Clinical Pharmacokinetics of Epidural and Spinal Anaesthesia

Abstract

Epidural and spinal anaesthesia results from the interaction of local anaesthetics with nerve structures, primarily those located within the subarachnoid space. Local anaesthetics can reach the sites of action along various distribution pathways. Uptake into extraneural tissues (in particular epidural fat) and systemic absorption compete with neural tissue distribution and thereby affect the clinical potency and duration of action. Consequently, epidural doses must be much higher than spinal doses. The systemic absorption of lignocaine (lidocaine), bupivacaine and etidocaine following lumbar epidural administration has been shown to be biphasic, with a rapid initial absorption phase followed by a much slower absorption phase. Initial absorption rates of lignocaine and bupivacaine following subarachnoid injection are much slower, but the late absorption rates are similar to those after epidural administration. The tissue distribution characteristics of various amide-type agents are similar, because more extensive plasma binding offsets the greater tissue affinity of the more lipophilic compounds bupivacaine and etidocaine. The amide-type agents are predominantly eliminated by hepatic metabolism, except prilocaine, which is also metabolised elsewhere in the body. Ester-type agents are rapidly hydrolysed in blood and liver and are eliminated much faster than amide-type agents. The blood concentrations attained depend primarily upon the dose administered. The addition of adrenaline (epinephrine) reduces the peak plasma drug concentrations; similarly, the age of the patient, disease states and drug interactions may alter the pharmacokinetics to various extents. Because of the low dose requirements, systemic toxicity is not a problem during spinal anaesthesia. During epidural anaesthesia, however, the safety margin is relatively small, and systemic toxicity is very likely to occur after inadvertent intravascular injection of an epidural dose.

Epidural and subarachnoid blockade in children

“…These data may not apply in infants due to anatomical and physiological differences, the significantly larger dose relative to body weight which is administered to infants compared to ........................................................................................................................................................................................................................................... of isobaric bupivacaine with 1/200 000 adrenaline [144]. These values are well below the estimated threshold plasma concentration for mild central nervous system toxicity in adults [163]. Bupivacaine is extensively bound to plasma proteins, mainly albumin and alpha-1 acid glycoprotein, and neonates have lower levels of these proteins than adults resulting in a decreased binding capacity for bupivacaine and an increased risk of toxicity from free bupivacaine.…”

A Population Pharmacokinetic Model of Epidural Lidocaine in Geriatric Patients: Effects of Low-Dose Dopamine

“…Lidocaine apparently moves from the epidural space and the epidural veins to the azygos vein, and then to the superior vena cava (17). It is probable that the low-dose dopamine slows the transfer from the epidural to the serum compartment by causing vasoconstriction of either the epidural veins and/or dural blood flow in general (17). Addition of epinephrine to local anesthetic solutions is also an established tool which anesthesiologists use to slow local anesthetic absorption (10).…”

Pharmacokinetics and systemic toxicity of local anesthetics in children

“…Since they are all lipid-soluble and bind to the tissue into which they are injected, they undergo a delayed absorption process. Bupivacaine and ropivacaine are more strongly bound to the tissue at the injection site and more slowly absorbed into the blood vessels than lidocaine [10], suggesting that their blood concentration increases slowly and their peak plasma concentrations tend to be low. On this basis, repeated epidural administration of lidocaine would result in a rapid increase of plasma concentration, leading to systemic toxicity.…”

“…Because of the decreased density of vascularities of the pia mater and the spinal cord, the rate of absorption of anesthetics from the subarachnoid space is much slower than after epidural administration [10]. Recently the safety and effectiveness of awake spinal anesthesia in neonates at risk of postoperative apnea has promoted the use of combined spinal and caudal epidural anesthesia for lower abdominal surgery.…”