Drugs

Not all procedures and physicians are created equal, at least regarding the amount of time needed to complete an operation. If anesthesiologists are to use regional techniques effectively, they must be able to choose a local anesthetic that lasts the right amount of time. To do this, they understand the local anesthetic timeline from the shorter-acting to the longer-acting agents (Fig. 1-1).

Figure 1-1. Local anesthetic timeline (length in minutes of surgical anesthesia).

All local anesthetics share the basic structure of aromatic end, intermediate chain, and amine end (Fig. 1-2). This basic structure is subdivided clinically into two classes of drugs, the amino esters and the amino amides. The amino esters possess an ester linkage between the aromatic end and the intermediate chain. These drugs include cocaine, procaine, 2-chloroprocaine, and tetracaine (Figs. 1-3 and 1-4). The amino amides contain an amide link between the aromatic end and the intermediate chain. These drugs include lidocaine, prilocaine, etidocaine, mepivacaine, bupivacaine, and ropivacaine (see Figs. 1-3 and 1-4).

Figure 1-2. Basic local anesthetic structure.

Figure 1-3. Local anesthetics commonly used in the United States. A, Amides. B, Esters.

Figure 1-4. Chemical structure of commonly used amino ester and amino amide local anesthetics.

Amino Esters

Cocaine was the first local anesthetic used clinically, and it is used today primarily for topical airway anesthesia. It is unique among the local anesthetics in that it is a vasoconstrictor rather than a vasodilator. Some anesthesia departments have limited the availability of cocaine because of fears of its abuse potential. In those institutions, mixtures of lidocaine and phenylephrine rather than cocaine are used to anesthetize the airway mucosa and shrink the mucous membranes.

Procaine was synthesized in 1904 by Einhorn, who was looking for a drug that was superior to cocaine and other solutions in use. Currently, procaine is seldom used for peripheral nerve or epidural blocks because of its low potency, slow onset, short duration of action, and limited power of tissue penetration. It is an excellent local anesthetic for skin infiltration, and its 10% form can be used as a short-acting (i.e., lasting <1 hour) spinal anesthetic.

Chloroprocaine has a rapid onset and a short duration of action. Its principal use is in producing epidural anesthesia for short procedures (i.e., lasting <1 hour). Its use declined during the early 1980s after reports of prolonged sensory and motor deficits resulting from unintentional subarachnoid administration of an intended epidural dose. Since that time, the drug formulation has changed. Short-lived yet annoying back pain may develop after large (>30 mL) epidural doses of 3% chloroprocaine.

Tetracaine, first synthesized in 1931, has become widely used in the United States for spinal anesthesia. It may be used as an isobaric, hypobaric, or hyperbaric solution for spinal anesthesia. Without epinephrine it typically lasts 1.5 to 2.5 hours, and with the addition of epinephrine it may last up to 4 hours for lower extremity procedures. Tetracaine is also an effective topical airway anesthetic, although caution must be used because of the potential for systemic side effects. Tetracaine is available as a 1% solution for intrathecal use or as anhydrous crystals that are reconstituted as tetracaine solution by adding sterile water immediately before use. Tetracaine is not as stable as procaine or lidocaine in solution, and the crystals also undergo deterioration over time. Nevertheless, when a tetracaine spinal anesthetic is ineffective, one should question technique before “blaming” the drug.

