RESEARCH shows that many procedures are painful and distressing to patients, and that greater attention to relieving procedural pain is needed. Clinicians are encouraged to form task forces to establish policies and procedures that address the provision of adequate analgesia and anesthesia prior to painful procedures, including minor procedures, such as venipuncture. Local anesthetics are first-line analgesics and anesthetics for procedural pain. They are versatile and well-tolerated by most patients. The local anesthetics discussed in this chapter include lidocaine infiltration, topical formulations of lidocaine alone or in combination with other local anesthetics, and other less used local anesthetics. All of the topical local anesthetics vary in the length of application time and duration of local anesthetic action, making these characteristics important considerations when determining the best formulation for the specific procedure. The mechanisms of action underlying local anesthetics have been discussed in Chapter 23.
Lidocaine 1% to 2% is the local anesthetic of choice when administered by infiltration at the site prior to painful procedures, ranging from IV starts to skin suturing, because it has a fast onset and can be administered in a wide range of doses with minimal risk of toxicity (Pasero, Wong, 1997). The onset of analgesia is rapid (i.e., within 2 minutes), and anesthesia lasts 1.5 to 2 hours (Achar, Kundu, 2002; Strichartz, Berde, 2005). The maximum recommended adult dose is 4 mg/kg, not to exceed 280 mg (Achar, Kundu, 2002).
Research shows that many patients fear dermal procedures, particularly venipuncture and IV catheter placement (Windle, Kwan, Warwick, et al., 2006). Lidocaine 1% given intradermally to anesthetize the site prior to venous or arterial puncture is an inexpensive, easy, and effective way of addressing this fear by minimizing the associated pain (see Figure 24-1 on p. 685 for intradermal site of action). All state boards of nursing in the United States approve this nursing function, and the Infusion Nurses Society Standards of Practice call for the nurse to consider providing local anesthesia prior to venipuncture (Infusion Nurses Society, 2006). Despite this, nurses, who perform a large number of venipunctures, rarely use local anesthetic even though they would prefer a local anesthetic if they were to undergo this type of procedure (Valero Marco, Martinez Castillo, Macia Solera, 2008). A lack of knowledge is the most common reason for failure to provide dermal local anesthetic, which underscores the need for nurse managers and educators to develop policies and procedures that support the nurse’s use of local anesthetics and to teach nurses who perform painful dermal procedures how to competently use them (Brown, 2002).
To administer intradermal local anesthesia, a wheal of approximately 1-cm diameter (approximately 0.05 to 0.1 mL) of lidocaine 1% is injected intradermally with a 29- or 30-gauge needle over or just distal to the vein or artery (Pasero, McCaffery, 1999). Patients often report burning and stinging with intradermal injection of lidocaine. This is caused by the acidic nature of the lidocaine solution and can be reduced by adding sodium bicarbonate to normalize the pH (buffering) (Strichartz, Berde, 2005; Wong, Pasero, 1997) (Box 28-1). Administration of buffered lidocaine 1% is recommended 2 minutes prior to venipuncture and has been shown to produce superior anesthesia compared with unbuffered lidocaine 1%, diphenhydramine 1%, and 0.9% saline placebo (Xia, Chen, Tibbits, et al., 2002). Warming the lidocaine by rolling the syringe between the hands several times and slowing the speed of injection can also reduce the pain associated with intradermal lidocaine. Lidocaine has been warmed to 40° to 42° C in a controlled warm-water bath but should never be warmed in a microwave (Achar, Kundu, 2002; Pasero, McCaffery, 1999).
Intradermal lidocaine was shown to produce superior anesthesia compared with another antihistamine (chlorpheniramine) and midazolam in healthy volunteers (Orhan, Yuksel, Bilgin, et al., 2007). However, bacteriostatic saline may be an even better choice than lidocaine to anesthetize the site prior to a venous or arterial puncture. A randomized controlled trial administered lidocaine 1%, bacteriostatic normal saline, or no intradermal anesthesia to 221 adults prior to outpatient or same-day surgery (Windle, Kwan, Warwick, et al., 2006). Venipuncture was significantly less painful with both lidocaine and bacteriostatic saline compared with placebo, and bacteriostatic saline produced better anesthesia than lidocaine. It is important to note that the saline must be bacteriostatic, because it is the 0.9% benzyl alcohol preservative that produces the local anesthetic effect (Pasero, McCaffery, 1999).
