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Byline: Christian H. Wakefield, P. Declan Carey, Sharmila Foulds, John R.T. Monson, Pierre J. Guillou Abstract: The fact that the incidence and mortality from postsurgical sepsis have remained unchanged over the past 15 years raises the possibility that some patients possess an idiosyncratic predisposition to the development of a postoperative sepsis response. Genetic polymorphisms of the neutrophil receptor for immunoglobulin G, CD16, are known, and their inheritance is associated with functional differences in neutrophil phagocytosis. The present studies were designed to provide preliminary data on the effects of surgery on the level of expression of CD16 and its metabolism preparatory to detailed examination of the relationship of these polymorphisms to sepsis responses. Author Affiliation: From the Academic Surgical Unit, Imperial College of Science, Technology and Medicine, St. Mary's Hospital Medical School, London, United Kingdom Article History: Received 11 February 1994; Accepted 8 September 1994

Bacterial sepsis is a bacterial infection of the blood. Bacterial sepsis has been associated with the development of adult respiratory distress syndrome (ARDS) and acute lung injury (ALI). ARDS and ALI are conditions characterized by the presence of damaged lung tissue and pulmonary edema (the leakage of fluid from blood vessels into the lungs). Animal models have been developed to study the changes in lung physiology that occur during ALI. The procedure involves inoculating animals with a bacteria (Pseudomonas aeruginosa) that causes sepsis and lung damage similar to that observed in humans who have ALI. A technique called bronchoalveolar lavage (BAL) is used to obtain samples of lung fluid and cells. BAL is performed by placing a tube in the mouth that reaches down into the lungs. A sterile saline solution is delivered through the tube into the lungs and then removed by gentle suction. The fluid removed from the lungs is called the BAL fluid, and contains lung cells and proteins. When sepsis and ALI are present, the BAL fluid will contain blood proteins and white blood cells. In order to determine if the drug ibuprofen is an effective way of preventing sepsis-induced ALI, pigs were inoculated with bacteria to create an animal model of sepsis, as described above. BAL fluid from inoculated pigs contained blood proteins and white blood cells. Pretreatment with ibuprofen prior to inoculation with bacteria completely prevented the leakage of blood proteins and cells from the blood vessels into the lung tissue. Ibuprofen may be beneficial in preventing sepsis-induced ALI. Further studies are needed to determine if ibuprofen will be an appropriate treatment for ALI or ARDS in humans. (Consumer Summary produced by Reliance Medical Information, Inc.)

• Tumor necrosis factor (TNF) is implicated in the pathophysiology of gram-negative sepsis. This study examined physiologic and biochemical effects of pretreatment with an anti-TNFα monoclonal antibody immediately before the onset of sepsis. Three groups of anesthetized ventilated pigs were studied for 300 minutes. Groups 1 (n=12) and 2 (n=6) received a 1-hour infusion of live Pseudomonas aeruginosa. Group 2 was pretreated with anti-TNFα monoclonal antibody (15 mg/kg). Group 3 (n=8) received intravenous sterile saline. Group 1 exhibited a significant rise in plasma TNF activity, which was abolished in group 2. Cardiac index was reduced in both groups 1 and 2 in the first hour but recovered in group 2 (3.3±0.4 L/min per square meter at 300 minutes in group 2 vs 1.3±0.2 L/min per square meter in group 1). Metabolic acidosis was attenuated (arterial pH, 7.39±0.01 in group 2 vs 7.16±0.03 at 300 minutes in group 1). Increased extravascular lung water was also attenuated (5.9±0.7 in group 2 vs 13.2±1.5 mL/kg at 300 minutes in group 1). However, pulmonary hypertension and hypoxemia, which are known cyclooxygenase effects, were not affected. In the early phase of the study, plasma thromboxane B2 levels were elevated in both groups 1 and 2. We conclude that anti-TNFα monoclonal antibody offered significant protection against the effects of sepsis, but that other mediators may be responsible for the early changes seen in this model.(Arch Surg. 1992;127:138-145)

• It has been suggested that major surgery induces polymorphonuclear leukocyte (PMNL) dysfunction, which exposes patients to the development of sepsis. Conversely, the sepsis response and multisystem organ failure in patients after surgery is thought to be mediated by activated PMNLs. In a preliminary attempt to investigate this paradox, we studied functional (hydrogen peroxide production) and phenotypic (the adhesion/complement receptor CD11b) markers of PMNL activation in 28 patients undergoing elective major resectional surgery; 11 (39%) of these patients developed postoperative sepsis (the septic group). The mean (SEM) preoperative level of neutrophil CD11b expression (97.8 [6.2] mean channel fluorescence [MCF] and 101.42 [7.9] MCF; P=.74) and hydrogen peroxide production (109.51 [4.91] MCF and 104.53 [6.3] MCF; P=.5) were similar for the uncomplicated and septic groups, respectively. However, on the first postoperative day, both mean CD11b expression and hydrogen peroxide production were greater in those patients who subsequently developed postoperative sepsis (192.5 [38] MCF vs 128.6 [8.1] MCF for the septic group vs the uncomplicated group, respectively [P<.05], and 120.43 [2.56] MCF vs 109.61 [3.05] MCF for the septic group vs the uncomplicated group, respectively [P<.0001]). We suggest that an exaggerated PMNL activation response to surgery is an early event in those patients destined to develop postsurgical sepsis.(Arch Surg. 1993;128:390-395)