- Question: Does the combination of 500-mL colloid preload and 500-mL crystalloid coload decrease the required ephedrine and improve maternal hemodynamics compared with 1000-mL crystalloid coload during spinal anesthesia for cesarean delivery?
- Findings: The required ephedrine dose and other maternal hemodynamics did not significantly differ between the 2 groups.
- Meaning: The specific administered fluid strategy does not significantly affect the incidence and severity of hypotension, and vasopressors are still required.
Hypotension occurs commonly during spinal anesthesia for cesarean delivery resulting in maternal discomfort, nausea/vomiting, and respiratory distress and may, if prolonged or severe, cause serious maternal or fetal adverse effects.1,2 Intravenous (IV) fluid loading is indicated to decrease the incidence and severity of hypotension and to decrease the required vasopressor dose.3
The strategies of fluid administration during spinal anesthesia for cesarean delivery vary regarding the infused volume, the fluid type (crystalloid or colloid), and the timing of administration (preload or coload).4,5 Of the possible strategies, crystalloid preload has been demonstrated to have minimal or no effect in reducing the incidence and severity of hypotension, and the other strategies (colloid preload and crystalloid or colloid coload) seem to be comparably effective.4,5 In our institution, we commonly use 1000-mL crystalloid coload rapidly administered at the start of spinal anesthesia for elective cesarean delivery6; however, hypotension still occurs with a high incidence, and large doses of vasopressors are commonly administered.
Recently, sonographic assessment of the inferior vena cava (IVC) has been introduced in anesthesia and intensive care practice to assess the volume status and predict fluid responsiveness, with a few studies performed on pregnant women.
The aim of this study was to combine the benefits of both colloid preloading (maintained intravascular volume expansion) and crystalloid coloading (rapid infusion during the first few minutes after intrathecal injection when sympathetic blockade and vasodilation occur) and evaluate this combination versus our currently used fluid strategy. We assessed the IVC at baseline and at subsequent time points after spinal anesthesia. We hypothesized that the combination of 500 mL of colloid preload and 500 mL of crystalloid coload would reduce the total ephedrine dose compared with 1000 mL of crystalloid coload.
This study adhered to the ethical principles outlined in the Declaration of Helsinki and is presented in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Institutional review board approval was obtained, and written informed consent was obtained from all participating subjects. The study was registered before subject enrollment at ClinicalTrials.gov (NCT02961842; principal investigator: M.M.T.; date of registration: November 10, 2016). The study was conducted at the obstetric department of Mansoura University Hospital in Mansoura, Egypt, from November 2016 to March 2017. Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancies scheduled for elective cesarean delivery under spinal anesthesia. Exclusion criteria were age <19 or >40 years; height <150 cm, weight <60 kg, and body mass index ≥40 kg/m2; women presenting in labor or having any contraindication to spinal anesthesia (increased intracranial pressure, coagulopathy, or local skin infection); chronic or pregnancy-induced hypertension; baseline systolic blood pressure (BP) >140 mm Hg; hemoglobin <10 g/dL; diabetes mellitus, cardiovascular, cerebrovascular, or renal disease; and polyhydramnios or known fetal abnormalities.
The study subjects were randomly assigned to 2 equal groups (combination and crystalloid coload) according to computer-generated codes using the permuted block randomization method with block size of 4, and the group allocation was concealed in sequentially numbered, sealed opaque envelopes that were opened only after obtaining the consent and recording all the baseline data. The study subjects and the investigators assessing the outcome were blinded to the study group. The second investigator (A.I.T.) assessed the patients for eligibility, obtained written informed consent, opened the sealed opaque envelopes containing group allocation, administered the specific study solutions, and recorded the fluid infusion time. The primary investigator (M.M.T.) and another investigator (A.M.E., K.A.A., or H.M.E.) recorded the baseline systolic BP and heart rate and obtained the baseline IVC image, then left the operating room and returned immediately after administration of spinal anesthesia to continue the anesthetic management and record the intraoperative and outcome data (systolic BP, heart rate, IVC images, ephedrine and atropine requirement, upper sensory level, nausea/vomiting, and spinal-to-delivery time). Spinal anesthesia was administered by an anesthesiology resident not involved in the study. The second investigator and the fluid bags and proximal parts of the infusion lines were separated from the patient and the other investigators by a large opaque screen. Neonatal Apgar scores were recorded by a pediatrician not involved in the study.
