Opioids and infections in the intensive care unit should clinicians and patients be concerned?
There is a large body of experimental evidence in research animals and in vitro models that opioids suppress the immune system. If this effect occurs in acute human disease, then patients cared for in Intensive Care Units (ICUs) would be a particularly vulnerable population. ICU patients have the most severe forms of acute infection, have the greatest risk of acquiring new infections in the hospital, and are exposed to high doses of opioids for long periods of time. We review the epidemiology of ICU infections and the pharmacoepidemiology of opioid use in critically ill patients. We critique the limited human research examining the relationship between opioids and infection and make recommendations on designing future clinical studies that could close the knowledge gap about the true hazards of opioid use in hospitalized patients.
Weinert
Craig R
CR
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota Medical School, MMC 276420 Delaware St, SE, Minneapolis, MN 55455, USA. weine006@umn.edu
Kethireddy
Shravan
S
Roy
Sabita
S
D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007239:Infections / Q000453:epidemiology*; D007362:Intensive Care Units
D000701:Analgesics, Opioid
Crit Care Med. 2001 Jul;29(7):1303-10
11445675
Intensive Care Med. 2002 Feb;28(2):108-21
11907653
Addiction. 1993 Feb;88(2):257-63
8220063
Anesthesiology. 2000 Jun;92(6):1677-84
10839919
J Infect Dis. 2000 Apr;181(4):1350-8
10762566
Ann Intern Med. 1993 Nov 1;119(9):906-7
8215003
Chest. 2000 Oct;118(4):1100-5
11035684
Crit Care Med. 1994 May;22(5):763-7
8181283
J Intensive Care Med. 2003 May-Jun;18(3):139-45
14984632
Chest. 2005 May;127(5):1722-8
15888852
Anesth Analg. 1998 Jun;86(6):1219-24
9620508
Am J Respir Crit Care Med. 1996 Mar;153(3):1012-8
8630539
Crit Care Med. 1999 Aug;27(8):1461-5
10470750
Am J Crit Care. 2001 May;10(3):156-65; quiz 166-7
11340738
Anaesthesia. 2001 Jan;56(1):4-8
11167428
Anesth Analg. 1998 Jan;86(1):159-65
9428872
Brain Behav Immun. 2007 Feb;21(2):195-201
16870392
Crit Care Med. 1998 Apr;26(4):676-84
9559604
Chest. 1992 Jun;101(6):1625-32
1600784
Arch Intern Med. 2008 May 26;168(10):1034-46
18504331
J Infect Dis. 2002 Nov 15;186(10):1526-9
12404175
Crit Care Med. 2006 May;34(5):1395-401
16540957
Chest. 2005 Oct;128(4):2749-57
16236951
Intensive Crit Care Nurs. 2003 Dec;19(6):350-62
14637295
Chest. 1993 Feb;103(2):557-64
8432154
J Neuroimmunol. 2004 Apr;149(1-2):90-100
15020069
Br J Pharmacol. 1997 Jun;121(4):834-40
9208156
Drugs R D. 2006;7(2):63-71
16542053
JAMA. 2001 Dec 5;286(21):2703-10
11730446
Crit Care Med. 2005 Jan;33(1):120-7
15644658
Acta Anaesthesiol Scand. 2004 Sep;48(8):944-50
15315610
Crit Care Med. 1995 Feb;23(2):286-93
7867354
Anesth Analg. 1998 Jun;86(6):1289-93
9620522
J Pharmacol Exp Ther. 1991 Nov;259(2):745-50
1941622
Crit Care Med. 2006 Sep;34(9):2302-8; quiz 2309
16849995
Lancet. 2004 May 22;363(9422):1673-82
15158628
J Clin Oncol. 2008 May 10;26(14):2396-404
18467732
Mol Pharmacol. 2004 Feb;65(2):437-42
14742686
N Engl J Med. 1997 Mar 27;336(13):912-8
9070471
Crit Care. 2005 Apr;9(2):R117-23
15774043
Semin Clin Neuropsychiatry. 2001 Oct;6(4):295-307
11607924
JAMA. 2002 Jan 16;287(3):345-55
11790214
Adv Exp Med Biol. 1998;437:21-31
9666253
Crit Care Med. 2007 Feb;35(2):393-401
17205015
Br J Anaesth. 2001 Aug;87(2):186-92
11493487
Crit Care Med. 2006 May;34(5):1326-32
16540958
J Immunol. 2005 Nov 15;175(10):6361-7
16272288
Intensive Care Med. 1997 Dec;23(12):1258-63
9470082
Crit Care Med. 2002 Nov;30(11):2468-72
12441756
Br J Anaesth. 1993 Mar;70(3):317-21
8471377
Anesth Analg. 2003 Sep;97(3):822-827
12933409
Crit Care Med. 1997 Jan;25(1):33-40
8989173
Crit Care Med. 2005 Apr;33(4):766-71
15818103
JAMA. 1991 Nov 27;266(20):2870-5
1942456
Ann Pharmacother. 1997 Feb;31(2):148-53
9034412
Infect Immun. 2006 Sep;74(9):5221-6
16926415
Aust Crit Care. 1997 Sep;10(3):90-3
9362609
JAMA. 2002 Sep 25;288(12):1499-507
12243637
Crit Care. 2007;11(4):R77
17629900
Cell Immunol. 2006 Jan;239(1):41-8
16698002
J Infect Dis. 1997 Jul;176(1):183-8
9207365
Pharmacotherapy. 2001 Apr;21(4):431-6
11310516
J Leukoc Biol. 2008 Mar;83(3):471-82
18171697
J Pharmacol Exp Ther. 1995 Mar;272(3):1246-51
7891340
Pharmacotherapy. 2000 Jan;20(1):75-82
10641977
J Pharmacol Exp Ther. 1990 Feb;252(2):605-9
2313590
Intensive Care Med. 2006 Aug;32(8):1137-42
16741692
Chest. 2001 Dec;120(6):2059-93
11742943
Intensive Crit Care Nurs. 2006 Feb;22(1):22-31
15927469
Ann Oncol. 1999 Dec;10(12):1511-4
10643545
Am J Surg. 2006 Jul;192(1):82-6
16769281
Chemotherapy. 1997 May-Jun;43(3):198-203
9142461
Crit Care Med. 2006 Apr;34(4):1016-24
16505703
Anesth Analg. 2008 Apr;106(4):1142-9, table of contents
18349186
Crit Care Med. 1999 Dec;27(12):2609-15
10628598
N Engl J Med. 2000 May 18;342(20):1471-7
10816184
JAMA. 2003 Jun 11;289(22):2983-91
12799407
Anesth Analg. 1998 Sep;87(3):695-700
9728856
J Neuropathol Exp Neurol. 2007 Oct;66(10):923-31
17917586
Infect Immun. 2005 Dec;73(12):7953-9
16299287
Nat Rev Drug Discov. 2005 Oct;4(10):854-65
16224456
Crit Care Med. 1994 Jun;22(6):974-80
8205830
Crit Care Med. 1999 Jul;27(7):1271-5
10446819
Crit Care Med. 2001 Dec;29(12):2258-63
11801819
J Opioid Manag. 2008 Jan-Feb;4(1):27-33
18444445
Pharmacol Rev. 2004 Sep;56(3):351-69
15317908
Lancet. 2008 Jan 12;371(9607):126-34
18191684
Microbiol Immunol. 2006;50(7):543-7
16858145
Heart Lung. 1994 Mar-Apr;23(2):169-76
8206776
J Neuroimmunol. 2000 Nov 1;111(1-2):139-45
11063831
Crit Care Med. 2004 Jan;32(1):39-52
14707558
Crit Care Med. 2006 Feb;34(2):374-80
16424717
N Engl J Med. 1999 Feb 11;340(6):409-17
9971864
Blood Rev. 2007 Nov;21(6):327-48
17804128
J Immunol. 2005 Jan 1;174(1):426-34
15611267
Crit Care Med. 2002 Jan;30(1):119-41
11902253
J Pharmacol Exp Ther. 1995 Feb;272(2):498-504
7853162
Ann Pharmacother. 2003 Apr;37(4):473-7
12659598
Intensive Care Med. 2000 Jul;26(7):922-8
10990107
Intensive Care Med. 1999 Feb;25(2):186-91
10193546
Chest. 1998 Aug;114(2):541-8
9726743
J Infect Dis. 2005 Mar 15;191(6):886-9
15717263
Ann Pharmacother. 1997 Jun;31(6):689-95
9184706