Part 11: Fluid Therapy in Obstetrics

52: Fluid Management for Cesarean Delivery

Chapter outlines

Maternal Hypotension in Spinal Anesthesia: Causes and Mechanisms

Management of Hypotension During Cesarean Delivery

Fluid loading

- Preloading

- Co-loading

Vasopressors

- Phenylephrine

- Ephedrine

- Phenylephrine versus ephedrine

- Norepinephrine as vasopressor

Non-Pharmacological Measures

Postoperative Care after Cesarean Delivery

INTRODUCTION

Spinal anesthesia is the most common type of anesthesia used in cesarean sections [1].

Maternal hypotension is the most common complication of spinal anesthesia for cesarean delivery. Maternal hypotension is defined as systolic blood pressure (SBP) <90 mmHg or a reduction in mean arterial blood pressure >30% fall from baseline [2].

The incidence of maternal hypotension during spinal anesthesia for elective cesarean delivery is much higher (70–80%) [3] as compared to the incidence of hypotension caused by spinal anesthesia in nonpregnant women (about 33%) [4].

Mechanism of maternal hypotension: Spinal anesthesia blocks the sympathetic nerve fibers innervating smooth muscles of arteries and veins, which causes reduced peripheral vascular resistance and vasodilatation. Vasodilatation in the lower part of the body is the crucial mechanism of the development of hypotension due to spinal anesthesia in uncomplicated pregnancy [5].

Consequences of maternal hypotension: Maternal hypotension after spinal anesthesia for cesarean section causes both maternal and fetal/neonatal adverse effects [6]. Spinal hypotension can result in maternal nausea, vomiting, and dizziness due to a reduction in cerebral perfusion, which induces transient brainstem ischemia [7]. In addition, treatment of spinal hypotension can cause iatrogenic pulmonary edema or severe maternal hypertension. Severe and sustained hypotension can decrease uteroplacental perfusion, which can cause fetal hypoxia, acidosis, and neonatal depression [8].

MANAGEMENT

The goal of management is to optimize maternal, uterine, and fetal perfusion, which is crucial for the mother’s safety and the baby’s wellbeing.

Major steps in treating spinal hypotension are fluid loading, vasopressor, and non-pharmacological measures. Combinations of interventions will be more effective than single ones [9].

THE GOAL OF BLOOD PRESSURE

Treatment aims to maintain systolic blood pressure ≥100 mmHg or ≥90% of an accurately measured baseline blood pressure [10, 11].

FLUID LOADING

Before the initiation of spinal anesthesia, it is important for the patient to have large-diameter intravenous access (preferably 16 or 18 gauge) in place. This will allow for the rapid administration of fluids, medications, and blood products if necessary.

The two most important determinants for the optimal and effective treatment of spinal hypotension are: (1) The type of fluid (crystalloid compared with colloid solutions) and, (2) The timing of administration [given before spinal anesthesia (preloading) or given immediately after spinal block placement (co-loading) as rapid infusions.

A. Preloading

Preloading is a method where IV fluid is administered immediately before spinal anesthesia to reduce post-spinal hypotension (PSH).

Crystalloid preloading: Rapid administration of 10–20 mL/kg of intravenous Ringer's lactate just 15–20 minutes before spinal anesthesia was previously a routine practice to minimize hypotension resulting from sympathetic blockade. But fluid preloading with crystalloid is clinically ineffective due to its rapid redistribution and therefore is currently not recommended before spinal anesthesia [9, 12, 13].

Colloid preloading: In contrast to crystalloid preloading, colloid preloading significantly reduces hypotension and improves maternal hemodynamics [9, 14].

As preloading is not superior to co-loading (irrespective of the type of IV solution used), one should not waste significant time in administering a predetermined IV fluid volume and consequently delay spinal anesthesia initiation [15].

B. Co-loading

In co-loading, IV fluids are rapidly administered and started simultaneously with spinal anesthesia to reduce post-spinal hypotension. Using co-loading protocols is less time consuming with better (or at least similar) effects than preloading [16].

Co-loading is a more rational and physiological approach. In fluid co-loading, IV fluid administration coincides precisely with the time of the maximal vasodilatory effect of spinal anesthesia and thereby compensates for the “relative hypovolemia” and prevents post-spinal hypotension [17].

