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Year : 2023  |  Volume : 22  |  Issue : 3  |  Page : 321-326  

Effect of Carbetocin on Uterine Tone during Cesarean Section: A Comparison between Subarachnoid Block and General Anesthesia

1 Obstetric Anaesthesia Unit, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
2 Department of Obstetrics and Gynaecology, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria

Date of Submission23-Apr-2022
Date of Acceptance09-Mar-2023
Date of Web Publication4-Jul-2023

Correspondence Address:
Sotonye Fyneface-Ogan
Department of Anaesthesia, Obstetric Anaesthesia Unit, University of Port Harcourt Teaching Hospital, Port Harcourt
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aam.aam_72_22

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Background: Postpartum hemorrhage remains a challenge in obstetric practice in developing climes and contributes immensely to the horrendous figures of maternal mortality worldwide. Aim: The aim was to compare the effect of intravenous (IV) carbetocin on uterine tone under different anesthetic techniques for elective cesarean section. Methods: Four hundred and seventy-eight consecutive women scheduled for elective cesarean section were recruited into two groups by convenience. While 445 parturients received subarachnoid block (SAB), 33 had general anesthesia (GA). At delivery, IV carbetocin was administered. The uterine tone was assessed manually and blood loss from intraoperative period to the 24th h was determined. Other variables such as hemodynamic profiles and Apgar scores were determined and recorded. Results: The bio-characteristics between the two groups were essentially the same in terms of age, weight, height, body mass index, preoperative hemoglobin, and gestational age. While the response to the administered carbetocin was slower in the GA group, there was no need for additional dose. The mean estimated intraoperative blood loss under SAB was 250.44 ± 50.59 ml and that under GA was 470.89 ± 35.70 ml, P = 0.000000. The ephedrine consumption was 6.25 ± 2.05 mg in the SAB group while it was 11.25 ± 2.49 mg, P = 0.000000. There was no further maternal blood loss observed after the intraoperative period until the end of 24-h period. The hemodynamic profiles were significantly different in terms of mean systolic blood pressure, mean diastolic blood pressure, and mean arterial blood pressure, P = 0.006, P = 0.002, and P = 0.003, respectively. However, the difference in the mean heart rate was not statistically significant, P = 0.304. While the Apgar scores between groups were not statistically significant, the mean umbilical pH was 7.34 ± 0.09 in the SAB group, it was 7.35 ± 0.02 in the GA group, P = 0.071. Conclusion: Intraoperative maternal blood loss was more among the parturients who received GA than subarachnoid blood. This could probably be due to the effect of the halogenated vapor used for the GA on the uterine tone. There was no further blood loss after the intraoperative period. The hemodynamic profile was better under SAB as evidenced by the total ephedrine consumption.
Contexte: L'hémorragie post-partum reste un défi dans la pratique obstétricale dans les pays en développement et contribue énormément à l'horrible chiffres de la mortalité maternelle dans le monde. Objectif: L'objectif était de comparer l'effet de la carbétocine intraveineuse (IV) sur le tonus utérin sous différentes techniques d'anesthésie pour la césarienne élective. Méthodes: Quatre cent soixante-dix-huit femmes consécutives devant subir une césarienne élective section ont été recrutés en deux groupes par commodité. Alors que 445 parturientes ont reçu un bloc sous-arachnoïdien (SAB), 33 ont eu une anesthésie générale (AG). À l'accouchement, de la carbétocine IV a été administrée. Le tonus utérin a été évalué manuellement et la perte de sang de la période peropératoire à la 24e heure a été déterminé. D'autres variables telles que les profils hémodynamiques et les scores d'Apgar ont été déterminées et enregistrées. Résultats: Les bio-caractéristiques entre les deux groupes étaient essentiellement les mêmes en termes d'âge, de poids, de taille, d'indice de masse corporelle, d'hémoglobine préopératoire et d'âge gestationnel. Tandis que le la réponse à la carbétocine administrée était plus lente dans le groupe GA, aucune dose supplémentaire n'était nécessaire. Le sang peropératoire moyen estimé la perte sous SAB était de 250,44 ± 50,59 ml et celle sous GA était de 470,89 ± 35,70 ml, P = 0,000000. La consommation d'éphédrine était de 6,25 ± 2,05 mg dans le groupe SAB alors qu'il était de 11,25 ± 2,49 mg, P = 0,000000. Il n'y a pas eu d'autre perte de sang maternel observée après la période peropératoire jusqu'à la fin de la période de 24 h. Les profils hémodynamiques étaient significativement différents en termes de tension artérielle systolique moyenne, de tension artérielle diastolique moyenne et la pression artérielle moyenne, P = 0,006, P = 0,002 et P = 0,003, respectivement. Cependant, la différence de fréquence cardiaque moyenne était pas statistiquement significatif, P = 0,304. Alors que les scores d'Apgar entre les groupes n'étaient pas statistiquement significatifs, le pH ombilical moyen était de 7,34 ± 0,09 dans le groupe SAB, elle était de 7,35 ± 0,02 dans le groupe AG, p = 0,071. Conclusion: La perte de sang maternel peropératoire était plus importante chez les parturientes ayant reçu GA que le sang sous-arachnoïdien. Cela pourrait probablement être dû à l'effet de la vapeur halogénée utilisée pour l'AG sur le tonus utérin. Il n'y avait pas perte de sang supplémentaire après la période peropératoire. Le profil hémodynamique était meilleur sous SAB comme en témoigne la consommation totale d'éphédrine.
Mots-clés: Perte de sang, anesthésie générale, carbétocine intraveineuse, bloc sous-arachnoïdien, tonus utérin

