is debated. Infusions titrated inthe range of 25100mg/min are highly effective formaintaining maternal BP [28]. Administration by bolusis simple but the optimal dose is unknown. Recent dose-finding studies [29,30] have suggested that the effectivedoses to prevent and treat hypotension may be larger thantypically used. This may explain why not all studies haveshown phenylephrine to be more efficacious than ephe-drine [31]. Tanaka et al. [29] using updown method-ology estimated the 95% effective dose (ED95) ofphenylephrine to prevent hypotension, nausea or bothto be 159mg (95% CI 122371mg). However, this dosewas higher than the doses actually used in the study andwas obtained by mathematical extrapolation. George et al.[30] using similar methodology estimated that the 90%effective dose (ED90) of bolus phenylephrine for treatinghypotension was 147mg (95% CI 98222mg). Note thatthese studies evaluated early phenylephrine therapy,given at a time when spinal block was evolving. Sub-sequent dose requirement at later times when the blockhas stabilized may be smaller.

Although phenylephrine is highly efficacious for main-taining BP, it causes reflex decreases in HR and mayreduce CO (Fig. 1) [16]. The clinical significance of thisis uncertain.

Combinations of phenylephrine and ephedrine giventogether in the same syringe have previously been advo-cated, although the optimal regimen has not been deter-mined. Ngan Kee et al. [32] investigated combinations ofphenylephrine and ephedrine in different ratios adminis-tered by infusion. They found that, as the proportion ofphenylephrine decreased and the proportion of ephe-drine increased, the incidences of hypotension and nau-sea/vomiting increased, haemodynamic control wasreduced and fetal pH and base excess decreased. Com-binations of vasopressors appeared to have no advantagecompared with phenylephrine alone.

The reason why ephedrine depresses fetal acidbasestatus more than phenylephrine is controversial. Olderstudies focused on differential effects of vasopressors onuteroplacental circulation. However, Ngan Kee et al. [33]showed that ephedrine crosses the placenta more readilythan phenylephrine (median umbilical venous/maternalarterial concentration ratio 1.13 versus 0.17, Fig. 2). Thiswas associated with greater fetal concentrations of lactate,glucose and catecholamines, and thus supports the hypo-thesis that depression of fetal pH and base excess withephedrine is caused by metabolic effects secondary tostimulation of fetal beta-adrenergic receptors.orized reproduction of this article is prohibited.

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308 Obstetric and gynaecological anaesthesia

Figure 2 Placental transfer of ephedrine and phenylephrine

Boxplots show UV/MA and UA/UV plasma concentration ratios forphenylephrine and ephedrine. The 25th, 50th and 75th percentilesare displayed as horizontal lines on a bar; whiskers above and belowthe box indicate the 90th and 10th percentiles; and data beyond the 10thand 90th percentiles are displayed as individual points. Data weresignificantly different between groups (P0.001) for both concen-tration ratios. MA, maternal arterial; UA, umbilical arterial; UV, umbilicalvenous. Reproduced with permission from [33].High-risk patientsMost clinical investigations of vasopressors have beenperformed in healthy low-risk elective patients in whomsmall differences in fetal pH, uteroplacental perfusion orboth are unlikely to have clinical impact. Few datacomparing vasopressors are available for patients withpotential fetal compromise in whom the margin of safetyfor uteroplacental perfusion may be reduced. Althoughprevious animal work does raise some concerns, noadverse effects of phenylephrine were reported in aclinical study of nonelective patients by Ngan Keeet al. [34]. They randomized 204 patients, including48 with potential fetal compromise, having nonelectivespinal caesarean section to receive either phenylephrineor ephedrine boluses to treat hypotension. Neonatal out-come and acidbase status were similar between groups.However, the ephedrine group had higher fetal lactateopyright Lippincott Williams & Wilkins. Unauthoconcentrations and more nausea and vomiting. Theauthors concluded that phenylephrine and ephedrineare both suitable vasopressors for use in nonelectivecaesarean section. Dyer et al. [15] described haemody-namic changes during spinal anaesthesia in patients withsevere preeclampsia. There were modest decreases inmean arterial pressure and systemic vascular resistancebut minimal changes in CO. Phenylephrine restored BPbut had minimal effect on CO.ConclusionManagement of hypotension during regional anaesthesiain obstetrics continues to be controversial. Improvementsin the understanding of the physiology support anemphasis on the use of vasopressors. Crystalloid pre-hydration should no longer be considered mandatoryand the current focus is on timing of fluids and use ofcolloids. Although most clinicians will continue to rely onnoninvasive BP and continuous HR monitoring, techno-logical advances broaden the options and CO monitoringmay prove useful in the future. Phenylephrine is estab-lished as a first-line vasopressor; compared with ephedrine,it is highly efficacious, especially when given by infusion.Ephedrine causes more depression of fetal acidbasestatus than phenylephrine, probably because ephedrinecrosses the placenta more readily and has direct metaboliceffects on the fetus. Further work is required to determinethe optimal therapy for hypotension in high-risk patients.AcknowledgementSupported solely by departmental and institutional funds.References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as: of special interest of outstanding interestAdditional references related to this topic can also be found in the CurrentWorld Literature section in this issue (pp. 428429).

