Central nerve blocks are the preferred method to provide anaesthesia for women in labour as well as for Caesarean section. Side-effects of neuraxial anaesthesia include significant maternal hypotension with the risk of diminished uterine blood flow (UBF), exposing the fetus to the risk of asphyxia. Anaesthetists frequently administer intravenous (i.v.) fluids and vasopressors to minimize the risk of maternal hypotension, although the benefits have been questioned repeatedly . Caveats include the type of volume chosen for preload, e.g. crystalloids vs. colloids, and the type of haemodynamic measurements performed. In studies failing to demonstrate any beneficial effects, volume preloading is typically performed with crystalloids and haemodynamic monitoring only includes maternal arterial pressure and/or pulsatility indices derived from Doppler measurements [2,3]. Maternal arterial pressure is at best an indirect parameter that does not necessarily correlate with fetal well-being. If maternal arterial pressure is raised above baseline with the use of ephedrine, fetal pH may indeed deteriorate as a consequence of uterine artery vasoconstriction . Pulsatility indices are used to describe the impedance to blood flow in the uteroplacental circulation due to increases in vascular resistance. Non-invasive Doppler measurements are widely applied to monitor high-risk pregnancies and pathological pulsatility indices serve as indicators of fetal distress . As the pulsatility index is independent of the angle of insonation, the reproducibility between measurements at different time points is improved. Direct non-invasive measurements of arterial flow velocity can be obtained by combining Doppler and B-mode techniques with simultaneous measurements of local blood flow and vessel diameter. We performed the present study to compare direct measurements of UBF velocity with standard pulsatility indices and maternal arterial pressure during volume preload-ing in women undergoing Caesarean section under epidural anaesthesia.
Institutional Review Board approval and written informed consent was obtained. We studied 14 consecutive healthy women scheduled for elective Caesarean section under epidural anaesthesia at term (ASA I-II). We only included women carrying a single fetus without known placental pathology, pregnancy-induced hypertension or intrauterine growth restriction. An epidural catheter was placed at the L3-L4 interspace in the sitting position, after which the patients were placed supine with a left lateral tilt. Each patient received an epidural injection of bupivacaine 0.5% 15-20 mL until a T4 block was achieved (a time period of 15 min (range 10-28 min)), tested by pinprick. During this time 1 L lactated Ringer's solution were given i.v.
During the injection and for 60 min thereafter, the electrocardiogram and maternal heart rate (HR) were monitored continuously and mean maternal arterial pressure (MMAP) was registered every minute by a Siemens Propac® monitor (Propac 102, Protocol Systems Inc, Beaverton, OR, USA). A systolic arterial pressure <100 mmHg or a decrease of 30% from baseline was treated with i.v. injections of ephedrine 5-10 mg. Fetal HR was measured continuously with a cardiotocograph (Hewlett Packard 8030A, Böblingen, Germany).
Once the epidural block extended to T4 without further spread a main branch of the dominant uterine artery was identified by colour Doppler and the blood velocity waveforms were recorded by pulsed Doppler technique with a 3.75 MHz probe (Hewlett Packard Sonos® 2500; Hewlett Packard, Palo Alto, CA, USA). The angle of the probe to the artery and the vessel diameter were determined and supplied to the computer. In order to obtain reproducible and comparable results, the Doppler probe was kept immobile, once a stable signal was obtained. After a measurement the angle was again determined and compared to the first angle. When the angle had not changed the maximal flow velocity from each measurement after the start of the infusion was compared to baseline and the maximum difference (percentage) reported. If a loss of the Doppler signal or change of angle occurred during the measurements, data were excluded from further analysis. Three consecutively imaged blood flow velocity waveforms were analysed every 5 min and their mean values were used for further analyses. After baseline measurements were performed, women were randomly assigned to receive either hydroxyethyl starch 500 mL (HAES 6%, 200/0.4; Fresenius, Germany) or gelatine 3% (500 mL Geloplasma®; Merieux, France) over 10 min using sealed envelopes. The bottles for hydroxyethyl starch and gelatine were prepared beforehand and were the same colour and size and numbered 1-14. In order to avoid inter-observer variations, all Doppler measurements were performed by a single investigator (M.A.M.), who was blinded to the type of colloid used. The measurements were made for 30 min (t = 0, start of the infusion). After all the measurements were made the surgery started.
Values are presented as mean ± SE and statistical analyses were performed using t-test for age, height and weight, and repeated measures of variance followed by Dunnett's t-test to compare haemodynamic variables. P < 0.05 was considered significant.
All 14 patients included in the study were analysed. The mother's age, height and weight, and the gestational age of pregnancy did not differ significantly between the two groups (Table 1).