Amino Amides

Lidocaine was the first clinically used amide local anesthetic, having been introduced by Lofgren in 1948. Lidocaine has become the most widely used local anesthetic in the world because of its inherent potency, rapid onset, tissue penetration, and effectiveness during infiltration, peripheral nerve block, and both epidural and spinal blocks. During peripheral nerve block, a 1% to 1.5% solution is often effective in producing an acceptable motor blockade, whereas during epidural block, a 2% solution seems most effective. In spinal anesthesia, a 5% solution in dextrose is most commonly used, although it may also be used as a 0.5% hypobaric solution in a volume of 6 to 8 mL. Others use lidocaine as a short-acting 2% solution in a volume of 2 to 3 mL. The suggestion that lidocaine causes an unacceptable frequency of neurotoxicity with spinal use needs to be balanced against its long history of use. I believe that the basic science research may not completely reflect the typical clinical situation. In any event, I have reduced the total dose of subarachnoid lidocaine I administer to less than 75 mg per spinal procedure, inject it more rapidly than in the past, and no longer use it for continuous subarachnoid techniques. Patients often report that lidocaine causes the most common local anesthetic allergies. However, many of these reported allergies are simply epinephrine reactions resulting from intravascular injection of the local anesthetic epinephrine mixture, often during dental injection.

Prilocaine is structurally related to lidocaine, although it causes significantly less vasodilation than lidocaine and thus can be used without epinephrine. Prilocaine is formulated for infiltration, peripheral nerve block, and epidural anesthesia. Its anesthetic profile is similar to that of lidocaine, although in addition to producing less vasodilation, it has less potential for systemic toxicity in equal doses. This attribute makes it particularly useful for intravenous regional anesthesia. Prilocaine is not more widely used because, when metabolized, it can produce both orthotoluidine and nitrotoluidine, agents in methemoglobin formation.

Etidocaine is chemically related to lidocaine and is a long-acting amide local anesthetic. Etidocaine is associated with profound motor blockade and is best used when this attribute can be of clinical advantage. It has a more rapid onset of action than bupivacaine but is used less frequently. Those clinicians using etidocaine often use it for the initial epidural dose and then use bupivacaine for subsequent epidural injections.

Mepivacaine is structurally related to lidocaine and the two drugs have similar actions. Overall, mepivacaine is slightly longer acting than lidocaine, and this difference in duration is accentuated when epinephrine is added to the solutions.

Bupivacaine is a long-acting local anesthetic that can be used for infiltration, peripheral nerve block, and epidural and spinal anesthesia. Useful concentrations of the drug range from 0.125% to 0.75%. By altering the concentration of bupivacaine, sensory and motor blockade can be separated. Lower concentrations provide sensory blockade principally, and as the concentration is increased, the effectiveness of motor blockade increases with it. If an anesthesiologist had to select a single drug and a single drug concentration, 0.5% bupivacaine would be a logical choice because at that concentration it is useful for peripheral nerve block, subarachnoid block, and epidural block. Cardiotoxicity during systemic toxic reactions with bupivacaine became a concern in the 1980s. Although it is clear that bupivacaine alters myocardial conduction more dramatically than lidocaine, the need for appropriate and rapid resuscitation during any systemic toxic reaction cannot be overemphasized. Levobupivacaine is the single enantiomer (l-isomer) of bupivacaine and appears to have a systemic toxicity profile similar to that of ropivacaine, and clinically it has effects similar to those of racemic bupivacaine.

Ropivacaine is another long-acting local anesthetic, similar to bupivacaine; it was introduced in the United States in 1996. It may offer an advantage over bupivacaine because experimentally it appears to be less cardiotoxic. Whether that experimental advantage is borne out clinically remains to be seen. Initial studies also suggest that ropivacaine may produce less motor block than that produced by bupivacaine, with similar analgesia. Ropivacaine may also be slightly shorter acting than bupivacaine, with useful drug concentrations ranging from 0.25% to 1%. Many practitioners believe that ropivacaine may offer particular advantages for postoperative analgesic infusions and obstetric analgesia.

Vasoconstrictors

Vasoconstrictors are often added to local anesthetics to prolong the duration of action and improve the quality of the local anesthetic block. Although it is still unclear whether vasoconstrictors actually allow local anesthetics to have a longer duration of block or are effective because they produce additional antinociception through α-adrenergic action, their clinical effect is not in question.

