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February 26, 1997, Vol 277, No. 8 >
ARTICLE | February 26, 1997

Relationship of Preoperative Antiendotoxin Core Antibodies and Adverse Outcomes Following Cardiac Surgery FREE

Elliott Bennett-Guerrero, MD; Liza Ayuso; Colin Hamilton-Davies, MD; William D. White, MPH; G. Robin Barclay, PhD; Peter K. Smith, MD; Sally A. King, MA; Lawrence H. Muhlbaier, PhD; Mark F. Newman, MD; Michael G. Mythen, MD
[+] Author Affiliations

Reprints: Elliott Bennett-Guerrero, MD, Department of Anesthesiology, Box 1010, The Mount Sinai Medical Center, 1 Gustave L. Levy PI, New York, NY 10029-6574.


JAMA. 1997;277(8):646-650. doi:10.1001/jama.1997.03540320048034
Text Size: A A A
Published online
Article
References

Objective.  —To test the hypothesis that low serum antiendotoxin core antibody (EndoCAb) level is an independent predictor of adverse outcome following cardiac surgery.

Design.  —Prospective, blinded, cohort study.

Setting.  —Tertiary care medical center.

Subjects.  —A total of 301 patients undergoing coronary artery bypass graft surgery and/or valvular heart surgery.

Design.  —Preoperative serum was assayed for IgM EndoCAb, IgG EndoCAb, total IgM, and total IgG levels. Known preoperative risk factors were assessed, and patients were assigned a risk score using a validated method.

Main Outcome Measure.  —A major complication, defined as either in-hospital death or postoperative length of stay greater than 10 days.

Results.  —Overall, a major complication occurred in 34 patients (11.3%). Lower IgM EndoCAb level independently predicted (P=.002) increased risk of major complication over and above the effects of preoperative risk score (P=.02), total IgG level (P=.07), and all other known perioperative risk factors. In contrast, IgG Endo-CAb and total IgM concentrations did not predict outcome. No association existed between risk score and level of IgM EndoCAb.

Conclusion.  —There is marked preoperative variability in humoral immunity against endotoxin core, which is not accounted for by differences in known preoperative risk factors. In this study, low levels of IgMEndoCAb were an important independent predictor of adverse postoperative outcome, which supports the theory that endotoxemia is a cause of postoperative morbidity.

REFERENCES

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Heart and Stroke Facts: 1995 Statistical Supplement. Dallas, Tex: American Heart Association; 1995:1-23.
2 +
Hammermeister KE, Burchfiel C, Johnson R, Grover FL.  Identification of patients at greatest risk for developing major complications at cardiac surgery . Circulation . 1990;;82:IV380-IV389.
3 +
Goris RJA, Boekhorst TPA, Nuytinck JKS, Gimbrère JSF.  Multiple-organ failure: generalized autodestructive inflammation? Arch Surg . 1985;;120:1109-1115.
4 +
Bone RC, Balk RA, Cerra FB, et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: ACCP/SCCM consensus conference . Chest . 1992;;101:1644-1655.
5 +
Suffredini AF, Fromm RE, Parker MM, et al.  The cardiovascular response of normal humans to the administration of endotoxin . N Engl J Med . 1989;;321:280-287.
6 +
Michie HR, Manogue KR, Spriggs DR, et al.  Detection of circulating tumor necrosis factor after endotoxin administration . N Engl J Med . 1988;;318:1481-1486.
7 +
Morrison DC, Ryan JL.  Endotoxins and disease mechanisms . Annu Rev Med . 1987;;38:417-432.
8 +
Natanson C, Eichenholz PW, Danner RL, et al.  Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock . J Exp Med . 1989;;169:823-832.
9 +
Morrison DC, Cochrane CG.  Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccahrides (endotoxins) . J Exp Med . 1974;; 140:797-811.
10 +
Fong Y, Moldawer LL, Marano M, et al.  Endotoxemia elicits increased circulating β2-IFN/IL-6 in man . J Immunol . 1989;;142:2321-2324.
11 +
Danner RL, Elin RJ, Hosseini JM, Wesley RA, Reilly JM, Parillo JE.  Endotoxemia in human septic shock . Chest . 1991;;99:169-175.
12 +
Andersen LW, Baek L, Degn H, Lehb J, Krasnik M, Rasmussen JP.  Presence of circulating endotoxins during cardiac operations . J Thorac Cardiovasc Surg . 1987;;93:115-119.
13 +
Riddington DW, Venkatesh B, Boivin CM, et al.  Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass . JAMA . 1996;;275:1007-1012.
14 +
Rocke DA, Gaffin SL, Wells MT, Koen Y, Brock-Utine JG.  Endotoxemia associated with cardiopulmonary bypass . J Thorac Cardiovasc Surg . 1987;; 93:832-837.
15 +
Martinez-Pellús AE, Merino P, Bru M, et al.  Can selective decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass? Crit Care Med . 1993;;21:1684-1691.
16 +
Watarida S, Mori A, Onoe M, et al.  A clinical study on the effects of pulsatile cardiopulmonary bypass on the blood endotoxin levels . J Thorac Cardiovasc Surg . 1994;;108:620-625.
17 +
Deitch EA, Berg R.  Bacterial translocation from the gut: a mechanism of infection . J Burn Care Rehabil . 1987;;8:475-482.
18 +
Deitch EA.  Bacterial translocation of the gut flora . J Trauma . 1990;;30:S184-S189.
19 +
Fink MP.  Effect of critical illness on microbial translocation and gastrointestinal mucosa permeability . Semin Respir Infec . 1994;;9:256-260.
20 +
Fink MP, Antonsson JB, Wang H, Rothschild HR.  Increased intestinal permeability in endotoxic pigs . Arch Surg . 1991;;126:211-218.
21 +
Hamilton-Davies C, Barclay GR, Machin SJ, Webb AR.  Relationship between endotoxin immune status and outcome following cardiac valve surgery . Br J Anaesth . 1995;;74:S34. Abstract.
22 +
Freeman R, Gould FK.  Prevention of fever and gram negative infection after open heart surgery by antiendotoxin . Thorax . 1985;;40:846-848.
23 +
Gould FK, Harvey JA, Dytrych JK.  Antibody to endotoxin is associated with decreased frequency of postoperative infection . Am J Obstet Gynecol . 1989;;160:317-319.
24 +
Barclay GR.  Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure: a review . In: Levin J, Alving CR, Munford RS, Redl H, eds. Bacterial Endotoxins: Lipopolysaccharides From Genes to Therapy . New York, NY: Wiley-Liss; 1995;:263-272.
25 +
Barclay GR, Scott BB.  Serological relationships between Escherichia coli and Salmonella smooth-and rough-mutant lipopolysaccharides as revealed by enzyme-linked immunosorbent assay for human immunoglobulin G antiendotoxin antibodies . Infect Immun . 1987;;55:2706-2714.
26 +
Whicher JT, Perry DE, Hobbs JR.  An evaluation of the Hyland laser nephelometer PDQ system for the measurement of immunoglobulins . Ann Clin Biochem . 1978;;15:77-85.
27 +
Parsonnet V, Dean D, Bernstein AD.  A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease . Circulation . 1989;;79:I-3—I-12.
28 +
Knaus WA, Draper EA, Wagner DP, Zimmerman JE.  APACHE II: a severity of disease classification system . Crit Care Med . 1985;;13:818-829.
29 +
Efron B, Tibshirani RJ. An Introduction to the Bootstrap . New York, NY: Chapman and Hall; 1993;.
30 +
Hosmer DW, Lemeshow S. Applied Logistic Regression . New York, NY: John Wiley and Sons; 1989;.
31 +
Hannan EL, Kilburn H, Racz M, Shields E, Chassin MR.  Improving the outcomes of coronary artery bypass surgery in New York State . JAMA . 1994;;271:761-766.
32 +
Higgins TL, Estafanous FG, Loop FD, et al.  Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients . JAMA . 1992;;267:2344-2348.
33 +
O'Connor GT, Plume SK, Olmstead EM, et al.  Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery . Circulation . 1992;;85:2110-2118.
34 +
Tu JV, Jaglal SB, Naylor CD, et al.  Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital length of stay after cardiac surgery . Circulation . 1995;;91:677-684.
35 +
Luderitz O, Staub AM, Westphal O.  Immunochemistry of O and R antigens of Salmonella and related Enterobacteriaceae . Bacteriol Rev . 1966;; 30:192-255.
36 +
Volk WA, Benjamin DC, Kadner RJ, Parsons JT. Medical Microbiology . Philadelphia, Pa: JB Lippincott; 1986;:396-398.
37 +
Poxton IR.  Antibodies to lipopolysaccharide . J Immunol Methods . 1995;;186:1-15.
38 +
Baumgartner JD.  Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal . Infect Dis Clin North Am . 1991;;5:915-927.
39 +
Evans ME, Pollack M, Koles NL, Hardegen NJ, Panopoulos D.  Lipopolysaccharide heterogeneity in Escherichia coli J5 variants: analysis by flow cytometry . J Infect Dis . 1992;;166:803-811.
40 +
Warren HS, Amato SF, Fitting C, et al.  Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide . J Exp Med . 1993;;177:89-97.
41 +
Quezado ZMN, Natanson C, Ailing DW, et al.  A controlled trial of HA-1A in a canine model of gram-negative septic shock . JAMA . 1993;;269:2221-2227.
42 +
Ziegler EJ, Fischer CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin . N Engl J Med . 1991;;324:429-436.
43 +
Greenman RL, Schein RMH, Martin MA, et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis . JAMA . 1991;;266:1097-1102.
44 +
Goldie AS, Fearon KCH, Ross JA, et al.  Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome . JAMA . 1995;;274:172-177.
45 +
De Camp MM, Demling R.  Posttraumatic multisystem organ failure . JAMA . 1988;;260:530-534.
46 +
Rush BF, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW.  Endotoxemia and bacteremia during hemorrhagic shock . Ann Surg . 1988;; 207:549-554.
47 +
Moore FA, Moore EE, Poggetti R, et al.  Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma . J Trauma . 1991;;31:629-638.
48 +
Ford EG, Baisden CE, Matteson ML, Picone AL.  Sepsis after coronary bypass grafting: evidence for loss of the gut mucosal barrier . Ann Thorac Surg . 1991;;52:514-517.
49 +
Munster AM, Smith-Meek M, Dickerson C, Winchurch RA.  Translocation: incidental phenomenon or true pathology? Ann Surg . 1993;;3:321-327.
50 +
Bion JF, Badger I, Crosby HA, et al.  Selective decontamination of the digestive tract reduces gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation . Crit Care Med . 1994;;22:40-49.
51 +
Deitch EA, Morrison J, Berg R, Specian RD.  Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats . Crit Care Med . 1990;;18:529-536.

Figures

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Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Heart and Stroke Facts: 1995 Statistical Supplement. Dallas, Tex: American Heart Association; 1995:1-23.
2 +
Hammermeister KE, Burchfiel C, Johnson R, Grover FL.  Identification of patients at greatest risk for developing major complications at cardiac surgery . Circulation . 1990;;82:IV380-IV389.
3 +
Goris RJA, Boekhorst TPA, Nuytinck JKS, Gimbrère JSF.  Multiple-organ failure: generalized autodestructive inflammation? Arch Surg . 1985;;120:1109-1115.
4 +
Bone RC, Balk RA, Cerra FB, et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: ACCP/SCCM consensus conference . Chest . 1992;;101:1644-1655.
5 +
Suffredini AF, Fromm RE, Parker MM, et al.  The cardiovascular response of normal humans to the administration of endotoxin . N Engl J Med . 1989;;321:280-287.
6 +
Michie HR, Manogue KR, Spriggs DR, et al.  Detection of circulating tumor necrosis factor after endotoxin administration . N Engl J Med . 1988;;318:1481-1486.
7 +
Morrison DC, Ryan JL.  Endotoxins and disease mechanisms . Annu Rev Med . 1987;;38:417-432.
8 +
Natanson C, Eichenholz PW, Danner RL, et al.  Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock . J Exp Med . 1989;;169:823-832.
9 +
Morrison DC, Cochrane CG.  Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccahrides (endotoxins) . J Exp Med . 1974;; 140:797-811.
10 +
Fong Y, Moldawer LL, Marano M, et al.  Endotoxemia elicits increased circulating β2-IFN/IL-6 in man . J Immunol . 1989;;142:2321-2324.
11 +
Danner RL, Elin RJ, Hosseini JM, Wesley RA, Reilly JM, Parillo JE.  Endotoxemia in human septic shock . Chest . 1991;;99:169-175.
12 +
Andersen LW, Baek L, Degn H, Lehb J, Krasnik M, Rasmussen JP.  Presence of circulating endotoxins during cardiac operations . J Thorac Cardiovasc Surg . 1987;;93:115-119.
13 +
Riddington DW, Venkatesh B, Boivin CM, et al.  Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass . JAMA . 1996;;275:1007-1012.
14 +
Rocke DA, Gaffin SL, Wells MT, Koen Y, Brock-Utine JG.  Endotoxemia associated with cardiopulmonary bypass . J Thorac Cardiovasc Surg . 1987;; 93:832-837.
15 +
Martinez-Pellús AE, Merino P, Bru M, et al.  Can selective decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass? Crit Care Med . 1993;;21:1684-1691.
16 +
Watarida S, Mori A, Onoe M, et al.  A clinical study on the effects of pulsatile cardiopulmonary bypass on the blood endotoxin levels . J Thorac Cardiovasc Surg . 1994;;108:620-625.
17 +
Deitch EA, Berg R.  Bacterial translocation from the gut: a mechanism of infection . J Burn Care Rehabil . 1987;;8:475-482.
18 +
Deitch EA.  Bacterial translocation of the gut flora . J Trauma . 1990;;30:S184-S189.
19 +
Fink MP.  Effect of critical illness on microbial translocation and gastrointestinal mucosa permeability . Semin Respir Infec . 1994;;9:256-260.
20 +
Fink MP, Antonsson JB, Wang H, Rothschild HR.  Increased intestinal permeability in endotoxic pigs . Arch Surg . 1991;;126:211-218.
21 +
Hamilton-Davies C, Barclay GR, Machin SJ, Webb AR.  Relationship between endotoxin immune status and outcome following cardiac valve surgery . Br J Anaesth . 1995;;74:S34. Abstract.
22 +
Freeman R, Gould FK.  Prevention of fever and gram negative infection after open heart surgery by antiendotoxin . Thorax . 1985;;40:846-848.
23 +
Gould FK, Harvey JA, Dytrych JK.  Antibody to endotoxin is associated with decreased frequency of postoperative infection . Am J Obstet Gynecol . 1989;;160:317-319.
24 +
Barclay GR.  Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure: a review . In: Levin J, Alving CR, Munford RS, Redl H, eds. Bacterial Endotoxins: Lipopolysaccharides From Genes to Therapy . New York, NY: Wiley-Liss; 1995;:263-272.
25 +
