What Should be Done for Perforation of the Gallbladder During Laparoscopic Cholecystectomy: Prophylaxis or Treatment?

Abstract

Background:

Iatrogenic perforation of the gallbladder during laparoscopic cholecystectomy (LC) is one of the most common intraoperative complications, and there is no clear consensus among surgeons on this issue and there are studies reporting the antibiotic treatment. The aim of this study is to determine the effect of type and duration of antibiotic use on infective complications between iatrogenic perforations of the gallbladder during LC patients.

Methods:

Patients who developed iatrogenic perforation of gallbladder during LC were subdivided into three groups according to antibiotic treatment; single dose intravenous (i.v.) antibiotic group, prophylactic antibiotic + additional dose i.v. antibiotic group, and prophylaxis + additional dose i.v. antibiotic + oral antibiotic group.

Results:

A total of 577 patients who underwent LC were included in the study, and 114 patients (19.8%) had iatrogenic perforation of gallbladder. No statistically significant difference was found in wound infection and surgical site infection in all three groups (P > .05).

Conclusions:

We suggest that single dose antibiotic use is sufficient to prevent infectious complications in patients who had iatrogenic perforation of the gallbladder during LC. Adding intravenous and/or oral antibiotics does not contribute to prevention of infective complications in these patients.

Introduction

Laparoscopic cholecystectomy (LC) is one of the most common operations performed in surgical clinics. It is carried out in a very effective and safe way and is considered as the gold standard treatment for cholelithiasis.¹ LC has significant advantages such as less postoperative pain compared to open surgery, shorter recovery time and shorter hospital stay, better cosmetic results, and lower total cost of treatment.¹ One of the most important advantages of LC compared to open surgery is that it has fewer postoperative infective complications compared with open surgery due to the use of smaller incision and presence of less tissue damage.² In the literature, the mean rate of development of infective complications after LC varies between 0.4% and 6.3% and is lower than open surgery.³

Some risk factors have been reported for the development of infective complications following LC, such as the sterilization of laparoscopic instruments, microdamage to reusable instruments, bacteriobilia, spillage of bile into the abdominal cavity, and antibiotic treatment. Although there are studies investigating the effects of iatrogenic gallbladder perforation (IGP), little is known about its impact on surgical site infections.⁴ IGP during LC is one of the most common intraoperative complications, and its incidence varies between 10% and 33%. It is usually seen in cases where gallbladder dissection is difficult and surgeon is inexperienced.^5,6

Prophylactic antibiotic use before LC, one of clean surgical procedures, is highly controversial. There are many studies reporting that prophylactic antibiotic administration to low-risk LC patients has no effect on infective complications and therefore should not be used.^2,7 In a study, it was concluded that prophylaxis should not be given before low-risk LC because there is no statistically significant difference in the incidence of postoperative surgical site infection between patients with and without prophylactic antibiotics.⁸

However, there is no clear consensus among surgeons on this issue, and there are studies reporting that prophylactic antibiotics should be given before LC.^9,10 If prophylactic antibiotic is to be administered before LC, it is reported that cefazolin, a first generation cephalosporin, should be given due to reasons such as sufficient distribution of antibiotic in gallbladder wall, reaching high concentration in bile, having large antimicrobial spectrum, low toxicity, and low cost.^11,12

In this study, we aimed to investigate the effect of antibiotic prophylaxis and duration of treatment on postoperative infective complications in patients who underwent LC and had IGP during surgery in our clinic.

Materials and Methods

This study was conducted between September 2017 and November 2019 on patients who underwent LC and signed the consent form in Alanya Alaaddin Keykubat University Training and Research Hospital and Başkent University, Alanya Hospital. Age, gender, body mass index, diabetes mellitus (DM), comorbid disease and smoking history, American Society of Anesthesiologists (ASA) score, duration of surgery, presence of cholecystitis findings during surgery, and use of surgical drainage were recorded in all patients who underwent LC. Patients who developed IGP during LC were included in the study group and subdivided into three groups according to antibiotic treatment. Patient groups were determined randomly.

Study groups

Group 1

Patients who did not receive prophylaxis (cefazolin 1gr i.v.) before LC, but who received a single dose of intravenous (i.v.) antibiotic (cefazolin 1 gr) after IGP, and patients who received prophylaxis, but who were not given i.v. and/or oral antibiotics after IGP (group of patients receiving only a single dose of i.v. antibiotics).

Group 2

Patients who received prophylactic antibiotics before LC and who were administered additional dose of i.v. antibiotic (cefazolin 1 gr) after IGP but not given oral antibiotics (Prophylactic antibiotic + additional dose i.v. antibiotic group).

Group 3

Patients who received prophylactic antibiotics before LC and who were administered additional dose of i.v. antibiotic (cefazolin 1 gr) after IGP, who were given oral antibiotics (cefaclor tablet 2 × 1 p.o. for 7 days) while being discharged (Prophylaxis + additional dose i.v. antibiotic + oral antibiotic group).

All surgeons who performed the operation had at least 5 years of surgical experience. LC was performed with a total of four ports, two of which were 10 mm and two were 5 mm, and the gallbladder was removed with a removal bag in all patients. Patients with acute cholecystitis detected during surgery were excluded from the study and those with chronic cholecystitis were included in the study. All patients who had conversion to open surgery for various reasons and those who received oral antibiotics except i.v. antibiotic and cefaclor tablets were excluded from the study.

Exclusion criteria

Patients under 18 and over 65 years of age, pregnant women, patients who used antibiotics in the last week before surgery, patients receiving immunosuppressive therapy, patients receiving steroid therapy regularly, patients with thalassemia major, patients with previous abdominal surgery, patients with a history of hepatic canal stone, obstructive jaundice, cholangitis, biliary pancreatitis, previous biliary surgery, patients who underwent ERCP within the last 1 week before surgery, patients with acute cholecystitis during the last 1 month before surgery, patients with acute cholecystitis detected during surgery, patients with cephalosporin hypersensitivity, those with allergies, patients who were converted to open surgery from laparoscopy, and patients who underwent antibiotic treatment other than those specified in the study groups.

The patients were followed up for early and late postoperative wound infection and surgical site infection. Any medical, interventional, or surgical treatments were recorded.

Statistical analysis

Mean, standard deviation, median lowest, highest, frequency, and ratio values were used in descriptive statistics of the data. Distribution of variables was measured by Kolmogorov–Smirnov test. Kruskal–Wallis test was used for the analysis of quantitative independent data. The chi-square test was used for the analysis of qualitative independent data, and the Fisher test was used when the chi-square test conditions were not met. SPSS 26.0 program was used for analysis.

Ethical approval

This study was approved by the Ethics Committee of Alanya Alaaddin Keykubat University of Medical Sciences, and all of the patients were informed regarding the details of the study, and they signed a consent form.

Results

A total of 577 patients who underwent LC were included in the study, and 114 patients (19.8%) had IGP. Prophylactic antibiotics were administered to 306 patients (53.0%), and 271 patients (47%) received no prophylactic antibiotics. Wound infection was seen in 24 patients (4.2%), and surgical site infection occurred in 3 patients (0.5%). Of 463 patients who did not have iatrogenic perforation of gallbladder during the operation, wound infection was seen in 18 (3.8%) and surgical site infection in 2 (0.4%). Demographic and clinical data of all patients undergoing LC are presented in Table 1.

Table 1.

Demographic and Clinical Data of All Patients Undergoing Laparoscopic Cholecystectomy

	Min–Max	Median	Mean ± SD/n-%
Age	18.0–72.0	49.0	48.6 ± 12.6
Gender
Female			413	71.6%
Male			164	28.4%
Weight (kg)	45.0–110.0	70.0	71.6 ± 10.4
Duration of complaints (year)	1.0–10.0	3.0	3.4 ± 2.5
Duration of operation (min.)	10.0–120.0	30.0	33.3 ± 15.4
Length of hospital stay (Day)	1.0–4.0	1.0	1.1 ± 0.4
DM			72	12.5%
Cigarette smoking			46	8.0%
Comorbid disease
(−)			479	83.0%
(+)			98	17.0%
ASA scores
I			190	32.9%
II			316	54.8%
III			71	12.3%
Gallbladder perforation
(−)			463	80.2%
(+)			114	19.8%
Prophylaxis			306	53.0%
Postoperative i.v. antibiotic			144	25.0%
Oral antibiotic			100	17.3%
Drain			454	78.7%
Preoperative cholecystitis			96	16.6%
Wound infection			24	4.2%
Surgical site infection			3	0.5%

ASA, American Society of Anesthesiologists; DM, diabetes mellitus.

The gender distribution of 114 patients with IGP during LC was 75 (68.8%) female and 39 male (34.2%). The mean operation time was 30 minutes, and the mean hospital stay was 1 day. Seventeen patients (14.9%) were detected to have chronic cholecystitis intraoperatively, and surgical drainage was performed in 99 patients (86.8%). Total wound infection rate was 5.3% (6 patients) in these patients, and surgical site infection was seen in 1 patient (0.9%). Demographic data and clinical characteristics of patients with IGP during LC are presented in Table 2.

Table 2.

Demographic Data and Clinical Characteristics of Patients with Iatrogenic Perforation of Gallbladder During Laparoscopic Cholecystectomy

	Min–Max	Median	Med. ± SD/n-%
Age	18.0–64.0	51.5	49.6 ± 12.5
Gender
Female			75	65.8%
Male			39	34.2%
Weight (kg)	50.0–110.0	72.0	71.6 ± 11.3
Duration of complaints (year)	1.0–10.0	3.0	3.6 ± 2.5
Duration of operation (min.)	10.0–65.0	30.0	32.5 ± 12.4
Length of hospital stay (Day)	1.0–3.0	1.0	1.1 ± 0.4
DM			10	8.8%
Cigarette smoking			13	11.4%
Comorbid disease
(−)			92	80.7%
(+)			22	19.3%
ASA scores
I			39	34.2%
II			57	50.0%
III			18	15.8%
Drain			99	86.8%
Preoperative cholecystitis			17	14.9%
Wound infection			6	5.3%
Surgical site infection			1	0.9%

ASA, American Society of Anesthesiologists; DM, diabetes mellitus.

The results of data obtained from the patients who had IGP and grouped according to the antibiotic treatment were evaluated. It was found that 31 patients were given single dose i.v. antibiotic (Group 1), 48 patients received an additional dose of i.v. antibiotic beside prophylactic antibiotics after gallbladder perforation (Group 2), and 35 patients were given oral antibiotic at the time of discharge in addition to prophylaxis and additional dose of i.v. antibiotic (Group 3). The wound infection rate was 6.5% (2 patients) in Group 1; 4.2% (2 patients) in Group 2; and 5.7% (2 patients) in Group 3. Surgical site infection was seen in 1 patient (3.2%) in Group 1, whereas no surgical site infection was detected in Group 2 and 3 patients (0%). No statistically significant difference was found in wound infection and surgical site infection in all three groups (P > .05); the distribution of wound and surgical site infections frequency for patients groups are presented in Figure 1.

FIG. 1.

There was no statistically significant difference in terms of wound infection and surgical site infection in the analysis of the data of patient groups subdivided according to the antibiotic treatment.

There was no statistically significant difference in age, gender, weight, duration of complaints, DM and smoking history, operation time, length of hospital stay, detection of cholecystitis during the operation, and surgical drainage use between the three groups. (P > .05) It was found that the number of patients with history of comorbid disease and ASA score III was significantly lower in those who received single dose i.v. antibiotics (Group 1) compared to the patients in Groups 2 and 3 (P < .05). The distribution of the patients with IGP according to the antibiotic treatment and the data obtained are presented in Table 3.

Table 3.

The Distribution of the Patients with Iatrogenic Perforation of Gallbladder According to the Antibiotic Treatment and the Demographic Data and Clinical Characteristics

	Group I			Group II			Group III			P
	Med. ± SD/n-%		Med	Med. ± SD/n-%		Med	Med. ± SD/n-%		Med	P
Age	46.8 ± 9.9		45.0	50.0 ± 13.8		52.0	51.6 ± 12.6		54.0	.146	K
Gender
Female	20	64.5%		33	68.8%		22	62.9%		.842	χ ²
Male	11	35.5%		15	31.3%		13	37.1%		.842	χ ²
Weight (kg)	72.6 ± 11.6		74.0	70.0 ± 11.7		70.0	72.8 ± 10.5		72.0	.348	K
Duration of complaints (year)	3.6 ± 2.6		3.0	3.6 ± 2.5		3.0	3.7 ± 2.7		3.0	.999	K
Duration of operation (Min)	31.9 ± 13.0		30.0	32.0 ± 12.7		30.0	33.7 ± 11.8		30.0	.658	K
Length of hospital stay (Day)	1.2 ± 0.5		1.0	1.1 ± 0.3		1.0	1.1 ± 0.2		1.0	.231	K
DM
(−)	28	90.3%		42	87.5%		34	97.1%		.302	χ ²
(+)	3	9.7%		6	12.5%		1	2.9%		.302	χ ²
Cigarette smoking
(−)	30	96.8%		41	85.4%		30	85.7%		.244	χ ²
(+)	1	3.2%		7	14.6%		5	14.3%		.244	χ ²
Comorbid disease
(−)	30	96.8%		39	81.3%		23	65.7%		.006	χ ²
(+)	1	3.2%		9	18.8%		12	34.3%		.006	χ ²
ASA scores
I	15	48.4%		14	29.2%		10	28.6%		.040	χ ²
II	16	51.6%		25	52.1%		16	45.7%
III	0	0.0%		9	18.8%		9	25.7%
Drain
(−)	3	9.7%		7	14.6%		5	14.3%		.797	χ ²
(+)	28	90.3%		41	85.4%		30	85.7%		.797	χ ²
Preoperative cholecystitis
(−)	29	93.5%		41	85.4%		27	77.1%		.174	χ ²
(+)	2	6.5%		7	14.6%		8	22.9%		.174	χ ²
Wound infection
(−)	29	93.5%		46	95.8%		33	94.3%		P > .05	χ ²
(+)	2	6.5%		2	4.2%		2	5.7%		P > .05	χ ²
Surgical site infection
(−)	30	96.8%		48	100.0%		35	100.0%		P > .05	χ ²
(+)	1	3.2%		0	0.0%		0	0.0%		P > .05	χ ²

Bold indicates significant values.

K, Kruskal–Wallis; χ², Chi-Square test (Fisher test).

ASA, American Society of Anesthesiologists; DM, diabetes mellitus.

Discussion

IGP during LC is a common problem. Although its incidence in LC operations varies between 10% and 33% on average, the incidence rates up to 40% have been reported.^5,13 IGP during LC is usually encountered at the stage where the gallbladder is dissected and manipulated by grasping forceps, during which traction is applied, at the stage where the gallbladder is being removed from the liver by electrocautery or at the stage where the trocar is being removed from its place.^14,15

Risk factors for IGP such as male sex, elderly patients, overweight patients, previous acute cholecystitis episode or previous laparotomy, clip slippage, presence of infected bile, laser use, and surgeon experience have been reported.^1,5 In our study, 577 patients who underwent LC were investigated, and 114 patients (19.8%) had IGP during surgery. The mean age of the patients was 51.5 years, and the mean weight was 72 kg. IGP was seen in 75 (18.7%) of 413 female patients who underwent LC, 39 (23.7%) of 164 male patients, 97 (20.1%) of 481 patients who did not have cholecystitis at the time of the surgery, and 17 (17.7%) of 96 patients who had cholecystitis at the time of the surgery.

Although long-term outcomes and complications of spillage of bile and gallbladder stones into the abdominal cavity due to IGP during LC are not well documented, it has been reported that IGP causes various complications such as increased pain in the early postoperative period, postoperative fever, ileus, increased frequency of infections, especially in trocar entry sites, and intra-abdominal abscess development.^5,16 It is believed that bile contamination due to IGP during LC, which is considered as an aseptic surgery in the absence of bile spillage into the abdominal cavity, will increase the complications such as surgical site infection, intra-abdominal residual abscess, and wound infection; however, it is assumed that abdominal lavage decreases the risk of developing surgical site infection.

In contrast, there is no clear consensus whether prophylactic antibiotic administration is sufficient or the continuation of antibiotic therapy should be commenced; therefore, the duration of antibiotic therapy is not clear.¹⁷ In a recent study of 591 cases who developed IGP during LC and had bile and stone spillage into the abdomen, the surgical site infection rate was reported as 7.1%, intra-abdominal abscess rate was 2.1%, and it has been concluded that IGP increases the risk of developing postoperative infections after LC.¹⁸ The surgical site infection rate was reported. Although there are studies indicating that IGP during LC increased the number of infectious complications such as fever and intra-abdominal abscess,^19,20 some other studies have reported that this condition does not increase complications and has no effect on reoperation rates.^21,22

In routine practice, the procedure used to prevent infective complications, especially when perforation occurs, includes irrigation and aspiration of the peritoneal cavity.¹³ In a study examining the effect of IGP during LC on the development of surgical site infection, no significant difference was found between the sexes; however, it was found that the risk of infection development increased with age, and it has been reported that the gallbladder perforation did not increase the risk of surgical site infection but positive bile culture (bacteriobilia) is a risk factor for the development of infective complications and that antibiotherapy is necessary only for elderly patients.⁴ In addition, it has been reported that presence of colic attacks in the last 1 month, ASA score, diabetes, and obesity are among the risk factors for the development of surgical site infection after LC.^2,23

Administration of prophylactic antibiotics before LC is controversial. Prophylactic antibiotic use before open cholecystectomy surgery, which is classified as clean-contaminated surgical procedure, is recommended with regard to the risk of infection development, whereas antibiotic prophylaxis before LC surgery, which is classified as clean surgical procedure, should be applied only to patients considered to be at high risk.^24,25 Pre-LC prophylaxis recommended and accepted in high-risk patients, including patients over 60 years, patients with diabetes, immunosuppression, biliary stones and obstruction, cholangitis, jaundice, patients with a history of colic attack within 30 days preoperatively, and patients with cholecystitis at the time of surgery and those with history of biliary surgery.^8,26

In addition to studies reporting no association between gallbladder perforation and postoperative surgical site infection, there are studies reporting that gallbladder perforation is a risk factor for the development of surgical site infections, and prophylactic antibiotics should be administered along with abdominal lavage in cases of IGP.^{2,4,10,14,27,28} In a study, routine antibiotic administration was not necessary in patients who developed IGP during LC, and prophylaxis would be sufficient in elderly patients, diabetic patients, patients with an ASA score greater than 3, and when operative time exceeded 70 minutes.⁶

In our study, patients with IGP during LC were divided into groups according to antibiotic treatments, and wound infection rate was 6.5% in Group 1, 4.2% in Group 2, and 5.7% in Group 3. Collection of intraoperative abdominal purulent fluid was observed in 1 patient (3.2%) in Group 1, whereas surgical site infection was not detected in Group 2 and 3 patients. There was no statistically significant difference between the three groups in terms of wound infection and surgical site infection. There was no statistically significant difference between the three groups in terms of age, gender, weight, duration of complaints, diabetes and smoking history, duration of surgery, length of hospital stay, detection of cholecystitis at the time of surgery, and surgical drain use. Therefore, in the evaluation of the patient groups, no negative factor affecting the outcome was observed in our study. It was found that the number of patients with a history of comorbid disease and those with an ASA score of III were significantly lower in patients receiving single dose i.v. antibiotics (Group 1) compared with those in Groups 2 and 3.

In all studies conducted on IGP during LC, bile spillage alone into the abdomen was not studied; gallbladder stones spilled into the abdominal cavity were investigated.⁶ In a retrospective study of 481 cases who developed IGP during LC and had bile and stone spillage into the abdomen, the patients were divided into two groups as antibiotic-treated and nonantibiotic-treated patients, and there was no significant difference in the development of infectious complications between the patients receiving and not receiving antibiotics.

In addition, it was reported that the retrospective nature of the study was a limiting factor and that no conclusion could be achieved about the effect of prophylactic antibiotic use and starting antibiotic treatment at the time of gallbladder perforation development on infectious complications.²⁹ In another recent study, IGP was observed in 37 of the 100 patients who underwent LC, and the patients with and without perforation were compared with regard to development of infectious complications. As a result of this study, it was reported that abdominal lavage during perforation reduced the bacteria levels in abdominal cavity, and perioperative antibiotic prophylaxis was sufficient in patients who developed perforation of gallbladder.¹⁷

There were some limitations to this study. First, increasing patient age (especially over 65 years) and having an ASA score greater than 3 increase the risk of infection development. Therefore, the change in the number of elderly and patients with ASA score greater than 3 may affect the overall infection rates. Second, the diagnosis of infections was assessed by only surgeons and it depending on their own clinical experiences.

In conclusion, although the dose and duration of antibiotic treatment in patients who developed IGP during LC are controversial, our study concluded that single dose antibiotic use in patients undergoing elective LC is sufficient to prevent infectious complications. In addition to prophylaxis or a single dose of antibiotics, adding intravenous and/or oral antibiotics does not contribute to prevention of infective complications in these patients. We also think that it may cause problems such as development of bacterial resistance, increasing the frequency of opportunistic nosocomial infections, and high cost.

Footnotes

Acknowledgment

We thank all our patients who participated in this study.

Disclosure Statement

The authors have no conflicts of interest relevant to this article.

Funding Information

No funding was received for this article.

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