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Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic maternal-fetal sheep preparation

Marcus, M. A. E.; Gogarten, W.; Vertommen, J. D.*; Buerkle, H.; Van Aken, H.

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European Journal of Anaesthesiology: May 1998 - Volume 15 - Issue 3 - p 320-323



A test-dose containing adrenaline 15 μg is one way to exclude an intravascular placement of an epidural catheter [1]. In addition, adrenaline improves and prolongs an epidural local anaesthetic block with lidocaine and chloroprocaine and may reduce drug requirements [2,3]. For these reasons adrenaline is widely used in combination with epidural anaesthetic drugs.

It has been shown that lumbar epidural anaesthesia in gravid ewes with 6-8 mL 1.5% 2-chloroprocaine in combination with 60-80 μg adrenaline produced a transient but significant fall in uterine blood flow [4]. This effect was not observed when the same amount of plain 2-chloroprocaine was injected. Epidural administration of lower doses of adrenaline, used for epidural analgesia, has not been studied. Furthermore it is not known whether repeated epidural injections of adrenaline have accumulative unwanted systemic side effects.

This randomized crossover study was designed to compare the effect of repeated epidural injections of two different doses of adrenaline (10 or 15 μg) on the circulation in a chronically instrumented pregnant sheep preparation.


After approval by the Committee on Animal Research, Katholieke Universiteit Leuven, Belgium, eight pregnant ewes with a mean gestational age of 120 days (range 118-122 days) were studied. Animals were fasted for 2 days and deprived of water for 1 day prior to surgery. After sedation with injection of ketamine 10 mg kg−1 intramuscularly (i.m.), each animal was anaesthesized with halothane in oxygen. After endotracheal intubation with an orotracheal tube the animals were mechanically ventilated (AV-I, Dräger, Lübeck), and anaesthesia was maintained using end-tidal halothane 1-1.5% in oxygen.

Using a sterile surgical technique, polyvinyl catheters were inserted by cutdown into the aorta via both, a carotid artery and a tibial artery, and into the inferior and superior vena cava via a tibial vein and a jugular vein, respectively, for blood sampling and continuous recording of the maternal blood pressure and heart rate. After a laparotomy, a well-fitting 20 MHz Doppler flow probe (Baylor College of Medicine, Houston, Tx), with internal diameter ranging from 4 to 5.5 mm, was secured around a branch of the uterine artery supplying the pregnant horn of the uterus. A hysterotomy was then performed, the fetal hindlimbs exteriorized, and the fetal postductal aorta cannulated via the tibial arteries and the fetal inferior cava vein via the tibial vein for blood sampling and continuous recording of the fetal blood pressure. A catheter was placed in the amniotic fluid cavity and secured to a fetal hindlimb for pressure measurements. Three electrocardiogram (ECG) electrodes were sutured directly to the fetus. After replacement of the approximate volume of the amniotic fluid lost during these procedures with normal saline, the catheters, the leads of the Doppler flow probe and the ECG electrodes were tunnelled subcutaneously and exteriorized through a small incision in the flank and placed in a pocket. After closure of the abdominal incision, an epidural catheter was inserted between lumbar processes L3-L4 of the ewe, using the loss of resistance technique [5].

After recovery from anaesthesia, the animals' condition was allowed to stabilize for 72 h. They received prophylactic antibiotics (cefamandol, gentamicin) daily. During this period, the catheters were irrigated once daily with sterile heparinized saline and the animals were allowed free access to water and food.

The animals were studied in the standing or sitting position in a study trolley. Each experiment was preceded by a period of 30 min during which baseline haemodynamic conditions were obtained. Three identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two doses (10 or 15 μg) were tested on different days. On the day after the final epidural experiment the same doses of adrenaline were given i.v. Between any two i.v. doses 30 min was allowed for values to return to base-line.

Maternal mean arterial pressure, maternal heart rate, amniotic pressure and fetal mean arterial pressure were measured using a disposable strain gauge (Uniflow 43-600F™, Baxter Healthcare Ltd, Bentley Laboraties, Uden, Holland). Fetal mean arterial pressure was obtained by subtracting amniotic pressure from fetal arterial pressure. Uterine blood flow, was measured using a Doppler flow meter (Baylor College of Medicine, Houston). Fetal heat rate was also recorded on a cardiotocograph (Hewlett Packard 8030A, Boeblingen, Germany). All variables were recorded continuously (Nihon Kohden WT-645G, Tokyo, Japan) starting 30 min before the first injection and for 30 min following each epidural dose and for 10 min following each i.v. dose. Maternal and fetal arterial blood gases and acid base status were determined immediately after sampling (ABL3; Radiometer, Copenhagen, Denmark) and corrected for maternal temperature (39 °C; normal temperature for a sheep).

