Abstract
Anesthetic and sedative agents are among the most commonly used medications in critically ill patients. They alleviate pain and anxiety, and facilitate intensive care unit (ICU) care by rendering tolerable interventions that would otherwise be akin to torture — mechanical ventilation, dressing changes, cardioversion, and invasive procedures such as line insertion or bronchoscopy, to name a few. These agents modulate the function of the central and peripheral nervous systems. However they have effects on other organs that are often unanticipated, and occasionally profound.
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References
Haverkos HW, Lange RW (1990) Serious infections other than human immunodeficiency virus among intravenous drug users. J Infect Dis 161:894–902
Stevenson GW, Hall SC, Rudnick S, Seleny FL, Stevenson HC (1990) The effect of anesthetic agents on the human immune response. Anesthesiology 72:542–552
Stefano GB, Scharrer B, Smith EM, et al (1996) Opioid and opiate immunoregulatory processes. Crit Rev Immunol 16:109–144
Cabot PJ (2001) Immune-derived opioids and peripheral antinociception. Clin Exp Pharmacol Physiol 28:230–232
Wybran J, Appelboom T, Famaey J, Govaerts A (1979) Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T-lymphocytes. J Immunol 123:1068–1070
Chuang LF, Chuang TK, Killiam KF, et al (1995) Expression of kappa opioid receptors in human and monkey lymphocytes. Biochem Biophys Res Commun 209:1003–1010
Sharp BM, Roy S, Bidlack JM (1998) Evidence for opioid receptors on cells involved in host defense and the immune system. J Neuroimmunol 83:45–56
Jaeger K, Scheinichen D, Heine J, et al (1998) Remifentanil, fentanyl and alfentanil have no effect on the respiratory burst of neutrophils in vitro. Acta Anaesth Scand 42:1110–1113
Krumholz W, Demel C, Jung S, Meuthen G, Hempelmann G (1993) The influence of fentanyl and alfentanil on functions of human polymorphonuclear leukocytes in vitro. Acta Anaesth Scand 37:386–389
Stefano GB, Hartman A, Bilfinger TV, et al (1995) Presence of the μ 3 opiate receptor in endothelial cells: coupling to nitric oxide production and vasodilation. J Biol Chem 270: 30290–30293
Welters ID, Mezenbach A, Goumon Y, et al (2000) Morphine inhibits NF-Kb nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology 92:1677–1684
Stefano GB, Scharrer B (1994) Endogenous morphine and related opiates, a new class of chemical messengers. Adv Neuroimmunol 4:57–67
Nelson JC, Schneider GM, Lysle DT (2000) Involvement of central μ-, but not δ- or k-opioid receptors in immunomodulation. Brain Behav Immunity 14:170–184
Marcoli M, Ricevuti G, Mazzone A, Bekkering M, Lecchini S, Frigo GM (1988) Opioid-induced modification of granulocyte function. Int J Immunopharmacol 10:425–433
Ni X, Gritman KR, Eisenstein TK, Adler MW, Arforks KE, Turna RF (2000) Morphine attenuates leukocytes/endothelial interactions. Microvasc Res 60:121–130
Rud B, Benestad HB, Opdahl H (1988) Dual effect of thiopentone on human granulocyte activation. Non-intervention by ketamine and morphine. Acta Anaesthesiol Scand 32:316–322
Luza J (1992) Effect of morphine on phagocytic activity of the polymorphonuclears and monocytes. Acta Univ Palacki Olomuc Fac Me 134:47–57
Rojavin M, Szabo I, Bussiere J, et al (1993) Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages. Life Sci 53:997–1006
Pacifi R, Di Carlo S, Bacosi A, Zuccaro P (1993) Macrophage functions in drugs of abuse-treated mice. Int J Immunopharmacol 15:711–716
Grimm MC, Ben-Baruch A, Taub DD, et al (1998) Opiates transdeactivate chemokine receptors: delta and mu opiate-receptor mediated heterologous desensitization. J Exp Med 188:317–325
Eisenstein TK, Meissler JJ, Rogers TJ, Geller EB, Adler MW (1995) Mouse strain differences in immunosuppression by opioids in vitro. J Pharmacol Exp Ther 275:1484–1489
Govitaprong P, Suttitum T, Kotchabhakdi N, Uneklabh T (1998) Alteration of immune functions in heroin addicts and heroin withdrawal subjects. J Pharmacol Exp Ther 286: 883–889
Lockwood LL, Silber LH, Fleshner M, Laudenslager ML, Watkins LR, Maier SF (1994) Morphine-induced decreases in in vivo antibody responses. Brain Behav Immunol 8:24–36
Peterson PK, Molitor TW, Chao CC (1998) The opioid-cytokine connection. J Neuroimmu-nol 83:63–69
Alicea C, Belkowski SM, Eisenstein TK, Adler MW, Rogers TJ (1996) Inhibition of primary murine macrophage cytokine production in vitro following treatment with the κ-opioid agonist U50,488H. J Neuroimmunol 64:83–90
Chao CC, Gekker G, Sheng WS, Tsang M, Peterson PK (1994) Priming effect of morphine on the production of tumor necrosis factor-α by microglia: implications in respiratory burst of activity and human immunodeficiency virus-1 expression. J Pharmacol Exp Ther 269:198–203
Roy S, Cain KJ, Chapin RB, Charboneau RG (1998) Morphine modulates NF-KB activation in macrophages. Biochem Biophys Res Commun 245:392–396
Chao CC, Hu S, Molitor TW (1992) Morphine potentiates transforming growth factor-α release from human peripheral blood mononuclear cell cultures. J Pharmacol Exp Ther 262:19–28
Miyagi T, Chuang LF, Doi RH, Carlos MP, Torres JV, Chuang RY (2000) Morphine induces gene expression of CCR5 in human CEM xl74 lymphocytes. J Biol Chem 275:31305–31310
Hilburger ME, Aldler MW, Roger TJ, Eisenstein TK (1997) Morphine alters macrophage and lymphocyte populations in the spleen and peritoneal cavity. J Neuroimmunol 80:106–114
Singhal PC, Reddy K, Franki N, Sanwal V, Gibbons N (1997) Morphine induces splenocyte apoptosis and enhanced mRNA expression of cathepsin-B. Inflammation 21:609–617
Singhal PC, Sharma P, Kapase A (1998) Morphine enhances macrophage apoptosis. J Immunol 160:1886–1893
Singhal PC, Kapasi AA, Franki N, Reddy K (2000) Morphine-induced macrophage apoptosis: the role of transforming growth factor-beta. Immunology 100:57–62
Weiss M, Birkhahn A, Krone M, Schneider EM (1996) Do etomidate and propofol influence oxygen radical production of neutrophils? Immunopharmacol Immunotoxicol 18:291–307
Mikawa K, Akamatsu H, Nishina K, et al (1998) Propofol inhibits human neutrophil functions. Anesth Analg 87:695–700
Heine J, Jaeger K, Weingaertner N, Scheinichen D, Marx G, Piepenbrock S (2001) Effects of different preparation of propofol, diazepam, and etomidate on human neutrophils in vitro Acta Anaesth Scand 45:213–220
Davidson JA, Boom SJ, Pearsall FJ, Shang P, Ramsay G (1995) Comparison of the effects of four i.v. anaesthetic agents on polymorphonuclear leukocyte function. Br J Anaesth 74: 315–318
Galley HF, Dubbles AM, Webster NR (1998) The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes. Anesth Analg 86:1289–1293
Heine J, Jaeger K, Osthaus A, et al (2000) Anaesthesia with propofol decreases FMLP-induced neutrophil respiratory burst but not phagocytosis compared with isoflurane. Br J Anaesth 85:424–430
Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner GA, Bauer M (1998) Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology 89:1218–1227
Heine J, Scheinichen D, Jaeger K, André M, Leuwer M (1999) In vitro influence of parenteral lipid emulsions on the respiratory burst of neutrophils. Nutrition 15:540–545
Nagata T, Kansha M, Irita K, Takahashi S (2001) Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and Chemotaxis in human neutrophils. Br J Anesth 86:853–858
Gavish M, Bachman I, Shoukrun R, et al (1999) Enigma of the peripheral benzodiazepine receptor. Pharm Rev 51:629–650
Zavala F (1997) Benzodiazepines, anxiety and immunity. Pharmacol Ther 75:199–216
Barbaccia ML, Berkovich A, Guarnieri P, Slobodyansky E (1990) DBI (diazepam binding inhibitor): the precursor of a family of endogenous modulators of GABAa receptor function: history, perspectives, and clinical implications. Neurochem Res 15:161–168
Consentino M, Marino F, Cattaneo S, et al (2000) Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function. J Leuk Biol 67:637–643
Taupin V, Gogusev J, Descamps-Latscha B, Zavala F (1993) Modulation of tumor necrosis factor-α, interleukin-1/?, interleukin-6, interleukin-8 and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontatetraneuropeptide evidence for a role of prostaglandins. Mol Pharmacol 43:64–69
Cahard D, Canat X, Carayon P, Roque C, Casellas P, Le Fur G (1994) Subcellular localization of peripheral benzodiazepine receptors on human leukocytes. Lab Invest. 70:23–28
Woods MJ, Williams DC (1996) Multiple forms and location for the peripheral-type benzodiazepine receptor. Biochem Pharmacol 52:1805–1814
Zavala F, Taupin V, Descamps-Latscha B (1990) In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin-1, tumor necrosis factor and interleukin-6. J Pharm Exp Ther 255:442–450
Finnerty M, Marczynski TJ, Amirault HJ, Urbancic M, Andersen BR (1991) Benzodiazepines inhibit neutrophil Chemotaxis and superoxide production in a stimulus dependent manner, PK-11195 antagonizes these effects. Immunopharmacol 22:185–193
Covelli W, Decandia P, Altamura M, Jirillo E (1989) Diazepam inhibits phagocytosis and killing exerted by polymorphonuclear cells and monocytes from healthy donors. In vitro studies. Immunopharmacol Immunotoxicol 11:701–714
Inada T, Taniuchi S, Shingu K, Kobayashi Y, Fujisawa J, Nakao S (2001) Propofol depressed neutrophil hydrogen peroxide production more than midazolam, whereas adhesion molecule expression was minimally affected by both anesthetics in rats with abdominal sepsis. Anesth Analg 92:437–441
Heller A, Heller S, Blecken S, Urbaschek R, Koch T (1998) Effects of intravenous anesthetics on bacterial elimination in human blood in vitro. Acta Anaesthesiol Scand 42:518–526
Szekely A, Heindl B, Zahler S, Conzen PF, Becker BF (2000) Nonuniform behavior of intravenous anesthetics on postischemic adhesion of neutrophils in the guinea pig heart. Anesth Analg 90:1293–1300
Ruff MR, Pert CB, Weber RJ, Wahl LM, Wahl SM, Paul SM (1985) Benzodiazepine receptor-mediated Chemotaxis of human monocytes. Science 229:1281–1283
Krumholz W, Reussner D, Hempelmann G (1999) The influence of several intravenous anaesthetics on the Chemotaxis of human monocytes in vitro. Eur J Anaesthesiol 16:547–549
Marino F, Cattaneo S, Cosentino M, et al (2001) Diazepam stimulates migration and phagocytosis of human neutrophils: possible contribution of peripheral type benzodiazepine receptors and intracellular calcium. Pharmacology 63:42–49
Schlumpf M, Lichtensteiger W, RamScier H (1993) Diazepam treatment of pregnant rats differentially affects interleukin-1 and interleukin-2 secretion in their offspring during different phases of postnatal development. Pharmacol Toxicol 73:335–340
