Skip to main content
Top
Published in: Critical Care 1/2020

Open Access 01-12-2020 | Septicemia | Research

Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial

Published in: Critical Care | Issue 1/2020

Login to get access

Abstract

Background

Administration of dexmedetomidine has been reported to improve inflammatory response in animals. We explored the effects of administering dexmedetomidine on the levels of C-reactive protein (CRP) and procalcitonin, and thus on inflammation, in patients with sepsis enrolled in a randomized clinical trial.

Methods

The DESIRE trial was a multicenter randomized clinical trial in which adult patients with sepsis were sedated with (DEX group) or without (non-DEX group) dexmedetomidine while on mechanical ventilators. As a prespecified sub-analysis, we compared CRP and procalcitonin levels during the first 14 days of treatment between the two groups. The 14-day mortality rate, albumin level, and the number of patients with disseminated intravascular coagulation (DIC) were also assessed. We used generalized linear models to estimate the differences in these outcomes between groups. We also used the Kaplan-Meier method to estimate the 14-day mortality rate and the log-rank test to assess between-group differences.

Results

Our study comprised 201 patients: 100 in the DEX group and 101 in the non-DEX group. CRP and procalcitonin levels were lower in the DEX vs. non-DEX group during the 14-day treatment period [CRP—range, 5.6–20.3 vs. 8.3–21.1 mg/dL (P = 0.03); procalcitonin—range, 1.2–37.4 vs. 1.7–52.9 ng/mL (P = 0.04)]. Albumin levels were higher in the DEX group (range, 2.3–2.6 g/dL) than in the non-DEX group (range, 2.1–2.7 g/dL; P = 0.01). The percentage of patients with DIC did not significantly differ between the groups (range, 21–59% and 17–56% for the DEX and non-DEX groups, respectively; P = 0.49). The 14-day mortality rates in the DEX and non-DEX groups were 13 and 21%, respectively (P = 0.16).

Conclusion

Sedation using dexmedetomidine reduced inflammation in patients with sepsis requiring mechanical ventilation.