All the IVC images were obtained by the primary investigator, who had performed >50 cases in a similar manner before starting the study, using the technique described by the American Society of Echocardiography.7 The IVC was scanned in the long axis using an 8-2 MHz curved array transducer (SonoAce R3; Samsung Medison, Seoul, South Korea) placed longitudinally in the subcostal region. The maximum and minimum IVC diameters occurring in a single respiratory cycle during normal spontaneous breathing were measured using the M-mode about 2 cm proximal (caudal) to the ostium of the right atrium and immediately proximal to the junction with the hepatic veins (Figure 1). The IVC collapsibility index (CI) was calculated using the following formula: IVC-CI = (maximum IVC diameter – minimum IVC diameter)/maximum IVC diameter, expressed as percentage. When obtaining the images intraoperatively, the investigator was separated from the surgical field by a sterile drape, and the ultrasound probe was covered with a sterile cover (Supplemental Digital Content 1, Figure 1, http://links.lww.com/AA/C275). The baseline and subsequent images were saved and retrieved after the end of each case to record the specific diameters.
Without receiving any premedication, the study subjects entered the operating room and lay supine with left lateral tilt (accomplished by slightly tilting the operating table); standard monitors (electrocardiography, pulse oximetry, and noninvasive BP) were applied. After adequate rest, the baseline systolic BP and heart rate were recorded; the baseline records were the average of 3 measurements taken 2 minutes apart with difference not exceeding 10%. The baseline IVC image was obtained using the technique described above; if the IVC image quality was inadequate, the patient was not included in the study.
An 18-gauge IV cannula was inserted in a large forearm vein. Patients in the combination group received 500 mL of 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride (Voluven; Fresenius Kabi, Bad Homburg, Germany) immediately before induction of spinal anesthesia and 500 mL of Ringer’s acetate starting immediately after intrathecal injection. Patients in the crystalloid coload group received 1000 mL of Ringer’s acetate starting immediately after intrathecal injection. All the study solutions in both groups were administered using a pressurizer adjusted to 250 mm Hg.
Spinal anesthesia was performed in the sitting position using a 27- or 25-gauge spinal needle at the L3–L4 or L4–L5 interspace; 2.5 mL of 0.5% hyperbaric bupivacaine (12.5 mg) and fentanyl 15 µg were intrathecally administered, then the subjects were placed again in the tilted supine position. Surgery started after attaining an upper sensory level of T6 or higher tested using pinprick. The upper sensory level after 20 minutes of intrathecal injection was recorded; a level below T6 was considered a failed spinal block, and the patient was excluded from the study. After administering the study solutions, Ringer’s acetate was attached to the IV cannula and administered at a rate of 1 mL/min; no other fluids were administered until the end of the study period (clamping of the umbilical cord).
Systolic BP was recorded every minute throughout the study period; ephedrine 3, 5, and 10 mg boluses were administered when the systolic BP decreased below 90%, 80%, and 70% of the baseline value, respectively. Hypotension was defined as systolic BP <80% of baseline, and severe hypotension was defined as systolic BP <70% of baseline. The maximum and minimum IVC diameters were measured at 1 and 5 minutes after intrathecal injection and immediately after delivery. The heart rate was recorded every minute; bradycardia (heart rate <50 beats/min) was treated with IV atropine 0.5 mg, repeated as appropriate. The occurrence of nausea (reported by the patient) and/or vomiting was recorded; nausea or vomiting occurring without hypotension or persisting after correction of hypotension was treated with IV metoclopramide 10 mg. The total infusion time for the study solutions was recorded for both groups. The duration from intrathecal injection to clamping of the umbilical cord (spinal-to-delivery time) was recorded. Neonatal Apgar scores were recorded at 1 and 5 minutes after delivery.
