S. C. Grice

Epinephrine enhances analgesia produced by epidural bupivacaine during labor

Reports on the analgesic and hemodynamic effects of epinephrine added to bupivacaine for epidural use in obstetrics are conflicting. In this study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine (n = 50) or 10 ml of 0.25% bupivacaine with 1:300,000 epinephrine (n =

Labor analgesia with epidural bupivacaine plus fentanyl: enhancement with epinephrine and inhibition with 2-chloroprocaine.

Epidural injection of drug combinations may decrease toxicity by decreasing the dose of each component, but may also result in detrimental drug interactions. In this study interactions among bupivaciane, fentanyl, epinephrine, 2-chloroprocaine, and lidocaine for epidural analgesia during labor were examined. In part 1 of the study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine with 5 micrograms/ml fentanyl (n = 50), or 10 ml of this combination with 3.33 micrograms/ml freshly added epinephrine (n = 50). Epinephrine prolonged the median duration of pain relief (180 vs. 138 min, P less than 0.05) without affecting duration of first or second stages of labor, or neonatal Apgar scores. Blood pressure decreased slightly more in those receiving epinephrine, although the incidence of hypotension requiring treatment did not differ between groups. Part 2 of the study evaluated the possibility that local anesthetic used for confirming catheter tip location may interfere with the analgesic action of this bupivacaine-fentanyl-epinephrine (BFE) combination. In 50 additional parturients, a test dose of either 2-chloroprocaine (n = 25) or lidocaine (n = 25) was injected through the epidural catheter and was followed by injection of the BFE mixture. The lidocaine test dose group had a greater duration of analgesia than the 2-chloroprocaine test dose group (median duration of 164 vs. 91 min, P less than 0.05). The authors conclude that the addition of epinephrine 3.33 micrograms/ml significantly increases the duration of analgesia obtained from 0.25% bupivacaine with 5 micrograms/ml fentanyl. However, prior injection of 2-chloroprocaine, but not lidocaine, significantly decreases the duration of analgesia achieved with this BFE mixture.

Epidural Clonidine Does Not Decrease Blood Pressure or Spinal Cord Blood Flow in Awake Sheep

Preliminary data in animals and humans suggest that epidurally administered clonidine produces antinociception and is not neurotoxic. However, clonidine can produce vasoconstriction, and epidurally administered clonidine decreases spinal cord blood flow in anesthetized pigs. To examine the effect of epidurally administered clonidine on spinal cord blood flow in awake animals, the authors inserted lumbar epidural, femoral arterial and venous, pulmonary arterial, and left ventricular catheters in 13 adult sheep. Following a 24-h recovery, the authors injected saline (N = 6) or clonidine, 750 μg (17–25 μg/kg; N = 7) epidurally, and measured arterial blood gas tensions; temperature; heart rate; systemic and pulmonary arterial, right atrial, and pulmonary capillary wedge pressures; and spinal cord and renal blood flows (by radioactive microsphere injection) before and at 45 min and 4 h following injection. Epidural saline injection did not affect measured variables. Heart rate decreased from 112 ± 9 to 86 ± 4 beats/min (mean ± SE; P = .003) and arterial PO1 decreased from 99 ± 3 to 78 ± 6 mmHg (P = .04) 45 min following clonidine injection. Temperature increased from 39.1 ± .2 to 40.6 ± 1° C (P = .0001) 4 h following clonidine injection. Epidural clonidine administration did not affect cardiac output, pulmonary and systemic pressures, or renal or spinal cord blood flows, except for an increase in mid-thoracic spinal cord blood flow 45 min following injection. The authors conclude that, in sheep, epidural clonidine does not produce dangerous cardiovascular depression or global spinal cord ischemia.

Intravenous clonidine hydrochloride toxicity in pregnant ewes

Administration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidines acute maternal and fetal effects were intravenously injected 300 micrograms clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity--intraamniotic pressure increased 97 +/- 27% (p less than 0.05), uterine blood flow decreased 55 +/- 7% (p less than 0.001), maternal and fetal serum glucose increased 158 +/- 23% and 249 +/- 91%, respectively (p less than 0.001), and maternal and fetal Po2 decreased to 44 mm Hg +/- 4 mm Hg and 13 mm Hg +/- 1 mm Hg, respectively (p less than 0.05). Maternal and fetal blood pressure and serum cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations less than 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial Po2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on alpha 2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology.