Pain-free Breast Biopsy: Myth or Reality?

Judy Wagner, RN

More than 150 years have passed since anesthesia was first used to alleviate the unbearable pain associated with essential surgical procedures. Patients no longer have to “bite the bullet” or faint due to excruciating pain for everything from tooth extraction to childbirth. Yet even with modern sophisticated analgesic agents, some women are still experiencing pain with image-guided needle breast biopsies. These diagnostic biopsies are state-of-the art procedures that could be undermined by women telling other women about the pain they may experience associated with the biopsy, if local anesthesia is not adequately administered for pain control.

The impetus to develop a local anesthesia involved a cultural change. The ability to withstand pain, especially the pain of childbirth, was considered a sign of strength and character. General anesthesia led the way in when dentists Horace Wells introduced nitrous oxide in 1844 and William Thomas Green Morton introduced ether in 1846. Dentists made the significant advances in anesthesia due to their need to alleviate pain, a significant problem in their daily practices. ¹

Local anesthesia became a reality due to the evolution of adequate compounds, and the capability to deliver these agents to a precise area of nerves via a vehicle—the syringe. The first syringes were too large to deliver miniscule volumes of anesthetic agents, but in 1852, Charles Gabriel Pravaz invented a silver hollow needle and a glass syringe, which held a volume of only 1.5mL, making delivery more exacting. ²

After experimenting with his friend Sigmund Freud, Karl Kohler performed the first operation using cocaine as a local anesthesia on a patient with glaucoma. However, as both physicians discovered, the substance had many disconcerting side effects as well as addictive properties.

New Generation Anesthetics

Pain control was now a reality, but researchers turned their attention to discovering a safer, nonaddictive, nontoxic agent. Although local anesthesia was desirable, concerns arose due to the complications that continually presented themselves. A synthetic alternative to cocaine did not become a reality until 1904 when Alfred Einhorn synthesized the first ester local anesthetic, procaine, or novocaine. However, ester anesthetics had the potential for more adverse allergic reactions, because when metabolized they release para-aminobenzoic acid (PABA), a known allergen. ³

The impetus for the development of local anesthetics with less allergic potential led Nils Lofgren to synthesize lidocaine, the first amide anesthetic in 1943. ³ Amide anesthetics had the following benefits over their predecessors, ester anesthetics: potential for fewer allergic reactions; longer duration of effect; greater potency; and more expansive choices for various procedures. ³

Both ester or amide local anesthetics have their own chemical structure, metabolic response, and allergic potential. New and improved local anesthetics continue to evolve, as does the extension of the capabilities for use in pain control during an expanded array of medical procedures. ³ If a patient has allergic responses to a particular agent, another type may be substituted from another anesthesia class.

To distinguish between ester and amide anesthetics, look at the spelling given to the generic name. Any “-caine” anesthetic containing the letter “i” (as in amide) in the prefix is an amide agent (eg, prilocaine). The ester agents do not contain an “i” in the prefix. ⁴

The development of surgical procedures requiring long-acting local anesthetics, with the desire for pain relief for a period of time after the procedure was completed, led to the development of another tier of local anesthetics. In 1957, after some initial disappointments with the long-acting agents, bupivacaine was synthesized by Ekenstam. ¹ This long-acting local anesthetic is approximately four times more potent than lidocaine and two to four times more longer acting. ⁴

It is important to note that pharmaceutical manufacturers add preservatives to ensure local anesthetics are safe for injection and to prolong shelf life. They use antioxidants, pH-adjusting agents, and sulfites. Preservatives are used to prevent contamination. Despite being labeled as “inactive” ingredients, these additives can have potential toxicities. Hypersensitivities have been reported from some of the additives such as bisulfites, which are antioxidants, and methylparaben, the most commonly used preservative found in cosmetics as well as in multi-dose amide local anesthetic vials. ⁵ The true number of immune-mediated adverse reactions to local anesthetic solutions is < 1%.⁵

Limiting Systemic Absorption

Limiting systemic absorption of local anesthetics is a strategy used to maximize the effectiveness of the anesthetic and is dependent on the type of anesthetic, site of injection, volume and concentration, and vasoconstrictive additives.

