Publications
APS Bulletin • Volume 18, Number 3, 2008
Innovations in Practice
Deb Gordon, MS RN FAAN, Department Editor
Intravenous Lidocaine for Postoperative Analgesia:
Renewed Interest in an Old Strategy
Deb Gordon, MS RN FAAN, Mark Schroeder, MD
It can be a challenge to provide effective analgesia after major surgery. Pain and postoperative ileus result from multiple factors such as surgical trauma, release of inflammatory mediators, sympathetic stimulation activating inhibitory reflexes, and postoperative opioid consumption (Artinyan et al., 2008).
Clinically innovative “fast-track” protocols to accelerate postoperative recovery are in high demand. This approach includes combinations of techniques designed to reduce surgical stress, control pain, and facilitate early feeding and mobilization (Kehlet & Dahl, 1993). The search for well-tolerated nonopioid analgesics to control pain after visceral operations is of particular interest, and the administration of perioperative intravenous (IV) lidocaine infusions for this purpose recently received renewed attention as an analgesic intervention.
Local Anesthetic Delivery Options and Mechanism of Action
Local anesthetics (LAs) traditionally are administered for analgesia via subcutaneous infiltration and regional nerve block procedures. The use of continuous neuraxial and perineural blockade with LAs is a common approach to manage pain after major operations, but this may not be an option for many hospitalized or outpatient surgery patients. Epidural anesthesia carries a number of risks, can be technically demanding, and, because of its segmental nature, may not block reflexes relayed through the prevertebral ganglia, an important contributing factor in postoperative ileus (Rimback, Cassuto, & Tollesson, 1990). Systemic lidocaine has previously demonstrated analgesic actions in patients with chronic neuropathic pain (Mao & Chen, 2000; Challapalli, Tremont-Lukats, McNicol, Lau, & Carr, 2005). Parenteral lidocaine is relatively safe for patients without cardiac conduction blocks, generally is well tolerated, and is inexpensive and easy to administer.
Systemic lidocaine is believed to inhibit spontaneous impulse generation arising from injured nerve fibers and the dorsal root ganglion and suppress inflammatory reactions mediated by immune cells (e.g., polymorphonuclear cells; Kawamata et al., 2006). These effects are thought to be mediated at levels below systemic toxicity by a variety of mechanisms including sodium channel blockade and inhibition of G protein-coupled receptors and N-methyl-D-aspartate receptors.
Systemic LA for Postoperative Visceral Pain
The use of IV LA infusions for postoperative pain control dates back to the 1940s when IV procaine was reported to provide analgesia for burns, abdominal surgery, and mastectomy (Gordon, 1943; Brittain, 1949; Gordon, 1950; Giffen 1953). The use of parenteral lidocaine for postoperative pain first was reported in 1961 (Bartlett & Hutaserani, 1961). A total of 302 patients undergoing various surgeries including cholecystectomy, appendectomy, and pelvic laparotomies were given total doses of 400 mg–800 mg of IV lidocaine during surgery and in the postanesthesia care unit (PACU), with reported dramatic reductions in pain and opioid use. More recently, studies in radical prostatectomy (Groudine et al., 1998) and colectomy (Kaba et al., 2007; Herroeder et al., 2007) suggest systemic lidocaine also promotes faster return of bowel function after visceral surgery and reduces pain with movement (Koppert et al., 2004; Table 1).
Groudine and colleagues (1998) performed a prospective, blinded, randomized, controlled trial of IV lidocaine in 38 patients undergoing radical retropubic prostatectomy. After tracheal intubation, patients in the active treatment group received a lidocaine infusion initiated at 3 mg/min if the patient weighed at least 70 kg, and 2 mg/min for patients weighing less than 70 kg. The lidocaine infusion was continued throughout the surgery and into the PACU, terminating 60 minutes after skin closure. Control patients received a saline infusion in a similar manner. Ketorolac (30 mg IV) was initiated for all patients in the PACU unless contraindicated and continued (15 mg IV) every 6 hours as needed. Morphine was used for rescue and for patients not receiving ketorolac due to contraindications. A 50% reduction in demand for morphine was observed in the PACU lidocaine group. Yet patients in the lidocaine group reported statistically significant differences in pain during their hospital stay, faster time to first flatus and first bowel movement, and shorter hospital stays than the control group (Table 1).