Epinephrine is the most common vasoconstrictor used; overall, the most effective concentration, excluding spinal anesthesia, is a 1:200,000 concentration. When epinephrine is added to local anesthetic in the commercial production process, it is necessary to add stabilizing agents because epinephrine rapidly loses its potency on exposure to air and light. The added stabilizing agents lower the pH of the local anesthetic solution into the 3 to 4 range and, because of the higher pKas of local anesthetics, slow the onset of effective regional block. Thus, if epinephrine is to be used with local anesthetics, it should be added at the time the block is performed, at least for the initial block. In subsequent injections made during continuous epidural block, commercial preparations of local anesthetic–epinephrine solutions can be used effectively.

Phenylephrine also has been used as a vasoconstrictor, principally with spinal anesthesia; effective prolongation of block can be achieved by adding 2 to 5 mg of phenylephrine to the spinal anesthetic drug. Norepinephrine also has been used as a vasoconstrictor for spinal anesthesia, although it does not appear to be as long lasting as epinephrine, or to have any advantages over it. Because most local anesthetics are vasodilators, the addition of epinephrine often does not decrease blood flow as many fear it will; rather, the combination of local anesthetic and epinephrine results in tissue blood flow similar to that before injection.

Needles, Catheters, and Syringes

Effective regional anesthesia requires comprehensive knowledge of equipment—that is, the needles, syringes, and catheters that allow the anesthetic to be injected into the desired area. In early years, regional anesthesia found many variations in the method of joining needle to syringe. Around the turn of the century, Schneider developed the first all-glass syringe for Hermann Wolfing-Luer. Luer is credited with the innovation of a simple conical tip for easy exchange of needle to syringe, but the “Luer-Lok” found in use on most syringes today is thought to have been designed by Dickenson in the mid-1920s. The Luer fitting became virtually universal, and both the Luer slip tip and the Luer-Lok were standardized in 1955.

In almost all disposable and reusable needles used in regional anesthesia, the bevel is cut on three planes. The design theoretically creates less tissue laceration and discomfort than the earlier styles did, and it limits tissue coring. Many needles that are to be used for deep injection during regional block incorporate a security bead in the shaft so that the needle can be easily retrieved on the rare occasions when the needle hub separates from the needle shaft. Figure 1-5 contrasts a blunt-beveled, 25-gauge needle with a 25-gauge “hypodermic” needle. Traditional teaching holds that the short-beveled needle is less traumatic to neural structures. There is little clinical evidence that this is so, and experimental data about whether sharp or blunt needle tips minimize nerve injury are equivocal.

Figure 1-5. Frontal, oblique, and lateral views of regional block needles. A, Blunt-beveled, 25-gauge axillary block needle. B, Long-beveled, 25-gauge (“hypodermic”) block needle. C, 22-gauge ultrasonography “imaging” needle. D, Short-beveled, 22-gauge regional block needle.

(A-D From Brown DL: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996. By permission of the Mayo Foundation, Rochester, Minn.)

Figure 1-6 shows various spinal needles. The key to their successful use is to find the size and bevel tip that allow one to cannulate the subarachnoid space easily without causing repeated unrecognized puncture. For equivalent needle size, rounded needle tips that spread the dural fibers are associated with a lesser incidence of headache than are those that cut fibers. The past interest in very-small-gauge spinal catheters to reduce the incidence of spinal headache, with controllability of a continuous technique, faded during the controversy over lidocaine neurotoxicity.

Figure 1-6. Frontal, oblique, and lateral views of common spinal needles. A, Sprotte needle. B, Whitacre needle. C, Greene needle. D, Quincke needle.

(A-D From Brown DL: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996. By permission of the Mayo Foundation, Rochester, Minn.)

Figure 1-7 depicts epidural needles. Needle tip design is often mandated by the decision to use a catheter with the epidural technique. Figure 1-8 shows two catheters available for either subarachnoid or epidural use. Although each has advantages and disadvantages, a single–end-hole catheter appears to provide the highest level of certainty of catheter tip location at the time of injection, whereas a multiple–side-hole catheter may be preferred for continuous analgesia techniques.

