Immune Function following Major Spinal Surgery and General Anesthesia

Lance M. Relland; Mark Hall; David P. Martin; Jyotsna Nateri; Lisa Hanson-Huber; Allan Beebe; Walter Samora; Jan Klamar; Jennifer Muszynski; Joseph D. Tobias

doi:10.1055/s-0040-1716668

Journal of Pediatric Intensive Care, Inhaltsverzeichnis

J Pediatr Intensive Care 2021; 10(04): 248-255
DOI: 10.1055/s-0040-1716668

Original Article

Immune Function following Major Spinal Surgery and General Anesthesia

Lance M. Relland

¹Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States

²Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Mark Hall

²Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States

³Department of Pediatrics, Division of Critical Care, Nationwide Children's Hospital, Columbus, Ohio, United States

,

David P. Martin

¹Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Jyotsna Nateri

²Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Lisa Hanson-Huber

²Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Allan Beebe

⁴Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Walter Samora

⁴Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Jan Klamar

⁴Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Jennifer Muszynski

²Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States

³Department of Pediatrics, Division of Critical Care, Nationwide Children's Hospital, Columbus, Ohio, United States

,

Joseph D. Tobias

¹Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States

› Institutsangaben

Abstract

There are reported differences in the effects that general anesthetics may have on immune function after minor surgery. To date, there are no prospective trials comparing total intravenous anesthesia (TIVA) with a volatile agent-based technique and its effects on immune function after major spinal surgery in adolescents. Twenty-six adolescents undergoing spinal fusion were randomized to receive TIVA with propofol-remifentanil or a volatile agent-based technique with desflurane-remifentanil. Immune function measures were based on the antigen-presenting and cytokine production capacity, and relative proportions of cell populations. Overall characteristics of the two groups did not differ in terms of perioperative times, hemodynamics, or fluid shifts, but those treated with propofol had lower bispectral index values. Experimental groups had relatively high baseline interleukin-10 values, but both showed a significant inflammatory response with similar changes in their respective immune functions. This included a shift toward a granulocytic predominance; a transient reduction in monocyte markers with significant decrease in antigen-presenting capacity and cytokine production capacity. Anesthetic choice does not appear to differentially impact immune function, but exposure to anesthetics and surgical trauma results in reproducibly measurable suppression of both innate and adaptive immunity in adolescents undergoing posterior spinal fusion. The magnitude of this suppression was modest when compared with pediatric and adult patients with critical illnesses. This study highlighted the need to evaluate immune function in a broader population of surgical patients with higher severity of illness.

Keywords

anesthesia - spinal fusion - immunity - immune suppression - cytokine - trauma

Volltext

Referenzen

References
1 Konieczny MR, Senyurt H, Krauspe R. Epidemiology of adolescent idiopathic scoliosis. J Child Orthop 2013; 7 (01) 3-9
2 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 (02) 161-165
3 McBride WT, Armstrong MA, McBride SJ. Immunomodulation: an important concept in modern anaesthesia. Anaesthesia 1996; 51 (05) 465-473
4 Salo M. Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol Scand 1992; 36 (03) 201-220
5 Islam MN, Bradley BA, Ceredig R. Sterile post-traumatic immunosuppression. Clin Transl Immunology 2016; 5 (04) e77
6 Schneemilch CE, Ittenson A, Ansorge S, Hachenberg T, Bank U. Effect of 2 anesthetic techniques on the postoperative proinflammatory and anti-inflammatory cytokine response and cellular immune function to minor surgery. J Clin Anesth 2005; 17 (07) 517-527
7 Shields BJ, Cohen DM, Harbeck-Weber C, Powers JD, Smith GA. Pediatric pain measurement using a visual analogue scale: a comparison of two teaching methods. Clin Pediatr (Phila) 2003; 42 (03) 227-234
8 Hall MW, Knatz NL, Vetterly C. et al. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011; 37 (03) 525-532
9 Hall MW, Geyer SM, Guo CY. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators. et al Innate immune function and mortality in critically ill children with influenza: a multicenter study. Crit Care Med 2013; 41 (01) 224-236
10 Muszynski JA, Nofziger R, Moore-Clingenpeel M. et al. Early immune function and duration of organ dysfunction in critically III children with sepsis. Am J Respir Crit Care Med 2018; 198 (03) 361-369
11 Oertelt-Prigione S. Immunology and the menstrual cycle. Autoimmun Rev 2012; 11 (6-7): A486-A492
12 Cheadle WG, Mercer-Jones M, Heinzelmann M, Polk Jr HC. Sepsis and septic complications in the surgical patient: who is at risk?. Shock 1996; 6 (Suppl. 01) S6-S9
13 Flohé S, Lendemans S, Schade FU, Kreuzfelder E, Waydhas C. Influence of surgical intervention in the immune response of severely injured patients. Intensive Care Med 2004; 30 (01) 96-102
14 Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Miyazaki M. Immunosuppression following surgical and traumatic injury. Surg Today 2010; 40 (09) 793-808
15 Volk HD, Reinke P, Döcke WD. Clinical aspects: from systemic inflammation to ‘immunoparalysis’. Chem Immunol 2000; 74: 162-177
16 Wakefield CH, Carey PD, Foulds S, Monson JR, Guillou PJ. Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 1993; 80 (02) 205-209
17 Allen ML, Peters MJ, Goldman A. et al. Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 2002; 30 (05) 1140-1145
18 Volk HD, Reinke P, Krausch D. et al. Monocyte deactivation--rationale for a new therapeutic strategy in sepsis. Intensive Care Med 1996; 22 (Suppl. 04) S474-S481
19 Majetschak M, Flach R, Kreuzfelder E. et al. The extent of traumatic damage determines a graded depression of the endotoxin responsiveness of peripheral blood mononuclear cells from patients with blunt injuries. Crit Care Med 1999; 27 (02) 313-318
20 Heagy W, Nieman K, Hansen C, Cohen M, Danielson D, West MA. Lower levels of whole blood LPS-stimulated cytokine release are associated with poorer clinical outcomes in surgical ICU patients. Surg Infect (Larchmt) 2003; 4 (02) 171-180
21 Maddux AB, Hiller TD, Overdier KH, Pyle LL, Douglas IS. Innate immune function and organ failure recovery in adults with sepsis. J Intensive Care Med 2019; 34 (06) 486-494
22 Muszynski JA, Nofziger R, Greathouse K. et al. Innate immune function predicts the development of nosocomial infection in critically injured children. Shock 2014; 42 (04) 313-321
23 Allen ML, Hoschtitzky JA, Peters MJ. et al. Interleukin-10 and its role in clinical immunoparalysis following pediatric cardiac surgery. Crit Care Med 2006; 34 (10) 2658-2665
24 Cornell TT, Sun L, Hall MW. et al. Clinical implications and molecular mechanisms of immunoparalysis after cardiopulmonary bypass. J Thorac Cardiovasc Surg 2012; 143 (05) 1160-1166.e1
25 Hotchkiss RS, Tinsley KW, Swanson PE. et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol 2001; 166 (11) 6952-6963
26 Felmet KA, Hall MW, Clark RS, Jaffe R, Carcillo JA. Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. J Immunol 2005; 174 (06) 3765-3772
27 Thakkar RK, Diltz Z, Drews JD. et al. Abnormal lymphocyte response after pediatric thermal injury is associated with adverse outcomes. J Surg Res 2018; 228: 221-227
28 Boomer JS, To K, Chang KC. et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011; 306 (23) 2594-2605
29 Cleary TG, Pickering LK. Mechanisms of intralipid effect on polymorphonuclear leukocytes. J Clin Lab Immunol 1983; 11 (01) 21-26
30 Fröhlich D, Rothe G, Schwall B, Schmitz G, Hobbhahn J, Taeger K. Thiopentone and propofol, but not methohexitone nor midazolam, inhibit neutrophil oxidative responses to the bacterial peptide FMLP. Eur J Anaesthesiol 1996; 13 (06) 582-588
31 Galley HF, Webster NR. Effects of propofol and thiopentone on the immune response. Anaesthesia 1997; 52 (09) 921-923