In 2004, Koppert and colleagues (2004) examined the effects of systemic lidocaine on morphine consumption after major abdominal surgery including prostatectomy, cystectomy, nephrectomy, colectomy, and lymph node dissection. Patients were randomized to receive either saline or an IV bolus injection of lidocaine (1.5 mg/kg in 10 min) followed by continuous IV infusion at 1.5 mg/kg/hr (starting at least 30 minutes before incision and terminating 60 minutes after skin closure). Pain intensity was evaluated every 15 minutes during the first several postoperative hours. If pain exceeded 4 (out of 10), IV patient-controlled analgesia was started using morphine 2 mg with a lockout of 10 min. If pain intensity exceeded 6 (out of 10) for at least 30 minutes, the demand dose was doubled for at least 12 hours. Median time to first PCA use was similar in both groups; however, the lidocaine group exercised fewer PCA attempts during the observation period of 72 hours compared to the control group, resulting in a significant reduction in morphine consumption (p < 0.05; Table 1). The lidocaine group also reported less pain during movement, but pain at rest and time to first bowel movement were similar between the two groups.
Two studies followed in 2007: one study in patients undergoing laparoscopic colectomy (Kaba et al., 2007), and the other in patients undergoing open colorectal surgery (Herroeder et al., 2007). Patients in the laparoscopic study received a bolus injection of 1.5 mg/kg lidocaine provided at anesthesia induction, followed by a continuous infusion of 2 mg/kg/hr for 24 hours postoperatively. Postoperative analgesia was provided to all patients with the combination of acetaminophen, ketorolac, and patientcontrolled piritramide (a synthetic opioid, Dipidolor), followed by tramadol if necessary. Time to first flatus, defecation, length of stay, opioid consumption, and postoperative pain and fatigues scores all were reported as significantly better in patients who received lidocaine versus the control group (Table 1). No significant differences were detected in endocrine (cortisol and catehcolamines) and metabolic response (leukocytecs, C-reactive protein, and glucose) as measured over 48 hours postoperatively.
Patients in the open-incision colorectal study (Herroeder et al., 2007) received a 1.5 mg/kg IV lidocaine bolus before general anesthesia induction, followed by a continuous lidocaine infusion (2 mg/min) until 4 hours postop. Lidocaine accelerated return of bowel function and shortened length of hospital stay by 1 day, but no difference was observed in daily pain ratings (Table 1). Elevated plasma levels of IL-6, IL-8, complement C3a, and IL-1ra, as well as expression of CD11b, L- and P-selectin, and platelet-leukocyte aggregates were significantly attenuated in the systemic lidocaine group.
Pharmacokinetics and Precautions
Many clinicians may hesitate to use IV lidocaine, fearing adverse cardiac and neurologic effects. First- and second-degree heart conduction blocks could be aggravated and progress to a higher degree of heart block with lidocaine administration. Lidocaine is contraindicated in patients with cardiovascular instability, those concomitantly using alpha agonists or beta blockers, and in patients with allergies to other amide local anesthetics (bupivacaine). Allergy to procaine (Novacaine) is not a contraindication to IV lidocaine use, as procaine is an ester local anesthetic. Side effects are more pronounced in patients with liver dysfunction, pulmonary diseases (when their predominant problem is carbon dioxide retention), and congestive heart failure. The side effects of lidocaine are directly related to serum lidocaine level. The half-life of lidocaine is relatively short compared to other LAs (Thomson Micromedex, n.d.). Lidocaine also is less cardiotoxic than other LAs such as bupivacaine. After initial parenteral bolus administration, lidocaine is cleared rapidly with a short half-life of approximately 10 minutes due to redistribution and extensive hepatic metabolism. After approximately 30 minutes, there is a slower elimination phase that lasts about 90 minutes, which means side effects typically dissipate within this time frame after an infusion stops. With continuous IV administration, a half-life of about 1.5–2 hours may be achieved; consequently, prolonged administration may be necessary to achieve the desired therapeutic result. Time to reach steady-state via IV is 6–12 hours. Given the short half-life of lidocaine, it is surprising that its analgesic effect may last much longer. No specific target serum level for pain relief has been identified in studies, as each person’s response and requirements vary. Serious side effects are rare within the 2–6 microgram/mL range.
