Need for Additional Control in Studies of Epidural Outcome
Johnson, Michael E. M.D., Ph.D.
To the Editor:—
The recent study of Carli et al.1
provides valuable evidence that enhanced postoperative analgesia with an epidural catheter can improve outcome in terms of quality of life. A mock epidural catheter in the control group might have added further assurance that nonblinding did not lead to differential treatment or expectations between the study groups, but the authors did an excellent job of standardizing postoperative care to minimize this effect.
However, recent advances in the study of pain treatments suggest that an additional control should be present in studies on the efficacy of epidural compared to intravenous analgesia. The group receiving intravenous analgesia should also receive low dose intravenous or subcutaneous local anesthetic, to produce plasma levels comparable to those in the epidural group. Local anesthetic at plasma levels achieved with nontoxic intravenous administration or prolonged epidural administration has been shown to have analgesic properties in animal models both in vitro2,3
and in vivo
and in humans. 4,5
Of particular relevance to the issue of whether “diminishing postoperative pain may decrease the incidence of long-term chronic pain”6
is the efficacy of intravenous local anesthetic in treating neuropathic pain models. 2,5
The mechanism(s) of this effect remains to be elucidated, but occurs at levels too low to block sodium channels, and may involve effects on neuronal calcium homeostasis 3,7
and frequency of sodium channel response to stimuli. 2
Low-dose local anesthetics also have significant antiinflammatory effects, 8
and the levels of acute phase inflammatory proteins may affect subjective acute postoperative physical well being. 9
This comment is not specific to Carli et al.1
Unfortunately, most if not all clinical studies of epidural anesthesia on outcome have neglected this control, even those that have rigorously included an epidural catheter in subjects not receiving epidural analgesia to blind the study;e.g.
, Norris et al.10
Michael E. Johnson, M.D., Ph.D.
1. Carli F, Mayo N, Klubien K, Schricker T, Trudel J, Belliveau P: Epidural analgesia enhances functional exercise capacity and health-related quality of life after colonic surgery: Results of a randomized trial. A nesthesiology 2002; 97: 540–9
2. Strichartz GR, Zhou Z, Sinnott C, Khodorova A: Therapeutic concentrations of local anaesthetics unveil the potential role of sodium channels in neuropathic pain. Novartis Found Symp 2002; 241: 189–201
3. Takenaka-Hamaya C, Strichartz GR: Local anesthetic actions on changes of intracellular calcium induced by bradykinin in model sensory neurons (abstract). A nesthesiology 2002; 96: A976
4. Koppert W, Ostermeier N, Sittl R, Weidner C, Schmelz M: Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action. Pain 2000; 85: 217–24
5. Wallace MS, Ridgeway BM, Leung AY, Gerayli A, Yaksh TL: Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. A nesthesiology 2000; 92: 75–83
6. Wu CL, Raja SN: Optimizing postoperative analgesia: The use of global outcome measures. A nesthesiology 2002; 97: 533–4
7. Hollmann MW, Difazio CA, Durieux ME: Ca-signaling G-protein-coupled receptors: A new site of local anesthetic action? (review). Reg Anesth Pain Med 2001; 26: 565–71
8. Hollmann MW, Durieux ME: Local anesthetics and the inflammatory response: A new therapeutic indication? (review) A nesthesiology 2000; 93: 858–75
9. Hall GM, Salmon P: Physiological and psychological influences on postoperative fatigue. Anesth Analg 2002; 95: 1446–50
10. Norris EJ, Beattie C, Perler BA, Martinez EA, Meinert CL, Anderson GF, Grass JA, Sakima NT, Gorman R, Achuff SC, Martin BK, Minken SL, Williams GM, Traystman RJ: Double-masked randomized trial comparing alternate combinations of intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery. A nesthesiology 2001; 95: 1054–67
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