Infiltrated lidocaine, particularly when buffered, provides an excellent option for controlling pain during more extensive procedures as well. A randomized controlled trial administered buffered lidocaine or unbuffered lidocaine to patients prior to posterior iliac crest bone marrow biopsy (Ruegg, Curran, Lamb, 2009). Those who received buffered lidocaine reported significantly lower pain scores leading the researchers to conclude that the use of unbuffered lidocaine for such a procedure should be questioned. Others have found similar results with buffered lidocaine (Vossinakis, Stavroulaki, Paleochorlidis, et al., 2004; Younis, Bhutiani, 2004) and warmed lidocaine (Yiannakopoulos, 2004) for other procedures.
Femoral artery sheath removal is a painful procedure, but there is no consensus on how best to manage the pain. Infiltrated lidocaine may not be the best choice for this particular procedure. Patients in one study were randomized to receive IV fentanyl and midazolam, or lidocaine 1% infiltrated around the femoral sheath, or both treatments, or neither treatment (Kiat Ang, Leung, Lo, et al., 2006). The highest pain scores and the highest incidence of vasovagal reactions were in the group who received local anesthesia only. These findings led the researchers to caution against the use of lidocaine infiltration prior to femoral sheath removal and suggest IV fentanyl and midazolam instead.
Adverse effects are rare with infiltrated local anesthetics such as lidocaine because there is minimal systemic absorption when they are given in small amounts for minor procedures. However, at low doses, local anesthetics have been known to produce vasoconstriction and hypertension in some patients (Achar, Kundu, 2002). The addition of epinephrine can slow absorption but can also further increase vasoconstriction and should not be used on tissues with end arteriole blood supply, such as fingers, toes, the penis, nose, or ears (Pasero, McCaffery, 1999). Signs of systemic toxicity include metallic taste, tinnitus, perioral numbness, lightheadedness, and confusion. If not detected, this can proceed to tremors, shivering, and ultimately seizures and respiratory and cardiovascular collapse (Achar, Kundu, 2002). Allergy to amide local anesthetics is rare but is a contraindication to use.
Eutectic mixture of local anesthetics (EMLA), available only by prescription in the United States (nonprescription in some other countries, e.g., Canada), combines lidocaine 2.5% and prilocaine 2.5% in a cream for topical application. Most anesthetic agents exist as solids preventing efficient skin penetration (Kundu, Achar, 2002). However, a eutectic mixture, which has a melting point lower than that of the two anesthetics alone, permits the drug to penetrate the skin (see Figure 24-1 on p. 685 for action site).
To create an area of dense sensory loss using EMLA, a relatively thick application must remain in contact with the skin for at least 1 hour (2.5 g [½ of a 5 g tube] per 20 to 25 cm2 [2 inch by 2 inch] area to a maximum of 10 g). This is usually covered with an occlusive dressing, but occlusion is optional and intended to help keep the drug in place. The application site can be expanded as needed for major dermal procedures. Clinical experience suggests that a 90- to 120-minute application time produces the best results. This time should be reduced significantly and the drug removed promptly when EMLA is applied to male genital skin and female genital mucous membranes (see EMLA drug package insert). The depth of anesthesia is approximately 3 mm after a 60-minute application and 5 mm after 120 minutes (Kundu, Achar, 2002). The 60- to 120-minute application time is a noted drawback of the drug because it requires preplanning (Eidelman, Weiss, Lau, et al., 2005); however, most procedures are not emergencies and allow for this. A benefit of EMLA is a comparatively long duration of anesthesia, reaching maximal anesthesia at 2 to 3 hours and lasting up to 2 hours after the cream is removed (Wong, 2003). This is an advantage for longer procedures or when pain is expected after the procedure is completed. Another commonly used topical local anesthetic, L.M.X.4, has a shorter duration of up to 60 minutes (see later in the chapter).
The manufacturer (AstraZeneca) recommends that EMLA be applied to intact skin and genital mucous membranes only; however, it has also been applied to or around extremity lacerations and other types of open wounds (Briggs, Nelson, 2003; Kundu, Achar, 2002). Variable penetration is reported when EMLA is applied to hands and soles of the feet (Kundu, Achar, 2002), and it should not be applied to eyes as this can result in severe irritation and corneal abrasion.
An extensive systematic review of research on local anesthetics for painful dermal procedures reported inconsistent findings with regard to comparisons between EMLA and infiltrated local anesthetic; half of the research favored EMLA, and half favored infiltrated local anesthetic (Eidelman, Weiss, Lau, et al., 2005). EMLA and L.M.X.4 were equally efficacious in this review, but the latter was described as preferable because it is commercially available, has a more rapid onset of action (L.M.X.4 = 30-minute application time), and is less expensive (Eidelman, Weiss, Lau, et al., 2005).