The primary outcome was the total ephedrine dose. The secondary outcomes were the number of patients requiring ephedrine; the incidence of hypotension, severe hypotension, bradycardia, and nausea/vomiting; the time to the first ephedrine dose; the serial changes of the maximum and minimum IVC diameters and the IVC-CI over time; and neonatal Apgar scores at 1 and 5 minutes.
Sample size calculation, data analysis, and graphical representation were performed using R software, version 3.3.2 (R Core Team, 2016; R Foundation for Statistical Computing, Vienna, Austria). We followed the modified intention-to-treat analysis; only subjects who were randomized and who received all of the study intervention were included in the final analysis. Continuous data were tested for normality using the histogram and the Kolmogorov–Smirnov test. Normally distributed data, nonnormally distributed data, and categorical data are presented as mean ± standard deviation, median (range), and number (percentage), respectively. The outcome data were compared between the combination and the crystalloid coload groups. The nonnormally distributed outcome data (the total ephedrine dose and neonatal Apgar scores) were compared using the Mann-Whitney U test. The median of the difference (95% nonparametric confidence interval) between groups in the total ephedrine dose (primary outcome) was obtained using the Hodges–Lehmann estimator. The categorical outcome data were compared using the χ2 test (the number of patients requiring ephedrine and the incidence of hypotension, severe hypotension, and nausea/vomiting) or the Fisher exact test (the incidence of bradycardia). The data for the time to the first ephedrine dose were analyzed using the Kaplan–Meier analysis and compared using the log-rank test.
Serial changes of the systolic BP, heart rate, maximum and minimum IVC diameters, and IVC-CI were analyzed using the linear mixed-effects model; the baseline value of the outcomes was included as a covariate, the fixed effects were the group, time, and group × time interaction, and the random effects were for the study subjects. The data for the 2 groups were compared at specific time points using the Tukey method for multiple comparisons. In addition, to examine the changes after spinal anesthesia and after delivery, the data for the IVC parameters within each group were compared between different time points using the paired t test with Bonferroni adjustment.
An additional post hoc exploratory analysis was performed. The study subjects were retrospectively grouped according to their baseline IVC-CI into 2 groups (the high CI group: including subjects with a baseline IVC-CI greater than the median value of all subjects, and the low CI group: including subjects with a baseline IVC-CI less than or equal to the median value of all subjects). The total ephedrine dose, the number of patients requiring ephedrine, and the incidence of hypotension and severe hypotension were compared between the 2 groups using the corresponding statistical tests mentioned above. Furthermore, each CI group was subdivided according to the administered fluid strategy; the total ephedrine dose was compared between groups using the Kruskal–Wallis test, and Bonferroni adjustment was used for multiple comparisons. An overall 2-tailed P value <.05 was considered statistically significant.
Before starting the study, we performed a pilot study on 20 subjects using 1000-mL crystalloid coload; the mean ± standard deviation of the total ephedrine dose was 15 ± 12 mg. Assuming α = .05 and β = .2 (80% power) and using the 2-tailed Student t test, 92 subjects were required in each group to detect a 5-mg difference between groups, which was considered the least clinically significant effect. To allow for subject dropouts, 100 subjects were assigned to each group.
Two hundred patients were randomized, and data from 198 patients (99 patients in each group) were analyzed; 2 patients (1 patient in each group) were excluded from the analysis due to failed spinal block (Figure 2). There were no clinically significant differences between the 2 groups in the patient characteristics, baseline values, and anesthetic data; however, the infusion time for the study solutions was slightly longer in the combination group compared with the crystalloid coload group (Table 1).
The median (range) of the total ephedrine dose was 11 (0–60) mg in the combination group and 13 (0–61) mg in the crystalloid coload group; the median of the difference (95% nonparametric confidence interval) was −2 (−5 to 0.00005) mg, P = .22 (Table 2).
There were no significant differences between the 2 groups in the number of patients requiring ephedrine, the incidence of hypotension and severe hypotension, and neonatal Apgar scores at 1 and 5 minutes; however, the study was not sufficiently powered to detect differences in the incidence of bradycardia and nausea/vomiting (Table 2). There was no significant difference between the 2 groups in the time to the first ephedrine dose (P = .27 using the log-rank test); 17 patients (17.2%) in the combination group and 18 patients (18.2%) in the crystalloid coload group did not require ephedrine.
