PERIOPERATIVE NORMOTHERMIA TO REDUCE THE INCIDENCE OF SURGICAL-WOUND INFECTION AND SHORTEN HOSPITALIZATION

Background. Mild perioperative hypothermia, which is common during major surgery, may promote surgical-wound infection by triggering thermoregulatory vasoconstriction, which decreases subcutaneous oxygen tension. Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen. Hypothermia also directly impairs immune function. We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization. Methods. Two hundred patients undergoing colorectal surgery were randomly assigned to routine intraoperative thermal care (the hypothermia group) or additional warming (the normothermia group). The patients’ anesthetic care was standardized, and they were all given cefamandole and metronidazole. In a double-blind protocol, their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks; wounds containing culture-positive pus were considered infected. The patients’ surgeons remained unaware of the patients’ group assignments. Results. The mean ( SD) final intraoperative core temperature was 34.7 0.6 C in the hypothermia group and 36.6 0.5 ° C in the normothermia group (P 0.001). Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia (19 percent) but in only 6 of 104 patients assigned to normothermia (6 percent, P 0.009). The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia (P 0.002), and the duration of hospitalization was prolonged by 2.6 days (approximately 20 percent) in the hypothermia group (P 0.01). Conclusions. Hypothermia itself may delay healing and predispose patients to wound infections. Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations. (N Engl J Med 1996;334:1209-15.) From the Thermoregulation Research Laboratory and the Department of Anesthesia, University of California, San Francisco (A.K., D.I.S.); and the Departments of Anesthesiology and General Intensive Care, University of Vienna, Vienna, Austria (A.K., D.I.S., R.L.). Address reprint requests to Dr. Sessler at the Department of Anesthesia, 374 Parnassus Ave., 3rd Fl. , University of California, San Francisco, CA 94143-0648. Supported in part by grants (GM49670 and GM27345) from the National Institutes of Health, by the Joseph Drown and Max Kade Foundations, and by Augustine Medical, Inc. The authors do not consult for, accept honorariums from, or own stock or stock options in any company whose products are related to the subject of this research. Presented in part at the International Symposium on the Pharmacology of Thermoregulation, Giessen, Germany, August 17–22, 1994, and at the Annual Meeting of the American Society of Anesthesiologists, Atlanta, October 21–25, 1995. *The study investigators are listed in the Appendix. W OUND infections are common and serious complications of anesthesia and surgery. A wound infection can prolong hospitalization by 5 to 20 days and substantially increase medical costs. 1,2 In patients undergoing colon surgery, the risk of such an infection ranges from 3 to 22 percent, depending on such factors as the length of surgery and underlying medical problems. 3 Mild perioperative hypothermia (approximately 2 ° C below the normal core body temperature) is common in colon surgery. 4 It results from anesthetic-induced impairment of thermoregulation, 5,6 exposure to cold, and altered distribution of body heat. 7 Although it is rarely desired, intraoperative hypothermia is usual because few patients are actively warmed. 8 Hypothermia may increase patients’ susceptibility to perioperative wound infections by causing vasoconstriction and impaired immunity. The presence of sufficient intraoperative hypothermia triggers thermoregulatory vasoconstriction, 9 and postoperative vasoconstriction is universal in patients with hypothermia. 10 Vasoconstriction decreases the partial pressure of oxygen in tissues, which lowers resistance to infection in animals 11,12 and humans (unpublished data). There is decreased microbial killing, partly because the production of oxygen and nitroso free radicals is oxygen-dependent in the range of the partial pressures of oxygen in wounds. 13,14 Mild core hypothermia can also directly impair immune functions, such as the chemotaxis and phagocytosis of granulocytes, the motility of macrophages, and the production of antibody. 15,16 Mild hypothermia, by decreasing the availability of tissue oxygen, impairs oxidative killing by neutrophils. And mild hypothermia during anesthesia lowers resistance to inoculations with Escherichia coli 17 and Staphylococcus aureus 18 in guinea pigs. Vasoconstriction-induced tissue hypoxia may decrease the strength of the healing wound independently of its ability to reduce resistance to infection. The formation  1996, Massachusetts Medical Society. The New England Journal of Medicine Downloaded from nejm.org on August 11, 2011. For personal use only. No other uses without permission. Copyright © 1996 Massachusetts Medical Society. All rights reserved. 1210 THE NEW ENGLAND JOURNAL OF MEDICINE May 9, 1996 of scar requires the hydroxylation of abundant proline and lysine residues to form the cross-links between strands of collagen that give healing wounds their tensile strength. 19 The hydroxylases that catalyze this reaction are dependent on oxygen tension, 20 making collagen deposition proportional to the partial pressure of arterial oxygen in animals 21 and to oxygen tension in wound tissue in humans. 22 Although safe and inexpensive methods of warming are available, 8 perioperative hypothermia remains common. 23 Accordingly, we tested the hypothesis that mild core hypothermia increases both the incidence of surgical-wound infection and the length of hospitalization in patients undergoing colorectal surgery.