Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-28T12:52:59.986Z Has data issue: false hasContentIssue false
  • English
  • Français

The Relationship Between Sedatives, Sedative Strategy, and Healthcare-Associated Infection: A Systematic Review

Published online by Cambridge University Press:  20 June 2016

Daniel A. Caroff ,
Paul M. Szumita  and
Michael Klompas
Daniel A. Caroff*
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Healthcare Institute, Boston, Massachusetts Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
Paul M. Szumita
Affiliation:
Pharmacy Department, Brigham and Women’s Hospital, Boston, Massachusetts
Michael Klompas
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Healthcare Institute, Boston, Massachusetts Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
*
Address correspondence to Daniel Caroff, MD, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Drive, Ste 401, Boston, MA 02215 ([email protected]).
Get access Rights & Permissions [Opens in a new window]

Abstract

BACKGROUND

Healthcare-associated infections (HAIs) cause significant morbidity in critically ill patients. An underappreciated but potentially modifiable risk factor for infection is sedation strategy. Recent trials suggest that choice of sedative agent, depth of sedation, and sedative management can influence HAI risk in mechanically ventilated patients.

OBJECTIVE

To better characterize the relationships between sedation strategies and infection.

METHODS

Systematic literature review.

RESULTS

We found 500 articles and accepted 70 for review. The 3 most common sedatives for mechanically ventilated patients (benzodiazepines, propofol, and dexmedetomidine) have different pharmacologic and immunomodulatory effects that may impact infection risk. Clinical data are limited but retrospective observational series have found associations between sedative use and pneumonia whereas prospective studies of sedative interruptions have reported possible decreases in bloodstream infections, pneumonia, and ventilator-associated events.

CONCLUSION

Infection rates appear to be highest with benzodiazepines, intermediate with propofol, and lowest with dexmedetomidine. More data are needed but studies thus far suggest that a better understanding of sedation practices and infection risk may help hospital epidemiologists and critical care practitioners find new ways to mitigate infection risk in critically ill patients.

Infect Control Hosp Epidemiol 2016;1–9

Type
Review Article
Information
Infection Control & Hospital Epidemiology , Volume 37 , Issue 10 , October 2016 , pp. 1234 - 1242
Copyright
© 2016 by The Society for Healthcare Epidemiology of America. All rights reserved 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Healthcare-associated infections (HAI) progress report. Centers for Disease Control and Prevention website. http://www.cdc.gov/hai/progress-report/. Published 2013. Accessed November 18, 2015.Google Scholar
2. Yokoe, DS, Anderson, DJ, Berenholtz, SM, et al. A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates. Infect Control Hosp Epidemiol 2014;35:S21–S31.Google Scholar
3. Hansen, TG. Sedative medications outside the operating room and the pharmacology of sedatives. Curr Opin Anaesthesiol 2015;28:446–452.CrossRefGoogle ScholarPubMed
4. McCollam, JS, O'Neil, MG, Norcross, ED, Byrne, TK, Reeves, ST. Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison. Crit Care Med 1999;27:2454–2458.Google Scholar
5. Zaal, IJ, Devlin, JW, Hazelbag, M, et al. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med 2015;41:2130–2137.Google Scholar
6. Pandharipande, P, Shintani, A, Peterson, J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21–26.Google Scholar
7. Larijani, GE, Gratz, I, Afshar, M, Jacobi, AG. Clinical pharmacology of propofol: an intravenous anesthetic agent [published correction appears in DICP 1990;24:102]. DICP 1989;23:743–749.Google Scholar
8. Trapani, G, Altomare, C, Liso, G, Sanna, E, Biggio, G. Propofol in anesthesia: mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 2000;7:249–271.Google Scholar
9. Jacobi, J, Fraser, GL, Coursin, DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002;30:119–141.Google Scholar
10. Crozier, TA. The “propofol infusion syndrome”: myth or menace? Eur J Anaesthesiol 2006;23:987–989.Google Scholar
11. Mirrakhimov, AE, Voore, P, Halytskyy, O, Khan, M, Ali, AM. Propofol infusion syndrome in adults: a clinical update. Crit Care Res Pract 2015;2015:260385.Google Scholar
12. Judge reverses Precedex patent invalidation following deal. Law 360 website. http://www.law360.com/articles/514139/judge-reverses-precedex-patent-invalidation-following-deal. Accessed November 11, 2015.Google Scholar
13. Xia, ZQ, Chen, SQ, Yao, X, Xie, CB, Wen, SH, Liu, KX. Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials. J Surg Res 2013;185:833–843.Google Scholar
14. Riker, RR, Shehabi, Y, Bokesch, PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301:489–499.Google Scholar
15. Hall, JE, Uhrich, TD, Barney, JA, Arain, SR, Ebert, TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699–705.Google Scholar
16. Le Guen, M, Liu, N, Tounou, F, et al. Dexmedetomidine reduces propofol and remifentanil requirements during bispectral index-guided closed-loop anesthesia: a double-blind, placebo-controlled trial. Anesth Analg 2014;118:946–955.Google Scholar
17. Bhana, N, Goa, KL, McClellan, KJ. Dexmedetomidine. Drugs 2000;59:263–268.Google Scholar
18. Smith, MA, Hibino, M, Falcione, BA, Eichinger, KM, Patel, R, Empey, KM. Immunosuppressive aspects of analgesics and sedatives used in mechanically ventilated patients: an underappreciated risk factor for the development of ventilator-associated pneumonia in critically ill patients. Ann Pharmacother 2013;48:77–85.Google Scholar
19. Nseir, S, Makris, D, Mathieu, D, Durocher, A, Marquette, CH. Intensive care unit-acquired infection as a side effect of sedation. Crit Care 2010;14:R30.Google Scholar
20. Miyawaki, T, Sogawa, N, Maeda, S, Kohjitani, A, Shimada, M. Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide. Cytokine 2001;15:320–327.Google Scholar
21. Galley, HF, Dubbels, AM, Webster, NR. The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes. Anesth Analg 1998;86:1289–1293.Google Scholar
22. Wei, M, Li, L, Meng, R, et al. Suppressive effect of diazepam on IFN-gamma production by human T cells. Int Immunopharmacol 2010;10:267–271.Google Scholar
23. Bidri, M, Royer, B, Averlant, G, Bismuth, G, Guillosson, JJ, Arock, M. Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines. Immunopharmacology 1999;43:75–86.Google Scholar
24. Matsumoto, T, Ogata, M, Koga, K, Shigematsu, A. Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice. Antimicrob Agents Chemother 1994;38:812–816.Google Scholar
25. Galdiero, F, Bentivoglio, C, Nuzzo, I, et al. Effects of benzodiazepines on immunodeficiency and resistance in mice. Life Sci 1995;57:2413–2423.Google Scholar
26. Ohta, N, Ohashi, Y, Takayama, C, Mashimo, T, Fujino, Y. Midazolam suppresses maturation of murine dendritic cells and priming of lipopolysaccharide-induced T helper 1-type immune response. Anesthesiology 2011;114:355–362.Google Scholar
27. Nishina, K, Akamatsu, H, Mikawa, K, et al. The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 1998;86:159–165.Google Scholar
28. Helmy, SA, Al-Attiyah, RJ. The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients. Anaesthesia 2001;56:4–8.CrossRefGoogle ScholarPubMed
29. Visvabharathy, L, Xayarath, B, Weinberg, G, Shilling, RA, Freitag, NE. Propofol increases host susceptibility to microbial infection by reducing subpopulations of mature immune effector cells at sites of infection. PLOS ONE 2015;10:e0138043.Google Scholar
30. Inada, T, Kubo, K, Kambara, T, Shingu, K. Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells. Can J Anaesth 2009;56:222–229.Google Scholar
31. Inada, T, Kubo, K, Shingu, K. Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E(2) production using intravenous anesthetic propofol. Int Immunopharmacol 2010;10:1200–1208.Google Scholar
32. Mikawa, K, Akamatsu, H, Nishina, K, et al. Propofol inhibits human neutrophil functions. Anesth Analg 1998;87:695–700.Google Scholar
33. O'Donnell, NG, McSharry, CP, Wilkinson, PC, Asbury, AJ. Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro in the presence or absence of human serum albumin. Br J Anaesth 1992;69:70–74.Google Scholar