1

Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaes-thesia: a lesson from preeclampsia. Br J Anaesth 2009; 102:291294.

A thought-provoking editorial with logical arguments explaining the possiblemechanism of hypotension.

2 Teoh WH, Ithnin F, Sia AT. Comparison of an equal-dose spinal anesthetic forcesarean section and for post partum tubal ligation. Int J Obstet Anesth 2008;17:228232.

3 Somboonviboon W, Kyokong O, Charuluxananan S, Narasethakamol A.Incidence and risk factors of hypotension and bradycardia after spinalanesthesia for cesarean section. J Med Assoc Thai 2008; 91:181187.

4 Ohpasanon P, Chinachoti T, Sriswasdi P, Srichu S. Prospective study ofhypotension after spinal anesthesia for cesarean section at Siriraj Hospital:incidence and risk factors, part 2. J Med Assoc Thai 2008; 91:675680.

5 Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotensionduring elective cesarean section and short-term neonatal outcome. Am JObstet Gynecol 2010; 202:56e156e5.

6 Roofthooft E, Van de Velde M. Low-dose spinal anaesthesia for Caesareansection to prevent spinal-induced hypotension. Curr Opin Anaesthesiol 2008;21:259262.

7 Turhanoglu S, Kaya S, Erdogan H. Is there an advantage in using low-doseintrathecal bupivacaine for cesarean section? J Anesth 2009; 23:353357.rized reproduction of this article is prohibited.

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Prevention of maternal hypotension Ngan Kee 3098 Qian XW, Chen XZ, Li DB. Low-dose ropivacainesufentanil spinal anaes-thesia for caesarean delivery: a randomised trial. Int J Obstet Anesth 2008;17:309314.

9 Leo S, Sng BL, Lim Y, Sia AT. A randomized comparison of low doses ofhyperbaric bupivacaine in combined spinalepidural anesthesia for cesareandelivery. Anesth Analg 2009; 109:16001605.

10 Horstman DJ, Riley ET, Carvalho B. A randomized trial of maximum cephaladsensory blockade with single-shot spinal compared with combined spinalepidural techniques for cesarean delivery. Anesth Analg 2009; 108:240245.

11 Macfarlane AJ, Pryn A, Litchfield KN, et al. Randomised controlled trial ofcombined spinal epidural vs. spinal anaesthesia for elective caesarean sec-tion: vasopressor requirements and cardiovascular changes. Eur J Anaes-thesiol 2009; 26:4751.

12

Cesur M, Alici HA, Erdem AF, et al. Spinal anesthesia with sequentialadministration of plain and hyperbaric bupivacaine provides satisfactoryanalgesia with hemodynamic stability in cesarean section. Int J Obstet Anesth2008; 17:217222.

An original study that found that sequential injection of half the intrathecalbupivacaine dose as plain solution followed by half as hyperbaric solution resultedin less hypotension and related symptoms. It would be useful to see these findingsconfirmed.

13 Clark RB. Hypotension and caesarean section. Br J Anaesth 2008; 101:882883.

14 Dyer RA, James MF. Maternal hemodynamic monitoring in obstetric anesthe-sia. Anesthesiology 2008; 109:765767.

15

Dyer RA, Piercy JL, Reed AR, et al. Hemodynamic changes associatedwith spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthe-siology 2008; 108:802811.

The authors of this study used invasive monitoring including CO measurementusing radial arterial pressure wave analysis to delineate haemodynamic changesduring spinal anaesthesia in patients with severe preeclampsia.

16

Langester E, Rosseland LA, Stubhaug A. Continuous invasive blood pres-sure and cardiac output monitoring during cesarean delivery: a randomized,double-blind comparison of low-dose versus high-dose spinal anesthesia withintravenous phenylephrine or placebo infusion. Anesthesiology 2008; 109:856863.

This study used CO measurement using radial arterial pressure wave analysisto compare haemodynamic changes in patients having combined spinalepi-dural anaesthesia with two different doses, with or without a phenylephrineinfusion.

17

Tamilselvan P, Fernando R, Bray J, et al. The effects of crystalloid and colloidpreload on cardiac output in the parturient undergoing planned cesareandelivery under spinal anesthesia: a randomized trial. Anesth Analg 2009;109:19161921.

These authors measured CO changes using suprasternal Doppler ultrasound afterprehydration with crystalloid or colloid. Prehydration increased CO in all groupsbut the effect was greater with colloid and more sustained in the larger volumecolloid group. However, there was no difference in the incidence of hypotensionamong groups.

18 Zhou ZQ, Shao Q, Zeng Q, et al. Lumbar wedge versus pelvic wedge inpreventing hypotension following combined spinal epidural anaesthesia forcaesarean delivery. Anaesth Intensive Care 2008; 36:835839.

19

Paech MJ. Should we take a different angle in managing pregnant women atdelivery? Attempting to avoid the supine hypotensive syndrome. AnaesthIntensive Care 2008; 36:775777.

An editorial providing a useful review of aortocaval compressions and methods ofpreventing it.

20 Allen TK, Muir HA, George RB, Habib AS. A survey of the management ofspinal-induced hypotension for scheduled cesarean delivery. Int J ObstetAnesth 2009; 18:356361.opyright Lippincott Williams & Wilkins. Unauth21 Madi-Jebara S, Ghosn A, Sleilaty G, et al. Prevention of hypotension afterspinal anesthesia for cesarean section: 6% hydroxyethyl starch 130/0.4(Voluven) versus lactated Ringers solution. J Med Liban 2008; 56:203207.

22 Teoh WH, Sia AT. Colloid preload versus coload for spinal anesthesia forcesarean delivery: the effects on maternal cardiac output. Anesth Analg 2009;108:15921598.

23 Carvalho B, Mercier FJ, Riley ET, et al. Hetastarch co-loading is as effective aspreloading for the prevention of hypotension following spinal anesthesia forcesarean delivery. Int J Obstet Anesth 2009; 18:150155.

24 Siddik-Sayyid SM, Nasr VG, Taha SK, et al. A randomized trial comparingcolloid preload to coload during spinal anesthesia for elective cesareandelivery. Anesth Analg 2009; 109:12191224.

25

Banerjee A, Stocche RM, Angle P, Halpern SH. Preload or coload for spinalanesthesia for elective cesarean delivery: a meta-analysis. Can J Anesth 2010;57:2431.

A meta-analysis of studies that compared prehydration with cohydration. Theauthors found that the incidence of hypotension was similar.

26 Arai YC, Kato N, Matsura M, et al. Transcutaneous electrical nerve stimulationat the PC-5 and PC-6 acupoints reduced the severity of hypotension afterspinal anaesthesia in patients undergoing caesarean section. Br J Anaesth2008; 100:7881.

27 Bjrnestad E, Iversen OE, Raeder J. Wrapping of the legs versus pheny-lephrine for reducing hypotension in parturients having epidural anaesthesiafor caesarean section: a prospective, randomized and double-blind study. EurJ Anaesthesiol 2009; 26:842846.

28 Smiley RM. Burden of proof. Anesthesiology 2009; 111:470472.

29

Tanaka M, Balki M, Parkes RK, Carvalho JC. ED95 of phenylephrine to preventspinal-induced hypotension and/or nausea at elective cesarean delivery. Int JObstet Anesth 2009; 18:125130.

This study used updown methodology and reported that the ED95 of bolus dosephenylephrine for preventing hypotension during spinal anaesthesia was largerthan typically used.

30

George RB, McKeen D, Columb MO, Habib AS. Up-down determination ofthe 90% effective dose of phenylephrine for the treatment of spinal anesthe-sia-induced hypotension in parturients undergoing cesarean delivery. AnesthAnalg 2009; 110:154158.

This study used updown methodology and reported that the ED90 of bolus dosephenylephrine for treating hypotension during spinal anaesthesia was larger thantypically used.

31 Magalhaes E, Goveia CS, Araujo Ladeira LC, et al. Ephedrine versus phe-nylephrine: prevention of hypotension during spinal block for cesarean sectionand effects on the fetus. Rev Bras Anestesiol 2009; 59:1120.

32 Ngan Kee WD,Lee A, Khaw KS,et al. A randomized double-blinded comparisonof phenylephrine and ephedrine combinations given by infusion to maintainblood pressure during spinal anesthesia for cesarean delivery: effects on fetalacid-base status and hemodynamic control. Anesth Analg 2008; 107:12951302.

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Ngan Kee WD, Khaw KS, Tan PE, et al. Placental transfer and fetal metaboliceffects of phenylephrine and ephedrine during spinal anesthesia for cesareandelivery. Anesthesiology 2009; 111:506512.

This studied showed that ephedrine crosses the placenta much more readily thanphenylephrine and causes increased levels of glucose, lactate and catecholaminesin the fetus. This provides an explanation for the propensity of ephedrine to depressfetal pH and base excess.

34

Ngan Kee WD, Khaw KS, Lau TK, et al. Randomized double-blinded compar-ison of phenylephrine versus ephedrine for maintaining blood pressure duringspinal anaesthesia for nonelective caesarean section. Anaesthesia 2008;63:13191326.

This study randomized 204 patients having nonelective spinal caesarean sectionto receive either phenylephrine or ephedrine boluses to treat hypotension. Neo-natal outcome and acidbase status were similar between groups.orized reproduction of this article is prohibited.

Prevention of maternal hypotension after regional anaesthesia for caesareansectionIntroductionMechanismsRisk factorsMonitoringAortocaval compressionIntravenous fluid therapyOther nonpharmacological methodsVasopressorsHigh-risk patientsConclusionAcknowledgementReferences and recommended reading