Background: Perforation peritonitis occurs due to the leak of gastrointestinal contents into the peritoneal cavity it is a surgical emergency. It can lead to severe infection therefore, peritoneal lavage with antimicrobials is a commonly employed method to decrease the microbial load during surgery. Imipenem, a broad-spectrum carbapenem, offers wider antibacterial activity. Metronidazole is used for its anaerobic spectrum of action. This was aimed to compare the efficacy of Imipenem versus Metronidazole lavage in improving clinical outcomes, infection control, and recovery in patients undergoing surgery for perforation peritonitis. Methods: This prospective comparative study was done on n=40 adult patients undergoing surgery for perforation peritonitis at our hospital. Patients were randomly divided into two equal groups: Group A (n=20) received intraoperative peritoneal lavage with Imipenem (500 mg in 1 liter NS), and Group B (n=20) received Metronidazole (500 mg in 1 liter NS). The standard surgical procedures and postoperative care were followed in all patients. Outcomes assessed included infection rates, recovery parameters, complications, and inflammatory markers. Results: Out of 40 patients included in the study, 20 received imipenem lavage Group A, and 20 received metronidazole Group B. Both groups were comparable at baseline in terms of age, gender, BMI, ASA grade, and primary diagnosis. Group A showed lower rates of surgical site infections (15% vs. 20%), intra-abdominal abscesses (10% vs. 25%), and reoperation (5% vs. 15%) compared to Group B. Postoperative recovery was better in Group A, with a shorter hospital stay, faster return to oral intake, and lower fever duration. Inflammatory markers (WBC, CRP, febrile days) were significantly lower in the imipenem group. Conclusion: This study concludes that Imipenem offers clinically superior outcomes. Although the difference in primary infection-related outcomes such as surgical site infections, intra-abdominal abscesses, and reoperation rates did not reach statistical significance, a favorable trend was observed in the Imipenem group. Statistically significant improvements were noted in secondary outcomes, including shorter hospital stay, faster return to oral intake, reduced fever duration, and better inflammatory marker profiles (WBC, CRP, and febrile days) in the Imipenem group.
Perforation peritonitis remains a significant surgical emergency worldwide and is associated with substantial morbidity and mortality. It typically results from perforation of a hollow viscus such as the stomach, small intestine, colon, or appendix, leading to contamination of the peritoneal cavity with gastrointestinal contents and microbes. Prompt surgical intervention and effective antimicrobial management are crucial for favorable outcomes in such cases [1]. Despite advances in surgical technique and intensive care, sepsis, and multiorgan dysfunction continue to complicate recovery and contribute to poor prognoses in affected individuals [2]. Peritoneal lavage, or intraoperative peritoneal irrigation, is commonly performed during laparotomy for perforation peritonitis to reduce the bacterial load, dilute endotoxins, and remove necrotic material. Traditionally, normal saline has been used for lavage, but the use of antibiotic solutions such as metronidazole or imipenem has gained attention in an attempt to provide local antimicrobial effects directly at the infection site [3]. Metronidazole is a nitroimidazole compound that is effective against anaerobic bacteria and protozoa. Its use in peritoneal lavage is based on the assumption that anaerobes play a significant role in intra-abdominal infections [4].
However, studies suggest that aerobic gram-negative organisms such as Escherichia coli and Klebsiella species also play a predominant role in secondary peritonitis, thus necessitating a broader-spectrum agent in severe cases. Imipenem, a carbapenem antibiotic, offers broad-spectrum coverage against gram-positive, gram-negative, and anaerobic organisms and has shown efficacy in complicated intra-abdominal infections when administered systemically [5]. Using imipenem in lavage aims to achieve high local antibiotic concentration with minimal systemic toxicity, potentially reducing bacterial load more effectively than metronidazole alone [6]. Comparative studies evaluating the effectiveness of different antibiotics in lavage solutions are limited. Some research indicates improved outcomes with imipenem lavage, including reduced postoperative infections, shorter hospital stays, and lower morbidity [7]. However, concerns regarding cost, antibiotic resistance, and possible hypersensitivity reactions persist. On the other hand, metronidazole remains widely used due to its established efficacy against anaerobes, lower cost, and fewer adverse effects, despite its limited spectrum [8]. The need for evidence-based practice in choosing intraoperative lavage solutions is pressing, particularly in resource-limited settings where antimicrobial stewardship is essential. This study aims to compare the efficacy of imipenem versus metronidazole as peritoneal lavage agents in adult patients undergoing surgery for perforation peritonitis. The primary outcomes assessed include postoperative infection rates, duration of hospital stay, need for re-intervention, and overall morbidity and mortality. By establishing whether one agent offers a clear clinical advantage over the other, this study seeks to inform surgical protocols and optimize management strategies for perforation peritonitis.