Group values are presented as mean ± SEM and statistical analysis was performed using repeated measures analysis of variance followed by Dunnett t-test. A P-value <0.05 was considered to be significant.


Twenty-seven experiments were performed in eight ewes. Mean maternal weight was 68 kg ± 10, mean fetal weight after the experiments was 2.4 kg ± 0.35.

Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow (Fig. 1), fetal mean arterial pressure, fetal heart rate, or maternal and fetal blood gases and acid-base status.

Fig. 1
Fig. 1:
Percentage change from baseline uterine blood flow (UBF) after three repeated doses of epidural adrenaline (10 or 15 μg adr). ▪ = adrenaline 10 μg; • = 15 μg adrenaline; ↓ = epidural dose of adrenaline. Data are expressed as mean ± sem.

Uterine blood flow decreased following i.v. adrenaline in a dose-dependent manner, with a maximum decrease of 43% after 15 μg adrenaline at 1 minute (P<0.001). (Fig. 2) This decrease was significant for three minutes after adrenaline 15 μg (P<0.05). For adrenaline 10 μg this decrease was significant for one minute (P<0.05).

Fig. 2
Fig. 2:
Percentage change from baseline uterine blood flow (UBF) after two doses of adrenaline i.v. (10 or 15 μg adr). ▪ = adrenaline 10 μg; • = 15 μg adrenaline. Data are expressed as mean ± sem. *P<0.05

The i.v. injection of the two doses of adrenaline did not affect maternal heart rate, maternal mean arterial pressure, fetal heart rate, fetal mean arterial pressure, amniotic pressure, blood gases, and acid-base status in the mother and the fetus.


In 1976 Wallis et al. studied the effects of local anaesthetic drugs with and without adrenaline on uterine blood flow in sheep. They showed a 14% decrease in uterine blood flow when local anaesthetics were combined with adrenaline. The effects of adrenaline in combination with local anaesthetics could have been masked by the subsequent i.v. fluid infusion. In the study by Wallis et al. (1976) a total of 2000 mL of crystalloids was infused to maintain the arterial blood pressure [4]. It is not known what effect any epidural bolus injection of adrenaline alone has on the uterine blood flow.

In our study neither single nor repeated epidural injections of adrenaline decreased uterine blood flow significantly. This corroborates the evidence that in normal pregnancies the use of epidural adrenaline causes no obvious problem [6,7]. However, with an impaired fetal blood supply the use of local anaesthesia in combination wth adrenaline may be of concern. Alahuhta et al. (1991) found that, when a pregnancy is complicated by hypertension and chronic fetal asphyxia, reflected as high umbilical vascular resistance, adrenaline combined with bupivacaine further increased Doppler velocity indices in the maternal uterine and placental arcuate arteries. This indicates increased resistance and impaired uteroplacental flow, which can be deleterious for the chronically asphyxiated human fetus [8].

In the present study the i.v. administration of adrenaline was taken as control. Several studies have reported the effects of i.v. adrenaline on uterine blood flow. Hood et al. (1986) found that i.v. injection of adrenaline 15 μg decreases uterine blood flow up to 60% for 3 min in pregnant ewes [9]. In our study, adrenaline i.v. bolus decreased uterine blood flow (α and β2 adrenergic effect), confirming the data of Hood et al. However, the i.v. adrenaline did not alter the maternal heart rate, which is in accordance with clinical experience during which i.v. injections of adrenaline to women in labour do not reliably lead to tachycardia [10,11].

In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effects on maternal and fetal haemodynamic performance, uterine blood flow, blood gases and acid-base status in the pregnant ewe. However, an i.v. injection of adrenaline 10 or 15 μg decreases uterine blood flow in pregnant ewes and might compromise the fetus without increasing the heart rate of the mother.


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EPIDURAL, haemodynamic responses; DRUGS, adrenaline

© 1998 European Society of Anaesthesiology