Method of Enteral Insufficiency Syndrome Correction in Patients with Generalized Peritonitis

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Introduction

The improvement of treatment results in patients with generalized peritonitis (GP) is one of the most important tasks of an urgent surgery. The mortality rate in abdominal sepsis comprises 20% - 30%, and in case it is accompanied by the multiple organ failure, it reaches 80% - 90%.

Although the intensive care and surgical techniques for GP are constantly refined, the progressive endogenous intoxication and the multiple organ failure remain the problematic issues [1]. In peritonitis pathogenesis, the enteral insufficiency syndrome (EIS) plays a substantial role. The EIS onset and progress are preconditioned by the reduced passage of the intestinal content. The syndrome involves the impairment of the motor, secretory, suction, immune and barrier functions of the small intestine and is accompanied by the bacteria and toxins translocation from the intestinal lumen to the abdominal cavity and systemic blood flow. The increased intestinal permeability, in its turn, contributes to the presence of infection in the abdominal cavity, aggravates endotoxicosis, thus the vicious circle of GP pathogenesis is formed [2].

            In the objective assessment of pathogenetically motivated treatment of GP, the following scales are used: APACHE II, SAPS, MODS, SOFA, and some others [2-5]. The mentioned scales are efficient in detecting the illness severity in patients in critical condition, but they do not reflect the dynamics of the pathological process during the complete treatment period.

In patients with generalized peritonitis, we consider it important to use such an assessment scale, which can evaluate the stage and the dynamics of the enteral insufficiency syndrome during the entire postoperative period, thus allowing for choosing the individual treatment tactics.

The development of a diagnostic and therapeutic algorithm for patients with enteral insufficiency syndrome is the subject of scientific research.

Objectives - to define a scheme of enteral insufficiency syndrome correction in patients with generalized peritonitis, using a differential approach to treatment.

Material and methods.

The Local Ethics Committee of the Samara State Medical University approved the study.

The study included 50 patients with GP admitted to the Department of Surgery in the Samara regional clinical hospital named after V.D. Seredavin in the period from 2017 to 2019.

The study was both retrospective and prospective. The patients were divided into two clinical groups. The Group I consisted of 29 patients, who had received treatment between 2017 and 2018. The Group II included 21 patient with generalized peritonitis, admitted to the hospital in the period from 2018 to 2019, whose treatment was supplemented by the differential approach to the enteral insufficiency syndrome correction.

The inclusion criteria were: the diagnosis of secondary generalized peritonitis, a patient's informed voluntary consent, the age over 18 years. The exclusion criteria were a concurrent oncopathology, systemic blood diseases, acute oral poisoning, congenital and acquired immunodeficiency conditions, and the age older than 75 years.

At the admission, all patients underwent the following examinations: a plain radiography of the chest and abdominal cavities, abdominal ultrasound, general clinical and biochemical blood tests, and a hemostasiogram. The clinical manifestations of EIS were registered in all the patients, see Table 1.

 

Table 1. Clinical signs of the enteral insufficiency syndrome in patients included in the study

	Group I, n = 29	Group II, n = 21	χ2, p
Bloating	24	19	χ2 = 1.00 p > 0.05
Abdominal pain	27	21	χ2 = 0.502 p > 0.05
Nausea, vomiting	25	21	χ2 = 0.129 p > 0.05
Absence of defecation and gases	24	18	χ2 = 1.00 p > 0.05
Tachycardia	23	17	χ2 = 1.00 p > 0.05
Hyperthermia >38 С°	15	12	χ2 = 0.008 p = 0.927
Multiple liquid defecation with the absence of peristalsis	6	3	χ2 = 0.716 p > 0.05

 

The patients' average age in Group I was 44.1±14.7 years, in Group II - 42.2 ± 13.4 years.

The assessment of the degree of the EIS in patients in both groups was done by means of the developed evaluation scale, in 12 hours after the initial surgery, on the 2d, 4th, 6th day of the postoperative period. In patients of Group I, the degree of enteric failure was defined using the data from medical records of hospital patients.