34. Taniguchi, T, Kanakura, H, Yamamoto, K. Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats. Crit Care Med 2002;30:904–907.Google Scholar
35. Gao, J, Zeng, BX, Zhou, LJ, Yuan, SY. Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats. Br J Anaesth 2004;92:277–279.Google Scholar
36. 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;32:1322–1326.CrossRefGoogle ScholarPubMed
37. 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.Google Scholar
38. Miranda, ML, Balarini, MM, Bouskela, E. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis. Anesthesiology 2015;122:619–630.Google Scholar
39. Yang, CL, Tsai, PS, Huang, CJ. Effects of dexmedetomidine on regulating pulmonary inflammation in a rat model of ventilator-induced lung injury. Acta Anaesthesiol Taiwan 2008;46:151–159.CrossRefGoogle Scholar
40. Geloen, A, Chapelier, K, Cividjian, A, et al. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med 2013;41:e431–e438.Google Scholar
41. Xu, L, Bao, H, Si, Y, Wang, X. Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice. Inflamm Res 2013;62:507–514.Google Scholar
42. Wu, L, Lv, H, Luo, W, Jin, S, Hang, Y. Effects of dexmedetomidine on cellular immunity of perioperative period in children with brain neoplasms. Int J Clin Exp Med 2015;8:2748–2753.Google Scholar
43. Tasdogan, M, Memis, D, Sut, N, Yuksel, M. Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth 2009;21:394–400.Google Scholar
44. Robinson, BR, Mueller, EW, Henson, K, Branson, RD, Barsoum, S, Tsuei, BJ. An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay. J Trauma 2008;65:517–526.Google Scholar
45. Shelly, MP, Sultan, MA, Bodenham, A, Park, GR. Midazolam infusions in critically ill patients. Eur J Anaesthesiol 1991;8:21–27.Google Scholar
46. Agarwal, V, O'Neill, PJ, Cotton, BA, et al. Prevalence and risk factors for development of delirium in burn intensive care unit patients. J Burn Care Res 2010;31:706–715.Google Scholar
47. Pandharipande, PP, Sanders, RD, Girard, TD, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care 2010;14:R38.Google Scholar
48. Bryczkowski, SB, Lopreiato, MC, Yonclas, PP, Sacca, JJ, Mosenthal, AC. Delirium prevention program in the surgical intensive care unit improved the outcomes of older adults. J Surg Res 2014;190:280–288.Google Scholar
49. Mehta, S, Cook, D, Devlin, JW, et al. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med 2015;43:557–566.Google Scholar
50. Lin, SM, Huang, CD, Liu, CY, et al. Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients. J Crit Care 2008;23:372–379.Google Scholar
51. Bellelli, G, Speciale, S, Barisione, E, Trabucchi, M. Delirium subtypes and 1-year mortality among elderly patients discharged from a post-acute rehabilitation facility. J Gerontol A Biol Sci Med Sci 2007;62:1182–1183.Google Scholar
52. Ely, EW, Shintani, A, Truman, B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753–1762.Google Scholar
53. Shehabi, Y, Riker, RR, Bokesch, PM, et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311–2318.Google Scholar
54. Jaber, S, Chanques, G, Altairac, C, et al. A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest 2005;128:2749–2757.CrossRefGoogle Scholar
55. Chanques, G, Jaber, S, Barbotte, E, et al. Impact of systematic evaluation of pain and agitation in an intensive care unit. Crit Care Med 2006;34:1691–1699.Google Scholar
56. de Irala Estevez, J, Fernandez-Crehuet Navajas, R, Diaz Molina, C, Martinez de la Concha, D, Salcedo Leal, I, Masa Calles, J. [Risk factors for pneumonia, bacteremia, and urinary tract infection in an intensive care unit]. Med Clin (Barc) 1997;109:733–737.Google Scholar
57. Klompas, M. Ventilator-associated events surveillance: a patient safety opportunity. Curr Opin Crit Care 2013;19:424–431.Google Scholar
58. Klompas, M. Potential strategies to prevent ventilator-associated events. Am J Respir Crit Care Med 2015;192:1420–1430.Google Scholar
59. Klompas, M, Magill, S, Robicsek, A, et al. Objective surveillance definitions for ventilator-associated pneumonia. Crit Care Med 2012;40:3154–3161.Google Scholar
60. Lewis, SC, Li, L, Murphy, MV, Klompas, M, CDC Prevention Epicenters Program. Risk factors for ventilator-associated events: a case-control multivariable analysis. Crit Care Med 2014;42:1839–1848.Google Scholar
61. Shehabi, Y, Bellomo, R, Reade, MC, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med 2012;186:724–731.Google Scholar
62. Shehabi, Y, Chan, L, Kadiman, S, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med 2013;39:910–918.Google Scholar
63. Quenot, JP, Ladoire, S, Devoucoux, F, et al. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med 2007;35:2031–2036.Google Scholar
64. Strøm, T, Martinussen, T, Toft, P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375:475–480.Google Scholar
65. Muscedere, J, Sinuff, T, Heyland, DK, et al. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 2013;144:1453–1460.Google Scholar
66. Posa, P BD, Bogan, B, DiGiovine, B, et al. Compliance with spontaneous breathing trial protocol associated with lower VAE rates. Crit Care Med 2014;42:A1547.Google Scholar
67. Klompas, M, Anderson, D, Trick, W, et al. The preventability of ventilator-associated events. The CDC Prevention Epicenters Wake Up and Breathe Collaborative. Am J Respir Crit Care Med 2015;191:292–301.Google Scholar
68. Schweickert, WD, Gehlbach, BK, Pohlman, AS, Hall, JB, Kress, JP. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med 2004;32:1272–1276.Google Scholar
69. Fraser, GL, Devlin, JW, Worby, CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med 2013;41:S30–S38.Google Scholar
70. Barr, J, Fraser, GL, Puntillo, K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263–306.Google Scholar
71. Lonardo, NW, Mone, MC, Nirula, R, et al. Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med 2014;189:1383–1394.Google Scholar
72. Klompas, M, Li, L, Szumita, P, Kleinman, K, Murphy, MV, CDC Prevention Epicenters Program. Associations between different sedatives and ventilator-associated events, length-of-stay, and mortality in mechanically ventilated patients. Chest 2015.Google Scholar