Local Anesthetic Agents
Most local anesthetic agents share a common structure consisting of a hydrophilic amino group connected by an intermediate chain to a lipophilic aromatic residue.
Their presumed mechanism of action is to block exchange of sodium and potassium ions across the cell membrane, probably through mechanical interruption of ion flow through cell wall channels.
Local anesthetic drugs are manufactured as chloride salts. The nonionized base is able to diffuse across tissues, while the ionized form is actually the active component. The amounts of nonionized (mobile) and ionized (active) drug depend on the pK a of the local anesthetic and tissue pH.
After injection of lidocaine (Xylocaine), the sensory nerve action potential decreases more sharply in pregnant women than in nonpregnant women. This implies that pregnant women have an increased susceptibility to the effects of local anesthetic agents ( 7).
Local anesthetics belong principally to two groups, those of ester and amide configurations. Ester drugs are generally characterized by their rapid onset of action, short duration, and low toxicity. Chloroprocaine (Nesacaine) is a representative of this group. It is rapidly metabolized by serum pseudocholinesterase, forming
paraaminobenzoic acid. Lidocaine, bupivacaine, ropivacaine, and levobupivacaine are representatives of the amide group. These drugs are more highly bound to protein and have a slower onset and a longer duration of action. They are metabolized in the liver. Toxicity is usually greater for amides than for drugs of the ester group ( Table 3.3).
TABLE 3.3. Characteristics of local anesthetics commonly used in obstetric anesthesia
Local anesthetic drugs are absorbed systemically. Distribution to the fetus depends on maternal tissue uptake, maternal blood concentration, uterine blood flow, and maternal and fetal metabolism and excretion. Fetal-tissue drug distribution is also affected by asphyxia. Fetal asphyxia leads to increased P aCO 2, which results in cerebral and coronary vessel dilation and increased brain and myocardial blood flow. The increased perfusion of these organs with anesthetic drug leads to greater toxicity. The decrease in pH seen with fetal asphyxia results in increased ionized (active) drug in the fetal circulation and tissues, a phenomenon referred to as ion trapping. The clinical significance of this is unclear.
Side Effects of Local Anesthetic Drugs
Systemic Toxicity Systemic complications involving the use of local anesthetics include toxic blood levels of the drug and allergic reactions, as well as reactions due to epinephrine that is often added to local anesthetic solutions to retard systemic absorption and prolong duration of action. Maximal safe doses for healthy young adults are 7 mg per kg (300 mg) of lidocaine, 2 to 3 mg per kg (175 mg) of bupivacaine, and 20 mg per kg (1000 mg) of chloroprocaine (see Table 3.3). The most common reason for high blood levels of local anesthetic drugs is accidental intravascular injection. This most commonly occurs when an epidural catheter has been placed or migrated into a vein. To minimize accidental intravenous injection, gentle aspiration should be undertaken before each injection. Injection should be done slowly and incrementally with only 2 to 5 mL of local anesthetic drug to reduce the chance of a sudden increase in plasma levels. A marker such as epinephrine may be added to the local anesthetic solution so that intravascular injection will manifest as tachycardia. The infiltration of a local anesthetic agent into an area rich in vessels, such as the region of the uterine artery (e.g., paracervical block), pudendal vessels, or the epidural space may be associated with absorption of the drug through blood vessel walls. The serum levels tend to rise slowly, and toxic manifestations usually occur only after multiple injections. Repeated injections of slowly metabolized local anesthetic drugs, such as the amides, may lead to accumulation in the serum such that toxic levels are achieved. This phenomenon does not occur readily with esters such as chloroprocaine, which are rapidly metabolized (maternal serum half-life of 21 seconds and fetal serum half-life of 43 seconds for chloroprocaine). To minimize the likelihood of producing high serum levels, care should be taken to record the amount and concentration of local anesthetic solution and to limit use to approximately 25% less than the maximal safe dose. Signs and symptoms of local anesthetic drug toxicity include, in order of their appearance, a relaxed feeling, drowsiness,
lightheadedness, tinnitus, circumoral paresthesias, metallic taste, slurred speech, blurred vision, unconsciousness, convulsions, and cardiac dysrhythmias and arrest.
In 1983, the U.S. Food and Drug Administration issued an advisory, warning that 0.75% bupivacaine should no longer be used in obstetrics because of reports of bupivacaine-induced cardiac arrest occurring at blood levels of only 3 to 5 µg per mL. The advisory stated that the resuscitation in these cases had been “difficult or impossible despite apparently adequate preparation and appropriate management.” Inadvertent intravascular injection causes high serum levels, which produce cardiac arrest through blockade of the cardiac sodium channels, inhibiting repolarization of the nerve cell membranes of the conduction system of the heart.
Bupivacaine has been found to bind avidly to nonspecific cardiac protein–binding sites, slowing the conduction of impulses arising in pacemaker cells and causing a dose-dependent reduction in the strength of myocardial contractility, leading to cardiac arrest. Management is best accomplished through prevention, as described previously. Therapy is symptomatic. Initial treatment includes the use of mask oxygen, a reliable intravenous line, and measures to ensure and protect the airway.
These include use of cricoid pressure to occlude the esophagus, the availability of adequate suction, and the capability to perform endotracheal intubation, if needed.
Adequacy of respirations must be ensured, if necessary by means of positive pressure ventilation with 100% inspired oxygen. The patient should be hyperventilated to help correct metabolic acidosis caused by seizure activity and decreased cardiac output. CNS hyperreactivity and convulsions are treated with thiopental (Pentothal) in small, incremental doses of 25 to 50 mg given intravenously, or with 1 to 5 mg of midazolam given intravenously. In the event of cardiovascular depression, elevate the lower extremities and verify left uterine displacement. Vasoactive drugs such as ephedrine, phenylephrine, epinephrine, and calcium may be employed to support the circulation. If cardiopulmonary resuscitation is indicated, the fetus should be delivered within 5 minutes to relieve maternal central venous compression and advanced cardiac life support (ACLS) protocols should be followed.
Use of Regional Anesthetic Blocks
Local Infiltration of the Perineum Local infiltration of the perineum is commonly performed when an episiotomy is needed and time or fetal head position does not allow a pudendal block to be administered. An average of 10 to 20 mL of local anesthetic solution is employed. The preferred drugs are lidocaine 1% or chloroprocaine 2%.
Pudendal Block The pudendal block provides analgesia of the vaginal introitus and perineum. There are several advantages of this analgesic technique. Because the elapsed time between administration and delivery is short, there is relatively little systemic absorption and therefore little opportunity for the drug to directly affect the fetus. The block is easy to accomplish and provides analgesia of the perineum only. The disadvantages include the need for large drug doses (i.e., 10 mL on each side) and the potential for local anesthetic toxicity, hematoma, and the possibility of infection leading to retropsoas or subgluteal abscess. With the transvaginal approach, the ischial spine must first be identified. Through a guide, a needle is inserted into the vagina and directed laterally and posteriorly to the ischial spine. A submucosal wheal is made, and the needle is advanced into the sacrospinous ligament, where resistance is felt. As the needle passes the ligament, a loss of
resistance is felt. The needle has now entered the pudendal canal, which contains the pudendal nerve and associated vessels ( Fig. 3.3). After aspirating the needle for blood, 3 to 5 mL of local anesthetic solution (usually lidocaine 1%) is injected, and the needle is advanced another 0.5 to 1 cm. If aspiration is again negative, 5 to 7 mL of solution is injected. A total of 10 mL is injected on each side. Approximately 10 minutes are required for anesthesia to occur. Chloroprocaine 1% to 2% may also be used for this block. Analgesia with chloroprocaine lasts less than 1 hour, but lidocaine analgesia is more prolonged.
FIG. 3.3. The pudendal nerve and its branches. The inferior hemorrhoidal nerve can arise higher up from the pudendal nerve or separately from the sacral plexus.
(Adapted from Abouleish E. Pain control in obstetrics. Philadelphia: JB Lippincott Co, 1977.)
Paracervical Block Paracervical block (PCB) anesthesia may be used when the active phase of labor begins, and it can be employed until approximately 8 cm of dilation has been achieved. Although formerly popular, this block has fallen into relative disuse since the description of bradycardia after PCB and its proven association with fetal acidosis. The PCB is useful when anesthesia personnel are unavailable and parenteral narcotics are inadequate. The PCB relieves the pain associated with uterine contractions, but it is not effective for pain associated with distention of the pelvic floor. The two drugs of choice are chloroprocaine and lidocaine in 1% concentrations. Typically, 6 mL of drug is administered superficially, just under the vaginal mucosa, at the 4- and 8-o'clock positions ( Fig. 3.4). In this way, bradycardia, which occurs in 10% to 30% of cases, is less likely to appear. The landmark study by Baxi and colleagues ( 8), using a transcutaneous oxygen
electrode attached to the fetal scalp, demonstrated that bradycardia is related to decreasing fetal oxygenation, which becomes marginal approximately 10 minutes after injection. This research has been corroborated by the study of isolated human uterine artery segments and by work in animals, indicating that direct uterine artery vasoconstriction and uterine hypertonus in response to the injection of a local anesthetic drug diminish uterine blood flow and fetal oxygenation.
FIG. 3.4. Technique of paracervical block. Notice the position of the hand and fingers in relation to the cervix and fetal head and the shallow depth of the needle insertion. No undue pressure is applied at the vaginal fornix by the fingers or needle guide. (Adapted from Abouleish E. Pain control in obstetrics. Philadelphia: JB Lippincott Co, 1977.)
Lumbar Epidural Analgesia
Standard Technique Lumbar epidural analgesia was first performed in 1884 by Corning, who recognized that analgesia could still occur when attempted spinal analgesia failed. In 1921, Pages applied the technique to surgery. Obstetric applications were made by Graffagnino and Seyler in 1935. The most commonly used
anesthetic agents for lumbar epidural analgesia for labor are bupivacaine 0.0625% to 0.25% and ropivacaine 0.1% to 0.2%. The technique of lumbar epidural analgesia involves the insertion of a 17- or 18-gauge hollow-bore needle through the ligamentum flavum into the epidural space at the L4-5, L3-4, or L2-3 interspace. Although the hanging-drop technique for identification of the epidural space is generally effective, most physicians prefer the loss-of-resistance technique as the one that affords the least risk of penetration of the dura. Use of air or saline may be used to identify the epidural space. A 20-gauge catheter is passed through the epidural needle for a distance of 3 to 5 cm within the epidural space. This catheter is securely taped in place and serves as an avenue for intermittent or continuous infusion of local
anesthetic agents or opioids.
Combined Spinal–Epidural Analgesia The combined spinal–epidural (CSE) technique adds a subarachnoid injection of an opioid with or without a small dose of local anesthetic in a needle-through-needle technique to provide a faster onset with a smaller dose of medication than is possible using epidural medications alone ( 9). The epidural catheter is still available for additional analgesia. A prospective, double-blinded, randomized study compared CSE analgesia with standard epidural analgesia in spontaneously laboring nulliparous parturients. There was no difference in the rate of progress of labor, the amount of epidural local anesthetic required, and the incidence of instrumental deliveries between the CSE and the standard epidural analgesia groups. However, analgesia was more complete and there was higher patient satisfaction in the CSE group than in the epidural analgesia group.
Patient-controlled Epidural Analgesia Patient-controlled epidural analgesia (PCEA) is a technique by which the patient self-administers on-demand doses of an analgesic mixture via an epidural catheter, whenever she perceives discomfort. To avoid overdosage, a lockout period follows each self-administration. This technique is associated with a decreased use of local anesthetic solution and less demand on staff time compared to continuous epidural infusion (CEI). Most studies have found patients will self-administer less local anesthetic solution than continuous infusions provide and that anesthesia workforce needs are reduced by about 40% ( 10).
Quality of analgesia, complications, and amount of motor block are similar between the two techniques.
Epidural Medications in Labor Epidural injection of opioids alone has been shown to be of limited value for the relief of labor pain. High doses of morphine (7.5 mg) have provided satisfactory analgesia, but only during the first stage of labor. Because of its slow onset of action (often 1 hour or more) and high incidence of side effects (nausea and pruritus), morphine is not a satisfactory agent for this use. Fentanyl and sufentanil used alone can provide analgesia for early labor, but require high doses—100 µg fentanyl or 30 µg sufentanil. In contrast, spinal injection of opioids alone provides excellent, although time-limited analgesia for labor in small doses—10 to 25 µg fentanyl or 5 to 10 µg sufentanil. Fortunately, the addition of opioids to dilute concentrations of epidural local anesthetics has been proven to be quite effective in the relief of labor pain. The combination is a rational one because local anesthetic solutions relieve somatic pain preferentially, whereas opioids are more effective in relieving visceral pain. By combining a lipid-soluble opioid such as fentanyl or sufentanil to bupivacaine or ropivacaine, the concentration of local anesthetic can be dramatically decreased and motor block can be minimized. The addition of fentanyl or sufentanil approximately doubles the analgesic efficacy of any concentration of bupivacaine or ropivacaine, while shortening the time to complete analgesia. Opioid and Chloroprocaine Mixtures. Mixtures of morphine with
chloroprocaine have not been shown to be useful, as chloroprocaine appears to antagonize the analgesic effects of the opioid, while increasing its side effects, particularly nausea and pruritus. The mechanism of this unfavorable interaction is unknown. Chloroprocaine may also prolong the onset of morphine analgesia and decrease the effectiveness of bupivacaine if used before these agents. The most satisfactory analgesia appears to be produced when opioids are combined with amide local anesthetics. The beneficial effects of epidural opioids in labor appear to be the following:
reduction in motor block, allowing improved mobility of the patient reduction in shivering
decreased incidence of hypotension
use of lower doses of local anesthetic agents
greater maternal satisfaction with the analgesia that they provide.
