Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of increased placental vascular resistance.
BACKGROUND
We hypothesized that ephedrine and phenylephrine are equal with respect to uterine and placental haemodynamics and fetal acid-base status after exposure to maternal hypoxaemia and hypotension in a chronic sheep model of increased placental vascular resistance (R(UA)).


METHODS
At 114-135 days gestation, chronically instrumented fetal sheep underwent placental embolization leading to increased R(UA). Twenty-four hours after embolization, the ewes were anaesthetized and randomized to receive boluses of ephedrine (n=7) or phenylephrine (n=6) for epidural-induced hypotension after maternal hypoxaemia. Uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and uterine vascular resistance (R(UtA)) and R(UA) were recorded. Uterine (PI(UtA)) and umbilical artery (PI(UA)) pulsatility indices were obtained by Doppler ultrasonography. Fetal arterial blood samples were analysed for acid-base values and lactate concentrations.


RESULTS
During hypotension, Q(UtA), fetal pH, BE, and Po(2) decreased whereas R(UtA), PI(UtA), R(UA), and fetal lactate concentration increased. With ephedrine, Q(UtA), R(UtA), PI(UtA), R(UA), and fetal Po(2) returned to baseline. Fetal pH, BE, and lactate concentration did not change from hypotensive values. With phenylephrine, Q(UtA) remained lower (P=0.007) and R(UtA) (P=0.007), PI(UtA) (P=0.013), and R(UA) (P=0.050) higher than at baseline. Fetal Po(2) returned to baseline and fetal pH and BE did not change from hypotensive values. However, fetal lactate concentration increased further (mean difference 1.49, 95% confidence interval 0.72-2.26 mmol litre(-1); P=0.004).


CONCLUSIONS
In a chronic sheep model of increased placental vascular resistance, compared with ephedrine administration, phenylephrine administration was associated with impaired uterine and placental haemodynamics and increased fetal lactate concentrations.
Erkinaro
T
T
Department of Anaesthesiology and Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 21, FIN-90029 OYS, Finland. tiina.erkinaro@pp.fimnet.fi
Kavasmaa
T
T
Päkkilä
M
M
Acharya
G
G
Mäkikallio
K
K
Alahuhta
S
S
Räsänen
J
J
D000767:Anesthesia, Epidural / Q000009:adverse effects; D000773:Anesthesia, Obstetrical / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D004809:Ephedrine / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood; D010656:Phenylephrine / Q000627:therapeutic use*; D021041:Placental Circulation / Q000187:drug effects*; D010927:Placental Insufficiency / Q000188:drug therapy / Q000503:physiopathology; D011247:Pregnancy; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019344:Lactic Acid; D004809:Ephedrine