Cardiovascular Alterations in the Parturient Undergoing Cesarean Delivery With Neuraxial Anesthesia

Katherine W Arendt; Jochen D Muehlschlegel; Lawrence C Tsen

Expert Rev of Obstet Gynecol. 2012;7(1):59-75.

Interventions to Prevent or Treat Post-neuraxial Anesthesia Hypotension

Maternal Positioning & Other Mechanical Interventions

Maternal positioning has been shown to affect hemodynamic changes following induction of spinal anesthesia. The full lateral position, which minimizes uterine aortocaval compression with term gestation, allows for greater CO than the supine position.^[96,128] The supine position in parturients following the induction of spinal anesthesia results in significant decreases in SV, CO and MAP.^[66] The 'left uterine displacement' (LUD) position tilts the parturient's abdomen and pelvis at least 15 degrees off the midline by placing a wedge under the right buttock; this position shifts the gravid uterus off of the aorta and vena cava.^[129,130] Although a significant improvement in CO can be observed relative to the full supine position,^[128,131] LUD does not completely decompress the aorta and inferior vena cava and further CO increases may be observed in the full lateral position.^[128,131] Therefore, if significant hypotension occurs in the LUD position, greater tilting of the parturient can be employed. It is important to note that experts do question "the exact contribution of tilt to reducing hypotension in spinal anesthesia" and call for more research on various contributing factors of hemodynamic changes associated with spinal anesthesia for CD.^[64]

Patient positioning for the administration of the neuraxial anesthetic technique may influence the maternal blood pressure response, but it may depend on the dose of agent used. In a study comparing the seated versus left lateral positions for administration of a CSE technique (spinal hyperbaric bupivacaine 12 mg with fentanyl 10 mcg, a greater degree of hypotension and vasopressor requirements were observed in the seated position.^[132] However, in a similar study of parturients undergoing a CSE with hyperbaric bupivacaine 6.6 mg with sufentanil 3.3 mcg, less ephedrine was used when the CSE was performed in the seated, versus left lateral, position.^[133] Of note, this may be related to the lower cephalad spread achieved in the seated position, which ultimately resulted in a greater need for epidural supplementation. As such, the use of the left lateral position may be of benefit for traditional dosing for spinal anesthesia for CD; however, the seated position may be better for low-dose dosing when lesser hypotension and vasopressor requirement is desired and an epidural is present for potential supplementation.

Leg wrapping, leg elevation, thromboembolic stockings, inflatable splints, inflatable boots and Trendelenburg positioning have been evaluated as a means of increasing central blood volume and decreasing the incidence of hypotension. A qualitative systematic review of these interventions indicated that leg wrapping and inflatable splints may modestly decrease the incidence of hypotension, but inflatable boots, leg elevation and Trendelenburg positioning appears ineffective.^[134]

Vasopressors

Healthy pregnant women have a diminished response to vasopressor administration, which can result in relatively greater dosage requirements than nonpregnant patients. However, ephedrine, phenylephrine and dopamine can all prevent spinal anesthesia-induced hypotension better than placebo,^[135–138] which has encouraged some practitioners to utilize prophylaxis instead of treatment only, to mitigate the effects of hypotension.

The selection of a vasopressor for the prophylaxis or treatment of spinal hypotension has been a subject of a number of investigations and several current comprehensive reviews.^[139,140] Recent studies have indicated that neuraxial anesthesia, particularly spinal anesthesia, may be associated with decreased fetal umbilical cord pH readings.^[141–143] Historical evidence that vasopressors with predominant α-adrenergic stimulation resulted in uteroplacental vasoconstriction^[144–147] led many anesthesiologists to avoid phenylephrine. Ephedrine, in contrast to α-agonists, demonstrated greater selectivity of systemic over uterine blood vessel constriction,^[148] and was shown to improve maternal blood pressure and uteroplacental blood flow during spinal anesthesia.^[149,150] Ephedrine was subsequently considered the vasopressor of choice to prevent or treat hypotension during neuraxial anesthesia for CD. However, recent evidence has suggested that previous concerns regarding uteroplacental vasoconstriction with the use of phenylephrine may have been overstated, whereas the detrimental effects of ephedrine to the fetus may have been understated.^[151]

The concern with ephedrine in the obstetric population is an association with fetal acidosis and decreases in fetal base excess,^[151–154] possibly in a dose-dependent manner.^[155] In 104 parturients undergoing spinal anesthesia for elective CD randomized to receive an infusion of phenylephrine or ephedrine,^[151] fetuses exposed to ephedrine demonstrated significantly lower pH and base excess, and significantly higher umbilical arterial and venous partial pressure CO₂, lactate, glucose and norepinephrine concentrations. Most interesting, the mean umbilical venous to maternal artery (UV/MA) plasma concentration ratios were significantly greater in the ephedrine group (1.13 vs 0.17), indicating ephedrine's greater ability to cross the placenta. In addition, the umbilical artery to umbilical venous (UA/UV) plasma concentration ratios were also significantly greater with ephedrine (0.83 vs 0.71), indicating that ephedrine likely undergoes less early metabolism and redistribution in the fetal plasma. The greater presence in fetal circulation thus results in an increase in fetal metabolism.