Epinephrine is most commonly used for its vasoconstrictive quality and was first utilized by Heinrich Braun in 1903 to increase the duration of cocaine’s action. Local anesthetics with premixed epinephrine have a pH of 3.5 to 5.5. Alkalization can decrease burning upon injection. Storing these premixed solutions, once they are opened, reduces the effect of the epinephrine. If premixed single dose vials are not available, epinephrine can be mixed just prior to injection. ⁶

Infiltration of local anesthetic has an intrinsic dilating effect on blood vessels, increasing blood flow to the site and resulting in greater absorption of the anesthetic into the circulatory system; an increase in plasma levels of the anesthetic with risk for toxicity; and a decrease in the duration of the local effect of the anesthetic at the site of injection.

Adding epinephrine to local anesthetics restricts their absorption into the bloodstream by as much as 30%, thus almost doubling the length of duration of the local anesthetic. The onset of optimal vasoconstriction is 5 minutes. ⁷ The duration time is dependent upon the local anesthetic used. In the case of lidocaine, which has a short duration of effect, there is a much greater prolongation of effect if epinephrine is added. Concentrations as low as 1:400,000 can reduce absorption and minimize surgical bleeding. ⁶ The amount of anesthetic that can be safely used is also increased. Maximum dosage of lidocaine is 4.5 mg/kg without epinephrine and 7 mg/kg with epinephrine. Complications of local anesthetics are rare, but include central nervous system and cardiovascular toxicity. Patients with diabetes, heart disease, heart block, and cerebrovascular disease may be more sensitive to epinephrine. ^6,7

Prior to the mid 90s, the majority of breast biopsies were open surgical incisions performed in the operating room under general anesthetic, with potential for complications. In the late 90s, image-guided needle breast biopsies became more commonplace as a method to obtain tissue for diagnosis of suspicious lesions on mammograms or palpable breast masses. These minimally invasive biopsies performed under local anesthesia had fewer complications, a less painful biopsy site, shorter healing times, and less expense, and resulted in an equal rate of diagnosis. If performed using proper protocol for administration of local anesthetics, this biopsy procedure, utilizing stereotactic or ultrasound equipment, should not include pain as a component of the biopsy. In most cases, women should not go away from this procedure with any recollection of pain, but have the experience of a biopsy procedure that results in a pain-free conclusive diagnosis. ⁸

The Next Perplexing Question

Just how does the physician control pain with needle-guided breast biopsies? To answer this question, one needs to understand the action of one of the most widely used amide local anesthetics: lidocaine; 1% lidocaine is marketed with a pH of 6.2, which increases shelf life to 3 to 4 years, but this pH causes burning discomfort with intradermal injection. Clinical trials have established that changing the pH to 7 (adding 8.4% sodium bicarbonate to the 1% lidocaine) significantly decreases the discomfort caused by burning. This can easily be accomplished by adding 1 mL of 8.4% NaHCO ₃ to a syringe of 10 mL of 1% lidocaine; the resulting 11 mL solution will have a pH of 7.2. ⁹

Altering the pH of 1% lidocaine does not alter the quality or duration of action, but may actually improve the onset and duration of action, since only the uncharged or nonionized form of local anesthetics diffuses through tissues and nerve membranes. ⁵ The degree of ionization is related to the local anesthetic’s pKa, which is the pH at which the amounts of charged and uncharged molecules are equal. It is the uncharged molecules that cross the cell membranes. When the pH of the local anesthetic is increased closer to its original pKa, it increases the number of uncharged molecules, facilitating the movement of the local anesthetic across the nerve sheath and membrane and thus resulting in a more rapid onset of action. ¹⁰ By increasing the pH to 7, a greater percentage of anesthetic will be uncharged or nonionized. If unbuffered, only 1% of the lidocaine is uncharged or nonionized, but if buffered, the uncharged or nonionized form increases to 11%. The only drawback is decreased shelf life. ⁹

Biopsy anesthetic Protocol

Whether a physician is performing a core needle biopsy, en-bloc® biopsy, or simple needle biopsy, it is critical to keep in mind that proper spatial arrangement of the anesthetic is of utmost importance. If the anesthetic agent is not adequately and properly placed, it can mean pain lasting from a few seconds to minutes and is often a lasting memory, relived every time a women tells the story of her needle-guided breast biopsy. Patience is the key factor in realizing the ultimate outcome for administration of local anesthesia, as well as reassurance of the patient. ¹¹

The following steps will ensure adequate local anesthesia for image-guided breast biopsy:

