Using a chronic sheep preparation, with induced foetal acidosis, the effects of low and high dose thiopentone and ketamine on maternal and foetal cardiovascular dynamics were studied. Ketamine 4 mg. kg -t and thiopentone 10 rag. kg -I were both associated with marked reductions in foetal cerebral blood flow and cerebral oxygen delivery. Blood pressure and cerebral blood flow in the acidotic foetus was better preserved, however, following the lower dose of ketamine 2 mg. kg -1 than following thiopentone 6 rag-kg -l. METHODSThe study was approved by our Animal Experimentation Committee as conforming to guidelines for the humane use of animals in research. Fourteen pregnant ewes with single foetuses estimated to be between 130 and 140 days of gestation (term-150 days) were used in the studies. The animals were prepared at least one day before any study in the following fashion. The ewe was anaesthetized with halothane and oxygen, intubated and ventilated to maintain, normal Paco:. A maternal femoral artery and vein were cannulated. The foetus was exposed through a hysterotomy incision, and a foetal axillary artery catheter was passed into the common brachiocephalic trunk. A catheter was also passed into the foetal inferior vena cava through the femoral vein, and a femoral artery catheter was inserted into the abdominal aorta. An inflatable cuff was placed around the umbilical cord. All lines were brought to the skin in the ewe's flank and the incisions were closed. Preparations similar to this have been used successfully in several previous studies from our laboratury. 2.6,7The mother and foetus were allowed to recover for 1-2 days before the study. On the morning of study, maternal and foetal blood gases, acid-base balance and blood pressure were measured. If these values were not in the normal range, the preparation was not used.
Amide local anaesthetics are weak bases with pK's of 7.80 or greater. Therefore, tissue acidosis may result in ionization and "trapping" of the basic local anaesthetics The following study was done in the pregnant ewe to determine if the highly protein-bound local anaesthetic bupivacaine demonstrates ion-trapping in the acidotic foetus. Six pregnant ewes of 135 days gestation were prepared surgically with catheters placed in maternal and foetal femoral arteries an veins. Bupivacaine was infused into the maternal femoral vein to maintain a constant concentration. After two hours of bupivacaine infusion the foetus was made acidotic by an infusion of lactic acid for 45 minutes. Then the acidosis was corrected by an infusion of bicarbonate for an additional 45 minutes. Maternal and foetal bupivacaine levels were measured at 15 minute intervals throughout the experiment. The bupivacaine levels in the foetus and the foetus-maternal ratio increased significantly during the period of foetal acidosis and declined to the control levels when the acidosis was corrected with bicarbonate. We conclude from this study that foetal acidosis results in ion-trapping of bupivacaine to a significant extent, despite protein binding in the maternal blood.
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