Role of Prophylactic Antibiotics in Laparoscopic Cholecystectomy and Risk Factors for Surgical Site Infection: A Randomized Controlled Trial

Patients and Methods

Results

During the period of the study, 146 laparoscopic cholecystectomies were performed of which 100 patients met the inclusion criteria and were enrolled in the study. There was no statistically appreciable difference in demographic or clinical characteristics between the two study groups (Table 1), as determined by the χ² method of analysis. According to laboratory culture, 18% of the patients in group A had infected bile, whereas 22% of patients in group B had infected bile (χ² = 0.25; p = 0.61). The most common organism in both groups was Escherichia coli (22%) followed by Klebsiella spp. (10%), Enterobacter spp. (6%), and Pseudomonas spp. (2%).

In group A, 4% of patients developed an SSI whereas in group B, 8% of patients had an SSI. This difference was not statistically significant (χ² = 0.71; p = 0.40). In group A, one patient with SSI had erythema only and responded to oral antibiotics and analgesics, whereas in another, the incision had to be opened because of pus discharge. Staphylococcus aureus was isolated from the pus, and the site healed with daily dressing. In group B, three patients had erythema and responded to oral antibiotics and analgesics, whereas in another, sutures had to be removed because of pus discharge. No organism was isolated from the pus in this patient. He likewise responded well to daily dressing. All patients who had SSIs did not have infected bile. None of the patients in either group had subhepatic fluid collection, pneumonia, or urinary tract infection. Two patients in group [A or B?] had one spike of fever (101°F) on postoperative day one, which responded to oral paracetamol.

Risk factors, including the age of the patient, sex, body mass index, American Society of Anesthesiologists (ASA) score, duration of pneumoperitoneum, gallbladder rupture, stone spillage, presence of diabetes mellitus, episode of colic within 30 days, presence of cirrhosis, and presence of infected bile, were analyzed with binary logistic regression analysis, which showed no contributing risk factor for SSI (Table 2).

Discussion

There are several factors to be taken into account to determine the relevance of prophylactic antibiotics. First, one needs to consider whether the two groups are reasonably comparable to show meaningful differences in the two treatment regimens. Table 1 clearly indicates that our two groups were statistically comparable with respect to age, sex, body mass index, ASA score, presence of diabetes mellitus, cirrhosis, episode of colic in the previous month, intraoperative gallbladder rupture, stone spillage, presence of an intrahepatic drain, duration of surgery, postoperative hospital stay, and the presence of bile infection. Second, is the antibiotic chosen right for its assigned task? Ceftriaxone sodium was used for prophylaxis, as it has long half-life (8 h), coverage of both gram-positive and gram-negative organisms with low toxicity, a high concentration in the bile, and good tissue penetration.

The presence of SSI was 4% when prophylactic antibiotics were given and 8% in the absence of prophylactic antibiotics, but his difference was not statistically significant (χ² = 0.71; p = 0.40). The high rate of SSI in our trial was attributable to our liberal definition of such infections. A single dose of ceftriaxone failed to lower the rate of SSI in laparoscopic cholecystectomy. This result is consistent with findings of other randomized controlled trials, as is evident from Table 3. Chang et al. [3] could not find any potential risk factor associated with SSI, whereas Tocchi et al. [6] identified an episode of colic within 30 days and the presence of diabetes mellitus as potential risk factors for SSI and recommended prophylactic antibiotic use in the presence of these risk factors. We could not identify any risk factor contributing to SSI, as shown by binary logistic regression analysis. It is interesting that the presence of infected bile is not a risk factor: None of the patients who developed SSI had infected bile. This conclusion is substantiated by the fact that gram-negative organisms were the isolates from bile, but they could not be isolated from the pus swabs taken from wounds. This is in contrast to findings of Shindolimath et al. [10], who showed infected bile to be the most important predictor of SSI, making this a controversial issue.

The low rate of SSI in laparoscopic cholecystectomy, which seems to be unrelated to the use of prophylactic antibiotics, may be attributed to many factors. Various factors, including smaller incisions, reduced tissue handling, less impact on the immune system, minimal exposure to the external environment, CO₂ pneumoperitoneum, and better visibility of tissues for dissection and hemostasis, have been advocated. Schietroma et al. [11] pointed out that laparoscopic cholecystectomy causes a lesser degree of systemic endotoxemia than does open cholecystectomy. Endotoxin is a potent stimulator of the release of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). West et al. [12] proposed that cellular acidification induced by peritoneal CO₂ insufflation contributes to blunting of the local inflammatory response during laparoscopic surgery. Subsequently, West et al. [13] provided additional experiments to study the kinetics of CO₂-induced alteration in cytokine secretion. A significant reversible inhibition of TNF and IL-1 was demonstrated in macrophages incubated in CO₂ but not with helium or air. Hanly et al. [14] concluded that intra-abdominal CO₂ during laparoscopy attenuates the acute-phase inflammatory response associated with perioperative sepsis.

Pneumoperitoneum directly affects the peritoneal defense system. Iwanaka et al. [15] observed a higher number and greater viability of peritoneal macrophages in CO₂ pneumoperitoneum as opposed to conventional open surgery. Watson et al. [16] evaluated the effect of different factors in ambient air on the inflammatory response during surgery. They observed a decrease in phagocyte activity with open surgery in comparison with laparoscopy. Thus, the peritoneal cell mechanisms display better preservation during laparoscopic than open surgery. This preservation of the immune system is a major cause of the lower frequency of SSI.

Injudicious use of antibiotics puts a financial burden on the already-overburdened health sector, which is particularly important in developing countries. Higgins et al. [7] estimated that US$30,060 could have been saved per year in their institution had they not used prophylactic antibiotics in laparoscopic cholecystectomy. Moreover, with the use of antibiotics, multidrug resistance may increase, a particularly undesirable outcome if the antibiotic use was not necessary.

Elective laparoscopic cholecystectomy is associated with a low risk of SSI, which could not be brought down with prophylactic antibiotics. Therefore, prophylactic antibiotics are not recommended in laparoscopic cholecystectomy. No risk factor contributing to SSI could be identified. Keeping in mind the small sample size of this study (underpowered) and the magnitude of the impact these findings may have on the health sector, the results need to be evaluated further with multicenter randomized controlled trials with larger numbers of patients.