32 Jensen AG, Dahlgren C, Eintrei C. Propofol decreases random and chemotactic stimulated locomotion of human neutrophils in vitro. Br J Anaesth 1993; 70 (01) 99-100
33 Kelbel I, Koch T, Weber A, Schiefer HG, van Ackern K, Neuhof H. Alterations of bacterial clearance induced by propofol. Acta Anaesthesiol Scand 1999; 43 (01) 71-76
34 Mikawa K, Akamatsu H, Nishina K. et al. Propofol inhibits human neutrophil functions. Anesth Analg 1998; 87 (03) 695-700
35 Murphy PG, Ogilvy AJ, Whiteley SM. The effect of propofol on the neutrophil respiratory burst. Eur J Anaesthesiol 1996; 13 (05) 471-473
36 Nagata T, Kansha M, Irita K, Takahashi S. Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils. Br J Anaesth 2001; 86 (06) 853-858
37 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 (01) 70-74
38 Ohmizo H, Iwama H, Sugita T. Complement activation by propofol and its effect during propofol anaesthesia. Anaesth Intensive Care 1999; 27 (06) 623-627
39 Skoutelis A, Lianou P, Papageorgiou E, Kokkinis K, Alexopoulos K, Bassaris H. Effects of propofol and thiopentone on polymorphonuclear leukocyte functions in vitro. Acta Anaesthesiol Scand 1994; 38 (08) 858-862
40 Ferrero E, Ferrero ME, Marni A. et al. In vitro effects of halothane on lymphocytes. Eur J Anaesthesiol 1986; 3 (04) 321-330
41 Fröhlich D, Rothe G, Schwall B. et al. Effects of volatile anaesthetics on human neutrophil oxidative response to the bacterial peptide FMLP. Br J Anaesth 1997; 78 (06) 718-723
42 Giraud O, Molliex S, Rolland C. et al. Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by rat alveolar type II cells in primary culture. Anesthesiology 2003; 98 (01) 74-81
43 Hamra JG, Yaksh TL. Halothane inhibits T cell proliferation and interleukin-2 receptor expression in rats. Immunopharmacol Immunotoxicol 1996; 18 (02) 323-336
44 Mitsuhata H, Shimizu R, Yokoyama MM. Suppressive effects of volatile anesthetics on cytokine release in human peripheral blood mononuclear cells. Int J Immunopharmacol 1995; 17 (06) 529-534
45 Nakagawara M, Takeshige K, Takamatsu J, Takahashi S, Yoshitake J, Minakami S. Inhibition of superoxide production and Ca2+ mobilization in human neutrophils by halothane, enflurane, and isoflurane. Anesthesiology 1986; 64 (01) 4-12
46 Stevenson GW, Hall S, Miller PJ. et al. The effect of anesthetic agents on human immune system function. I. Design of a system to deliver inhalational anesthetic agents to leukocyte cultures in vitro. J Immunol Methods 1986; 88 (02) 277-283
47 Welch WD. Halothane reversibly inhibits human neutrophil bacterial killing. Anesthesiology 1981; 55 (06) 650-654
48 Pirttikangas CO, Perttilä J, Salo M. Propofol emulsion reduces proliferative responses of lymphocytes from intensive care patients. Intensive Care Med 1993; 19 (05) 299-302
49 Salo M, Pirttikangas CO, Pulkki K. Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro. Anaesthesia 1997; 52 (04) 341-344
50 Hoff G, Bauer I, Larsen B, Bauer M. Modulation of endotoxin-stimulated TNF-alpha gene expression by ketamine and propofol in cultured human whole blood. Anaesthesist 2001; 50 (07) 494-499
51 Larsen B, Hoff G, Wilhelm W, Buchinger H, Wanner GA, Bauer M. Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology 1998; 89 (05) 1218-1227
52 Kotani N, Takahashi S, Sessler DI. et al. Volatile anesthetics augment expression of proinflammatory cytokines in rat alveolar macrophages during mechanical ventilation. Anesthesiology 1999; 91 (01) 187-197
53 Pirttikangas CO, Salo M, Mansikka M, Grönroos J, Pulkki K, Peltola O. The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane. Anaesthesia 1995; 50 (12) 1056-1061
54 Brune IB, Wilke W, Hensler T, Holzmann B, Siewert JR. Downregulation of T helper type 1 immune response and altered pro-inflammatory and anti-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery. Am J Surg 1999; 177 (01) 55-60
55 Cata JP, Bauer M, Sokari T. et al. Effects of surgery, general anesthesia, and perioperative epidural analgesia on the immune function of patients with non-small cell lung cancer. J Clin Anesth 2013; 25 (04) 255-262
56 Faist E, Kupper TS, Baker CC, Chaudry IH, Dwyer J, Baue AE. Depression of cellular immunity after major injury. Its association with posttraumatic complications and its reversal with immunomodulation. Arch Surg 1986; 121 (09) 1000-1005
57 Salo M. Cytokines and attenuation of responses to surgery. Acta Anaesthesiol Scand 1996; 40 (02) 141-142
58 Monneret G, Lepape A, Voirin N. et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 2006; 32 (08) 1175-1183
59 Ho YP, Sheen IS, Chiu CT, Wu CS, Lin CY. A strong association between down-regulation of HLA-DR expression and the late mortality in patients with severe acute pancreatitis. Am J Gastroenterol 2006; 101 (05) 1117-1124
60 Wong HR, Cvijanovich NZ, Anas N. et al. Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med 2015; 191 (03) 309-315
61 Muszynski JA, Nofziger R, Greathouse K. et al. Early adaptive immune suppression in children with septic shock: a prospective observational study. Crit Care 2014; 18 (04) R145