Figure 1-7. Frontal, oblique, and lateral views of common epidural needles. A, Crawford needle. B, Tuohy needle; the inset shows a winged hub assembly common to winged needles. C, Hustead needle. D, Curved, 18-gauge epidural needle. E, Whitacre, 27-gauge spinal needle.

(A-E From Brown DL: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996. By permission of the Mayo Foundation, Rochester, Minn.)

Figure 1-8. Epidural catheter designs. A, Single distal orifice. B, Closed tip with multiple side orifices.

(A and B From Brown DL: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996. By permission of the Mayo Foundation, Rochester, Minn.)

Nerve Stimulators

In recent years, use of nerve stimulators has increased from occasional use to common use and often critical importance. The growing emphasis on techniques that use either multiple injections near individual nerves or placement of stimulating catheters has provided impetus for this change. The primary impediment to successful use of a nerve stimulator in a clinical practice is that it is at least a three-handed or two-individual technique (Fig. 1-9), although there are devices allowing control of the stimulator current using a foot control, eliminating the need for a third hand or a second individual. In those situations requiring a second set of hands, correct operation of contemporary peripheral nerve stimulators is straightforward and easily taught during the course of the block. There are a variety of circumstances in which a nerve stimulator is helpful, such as in children and adults who are already anesthetized when a decision is made that regional block is an appropriate technique; in individuals who are unable to report paresthesias accurately; in performing local anesthetic administration on specific nerves; and in placement of stimulating catheters for anesthesia or postoperative analgesia. Another group that may benefit from the use of a nerve stimulator is patients with chronic pain, in whom accurate needle placement and reproduction of pain with electrical stimulation or elimination of pain with accurate administration of small volumes of local anesthetic may improve diagnosis and treatment.

Figure 1-9. Nerve stimulator technique.

When nerve stimulation is used during regional block, insulated needles are most appropriate because the current from such needles results in a current sphere around the needle tip, whereas uninsulated needles emit current at the tip as well as along the shaft, potentially resulting in less precise needle location. A peripheral nerve stimulator should allow between 0.1 and 10 milliamperes (mA) of current in pulses lasting approximately 200 msec at a frequency of 1 or 2 pulses per second. The peripheral nerve stimulator should have a readily apparent readout of when a complete circuit is present, a consistent and accurate current output over its entire range, and a digital display of the current delivered with each pulse. This facilitates generalized location of the nerve while stimulating at 2 mA and allows refinement of needle positioning as the current pulse is reduced to 0.5 to 0.1 mA. The nerve stimulator should have the polarity of the terminals clearly identified because peripheral nerves are most effectively stimulated by using the needle as the cathode (negative terminal). Alternatively, if the circuit is established with the needle as anode (positive terminal), approximately four times as much current is necessary to produce equivalent stimulation. The positive lead of the stimulator should be placed in a site remote from the site of stimulation by connecting the lead to a common electrocardiographic electrode (see Fig. 1-9).

Figure 1-10. Ultrasound wave basics.

The use of a nerve stimulator is not a substitute for a complete knowledge of anatomy and careful site selection for needle insertion; in fact, as much attention should be paid to the anatomy and technique when using a nerve stimulator as when not using it. Large myelinated motor fibers are stimulated by less current than are smaller unmyelinated fibers, and muscle contraction is most often produced before patient discomfort. The needle should be carefully positioned to a point where muscle contraction can be elicited with 0.5 to 0.1 mA. If a pure sensory nerve is to be blocked, a similar procedure is followed; however, correct needle localization will require the patient to report a sense of pulsed “tingling or burning” over the cutaneous distribution of the sensory nerve. Once the needle is in the final position and stimulation is achieved with 0.5 to 0.1 mA, 1 mL of local anesthetic should be injected through the needle. If the needle is accurately positioned, this amount of solution should rapidly abolish the muscle contraction or the sensation with pulsed current.