The spread of analgesia was comparable between the two groups, with a cephalad dermatomal level for sensory anaesthesia of T4. No woman developed severe hypotension necessitating treatment with ephedrine. Induction of epidural anaesthesia and infusion of either colloid did not influence fetal HR. Fetal HRs remained stable between 120 and 160 beats min−1 with short-term variability present and without decelerations during the study period.
After the infusion of 500 mL of gelatine or hydroxyethyl starch, maternal HR and maternal arterial pressure did not change over the time period studied. In addition, the pulsatility index did not change from baseline (Table 2). However, systolic peak velocities increased by 18% within 15 min after start of gelatine infusion and by 22% after hydroxyethyl starch (Fig. 1). These changes were not reflected in the pulsatility index.
The debate on how to best preserve UBF and fetal well-being during neuraxial anaesthesia for Caesarean section has not diminished. Caritis and colleagues  demonstrated significant fetal acidosis associated with spinal anaesthesia when maternal arterial pressure was not tightly controlled. Although maternal arterial pressure is frequently used to estimate UBF, a clear relationship between both parameters has not been established. In chronically instrumented sheep  and in pregnant women  infusion of magnesium sulphate decreases maternal arterial pressure but increases UBF. On the other hand, vasopressors used to maintain maternal pressure may be detrimental to UBF due to constriction of the uterine artery - despite a rise in systemic arterial pressure. Ephedrine has been the vasopressor of choice for use in pregnant women, because of its relatively sparing effect on the uterine vasculature . It increases pulsatility indices derived from the uteroplacental circulation less than the α-agonist phenylephrine . Increases in pulsatility indices frequently serve as an indicator of fetal distress [10,11]. Despite these findings, a recent meta-analysis showed that fetal pH is better maintained with the use of phenylephrine . These results indicate that changes of maternal arterial pressure, pulsatility indices and fetal oxygenation do not always change in parallel, but that the relationship is more complex than previously thought.
Indices from Doppler measurements of the uterine or umbilical circulation are advantageous - because they do not require measurements of the vessel diameter or the angle of insonation - whereas direct measurements of uteroplacental blood flow were previously only performed in animals with direct vessel access . Measurements are thus reduced to a single number and much of the information of the original waveform is lost. While indices reliably reflect increases in uteroplacental vascular resistance, they may not correctly assess the proximal circulation and increases in systolic and mean blood flow will frequently go unnoticed . Further confounding proximal circulatory effects include maternal cardiac output, the elasticity of the arterial wall and blood viscosity . Although we did not measure cardiac output, previous studies in pregnant women demonstrated significant increases in maternal cardiac output after volume expansion with colloids . In pregnant ewes, infusion of hydroxyethyl starch 500 mL increases maternal cardiac output by 23% and UBF by 18% within 30 min of infusion, whereas Ringer's lactate solution 500 mL had no effect . Increases in maternal arterial pressure did not account for this effect.
Improvements in technique and the development of colour Doppler methods permit repeated direct measurements of blood flow in human beings. Blood flow measurements, applying colour Doppler modes, have been demonstrated to correlate well with pulsatility indices in growth-restricted fetuses . We therefore performed the present study to evaluate the beneficial effects of volume expansion on uteroplacental blood flow that may be missed by pulsatility indices and were able to demonstrate significant changes in systolic blood flow velocity without concurrent changes in pulsatility indices. This discrepancy may be explained by the way pulsatility indices are computed ((systolic blood flow velocity - diastolic blood flow velocity)/mean blood flow velocity). If for instance, systolic and mean blood flow increase while the diastolic blood flow remains unchanged, there is an increase in overall blood flow which will not be reflected by the pulsatility indexes, because the numerator and the denominator are changed in the same direction.
We did not include a control group receiving saline because of its inferior inefficacy to maintain maternal arterial pressure during spinal anaesthesia  and the lack of effect in Doppler studies . In addition, infusion of saline as opposed to colloids would have to be corrected for the different volume effects and larger amounts of fluids would have to be infused in the set time frame of 10 min.
Vercauteren and colleagues  demonstrated that maternal arterial pressure is better preserved using hydroxyethyl starch compared to gelatine for volume preloading before spinal anaesthesia. We did not observe effects of different magnitude with either colloid. However, in the present study, colloids were only administered after the establishment of epidural anaesthesia and its influence on maternal arterial pressure and thus after the establishment of sympatholysis. The study design was intended to separate the confounding influences of changes in maternal HR and arterial pressure from the effects of colloids on UBF. We conclude that increases in maternal cardiac output and decreases in blood viscosity may have accounted for the observed increases in UBF, but of course this is not supported by data in this paper. Although the UBF increased promptly after the use of gelatine, after hydroxyethyl starch this increase came on only after 15 min. We are unable to explain this finding. In summary our results demonstrate that changes in UBF may occur in the absence of changes in maternal arterial pressure or pulsatility indices currently used to indirectly assess fetal well-being.
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