The use of local anesthetics (LA) may be accompanied by systemic and Iocalised adverse reactions, usually secondary to:
1. accidental intravascular injection (Chapter 36),
2. inadvertent intrathecal injection, or
3. administration of an excessive dose.
Intravenous injection of 20-25 mg of bupivacaine has been reported to induce fatal cardiovascular collapse (Table 36.6) (1).
Factors which can diminish the incidence of toxic reactions are:
1. fractionation of the injected dose,
2. aspiration before injection,
3. selection of less toxic LAs (Chapter 60),
4. reduction in the concentration of LA, and
5. test-dosing before injection of the main dose.
The diagnosis of inadvertent intravascular placement of an epidural needle or catheter can be made by using either air or a sympathomimetic amine as the 'marker' agent. Unintended intrathecal placement can be diagnosed by the injection of an appropriately small dose of a rapid onset LA.
Injection of 1 ml of air into an epidural catheter can be a highly specific and sensitive marker of intravascular catheter Iocalisation (3), but the safety of the doppler test has yet to be proven and, moreover, a precordial doppler and an extra person have to be available (2).
Epinephrine, the catecholamine currently used in most test-doses, has several disadvantages. This mixed alpha- and beta-adrenergic agent does not consistently produce maternal tachycardia in laboring women. Cyclic maternal heart rate changes, due to painful uterine contractions, occur normally in unanesthetised parturients. The effect of epinephrine superimposed on these physiological changes in heart rate is not always discernible. Moreover, a major adverse effect of systemic epinephrine is its inhibition of uterine blood flow (UBF). This reduction of UBF has been demonstrated in gravid ewes and lasts for 2-5 minutes (2).
Although the chronotropic response in term pregnant women is reduced, a test dose containing 5 mcg of isoproterenol (isoprenaline) might be a safer and more effective alternative (3). Isoproterenol produces a superior increase in maternal heart rate with minor effects on uterine blood flow in the chronic maternal fetal sheep preparation (4). In this animal model, incorporation of isoproterenol as a test dose does not produce neurotoxicty (5, 6). These results suggest that isoproterenol may be safe for use as an epidural test dose in pregnant women.
Questions still to be solved are:
1. Will the required amount of local anesthetics increase, if isoproterenol is used as test-dose?
2. Is the relief of pain adequate when isoproterenol is used as an epidural test-dose?
3. What is the effect of isoproterenol on uterine blood flow?
Some contradictory results exist concerning the increased sensitivity, during pregnancy, to the toxicity of local anesthetics. Santos et al. (7) compared the systemic toxicity of ropivacaine (Chapter 4) and bupivacaine in non-pregnant and pregnant ewes and concluded that..."The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which cardiotoxicity of bupivacaine was enhanced during ovine pregnancy." (8).
A major concern in pregnancy is the trans-placental distribution of local anesthetics (Chapter 77). Differences in the cord-to-maternal plasma drug concentration ratio essentially reflect trans-placental differences in the extent of plasma binding (Chapter 50). When this ratio is high there should be a delay in the equilibration of drug in fetal tissues. Conversely, similar umbilical artery and umbilical vein concentration ratios observed for the various agents argue against large differences in their equilibration rates in the fetus. Thus, the impact, if any, of plasma binding on the risks of fetal toxicity is unclear (9).
The prevention of toxicity of local anesthetics (Chapter 89) in the mother and the fetus is of utmost importance but, in this field, many questions remain to be answered.
References:
1. Van Zundert A. Is there a need for chloroprocaine 3% and bupivacaine 0.75 %? Acta Anesth Belg 1988;39;151.
2. Shnider SM, Levinson G, Ralston DH. Regional anesthesia for labor and delivery. In: Anesthesia for obstetrics ed. Shnider SM, Levinson G; Williams & Wilkins pp 137-141
3. Leighton BL, Desimone CA, Norris MC, et al. Isoproterenol is an effective marker of intravenous injection in laboring women. Anesthesiology 1989;71 ;206-209.
4. Marcus MAE, Vertommen JD, Van Aken H, et al. The hemodynamic effects of different doses of isoproterenol in the pregnant ewe. Anesth Analg 1994;78,s267
5. Marcus MAE, Vertommen JD, Van Aken H, et al. Light microscopic neuropathological observations after intrathecal bolus injections of isoproterenol. Anesthesiology 1994;V81 ;A1175.
6. Marcus MAE, Bruyninckx F, Vertommen et al. Effects of epidural isoproterenol on spinal somatosensory evoked potentials in the pregnant ewe and the non pregnant ewe. Anesth Analg 1995;80;s295
7. Santos AL, Arthur R, Wlody D, et al. Comparative systemic toxicity of ropivacaine and bupivacaine in non-pregnant and pregnant ewes. Anesthesiology 1995;82;734-740
8. Morishima HO, Pedersen H, Finster M, et al. Bupivacaine toxicity in pregnant and non-pregnant ewes. Anesthesiology 1985 ;63;134-139.
9. Tucker GT. Safety in numbers. The role of pharmacokinetics in local anesthetic toxicity: the 1993 ASRA lecture. Reg Anesth 1994;19(3);155-63.