Trial registration

ClinicalTrials.gov, NCT01760967. Registered on 4 January 2013.
Appendix
Available only for authorised users
Literature
1.
go back to reference Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2006;274:330–53.CrossRef Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2006;274:330–53.CrossRef
2.
go back to reference Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. 1999;340:207–14.CrossRef Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. 1999;340:207–14.CrossRef
3.
go back to reference Povoa P. C-reactive protein: a valuable marker of sepsis. Intensive Care Med. 2002;28:235–43.CrossRef Povoa P. C-reactive protein: a valuable marker of sepsis. Intensive Care Med. 2002;28:235–43.CrossRef
4.
go back to reference Nijsten MW, Olinga P, The TH, de Vries EG, Koops HS, Groothuis GM, Limburg PC, ten Duis HJ, Moshage H, Hoekstra HJ, Bijzet J, Zwaveling JH. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 2000;28:458–61.CrossRef Nijsten MW, Olinga P, The TH, de Vries EG, Koops HS, Groothuis GM, Limburg PC, ten Duis HJ, Moshage H, Hoekstra HJ, Bijzet J, Zwaveling JH. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 2000;28:458–61.CrossRef
5.
go back to reference Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426–35.CrossRef Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426–35.CrossRef
6.
go back to reference Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia. 1999;54:1136–42.CrossRef Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia. 1999;54:1136–42.CrossRef
7.
go back to reference Xu L, Bao H, Si Y, Wang X. Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice. Inflamm Res. 2013;62:507–14.CrossRef Xu L, Bao H, Si Y, Wang X. Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice. Inflamm Res. 2013;62:507–14.CrossRef
8.
go back to reference Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004;32:1322–6.CrossRef Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004;32:1322–6.CrossRef
9.
go back to reference Li Y, He R, Chen S, Qu Y. Effect of dexmedetomidine on early postoperative cognitive dysfunction and peri-operative inflammation in elderly patients undergoing laparoscopic cholecystectomy. Exp Ther Med. 2015;10:1635–42.CrossRef Li Y, He R, Chen S, Qu Y. Effect of dexmedetomidine on early postoperative cognitive dysfunction and peri-operative inflammation in elderly patients undergoing laparoscopic cholecystectomy. Exp Ther Med. 2015;10:1635–42.CrossRef
10.
go back to reference Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial. JAMA. 2017;317:1321–8.CrossRef Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial. JAMA. 2017;317:1321–8.CrossRef
11.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRef Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–55.CrossRef
12.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRef Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRef
13.
go back to reference Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O’Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166:1338–44.CrossRef Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O’Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166:1338–44.CrossRef
14.
go back to reference Oda S, Aibiki M, Ikeda T, Imaizumi H, Endo S, Ochiai R, Kotani J, Shime N, Nishida O, Noguchi T, Matsuda N, Hirasawa H. The Japanese guidelines for the management of sepsis. J Intensive Care. 2014;2:55.CrossRef Oda S, Aibiki M, Ikeda T, Imaizumi H, Endo S, Ochiai R, Kotani J, Shime N, Nishida O, Noguchi T, Matsuda N, Hirasawa H. The Japanese guidelines for the management of sepsis. J Intensive Care. 2014;2:55.CrossRef
15.
go back to reference Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal. 1999;13:273–9.CrossRef Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal. 1999;13:273–9.CrossRef
16.
go back to reference Kushimoto S, Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, Ishikura H, Iba T, Ueyama M, Eguchi Y, Otomo Y, Okamoto K, Endo S, Shimazaki S. Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma. Thromb Haemost. 2008;100:1099–105.CrossRef Kushimoto S, Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, Ishikura H, Iba T, Ueyama M, Eguchi Y, Otomo Y, Okamoto K, Endo S, Shimazaki S. Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma. Thromb Haemost. 2008;100:1099–105.CrossRef
17.
go back to reference Szelenyi J, Kiss JP, Vizi ES. Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-α production by α2- and β-adrenoceptors in mice. J Neuroimmunol. 2000;103:34–40.CrossRef Szelenyi J, Kiss JP, Vizi ES. Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-α production by α2- and β-adrenoceptors in mice. J Neuroimmunol. 2000;103:34–40.CrossRef
18.
go back to reference Klimscha W, Tong C, Eisenach JC. Intrathecal α2-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo microdialysis study. Anesthesiology. 1997;87:110–6.CrossRef Klimscha W, Tong C, Eisenach JC. Intrathecal α2-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo microdialysis study. Anesthesiology. 1997;87:110–6.CrossRef
19.
go back to reference Maes M, Lin A, Kenis G, Egyed B, Bosmans E. The effects of noradrenaline and alpha-2 adrenoceptor agents on the production of monocytic products. Psychiatry Res. 2000;96:245–53.CrossRef Maes M, Lin A, Kenis G, Egyed B, Bosmans E. The effects of noradrenaline and alpha-2 adrenoceptor agents on the production of monocytic products. Psychiatry Res. 2000;96:245–53.CrossRef