Crystalloid co-loading: A balanced electrolyte solution (e.g., Ringer’s lactate solution) is the most commonly used intravenous fluid for bolus administration. Usually, a bolus of about 10–15 ml per kg or 500 to 1000 mL of Ringer’s lactate is infused as fast as possible in fluid co-loading.

Use dextrose free IV fluids for crystalloid co-loading because it avoids maternal hyperglycemia. The immediate effect of maternal hyperglycemia is fetal hyperglycemia, but it may cause neonatal hypoglycemia after delivery. When dextrose containing IV fluid is administered to the mother before delivery, glucose crosses the placental barrier and can result in fetal hyperglycemia and and hyperinsulinemia. After delivery, the glucose supply is ceased, but neonatal insulin levels are still elevated, which causes neonatal hypoglycemia [18].

The volume of fluid given during spinal anesthesia may vary depending on the patient’s underlying co-morbidities and their current volume status, with a smaller volume typically being given to patients with severe preeclampsia.

Crystalloid co-loading is more effective than crystalloid preloading in preventing hypotension during spinal anesthesia for elective cesarean delivery [19–22]. Additionally, crystalloid co-loading is similar in effectiveness to colloid preloading [23].

Colloid co-loading: For colloid co-loading third generation colloids such as tetrastarch (Hydroxyethyl starch 130/0.4) seem safer than other colloids [24]. Colloid co-loading is not superior to colloid preloading [17].

Both crystalloid and colloid co-loading are equally effective in decreasing the incidence of spinal hypotension in cesarean delivery [21, 25]. However, the volume needed for colloid co-loading is less than that required for crystalloid co-loading [23].

Because of less adverse effects, lesser cost, ready availability, and restricted or second line usage of colloids in most studies [26], current literature recommends the use of crystalloids than colloids co-loading in cesarean delivery [27].

Factors affecting fluid requirements: Total requirement of intravenous fluids (crystalloids) during and after cesarean delivery varies considerably but is usually 2 to 3 liters. The requirement of fluid volume may be higher in patients with sepsis syndrome, vomiting, prolonged labor without adequate fluid intake, and increased blood loss.

In patients with preeclampsia, spinal anesthesia tends to cause less hypotension than it does in normal pregnant women. Therefore, it is recommended to use mild to moderate intravascular volume loading during spinal anesthesia in patients with preeclampsia.

The loading of a large volume of fluid carries the risk of pulmonary edema in preeclampsia [19].

VASOPRESSORS

Vasopressor therapy is a crucial component in minimizing spinal hypotension. Fluid loading protocols alone are not usually sufficient to achieve reasonable control in post-spinal hypotension [16]. Besides crystalloid or colloid co-loading, a significant proportion of patients require vasopressors to control spinal hypotension [28].

Vasopressor treatment aims to restore systemic vascular resistance. Alpha-adrenergic agonist drugs are the most appropriate agents to treat or prevent hypotension following spinal anesthesia [11]. In addition, prophylactic vasopressors are superior in preventing adverse neonatal outcomes compared to reactive treatment [29].

Phenylephrine and ephedrine are the two most widely used and recommended vasoconstrictor agents in treating spinal hypotension [15]. Phenylephrine is a synthetic selective direct alpha-adrenergic agonist. Ephedrine is a synthetic mixed adrenergic agonist. Ephedrine is a stimulant that directly activates alpha and beta-adrenergic receptors and indirectly stimulates the release of endogenously stored norepinephrine. Recently, even norepinephrine (noradrenaline) has been found to be helpful in preventing and treating spinal hypotension during cesarean delivery.

A. Phenylephrine

A combined approach using titrated phenylephrine with crystalloid co-loading is probably the best option for the management of hypotension during spinal anesthesia for cesarean section [6, 21]. Phenylephrine infusions co-administered with crystalloid has shown to eliminate the likelihood of spinal hypotension [30].

Pharmacology: Phenylephrine is a drug that acts selectively on the alpha-1 adrenergic receptors found on the vascular smooth muscle cells in blood vessels, resulting in vasoconstriction. It is a potent agent that increases total peripheral vascular resistance and increases both systolic and diastolic blood pressure. The onset of action is <1 minute, and its duration of effect is short lasting (15 to 20 minutes). At higher doses, phenylephrine can cause bradycardia due to the activation of baroreceptors, which can lead to a reduction in maternal cardiac output [31].

Preparation: Injection phenylephrine, available as a 1 ml ampoule, contains 10 mg of phenylephrine.

Method of administration (bolus vs. infusion)

In the treatment of spinal hypotension, prophylactic phenylephrine infusion is superior to bolus administration because of the lower incidence of intraoperative nausea and vomiting [32, 33]. An international consensus statement for the management of spinal hypotension by AAGBI (2018) recommends prophylactic phenylephrine infusion as the first line of management [11].

Dose: To prepare an infusion, add 1 ml (10 mg) of phenylephrine solution in 100 ml of normal saline. Each ml of this infusion will provide 100 mcg of phenylephrine (100 mcg/ml solution).
IV bolus: A commonly used dose of a prophylactic bolus of IV phenylephrine is 50 to 100 mcg (0.5 to 1 ml). Repeat the dose every 2 to 5 minutes as required, but do not give more than a total dose of 200 micrograms (mcg).
IV infusion: Currently recommended dose of phenylephrine infusion is 25–50 mcg/min. (0.25 to 0.5 ml/min) [11, 16] Prophylactic phenylephrine infusion is started with an infusion pump as soon as the spinal anesthesia is given. The dose is titrated according to maternal systolic blood pressure response and pulse rate. A higher incidence of post-spinal hypotension occurs with the lower dose (25 mcg/min), and a higher incidence of reactive hypertension and bradycardia occurs with the higher dose (50 mcg/min) [31, 34].
IV bolus followed by infusion: When phenylephrine is infused after spinal anesthesia, there will be a delay in achieving adequate blood pressure levels. However, an initial phenylephrine bolus immediately after the spinal anesthesia, followed by a phenylephrine infusion, will maintain blood pressure without adverse effects [5].

B. Ephedrine

Ephedrine is a sympathomimetic drug that stimulates both alpha and beta-adrenergic receptors. As a result, it stimulates the heart rate, increases cardiac output, and variably increases peripheral resistance, leading to an increase in blood pressure.

Previously, ephedrine was the first-line treatment for spinal hypotension. But the trend to use ephedrine in the treatment of post-spinal anesthesia hypotension is decreasing because:

Repeated administration of ephedrine diminishes its vasoconstrictive effect [35].
Delayed onset of action of ephedrine may result in a longer period of hypotension than phenylephrine.
The relatively long duration of the effect of ephedrine makes accurate titration of blood pressure difficult [36].
Ephedrine may increase the risk of fetal acidosis by crossing the placenta to a greater extent [37].

Currently, ephedrine is preferred to treat spinal hypotension in a pregnant patient with bradycardia, as it typically increases heart rate.

The commonly used dose of ephedrine is 5 to 10 mg IV boluses or 1 to 5 mg/min IV infusion.

C. Phenylephrine versus ephedrine

Ephedrine was previously the first-line therapy for parturients with spinal hypotension [38]. But phenylephrine is currently vasopressor of choice in the treatment of spinal hypotension in the absence of maternal bradycardia [39–41]. Reflex bradycardia and decreased cardiac output are the primary concerns associated with phenylephrine.

As compared to ephedrine, phenylephrine is preferred and superior because of its faster onset [42], ease to titrate, better preservation of uterine blood flow, does not cause or worsen maternal tachycardia [43, 44], less reactive hypertension [45], less incidence of fetal acidosis [46], and less maternal nausea and vomiting [47, 48].

However, ephedrine may be more beneficial in patients with bradycardia, compromised cardiac functions, uteroplacental insufficiency, and preeclampsia [16].

Vasopressor selection based on maternal heart rate:

Hypotension and tachycardia: This is the usual response to spinal anesthesia, and phenylephrine is a preferred vasoconstrictor agent in treatment.
Hypotension and bradycardia: This is the unusual response that resembles a vagal reaction; rather than ‘appropriate’ tachycardia and vasoconstriction. Ephedrine is a preferred vasoconstrictor agent for spinal hypotension associated with bradycardia [40].

D. Norepinephrine as vasopressor

Norepinephrine (NE, noradrenalin) is recently introduced to prevent and treat spinal hypotension during cesarean delivery [49, 50]. Norepinephrine (NE) is a potent vasopressor having both alpha-adrenergic agonistic activity, and weak beta-adrenergic agonistic activity. NE has minimal cardiac depressant effect [51]. NE has a similar effect to phenylephrine in maintaining blood pressure but may be associated with higher heart rates (closer to baseline), and greater cardiac output [52, 53].

