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Intravenous Lidocaine to Treat Postoperative Pain Management: Novel Strategy with a Long-established Drug

Omote, Keiichi M.D.

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MANY surgical patients still experience moderate to severe pain after surgery, despite efforts to develop new drugs and techniques for postoperative analgesia. We have recognized for some time that postoperative pain is not only a transient, uncomfortable experience for the patient, but can also have long-term sequelae, including chronic pain.1 In addition, adequate control of postoperative pain represents one of the most important factors in determining the time when patients can be safely discharged from a surgical facility. Adequate postoperative analgesia clearly enhances patient satisfaction and facilitates earlier mobilization and rehabilitation. Although perioperative analgesia has been traditionally provided by systemically administered opioids, extensive use of opioids is associated with a variety of perioperative side effects that can delay hospital discharge. Therefore, surgical patients would greatly benefit from a perioperative analgesic regimen that is effective, has minimal side effects, demonstrates a wide margin of safety, and can be easily managed away from the hospital. Practitioners are increasingly turning to alternatives to systemic opioids, including epidural or perineural infusions, for managing pain during the perioperative period to minimize the adverse effects of analgesic medications. These methods are cumbersome and expensive to apply, and recent studies using a simpler approach, intravenous lidocaine infusion, have shown significant beneficial effects.2–4 In the current issue of Anesthesiology, Kaba et al.2 demonstrate, using a randomized, controlled, double-blind design, that a simple infusion of intravenous lidocaine produced effective analgesia after laparoscopic colectomy and allowed for a more rapid rehabilitation and quicker hospital discharge.
Systemic administration of lidocaine has previously been demonstrated to have analgesic actions in patients with chronic neuropathic pain.5 The prolonged effect of lidocaine is thought to reflect its inhibition of spontaneous impulse generation arising from injured nerve fibers and from dorsal root ganglion neurons proximal to the injured nerve segments6 and by suppressing primary afferent-evoked polysynaptic reflexes in the spinal dorsal horn.7 These effects are thought to be mediated by a variety of mechanisms, including sodium channel blockade,7 as well as inhibition of G protein–coupled receptors8,9 and N-methyl-d-aspartate receptors.10 In addition, intravenous lidocaine is an effective modality for treating visceral pain.11 Postoperative pain after abdominal surgery includes many forms of distress, such as spontaneous pain at rest; pain during movement, including that of respiration; and visceral pain arising from damage to internal organs during surgery. Based on these observations and the similarity in some underlying processes of postoperative and neuropathic pain, systemic administration of lidocaine might be expected to improve postoperative pain and discomfort and aid in better mobilization. In addition, lidocaine would predictably have a greater effect when administered perioperatively, i.e., during the presence of significant nociceptive input. Kaba et al.2 emphasized that perioperative (before, during, and after surgery) intravenous infusion of lidocaine, in a low dose as used for the treatment or prophylaxis of ventricular arrythmias,8 was able to improve postoperative analgesia.
Rimback et al.12 and Groudine et al.4 have shown that continuous intravenous lidocaine infusion provided a faster return of bowel function after surgery. Similarly, in the study of Kaba et al.,2 systemic lidocaine improved postoperative bowel function, as evidenced by shortened times to first flatus and defecation after surgery. Postoperative ileus results from several etiologies, including postoperative opioid consumption, visceral inflammation secondary to surgery, and postoperative sympathetic stimulation. Which of these are most affected by systemic lidocaine remains a subject for future study, but the patient benefit is clear and now reproduced in several studies.
So where does intravenous lidocaine sit among treatments of moderate to severe postoperative pain? Continuous epidural infusion and continuous peripheral nerve blocks have been applied with increasing frequency for the management of postoperative pain and clearly improve analgesia compared with traditional methods. In Japan, most anesthesiologists prefer continuous epidural analgesia over systemic opioids for the management of pain after abdominal surgery. Although most studies indicate that epidural and peripheral nerve block techniques provide superior analgesia (particularly when local anesthetics are used) compared with systemic opioids, whether they reduce morbidity and mortality remains a subject of controversy and research.
We are becoming increasingly aware of the risks associated with the use of invasive techniques in the treatment of postoperative pain, and how the clinician can properly weigh the risks and benefits of these techniques on an individual basis is uncertain. The study by Kaba et al.2 suggests that intravenous lidocaine may be considered as another option in this setting to accelerate acute rehabilitation and facilitate earlier patient discharge. Epidural infusions are certainly more expensive and invasive than intravenous infusions. Furthermore, modern thromboprophylaxis practice with low-molecular-weight heparins often preclude the use of continuous epidural therapy because of the concern over risk of epidural bleeding and hematoma with catastrophic outcomes due to spinal cord or nerve root compression. The safety of intravenous lidocaine for postoperative analgesia is far from assured by small studies such as those currently available, and there is an accumulation of lidocaine in the blood during the period of infusion, even at these low doses.2 Although many studies have reported that the therapeutic dose of lidocaine for ventricular arrhythmias remains well below toxic concentrations,8 whether this applies in the postoperative setting with the multiple influences on drug distribution and elimination remains unknown. Therefore, intravenous lidocaine is appealing as a simple and inexpensive method to gain the same benefits as more invasive and costly techniques, but we currently lack large numbers of patient exposures to define its safety and direct head-to-head comparisons to compare its efficacy.
As in all areas of medicine, we search in postoperative pain management for an ideal drug or technique that is effective, simple, inexpensive, and safe. Further studies are needed to clarify and establish where intravenous lidocaine sits in the spectrum of currently available agents in this regard. The best dose of lidocaine to obtain maximum efficacy for postoperative treatment of somatic and visceral pain and improved bowel function while minimizing adverse effects has not been defined. But studies like that of Kaba et al.2 with this relatively novel strategy using a long-established drug may help to develop and implement effective therapeutic management strategies to improve our treatment of postoperative pain and perioperative morbidity.
Keiichi Omote, M.D.
Sapporo South-3 Hospital and Sapporo Medical University School of Medicine, Sapporo, Japan. komote@sapmed.ac.jp
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References