Keywords: Blood loss, general anesthesia, intravenous carbetocin, subarachnoid block, uterine tone

How to cite this article:
Fyneface-Ogan S, Fiebai PO, Orazulike NC. Effect of Carbetocin on Uterine Tone during Cesarean Section: A Comparison between Subarachnoid Block and General Anesthesia. Ann Afr Med 2023;22:321-6

How to cite this URL:
Fyneface-Ogan S, Fiebai PO, Orazulike NC. Effect of Carbetocin on Uterine Tone during Cesarean Section: A Comparison between Subarachnoid Block and General Anesthesia. Ann Afr Med [serial online] 2023 [cited 2023 Sep 28];22:321-6. Available from:

   Introduction Top

Globally, there is an upward trend in the proportion of parturients giving birth by cesarean section, performed as a result of intercurrent medical diseases, complications of pregnancy, and labor, or by the woman's request.[1] Cesarean section can be performed under general anesthesia (GA) or regional anesthesia such as subarachnoid block (SAB), epidural anesthesia, or combined spinal-epidural anesthesia (CSE).

The choice of regional anesthesia, especially SAB, is gaining more attention worldwide for elective cesarean section due to the avoidance of the airway manipulation, less risk of aspiration of gastric content, and ease to perform. Although SAB is safe and effective, it does have complications such as postdural puncture headache, nerve damage, local anesthetic toxicity, and hypotension.[2]

On the other hand, GA refers to the loss of ability to perceive pain associated with loss of consciousness produced by intravenous (IV) or inhalation anesthetic agents or a combination of both. Many induction agents such as propofol, thiopentone, and ketamine are available for use during the conduct of GA for cesarean section. The use of suxamethonium is required to facilitate laryngoscopy and tracheal intubation for positive pressure ventilation with oxygen-enriched halogenated vapor. The risks include the aspiration of stomach contents, awareness of the surgical procedure (due to inadequate anesthesia), failed intubations, and respiratory problems for both mother and baby. The use of a halogenated agent increases the tendency for greater risk of moderate-to-severe maternal blood loss compared to SAB.[3] It is well known that the use of halogenated anesthesia is considered a predisposing factor for uterine atony and hemorrhage following a cesarean section.[4]

Following the use of either of the anesthetic techniques, a good uterine tone should be adequately maintained to prevent avoidable blood loss from a hypotonic uterus. Most often, oxytocics are used to prevent postpartum uterine atony and hemorrhage. However, the optimal dose of oxytocics to be used remains unclear and continues to generate controversy among anesthetists and obstetricians.

Our clinical impression was that carbetocin could have the same effect on the uterus and produce adequate uterine contraction and tone during cesarean section under GA and SAB. Hence, in the present study, we compared the effect of IV carbetocin on uterine tone and blood loss after delivery of the fetus under two anesthetic techniques during cesarean section.

