EDITORIAL OPINION

Concealed Progress in the Management of Severe Surgical Infection

R emarkable advances have occurred in surgical care in this century. The transition from Lister’s antisepsis

to modem surgical asepsis is the first case in point and has been associated with other surgical technical refinements that would stagger our surgical grandfathers’ wildest imaginations. The overall impact of antibiotics in medical care has been profound. While there are numerous gener- ations who have been spared the horrendous effects of post-streptococcal damage to cardiac valves and renal parenchyma, not to mention other organs, the panacea of surgical antibiotic use has been to some extent illusory. Clearly, there is a role for antibiotics, and it is perhaps most surgically apparent in the wide acceptance and broad use of systemic antibiotic prophylaxis of operative wound infection. Notwithstanding same, there is, and has been recognized for a long time by many of us, a finite sequence of limitations to antibiotic use. There continues to be a school of surgical therapy whose members simply review the resistances and sensitivities of antibiotics and believe in an ever-widening umbrella of antimicrobial chemotherapy. Such surgeons ignore the ultimate impact of such treatment not only on the individual patient with the emergence of resistant organisms but upon future patients who will use that same facility and find a modem hospital heavily populated with highly and broadly resis- tant microorganisms. The clear lesson of the last 20 years has been that anything other than relatively brief perio- perative prophylaxis is an unequivocal two-edged sword! There are finite achievements that can be accomplished with antibiotic therapy, and there is little additional bene- fit to be achieved from the eighth generation of cephalo- sporins. This recognition has occurred during a time in which a number of laboratories, both within and without surgery, have tried to re-focus their research and thoughts on matters that are truly physiologically influ- ential with respect to infection in surgical patient care. I wish to enumerate just a few of those trends.

No one would debate the fact that some significant portion of multisystem organ failure, as it occurs even today, continues to be associated with infection, often remote from the failing organ. The mechanism by which remote organ failure has been accomplished depends on a variety of circulating agents and/or mediators, perhaps most simply viewed as microembolic aggregations of a variety of activated leukocytes and other circulating de- bris. Despite the capability of superb organ support sys- tems, there is a general appreciation that it is the treat- ment of the underlying infection that most profoundly influences the rate, frequency, and fatality of these relat- ed organ dysfunctions.

For more than two decades, we have sought to define the ultimate role of advances in nutrition in the recovery of surgical patients, leading to successful patient dis- charge from the hospital. This has been difficult to prove and perhaps is analogous to the era of burn care that

ended almost three decades ago. Successful burn resusci- tation had prolonged survival, but patients uniformly died of progressive bum wound infection until the advent of topical chemotherapy for burns, whereupon the pro- longed survival shifted, in a large step forward, to a true decrease in death rates and to a sharp enhancement in recovery. The same may be true of nutrition, i.e., we now have a variety of methods to prolong survival, but require an additional push or lift to get over that final hump, which will be reflected in being discharged from the hos- pital alive! As an occasional critic of this line of work, I admit that it has played a critical role in our understand- ing of surgical metabolism. Furthermore, I believe that it now only requires a similar and parallel advance in our understanding of the interaction between microbes and the host to accomplish exactly what topical silver nitrate and Sulfamylon did three decades ago for burns. A part and parcel of the nutrition enigma has related to the route of administration and the wideningly fashionable subject of intestinal translocation of bacteria. This fundamental abnormality has been suspected for more than a decade as an expression of failure of the intestinal host defense barrier, which was directly related to clinical outcome. Obviously, this is true; a small forest has been sacrificed to produce papers that confirm endless variations on that theme. It is also true that the capacity to utilize the alimentary tract as God intended it, for so-called enteral nutrition, tends to not only provide better nutrition but protect it from what Border and others have recognized as dysfunction of the gut-hepatic system. I believe these concepts are contributors, but certainly of secondary or even tertiary importance.

The entire field of surgical infection has been ham- pered by several common retardants. Briefly stated, they include the promulgation of a variety of clinically irrele vant experimental animal models of infection, incestuous research protocols, and granting entities and societies that find it much easier to endorse a study of interleukin- (Y than to recognize any contribution to basic new knowl- edge of the host-microbe relationship.

I do believe that several priorities are emerging, and I would encourage the readers of the Journal to continue to put many of the observations in perspective. I believe that our own observations about the very important role of monocyte surface expression of HLA-DR antigens are correct and that this is a valid predictor of and/or funda- mental mechanism for the development of surgical sepsis. It provides a ready focal point for further inquiry, and several investigators have now shown that this parameter is both favorably and adversely influenced by a number of physiologic and pharmacologic materials.

One should also understand that the vast array of mediators, messengers, kinins, toxins, and antibodies are exactly that. It is perhaps best to realize that in one dose, and at one time, many of these agents are helpful and

THE AMERICAN JOURNAL OF SURGERY VOLUME 162 SEPTEMBER 1991 195

protective; it is similarly important to realize that in a different dose, and in a different time or sequence, most of these materials are toxins. What is today’s mediator and host defense-enhancing agent is tomorrow’s toxin and deleterious material. Even the most senior of regular readers of the Journal will realize that endotoxin or lipo- polysaccharide is an old and well-appreciated example of such paradoxes. We have long known that large doses of endotoxin are fatal, and we have known almost as long that small, repetitive doses provide permanent and effec- tive immunization. The same, no doubt, applies to the currently fashionable interleukins, kinins, prostaglandins, and other materials. The practicing surgeon needs to wait out the proliferation of salami-sliced research in these fields and realize that it is going to be an extremely complex puzzle to unravel, with particular reference to timing, doses, and combinations complemented enor- mously by the question of sequencing which mediator, in which order, at which time, for which patient. We need a parameter for host-defense therapy as instantly useful as pulse oximetry has been to tissue oxygenation.

These latter issues are complicated by the fact that clinical trials to determine true therapeutic significance are going to be even more complex and will require large numbers of patients, a number of centers, and the most careful, sophisticated analysis. Implicit is the major dol- lar costs thereof. Furthermore, far too many of the puta- tive helpful agents are in the hands of small companies with little history and/or intent of long-term commitment to the advancement of medical science. Indeed, they have

far more in common with the junk bond traders than they do with fundamental science. Some of these companies give promises of emergence as genuine, long-term scien- tific contributors, and their efforts should be particularly appreciated.

These queries relative to immunomodulation in the surgical patient employ only new buzz words; the con- cepts are old ones. Which antibiotic or combination of antibiotics is best for a given patient? Is the enteric, parenteral, or topical route best? Should I nourish this patient enterally or parenterally? Just as we have learned to consider antibiotic sensitivities and resistances, so shall we also have to learn to monitor mediators and kinins and adjust our therapy from day to day, depending on docu- mented physiologic need. At the same time, ideal therapy must change dependent not on daily cultures and twice- weekly bum wound biopsies but on something that may change from moment to moment, as is evident by the current use of pulse oximetry. That very recognition rep resents real progress!

The subjects are complex and the answers will be a long time in coming, fully taxing the patience of the practicing surgeon as well as the intensity and clearhead- edness of both the bench and clinical investigator. The price will ultimately be handsomely repaid in patient well-being!

Hiram C. Polk, Jr., MD Editor

American Journal of Surgery Louisville, Kentucky

196 THE AMERICAN JOURNAL OF SURGERY VOLUME 162 SEPTEMBER 1991