Because of beneficial cardiac effects and potency, NE may be preferred in mothers with low baseline heart rates or poor cardiac function, where phenylephrine is relatively contraindicated [51].

More research is needed to evaluate the safety and efficacy of norepinephrine before its routine use in obstetric patients [51, 54]. Table 52.1 summarizes all vasopressors used in spinal hypotension during cesarean delivery.

Table 52.1 Vasopressors in spinal hypotension during cesarean delivery
Vasopressor	Phenylephrine	Ephedrine	Norepinephrine (noradrenaline)
Mechanism of action	Selective direct α 1 receptor agonist	Direct α and β agonist and indirect release of norepinephrine	Direct α 1 and β 1 agonist
Arterial vasoconstriction	Potent	Less potent	Potent
Chronotropic effect	Negative	Positive	Positive
Maternal heart rate	Reflex bradycardia	Tachycardia	Increased
Cardiac output	Decrease	Increase	Modest increase
Onset of action	Faster	Slower	Immediate
Duration of action	Short-acting (15 to 20 minutes)	Relatively long duration (about 60 min), so longer period of hypotension	Very short (1 to 2 minutes)
Advantage	No maternal tachycardia, better titratability	No maternal bradycardia	Less negative effects on heart rate and cardiac output
Selection	Currently preferred vasopressor in post-spinal hypotension. Preferred in maternal tachycardia	Preferred in maternal bradycardia in post-spinal hypotension	Beneficial effects in mothers with bradycardia and compromised cardiac function in recent studies
Strength of injectable solution and dilution	10 mg/mL (1 mL diluted in 100 ml of normal saline equals 100 mcg/mL)	30 mg/mL, 50 mg/mL (1 mL diluted in 10 ml of normal saline equals 3 mg/mL or 5 mg/mL)	1mg/mL (2 mL diluted in 500 ml of D5W or DSNS equals 4 mcg/mL)
Commonly used doses	50 to 100 mcg IV bolus or 25 to 100 mcg/min IV infusion	5 to 10 mg IV boluses or 1 to 5 mg/min IV infusion	Further studies are required before its routine use

NON-PHARMACOLOGICAL MEASURES

In the supine position, the gravid uterus compresses the maternal abdominal aorta and inferior vena cava, which decreases cardiac output [55]. Positioning protocols for the prevention of post-spinal hypotension are targeted to relieve aortocaval compression imparted by the gravid uterus and increase venous return [16]. Left lateral uterine displacement with 15° table tilt reduces inferior vena cava compression and is routinely recommended in addition to other measures [11, 56, 57].

POSTOPERATIVE CARE AFTER CESAREAN DELIVERY

Early oral intake

After cesarean delivery, fluids or food is traditionally avoided until bowel functions return (confirmed by bowel sounds or passage of flatus or stools). But in uncomplicated cesarean delivery, evidences to justify the restriction of oral fluids or food is lacking.

Current evidence suggests that early oral intake (within six hours of delivery) may have several benefits for postpartum care. These benefits include promoting the return of bowel function (through the stimulation of the gastrocolic reflex), encouraging early ambulation, reducing the duration of intravenous fluid administration, decreasing the risk of sepsis, shortening the time to breastfeeding, decreasing the length of hospital stay, and reducing the cost of hospitalization [58–61].

Nausea and vomiting after cesarean delivery can delay early oral intake. In the management of postoperative nausea and vomiting (PONV), the combination of anti-emetics is more effective than monotherapy [62].

During cesarean delivery, intraoperative nausea and vomiting (IONV) are common [7]. Measures to reduce IONV during cesarean are the prevention of hypotension with liberal perioperative administration of IV fluids, maintaining normal blood pressure with prophylactic use of vasopressors (i.e., phenylephrine or ephedrine), administration of anti-emetics (metoclopramide and ondansetron) and minimizing visceral manipulation (e.g., uterine exteriorization) [63, 64].

REFERENCES

Shibli KU, Russell IF. A survey of anaesthetic techniques used for caesarean section in the UK in 1997. Int J Obstet Anesth 2000;9(3):160–7.
Miller RD. Miller’s Anaesthesia. 8th ed. Saunders, an Imprint of Elsevier Inc; 2015. Chapter 56:p.1773.
Mercier FJ, Augè M, Hoffmann C, et al. Maternal Hypotension during Spinal Anesthesia for Caesarean Delivery. Minerva Anestesiol 2013;79(1):62–73.
Montoya BH, Oliveros CI, Moreno DA. Managing Hypotension Induced by Spinal Anesthesia for Caesarean Section. Rev. Col. Anest. Mayo-Julio 2009;37(2):131–140.
Kuhn JC, Hauge TH, Rosseland LA, et al. Hemodynamics of Phenylephrine Infusion Versus Lower Extremity Compression during Spinal Anesthesia for Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Study. Anesthesia and Analgesia 2016;122(4):1120–9.
Butwick AJ, Columb MO, Carvalho B. Preventing Spinal Hypotension during Caesarean Delivery: What is the latest? Br J Anaesth. 2015;114(2):183–6.
Balki M, Carvalho JC. Intraoperative Nausea and Vomiting during Cesarean Section under Regional Anesthesia. Int J Obstet Anesth 2005;14(3):230–41.
Mueller MD, Brühwiler H, Schüpfer GK, et al. Higher Rate of Fetal Acidemia after Regional Anesthesia For Elective Cesarean Delivery. Obstet Gynecol 1997;90(1):131–4.
Chooi C, Cox JJ, Lumb RS, et al. Techniques for Preventing Hypotension during Spinal Anaesthesia for Caesarean Section. Cochrane Database Syst Rev. 2017;8(8):CD002251.
Klöhr S, Roth R, Hofmann T, et al. Definitions of Hypotension after Spinal Anaesthesia for Caesarean Section: Literature Search and Application to Parturients. Acta Anaesthesiol Scand 2010;54(8):909–21.
Kinsella SM, Carvalho B, Dyer RA, et al. International Consensus Statement on the Management of Hypotension with Vasopressors during Caesarean Section under Spinal Anaesthesia. Anaesthesia 2018;73(1):71–92.
Mercier FJ. Fluid Loading for Cesarean Delivery under Spinal Anesthesia: Have we studied all the Options? Anesth Analg. 2011;113(4):677–80.
Kee WDN. Prevention of Maternal Hypotension after Regional Anaesthesia for Caesarean Section. Current Opinion in Anaesthesiology 2010;23(3):304–9.
Melchor JR, Espinosa Á, Hurtado EM, et al. Colloids Versus Crystalloids in the Prevention of Hypotension Induced by Spinal Anesthesia in Elective Cesarean Section. A Systematic Review and Meta-Analysis. Minerva Anestesiologica 2015;81(9):1019–30.
Apfelbaum JL, Hawkins JL, Agarkar M, et al. Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology. Anesthesiology 2016;124(2):270–300.
Hasanina A, Mokhtar AM, Badawy A, et al. Post-Spinal Anesthesia Hypotension during Cesarean Delivery, a Review Article. Egyptian Journal of Anaesthesia 2017;33(2):189–193.
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(2):150–5.
Sumikura H. Neonatal Hypoglycemia after Cesarean Section. J Anesth 2013;27(2):167–168.
Loubert C. Fluid and Vasopressor Management for Cesarean Delivery under Spinal Anesthesia: Continuing Professional Development. Can J Anaesth 2012;59(6):604–19.
Ni HF, Liu HY, Zhang J, et al. Crystalloid Coload Reduced the Incidence of Hypotension in Spinal Anesthesia for Cesarean Delivery, When Compared to Crystalloid Preload: A Meta-Analysis. Biomed Res Int. 2017;2017:3462529.
Ferre F, Martin C, Bosch L, et al. Control of spinal anesthesia-induced hypotension in adults. Local Reg Anesth 2020;13:39–46.
Artawan IM, Sarim BY, Sagita S, et al. Comparison the effect of preloading and coloading with crystalloid fluid on the incidence of hypotension after spinal anesthesia in cesarean section. Bali J Anaesthesiol 2020;4(1):3–7.
Tawfik MM, Hayes SM, Jacoub FY, et al. Comparison between Colloid Preload and Crystalloid Co-Load in Cesarean Section under Spinal Anesthesia: A Randomized Controlled Trial. International Journal of Obstetric Anesthesia 2014;23(4):317–23.