This prospective comparative study was conducted in the Department of General Surgery over a period of 12 months. A total of 40 patients diagnosed intraoperatively with perforation peritonitis were included after obtaining informed consent. The study aimed to evaluate and compare the efficacy of peritoneal lavage using imipenem versus metronidazole during emergency laparotomy.
Inclusion Criteria
Exclusion Criteria:
Grouping: The patients were randomly divided into two equal groups of 20 each using a simple random sampling method:
All patients underwent standard surgical management depending on the site of perforation (closure, resection-anastomosis, or stoma formation). Postoperative care included systemic broad-spectrum antibiotics (not including lavage drugs), supportive care, and monitoring in a ward or ICU setting as needed.
Outcome Measures: The following clinical parameters were recorded and compared between both groups. Postoperative fever (>38°C), Wound infection, Duration of hospital stay, Need for re-laparotomy, Intra-abdominal abscess formation, and Mortality.
Statistical analysis: All the available data was segregated, refined, and uploaded to an MS Excel spreadsheet and the data were statistically analyzed using SPSS 24 software in Windows format. Categorical variables were compared using Chi-square or Fisher’s exact test, and continuous variables were analyzed using Student’s t-test. A p-value <0.05 was considered statistically significant.
A total of 40 cases undergoing peritoneal lavage for perforation peritonitis were included in the study. They were equally distributed into two groups group A (Imipenem) and group B (metronidazole). The comparative analysis of the two groups is given in Table 1. The mean age of both groups was similar to Group A (48.3 ± 12.7 years) and Group B (50.1 ± 11.9 years), with no statistical significance. The gender-wise distribution showed that males were 60% in group A and 70% in group B and p values were not significant. Similarly, the BMI and ASA categories showed equal and comparable distribution. The most frequent primary diagnosis was perforated appendicitis and peptic ulcer perforation, with similar frequencies across both groups. The overall comparison reveals that both groups were similar at baseline levels for outcome comparison.
Table 1: Baseline Demographic and Clinical Characteristics (Ensures group comparability at enrollment) |
|||
Characteristic |
Group A (Imipenem) |
Group B (Metronidazole) |
p-value |
Sample size |
(n=20) |
(n=20) |
|
Age (years), mean ± SD |
48.3 ± 12.7 |
50.1 ± 11.9 |
0.62 |
Gender (Male) (%) |
12 (60.0%) |
14 (70.0%) |
0.52 |
BMI (kg/m2), mean ± SD |
25.4± 3.1 |
24.9 ± 2.8 |
0.58 |
ASA Grade, n (%) |
|||
I/II |
15(75.0%) |
13(65.0%) |
|
III/IV |
5(25.0%) |
7(35.0%) |
|
Primary Diagnosis |
|||
Perforated appendicitis |
10 (50.0%) |
8 (40.0%) |
0.54 |
Peptic ulcer perforation |
7 (35.0%) |
9 (45.0%) |
|
Other |
3 (15.0%) |
3 (15.0%) |
Table 2 shows the primary clinical outcomes of the two groups included in the study. A critical analysis of the table shows that surgical site infections occurred in 15% of group A cases and 20% of group B cases, and the p values were not significant. Similarly, the frequency of intra-abdominal abscesses was 10% in group A and 25% in group B (p=0.23). The overall infection rate was higher in Group B than in Group A (p=0.19). Reoperation was required in 5% of group A cases and 15% of group B cases. These results show a trend towards better results with imipenem; however, the values were not significant for any single outcome.