Serial changes of the systolic BP and heart rate over time were analyzed up to 9 minutes after intrathecal injection, which was the shortest spinal-to-delivery time (Figure 3). For the systolic BP data, the group × time interaction was significant (P = .0066), and the systolic BP was significantly higher in the combination group than in the crystalloid coload group only at 3 minutes after intrathecal injection; the difference in means (95% confidence interval) was 7.6 (2.6–12.6) mm Hg, P = .0027. For the heart rate data, the group × time interaction was nonsignificant (P = .14), and the difference in means (95% confidence interval) between groups collapsing over time was 3.4 (−0.02 to 6.8) beats/min, P = .053.
Serial changes of the maximum and minimum IVC diameters and the IVC-CI were analyzed at 1 and 5 minutes after intrathecal injection and after delivery (Figure 4). For the maximum IVC diameter data, the group × time interaction was nonsignificant (P = .07), and the difference in means (95% confidence interval) between groups collapsing over time was 0.16 (0.09–0.24) cm, P < .0001. For the minimum IVC diameter data, the group × time interaction was nonsignificant (P = .62), and the difference in means (95% confidence interval) between groups collapsing over time was 0.16 (0.1–0.23) cm, P < .0001. For the IVC-CI data, the group × time interaction was nonsignificant (P = .22), and the difference in means (95% confidence interval) between groups collapsing over time was −2.5% (−0.4% to −4.5%), P = .021.
In the combination group, the maximum and minimum IVC diameters increased at each time point compared with baseline, and the IVC-CI did not significantly change at any time point compared with baseline. In the crystalloid coload group, the maximum IVC diameter increased at each time point compared with baseline, the minimum IVC diameter increased at 5 minutes and after delivery compared with baseline, and the IVC-CI increased after delivery compared with baseline. In both groups, the maximum and minimum IVC diameters increased after delivery compared with all the predelivery values.
The results of the exploratory analysis are presented in Supplemental Digital Content 2, Table, http://links.lww.com/AA/C276, and Supplemental Digital Content 1, Figure 2, http://links.lww.com/AA/C275. The median (range) of the total ephedrine dose was 9 (0–60) mg in the high CI group and 15 (0–61) mg in the low CI group; the median of the difference (95% nonparametric confidence interval) was −4 (−0.00006 to −7) mg, P = .0081. The subjects with a high IVC-CI who received combination strategy required less ephedrine than those with a low IVC-CI who received crystalloid coload; the median of the difference (95% nonparametric confidence interval) was −6 (−1 to −12) mg, P = .036 after Bonferroni adjustment. No significant differences were found between subjects receiving different fluid strategies in either CI group.
This double-blind, randomized controlled trial failed to demonstrate a significant difference in the total ephedrine dose during spinal anesthesia for elective cesarean delivery when using a combination of 500-mL colloid preload and 500-mL crystalloid coload compared with 1000-mL crystalloid coload. The number of patients requiring ephedrine, the incidence of hypotension and severe hypotension, the time to the first ephedrine dose, and neonatal Apgar scores at 1 and 5 minutes did not significantly differ between the 2 groups. The IVC diameters increased over time in both groups and were larger in the combination group compared with the crystalloid coload group. The IVC-CI after delivery was higher in the crystalloid coload group than in the combination group.