20.
go back to reference Lai YC, Tsai PS, Huang CJ. Effects of dexmedetomidine on regulating endotoxin-induced up-regulation of inflammatory molecules in murine macrophages. J Surg Res. 2009;154:212–9.CrossRef Lai YC, Tsai PS, Huang CJ. Effects of dexmedetomidine on regulating endotoxin-induced up-regulation of inflammatory molecules in murine macrophages. J Surg Res. 2009;154:212–9.CrossRef
21.
go back to reference Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats. BMC Anesthesiol. 2015;15:68.CrossRef Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats. BMC Anesthesiol. 2015;15:68.CrossRef
22.
go back to reference Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, Zhou C, Huang L, Li X, Zhou C. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway. Mediat Inflamm. 2013;2013:562154. Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, Zhou C, Huang L, Li X, Zhou C. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway. Mediat Inflamm. 2013;2013:562154.
23.
go back to reference Qiao H, Sanders RD, Ma D, Wu X, Maze M. Sedation improves early outcome in severely septic Sprague Dawley rats. Crit Care. 2009;13:R136.CrossRef Qiao H, Sanders RD, Ma D, Wu X, Maze M. Sedation improves early outcome in severely septic Sprague Dawley rats. Crit Care. 2009;13:R136.CrossRef
24.
go back to reference Xiang H, Hu B, Li Z, Li J. Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Inflammation. 2014;37:1763–70.CrossRef Xiang H, Hu B, Li Z, Li J. Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Inflammation. 2014;37:1763–70.CrossRef
25.
go back to reference Zamani MM, Keshavarz-Fathi M, Fakhri-Bafghi MS, Hirbod-Mobarakeh A, Rezaei N, Bahrami A, Nader ND. Survival benefits of dexmedetomidine used for sedating septic patients in intensive care setting: a systematic review. J Crit Care. 2016;32:93–100.CrossRef Zamani MM, Keshavarz-Fathi M, Fakhri-Bafghi MS, Hirbod-Mobarakeh A, Rezaei N, Bahrami A, Nader ND. Survival benefits of dexmedetomidine used for sedating septic patients in intensive care setting: a systematic review. J Crit Care. 2016;32:93–100.CrossRef
26.
go back to reference Gatta A, Verardo A, Bolognesi M. Hypoalbuminemia. Intern Emerg Med. 2012;7(Suppl 3):S193–9.CrossRef Gatta A, Verardo A, Bolognesi M. Hypoalbuminemia. Intern Emerg Med. 2012;7(Suppl 3):S193–9.CrossRef
27.
go back to reference Chelazzi C, Villa G, Mancinelli P, De Gaudio AR Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015;19:26.CrossRef Chelazzi C, Villa G, Mancinelli P, De Gaudio AR Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015;19:26.CrossRef
28.
go back to reference Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38–44.CrossRef Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38–44.CrossRef
29.
go back to reference Patel P, Walborn A, Rondina M, Fareed J, Hoppensteadt D. Markers of inflammation and infection in sepsis and disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2019;25:1076029619843338.CrossRef Patel P, Walborn A, Rondina M, Fareed J, Hoppensteadt D. Markers of inflammation and infection in sepsis and disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2019;25:1076029619843338.CrossRef
30.
go back to reference Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22:221–8.CrossRef Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22:221–8.CrossRef
31.
go back to reference Otto GP, Sossdorf M, Claus RA, Rodel J, Menge K, Reinhart K, Bauer M, Riedemann NC. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care. 2011;15:R183.CrossRef Otto GP, Sossdorf M, Claus RA, Rodel J, Menge K, Reinhart K, Bauer M, Riedemann NC. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care. 2011;15:R183.CrossRef
32.
go back to reference Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003;123:2043–9.CrossRef Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003;123:2043–9.CrossRef
33.
go back to reference Ranzani OT, Prada LF, Zampieri FG, Battaini LC, Pinaffi JV, Setogute YC, Salluh JI, Povoa P, Forte DN, Azevedo LC, Park M. Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: a cohort study. J Crit Care. 2012;27:525.e529–15.CrossRef Ranzani OT, Prada LF, Zampieri FG, Battaini LC, Pinaffi JV, Setogute YC, Salluh JI, Povoa P, Forte DN, Azevedo LC, Park M. Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: a cohort study. J Crit Care. 2012;27:525.e529–15.CrossRef
34.
go back to reference Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39:206–17.CrossRef Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39:206–17.CrossRef
36.
go back to reference Oh TK, Song IA, Lee JH. Clinical usefulness of C-reactive protein to albumin ratio in predicting 30-day mortality in critically ill patients: a retrospective analysis. Sci Rep. 2018;8:14977.CrossRef Oh TK, Song IA, Lee JH. Clinical usefulness of C-reactive protein to albumin ratio in predicting 30-day mortality in critically ill patients: a retrospective analysis. Sci Rep. 2018;8:14977.CrossRef
Metadata
Title
Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial
Publication date
01-12-2020
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03207-8

Other articles of this Issue 1/2020

Critical Care 1/2020 Go to the issue