Ultrasonography (see Video 1: Introduction to Ultrasound on the Expert Consult Website)

In the last decade, image-guided peripheral nerve blocks have become the norm for anesthesiologists at the forefront of regional anesthesia innovation. The dominant method of imaging is ultrasonography. Ultrasonographic imaging devices are noninvasive, portable, and moderately priced. Most work has been done using scanning probes with frequencies in the range of 5 to 10 megahertz (MHz). These devices are capable of identifying vascular and bony structures but not nerves. Contemporary devices using high-resolution probes (12 to 15 MHz) and compound imaging allow clear visualization of nerves, vessels, catheters, and local anesthetic injection and can potentially improve the techniques of ultrasonography-assisted peripheral nerve block. Use of these devices is limited by their cost, the need for training in their use and familiarity with ultrasonographic image anatomy, and the extra set of hands required. They work best with superficial nerve plexuses and can be limited by excessive obesity or anatomically distant structures. One of the keys to using this technology effectively is a sound understanding of the physics behind ultrasonography. A corollary to understanding the physics is the need for study and appreciation of the relevant human anatomy.

Ultrasound Generation

Ultrasound is generated when multiple piezoelectric crystals inside a transducer rapidly vibrate in response to an alternating electric current. Ultrasound then travels into the body where, on contact with various tissues, it can be reflected, refracted, and scattered (Fig. 1-11).

Figure 1-11. Production of an ultrasonographic image. This figure demonstrates the many responses that an ultrasound wave produces when traveling through tissue. A, Scatter reflection: the ultrasound wave is deflected in several random directions both toward and away from the probe. Scattering occurs with small or irregular objects. B, Transmission: the ultrasound wave continues through the tissue away from the probe. C, Refraction: when an ultrasound wave contacts the interface between two media with different propagation velocities, the wave is refracted (bent) to an extent depending on the difference in velocities. D, Specular reflection: a large, smooth object (e.g., the needle) returns (reflects) the ultrasound wave toward the probe when it is perpendicular to the ultrasound beam.

To generate a clinically useful image, ultrasound waves must reflect off tissues and return to the transducer. The transducer, after emitting the wave, switches to a receive mode. When ultrasound waves return to the transducer, the piezoelectric crystals will vibrate once again, this time transforming the sound energy back into electrical energy. This process of transmission and reception can be repeated over 7000 times per second and, when coupled with computer processing, results in the generation of a real-time two-dimensional image that appears seamless. By convention, whiter (hyperechoic) objects represent a larger degree of reflection and higher signal intensities, whereas darker (hypoechoic) images represent less reflection and weaker signal intensities.

Clinical Issues Related to Physics

Resolution

Resolution refers to the ability to clearly distinguish two structures lying beside one another. Although there are several different types of resolution, anesthesiologists are mostly concerned with lateral resolution (left–right distinction) and axial resolution (front–back distinction). Ultrasonography systems with higher frequencies have better resolution and can effectively discriminate closely spaced peripheral neural structures. However, because of a process known as attenuation, high-frequency ultrasound cannot penetrate into deep tissue (Fig. 1-12). Attenuation is the loss of ultrasound energy into the surrounding tissue, primarily as heat. For superficial blocks between 1 and 4 cm in depth, frequencies greater than 10 MHz are preferred. For blocks at depths greater than 4 cm, frequencies less than 8 MHz should result in adequate tissue penetration, with a predictable degradation in resolution.

Figure 1-12. Probe frequency and depth of tissue penetration. Higher-frequency ultrasound attenuates to a larger degree at more superficial depths, although it provides more image detail.

