Skip to main content
Top
Published in: Journal of Anesthesia 5/2011

01-10-2011 | Original Article

A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery

Authors: Richard C. D’Alonzo, Elliott Bennett-Guerrero, Mihai Podgoreanu, Thomas A. D’Amico, David H. Harpole, Andrew D. Shaw

Published in: Journal of Anesthesia | Issue 5/2011

Login to get access

Abstract

Purpose

We hypothesized that patients who received ketamine during thoracic surgery would benefit from suppression of the inflammatory cascade, represented by lower interleukin (IL)-6 and C-reactive protein (CRP) plasma levels.

Methods

This study was a randomized, double blind, placebo controlled clinical trial of ketamine in patients undergoing thoracic surgery. The setting was a single university teaching hospital. Forty patients who presented to the preoperative clinic prior to thoracic surgery (20 control, 20 treatment) were randomized to receive either a 0.5 mg/kg ketamine bolus or an equivalent volume of normal saline intravenously prior to chest wall incision. Plasma samples taken prior to induction of anesthesia and at 24 h following surgery were assayed for IL-6 and CRP levels. Verbal pain scores were reported at 4 and 24 h following surgery and at discharge.

Results

IL-6 plasma levels did not differ significantly at 24 h for patients receiving ketamine (245 ± 287 pg/ml, mean ± SD) compared to patients who received placebo (269 ± 210 pg/ml), p = 0.39. Additionally, CRP levels at 24 h were not significantly different (8.8 ± 4.5 mg/dl for ketamine, 9.3 ± 5.6 mg/dl for placebo patients), p = 0.37. Finally, verbal pain scores were not significantly different between patient groups at 4 or 24 h, or at discharge.

Conclusions

These findings suggest that the routine use of a single dose of ketamine prior to chest wall incision is not effective at reducing pain or inflammation in thoracic surgery patients at 24 h postoperatively.
Literature
1.
go back to reference Shaw AD, Vaporciyan AA, Wu X, King TM, Spitz MR, Putnam JB, Dickey BF. Inflammatory gene polymorphisms influence risk of postoperative morbidity after lung resection. Ann Thorac Surg. 2005;79:1704–10.PubMedCrossRef Shaw AD, Vaporciyan AA, Wu X, King TM, Spitz MR, Putnam JB, Dickey BF. Inflammatory gene polymorphisms influence risk of postoperative morbidity after lung resection. Ann Thorac Surg. 2005;79:1704–10.PubMedCrossRef
2.
go back to reference Vaporciyan AA, Correa AM, Rice DC, Roth JA, Smythe WR, Swisher SG, Walsh GL, Putnam JB. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg. 2004;127:779–86.PubMedCrossRef Vaporciyan AA, Correa AM, Rice DC, Roth JA, Smythe WR, Swisher SG, Walsh GL, Putnam JB. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg. 2004;127:779–86.PubMedCrossRef
3.
go back to reference Onaitis MW, Petersen RP, Balderson SS, Toloza E, Burfeind WR, Harpole DH, D’Amico TA. Thoracoscopic lobectomy is a safe and versatile procedure: experience with 500 consecutive patients. Ann Surg. 2006;244:420–5.PubMed Onaitis MW, Petersen RP, Balderson SS, Toloza E, Burfeind WR, Harpole DH, D’Amico TA. Thoracoscopic lobectomy is a safe and versatile procedure: experience with 500 consecutive patients. Ann Surg. 2006;244:420–5.PubMed
4.
go back to reference Issac TT, Dokainish H, Lakkis NM. Role of inflammation in initiation and perpetuation of atrial fibrillation: a systematic review of the published data. J Am Coll Cardiol. 2007;50:2021–8.PubMedCrossRef Issac TT, Dokainish H, Lakkis NM. Role of inflammation in initiation and perpetuation of atrial fibrillation: a systematic review of the published data. J Am Coll Cardiol. 2007;50:2021–8.PubMedCrossRef
5.
go back to reference Tompkins RG. The role of proinflammatory cytokines in inflammatory and metabolic responses. Ann Surg. 1997;225:243–5.PubMedCrossRef Tompkins RG. The role of proinflammatory cytokines in inflammatory and metabolic responses. Ann Surg. 1997;225:243–5.PubMedCrossRef
6.
go back to reference Bartoc C, Frumento RJ, Jalbout M, Bennett-Guerrero E, Du E, Nishanian E. A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2006;20:217–22.PubMedCrossRef Bartoc C, Frumento RJ, Jalbout M, Bennett-Guerrero E, Du E, Nishanian E. A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2006;20:217–22.PubMedCrossRef
7.
go back to reference Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004;62:499–506.PubMedCrossRef Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004;62:499–506.PubMedCrossRef
8.
go back to reference Oka Y, Murata A, Nishijima J, Yasuda T, Hiraoka N, Ohmachi Y, Kitagawa K, Toda H, Tanaka N. Circulating interleukin 6 as a useful marker for predicting postoperative complications. Cytokine. 1992;4:298–304. Oka Y, Murata A, Nishijima J, Yasuda T, Hiraoka N, Ohmachi Y, Kitagawa K, Toda H, Tanaka N. Circulating interleukin 6 as a useful marker for predicting postoperative complications. Cytokine. 1992;4:298–304.
9.
go back to reference Deng MC, Dasch B, Erren M, Mollhoff T, Scheld HH. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg. 1996;62:184–90.PubMedCrossRef Deng MC, Dasch B, Erren M, Mollhoff T, Scheld HH. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg. 1996;62:184–90.PubMedCrossRef
10.
go back to reference Holmes JHt, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, Hall RA. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res. 2002;51:579–86.PubMedCrossRef Holmes JHt, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, Hall RA. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res. 2002;51:579–86.PubMedCrossRef
11.
go back to reference Craig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg. 2001;20:455–63.PubMedCrossRef Craig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg. 2001;20:455–63.PubMedCrossRef
12.
go back to reference Tashima T, Yamashita J, Nakano S, Joutsuka T, Hayashi N, Saishoji T, Ogawa M. Comparison of video-assisted minithoracotomy and standard open thoracotomy for the treatment of non-small cell lung cancer. Minim Invasive Ther Allied Technol. 2005;14:203–8.PubMedCrossRef Tashima T, Yamashita J, Nakano S, Joutsuka T, Hayashi N, Saishoji T, Ogawa M. Comparison of video-assisted minithoracotomy and standard open thoracotomy for the treatment of non-small cell lung cancer. Minim Invasive Ther Allied Technol. 2005;14:203–8.PubMedCrossRef
13.
go back to reference Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses compared with conventional surgery. Ann Thorac Surg. 2000;70:243–7.PubMedCrossRef Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses compared with conventional surgery. Ann Thorac Surg. 2000;70:243–7.PubMedCrossRef
14.