The degree of EIS and the time of its onset registration in patients of the compared groups are presented in Table 2.

 

Table 2. Distribution of patients of study groups by the degree of enteral insufficiency in relation to the period from the disease onset.

Period from the disease onset	Enteral insufficiency degree						Total
	I		II		III
	Group II	Group I	Group II	Group I	Group II	Group I
< 24 hours	4	7	-	-	-	-	11
24 - 72 hours	-	-	6	9	2	2	19
> 72 hours	-	-	1	-	8	11	20
Total	4	7	7	9	10	13	50

 

As it can be seen from Table 2, the majority of patients, 17 (80.9%) in the Group II and 22 (75.8%) in the Group I, was admitted later than 24 hours after the onset of the disease, with II and III degree of EIS. In these patients, the toxic and terminal stages of peritonitis were observed. The first stage of EIS was registered in 11 patients: in 4 (19%) patients of the Group II and in 7 (24.2%) of the Group I, χ2 = 0.007, p = 0.934.

The severity of generalized peritonitis was evaluated using the Mannheim peritonitis index (MPI): I grade severity (MPI score lower than 21) was observed in 4 (23.8%) patients of the Group II and in 6 (27.6%) patients of the Group I, χ2 = 0.046, p = 0.830; II grade severity (MPI score 21-29) was registered in 7 (52.4%) patients of the Group II and in 10 (41.4%) persons of the Group I, χ2 = 0.047, p = 0.828; in the Group II, the III grade severity (MPI score higher than 29) was diagnosed in 10 (23.8%) patients, in the Group I - in 13 (37.9%) patients, χ2 = 0.008, p = 0.927.

In the participants of the study, the various surgical diseases determined the GP aetiology, as presented in Table 3.

 

Table 3. Causes of generalized peritonitis in patients included in the study

Diagnosis	Group I, n = 29	Group II, n = 21	χ2, p
Acute intestinal obstruction	6	8	χ2 = 0.059, p = 0.809
Abdominal adhesions	5	7	χ2 = 1.000,  p > 0.05
Perforation of a stomach and/or duodenal ulcer	5	6	χ2 = 1.000, p > 0.05
Small intestine necrosis	2	4	χ2=1.000,  p > 0.05
Pancreonecrosis	2	1	χ2 = 0.565, p > 0.05
Destructive appendicitis	1	3	χ2 = 0.629, p > 0.05

 

The patients in both groups had generalized secondary peritonitis, while 23 (79.3%) patients in the Group I and 17 (80.9%) patients in the Group II had primary surgical interventions for GP. In 6 (20.7%) patients of the Group I and in 4 (19.1%) patients of the Group II, the indication for surgical treatment was postoperative peritonitis, as a complication of previously performed operations, χ2 = 0.046, p = 0.830.

After a short preoperative preparation, all the patients underwent surgery. The surgical interventions during the first operation in both groups included the laparotomy, elimination of the source of peritonitis or delimitation of a suppurative focus, in case it was impossible to eliminate it at once, the lavage of the abdominal cavity, and intestinal intubation. In the postoperative period, the infusion, antibacterial, analgesic therapy, and medicamentous intestine stimulation continued in accordance with the generally accepted standards of treatment. In addition, the hyperbaric oxygenation and, if medically required, the slow-flow hemodiafiltration were performed.

The analysis of the treatment results in patients of the Group I showed that, despite the clinical complex surgical treatment of generalized peritonitis, the patients retained the clinical signs of enteral insufficiency syndrome. This was a background for the development and implementation of a therapeutic and diagnostic algorithm for timely correction of EIS. This algorithm was used in all patients of the Group II [15].

The developed algorithm for EIS correction is presented in Figure 1.

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1. Enteral insufficiency correction algorithm

 

The proposed algorithm reflects the differential approach in choosing the volume, composition, and mode of the infusion and enteral therapy, as well as the additional detoxification methods, depending on the degree of the enteral insufficiency. In its turn, the EIS dynamics influenced the surgical tactics in patients with GP, which involved a set of surgical measures for decompression of the abdominal cavity, lavage of the infectious focus and evaluation of the intestinal intubation efficacy.

The statistical data processing was performed using the "Statistica 6.0" software. As a method of comparative statistics, we used the χ²criterion with Yates's correction, as well as the Student's t-test. The mean values are presented in terms of mathematical expectation and standard deviation (M±s).

Results.

The response to treatment of GP in the Group I in most patients was a reduction of EIS clinical manifestations, like pain syndrome, nausea, vomiting, and hyperthermia. However, the positive dynamics in these patients was short-term, and the normalization of clinical and laboratory conditions was insufficient.

To define the treatment effectiveness in both groups, we considered the change in plasma albumin and C-reactive protein (CRP) levels, as the objective and most informative markers of peritonitis' regression (see Figure 2).

 

 

Figure 2. Laboratory tests data dynamics in patients of the study groups.

 

At the beginning of the follow-up period, the albumin level in both groups was within the physiological norm (39.5±6.05 g/l in the Group I and 37.33±4.69 g/l in the Group II, p = 0.164). On the 6th day after surgery, the patients in the Group II had a relative hypoalbuminemia of 28.31±0.77 g/l, while in the Group II the level of albumin was significantly lower: 19.3±0.51 g/l, p = 0.00001. In this control point of observation, 17 out of 21 (80.9%) patients in the Group II had peristalsis and defecation. In addition to specialized enteral mixtures, these patients received components of a smooth diet.

            The level of C-reactive protein in patients of the study groups before the first operation was 229.38±58.29 mg/l in the Group I and 226.52±61.86 mg/l in the Group II, p = 0.866. To stop the endotoxicosis signs, in 11 (52.4%) patients of the Group II, it required from 2 to 10 sessions of hyperbaric oxygenation (HBO) and from 3 to 6 sessions of slow-flow hemodiafiltration. In the Group I, HBO was performed in 5 (17.3%) patients, and extracorporeal detoxification - in 2 (6.9%) patients. Till the sixth day of the postoperative period, the levels of CRP in the compared groups had statistically significant difference: in the Group I - 104.76±13.49 mg/l, and in the Group II - 58.00±29.05 mg/l, (p = 0.003).

The dynamics of the amount of enteric effluent, detached by the intestinal tube, in patients of both groups was also different, see Table 4.

 

 

 

Table 4. Dynamics of the daily detachable probe in Group I and Group II according to the intestinal probe

	Day of the first operation, ml/day	2th day, ml/day	4th day, ml/day	6th day, ml/day
Group I, n = 29	2190.00±864.56	1777.93± 781.33	1210.34± 448.49	783.79± 469.24
Group II, n = 21	1921.43±367.43	1544.71± 279.70	559.05± 184.31	482.40± 112.87*

* Calculation of the volume of intestinal effluent discharged is given for five patients.

 

On the day of the first operation, there was no statistically significant difference in the volume of intestinal effluent in patients of both groups, p = 0.141, which corresponded to the II and III degrees of enteral insufficiency. In the patients of Group II, there was a decrease in the volume of enteric effluent, detached by the intestinal tube, by the 4th day, which coincided with the appearance of peristalsis and the discharge of gases. In 5 (23.8%) patients of the Group II, it took longer to intubate the small intestine, since the intestinal tube was used to prevent an early adhesive obstruction. In these patients, the enteral therapy regimen was changed due to the delayed EIS relief; the volume of enteric effluent, detached by the intestinal tube, was significantly lower by day 6 (482.40±112.87 ml/day) than in the Group I (783.79±469.24 ml/day), p = 0.0073.

Other important criteria of EIS reduction were active peristalsis and defecation, see Figure 3.