Multiple recent studies have indicated that phenylephrine is more effective with lesser fetal acid base alterations than ephedrine when used either as prophylaxis or treatment for hypotension in both elective and nonelective cesarean deliveries.^[153,156] A randomized double-blinded comparison study of phenylephrine and ephedrine, and their combinations, indicated that decreasing proportions of phenylephrine were associated with worse hemodynamic control and fetal acid-base status.^[157] The weight of the evidence for phenylephrine use for neuraxial anesthesia-induced hypotension during CD has now appeared to equal 'the burden of proof'.^[158] However, in high-risk patients with significant hypertensive disease of pregnancy, comorbid conditions affecting placental physiology, or, in the cases of emergency CD, with impaired or at-risk fetuses, there are insufficient data to support its safety, and there may be some cause for concern.^[159] Further investigations will be necessary to determine the role of α-adrenergic agonists versus other vasopressor agents in these settings.

The efficacy of prophylactic phenylephrine in preventing spinal hypotension is undoubted. A prophylactic phenylephrine infusion, particularly when combined with crystalloid co-hydration, is highly effective in maintaining hemodynamic stability. Ngan Kee and colleagues observed that an intravenous infusion of phenylephrine 100 mcg/min titrated with blood pressure readings carried out each minute nearly eliminated hypotension (defined as SBP <80% baseline) in nonlaboring parturients undergoing spinal anesthesia for elective CD.^[160] Although hypotension occurred in 15 subjects (28.3%; 95% CI: 18.0–41.6%) in the maintenance fluid group (n = 55), only one subject (1.9%; 95% CI: 0.3–9.9%) experienced this in the rapid infusion crystalloid group (n = 57).

Determining the precise dosing regimen for phenylephrine to consistently prevent spinal hypotension while minimizing episodes of undertreatment (hypotension and/or nausea) or over-treatment (hypertension and/or bradycardia) has been recently extensively studied.^{[80,157,160–163]} One study indicates that a fixed rate of 75 or 100 mcg/min phenylephrine is associated with more episodes of hypertension (than placebo or rates of 25 or 50 mcg/min) and a 100 mcg/min infusion was associated with episodes of sinus bradycardia requiring treatment with glycopyrrolate.^[164] Citing a study that shows that bolus phenylephrine reduces maternal CO in close correlation to maternal HR,^[41] other experts feel that phenylephrine can be administered in bolus doses titrated to maintain a stable HR. This, in turn, will maintain an adequate SVR to maintain a stable maternal MAP.^[65]

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Next Section

Abstract and Introduction
Cardiovascular Changes During Pregnancy
Hemodynamic Measurement Techniques in Pregnancy
Hemodynamic Changes During Cesarean Delivery With Neuraxial Anesthesia
Neuraxial Anesthesia Onset: Spinal
Neuraxial Anesthesia Onset: Epidural
Neuraxial Anesthesia Onset: Combined Spinal Epidural
Delivery of the Fetus
Patient Populations With Variations in Hemodynamic Responses
Interventions to Prevent or Treat Post-neuraxial Anesthesia Hypotension
Conclusion
Expert Commentary
Five-year View
References
Sidebar

Table 1. Hemodynamic variables in pregnancy.
Variable	% change (gestational age by which change occurs)	Ref.
Peripheral vascular resistance	30% decrease (20 weeks)	[6,11]
Plasma volume	50% increase (30 weeks)	[8]
Cardiac output	30–50% increase (32–36 weeks)	[11,15,165]
Heart rate	29% increase (33–36 weeks)	[15]
Stroke volume	18% increase (36–39 weeks)	[15]

Table 2. Cardiac output measurements during epidural anesthesia for elective cesarean delivery.
Study (year)	Measurement technique	Confounding factors	Epidural drug	CO after prehyd (l/min)	CO after block (l/min)	CO after placental delivery (l/min)	CO 1 h after birth (l/min)	Ref.
Ueland et al.(1972)	Dye dilution	Prehyd: NA Level: T2–T10 Position: supine LUD performed if significant drop in BP occurred	2% mepivacaine (13.5–17.5 ml)	5.88 ± 1.31	5.52 ± 1.77 ↓6%^†	7.34 ± 1.84 ↑25%^† ↑33%^‡	6.71 ± 1.95 ↑14%^† ↑22%^‡ ↓9%^§	[96]
Maruta (1982)	Echo	Prehyd: <1 l Level: NA Position: NA	NA	5.95 ± 1.49	5.05 ± 1.59 ↓15%^†	6.08 ± 1.31 ↑2%^† ↑20%^†	5.41 ± 0.91 ↓9%^† ↑7%^‡ ↓11%^§	[89]
James et al. (1989)	Suprasternal Doppler (aortic orifice measured by cross-section)	Prehyd: 15 ml/kg LR Level: T4–T8 Position: LUD	2% lidocaine + 1:200,000 epi	6.63 ± 1.33	7.88 ± 1.6 ↑19%^†	9.05 ± 1.39 ↑36%^† ↑15%^‡	7.11 ± 1.7 ↑7%^† ↓10%^‡ ↓21%^§	[97]
Milsom et al. (1985)	Impedance cardiography	Co-load: 1.5–2.0 l Level: NA Position: LUD Atropine 0.5 mg iv. prior to epidural Subjects requiring ephedrine excluded	0.5% bup (23–28 ml)	NA	Before to after block: increased by 0.7 ± 0.2 ↑^¶	Before to after delivery: increased by 1.1 ± 0.3 (33%) ↑^¶	NA	[39]
Robson et al. (1992)	Suprasternal Doppler (aortic orifice measured by cross-section)	Prehyd: 1 l crystalloid 1.2 ± 0.2 l total fluids Ephedrine administered 60 mg/l in iv. fluids after prehyd Level: T2–T6 Position: LUD	0.5% bup + 1:200,000 epi (18–30 ml)	7.83	10 min after 8.20 ↑5% 30 min after 7.96 ↑2%	NA	NA	[52]
Robson et al. (1989)	Suprasternal Doppler (aortic orifice measured with cross-sectional echo)	Prehyd: 500 ml crystalloid Level: >T5 Position: LUD Subjects requiring ephedrine excluded	0.5% bup (21 ± 3 ml)	7.14	7.08 ↓<1%^†	7.69 ↑8%^† ↑9%^‡	6.65 ↓7%^† ↓6%^‡ ↓14%^§	[98]
Robson et al. (1989)	Suprasternal Doppler (aortic orifice measured with cross-sectional echo)	Prehyd: 0.8 l mean Level: T2–T6 Position: LUD Subjects requiring ephedrine excluded	0.5% bup (20 ± 5 ml)	7.82	10 min after 7.34 ↓6%^† 30 min after 7.12 ↓9%^†	NA	NA	[53]

^†From CO after prehydration.
^‡From CO after block.
^§From CO after delivery of placenta.
^¶Not enough data available to calculate percent change.
BP: Blood pressure; bup: Bupivacaine; CO: Cardiac output; epi: Epinephrine; iv.: Intravenous; LR: Lactated Ringers; LUD: Left uterine displacement; NA: Data not available in the paper; Prehyd: Prehydration.

Table 3. Cardiac output measurements during spinal anesthesia for elective cesarean delivery.
Study (year)	Measurement technique	Confounding factors	Intrathecal drug	CO after prehyd (l/min)	CO after block (l/min)	CO after delivery of placenta (l/min)	CO 1 h after CD (l/min)	Ref.
Ueland et al. (1968)	Dye dilution	Prehyd: NA Level: T2–T8 Position: supine	Tetracaine 7–10 mg + epi 200 mcg	5.4 ± 1.8	3.5 ± 1.2 ↓35%^†	8.4 ± 2.6 ↑61%^† ↑140%^‡	NA	[66]
Niswonger et al. (1970)	Dye dilution	Prehyd: NA Level: T4–T9 Position: NA 9 patients: 8 with spinal, 1 with epidural anesthetic 2 out of 9 were less than 36 weeks gestation	NA	6.29 ± 1.75	6.95 ± 2.43 ↑10%^†	8.81 ± 3.26 ↑40%^† ↑27%^‡	6.83 ± 2.50 ↑9%^† ↓2%^‡ ↓22%^§	[61]
Robson et al. (1992)	Suprasternal Doppler (aortic orifice measured by cross section)	Prehyd: 1.39 ± 0.18 l crystalloid Level: T1–T4 Position: LUD Ephedrine administered 60 mg/l in iv. fluids, and in boluses	HB bup 10–12.5 mg	7.90	5 min after block: 6.73 ↓15%^† 15 min after block: 7.36 ↓7%^†	NA	NA	[52]
Tihtonen et al. (2005)	Whole-body impedance cardiography	Prehyd: 10 ml/kg 6% hydroxyethyl starch Level: NA Position: LUD Hypotension treated with 50 mg/100 ml ephedrine infusion Mean dose 0.53 mg/kg	HB bup 12–13.5 mg	CI: 3.6 ± 0.2 l/min/m²	CI: 4.1 ± 0.5 l/min/m² ↑11%^†	CI: 4.7 ± 0.2 l/min/m² ↑31%^† ↑15%^‡(↓39% SVRI and stable MAP)	CI: 3.7 ± 0.3 l/min/m² ↑3%^† ↓10%^‡ ↓21%^§	[40]
Langesaeter et al. (2008)	LiDCOplus	Prehyd: None Co-load of 750 ml over 20 min Level: NA Postion: LUD Prophylactic phenylephrine infusion 0.25 mcg/kg/min	IB bup 7 mg	6.1 ± 0.3	Initial immediate ↑32.8%^† in first 200 s, then ↓16.8%^† approximately 6 min after block	NA	NA	[63]

