◊ BACKGROUND AND OBJECTIVES:
Experimental nerve block in animals inhibits the inflammatory response. The purpose of this study was to determine to what extent a 48-hour local anesthetic block of all afferent and efferent nerve fibers of the knee area has an impact on postoperative inflammatory response.
◊ METHODS:
Twelve patients scheduled for primary total knee arthroplasty received spinal anesthesia, and then were randomly allocated to either patient-controlled analgesia with morphine (n = 6) or a combination of continuous lumbar plexus and sciatic nerve blocks (continuous peripheral nerve block; CPNB) with ropivacaine 0.2% for 48 hours. Blood samples were collected before surgery and at 3, 8, 24, and 48 hours after surgical incision to measure plasma glucose, serum insulin and cortisol, C-reactive protein, interleukin-6, and leukocyte count. Pain visual analog scale at rest and on knee flexion were recorded and complications classified.
◊ RESULTS:
Visual analog scale was lower in the CPNB group at rest and on knee flexion on postoperative days 1 and 2 (P < .05). There were no differences in circulating levels of glucose, insulin, and cortisol. C-reactive protein and leukocyte count were lower in the CPNB group (P < .05). There was a positive correlation between the peak leukocyte count and the inflammatory markers (P < .03). Three patients in the patient-controlled analgesia group and one in the CPNB group had complications requiring conservative management.
◊ CONCLUSIONS:
Continuous lumbar plexus and sciatic nerve blocks with ropivacaine contribute to the attenuation of the postoperative inflammatory response.
◊ Reviewed by C. Stein, MD, PhD
Chairman, Dept. of Anesthesiology and Critical Care Medicine
Freie Universität and Charité Campus Benjamin Franklin, Berlin, Germany.
AND
R. Moshourab, MD
Research associate
Freie Universität and Charité Campus Benjamin Franklin, Berlin, Germany.
This study explored the relationship between the nervous and the immune system during the local inflammatory response following arthroplasty. Peripheral nociceptive nerve endings innervating the surgical site are involved in the inflammatory response. According to the authors, there are two relevant neural aspects: an afferent one which is responsible for the development of hyperalgesia and an efferent one which is responsible for the control of the release of neurogenic substances. Blocking the propagation of impulses from and to the central nervous system at a distant site not only results in analgesia but also in the attenuation of the local inflammatory response as measured by inflammatory markers. This inhibitory modulation can lead to earlier mobilization and might reduce the risk of infection.
The topic is of importance but the way it has been tackled poses some problems for the interpretation of data. The number of patients recruited in this study is small. Although the operation was done by the same surgeon the extent of surgical injury for each individual patient (the amount of injury/stress) remains unknown. To this end, the authors could have assessed edema by grossly analysing the change in extremity circumference at the surgical site. VAS scores were not similar in both groups. Ideally, inflammatory markers should be measured at the injury site. Their concentrations in blood are always difficult to interpret. IL-6 and CRP levels had similar increasing trends in the PCA and CPNB groups; however, CRP levels were significantly higher and leukocytosis developed in the former group (two CRP levels were very high). According to a previous study, CRP levels correlated with postoperative pain (confirmed by this study), whereas IL-6 levels correlated with delay in mobilization (Hall et al., 2001). Two patients in the PCA group developed wound complications (one hematoma and one infection). Postoperative wound infections can increase CRP levels and leukocyte counts regardless of the level of analgesia.The positive outcome may be explained by variation in the natural healing process of patients or the development of infectious complications. It would be interesting to reanalyse the data excluding wound infection and other complications because CPNB may have reduced the postoperative risk of infection. Is wound infection an independent confounding factor or is it the result of the modified inflammatory response in the PCA group? Here lies a major limitation of the study as data do not allow distinction of cause and effect. Excluding patients with inflammatory disease should decrease the variation in blood inflammatory markers it is extremely difficult to assess the local inflammatory response by the use of blood cytokine and CRP levels and to come to firm conclusions based on these.
One study was mentioned that was not in line with the main conclusion of the article. Based on fairly comparable methods, this study recruited 16 patients who underwent general anaesthesia with or without epidural analgesia for hysterectomy. Although hormonal responses were attenuated in the epidural group, IL-6 and CRP concentrations did not significantly differ between both groups [1]. The issue is even more complex when it comes to animal studies. For instance, Beloeil and colleagues did a comparable study in rats in which sciatic block with bupivacaine (1) decreased carrageenan-induced edema and hyperalgesia; (2) decreased blood cytokine levels (TNF and IL-1) irrespective of the route of administration; and (3) had no modulating effects, neither on the dorsal root ganglion nor on spinal cord p38 mitogen-activated protein kinase and cytokine levels [2]. Interestingly, the sodium channel blocker tetrodotoxin did not exhibit similar effects. Thus, there are definitely more issues to resolve.
This study opens the discussion for future investigations. The modulation of the inflammatory response by the peripheral nervous system is an established concept with evidence from basic research. This needs to be explored in more detail in clinical studies.
◊ REFERENCES
[1] Moore CM, Desborough JP, Powell H, Burrin JM, Hall GM. Br J Anaesth. 1994 72, 272
[2] Beloeil H, Ababneh Z, Chung R, Zurakowski D, Mulkern RV, Berde CB. Anesthesiology. 2006 105,128
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