 

Figure 3. Timing of peristalsis and defecation in patients of the study groups

 

By the 7th postoperative day, all patients in the Group II had active intestinal peristalsis, whereas in the Group I, peristalsis was detected only in 23 (86.2%) patients (χ2 = 3.172, p = 0.075). In all patients of the Group II, the defecation was registered by the 7th day, and in the Group I, by this time, only 21 (72.4%) patient had defecation (χ2 = 4,997, p = 0.026).

 In the Group I, it required an average of 4.5±2.5 repeated abdominal interventions to stop generalized peritonitis. In the Group II, an average of 2.3±0.9 operations were performed, which is 1.9 times less than in the Group I, p = 0.000171.

            Along with the clinical and laboratory indicators of the dynamics of enteral insufficiency syndrome, the complications in the early postoperative period in patients of both groups were assessed. The severity of postoperative complications was evaluated using the Clavien-Dindo classification, Figure 4.

 

Figure 4. The number and the degree of surgical complications in patients of the study groups.

 

When applying the EIS correction algorithm, a decrease in the total number of complications and mortality was observed in the Group II. In the Group I 6 (20.7%) patients died, while in the Group II there were 3 (14.3%) lethal outcomes. The causes of death in the Group I were the progressive multiple organ failure (4 patients) and acute heart failure (in 2 patients). In the Group II, the acute circulatory failure, which led to a fatal outcome, had developed in 2 patients, and in 1 patient, the cause of death was the progressive renal failure.

Discussion.

The literature review on the problem of GP draws one's attention to a vast number of existing laboratory and instrumental methods for evaluating the degree of enteral insufficiency syndrome. These methods include detection of the level of middle molecules weight and the plasma toxicity index based on the total and effective albumin concentration in the local and systemic blood flow]; laser Doppler flowmetry of the serous-muscular membrane of the small intestine, determining the degree of EIS by the level of endotoxin of gram-negative flora in the intestinal contents using a LAL test, diagnosing the degree of EIS by ultrasound data on the state of the intestinal wall. Also, one of the well-known evaluation scales of the degree of enteral insufficiency is the system developed by Yu.M. Gain et al. [6], which contains 42 criteria, including a set of indicators that determine the immune status of the patient.

However, in practice, the technical complexity of the implementation and the duration of obtaining the results of these clinical and laboratory studies do not allow during a short time to determine the degree, the dynamics of the enteral insufficiency syndrome, as well as to correct the selected treatment for a particular patient.

In our practice, we came to the conclusion that it is necessary to create a scale that is easier to use, which can help to determine not only the degree, but also the dynamics of enteral insufficiency at any time of the postoperative period (patent of the Russian Federation 2019612419). The developed scale consists of three blocks: the laboratory block (the level of albumin, C-reactive protein, and serum potassium evaluation); the instrumental block (the measurement of the level of intraperitoneal pressure, the evaluation of the intestine state by plain abdominal radiography); and the clinical block (registration of the intraoperative data). This system assumes score intervals (1-15, 16-30, and 31-45 points) that define the three degrees of enteral insufficiency.

Nutritional support (NS) was an important component of the EIS correction algorithm. V. M. Luft et.al.divide the NS of patients into actual, auxiliary and artificial[7]. Actual NS allows you to strengthen the effect of therapeutic diet therapy by introducing additional highly nutritious enteral mixtures.

 Auxiliary NS is aimed at eliminating metabolic (micronutrient) enteral insufficiency and is the main type of nutrition for patients on the first day of the postoperative period. This type of nutrition allows you to deliver nutrients to enterocytes without energy consumption, which reduces the probability of detachment of healthy epithelial cells of the intestinal wall.

 Artificial NS is carried out in the form of enteral nutrition (enteral mixtures) and parenteral administration of nutrients. The type, variant, and speed of enteral mixtures administration and parenteral nutrition were determined based on the severity of EIS , following the protocols developed by V. M. Luft.

The enteral therapy was started within 12-24 hours after the first operation, according to the algorithm for correction of enteral insufficiency syndrome. The dynamics of enteral insufficiency was evaluated 48 hours after surgery.