EMLA has been shown to reduce pain of needle puncture when applied prior to local anesthetic blockade (Raber, Scattoni, Roscigno, et al., 2008; Samson, Minville, Chassery, et al., 2007), IV catheter placement, and lab blood tests (Eidelman, Weiss, Lau, et al., 2005). A Cochrane Collaboration Review concluded that EMLA produced effective pain relief for venous leg ulcer debridement, but suggested further research to determine its impact on ulcer healing (Briggs, Nelson, 2003). A case report described the development of hemorrhagic margins around leg ulcers that led to ischemia and necrosis following application of EMLA for debridement (Stahl, Meyer, Haas, et al., 2008). EMLA was ineffective for treatment of pain during vasectomy (Thomas, Nguyen, Dhar, et al., 2008) and amniocentesis (Pongrojpaw, Somprasit, Chanthasenanont, 2008).
The use of topical analgesics is strongly encouraged in pediatric patients undergoing painful procedures. As a result, the vast majority of research showing EMLA to be safe and effective for painful procedures has been conducted in that population and findings extrapolated to adults. The reader is referred to the pediatric literature for more research. Some of the studies showing efficacy in adults are listed as follows.
• Fine-needle aspiration biopsy (Gursoy, Ertugrul, Sahin, et al., 2007)
• Transrectal prostate biopsy (Giannarini, Autorino, Valent, et al., 2009; Tiong, Liew, Samuel, et al., 2007)
• Hysterosalpingography (Liberty, Gal, Halevy-Shalem, et al., 2007)
• Shockwave lithotripsy (Kumar, Gupta, Hemal, et al., 2007)
• Perineal repair (Franchi, Cromi, Scarperi, et al., 2009)
• Hemorrhoidectomy (Shiau, Hung, Chen, et al., 2007; Shiau, Su, Chen, et al., 2008)
• Chest tube removal (Valenzuela, Rosen, 1999)
• Fiberoptic endotracheal intubation (Larijani, Cypel, Gratz, et al., 2000)
• Variety of cosmetic dermatologic procedures (Kaweski, 2008; Railan, Alster, 2007).
The most common adverse effects associated with EMLA are mild, transient local skin reactions, including erythema, blanching, edema, and rare blistering. Several studies have shown that when EMLA is applied as recommended, serum lidocaine and prilocaine concentrations are approximately 0.12 mcg/mL and 0.07 mcg/mL, respectively, which are well below toxicity levels. (The signs of local anesthetic toxicity are described in Chapter 23.) Caution is recommended when EMLA is used concomitantly with other local anesthetics or antiarrhythmics, such as mexiletine and tocainide, which can result in an additive effect. Methemoglobinemia, which impairs the ability of hemoglobin to transport oxygen, has been linked to the use of EMLA, caused by systemic absorption of prilocaine. Some patients, such as premature infants, are predisposed to methemoglobinemia, and co-administration of certain medications, such as phenytoin and nitroglycerin, can increase the incidence of this condition. The incidence is minimized when precautions are taken such as not exceeding the maximum recommended dose and removing EMLA promptly after use (Shachor-Meyouhas, Galbraith, Shavit, 2008). A rare adverse effect is petechial and purpuric eruption following EMLA application (Roldan-Marin, de-la Barreda Becerril, 2009). Allergy to amide local anesthetics is a contraindication to the use of EMLA.
L.M.X.4 (lidocaine cream 4%, formerly ELAMax) is another commonly used topical local anesthetic for procedural pain management. Advantages of this drug over EMLA are that it is commercially available in the United States and has a shorter 30-minute application time. This shorter application time is a major benefit given the current focus on reduced length of stay in all health care settings.
L.M.X.4 is applied by rubbing a small amount into the site for about 30 seconds followed by application of a 2-cm-thick coating. Although optional, this is usually covered with an occlusive dressing to keep the drug in place for the 30-minute application time. As with EMLA, depth of anesthesia increases as application time increases, and the drug should be removed promptly after use. A drawback of L.M.X.4 is a relatively short duration of anesthesia of 30 to 60 minutes after removal (Wong, 2003). Maximum serum concentration following recommended topical application is low at 0.3 mcg/mL. Adverse effects and signs of local anesthetic toxicity associated with L.M.X.4 are similar to other topical local anesthetics except that it does not contain prilocaine so is not associated with methemoglobinemia (see discussion of EMLA regarding this condition).
L.M.X.4 is an appropriate alternative to EMLA. A review of research conducted primarily in children comparing L.M.X.4 and EMLA showed similar efficacy (Wong, 2003). A more recent systematic review of topical anesthetics for dermal pain concluded that although the two are essentially equally efficacious, L.M.X.4 has the previously mentioned advantages of being commercially available, faster acting, and less expensive (Eidelman, Weiss, Lau, et al., 2005).