The effectiveness of preloading with colloids and its lack with crystalloids can be described in terms of 1- and 2-volume pharmacokinetic models, respectively.8 The infused colloid solution is distributed into the intravascular compartment and remains for a considerable time resulting in its expansion.8,9 In contrast, the infused crystalloid solution is distributed initially into the intravascular compartment then redistributed, within 20–30 minutes, to the interstitial compartment.8 In this study, we evaluated the combination of 2 commonly used regimens (colloid preload and crystalloid coload); the effectiveness of each had been previously evaluated,6 but their combination had not been studied before. We administered ephedrine when the systolic BP decreased below 90% of the baseline value, in accordance with the currently recommended practice of using a lower threshold for vasopressor administration before actual hypotension occurs.2,4,10
In nonpregnant patients, sonographic measurement of the IVC diameters and calculation of the IVC-CI provide a reliable noninvasive tool for assessment of the central venous pressure,7,11 prediction of fluid responsiveness in critically ill patients,12 prediction of hypotension after induction of general anesthesia,13 and guidance of intraoperative fluid and vasopressor management in high-risk patients.14
Three studies have used ultrasonography to assess the IVC in obstetric population. Fields et al15 studied third trimester pregnant women in 3 different positions (supine and left and right lateral tilts) using the intercostal (anterior axillary) window; they demonstrated that the majority of subjects had the largest maximum IVC diameter with left lateral tilt. Kundra et al16 studied full-term parturients presenting for cesarean delivery under spinal anesthesia in 3 different positions (supine, recumbent with wedge, and left lateral) using the subcostal approach; they demonstrated that parturients had larger maximum IVC diameter and lower CI in the left lateral position, and that parturients who experienced hypotension after spinal anesthesia had a higher CI in the recumbent with wedge position. Hernandez et al17 studied full-term parturients presenting for labor epidural analgesia at 4 time points (baseline, after 1 L crystalloid administration, after initiation of the epidural block, and at 24 hours after delivery) using the subcostal long-axis view; they demonstrated that the IVC diameters linearly increased with fluid administration, slightly increased after induction of the epidural block, then decreased to around the baseline values at 24 hours after delivery.
In this study, we successfully used the subcostal long-axis view before and during cesarean delivery; an adequate IVC image quality could not be obtained in 5 parturients only who were not included in the study (Figure 2). This technique may be used to assess the volume status in healthy parturients undergoing routine cesarean delivery, as well as in high-risk parturients (eg, with preeclampsia or with cardiac or renal disease) or during massive fluid/blood transfusion (eg, placenta accreta).
The following conclusions can be deduced from studying the serial changes of the IVC diameters and CI (Figure 4):
- The IVC diameters increased with fluid administration: the maximum and minimum IVC diameters were larger in the combination group than in the crystalloid coload group at 1 minute after intrathecal injection, demonstrating the effect of the administration of 500-mL colloid before spinal anesthesia (preload).
- The IVC diameters increased after spinal anesthesia: the maximum and minimum IVC diameters increased and the CI did not change, compared with baseline, in response to spinal anesthesia in both groups (with concomitant administration of IV fluids and administration of ephedrine in most of the patients), indicating maintained or increased venous return; a finding consistent with previous studies demonstrating an increase in the stroke volume and cardiac output after spinal anesthesia.18–20 This supports the recently proposed mechanism relating spinal-induced hypotension to a decreased systemic vascular resistance resulting from arterial vasodilation rather than a decreased venous return and cardiac output.21
- The IVC diameters increased after delivery: the maximum and minimum IVC diameters increased after delivery, compared with predelivery values, in both groups, demonstrating the increase in venous return that occurs in the immediate postpartum period.22
- The IVC-CI after delivery was higher in the crystalloid coload group compared with the combination group. This might be due to the persistence in the intravascular space of 100% of the infused colloid versus 70% of the infused crystalloid by the time of delivery.23 However, the difference was small and does not seem to have any clinical significance; difference in means (95% confidence interval) was 4.7% (1.2%–8.1%).
The exploratory analysis (Supplemental Digital Content 1–2, Figure 2, http://links.lww.com/AA/C275, Table, http://links.lww.com/AA/C276) suggests that the subjects with a high baseline IVC-CI (lower intravascular volume) got more benefit from fluid transfusion and, therefore, required less ephedrine after spinal-induced vasodilation than those with a low baseline IVC-CI. Further subanalysis suggests that the administered fluid strategy did not affect ephedrine requirement in each CI group, and that subjects who got the greatest benefit from fluid transfusion were those with a preoperative high IVC-CI (volume depletion) who received colloid preload as a part of the combination strategy.
Several issues in the study methodology and results should be addressed. First, parturients with a height <150 cm or body mass index ≥40 kg/m2 were excluded from the study because they would have required modified doses of the intrathecal local anesthetic and might have been associated with a relatively different incidence of hypotension. Second, parturients with a baseline systolic BP >140 mm Hg were excluded from the study because, in the absence of previously diagnosed hypertension, this BP elevation could be due to preoperative anxiety and might have produced a false impression of intraoperative hypotension. Third, although phenylephrine is the currently preferred vasopressor in obstetric anesthesia and is associated with less fetal acidosis,21 we used ephedrine in this study because it is still commonly used in our institution and phenylephrine is currently unavailable. According to the latest American Society of Anesthesiologists guidelines,3 both vasopressors may be used during cesarean delivery to treat spinal-induced hypotension.
Fourth, we measured the IVC diameters during normal spontaneous breathing and did not ask the patients to take a deep breath or a sniff. This should be considered when comparing the values of the minimum IVC diameter and the IVC- CI of this study with those of other studies in which deep breathing or sniffing was applied. Fifth, only 1 operator obtained all the IVC images and measured the IVC diameters to increase the internal validity of the study and avoid interrater variability.24 The operator used nearly identical settings during IVC assessment in each patient (eg, the same site of scanning, similar method for M-mode application and diameter measurement, and similar breathing pattern for each patient25). Moreover, to avoid detection bias and help operator blinding, the images were saved and retrieved for recording the diameters after the end of each case. Sixth, the IVC diameters were measured in 1 respiratory cycle only. An alternative was to obtain the average of measurements in several cycles; however, this would have increased the complexity of the procedure considering the assessment at the 4 specified time points.
Seventh, we did not analyze the umbilical blood gases because data from previous studies demonstrated that neonatal acid-base status was not affected by the specific fluid strategy as long as maternal hypotension was reliably treated.4,6,10 Eighth, the 95% confidence interval of the difference in the total ephedrine dose extends to a difference of 5 mg, which was the value used for calculating the sample size, hence, a type II error cannot be excluded. Last, the additional exploratory analysis was not planned before conducting the study. It includes nonrandomized comparisons for which results should not be considered definitive. Moreover, the study subjects were grouped according to their baseline IVC-CI values into high and low CI groups using the median value of all subjects as an arbitrary value; however, more precise definitions for “high” and “low” IVC-CI are needed.
In conclusion, the combination of 500-mL colloid preload and 500-mL crystalloid coload did not significantly reduce the total ephedrine dose or improve other maternal outcomes compared with 1000-mL crystalloid coload during spinal anesthesia for elective cesarean delivery in healthy parturients. The IVC can be reliably viewed in the long axis using the subcostal window in parturients before and during cesarean delivery, and the maximum and minimum IVC diameters and the IVC-CI can be used to assess the volume status during cesarean delivery.
Name: Mohamed Mohamed Tawfik, MD.
Contribution: This author helped design and conduct the study, analyze the data, and prepare the manuscript.
Name: Amany Ismail Tarbay, MSc.
Contribution: This author helped design and conduct the study.
Name: Ahmed Mohamed Elaidy, MSc.
Contribution: This author helped conduct the study.
Name: Karim Ali Awad, MSc.
Contribution: This author helped conduct the study.
Name: Hanaa Mohamed Ezz, MSc.
Contribution: This author helped conduct the study.
Name: Mohamed Ahmed Tolba, MSc.
Contribution: This author helped analyze the data and prepare the manuscript.
This manuscript was handled by: Jill M. Mhyre, MD.
1. Mercier FG. Fluid loading for cesarean delivery under spinal anesthesia: have we studied all the options? Anesth Analg. 2011;113:677–680.
2. Loubert C. Fluid and vasopressor management for cesarean delivery under spinal anesthesia: continuing professional development. Can J Anesth. 2012;59:604–619.
3. American Society of Anesthesiologists Committee on Standards and Practice Parameters. 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;124:270–300.
4. Banerjee A, Stocche RM, Angle P, Halpern SH. Preload or coload for spinal anesthesia for elective cesarean delivery: a meta-analysis. Can J Anesth. 2010;57:24–31.
5. Ripollés Melchor J, Espinosa Á, Martínez Hurtado E. Colloids versus crystalloids in the prevention of hypotension induced by spinal anesthesia in elective cesarean section. A systematic review and meta-analysis. Minerva Anestesiol. 2015;81:1019–1030.