1. Perkins FM, Kehlet H: Chronic pain as an outcome of surgery: A review of predictive factors. Anesthesiology 2000; 93:1123–33

2. Kaba A, Laurent SR, Detroz BJ, Sessler DI, Durieux ME, Lamy ML, Joris JL: Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy. Anesthesiology 2007; 106:11–8.

3. Koppert W, Weignd M, Neumann F, Sittl R, Schuettler J, Schmelz M, Hering W: Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg 2004; 98:1050–5

4. Groudine SB, Fisher HA, Kaufman RP Jr, Patel MK, Wilkins LJ, Mehta SA, Lumb PD: Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostectomy. Anesth Analg 1998; 86:253–9

5. Kingery WS: A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndrome. Pain 1997; 73:123–39

6. Devor M, Wall PD, Catalan N: Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992; 48:261–8

7. Woolf CJ, Wiesenfield-Hallin Z: The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre-evoked activity in the spinal cord. Pain 1985; 23:361–74

8. Hollmann MW, Durieux ME: Local anesthetics and the inflammatory response: A new therapeutic indication? Anesthesiology 2000; 93:858–75

9. Hollmann MW, Strumper D, Herroeder S, Durieux ME: Receptors, G proteins, and their interactions. Anesthesiology 2005; 103:1066–78

10. Sugimoto M, Uchida I, Mashimo T: Local anaesthetics have different mechanisms and sites of action at the recombinant N-methyl-D-aspartate (NMDA) receptors. Br J Pharmacol 2003; 138:876–82

11. Ness TJ. Intravenous lidocaine inhibits visceral nociceptive reflexes and spinal neurons in the rat. Anesthesiology 2000; 92:1685–91.2006

12. Rimback G, Cassuto J, Tollesson PO: Treatment of postoperative paralytic ileus by intravenous lidocaine infusion. Anesth Analg 1990; 70:414–9

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