go back to reference Sakai T, Ichiyama T, Whitten CW, Giesecke AH, Lipton JM. Ketamine suppresses endotoxin-induced NF-kappaB expression. Can J Anaesth. 2000;47:1019–24.PubMedCrossRef Sakai T, Ichiyama T, Whitten CW, Giesecke AH, Lipton JM. Ketamine suppresses endotoxin-induced NF-kappaB expression. Can J Anaesth. 2000;47:1019–24.PubMedCrossRef
15.
go back to reference Sun J, Wang XD, Liu H, Xu JG. Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine. Acta Anaesthesiol Scand. 2004;48:317–21.PubMedCrossRef Sun J, Wang XD, Liu H, Xu JG. Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine. Acta Anaesthesiol Scand. 2004;48:317–21.PubMedCrossRef
16.
go back to reference Roytblat L, Talmor D, Rachinsky M, Greemberg L, Pekar A, Appelbaum A, Gurman GM, Shapira Y, Duvdenani A. Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg. 1998;87:266–71.PubMed Roytblat L, Talmor D, Rachinsky M, Greemberg L, Pekar A, Appelbaum A, Gurman GM, Shapira Y, Duvdenani A. Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg. 1998;87:266–71.PubMed
17.
go back to reference Burfeind WR, D’Amico TA. Thoracoscopic lobectomy. Oper Tech Thorac Cardiovasc Surg. 2004;9:98–114.CrossRef Burfeind WR, D’Amico TA. Thoracoscopic lobectomy. Oper Tech Thorac Cardiovasc Surg. 2004;9:98–114.CrossRef
18.
go back to reference Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond). 1990;79:161–5. Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond). 1990;79:161–5.
19.
go back to reference Beilin B, Rusabrov Y, Shapira Y, Roytblat L, Greemberg L, Yardeni IZ, Bessler H. Low-dose ketamine affects immune responses in humans during the early postoperative period. Br J Anaesth. 2007;99:522–7.PubMedCrossRef Beilin B, Rusabrov Y, Shapira Y, Roytblat L, Greemberg L, Yardeni IZ, Bessler H. Low-dose ketamine affects immune responses in humans during the early postoperative period. Br J Anaesth. 2007;99:522–7.PubMedCrossRef
20.
go back to reference Elia N, Tramer MR. Ketamine and postoperative pain—a quantitative systematic review of randomised trials. Pain. 2005;113:61–70.PubMedCrossRef Elia N, Tramer MR. Ketamine and postoperative pain—a quantitative systematic review of randomised trials. Pain. 2005;113:61–70.PubMedCrossRef
21.
go back to reference Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for postoperative pain relief in children after adenotonsillectomy. Paediatr Anaesth. 2001;11:333–6.PubMedCrossRef Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for postoperative pain relief in children after adenotonsillectomy. Paediatr Anaesth. 2001;11:333–6.PubMedCrossRef
22.
go back to reference Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS, Chung MK. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003;108:3006–10. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS, Chung MK. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003;108:3006–10.
23.
go back to reference Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol. 2005;95:764–7.PubMedCrossRef Psychari SN, Apostolou TS, Sinos L, Hamodraka E, Liakos G, Kremastinos DT. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation. Am J Cardiol. 2005;95:764–7.PubMedCrossRef
24.
go back to reference Burzotta F, Iacoviello L, Di Castelnuovo A, Glieca F, Luciani N, Zamparelli R, Schiavello R, Donati MB, Maseri A, Possati G, Andreotti F. Relation of the −174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol. 2001;88:1125–8.PubMedCrossRef Burzotta F, Iacoviello L, Di Castelnuovo A, Glieca F, Luciani N, Zamparelli R, Schiavello R, Donati MB, Maseri A, Possati G, Andreotti F. Relation of the −174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol. 2001;88:1125–8.PubMedCrossRef
25.
go back to reference Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A, Possati G. The −174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Circulation. 2003;108 Suppl 1:II195–9. Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A, Possati G. The −174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Circulation. 2003;108 Suppl 1:II195–9.
26.
go back to reference Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth. 1981;53:27–30.PubMedCrossRef Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth. 1981;53:27–30.PubMedCrossRef
27.
go back to reference Slogoff S, Allken G, Wessels J, Cheney P. Clinical experiences with subanesthetic ketamine. Anesth Analg. 1974;53:354–8.PubMed Slogoff S, Allken G, Wessels J, Cheney P. Clinical experiences with subanesthetic ketamine. Anesth Analg. 1974;53:354–8.PubMed
Metadata
Title
A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery
Authors
Richard C. D’Alonzo
Elliott Bennett-Guerrero
Mihai Podgoreanu
Thomas A. D’Amico
David H. Harpole
Andrew D. Shaw
Publication date
01-10-2011
Publisher
Springer Japan
Published in
Journal of Anesthesia / Issue 5/2011
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-011-1206-4

Other articles of this Issue 5/2011

Journal of Anesthesia 5/2011 Go to the issue