   Methods Top

Following approval by the Ethics and Research Committee of the University of Port Harcourt Teaching Hospital, Port Harcourt, informed consent was obtained from parturients undergoing elective cesarean section under either SAB or GA. In a nonrandom convenient sampling method, parturients were recruited into either of the two groups based on the parturient's choice of anesthesia. Those parturients who rejected the offer for SAB and those with hypersensitivity for the local anesthetic agent used were allocated to receive GA for cesarean section. All parturients in both the groups received IV ranitidine 50 mg in the morning of surgery. In the operating room, IV access was secured with a size 16 or 18 G cannula and monitoring for pulse, noninvasive blood pressure, electrocardiogram, and peripheral oxygen saturation were commenced.

The parturients who received SAB were placed in sitting position after a preload with 1000 ml Ringer's lactate over 15 min, with further IV fluids administered at the discretion of the attending anesthetist. Following aseptic protocol, they received a subarachnoid injection of 10 mg 0.5% heavy bupivacaine with 25 mcg fentanyl admixtures using a 25 G Quincke needle. After the injection, a light dressing was placed over the puncture site and the parturient returned to supine position with a wedge under the right flank to achieve a left lateral displacement of the gravid uterus. Surgery commenced after the attainment of T6 sensory block height.

For the group of parturients who received GA, preoxygenation with 100% oxygen was performed for 3–5 min, and lidocaine (1–2 mg/kg) was administered to blunt the laryngeal reflexes. The induction agent propofol (2.5 mg/kg) was administered, cricoid pressure was applied, and suxamethonium (1.5 mg/kg) was given intravenously to facilitate laryngoscopy and tracheal intubation. Correct placement was confirmed and secured within 2 min. The patient was maintained on 1-1.5% isoflurane in 100% oxygen flowing at 8 L/min and maintained throughout the surgical procedure until skin closure. Nitrous oxide was not used as the agent is unavailable in our hospital.

In both the groups, carbetocin 100 mcg bolus was administered intravenously after delivering the baby's shoulders. Pain was controlled by administering 100 mcg of fentanyl after the baby's umbilical cord was clamped in the GA group. Rectal diclofenac 100 mg was also administered at the end of the procedure in both the groups. All the parturients in both the groups received 1500 ml of crystalloids (normal saline or lactated Ringer's solution). If hypotension, which was defined as a 20% reduction from the baseline blood pressure, occurred, then additional crystalloids and bolus doses of 3 mg ephedrine were administered at the discretion of the attending anesthetist.

Primary outcomes

The postoperative blood loss over a 24-h period was assessed. The intraoperative uterine tone after administration of the IV carbetocin 100 mcg was also assessed.

Secondary outcomes

The total ephedrine consumption, hemodynamic profile, and neonatal Apgar scores recorded at 1 and 5 min after the umbilical cord was clamped were assessed.

Data analysis

Data analyses were performed using SPSS version 25 (SPSS Inc., Chicago, Illinois, USA). Data obtained were tabulated with continuous variables expressed as mean ± standard deviation and median (interquartile range) and number and percentages. Categorical variables such as Apgar scores were expressed as median (interquartile range) while continuous variables were compared and analyzed between the groups recruited by convenient sampling using the unequal sample independent Welch t-test. Apgar <7 at 1 min, Apgar <7 at 5 min, and umbilical cord blood pH <7.2 were considered predictors of adverse neonatal outcome. All hypothesis tests were two-sided with P < 0.05 considered statistically significant.

   Results Top

A total of 478 consecutive high-risk parturients scheduled for elective cesarean section participated throughout the study.

[Table 1] shows the bio-characteristics of the women who received either SAB or GA for the surgery. The two groups were comparable in their bio-characteristics in terms of age, weight, height, body mass index, preoperative hemoglobin, and gestational age. The differences in these variables were not statistically significant.
Table 1: Bio-characteristics of women undergoing elective cesarean section under general anesthesia or subarachnoid block

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The case mix was also essentially the same in both the groups in terms of indications for surgery. This is demonstrated in [Table 2].
Table 2: Case mix of surgeries in the two groups

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[Table 3] shows the clinical outcomes following the use of IV carbetocin in the two groups. The uterine tone following the administration of carbetocin 100 mcg shows that at 0 min, while it was poor in the SAB group, the tone was very poor in the parturients who received GA. At 1 min after carbetocin, the uterine tone was firm in the SAB group and fairly firm in those who had GA. At 2 min, the uterine tone was observed to be strong in the SAB group while it was reported to be firm in the GA group. At the 5th min, the tone was observed to be strong in both the groups. None of the parturients in the two groups had the need for additional carbetocin. However, while the estimated intraoperative blood loss in the SAB group was 250.44 ± 50.59 ml, it was observed to be 470.89 ± 35.70. The difference in the blood loss was statistically significant, P = 0.000000. The table also shows the amount of IV ephedrine consumed intraoperatively. While the SAB group received a mean dose of 6.25 ± 2.05 mg, the GA group had 11.25 ± 2.49 mg, P = 0.000000. The difference in the ephedrine need was more in the GA group, and this was statistically significant.
Table 3: Clinical outcomes following the use of carbetocin

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[Table 4] shows the distribution of maternal blood loss over a 24-h period. Result shows that there was no further blood loss after the cesarean section. While 251 (56.4%) parturients in the SAB group had between 151 and 250 ml of intraoperative blood loss, only 4 (12.1%) parturients in the GA group lost the same volume range. Twenty-three (60.7%) parturients in the GA group had between 251 and 500 ml of blood loss while 89 (20%) lost the same volume in the SAB group. While the general blood loss was limited to <500 ml in the SAB group, 6 (18.2%) parturients in the GA group loss >500 ml. There was no further blood loss observed in both the groups after the 6th h till the end of the 24th h.
Table 4: Maternal blood loss over a 24-h period

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[Table 5] shows the hemodynamic data of the two groups of parturients. Result shows no statistically significant difference in terms of the heart rates between the two groups. However, the GA group had lower values of the mean systolic, mean diastolic, and mean arterial pressure compared to those of the SAB group; P = 0.006, P = 0.002, and P = 0.003, respectively. The differences are statistically significant.
Table 5: Hemodynamic profiles of the parturients in the two groups

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The neonatal outcomes are shown in [Table 6]. While the Apgar score at 1 min was 9 (ranging between 8 and 10) in the SAB group, it was also 9 (ranging between 8 and 10) in the GA group. However, at 5 min, it was 10 (ranging between 9 and 10) in the SAB group and 9 (ranging between 9 and 10) in the GA group. The table also shows the values of the umbilical vein blood pH. While it was 7.34 ± 0.09 in the babies delivered under SAB, it was 7.35 ± 0.02 in the GA group, P = 0.071. This difference was not statistically significant.
Table 6: Neonatal outcomes of delivery from elective cesarean section under general anesthesia or subarachnoid block

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   Discussion Top

To the best of our knowledge, there have been no previous studies comparing the effect of IV carbetocin administration in parturients scheduled for elective cesarean section under GA and SAB. Our findings in this study showed that the uterine tone was better and faster achieved after carbetocin injection in parturients who received SAB than those that had GA during cesarean section. A more significant intraoperative blood loss was also observed in the GA group than the SAB group.

It is well known that regional anesthesia, especially SAB, is the preferred mode of anesthesia for elective cesarean section following the lower risks associated with it.[1],[3] From our results, it can be deduced that both GA and SAB were available for these parturients. While most parturients chose to have SAB for the cesarean birth in this index study, others specifically requested for GA. Some of the modes of anesthesia were determined by the attending anesthetist following a diagnosed coagulopathy or if there was an anticipated difficulty in securing the airway under anesthesia.

Following the administration of GA on our parturients, it was observed that the response to a good uterine tone was slower than those who delivered under SAB. It is well known that all volatile halogenated anesthetic agents produce a dose-related relaxation of the uterus which may lead to increased blood loss during cesarean section. From induction to delivery of the infant, 1.5 MAC is administered to prevent maternal awareness but was later reduced to 1 MAC of isoflurane after delivery and carbetocin. Lower MAC values tend to have less likelihood to promote uterine atony. Volatile anesthetics are known to act on gamma-aminobutyric acid 1 receptors and voltage-sensitive Ca2+ and Na+ channels.[4],[5],[6] This is important in obstetrics because all halogenated anesthetic agents including isoflurane used in this study promote uterine atony. The levels needed for surgical anesthesia with a halogenated vapor as the sole agent may increase blood loss at delivery despite the use of uterotonics (oxytocin).[7],[8] This could account for the higher amount of intraoperative blood loss observed among the GA group in our study compared to the group of parturients who had SAB, a finding that corroborates with that of Lertakyamanee et al.[9]

Assessment of uterine tone during cesarean section could suffer inter- and intraobserver variability. Assessment of the strength of the uterine tone is quite subjective. However, the tactile assessment carried out and visual observations tend to corroborate with each other in our study. There was a delay in attaining a firm to strong uterine tone in those who had GA despite receiving the same dose of carbetocin with the SAB group. It can be deduced therefore that the administration of carbetocin following GA might produce a delayed response for a better uterine tone. Our study could not demonstrate an additional carbetocin need during and after cesarean section in all the women in the two groups; a finding that corroborates with that of Dansereau et al.[10] We also observed the effectiveness of carbetocin regarding the uterine contraction, tonicity, and the reported no further blood loss at 6, 12, and 24 h after cesarean section in both the groups.

It is well known that the use of uterotonics impacts negatively on the hemodynamic parameters of parturients.[11] The exact mechanism of this action is still a subject of controversy. This action may be worse in the event of severe maternal hemorrhage during cesarean section under GA. The hemodynamic effects of bolus doses of most uterotonics (oxytocic derivatives) consist of systemic vasodilatation, with resultant hypotension, tachycardia, and increase of cardiac output. One study by Moertl et al. showed a better hemodynamic profile in parturients who received carbetocin than those who had oxytocin during cesarean section under SAB.[12] Our present study showed that those who had IV carbetocin 100 mcg under SAB demonstrated a better hemodynamic profile than the GA group. The mean arterial blood pressure was significantly lower in the GA group which could have accounted for a higher consumption of the vasopressor – ephedrine in that group. Isoflurane used in our study is a well-known potent systemic vasodilator. The exact mechanism of vasodilatation is not well known. Schwinn et al.[13] had proposed that isoflurane could cause vasodilatation by direct arteriolar relaxation leading to decreases in systemic vascular resistance, hence the higher dose of ephedrine used.

However, isoflurane may interact with or inhibit other systems responsible for vasoconstriction such as α2-adrenergic agonists, angiotensin II, endothelin, or renin. It could also interact with vasodilators such as atrial natriuretic factor or endothelial relaxing factor or calcium channels, although one study suggests that isoflurane vasodilation is mediated by mechanisms other than calcium-entry blockade.[11] In addition, isoflurane causes some myocardial depression, hence a reduction in cardiac output and concomitant fall in systemic blood pressure.[14] This could explain the observation made on the hemodynamic profile of the parturients in the GA group which showed a lower blood pressure profile and a higher dose of ephedrine needed in our study. This finding is clinically important because it demonstrates that α1-adrenergic stimulation with phenylephrine could be effective in correcting hypotension in patients receiving isoflurane anesthesia and that the expected response will be similar to those who had SAB and received ephedrine treatment for hypotension. Although the group that had SAB also showed a decrease in the mean arterial blood pressure, this was not as steep as that observed in the GA group. SAB is well known to cause vasodilatation through the inhibition of the sympathetic nervous system which is amenable to treatment with ephedrine.

In our study, the incision to delivery interval was not studied. However, before the delivery of the baby in the GA group, the induction agent and volatile vapor were the primary anesthetic. If a significantly prolonged length of time occurs between induction of GA and delivery, cardiorespiratory depression and decreased tone of the infant should be anticipated.[15] The neonatal outcomes of babies delivered in this present study were comparable in both the groups in terms of Apgar scores and umbilical blood pH though the fetal washout of the volatile vapor used in the GA group was not measured.

The main limitation of our study is its prospective observational design. Specifically, we could not randomize the patients because we followed the appropriate medical indication for the elective cesarean section and the choice of technique by the parturients which gave rise to the unequal sample sizes observed in the two groups.