Barclay GR, Scott BB.  Serological relationships between Escherichia coli and Salmonella smooth-and rough-mutant lipopolysaccharides as revealed by enzyme-linked immunosorbent assay for human immunoglobulin G antiendotoxin antibodies . Infect Immun . 1987;;55:2706-2714.
26 +
Whicher JT, Perry DE, Hobbs JR.  An evaluation of the Hyland laser nephelometer PDQ system for the measurement of immunoglobulins . Ann Clin Biochem . 1978;;15:77-85.
27 +
Parsonnet V, Dean D, Bernstein AD.  A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease . Circulation . 1989;;79:I-3—I-12.
28 +
Knaus WA, Draper EA, Wagner DP, Zimmerman JE.  APACHE II: a severity of disease classification system . Crit Care Med . 1985;;13:818-829.
29 +
Efron B, Tibshirani RJ. An Introduction to the Bootstrap . New York, NY: Chapman and Hall; 1993;.
30 +
Hosmer DW, Lemeshow S. Applied Logistic Regression . New York, NY: John Wiley and Sons; 1989;.
31 +
Hannan EL, Kilburn H, Racz M, Shields E, Chassin MR.  Improving the outcomes of coronary artery bypass surgery in New York State . JAMA . 1994;;271:761-766.
32 +
Higgins TL, Estafanous FG, Loop FD, et al.  Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients . JAMA . 1992;;267:2344-2348.
33 +
O'Connor GT, Plume SK, Olmstead EM, et al.  Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery . Circulation . 1992;;85:2110-2118.
34 +
Tu JV, Jaglal SB, Naylor CD, et al.  Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital length of stay after cardiac surgery . Circulation . 1995;;91:677-684.
35 +
Luderitz O, Staub AM, Westphal O.  Immunochemistry of O and R antigens of Salmonella and related Enterobacteriaceae . Bacteriol Rev . 1966;; 30:192-255.
36 +
Volk WA, Benjamin DC, Kadner RJ, Parsons JT. Medical Microbiology . Philadelphia, Pa: JB Lippincott; 1986;:396-398.
37 +
Poxton IR.  Antibodies to lipopolysaccharide . J Immunol Methods . 1995;;186:1-15.
38 +
Baumgartner JD.  Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal . Infect Dis Clin North Am . 1991;;5:915-927.
39 +
Evans ME, Pollack M, Koles NL, Hardegen NJ, Panopoulos D.  Lipopolysaccharide heterogeneity in Escherichia coli J5 variants: analysis by flow cytometry . J Infect Dis . 1992;;166:803-811.
40 +
Warren HS, Amato SF, Fitting C, et al.  Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide . J Exp Med . 1993;;177:89-97.
41 +
Quezado ZMN, Natanson C, Ailing DW, et al.  A controlled trial of HA-1A in a canine model of gram-negative septic shock . JAMA . 1993;;269:2221-2227.
42 +
Ziegler EJ, Fischer CJ, Sprung CL, et al.  Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin . N Engl J Med . 1991;;324:429-436.
43 +
Greenman RL, Schein RMH, Martin MA, et al.  A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis . JAMA . 1991;;266:1097-1102.
44 +
Goldie AS, Fearon KCH, Ross JA, et al.  Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome . JAMA . 1995;;274:172-177.
45 +
De Camp MM, Demling R.  Posttraumatic multisystem organ failure . JAMA . 1988;;260:530-534.
46 +
Rush BF, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW.  Endotoxemia and bacteremia during hemorrhagic shock . Ann Surg . 1988;; 207:549-554.
47 +
Moore FA, Moore EE, Poggetti R, et al.  Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma . J Trauma . 1991;;31:629-638.
48 +
Ford EG, Baisden CE, Matteson ML, Picone AL.  Sepsis after coronary bypass grafting: evidence for loss of the gut mucosal barrier . Ann Thorac Surg . 1991;;52:514-517.
49 +
Munster AM, Smith-Meek M, Dickerson C, Winchurch RA.  Translocation: incidental phenomenon or true pathology? Ann Surg . 1993;;3:321-327.
50 +
Bion JF, Badger I, Crosby HA, et al.  Selective decontamination of the digestive tract reduces gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation . Crit Care Med . 1994;;22:40-49.
51 +
Deitch EA, Morrison J, Berg R, Specian RD.  Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats . Crit Care Med . 1990;;18:529-536.

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