Cardiopulmonary bypass with adequate flow and perfusion pressures prevents endotoxaemia and pathologic cytokine production

Abstract

Endotoxin and cytokine inflammatory mediators comprise the afferent and efferent limbs of the 'acute phase response'. During cardiopulmonary bypass (CPB) there may be gut translocation of endotoxin and contact activation of lymphocytes. It has been hypothesized that the haemodynamic instability encountered following CPB is caused by the 'acute phase response'. In this study we attempted to quantify the acute phase response in patients undergoing open-heart surgery and determine the influence of these cytokines on perioperative morbidity. Four perioperative blood samples were drawn from 20 consecutive patients undergoing coronary artery bypass grafting (CABG). These samples were assayed for endotoxin and four cytokines. In all cases the cardiac index was maintained > 2.4 l/min/m² during nonpulsatile normothermic bypass (37°C) and > 1.8 l/min/m² during nonpulsatile hypothermic bypass (28°C), and the perfusion pressure > 60 mmHg.

Endotoxin was not detected in any of the test samples despite positive nonpatient controls. Interleukin 6 (IL-6) and tumour necrosis factor (TNF) were not detected despite an assay sensitivity of 80 and 10 pg/ml, respectively. TNF was detectable with an assay sensitivity of 0.5 pg/ml although there were no significant differences within the group. Interleukin 1 (IL-1) was detected (range = 0.98 - 9.09 ng/ml) in patients and again there were no trends within the group. The platelet activating factor (PAF) values peaked at crossclamp release (1.3 ng/ml versus a baseline of 0.2 ng/ml); however, there was no significant difference within the study.

The perioperative rise in PAF suggests that of all the mediators assayed this cytokine has the lowest synthesis threshold in response to stress, related to nonpulsatile CPB, and is unrelated to endotoxaemia (as detected by the limulus amoebocyte lysate (LAL) assay). Despite recent reports outlining the incidence of endotoxaemia, cytokine activation and the benefits of anti inflammatory therapy during CPB, our data suggest that maintenance of high flow and perfusion pressures during nonpulsatile CPB reduces the incidence of any 'acute phase response' of clinical significance.

Get full access to this article

View all access options for this article.

References

Markewitz A. , Faist E. , Lang S. , Endres S. , Hultner L. , Reichart B. Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thor Surg 1993; 55: 389-94.

Markewitz A. , Faist E. , Lang S. , Endres S. , Fuchs D. , Reichart B. Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation. J Thorac Cardiovasc Surg 1993; 105: 15-24.

Kharazmi A. , Andersen L. , Baek L. , Valerius NH , Laub M. , Rasmussen JP Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989; 98: 831-35.

Rocke DA , Gaffin SL , Wells MT , Koen Y. , Brock-Utine JG Endotoxemia associated with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989; 93: 832-37.

Butler J. , Pillai R. , Rocker GM , Westaby S. , Parker D. , Shale DJ

Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumour necrosis factor. J Thor

Cardiovasc Surg 1993; 105: 25-30.

Dinarello CA Interleukin-1 and the pathogenesis of acute phase response. N Engl J Med 1984; 311: 1413-18.

Casey LC Role of cytokines in the pathogenesis of cardiopulmonary induced multisystem organ failure. Ann Thor Surg 1993; 56: S92-96.

Bone R. , Balk R. , Cerra F. et al. Definitions for sepsis and organ failure and guidelines for use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. Chest 1992 ; 101: 1644-55.

Dinarello C. Interleukin-1. Rev Infect Dis 1984; 6: 51-95.

10.

Hack C. , DeGrout E. , Felt-Bermsa R. et al. Increased plasma levels of interleukin-6 in sepsis. Blood 1989; 74: 1704-10.

11.

Beutler B. , Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med 1987; 316: 379-85.

12.

Braquet P. , Touqui L. , Shen TY , Vargaftig BB Perspectives in platelet-activating factor research. Pharmacol Rev 1987; 39: 96-145.

13.

Lefer AM , Lefer DJ Pharmacology of the endothelium in ischaemia-reperfusion and circulatory shock . Annu Rev Pharmacol Toxicol 1993; 33: 71-90.

14.

MacKendrick W. , Hill N. , Hsueh W. , Caplan M. Increase in plasma platelet-activating factor levels in enterally fed preterm infants. Biol Neonate 1993; 64: 89-95.

15.

Folch J. , Lees M. , Sloane-Stanley GH A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509.

16.

Caplan MS , Sun X-M. , Hsueh W. , Hageman JR Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr 1990; 116: 960-65.

17.

Rush BF Jr , Sori AJ , Murphy TF , Smith S. , Flanagan JJ Jr , Machiedo GW Endotoxemia and bacteremia during hemorrhagic shock. The link between trauma and sepsis? Ann Surg 1988; 207: 549-54.

18.

Martinez-Pellus AE , Merino P. , Brum et al. Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass? Crit Care Med 1993; 21: 1684-91.

19.

Deitch EA The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg 1990; 125:403-404.

20.

Ledingham Imca , McCartney AC , Ramsay G. , Wright I. Endotoxins as mediators. Prog Clin Biol Res 1988; 264: 125-30.

21.

McCartney AC , Piotrowicz BI , Edlin S. , Ledingham IM Measurement of endotoxin in the acute phase of septic shock. Prog Clin Biol Res 1988; 272: 225-29.

22.

Andersen LW , Baek L. , Degn H. , Lehd J. , Krasnik M. , Rasmussen JP Presence of circulating endotoxins during cardiac operations. J Thorac Cardiovasc Surg 1987; 93: 115-19.

23.

Andersen LW , Baek L. , Thomsen BS , Rasmussen JP Effect of methylprednisolone on endotoxin and complement activation during cardiac surgery. J Cardiothorac Vasc Anesth 1989; 3: 544-49.

24.

Karlstad MD , Patteson SK , Guszcza JA , Langdon R. , Chesney JT Methylprednisolone does not influence endotoxin translocation during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1993; 7: 23-27.