Serum lidocaine levels varied between 1.1 and 4.6 micrograms/mL (with the exception of one peak bolus value of 5.8) in four recent visceral postoperative pain studies (Table 2), and no identifiable lidocaine-related adverse events were reported. Overdosage treatment, if needed, would include airway support, oxygenation and hyperventilation to raise the seizure threshold, diazepam for seizure, IV fluids and trendelenberg to increase fluid volume, and cardiovascular depression treatment including IV fat emulsion as an antidote (Turner-Lawrence & Kerns, 2008).
An important clinical consideration in using parenteral LA infusions in the perioperative setting is the potential for medication error, such as mix-ups regarding epidural and IV routes of administration. Inadvertent IV administration of infusions of LAs such as bupivacaine, which is intended for epidural infusion, have resulted in death (Koczmara, Hyland, & Cheng, 2007; Hew & Simmons, 2003). The Institute of Safe Medication Practices recommends establishing safeguards to reduce risk of harm (Koczmara et al., 2007); these safeguards include implementing processes in the medication-use system for handling and administration such as segregated storage, medication labeling, an independent double-check policy, and training and competency assessment of all involved staff.
Limitations and Future Directions
Many questions remain unanswered about when and how to apply systemic lidocaine in the perioperative arena. Which surgeries and patients are most suited to this application? What are the proper bolus amounts and infusion rates and durations? No work has been done to examine the factors that may affect analgesic response to IV lidocaine under postoperative pain conditions— such factors would include age, gender, and preexisting pain. Martin and colleagues (2008) found lidocaine infusions given to patients undergoing total hip arthroplasty in a manner similar to infusions given in visceral studies produced no opioid-sparing, significant difference in pain ratings, tactile pain thresholds, or maximal degree of active hip-flexion, which raises questions about the effectiveness of lidocaine infusions for somatic pain. Significant limitations exist on all available data. The power of the studies described in this article to examine analgesic response and safety is limited by the small number of patients studied. There is no mention of arrhythmia monitoring. Outcome measures and data points for pain and bowel function are inconsistent and somewhat ill-defined, making it difficult to compare studies. Results also may be confounded by the use of varying opioid rescue regimens and the use of ketorolac, which may exert its own effect on inflammation, analgesia, and return of bowel function. Larger-scale trials clearly are needed to determine indications, dosing, and safety.
Summary
The mechanisms and best treatment regimens for pain and ileus experienced after visceral operations are not well understood. Although work is ongoing to discover new, tolerable compounds that provide effective analgesia and reduce peripheral and central sensitization, few promising compounds are on the horizon. The 2005 Acute Pain Summit (Rathmell et al., 2006) found that—with the exception of epidural LAs—there is little evidence to support the common belief that opioid-sparing regimens facilitate earlier return of bowel function after colonic surgery. Data reviewed by the Summit (not including data on parenteral lidocaine) suggest that even at very low doses, the gastrointestinal tract is exquisitely sensitive to opioids, and other techniques need to be employed to reduce postoperative ileus. Epidural and systemic LA may improve bowel function after surgery via several mechanisms independent of sparing opioids, including blockade of afferent and efferent inhibitory reflexes, efferent sympathetic blockade with concomitant increase in splanchnic blood flow, and antiinflammatory effects. Perioperative IV administration of lidocaine is an old technique that consistently has been shown to contribute to analgesia without respiratory depression, significant nausea, and other side effects common with opioid analgesics. A closer examination to determine an optimal regimen after visceral operations and its potential for use in other postoperative pain states is warranted.
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Deb Gordon, MS RN FAAN, is Senior Clinical Nurse Specialist, Nursing Practice Innovations, at the University of Wisconsin Hospital and Clinics, Madison, WI.
Mark Schroeder, MD, is associate professor of anesthesiology at the University of Wisconsin School of Medicine and Public Health, Madison, WI.