• Use buffered 1% lidocaine, without epinephrine, to form a wheal at the level of the skin. Buffered lidocaine decreases burning. ¹¹
• Anesthetizing the skin is followed by the anesthetic envelopment of the entire lesion. To prevent movement of the lesion, the anesthetic is distributed around the lesion, using equal amounts in all four quadrants, 3 o’clock, then 9 o’clock, 6 o’clock, then 12 o’clock. Using 3 to 5 mL of lidocaine with or without epinephrine in each quadrant, inject the lidocaine continuously while pulling back on the needle in order to place the lidocaine deep and proximal along each quadrant. ¹¹
• It is also important to place an additional bolus of anesthesia in the area behind the lesion. This then forms a sleeve around the lesion and improves pain control as the core samples are being taken. This is accomplished by inserting the needle (use a spinal needle if the lesion is deep and difficult to reach) through the lesion and injecting 2 to 4 mL into that area. ¹¹
• It is important to anesthetize the probe track by injecting anesthetic as the needle is removed. This prevents discomfort as the probe is inserted for the biopsy. ¹¹
• Local anesthetics work rapidly in the area of direct contact, but waiting for 5 minutes enables the anesthetic to diffuse outside of the injection area and helps improve patient comfort. The “5 minute rule” allows for an adequate time frame for the physician to chat with the patient and gain her confidence, then perform a postlidocaine stereotactic pair to confirm the target point and assure that the lesion has not been displaced by the anesthesia. ¹¹
• Once the effects of local anesthesia are assured, the breast biopsy can be accomplished without pain as a component of the procedure.

There has been some concern among physicians that the injection of large volumes of lidocaine at the site of the incision will obscure the faint calcifications or lesions, but this rarely is an issue for concern. If the lesion is obscured, waiting for several minutes allows the anesthetic to be absorbed. This is yet another reason to take a little extra time in any biopsy procedure. Also, minimizing micro air bubbles when injecting anesthetics improves image quality. ¹¹

Patient as Recipient

Each physician will establish their preferred technique for administration and types of local anesthetic agents through their experience. Basic premises need to be kept in mind no matter which “formula” of agents works best for you. The primary concern is patient comfort, which is achieved when the physician takes the time to reassure the patient, remembers the “5 minute rule,” and uses proper technique for administration. The patient should be your messenger to tell other women the benefits of relatively painless needle-guided breast biopsies. Pain control has evolved in the last 150 years, and patients deserve to be recipients of this evolution.

Judy Wagner, RN, is a nurse who has worked for 20 years in intensive care and 10 years in home intravenous therapy. She is a member of the National Consortium of Breast Centers and is married to a radiologist who practices in the Milwaukee Metropolitan Area.

References:

1. Calatayud J, Gonzalez A. History of the development and evolution of local anesthesia since the coca leaf. Anesthesiology. 2003;98:1503–8.
2. Ruetsch YA, Boni T, Borgeat A. From cocaine to ropivacaine: the history of local anesthetic drugs. Current Topics in Medicinal Chemistry. 2001;3:175-182.
3. Gymrek R, Dahdah M. Local anesthesia and regional nerve block anesthesia. emedicine. Available at: www.emedicine.com/derm/SURGICAL.htm. Accessed on April 18, 2006.
4. Smith DW, Peterson MR, DeBerard SC. Local anesthesia: topical application, local infiltration, and field block. Post Graduate Medicine online—Procedures in Primary Care. 1999;102(2). Available at: www.postgradmed.com/issues/1999/08_99/aug99.htm. Accessed on April 12, 2006.
5. Rosenberg PH. Local anesthetic additives to increase stability and prevent organism growth. Techniques in Regional Anesthesia and Pain Management. 2004;3:114-118.
6. Haider N. Additives used to limit systemic absorption. Techniques in Regional Anesthesia and Pain Management. 2004;3:119-122.
7. Kundu S, Achar S. Principles of office anesthesia: part II. Topical anesthesia. Am Fam Physician. 2002;66(1):99-102.
8. Finch E. The breast biopsy puzzle. Decisions in Axis Imaging News. 2001; 14(6):20-23,40.
9. Matsumoto AH, Reifsnyder AC, Hartwell GD, Angle JF, Selby JB Jr, Tegtmeyer CJ. Reducing the discomfort of lidocaine administration through pH buffering. J Vasc Interv Radiol. 1994;1:171-175.
10. Joseph RS, McDonald SB. Facilitating the onset of regional anesthetic blocks. Techniques in Regional Anesthesia and Pain Management. 2004;3:110-113.
11. Anesthetic protocol for Intact™ Breast Lesion Excision System. Available at: www.intactmedical.com/med-fortechs.php. Accessed on April 18, 2006.