Focus

Although axial resolution is related simply to the frequency of ultrasound, lateral resolution also depends on beam thickness. Any maneuver that generates a narrow beam will increase the lateral resolution. Most ultrasonography machines have an electronic focus that generates a focal point (narrowest part of the beam) that can be placed directly over the target of interest. However, this increases the divergence of the beam beyond the region of the focus point (far field), resulting in image degradation of structures beyond this focal point. Thus, the beam focus should be placed at the level of the object that is being assessed to provide the clearest possible picture of the object (Fig. 1-13).

Figure 1-13. Basics of ultrasonographic probe focusing.

Gain

The overall gain and time gain compensation (TGC) controls allow the operator to increase or decrease the signal intensity. In clinical terms, the gain controls the “brightness” of the ultrasonographic image. The TGC control allows the operator to adjust gain at specific depths of the image. By increasing the overall gain or the TGC, one can compensate for the darker aspects of the ultrasonographic image, which are simply the result of ultrasound attenuation. Inappropriately low gain settings may result in the apparent absence of an existing structure (i.e., “missing structure” artifact), whereas inappropriately high gain settings can easily obscure existing structures.

General Principles of an Ultrasonography-Guided Nerve Block

During ultrasonographic needle guidance, most nerves are imaged in cross-section (short axis). Alternatively, if the transducer is moved 90 degrees from the short-axis view, the long-axis view is generated. The short-axis view is generally preferred because it allows the operator to assess the lateromedial perspective of the target nerve, which is lost in the long-axis view (Fig. 1-14).

Figure 1-14. Short-axis (top) and long-axis (bottom) imaging of the median nerve.

Two techniques have emerged regarding the orientation of the needle with respect to the ultrasound beam (Fig. 1-15). The in-plane approach generates a long-axis view of the needle, allowing full visualization of the shaft and tip of the needle. The out-of-plane view generates a short-axis view of the needle. One disadvantage of the in-plane approach is the challenge of maintaining needle imaging with a very thin ultrasound beam. A limitation of the out-of-plane view is that it generates a short-axis view of the block needle, which may be very hard to visualize. With the out-of-plane view, the operator cannot confirm that the needle tip (rather than part of the shaft) is being imaged, and therefore the needle location is often inferred from tissue movement or small injections of solution.

Figure 1-15. The in-plane (right) and out-of-plane (left) needle approaches for needle insertion and ultrasonographic visualization.

In the pertinent images in this text, we provide a key for the recommended starting setup for each block used with ultrasonographic guidance in a corner of the image (Fig. 1-16). (Remember that because of anatomic variability among patients, these base settings may have to be adjusted based on clinical and patient variables.)

Figure 1-16. Our system for ultrasonographic needle guidance recommendations. For a block for which we would recommend a high-frequency setting with the in-plane (IP) technique of needle visualization, a red scan plane with an “IP” inside the plane is shown. For a low-frequency setting with the out-of-plane (OP) technique for needle visualization, we show a green scan plane with an “OP” in the plane. The mid-frequency setting is indicated by a blue scan plane. An example is shown in the upper right of the figure. In this case, we recommend starting with a high-frequency probe setting and an in-plane technique for needle visualization.

Regardless of the machine or transducer selected, there are four basic transducer manipulation techniques, which can be described as the “PART” of scanning:

Pressure (P): Various degrees of pressure are applied to the transducer that are translated onto the skin.

Alignment (A): Sliding the transducer defines the lengthwise course of the nerve and reference structures.

Rotation (R): The transducer is turned in either a clockwise or counterclockwise direction to optimize the image (either long- or short-axis) of the nerve and needle.

Tilting (T): The transducer is tilted in both directions to maximize the angle of incidence of the ultrasound beam to the target nerve, thereby maximizing reflection and optimizing image quality.

The primary objective of PART maneuvers is to optimize the amount of ultrasound that reflects off an object and returns to the transducer (Fig. 1-17).

Figure 1-17. PART maneuvers: pressure, alignment, rotation, and tilting.