Another limitation was from the assessment of the uterine tone. The assessment could have been limited by both inter- and intraobserver variability. The use of a tocodynamometer could give a near-proper assessment of the uterine tone/contraction following the administration of the IV carbetocin in our study population.

   Conclusion Top

This study showed that the intraoperative maternal blood loss was less among the parturients who received subarachnoid blood. The higher volume of blood loss under GA could probably be due to the effect of the halogenated vapor used for the GA on the uterine tone. There was no further blood loss after the intraoperative period. The hemodynamic profile was better under SAB as evidenced by the total ephedrine consumption.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Ghaffari S, Dehghanpisheh L, Tavakkoli F, Mahmoudi H. The effect of spinal versus general anesthesia on quality of life in women undergoing cesarean delivery on maternal request. Cureus 2018;10:e3715.  Back to cited text no. 1
Afolabi BB, Lesi FE. Regional versus general anaesthesia for caesarean section. Cochrane Database Syst Rev 2012;10:CD004350.  Back to cited text no. 2
Aksoy H, Aksoy Ü, Yücel B, Özyurt SS, Açmaz G, Babayiğit MA, et al. Blood loss in elective cesarean section: Is there a difference related to the type of anesthesia? A randomized prospective study. J Turk Ger Gynecol Assoc 2015;16:158-63.  Back to cited text no. 3
Milligan KR. Use of halogenated anesthesia with maternal hemorrhage. NAACOGS Clin Issu Perinat Womens Health Nurs 1991;2:396-401.  Back to cited text no. 4
Bloom SL, Spong CY, Weiner SJ, Landon MB, Rouse DJ, Varner MW, et al. Complications of anesthesia for cesarean delivery. Obstet Gynecol 2005;106:281-7.  Back to cited text no. 5
Hemmings HC Jr. Sodium channels and the synaptic mechanisms of inhaled anaesthetics. Br J Anaesth 2009;103:61-9.  Back to cited text no. 6
Cyna AM, Dodd J. Clinical update: Obstetric anaesthesia. Lancet 2007;370:640-2.  Back to cited text no. 7
Yoo KY, Lee JC, Yoon MH, Shin MH, Kim SJ, Kim YH, et al. The effects of volatile anesthetics on spontaneous contractility of isolated human pregnant uterine muscle: A comparison among sevoflurane, desflurane, isoflurane, and halothane. Anesth Analg 2006;103:443-7.  Back to cited text no. 8
Lertakyamanee J, Chinachoti T, Tritrakarn T, Muangkasem J, Somboonnanonda A, Kolatat T. Comparison of general and regional anesthesia for cesarean section: Success rate, blood loss and satisfaction from a randomized trial. J Med Assoc Thai 1999;82:672-80.  Back to cited text no. 9
Dansereau J, Joshi AK, Helewa ME, Doran TA, Lange IR, Luther ER, et al. Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section. Am J Obstet Gynecol 1999;180:670-6.  Back to cited text no. 10
Larciprete G, Montagnoli C, Frigo M, Panetta V, Todde C, Zuppani B, et al. Carbetocin versus oxytocin in caesarean section with high risk of post-partum haemorrhage. J Prenat Med 2013;7:12-8.  Back to cited text no. 11
Moertl MG, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach D. Haemodynamic effects of carbetocin and oxytocin given as intravenous bolus on women undergoing caesarean delivery: A randomised trial. BJOG 2011;118:1349-56.  Back to cited text no. 12
Schwinn DA, McIntyre RW, Reves JG. Isoflurane-induced vasodilation: Role of the alpha-adrenergic nervous system. Anesth Analg 1990;71:451-9.  Back to cited text no. 13
Blaise GA, Girard DC, Caille G, Hollman C, Buluran J, Meloche R. Is isoflurane a calcium antagonist?. Ann Fr Anesth Reanim 1989;8:42-5.  Back to cited text no. 14
Dwyer R, Fee JP, Moore J. Uptake of halothane and isoflurane by mother and baby during caesarean section. Br J Anaesth 1995;74:379-83.  Back to cited text no. 15


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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