EMLA’s 60- to 120-minute application time has long been cited as a reason for not using it in the emergency department (ED) setting where time is often of the essence. A prospective, double-blind study randomized patients admitted to the ED to receive L.M.X.4 or placebo 30 minutes prior to IV catheter placement (Valdovinos, Reddin, Bernard, et al., 2009). Those who received L.M.X.4 reported significantly lower pain scores even after adjustments were made for difficulty of cannulation.
Synera (also called S-Caine in some studies) is a 6.25 cm by 7.5 cm (approximately 2.5 inch by 3 inch) oval patch containing lidocaine 70 mg and tetracaine 70 mg that is approved for dermal procedural pain. The patch is unique in that it has an integrated oxygen-activated heating component that enhances the absorption of the local anesthetics. As soon as the patch is removed from its pouch, the component is exposed to air and begins to warm the drug. The backing is peeled off, and the patch is simply placed on the target site (similar to placing an adhesive bandage) and left in place for 20 to 30 minutes. This short application time and the ease of application compared with local anesthetic cream formulations are major advantages of this drug. Similar to other topical local anesthetics, serum local anesthetic levels are low when the drug is used as directed (Sethna, Verghese, Hannallah, et al., 2005). Adverse effects and signs of local anesthetic toxicity are similar to other topical local anesthetics (see previous discussion).
Research is lacking on the use of Synera because it is a relatively new topical local anesthetic formulation. A randomized, double-blind, paired study compared Synera with a placebo patch in 40 adult volunteers (Curry, Finkel, 2007). Subjects received simultaneous Synera and placebo patch applications for 20 minutes followed by a vascular access procedure. All subjects favored Synera over placebo; 49% had lower pain scores with Synera compared with 17% with placebo; 63% reported having no pain with Synera compared with 33% with placebo. Adverse effects were mild dermal reactions in 2 patients, which resolved within 3 hours of patch removal. A randomized, double-blind trial applied Synera or a placebo patch 20 minutes prior to venipuncture in children at two different medical centers (Sethna, Verghese, Hannallah, et al., 2005). More than half (59%) of the children who received Synera reported no pain during the procedure compared with 20% of those who received a placebo patch. The most common adverse effects were mild, transient erythema and edema at the application site, which occurred with similar frequency in both groups.
In a double-blind, paired study, 82 volunteers were randomized to receive Synera or EMLA cream prior to vascular access (Sawyer, Febbraro, Masud, et al., 2009). Application time was shorter (as short as 10 minutes in some patients), and analgesia was best with Synera. EMLA was associated with more blanching, and Synera was associated with more erythema.
Synera has major advantages over other topical anesthetic products for superficial procedures such as vascular access in that the product is easy to use (peel and stick), nonmessy, allows uniform distribution of the drug, and has a short application time. Research comparing it with other topical local anesthetics for penetration, duration of anesthesia, patient satisfaction, and cost is needed.
Jet injection (J-Tip) is a needless device that delivers 0.25 to 0.5 mL lidocaine under pressure into the subcutaneous tissue. It provides rapid (0.2 seconds) anesthesia at a depth of 3 to 8 mm so is appropriate only for very brief dermal procedures such as IV catheter placement or venipuncture for lab work. This product is increasingly used for brief vascular access-type procedures; well-controlled studies comparing it with other local anesthetics for penetration, duration of analgesia, patient satisfaction, and cost are needed. One early study of 72 adults who were consecutively admitted for surgery compared 0.3 mL of 1% plain lidocaine given subcutaneously by J-tip or by conventional syringe and 25-gauge needle prior to large-bore IV cannulation and found significant reductions in pain with J-tip and no difference in number of failed cannulations between the two groups (Cooper, Bromley, Baranowski, et al., 2000). However, these researchers suggested that J-tip appears to be less effective when subcutaneous access is small and recommended its use when the subcutaneous space is deeper. A study of 116 children found J-Tip application before IV cannulation was not painful and produced better anesthesia than EMLA (average EMLA application time was 69 minutes) (Jimenez, Bradford, Seidel, et al., 2006). A later study of 70 children found J-tip produced better anesthesia than a 30-minute application of L.M.X.4 prior to IV cannulation (Spanos, Booth, Koenig, et al., 2008).