6. Tawfik MM, Hayes SM, Jacoub FY. Comparison between colloid preload and crystalloid co-load in cesarean section under spinal anesthesia: a randomized controlled trial. Int J Obstet Anesth. 2014;23:317–323.
7. Rudski LG, Lai WW, Afilalo J. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685–713.
8. Hahn RG. Volume kinetics for infusion fluids. Anesthesiology. 2010;113:470–481.
9. Westphal M, James MF, Kozek-Langenecker S, Stocker R, Guidet B, Van Aken H. Hydroxyethyl starches: different products–different effects. Anesthesiology. 2009;111:187–202.
10. Mercier FJ, Diemunsch P, Ducloy-Bouthors AS, et al. CAESAR Working Group. 6% Hydroxyethyl starch (130/0.4) vs Ringer’s lactate preloading before spinal anaesthesia for caesarean delivery: the randomized, double-blind, multicentre CAESAR trial. Br J Anesth. 2014;113:459–467.
11. Ciozda W, Kedan I, Kehl DW, Zimmer R, Khandwalla R, Kimchi A. The efficacy of sonographic measurement of inferior vena cava diameter as an estimate of central venous pressure. Cardiovasc Ultrasound. 2016;14:33–40.
12. Zhang Z, Xu X, Ye S, Xu L. Ultrasonographic measurement of the respiratory variation in the inferior vena cava diameter is predictive of fluid responsiveness in critically ill patients: systematic review and meta-analysis. Ultrasound Med Biol. 2014;40:845–853.
13. Zhang J, Critchley LA. Inferior vena cava ultrasonography before general anesthesia can predict hypotension after induction. Anesthesiology. 2016;124:580–589.
14. Saranteas T, Manikis D, Papadimos T, Mavrogenis AF, Kostopanagiotou G, Panou F. Intraoperative TTE inferior vena cava monitoring in elderly orthopaedic patients with cardiac disease and spinal-induced hypotension. J Clin Monit Comput. 2016;31:919–926.
15. Fields JM, Catallo K, Au AK. Resuscitation of the pregnant patient: what is the effect of patient positioning on inferior vena cava diameter? Resuscitation. 2013;84:304–308.
16. Kundra P, Arunsekar G, Vasudevan A, Vinayagam S, Habeebullah S, Ramesh A. Effect of postural changes on inferior vena cava dimensions and its influence on haemodynamics during caesarean section under spinal anaesthesia. J Obstet Gynaecol. 2015;35:667–671.
17. Hernandez CA, Reed KL, Juneman EB, Cohen WR. Changes in sonographically measured inferior vena caval diameter in response to fluid loading in term pregnancy. J Ultrasound Med. 2016;35:389–394.
18. Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology. 2008;109:856–863.
19. Dyer RA, Reed AR, van Dyk D. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009;111:753–765.
20. McDonald S, Fernando R, Ashpole K, Columb M. Maternal cardiac output changes after crystalloid or colloid coload following spinal anesthesia for elective cesarean delivery: a randomized controlled trial. Anesth Analg. 2011;113:803–810.
21. Langesæter E, Dyer RA. Maternal haemodynamic changes during spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol. 2011;24:242–248.
22. Gaiser R. Chestnut DH, Wong CA, Tsen LC, et al. Physiologic changes of pregnancy. In: Chestnut’s Obstetric Anesthesia: Principles and Practice. 2014:5th ed. Philadelphia: Elsevier Inc, 15–38.
23. Svensen CH, Rodhe PM, Olsson J, Børsheim E, Aarsland A, Hahn RG. Arteriovenous differences in plasma dilution and the distribution kinetics of lactated Ringer’s solution. Anesth Analg. 2009;108:128–133.
24. Saul T, Lewiss RE, Langsfeld A, Radeos MS, Del Rios M. Inter-rater reliability of sonographic measurements of the inferior vena cava. J Emerg Med. 2012;42:600–605.
25. Kimura BJ, Dalugdugan R, Gilcrease GW 3rd, Phan JN, Showalter BK, Wolfson T. The effect of breathing manner on inferior vena caval diameter. Eur J Echocardiogr. 2011;12:120–123.