One of the important criteria that reflect the regression of enteral insufficiency syndrome is considered to be a decrease in a daily volume and a change in the nature of enteric effluent, detached by the intestinal tube. These effects are connected to the presence of peristalsis of the small intestine and the movement of chyme to the distal parts of the gastrointestinal tract.

However, an early removal of the intubation can lead to a recurrence and an increase in the dynamic small bowel obstruction, and an elevation of endogenous intoxication due to incompletely arrested paresis. Thus, 4 (13.8%) patients in the Group I required the repeated surgery within 24 hours after removal of the intestinal tube, aimed at reintubation of the small intestine and elimination of intraabdominal hypertension.

At the same time, the absence of the positive dynamics (a decrease in the scores or the degree of EIS), during this period, indirectly indicated an escalation of endogenous intoxication and the presence of undrained infectious foci in the abdominal cavity. This was an indication for performing a repeated laparotomy for sanation.

The number of severe complications, (grade III-V) according to Clavien-Dindo, in patients of the Group II was lower than in the Group I, which may be associated with an early relief of EIS manifestations, although the difference in the absolute number of complications in the compared groups is statistically unreliable (χ2 = 0.003, p = 0.954). Thus, complications of the grades I and II were registered in the majority of patients of the Group II, which required an additional conservative treatment. In the Group I, the complications of grade III and IV prevailed and required the additional surgical interventions.

Consequently, the implementation of the proposed treatment and diagnostic algorithm allows improving the results of treatment in patients with GP, which is confirmed by the early relief of endogenous intoxication, the reduction of the number of complications and repeated surgeries.

            Conclusion.

1. For EIS correction, it is advisable to start the enteral therapy according to the developed algorithm within the first 12-24 hours postoperatively.
2. The absence of a positive EIS dynamics during the first 48 hours after surgery is a predictor of the progression of endogenous intoxication, which is an indication for a repeated laparotomy for sanation. The use of the differential approach to the choice of treatment tactics for EIS in patients with generalized peritonitis helps to eliminate endotoxicosis effectively, to stop the development of multiple organ failure, and to reduce the number of postoperative complications and repeated operations.

About the authors

Evgeny A. Korymasov

1. Samara State Medical University
2. Samara Regional Hospital Seredavina

Email: korymasov@mail.ru
ORCID iD: 0000-0001-9732-5212
Scopus Author ID: 6603084839

Doctor of Medical Sciences, Professor, Head of the Department of Surgery of IPE, Chief non-staff surgeon of the Ministry of Health of the Samara region

Russian Federation, 1. 443099, Russian Federation, Samara, st. Chapayevskaya, 89 2. 443095, Russian Federation, Samara, st. Tashkentskaya, 159

Sergey A. Ivanov

Samara State Medical University

Email: docisa@mail.ru
ORCID iD: 0000-0001-7131-3985
SPIN-code: 8732-7730

Doctor of Medical Sciences, Professor of the Department of Surgery of IPE

Russian Federation, 443095, Russian Federation, Samara, st. Tashkentskaya, 159

Mariya Kenarskaya

1. Samara State Medical University
2. Samara Regional Hospital Seredavina

Author for correspondence.
Email: mary.kenarskaya@gmail.com
ORCID iD: 0000-0003-1812-4143
SPIN-code: 2944-9058

surgeon of the Samara Regional Hospital Seredavina

Russian Federation, 1. 443099, Russian Federation, Samara, st. Chapayevskaya, 89 2. 443095, Russian Federation, Samara, st. Tashkentskaya, 159

Maxim U. Khoroshilov

Samara State Medical University

Email: khor-maksim@yandex.ru
ORCID iD: 0000-0002-9659-8881
SPIN-code: 6048-6009

Ph.D., assistant of the Department of Surgery of IPE

Russian Federation, 443095, Russian Federation, Samara, st. Tashkentskaya, 159

References

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