Effects of Epidural Analgesia on Uterine Blood Flow Studies investigating changes in intervillous blood flow and mean arterial pressure with lumbar epidural analgesia in adequately preloaded patients have demonstrated only a negligible reduction in these parameters with the onset of effective analgesia. Well-hydrated patients with preeclampsia have experienced improvement in intervillous blood flow along with a slight decrease in blood pressure.
Advantages and Disadvantages of Lumbar Epidural Analgesia There are three principal advantages of lumbar epidural analgesia:
the parturient remains awake and cooperative.
the incidence of complications is very low when the technique is used correctly.
once an epidural catheter is in place, it can be used to provide analgesia or anesthesia for a vaginal or cesarean delivery.
The disadvantages of lumbar epidural analgesia include:
Indications and Contraindications for Lumbar Epidural Analgesia Indications for lumbar epidural analgesia include pain in labor, management of the patient with preeclampsia who does not have a coagulation abnormality, management of labor in patients with certain cardiac lesions, and management of breech delivery. A joint statement by the American College of Obstetricians and Gynecologists (ACOG) and the American Society of Anesthesiologists (ASA) ( 11) notes that: “Labor results in severe pain for many women. There is no other circumstance in which it is considered acceptable for a person to experience untreated severe pain, amenable to safe intervention, while under a physician's care. In the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor.
Of the various pharmacologic methods of pain relief used in labor and delivery, regional analgesia techniques—spinal, epidural and combined spinal epidural (CSE) are the most flexible, effective, and least depressing to the CNS, allowing for an alert, participating mother and an alert neonate.” There are absolute and relative
contraindications to the induction of lumbar epidural analgesia. Absolute contraindications include the following: patient refusal, hemodynamic instability, infection at the anticipated site of puncture, and absence of resuscitation equipment. Relative contraindications may include fever, preexisting CNS disease, hypovolemia,
hypotension, lack of experience by the anesthetist, and blood coagulation defects. Although an arbitrary platelet count of 100,000 per mm 3 has been advocated as the lower limit for safe lumbar epidural analgesia, successful blocks without epidural bleeding complications have been obtained with platelet counts as low as 50,000 per mm 3. In one report, Beilin and colleagues ( 12) described a study of 80 women who presented for labor and delivery and had platelet counts less than 100,000 per mm
3 during the peripartum period. Of these 80, 30 were given an epidural anesthetic. The range of platelet counts was 69,000 to 98,000 per mm 3. No patient had any documented neurologic complication. These authors concluded that regional anesthesia should not necessarily be withheld when the platelet count is less than
100,000 per mm 3. However, given that the risk of epidural hematoma is extremely rare, a study this small would be unlikely to reveal a problem. The underlying cause of the thrombocytopenia is also important and must be considered along with any absolute number. For example, the patient with idiopathic thrombocytopenic purpura or gestational thrombocytopenia is much less likely to bleed at a low platelet count than the patient with HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. The best indicator of potential bleeding is a patient history of bruises, contusions, petechiae, bleeding from the gums, and so on.
Subarachnoid Analgesia Subarachnoid or spinal analgesia for labor has become increasingly popular. The major advantages of spinal analgesia include (a) use of a very low dose of local anesthetic or narcotic analgesic drug and (b) the excellent analgesia provided. Onset of action is rapid, and uterine activity is not affected. The disadvantages include (a) the possibility of postdural puncture headache (PDPH) which is increasingly rare with the use of pencil-point needles and (b) the time-limited nature of a single-shot technique. For this reason spinal analgesia is commonly combined with an epidural catheter as a CSE technique. Indications and
contraindications are similar to epidural analgesia. Morphine and fentanyl can provided analgesia during labor when administered intrathecally in small doses. Labor analgesia usually lasts for 4 to 8 hours and is not accompanied by motor block. The major disadvantages include pruritus and nausea. Pruritus can be antagonized with small doses of intravenous naloxone or oral naltrexone. PDPH can be minimized through the use of 22- to 27-gauge Whitacre, Sprotte, or other pencil-point needles. A 28-gauge microcatheter can be passed through 22-gauge spinal needles, permitting the use of continuous spinal analgesia in labor and surgery. These catheters were withdrawn from the market because of associated cauda equina syndrome, probably related to local anesthetic neurotoxicity.
Complications of Regional Block Analgesia
Hypotension Hypotension is common, occurring in 10% to 20% of patients undergoing epidural analgesia for labor and 50% to 80% for cesarean delivery. It often occurs despite left uterine displacement and administration of an adequate vascular preload. Treatment should consist of the following steps:
Hypotension Hypotension is common, occurring in 10% to 20% of patients undergoing epidural analgesia for labor and 50% to 80% for cesarean delivery. It often occurs despite left uterine displacement and administration of an adequate vascular preload. Treatment should consist of the following steps: