Open or closed abdomen post laparotomy to control severe abdominal sepsis: a survival analysis

ABSTRACT Introduction: severe abdominal sepsis, accompained by diffuse peritonitis, poses a significant challenge for most surgeons. It often requires repetitive surgical interventions, leading to complications and resulting in high morbidity and mortality rates. The open abdomen technique, facilitated by applying a negative-pressure wound therapy (NPWT), reduces the duration of the initial surgical procedure, minimizes the accumulation of secretions and inflammatory mediators in the abdominal cavity and lowers the risk of abdominal compartment syndrome and its associated complications. Another approach is primary closure of the abdominal aponeurosis, which involves suturing the layers of the abdominal wall. Methods: the objective of this study is to conduct a survival analysis comparing the treatment of severe abdominal sepsis using open abdomen technique versus primary closure after laparotomy in a public hospital in the South of Brazil. We utilized data extracted from electronic medical records to perform both descriptive and survival analysis, employing the Kaplan-Meier curve and a log-rank test. Results: the study sample encompassed 75 laparotomies conducted over a span of 5 years, with 40 cases employing NPWT and 35 cases utilizing primary closure. The overall mortality rate observed was 55%. Notably, survival rates did not exhibit statistical significance when comparing the two methods, even after stratifying the data into separate analysis groups for each technique. Conclusion: recent publications on this subject have reported some favorable outcomes associated with the open abdomen technique underscoring the pressing need for a standardized approach to managing patients with severe, complicated abdominal sepsis.


INTRODUCTION
S epsis is one of the main causes of death in the world1,2 , and intra-abdominal sepsis is the second most common form of sepsis 3 .Generalized peritonitis, which then progress to severe complicated abdominal sepsis (SCAS), represents one of the most challenging clinical situations that surgeons face in their daily care routine.
It can quickly progress to shock and failure of multiple organs and systems, leading to relevant morbidity and mortality rates [4][5][6][7] .
This condition very commonly requires reoperations to review the abdominal cavity to eliminate persistent or recurrent peritonitis or to treat complications from the progression of infection, even for those patients who receive expanded antimicrobial therapy and adequate clinical support after an initial surgical approach [8][9][10] .

One of the therapeutic strategies is treatment
with an open abdomen, without primary closure of the abdominal wall at the end of a laparotomy, applying negative pressure therapy (NPT) to remove the accumulation of fecal, enteric, purulent, inflammatory, and/or infectious ascites, to try and control the septic focus 4,6,9,[11][12][13] .The other strategy is the primary synthesis of the cavity at the end of the first operative approach, which is part of the routine of any abdominal surgery.

Publications on the subject demonstrate results
favorable to NPT [14][15][16][17] .Complications such as enteric fistula and inability to close the aponeurosis, with progression to incisional hernia, were more frequent when the primary synthesis of the abdominal wall was not performed and the abdomen was left open in a peritoneostomy, without negative pressure applied 6,8,18 -21 .
To reduce complications and harm to these patients, diagnosis and appropriate therapy must be carried out as soon as possible 22 .The delay in decisionmaking and/or in referring the patient to a specialized center causes morbidity and mortality to increase significantly 22 .Therefore, reference hospitals must be prepared for a surgical approach, in addition to providing excellent clinical and hemodynamic support for patients with SCAS.
A global consensus on the best approach has not yet been defined, that is, primary synthesis of the aponeurosis in the first operation or performance of NPT.
Although primary synthesis is still used for treatment, many studies have already demonstrated satisfactory results with NPT 4,5,[14][15][16]23,[24][25][26][27] . Current esearch shows that this therapeutic approach, especially after the development and improvement of advanced therapies, has been a reliable and feasible option, providing greater safety to the abdominal viscera and greater control of the spread of inflammatory mediators of abdominal sepsis 14,23 .
The objective of this study was to carry out a survival analysis of patients treated at a university hospital in southern Brazil, comparing treatments for severe intra-abdominal sepsis with Barker-type, openabdomen negative pressure therapy (NPT) or with primary aponeurosis synthesis after laparotomy.

Study design and location
We conducted an observational, retrospective research, based on secondary data obtained from electronic medical records of patients with diffuse peritonitis that progressed to SCAS treated at the Hospital Universitário Regional de Maringá (HURM) between 2017 and 2021.
HURM is a reference center for more than 115 counties in the northwestern macro-region of the state of Paraná, Southern Brazil, serving a population of approximately two million for various causes.Among these, acute abdomen stands out, most patients being referred to the tertiary hospital from health services that lack the capacity for definitive treatment.

Inclusion and exclusion criteria
We included individuals over eighteen years old with known or suspected infectious cause of abdominal focus and one or more signs of hemodynamic instability (volume-refractory hypotension, tachypnea, tachycardia, lability of body temperature, change in level of consciousness, oliguria, cold extremities, and/ or thin pulses with signs of poor perfusion, among others) [1][2][3]5,7 , with intraoperative evidence of purulent spillage and presence of free enteric content in the abdominal cavity, who underwent closure with primary aponeurosis synthesis or NPT 27 .
The NPT used in the service was the Barker technique, which consists of a fenestrated, nonadherent polyethylene sheet placed over the viscera and covered with sterile surgical pads.Two surgical drains are positioned between the pads, the abdomen is sealed with a large adhesive dressing, and the drains are connected to a continuous suction system 28 .
Exclusion criteria were pregnancy, trauma, laparoscopy, inability to close the cavity due to undue tension or inducing abdominal hypertension, and uncontrollable bleeding.We also excluded patients with data considered insufficient for analysis or barely present in the medical records, minimizing potential bias.
Due to high-cost issues, no commercial dressings were used in the hospital service for the treatment of severe intra-abdominal sepsis.

Data source
Secondary data collected from patients' electronic medical records were stored in an Microsoft Excel spreadsheet.Subsequently, they were analyzed in a descriptive and inferential way using the R software.
The variables used in the study include demographics

Data analysis
After the descriptive analysis, we used the chi-square statistical test to make comparisons between the two abdominal wall closure techniques as to the described variables of interest, adopting a significance level of 5% (p≤0.05).
Survival analysis was performed using the Kaplan-Meier method.Initially, an overall survival curve was constructed, representing patient survival throughout hospitalization.Then, a second curve was created to compare patients who underwent the primary aponeurosis closure technique with those who received NPT, applying the log-rank test.Furthermore, for a more comprehensive analysis, we established a categorization criterion that involved the definition of a specific therapeutic group for each of the two surgical techniques studied.This distinction was made as follows: if in the first surgery in which primary synthesis was adopted as the closure technique patients subsequently required a second surgical intervention, they were considered as members of the group.This occurred when the initial approach was not sufficient to resolve the problem.On the other hand, if in the first surgery in which NPT was used and in the subsequent intervention it was not possible to close the abdominal wall, these cases were also included in the analysis of this portion of the sample.This indicates that the initial technique did not achieve the desired result.
The final manuscript of the present study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines, which guarantee transparent reporting and are considered the standard for observational studies 30

RESULTS
There were 75 laparotomies for abdominal infectious causes during the five-year period, 48 male patients (64%) and 27 females (36%).The average age was 59.52 years, with a standard deviation of 17.32 and a median of 61.
The indications for surgical treatment were divided into the different types of acute abdomen, such as perforating, inflammatory, obstructive, and ischemic (Table 1).There was no hemorrhagic abdomen within the sample.Patients who required re-approach were typically for review of the cavity and lavage, in addition to evaluation of complications.The distribution approximated an average of three operations from the first intervention and a standard deviation of 2.76.
Among fistula-type complications, enteric fistula was the most frequent, represented by 47.8% of cases, followed by colonic one, in 21.7% of cases (Table 2).However, age presented a significant p-value, demonstrating homogeneous distribution between age groups for patients undergoing NPT versus primary synthesis.
Patient survival was analyzed with the Kaplan-Meier method, allowing a clear observation of the relationship between a lower chance of survival and increased length of stay (Figures 1 and 2).This downward trend, although relatively constant, did not allow the identification of a clear cut-off period.When comparing open abdomen with primary synthesis (Figure 2), the log-rank test resulted in a p-value of 0.43, not statistically significant.Therefore, there is insufficient evidence to reject the null hypothesis that the two techniques have the same effect on survival.
Furthermore, we can observe a similarity in the curves, with a slight advantage for primary closure in the initial days after surgery.For example, NPT reached 50% mortality just after the 20 th day, while primary synthesis did it close to the 30 th day.As for stratification by cause, we found a high incidence of perforating acute abdomen.Perhaps due to the delay in transferring a patient to the reference center or even due to the epidemiological profile of the sample, with patients with various comorbidities and advanced age, gastroduodenal ulcers, for example, prevailed.Another important point is the absence of acute hemorrhagic abdomen, which is easily explained, as trauma was considered an exclusion criterion.
Among the complications detected, the sample deviates from some numbers frequently reported in other services.The Atema 20 meta-analysis brought variations Despite the lack of statistical significance when comparing the treatments (Figure 2), when exploring survival between the techniques in more depth (Figure 3), we observed that the survival analysis curves for the two different approaches are remarkably similar, with a p-value of 0.7, confirming the lack of statistically significant difference between them.Although at times patients with prolonged hospitalization on NPT seem to have a favorable evolution, mainly from the second week of hospitalization on, it is important to highlight that the curves cross on three distinct occasions during the period studied.This points to a continuous oscillation between the approaches and any conclusive statement about the superiority of one over the other would be premature based on these results, so a data set with a larger number of participants would allow for a more robust and conclusive analysis.from 5.7% to 17.2% for fistulas.These values, although focused on the abdominal wall closure technique, are lower than the 29.3% in our institution.Other complications are less common and are consistent with other surveys 20,21 .
The approach to sepsis requires effective decisionmaking as soon as patient care begins 31 .The treatment of abdominal sepsis has the surgical approach as the main therapeutic pillar.It also includes immediate elimination of the infectious focus, with intensive resuscitation support and antimicrobial therapy, in addition to reoperations 15,19 .
In the literature, there is still no consensus on which patients should undergo relaparotomy 8,15 .The decision is often challenging and difficult, especially when faced with critically ill patients with non-specific signs and symptoms of sepsis.The need and timing of relaparotomy is also still very subjective 10 , as without standardization of conduct, optimized results may not be achieved.
In a large Dutch study conducted by Van Ruler 8 , 42% of patients required relaparotomy to control persistent or suspected peritonitis.Unusually, 31% of these patients had a negative laparotomy.They observed that in the group of critically ill patients, mortality was not lower with planned relaparotomy, contrary to what is currently widely accepted.The results, then, concluded that on-demand laparotomy versus planned laparotomy really was the most rational approach at the time.However, a criticism to consider in understanding surgical source control is that Van Ruler8 did not use a contemporary open abdomen approach in either arm of his study and that the abdominal aponeurosis was formally closed in both groups.
Aspects other than the mortality rate are under discussion.Some studies indicate that ondemand laparotomy substantially reduces the number of relaparotomies, the need for Intensive Care Unit (ICU), and medical costs 32 .According to Scriba 32 , the ICU admission rate was 45% lower in on-demand laparotomy.
A meta-analysis of retrospective studies by Lamme 33 and a subsequent randomized clinical trial by Van Ruler 8 (aptly called the "RELAP" trial) both concluded that planned relaparotomy does not bring a survival advantage, may in fact increase morbidity, and leads to significant increases in healthcare costs.
Despite the advancement and improvement of intensive therapy 31 , isolated pharmacological therapies are not the answer to controlling generalized infection and organ dysfunction.Several trials in this regard were proposed to contain post-infectious inflammation, proving, however, to be extremely expensive and frustrating, without beneficial results for patients 34,35 .
The results from the study's institution, from 2017 to 2021, did not show statistically significant outcomes when comparing the primary closure of the aponeurosis and the application of a vacuum dressing for the treatment of SCAS.We also observed, for patients undergoing NPT in the first operation, a lack of standardization regarding the best time for re-approaches, the external appearance of the dressing often being the reason for the decision on when to perform a new procedure.Overall, the survival curves demonstrated limited results, but with some important points of discussion.The individual general clinical picture appears to be a primary and independent factor in mortality.However, if the patient survives long enough for long-term assessment, little difference is noted in the two techniques used.Therefore, it is important to highlight that, in agreement with their condition, critically ill patient groups undergo more interventions, the need for early re-approach being a clear factor in indicating NPT.
This proves that establishing a systematization for the treatment of patients with SCAS is essential to obtain optimized results that follow updated research on the topic 15,17,[36][37][38] .
The open abdomen (OA) strategy in general surgery has been increasingly reported in uncontrolled series as a potentially beneficial option for patients with severe complicated abdominal sepsis 5,8,9,12,13,39

(
age and sex), type of procedure and duration, ASA score (American Society of Anesthesiologist), surgical indication, time of onset of symptoms, closure technique of the first approach, duration of NPT in days, number of surgical interventions, number of complications, days of intensive care, time from arrival to outcome, and interval in days between the procedures. .
The project was approved by the Academic Activities Regulation Commission (COREA) of HURM (n° 059/2020) and by the Permanent Ethics Committee on Research with human beings of the State University of Maringá (COPEP/UEM) -(CAAE: 63638822.4.0000.0104).

( 22 )
, the remainder being six cases.The time from onset of symptoms to the operation in question resulted in an average of three days, indicating a rapid evolution of symptoms.In the medical records analyzed, we found two main techniques for closing the abdominal wall for the treatment of SCAS.In total, there were 40 NPTs implemented using the Barker technique and 35 primary syntheses.Of the patients with a known outcome, excluding those who were transferred or evaded medical care, 31 (45%) were discharged and 38 (55%) died.

Figure 1 .
Figure 1.Univariate analysis of survival after the first intervention.
whom NPT was used, its average duration was 6.66 days, standard deviation of 8.55, and median of 3, with a maximum of 39 days.The average length of stay in an intensive care environment was 14.73 days, with a standard deviation of 18.86.The time from NPT to outcome was quite variable, with a mean of 20.19 days, a median of 18, and a standard deviation of 16.94 days.Table 3 demonstrates the distribution of variables by type of treatment instituted.The chi-square test, based on the distribution between groups and associated variables, such as sex, ASA, and number of complications, did not show statistical significance.

Figure 1
Figure 1 demonstrates the overall survival of patients throughout hospitalization.The median survival occurs approximately on the 28 th day, so that at the end of the first month of hospitalization, half of the patients remained alive, not considering the patients who were discharged, represented by the crosses (+) in the graph.

Figure 2 .
Figure 2. Survival time until outcome according to the technique used in the first intervention.

Figure 3 .
Figure 3. Survival curve according to the closure technique used.

Table 1 -
Distribution of patients according to the type of acute abdomen.

Table 2 -
Description of the types of fistulas.

Table 3 -
Comparison of variables by therapy group.