Table 2: Primary clinical outcomes of the cases included in the study |
|||
Outcome |
Group A (Imipenem) |
Group B (Metronidazole) |
P value |
Sample size |
N= 20 |
N=20 |
|
Surgical site infection (SSI) n(%) |
3 (15.0%) |
4 (20.0%) |
0.68 |
Intra-abdominal abscess n(%) |
2 (10.0%) |
5 (25.0%) |
0.23 |
Overall infection rate n(%) |
5 (25.0%) |
9 (45.0%) |
0.19 |
Reoperation required n(%) |
1 (5.0%) |
3 (15.0%) |
0.29 |
The postoperative recovery parameters that indicate secondary efficacy outcomes are listed in Table 3. Patients in the imipenem group had a significantly shorter hospital stay (6.2 ± 1.8 days) than those in the metronidazole group (7.8 ± 2.4 days; p=0.02). The time interval to resume oral intake was shorter in the imipenem group (2.1 ± 0.7 days vs. 3.0 ± 1.2 days; p=0.01), and the duration of fever was also shorter in the imipenem group (1.5 ± 0.6 days vs. 2.3 ± 0.9 days; p=0.003) than in the metronidazole group. The number of ICU admissions was lower in the imipenem group 9! 0%) compared to 25% in the Metronidazole group the values were not statistically significant (p=0.23).
Table 3: Postoperative Recovery Parameters |
|||
Parameter |
Group A (Imipenem) |
Group B (Metronidazole) |
p-value |
Sample size |
(n=20) |
(n=20) |
|
Hospital stay (days), Mean ± SD |
6.2 ± 1.8 |
7.8±24 |
0.02* |
Time to oral intake (days), Mean ± SD |
2.1 ±0.7 |
3.0± 1.2 |
0.01* |
Fever duration (days), Mean ± SD |
15±0.6 |
2.3 ± 09 |
0.003* |
ICU admission, n (%) |
2 (100) |
5 (25.0) |
0.23 |
*Significant
The assessment of complications and adverse events was done in both groups of cases as given in Table 4. The incidence of anastomotic leak was 5% in group A and 0% in group B and (p=0.31) was not significant. Wound dehiscence occurred only in one patient in group B. Renal impairment was seen in 10% of patients in the Imipenem group, while none occurred in the Metronidazole group (p=0.15). One allergic reaction was noted in the Imipenem group. Thirty-day mortality was 0% in Group A and 5% in Group B. None of these differences reached statistical significance.
Table 4: Complications and Adverse Events |
|||
Complication |
Group A (Imipenem) |
Group B (Metronidazole) |
p-value |
(n=20) |
(n=20) |
||
Anastomotic leak, n (%) |
1 (5.0%) |
0 (0.0%) |
0.31 |
Wound dehiscence, n (%) |
0 (0.0%) |
1 (5.0%) |
0.31 |
Renal impairment, n (%) |
2 (10.0%) |
0 (0.0%) |
0.15 |
Allergic reaction, n (%) |
1 (5.0%) |
0 (0.0%) |
0.31 |
30-day mortality, n (%) |
0 (0.0%) |
1 (5.0%) |
0.31 |
Table 5 shows the inflammatory marker dynamics, highlighting the laboratory evidence of infection control in both groups. Preoperative white blood cell (WBC) counts were comparable between Group A (Imipenem) and Group B (Metronidazole) (p=0.42). However, by postoperative day 3, Group A had significantly lower WBC counts (8.1 ± 1.6) compared to Group B (10.3 ± 2.2) (p=0.001). C-reactive protein (CRP) levels on day 3 were also significantly lower in the Imipenem group (35.4 ± 12.7 mg/L) than in the Metronidazole group (58.9 ± 18.3 mg/L) (p<0.001). Febrile days were fewer in Group A (1.1 ± 0.4) versus Group B (1.9 ± 0.7) (p<0.001), suggesting better infection control with Imipenem.