Van Der Linden P, James M, Mythen M, et al. Safety of Modern Starches used During Surgery. Anesth Analg. 2013;116(1):35–48.
Wani SA, Pandit BH, Din MU, et al. Comparative Study to Evaluate the Effect of Colloid Coloading Versus Crystalloid Coloading for Prevention of Spinal Anaesthesia Induced Hypotension and Effect on Fetal Apgar score in Patients Undergoing Elective Lower Segment Caesarean Section: A Prospective Observational Study. Int J Reprod Contracept Obstet Gynecol 2018;7(5):1868–1875.
Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–1247.
Rijs K, Mercier FJ, Lucas DN, et al. Fluid loading therapy to prevent spinal hypotension in women undergoing elective caesarean section: Network meta-analysis, trial sequential analysis and meta-regression. Eur J Anaesthesiol. 2020;37(12):1126–1142.
Jacob JJ, Williams A, Verghese M, et al. Crystalloid preload versus crystalloid coload for parturients undergoing cesarean section under spinal anesthesia. Journal of Obstetric Anesthesia and Critical Care 2012;2(1):10–15.
Mercier FJ. Cesarean Delivery Fluid Management. Curr Opin Anaesthesiol. 2012;25(3):286–91.
Kee WDN, 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(4):744–50.
Stewart A, Fernando R, McDonald S, et al. The Dose-Dependent Effects of Phenylephrine for Elective Cesarean Delivery under Spinal Anesthesia. Anesthesia and Analgesia 2010;111(5):1230–7.
Siddik-Sayyid SM, Taha SK, Kanazi GE, et al. A Randomized Controlled Trial of Variable Rate Phenylephrine Infusion with Rescue Phenylephrine Boluses versus Rescue Boluses Alone on Physician Interventions during Spinal Anesthesia for Elective Cesarean Delivery. Anesth Analg. 2014;118(30:611–8.
George RB, McKeen DM, Dominguez JE, et al. Randomized Trial of Phenylephrine Infusion Vs. Bolus for Nausea & Vomiting during Cesarean in Obese Women. Can J Anaesth. 2018;65(3):254–262.
Allen TK, George RB, White WD, et al. A Double-Blind, Placebo-controlled Trial of Four Fixed Rate Infusion Regimens of Phenylephrine for Hemodynamic Support during Spinal Anesthesia for Cesarean Delivery. Anesth Analg. 2010;111(5):1221–9.
Kee WDN, Khaw KS. Vasopressors in obstetrics: What should we be using? Curr Opin Anaesthesiol 2006;19(3):238–43.
Kee WDN, Khaw KS, Lee BB, et al. A Randomized Controlled Study of colloid Preload before Spinal Anaesthesia for Caesarean Section. Br J Anaesth. 2001;87(5):772–4.
Kee WDN, Khaw KS, Tan PE, et al. Placental transfer and Fetal Metabolic Effects of Phenylephrine and Ephedrine during Spinal Anesthesia for Cesarean Delivery. Anesthesiology 2009;111(3):506–12.
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(4):354–370.
Van De Velde M. Belgian Guidelines for Safe Regional Anesthesia and Obstetric Anesthesia and Analgesia. Acta Anaesthesiol Belg 2013;64(3):95–96.
Nag DS, Samaddar DP, Chatterjee A, et al. Vasopressors in Obstetric Anesthesia: A Current Perspective. World J Clin Cases. 2015;3(1):58–64.
Heesen M, Stewart A, Fernando R. Vasopressors for the Treatment of Maternal Hypotension Following Spinal Anaesthesia for Elective Caesarean Section: Past, Present and Future. Anaesthesia 2015;70(3):252–7.
Dyer RA, Reed AR, Dyk DV, et al. Hemodynamic Effects of Ephedrine, Phenylephrine, and the Coadministration of Phenylephrine with Oxytocin during Spinal Anesthesia for Elective Cesarean Delivery. Anesthesiology 2009;111(4):753–65.
Cooper DW, Carpenter M, Mowbray P, et al. Fetal and Maternal Effects of Phenylephrine and Ephedrine during Spinal Anesthesia for Cesarean Delivery. Anesthesiology 2002;97(6):1582–1590.
Gunda CP, Malinowski J, Tegginmath A, et al. Vasopressor Choice for Hypotension in Elective Cesarean Section: Ephedrine or Phenylephrine. Arch Med Sci 2010;6(2):257–263.