A randomized, double-blind study of children undergoing needle insertion in the ED found no difference in local anesthesia between jet-injection lidocaine and jet-injection normal saline, and the researchers concluded that both treatments may provide superior analgesia compared with no pretreatment (Auerbach, Tunik, Mojica, 2009). The majority of patients in the study said they would request the jet device for future needle insertions, and clinicians reported similar visualization with or without the use of a jet device. (See discussion previously in the chapter regarding the anesthetic effect of bacteriostatic normal saline.) A randomized controlled trial of 400 children undergoing peripheral IV cannulation in the ED involved administration of jet injection of saline or jet injection of lidocaine and reported lower pain scores compared with no intervention but no differences in effectiveness between lidocaine and saline jet injection (Lysakowski, Dumont, Tramer, et al., 2003). The researchers also noted that the use of jet injection was not painless (patients reported at least moderate pain because of the treatment itself) and the number of technical failures was large. The researchers suggested carefully considering costs and identifying patients who would benefit most when deciding to routinely use local anesthetic prior to this procedure.
Various mixtures of local anesthetics, including tetracaine, lidocaine, and cocaine (TLC); tetracaine, adrenaline (epinephrine) and cocaine (TAC); and lidocaine, epinephrine, and tetracaine (LET), have been compounded and applied topically for dermal anesthesia. The maximum safe total doses for healthy 70 kg adults are 50 mg of tetracaine, 500 mg of lidocaine, and 200 mg of cocaine (Pasero, McCaffery, 1999).
These combinations are used most often before wound cleaning and repairing uncomplicated facial and scalp lacerations. The gel form is preferred because it is easier to control the application (see Box 28-2 for preparation and use of LET topical gel). It is recommended that the gel or solution be painted into and around the wound with cotton-tipped applicators and left for a minimum of 10 minutes and a maximum of 30 minutes; then the wound is irrigated to remove the LET. Peak anesthetic effect after topical mixtures that contain cocaine or lidocaine is 2 to 5 minutes and 3 to 8 minutes for tetracaine combinations. Anesthesia is superficial and does not extend to submucosal structures (Pasero, McCaffery, 1999). These mixtures are used less today with the introduction and more widespread availability of the other previously discussed topical local anesthetics; however, an advantage is that they can be applied to a wound.
Although other products are used for procedural pain, there is a general lack of research to adequately evaluate their safety and effectiveness. Some examples follow.
• Refrigerant sprays (e.g., Pain Ease) provide anesthesia by rapid cooling of the skin. The target site is sprayed 4 to 10 seconds from a distance of 3 to 7 inches just until the skin begins to blanch. Care must be taken not to freeze (frost) the skin. The anesthetic effect lasts just 60 seconds, so refrigerant sprays are appropriate only for very brief and superficial dermal procedures such as injections and immunizations. They are ideal for settings such as the ED where a topical anesthetic with a rapid onset of analgesia is particularly important. One randomized, placebo-controlled study showed that vapocoolant spray used immediately prior to venipuncture produced effective and safe anesthesia for IV catheter placement in adults in the ED (Hijazi, Taylor, Richardson, 2009). Successful IV start rates were similar between groups, and 62% of the patients said they would choose the vapocoolant spray again. Vapocoolant spray was shown to be ineffective in reducing intramuscular immunization pain in children (Cohen, MacLaren, DeMore, et al., 2009).
• Topical benzocaine 20% spray (Hurricaine) is used for some procedures. A meta-analysis concluded that topical anesthetic sprays (e.g., lidocaine, tetracaine, and benzocaine) used prior to endoscopic procedures improves ease of endoscopy and patient tolerance but cited concerns about related adverse effects, such as methemogloginemia (see previous discussion), anaphylactic reactions, and aspiration (Evans, Saberi, Kim, et al., 2006). It was shown to be safe but had limited effectiveness as an anesthetic prior to minor gynecologic surgery (Einarsson, Henao, Young, 2005). Numerous cases of methemoglobinemia have been linked to the use of topical benzocaine and attributed to a lack of precise dosing such as might be possible with a metered dose; stricter labeling and very cautious use are recommended (Moore, Walsh, Cohen, 2004).
• Viscous lidocaine (e.g., 2%) is sometimes used for inflamed oral mucosa or on gums prior to dental procedures and prior to ureteral catheterization (Pasero, McCaffery, 1999). Attention to dosing is recommended as amounts greater than 240 mg/day have been associated with lidocaine toxicity (Yamashita, Sato, Kakiuchi, et al., 2002).
The distress and pain associated with procedures are often underestimated and ignored by those who perform them. Clinicians are encouraged to establish policies and procedures that address the provision of adequate analgesia and anesthesia with first-line agents, such as local anesthetics, prior to painful procedures, including minor procedures such as venipuncture. Local anesthetics are versatile and well-tolerated by most patients. There are several formulations to choose from, and more are in development.