^†From CO after prehydration.
^‡From CO after block.
^§From CO after delivery of placenta.
bup: Bupivacaine; CD: Cesarean delivery; CI: Cardiac index; CO: Cardiac output; epi: Epinephrine; HB: Hyperbaric; IB: Isobaric; iv.: Intravenous; LUD: Left uterine displacement; MAP: Mean arterial pressure; NA: Data not available in the paper; Prehyd: Prehydration; SVRI: Systemic vascular resistance index.

Box 1. Techniques to decrease hypotension with neuraxial anesthesia for cesarean delivery.
Leg wrapping [134] Prehydration or co-load with intravenous colloid solution [57] Co-load with crystalloid intravenous solution [57] Lower dose intrathecal local anesthesia supplemented with opioid [86] Maternal left uterine displacement positioning [128] Consider epidural instead of spinal anesthesia [95] Phenylephrine infusion with rapid crystalloid co-load [160] Phenylephrine infusion with low-dose intrathecal bupivacaine [63] Phenylephrine infusion or boluses titrated to maintain a consistent heart rate [41,63]

Sidebar

Key Issues

Relatively noninvasive and accurate modes of cardiac output (CO) measurements in the parturient undergoing cesarean delivery (CD) include photometric dye dilution techniques, Doppler, 2D or 3D echocardiography, and a lithium dilution (LiDCO) technique. Bioimpedance and LiDCO techniques allow a beat-to-beat determination of CO.
The major hemodynamic changes during CD with neuraxial anesthesia occur during prehydration, block onset and birth.
Neuraxial anesthesia-induced hypotension in parturients undergoing CD is frequent. The maternal and fetal morbidity and mortality associated with hypotension has investigators seeking clinically feasible and reliable ways to predict which parturients are at greatest risk, and which treatment regimens are the most appropriate.
The factors that influence the degree of neuraxial anesthesia-induced hypotension include hydration; maternal positioning during and after the block; block type, height and density; the addition of epinephrine to epidural local anesthetic; the presence of hypertensive disorders of pregnancy; gestational age; the number of gestations; the presence of labor; and the prophylactic or therapeutic use of vasoactive substances. Vascular tone and reactivity to neuraxial anesthesia is a complex system unique to each individual woman.
The most effective strategies for prevention of spinal-induced hypotension include prehydration with a sufficient amount of colloid or co-loading with sufficient crystalloid or colloid, positioning the parturient for surgery in the left uterine displacement position, using a lower dose of intrathecal bupivacaine and, most notably, administering a prophylactic vasoactive agent such as phenylephrine.
Hydration prior to (i.e., 'prehydration') or during (i.e., 'co-loading') neuraxial anesthesia placement can not reliably prevent post-spinal hypotension. Crystalloid solutions are more beneficial in preventing hypotension when used as a co-load instead of as prehydration, whereas colloid solutions can be as beneficial when used in either of these time frames.
As the uterus achieves a contracted state following fetal delivery, aortocaval decompression and an autotransfusion of uterine blood occur, resulting in an increase in cardiac preload. This preload augmentation typically results in an increase in CO through increases in heart rate and stroke volume. A decrease in systemic vascular resistance typically results in an unchanged mean arterial pressure at the time of delivery.
Neuraxial anesthesia, including via the spinal technique, are now considered acceptable methods for providing anesthesia for stable, noncoagulopathic severe preeclamptic parturients undergoing cesarean delivery.
Multiple recent studies have indicated that phenylephrine is more effective with lesser fetal acid base alterations than ephedrine when used either as prophylaxis or treatment for hypotension in both elective and nonelective cesarean deliveries.
The prophylactic administration of phenylephrine, as either an infusion or bolus, has been found to be effective in preventing post-spinal hypotension. Maternal bradycardia may occur.

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