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Ann Thorac Surg 1996;61:1607-1608
© 1996 The Society of Thoracic Surgeons

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Editorial

SIRS-The Systemic Inflammatory Response Syndrome After Cardiac Operations

Department of Cardiac Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, England

Sirs: I have found you an argument. I am not obliged to find you an understanding. Dr Samuel Johnson (1709--1784)

Although Samuel Johnson's observation was addressed to his colleagues, not to SIRS (the acronym for the systemic inflammatory response syndrome), the point he makes is nonetheless relevant. Awareness of this aspect of cardiac surgery pathophysiology is increasing, but real understanding of the mechanisms involved is still sadly lacking. The article by Cremer and colleagues [1] published in this issue attempts to develop our understanding, focusing on the hemodynamic changes and the patterns of cytokine release that are features of this syndrome.

It is important to define what syndrome we are talking about. In 1991, a Consensus Conference convened by the Society of Critical Care Medicine and the American College of Chest Physicians produced the following definition of SIRS [2]: "The response to a variety of severe clinical insults (either infectious or non-infectious). The response is manifested by two or more of the following conditions

See also 1714.

• temperature >38°C
  
• heart rate >90 beats/min
  
• respiratory rate >20 breaths/min
  
• or
  
• pCO₂[carbon dioxide tension] <32 mm Hg
  
• white blood cell count >12,000/mm³[>12,000/µL]
  
• or
  
• white blood cell count <4,000/mm³[<4,000/µL]
  
• or
  
• immature (band) forms accounting for >10% of neutrophils."
  

The observant reader may note the breadth of this definition. Conditions leading to the response are "a variety of severe clinical insults." They may be infectious or noninfectious. The clinical features are similarly remarkably nonspecific; for example, the presence of pyrexia of more than 38°C and a moderate tachycardia are sufficient to include a patient in the syndrome.

The questions for us must surely be the following: Is cardiac operation per se one of those "severe clinical insults" leading to SIRS? Is SIRS the inevitable result of a cardiac operation or is it seen only in particular patient groups? Is the pattern of the response in cardiac surgical patients the same as or different from the SIRS pattern generally described?

In relation to the first question, the answer must be in the affirmative. From the early studies of Kirklin and colleagues [3] to the increasing number of recent reports, it is clear that cardiac operations, specifically those with cardiopulmonary bypass, induce those hemodynamic, respiratory, and hematologic changes necessary for inclusion in SIRS definition.

But is it inevitable? Do we induce SIRS every time we carry out a cardiac operation? The answer to this question is less clear. Cremer and colleagues [1] state in their Comment section that they believe SIRS occurs in about 10% of all their cases. Their group 1 patients, however, are characterized by major hemodynamic changes with low systemic vascular resistance (<800 dynes•s•cm^-5), hyperdynamic circulation, and the need for norepinephrine infusion. By contrast, their group 2 patients had none of these severe features, although even in these more routine cases most of the inflammatory mediators measured were elevated in the postoperative period, and one suspects that, on the basis of the definition criteria, they too would be included as exhibiting the features of SIRS.

It may be possible to resolve this apparent dilemma if we view SIRS not as a single clinical entity but as a spectrum of response, which may range from the relatively mild to the severe and potentially life-threatening exemplified by Cremer and associates' group 1 patients. On this basis it seems reasonable to conclude that a systemic inflammatory response is induced in all patients undergoing open heart operations, but that the severity of the response syndrome is variable, and only in a minority of patients does it manifest the severe hemodynamic disturbance well described by Cremer and associates. They suggest that the "hyperdynamic circulation" (or sepsis-like syndrome, as it has previously been described) occurs in 10% of their patients, but this may be an overestimate.

Perhaps the most important question relates to the pattern of the systemic inflammatory response in the cardiac surgical patient. Systemic inflammatory response syndrome has been described in a wide range of clinical situations, but is the pattern of the response the same irrespective of the initial insult or initial pathology? This is a fundamental question for us as cardiac surgeons. If SIRS is identical in nature in all situations, we may reasonably pool the research data (including strategies for therapy and prevention) from one discipline to another. If the pattern of SIRS is fundamentally different in cardiac surgical patients, for example, if it relates directly to cardiopulmonary bypass, it has to be studied specifically in its own right. We should note one advantage we have over other workers in this area: we know when the insult that initiates the response is going to occur. We can study the pre-SIRS phase, we can be proactive in strategies for prevention and therapy rather than in other disciplines, where most often research studies and therapy have to be reactive to a response already established.

We delude ourselves if we think we already know the answers to this third question. The inflammatory response is one of the most basic of our body's defense systems, and it is exceedingly complex.

There are, however, particular aspects of the inflammatory response that may be identified for focused research in cardiac surgery patients. These include the release patterns of cytokines, the role of endotoxin, and the changes in systemic hemodynamics and myocardial performance.

It is generally accepted that different cytokines are released at different times and for different periods during the development of SIRS. Hesse and colleagues [4] used endotoxin infusion as the standardized insult to study cytokine release patterns in SIRS. Tumor necrosis factor appeared early, within 30 minutes, peaked at 1 hours, and returned to baseline by 3 to 4 hours. Interleukin-6 did not appear in the circulation until 1 hours, and its peak was delayed to after 8 hours. Cremer and associates [1] rightly point to the fact that their lack of tumor necrosis factor peak detection may be because they sampled too late to detect it. However, it is worth noting the discrepant results in previous cardiac surgical studies, where some researchers found an early tumor necrosis factor peak (Menasché and associates [5]), whereas others did not (Butler and co-workers [6], Sawa and colleagues [7]). The high level of interleukin-6 found by Cremer and associates [1] in the group 1 patients is an interesting observation. Of note, however, in their results for virtually all the inflammatory mediators measured is the very considerable patient-to-patient variability, with very high standard deviation values for both group 1 and group 2 patients.

The role of endotoxin in SIRS is another important issue, because there are conflicting data regarding the incidence of endotoxemia in cardiac surgical patients, particularly during the cardiopulmonary bypass period. There is evidence that splanchnic ischemia/gut reperfusion injury does occur routinely during and after cardiopulmonary bypass with consequent disturbance of gut barrier function [8]. Endotoxemia has been detected, but not consistently, and not in all patients [9, 10], consistent with Cremer and associates' current findings [1].

Endotoxin is also relevant in considering the hemodynamic changes and disturbed myocardial performance that were features of group 1 patients in Cremer and associates' study. The "hyperdynamic circulation" they describe is undoubtedly similar if not identical to that reported in the earlier phases of sepsis or endotoxemia. Until recently it was thought that endotoxin exerted its myocardial depressant effects by reducing the response to adrenergic stimulation by desensitization of the B-1 receptor. This traditional view has recently been challenged by new research indicating that a family of proteins known as G-proteins (guanine nucleotide binding proteins) may be the mediators of endotoxin-induced defects in inotropic regulation [11].

The putative roles of cytokines, endotoxin, G-proteins, selectins, and nitric oxide all must be defined in relation to SIRS in general and to SIRS in cardiac surgery in particular. Understanding of their roles will facilitate the development of appropriate therapeutic and preventative strategies. Systemic inflammatory response syndrome does indeed provide us with a rich source of research and of argument. Doctor Johnson felt no obligation to his Sirs to progress toward an understanding ...but we must to ours.

Footnotes

Address reprint requests to Dr Taylor, Cardiothoracic Surgical Unit, Royal Postgraduate Medical School, Hammersmith Hospital, B Block, 2nd Floor, Du Cane Rd, London W12 0NN, England.

References

1. Cremer J, Martin M, Redl H, et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 1996;61:1714–20.[Abstract/Free Full Text]
2. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definition for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864–8.[Medline]
3. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:856–7.
4. Hesse DG, Tracey KJ, Fong Y, et al. Cytokine appearance in human endotoxaemia and primate bacteraemia. Surg Gynecol Obstet 1988;166:147–54.[Medline]
5. Menasché P, Haydar S, Peynet J, et al. One potential mechanism of vasodilation after warm heart surgery: the temperature-dependent release of cytokines. J Thorac Cardiovasc Surg 1994;107:293–9.[Abstract/Free Full Text]
6. Butler J, Chong GL, Baigie RJ, Pillai R, Westaby S, Rocker GM. Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833–8.[Abstract]
7. Sawa Y, Shimazaki Y, Kadoba K, et al. Attenuation of cardiopulmonary bypass-derived inflammations reaction reduces myocardial reperfusion injury in cardiac operations. J Thorac Cardiovasc Surg 1996;111:29–36.[Abstract/Free Full Text]
8. Ohri SK, Bowles CT. Gastrointestinal complications of cardiopulmonary bypass. In: Pepper J, Yacoub MH, eds. Annual of cardiac surgery, 8th ed. London: Current Science, 1995: 74-86.
9. Rocke DA, Gaitin SL, Wells MT, et al. Endotoxemia associated with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1987;93:832–7.[Abstract]
10. Andersen LW, Baek L, Degn H, et al. Presence of circulating endotoxins during cardiac operations. J Thorac Cardiovasc Surg 1987;93:115–9.[Abstract]
11. Campbell KL, Forse RA. Endotoxic rat atria show G-protein based deficits in inotropic regulation. Surgery 1993;114:471–9.[Medline]

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kenneth M. Taylor Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, K. M. Search for Related Content PubMed PubMed Citation Articles by Taylor, K. M. Related Collections Related Article