Oh YJ, Francis JW, Markelonis GJ, Oh TH (1992) Interleukin-lß and tumor necrosis factor-α increase peripheral-type benzodiazepine binding sites in cultured polygonal astrocytes. J Neurochem 58:2131–2138
Galdiero F, Bentivoglio C, Nuzzo I, et al (1995) Effects of benzodiazepines and resistance in mice. Life Sci 57:2413–2423
Salo M, Pirttikangas C-O, Pulkki K (1997) Effects of propofol emulsion and thiopentone on T helper type-1/type-2 balance in vitro. Anaesthesia 52:341–344
Nishina K, Akamatsu H, Mikakawa K, et al (1998) The inhibitory effects of thiopental, midazolan and ketamine on human neutrophil functions. Anesth Analg 86:159–165
Swanton BJ, Iohom G, Wang JH, Redmond HP, Shorten GD (2001) The effect of lidocaine on neutrophil respiratory burst during induction of general anaesthesia and tracheal intubation. Eur J Anaesth 18:524–529
Hofbauer R, Moser D, Salfinger H, Frass M, Kapiotis S (1998) Thiopental inhibits migration of human leukocytes through human endothelial cell monolayers in vitro. Intensive Care Med 24:973–976
Galley HF, DiMatteo MA, Webster NR (2000) Immunomodulation by anaesthetic, sedative and analgesic agents: does it matter? Intensive Care Med 26:267–274
Schalen W, Messeter K, Nordstrom C-H (1992) Complications and side effects during thiopentone therapy in patients with severe head injuries. Acta Anaesth Scand 36:369–377
Stover JF, Stocker R (1998) Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury. Eur J Clin Pharmacol 54:529–534
Ishikawa K, Tanaka H, Shiozaki T, et al (2000) Characteristics of infection and leukocyte count in severely head-injured patients treated with mild hypothermia. J Trauma 49:912–922
Martinsson T, Oda T, Fernvik E, Roempke K, Dalsgaard C, Svensjo E (1997) Ropivacaine inhibits leukocyte rolling, adhesion and CDllb/CD18 expression. J Pharm Exp Ther 283: 59–65
Schmidt W, Schmidt H, Bauer H, Gebhard MM, Martin E (1997) Influence of lidocaine on endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo. Anaesthesiology 87:617–624
Azuma Y, Shinohara M, Wang P, Suese Y, Yasuda H, Ohura K (2000) Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils. Int J Immunopharm 22:789–796
Welters ID, Menzebach A, Langefeld TW, Menzebach M, Hempelmann G (2001) Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function. Acta Anaesth Scand 45:570–575
Hammer R, Dahlgren C, Stendahl O (1985) Inhibition of human leukocyte metabolism and random mobility by local anaesthesia. Acta Anaesth Scand 29:520–523
Hollman MW, Gross A, Jelacin N, Duriex ME (2001) Local anesthetic effects on priming and activation of human neutrophils. Anesthesiology 95:113–122
Takao Y, Mikawa K, Nishina K, Maekawa N, Obara H (1996) Lidocaine attenuates hyperoxic lung injury in rabbits. Acta Anaesth Scand 40:318–325
Kiyonar Y, Nishina K, Mikawa K, Maekawa N, Obara H (2000) Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin. Crit Care Med 28:484–489
Nishina K, Mikawa K, Takao Y, Shiga M, Maekawa N, Obara H (1998) Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits. Anesthesiology 88:1300–1309
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Kummer, C., Netto, F.S., Marshall, J.C. (2002). The Immunomodulatory Effects of Anesthetic and Analgesic Agents. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine 2002. Yearbook of Intensive Care and Emergency Medicine 2002, vol 2002. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56011-8_14
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DOI: https://doi.org/10.1007/978-3-642-56011-8_14
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