Role of cytokines in the restoration of the delayed-type hypersensitivity reaction of anergic patients.

Soluble mediators from peripheral blood lymphocytes activated either by skin test antigens or by alloantigens restored the delayed type hypersensitivity (DTH) reaction in the majority of anergic surgical patients who are at increased risk for sepsis and mortality. Antigen had to be injected together with the mediators and the individual had to be reactive to the antigen for restoration. These results suggest that restoration of the DTH response depends on the ability of cytokines produced and acting in a non-specific manner to promote the response of the anergic patients' specific antigen-sensitive cells to antigen.     

Antibiotic prophylaxis for surgery in morbidly obese patients

The rate of wound infections in morbidly obese patients who underwent gastroplasty surgery at our institution was 16.5% compared with a rate of 2.5% in normal-weight patients who underwent clean-contaminated surgery. Both groups received 1 gm of cefazolin intramuscularly before surgery was performed. We hypothesized that this regimen of prophylaxis did not provide adequate tissue levels in the morbidly obese. Morbidly obese patients who were undergoing gastroplasty were randomly selected to receive 1 gm cefazolin in the buttock fat, buttock muscle, or by intravenous injection. A fourth group of morbidly obese patients received 2 gm of cefazolin intravenously. Normal-weight patients who were undergoing upper abdominal surgery received 1 gm of cefazolin intravenously. At incision and closure, both blood and tissue levels of cefazolin were significantly (p less than 0.001) lower for all morbidly obese patients who received 1 gm cefazolin when compared with the blood and tissue levels of the drug found in normal-weight patients. The cefazolin levels obtained were below the minimal inhibitory concentrations of greater than 2 micrograms/ml for gram-positive cocci and of greater than 4 micrograms/ml for gram-negative rods. Only when the morbidly obese patient received 2 gm cefazolin were both the serum and adipose tissue levels adequate. For a 4-month period, all morbidly obese patients received 2 gm cefazolin prophylaxis, and the wound infection rate dropped to 5.6% compared with the previous rate of 16.5% (p less than 0.03). We conclude that antibiotic prophylaxis must be specially tailored to the needs of these obese patients.     

Cardiopulmonary abnormalities after smoking cocaine

We recently treated a young man who had chest pain after smoking "freebase" cocaine. Pneumomediastinum was diagnosed, and the electrocardiographic changes that developed were characteristic of coronary artery spasm. Although pneumomediastinum has been linked to "freebasing," we believe electrocardiographic abnormalities in this situation have not been previously reported.     

Predicting mortality based on body composition analysis.

The role of the Nae/Ke ratio (the ratio of exchangeable sodium to exchangeable potassium) was examined as a nutritional marker in surgical patients in relation to anthropometrical and biochemical indexes by its ability to identify patients at risk for mortality after hospitalization. In 73 patients with sepsis and malnutrition (Training Group, Madrid) the following were determined: percentage of recent weight loss, triceps skin fold, midarm muscle circumference, serum albumin, serum transferrin, delayed hypersensitivity skin test response, total lymphocytes, and Nae/Ke ratio by multiple isotope dilution. The predictive power of Nae/Ke ratio was so strong (F = 105.1; p less than 0.00001) that it displaced anthropometric, biochemical, and immunologic variables from the linear equation derived from stepwise discriminant analysis using hospital mortality as the dependent variable. A theoretical curve of expected deaths was developed, based on an equation obtained by logistic regression analysis: Pr/death/ = 1/(1 + e[11.8-5.2 Nae/Ke]). Pre- and post-test probabilities on that curve allowed us to determine two cut-off values, Nae/Ke ratios of 1.5 and 2.5, which were markers for nonrisk and mortality, respectively. The model was tested in a heterogeneous data base of surgical patients (n = 417) in another hospital (Validation Group, Montreal). For patients exhibiting an abnormal Nae/Ke ratio (greater than 1.2) and a greater than 10% of probability of death, 54 deaths were expected and 53 observed (X2 = 1.8 NS). Two tests confirmed the basic agreement between the model and its performance, a G statistic of -0.704 and the area beneath the "receiver-operating-characteristic" (ROC) curve (Az = 0.904 + 0.0516 for the Madrid group vs. Az = 0.915 + 0.0349 for the Montreal group, NS). It was concluded from this analysis that, compared with the usual anthropometric measurements, the Nae/Ke ratio, if available, is the best method for identifying malnourished patients at risk of dying.     

Alveolar-Membrane Diffusing Capacity Improves in the Morbidly Obese after Bariatric Surgery

Background Morbidly obese individuals may have impaired alveolar-membrane diffusing capacity (DmCO). The purpose of this study was to measure pulmonary diffusing capacity for NO (DLNO) as an index of DmCO pre- and postbariatric surgery in the morbidly obese. Methods Twenty-one patients [age = 40 ± 9 years, body mass index (BMI) = 48.5 ± 7.2 kg/m²] with an excess weight of 72 ± 17 kg scheduled for bariatric surgery were recruited. Pulmonary function and arterial blood-gases were measured pre- and postsurgery. Results DmCO was 88 ± 23% of predicted before surgery (p < 0.05). There was loss in BMI and excess weight of 7.7 ± 2.0 kg/m² and 31 ± 8%, respectively. Because DmCO = DLNO/2.42, the increase in DLNO postsurgery resulted in a normalization of the predicted DmCO to 97 ± 29% predicted, or an improvement of DLNO by 11 ± 18 (95% CI = 3.5, 19.1; p = 0.01) milliliters per minute per millimeter of mercury without any improvement in DLCO. The DLNO/DLCO ratio and alveolar volume both increased, respectively (p < 0.05), and pulmonary capillary blood volume to DmCO ratio decreased postsurgery (p < 0.01). Multiple linear regression revealed that the change in DLNO was most strongly associated with changes in alveolar volume and the waist-to-hip ratio (adjusted r ² = 0.76; p < 0.001) and was not related to the reduction in the alveolar-to-arterial PO₂ difference. Conclusion Alveolar-membrane diffusion normalizes within 10 weeks after bariatric surgery. This is likely due to the increase in alveolar volume from the reduction in the waist-to-hip ratio. G.S. Zavorsky is the recipient of the 2005 Baxter Corporation Award in Anesthesia from the Canadian Anesthesiologist’s Society. G.S. Zavorsky was a previous Research Scholar – Junior 1 from the Quebec Health Research Foundation (Fonds de la Recherche en Santé du Québec, FRSQ). N.V. Christou is a consultant for Ethicon Endo-Surgery and has stock ownership in Weight Loss Surgery.     

Anastomotic leaks after bariatric surgery: it is the host response that matters

BACKGROUND: Anastomotic leaks after bariatric surgery can lead to severe complications and adverse outcomes. We tested the hypothesis that not all patients with an anastomotic leak after bariatric surgery present with clinical symptoms and that their outcome is dependent on the aggressiveness of the host inflammatory response. METHODS: This was a retrospective analysis of prospectively collected clinical data from 2384 bariatric surgeries from 1983 to 2006. All anastomotic leaks were identified from the database, and the vital signs, hematologic and biochemical data, mode of diagnosis, treatment, and outcome were recorded and analyzed. RESULTS: We identified 55 anastomotic leaks (2.3%) at a median of 4 days (range 1-26) after surgery. In 37 patients (67.3%), the leaks were identified at a median of 5 days (range 1-26) postoperatively because of clinical signs and symptoms of a systemic inflammatory response (SIRS leaks). In contrast, in 18 patients (32.7%), the leaks were identified at a median of 1.5 days (range 1-16) postoperatively only after routine contrast studies (non-SIRS leaks). Treatment included antibiotics and open drainage in 41.8%, laparoscopic drainage in 21.8%, computed tomography-guided drainage in 12.7%, conservative treatment in 14.5%, and other in 9.2%. All 6 deaths (4 men and 2 women, 10.9%) occurred in the SIRS group. Using logistic regression analysis, temperature (inflammatory response) and body mass index were independent predictors of mortality. CONCLUSION: The results of our study have shown that one third of patients with anastomotic leaks after bariatric surgery present with minimal clinical symptoms (non-SIRS) and are only detected if contrast studies are performed. Such leaks are unlikely to lead to death. Two thirds of patients with anastomotic leaks present with a systemic inflammatory response to the leak. Such leaks require urgent treatment that might not always prevent death.     

The effect of indomethacin on burn-induced immunosuppression

Recent interest in the role of prostaglandin inhibitors as immunomodulators following major injury prompted us to study the effect of indomethacin on burn-induced immunosuppression in rats as measured by the delayed-type hypersensitivity (DTH) skin test response, ability to contain an intradermal bacterial challenge (10(8) Staphylococcus aureus 502A injected intradermally), and overall survival from spontaneous burn wound sepsis. Fifty male Sprague-Dawley rats sensitized to keyhole limpet hemocyanin (KLH) were subjected to a 30% full-thickness scald burn. Group 1 (n = 24) received indomethacin at 0.5 mg/kg intraperitoneally once daily with the first dose given immediately following the burn. Group 2 (n = 24) received vehicle only. Prostaglandin E2 measured by radioimmunoassay on day 17 was 2553 +/- 832 pcg/ml serum (+/- SEM) in the vehicle group and 1042 +/- 231 pcg/ml in the indomethacin group (P = 0.058, unpaired t test). Burn injury induced a decrease in the DTH response to KLH and an increase in the Staph lesion size (P less than 0.05) which was not corrected by indomethacin treatment. All animals developed spontaneous burn wound sepsis by day 14. Survival after 17 days in the indomethacin group was 100% compared to that of the vehicle group, 79%, P less than 0.05 (Fisher exact test). We conclude that despite unmeasurable corrections of the burn-induced suppression of the DTH response and local nonspecific bacterial defenses, low-dose indomethacin improves survival following burn sepsis.