Table 5: Inflammatory Marker Dynamics (Laboratory evidence of infection control) |
|||
Parameter |
Group A (Imipenem) |
Group B (Metronidazole) |
P value |
Sample size |
N= 20 |
N= 20 |
|
Pre-op WBC (x10 3/uL), mean ± SD |
142 ± 3.1 |
15.0 ± 34 |
0.42 |
Post-op Day 3 WBC, mean ± SD |
8.1 ± 1.6 |
10.3 ± 2.2 |
0.001* |
CRP (mg/L) on Day 3, mean ± SD |
35.4 ± 12.7 |
58.9 ± 18.3 |
< 0.001* |
Febrile days (>38°C), mean ± SD |
1.1 ± 04 |
1.9 ± 0.7 |
< 0.001* |
*Significant
This study included 40 patients with perforation peritonitis who underwent peritoneal lavage at our hospital. The patients were randomly divided into two equal groups. The evaluation of the two groups at baseline is presented in (Table 1). The mean ages of groups A and B cases were (48.3 and 50.1 years), respectively. The sex distribution, BMI, ASA grade, and primary diagnoses (perforated appendicitis or peptic ulcer perforation) were similar between Groups A (imipenem) and B (metronidazole) (all p>0.05). This comparability minimizes confounding factors when assessing clinical endpoints. In this study, we found that the incidence of SSI) was lower in group A than in group B (15% vs. 20%; p=0.68), and the incidence of intra-abdominal abscesses was lower in group A compared to 25% in group B (10% vs. 25 %; p=0.23). The overall infection rates and need for reoperation were lower in group A than in group B, although none reached statistical significance. These findings were in agreement with previous similar studies where they found that broad-spectrum carbapenem lavage could reduce peritoneal contamination more effectively than anaerobe-targeted agents such as metronidazole alone [9, 10] Although the incidence of surgical site infection (SSI) was lower in the imipenem group (15% vs. 20%; p=0.68) and intra-abdominal abscesses trended downward (10% vs. 25%; p=0.23) (Table 2), none reached statistical significance. The overall infection rates (25% vs. 45%; p=0.19) and reoperation frequencies (5% vs. 15%; p=0.29) also favored imipenem. These findings align with previous studies suggesting that broad-spectrum carbapenem lavage may reduce peritoneal contamination more effectively than anaerobe-targeted agents alone [11, 12]. The assessment of secondary efficacy parameters showed significant advantages in Group A using imipenem, as shown in Table 3. Early oral intake, a key marker of postoperative recovery, occurred sooner after imipenem lavage (2.1±0.7 vs. 3.0±1.2 days; p=0.01). Fever duration also decreased significantly (1.5±0.6 vs. 2.3±0.9 days; p=0.003). Although ICU admissions were fewer with imipenem (10% vs. 25%; p=0.23), this difference did not reach significance. Rapid resolution of fever and inflammation likely facilitates earlier mobilization and feeding, contributing to shorter hospitalization [13]. The current study also assessed the complication rates in both groups. We found a similar complication profile in both groups. One anastomotic leak (5%) and two cases of renal impairment (10%) occurred in the imipenem group, versus one wound dehiscence (5%) and one 30-day mortality (5%) in the metronidazole group (all p>0.05). Allergic reactions (5%) were reported only with imipenem. Overall, both regimens were well tolerated without significant adverse events. These observations concur with those of prior studies showing low complication rates with local antibiotic lavage [6].
The laboratory markers of inflammation are presented in Table 5. Preoperative WBC counts were comparable (p=0.42), but by postoperative day 3, Group A exhibited significantly lower WBC (8.1±1.6 vs. 10.3 ± 2.2 ×10³/μL; p=0.001) and CRP levels (35.4 ± 12.7 vs. 58.9 ± 18.3 mg/L; p<0.001). Febrile days also decreased (1.1 ± 0.4 vs. 1.9±0.7 days; p<0.001). These results suggest more effective infection control with imipenem lavage, consistent with its broad-spectrum activity in reducing both aerobic and anaerobic bacterial loads [14]. The early normalization of inflammatory markers likely underlies the improved clinical recovery observed. Based on the above results, we noticed that the imipenem group yielded faster resolution of inflammation, less fever, and shorter duration of hospital stay. Similar results were shown by Kamath et al. [12], who observed reduced postoperative morbidity in the imipenem irrigation group. Although the lack of significance suggests that both regimens are generally similar, imipenem enhanced the spectrum of action, providing additional benefits and accelerating recovery.
Limitations include the relatively small cohort and short follow-up period, which may underestimate late complications. Future large-scale randomized trials could clarify whether imipenem lavage significantly reduces infection rates or reoperations. Overall, our findings support the use of imipenem as a preferred lavage agent in perforation peritonitis, particularly when broad antimicrobial coverage is warranted.
The present comparative study evaluating the efficacy of Imipenem versus Metronidazole peritoneal lavage in patients with perforation peritonitis demonstrates that Imipenem offers clinically superior outcomes. Although the difference in primary infection-related outcomes such as surgical site infections, intra-abdominal abscesses, and reoperation rates did not reach statistical significance, a favorable trend was observed in the Imipenem group. Statistically significant improvements were noted in secondary outcomes, including shorter hospital stay, faster return to oral intake, reduced fever duration, and better inflammatory marker profiles (WBC, CRP, and febrile days) in the Imipenem group. Thus, Imipenem lavage may be considered a more effective option for improving recovery and controlling infection in perforation peritonitis cases.