Lee A, NganKee WD, Gin T. A Dose-Response Meta-Analysis of Prophylactic Intravenous Ephedrine for the Prevention of Hypotension during Spinal Anesthesia for Elective Cesarean Delivery. Anesth Analg 2004;98(2):483–439.
Veeser M, Hofmann T, Roth R, et al. Vasopressors for the Management of Hypotension after Spinal Anesthesia for Elective Caesarean Section. Systematic Review and Cumulative Meta-Analysis. Acta Anaesthesiol Scand 2012;56(7):810–6.
Prakash S, Pramanik V, Chellani H, et al. Maternal and Neonatal Effects of Bolus Administration of Ephedrine and Phenylephrine during Spinal Anaesthesia for Caesarean Delivery: A Randomised Study. Int J Obstet Anesth 2010;19(1):24–30.
Habib AS. A Review of the Impact of Phenylephrine Administration on Maternal Hemodynamics and Maternal and Neonatal Outcomes in Women Undergoing Cesarean Delivery under Spinal Anesthesia. Anesth Analg 2012;114(2):377–90.
Kee WDN, Lee SW, Ng FF, et al. Randomized Double-Blinded Comparison of Norepinephrine and Phenylephrine for Maintenance of Blood Pressure during Spinal Anesthesia for Cesarean Delivery. Anesthesiology 2015;122(4):736–45.
Onwochei DN, Kee WDN, Fung L, et al. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension during Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg 2017;125(1):212–8.
Hasanin AM, Amin SM, Agiza NA, et al. Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension during Cesarean Delivery: A Randomized Dose-finding Trial. Anesthesiology 2019;130(1):55–62.
Kee WDN. The Use of Vasopressors during Spinal Anaesthesia for Caesarean Section. Curr Opin Anaesthesiol 2017;30(3):319–325.
Kee WDN, Lee SWY, Ng FF, et al. Prophylactic Norepinephrine Infusion for Preventing Hypotension during Spinal Anesthesia for Cesarean Delivery. Anesth Analg 2018;126(6):1989–1994.
Dong L, Dong Q, Song X, et al. Comparison of Prophylactic Bolus Norepinephrine and Phenylephrine on Hypotension during Spinal Anesthesia for Cesarean Section. Int J Clin Exp Med. 2017;10(8):12315–12321.
Lees MM, Scott DB, Kerr MG, et al. The Circulatory Effects of Recumbent Postural Change in Late Pregnancy. Clin Sci 1967;32(3):453–465.
Lee SWY, Khaw KS, Kee WDN, et al. Haemodynamic effects from aortocaval compression at different angles of lateral tilt in non-labouring term pregnant women. British Journal of Anaesthesia 2012;109(6):950–6.
Kundra P, Velraj J, Amirthalingam U, et al. Effect of positioning from supine and left lateral positions to left lateral tilt on maternal blood flow velocities and waveforms in full-term parturients. Anaesthesia 2012;67(8):889–93.
Guo J, Long S, Li H, et al. Early versus Delayed Oral Feeding for Patients after Cesarean. Int J Gynaecol Obstet. 2015;128(2):100–5.
Huang H, Wang H, He M. Early Oral Feeding Compared with Delayed Oral Feeding after Cesarean Section: A Meta-Analysis. J Matern Fetal Neonatal Med. 2016;29(3):423–9.
Hsu YY, Hung HY, Chang SC, et al. Early Oral Intake and Gastrointestinal Function after Cesarean Delivery: A Systematic Review and Meta-Analysis. Obstet Gynecol. 2013;121(6):1327–34.
Ogbadua AO, Agida TE, Akaba GO, et al. Early Versus Delayed Oral Feeding after Uncomplicated Cesarean Section under Spinal Anesthesia: A Randomized Controlled Trial. Niger J Surg. 2018;24(1):6–11.
Ituk U, Habib AS. Enhanced Recovery after Cesarean Delivery. F1000Research 2018;7:F1000 Faculty Rev-513.
Habib AS, George RB, McKeen DM, et al. Antiemetics Added to Phenylephrine Infusion during Cesarean Delivery: A Randomized Controlled Trial. Obstet Gynecol. 2013;121(3):615–23.
Jelting Y, Klein C, Harlander T, et al. Preventing nausea and vomiting in women undergoing regional anesthesia for cesarean section: challenges and solutions. Local Reg Anesth. 2017;10:83–90.